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Sample records for significantly improved cell

  1. Histone deacetylase inhibitor significantly improved the cloning efficiency of porcine somatic cell nuclear transfer embryos.

    Science.gov (United States)

    Huang, Yongye; Tang, Xiaochun; Xie, Wanhua; Zhou, Yan; Li, Dong; Yao, Chaogang; Zhou, Yang; Zhu, Jianguo; Lai, Liangxue; Ouyang, Hongsheng; Pang, Daxin

    2011-12-01

    Valproic acid (VPA), a histone deacetylase inbibitor, has been shown to generate inducible pluripotent stem (iPS) cells from mouse and human fibroblasts with a significant higher efficiency. Because successful cloning by somatic cell nuclear transfer (SCNT) undergoes a full reprogramming process in which the epigenetic state of a differentiated donor nuclear is converted into an embryonic totipotent state, we speculated that VPA would be useful in promoting cloning efficiency. Therefore, in the present study, we examined whether VPA can promote the developmental competence of SCNT embryos by improving the reprogramming state of donor nucleus. Here we report that 1 mM VPA for 14 to 16 h following activation significantly increased the rate of blastocyst formation of porcine SCNT embryos constructed from Landrace fetal fibroblast cells compared to the control (31.8 vs. 11.4%). However, we found that the acetylation level of Histone H3 lysine 14 and Histone H4 lysine 5 and expression level of Oct4, Sox2, and Klf4 was not significantly changed between VPA-treated and -untreated groups at the blastocyst stage. The SCNT embryos were transferred to 38 surrogates, and the cloning efficiency in the treated group was significantly improved compared with the control group. Taken together, we have demonstrated that VPA can improve both in vitro and in vivo development competence of porcine SCNT embryos.

  2. Integration of biomimicry and nanotechnology for significantly improved detection of circulating tumor cells (CTCs).

    Science.gov (United States)

    Myung, Ja Hye; Park, Sin-Jung; Wang, Andrew Z; Hong, Seungpyo

    2017-12-13

    Circulating tumor cells (CTCs) have received a great deal of scientific and clinical attention as a biomarker for diagnosis and prognosis of many types of cancer. Given their potential significance in clinics, a variety of detection methods, utilizing the recent advances in nanotechnology and microfluidics, have been introduced in an effort of achieving clinically significant detection of CTCs. However, effective detection and isolation of CTCs still remain a tremendous challenge due to their extreme rarity and phenotypic heterogeneity. Among many approaches that are currently under development, this review paper focuses on a unique, promising approach that takes advantages of naturally occurring processes achievable through application of nanotechnology to realize significant improvement in sensitivity and specificity of CTC capture. We provide an overview of successful outcome of this biomimetic CTC capture system in detection of tumor cells from in vitro, in vivo, and clinical pilot studies. We also emphasize the clinical impact of CTCs as biomarkers in cancer diagnosis and predictive prognosis, which provides a cost-effective, minimally invasive method that potentially replaces or supplements existing methods such as imaging technologies and solid tissue biopsy. In addition, their potential prognostic values as treatment guidelines and that ultimately help to realize personalized therapy are discussed. Copyright © 2017. Published by Elsevier B.V.

  3. Transplantation of N-Acetyl Aspartyl-Glutamate Synthetase-Activated Neural Stem Cells after Experimental Traumatic Brain Injury Significantly Improves Neurological Recovery

    Directory of Open Access Journals (Sweden)

    Mingfeng Li

    2013-12-01

    Full Text Available Background/Aims: Neural stem cells (NSCs hold considerable potential as a therapeutic tool for repair of the damaged nervous system. In the current study, we examined whether transplanted N-acetyl aspartyl-glutamate synthetase (NAAGS-activated NSCs (NAAGS/NSCs further improve neurological recovery following traumatic brain injury (TBI in Sprague-Dawley rats. Methods: Animals received TBI and stereotactic injection of NSCs, NAAGS/NSCs or phosphate buffered saline without cells (control into the injured cortex. NAAGS protein expression was detected through western blot analysis. Dialysate NAAG levels were analyzed with radioimmunoassay. Cell apoptosis was detected via TUNEL staining. The expression levels of specific pro-inflammatory cytokines were detected with enzyme-linked immunosorbent assay. Results: Groups with transplanted NSCs and NAAGS/NSCs displayed significant recovery of the motor behavior, compared to the control group. At 14 and 21 days post-transplantation, the motor behavior in NAAGS/NSC group was significantly improved than that in NSC group (pConclusion: Our results collectively demonstrate that NAAGS/NSCs provide a more powerful autoplastic therapy for the injured nervous system.

  4. Radiotherapy is associated with significant improvement in local and regional control in Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Kang, Susan H; Haydu, Lauren E; Goh, Robin Yeong Hong; Fogarty, Gerald B

    2012-01-01

    Merkel cell carcinoma (MCC) is a rare tumour of skin. This study is a retrospective audit of patients with MCC from St Vincent’s and Mater Hospital, Sydney, Australia. The aim of this study was to investigate the influence of radiotherapy (RT) on the local and regional control of MCC lesions and survival of patients with MCC. The data bases in anatomical pathology, RT and surgery. We searched for patients having a diagnosis of MCC between 1996 and 2007. Patient, tumour and treatment characteristics were collected and analysed. Univariate survival analysis of categorical variables was conducted with the Kaplan-Meier method together with the Log-Rank test for statistical significance. Continuous variables were assessed using the Cox regression method. Multivariate analysis was performed for significant univariate results. Sixty seven patients were found. Sixty two who were stage I-III and were treated with radical intent were analysed. 68% were male. The median age was 74 years. Forty-two cases (68%) were stage I or II, and 20 cases (32%) were stage III. For the subset of 42 stage I and II patients, those that had RT to their primary site had a 2-year local recurrence free survival of 89% compared with 36% for patients not receiving RT (p<0.001). The cumulative 2-year regional recurrence free survival for patients having adjuvant regional RT was 84% compared with 43% for patients not receiving this treatment (p<0.001). Immune status at initial surgery was a significant predictor for OS and MCCSS. In a multivariate analysis combining macroscopic size (mm) and immune status at initial surgery, only immune status remained a significant predictor of overall survival (HR=2.096, 95% CI: 1.002-4.385, p=0.049). RT is associated with significant improvement in local and regional control in Merkel cell carcinoma. Immunosuppression is an important factor in overall survival

  5. Improved endothelial cell seeding with cultured cells and fibronectin-coated grafts

    International Nuclear Information System (INIS)

    Seeger, J.M.; Klingman, N.

    1985-01-01

    A possible approach to the low seeding efficiency of endothelial cells into prosthetic grafts is to increase the number of cells to be seeded in cell culture and improve seeding efficiency by graft precoating with fibronectin. The effect of cell culture on cell adhesion is unknown, however, and fibronectin also binds fibrin, which may increase the thrombogenicity of the graft luminal surface. To investigate these questions, freshly harvested canine jugular vein endothelial cells from six animals and similar cells harvested from six primary and eight secondary cell cultures were labeled with 111 Indium and seeded into 5 cm, 4 mm PTFE grafts coated with fibronectin, using similar uncoated PTFE grafts as controls. Platelet accumulation and distribution on six similar coated and uncoated grafts placed in canine carotid, external jugular arterial venous shunts for 2 hr were also determined using autogenous 111 Indium-labeled platelets. Significant differences between group means were determined using the paired Student's t test. Results reveal that seeding efficiency is significantly better in all groups of coated grafts compared to uncoated grafts (P less than 0.01). Cells derived from cell culture also had significantly higher seeding efficiencies than freshly harvested cells when seeded into coated grafts (P less than 0.05) and tended to have higher seeding efficiencies than harvested cells when seeded into uncoated grafts (P = 0.53). Fibronectin coating increased mean platelet accumulation on the entire graft luminal surface, but not to a statistically significant degree (P greater than 0.1). Whether this increased seeding efficiency will improve graft endothelialization remains to be investigated

  6. An On-Chip RBC Deformability Checker Significantly Improves Velocity-Deformation Correlation

    Directory of Open Access Journals (Sweden)

    Chia-Hung Dylan Tsai

    2016-10-01

    Full Text Available An on-chip deformability checker is proposed to improve the velocity–deformation correlation for red blood cell (RBC evaluation. RBC deformability has been found related to human diseases, and can be evaluated based on RBC velocity through a microfluidic constriction as in conventional approaches. The correlation between transit velocity and amount of deformation provides statistical information of RBC deformability. However, such correlations are usually only moderate, or even weak, in practical evaluations due to limited range of RBC deformation. To solve this issue, we implemented three constrictions of different width in the proposed checker, so that three different deformation regions can be applied to RBCs. By considering cell responses from the three regions as a whole, we practically extend the range of cell deformation in the evaluation, and could resolve the issue about the limited range of RBC deformation. RBCs from five volunteer subjects were tested using the proposed checker. The results show that the correlation between cell deformation and transit velocity is significantly improved by the proposed deformability checker. The absolute values of the correlation coefficients are increased from an average of 0.54 to 0.92. The effects of cell size, shape and orientation to the evaluation are discussed according to the experimental results. The proposed checker is expected to be useful for RBC evaluation in medical practices.

  7. Nanodiamonds on tetrahedral amorphous carbon significantly enhance dopamine detection and cell viability.

    Science.gov (United States)

    Peltola, Emilia; Wester, Niklas; Holt, Katherine B; Johansson, Leena-Sisko; Koskinen, Jari; Myllymäki, Vesa; Laurila, Tomi

    2017-02-15

    We hypothesize that by using integrated carbon nanostructures on tetrahedral amorphous carbon (ta-C), it is possible to take the performance and characteristics of these bioelectrodes to a completely new level. The integrated carbon electrodes were realized by combining nanodiamonds (NDs) with ta-C thin films coated on Ti-coated Si-substrates. NDs were functionalized with mixture of carboxyl and amine groups ND andante or amine ND amine , carboxyl ND vox or hydroxyl groups ND H and drop-casted or spray-coated onto substrate. By utilizing these novel structures we show that (i) the detection limit for dopamine can be improved by two orders of magnitude [from 10µM to 50nM] in comparison to ta-C thin film electrodes and (ii) the coating method significantly affects electrochemical properties of NDs and (iii) the ND coatings selectively promote cell viability. ND andante and ND H showed most promising electrochemical properties. The viability of human mesenchymal stem cells and osteoblastic SaOS-2 cells was increased on all ND surfaces, whereas the viability of mouse neural stem cells and rat neuroblastic cells was improved on ND andante and ND H and reduced on ND amine and ND vox. The viability of C6 cells remained unchanged, indicating that these surfaces will not cause excess gliosis. In summary, we demonstrated here that by using functionalized NDs on ta-C thin films we can significantly improve sensitivity towards dopamine as well as selectively promote cell viability. Thus, these novel carbon nanostructures provide an interesting concept for development of various in vivo targeted sensor solutions. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Direct fuel cell product design improvement

    Energy Technology Data Exchange (ETDEWEB)

    Maru, H.C.; Farooque, M. [Energy Research Corp., Danbury, CT (United States)

    1996-12-31

    Significant milestones have been attained towards the technology development field testing and commercialization of direct fuel cell power plant since the 1994 Fuel Cell Seminar. Under a 5-year cooperative agreement with the Department of Energy signed in December 1994, Energy Research Corporation (ERC) has been developing the design for a MW-scale direct fuel cell power plant with input from previous technology efforts and the Santa Clara Demonstration Project. The effort encompasses product definition in consultation with the Fuel Cell Commercialization Group, potential customers, as well as extensive system design and packaging. Manufacturing process improvements, test facility construction, cell component scale up, performance and endurance improvements, stack engineering, and critical balance-of-plant development are also addressed. Major emphasis of this product design improvement project is on increased efficiency, compactness and cost reduction to establish a competitive place in the market. A 2.85 MW power plant with an efficiency of 58% and a footprint of 420 m{sup 2} has been designed. Component and subsystem testing is being conducted at various levels. Planning and preparation for verification of a full size prototype unit are in progress. This paper presents the results obtained since the last fuel cell seminar.

  9. Multispectral fingerprinting for improved in vivo cell dynamics analysis

    Directory of Open Access Journals (Sweden)

    Cooper Cameron HJ

    2010-09-01

    Full Text Available Abstract Background Tracing cell dynamics in the embryo becomes tremendously difficult when cell trajectories cross in space and time and tissue density obscure individual cell borders. Here, we used the chick neural crest (NC as a model to test multicolor cell labeling and multispectral confocal imaging strategies to overcome these roadblocks. Results We found that multicolor nuclear cell labeling and multispectral imaging led to improved resolution of in vivo NC cell identification by providing a unique spectral identity for each cell. NC cell spectral identity allowed for more accurate cell tracking and was consistent during short term time-lapse imaging sessions. Computer model simulations predicted significantly better object counting for increasing cell densities in 3-color compared to 1-color nuclear cell labeling. To better resolve cell contacts, we show that a combination of 2-color membrane and 1-color nuclear cell labeling dramatically improved the semi-automated analysis of NC cell interactions, yet preserved the ability to track cell movements. We also found channel versus lambda scanning of multicolor labeled embryos significantly reduced the time and effort of image acquisition and analysis of large 3D volume data sets. Conclusions Our results reveal that multicolor cell labeling and multispectral imaging provide a cellular fingerprint that may uniquely determine a cell's position within the embryo. Together, these methods offer a spectral toolbox to resolve in vivo cell dynamics in unprecedented detail.

  10. Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells

    DEFF Research Database (Denmark)

    Zhang, Wen; Bao, Li; Yang, Shaoxing

    2016-01-01

    Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase......-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326...

  11. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

    KAUST Repository

    Kothandaraman, Narasimhan

    2010-02-24

    Background: Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.Methods: Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.Results: Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity

  12. Significance of Nuclear Accumulation of Foxo3a in Esophageal Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Chen, M.-F.; Fang, F.-M.; Lu, C.-H.; Lu, M.-S.; Chen, W.-C.; Lee, K.-D.; Lin, P.-Y.

    2008-01-01

    Purpose: To investigate the value of Foxo3a in predicting the response to neoadjuvant treatment of, and prognosis for, esophageal squamous cell carcinoma. Methods and Materials: Immunohistochemical staining was performed in a retrospective series of 60 biopsied esophageal squamous cell carcinomas, and the correlation between nuclear accumulation of Foxo3a and clinicopathologic features was analyzed, including patient survival. In addition, in vitro biologic changes, radiosensitivity, and in vivo tumorigenicity of esophageal carcinoma cells after experimental manipulation of Foxo3a expression levels were determined. Results: Clinical findings point to a significant correlation between the nuclear accumulation of Foxo3a and the survival rate of esophageal cancer patients. In addition, Foxo3a is a significant predictor for the response to neoadjuvant therapy. In cell culture, irradiation and oxidative stress seemed to result in nuclear accumulation of Foxo3a. Down-regulation of Foxo3a significantly decreased radiosensitivity but had no obvious effect on tumor growth, as measured by a clonogenic assay in vitro and growth delay in vivo. Conclusions: Nuclear accumulation of Foxo3a in tumor cells was correlated with increased radiosensitivity and with improved patient survival. Thus, it is suggested that Foxo3a may be a potential marker for esophageal cancer

  13. pEPito: a significantly improved non-viral episomal expression vector for mammalian cells

    Directory of Open Access Journals (Sweden)

    Ogris Manfred

    2010-03-01

    Full Text Available Abstract Background The episomal replication of the prototype vector pEPI-1 depends on a transcription unit starting from the constitutively expressed Cytomegalovirus immediate early promoter (CMV-IEP and directed into a 2000 bp long matrix attachment region sequence (MARS derived from the human β-interferon gene. The original pEPI-1 vector contains two mammalian transcription units and a total of 305 CpG islands, which are located predominantly within the vector elements necessary for bacterial propagation and known to be counterproductive for persistent long-term transgene expression. Results Here, we report the development of a novel vector pEPito, which is derived from the pEPI-1 plasmid replicon but has considerably improved efficacy both in vitro and in vivo. The pEPito vector is significantly reduced in size, contains only one transcription unit and 60% less CpG motives in comparison to pEPI-1. It exhibits major advantages compared to the original pEPI-1 plasmid, including higher transgene expression levels and increased colony-forming efficiencies in vitro, as well as more persistent transgene expression profiles in vivo. The performance of pEPito-based vectors was further improved by replacing the CMV-IEP with the human CMV enhancer/human elongation factor 1 alpha promoter (hCMV/EF1P element that is known to be less affected by epigenetic silencing events. Conclusions The novel vector pEPito can be considered suitable as an improved vector for biotechnological applications in vitro and for non-viral gene delivery in vivo.

  14. Continued SOFC cell and stack technology and improved production methods

    Energy Technology Data Exchange (ETDEWEB)

    Wandel, M.; Brodersen, K.; Phair, J. (and others)

    2009-05-15

    Within this project significant results are obtained on a number of very diverse areas ranging from development of cell production, metallic creep in interconnect to assembling and test of stacks with foot print larger than 500 cm2. Out of 38 milestones 28 have been fulfilled and 10 have been partly fulfilled. This project has focused on three main areas: 1) The continued cell development and optimization of manufacturing processes aiming at production of large foot-print cells, improving cell performance and development environmentally more benign production methods. 2) Stack technology - especially stacks with large foot print and improving the stack design with respect to flow geometry and gas leakages. 3) Development of stack components with emphasis on sealing (for 2G as well as 3G), interconnect (coat, architecture and creep) and test development. Production of cells with a foot print larger than 500 cm2 is very difficult due to the brittleness of the cells and great effort has been put into this topic. Eight cells were successfully produced making it possible to assemble and test a real stack thereby giving valuable results on the prospects of stacks with large foot print. However, the yield rate is very low and a significant development to increase this yield lies ahead. Several lessons were learned on the stack level regarding 'large foot print' stacks. Modelling studies showed that the width of the cell primarily is limited by production and handling of the cell whereas the length (in the flow direction) is limited by e.g. pressure drop and necessary manifolding. The optimal cell size in the flow direction was calculated to be between approx20 cm and < 30 cm. From an economical point of view the production yield is crucial and stacks with large foot print cell area are only feasible if the cell production yield is significantly enhanced. Co-casting has been pursued as a production technique due to the possibilities in large scale production

  15. Bone marrow-derived cells for cardiovascular cell therapy: an optimized GMP method based on low-density gradient improves cell purity and function.

    Science.gov (United States)

    Radrizzani, Marina; Lo Cicero, Viviana; Soncin, Sabrina; Bolis, Sara; Sürder, Daniel; Torre, Tiziano; Siclari, Francesco; Moccetti, Tiziano; Vassalli, Giuseppe; Turchetto, Lucia

    2014-09-27

    Cardiovascular cell therapy represents a promising field, with several approaches currently being tested. The advanced therapy medicinal product (ATMP) for the ongoing METHOD clinical study ("Bone marrow derived cell therapy in the stable phase of chronic ischemic heart disease") consists of fresh mononuclear cells (MNC) isolated from autologous bone marrow (BM) through density gradient centrifugation on standard Ficoll-Paque. Cells are tested for safety (sterility, endotoxin), identity/potency (cell count, CD45/CD34/CD133, viability) and purity (contaminant granulocytes and platelets). BM-MNC were isolated by density gradient centrifugation on Ficoll-Paque. The following process parameters were optimized throughout the study: gradient medium density; gradient centrifugation speed and duration; washing conditions. A new manufacturing method was set up, based on gradient centrifugation on low density Ficoll-Paque, followed by 2 washing steps, of which the second one at low speed. It led to significantly higher removal of contaminant granulocytes and platelets, improving product purity; the frequencies of CD34+ cells, CD133+ cells and functional hematopoietic and mesenchymal precursors were significantly increased. The methodological optimization described here resulted in a significant improvement of ATMP quality, a crucial issue to clinical applications in cardiovascular cell therapy.

  16. Immunogenic Cell Death Induced by Ginsenoside Rg3: Significance in Dendritic Cell-based Anti-tumor Immunotherapy.

    Science.gov (United States)

    Son, Keum-Joo; Choi, Ki Ryung; Lee, Seog Jae; Lee, Hyunah

    2016-02-01

    Cancer is one of the leading causes of morbidity and mortality worldwide; therefore there is a need to discover new therapeutic modules with improved efficacy and safety. Immune-(cell) therapy is a promising therapeutic strategy for the treatment of intractable cancers. The effectiveness of certain chemotherapeutics in inducing immunogenic tumor cell death thus promoting cancer eradication has been reported. Ginsenoside Rg3 is a ginseng saponin that has antitumor and immunomodulatory activity. In this study, we treated tumor cells with Rg3 to verify the significance of inducing immunogenic tumor cell death in antitumor therapy, especially in DC-based immunotherapy. Rg3 killed the both immunogenic (B16F10 melanoma cells) and non-immunogenic (LLC: Lewis Lung Carcinoma cells) tumor cells by inducing apoptosis. Surface expression of immunogenic death markers including calreticulin and heat shock proteins and the transcription of relevant genes were increased in the Rg3-dying tumor. Increased calreticulin expression was directly related to the uptake of dying tumor cells by dendritic cells (DCs): the proportion of CRT(+) CD11c(+) cells was increased in the Rg3-treated group. Interestingly, tumor cells dying by immunogenic cell death secreted IFN-γ, an effector molecule for antitumor activity in T cells. Along with the Rg3-induced suppression of pro-angiogenic (TNF-α) and immunosuppressive cytokine (TGF-β) secretion, IFN-γ production from the Rg3-treated tumor cells may also indicate Rg3 as an effective anticancer immunotherapeutic strategy. The data clearly suggests that Rg3-induced immunogenic tumor cell death due its cytotoxic effect and its ability to induce DC function. This indicates that Rg3 may be an effective immunotherapeutic strategy.

  17. Migration ability and Toll-like receptor expression of human mesenchymal stem cells improves significantly after three-dimensional culture.

    Science.gov (United States)

    Zhou, Panpan; Liu, Zilin; Li, Xue; Zhang, Bing; Wang, Xiaoyuan; Lan, Jing; Shi, Qing; Li, Dong; Ju, Xiuli

    2017-09-16

    While the conventional two-dimensional (2D) culture protocol is well accepted for the culture of mesenchymal stem cells (MSCs), this method fails to recapitulate the in vivo native three-dimensional (3D) cellular microenvironment, and may result in phenotypic changes, and homing and migration capacity impairments. MSC preparation in 3D culture systems has been considered an attractive preparatory and delivery method recently. We seeded human umbilical cord-derived MSCs (hUCMSCs) in a 3D culture system with porcine acellular dermal matrix (PADM), and investigated the phenotypic changes, the expression changes of some important receptors, including Toll-like receptors (TLRs) and C-X-C chemokine receptor type 4 (CXCR4) when hUCMSCs were transferred from 2D to 3D systems, as well as the alterations in in vivo homing and migration potential. It was found that the percentage of CD105-positive cells decreased significantly, whereas that of CD34- and CD271-positive cells increased significantly in 3D culture, compared to that in 2D culture. The mRNA and protein expression levels of TLR2, TLR3, TLR4, TLR6, and CXCR4 in hUCMSCs were increased significantly upon culturing with PADM for 3 days, compared to the levels in 2D culture. The numbers of migratory 3D hUCMSCs in the heart, liver, spleen, and bone marrow were significantly greater than the numbers of 2D hUCMSCs, and the worst migration occurred in 3D + AMD3100 (CXCR4 antagonist) hUCMSCs. These results suggested that 3D culture of hUCMSCs with PADM could alter the phenotypic characteristics of hUCMSCs, increase their TLR and CXCR4 expression levels, and promote their migratory and homing capacity in which CXCR4 plays an important role. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Mobarak, Halimeh; Fathi, Ezzatollah; Farahzadi, Raheleh; Zarghami, Nosratollah; Javanmardi, Sara

    2017-03-01

    Mesenchymal stem cells are undifferentiated cells that have the ability to divide continuously and tissue regeneration potential during the transplantation. Aging and loss of cell survival, is one of the main problems in cell therapy. Since the production of free radicals in the aging process is effective, the use of antioxidant compounds can help in scavenging free radicals and prevent the aging of cells. The aim of this study is evaluate the effects of L-carnitine (LC) on proliferation and aging of rat adipose tissue-derived mesenchymal stem cells (rADSC). rADSCs were isolated from inguinal region of 5 male Rattus rats. Oil red-O, alizarin red-S and toluidine blue staining were performed to evaluate the adipogenic, osteogenic and chondrogenic differentiation of rADSCs, respectively. Flow cytometric analysis was done for investigating the cell surface markers. The methyl thiazol tetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to different concentrations of LC. rADSCs aging was evaluated by beta-galactosidase staining. The results showed significant proliferation of rADSCs 48 h after treatment with concentrations of 0.2 mM LC. In addition, in the presence of 0.2 mM LC, rADSCs appeared to be growing faster than control group and 0.2 mM LC supplementation could significantly decrease the population doubling time and aging of rADSCs. It seems that LC would be a good antioxidant to improve lifespan of rADSCs due to the decrease in aging.

  19. IMHEX fuel cell repeat component manufacturing continuous improvement accomplishments

    Energy Technology Data Exchange (ETDEWEB)

    Jakaitis, L.A.; Petraglia, V.J.; Bryson, E.S. [M-C Power Corp., Burr Ridge, IL (United States)] [and others

    1996-12-31

    M-C Power is taking a power generation technology that has been proven in the laboratory and is making it a commercially competitive product. There are many areas in which this technology required scale up and refinement to reach the market entry goals for the IMHEX{reg_sign} molten carbonate fuel cell power plant. One of the primary areas that needed to be addressed was the manufacturing of the fuel cell stack. Up to this point, the fuel cell stack and associated components were virtually hand made for each system to be tested. M-C Power has now continuously manufactured the repeat components for three 250 kW stacks. M-C Power`s manufacturing strategy integrated both evolutionary and revolutionary improvements into its comprehensive commercialization effort. M-C Power`s objectives were to analyze and continuously improve stack component manufacturing and assembly techniques consistent with established specifications and commercial scale production requirements. Evolutionary improvements are those which naturally occur as the production rates are increased and experience is gained. Examples of evolutionary (learning curve) improvements included reducing scrap rates and decreasing raw material costs by buying in large quantities. Revolutionary improvements result in significant design and process changes to meet cost and performance requirements of the market entry system. Revolutionary changes often involve identifying new methods and developing designs to accommodate the new process. Based upon our accomplishments, M-C Power was able to reduce the cost of continuously manufactured fuel cell repeat components from the first to third 250 kW stack by 63%. This paper documents the continuous improvement accomplishments realized by M-C Power during IMHEX{reg_sign} fuel cell repeat component manufacturing.

  20. PXD101 significantly improves nuclear reprogramming and the in vitro developmental competence of porcine SCNT embryos

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Jun-Xue; Kang, Jin-Dan; Li, Suo; Jin, Long; Zhu, Hai-Ying; Guo, Qing; Gao, Qing-Shan; Yan, Chang-Guo; Yin, Xi-Jun, E-mail: yinxj33@msn.com

    2015-01-02

    Highlights: • First explored that the effects of PXD101 on the development of SCNT embryos in vitro. • 0.5 μM PXD101 treated for 24 h improved the development of porcine SCNT embryos. • Level of AcH3K9 was significantly higher than control group at early stages. - Abstract: In this study, we investigated the effects of the histone deacetylase inhibitor PXD101 (belinostat) on the preimplantation development of porcine somatic cell nuclear transfer (SCNT) embryos and their expression of the epigenetic markers histone H3 acetylated at lysine 9 (AcH3K9). We compared the in vitro developmental competence of SCNT embryos treated with various concentrations of PXD101 for 24 h. Treatment with 0.5 μM PXD101 significantly increased the proportion of SCNT embryos that reached the blastocyst stage, in comparison to the control group (23.3% vs. 11.5%, P < 0.05). We tested the in vitro developmental competence of SCNT embryos treated with 0.5 μM PXD101 for various amounts of times following activation. Treatment for 24 h significantly improved the development of porcine SCNT embryos, with a significantly higher proportion of embryos reaching the blastocyst stage in comparison to the control group (25.7% vs. 10.6%, P < 0.05). PXD101-treated SCNT embryos were transferred into two surrogate sows, one of whom became pregnant and four fetuses developed. PXD101 treatment significantly increased the fluorescence intensity of immunostaining for AcH3K9 in embryos at the pseudo-pronuclear and 2-cell stages. At these stages, the fluorescence intensities of immunostaining for AcH3K9 were significantly higher in PXD101-treated embryos than in control untreated embryos. In conclusion, this study demonstrates that PXD101 can significantly improve the in vitro and in vivo developmental competence of porcine SCNT embryos and can enhance their nuclear reprogramming.

  1. Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

    Science.gov (United States)

    Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

    2007-01-01

    Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

  2. Improved performance in GaInNAs solar cells by hydrogen passivation

    International Nuclear Information System (INIS)

    Fukuda, M.; Whiteside, V. R.; Keay, J. C.; Meleco, A.; Sellers, I. R.; Hossain, K.; Golding, T. D.; Leroux, M.; Al Khalfioui, M.

    2015-01-01

    The effect of UV-activated hydrogenation on the performance of GaInNAs solar cells is presented. A proof-of-principle investigation was performed on non-optimum GaInNAs cells, which allowed a clearer investigation of the role of passivation on the intrinsic nitrogen-related defects in these materials. Upon optimized hydrogenation of GaInNAs, a significant reduction in the presence of defect and impurity based luminescence is observed as compared to that of unpassivated reference material. This improvement in the optical properties is directly transferred to an improved performance in solar cell operation, with a more than two-fold improvement in the external quantum efficiency and short circuit current density upon hydrogenation. Temperature dependent photovoltaic measurements indicate a strong contribution of carrier localization and detrapping processes, with non-radiative processes dominating in the reference materials, and evidence for additional strong radiative losses in the hydrogenated solar cells

  3. Addition of 2-(ethylamino)acetonitrile group to nitroxoline results in significantly improved anti-tumor activity in vitro and in vivo.

    Science.gov (United States)

    Mitrović, Ana; Sosič, Izidor; Kos, Špela; Tratar, Urša Lampreht; Breznik, Barbara; Kranjc, Simona; Mirković, Bojana; Gobec, Stanislav; Lah, Tamara; Serša, Gregor; Kos, Janko

    2017-08-29

    Lysosomal cysteine peptidase cathepsin B, involved in multiple processes associated with tumor progression, is validated as a target for anti-cancer therapy. Nitroxoline, a known antimicrobial agent, is a potent and selective inhibitor of cathepsin B, hence reducing tumor progression in vitro and in vivo . In order to further improve its anti-cancer properties we developed a number of derivatives using structure-based chemical synthesis. Of these, the 7-aminomethylated derivative (compound 17 ) exhibited significantly improved kinetic properties over nitroxoline, inhibiting cathepsin B endopeptidase activity selectively. In the present study, we have evaluated its anti-cancer properties. It was more effective than nitroxoline in reducing tumor cell invasion and migration, as determined in vitro on two-dimensional cell models and tumor spheroids, under either endpoint or real time conditions. Moreover, it exhibited improved action over nitroxoline in impairing tumor growth in vivo in LPB mouse fibrosarcoma tumors in C57Bl/6 mice. Taken together, the addition of a 2-(ethylamino)acetonitrile group to nitroxoline at position 7 significantly improves its pharmacological characteristics and its potential for use as an anti-cancer drug.

  4. IL-15 improves the cytotoxicity of cytokine-induced killer cells against leukemia cells by upregulating CD3+CD56+ cells and downregulating regulatory T cells as well as IL-35.

    Science.gov (United States)

    Tao, Qianshan; Chen, Tianping; Tao, Lili; Wang, Huiping; Pan, Ying; Xiong, Shudao; Zhai, Zhimin

    2013-01-01

    Cytokine-induced killer (CIK) cells are usually generated from peripheral blood mononuclear cells with the stimulation of IL-2 in vitro. Unlike the conventional IL-2-stimulated CIK cells (IL-2-CIK cells), we investigated the characteristics and potential mechanism of IL-15-stimulated CIK cells (IL-15-CIK cells) in this study. Compared with IL-2-CIK cells, the percentage of CD3CD56 cells was significantly increased in IL-15-CIK cells, but the expression of regulatory T (Treg) cells and IL-35 was significantly decreased in IL-15-CIK cells. Meanwhile, the in vitro cytotoxicity against human myeloid leukemia cells K562 of IL-15-CIK cells was significantly augmented compared with IL-2-CIK cells. These data suggest that IL-15 may improve the cytotoxicity of CIK cells against leukemia cells by upregulating CD3CD56 cells and downregulating Treg cells and IL-35.

  5. Improving CART-Cell Therapy of Solid Tumors with Oncolytic Virus-Driven Production of a Bispecific T-cell Engager.

    Science.gov (United States)

    Wing, Anna; Fajardo, Carlos Alberto; Posey, Avery D; Shaw, Carolyn; Da, Tong; Young, Regina M; Alemany, Ramon; June, Carl H; Guedan, Sonia

    2018-05-01

    T cells expressing chimeric antigen receptors (CART) have shown significant promise in clinical trials to treat hematologic malignancies, but their efficacy in solid tumors has been limited. Oncolytic viruses have the potential to act in synergy with immunotherapies due to their immunogenic oncolytic properties and the opportunity of incorporating therapeutic transgenes in their genomes. Here, we hypothesized that an oncolytic adenovirus armed with an EGFR-targeting, bispecific T-cell engager (OAd-BiTE) would improve the outcome of CART-cell therapy in solid tumors. We report that CART cells targeting the folate receptor alpha (FR-α) successfully infiltrated preestablished xenograft tumors but failed to induce complete responses, presumably due to the presence of antigen-negative cancer cells. We demonstrated that OAd-BiTE-mediated oncolysis significantly improved CART-cell activation and proliferation, while increasing cytokine production and cytotoxicity, and showed an in vitro favorable safety profile compared with EGFR-targeting CARTs. BiTEs secreted from infected cells redirected CART cells toward EGFR in the absence of FR-α, thereby addressing tumor heterogeneity. BiTE secretion also redirected CAR-negative, nonspecific T cells found in CART-cell preparations toward tumor cells. The combinatorial approach improved antitumor efficacy and prolonged survival in mouse models of cancer when compared with the monotherapies, and this was the result of an increased BiTE-mediated T-cell activation in tumors. Overall, these results demonstrated that the combination of a BiTE-expressing oncolytic virus with adoptive CART-cell therapy overcomes key limitations of CART cells and BiTEs as monotherapies in solid tumors and encourage its further evaluation in human trials. Cancer Immunol Res; 6(5); 605-16. ©2018 AACR . ©2018 American Association for Cancer Research.

  6. Prognostic significance of metallothionein in B-cell lymphomas

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Borregaard, Niels

    2006-01-01

    -cell (ABC) and 3 of 9 type-3 lesions. In contrast, MT mRNA was low to undetectable in 16 germinal center B-cell (GCB)-type DLBCLs. Only 1 of 15 patients with up-regulated MT mRNA achieved a sustained remission, suggesting that up-regulated MT mRNA constitutes a significant risk factor for treatment failure...

  7. Improving sensitivity of linear regression-based cell type-specific differential expression deconvolution with per-gene vs. global significance threshold.

    Science.gov (United States)

    Glass, Edmund R; Dozmorov, Mikhail G

    2016-10-06

    The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from blood samples suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. Combined with cell counts, heterogeneous gene expression may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression, and a global cutoff to judge significance, such as False Discovery Rate (FDR). Yet, they do not consider many artifacts hidden in high-dimensional gene expression data that may negatively affect linear regression. In this paper we quantify the parameter space affecting the performance of linear regression (sensitivity of cell type-specific differential expression detection) on a per-gene basis. We evaluated the effect of sample sizes, cell type-specific proportion variability, and mean squared error on sensitivity of cell type-specific differential expression detection using linear regression. Each parameter affected variability of cell type-specific expression estimates and, subsequently, the sensitivity of differential expression detection. We provide the R package, LRCDE, which performs linear regression-based cell type-specific differential expression (deconvolution) detection on a gene-by-gene basis. Accounting for variability around cell type-specific gene expression estimates, it computes per-gene t-statistics of differential detection, p-values, t-statistic-based sensitivity, group-specific mean squared error, and several gene-specific diagnostic metrics. The sensitivity of linear regression-based cell type-specific differential expression detection differed for each gene as a function of mean squared error, per group sample sizes, and variability of the proportions

  8. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Li, Ling; Byrd, John C

    2016-01-01

    CD37 (tetraspanin TSPAN26) is a B-cell surface antigen widely expressed on mature B cells. CD37 is involved in immune regulation and tumor suppression but its function has not been fully elucidated. We assessed CD37 expression in de novo diffuse large B-cell lymphoma (DLBCL), and investigated its...

  9. Resveratrol Improves Cell Cycle Arrest in Chronic Prostatitis Rats, by C-kit/SCF Suppression.

    Science.gov (United States)

    He, Yi; Zeng, Huizhi; Yu, Yang; Zhang, Jiashu; Zeng, Xiaona; Gong, Fengtao; Liu, Qi; Yang, Bo

    2017-08-01

    Chronic prostatitis (CP) with complex pathogenesis is difficult for treatment. c-kit has been associated with the control of cell proliferation of prostate cells. This study aims to evaluate the role of resveratrol, an activator of Sirt1, in regulating the expression of c-kit in CP and investigate the consequent effects on cell cycle. Rat model of CP was established through subcutaneous injections of diphtheria-pertussis-tetanus vaccine and subsequently treated with resveratrol. Hematoxylin and eosin staining was performed to identify the histopathological changes in prostates. Western blotting and immunohistochemical staining examined the expression level of c-kit, stem cell factor (SCF), Sirt1, and cell cycle-associated proteins. The model group exhibited severe diffuse chronic inflammation, characterized by leukocyte infiltration and papillary frond protrusion into the gland cavities, and a notable increase in prostatic epithelial height. Gland lumen diameter was also significantly smaller; the activity of c-kit/SCF in the CP rats was increased significantly compared to the control group. Meanwhile, the cell cycle proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. Dysregulation of cell cycle was involved in the pathological processes of CP, which was improved after resveratrol treatment by the downregulation of c-kit/SCF by activating Sirt1.

  10. Bacterial cells with improved tolerance to polyamines

    DEFF Research Database (Denmark)

    2017-01-01

    Provided are bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as polyamines, and methods of preparing and using such bacterial cells for production of polyamines and other compounds.......Provided are bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as polyamines, and methods of preparing and using such bacterial cells for production of polyamines and other compounds....

  11. Polymer-Polymer Förster Resonance Energy Transfer Significantly Boosts the Power Conversion Efficiency of Bulk-Heterojunction Solar Cells.

    Science.gov (United States)

    Gupta, Vinay; Bharti, Vishal; Kumar, Mahesh; Chand, Suresh; Heeger, Alan J

    2015-08-01

    Optically resonant donor polymers can exploit a wider range of the solar spectrum effectively without a complicated tandem design in an organic solar cell. Ultrafast Förster resonance energy transfer (FRET) in a polymer-polymer system that significantly improves the power conversion efficiency in bulk heterojunction polymer solar cells from 6.8% to 8.9% is demonstrated, thus paving the way to achieving 15% efficient solar cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Significance of neo-angiogenesis and immuno-surveillance cells in squamous cell carcinoma of the tongue

    Directory of Open Access Journals (Sweden)

    Juma O. Alkhabuli

    2007-02-01

    Full Text Available Background: Neo-angiogenesis is an essential process in physiological and pathological conditions. However, it is a complex process. Several studies demonstrated that intra-tumoural microvessel number is a significant predictor of metastasis and clinical outcome in many tumours, including oral malignancies. The immuno-surveillance cells, mast cells and eosinophils are implicated in the biological behaviour of tumours. Nevertheless, their function in tissues is uncertain. Mast cells are involved in homeostatic regulation of blood vessels as well as host defence. In some malignancies, high mast cell density has been found to correlate with favourable prognosis. However, others reported unfavourable associations. Tumour associated tissue eosinophilia is a well-known phenomena. It has been associated with good and poor prognosis. However, the role of eosinophils in tumours remains controversial. Therefore, this study was designed to investigate the prognostic value of microvessel, mast cell and eosinophil densities in the context of clinico-pathological parameters and survival in squamous cell carcinoma of the tongue.Materials and Methods: Anti-CD105 and anti-tryptase monoclonal antibodies were utilized to highlight and count microvessels and mast cells respectively in 81 cases of tongue squamous cell carcinoma. Eosinophils were demonstrated using carbol chromotrope histochemical stain. The densities were counted per mm2 and correlated with patients’ outcome and other clinico-pathological parameters using non-parametric tests and student’s t-test. Clinically, the cases were divided into 4 main groups depending on survival time, lymph-node or distant metastasis.Results: The 5 year survival was significantly lower in patients with a low mast cell density than those with a high density (p=0.006, Kruskal-Wallis test. The survival group-A demonstrated significantly higher mast cell and microvessel numbers than group-D (p=0.007, student’s t

  13. Ferritin nanoparticles for improved self-renewal and differentiation of human neural stem cells.

    Science.gov (United States)

    Lee, Jung Seung; Yang, Kisuk; Cho, Ann-Na; Cho, Seung-Woo

    2018-01-01

    Biomaterials that promote the self-renewal ability and differentiation capacity of neural stem cells (NSCs) are desirable for improving stem cell therapy to treat neurodegenerative diseases. Incorporation of micro- and nanoparticles into stem cell culture has gained great attention for the control of stem cell behaviors, including proliferation and differentiation. In this study, ferritin, an iron-containing natural protein nanoparticle, was applied as a biomaterial to improve the self-renewal and differentiation of NSCs and neural progenitor cells (NPCs). Ferritin nanoparticles were added to NSC or NPC culture during cell growth, allowing for incorporation of ferritin nanoparticles during neurosphere formation. Compared to neurospheres without ferritin treatment, neurospheres with ferritin nanoparticles showed significantly promoted self-renewal and cell-cell interactions. When spontaneous differentiation of neurospheres was induced during culture without mitogenic factors, neuronal differentiation was enhanced in the ferritin-treated neurospheres. In conclusion, we found that natural nanoparticles can be used to improve the self-renewal ability and differentiation potential of NSCs and NPCs, which can be applied in neural tissue engineering and cell therapy for neurodegenerative diseases.

  14. Improved biolistic transfection of hair cells.

    Directory of Open Access Journals (Sweden)

    Hongyu Zhao

    Full Text Available Transient transfection of hair cells has proven challenging. Here we describe modifications to the Bio-Rad Helios Gene Gun that, along with an optimized protocol, improve transfection of bullfrog, chick, and mouse hair cells. The increased penetrating power afforded by our method allowed us to transfect mouse hair cells from the basal side, through the basilar membrane; this configuration protects hair bundles from damage during the procedure. We characterized the efficiency of transfection of mouse hair cells with fluorescently-tagged actin fusion protein using both the optimized procedure and a published procedure; while the efficiency of the two methods was similar, the morphology of transfected hair cells was improved with the new procedure. In addition, using the improved method, we were able to transfect hair cells in the bullfrog sacculus and chick cochlea for the first time. We used fluorescent-protein fusions of harmonin b (USH1C and PMCA2 (ATP2B2; plasma-membrane Ca(2+-ATPase isoform 2 to examine protein distribution in hair cells. While PMCA2-EGFP localization was similar to endogenous PMCA2 detected with antibodies, high levels of harmonin-EGFP were found at stereocilia tapers in bullfrog and chick, but not mouse; by contrast, harmonin-EGFP was concentrated in stereocilia tips in mouse hair cells.

  15. Expression and significance of Axin2 in pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    ZHANG Tao

    2016-05-01

    Full Text Available ObjectiveTo investigate the expression of Axin2 in pancreatic cancer cells, and to observe the influence of Axin2 on the proliferation, invasion, and migration of human pancreatic cancer cells (PANC-1. MethodsQuantitative real-time PCR was used to measure the expression of Axin2 in pancreatic cancer cell lines with different invasive abilities (PANC-1, Mia PaCa-2, and BxPC-3 and immortalized normal pancreatic cells (H6C7. PANC-1 cells with low expression were transfected with over-expressed Axin2 plasmid by transient transfection. MTT assay, Transwell assay, and scratch assay were used to determine the proliferation, invasion, and migration of cells transfected with over-expressed Axin2. One-way analysis of variance was used for comparison between multiple groups, and SNK-q test was used for comparison between any two groups. ResultsThe relative expression levels of Axin2 in PANC-1, BxPC-3, Mia PaCa-2, and H6C7 cells were 0.13±0.01, 0.42±0.05, 0.24±0.011, and 1.00±0.00, respectively, and PANC-1 cells had the lowest expression level of Axin2, with significant differences compared with the other cells (all P<0.05. When PANC-1 cells were transfected with over-expressed Axin2 plasmid, the cells in the over-expression group had a significant increase in the expression level of Axin2 compared with those in the blank group and the negative control group (both P<0.05. Compared with those in the non-transfection group and the blank group, PANC-1 cells in the over-expression group showed significant reductions in the proliferation, invasion, and migration abilities. ConclusionThe expression of Axin2 is down-regulated in pancreatic cancer cell lines and decreases with the increasing invasion ability, suggesting the role of tumor suppressor gene. High expression of Axin2 can reduce the proliferation, invasion, and migration abilities of PANC-1 cells.

  16. Bacterial cells with improved tolerance to polyols

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention relates to bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as diols and other polyols, and to methods of preparing and using such bacterial cells for production of polyols and other compounds.......The present invention relates to bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as diols and other polyols, and to methods of preparing and using such bacterial cells for production of polyols and other compounds....

  17. Orbiter fuel cell improvement assessment

    International Nuclear Information System (INIS)

    Johnson, R.E.

    1981-08-01

    The history of fuel cells and the theory of fuel cells is given. Expressions for thermodynamic and electrical efficiencies are developed. The voltage losses due to electrode activation, ohmic resistance and ionic diffusion are discussed. Present limitations of the Orbiter Fuel Cell, as well as proposed enhancements, are given. These enhancements are then evaluated and recommendations are given for fuel cell enhancement both for short-range as well as long-range performance improvement. Estimates of reliability and cost savings are given for enhancements where possible

  18. Significant improvement in the thermal annealing process of optical resonators

    Science.gov (United States)

    Salzenstein, Patrice; Zarubin, Mikhail

    2017-05-01

    Thermal annealing performed during process improves the quality of the roughness of optical resonators reducing stresses at the periphery of their surface thus allowing higher Q-factors. After a preliminary realization, the design of the oven and the electronic method were significantly improved thanks to nichrome resistant alloy wires and chopped basalt fibers for thermal isolation during the annealing process. Q-factors can then be improved.

  19. Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

    Science.gov (United States)

    Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun

    2014-10-20

    Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

  20. Pathological significance and prognostic roles of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios in clear cell renal cell carcinoma.

    Science.gov (United States)

    Nakanishi, Hiromi; Miyata, Yasuyoshi; Mochizuki, Yasushi; Yasuda, Takuji; Nakamura, Yuichiro; Araki, Kyohei; Sagara, Yuji; Matsuo, Tomohiro; Ohba, Kojiro; Sakai, Hideki

    2018-05-19

    The immune system is closely associated with malignant behavior in renal cell carcinoma (RCC). Therefore, understanding the pathological roles of immune cells in tumor stroma is essential to discuss the pathological characteristics of RCC. In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. Proliferation index (PI), apoptotic index (AI), and microvessel density (MVD) were evaluated by using anti-Ki-67, anti-cleaved caspase-3, and anti-CD31 antibodies, respectively. The density of CD57+ cell was negatively correlated with grade, pT stage, and metastasis, although densities of CD68+ cell and mast cell were positively correlated. Ratios of CD68+ cell/CD57+ cell and mast cell/CD57+ cell were significantly correlated with grade, pT stage, and metastasis. Survival analyses showed that the CD68+ cell/CD57+ cell ratio was a significant predictor for cause-specific survival by multi-variate analyses (hazard ratio=1.41, 95% confidential interval=1.03-1.93, P=.031), and was significantly correlated with PI, AI, and MVD (r=.47; P <. 001, r=-.31, P<.001, and r=.40, P<.001, respectively). In conclusion, CD57+ cell, CD68+ cell, and mast cell played important roles in malignancy in clear cell RCC. The CD68+ cell/CD57+ cell ratio was strongly correlated with pathological features and prognosis in these patients because this ratio reflected the status of cancer cell proliferation, apoptosis, and angiogenesis. Copyright © 2018. Published by Elsevier Inc.

  1. A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

    Directory of Open Access Journals (Sweden)

    Brian G. Ballios

    2015-06-01

    Full Text Available The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs. The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.

  2. Significant Improvement of Catalytic Efficiencies in Ionic Liquids

    International Nuclear Information System (INIS)

    Song, Choong Eui; Yoon, Mi Young; Choi, Doo Seong

    2005-01-01

    The use of ionic liquids as reaction media can confer many advantages upon catalytic reactions over reactions in organic solvents. In ionic liquids, catalysts having polar or ionic character can easily be immobilized without additional structural modification and thus the ionic solutions containing the catalyst can easily be separated from the reagents and reaction products, and then, be reused. More interestingly, switching from an organic solvent to an ionic liquid often results in a significant improvement in catalytic performance (e.g., rate acceleration, (enantio)selectivity improvement and an increase in catalyst stability). In this review, some recent interesting results which can nicely demonstrate these positive 'ionic liquid effect' on catalysis are discussed

  3. Uterine-derived progenitor cells are immunoprivileged and effectively improve cardiac regeneration when used for cell therapy.

    Science.gov (United States)

    Ludke, Ana; Wu, Jun; Nazari, Mansoreh; Hatta, Kota; Shao, Zhengbo; Li, Shu-Hong; Song, Huifang; Ni, Nathan C; Weisel, Richard D; Li, Ren-Ke

    2015-07-01

    Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is less effective in aged patients because aged cells have decreased regenerative capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually rejected. Maintaining transplanted SC immunoprivilege may dramatically improve regenerative outcomes. The uterus has distinct immune characteristics, and we showed that reparative uterine SCs home to the myocardium post-MI. Here, we identify immunoprivileged uterine SCs and assess their effects on cardiac regeneration after allogeneic transplantation. We found more than 20% of cells in the mouse uterus have undetectable MHC I expression by flow cytometry. Uterine MHC I((neg)) and MHC I((pos)) cells were separated by magnetic cell sorting. The MHC I((neg)) population expressed the SC markers CD34, Sca-1 and CD90, but did not express MHC II or c-kit. In vitro, MHC I((neg)) and ((pos)) SCs show colony formation and endothelial differentiation capacity. In mixed leukocyte co-culture, MHC I((neg)) cells showed reduced cell death and leukocyte proliferation compared to MHC I((pos)) cells. MHC I((neg)) and ((pos)) cells had significantly greater angiogenic capacity than mesenchymal stem cells. The benefits of intramyocardial injection of allogeneic MHC I((neg)) cells after MI were comparable to syngeneic bone marrow cell transplantation, with engraftment in cardiac tissue and limited recruitment of CD4 and CD8 cells up to 21 days post-MI. MHC I((neg)) cells preserved cardiac function, decreased infarct size and improved regeneration post-MI. This new source of immunoprivileged cells can induce neovascularization and could be used as allogeneic cell therapy for regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Clinicopathological significance of c-MYC in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Lian, Yu; Niu, Xiangdong; Cai, Hui; Yang, Xiaojun; Ma, Haizhong; Ma, Shixun; Zhang, Yupeng; Chen, Yifeng

    2017-07-01

    Esophageal squamous cell carcinoma is one of the most common malignant tumors. The oncogene c-MYC is thought to be important in the initiation, promotion, and therapy resistance of cancer. In this study, we aim to investigate the clinicopathologic roles of c-MYC in esophageal squamous cell carcinoma tissue. This study is aimed at discovering and analyzing c-MYC expression in a series of human esophageal tissues. A total of 95 esophageal squamous cell carcinoma samples were analyzed by the western blotting and immunohistochemistry techniques. Then, correlation of c-MYC expression with clinicopathological features of esophageal squamous cell carcinoma patients was statistically analyzed. In most esophageal squamous cell carcinoma cases, the c-MYC expression was positive in tumor tissues. The positive rate of c-MYC expression in tumor tissues was 61.05%, obviously higher than the adjacent normal tissues (8.42%, 8/92) and atypical hyperplasia tissues (19.75%, 16/95). There was a statistical difference among adjacent normal tissues, atypical hyperplasia tissues, and tumor tissues. Overexpression of the c-MYC was detected in 61.05% (58/95) esophageal squamous cell carcinomas, which was significantly correlated with the degree of differentiation (p = 0.004). The positive rate of c-MYC expression was 40.0% in well-differentiated esophageal tissues, with a significantly statistical difference (p = 0.004). The positive rate of c-MYC was 41.5% in T1 + T2 esophageal tissues and 74.1% in T3 + T4 esophageal tissues, with a significantly statistical difference (p = 0.001). The positive rate of c-MYC was 45.0% in I + II esophageal tissues and 72.2% in III + IV esophageal tissues, with a significantly statistical difference (p = 0.011). The c-MYC expression strongly correlated with clinical staging (p = 0.011), differentiation degree (p = 0.004), lymph node metastasis (p = 0.003), and invasion depth (p = 0.001) of patients with esophageal squamous cell carcinoma. The c-MYC was

  5. Training directionally selective motion pathways can significantly improve reading efficiency

    Science.gov (United States)

    Lawton, Teri

    2004-06-01

    This study examined whether perceptual learning at early levels of visual processing would facilitate learning at higher levels of processing. This was examined by determining whether training the motion pathways by practicing leftright movement discrimination, as found previously, would improve the reading skills of inefficient readers significantly more than another computer game, a word discrimination game, or the reading program offered by the school. This controlled validation study found that practicing left-right movement discrimination 5-10 minutes twice a week (rapidly) for 15 weeks doubled reading fluency, and significantly improved all reading skills by more than one grade level, whereas inefficient readers in the control groups barely improved on these reading skills. In contrast to previous studies of perceptual learning, these experiments show that perceptual learning of direction discrimination significantly improved reading skills determined at higher levels of cognitive processing, thereby being generalized to a new task. The deficits in reading performance and attentional focus experienced by the person who struggles when reading are suggested to result from an information overload, resulting from timing deficits in the direction-selectivity network proposed by Russell De Valois et al. (2000), that following practice on direction discrimination goes away. This study found that practicing direction discrimination rapidly transitions the inefficient 7-year-old reader to an efficient reader.

  6. Significance of apoptotic cell death after γ-irradiation

    International Nuclear Information System (INIS)

    Wu, H.G.; Kim, I.H.; Ha, S.W.; Park, C.I.

    2003-01-01

    Full text: The objectives of this study are to investigate the significance of apoptotic death compared to total cell death after γ-ray irradiation in human Hand N cancer cell lines and to find out correlation between apoptosis and radiation sensitivity. Materials and Method: Head and neck cancer cell lines (PCI-1, PCI-13, and SNU-1066), leukemia cell line (CCRF-CEM), and fibroblast cell line (LM217) as a normal control were used for this study. Cells were irradiated using Cs-137 animal experiment irradiator. Total cell death was measured by clonogenic assay. Annexin-V staining was used to detect the fraction of apoptotic death. The resulting data was analyzed with two parameters, apoptotic index (AI) and apoptotic fraction(AF). AI is ratio of apoptotic cells to total cells, and AF is ration of apoptotic cell death to mutant frequencytion ex(Number of apoptotic cells) / (Number of total cells counted) AF = {(AI) / (1-survival fraction)} x 100 (%) Results. Surviving fraction at 2 Gy (SF2) were 0.741, 0.544, 0.313, 0.302, and 0.100 for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217 cell lines, respectively. Apoptosis was detected in all cell lines. Apoptotic index reached peak value at 72 hours after irradiation in head and neck cancer cell lines, and that was at 24 hours in CCRF-CEM and LM217. Total cell death increased exponentially with increasing radiation dose from 0 Gy to 8 Gy, but the change was minimal in apoptotic index (Fig. 1.). Apoptotic fractions at 2 Gy were 46%, 48%, 46%, 24%, and 19% and at 6 Gy were 20%, 33%, 35%, 17%, and 20% for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217, respectively. The radioresistant cell lines showed more higher apoptotic fraction at 2 Gy (Table 1.), but there was not such correlation at 6 Gy. Conclusion: All cell lines used in this study showed apoptosis after irradiation, but time course of apoptosis was different from that of leukemia cell line and normal fibroblast cell line. Reproductive cell death was more important

  7. Modeling cell-in-cell structure into its biological significance

    OpenAIRE

    He, M-f; Wang, S; Wang, Y; Wang, X-n

    2013-01-01

    Although cell-in-cell structure was noted 100 years ago, the molecular mechanisms of ?entering' and the destination of cell-in-cell remain largely unclear. It takes place among the same type of cells (homotypic cell-in-cell) or different types of cells (heterotypic cell-in-cell). Cell-in-cell formation affects both effector cells and their host cells in multiple aspects, while cell-in-cell death is under more intensive investigation. Given that cell-in-cell has an important role in maintainin...

  8. Bacterial cells with improved tolerance to isobutyric acid

    DEFF Research Database (Denmark)

    2017-01-01

    Bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as isobutyric acid and related compounds, and methods of preparing and using such bacterial cells for production of isobutyric acid and related compounds.......Bacterial cells genetically modified to improve their tolerance to certain commodity chemicals, such as isobutyric acid and related compounds, and methods of preparing and using such bacterial cells for production of isobutyric acid and related compounds....

  9. Intraocular Injection of ES Cell-Derived Neural Progenitors Improve Visual Function in Retinal Ganglion Cell-Depleted Mouse Models

    Directory of Open Access Journals (Sweden)

    Mundackal S. Divya

    2017-09-01

    Full Text Available Retinal ganglion cell (RGC transplantation is a promising strategy to restore visual function resulting from irreversible RGC degeneration occurring in glaucoma or inherited optic neuropathies. We previously demonstrated FGF2 induced differentiation of mouse embryonic stem cells (ESC to RGC lineage, capable of retinal ganglion cell layer (GCL integration upon transplantation. Here, we evaluated possible improvement of visual function by transplantation of ES cell derived neural progenitors in RGC depleted glaucoma mice models. ESC derived neural progenitors (ES-NP were transplanted into N-Methyl-D-Aspartate (NMDA injected, RGC-ablated mouse models and a pre-clinical glaucoma mouse model (DBA/2J having sustained higher intra ocular pressure (IOP. Visual acuity and functional integration was evaluated by behavioral experiments and immunohistochemistry, respectively. GFP-expressing ES-NPs transplanted in NMDA-injected RGC-depleted mice differentiated into RGC lineage and possibly integrating into GCL. An improvement in visual acuity was observed after 2 months of transplantation, when compared to the pre-transplantation values. Expression of c-Fos in the transplanted cells, upon light induction, further suggests functional integration into the host retinal circuitry. However, the transplanted cells did not send axonal projections into optic nerve. Transplantation experiments in DBA/2J mouse showed no significant improvement in visual functions, possibly due to both host and transplanted retinal cell death which could be due to an inherent high IOP. We showed that, ES NPs transplanted into the retina of RGC-ablated mouse models could survive, differentiate to RGC lineage, and possibly integrate into GCL to improve visual function. However, for the survival of transplanted cells in glaucoma, strategies to control the IOP are warranted.

  10. Mesenchymal stem cells increase T-regulatory cells and improve healing following trauma and hemorrhagic shock.

    Science.gov (United States)

    Gore, Amy V; Bible, Letitia E; Song, Kimberly; Livingston, David H; Mohr, Alicia M; Sifri, Ziad C

    2015-07-01

    Rodent lungs undergo full histologic recovery within 1 week following unilateral lung contusion (LC). However, when LC is followed by hemorrhagic shock (HS), healing is impaired. We hypothesize that the intravenous administration of mesenchymal stem cells (MSCs) in animals undergoing combined LC followed by HS (LCHS) will improve wound healing. Male Sprague-Dawley rats (n = 5-6 per group) were subjected to LCHS with or without the injection of a single intravenous dose of 5 × 10 MSCs following return of shed blood after HS. Rats were sacrificed 7 days following injury. Flow cytometry was used to determine the T-regulatory cell (Treg) population in peripheral blood. Lung histology was graded using a well-established lung injury score (LIS). Components of the LIS include average inflammatory cells per high-power field over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity, with total scores ranging from 0 to 11. Data were analyzed by analysis of variance followed by Tukey's multiple comparison test, expressed as mean (SD). p healing with an LIS unchanged from naive. The addition of HS resulted in a persistently elevated LIS score, whereas the addition of MSCs to LCHS decreased the LIS score back to naive levels. The change in LIS was driven by a significant decrease in edema scores. In rats undergoing LC alone, 10.5% (3.3%) of CD4 cells were Tregs. The addition of HS caused no significant change in Treg population (9.3% [0.7%]), whereas LCHS + MSC significantly increased the population to 18.2% (6.8%) in peripheral blood (p healing following trauma and HS is improved by a single dose of MSCs given immediately after injury. This enhanced healing is associated with an increase in the Treg population and a significant decrease in lung edema score as compared with animals undergoing LCHS. Further study into the role of Tregs in MSC-mediated wound healing is warranted.

  11. Fine-tuning the CAR spacer improves T-cell potency

    Science.gov (United States)

    Watanabe, Norihiro; Bajgain, Pradip; Sukumaran, Sujita; Ansari, Salma; Heslop, Helen E.; Rooney, Cliona M.; Brenner, Malcolm K.; Leen, Ann M.; Vera, Juan F.

    2016-01-01

    ABSTRACT The adoptive transfer of genetically engineered T cells expressing chimeric antigen receptors (CARs) has emerged as a transformative cancer therapy with curative potential, precipitating a wave of preclinical and clinical studies in academic centers and the private sector. Indeed, significant effort has been devoted to improving clinical benefit by incorporating accessory genes/CAR endodomains designed to enhance cellular migration, promote in vivo expansion/persistence or enhance safety by genetic programming to enable the recognition of a tumor signature. However, our efforts centered on exploring whether CAR T-cell potency could be enhanced by modifying pre-existing CAR components. We now demonstrate how molecular refinements to the CAR spacer can impact multiple biological processes including tonic signaling, cell aging, tumor localization, and antigen recognition, culminating in superior in vivo antitumor activity. PMID:28180032

  12. Improvements to the hierarchically structured ZnO nanosphere based dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Yongzhe; Wu Lihui; Liu Yanping; Xie Erqing, E-mail: zhangyzh04@126.co, E-mail: xieeq@lzu.edu.c [School of Physical Science and Technology, Lanzhou University, Lanzhou 730000 (China)

    2009-04-21

    Hierarchically structured ZnO nanospheres are synthesized by a wet-chemical method and ZnO sphere-consisting films are applied to dye-sensitized solar cells (DSSCs). It is found that the overall light-to-electricity conversion efficiency ({eta}) is significantly enhanced from 0.474% to 1.03% due to light scattering compared with the ZnO nanoparticle-based DSSC. However, the fill factor (FF) and open-circuit voltage (V{sub oc}) decrease obviously. After annealing the films in an oxygen environment and placing a ZnO blocking layer on the fluorine-doped SnO{sub 2} (FTO) conducting substrate, the FF and V{sub oc} are greatly improved and {eta} increases from 1.03% to 1.59% and 2.25%, respectively. According to the results of x-ray diffraction and photoluminescence, the significant improvements in the cell performances might be due to the suppression of the recombination and the decrease in the resistances existing in the cell.

  13. The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Cheng CHEN

    2009-08-01

    Full Text Available Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 on lung cancer cell lines and its role in interaction of CTL and target cells was investigated. Methods Human PBMC derived DCs were loaded with apoptotic tumor cells and stimulated by CD40 mAb (5C11. Tumor specific CTL was generated in vitro by autologous T cells co-cultured with mature DCs. Expression of PD-L1 on lung cancer cell lines H1299 and A549 were analyzed by FCM. JAM assay was used to detect the cytolytic activity of CTL with or without blocking PD-L1 by PD-L1 mAb respectively. The concentrations of IFN-γ in supernatants from distinct groups were analyzed by ELISA. Results Tumor cells-loaded mature DCs could induce the generation of the tumor specific CTL. Expression of PD-L1 was low on A549 cell, but high on H1299 cell. Blockade of PD-L1 on A549 could not improve cytolytic effect of CTL on target cells and IFN-γ production, but fragmentation of H1299 cells and IFN-γ production were significantly enhanced by the combination of PD-L1 mAb and CTL. Conclusion Expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.

  14. The ROCK inhibitor Y-27632 improves recovery of human embryonic stem cells after fluorescence-activated cell sorting with multiple cell surface markers.

    Directory of Open Access Journals (Sweden)

    Nil Emre

    Full Text Available BACKGROUND: Due to the inherent sensitivity of human embryonic stem cells (hESCs to manipulations, the recovery and survival of hESCs after fluorescence-activated cell sorting (FACS can be low. Additionally, a well characterized and robust methodology for performing FACS on hESCs using multiple-cell surface markers has not been described. The p160-Rho-associated coiled kinase (ROCK inhibitor, Y-27632, previously has been identified as enhancing survival of hESCs upon single-cell dissociation, as well as enhancing recovery from cryopreservation. Here we examined the application of Y-27632 to hESCs after FACS to improve survival in both feeder-dependent and feeder-independent growth conditions. METHODOLOGY/PRINCIPAL FINDINGS: HESCs were sorted using markers for SSEA-3, TRA-1-81, and SSEA-1. Cells were plated after sorting for 24 hours in either the presence or the absence of Y-27632. In both feeder-dependent and feeder-independent conditions, cell survival was greater when Y-27632 was applied to the hESCs after sort. Specifically, treatment of cells with Y-27632 improved post-sort recovery up to four fold. To determine the long-term effects of sorting with and without the application of Y-27632, hESCs were further analyzed. Specifically, hESCs sorted with and without the addition of Y-27632 retained normal morphology, expressed hESC-specific markers as measured by immunocytochemistry and flow cytometry, and maintained a stable karyotype. In addition, the hESCs could differentiate into three germ layers in vitro and in vivo in both feeder-dependent and feeder-independent growth conditions. CONCLUSIONS/SIGNIFICANCE: The application of Y-27632 to hESCs after cell sorting improves cell recovery with no observed effect on pluripotency, and enables the consistent recovery of hESCs by FACS using multiple surface markers. This improved methodology for cell sorting of hESCs will aid many applications such as removal of hESCs from secondary cell types

  15. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

    Science.gov (United States)

    Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

    2015-01-01

    Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

  16. Stem Cell Therapy to Improve Burn Wound Healing

    Science.gov (United States)

    2017-03-01

    Award Number: W81XWH-13-2-0024 TITLE: Stem Cell Therapy to Improve Burn Wound Healing PRINCIPAL INVESTIGATOR: Carl Schulman, MD, PhD, MSPH...NUMBER Stem Cell Therapy to Improve Burn Wound Healing 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Carl Schulman, MD, PhD, MSPH...treatments, steroid injections, and compression garments. Mesenchymal stem cells (MSC’s) have been used in a variety of clinical applications to repair

  17. Prognostic Significance of Progesterone Receptor–Positive Tumor Cells Within Immunohistochemically Defined Luminal A Breast Cancer

    Science.gov (United States)

    Prat, Aleix; Cheang, Maggie Chon U.; Martín, Miguel; Parker, Joel S.; Carrasco, Eva; Caballero, Rosalía; Tyldesley, Scott; Gelmon, Karen; Bernard, Philip S.; Nielsen, Torsten O.; Perou, Charles M.

    2013-01-01

    Purpose Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Patients and Methods Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) –positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Results Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) –positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Conclusion Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A

  18. MOLTEN CARBONATE FUEL CELL PRODUCT DESIGN IMPROVEMENT

    Energy Technology Data Exchange (ETDEWEB)

    H.C. Maru; M. Farooque

    2003-03-01

    The program efforts are focused on technology and system optimization for cost reduction, commercial design development, and prototype system field trials. The program is designed to advance the carbonate fuel cell technology from full-size field test to the commercial design. FuelCell Energy, Inc. (FCE) is in the later stage of the multiyear program for development and verification of carbonate fuel cell based power plants supported by DOE/NETL with additional funding from DOD/DARPA and the FuelCell Energy team. FCE has scaled up the technology to full-size and developed DFC{reg_sign} stack and balance-of-plant (BOP) equipment technology to meet product requirements, and acquired high rate manufacturing capabilities to reduce cost. FCE has designed submegawatt (DFC300A) and megawatt (DFC1500 and DFC3000) class fuel cell products for commercialization of its DFC{reg_sign} technology. A significant progress was made during the reporting period. The reforming unit design was optimized using a three-dimensional stack simulation model. Thermal and flow uniformities of the oxidant-In flow in the stack module were improved using computational fluid dynamics based flow simulation model. The manufacturing capacity was increased. The submegawatt stack module overall cost was reduced by {approx}30% on a per kW basis. An integrated deoxidizer-prereformer design was tested successfully at submegawatt scale using fuels simulating digester gas, coal bed methane gas and peak shave (natural) gas.

  19. MOLTEN CARBONATE FUEL CELL PRODUCT DESIGN IMPROVEMENT

    Energy Technology Data Exchange (ETDEWEB)

    H.C. Maru; M. Farooque

    2005-03-01

    The program was designed to advance the carbonate fuel cell technology from full-size proof-of-concept field test to the commercial design. DOE has been funding Direct FuelCell{reg_sign} (DFC{reg_sign}) development at FuelCell Energy, Inc. (FCE, formerly Energy Research Corporation) from an early state of development for stationary power plant applications. The current program efforts were focused on technology and system development, and cost reduction, leading to commercial design development and prototype system field trials. FCE, in Danbury, CT, is a world-recognized leader for the development and commercialization of high efficiency fuel cells that can generate clean electricity at power stations, or at distributed locations near the customers such as hospitals, schools, universities, hotels and other commercial and industrial applications. FCE has designed three different fuel cell power plant models (DFC300A, DFC1500 and DFC3000). FCE's power plants are based on its patented DFC{reg_sign} technology, where a hydrocarbon fuel is directly fed to the fuel cell and hydrogen is generated internally. These power plants offer significant advantages compared to the existing power generation technologies--higher fuel efficiency, significantly lower emissions, quieter operation, flexible siting and permitting requirements, scalability and potentially lower operating costs. Also, the exhaust heat by-product can be used for cogeneration applications such as high-pressure steam, district heating and air conditioning. Several sub-MW power plants based on the DFC design are currently operating in Europe, Japan and the US. Several one-megawatt power plant design was verified by operation on natural gas at FCE. This plant is currently installed at a customer site in King County, WA under another US government program and is currently in operation. Because hydrogen is generated directly within the fuel cell module from readily available fuels such as natural gas and

  20. Inhaler Reminders Significantly Improve Asthma Patients' Use of Controller Medications

    Science.gov (United States)

    ... controller medications Share | Inhaler reminders significantly improve asthma patients’ use of controller medications Published Online: July 22, ... the burden and risk of asthma, but many patients do not use them regularly. This poor adherence ...

  1. Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells.

    Science.gov (United States)

    Fan, Lianchun; Kadura, Ibrahim; Krebs, Lara E; Hatfield, Christopher C; Shaw, Margaret M; Frye, Christopher C

    2012-04-01

    significantly increased, as indicated by the large reduction of non-producing and low-producing cells after 25 µM L-MSX selection, and resulted in a six-fold efficiency improvement in identifying similar numbers of high-productive cell lines for a given recombinant monoclonal antibody. The potential impact of GS-knockout cells on recombinant protein quality is also discussed. Copyright © 2011 Wiley Periodicals, Inc.

  2. Improvements in numerical modelling of highly injected crystalline silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Altermatt, P.P. [University of New South Wales, Centre for Photovoltaic Engineering, 2052 Sydney (Australia); Sinton, R.A. [Sinton Consulting, 1132 Green Circle, 80303 Boulder, CO (United States); Heiser, G. [University of NSW, School of Computer Science and Engineering, 2052 Sydney (Australia)

    2001-01-01

    We numerically model crystalline silicon concentrator cells with the inclusion of band gap narrowing (BGN) caused by injected free carriers. In previous studies, the revised room-temperature value of the intrinsic carrier density, n{sub i}=1.00x10{sup 10}cm{sup -3}, was inconsistent with the other material parameters of highly injected silicon. In this paper, we show that high-injection experiments can be described consistently with the revised value of n{sub i} if free-carrier induced BGN is included, and that such BGN is an important effect in silicon concentrator cells. The new model presented here significantly improves the ability to model highly injected silicon cells with a high level of precision.

  3. Tailoring cyanobacterial cell factory for improved industrial properties.

    Science.gov (United States)

    Luan, Guodong; Lu, Xuefeng

    Photosynthetic biomanufacturing provides a promising solution for sustainable production of biofuels and biochemicals. Cyanobacteria are among the most promising microbial platforms for the construction of photosynthetic cell factories. Metabolic engineering of cyanobacteria has enabled effective photosynthetic synthesis of diverse natural or non-natural metabolites, while commercialization of photosynthetic biomanufacturing is usually restricted by process and economic feasibilities. In actual outdoor conditions, active cell growth and product synthesis is restricted to narrow light exposure windows of the day-night cycles and is threatened by diverse physical, chemical, and biological environmental stresses. For biomass harvesting and bioproduct recovery, energy and cost consuming processing and equipment is required, which further decreases the economic and environmental competitiveness of the entire process. To facilitate scaled photosynthetic biomanufacturing, lots of efforts have been made to engineer cyanobacterial cell properties required by robust & continual cultivation and convenient & efficient recovery. In this review, we specifically summarized recently reported engineering strategies on optimizing industrial properties of cyanobacterial cells. Through systematically re-editing the metabolism, morphology, mutualism interaction of cyanobacterial chassis cells, the adaptabilities and compatibilities of the cyanobacterial cell factories to the industrial process could be significantly improved. Cell growth and product synthesis of the tailored cyanobacterial cells could be expanded and maintained at night and in stressful environments, while convenient biomass harvesting could also be expected. For developing more feasible cyanobacterial photosynthetic biomanufacturing in large scale, we here propose the importance of tailoring industrial properties of cyanobacteria and outline the directions that should be exploited in the future. Copyright © 2018

  4. Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

    Science.gov (United States)

    Patel, Vivek; Joseph, Gravil; Patel, Amit; Patel, Samik; Bustin, Devin; Mawson, David; Tuesta, Luis M.; Puentes, Rocio; Ghosh, Mousumi

    2010-01-01

    Abstract Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application. PMID:20144012

  5. Colonic inflammation in mice is improved by cigarette smoke through iNKT cells recruitment.

    Directory of Open Access Journals (Sweden)

    Muriel Montbarbon

    Full Text Available Cigarette smoke (CS protects against intestinal inflammation during ulcerative colitis. Immunoregulatory mechanisms sustaining this effect remain unknown. The aim of this study was to assess the effects of CS on experimental colitis and to characterize the intestinal inflammatory response at the cellular and molecular levels. Using the InExpose® System, a smoking device accurately reproducing human smoking habit, we pre-exposed C57BL/6 mice for 2 weeks to CS, and then we induced colitis by administration of dextran sodium sulfate (DSS. This system allowed us to demonstrate that CS exposure improved colonic inflammation (significant decrease in clinical score, body weight loss and weight/length colonic ratio. This improvement was associated with a significant decrease in colonic proinflammatory Th1/Th17 cytokine expression, as compared to unexposed mice (TNF (p=0.0169, IFNγ (p<0.0001, and IL-17 (p=0.0008. Smoke exposure also induced an increased expression of IL-10 mRNA (p=0.0035 and a marked recruitment of iNKT (invariant Natural Killer T; CD45+ TCRβ+ CD1d tetramer+ cells in the colon of DSS-untreated mice. Demonstration of the role of iNKT cells in CS-dependent colitis improvement was performed using two different strains of NKT cells deficient mice. Indeed, in Jα18KO and CD1dKO animals, CS exposure failed to induce significant regulation of DSS-induced colitis both at the clinical and molecular levels. Thus, our study demonstrates that iNKT cells are pivotal actors in the CS-dependent protection of the colon. These results highlight the role of intestinal iNKT lymphocytes and their responsiveness to environmental stimuli. Targeting iNKT cells would represent a new therapeutic way for inflammatory bowel diseases.

  6. Considerably improved photovoltaic performance of carbon nanotube-based solar cells using metal oxide layers

    Science.gov (United States)

    Wang, Feijiu; Kozawa, Daichi; Miyauchi, Yuhei; Hiraoka, Kazushi; Mouri, Shinichiro; Ohno, Yutaka; Matsuda, Kazunari

    2015-02-01

    Carbon nanotube-based solar cells have been extensively studied from the perspective of potential application. Here we demonstrated a significant improvement of the carbon nanotube solar cells by the use of metal oxide layers for efficient carrier transport. The metal oxides also serve as an antireflection layer and an efficient carrier dopant, leading to a reduction in the loss of the incident solar light and an increase in the photocurrent, respectively. As a consequence, the photovoltaic performance of both p-single-walled carbon nanotube (SWNT)/n-Si and n-SWNT/p-Si heterojunction solar cells using MoOx and ZnO layers is improved, resulting in very high photovoltaic conversion efficiencies of 17.0 and 4.0%, respectively. These findings regarding the use of metal oxides as multifunctional layers suggest that metal oxide layers could improve the performance of various electronic devices based on carbon nanotubes.

  7. Considerably improved photovoltaic performance of carbon nanotube-based solar cells using metal oxide layers.

    Science.gov (United States)

    Wang, Feijiu; Kozawa, Daichi; Miyauchi, Yuhei; Hiraoka, Kazushi; Mouri, Shinichiro; Ohno, Yutaka; Matsuda, Kazunari

    2015-02-18

    Carbon nanotube-based solar cells have been extensively studied from the perspective of potential application. Here we demonstrated a significant improvement of the carbon nanotube solar cells by the use of metal oxide layers for efficient carrier transport. The metal oxides also serve as an antireflection layer and an efficient carrier dopant, leading to a reduction in the loss of the incident solar light and an increase in the photocurrent, respectively. As a consequence, the photovoltaic performance of both p-single-walled carbon nanotube (SWNT)/n-Si and n-SWNT/p-Si heterojunction solar cells using MoOx and ZnO layers is improved, resulting in very high photovoltaic conversion efficiencies of 17.0 and 4.0%, respectively. These findings regarding the use of metal oxides as multifunctional layers suggest that metal oxide layers could improve the performance of various electronic devices based on carbon nanotubes.

  8. Synthesis and characterization of Ag nanowires: Improved performance in dye sensitized solar cells

    Directory of Open Access Journals (Sweden)

    Safia A. Kazmi

    2016-09-01

    Full Text Available Development of highly efficient dye-sensitized solar cells (DSSCs with good photovoltaic parameters is an active research area of current global interest. Recently, one dimensional nanomaterial, such as nanorods and nanotubes has replaced the nanoparticles used in DSSCs anode because of their ability to improve the electron transport leading to enhanced electron collection efficiency. In the present work, rapid synthesis of silver nanowires (AgNWs was done. The XRD characterization was performed to confirm the formation and size of synthesized AgNWs. It was observed that FWHM of the diffraction peaks was increased with AgNWs concentration in TiO2. The synthesized TiO2AgNWs nanocomposite was used as the photo anode of Dye sensitized solar cell. The I–V characteristics of the solar cell were drawn using standard conditions. It was observed that TiO2AgNWs based solar cells have significantly increased photocurrent density resulting in improved conversion efficiency as compared to pure TiO2 based DSSC.

  9. Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer

    International Nuclear Information System (INIS)

    Kishigami, Satoshi; Mizutani, Eiji; Ohta, Hiroshi; Hikichi, Takafusa; Thuan, Nguyen Van; Wakayama, Sayaka; Bui, Hong-Thuy; Wakayama, Teruhiko

    2006-01-01

    The low success rate of animal cloning by somatic cell nuclear transfer (SCNT) is believed to be associated with epigenetic errors including abnormal DNA hypermethylation. Recently, we elucidated by using round spermatids that, after nuclear transfer, treatment of zygotes with trichostatin A (TSA), an inhibitor of histone deacetylase, can remarkably reduce abnormal DNA hypermethylation depending on the origins of transferred nuclei and their genomic regions [S. Kishigami, N. Van Thuan, T. Hikichi, H. Ohta, S. Wakayama. E. Mizutani, T. Wakayama, Epigenetic abnormalities of the mouse paternal zygotic genome associated with microinsemination of round spermatids, Dev. Biol. (2005) in press]. Here, we found that 5-50 nM TSA-treatment for 10 h following oocyte activation resulted in more efficient in vitro development of somatic cloned embryos to the blastocyst stage from 2- to 5-fold depending on the donor cells including tail tip cells, spleen cells, neural stem cells, and cumulus cells. This TSA-treatment also led to more than 5-fold increase in success rate of mouse cloning from cumulus cells without obvious abnormality but failed to improve ES cloning success. Further, we succeeded in establishment of nuclear transfer-embryonic stem (NT-ES) cells from TSA-treated cloned blastocyst at a rate three times higher than those from untreated cloned blastocysts. Thus, our data indicate that TSA-treatment after SCNT in mice can dramatically improve the practical application of current cloning techniques

  10. Improved photovoltaic cells and electrodes

    Science.gov (United States)

    Skotheim, T.A.

    1983-06-29

    Improved photovoltaic cells and electrodes for use therein, particularly electrodes employing amorphous silicon or polyacetylene coating are produced by a process which includes filling pinholes or porous openings in the coatings by electrochemical oxidation of selected monomers to deposit insulating polymer in the openings.

  11. VEGF improves survival of mesenchymal stem cells in infarcted hearts

    International Nuclear Information System (INIS)

    Pons, Jennifer; Huang Yu; Arakawa-Hoyt, Janice; Washko, Daniel; Takagawa, Junya; Ye, Jianqin; Grossman, William; Su Hua

    2008-01-01

    Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16 INK , p21 and p19 ARF . VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI

  12. Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.

    Science.gov (United States)

    Li, Wen; Wang, Li; Chu, Xiaoqian; Cui, Huantian; Bian, Yuhong

    2017-04-01

    At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

  13. Co-overexpressing a Plasma Membrane and a Vacuolar Membrane Sodium/Proton Antiporter Significantly Improves Salt Tolerance in Transgenic Arabidopsis Plants

    Science.gov (United States)

    Pehlivan, Necla; Sun, Li; Jarrett, Philip; Yang, Xiaojie; Mishra, Neelam; Chen, Lin; Kadioglu, Asim; Shen, Guoxin; Zhang, Hong

    2016-01-01

    The Arabidopsis gene AtNHX1 encodes a vacuolar membrane-bound sodium/proton (Na+/H+) antiporter that transports Na+ into the vacuole and exports H+ into the cytoplasm. The Arabidopsis gene SOS1 encodes a plasma membrane-bound Na+/H+ antiporter that exports Na+ to the extracellular space and imports H+ into the plant cell. Plants rely on these enzymes either to keep Na+ out of the cell or to sequester Na+ into vacuoles to avoid the toxic level of Na+ in the cytoplasm. Overexpression of AtNHX1 or SOS1 could improve salt tolerance in transgenic plants, but the improved salt tolerance is limited. NaCl at concentration >200 mM would kill AtNHX1-overexpressing or SOS1-overexpressing plants. Here it is shown that co-overexpressing AtNHX1 and SOS1 could further improve salt tolerance in transgenic Arabidopsis plants, making transgenic Arabidopsis able to tolerate up to 250 mM NaCl treatment. Furthermore, co-overexpression of AtNHX1 and SOS1 could significantly reduce yield loss caused by the combined stresses of heat and salt, confirming the hypothesis that stacked overexpression of two genes could substantially improve tolerance against multiple stresses. This research serves as a proof of concept for improving salt tolerance in other plants including crops. PMID:26985021

  14. The pathological significance of Notch1 in oral squamous cell carcinoma.

    Science.gov (United States)

    Yoshida, Ryoji; Nagata, Masashi; Nakayama, Hideki; Niimori-Kita, Kanako; Hassan, Wael; Tanaka, Takuji; Shinohara, Masanori; Ito, Takaaki

    2013-10-01

    Notch signaling has been reported to be involved in several types of malignant tumors; however, the role and activation mechanism of Notch signaling in oral squamous cell carcinoma (OSCC) remains poorly characterized. The purpose of this study was to elucidate the pathological significance of Notch signaling and its activation mechanism in the development and progression of OSCC. In this study, we showed that the expression of Notch1 and intracellular Notch domain (NICD) are upregulated in OSCCs. In addition, Notch1 and NICD were found to be characteristically localized at the invasive tumor front. TNF-α, a major inflammatory cytokine, significantly activated Notch signaling in vitro. In a clinicopathological analysis, Notch1 expression correlated with both the T-stage and the clinical stage. Furthermore, loss of Notch1 expression correlated with the inhibition of cell proliferation and TNF-α-dependent invasiveness in an OSCC cell line. In addition, γ-secretase inhibitor (GSI) prevented cell proliferation and TNF-α-dependent invasion of OSCC cells in vitro. These results indicate that altered expression of Notch1 is associated with increased cancer progression and that Notch1 regulates the steps involved in cell metastasis in OSCC. Moreover, inactivating Notch signaling with GSI could therefore be a useful approach for treating patients with OSCC.

  15. Markers of stem cells in human ovarian granulosa cells: is there a clinical significance in ART?

    Directory of Open Access Journals (Sweden)

    Varras Michail

    2012-11-01

    Full Text Available Abstract Background The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART. Methods Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard. Results G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21. The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum. No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly. Conclusions Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47

  16. Biphasic electrical targeting plays a significant role in schwann cell activation.

    Science.gov (United States)

    Kim, In Sook; Song, Yun Mi; Cho, Tae Hyung; Pan, Hui; Lee, Tae Hyung; Kim, Sung June; Hwang, Soon Jung

    2011-05-01

    Electrical stimulation (ES) is a promising technique for axonal regeneration of peripheral nerve injuries. However, long-term, continuous ES in the form of biphasic electric current (BEC) to stimulate axonal regeneration has rarely been attempted and the effects of BEC on Schwann cells are unknown. We hypothesized that long-term, continuous ES would trigger the activation of Schwann cells, and we therefore investigated the effect of BEC on the functional differentiation of primary human mesenchymal stromal cells (hMSCs) into Schwann cells, as well as the activity of primary Schwann cells. Differentiation of hMSCs into Schwann cells was determined by coculture with rat pheochromocytoma cells (PC12 cell line). We also investigated the in vivo effects of long-term ES (4 weeks) on axonal outgrowth of a severed sciatic nerve with a 7-mm gap after retraction of the nerve ends in rats by implanting an electronic device to serve as a neural conduit. PC12 cells cocultured with hMSCs electrically stimulated during culture in Schwann cell differentiation medium (Group I) had longer neurites and a greater percentage of PC12 cells were neurite-sprouting than when cocultured with hMSCs cultured in growth medium (control group) or unstimulated hMSCs in the same culture conditions as used for Group I (Group II). Group I cells showed significant upregulation of Schwann cell-related neurotrophic factors such as nerve growth factor and glial-derived neurotrophic factor compared to Group II cells at both the mRNA and protein levels. Primary Schwann cells responded to continuous BEC with increased proliferation and the induction of nerve growth factor and glial-derived neurotrophic factor, similar to Group I cells, and in addition, induction of brain-derived neurotrophic factor was observed. Immunohistochemical investigation of sciatic nerve regenerates revealed that BEC increased axonal outgrowth significantly. These results demonstrate that BEC enhanced the functional activity of

  17. Significant effect of Ca2+ on improving the heat resistance of lactic acid bacteria.

    Science.gov (United States)

    Huang, Song; Chen, Xiao Dong

    2013-07-01

    The heat resistance of lactic acid bacteria (LAB) has been extensively investigated due to its highly practical significance. Reconstituted skim milk (RSM) has been found to be one of the most effective protectant wall materials for microencapsulating microorganisms during convective drying, such as spray drying. In addition to proteins and carbohydrate, RSM is rich in calcium. It is not clear which component is critical in the RSM protection mechanism. This study investigated the independent effect of calcium. Ca(2+) was added to lactose solution to examine its influence on the heat resistance of Lactobacillus rhamnosus ZY, Lactobacillus casei Zhang, Lactobacillus plantarum P8 and Streptococcus thermophilus ND03. The results showed that certain Ca(2+) concentrations enhanced the heat resistance of the LAB strains to different extents, that is produced higher survival and shorter regrowth lag times of the bacterial cells. In some cases, the improvements were dramatic. More scientifically insightful and more intensive instrumental study of the Ca(2+) behavior around and in the cells should be carried out in the near future. In the meantime, this work may lead to the development of more cost-effective wall materials with Ca(2+) added as a prime factor. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  18. Bedtime Blood Pressure Chronotherapy Significantly Improves Hypertension Management.

    Science.gov (United States)

    Hermida, Ramón C; Ayala, Diana E; Fernández, José R; Mojón, Artemio; Crespo, Juan J; Ríos, María T; Smolensky, Michael H

    2017-10-01

    Consistent evidence of numerous studies substantiates the asleep blood pressure (BP) mean derived from ambulatory BP monitoring (ABPM) is both an independent and a stronger predictor of cardiovascular disease (CVD) risk than are daytime clinic BP measurements or the ABPM-determined awake or 24-hour BP means. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of 6 different classes and their combinations significantly improves BP control, particularly sleep-time BP, and reduces adverse effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Improvement on LiFePO4 Cell Balancing Algorithm

    OpenAIRE

    Vencislav C. Valchev; Plamen V. Yankov; Dimo D. Stefanov

    2018-01-01

    The paper presents improvement on operation time of cell balancing algorithm compared to conventional multiple cell LiFePO4 charge methodology. A flowchart is synthesised to explain the main steps of the software design, which afterwards is implemented in a microcontroller. Experimental results are provided to clarify the transition between charge and balance process. Graphical data for a voltage equalization of eight cells is presented to verify the proposed improvement.

  20. National Emergency Preparedness and Response: Improving for Incidents of National Significance

    National Research Council Canada - National Science Library

    Clayton, Christopher M

    2006-01-01

    The national emergency management system has need of significant improvement in its contingency planning and early consolidation of effort and coordination between federal, state, and local agencies...

  1. Trehalose improves cell proliferation and dehydration tolerance of human HaCaT cells

    Directory of Open Access Journals (Sweden)

    Lee Kyung Eun

    2015-01-01

    Full Text Available Trehalose is a disaccharide molecule that serves as a natural osmotic regulator in halophilic microorganisms and plants but not in mammals. We observed that human HaCaT cells supplied with trehalose improved cell proliferation and extended viability under dehydration. In HaCaT cells, in response to increasing concentrations of exogenous trehalose, the levels of heat shock protein (HSP 70 increased and matrix metalloproteinase (MMP 1 decreased. Proteome analysis of trehalose-treated HaCaT cells revealed remarkable increases in the levels of proteins involved in cell signaling and the cell cycle, including p21 activated kinase I, Sec I family domain protein and elongation factor G. Moreover, the proteins for cell stress resistance, tryptophan hydroxylase, serine/cysteine proteinase inhibitors and vitamin D receptors were also increased. In addition, the proteins responsible for the maintenance of the cytoskeleton and cellular structures including procollagen-lysine dioxygenase, vinculin and ezrin were increased. Proteomic data revealed that trehalose affected HaCaT cells by inducing the proteins involved in cell proliferation. These results suggest that trehalose improves the proliferation and dehydration tolerance of HaCaT cells by inducing proteins involved in cell growth and dehydration protection.

  2. Does injection of metanephric mesenchymal cells improve renal function in rats?

    Directory of Open Access Journals (Sweden)

    Yu-qing Jiao

    2011-01-01

    Full Text Available Chronic kidney disease (CKD is a massive global health-care problem. Cell therapy offers a potential treatment for CKD. The aim of this study was to investigate whether the administration of a population of stem cells could be used to treat adriamycin (ADR-induced glomerulopathy in rats, a form of CKD. We intravenously transplanted metanephric mesenchymal cells (MMCs into rats treated with ADR. We also induced MMC differentiation in vitro using a medium derived from serum and homogenates of ADR-induced glomerulopathy rats. We detected the induction of an early epithelial phenotype (cytokeratin-18 expression and a proximal tubule phenotype (vitamin D receptor expression in vitro, and MMC-derived epithelial cells corresponding to the proximal tubule and glomeruli in vivo. Transplantation of MMCs after induction of glomerulopathy significantly increased the creatinine clearance rate (Ccr, a marker for glomerular filtration rate, but had no significant effect on other parameters (24-hour urinary protein excretion, serum albumin, total cholesterol. In addition, there was no significant difference in blood urea nitrogen or serum creatinine levels in rats with and without ADR administration. Our results indicate that MMCs might survive, engraft and differentiate into renal epithelia in vivo when transplanted into ADR-treated rats. However, further studies are needed to determine whether MMC transplantation improves renal function and causes renal repair in this model.

  3. Reducing macrophages to improve bone marrow stromal cell survival in the contused spinal cord.

    NARCIS (Netherlands)

    Ritfeld, G.J.; Nandoe Tewarie, R.D.S.; Rahiem, S.T.; Hurtado, A.; Roos, R.A.; Grotenhuis, A.; Oudega, M.

    2010-01-01

    We tested whether reducing macrophage infiltration would improve the survival of allogeneic bone marrow stromal cells (BMSC) transplanted in the contused adult rat thoracic spinal cord. Treatment with cyclosporine, minocycline, or methylprednisolone all resulted in a significant decrease in

  4. Improvement on LiFePO4 Cell Balancing Algorithm

    Directory of Open Access Journals (Sweden)

    Vencislav C. Valchev

    2018-02-01

    Full Text Available The paper presents improvement on operation time of cell balancing algorithm compared to conventional multiple cell LiFePO4 charge methodology. A flowchart is synthesised to explain the main steps of the software design, which afterwards is implemented in a microcontroller. Experimental results are provided to clarify the transition between charge and balance process. Graphical data for a voltage equalization of eight cells is presented to verify the proposed improvement.

  5. Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome.

    Science.gov (United States)

    King, Aileen J F; Griffiths, Lisa A; Persaud, Shanta J; Jones, Peter M; Howell, Simon L; Welsh, Nils

    2016-05-01

    Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo models. The aim of this study was to investigate whether imatinib could be used to improve islet transplantation outcome. Methods Islets were isolated from C57Bl/6 mice and pre-cultured with imatinib prior to exposure to streptozotocin and cytokines in vitro. Cell viability and glucose-induced insulin secretion were measured. For transplantation experiments, islets were pre-cultured with imatinib for either 72 h or 24 h prior to transplantation into streptozotocin-diabetic C57Bl/6 mice. In one experimental series mice were also administered imatinib after islet transplantation. Results Imatinib partially protected islets from beta cell death in vitro. However, pre-culturing islets in imatinib or administering the drug to the mice in the days following islet transplantation did not improve blood glucose concentrations more than control-cultured islets. Conclusion Although imatinib protected against beta cell death from cytokines and streptozotocin in vitro, it did not significantly improve syngeneic islet transplantation outcome.

  6. Basic aspects for improving the energy conversion efficiency of hetero-junction organic photovoltaic cells.

    Science.gov (United States)

    Ryuzaki, Sou; Onoe, Jun

    2013-01-01

    Hetero-junction organic photovoltaic (OPV) cells consisting of donor (D) and acceptor (A) layers have been regarded as next-generation PV cells, because of their fascinating advantages, such as lightweight, low fabrication cost, resource free, and flexibility, when compared to those of conventional PV cells based on silicon and semiconductor compounds. However, the power conversion efficiency (η) of the OPV cells has been still around 8%, though more than 10% efficiency has been required for their practical use. To fully optimize these OPV cells, it is necessary that the low mobility of carriers/excitons in the OPV cells and the open circuit voltage (V OC), of which origin has not been understood well, should be improved. In this review, we address an improvement of the mobility of carriers/excitons by controlling the crystal structure of a donor layer and address how to increase the V OC for zinc octaethylporphyrin [Zn(OEP)]/C60 hetero-junction OPV cells [ITO/Zn(OEP)/C60/Al]. It was found that crystallization of Zn(OEP) films increases the number of inter-molecular charge transfer (IMCT) excitons and enlarges the mobility of carriers and IMCT excitons, thus significantly improving the external quantum efficiency (EQE) under illumination of the photoabsorption band due to the IMCT excitons. Conversely, charge accumulation of photo-generated carriers in the vicinity of the donor/acceptor (D/A) interface was found to play a key role in determining the V OC for the OPV cells.

  7. Performance improvement of silicon solar cells by nanoporous silicon coating

    Directory of Open Access Journals (Sweden)

    Dzhafarov T. D.

    2012-04-01

    Full Text Available In the present paper the method is shown to improve the photovoltaic parameters of screen-printed silicon solar cells by nanoporous silicon film formation on the frontal surface of the cell using the electrochemical etching. The possible mechanisms responsible for observed improvement of silicon solar cell performance are discussed.

  8. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  9. Significant improvement of pig cloning efficiency by treatment with LBH589 after somatic cell nuclear transfer.

    Science.gov (United States)

    Jin, Jun-Xue; Li, Suo; Gao, Qing-Shan; Hong, Yu; Jin, Long; Zhu, Hai-Ying; Yan, Chang-Guo; Kang, Jin-Dan; Yin, Xi-Jun

    2013-10-01

    The low success rate of animal cloning by somatic cell nuclear transfer (SCNT) associates with epigenetic aberrancy, including the abnormal acetylation of histones. Altering the epigenetic status by histone deacetylase inhibitors (HDACi) enhances the developmental potential of SCNT embryos. In the current study, we examined the effects of LBH589 (panobinostat), a novel broad-spectrum HDACi, on the nuclear reprogramming and development of pig SCNT embryos in vitro. In experiment 1, we compared the in vitro developmental competence of nuclear transfer embryos treated with different concentrations of LBH589. Embryos treated with 50 nM LBH589 for 24 hours showed a significant increase in the rate of blastocyst formation compared with the control or embryos treated with 5 or 500 nM LBH589 (32.4% vs. 11.8%, 12.1%, and 10.0%, respectively, P < 0.05). In experiment 2, we examined the in vitro developmental competence of nuclear transfer embryos treated with 50 nM LBH589 for various intervals after activation and 6-dimethylaminopurine. Embryos treated for 24 hours had higher rates of blastocyst formation than the other groups. In experiment 3, when the acetylation of H4K12 was examined in SCNT embryos treated for 6 hours with 50 nM LBH589 by immunohistochemistry, the staining intensities of these proteins in LBH589-treated SCNT embryos were significantly higher than in the control. In experiment 4, LBH589-treated nuclear transfer and control embryos were transferred into surrogate mothers, resulting in three (100%) and two (66.7%) pregnancies, respectively. In conclusion, LBH589 enhances the nuclear reprogramming and developmental potential of SCNT embryos by altering the epigenetic status and expression, and increasing blastocyst quality. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  10. Improving Energy Efficiency and Enabling Water Recycle in Biorefineries Using Bioelectrochemical Cells

    International Nuclear Information System (INIS)

    Borole, Abhijeet P.

    2010-01-01

    Improving biofuel yield and water reuse are two important issues in further development of biorefineries. The total energy content of liquid fuels (including ethanol and hydrocarbon) produced from cellulosic biomass via biochemical or hybrid bio-thermochemical routes can vary from 49% to 70% of the biomass entering the biorefinery, on an energy basis. Use of boiler for combustion of residual organics and lignin results in significant energy and water losses. An alternate process to improve energy recovery from the residual organic streams is via use of bioelectrochemical systems such as microbial fuel cells (MFCs) microbial electrolysis cells (MECs). The potential advantages of this alternative scheme in a biorefinery include minimization of heat loss and generation of a higher value product, hydrogen. The need for 5-15 gallons of water per gallon of ethanol can be reduced significantly via recycle of water after MEC treatment. Removal of inhibitory byproducts such as furans, phenolics and acetate in MFC/MECs to generate energy, thus, has dual advantages including improvements in energy efficiency and ability to recycle water. Conversion of the sugar- and lignin- degradation products to hydrogen is synergistic with biorefinery hydrogen requirements for upgrading F-T liquids and other byproducts to high-octane fuels and/or high value products. Some of these products include sorbitol, succinic acid, furan and levulinate derivatives, glycols, polyols, 1,4-butenadiol, phenolics polymers, etc. Potential process alternatives utilizing MECs in biorefineries capable of improving energy efficiency by up to 30% are discussed.

  11. Room temperature electrocompetent bacterial cells improve DNA transformation and recombineering efficiency.

    Science.gov (United States)

    Tu, Qiang; Yin, Jia; Fu, Jun; Herrmann, Jennifer; Li, Yuezhong; Yin, Yulong; Stewart, A Francis; Müller, Rolf; Zhang, Youming

    2016-04-20

    Bacterial competent cells are essential for cloning, construction of DNA libraries, and mutagenesis in every molecular biology laboratory. Among various transformation methods, electroporation is found to own the best transformation efficiency. Previous electroporation methods are based on washing and electroporating the bacterial cells in ice-cold condition that make them fragile and prone to death. Here we present simple temperature shift based methods that improve DNA transformation and recombineering efficiency in E. coli and several other gram-negative bacteria thereby economizing time and cost. Increased transformation efficiency of large DNA molecules is a significant advantage that might facilitate the cloning of large fragments from genomic DNA preparations and metagenomics samples.

  12. DOT1L inhibitor improves early development of porcine somatic cell nuclear transfer embryos

    DEFF Research Database (Denmark)

    Tao, Jia; Zhang, Yu; Zuo, Xiaoyuan

    2017-01-01

    Incomplete epigenetic reprogramming of the genome of donor cells causes poor early and full-term developmental efficiency of somatic cell nuclear transfer (SCNT) embryos. Previous research indicate that inhibition of the histone H3 K79 methyltransferase DOT1L, using a selective pharmacological...... inhibitor EPZ004777 (EPZ), significantly improved reprogramming efficiency during the generation of mouse induced pluripotent stem cells. However, the roles of DOT1L in porcine nuclear transfer-mediated cellular reprogramming are not yet known. Here we showed that DOT1L inhibition via 0.5 nM EPZ treatment...

  13. Co-overexpressing a Plasma Membrane and a Vacuolar Membrane Sodium/Proton Antiporter Significantly Improves Salt Tolerance in Transgenic Arabidopsis Plants.

    Science.gov (United States)

    Pehlivan, Necla; Sun, Li; Jarrett, Philip; Yang, Xiaojie; Mishra, Neelam; Chen, Lin; Kadioglu, Asim; Shen, Guoxin; Zhang, Hong

    2016-05-01

    The Arabidopsis gene AtNHX1 encodes a vacuolar membrane-bound sodium/proton (Na(+)/H(+)) antiporter that transports Na(+) into the vacuole and exports H(+) into the cytoplasm. The Arabidopsis gene SOS1 encodes a plasma membrane-bound Na(+)/H(+) antiporter that exports Na(+) to the extracellular space and imports H(+) into the plant cell. Plants rely on these enzymes either to keep Na(+) out of the cell or to sequester Na(+) into vacuoles to avoid the toxic level of Na(+) in the cytoplasm. Overexpression of AtNHX1 or SOS1 could improve salt tolerance in transgenic plants, but the improved salt tolerance is limited. NaCl at concentration >200 mM would kill AtNHX1-overexpressing or SOS1-overexpressing plants. Here it is shown that co-overexpressing AtNHX1 and SOS1 could further improve salt tolerance in transgenic Arabidopsis plants, making transgenic Arabidopsis able to tolerate up to 250 mM NaCl treatment. Furthermore, co-overexpression of AtNHX1 and SOS1 could significantly reduce yield loss caused by the combined stresses of heat and salt, confirming the hypothesis that stacked overexpression of two genes could substantially improve tolerance against multiple stresses. This research serves as a proof of concept for improving salt tolerance in other plants including crops. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

  14. Synthesis and SAR of novel imidazoquinoxaline-based Lck inhibitors: improvement of cell potency.

    Science.gov (United States)

    Chen, Ping; Iwanowicz, Edwin J; Norris, Derek; Gu, Henry H; Lin, James; Moquin, Robert V; Das, Jagabandhu; Wityak, John; Spergel, Steven H; de Fex, Henry; Pang, Suhong; Pitt, Sydney; Shen, Ding Ren; Schieven, Gary L; Barrish, Joel C

    2002-11-04

    A series of anilino(imidazoquinoxaline) analogues bearing solubilizing side chains at the 6- and 7-positions of the fused phenyl ring has been prepared and evaluated for inhibition against Lck enzyme and of T-cell proliferation. Significant improvement of the cellular activity was achieved over the initial lead, compound 2.

  15. Cell surface glycan engineering of neural stem cells augments neurotropism and improves recovery in a murine model of multiple sclerosis

    KAUST Repository

    Merzaban, Jasmeen S.

    2015-09-13

    Neural stem cell (NSC)-based therapies offer potential for neural repair in central nervous system (CNS) inflammatory and degenerative disorders. Typically, these conditions present with multifocal CNS lesions making it impractical to inject NSCs locally, thus mandating optimization of vascular delivery of the cells to involved sites. Here, we analyzed NSCs for expression of molecular effectors of cell migration and found that these cells are natively devoid of E-selectin ligands. Using glycosyltransferase-programmed stereosubstitution (GPS), we glycan engineered the cell surface of NSCs ("GPS-NSCs") with resultant enforced expression of the potent E-selectin ligand HCELL (hematopoietic cell E-/L-selectin ligand) and of an E-selectin-binding glycoform of neural cell adhesion molecule ("NCAM-E"). Following intravenous (i.v.) injection, short-term homing studies demonstrated that, compared with buffer-treated (control) NSCs, GPS-NSCs showed greater neurotropism. Administration of GPS-NSC significantly attenuated the clinical course of experimental autoimmune encephalomyelitis (EAE), with markedly decreased inflammation and improved oligodendroglial and axonal integrity, but without evidence of long-term stem cell engraftment. Notably, this effect of NSC is not a universal property of adult stem cells, as administration of GPS-engineered mouse hematopoietic stem/progenitor cells did not improve EAE clinical course. These findings highlight the utility of cell surface glycan engineering to boost stem cell delivery in neuroinflammatory conditions and indicate that, despite the use of a neural tissue-specific progenitor cell population, neural repair in EAE results from endogenous repair and not from direct, NSC-derived cell replacement.

  16. Data on clinical significance of GAS2 in colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Chun-Chao Chang

    2016-09-01

    Full Text Available The growth arrest-specific 2 (GAS2 was cloned and found to be upregulated in the feces of recurrent CRC patients. This overexpressed GAS2 induced different patterns of gene expressions in CRC cells. Briefly, one cell proliferation marker, Ki-67 antigen (Ki-67, was upregulated in the cells with overexpressed GAS2, “Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer” [1]. Whereas, the expression of another cell proliferation marker, proliferating cell nuclear antigen (PCNA, changed insignificantly [1]. In addition, the mRNA level of one cyclin involving in both cell cycle G1/S and G2/M transitions was also not affected by GAS2 overexpression, “Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A” [2]. The experimental design and procedures in this article can be helpful for understanding the molecular significance of GAS2 in SW480 and SW620 CRC cells.

  17. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment

    International Nuclear Information System (INIS)

    Iso, Yoshitaka; Spees, Jeffrey L.; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J.

    2007-01-01

    The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion

  18. Improving the Quality of the Deteriorated Regions of Multicrystalline Silicon Ingots during General Solar Cell Processes

    International Nuclear Information System (INIS)

    Wu Shan-Shan; Wang Lei; Yang De-Ren

    2011-01-01

    The behavior of wafers and solar cells from the border of a multicrystalline silicon (mc-Si) ingot, which contain deteriorated regions, is investigated. It is found that the diffusion length distribution of minority carriers in the cells is uniform, and high efficiency of the solar cells (about 16%) is achieved. It is considered that the quality of the deteriorated regions could be improved to be similar to that of adjacent regions. Moreover, it is indicated that during general solar cell fabrication, phosphorus gettering and hydrogen passivation could significantly improve the quality of deteriorated regions, while aluminum gettering by RTP could not. Therefore, it is suggested that the border of a mc-Si ingot could be used to fabricate high efficiency solar cells, which will increase mc-Si utilization effectively. (condensed matter: structure, mechanical and thermal properties)

  19. Improved performance of mesostructured perovskite solar cells via an anti-solvent method

    Science.gov (United States)

    Hao, Jiabin; Hao, Huiying; Cheng, Feiyu; Li, Jianfeng; Zhang, Haiyu; Dong, Jingjing; Xing, Jie; Liu, Hao; Wu, Jian

    2018-06-01

    One-step solution process is a facile and widely used procedure to prepare organic-inorganic perovskite materials. However, the poor surface morphology of the films attributed to the uncontrollable nucleation and crystal growth in the process is unfavorable to solar cells. In this study, an anti-solvent treatment during the one-step solution process, in which ethyl acetate (EA) was dropped on the sample during spinning the precursor solution containing CH3NH3Cl, was adopted to fabricate perovskite materials and solar cells. It was found that the morphology of the perovskite film was significantly improved due to the rapid nucleation and slow crystal growth process. The modified process enabled us to fabricate the mesoporous solar cell with power conversion efficiency of 14%, showing an improvement of 40% over the efficiency of 9.7% of the device prepared by conventional one-step method. The controlling effect of annealing time on the morphology, crystal structure and transport properties of perovskite layer as well as the performance of device fabricated by the anti-solvent method were investigated and the possible mechanism was discussed.

  20. Significantly improved photovoltaic performance in polymer bulk heterojunction solar cells with graphene oxide /PEDOT:PSS double decked hole transport layer

    Science.gov (United States)

    Rafique, Saqib; Abdullah, Shahino Mah; Shahid, Muhammad Mehmood; Ansari, Mohammad Omaish; Sulaiman, Khaulah

    2017-01-01

    This work demonstrates the high performance graphene oxide (GO)/PEDOT:PSS doubled decked hole transport layer (HTL) in the PCDTBT:PC71BM based bulk heterojunction organic photovoltaic device. The devices were tested on merits of their power conversion efficiency (PCE), reproducibility, stability and further compared with the devices with individual GO or PEDOT:PSS HTLs. Solar cells employing GO/PEDOT:PSS HTL yielded a PCE of 4.28% as compared to either of individual GO or PEDOT:PSS HTLs where they demonstrated PCEs of 2.77 and 3.57%, respectively. In case of single GO HTL, an inhomogeneous coating of ITO caused the poor performance whereas PEDOT:PSS is known to be hygroscopic and acidic which upon direct contact with ITO reduced the device performance. The improvement in the photovoltaic performance is mainly ascribed to the increased charge carriers mobility, short circuit current, open circuit voltage, fill factor, and decreased series resistance. The well matched work function of GO and PEDOT:PSS is likely to facilitate the charge transportation and an overall reduction in the series resistance. Moreover, GO could effectively block the electrons due to its large band-gap of ~3.6 eV, leading to an increased shunt resistance. In addition, we also observed the improvement in the reproducibility and stability.

  1. Significantly improved photovoltaic performance in polymer bulk heterojunction solar cells with graphene oxide /PEDOT:PSS double decked hole transport layer.

    Science.gov (United States)

    Rafique, Saqib; Abdullah, Shahino Mah; Shahid, Muhammad Mehmood; Ansari, Mohammad Omaish; Sulaiman, Khaulah

    2017-01-13

    This work demonstrates the high performance graphene oxide (GO)/PEDOT:PSS doubled decked hole transport layer (HTL) in the PCDTBT:PC 71 BM based bulk heterojunction organic photovoltaic device. The devices were tested on merits of their power conversion efficiency (PCE), reproducibility, stability and further compared with the devices with individual GO or PEDOT:PSS HTLs. Solar cells employing GO/PEDOT:PSS HTL yielded a PCE of 4.28% as compared to either of individual GO or PEDOT:PSS HTLs where they demonstrated PCEs of 2.77 and 3.57%, respectively. In case of single GO HTL, an inhomogeneous coating of ITO caused the poor performance whereas PEDOT:PSS is known to be hygroscopic and acidic which upon direct contact with ITO reduced the device performance. The improvement in the photovoltaic performance is mainly ascribed to the increased charge carriers mobility, short circuit current, open circuit voltage, fill factor, and decreased series resistance. The well matched work function of GO and PEDOT:PSS is likely to facilitate the charge transportation and an overall reduction in the series resistance. Moreover, GO could effectively block the electrons due to its large band-gap of ~3.6 eV, leading to an increased shunt resistance. In addition, we also observed the improvement in the reproducibility and stability.

  2. Incorporation of bone marrow cells in pancreatic pseudoislets improves posttransplant vascularization and endocrine function.

    Directory of Open Access Journals (Sweden)

    Christine Wittig

    Full Text Available Failure of revascularization is known to be the major reason for the poor outcome of pancreatic islet transplantation. In this study, we analyzed whether pseudoislets composed of islet cells and bone marrow cells can improve vascularization and function of islet transplants. Pancreatic islets isolated from Syrian golden hamsters were dispersed into single cells for the generation of pseudoislets containing 4×10(3 cells. To create bone marrow cell-enriched pseudoislets 2×10(3 islet cells were co-cultured with 2×10(3 bone marrow cells. Pseudoislets and bone marrow cell-enriched pseudoislets were transplanted syngeneically into skinfold chambers to study graft vascularization by intravital fluorescence microscopy. Native islet transplants served as controls. Bone marrow cell-enriched pseudoislets showed a significantly improved vascularization compared to native islets and pseudoislets. Moreover, bone marrow cell-enriched pseudoislets but not pseudoislets normalized blood glucose levels after transplantation of 1000 islet equivalents under the kidney capsule of streptozotocin-induced diabetic animals, although the bone marrow cell-enriched pseudoislets contained only 50% of islet cells compared to pseudoislets and native islets. Fluorescence microscopy of bone marrow cell-enriched pseudoislets composed of bone marrow cells from GFP-expressing mice showed a distinct fraction of cells expressing both GFP and insulin, indicating a differentiation of bone marrow-derived cells to an insulin-producing cell-type. Thus, enrichment of pseudoislets by bone marrow cells enhances vascularization after transplantation and increases the amount of insulin-producing tissue. Accordingly, bone marrow cell-enriched pseudoislets may represent a novel approach to increase the success rate of islet transplantation.

  3. Use of Eltrombopag in Improving Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Samip Master

    2018-03-01

    Full Text Available Eltrombopag is a thrombopoietin agonist and has been used in aplastic anemia and post-transplantation thrombocytopenia. The c-MPL receptor is present on hematopoietic stem cells. There are no reports of eltrombopag utilization for improving poor graft function in the post-transplant setting. Here were report a case of a young female with post-transplant poor graft function as evident from the low absolute neutrophil count, anemia, and thrombocytopenia on day 60. Eltrombopag was started on day 72 and resulted in improvement in all 3 cell lines. The counts continued to be stable even after eltrombopag was discontinued. The patient tolerated the drug without significant side effects for 1 year.

  4. Clinical Significance of Immuno phenotypic Markers in Pediatric T-cell Acute Lymphoblastic Leukemia

    International Nuclear Information System (INIS)

    SIDHOM, I.; SHAABAN, Kh.; SOLIMAN, S.; HAMDY, N.; YASSIN, D.; SALEM, Sh.; HASSANEIN, H.; MANSOUR, M.T.; EZZAT, S.; EL-ANWAR, W.

    2008-01-01

    Background: Cell-marker profiling has led to conflicting conclusions about its prognostic significance in T-ALL. Aim: To investigate the prevalence of the expression of CD34, CD10 and myeloid associated antigens (CD13/ CD33) in childhood T-ALL and to relate their presence to initial clinical and biologic features and early response to therapy. Patients and Methods: This study included 67 consecutive patients with newly diagnosed T-ALL recruited from the Children's Cancer Hospital in Egypt during the time period from July 2007 to June 2008. Immuno phenotypic markers and minimal residual disease (MRD) were studied by five-color flow cytometry. Results: The frequency of CD34 was 34.9%, CD10 33.3%, while CD13/CD33 was 18.8%. No significant association was encountered between CD34, CD10 or myeloid antigen positivity and the presenting clinical features as age, sex, TLC and CNS leukemia. Only CD10+ expression had significant association with initial CNS involvement (p=0.039). CD34 and CD13/CD33 expression was significantly associated with T-cell maturation stages (p<0.05). No relationship was observed for age, TLC, gender, NCI risk or CNS involvement with early response to therapy illustrated by BM as well as MRD day 15 and day 42. CD34+, CD13/CD33+ and early T-cell stage had high MRD levels on day 15 that was statistically highly significant (p<0.01), but CD10+ had statistically significant lower MRD level on day 15 (p=0.049). However, only CD34 retained its significance at an MRD cut-off level of 0.01%. Conclusion: CD34, CD10, CD13/CD33 expression, as well as T-cell maturation stages, may have prognostic significance in pediatric T-ALL as they have a significant impact on early clearance of leukemic cells detected by MRD day 15.

  5. Donor Satellite Cell Engraftment is Significantly Augmented When the Host Niche is Preserved and Endogenous Satellite Cells are Incapacitated

    Science.gov (United States)

    Boldrin, Luisa; Neal, Alice; Zammit, Peter S; Muntoni, Francesco; Morgan, Jennifer E

    2012-01-01

    Stem cell transplantation is already in clinical practice for certain genetic diseases and is a promising therapy for dystrophic muscle. We used the mdx mouse model of Duchenne muscular dystrophy to investigate the effect of the host satellite cell niche on the contribution of donor muscle stem cells (satellite cells) to muscle regeneration. We found that incapacitation of the host satellite cells and preservation of the muscle niche promote donor satellite cell contribution to muscle regeneration and functional reconstitution of the satellite cell compartment. But, if the host niche is not promptly refilled, or is filled by competent host satellite cells, it becomes nonfunctional and donor engraftment is negligible. Application of this regimen to aged host muscles also promotes efficient regeneration from aged donor satellite cells. In contrast, if the niche is destroyed, yet host satellite cells remain proliferation-competent, donor-derived engraftment is trivial. Thus preservation of the satellite cell niche, concomitant with functional impairment of the majority of satellite cells within dystrophic human muscles, may improve the efficiency of stem cell therapy. Stem Cells2012;30:1971–1984 PMID:22730231

  6. Improved Performance in Mammalian Cell Perfusion Cultures by Growth Inhibition.

    Science.gov (United States)

    Wolf, Moritz K F; Closet, Aurélie; Bzowska, Monika; Bielser, Jean-Marc; Souquet, Jonathan; Broly, Hervé; Morbidelli, Massimo

    2018-05-21

    Mammalian cell perfusion cultures represent a promising alternative to the current fed-batch technology for the production of various biopharmaceuticals. Long-term operation at a fixed viable cell density (VCD) requires a viable culture and a constant removal of excessive cells. Product loss in the cell removing bleed stream deteriorates the process yield. In this study, the authors investigate the use of chemical and environmental growth inhibition on culture performance by either adding valeric acid (VA) to the production media or by reducing the culture temperature (33.0 °C) with respect to control conditions (36.5 °C, no VA). Low temperature significantly reduces cellular growth, thus, resulting in lower bleed rates accompanied by a reduced product loss of 11% compared to 26% under control conditions. Additionally, the cell specific productivity of the target protein improves and maintained stable leading to media savings per mass of product. VA shows initially an inhibitory effect on cellular growth. However, cells seemed to adapt to the presence of the inhibitor resulting in a recovery of the cellular growth. Cell cycle and Western blot analyses support the observed results. This work underlines the role of temperature as a key operating variable for the optimization of perfusion cultures. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Distinct Responses of Stem Cells to Telomere Uncapping-A Potential Strategy to Improve the Safety of Cell Therapy.

    Science.gov (United States)

    Liu, Chang Ching; Ma, Dong Liang; Yan, Ting-Dong; Fan, XiuBo; Poon, Zhiyong; Poon, Lai-Fong; Goh, Su-Ann; Rozen, Steve G; Hwang, William Ying Khee; Tergaonkar, Vinay; Tan, Patrick; Ghosh, Sujoy; Virshup, David M; Goh, Eyleen L K; Li, Shang

    2016-10-01

    In most human somatic cells, the lack of telomerase activity results in progressive telomere shortening during each cell division. Eventually, DNA damage responses triggered by critically short telomeres induce an irreversible cell cycle arrest termed replicative senescence. However, the cellular responses of human pluripotent stem cells to telomere uncapping remain unknown. We generated telomerase knockout human embryonic stem (ES) cells through gene targeting. Telomerase inactivation in ES cells results in progressive telomere shortening. Telomere DNA damage in ES cells and neural progenitor cells induces rapid apoptosis when telomeres are uncapped, in contrast to fibroblast cells that enter a state of replicative senescence. Significantly, telomerase inactivation limits the proliferation capacity of human ES cells without affecting their pluripotency. By targeting telomerase activity, we can functionally separate the two unique properties of human pluripotent stem cells, namely unlimited self-renewal and pluripotency. We show that the potential of ES cells to form teratomas in vivo is dictated by their telomere length. By controlling telomere length of ES cells through telomerase inactivation, we can inhibit teratoma formation and potentially improve the safety of cell therapies involving terminally differentiated cells as well as specific progenitor cells that do not require sustained cellular proliferation in vivo, and thus sustained telomerase activity. Stem Cells 2016;34:2471-2484. © 2016 AlphaMed Press.

  8. [Improvement of Phi bodies stain and its clinical significance].

    Science.gov (United States)

    Gong, Xu-Bo; Lu, Xing-Guo; Yan, Li-Juan; Xiao, Xi-Bin; Wu, Dong; Xu, Gen-Bo; Zhang, Xiao-Hong; Zhao, Xiao-Ying

    2009-02-01

    The aim of this study was to improve the dyeing method of hydroperoxidase (HPO), to analyze the morphologic features of Phi bodies and to evaluate the clinical application of this method. 128 bone marrow or peripheral blood smears from patients with myeloid and lymphoid malignancies were stained by improved HPO staining. The Phi bodies were observed with detection rate of Phi bodies in different leukemias. 69 acute myeloid leukemia (AML) specimens were chosen randomly, the positive rate and the number of Phi bodies between the improved HPO and POX stain based on the same substrate of 3, 3'diaminobenzidine were compared. The results showed that the shape of bundle-like Phi bodies was variable, long or short. while the nubbly Phi bodies often presented oval and smooth. Club-like Phi bodies were found in M(3). The detection rates of bundle-like Phi bodies in AML M(1)-M(5) were 42.9% (6/14), 83.3% (15/18), 92.0% (23/25), 52.3% (11/21), 33.3% (5/15) respectively, and those of nubbly Phi bodies were 28.6% (4/14), 66.7% (12/18), 11.1% (3/25), 33.3% (7/21), 20.0% (3/15) respectively. The detection rate of bundle-like Phi bodies in M(3) was significantly higher than that in (M(1) + M(2)) or (M(4) + M(5)) groups. The detection rate of nubbly Phi bodies in (M(1) + M(2)) group was higher than that in M(3) group. In conclusion, after improvement of staining method, the HPO stain becomes simple, the detection rate of Phi bodies is higher than that by the previous method, the positive granules are more obvious, and the results become stable. This improved method plays an important role in differentiating AML from ALL, subtyping AML, and evaluating the therapeutic results.

  9. Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy.

    Science.gov (United States)

    Tsang, Yuk-Wah; Huang, Cheng-Chung; Yang, Kai-Lin; Chi, Mau-Shin; Chiang, Hsin-Chien; Wang, Yu-Shan; Andocs, Gabor; Szasz, Andras; Li, Wen-Tyng; Chi, Kwan-Hwa

    2015-10-15

    The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs. The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied. mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity. This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy.

  10. Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats.

    Science.gov (United States)

    Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

    2016-07-06

    Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1- Control 2- Heart Failure (HF) 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×10 6 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001). Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters.

  11. Improved lithium-vanadium pentoxide cell and comparison with a lithium-thionyl chloride cell

    Energy Technology Data Exchange (ETDEWEB)

    Voorn, G.

    1985-01-15

    This paper describes a programme of experiments conducted to assess the effects of: (a) diluting the electrolyte in lithium-vanadium pentoxide cells; (b) optimizing the volume of electrolyte per unit cathode mass. This programme led to the development of an improved cell, the performance of which is compared with that of a lithium-thionyl chloride cell of similar configuration.

  12. An improved ghost-cell immersed boundary method for compressible flow simulations

    KAUST Repository

    Chi, Cheng

    2016-05-20

    This study presents an improved ghost-cell immersed boundary approach to represent a solid body in compressible flow simulations. In contrast to the commonly used approaches, in the present work ghost cells are mirrored through the boundary described using a level-set method to farther image points, incorporating a higher-order extra/interpolation scheme for the ghost cell values. A sensor is introduced to deal with image points near the discontinuities in the flow field. Adaptive mesh refinement (AMR) is used to improve the representation of the geometry efficiently in the Cartesian grid system. The improved ghost-cell method is validated against four test cases: (a) double Mach reflections on a ramp, (b) smooth Prandtl-Meyer expansion flows, (c) supersonic flows in a wind tunnel with a forward-facing step, and (d) supersonic flows over a circular cylinder. It is demonstrated that the improved ghost-cell method can reach the accuracy of second order in L1 norm and higher than first order in L∞ norm. Direct comparisons against the cut-cell method demonstrate that the improved ghost-cell method is almost equally accurate with better efficiency for boundary representation in high-fidelity compressible flow simulations. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Improvements to the solar cell efficiency and production yields of low-lifetime wafers with effective phosphorus gettering

    International Nuclear Information System (INIS)

    Lu, Jiunn-Chenn; Chen, Ping-Nan; Chen, Chih-Min; Wu, Chung-Han

    2013-01-01

    Highlights: • Variable-temperature gettering improves efficiencies when the wafer quality is poor. • High-quality wafers need not be used for variable-temperature gettering. • The proposed gettering method is based on an existing diffusion process. • It has a potential interest for hot-spot prevention. -- Abstract: This research focuses on the improvement of solar cell efficiencies in low-lifetime wafers by implementing an appropriate gettering method of the diffusion process. The study also considers a reduction in the value of the reverse current at −12 V, an important electrical parameter related to the hot-spot heating of solar cells and modules, to improve the product's quality during commercial mass production. A practical solar cell production case study is examined to illustrate the use of the proposed method. The results of this case study indicate that variable-temperature gettering significantly improves solar cell efficiencies by 0.14% compared to constant-temperature methods when the wafer quality is poor. Moreover, this study finds that variable-temperature gettering raises production yields of low quality wafers by more than 30% by restraining the measurement value of the reverse current at −12 V during solar cell manufacturing

  14. Improved Erythrocyte Osmotic Fragility and Packed Cell Volume ...

    African Journals Online (AJOL)

    Improved Erythrocyte Osmotic Fragility and Packed Cell Volume following administration of Aloe barbadensis Juice Extract in Rats. ... Abstract. Aloe barbadensis is a popular house plant that has a long history of a multipurpose folk remedy. ... Keywords: osmotic fragility, packed cell volume, haemoglobin, Aloe vera ...

  15. Neurite outgrowth is significantly increased by the simultaneous presentation of Schwann cells and moderate exogenous electric fields

    Science.gov (United States)

    Koppes, Abigail N.; Seggio, Angela M.; Thompson, Deanna M.

    2011-08-01

    Axonal extension is influenced by a variety of external guidance cues; therefore, the development and optimization of a multi-faceted approach is probably necessary to address the intricacy of functional regeneration following nerve injury. In this study, primary dissociated neonatal rat dorsal root ganglia neurons and Schwann cells were examined in response to an 8 h dc electrical stimulation (0-100 mV mm-1). Stimulated samples were then fixed immediately, immunostained, imaged and analyzed to determine Schwann cell orientation and characterize neurite outgrowth relative to electric field strength and direction. Results indicate that Schwann cells are viable following electrical stimulation with 10-100 mV mm-1, and retain a normal morphology relative to unstimulated cells; however, no directional bias is observed. Neurite outgrowth was significantly enhanced by twofold following exposure to either a 50 mV mm-1 electric field (EF) or co-culture with unstimulated Schwann cells by comparison to neurons cultured alone. Neurite outgrowth was further increased in the presence of simultaneously applied cues (Schwann cells + 50 mV mm-1 dc EF), exhibiting a 3.2-fold increase over unstimulated control neurons, and a 1.2-fold increase over either neurons cultured with unstimulated Schwann cells or the electrical stimulus alone. These results indicate that dc electric stimulation in combination with Schwann cells may provide synergistic guidance cues for improved axonal growth relevant to nerve injuries in the peripheral nervous system.

  16. Alterations in regulatory T cells induced by specific oligosaccharides improve vaccine responsiveness in mice.

    Directory of Open Access Journals (Sweden)

    Marcel A Schijf

    Full Text Available Prophylactic vaccinations are generally performed to protect naïve individuals with or without suppressed immune responsiveness. In a mouse model for Influenza vaccinations the specific alterations of CD4(+CD25(+Foxp3(+ regulatory T-cells (Tregs in the immune modulation induced by orally supplied oligosaccharides containing scGOS/lcFOS/pAOS was assessed. This dietary intervention increased vaccine specific DTH responses. In addition, a significant increased percentage of T-bet(+ (Th1 activated CD69(+CD4(+ T cells (p<0.001 and reduced percentage of Gata-3(+ (Th2 activated CD69(+CD4(+T cells (p<0.001 was detected in the mesenteric lymph nodes (MLN of mice receiving scGOS/lcFOS/pAOS compared to control mice. Although no difference in the number or percentage of Tregs (CD4(+Foxp3(+ could be determined after scGOS/lcFOS/pAOS intervention, the percentage of CXCR3 (+ /T-bet(+ (Th1-Tregs was significantly reduced (p<0.05 in mice receiving scGOS/lcFOS/pAOS as compared to mice receiving placebo diets. Moreover, although no absolute difference in suppressive capacity could be detected, an alteration in cytokine profile suggests a regulatory T cell shift towards a reducing Th1 suppression profile, supporting an improved vaccination response.These data are indicative for improved vaccine responsiveness due to reduced Th1 suppressive capacity in the Treg population of mice fed the oligosaccharide specific diet, showing compartmentalization within the Treg population. The modulation of Tregs to control immune responses provides an additional arm of intervention using alternative strategies possibly leading to the development of improved vaccines.

  17. Significance of adipose tissue-derived stem cells regulate CD4+ T cell immune in the treatment of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Yong-lin XIE

    2014-10-01

    Full Text Available Adipose tissue-derived stem cells (ADSCs are genetically engineered seed cells with immunomodulatory effects, widely used in the treatment of autoimmune diseases. This article focuses on the immunomodulatory effects of adipose tissue-derived stem cells on CD4+ T cell subsets, including T helper cell (Th 1, 2, 17 and regulatory T cell (Treg, and its clinical significance in the treatment of multiple sclerosis. doi: 10.3969/j.issn.1672-6731.2014.10.005

  18. Nanoscale Light Manipulation for Improved Organic Solar Cells

    Science.gov (United States)

    Fisher, Brett

    Organic Solar Cells can be made to be flexible, semi-transparent, and low-cost making them ideal for novel energy harvesting applications such as in greenhouses. However, the main disadvantage of this technology is its low energy conversion efficiency (technologies, such as thinfilm GaAs (>30% Efficiency), and Si-based (>20% Efficiency), solar cells, where recombination within these technologies is much less than Organic Solar Cells. There are still many challenges to overcome to improve the efficiency of Organic Solar Cells. Some of these challenges include: Maximising the absorption of the solar spectrum; improving the charge dynamics; and increasing the lifetime of the devices. One method to address some of these challenges is to include plasmonic nanoparticles into the devices, which has been shown to increase the absorption through scattering, and improve the charge dynamic through localised surface plasmon resonance effects. However, including nanoparticles into Organic Solar Cells has shown to adversely affect the performance of the devices in other ways, such as increasing the recombination of excitons. To address this, an additional (insulating) coating around the nanoparticles supresses this increase, and has shown to be able to increase the performance of the solar cells. In this work, we demonstrate the use of our all-inclusive optical model in the design and optimisation of bespoke colour-specific windows (i.e. Red, Green, and Blue), where the solar cells can be made to have a specific transparency and colour, whilst maximizing their efficiency. For example, we could specify that we wish the colour to be red, with 50% transmissivity; the model will then maximise the Power Conversion Efficiency. We also demonstrate how our extension to Mie theory can simulate nanoparticle systems and can be used to tune the plasmon resonance utilising different coatings, and configurations thereof.

  19. Cleaning the Air and Improving Health with Hydrogen Fuel-Cell Vehicles

    Science.gov (United States)

    Jacobson, M. Z.; Colella, W. G.; Golden, D. M.

    2005-06-01

    Converting all U.S. onroad vehicles to hydrogen fuel-cell vehicles (HFCVs) may improve air quality, health, and climate significantly, whether the hydrogen is produced by steam reforming of natural gas, wind electrolysis, or coal gasification. Most benefits would result from eliminating current vehicle exhaust. Wind and natural gas HFCVs offer the greatest potential health benefits and could save 3700 to 6400 U.S. lives annually. Wind HFCVs should benefit climate most. An all-HFCV fleet would hardly affect tropospheric water vapor concentrations. Conversion to coal HFCVs may improve health but would damage climate more than fossil/electric hybrids. The real cost of hydrogen from wind electrolysis may be below that of U.S. gasoline.

  20. A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

    Directory of Open Access Journals (Sweden)

    Simon D Angus

    Full Text Available Multi-dose radiotherapy protocols (fraction dose and timing currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5% and 7.1% (13.3% improvement (reduction on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h, leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost

  1. A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

    Science.gov (United States)

    Angus, Simon D; Piotrowska, Monika Joanna

    2014-01-01

    Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means

  2. Microstructured Electrolyte Membranes to Improve Fuel Cell Performance

    Science.gov (United States)

    Wei, Xue

    Fuel cells, with the advantages of high efficiency, low greenhouse gas emission, and long lifetime are a promising technology for both portable power and stationary power sources. The development of efficient electrolyte membranes with high ionic conductivity, good mechanical durability and dense structure at low cost remains a challenge to the commercialization of fuel cells. This thesis focuses on exploring novel composite polymer membranes and ceramic electrolytes with the microstructure engineered to improve performance in direct methanol fuel cells (DMFCs) and solid oxide fuel cells (SOFCs), respectively. Polymer/particle composite membranes hold promise to meet the demands of DMFCs at lower cost. The structure of composite membranes was controlled by aligning proton conducting particles across the membrane thickness under an applied electric field. The field-induced structural changes caused the membranes to display an enhanced water uptake, proton conductivity, and methanol permeability in comparison to membranes prepared without an applied field. Although both methanol permeability and proton conductivity are enhanced by the applied field, the permeability increase is relatively lower than the proton conductivity improvement, which results in enhanced proton/methanol selectivity and improved DMFC performance. Apatite ceramics are a new class of fast ion conductors being studied as alternative SOFC electrolytes in the intermediate temperature range. An electrochemical/hydrothermal deposition method was developed to grow fully dense apatite membranes containing well-developed crystals with c-axis alignment to promote ion conductivity. Hydroxyapatite seed crystals were first deposited onto a metal substrate electrochemically. Subsequent ion substitution during the hydrothermal growth process promoted the formation of dense, fully crystalline films with microstructure optimal for ion transport. The deposition parameters were systematically investigated, such as

  3. [Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

    Science.gov (United States)

    Ren, K; Qian, D; Wang, Y W; Pang, Q S; Zhang, W C; Yuan, Z Y; Wang, P

    2018-01-23

    Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference ( P =0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P =0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results ( P =0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients( P <0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast

  4. Improving chemotherapy for patients with advanced non-small cell lung cancer

    DEFF Research Database (Denmark)

    von Plessen, Christian

    2011-01-01

    INTRODUCTION: Lung cancer is the third most common mortal disease in industrialised countries and the prognosis has been slow to improve. The largest subgroup has locally advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, these patients can usually not be cured and the main...... project. The description of the experiences can serve as an example for the improvement of microsystems in settings with similar problems. Finally, in the registry study of Norwegian patients with lung cancer, we found significant geographical and temporal variations of the utilisation of chemotherapy...... that were related to survival. Potential areas of improvement in the system of care for lung cancer are recruitment of patients in clinical studies, standardisation of the processes of care in outpatient clinics, definition of strategic aims of quality, development of balanced quality indicators, as well...

  5. Functional high-intensity training improves pancreatic β-cell function in adults with type 2 diabetes.

    Science.gov (United States)

    Nieuwoudt, Stephan; Fealy, Ciarán E; Foucher, Julie A; Scelsi, Amanda R; Malin, Steven K; Pagadala, Mangesh; Rocco, Michael; Burguera, Bartolome; Kirwan, John P

    2017-09-01

    Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R 2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R 2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D. Copyright © 2017 the American Physiological Society.

  6. An Improved Ghost-cell Immersed Boundary Method for Compressible Inviscid Flow Simulations

    KAUST Repository

    Chi, Cheng

    2015-05-01

    This study presents an improved ghost-cell immersed boundary approach to represent a solid body in compressible flow simulations. In contrast to the commonly used approaches, in the present work ghost cells are mirrored through the boundary described using a level-set method to farther image points, incorporating a higher-order extra/interpolation scheme for the ghost cell values. In addition, a shock sensor is in- troduced to deal with image points near the discontinuities in the flow field. Adaptive mesh refinement (AMR) is used to improve the representation of the geometry efficiently. The improved ghost-cell method is validated against five test cases: (a) double Mach reflections on a ramp, (b) supersonic flows in a wind tunnel with a forward- facing step, (c) supersonic flows over a circular cylinder, (d) smooth Prandtl-Meyer expansion flows, and (e) steady shock-induced combustion over a wedge. It is demonstrated that the improved ghost-cell method can reach the accuracy of second order in L1 norm and higher than first order in L∞ norm. Direct comparisons against the cut-cell method demonstrate that the improved ghost-cell method is almost equally accurate with better efficiency for boundary representation in high-fidelity compressible flow simulations. Implementation of the improved ghost-cell method in reacting Euler flows further validates its general applicability for compressible flow simulations.

  7. Demonstrating the benefits of fuel cells: further significant progress towards commercialisation

    Energy Technology Data Exchange (ETDEWEB)

    Anon,

    1995-01-01

    The fourteenth Fuel Cell Seminar held in San Diego, California in 1994 is reported. The phosphoric acid fuel cell (PAFC) is the closest to widespread commercialization. PAFC cogeneration plants have to be shown to compare favourable in reliability with current mature natural gas-fuelled engine and turbine technologies. Although highly efficient, further development is necessary to produce cost effective generators. Progress is being made on proton exchange membrane fuel cell (PEMFC) stationary power plants, too, which may prove to be cost effective. In view of its lower operating temperature, at below 100[sup o]C compared with about 200[sup o]C for the PAFC, the principal use of the PEMFC has been identified as powering vehicles. Fuel cells have significant environmental advantages but further capital cost reductions are necessary if they are to compete with established technologies. (UK)

  8. Improved Cell Culture Method for Growing Contracting Skeletal Muscle Models

    Science.gov (United States)

    Marquette, Michele L.; Sognier, Marguerite A.

    2013-01-01

    An improved method for culturing immature muscle cells (myoblasts) into a mature skeletal muscle overcomes some of the notable limitations of prior culture methods. The development of the method is a major advance in tissue engineering in that, for the first time, a cell-based model spontaneously fuses and differentiates into masses of highly aligned, contracting myotubes. This method enables (1) the construction of improved two-dimensional (monolayer) skeletal muscle test beds; (2) development of contracting three-dimensional tissue models; and (3) improved transplantable tissues for biomedical and regenerative medicine applications. With adaptation, this method also offers potential application for production of other tissue types (i.e., bone and cardiac) from corresponding precursor cells.

  9. 16.1% Efficient Hysteresis-Free Mesostructured Perovskite Solar Cells Based on Synergistically Improved ZnO Nanorod Arrays

    KAUST Repository

    Mahmood, Khalid; Swain, Bhabani Sankar; Amassian, Aram

    2015-01-01

    Significant efficiency improvements are reported in mesoscopic perovskite solar cells based on the development of a low-temperature solution-processed ZnO nanorod (NR) array exhibiting higher NR aspect ratio, enhanced electron density

  10. An improved lithium-vanadium pentoxide cell and comparison with a lithium-thionyl chloride cell

    Science.gov (United States)

    Voorn, G.

    1985-03-01

    This paper describes a programme of experiments conducted to assess the effects of: (a) diluting the electrolyte in lithium-vanadium pentoxide cells; (b) optimizing the volume of electrolyte per unit cathode mass. This programme led to the development of an improved cell, the performance of which is compared with that of a lithium-thionyl chloride cell of similar configuration.

  11. Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy

    International Nuclear Information System (INIS)

    Tsang, Yuk-Wah; Huang, Cheng-Chung; Yang, Kai-Lin; Chi, Mau-Shin; Chiang, Hsin-Chien; Wang, Yu-Shan; Andocs, Gabor; Szasz, Andras; Li, Wen-Tyng; Chi, Kwan-Hwa

    2015-01-01

    The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs. The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied. mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity. This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy. The online version of this article (doi:10.1186/s12885-015-1690-2) contains supplementary material, which is available to

  12. Expression and Its Clinical Significance of SLC22A18 in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ming LEI

    2012-01-01

    Full Text Available Background and objective It has been proven that multidrug resistance (MDR is the main cause of chemotherapy failure in lung cancer. Research on emergence mechanisms of MDR has great clinical significance in improving the curative efficiency of lung cancer chemotherapy. Proteins encoded by the SLC22A18 gene, which is similar to the transmembrane transporter, may influence the sensitivity of chemotherapeutics as well as the metabolism and growth of cells. In addition, these proteins probably have some effect on the development of lung cancer MDR. The aim of the present study is to investigate the expression of SLC22A18 protein in non-small cell lung cancer (NSCLC as well as in corresponding normal lung tissue. Furthermore, the relationship between SLC22A18 expression and pathological grade and TNM stage is analyzed. Methods The expression of SLC22A18 was detected by EnVinsion in 96 cases with NSCLC and in corresponding normal lung tissue. Statistical analysis was performed using SPSS 17.0 statistical software. Results SLC22A18 was mainly located in cell membrane and cytoplasm. The expression level of SLC22A18 in NSCLC was significantly higher than that in normal tissue (P<0.01. The positive rates in squamous cell lung cancer and lung adenocarcinoma were 68% and 78.2%, respectively (P<0.05. Moreover, the higher expression of SLC22A18 was associated with lower histological grade and later TNM stage (P<0.05. Conclusion SLC22A18 protein is overexpressed in NSCLC, and its expression is correlated with pathological grade and TNM stage. These findings provide the experimental basis for investigating the role of tumor and chemoresistance.

  13. An improved ontological representation of dendritic cells as a paradigm for all cell types

    Directory of Open Access Journals (Sweden)

    Mungall Chris

    2009-02-01

    Full Text Available Abstract Background Recent increases in the volume and diversity of life science data and information and an increasing emphasis on data sharing and interoperability have resulted in the creation of a large number of biological ontologies, including the Cell Ontology (CL, designed to provide a standardized representation of cell types for data annotation. Ontologies have been shown to have significant benefits for computational analyses of large data sets and for automated reasoning applications, leading to organized attempts to improve the structure and formal rigor of ontologies to better support computation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL's utility for computation and for cross-species data integration. Results To enhance the CL's utility for computational analyses, we developed a method for the ontological representation of cells and applied this method to develop a dendritic cell ontology (DC-CL. DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. We avoid multiple uses of is_a by linking DC-CL terms to terms in other ontologies via additional, formally defined relations such as has_function. Conclusion This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. Accordingly, we propose our method as a general strategy for the ontological representation of cells. DC-CL is available from http://www.obofoundry.org.

  14. An analysis of radioisotope power systems using improved ATEC cells

    International Nuclear Information System (INIS)

    El-Genk, M.S.; Tournier, J.M.

    1998-01-01

    Recently, a ground demo of eight AMTEC (PX-3G) cells has been tested successfully in vacuum at the Air Force Research laboratory (AFRL). Results showed that the electric power output and voltage of the best performing PX-3G cell are short of meeting the requirements of the Pluto/Express (PX) mission. Using the basic configuration of the PX-3G cell, several design changes are explored, to improve the cell performance. Also, several integration options of the improved PX-3G cells with General-Purpose Heat Source (GPHS) modules are investigated for an electric power level of 130 W e and a 15-year mission. The options explored include varying the number of GPHS modules and AMTEC cells, and using fresh or aged fuel. The effects of changing the generators' output voltage (24 V or 28 V) on the evaporator and BASE metal-ceramic brazes temperatures and temperature margin in the cell are also examined

  15. Cell-laden hydrogel/titanium microhybrids: Site-specific cell delivery to metallic implants for improved integration.

    Science.gov (United States)

    Koenig, Geraldine; Ozcelik, Hayriye; Haesler, Lisa; Cihova, Martina; Ciftci, Sait; Dupret-Bories, Agnes; Debry, Christian; Stelzle, Martin; Lavalle, Philippe; Vrana, Nihal Engin

    2016-03-01

    Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion. The ability to control the cell types in different regions of an implant is important in applications where the target tissue (i) has structural heterogeneity (multiple cell types with a defined spatial configuration with respect to each other); (ii) has physical property gradients essential for its function (such as in the case of osteochondral tissue transition). Due to their near immediate gelation, such gels can also be used for site-specific modification of porous titanium structures, particularly for implants which would face different tissues at different locations. Herein, we describe a step by step design of a model system: the model cell-laden gel-containing porous titanium implants in the form of titanium microbead/hydrogel (maleimide-dextran or maleimide-PVA based) microhybrids. These systems enable the determination of the effect of titanium presence on gel properties and encapsulated cell behaviour as a miniaturized version of full-scale implants, providing a system compatible with conventional analysis methods. We used a fibroblast/vascular endothelial cell co-cultures as our model system and by utilising single microbeads we have quantified the effect of gel microenvironment (degradability, presence of RGD peptides within gel formulation) on cell behaviour and the effect of the titanium presence on cell behaviour and gel formation. Titanium presence slightly changed gel properties without hindering gel formation or affecting cell viability. Cells showed a preference to move towards

  16. Flow cytometric detection of growth factor receptors in autografts and analysis of growth factor concentrations in autologous stem cell transplantation: possible significance for platelet recovery

    DEFF Research Database (Denmark)

    Schiødt, I; Jensen, Charlotte Harken; Kjaersgaard, E

    2000-01-01

    In order to improve prediction of hematopoietic recovery, we conducted a pilot study, analyzing the significance of growth factor receptor expression in autografts as well as endogenous growth factor levels in blood before, during and after stem cell transplantation. Three early acting (stem cell......-CSF receptor positive, CD34+ progenitor cells were measured by flow cytometry in the leukapheresis product used for transplantation in a subgroup of 15 patients (NHL, n = 8, MM, n = 7). Three factors were identified as having a significant impact on platelet recovery. First, the level of Tpo in blood...... at the time of the nadir (day +7). Second, the percentage of re-infused thrombopoietin receptor positive progenitors and finally, the percentage of Flt3 receptor positive progenitors. On the other hand, none of the analyzed factors significantly predicted myeloid or erythroid recovery. These findings need...

  17. Using silicon nanostructures for the improvement of silicon solar cells' efficiency

    International Nuclear Information System (INIS)

    Torre, J. de la; Bremond, G.; Lemiti, M.; Guillot, G.; Mur, P.; Buffet, N.

    2006-01-01

    Silicon nanostructures (ns-Si) show interesting optical and electrical properties as a result of the band gap widening caused by quantum confinement effects. Along with their potential utilization for silicon-based light emitters' fabrication, they could also represent an appealing option for the improvement of energy conversion efficiency in silicon-based solar cells whether by using their luminescence properties (photon down-conversion) or the excess photocurrent produced by an improved high-energy photon's absorption. In this work, we report on the morphological and optical studies of non-stoichiometric silica (SiO x ) and silicon nitride (SiN x ) layers containing silicon nanostructures (ns-Si) in view of their application for solar cell's efficiency improvement. The morphological studies of the samples performed by transmission electron microscopy (TEM) unambiguously show the presence of ns-Si in a crystalline form for high temperature-annealed SiO x layers and for low temperature deposition of SiN x layers. The photoluminescence emission (PL) shows a rather high efficiency in both kind of layers with an intensity of only a factor ∼ 100 lower than that of porous silicon (pi-Si). The photocurrent spectroscopy (PC) shows a significant increase of absorption at high photon energy excitation most probably related to photon absorption within ns-Si quantized states. Moreover, the absorption characteristics obtained from PC spectra show a good agreement with the PL emission states unambiguously demonstrating a same origin, related to Q-confined excitons within ns-Si. Finally, the major asset of this material is the possibility to incorporate it to solar cells manufacturing processing for an insignificant cost

  18. Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

    Directory of Open Access Journals (Sweden)

    Yoga Yuniadi

    2016-01-01

    Full Text Available Background. Proangiogenic Hematopoietic Cells (PHC which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4±7.40 yo preimplant NT proBNP level is 5124.5±4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87±0.41, 0.63±0.66, 99.00±2.60, and 3.22±3.79%, respectively. LVEF was improved (22±5.68 versus 26.8±7.93, p<0.001 during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity.

  19. Cell adhesion-mediated radioresistance (CAM-RR). Extracellular matrix-dependent improvement of cell survival in human tumor and normal cells in vitro

    International Nuclear Information System (INIS)

    Cordes, N.; Meineke, V.

    2003-01-01

    Background: Cell-extracellular matrix (ECM) contact is thought to have great impact on cellular mechanisms resulting in increased cell survival upon exposure to ionizing radiation. Several human tumor cell lines and normal human fibroblastic cell strains of different origin, all of them expressing the wide-spread and important integrin subunit β1, were irradiated, and clonogenic cell survival, β1-integrin cell surface expression, and adhesive functionality were investigated. Material and Methods: Human tumor cell lines A172 (glioblastoma), PATU8902 (pancreas carcinoma), SKMES1 (lung carcinoma), A549 (lung carcinoma), and IPC298 (melanoma) as well as normal human skin (HSF1) and lung fibroblasts (CCD32) and human keratinocytes (HaCaT) were irradiated with 0-8 Gy. Besides colony formation assays, β1-integrin cell surface expression by flow cytometry and adhesive functionality by adhesion assays were analyzed. Results: All cell lines showed improved clonogenic survival after irradiation in the presence of fibronectin as compared to plastic. Irradiated cells exhibited a significant, dose-dependent increase in β1-integrin cell surface expression following irradiation. As a parameter of the adhesive functionality of the β1-integrin, a radiation-dependent elevation of cell adhesion to fibronectin in comparison with adhesion to plastic was demonstrated. Conclusion: The in vitro cellular radiosensitivity is highly influenced by fibronectin according to the phenomenon of cell adhesion-mediated radioresistance. Additionally, our emerging data question the results of former and current in vitro cytotoxicity studies performed in the absence of an ECM. These findings might also be important for the understanding of malignant transformation, anchorage-independent cell growth, optimization of radiotherapeutic regimes and the prevention of normal tissue side effects on the basis of experimental radiobiological data. (orig.)

  20. Significance of lymph node capsular invasion in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Sakai, Makoto; Suzuki, Shigemasa; Sano, Akihiko; Tanaka, Naritaka; Inose, Takanori; Sohda, Makoto; Nakajima, Masanobu; Miyazaki, Tatsuya; Kuwano, Hiroyuki

    2012-06-01

    Extranodal invasion (ENI) has been reported to be associated with a poor prognosis in several malignancies. However, previous studies have included perinodal fat tissue tumor deposits in their definitions of ENI. To investigate the precise nature of ENI in esophageal squamous cell carcinoma (ESCC), we excluded these tumor deposits from our definition of ENI and defined tumor cell invasion through the lymph node capsule and into the perinodal tissues as lymph node capsular invasion (LNCI). The aim of the current study was to elucidate the significance of LNCI in ESCC. We investigated the associations between LNCI and other clinicopathologic features in 139 surgically resected ESCC. We also investigated the prognostic significance of LNCI in ESCC. LNCI was detected in 35 (25.2%) of 139 patients. The overall survival rate of the ESCC patients with LNCI was significantly lower than that of the ESCC patients with lymph node metastasis who were negative for LNCI. The survival difference between the patients with 1–3 lymph node metastases without LNCI and those with no lymph node metastasis was not significant. LNCI was significantly associated with distant organ recurrence. LNCI was also found to be an independent predictor of overall survival in addition to the number of lymph node metastases. LNCI in ESCC patients is an indicator of distant organ recurrence and a worse prognosis. LNCI could be used as a candidate marker for designing more precise staging and therapeutic strategies for ESCC.

  1. Regenerative capacity of old muscle stem cells declines without significant accumulation of DNA damage.

    Directory of Open Access Journals (Sweden)

    Wendy Cousin

    Full Text Available The performance of adult stem cells is crucial for tissue homeostasis but their regenerative capacity declines with age, leading to failure of multiple organs. In skeletal muscle this failure is manifested by the loss of functional tissue, the accumulation of fibrosis, and reduced satellite cell-mediated myogenesis in response to injury. While recent studies have shown that changes in the composition of the satellite cell niche are at least in part responsible for the impaired function observed with aging, little is known about the effects of aging on the intrinsic properties of satellite cells. For instance, their ability to repair DNA damage and the effects of a potential accumulation of DNA double strand breaks (DSBs on their regenerative performance remain unclear. This work demonstrates that old muscle stem cells display no significant accumulation of DNA DSBs when compared to those of young, as assayed after cell isolation and in tissue sections, either in uninjured muscle or at multiple time points after injury. Additionally, there is no significant difference in the expression of DNA DSB repair proteins or globally assayed DNA damage response genes, suggesting that not only DNA DSBs, but also other types of DNA damage, do not significantly mark aged muscle stem cells. Satellite cells from DNA DSB-repair-deficient SCID mice do have an unsurprisingly higher level of innate DNA DSBs and a weakened recovery from gamma-radiation-induced DNA damage. Interestingly, they are as myogenic in vitro and in vivo as satellite cells from young wild type mice, suggesting that the inefficiency in DNA DSB repair does not directly correlate with the ability to regenerate muscle after injury. Overall, our findings suggest that a DNA DSB-repair deficiency is unlikely to be a key factor in the decline in muscle regeneration observed upon aging.

  2. Engineering CHO cells with an oncogenic KIT improves cells growth, resilience to stress, and productivity.

    Science.gov (United States)

    Mahameed, Mohamed; Tirosh, Boaz

    2017-11-01

    An optimized biomanufacturing process in mammalian cells is contingent on the ability of the producing cells to reach high viable cell densities. In addition, at the peak of growth, cells need to continue producing the biological entity at a consistent quality. Thus, engineering cells with robust growth performance and resilience to variable stress conditions is highly desirable. The tyrosine kinase receptor, KIT, plays a key role in cell differentiation and the survival of several immune cell types. Its oncogenic mutant, D816V, endows cells with high proliferation capacity, and resistance to kinase inhibitors. Importantly, this onco-KIT mutant when introduced into various cell types is arrested in the endoplasmic reticulum in a constitutively active form. Here, we investigated the effect of oncogenic D816V KIT on the performance of CHO-K1 cells under conventional tissue culture growth settings and when adapted, to shaking conditions. The onco-KIT promoted global protein synthesis, elevated the expression of a secretable transgene, enhanced proliferation, and improved the overall titers of a model glycoprotein. Moreover, the expression of the onco-KIT endowed the cells with a remarkable resistance to various stress conditions. Our data suggest that the introduction of onco-KIT can serve as a strategy for improving glycoprotein biomanufacturing. Biotechnol. Bioeng. 2017;114: 2560-2570. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Efficiency Improvement of HIT Solar Cells on p-Type Si Wafers.

    Science.gov (United States)

    Wei, Chun-You; Lin, Chu-Hsuan; Hsiao, Hao-Tse; Yang, Po-Chuan; Wang, Chih-Ming; Pan, Yen-Chih

    2013-11-22

    Single crystal silicon solar cells are still predominant in the market due to the abundance of silicon on earth and their acceptable efficiency. Different solar-cell structures of single crystalline Si have been investigated to boost efficiency; the heterojunction with intrinsic thin layer (HIT) structure is currently the leading technology. The record efficiency values of state-of-the art HIT solar cells have always been based on n-type single-crystalline Si wafers. Improving the efficiency of cells based on p-type single-crystalline Si wafers could provide broader options for the development of HIT solar cells. In this study, we varied the thickness of intrinsic hydrogenated amorphous Si layer to improve the efficiency of HIT solar cells on p-type Si wafers.

  4. Improved Cathode Structure for a Direct Methanol Fuel Cell

    Science.gov (United States)

    Valdez, Thomas; Narayanan, Sekharipuram

    2005-01-01

    An improved cathode structure on a membrane/electrode assembly has been developed for a direct methanol fuel cell, in a continuing effort to realize practical power systems containing such fuel cells. This cathode structure is intended particularly to afford better cell performance at a low airflow rate. A membrane/electrode assembly of the type for which the improved cathode structure was developed (see Figure 1) is fabricated in a process that includes brush painting and spray coating of catalyst layers onto a polymer-electrolyte membrane and onto gas-diffusion backings that also act as current collectors. The aforementioned layers are then dried and hot-pressed together. When completed, the membrane/electrode assembly contains (1) an anode containing a fine metal black of Pt/Ru alloy, (2) a membrane made of Nafion 117 or equivalent (a perfluorosulfonic acid-based hydrophilic, proton-conducting ion-exchange polymer), (3) a cathode structure (in the present case, the improved cathode structure described below), and (4) the electrically conductive gas-diffusion backing layers, which are made of Toray 060(TradeMark)(or equivalent) carbon paper containing between 5 and 6 weight percent of poly(tetrafluoroethylene). The need for an improved cathode structure arises for the following reasons: In the design and operation of a fuel-cell power system, the airflow rate is a critical parameter that determines the overall efficiency, cell voltage, and power density. It is desirable to operate at a low airflow rate in order to obtain thermal and water balance and to minimize the size and mass of the system. The performances of membrane/electrode assemblies of prior design are limited at low airflow rates. Methanol crossover increases the required airflow rate. Hence, one way to reduce the required airflow rate is to reduce the effect of methanol crossover. Improvement of the cathode structure - in particular, addition of hydrophobic particles to the cathode - has been

  5. Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes.

    Science.gov (United States)

    Alam, Imranul; Reilly, Austin M; Alkhouli, Mohammed; Gerard-O'Riley, Rita L; Kasipathi, Charishma; Oakes, Dana K; Wright, Weston B; Acton, Dena; McQueen, Amie K; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G; Econs, Michael J

    2017-04-01

    Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice overexpressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole-body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions.

  6. Polyvinylpyrrolidone-Based Bio-Ink Improves Cell Viability and Homogeneity during Drop-On-Demand Printing

    Directory of Open Access Journals (Sweden)

    Wei Long Ng

    2017-02-01

    Full Text Available Drop-on-demand (DOD bioprinting has attracted huge attention for numerous biological applications due to its precise control over material volume and deposition pattern in a contactless printing approach. 3D bioprinting is still an emerging field and more work is required to improve the viability and homogeneity of printed cells during the printing process. Here, a general purpose bio-ink was developed using polyvinylpyrrolidone (PVP macromolecules. Different PVP-based bio-inks (0%–3% w/v were prepared and evaluated for their printability; the short-term and long-term viability of the printed cells were first investigated. The Z value of a bio-ink determines its printability; it is the inverse of the Ohnesorge number (Oh, which is the ratio between the Reynolds number and a square root of the Weber number, and is independent of the bio-ink velocity. The viability of printed cells is dependent on the Z values of the bio-inks; the results indicated that the cells can be printed without any significant impairment using a bio-ink with a threshold Z value of ≤9.30 (2% and 2.5% w/v. Next, the cell output was evaluated over a period of 30 min. The results indicated that PVP molecules mitigate the cell adhesion and sedimentation during the printing process; the 2.5% w/v PVP bio-ink demonstrated the most consistent cell output over a period of 30 min. Hence, PVP macromolecules can play a critical role in improving the cell viability and homogeneity during the bioprinting process.

  7. Rehearsal significantly improves immediate and delayed recall on the Rey Auditory Verbal Learning Test.

    Science.gov (United States)

    Hessen, Erik

    2011-10-01

    A repeated observation during memory assessment with the Rey Auditory Verbal Learning Test (RAVLT) is that patients who spontaneously employ a memory rehearsal strategy by repeating the word list more than once achieve better scores than patients who only repeat the word list once. This observation led to concern about the ability of the standard test procedure of RAVLT and similar tests in eliciting the best possible recall scores. The purpose of the present study was to test the hypothesis that a rehearsal recall strategy of repeating the word list more than once would result in improved scores of recall on the RAVLT. We report on differences in outcome after standard administration and after experimental administration on Immediate and Delayed Recall measures from the RAVLT of 50 patients. The experimental administration resulted in significantly improved scores for all the variables employed. Additionally, it was found that patients who failed effort screening showed significantly poorer improvement on Delayed Recall compared with those who passed the effort screening. The general clear improvement both in raw scores and T-scores demonstrates that recall performance can be significantly influenced by the strategy of the patient or by small variations in instructions by the examiner.

  8. Fabrication approaches for plasmon-improved photovoltaic cells

    DEFF Research Database (Denmark)

    Gritti, Claudia; Malureanu, Radu; Kardynal, B.

    During this talk we will present various fabrication approaches to improve the performance of photovoltaic (PV) cells by using metallic nanoparticles in order to generate photocurrent below the bandgap. This effect is possible due to the generation of surface plasmon polaritons (SPPs) in optimized...

  9. Highly efficient local delivery of endothelial progenitor cells significantly potentiates angiogenesis and full-thickness wound healing.

    Science.gov (United States)

    Wang, Chenggui; Wang, Qingqing; Gao, Wendong; Zhang, Zengjie; Lou, Yiting; Jin, Haiming; Chen, Xiaofeng; Lei, Bo; Xu, Huazi; Mao, Cong

    2018-03-15

    Wound therapy with a rapid healing performance remains a critical clinical challenge. Cellular delivery is considered to be a promising approach to improve the efficiency of healing, yet problems such as compromised cell viability and functionality arise due to the inefficient delivery. Here, we report the efficient delivery of endothelial progenitor cells (EPCs) with a bioactive nanofibrous scaffold (composed of collagen and polycaprolactone and bioactive glass nanoparticles, CPB) for enhancing wound healing. Under the stimulation of CPB nanofibrous system, the viability and angiogenic ability of EPCs were significantly enhanced through the activation of Hif-1α/VEGF/SDF-1α signaling. In vivo, CPB/EPC constructs significantly enhanced the formation of high-density blood vessels by greatly upregulating the expressions of Hif-1α, VEGF, and SDF-1α. Moreover, owing to the increased local delivery of cells and fast neovascularization within the wound site, cell proliferative activity, granulation tissue formation, and collagen synthesis and deposition were greatly promoted by CPB/EPC constructs resulting in rapid re-epithelialization and regeneration of skin appendages. As a result, the synergistic enhancement of wound healing was observed from CPB/EPC constructs, which suggests the highly efficient delivery of EPCs. CPB/EPC constructs may become highly competitive cell-based therapeutic products for efficient impaired wound healing application. This study may also provide a novel strategy to develop bioactive cell therapy constructs for angiogenesis-related regenerative medicine. This paper reported a highly efficient local delivery of EPCs using bioactive glass-based CPB nanofibrous scaffold for enhancing angiogenesis and wound regeneration. In vitro study showed that CPB can promote the proliferation, migration, and tube formation of EPCs through upregulation of the Hif-1α/VEGF/SDF-1α signaling pathway, indicating that the bioactivity and angiogenic ability of

  10. Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function.

    Directory of Open Access Journals (Sweden)

    Christos Rammos

    Full Text Available Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO. NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR.Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%. Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03 and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001. PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02 and improved endothelial functions (FMD 4.8±1.0%, p<0.0001.We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function.

  11. Endothelial Progenitor Cell Mobilization in Preterm Infants With Sepsis Is Associated With Improved Survival.

    Science.gov (United States)

    Siavashi, Vahid; Asadian, Simin; Taheri-Asl, Masoud; Keshavarz, Samaneh; Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi

    2017-10-01

    Microvascular dysfunction plays a key role in the pathology of sepsis, leading to multi-organ failure, and death. Circulating endothelial progenitor cells (cEPCs) are critically involved in the maintenance of the vascular homeostasis in both physiological and pathological contexts. In this study, concentration of cEPCs in preterm infants with sepsis was determined to recognize whether the EPC mobilization would affect the clinical outcome of infantile sepsis. One hundred and thirty-three preterm infants (81 with sepsis and 52 without sepsis) were enrolled in this study. The release of EPCs in circulation was first quantified. Thereafter, these cells were cultivated and biological features of these cells such as, proliferation and colony forming efficiency were analyzed. The levels of chemoattractant cytokines were also measured in infants. In mouse models of sepsis, effects of VEGF and SDF-1 as well as anti-VEGF and anti-SDF-1 were evaluated in order to shed light upon the role which the EPC mobilization plays in the overall survival of septic animals. Circulating EPCs were significantly higher in preterm infants with sepsis than in the non-sepsis group. Serum levels of VEGF, SDF-1, and Angiopoietin-2 were also higher in preterm infants with sepsis than in control non-sepsis. In the animal experiments, injection of VEGF and SDF-1 prompted the mobilization of EPCs, leading to an improvement in survival whereas injection of anti-VEGF and anti-SDF-1 was associated with significant deterioration of survival. Overall, our results demonstrated the beneficial effects of EPC release in preterm infants with sepsis, with increased mobilization of these cells was associated with improved survival. J. Cell. Biochem. 118: 3299-3307, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Change in expression of cyclin G2 in kidney cancer cell and its significance.

    Science.gov (United States)

    Cui, D W; Sun, G G; Cheng, Y J

    2014-04-01

    This study aims to analyze the expression and clinical significance of cyclin G2 (CCNG2) in kidney carcinoma, and the biological effect in its cell line by CCNG2 overexpression. Immunohistochemistry and western blot were used to analyze CCNG2 protein expression in 63 cases of kidney cancer and normal tissues to study the relationship between CCNG2 expression and clinical factors. CCNG2 lentiviral vector and empty vector were respectively transfected into kidney ACHN cell line. During immunohistochemistry, the level of CCNG2 protein expression was found to be significantly lower in kidney cancer tissue than normal tissues (P kidney cancer tissue was respectively found to be significantly lower than in normal tissues (P 0.05), but it was correlated with lymph node metastasis, clinic stage, and histological grade (P kidney cancer and correlated significantly with lymph node metastasis, clinical stage, histological grade, and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator to kidney cancer ACHN cell by promoting degradation of CDK2.

  13. An Epigenetic Modifier Results in Improved In Vitro Blastocyst production after Somatic Cell Nuclear Transfer

    DEFF Research Database (Denmark)

    Zhang, Yunhai; Li, Juan; Villemoes, Klaus

    2007-01-01

    The present study was designed to examine the effect of trichostatin A (TSA), an inhibitor of histone deacetylase, on development of porcine cloned embryos. Our results showed that treatment of cloned embryos derived from sow oocytes with 50 nM TSA for up to 24 h after the onset of activation cou...... were tested, and for all cell lines an enhancement in blastocyst development compared to their corresponding control was observed. Our data demonstrate that TSA treatment after somatic cell nuclear transfer in the pig can significantly improve the in vitro blastocyst production...

  14. Integrated cell and process engineering for improved transient production of a "difficult-to-express" fusion protein by CHO cells.

    Science.gov (United States)

    Johari, Yusuf B; Estes, Scott D; Alves, Christina S; Sinacore, Marty S; James, David C

    2015-12-01

    Based on an optimized electroporation protocol, we designed a rapid, milliliter-scale diagnostic transient production assay to identify limitations in the ability of Chinese hamster ovary (CHO) cells to produce a model "difficult-to-express" homodimeric Fc-fusion protein, Sp35Fc, that exhibited very low volumetric titer and intracellular formation of disulfide-bonded oligomeric aggregates post-transfection. As expression of Sp35Fc induced an unfolded protein response in transfected host cells, we utilized the transient assay to compare, in parallel, multiple functionally diverse strategies to engineer intracellular processing of Sp35Fc in order to increase production and reduce aggregation as two discrete design objectives. Specifically, we compared the effect of (i) co-expression of ER-resident molecular chaperones (BiP, PDI, CypB) or active forms of UPR transactivators (ATF6c, XBP1s) at varying recombinant gene load, (ii) addition of small molecules known to act as chemical chaperones (PBA, DMSO, glycerol, betaine, TMAO) or modulate UPR signaling (PERK inhibitor GSK2606414) at varying concentration, (iii) a reduction in culture temperature to 32°C. Using this information, we designed a biphasic, Sp35Fc-specific transient manufacturing process mediated by lipofection that utilized CypB co-expression at an optimal Sp35Fc:CypB gene ratio of 5:1 to initially maximize transfected cell proliferation, followed by addition of a combination of PBA (0.5 mM) and glycerol (1% v/v) at the onset of stationary phase to maximize cell specific production and eliminate Sp35Fc aggregation. Using this optimal, engineered process transient Sp35Fc production was significantly increased sixfold over a 12 day production process with no evidence of disulfide-bonded aggregates. Finally, transient production in clonally derived sub-populations (derived from parental CHO host) screened for a heritably improved capability to produce Sp35Fc was also significantly improved by the optimized

  15. Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma.

    Science.gov (United States)

    Kremer, Veronika; Ligtenberg, Maarten A; Zendehdel, Rosa; Seitz, Christina; Duivenvoorden, Annet; Wennerberg, Erik; Colón, Eugenia; Scherman-Plogell, Ann-Helén; Lundqvist, Andreas

    2017-09-19

    Adoptive natural killer (NK) cell transfer is being increasingly used as cancer treatment. However, clinical responses have so far been limited to patients with hematological malignancies. A potential limiting factor in patients with solid tumors is defective homing of the infused NK cells to the tumor site. Chemokines regulate the migration of leukocytes expressing corresponding chemokine receptors. Various solid tumors, including renal cell carcinoma (RCC), readily secrete ligands for the chemokine receptor CXCR2. We hypothesize that infusion of NK cells expressing high levels of the CXCR2 chemokine receptor will result in increased influx of the transferred NK cells into tumors, and improved clinical outcome in patients with cancer. Blood and tumor biopsies from 14 primary RCC patients were assessed by flow cytometry and chemokine analysis. Primary NK cells were transduced with human CXCR2 using a retroviral system. CXCR2 receptor functionality was determined by Calcium flux and NK cell migration was evaluated in transwell assays. We detected higher concentrations of CXCR2 ligands in tumors compared with plasma of RCC patients. In addition, CXCL5 levels correlated with the intratumoral infiltration of CXCR2-positive NK cells. However, tumor-infiltrating NK cells from RCC patients expressed lower CXCR2 compared with peripheral blood NK cells. Moreover, healthy donor NK cells rapidly lost their CXCR2 expression upon in vitro culture and expansion. Genetic modification of human primary NK cells to re-express CXCR2 improved their ability to specifically migrate along a chemokine gradient of recombinant CXCR2 ligands or RCC tumor supernatants compared with controls. The enhanced trafficking resulted in increased killing of target cells. In addition, while their functionality remained unchanged compared with control NK cells, CXCR2-transduced NK cells obtained increased adhesion properties and formed more conjugates with target cells. To increase the success of NK

  16. Nanoscale dimples for improved absorption in organic solar cells

    DEFF Research Database (Denmark)

    Goszczak, Arkadiusz Jaroslaw; Rubahn, Horst-Günter; Madsen, Morten

    Organic solar cells (OSC’s) have attracted much attention in the past years due to their potential low-cost, light-weight and mechanical flexibility. A method for improving the power conversion efficiencies of the devices is by incorporating structured electrodes in the solar cell architecture......, as they can improve light absorption in the active layers of the devices. In this direction, a cheap and large-scale compatible method for structuring the electrodes in OSC’s is by the use of Anodic Alumina Oxide (AAO) membranes. In the present work, Al films of high purity and low roughness are formed via e...

  17. Significant efficiency enhancement of hybrid solar cells using core-shell nanowire geometry for energy harvesting.

    Science.gov (United States)

    Tsai, Shin-Hung; Chang, Hung-Chih; Wang, Hsin-Hua; Chen, Szu-Ying; Lin, Chin-An; Chen, Show-An; Chueh, Yu-Lun; He, Jr-Hau

    2011-12-27

    A novel strategy employing core-shell nanowire arrays (NWAs) consisting of Si/regioregular poly(3-hexylthiophene) (P3HT) was demonstrated to facilitate efficient light harvesting and exciton dissociation/charge collection for hybrid solar cells (HSCs). We experimentally demonstrate broadband and omnidirectional light-harvesting characteristics of core-shell NWA HSCs due to their subwavelength features, further supported by the simulation based on finite-difference time domain analysis. Meanwhile, core-shell geometry of NWA HSCs guarantees efficient charge separation since the thickness of the P3HT shells is comparable to the exciton diffusion length. Consequently, core-shell HSCs exhibit a 61% improvement of short-circuit current for a conversion efficiency (η) enhancement of 31.1% as compared to the P3HT-infiltrated Si NWA HSCs with layers forming a flat air/polymer cell interface. The improvement of crystal quality of P3HT shells due to the formation of ordering structure at Si interfaces after air mass 1.5 global (AM 1.5G) illumination was confirmed by transmission electron microscopy and Raman spectroscopy. The core-shell geometry with the interfacial improvement by AM 1.5G illumination promotes more efficient exciton dissociation and charge separation, leading to η improvement (∼140.6%) due to the considerable increase in V(oc) from 257 to 346 mV, J(sc) from 11.7 to 18.9 mA/cm(2), and FF from 32.2 to 35.2%, which is not observed in conventional P3HT-infiltrated Si NWA HSCs. The stability of the Si/P3HT core-shell NWA HSCs in air ambient was carefully examined. The core-shell geometry should be applicable to many other material systems of solar cells and thus holds high potential in third-generation solar cells.

  18. Unified Health Gamification can significantly improve well-being in corporate environments.

    Science.gov (United States)

    Shahrestani, Arash; Van Gorp, Pieter; Le Blanc, Pascale; Greidanus, Fabrizio; de Groot, Kristel; Leermakers, Jelle

    2017-07-01

    There is a multitude of mHealth applications that aim to solve societal health problems by stimulating specific types of physical activities via gamification. However, physical health activities cover just one of the three World Health Organization (WHO) dimensions of health. This paper introduces the novel notion of Unified Health Gamification (UHG), which covers besides physical health also social and cognitive health and well-being. Instead of rewarding activities in the three WHO dimensions using different mHealth competitions, UHG combines the scores for such activities on unified leaderboards and lets people interact in social circles beyond personal interests. This approach is promising in corporate environments since UHG can connect the employees with intrinsic motivation for physical health with those who have quite different interests. In order to evaluate this approach, we realized an app prototype and we evaluated it in two corporate pilot studies. In total, eighteen pilot users participated voluntarily for six weeks. Half of the participants were recruited from an occupational health setting and the other half from a treatment setting. Our results suggest that the UHG principles are worth more investigation: various positive health effects were found based on a validated survey. The mean mental health improved significantly at one pilot location and at the level of individual pilot participants, multiple other effects were found to be significant: among others, significant mental health improvements were found for 28% of the participants. Most participants intended to use the app beyond the pilot, especially if it would be further developed.

  19. Culturing bone marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet structure.

    Science.gov (United States)

    Akahane, M; Shimizu, T; Kira, T; Onishi, T; Uchihara, Y; Imamura, T; Tanaka, Y

    2016-11-01

    To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone. Osteogenic cell sheets were prepared by culturing rat bone marrow stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex, and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA expression were assessed in vitro, and the appearance of the cell sheets was observed after mechanical retrieval using a scraper. β-tricalcium phosphate (β-TCP) was then wrapped with the cell sheets from the four different groups and subcutaneously implanted into rats. After mechanical retrieval, the osteogenic cell sheets from the MEM, MEM with AscP, and MEM with Dex groups appeared to be fragmented or incomplete structures. The cell sheets cultured with Dex/AscP remained intact after mechanical retrieval, without any identifiable tears. Culture with Dex/AscP increased the mRNA and protein expression of extracellular matrix proteins and cell number compared with those of the other three groups. More bridging bone formation was observed after transplantation of the β-TCP scaffold wrapped with cell sheets cultured with Dex/AscP, than in the other groups. These results suggest that culture with Dex/AscP improves the mechanical integrity of the osteogenic cell sheets, allowing retrieval of the confluent cells in a single cell sheet structure. This method may be beneficial when applied in cases of difficult tissue reconstruction, such as nonunion, bone defects, and osteonecrosis.Cite this article: M. Akahane, T. Shimizu, T. Kira, T. Onishi, Y. Uchihara, T. Imamura, Y. Tanaka. Culturing bone marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet structure. Bone Joint Res 2016;5:569-576. DOI: 10.1302/2046-3758.511.BJR-2016-0013.R1. © 2016 Akahane et al.

  20. Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

    Science.gov (United States)

    Ahmed, Lamiaa A; Rizk, Sherine M; El-Maraghy, Shohda A

    2017-08-15

    Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats

  1. Reliable B cell epitope predictions: impacts of method development and improved benchmarking

    DEFF Research Database (Denmark)

    Kringelum, Jens Vindahl; Lundegaard, Claus; Lund, Ole

    2012-01-01

    biomedical applications such as; rational vaccine design, development of disease diagnostics and immunotherapeutics. However, experimental mapping of epitopes is resource intensive making in silico methods an appealing complementary approach. To date, the reported performance of methods for in silico mapping...... evaluation data set improved from 0.712 to 0.727. Our results thus demonstrate that given proper benchmark definitions, B-cell epitope prediction methods achieve highly significant predictive performances suggesting these tools to be a powerful asset in rational epitope discovery. The updated version...

  2. Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice.

    Science.gov (United States)

    Brooks, Matthew J; Hajira, Ameena; Mohamed, Junaith S; Alway, Stephen E

    2018-02-22

    Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a non-damaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice (n=6/group) were randomly placed into 5 groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: non-suspended mice-cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation, was evaluated by providing mice 5-bromo-2'-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force and decreased the in vivo fatigability and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type type I and IIa MHC abundance, increased fiber cross sectional area (CSA), and an increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7 positive nuclei inside muscle fibers and a greater MyoD to Pax 7 protein ratio when compared to HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR had lower levels of the inactive phosphorylated YAP serine127 which may have contributed to increased satellite cell activation creased with reloading after HSU. These results indicate that voluntary wheel running increased YAP

  3. Gemtuzumab Ozogamicin (GO Inclusion to Induction Chemotherapy Eliminates Leukemic Initiating Cells and Significantly Improves Survival in Mouse Models of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Cathy C Zhang

    2018-01-01

    Full Text Available Gemtuzumab ozogamicin (GO is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML. Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs. Herein, we use cell line and patient-derived xenograft (PDX AML models to evaluate the combination of GO with daunorubicin and cytarabine (DA induction chemotherapy on AML blast growth and animal survival. DA chemotherapy and GO as separate treatments reduced AML burden but left significant chemoresidual disease in multiple AML models. The combination of GO and DA chemotherapy eliminated nearly all AML burden and extended overall survival. In two small subsets of AML models, chemoresidual disease following DA chemotherapy displayed hallmark markers of leukemic LICs (CLL1 and CD34. In vivo, the two chemoresistant subpopulations (CLL1+/CD117− and CD34+/CD38+ showed higher ability to self-renewal than their counterpart subpopulations, respectively. CD33 was coexpressed in these functional LIC subpopulations. We demonstrate that the GO and DA induction chemotherapy combination more effectively eliminates LICs in AML PDX models than either single agent alone. These data suggest that the survival benefit seen by the combination of GO and induction chemotherapy, nonclinically and clinically, may be attributed to the enhanced reduction of LICs.

  4. Radiolabeled blood cells: radiation dosimetry and significance

    International Nuclear Information System (INIS)

    Thakur, M.L.

    1986-01-01

    Over the past few years blood cells labeled with In-111 have become increasingly useful in clinical diagnosis and biomedical research. Indium-111 by the virtue of its physical characteristics and ability to bind to cell cytoplasmic components, provides an excellent cell tracer and thereby, allows investigators to monitor in vivo cell distribution by external imaging and help determine a course of regimen in treating life threatening diseases. Due to natural phenomena such as margination, blood pool, and reticuloendothelial cell activity, in the normal state, depending upon the cell type and the quality of cell preparations, 30%-50% of the administered radioactivity is immediately distributed in the liver, spleen and bone marrow. Over a period of time the radioactivity in these organs slightly increases and decays with a physical half-life of In-111. The resulting radiation dose to these organs ranges between 1-25 rads/mCi In-111 administered. The authors have developed a new In-111 labeling technique which preserves platelet ultrastructure and shown that human lymphocytes labeled with In-111 in mixed leukocytes preparations a) are only 0.003% of the total -body lymphocytes population and b) are killed. The consequence if any may be considered insignificant, particularly because 5.6% metaphases from normal men and 6.5% metaphases from normal women in the US have at least one chromosome aberration. Calculations have shown that the risk of fatal hematological malignancy, over a 30 year period, in recipients of 100 million lymphocytes labeled with 100 μCi In-111 is 1/million patients studied. This risk is less than 0.025% of the 1981 spontaneous cancer patient rate in the country. 32 references, 10 tables

  5. Frameworks for improvement: clinical audit, the plan-do-study-act cycle and significant event audit.

    Science.gov (United States)

    Gillam, Steve; Siriwardena, A Niroshan

    2013-01-01

    This is the first in a series of articles about quality improvement tools and techniques. We explore common frameworks for improvement, including the model for improvement and its application to clinical audit, plan-do-study-act (PDSA) cycles and significant event analysis (SEA), examining the similarities and differences between these and providing examples of each.

  6. Prognostic significance of CD44s expression in resected non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ko Yoon

    2011-08-01

    Full Text Available Abstract Background CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC. Methods Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82 and squamous cell carcinoma (SCC; n = 77. Additionally, the immunoreactivity of cyclooxygenase (COX-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. Results High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7% than in those with AC histology (P 0.001. Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021. In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P P = 0.046, and high CD44s expression (P = 0.014. For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015. No significant association was found between CD44s and clinical outcome (P = 0.311. Conclusions High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

  7. Prognostic significance of CD44s expression in resected non-small cell lung cancer

    International Nuclear Information System (INIS)

    Ko, Yoon Ho; Won, Hye Sung; Jeon, Eun Kyoung; Hong, Sook Hee; Roh, Sang Young; Hong, Young Seon; Byun, Jae Ho; Jung, Chan-Kwon; Kang, Jin Hyoung

    2011-01-01

    CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC). Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82) and squamous cell carcinoma (SCC; n = 77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (P <0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P < 0.001), high-grade tumor differentiation (P = 0.046), and high CD44s expression (P = 0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015). No significant association was found between CD44s and clinical outcome (P = 0.311). High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage

  8. Improving the photovoltaic performance of perovskite solar cells with acetate

    Science.gov (United States)

    Zhao, Qian; Li, G. R.; Song, Jian; Zhao, Yulong; Qiang, Yinghuai; Gao, X. P.

    2016-01-01

    In an all-solid-state perovskite solar cell, methylammonium lead halide film is in charge of generating photo-excited electrons, thus its quality can directly influence the final photovoltaic performance of the solar cell. This paper accentuates a very simple chemical approach to improving the quality of a perovskite film with a suitable amount of acetic acid. With introduction of acetate ions, a homogeneous, continual and hole-free perovskite film comprised of high-crystallinity grains is obtained. UV-visible spectra, steady-state and time-resolved photoluminescence (PL) spectra reveal that the obtained perovskite film under the optimized conditions shows a higher light absorption, more efficient electron transport, and faster electron extraction to the adjoining electron transport layer. The features result in the optimized perovskite film can provide an improved short-circuit current. The corresponding solar cells with a planar configuration achieves an improved power conversion efficiency of 13.80%, and the highest power conversion efficiency in the photovoltaic measurements is up to 14.71%. The results not only provide a simple approach to optimizing perovskite films but also present a novel angle of view on fabricating high-performance perovskite solar cells. PMID:27934924

  9. Improving the photovoltaic performance of perovskite solar cells with acetate.

    Science.gov (United States)

    Zhao, Qian; Li, G R; Song, Jian; Zhao, Yulong; Qiang, Yinghuai; Gao, X P

    2016-12-09

    In an all-solid-state perovskite solar cell, methylammonium lead halide film is in charge of generating photo-excited electrons, thus its quality can directly influence the final photovoltaic performance of the solar cell. This paper accentuates a very simple chemical approach to improving the quality of a perovskite film with a suitable amount of acetic acid. With introduction of acetate ions, a homogeneous, continual and hole-free perovskite film comprised of high-crystallinity grains is obtained. UV-visible spectra, steady-state and time-resolved photoluminescence (PL) spectra reveal that the obtained perovskite film under the optimized conditions shows a higher light absorption, more efficient electron transport, and faster electron extraction to the adjoining electron transport layer. The features result in the optimized perovskite film can provide an improved short-circuit current. The corresponding solar cells with a planar configuration achieves an improved power conversion efficiency of 13.80%, and the highest power conversion efficiency in the photovoltaic measurements is up to 14.71%. The results not only provide a simple approach to optimizing perovskite films but also present a novel angle of view on fabricating high-performance perovskite solar cells.

  10. Significance of the neurotensin receptor Na+/H+-exchanger 1 axis in human pancreatic cancer cells

    International Nuclear Information System (INIS)

    Olszewski, U.

    2009-01-01

    Pancreatic cancer is characterized by early dissemination and rapid acquisition of drug resistance, resulting in dismal prognosis in patients. New targeted therapies failed to improve the low five-year survival rates. Characterization of neuropeptides as growth factors for pancreatic cancer cells stimulated interest in the development of suitable inhibitors. In particular, neurotensin (NT) stimulated proliferation of cancer cell lines, and the NT receptor 1 (NTR1) antagonist SR48692 was found to inhibit growth of tumor xenografts. However, clinical application of SR48692 in small cell lung cancer failed to yield significant responses. Nevertheless, expression of NTRs in more than 90% of pancreatic tumors points to an important role of the NT - NTR system in this tumor entity. Therefore, the present study aimed at investigation of the significance of NT - NTR signaling by use of BxPC-3, PANC-1 and MIA PaCa-2 pancreatic cancer cells and the NTR-positive HT-29 colon carcinoma cell line for comparison. Functional NTR1 that triggers release of intracellular Ca 2+ upon binding of the stable NT analog Lys 8 -Ψ-Lys 9 NT(8-13) was confirmed in all pancreatic cancer cell lines. The fraction of cells in S phase was increased in response to the NT analog and proliferation of the pancreatic cancer cells stimulated to a limited extent. In contrast to epidermal growth factor receptor (EGFR), NTR1 expression was found to reach a maximum in confluent cultures of resting (G1/0 phase) BxPC-3 and PANC-1 cells. In addition, again unlike EGFR, expression of NTR1 proved to be dependent on extracellular pH with highest levels under acidic conditions. Accordingly, Lys 8 -Ψ-Lys 9 NT(8-13) induced marked intracellular alkalinization in BxPC-3, PANC-1 and a panel of colon cancer cell lines and slight acidification in MIA PaCa-2 cells under conditions that confine regulation of intracellular pH to the ubiquitously expressed Na + /H + exchanger 1 (NHE1). Similar results were obtained in

  11. Determination of significance in Ecological Impact Assessment: Past change, current practice and future improvements

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, Sam; Hudson, Malcolm D., E-mail: mdh@soton.ac.uk

    2013-01-15

    Ecological Impact Assessment (EcIA) is an important tool for conservation and achieving sustainable development. 'Significant' impacts are those which disturb or alter the environment to a measurable degree. Significance is a crucial part of EcIA, our understanding of the concept in practice is vital if it is to be effective as a tool. This study employed three methods to assess how the determination of significance has changed through time, what current practice is, and what would lead to future improvements. Three data streams were collected: interviews with expert stakeholders, a review of 30 Environmental Statements and a broad-scale survey of the United Kingdom Institute of Ecology and Environmental Management (IEEM) members. The approach taken in the determination of significance has become more standardised and subjectivity has become constrained through a transparent framework. This has largely been driven by a set of guidelines produced by IEEM in 2006. The significance of impacts is now more clearly justified and the accuracy with which it is determined has improved. However, there are limitations to accuracy and effectiveness of the determination of significance. These are the quality of baseline survey data, our scientific understanding of ecological processes and the lack of monitoring and feedback of results. These in turn are restricted by the limited resources available in consultancies. The most notable recommendations for future practice are the implementation of monitoring and the publication of feedback, the creation of a central database for baseline survey data and the streamlining of guidance. - Highlights: Black-Right-Pointing-Pointer The assessment of significance has changed markedly through time. Black-Right-Pointing-Pointer The IEEM guidelines have driven a standardisation of practice. Black-Right-Pointing-Pointer Currently limited by quality of baseline data and scientific understanding. Black-Right-Pointing-Pointer Monitoring

  12. Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    Full Text Available Insulin-like growth factor 1 (IGF-1 and hepatocyte growth factor (HGF are two potent cell survival and regenerative factors in response to myocardial injury (MI. We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, P<0.01. IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, P<0.01 and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

  13. Cell phone–based health education messaging improves health ...

    African Journals Online (AJOL)

    SMS), provides new and innovative opportunities for disease prevention and health education. Objective: To explore the use of cell phone–based health education SMS to improve the health literacy of community residents in China. Methods: ...

  14. Significance of atypical squamous cells of undetermined significance on ThinPrep papanicolaou smears.

    Science.gov (United States)

    Eltabbakh, G H; Lipman, J N; Mount, S L; Morgan, A

    2000-10-01

    The aim of this study was to assess the prevalence and risk factors predictive of dysplasia among women seen in a gynecologic oncology service with the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) on Papanicolaou smears obtained by the ThinPrep method. Patients with ASCUS ThinPrep Papanicolaou smears seen at the Division of Gynecologic Oncology, University of Vermont, between 1997 and 1999 were identified. The cytologic smears were reviewed and subtyped into reactive or suggestive of squamous intraepithelial lesion (SIL). The charts of these patients were reviewed and the following information was abstracted: age, gravidity, parity, menopausal status, use of hormonal replacement therapy, smoking, history of pelvic cancer, history of radiation therapy, history of abnormal Papanicolaou smear and its treatment, history of human papillomavirus (HPV) infection, and follow-up information including results of repeat Papanicolaou smears, colposcopy, and biopsies. The prevalence of dysplasia was calculated. The demographic features of women with ASCUS, reactive, were compared with those with ASCUS, SIL, using a two-sample t test, chi(2), and Fisher's exact test. Risk factors predictive of dysplasia were calculated using the odds ratio and the 95% confidence interval. P ASCUS on ThinPrep Papanicolaou smear were identified; 63 patients had ASCUS, reactive, and 63 patients had ASCUS, SIL. The demographic features of both groups were similar. The overall prevalence of dysplasia was 15.9% and was significantly higher among women with ASCUS, SIL, than among women with ASCUS, reactive (25.4% versus 6.4%, P = 0.003). The type of ASCUS cytology (reactive versus SIL), smoking, and history of HPV were significant risk factors for dysplasia (P = 0.003, 0.037, and 0. 042, respectively). The prevalence of dysplasia among women seen in a gynecologic oncology service with ASCUS cytology on ThinPrep Papanicolaou smears is 15.9%. Women with ASCUS favor

  15. WIF-1 and Ihh Expression and Clinical Significance in Patients With Lung Squamous Cell Carcinoma and Adenocarcinoma.

    Science.gov (United States)

    Zhang, Yue; Hu, Chunhong

    2016-10-31

    This study investigated the expression of wingless-type inhibitory factor-1 (WIF-1) and Ihh protein in tumor tissues and their clinical significance in patients with lung squamous cell carcinoma and adenocarcinoma. The expression of WIF-1 and Ihh protein in 74 squamous cell carcinomas and 76 adenocarcinomas was measured by immunohistochemistry. The percentage of positive WIF-1 protein expression was significantly higher, while positive Ihh protein expression was significantly lower in patients with well-differentiated lung squamous cell carcinoma and adenocarcinoma, tumor node metastasis (TNM) stage I disease, and lymph node metastasis than that in patients with poorly differentiated tumor, TNM stage III disease, and lymph node metastasis (PIhh protein expression survived significantly shorter than patients with negative Ihh protein expression. In contrast, no significant difference in mean survival was observed in patients with lung squamous cell carcinoma and adenocarcinoma with positive and negative WIF-1 protein expression (P>0.05). Ihh is a marker for poor prognosis in patients with lung squamous cell carcinoma and adenocarcinoma. WIF-1 is not a predictive marker for lung cancer.

  16. Improved functional assessment of osteoarthritic knee joint after chondrogenically induced cell treatment.

    Science.gov (United States)

    Ude, C C; Ng, M H; Chen, C H; Htwe, O; Amaramalar, N S; Hassan, S; Djordjevic, I; Rani, R A; Ahmad, J; Yahya, N M; Saim, A B; Idrus, R B Hj

    2015-08-01

    Our previous studies on osteoarthritis (OA) revealed positive outcome after chondrogenically induced cells treatment. Presently, the functional improvements of these treated OA knee joints were quantified followed by evaluation of the mechanical properties of the engineered cartilages. Baseline electromyogram (EMGs) were conducted at week 0 (pre-OA), on the locomotory muscles of nine un-castrated male sheep (Siamese long tail cross) divided into controls, adipose-derived stem cells (ADSCs) and bone marrow stem cells (BMSCs), before OA inductions. Subsequent recordings were performed at week 7 and week 31 which were post-OA and post-treatments. Afterwards, the compression tests of the regenerated cartilage were performed. Post-treatment EMG analysis revealed that the control sheep retained significant reductions in amplitudes at the right medial gluteus, vastus lateralis and bicep femoris, whereas BMSCs and ADSCs samples had no further significant reductions (P < 0.05). Grossly and histologically, the treated knee joints demonstrated the presence of regenerated neo cartilages evidenced by the fluorescence of PKH26 tracker. Based on the International Cartilage Repair Society scores (ICRS), they had significantly lower grades than the controls (P < 0.05). The compression moduli of the native cartilages and the engineered cartilages differed significantly at the tibia plateau, patella femoral groove and the patella; whereas at the medial femoral condyle, they had similar moduli of 0.69 MPa and 0.40-0.64 MPa respectively. Their compression strengths at all four regions were within ±10 MPa. The tissue engineered cartilages provided evidence of functional recoveries associated to the structural regenerations, and their mechanical properties were comparable with the native cartilage. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  17. Improving the characterization of endothelial progenitor cell subsets by an optimized FACS protocol.

    Directory of Open Access Journals (Sweden)

    Karin Huizer

    Full Text Available The characterization of circulating endothelial progenitor cells (EPCs is fundamental to any study related to angiogenesis. Unfortunately, current literature lacks consistency in the definition of EPC subsets due to variations in isolation strategies and inconsistencies in the use of lineage markers. Here we address critical points in the identification of hematopoietic progenitor cells (HPCs, circulating endothelial cells (CECs, and culture-generated outgrowth endothelial cells (OECs from blood samples of healthy adults (AB and umbilical cord (UCB. Peripheral blood mononuclear cells (PBMCs were enriched using a Ficoll-based gradient followed by an optimized staining and gating strategy to enrich for the target cells. Sorted EPC populations were subjected to RT-PCR for tracing the expression of markers beyond the limits of cell surface-based immunophenotyping. Using CD34, CD133 and c-kit staining, combined with FSC and SSC, we succeeded in the accurate and reproducible identification of four HPC subgroups and found significant differences in the respective populations in AB vs. UCB. Co-expression analysis of endothelial markers on HPCs revealed a complex pattern characterized by various subpopulations. CECs were identified by using CD34, KDR, CD45, and additional endothelial markers, and were subdivided according to their apoptotic state and expression of c-kit. Comparison of UCB-CECs vs. AB-CECs revealed significant differences in CD34 and KDR levels. OECs were grown from PBMC-fractions We found that viable c-kit+ CECs are a candidate circulating precursor for CECs. RT-PCR to angiogenic factors and receptors revealed that all EPC subsets expressed angiogenesis-related molecules. Taken together, the improvements in immunophenotyping and gating strategies resulted in accurate identification and comparison of better defined cell populations in a single procedure.

  18. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  19. Improved genome recovery and integrated cell-size analyses of individual uncultured microbial cells and viral particles.

    Science.gov (United States)

    Stepanauskas, Ramunas; Fergusson, Elizabeth A; Brown, Joseph; Poulton, Nicole J; Tupper, Ben; Labonté, Jessica M; Becraft, Eric D; Brown, Julia M; Pachiadaki, Maria G; Povilaitis, Tadas; Thompson, Brian P; Mascena, Corianna J; Bellows, Wendy K; Lubys, Arvydas

    2017-07-20

    Microbial single-cell genomics can be used to provide insights into the metabolic potential, interactions, and evolution of uncultured microorganisms. Here we present WGA-X, a method based on multiple displacement amplification of DNA that utilizes a thermostable mutant of the phi29 polymerase. WGA-X enhances genome recovery from individual microbial cells and viral particles while maintaining ease of use and scalability. The greatest improvements are observed when amplifying high G+C content templates, such as those belonging to the predominant bacteria in agricultural soils. By integrating WGA-X with calibrated index-cell sorting and high-throughput genomic sequencing, we are able to analyze genomic sequences and cell sizes of hundreds of individual, uncultured bacteria, archaea, protists, and viral particles, obtained directly from marine and soil samples, in a single experiment. This approach may find diverse applications in microbiology and in biomedical and forensic studies of humans and other multicellular organisms.Single-cell genomics can be used to study uncultured microorganisms. Here, Stepanauskas et al. present a method combining improved multiple displacement amplification and FACS, to obtain genomic sequences and cell size information from uncultivated microbial cells and viral particles in environmental samples.

  20. Carotid endarterectomy significantly improves postoperative laryngeal sensitivity.

    Science.gov (United States)

    Hammer, Georg Philipp; Tomazic, Peter Valentin; Vasicek, Sarah; Graupp, Matthias; Gugatschka, Markus; Baumann, Anneliese; Konstantiniuk, Peter; Koter, Stephan Herwig

    2016-11-01

    sensory threshold on the operated-on side (6.08 ± 2.02 mm Hg) decreased significantly at the 6-week follow-up, even in relation to the preoperative measure (P = .022). With the exception of one patient with permanent unilateral vocal fold immobility, no signs of nerve injury were detected. In accordance with previous reports, injuries to the recurrent laryngeal nerve during CEA seem to be rare. In most patients, postoperative symptoms (globus, dysphagia, dysphonia) and signs fade within a few weeks without any specific therapeutic intervention. This study shows an improved long-term postoperative superior laryngeal nerve function with regard to laryngopharyngeal sensitivity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Improved Accelerated Stress Tests Based on Fuel Cell Vehicle Data

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, Timothy [Research Engineer; Motupally, Sathya [Research Engineer

    2012-06-01

    UTC will led a top-tier team of industry and national laboratory participants to update and improve DOE’s Accelerated Stress Tests (AST’s) for hydrogen fuel cells. This in-depth investigation will focused on critical fuel cell components (e.g. membrane electrode assemblies - MEA) whose durability represented barriers for widespread commercialization of hydrogen fuel cell technology. UTC had access to MEA materials that had accrued significant load time under real-world conditions in PureMotion® 120 power plant used in transit buses. These materials are referred to as end-of-life (EOL) components in the rest of this document. Advanced characterization techniques were used to evaluate degradation mode progress using these critical cell components extracted from both bus power plants and corresponding materials tested using the DOE AST’s. These techniques were applied to samples at beginning-of-life (BOL) to serve as a baseline. These comparisons advised the progress of the various failure modes that these critical components were subjected to, such as membrane degradation, catalyst support corrosion, platinum group metal dissolution, and others. Gaps in the existing ASTs predicted the degradation observed in the field in terms of these modes were outlined. Using the gaps, new AST’s were recommended and tested to better reflect the degradation modes seen in field operation. Also, BOL components were degraded in a test vehicle at UTC designed to accelerate the bus field operation.

  2. Rational design of nanoparticles towards targeting antigen-presenting cells and improved T cell priming.

    Science.gov (United States)

    Zupančič, Eva; Curato, Caterina; Paisana, Maria; Rodrigues, Catarina; Porat, Ziv; Viana, Ana S; Afonso, Carlos A M; Pinto, João; Gaspar, Rogério; Moreira, João N; Satchi-Fainaro, Ronit; Jung, Steffen; Florindo, Helena F

    2017-07-28

    Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules. Ovalbumin (OVA) was used as a model antigen in combination with the engraftment of CD4 + and CD8 + T cells, carrying a transgenic OVA-responding T cell receptor (TCR), to trace and characterize the activation of antigen-specific CD4 + and CD8 + lymph node T cells upon NP vaccination. Accordingly, the phenotype and frequency of immune cell stimulation induced by the NP loaded with OVA, isolated or in combination with synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) motifs, were characterized. DC-NP interactions increased with incubation time, presenting internalization values between 50 and 60% and 30-40%, in vitro and in vivo, respectively. Interestingly, animal immunization with antigen-adsorbed NP up-regulated major histocompatibility complex (MHC) class II (MHCII), while NP entrapping the antigen up-regulated MHCI, suggesting a more efficient cross-presentation. On the other hand, rather surprisingly, the surfactant used in the NP formulation had a major impact on the activation of antigen presenting cells (APC). In fact, DC collected from lymph nodes of animals immunized with NP prepared using poly(vinil alcohol) (PVA), as a surfactant, expressed significantly higher levels of CD86, MHCI and MHCII. In addition, those NP prepared with PVA and co-entrapping OVA and the toll

  3. PCI-24781 can improve in vitro and in vivo developmental capacity of pig somatic cell nuclear transfer embryos.

    Science.gov (United States)

    Jin, Long; Zhu, Hai-Ying; Guo, Qing; Li, Xiao-Chen; Zhang, Yu-Chen; Zhang, Guang-Lei; Xing, Xiao-Xu; Xuan, Mei-Fu; Luo, Qi-Rong; Yin, Xi-Jun; Kang, Jin-Dan

    2016-09-01

    To examine the effect of PCI-24781 (abexinostat) on the blastocyst formation rate in pig somatic cell nuclear transferred (SCNT) embryos and acetylation levels of the histone H3 lysine 9 and histone H4 lysine 12. Treatment with 0.5 nM PCI-24781 for 6 h significantly improved the development of cloned embryos, in comparison to the control group (25.3 vs. 10.5 %, P PCI-24781 treatment led to elevated acetylation of H3K9 and H4K12. TUNEL assay and Hoechst 33342 staining revealed that the percentage of apoptotic cells in blastocysts was significantly lower in PCI-24781-treated SCNT embryos than in untreated embryos. Also, PCI-24781-treated embryos were transferred into three surrogate sows, one of whom became pregnant and two fetuses developed. PCI-24781 improves nuclear reprogramming and the developmental potential of pig SCNT embryos.

  4. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

    Directory of Open Access Journals (Sweden)

    Shou Chengcao

    2009-12-01

    Full Text Available Abstract Background HIWI, the human homologue of Piwi family, is present in CD34+ hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients. Methods With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features. Results The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5% cases, 16 (10.5% cases were negative in both nuclei and cytoplasm. 86 (56.2% were strongly positive in cytoplasm, while 49 (32.0% were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (P = 0.011, T stage (P = 0.035, and clinic outcome (P Conclusion The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development.

  5. Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration.

    Science.gov (United States)

    Pisconti, Addolorata; Banks, Glen B; Babaeijandaghi, Farshad; Betta, Nicole Dalla; Rossi, Fabio M V; Chamberlain, Jeffrey S; Olwin, Bradley B

    2016-01-01

    The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells. Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts. Additionally, muscle aging is improved in syndecan-3 null mice. Since syndecan-3 null myofiber-associated satellite cells downregulate Pax7 and migrate away from the niche more readily than wild type cells, syxndecan-3 appears to regulate satellite cell homeostasis and satellite cell homing to the niche. Manipulating syndecan-3 provides a promising target for development of therapies to enhance muscle regeneration in muscular dystrophies and in aged muscle.

  6. Minimal RED Cell Pairs Markedly Improve Electrode Kinetics and Power Production in Microbial Reverse Electrodialysis Cells

    KAUST Repository

    Cusick, Roland D.

    2013-12-17

    Power production from microbial reverse electrodialysis cell (MRC) electrodes is substantially improved compared to microbial fuel cells (MFCs) by using ammonium bicarbonate (AmB) solutions in multiple RED cell pair stacks and the cathode chamber. Reducing the number of RED membranes pairs while maintaining enhanced electrode performance could help to reduce capital costs. We show here that using only a single RED cell pair (CP), created by operating the cathode in concentrated AmB, dramatically increased power production normalized to cathode area from both acetate (Acetate: from 0.9 to 3.1 W/m 2-cat) and wastewater (WW: 0.3 to 1.7 W/m2), by reducing solution and charge transfer resistances at the cathode. A second RED cell pair increased RED stack potential and reduced anode charge transfer resistance, further increasing power production (Acetate: 4.2 W/m2; WW: 1.9 W/m2). By maintaining near optimal electrode power production with fewer membranes, power densities normalized to total membrane area for the 1-CP (Acetate: 3.1 W/m2-mem; WW: 1.7 W/m2) and 2-CP (Acetate: 1.3 W/m2-mem; WW: 0.6 W/m2) reactors were much higher than previous MRCs (0.3-0.5 W/m2-mem with acetate). While operating at peak power, the rate of wastewater COD removal, normalized to reactor volume, was 30-50 times higher in 1-CP and 2-CP MRCs than that in a single chamber MFC. These findings show that even a single cell pair AmB RED stack can significantly enhance electrical power production and wastewater treatment. © 2013 American Chemical Society.

  7. Minimal RED Cell Pairs Markedly Improve Electrode Kinetics and Power Production in Microbial Reverse Electrodialysis Cells

    KAUST Repository

    Cusick, Roland D.; Hatzell, Marta; Zhang, Fang; Logan, Bruce E.

    2013-01-01

    Power production from microbial reverse electrodialysis cell (MRC) electrodes is substantially improved compared to microbial fuel cells (MFCs) by using ammonium bicarbonate (AmB) solutions in multiple RED cell pair stacks and the cathode chamber. Reducing the number of RED membranes pairs while maintaining enhanced electrode performance could help to reduce capital costs. We show here that using only a single RED cell pair (CP), created by operating the cathode in concentrated AmB, dramatically increased power production normalized to cathode area from both acetate (Acetate: from 0.9 to 3.1 W/m 2-cat) and wastewater (WW: 0.3 to 1.7 W/m2), by reducing solution and charge transfer resistances at the cathode. A second RED cell pair increased RED stack potential and reduced anode charge transfer resistance, further increasing power production (Acetate: 4.2 W/m2; WW: 1.9 W/m2). By maintaining near optimal electrode power production with fewer membranes, power densities normalized to total membrane area for the 1-CP (Acetate: 3.1 W/m2-mem; WW: 1.7 W/m2) and 2-CP (Acetate: 1.3 W/m2-mem; WW: 0.6 W/m2) reactors were much higher than previous MRCs (0.3-0.5 W/m2-mem with acetate). While operating at peak power, the rate of wastewater COD removal, normalized to reactor volume, was 30-50 times higher in 1-CP and 2-CP MRCs than that in a single chamber MFC. These findings show that even a single cell pair AmB RED stack can significantly enhance electrical power production and wastewater treatment. © 2013 American Chemical Society.

  8. EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve local control: Differential response of cancer stem cells and nontumourigenic cells?

    International Nuclear Information System (INIS)

    Krause, Mechthild; Prager, Jenny; Zhou Xuanjing; Yaromina, Ala; Doerfler, Annegret; Eicheler, Wolfgang; Baumann, Michael

    2007-01-01

    Background and purpose: Waiting times before radiotherapy may reduce tumour control probability due to proliferation of tumour cells. The aim of the experiment was to test whether the growth inhibiting effect of epidermal growth factor receptor (EGFR)-inhibitors after surgery or tumour transplantation results in a lower tumour mass at time of irradiation and can thereby improve local tumour control. Materials and methods: The EGFR-tyrosine kinase inhibitor BIBX1382BS was applied over 14 days starting from microscopically non-in-sano-resection of FaDu tumours or from tumour transplantation, followed by irradiation (5f/5d). Endpoint was local tumour control. In addition, vital tumour areas, pimonidazole hypoxic fraction, BrdU labelling index, and colony forming ability in vitro were tested in control tumours and after BIBX1382BS treatment (starting from transplantation). Results: The tumour volume at start of irradiation was significantly lower in the BIBX1382BS treated tumours as compared to the control groups by factors of 11 (post-surgery setting) and 2.7 (transplantation setting). However, the reduced volume did not translate into improved local control after irradiation. The TCD 50 values after surgery were 25.4 Gy [95% CI 18; 33 Gy] in the control group and 30.5 Gy [24; 37] in the BIBX1382BS group (p = 0.25). Treatment after transplantation resulted in TCD 50 values of 41.1 Gy [35; 47] in the control group and 41.1 Gy [33; 49] in the BIBX1382BS group (p = 1). While the proportion of S-phase cells decreased after BIBX1382BS treatment, no differences were observed between the pimonidazole hypoxic fractions and in vitro colony forming ability. Conclusions: EGFR-TK inhibition with BIBX1382BS over 14 days between macroscopically complete tumour resection or tumour transplantation and start of radiotherapy significantly reduced tumour volume but did not improve local tumour control. One possible explanation is that the EGFR-TK inhibitor has a higher activity in

  9. A case of gastric endocrine cell carcinoma which was significantly reduced in size by radiotherapy

    International Nuclear Information System (INIS)

    Azakami, Kiyoshi; Nishida, Kouji; Tanikawa, Ken

    2016-01-01

    In 2010, the World Health Organization classified gastric neuroendocrine tumors (NETs) into three types: NET grade (G) 1, NET G2 and neuroendocrine carcinoma (NEC). NECs are associated with a very poor prognosis. The patient was an 84-year-old female who was initially diagnosed by gastrointestinal endoscope with type 3 advanced gastric cancer with stenosis of the gastric cardia. Her overall status and performance status did not allow for operations or intensive chemotherapy. Palliative radiotherapy was performed and resulted in a significant reduction in the size of the tumor as well as the improvement of the obstructive symptoms. She died 9 months after radiotherapy. An autopsy provided a definitive diagnosis of gastric endocrine cell carcinoma, and the effectiveness of radiotherapy was pathologically-confirmed. Palliative radiotherapy may be a useful treatment option for providing symptom relief, especially for old patients with unresectable advanced gastric neuroendocrine carcinoma. (author)

  10. Enhanced mesenchymal cell engraftment by IGF-1 improves left ventricular function in rats undergoing myocardial infarction.

    Science.gov (United States)

    Enoki, Chiharu; Otani, Hajime; Sato, Daisuke; Okada, Takayuki; Hattori, Reiji; Imamura, Hiroji

    2010-01-07

    We hypothesized that enhanced mesenchymal cell (MC) engraftment with insulin-like growth factor-1 (IGF-1) improves left ventricular (LV) function and survival. IGF-1 (10 microg/ml) increased adhesion and inhibited apoptosis under hypoxia in vitro through activation of phosphatidylinositol 3-kinase (PI3K) in bone marrow-derived MCs obtained from transgenic rats expressing green fluorescence protein. Myocardial infarction (MI) in rats was produced by ligature of the left coronary artery. One month after MI, rat hearts were injected with MCs in the presence or absence of 10 microg/ml IGF-1 with or without PI3K inhibitor, 5 microM LY294002. IGF-1 significantly increased engraftment of MCs between 6 h and 3 days after transplantation associated with the increase in stromal cell-derived factor-1alpha in the infracted LV. The transplanted MCs had disappeared 1 month after transplantation in all groups. MC transplantation with IGF-1 significantly increased neovascularization and inhibited cardiomyocyte apoptosis 3 days and 1 month after MC transplantation. This was associated with improved LV function 1 month after MC transplantation and eventually survival. LY294002 abrogated all of the beneficial effects of MC transplantation with IGF-1. IGF-1 alone had no effect on neovascularization and did not improve LV function and/or survival. These results suggest that IGF-1 improves engraftment of MCs at the time of transplantation via activation of PI3K and this improved engraftment of MCs may be attributed to an increased neovascularization and inhibition of cardiomyocyte death, leading to improvement of LV function and prolongation of survival despite the eventual loss of the transplanted MCs.

  11. Prognostic significance of surgical extranodal extension in head and neck squamous cell carcinoma patients.

    Science.gov (United States)

    Matsumoto, Fumihiko; Mori, Taisuke; Matsumura, Satoko; Matsumoto, Yoshifumi; Fukasawa, Masahiko; Teshima, Masanori; Kobayashi, Kenya; Yoshimoto, Seiichi

    2017-08-01

    Lymph node metastasis with extranodal extension represents one of the most important adverse prognostic factors for survival in patients with head and neck squamous cell carcinoma. We propose that extranodal extension occurs to differing extents. The aim of this study was to determine the prognostic significance of extranodal extension in patients with head and neck squamous cell carcinoma. Two hundred and ninety-eight patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection were included. Cervical lymph nodes were classified into four categories: (i) pathological N negative, (ii) extranodal extension negative, (iii) non-surgical extranodal extension and (iv) surgical extranodal extension. Lymph node metastases were detected in 67.1% of laryngeal/hypopharyngeal cancer patients and 52.7% of oral cancer patients. The 3-year disease-specific survival rates for patients in the pathological N negative, extranodal extension negative, non-surgical extranodal extension and surgical extranodal extension groups were 90.9%, 79.6%, 63.8% and 48.3%, respectively. In laryngeal/hypopharyngeal cancer patients, surgical extranodal extension was associated with a significantly poorer disease-specific survival than a pathological N negative, extranodal extension negative or non-surgical extranodal extension status. In oral cancer patients, no significant differences were observed between the non-surgical and surgical extranodal extension groups. However, non-surgical extranodal extension was associated with a poorer disease-specific survival than a pathological N negative or extranodal extension negative status. Surgical extranodal extension was a poor prognostic factor in patients with head and neck squamous cell carcinoma. The prognostic significance of surgical extranodal extension differed between laryngeal/hypopharyngeal and oral cancer patients. The clinical significance of surgical extranodal extension was much greater for

  12. Solid-State NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization

    International Nuclear Information System (INIS)

    Takahashi, Hiroki; Bardet, Michel; De Paepe, Gael; Hediger, Sabine; Ayala, Isabel; Simorre, Jean-Pierre

    2013-01-01

    Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool. (authors)

  13. Solid-state NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization.

    Science.gov (United States)

    Takahashi, Hiroki; Ayala, Isabel; Bardet, Michel; De Paëpe, Gaël; Simorre, Jean-Pierre; Hediger, Sabine

    2013-04-03

    Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool.

  14. Heterostructured TiO2/NiTiO3 Nanorod Arrays for Inorganic Sensitized Solar Cells with Significantly Enhanced Photovoltaic Performance and Stability.

    Science.gov (United States)

    Li, Yue-Ying; Wang, Jian-Gan; Sun, Huan-Huan; Wei, Bingqing

    2018-04-11

    Organic dyes used in the conventional dye-sensitized solar cells (DSSCs) suffer from poor light stability and high cost. In this work, we demonstrate a new inorganic sensitized solar cell based on ordered one-dimensional semiconductor nanorod arrays of TiO 2 /NiTiO 3 (NTO) heterostructures prepared via a facile two-step hydrothermal approach. The semiconductor heterostructure arrays are highly desirable and promising for DSSCs because of their direct charge transport capability and slow charge recombination rate. The low-cost NTO inorganic semiconductor possesses an appropriate band gap that matches well with TiO 2 , which behaves like a "dye" to enable efficient light harvesting and fast electron-hole separation. The solar cells constructed by the ordered TiO 2 /NTO heterostructure photoanodes show a significantly improved power conversion efficiency, high fill factor, and more promising, outstanding life stability. The present work will open up an avenue to design heterostructured inorganics for high-performance solar cells.

  15. Modeling coverage gaps in haplotype frequencies via Bayesian inference to improve stem cell donor selection.

    Science.gov (United States)

    Louzoun, Yoram; Alter, Idan; Gragert, Loren; Albrecht, Mark; Maiers, Martin

    2018-05-01

    Regardless of sampling depth, accurate genotype imputation is limited in regions of high polymorphism which often have a heavy-tailed haplotype frequency distribution. Many rare haplotypes are thus unobserved. Statistical methods to improve imputation by extending reference haplotype distributions using linkage disequilibrium patterns that relate allele and haplotype frequencies have not yet been explored. In the field of unrelated stem cell transplantation, imputation of highly polymorphic human leukocyte antigen (HLA) genes has an important application in identifying the best-matched stem cell donor when searching large registries totaling over 28,000,000 donors worldwide. Despite these large registry sizes, a significant proportion of searched patients present novel HLA haplotypes. Supporting this observation, HLA population genetic models have indicated that many extant HLA haplotypes remain unobserved. The absent haplotypes are a significant cause of error in haplotype matching. We have applied a Bayesian inference methodology for extending haplotype frequency distributions, using a model where new haplotypes are created by recombination of observed alleles. Applications of this joint probability model offer significant improvement in frequency distribution estimates over the best existing alternative methods, as we illustrate using five-locus HLA frequency data from the National Marrow Donor Program registry. Transplant matching algorithms and disease association studies involving phasing and imputation of rare variants may benefit from this statistical inference framework.

  16. Intracerebral neural stem cell transplantation improved the auditory of mice with presbycusis.

    Science.gov (United States)

    Ren, Hongmiao; Chen, Jichuan; Wang, Yinan; Zhang, Shichang; Zhang, Bo

    2013-01-01

    Stem cell-based regenerative therapy is a potential cellular therapeutic strategy for patients with incurable brain diseases. Embryonic neural stem cells (NSCs) represent an attractive cell source in regenerative medicine strategies in the treatment of diseased brains. Here, we assess the capability of intracerebral embryonic NSCs transplantation for C57BL/6J mice with presbycusis in vivo. Morphology analyses revealed that the neuronal rate of apoptosis was lower in the aged group (10 months of age) but not in the young group (2 months of age) after NSCs transplantation, while the electrophysiological data suggest that the Auditory Brain Stem Response (ABR) threshold was significantly decreased in the aged group at 2 weeks and 3 weeks after transplantation. By contrast, there was no difference in the aged group at 4 weeks post-transplantation or in the young group at any time post-transplantation. Furthermore, immunofluorescence experiments showed that NSCs differentiated into neurons that engrafted and migrated to the brain, even to sites of lesions. Together, our results demonstrate that NSCs transplantation improve the auditory of C57BL/6J mice with presbycusis.

  17. Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.

    Science.gov (United States)

    Jiang, Bin; Suen, Rachel; Wertheim, Jason A; Ameer, Guillermo A

    2016-12-12

    Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.

  18. Significantly lengthened telomere in granulosa cells from women with polycystic ovarian syndrome (PCOS).

    Science.gov (United States)

    Wei, Duo; Xie, Juanke; Yin, Baoli; Hao, Haoying; Song, Xiaobing; Liu, Qi; Zhang, Cuilian; Sun, Yingpu

    2017-07-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women at reproductive age. However, its etiology remains poorly understood. Recent studies indicated that telomere length was related to PCOS. However, the association between telomere length and PCOS has only been shown in leucocytes and remained controversial across different studies. To clarify the association between telomere length and PCOS, the current study interrogated telomere length not only in leucocytes, but also in follicular granulosa cells, which is essential for folliculogenesis and steroidogenesis. Seventy-five patients with PCOS and 81 controls with mechanical infertility undergoing their first in vitro fertilization cycle were enrolled. Their peripheral blood and granulosa cells were collected on the oocyte retrieval day. Telomere length of both leucocytes in the blood and granulosa cells was assayed by quantitative polymerase chain reaction. No significant difference was found in the leucocyte telomere length between controls and PCOS patients (0.99 ± 0.44 vs. 1.00 ± 0.38, p = 0.93). Interestingly, when comparing telomere length in granulosa cells between controls and PCOS subjects, significantly lengthened telomere length was found in PCOS subjects (1.00 ± 0.37 vs. 1.57±0.67, p < 0.0001). After adjustments for age and body mass index, the p value remained significant (p < 0.0001). This finding reinforced the association between telomere abnormalities and PCOS. Given the importance of telomere length in cellular proliferation, our findings provided novel insights into the pathophysiology of PCOS that abnormalities in telomere length possibly disturb folliculogenesis and subsequently result in PCOS.

  19. Expression of HIWI in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis

    International Nuclear Information System (INIS)

    He, Wei; Wang, Zhihui; Wang, Qi; Fan, Qingxia; Shou, Chengcao; Wang, Junsheng; Giercksky, Karl-Erik; Nesland, Jahn M; Suo, Zhenhe

    2009-01-01

    HIWI, the human homologue of Piwi family, is present in CD34 + hematopoietic stem cells and germ cells, but not in well-differentiated cell populations, indicating that HIWI may play an impotent role in determining or maintaining stemness of these cells. That HIWI expression has been detected in several type tumours may suggest its association with clinical outcome in cancer patients. With the methods of real-time PCR, western blot, immunocytochemistry and immunohistochemistry, the expression of HIWI in three esophageal squamous cancer cell lines KYSE70, KYSE140 and KYSE450 has been characterized. Then, we investigated HIWI expression in a series of 153 esophageal squamous cell carcinomas using immunohistochemistry and explored its association with clinicopathological features. The expression of HIWI was observed in tumour cell nuclei or/and cytoplasm in 137 (89.5%) cases, 16 (10.5%) cases were negative in both nuclei and cytoplasm. 86 (56.2%) were strongly positive in cytoplasm, while 49 (32.0%) were strongly positive in nuclei. The expression level of HIWI in cytoplasm of esophageal cancer cells was significantly associated with histological grade (P = 0.011), T stage (P = 0.035), and clinic outcome (P < 0.001), while there was no correlation between the nuclear HIWI expression and clinicopathological features. The expression of HIWI in the cytoplasm of esophageal cancer cells is significantly associated with higher histological grade, clinical stage and poorer clinical outcome, indicating its possible involvement in cancer development

  20. Improved hydroxyurea effect with the use of text messaging in children with sickle cell anemia.

    Science.gov (United States)

    Estepp, Jeremie H; Winter, Bryan; Johnson, Margery; Smeltzer, Matthew P; Howard, Scott C; Hankins, Jane S

    2014-11-01

    In children with sickle cell anemia (SCA), hydroxyurea reduces morbidity, but adherence is frequently suboptimal. Because most families of children with SCA have access to cellular telephone services, we assessed the impact of text messaged reminders as a tool to improve adherence to hydroxyurea. All patients hydroxyurea at a maximal tolerated dosage (MTD) at St. Jude Children's Research Hospital Comprehensive Pediatric Sickle Cell Program and who received automated text message reminders (SIMON®) were retrospectively identified. Laboratory parameters, hospitalizations, and medication possession ratios (MPR) prior to and after initiation of SIMON® were compared to assess the impact of SIMON®. Of the 97.3% of families with access to a cell phone, 91% elected to receive text message reminders. Among 55 children receiving hydroxyurea at MTD, laboratory parameters reflected waning medication compliance during the 12 months prior to SIMON®. Following initiation of SIMON®, children had higher mean corpuscular volumes, hemoglobin levels and fetal hemoglobin percentages and lower absolute reticulocyte counts and bilirubin levels, suggesting improved medication adherence. Hospitalizations were uncommon before and after SIMON®, and medication possession ratios (MPRs) were high before and after SIMON®, neither was significantly changed. SIMON® was feasible and improved hematologic parameters in children with SCA receiving hydroxyurea at a MTD. Future work will include extension of this technology to children with other chronic medical conditions who require daily use of medication. © 2014 Wiley Periodicals, Inc.

  1. Cell fusion as a tool for rice improvement

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Y; Kyozuka, J; Terada, R; Nishibayashi, S; Shimamoto, K [Plantech Research Institute, Kamoshida, Midori-ku, Yokohama (Japan)

    1990-01-01

    Full text: Cell fusion offers a unique opportunity to hybridize sexually incompatible species and to mix cytoplasmic genomes in higher plants. Recent progress in plant regeneration from rice protoplasts facilitates an evaluation of the cell fusion method for rice improvement. By using electrofusion of protoplasts, we obtained hybrid/cybrid plants of the following combinations: Hybrids of rice x barnyard grass (E. oryzicola); Hybrids of rice x wild Oryza species; Cybrids of rice with transferred cms cytoplasm. For the latter, protoplasts irradiated with 70 krad x-rays were used. (author)

  2. Improving efficacy of cancer immunotherapy by genetic modification of natural killer cells.

    Science.gov (United States)

    Burga, Rachel A; Nguyen, Tuongvan; Zulovich, Jane; Madonna, Sarah; Ylisastigui, Loyda; Fernandes, Rohan; Yvon, Eric

    2016-11-01

    Natural killer (NK) cells are members of the innate immune system that recognize target cells via activating and inhibitory signals received through cell receptors. Derived from the lymphoid lineage, NK cells are able to produce cytokines and exert a cytotoxic effect on viral infected and malignant cells. It is their unique ability to lyse target cells rapidly and without prior education that renders NK cells a promising effector cell for adoptive cell therapy. However, both viruses and tumors employ evasion strategies to avoid attack by NK cells, which represent biological challenges that need to be harnessed to fully exploit the cytolytic potential of NK cells. Using genetic modification, the function of NK cells can be enhanced to improve their homing, cytolytic activity, in vivo persistence and safety. Examples include gene modification to express chemokine, high-affinity Fc receptor and chimeric antigen receptors, suicide genes and the forced expression of cytokines such as interleukin (IL)-2 and IL-15. Preclinical studies have clearly demonstrated that such approaches are effective in improving NK-cell function, homing and safety. In this review, we summarize the recent advances in the genetic manipulations of NK cells and their application for cellular immunotherapeutic strategies. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  3. An improved ghost-cell immersed boundary method for compressible flow simulations

    KAUST Repository

    Chi, Cheng; Lee, Bok Jik; Im, Hong G.

    2016-01-01

    This study presents an improved ghost-cell immersed boundary approach to represent a solid body in compressible flow simulations. In contrast to the commonly used approaches, in the present work ghost cells are mirrored through the boundary

  4. Neuro-Linguistic Programming: Improving Rapport between Track/Cross Country Coaches and Significant Others

    Science.gov (United States)

    Helm, David Jay

    2017-01-01

    This study examines the background information and the components of N.L.P., being eye movements, use of predicates, and posturing, as they apply to improving rapport and empathy between track/cross country coaches and their significant others in the arena of competition to help alleviate the inherent stressors.

  5. Serum Copper Level Significantly Influences Platelet Count, Lymphocyte Count and Mean Cell Hemoglobin in Sickle Cell Anemia

    Directory of Open Access Journals (Sweden)

    Okocha Chide

    2015-12-01

    Full Text Available Background Changes in serum micro nutrients levels affect a number of critically important metabolic processes; these could potentially influence blood counts and ultimately disease presentation in patients with sickle cell anemia (SCA. Objectives To evaluate the influence of serum micro-nutrients levels; zinc, copper, selenium and magnesium on blood counts in steady state SCA patients. Methods A cross sectional study that involved 28 steady state adult SCA subjects. Seven milliliters (mls of blood was collected; 3 mls was for hemoglobin electrophoresis and full blood count determination while 4 mls was for measurement of serum micro nutrients levels, by the atomic absorption spectrophotometry. Correlation between serum micro-nutrient levels and blood counts was done by the Pearson’s linear regression. Ethical approval was obtained from the institutional review board and each participant gave informed consent. All data was analyzed by SPSS software version 20. Results There was a significant correlation between serum copper levels and mean cell hemoglobin (MCH, platelet and lymphocyte counts (r = 0.418; P = 0.02, r = -0.376; P = 0.04 and r = -0.383; P = 0.04, respectively. There were no significant correlations between serum levels of other micro nutrients (selenium, zinc and magnesium and blood counts. Conclusions Copper influences blood count in SCA patients probably by inducing red cell haemolysis, oxidant tissue damage and stimulating the immune system.

  6. Significance of myofibroblasts in oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Thode, Christenze; Jørgensen, Trine G.; Dabelsteen, Erik

    2011-01-01

    -smooth muscle actin-positive myofibroblast that often represent the majority of tumor stromal cells. Their production of growth factors chemokines and extracellular matrix facilitates tumor growth. Myofibroblast have been demonstrated in close to 50% of oral squamous cell carcinomas. In this review, we...... highlight the histological distribution of myofibroblast in oral squamous cell and the myofibroblast relation to tumor growth on prognosis....

  7. The occurrence and significance of V gene mutations in B cell-derived human malignancy.

    Science.gov (United States)

    Stevenson, F K; Sahota, S S; Ottensmeier, C H; Zhu, D; Forconi, F; Hamblin, T J

    2001-01-01

    The classification of B cell tumors has relevance for refining and improving clinical strategies. However, consensus has been difficult to establish, and although a scheme is now available, objective criteria are desirable. Genetic technology will underpin and extend current knowledge, and it is certain to reveal further subdivisions of current tumor categories. The Ig variable region genes of B cell tumors present a considerable asset for this area of investigation. The unique sequences carried in neoplastic B cells are easily isolated and sequenced. In addition to acting as clone-specific markers of each tumor, they indicate where the cell has come from and track its history following transformation. There is emerging clinical value in knowing whether the cell of origin has encountered antigen and has moved from the naive compartment to the germinal center, where somatic mutation is activated. This is amply illustrated by the subdivision of chronic lymphocytic leukemia into two subsets, unmutated or mutated, each with very different prognosis. Other tumors may be subdivided in a similar way. Microarray technology is developing rapidly to probe gene expression and to further divide tumor categories. All these genetic analyses will provide objective data to enhance both our understanding of B cell tumors and our ability to treat them.

  8. Expression and clinical significance of PIWIL2 in hilar cholangiocarcinoma tissues and cell lines.

    Science.gov (United States)

    Chen, Y J; Xiong, X F; Wen, S Q; Tian, L; Cheng, W L; Qi, Y Q

    2015-06-26

    The objective of this study was to explore the relationship between PIWI-like protein 2 (PIWIL2) and clinicopathological charac-teristics and prognosis after radical resection. To accomplish this, we analyzed PIWIL2 expression in hilar cholangiocarcinoma tissues and cell lines. PIWIL2 expression was detected by immunohistochemistry in 41 hilar cholangiocarcinoma samples and 10 control tissues. Western blotting and immunocytofluorescence were used to investigate PIWIL2 expression in the cholangiocarcinoma cell line QBC939 and the bile duct epithelial cell line HIBEpic. Univariate and multivariate surviv-al analyses were performed using the Kaplan-Meier method for hilar cholangiocarcinoma patients who underwent radical resection. PIWIL2 expression was significantly higher in the hilar cholangiocarcinoma tissues and QBC939 cells than in control tissues and HIBEpic cells, respectively (P hilar cholangiocarcinoma (P hilar cholangiocarcinoma.

  9. Super-resolution structure of DNA significantly differs in buccal cells of controls and Alzheimer's patients.

    Science.gov (United States)

    Garcia, Angeles; Huang, David; Righolt, Amanda; Righolt, Christiaan; Kalaw, Maria Carmela; Mathur, Shubha; McAvoy, Elizabeth; Anderson, James; Luedke, Angela; Itorralba, Justine; Mai, Sabine

    2017-09-01

    The advent of super-resolution microscopy allowed for new insights into cellular and physiological processes of normal and diseased cells. In this study, we report for the first time on the super-resolved DNA structure of buccal cells from patients with Alzheimer's disease (AD) versus age- and gender-matched healthy, non-caregiver controls. In this super-resolution study cohort of 74 participants, buccal cells were collected and their spatial DNA organization in the nucleus examined by 3D Structured Illumination Microscopy (3D-SIM). Quantitation of the super-resolution DNA structure revealed that the nuclear super-resolution DNA structure of individuals with AD significantly differs from that of their controls (p structure of AD significantly differs in mild, moderate, and severe disease with respect to the DNA-containing and DNA-free/poor spaces. We conclude that whole genome remodeling is a feature of buccal cells in AD. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  10. Significance of MPEG-7 textural features for improved mass detection in mammography.

    Science.gov (United States)

    Eltonsy, Nevine H; Tourassi, Georgia D; Fadeev, Aleksey; Elmaghraby, Adel S

    2006-01-01

    The purpose of the study is to investigate the significance of MPEG-7 textural features for improving the detection of masses in screening mammograms. The detection scheme was originally based on morphological directional neighborhood features extracted from mammographic regions of interest (ROIs). Receiver Operating Characteristics (ROC) was performed to evaluate the performance of each set of features independently and merged into a back-propagation artificial neural network (BPANN) using the leave-one-out sampling scheme (LOOSS). The study was based on a database of 668 mammographic ROIs (340 depicting cancer regions and 328 depicting normal parenchyma). Overall, the ROC area index of the BPANN using the directional morphological features was Az=0.85+/-0.01. The MPEG-7 edge histogram descriptor-based BPNN showed an ROC area index of Az=0.71+/-0.01 while homogeneous textural descriptors using 30 and 120 channels helped the BPNN achieve similar ROC area indexes of Az=0.882+/-0.02 and Az=0.877+/-0.01 respectively. After merging the MPEG-7 homogeneous textural features with the directional neighborhood features the performance of the BPANN increased providing an ROC area index of Az=0.91+/-0.01. MPEG-7 homogeneous textural descriptor significantly improved the morphology-based detection scheme.

  11. Ceramic Composite Intermediate Temperature Stress-Rupture Properties Improved Significantly

    Science.gov (United States)

    Morscher, Gregory N.; Hurst, Janet B.

    2002-01-01

    Silicon carbide (SiC) composites are considered to be potential materials for future aircraft engine parts such as combustor liners. It is envisioned that on the hot side (inner surface) of the combustor liner, composites will have to withstand temperatures in excess of 1200 C for thousands of hours in oxidizing environments. This is a severe condition; however, an equally severe, if not more detrimental, condition exists on the cold side (outer surface) of the combustor liner. Here, the temperatures are expected to be on the order of 800 to 1000 C under high tensile stress because of thermal gradients and attachment of the combustor liner to the engine frame (the hot side will be under compressive stress, a less severe stress-state for ceramics). Since these composites are not oxides, they oxidize. The worst form of oxidation for strength reduction occurs at these intermediate temperatures, where the boron nitride (BN) interphase oxidizes first, which causes the formation of a glass layer that strongly bonds the fibers to the matrix. When the fibers strongly bond to the matrix or to one another, the composite loses toughness and strength and becomes brittle. To increase the intermediate temperature stress-rupture properties, researchers must modify the BN interphase. With the support of the Ultra-Efficient Engine Technology (UEET) Program, significant improvements were made as state-of-the-art SiC/SiC composites were developed during the Enabling Propulsion Materials (EPM) program. Three approaches were found to improve the intermediate-temperature stress-rupture properties: fiber-spreading, high-temperature silicon- (Si) doped boron nitride (BN), and outside-debonding BN.

  12. Factors Related to Significant Improvement of Estimated Glomerular Filtration Rates in Chronic Hepatitis B Patients Receiving Telbivudine Therapy

    Directory of Open Access Journals (Sweden)

    Te-Fu Lin

    2017-01-01

    Full Text Available Background and Aim. The improvement of estimated glomerular filtration rates (eGFRs in chronic hepatitis B (CHB patients receiving telbivudine therapy is well known. The aim of this study was to clarify the kinetics of eGFRs and to identify the significant factors related to the improvement of eGFRs in telbivudine-treated CHB patients in a real-world setting. Methods. Serial eGFRs were calculated every 3 months using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equation. The patients were classified as CKD-1, -2, or -3 according to a baseline eGFR of ≥90, 60–89, or <60 mL/min/1.73 m2, respectively. A significant improvement of eGFR was defined as a more than 10% increase from the baseline. Results. A total of 129 patients were enrolled, of whom 36% had significantly improved eGFRs. According to a multivariate analysis, diabetes mellitus (DM (p=0.028 and CKD-3 (p=0.043 were both significantly related to such improvement. The rates of significant improvement of eGFR were about 73% and 77% in patients with DM and CKD-3, respectively. Conclusions. Telbivudine is an alternative drug of choice for the treatment of hepatitis B patients for whom renal safety is a concern, especially patients with DM and CKD-3.

  13. Mesenchymal Stem Cells Enhance Liver Regeneration via Improving Lipid Accumulation and Hippo Signaling

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2018-01-01

    Full Text Available The liver has the potential to regenerate after injury. It is a challenge to improve liver regeneration (LR after liver resection in clinical practice. Bone morrow-derived mesenchymal stem cells (MSCs have shown to have a role in various liver diseases. To explore the effects of MSCs on LR, we established a model of 70% partial hepatectomy (PHx. Results revealed that infusion of MSCs could improve LR through enhancing cell proliferation and cell growth during the first 2 days after PHx, and MSCs could also restore liver synthesis function. Infusion of MSCs also improved liver lipid accumulation partly via mechanistic target of rapamycin (mTOR signaling and enhanced lipid β-oxidation support energy for LR. Rapamycin-induced inhibition of mTOR decreased liver lipid accumulation at 24 h after PHx, leading to impaired LR. And after infusion of MSCs, a proinflammatory environment formed in the liver, evidenced by increased expression of IL-6 and IL-1β, and thus the STAT3 and Hippo-YAP pathways were activated to improve cell proliferation. Our results demonstrated the function of MSCs on LR after PHx and provided new evidence for stem cell therapy of liver diseases.

  14. Significance of the proportion of binucleate cells in the micronucleus assay

    International Nuclear Information System (INIS)

    Imamura, Masahiro; Edgren, M.R.

    1994-01-01

    Using treatment with cytochalasin-B (Cyt-B) for the induction of a cytokinetic block, the significance of the proportion of binucleate cells (BNC) in the micronucleus (MN) assay was investigated in a methodological study. A Chinese hamster cell line V79 was used in which MN were induced by radiation. In complementary tests the radiation effect in inducing MN was enhanced by depletion of the cellular glutathione content with buthionine sulfoximine (BSO). The data indicated that the concentration of Cyt-B is the major factor which determines the proportion of BNC. This proportion was shown to be independent of radiation dose and of BSO. Furthermore, the MN frequency was not related to the percentage of BNC. Therefore, a high proportion of BNC may be practical for the MN assay, but may not make the technique more accurate. (author)

  15. Improvement of organic solar cells by flexible substrate and ITO surface treatments

    International Nuclear Information System (INIS)

    Cheng, Yuang-Tung; Ho, Jyh-Jier; Wang, Chien-Kun; Lee, William; Lu, Chih-Chiang; Yau, Bao-Shun; Nain, Jhen-Liang; Chang, Shun-Hsyung; Chang, Chiu-Cheng; Wang, Kang L.

    2010-01-01

    In this paper, surface treatments on polyethylene terephthalate with polymeric hard coating (PET-HC) substrates are described. The effect of the contact angle on the treatment is first investigated. It has been observed that detergent is quite effective in removing organic contamination on the flexible PET-HC substrates. Next, using a DC-reactive magnetron sputter, indium tin oxide (ITO) thin films of 90 nm are grown on a substrate treated by detergent. Then, various ITO surface treatments are made for improving the performance of the finally developed organic solar cells with structure Al/P3HT:PCBM/PEDOT:PSS/ITO/PET. It is found that the parameters of the ITO including resistivity, carrier concentration, transmittance, surface morphology, and work function depended on the surface treatments and significantly influence the solar cell performance. With the optimal conditions for detergent treatment on flexible PET substrates, the ITO film with a resistivity of 5.6 x 10 -4 Ω cm and average optical transmittance of 84.1% in the visible region are obtained. The optimal ITO surface treated by detergent for 5 min and then by UV ozone for 20 min exhibits the best WF value of 5.22 eV. This improves about 8.30% in the WF compared with that of the untreated ITO film. In the case of optimal treatment with the organic photovoltaic device, meanwhile, 36.6% enhancement in short circuit current density (J sc ) and 92.7% enhancement in conversion efficiency (η) over the untreated solar cell are obtained.

  16. Radiation damage and repair in cells and cell components. Part 2. Physical radiations and biological significance. Final report

    International Nuclear Information System (INIS)

    Fluke, D.J.

    1984-08-01

    The report comprises a teaching text, encompassing all physical radiations likely to be of biological interest, and the relevant biological effects and their significance. Topics include human radiobiology, delayed effects, radiation absorption in organisms, aqueous radiation chemistry, cell radiobiology, mutagenesis, and photobiology

  17. High Densities of Tumor-Associated Plasma Cells Predict Improved Prognosis in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Joe Yeong

    2018-05-01

    Full Text Available Breast cancer is the most common malignancy affecting women, but the heterogeneity of the condition is a significant obstacle to effective treatment. Triple negative breast cancers (TNBCs do not express HER2 or the receptors for estrogen or progesterone, and so often have a poor prognosis. Tumor-infiltrating T cells have been well-characterized in TNBC, and increased numbers are associated with better outcomes; however, the potential roles of B cells and plasma cells have been large. Here, we conducted a retrospective correlative study on the expression of B cell/plasma cell-related genes, and the abundance and localization of B cells and plasma cells within TNBCs, and clinical outcome. We analyzed 269 TNBC samples and used immunohistochemistry to quantify tumor-infiltrating B cells and plasma cells, coupled with NanoString measurement of expression of immunoglobulin metagenes. Multivariate analysis revealed that patients bearing TNBCs with above-median densities of CD38+ plasma cells had significantly better disease-free survival (DFS (HR = 0.44; 95% CI 0.26–0.77; p = 0.004 but not overall survival (OS, after adjusting for the effects of known prognostic factors. In contrast, TNBCs with higher immunoglobulin gene expression exhibited improved prognosis (OS p = 0.029 and DFS p = 0.005. The presence of B cells and plasma cells was positively correlated (p < 0.0001, R = 0.558, while immunoglobulin gene IGKC, IGHM, and IGHG1 mRNA expression correlated specifically with the density of CD38+ plasma cells (IGKC p < 0.0001, R = 0.647; IGHM p < 0.0001, R = 0.580; IGHG1 p < 0.0001, R = 0.655. Interestingly, after adjusting the multivariate analysis for the effect of intratumoral CD38+ plasma cell density, the expression levels of all three genes lost significant prognostic value, suggesting a biologically important role of plasma cells. Last but not least, the addition of intratumoral CD38+ plasma cell

  18. Long-Term Engraftment of Primary Bone Marrow Stromal Cells Repairs Niche Damage and Improves Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Abbuehl, Jean-Paul; Tatarova, Zuzana; Held, Werner; Huelsken, Joerg

    2017-08-03

    Hematopoietic stem cell (HSC) transplantation represents a curative treatment for various hematological disorders. However, delayed reconstitution of innate and adaptive immunity often causes fatal complications. HSC maintenance and lineage differentiation are supported by stromal niches, and we now find that bone marrow stroma cells (BMSCs) are severely and permanently damaged by the pre-conditioning irradiation required for efficient HSC transplantation. Using mouse models, we show that stromal insufficiency limits the number of donor-derived HSCs and B lymphopoiesis. Intra-bone transplantation of primary, but not cultured, BMSCs quantitatively reconstitutes stroma function in vivo, which is mediated by a multipotent NT5E + (CD73) + ENG - (CD105) - LY6A + (SCA1) + BMSC subpopulation. BMSC co-transplantation doubles the number of functional, donor-derived HSCs and significantly reduces clinically relevant side effects associated with HSC transplantation including neutropenia and humoral immunodeficiency. These data demonstrate the potential of stroma recovery to improve HSC transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Electrical properties improvement of multicrystalline silicon solar cells using a combination of porous silicon and vanadium oxide treatment

    International Nuclear Information System (INIS)

    Derbali, L.; Ezzaouia, H.

    2013-01-01

    In this paper, we will report the enhancement of the conversion efficiency of multicrystalline silicon solar cells after coating the front surface with a porous silicon layer treated with vanadium oxide. The incorporation of vanadium oxide into the porous silicon (PS) structure, followed by a thermal treatment under oxygen ambient, leads to an important decrease of the surface reflectivity, a significant enhancement of the effective minority carrier lifetime (τ eff ) and a significant enhancement of the photoluminescence (PL) of the PS structure. We Obtained a noticeable increase of (τ eff ) from 3.11 μs to 134.74 μs and the surface recombination velocity (S eff ) have decreased from 8441 cm s −1 to 195 cm s −1 . The reflectivity spectra of obtained films, performed in the 300–1200 nm wavelength range, show an important decrease of the average reflectivity from 40% to 5%. We notice a significant improvement of the internal quantum efficiency (IQE) in the used multicrystalline silicon substrates. Results are analyzed and compared to those carried out on a reference (untreated) sample. The electrical properties of the treated silicon solar cells were improved noticeably as regard to the reference (untreated) sample.

  20. Improved cell activity on biodegradable photopolymer scaffolds using titanate nanotube coatings

    Energy Technology Data Exchange (ETDEWEB)

    Beke, S., E-mail: szabolcs.beke@iit.it [Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Barenghi, R. [IEIIT, National Research Council (CNR), Via De Marini 6, 16149 Genova (Italy); Farkas, B.; Romano, I. [Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Kőrösi, L. [Department of Biotechnology, Nanophage Therapy Center, Enviroinvest Corporation, Kertváros u. 2, H-7632 Pécs (Hungary); Scaglione, S. [IEIIT, National Research Council (CNR), Via De Marini 6, 16149 Genova (Italy); Brandi, F. [Nanophysics, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, 56124-Pisa (Italy)

    2014-11-01

    The development of bioactive materials is in the premise of tissue engineering. For several years, surface functionalization of scaffolds has been one of the most promising approaches to stimulate cellular activity and finally improve implant success. Herein, we describe the development of a bioactive composite scaffold composed of a biodegradable photopolymer scaffold and titanate nanotubes (TNTs). The biodegradable photopolymer scaffolds were fabricated by applying mask-projection excimer laser photocuring at 308 nm. TNTs were synthesized and then spin-coated on the porous scaffolds. Upon culturing fibroblast cells on scaffolds, we found that nanotubes coating affects cell viability and proliferation demonstrating that TNT coatings enhance cell growth on the scaffolds by further improving their surface topography. - Highlights: • Biodegradable scaffolds were produced by mask-assisted UV laser photocuring. • Titanate nanotube deposition was carried out without binding compounds or additives. • Titanate nanotube coatings enhanced cell viability and proliferation.

  1. Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Yang, Jun; Tan, Dongfeng; Ramnath, Nithya; Moysich, Kirsten B; Asch, Harold L; Swede, Helen; Alrawi, Sadir J; Huberman, Joel; Geradts, Joseph; Brooks, John SJ

    2006-01-01

    Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G 0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC). 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample. The results suggest

  2. Improved Anode for a Direct Methanol Fuel Cell

    Science.gov (United States)

    Valdez, Thomas; Narayanan, Sekharipuram

    2005-01-01

    A modified chemical composition has been devised to improve the performance of the anode of a direct methanol fuel cell. The main feature of the modified composition is the incorporation of hydrous ruthenium oxide into the anode structure. This modification can reduce the internal electrical resistance of the cell and increase the degree of utilization of the anode catalyst. As a result, a higher anode current density can be sustained with a smaller amount of anode catalyst. These improvements can translate into a smaller fuel-cell system and higher efficiency of conversion. Some background information is helpful for understanding the benefit afforded by the addition of hydrous ruthenium oxide. The anode of a direct methanol fuel cell sustains the electro-oxidation of methanol to carbon dioxide in the reaction CH3OH + H2O--->CO2 + 6H(+) + 6e(-). An electrocatalyst is needed to enable this reaction to occur. The catalyst that offers the highest activity is an alloy of approximately equal numbers of atoms of the noble metals platinum and ruthenium. The anode is made of a composite material that includes high-surface-area Pt/Ru alloy particles and a proton-conducting ionomeric material. This composite is usually deposited onto a polymer-electrolyte (proton-conducting) membrane and onto an anode gas-diffusion/current-collector sheet that is subsequently bonded to the proton-conducting membrane by hot pressing. Heretofore, the areal density of noble-metal catalyst typically needed for high performance has been about 8 mg/cm2. However, not all of the catalyst has been utilized in the catalyzed electro-oxidation reaction. Increasing the degree of utilization of the catalyst would make it possible to improve the performance of the cell for a given catalyst loading and/or reduce the catalyst loading (thereby reducing the cost of the cell). The use of carbon and possibly other electronic conductors in the catalyst layer has been proposed for increasing the utilization of the

  3. Solid polymeric electrolyte based dye-sensitized solar cell with improved stability

    Science.gov (United States)

    Prasad, Narottam; Kumar, Manish; Patel, K. R.; Roy, M. S.

    2018-05-01

    The impact of polymeric electrolyte was investigated over the performance of dye-sensitized solar cell made with Rose Bengal as sensitizer. Further, the selective influence of TiCl4 treatment and pre-sensitizer deoxycholic acid on nc-TiO2 photoanode was determined in terms of improvement in conversion efficiency of the cell. It is found that the effect of TiCl4 treatment was comparatively more than pre-sensitization with de-oxy cholic acid towards improving the efficiency of the cell. The conversion efficiency on TiCl4 treatment was 0.2% whereas on pre-sensitization with deoxy chollic acid it was 0.1%. The combined effect of both TiCl4 treatment & pre-sensitization with deoxycholic acid leads conversion efficiency to 0.33%.

  4. Mechanisms of transcriptional regulation and prognostic significance of activated leukocyte cell adhesion molecule in cancer

    Directory of Open Access Journals (Sweden)

    Chen Hairu

    2010-10-01

    Full Text Available Abstract Background Activated leukocyte cell adhesion molecule (ALCAM is implicated in the prognosis of multiple cancers with low level expression associated with metastasis and early death in breast cancer. Despite this significance, mechanisms that regulate ALCAM gene expression and ALCAM's role in adhesion of pre-metastatic circulating tumor cells have not been defined. We studied ALCAM expression in 20 tumor cell lines by real-time PCR, western blot and immunochemistry. Epigenetic alterations of the ALCAM promoter were assessed using methylation-specific PCR and bisulfite sequencing. ALCAM's role in adhesion of tumor cells to the vascular wall was studied in isolated perfused lungs. Results A common site for transcription initiation of the ALCAM gene was identified and the ALCAM promoter sequenced. The promoter contains multiple cis-active elements including a functional p65 NF-κB motif, and it harbors an extensive array of CpG residues highly methylated exclusively in ALCAM-negative tumor cells. These CpG residues were modestly demethylated after 5-aza-2-deoxycytidine treatment. Restoration of high-level ALCAM expression using an ALCAM cDNA increased clustering of MDA-MB-435 tumor cells perfused through the pulmonary vasculature of ventilated rat lungs. Anti-ALCAM antibodies reduced the number of intravascular tumor cell clusters. Conclusion Our data suggests that loss of ALCAM expression, due in part to DNA methylation of extensive segments of the promoter, significantly impairs the ability of circulating tumor cells to adhere to each other, and may therefore promote metastasis. These findings offer insight into the mechanisms for down-regulation of ALCAM gene expression in tumor cells, and for the positive prognostic value of high-level ALCAM in breast cancer.

  5. 24% efficient PERL structure silicon solar cells

    International Nuclear Information System (INIS)

    Zhao, J.; Wang, A.; Green, M.A.

    1990-01-01

    This paper reports that the performance of silicon solar cells have been significantly improved using an improved PERL (passivated emitter, rear locally-diffused) cell structure. This structure overcomes deficiencies in an earlier PERC (passivated emitter and rear cell) cell structure by locally diffusing boron into contact areas at the rear of the cells. Terrestrial energy conversion efficiencies up to 24% are reported for silicon cells for the first time. Air Mass O efficiencies approach 21%. The first batches of concentrator cells using the new structure have demonstrated significant improvement with 29% efficient concentrator silicon cells expected in the near future

  6. Resveratrol self-emulsifying system increases the uptake by endothelial cells and improves protection against oxidative stress-mediated death.

    Science.gov (United States)

    Amri, Ahmed; Le Clanche, Solenn; Thérond, Patrice; Bonnefont-Rousselot, Dominique; Borderie, Didier; Lai-Kuen, René; Chaumeil, Jean-Claude; Sfar, Souad; Charrueau, Christine

    2014-04-01

    The aim of the present study was to develop and characterize a resveratrol self-emulsifying drug delivery system (Res-SEDDS), and to compare the uptake of resveratrol by bovine aortic endothelial cells (BAECs), and the protection of these cells against hydrogen peroxide-mediated cell death, versus a control resveratrol ethanolic solution. Three Res-SEDDSs were prepared and evaluated. The in vitro self-emulsification properties of these formulations, the droplet size and the zeta potential of the nanoemulsions formed on adding them to water under mild agitation conditions were studied, together with their toxicity on BAECs. An optimal atoxic formulation (20% Miglyol® 812, 70% Montanox® 80, 10% ethanol 96% v/v) was selected and further studied. Pre-incubation of BAECs for 180 min with 25 μM resveratrol in the nanoemulsion obtained from the selected SEDDS significantly increased the membrane and intracellular concentrations of resveratrol (for example, 0.076±0.015 vs. ethanolic solution 0.041±0.016 nmol/mg of protein after 60 min incubation, p<0.05). Resveratrol intracellular localization was confirmed by fluorescence confocal microscopy. Resveratrol nanoemulsion significantly improved the endothelial cell protection from H2O2-induced injury (750, 1000 and 1500 μM H2O2) in comparison with incubation with the control resveratrol ethanolic solution (for example, 55±6% vs. 38±5% viability after 1500 μM H2O2 challenge, p<0.05). In conclusion, formulation of resveratrol as a SEDDS significantly improved its cellular uptake and potentiated its antioxidant properties on BAECs. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Cellular immunotherapy using irradiated lung cancer cell vaccine co-expressing GM-CSF and IL-18 can induce significant antitumor effects

    International Nuclear Information System (INIS)

    Tian, Hongwei; Zhang, Xiaomei; Dai, Lei; Chen, Xiaolei; Zhang, Shuang; Yang, Yang; Yu, Dechao; Wei, Yuquan; Deng, Hongxin; Shi, Gang; Yang, Guoyou; Zhang, Junfeng; Li, Yiming; Du, Tao; Wang, Jianzhou; Xu, Fen; Cheng, Lin

    2014-01-01

    Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. Tumor cells genetically modified to secrete immune activating cytokines have been proved to be more immunogenic. IL-18 could augment proliferation of T cells and cytotoxicity of NK cells. GM-CSF could stimulate dendritic cells, macrophages and enhance presentation of tumor antigens. In our study, we used mouse GM-CSF combined with IL-18 to modify Lewis lung cancer LL/2, then investigated whether vaccination could suppress tumor growth and promote survival. The Lewis lung cancer LL/2 was transfected with co-expressing mouse GM-CSF and IL-18 plasmid by cationic liposome, then irradiated with a sublethal dose X ray (100 Gy) to prepare vaccines. Mice were subcutaneously immunized with this inactivated vaccine and then inoculated with autologous LL/2 to estimate the antitumor efficacy. The studies reported here showed that LL/2 tumor cell vaccine modified by a co-expressing mouse GM-CSF and IL-18 plasmid could significantly inhibit tumor growth and increased survival of the mice bearing LL/2 tumor whether prophylactic or adoptive immunotherapy in vivo. A significant reduction of proliferation and increase of apoptosis were also observed in the tumor treated with vaccine of co-expressing GM-CSF and IL-18. The potent antitumor effect correlated with higher secretion levels of pro-inflammatory cytokines such as IL-18, GM-CSF, interferon-γ in serum, the proliferation of CD4 + IFN-γ + , CD8 + IFN-γ + T lymphocytes in spleen and the infiltration of CD4 + , CD8 + T in tumor. Furthermore, the mechanism of tumor-specific immune response was further proved by 51 Cr cytotoxicity assay in vitro and depletion of CD4, CD8, NK immune cell subsets in vivo. The results suggested that the antitumor mechanism was mainly depended on CD4 + , CD8 + T lymphocytes. These results provide a new insight into therapeutic mechanisms

  8. Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.

    Science.gov (United States)

    Cilliers, Cornelius; Menezes, Bruna; Nessler, Ian; Linderman, Jennifer; Thurber, Greg M

    2018-02-01

    Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo , yet improves the effectiveness of T-DM1 in vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758-68. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Radiobiologic significance of apoptosis and micronucleation in quiescent cells within solid tumors following γ-ray irradiation

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Kinashi, Yuko; Takagaki, Masao

    2001-01-01

    Purpose: To determine the frequency of apoptosis in quiescent (Q) cells within solid tumors following γ-ray irradiation, using four different tumor cell lines. In addition, to assess the significance of detecting apoptosis in these cell lines. Methods and Materials: C3H/He mice bearing SCC VII or FM3A tumors, Balb/c mice bearing EMT6/KU tumors, and C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received γ-ray irradiation at a dose of 4-25 Gy while alive or after tumor clamping. Immediately after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 hours after irradiation, tumor cell suspensions obtained in the same manner were fixed. The apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: In total cells, SCC VII, FM3A, and EMT6/KU cells showed reasonable relationships between MN frequency and surviving fraction (SF). However, fewer micronuclei were induced in EL4 cells than the other cell lines. In contrast, a comparatively close relationship between apoptosis frequency and SF was found in total cells of EL4 cell line. Less apoptosis was observed in the other cell lines. Quiescent tumor cells exhibited significantly lower values of MN and apoptosis frequency probably due to their large hypoxic fraction, similar to total tumor cells on clamped irradiation. Conclusion: γ-ray irradiation induced MN formation in SCC VII, FM3A, and EMT6/KU tumor cells, and the apoptosis was marked in EL4 cells compared with

  10. Improving the electrocatalytic properties of Pd-based catalyst for direct alcohol fuel cells: effect of solid solution.

    Science.gov (United States)

    Wen, Cuilian; Wei, Ying; Tang, Dian; Sa, Baisheng; Zhang, Teng; Chen, Changxin

    2017-07-07

    The tolerance of the electrode against the CO species absorbed upon the surface presents the biggest dilemma of the alcohol fuel cells. Here we report for the first time that the inclusion of (Zr, Ce)O 2 solid solution as the supporting material can significantly improve the anti-CO-poisoning as well as the activity of Pd/C catalyst for ethylene glycol electro-oxidation in KOH medium. In particular, the physical origin of the improved electrocatalytic properties has been unraveled by first principle calculations. The 3D stereoscopic Pd cluster on the surface of (Zr, Ce)O 2 solid solution leads to weaker Pd-C bonding and smaller CO desorption driving force. These results support that the Pd/ZrO 2 -CeO 2 /C composite catalyst could be used as a promising effective candidate for direct alcohol fuel cells application.

  11. Cryptosporidium and other intestinal parasitic infections among HIV patients in southern Ethiopia: significance of improved HIV-related care.

    Science.gov (United States)

    Shimelis, Techalew; Tassachew, Yayehyirad; Lambiyo, Tariku

    2016-05-10

    Intestinal parasitic infections are known to cause gastroenteritis, leading to higher morbidity and mortality, particularly in people living with HIV/AIDS. This study aimed to determine the prevalence of Cryptosporidium and other intestinal parasitic infections among HIV patients receiving care at a hospital in Ethiopia where previous available baseline data helps assess if improved HIV-related care has reduced infection rates. A cross-sectional study was conducted at Hawassa University Hospital in southern Ethiopia from May, 2013 to March, 2014. A consecutive sample of 491 HIV- infected patients with diarrhea or a CD4 T cell count intestinal parasites. The study was approved by the Institutional Review Board of the College of Medicine and Health Sciences, Hawassa University. Physicians managed participants found to be infected with any pathogenic intestinal parasite. The overall prevalence of intestinal parasitic infections among the study population was 35.8 %. The most prevalent parasites were Cryptosporidium (13.2 %), followed by Entamoeba histolytica/dispar (10.2 %), and Giardia lamblia (7.9 %). The rate of single and multiple infections were 25.5 and 10.3 %, respectively. Patients with a CD4 T cell count intestinal parasitic infection or cryptosporidiosis compared to those with counts ≥ 200 cells/μl, but with some type of diarrhea. The study shows high prevalence of intestinal parasitic infections in the study population. However, the results in the current report are significantly lower compared to previous findings in the same hospital. The observed lower infection rate is encouraging and supports the need to strengthen and sustain the existing intervention measures in order to further reduce intestinal parasitic infections in people living with HIV/AIDS.

  12. Significant improvement of thermal stability of glucose 1-dehydrogenase by introducing disulfide bonds at the tetramer interface.

    Science.gov (United States)

    Ding, Haitao; Gao, Fen; Liu, Danfeng; Li, Zeli; Xu, Xiaohong; Wu, Min; Zhao, Yuhua

    2013-12-10

    Rational design was applied to glucose 1-dehydrogenase (LsGDH) from Lysinibacillus sphaericus G10 to improve its thermal stability by introduction of disulfide bridges between subunits. One out of the eleven mutants, designated as DS255, displayed significantly enhanced thermal stability with considerable soluble expression and high specific activity. It was extremely stable at pH ranging from 4.5 to 10.5, as it retained nearly 100% activity after incubating at different buffers for 1h. Mutant DS255 also exhibited high thermostability, having a half-life of 9900min at 50°C, which was 1868-fold as that of its wild type. Moreover, both of the increased free energy of denaturation and decreased entropy of denaturation of DS255 suggested that the enzyme structure was stabilized by the engineered disulfide bonds. On account of its robust stability, mutant DS255 would be a competitive candidate in practical applications of chiral chemicals synthesis, biofuel cells and glucose biosensors. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Improving poor fill factors for solar cells via light-induced plating

    International Nuclear Information System (INIS)

    Xing Zhao; Jia Rui; Ding Wuchang; Meng Yanlong; Jin Zhi; Liu Xinyu

    2012-01-01

    Silicon solar cells are prepared following the conventional fabrication processes, except for the metallization firing process. The cells are divided into two groups with higher and lower fill factors, respectively. After light-induced plating (LIP), the fill factors of the solar cells in both groups with different initial values reach the same level. Scanning electron microscope (SEM) images are taken under the bulk silver electrodes, which prove that the improvement for cells with a poor factor after LIP should benefit from sufficient exploitation of the high density silver crystals formed during the firing process. Moreover, the application of LIP to cells with poor electrode contact performance, such as nanowire cells and radial junction solar cells, is proposed. (semiconductor devices)

  14. The challenges of ESRD care in developing economies: sub-Saharan African opportunities for significant improvement.

    Science.gov (United States)

    Bamgboye, Ebun Ladipo

    Chronic kidney disease (CKD) is a significant cause of morbidity and mortality in sub-Saharan Africa. This, along with other noncommunicable diseases like hypertension, diabetes, and heart diseases, poses a double burden on a region that is still struggling to cope with the scourge of communicable diseases like malaria, tuberculosis, HIV, and more recently Ebola. Causes of CKD in the region are predominantly glomerulonephritis and hypertension, although type 2 diabetes is also becoming a significant cause as is the retroviral disease. Patients are generally younger than in the developed world, and there is a significant male preponderance. Most patients are managed by hemodialysis, with peritoneal dialysis and kidney transplantation being available in only few countries in the region. Government funding and support for dialysis is often unavailable, and when available, often with restrictions. There is a dearth of trained manpower to treat the disease, and many countries have a limited number of units, which are often ill-equipped to deal adequately with the number of patients who require end-stage renal disease (ESRD) care in the region. Although there has been a significant improvement when compared with the situation, even as recently as 10 years ago, there is also the potential for further improvement, which would significantly improve the outcomes in patients with ESRD in the region. The information in this review was obtained from a combination of renal registry reports (published and unpublished), published articles, responses to a questionnaire sent to nephrologists prior to the World Congress of Nephrology (WCN) in Cape Town, and from nephrologists attending the WCN in Cape Town (March 13 - 17, 2015).

  15. Agonist anti-GITR antibody significantly enhances the therapeutic efficacy of Listeria monocytogenes-based immunotherapy.

    Science.gov (United States)

    Shrimali, Rajeev; Ahmad, Shamim; Berrong, Zuzana; Okoev, Grigori; Matevosyan, Adelaida; Razavi, Ghazaleh Shoja E; Petit, Robert; Gupta, Seema; Mkrtichyan, Mikayel; Khleif, Samir N

    2017-08-15

    We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4 + and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment. Here we tested the immune and therapeutic efficacy of Listeria-based immunotherapy combination with agonist antibody to glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) in TC-1 mouse tumor model. We evaluated the potency of combination on tumor growth and survival of treated animals and profiled tumor microenvironment for effector and suppressor cell populations. We demonstrate that combination of Listeria-based immunotherapy with agonist antibody to GITR synergizes to improve immune and therapeutic efficacy of treatment in a mouse tumor model. We show that this combinational treatment leads to significant inhibition of tumor-growth, prolongs survival and leads to complete regression of established tumors in 60% of treated animals. We determined that this therapeutic benefit of combinational treatment is due to a significant increase in tumor infiltrating effector CD4 + and CD8 + T cells along with a decrease of inhibitory cells. To our knowledge, this is the first study that exploits Lm-based immunotherapy combined with agonist anti-GITR antibody as a potent treatment strategy that simultaneously targets both the effector and suppressor arms of the immune system, leading to significantly improved anti-tumor efficacy. We believe that our findings depicted in this manuscript provide a promising and translatable strategy that can enhance the overall

  16. Methods For Improving Polymeric Materials For Use In Solar Cell Applications

    Science.gov (United States)

    Hanoka, Jack I.

    2003-07-01

    A method of manufacturing a solar cell module includes the use of low cost polymeric materials with improved mechanical properties. A transparent encapsulant layer is placed adjacent a rear surface of a front support layer. Interconnected solar cells are positioned adjacent a rear surface of the transparent encapsulant layer to form a solar cell assembly. A backskin layer is placed adjacent a rear surface of the solar cell assembly. At least one of the transparent encapsulant layer and the backskin layer are predisposed to electron beam radiation.

  17. Ultrathin high band gap solar cells with improved efficiencies from the world's oldest photovoltaic material.

    Science.gov (United States)

    Todorov, Teodor K; Singh, Saurabh; Bishop, Douglas M; Gunawan, Oki; Lee, Yun Seog; Gershon, Talia S; Brew, Kevin W; Antunez, Priscilla D; Haight, Richard

    2017-09-25

    Selenium was used in the first solid state solar cell in 1883 and gave early insights into the photoelectric effect that inspired Einstein's Nobel Prize work; however, the latest efficiency milestone of 5.0% was more than 30 years ago. The recent surge of interest towards high-band gap absorbers for tandem applications led us to reconsider this attractive 1.95 eV material. Here, we show completely redesigned selenium devices with improved back and front interfaces optimized through combinatorial studies and demonstrate record open-circuit voltage (V OC ) of 970 mV and efficiency of 6.5% under 1 Sun. In addition, Se devices are air-stable, non-toxic, and extremely simple to fabricate. The absorber layer is only 100 nm thick, and can be processed at 200 ˚C, allowing temperature compatibility with most bottom substrates or sub-cells. We analyze device limitations and find significant potential for further improvement making selenium an attractive high-band-gap absorber for multi-junction device applications.Wide band gap semiconductors are important for the development of tandem photovoltaics. By introducing buffer layers at the front and rear side of solar cells based on selenium; Todorov et al., reduce interface recombination losses to achieve photoconversion efficiencies of 6.5%.

  18. [Expression and clinical significance of Pokemon in non-small cell lung cancer].

    Science.gov (United States)

    Zhao, Zhihong; Wang, Shengfa; Zhang, Tiewa

    2007-12-20

    Proto-oncogene Pokemon is the special transcription inhibitor of ARF,which can regulate cell growth and differentiation by ARF-P53 path.It may be the important monitoring target of tumor because of being upstream region of many tumor suppressor genes and proto-oncogenes.The aim of this study is to explore the clinical significance of Pokemon gene in non-small cell lung cancer(NSCLC). Immunohistochemistry was applied to detect the expression of Pokemon protein in 92 cases of NSCLC and 20 cases of paracancerous lung tissues.Correlation between abnormal expression of Pokemon with pathologic characteristics and prognosis of NSCLC was analyzed. Pokemon was not expressed in paracancerous lung tissues and was found in 66 of 92(71.7%) cases of lung cancer tissues.Expression of Pokemon was closely related to TNM stages(P=0.011).Survival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression(P=0.0015).Pokemon expression was demonstrated as independent prognostic factor of NSCLC. Pokemon is expressed in NSCLC and it may be identified as a new diagnostic marker.High expression of Pokemon may indicate poor prognosis of patients with NSCLC.

  19. Survival prediction algorithms miss significant opportunities for improvement if used for case selection in trauma quality improvement programs.

    Science.gov (United States)

    Heim, Catherine; Cole, Elaine; West, Anita; Tai, Nigel; Brohi, Karim

    2016-09-01

    Quality improvement (QI) programs have shown to reduce preventable mortality in trauma care. Detailed review of all trauma deaths is a time and resource consuming process and calculated probability of survival (Ps) has been proposed as audit filter. Review is limited on deaths that were 'expected to survive'. However no Ps-based algorithm has been validated and no study has examined elements of preventability associated with deaths classified as 'expected'. The objective of this study was to examine whether trauma performance review can be streamlined using existing mortality prediction tools without missing important areas for improvement. We conducted a retrospective study of all trauma deaths reviewed by our trauma QI program. Deaths were classified into non-preventable, possibly preventable, probably preventable or preventable. Opportunities for improvement (OPIs) involve failure in the process of care and were classified into clinical and system deviations from standards of care. TRISS and PS were used for calculation of probability of survival. Peer-review charts were reviewed by a single investigator. Over 8 years, 626 patients were included. One third showed elements of preventability and 4% were preventable. Preventability occurred across the entire range of the calculated Ps band. Limiting review to unexpected deaths would have missed over 50% of all preventability issues and a third of preventable deaths. 37% of patients showed opportunities for improvement (OPIs). Neither TRISS nor PS allowed for reliable identification of OPIs and limiting peer-review to patients with unexpected deaths would have missed close to 60% of all issues in care. TRISS and PS fail to identify a significant proportion of avoidable deaths and miss important opportunities for process and system improvement. Based on this, all trauma deaths should be subjected to expert panel review in order to aim at a maximal output of performance improvement programs. Copyright © 2016 Elsevier

  20. Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2α Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model

    Directory of Open Access Journals (Sweden)

    Weifeng Lu

    2017-01-01

    Full Text Available Mesenchymal stem cells (MSCs have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all P<0.05. rMSCHIF-2α transplantation also markedly increased the expression of proangiogenic factors VEGF, bFGF, and SDF1 and Notch signaling proteins including DII4, NICD, Hey1, and Hes1, whereas it reduced the expression of proapoptotic factor Bax in the muscle of the ischemic hindlimb. Overexpression of HIF-2α did not affect rMSC stemness and proliferation under normoxia but significantly increased rMSC migration and tube formation in matrigel under hypoxia (all P<0.05. RMSCsHIF-2α stimulated endothelial cell invasion under hypoxia significantly (P<0.05. Genetic modification of rMSCs via overexpression of HIF-2α improves posttransplantation outcomes in a rat hindlimb ischemia model possibly by stimulating proangiogenic growth factors and cytokines.

  1. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Che K

    2017-02-01

    Full Text Available Keying Che,1,* Yang Zhao,2,3,* Xiao Qu,1 Zhaofei Pang,1 Yang Ni,4 Tiehong Zhang,4 Jiajun Du,1,5 Hongchang Shen4 1Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 2Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 4Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 5Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Gastric carcinoma (GC is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.Materials and methods: Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS was statistically analyzed.Results: Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145 of them. Single cell invasion and large cell invasion were observed in 62.8% (186 and 16.9% (50 of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0

  2. Differentiated cells derived from fetal neural stem cells improve motor deficits in a rat model of Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Hao Song; Aifang Shen; Chao Chen; Yanming Liu; Yabing Dong; Fabin Han

    2015-01-01

    Objective: Parkinson’s disease(PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine(DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells(NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods: NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers: βⅢ‐tubulin and microtubule‐associated protein 2(neurons), tyrosine hydroxylase(DA neurons), and glial fibrillary acidic protein(glial cells). After a 6‐hydroxydopamine(6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results: The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions: Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

  3. Cell Adhesion Molecules and Ubiquitination—Functions and Significance

    Science.gov (United States)

    Homrich, Mirka; Gotthard, Ingo; Wobst, Hilke; Diestel, Simone

    2015-01-01

    Cell adhesion molecules of the immunoglobulin (Ig) superfamily represent the biggest group of cell adhesion molecules. They have been analyzed since approximately 40 years ago and most of them have been shown to play a role in tumor progression and in the nervous system. All members of the Ig superfamily are intensively posttranslationally modified. However, many aspects of their cellular functions are not yet known. Since a few years ago it is known that some of the Ig superfamily members are modified by ubiquitin. Ubiquitination has classically been described as a proteasomal degradation signal but during the last years it became obvious that it can regulate many other processes including internalization of cell surface molecules and lysosomal sorting. The purpose of this review is to summarize the current knowledge about the ubiquitination of cell adhesion molecules of the Ig superfamily and to discuss its potential physiological roles in tumorigenesis and in the nervous system. PMID:26703751

  4. Prognostic significance of overexpressed long non-coding RNA TUG1 in patients with clear cell renal cell carcinoma.

    Science.gov (United States)

    Wang, P-Q; Wu, Y-X; Zhong, X-D; Liu, B; Qiao, G

    2017-01-01

    The long non-coding RNAs (lncRNAs) study has gradually become one of the hot topics in the field of RNA biology. However, little is known about the pathological role of lncRNA TUG1 in clear cell renal cell carcinoma (ccRCC) patients. This study attempted to investigate the association of lncRNA TUG1 expression with progression and prognosis in ccRCC patients. Using qRT-PCR, the expression of TUG1 was measured in 203 ccRCC tissues and 45 adjacent non-cancerous tissues. Then, the relationships between TUG1 level and the clinicopathological factors of patients with ccRCC were analyzed. The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. The relative level of TUG1was significantly higher in ccRCC tissues compared to the adjacent non-tumor tissues (p TUG1 was associated significantly with histological grade, tumor stage, lymph node metastasis and distant metastasis (all p TUG1 expression levels were associated with a shorter overall survival (p TUG1 expression was an independent prognostic marker of poor outcome. These findings suggested that TUG1 may act as a tumor promoter in ccRCC and could serve as a potential therapeutic target for this tumor.

  5. Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation

    Directory of Open Access Journals (Sweden)

    Xiaojun Liu

    2017-05-01

    Full Text Available ABSTRACT The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell-based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB. The expanded T cells were phenotypically and functionally similar to T cells expanded by OKT3/IL-2. Moreover, co-electroporation of CD86 and 4-1BBL could further change the phenotype and enhance the in vivo anti-tumor activity. Although T cells expanded by the co-electroporation of OKT3-28BB with CD86 and 4-1BBL showed an increased central memory phenotype, the T cells still maintained tumor lytic activities as potent as those of OKT3/IL-2 or OKT3-28BB-stimulated T cells. In different tumor mouse models, T cells expanded by OKT3-28BB RNA electroporation showed anti-tumor activities superior to those of OKT3/IL-2 T cells. Hence, T cells with both a less differentiated phenotype and potent tumor killing ability can be generated by RNA electroporation, and this T cell manufacturing procedure can be further optimized by simply co-delivering other splices of RNA, thus providing a simple and cost-effective method for generating high-quality T cells for adoptive immunotherapy.

  6. An Improved Ghost-cell Immersed Boundary Method for Compressible Inviscid Flow Simulations

    KAUST Repository

    Chi, Cheng

    2015-01-01

    This study presents an improved ghost-cell immersed boundary approach to represent a solid body in compressible flow simulations. In contrast to the commonly used approaches, in the present work ghost cells are mirrored through the boundary

  7. l-asparaginase-based regimens followed by allogeneic hematopoietic stem cell transplantation improve outcomes in aggressive natural killer cell leukemia

    Directory of Open Access Journals (Sweden)

    Ki Sun Jung

    2016-04-01

    Full Text Available Abstract Aggressive nature killer cell leukemia (ANKL is a mature NK-T cell lymphoma with worse prognosis, but optimal treatment is unclear. Therefore, we analyzed the efficacy of l-asparaginase-based regimens for ANKL patients. Twenty-one patients who received dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE or etoposide, ifosfamide, dexamethasone, and l-asparaginase (VIDL chemotherapy at Samsung Medical Center were selected. The overall response rate for all patients was 33 % (7/21; 38 % (5/13 in SMILE and 40 % (2/5 in VIDL, respectively. The median progression-free survival was 3.9 months (95 % CI 0.0–8.1 months and median overall survival was 7.0 months (95 % CI 2.3–11.7 months. Treatment response (P = 0.001, hematopoietic stem cell transplantation (HSCT (P = 0.007 and negative conversion of Epstein-Barr virus (EBV DNA titer after treatment (P = 0.004 were significantly associated with survival. Thus, l-asparaginase-based regimens followed by allogeneic HSCT seem to improve the outcome for ANKL patients.

  8. Melatonin improves spermatogonial stem cells transplantation efficiency in azoospermic mice

    Directory of Open Access Journals (Sweden)

    Mohammadreza Gholami

    2014-02-01

    Conclusion: Administration of melatonin (20 mg/kg simultaneously with transplantation of spermatogonial stem cells in azoospermia mouse testis increases the efficiency of transplantation and improves structural properties of the testes tissue.

  9. An Improved Model for FE Modeling and Simulation of Closed Cell Al-Alloy Foams

    OpenAIRE

    Hasan, MD. Anwarul

    2010-01-01

    Cell wall material properties of Al-alloy foams have been derived by a combination of nanoindentation experiment and numerical simulation. Using the derived material properties in FE (finite element) modeling of foams, the existing constitutive models of closed-cell Al-alloy foams have been evaluated against experimental results. An improved representative model has been proposed for FE analysis of closed-cell Al-alloy foams. The improved model consists of a combination of spherical and cruci...

  10. Linnorm: improved statistical analysis for single cell RNA-seq expression data.

    Science.gov (United States)

    Yip, Shun H; Wang, Panwen; Kocher, Jean-Pierre A; Sham, Pak Chung; Wang, Junwen

    2017-12-15

    Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Cone-beam computed tomography analysis of accessory maxillary ostium and Haller cells: Prevalence and clinical significance

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Ibrahim K.; Sansare, Kaustubh; Karjodkar, Freny R.; Vanga, Kavita; Salve, Prashant [Dept. of Oral Medicine and Radiology, Nair Hospital Dental College, Mumbai (India); Pawar, Ajinkya M. [Dept. of Conservative Dentistry and Endodontics, Nair Hospital Dental College, Mumbai (India)

    2017-03-15

    This study aimed to evaluate the prevalence of Haller cells and accessory maxillary ostium (AMO) in cone-beam computed tomography (CBCT) images, and to analyze the relationships among Haller cells, AMO, and maxillary sinusitis. Volumetric CBCT scans from 201 patients were retrieved from our institution's Digital Imaging and Communications in Medicine archive folder. Two observers evaluated the presence of Haller cells, AMO, and maxillary sinusitis in the CBCT scans. AMO was observed in 114 patients, of whom 27 (23.7%) had AMO exclusively on the right side, 26 (22.8%) only on the left side, and 61 (53.5%) bilaterally. Haller cells were identified in 73 (36.3%) patients. In 24 (32.9%) they were present exclusively on the right side, in 17 (23.3%) they were only present on the left side, and in 32 (43.8%) they were located bilaterally. Of the 73 (36.3%) patients with Haller cells, maxillary sinusitis was also present in 50 (68.5%). On using chi-square test, a significant association was observed between AMO and maxillary sinusitis in the presence of Haller cells. Our results showed AMO and Haller cells to be associated with maxillary sinusitis. This study provides evidence for the usefulness of CBCT in imaging the bony anatomy of the sinonasal complex with significantly higher precision and a smaller radiation dose.

  12. Total sensitivity and uncertainty analysis for LWR pin-cells with improved UNICORN code

    International Nuclear Information System (INIS)

    Wan, Chenghui; Cao, Liangzhi; Wu, Hongchun; Shen, Wei

    2017-01-01

    Highlights: • A new model is established for the total sensitivity and uncertainty analysis. • The NR approximation applied in S&U analysis can be avoided by the new model. • Sensitivity and uncertainty analysis is performed to PWR pin-cells by the new model. • The effects of the NR approximation for the PWR pin-cells are quantified. - Abstract: In this paper, improvements to the multigroup cross-section perturbation model have been proposed and applied in the self-developed UNICORN code, which is capable of performing the total sensitivity and total uncertainty analysis for the neutron-physics calculations by applying the direct numerical perturbation method and the statistical sampling method respectively. The narrow resonance (NR) approximation was applied in the multigroup cross-section perturbation model, implemented in UNICORN. As improvements to the NR approximation to refine the multigroup cross-section perturbation model, an ultrafine-group cross-section perturbation model has been established, in which the actual perturbations are applied to the ultrafine-group cross-section library and the reconstructions of the resonance cross sections are performed by solving the neutron slowing-down equation. The total sensitivity and total uncertainty analysis were then applied to the LWR pin-cells, using both the multigroup and the ultrafine-group cross-section perturbation models. The numerical results show that the NR approximation overestimates the relative sensitivity coefficients and the corresponding uncertainty results for the LWR pin-cells, and the effects of the NR approximation are significant for σ_(_n_,_γ_) and σ_(_n_,_e_l_a_s_) of "2"3"8U. Therefore, the effects of the NR approximation applied in the total sensitivity and total uncertainty analysis for the neutron-physics calculations of LWR should be taken into account.

  13. Development of CAR T cells designed to improve antitumor efficacy and safety

    OpenAIRE

    Jaspers, Janneke E.; Brentjens, Renier J.

    2017-01-01

    Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are ‘on-target, off-tumor’ toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how ...

  14. Cytogenetic 'rogue' cells: Their frequency, origin, and evolutionary significance

    International Nuclear Information System (INIS)

    Awa, A.A.; Neel, J.V.

    1986-07-01

    Among 102,170 cultured lymphocytes obtained from 9,818 Hiroshima Japanese aged 9 to 37 years and scored for chromosomal abnormalities, 24 cells exhibiting an extreme degree of damage were encountered. The damage consists of multiple dicentric and even tricentric chromosomes, as well as numerous fragments, many with the appearance of 'double minutes'. The occurrence of these cells was not correlated with parental exposure to the atomic bomb, age, sex, year, or season. The distribution of chromosomal abnormalities by individual was nonrandom. Such cells were originally described in South American Indians, and have also been recorded in United States and United Kingdom inhabitants; this appears to be a worldwide phenomenon. Their cause remains unknown, nor is it known whether they occur in other somatic and also germ-line cells. Should the latter be the case, and should the least damaged of these cells occasionally successfully complete mitosis and meiosis, the possible role of such cells in oncogenesis and evolution must be considered. (author)

  15. Cytogenetic 'rogue' cells: Their frequency, origin, and evolutionary significance

    Energy Technology Data Exchange (ETDEWEB)

    Awa, A A; Neel, J V [Department of Genetics, University of Michigan Medical School (United States)

    1986-07-15

    Among 102,170 cultured lymphocytes obtained from 9,818 Hiroshima Japanese aged 9 to 37 years and scored for chromosomal abnormalities, 24 cells exhibiting an extreme degree of damage were encountered. The damage consists of multiple dicentric and even tricentric chromosomes, as well as numerous fragments, many with the appearance of 'double minutes'. The occurrence of these cells was not correlated with parental exposure to the atomic bomb, age, sex, year, or season. The distribution of chromosomal abnormalities by individual was nonrandom. Such cells were originally described in South American Indians, and have also been recorded in United States and United Kingdom inhabitants; this appears to be a worldwide phenomenon. Their cause remains unknown, nor is it known whether they occur in other somatic and also germ-line cells. Should the latter be the case, and should the least damaged of these cells occasionally successfully complete mitosis and meiosis, the possible role of such cells in oncogenesis and evolution must be considered. (author)

  16. Improved neurological outcome by intramuscular injection of human amniotic fluid derived stem cells in a muscle denervation model.

    Directory of Open Access Journals (Sweden)

    Chun-Jung Chen

    Full Text Available The skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model.Seventy two Sprague-Dawley rats weighing 200-250 gm were enrolled in this study. Muscle denervation model was conducted by transverse resection of a sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve anastomosis model was performed by transverse resection of the sciatic nerve followed by four stitches reconnection. These animals were allocated to three groups: control, electrical muscle stimulation, and AFS groups.NT-3 (Neurotrophin 3, BDNF (Brain derived neurotrophic factor, CNTF (Ciliary neurotrophic factor, and GDNF (Glia cell line derived neurotrophic factor were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology.Intramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection furthermore improves the nerve

  17. Improved coking resistance of direct ethanol solid oxide fuel cells with a Ni-Sx anode

    Science.gov (United States)

    Yan, Ning; Luo, Jing-Li; Chuang, Karl T.

    2014-03-01

    In this study, the coking resistance of anode supported direct ethanol solid oxide fuel cell with a Ni-Sx anode was investigated comparatively with the conventional cell using pure Ni catalyst. The surface catalytic properties of Ni were manipulated via depositing a layer of S atoms. It was confirmed that on the surface of Ni, a combination of S monolayer and elemental S was formed without producing Ni3S2 phase. The developed Ni-Sx cell exhibited a significantly improved coke resistivity in ethanol feed while maintaining an adequately high performance. The S species on Ni enabled the suppression of the coke formation as well as the alleviation of the metal dusting effect of the anode structure. After operating in ethanol fuel for identical period of time at 850 °C, a maximum power density of 400 mW cm-2 was sustained whereas the conventional cell performance decreased to less than 40 mW cm-2 from the original 704 mW cm-2. In an optimized stability test, the Ni-Sx cell operated at 750 °C for more than 22 h until the fuel drained without any degradation.

  18. Cell culture medium improvement by rigorous shuffling of components using media blending.

    Science.gov (United States)

    Jordan, Martin; Voisard, Damien; Berthoud, Antoine; Tercier, Laetitia; Kleuser, Beate; Baer, Gianni; Broly, Hervé

    2013-01-01

    A novel high-throughput methodology for the simultaneous optimization of many cell culture media components is presented. The method is based on the media blending approach which has several advantages as it works with ready-to-use media. In particular it allows precise pH and osmolarity adjustments and eliminates the need of concentrated stock solutions, a frequent source of serious solubility issues. In addition, media blending easily generates a large number of new compositions providing a remarkable screening tool. However, media blending designs usually do not provide information on distinct factors or components that are causing the desired improvements. This paper addresses this last point by considering the concentration of individual medium components to fix the experimental design and for the interpretation of the results. The extended blending strategy was used to reshuffle the 20 amino acids in one round of experiments. A small set of 10 media was specifically designed to generate a large number of mixtures. 192 mixtures were then prepared by media blending and tested on a recombinant CHO cell line expressing a monoclonal antibody. A wide range of performances (titers and viable cell density) was achieved from the different mixtures with top titers significantly above our previous results seen with this cell line. In addition, information about major effects of key amino acids on cell densities and titers could be extracted from the experimental results. This demonstrates that the extended blending approach is a powerful experimental tool which allows systematic and simultaneous reshuffling of multiple medium components.

  19. Effect of Non-Stoichiometric Solution Chemistry on Improving the Performance of Wide-Bandgap Perovskite Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Kai [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Yang, Mengjin [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kim, Donghoe [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Li, Zhen [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Reid, Obadiah G [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Yu, Yue [University of Toledo; Song, Zhaoning [University of Toledo; Zhao, Dewei [University of Toledo; Wang, Changlei [University of Toledo; Li, Liwei [ENN Energy Research Institute; ENN Solar Energy Co., Ltd.; Meng, Yuan [ENN Energy Research Institute; ENN Solar Energy Co., Ltd.; Guo, Ted [ENN Energy Research Institute; ENN Solar Energy Co., Ltd.; Yan, Yanfa [University of Toledo

    2017-10-18

    A high-efficiency wide-bandgap (WBG) perovskite solar cell is critical for developing perovskite-related (e.g., all-perovskite, perovskite/Si, or perovskite/Cu(In,Ga)Se2) tandem devices. Here, we demonstrate the use of non-stoichiometric precursor chemistry with excess methylammonium halides (MAX; X = I, Br, or Cl) for preparing high-quality ~1.75-eV FA0.83Cs0.17Pb(I0.6Br0.4)3 perovskite solar cells. Among various methylammonium halides, using excess MABr in the non-stoichiometric precursor exhibits the strongest effect on improving perovskite crystallographic properties and device characteristics without affecting the perovskite composition. In contrast, using excess MAI significantly reduces the bandgap of perovskite due to the replacement of Br with I. Using 40% excess MABr, we demonstrate a single-junction WBG perovskite solar cell with stabilized efficiency of 16.4%. We further demonstrate a 20.3%-efficient 4-terminal tandem device by using a 14.7%-efficient semi-transparent WBG perovskite top cell and an 18.6%-efficient unfiltered (5.6%-efficient filtered) Si bottom cell.

  20. Methods for Using Small Non-Coding RNAs to Improve Recombinant Protein Expression in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Sarah Inwood

    2018-01-01

    Full Text Available The ability to produce recombinant proteins by utilizing different “cell factories” revolutionized the biotherapeutic and pharmaceutical industry. Chinese hamster ovary (CHO cells are the dominant industrial producer, especially for antibodies. Human embryonic kidney cells (HEK, while not being as widely used as CHO cells, are used where CHO cells are unable to meet the needs for expression, such as growth factors. Therefore, improving recombinant protein expression from mammalian cells is a priority, and continuing effort is being devoted to this topic. Non-coding RNAs are RNA segments that are not translated into a protein and often have a regulatory role. Since their discovery, major progress has been made towards understanding their functions. Non-coding RNA has been investigated extensively in relation to disease, especially cancer, and recently they have also been used as a method for engineering cells to improve their protein expression capability. In this review, we provide information about methods used to identify non-coding RNAs with the potential of improving recombinant protein expression in mammalian cell lines.

  1. Mechanical Adaptability of the MMP-Responsive Film Improves the Functionality of Endothelial Cell Monolayer.

    Science.gov (United States)

    Hu, Mi; Chang, Hao; Zhang, He; Wang, Jing; Lei, Wen-Xi; Li, Bo-Chao; Ren, Ke-Feng; Ji, Jian

    2017-07-01

    Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Use of piracetam improves sickle cell deformability in vitro and in vivo.

    Science.gov (United States)

    Gini, E K; Sonnet, J

    1987-01-01

    Microsieving diluted suspensions of oxygenated sickle cell anaemia (HbSS) cells on polycarbonate filters shows that piracetam improves the red cell deformability in vitro. In vivo an oral intake of 160 mg/kg/day divided in four doses enhances the HbSS cell deformability as actively as it does in in vitro experiments. The drug is also able partially to restore the impaired deformability of physiologically deoxygenated HbSS cells. These findings are consistent with the results of clinical trials, which show that continuous treatment with piracetam reduces the incidence of vaso-occlusive crises in patients with sickle cell disease. PMID:3818978

  3. Improvement of mouse cloning using nuclear transfer-derived embryonic stem cells and/or histone deacetylase inhibitor.

    Science.gov (United States)

    Wakayama, Sayaka; Wakayama, Teruhiko

    2010-01-01

    Nuclear transfer-derived ES (ntES) cell lines can be established from somatic cell nuclei with a relatively high success rate. Although ntES cells have been shown to be equivalent to ES cells, there are ethical objections concerning human cells, such as the use of fresh oocyte donation from young healthy woman. In contrast, the use of induced pluripotent stem (iPS) cells for cloning poses few ethical problems and is a relatively easy technique compared with nuclear transfer. Therefore, although there are several reports proposing the use of ntES cells as a model of regenerative medicine, the use of these cells in preliminary medical research is waning. However, in theory, 5 to 10 donor cells can establish one ntES cell line and, once established, these cells will propagate indefinitely. These cells can be used to generate cloned animals from ntES cell lines using a second round of NT. Even in infertile and "unclonable" strains of mice, we can generate offspring from somatic cells by combining cloning with ntES technology. Moreover, cloned offspring can be generated potentially even from the nuclei of dead bodies or freeze-dried cells via ntES cells, such as from an extinct frozen animal. Currently, only the ntES technology is available for this purpose, because all other techniques, including iPS cell derivation, require significant numbers of living donor cells. This review describes how to improve the efficiency of cloning, the establishment of clone-derived embryonic stem cells and further applications.

  4. Improvement of mammalian cell culture performance through surfactant enabled concentrated feed media.

    Science.gov (United States)

    Hossler, Patrick; McDermott, Sean; Racicot, Christopher; Fann, John C H

    2013-01-01

    The design of basal and feed media in mammalian cell culture is paramount towards ensuring acceptable upstream process performance in various operation modes, especially fed-batch culture. Mammalian cell culture media designs have evolved from the classical formulations designed by Eagle and Ham, to today's formulations designed from continuous improvement and statistical frameworks. Feed media is especially important for ensuring robust cell growth, productivity, and ensuring the product quality of recombinant therapeutics are within acceptable ranges. Numerous studies have highlighted the benefit of various media designs, supplements, and feed addition strategies towards the resulting cell culture process. In this work we highlight the use of a top-down level approach towards feed media design enabled by the use of select surfactants for the targeted enrichment of a chemically defined feed media. The use of the enriched media was able to improve product titers at g/L levels, without adversely impacting the growth of multiple Chinese Hamster Ovary cell lines or the product quality of multiple recombinant antibodies. © 2013 American Institute of Chemical Engineers.

  5. The significance of caveolin-1 expression in parietal epithelial cells of Bowman's capsule.

    Science.gov (United States)

    Ostalska-Nowicka, D; Nowicki, M; Zachwieja, J; Kasper, M; Witt, M

    2007-11-01

    To analyse the expression of caveolin-1 in normal human kidney and during diseases leading to nephrotic syndrome in children and to compare its pattern with those observed in control samples, both human and animal. The study group was composed of 104 children diagnosed with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), lupus glomerulonephritis (LGN) and Schönlein-Henoch glomerulopathy (SH). The research protocol employed direct immunohistochemical assay with the use of mono- and polyclonal antibodies against caveolins. Kidney samples of Wistar rats, wild-type mice and caveolin-1-deficient mice were also analysed. In the control human samples, caveolin-1 was most abundant in the muscle layer of blood vessels and parietal epithelial cells (PECs). Its expression in PECs was significantly lower in children diagnosed with FSGS and LGN than in those with MCD, SH or in controls. In the control animal tissues, except for knock-out mice, caveolin-1 was present in distal convoluted tubules, PECs, endothelial cells and muscle. Caveolae are extremely stable elements of PECs and can be excluded from their cell membrane only in response to the dramatic cell reconstruction observed in FSGS and LGN.

  6. Nanoscale Dimples for Improved Absorption in and Efficiency of Organic Solar Cells

    DEFF Research Database (Denmark)

    Goszczak, Arkadiusz Jaroslaw; Adam, Jost; Cielecki, Pawel Piotr

    Organic solar cells (OSC’s) have attracted much attention in the past years due to their low costs, light weight and mechanical flexibility. A promising method for improving the power conversion efficiencies of the devices is by incorporating structured electrodes in the solar cell architecture....... That way light absorption in the active layers of the devices can be improved. A cheap and large-scale production compatible method for structuring the electrodes in OSC’s is by the use of Anodic Alumina Oxide (AAO) membranes. Here, nano-scale pores of controlled dimensions are formed through anodic...

  7. High Intensity Interval Training Improves Glycaemic Control and Pancreatic β Cell Function of Type 2 Diabetes Patients

    Science.gov (United States)

    Madsen, Søren Møller; Thorup, Anne Cathrine; Overgaard, Kristian; Jeppesen, Per Bendix

    2015-01-01

    Physical activity improves the regulation of glucose homeostasis in both type 2 diabetes (T2D) patients and healthy individuals, but the effect on pancreatic β cell function is unknown. We investigated glycaemic control, pancreatic function and total fat mass before and after 8 weeks of low volume high intensity interval training (HIIT) on cycle ergometer in T2D patients and matched healthy control individuals. Study design/method: Elderly (56 yrs±2), non-active T2D patients (n = 10) and matched (52 yrs±2) healthy controls (CON) (n = 13) exercised 3 times (10×60 sec. HIIT) a week over an 8 week period on a cycle ergometer. Participants underwent a 2-hour oral glucose tolerance test (OGTT). On a separate day, resting blood pressure measurement was conducted followed by an incremental maximal oxygen uptake (V˙O2max) cycle ergometer test. Finally, a whole body dual X-ray absorptiometry (DXA) was performed. After 8 weeks of training, the same measurements were performed. Results: in the T2D-group, glycaemic control as determined by average fasting venous glucose concentration (p = 0.01), end point 2-hour OGTT (p = 0.04) and glycosylated haemoglobin (p = 0.04) were significantly reduced. Pancreatic homeostasis as determined by homeostatic model assessment of insulin resistance (HOMA-IR) and HOMA β cell function (HOMA-%β) were both significantly ameliorated (p = 0.03 and p = 0.03, respectively). Whole body insulin sensitivity as determined by the disposition index (DI) was significantly increased (p = 0.03). During OGTT, the glucose continuum was significantly reduced at -15 (p = 0.03), 30 (p = 0.03) and 120 min (p = 0.03) and at -10 (p = 0.003) and 0 min (p = 0.003) with an additional improvement (p = 0.03) of its 1st phase (30 min) area under curve (AUC). Significant abdominal fat mass losses were seen in both groups (T2D: p = 0.004 and CON: p = 0.02) corresponding to a percentage change of -17.84%±5.02 and -9.66%±3.07, respectively. Conclusion: these results

  8. High Intensity Interval Training Improves Glycaemic Control and Pancreatic β Cell Function of Type 2 Diabetes Patients.

    Directory of Open Access Journals (Sweden)

    Søren Møller Madsen

    Full Text Available Physical activity improves the regulation of glucose homeostasis in both type 2 diabetes (T2D patients and healthy individuals, but the effect on pancreatic β cell function is unknown. We investigated glycaemic control, pancreatic function and total fat mass before and after 8 weeks of low volume high intensity interval training (HIIT on cycle ergometer in T2D patients and matched healthy control individuals. Study design/method: Elderly (56 yrs±2, non-active T2D patients (n = 10 and matched (52 yrs±2 healthy controls (CON (n = 13 exercised 3 times (10×60 sec. HIIT a week over an 8 week period on a cycle ergometer. Participants underwent a 2-hour oral glucose tolerance test (OGTT. On a separate day, resting blood pressure measurement was conducted followed by an incremental maximal oxygen uptake (VO2max cycle ergometer test. Finally, a whole body dual X-ray absorptiometry (DXA was performed. After 8 weeks of training, the same measurements were performed. Results: in the T2D-group, glycaemic control as determined by average fasting venous glucose concentration (p = 0.01, end point 2-hour OGTT (p = 0.04 and glycosylated haemoglobin (p = 0.04 were significantly reduced. Pancreatic homeostasis as determined by homeostatic model assessment of insulin resistance (HOMA-IR and HOMA β cell function (HOMA-%β were both significantly ameliorated (p = 0.03 and p = 0.03, respectively. Whole body insulin sensitivity as determined by the disposition index (DI was significantly increased (p = 0.03. During OGTT, the glucose continuum was significantly reduced at -15 (p = 0.03, 30 (p = 0.03 and 120 min (p = 0.03 and at -10 (p = 0.003 and 0 min (p = 0.003 with an additional improvement (p = 0.03 of its 1st phase (30 min area under curve (AUC. Significant abdominal fat mass losses were seen in both groups (T2D: p = 0.004 and CON: p = 0.02 corresponding to a percentage change of -17.84%±5.02 and -9.66%±3.07, respectively. Conclusion: these results

  9. The effect of isolation and culture methods on epithelial stem cell populations and their progeny-toward an improved cell expansion protocol for clinical application.

    Science.gov (United States)

    Lenihan, Catherine; Rogers, Caroline; Metcalfe, Anthony D; Martin, Yella H

    2014-12-01

    The use of cultured epithelial keratinocytes in the treatment of burns and skin graft donor sites is well established in clinical practice. The most widely used culture method for clinical use was originally developed by Rheinwald and Green 40 years ago. This system uses irradiated mouse dermal fibroblasts as a feeder cell layer to promote keratinocyte growth, a process that is costly and labor-intensive for health care providers. The medium formulation contains several components of animal origin, which pose further safety risks for patients. Improvements and simplification in the culturing process would lead to clear advantages: improved safety through reduction of xenobiotic components and reduction in cost for health care providers by dispensing with feeder cells. We compared the Rheinwald and Green method to culture in three commercially available, feeder-free media systems with defined/absent components of animal origin. During the isolation process, short incubation times in high-strength trypsin resulted in increased numbers of liberated keratinocyte stem cells compared with longer incubation times. All three commercially available media tested in this study could support the expansion of keratinocytes, with phenotypes comparable to cells expanded using the established Rheinwald and Green method. Growth rates varied, with two of the media displaying comparable growth rates, whereas the third was significantly slower. Our study demonstrates the suitability of such feeder-free media systems in clinical use. It further outlines a range of techniques to evaluate keratinocyte phenotype when assessing the suitability of cells for clinical application. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  10. Tumor-Infiltrating Merkel Cell Polyomavirus-Specific T Cells Are Diverse and Associated with Improved Patient Survival. | Office of Cancer Genomics

    Science.gov (United States)

    Tumor-infiltrating CD8+ T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8+ T-cell infiltration is robust in only 4% to 18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome.

  11. Improving the Efficiency of Organic Solar Cells upon Addition of Polyvinylpyridine

    Directory of Open Access Journals (Sweden)

    Rita Rodrigues

    2014-12-01

    Full Text Available We report on the efficiency improvement of organic solar cells (OPVs based on the low energy gap polyfluorene derivative, APFO-3, and the soluble C60 fullerene PCBM, upon addition of a residual amount of poly (4-vinylpyridine (PVP. We find that the addition of 1% by weight of PVP with respect to the APFO-3 content leads to an increase of efficiency from 2.4% to 2.9%. Modifications in the phase separation details of the active layer were investigated as a possible origin of the efficiency increase. At high concentrations of PVP, the blend morphology is radically altered as observed by Atomic Force Microscopy. Although the use of low molecular weight additives is a routine method to improve OPVs efficiency, this report shows that inert polymers, in terms of optical and charge transport properties, may also improve the performance of polymer-based solar cells.

  12. The presence and prognostic significance of human papillomavirus in squamous cell carcinoma of the larynx.

    Science.gov (United States)

    Erkul, Evren; Yilmaz, Ismail; Narli, Gizem; Babayigit, Mustafa Alparslan; Gungor, Atila; Demirel, Dilaver

    2017-07-01

    The aim of the present study was to evaluate the role of HPV in laryngeal squamous cell carcinoma and correlate it with patients' clinicopathological data. In total, 78 laryngeal squamous cell carcinoma patients enrolled in this study. The presence of genotype-specific HPV DNA was evaluated using Genotyping Assay in formalin-fixed paraffin-embedded tissue which was diagnosed between 2005 and 2015. All samples were also evaluated for p16 immunohistochemical staining. HPV DNA and p16 status were assessed in terms of location, smoking, alcohol consumption, lymph node status, tumor stage, overall survival, disease-free survival, perineural invasion, and vascular invasion retrospectively. Five test samples were excluded from the study due to inadequate deoxyribonucleic acid purity. HPV DNA was detected in 19 of 73 (26.02%) in patients with laryngeal squamous cell carcinoma. Human papilloma virus genotyping revealed double human papilloma virus in one case (types 16 and 59) and HPV 16 in the remaining cases. Although HPV-positive cases showed slightly better 3 years survival than HPV-negative ones, this finding was not statistically significant (overall survival p = 0.417, HPV positive: 92.3%, HPV negative: 81.4%, and disease-free survival p = 0.526, HPV positive: 93.8%, HPV negative: 80.9%). The presence of HPV DNA was not significantly associated with any clinicopathological features (p > 0.05). Among 73 patients, only 4 had an immunohistochemical staining of p16 and these patients were also HPV DNA 16 positive. Although our study results revealed a slightly better survival in patients with HPV DNA positivity for HPV 16 compared to the negative ones, the difference was not statistically significant. However, an increasing rate in especially high-risk-type HPV-16 prevalence in laryngeal squamous cell carcinoma by RT-PCR method was observed compared to our previous study. Although the presence of HPV in laryngeal SCCs seems to be associated with slightly better

  13. [Detection of NK and NKT cells in peripheral blood of patients with cGVHD and its significance].

    Science.gov (United States)

    Zhou, Mao-Hua; Wang, Chun-Miao; Gong, Cai-Ping; Luo, Yin; Zhang, Min

    2012-10-01

    The aim of this study was to investigate the correlation of NK and NKT cells in peripheral blood of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (cGVHD). 64 patients undergoing allo-HSCT in Guangdong Provincial People Hospital were studied retrospectively. Among 64 cases, 21 cases were did not develop with cGVHD, 43 cases (mild 15, moderate 18, severe 10) were recorded with cGVHD. The frequency of NK and NKT cells in peripheral blood of patients were measured by flow cytometry. The counts of NK and NKT cells were measured by automatic five sort hematology cyto-analyser (LH-750). The frequency and counts of NK and NKT cells between patients with non-cGVHD and patients with different status of cGVHD were analysed. The results indicated that as compared with the non-cGVHD patients, the frequency and counts of NK cells in patients with cGVHD obviously reduced (P NKT cells were did not changed significantly. The frequency and counts of NK cells gradually decreased within the different status of cGVHD, the frequency and counts of NK cells in severe-cGVHD were significantly lower than that in mild-cGVHD. It is concluded that NK cells may play an important role in the incidence and development of cGVHD. The detection of frequency and counts of NK cells should be helpful to early diagnose cGVHD and provide valuable clues for assessing the severity of illnesses. NKT cells may have little effect on the incidence and development of cGVHD.

  14. Improved contact metallization for high efficiency EFG polycrystalline silicon solar cells

    International Nuclear Information System (INIS)

    Dube, C.E.; Gonsiorawski, R.C.

    1990-01-01

    Improvements in the performance of polycrystalline silicon solar cells based on a novel, laser patterned contact process are described. Small lots of cells having an average conversion efficiency of 14 + %, with several cells approaching 15%, are reported for cells of 45 cm 2 area. The high efficiency contact design is based on YAG laser patterning of the silicon nitride anti-reflection coating. The Cu metallization is done using light-induced plating, with the cell providing the driving voltage for the plating process. The Cu electrodeposits into the laser defined windows in the AR coating for reduced contact area, following which the Cu bridges on top of the Ar coating to form a continuous finger pattern. The higher cell conversion efficiency is attributed to reduced shadow loss, higher junction quality, and reduced metal-semiconductor interfacial area

  15. Significant improvement in one-dimensional cursor control using Laplacian electroencephalography over electroencephalography

    Science.gov (United States)

    Boudria, Yacine; Feltane, Amal; Besio, Walter

    2014-06-01

    Objective. Brain-computer interfaces (BCIs) based on electroencephalography (EEG) have been shown to accurately detect mental activities, but the acquisition of high levels of control require extensive user training. Furthermore, EEG has low signal-to-noise ratio and low spatial resolution. The objective of the present study was to compare the accuracy between two types of BCIs during the first recording session. EEG and tripolar concentric ring electrode (TCRE) EEG (tEEG) brain signals were recorded and used to control one-dimensional cursor movements. Approach. Eight human subjects were asked to imagine either ‘left’ or ‘right’ hand movement during one recording session to control the computer cursor using TCRE and disc electrodes. Main results. The obtained results show a significant improvement in accuracies using TCREs (44%-100%) compared to disc electrodes (30%-86%). Significance. This study developed the first tEEG-based BCI system for real-time one-dimensional cursor movements and showed high accuracies with little training.

  16. Improving B-cell depletion in systemic lupus erythematosus and rheumatoid arthritis.

    Science.gov (United States)

    Mota, Pedro; Reddy, Venkat; Isenberg, David

    2017-07-01

    Rituximab-based B-cell depletion (BCD) therapy is effective in refractory rheumatoid arthritis (RA) and although used to treat patients with refractory systemic lupus erythematosus (SLE) in routine clinical practice, rituximab failed to meet the primary endpoints in two large randomised controlled trials (RCTs) of non-renal (EXPLORER) and renal (LUNAR) SLE. Areas covered: We review how BCD could be improved to achieve better clinical responses in RA and SLE. Insights into the variability in clinical response to BCD in RA and SLE may help develop new therapeutic strategies. To this end, a literature search was performed using the following terms: rheumatoid arthritis, systemic erythematosus lupus, rituximab and B-cell depletion. Expert commentary: Poor trial design may have, at least partly, contributed to the apparent lack of response to BCD in the two RCTs of patients with SLE. Enhanced B-cell depletion and/or sequential therapy with belimumab may improve clinical response at least in some patients with SLE.

  17. Lanthanide-Doped Ceria Nanoparticles as Backside Coaters to Improve Silicon Solar Cell Efficiency.

    Science.gov (United States)

    Hajjiah, Ali; Samir, Effat; Shehata, Nader; Salah, Mohamed

    2018-05-23

    This paper introduces lanthanide-doped ceria nanoparticles as silicon solar cell back-side coaters, showing their influence on the solar cell efficiency. Ceria nanoparticles can be synthesized to have formed oxygen vacancies (O-vacancies), which are associated with converting cerium ions from the Ce 4+ state ions to the Ce 3+ ones. These O-vacancies follow the rule of improving silicon solar cell conductivity through a hopping mechanism. Besides, under near-ultra violet (near-UV) excitation, the reduced trivalent cerium Ce 3+ ions are directly responsible for down converting the un-absorbed UV wavelengths to a resultant green photo-luminescence emission at ~520 nm, which is absorbed through the silicon solar cell’s active layer. Adding lanthanide elements such as Neodymium “Nd” as ceria nanoparticle dopants helps in forming extra oxygen vacancies (O-vacancies), followed by an increase in the number of Ce 4+ to Ce 3+ ion reductions, thus enhancing the conductivity and photoluminescence down conversion mechanisms. After introducing lanthanide-doped ceria nanoparticles on a silicon solar cell surface, a promising enhancement in the behavior of the solar cell current-voltage curve is observed, and the efficiency is improved by about 25% of its initial value due to the mutual impact of improving both electric conductivity and optical conversions.

  18. Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines.

    Science.gov (United States)

    Romano, Paolo; Manniello, Assunta; Aresu, Ottavia; Armento, Massimiliano; Cesaro, Michela; Parodi, Barbara

    2009-01-01

    The Cell Line Data Base (CLDB) is a well-known reference information source on human and animal cell lines including information on more than 6000 cell lines. Main biological features are coded according to controlled vocabularies derived from international lists and taxonomies. HyperCLDB (http://bioinformatics.istge.it/hypercldb/) is a hypertext version of CLDB that improves data accessibility by also allowing information retrieval through web spiders. Access to HyperCLDB is provided through indexes of biological characteristics and navigation in the hypertext is granted by many internal links. HyperCLDB also includes links to external resources. Recently, an interest was raised for a reference nomenclature for cell lines and CLDB was seen as an authoritative system. Furthermore, to overcome the cell line misidentification problem, molecular authentication methods, such as fingerprinting, single-locus short tandem repeat (STR) profile and single nucleotide polymorphisms validation, were proposed. Since this data is distributed, a reference portal on authentication of human cell lines is needed. We present here the architecture and contents of CLDB, its recent enhancements and perspectives. We also present a new related database, the Cell Line Integrated Molecular Authentication (CLIMA) database (http://bioinformatics.istge.it/clima/), that allows to link authentication data to actual cell lines.

  19. Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer

    Science.gov (United States)

    Diniz, Bruno; Thomas, Padmaja; Thomas, Biju; Ribeiro, Ramiro; Hu, Yuntao; Brant, Rodrigo; Ahuja, Ashish; Zhu, Danhong; Liu, Laura; Koss, Michael; Maia, Mauricio; Chader, Gerald; Hinton, David R.; Humayun, Mark S.

    2013-01-01

    Purpose. To evaluate cell survival and tumorigenicity of human embryonic stem cell–derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM). Methods. Sixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker). Results. The implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group. Conclusions. hESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. The lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects. PMID:23833067

  20. A clinically based prognostic index for diffuse large B-cell lymphoma with a cut-off at 70 years of age significantly improves prognostic stratification

    DEFF Research Database (Denmark)

    Gang, Anne O.; Pedersen, Michael; d'Amore, Francesco

    2015-01-01

    The introduction of rituximab and generally improved health among elderly patients have increased the survival of patients with diffuse large B-cell lymphoma (DLBCL). The International Prognostic Index (IPI) from 1992 is based on pre-rituximab data from clinical trials including several lymphoma ...... dehydrogenase (LDH), stage and albumin level, and (2) a separate age-adjusted DLBCL-PI for patients 1 extranodal lesion, however excluding stage....... subtypes. We applied IPI factors to a population-based rituximab-treated cohort of 1990 patients diagnosed 2000-2010 and explored new factors and the optimal prognostic age cut-off for DLBCL. Multivariate-analyses (MVA) confirmed the prognostic value of all IPI factors except the presence of > 1 extranodal...... lesion. The optimal age cut-off was 70 years. In a MVA of albumin, lymphocyte count, sex, immunoglobulin G, bulky disease, hemoglobin and B-symptoms, only albumin was prognostic. We propose: (1) a modified DLBCL prognostic index (DLBCL-PI) including: age (70 years), performance status (PS), lactate...

  1. An improved out-cell to in-cell rapid transfer system at the HFEF-south

    International Nuclear Information System (INIS)

    Bacca, J.P.; Sherman, E.K.

    1990-01-01

    The Argonne National Laboratory (ANL) Hot Fuel Examination Facility-South (HFEF-S), located at the ANL-West site of the Idaho National Engineering Laboratory, is currently undergoing extensive refurbishment and modifications in preparation for its use, beginning in 1991, in demonstrating remote recycling of fast reactor, metal-alloy fuel as part of the US Department of Energy liquid-metal reactor, Integral Fast Reactor (IFR) program. Included in these improvements to HFEF-S is a new, small-item, rapid transfer system (RTS). When installed, this system will enable the rapid transfer of small items from the hot-cell exterior into the argon cell (argon-gas atmosphere) of the facility without necessitating the use of time-consuming and laborious procedures. The new RTS will also provide another important function associated with HFEF-S hot-cell operation in the IFR Fuel Recycle Program; namely, the rapid insertion of clean, radioactive contamination-measuring smear paper specimens into the hot cells for area surveys, and the expedited removal of these contaminated (including alpha as well as beta/gamma contamination) smears from the argon cell for transfer to an adjacent health physics field laboratory in the facility for nuclear contamination/radiation counting

  2. Improvement in therapeutic ability of wharton's jelly derived mesenchymal stem cells with vitamin e in breast cancer

    International Nuclear Information System (INIS)

    Wajid, N.; Azam, M.; Khalid, S.; Qazi, M.H.

    2017-01-01

    To assess the role of Vitamin E to improve the survival of Wharton's jelly derived mesenchymal stem cells (WJMSCs) in breast cancer conditions. Study Design:An experimental study. Place and Duration of Study:Centre for Research in Molecular Medicine, University of Lahore, from November 2016 to March 2017. Methodology:WJMSCs were obtained from umbilical cord tissue with enzyme digestion method. Isolated cells were characterized for CD90 and CD45 by immunocytochemistry. Pretreatment and conjugation therapies of vitamin E in 50mM and 100mM concentration were used on WJMSCs and breast cancer plasma was provided to mimic the cancer conditions, while WJMSCs provided with normal plasma were considered control. Cells' viability, proliferation and death were evaluated by crystal violet staining, MTT assay and LDH assay, respectively. Oxidative stress was observed by activity of anti-oxidant enzymes (GSH, catalase, SOD) and reactive oxygen species (MDA). Results:The isolated cells expressed mesenchymal stem cells marker CD90 and lacked hematopoietic marker CD45. Vitamin E improved the viability and proliferation of WJMSCs in normal plasma, in conjugation with breast cancer plasma and in pretreatment groups but conjugation group showed even better results with concentration of 100mM as compared to the pretreatment group and opposite was observed for LDH assay for cells death analysis. Vitamin E also reduced the oxidative stress in 100mM more pronounced in conjugation group as compared to pretreatment group while left no harmful effects on WJMSCs in normal plasma. Conclusion:Vitamin E conjugation with breast cancer conditions significantly improved growth of WJMSCs. Thus vitamin E treated WJMSCs are better therapeutic options for breast cancer. (author)

  3. Clinicopathological significance of fascin-1 expression in patients with non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ling XL

    2015-06-01

    Full Text Available Xiao-Ling Ling,* Tao Zhang,* Xiao-Ming Hou, Da Zhao Department of Oncology, The First Hospital of Lanzhou University (The Branch Hospital of Donggang, Lanzhou, Gansu Province, People’s Republic of China *These authors contributed equally to this work Purpose: Fascin-1 promotes the formation of filopodia, lamellipodia, and microspikes of cell membrane after its cross-linking with F-actin, thereby enhancing the cell movement and metastasis and invasion of tumor cells. This study explored the fascin-1 protein’s expression in non-small cell lung cancer (NSCLC tissues and its relationship with clinical pathology and prognostic indicators.Methods: Immunohistochemical analysis was used to determine the expression of fascin-1 in NSCLC tissues. We used quantitative real-time polymerase chain reaction and western blot analysis to further verify the results. The fascin-1 expression and statistical method for clinical pathological parameters are examined by χ2. Kaplan–Meier method is used for survival analysis. Cox’s Proportional Hazard Model was used to conduct a combined-effect analysis for each covariate.Results: In 73 of the 128 cases, NSCLC cancer tissues (57.0% were found with high expression of fascin-1, which was significantly higher than the adjacent tissues (35/128, 27.3%. The results suggested that the high expression of fascin-1 was significantly correlated with lymph node metastasis (P=0.022 and TNM stage (P=0.042. The high fascin-1 expression patients survived shorter than those NSCLC patients with low fascin-1 expression (P<0.05. Univariate analysis revealed that lymph node metastasis, TNM stage, and fascin-1 expression status were correlated with the overall survival. Similarly, lymph node metastasis, TNM stage, and fascin-1 expression status were significantly associated with the overall survival in multivariate analyses by using the Cox regression model.Conclusion: The fascin-1 protein may be a useful prognostic indicator and

  4. Improved differentiation of umbilical cord blood-derived mesenchymal stem cells into insulin-producing cells by PDX-1 mRNA transfection.

    Science.gov (United States)

    Van Pham, Phuc; Thi-My Nguyen, Phuoc; Thai-Quynh Nguyen, Anh; Minh Pham, Vuong; Nguyen-Tu Bui, Anh; Thi-Tung Dang, Loan; Gia Nguyen, Khue; Kim Phan, Ngoc

    2014-06-01

    Numerous studies have sought to identify diabetes mellitus treatment strategies with fewer side effects. Mesenchymal stem cell (MSC) therapy was previously considered as a promising therapy; however, it requires the cells to be trans-differentiated into cells of the pancreatic-endocrine lineage before transplantation. Previous studies have shown that PDX-1 expression can facilitate MSC differentiation into insulin-producing cells (IPCs), but the methods employed to date use viral or DNA-based tools to express PDX-1, with the associated risks of insertional mutation and immunogenicity. Thus, this study aimed to establish a new method to induce PDX-1 expression in MSCs by mRNA transfection. MSCs were isolated from human umbilical cord blood and expanded in vitro, with stemness confirmed by surface markers and multipotentiality. MSCs were transfected with PDX-1 mRNA by nucleofection and chemically induced to differentiate into IPCs (combinatorial group). This IPC differentiation was then compared with that of untransfected chemically induced cells (inducer group) and uninduced cells (control group). We found that PDX-1 mRNA transfection significantly improved the differentiation of MSCs into IPCs, with 8.3±2.5% IPCs in the combinatorial group, 3.21±2.11% in the inducer group and 0% in the control. Cells in the combinatorial group also strongly expressed several genes related to beta cells (Pdx-1, Ngn3, Nkx6.1 and insulin) and could produce C-peptide in the cytoplasm and insulin in the supernatant, which was dependent on the extracellular glucose concentration. These results indicate that PDX-1 mRNA may offer a promising approach to produce safe IPCs for clinical diabetes mellitus treatment. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  5. Evidence Supporting Intralesional Stem Cell Therapy to Improve Equine Flexor Tendon Healing

    Directory of Open Access Journals (Sweden)

    Sushmitha Durgam

    2017-01-01

    Full Text Available Clinical bottom lineCurrent experimental evidence suggests that intralesional stem cell administration improves the histological characteristics and matrix organisation of healing equine superficial digital flexor tendons (SDFT; however, the clinical relevance of these findings are not clear. Current case-based evidence suggests that cell-based therapies improve the quality of tendon healing and reduce the recurrence rates of SDFT injuries but the lack of any randomised, controlled prospective studies with function-based outcomes is still concerning, given the widespread advocacy for and use of ‘stem cell’ therapies for the treatment of equine tendon injuries. 

  6. Phasic firing in vasopressin cells: understanding its functional significance through computational models.

    Directory of Open Access Journals (Sweden)

    Duncan J MacGregor

    Full Text Available Vasopressin neurons, responding to input generated by osmotic pressure, use an intrinsic mechanism to shift from slow irregular firing to a distinct phasic pattern, consisting of long bursts and silences lasting tens of seconds. With increased input, bursts lengthen, eventually shifting to continuous firing. The phasic activity remains asynchronous across the cells and is not reflected in the population output signal. Here we have used a computational vasopressin neuron model to investigate the functional significance of the phasic firing pattern. We generated a concise model of the synaptic input driven spike firing mechanism that gives a close quantitative match to vasopressin neuron spike activity recorded in vivo, tested against endogenous activity and experimental interventions. The integrate-and-fire based model provides a simple physiological explanation of the phasic firing mechanism involving an activity-dependent slow depolarising afterpotential (DAP generated by a calcium-inactivated potassium leak current. This is modulated by the slower, opposing, action of activity-dependent dendritic dynorphin release, which inactivates the DAP, the opposing effects generating successive periods of bursting and silence. Model cells are not spontaneously active, but fire when perturbed by random perturbations mimicking synaptic input. We constructed one population of such phasic neurons, and another population of similar cells but which lacked the ability to fire phasically. We then studied how these two populations differed in the way that they encoded changes in afferent inputs. By comparison with the non-phasic population, the phasic population responds linearly to increases in tonic synaptic input. Non-phasic cells respond to transient elevations in synaptic input in a way that strongly depends on background activity levels, phasic cells in a way that is independent of background levels, and show a similar strong linearization of the response

  7. Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

    Science.gov (United States)

    Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

    2017-11-30

    Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

  8. Modular Approach for Continuous Cell-Level Balancing to Improve Performance of Large Battery Packs: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Muneed ur Rehman, M.; Evzelman, M.; Hathaway, K.; Zane, R.; Plett, G. L.; Smith, K.; Wood, E.; Maksimovic, D.

    2014-10-01

    Energy storage systems require battery cell balancing circuits to avoid divergence of cell state of charge (SOC). A modular approach based on distributed continuous cell-level control is presented that extends the balancing function to higher level pack performance objectives such as improving power capability and increasing pack lifetime. This is achieved by adding DC-DC converters in parallel with cells and using state estimation and control to autonomously bias individual cell SOC and SOC range, forcing healthier cells to be cycled deeper than weaker cells. The result is a pack with improved degradation characteristics and extended lifetime. The modular architecture and control concepts are developed and hardware results are demonstrated for a 91.2-Wh battery pack consisting of four series Li-ion battery cells and four dual active bridge (DAB) bypass DC-DC converters.

  9. Improvement of spatial memory of male parkinsonian rats after treatment with adipose stem cells and rosemary leaf extract

    Directory of Open Access Journals (Sweden)

    Mahdieh Ramezanihossienabadi

    2018-01-01

    Full Text Available Background: Due to the neuroprotective effect of rosemary extract, this study aimed at examining the effect of co-treatment of adipose stem cells transplantation and the extract on memory disability of parkinsonian rats. Materials and Methods: In this experimental study, male parkinsonian rats were prepared by bilateral injection of 6-OHDA. The sham group was injected normal saline into the substantia nigra. The extract+medium group was gavaged with the extract 14 days before until 8 weeks after the injury, and the medium was intravenously injected. The extract+cell group was orally gavaged with the extract and the cells were injected. Morris water maze training was conducted one week before and after the lesion and also a retrieval test was performed 4 and 8 weeks after the lesion. Results: There was no significant difference in distance moved and escape latency at training days, before the injury, between the groups. However, a week after the injury, learning ability in lesioned animals was significantly decreased as compared to the sham group (P<0.05. Results of retention tests in four and eight weeks were similar. Duration of escape latency and time spent in target quadrant of lesioned rats were significantly increased and decreased respectively as compared to the sham (P<0.05. The extract+medium and extract+cell groups showed significant decrease and increase in escape latency and time spent in target quadrant as compared to the lesioned group (P<0.05, respectively. Conclusion: The cell therapy accompanied with orally administration of the rosemary extract can improve memory deficit in Parkinson’s disease.

  10. Optimization of Human NK Cell Manufacturing: Fully Automated Separation, Improved Ex Vivo Expansion Using IL-21 with Autologous Feeder Cells, and Generation of Anti-CD123-CAR-Expressing Effector Cells.

    Science.gov (United States)

    Klöß, Stephan; Oberschmidt, Olaf; Morgan, Michael; Dahlke, Julia; Arseniev, Lubomir; Huppert, Volker; Granzin, Markus; Gardlowski, Tanja; Matthies, Nadine; Soltenborn, Stephanie; Schambach, Axel; Koehl, Ulrike

    2017-10-01

    depletion and CD56 enrichment steps. Manually performed experiments to test different culture media demonstrated significantly higher NK cell expansion rates and an approximately equal distribution of CD56 dim CD16 pos and CD56 bright CD16 dim&neg NK subsets on day 14 with cells cultivated in NK MACS ® media. Moreover, effector cell expansion in manually performed experiments with NK MACS ® containing IL-2 and irradiated autologous FCs and IL-21, both added at the initiation of the culture, induced an 85-fold NK cell expansion. Compared to freshly isolated NK cells, expanded NK cells expressed significantly higher levels of NKp30, NKp44, NKG2D, TRAIL, FasL, CD69, and CD137, and showed comparable cell viabilities and killing/degranulation activities against tumor and leukemic cell lines in vitro. NK cells used for CAR transduction showed the highest anti-CD123 CAR expression on day 3 after gene modification. These anti-CD123 CAR-engineered NK cells demonstrated improved cytotoxicity against the CD123 pos AML cell line KG1a and primary AML blasts. In addition, CAR NK cells showed higher degranulation and enhanced secretion of tumor necrosis factor alpha, interferon gamma, and granzyme A and B. In fluorescence imaging, specific interactions that initiated apoptotic processes in the AML target cells were detected between CAR NK cells and KG1a. After the fully automated NK cell separation process on Prodigy, a new NK cell expansion protocol was generated that resulted in high numbers of NK cells with potent antitumor activity, which could be modified efficiently by novel third-generation, alpha-retroviral SIN vector constructs. Next steps are the integration of the manual expansion procedure in the fully integrated platform for a standardized GMP-compliant overall process in this closed system that also may include gene modification of NK cells to optimize target-specific antitumor activity.

  11. Significance of a diagnosis of atypical squamous cells of undetermined significance for Papanicolaou smears in perimenopausal and postmenopausal women.

    Science.gov (United States)

    Keating, J T; Wang, H H

    2001-04-25

    The current study was conducted to determine the significance of a diagnosis of atypical squamous cells of undetermined significance (ASCUS) in perimenopausal and postmenopausal women. The reports for all Papanicolaou (Pap) smears viewed in the study institution's cytology laboratory over a 6-month period were reviewed. Women were divided into premenopausal (age ages 46-54 years), and postmenopausal (age > or = 55 years) categories. Slide review and 2-year follow-up were obtained for selected cases diagnosed as ASCUS. ASCUS cases among the perimenopausal women were compared with an age-matched control group. The total number of abnormal Pap smears in the premenopausal, perimenopausal, and postmenopausal categories were 770 (6.8%), 104 (4.3%), and 67 (2.9%), with 482, 83, and 41 diagnoses of ASCUS, respectively. The ratio of ASCUS to squamous intraepithelial lesions (SIL) was 2.2 overall and 1.9, 7.5, and 4.1, respectively, for each group (P ASCUS cases appeared to have a higher percentage of nuclear-cytoplasmic ratio increase and nuclear membrane irregularities compared with the other categories (P = 0.03 and P = 0.02, respectively) and the perimenopausal group was found to have more ASCUS in metaplastic cells (P = 0.03). In perimenopausal women, slides diagnosed as ASCUS demonstrated more air-drying artifact than the control group (P = 0.004) but had less obvious atrophy (P = 0.01). Despite a decreased abnormality rate with increasing age, the results of the current study show that the perimenopausal and postmenopausal groups appear to have elevated ASCUS-to-SIL ratios. ASCUS appears to have a particularly low positive predictive value for SIL in perimenopausal women, and therefore most likely is overcalled in this age group. This may be attributable in part to air-drying artifact and subtle atrophic changes.

  12. SH2 modified STAT1 induces HLA-I expression and improves IFN-γ signaling in IFN-α resistant HCV replicon cells.

    Directory of Open Access Journals (Sweden)

    Bret Poat

    2010-09-01

    Full Text Available We have developed multiple stable cell lines containing subgenomic HCV RNA that are resistant to treatment with interferon alpha (IFN-α. Characterization of these IFN-α resistant replicon cells showed defects in the phosphorylation and nuclear translocation of STAT1 and STAT2 proteins due to a defective Jak-STAT pathway.In this study, we have developed an alternative strategy to overcome interferon resistance in a cell culture model by improving intracellular STAT1 signaling. An engineered STAT1-CC molecule with double cysteine substitutions in the Src-homology 2 (SH2 domains of STAT1 (at Ala-656 and Asn-658 efficiently phosphorylates and translocates to the nucleus of IFN-resistant cells in an IFN-γ dependent manner. Transfection of a plasmid clone containing STAT1-CC significantly activated the GAS promoter compared to wild type STAT1 and STAT3. The activity of the engineered STAT1-CC is dependent upon the phosphorylation of tyrosine residue 701, since the construct with a substituted phenylalanine residue at position 701 (STAT1-CC-Y701F failed to activate GAS promoter in the replicon cells. Intracellular expression of STAT1-CC protein showed phosphorylation and nuclear translocation in the resistant cell line after IFN-γ treatment. Transient transfection of STAT1-CC plasmid clone into an interferon resistant cell line resulted in inhibition of viral replication and viral clearance in an IFN-γ dependent manner. Furthermore, the resistant replicon cells transfected with STAT1-CC constructs significantly up regulated surface HLA-1 expression when compared to the wild type and Y to F mutant controls.These results suggest that modification of the SH2 domain of the STAT1 molecule allows for improved IFN-γ signaling through increased STAT1 phosphorylation, nuclear translocation, HLA-1 surface expression, and prolonged interferon antiviral gene activation.

  13. BIX-01294 increases pig cloning efficiency by improving epigenetic reprogramming of somatic cell nuclei.

    Science.gov (United States)

    Huang, Jiaojiao; Zhang, Hongyong; Yao, Jing; Qin, Guosong; Wang, Feng; Wang, Xianlong; Luo, Ailing; Zheng, Qiantao; Cao, Chunwei; Zhao, Jianguo

    2016-01-01

    Accumulating evidence suggests that faulty epigenetic reprogramming leads to the abnormal development of cloned embryos and results in the low success rates observed in all mammals produced through somatic cell nuclear transfer (SCNT). The aberrant methylation status of H3K9me and H3K9me2 has been reported in cloned mouse embryos. To explore the role of H3K9me2 and H3K9me in the porcine somatic cell nuclear reprogramming, BIX-01294, known as a specific inhibitor of G9A (histone-lysine methyltransferase of H3K9), was used to treat the nuclear-transferred (NT) oocytes for 14-16 h after activation. The results showed that the developmental competence of porcine SCNT embryos was significantly enhanced both in vitro (blastocyst rate 16.4% vs 23.2%, Pcloning rate 1.59% vs 2.96%) after 50 nm BIX-01294 treatment. BIX-01294 treatment significantly decreased the levels of H3K9me2 and H3K9me at the 2- and 4-cell stages, which are associated with embryo genetic activation, and increased the transcriptional expression of the pluripotency genes SOX2, NANOG and OCT4 in cloned blastocysts. Furthermore, the histone acetylation levels of H3K9, H4K8 and H4K12 in cloned embryos were decreased after BIX-01294 treatment. However, co-treatment of activated NT oocytes with BIX-01294 and Scriptaid rescued donor nuclear chromatin from decreased histone acetylation of H4K8 that resulted from exposure to BIX-01294 only and consequently improved the preimplantation development of SCNT embryos (blastocyst formation rates of 23.7% vs 21.5%). These results indicated that treatment with BIX-01294 enhanced the developmental competence of porcine SCNT embryos through improvements in epigenetic reprogramming and gene expression. © 2016 Society for Reproduction and Fertility.

  14. Disintegration of Nannochloropsis sp. cells in an improved turbine bead mill.

    Science.gov (United States)

    Pan, Zhidong; Huang, Ying; Wang, Yanmin; Wu, Zhiwei

    2017-12-01

    The Nannochloropsis sp. cells in aqueous solution were disintegrated in an improved bead mill with turbine agitator. The disintegration rates of cell samples disrupted under various operating parameters (i.e., circumferential speed, bead size, disintegration time, and cell concentration) were analyzed. An experimental strategy to optimize the parameters affecting the cell disintegration process was proposed. The results show that Nannochloropsis sp. cells can be effectively disintegrated in the turbine stirred bead mill under the optimum condition (i.e., circumferential speed of 2.3m/s, concentration of 15vol.%, disintegration time of 40min and bead size of 0.3-0.4mm). The disintegration mechanism was discussed via the selection and breakage functions from population balance modelling. It is revealed that the impact and compression effects of stirring beads are more effective for the disruption of coarser fraction of cells, and the shear effect dominates the production of finer fractions of disintegrated cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Physiological significance of polyploidization in mammalian cells.

    Science.gov (United States)

    Pandit, Shusil K; Westendorp, Bart; de Bruin, Alain

    2013-11-01

    Programmed polyploidization occurs in all mammalian species during development and aging in selected tissues, but the biological properties of polyploid cells remain obscure. Spontaneous polyploidization arises during stress and has been observed in a variety of pathological conditions, such as cancer and degenerative diseases. A major challenge in the field is to test the predicted functions of polyploidization in vivo. However, recent genetic mouse models with diminished polyploidization phenotypes represent novel, powerful tools to unravel the biological function of polyploidization. Contrary to a longstanding hypothesis, polyploidization appears to not be required for differentiation and has no obvious impact on proliferation. Instead, polyploidization leads to increased cell size and genetic diversity, which could promote better adaptation to chronic injury or stress. We discuss here the consequences of reducing polyploidization in mice and review which stress responses and molecular signals trigger polyploidization during development and disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

    Science.gov (United States)

    Sun, Hongyu; Zhou, Jing; Huang, Zhu; Qu, Linlin; Lin, Ning; Liang, Chengxiao; Dai, Ruiwu; Tang, Lijun; Tian, Fuzhou

    2017-01-01

    Carbon nanotubes (CNTs) provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col) hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt%) exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. PMID:28450785

  17. Significant improvement of optical traps by tuning standard water immersion objectives

    International Nuclear Information System (INIS)

    Reihani, S Nader S; Mir, Shahid A; Richardson, Andrew C; Oddershede, Lene B

    2011-01-01

    Focused infrared lasers are widely used for micromanipulation and visualization of biological specimens. An inherent practical problem is that off-the-shelf commercial microscope objectives are designed for use with visible and not infrared wavelengths. Less aberration is introduced by water immersion objectives than by oil immersion ones, however, even water immersion objectives induce significant aberration. We present a simple method to reduce the spherical aberration induced by water immersion objectives, namely by tuning the correction collar of the objective to a value that is ∼ 10% lower than the physical thickness of the coverslip. This results in marked improvements in optical trapping strengths of up to 100% laterally and 600% axially from a standard microscope objective designed for use in the visible range. The results are generally valid for any water immersion objective with any numerical aperture

  18. Improving Perovskite Solar Cells: Insights From a Validated Device Model

    NARCIS (Netherlands)

    Sherkar, Tejas S.; Momblona, Cristina; Gil-Escrig, Lidon; Bolink, Henk J.; Koster, L. Jan Anton

    2017-01-01

    To improve the efficiency of existing perovskite solar cells (PSCs), a detailed understanding of the underlying device physics during their operation is essential. Here, a device model has been developed and validated that describes the operation of PSCs and quantitatively explains the role of

  19. Thermosensitive Hydrogel Mask Significantly Improves Skin Moisture and Skin Tone; Bilateral Clinical Trial

    Directory of Open Access Journals (Sweden)

    Anna Quattrone

    2017-06-01

    Full Text Available Objective: A temperature-sensitive state-changing hydrogel mask was used in this study. Once it comes into contact with the skin and reaches the body temperature, it uniformly and quickly releases the active compounds, which possess moisturizing, anti-oxidant, anti-inflammatory and regenerative properties. Methods: An open label clinical trial was conducted to evaluate the effects of the test product on skin hydration, skin tone and skin ageing. Subjects applied the product to one side of their face and underwent Corneometer® and Chromameter measurements, Visual assessment of facial skin ageing and facial photography. All assessments and Self-Perception Questionnaires (SPQ were performed at baseline, after the first application of the test product and after four applications. Results: After a single treatment we observed an increase in skin moisturisation, an improvement of skin tone/luminosity and a reduction in signs of ageing, all statistically significant. After four applications a further improvement in all measured parameters was recorded. These results were confirmed by the subjects’ own perceptions, as reported in the SPQ both after one and four applications. Conclusion: The hydrogel mask tested in this study is very effective in improving skin hydration, skin radiance and luminosity, in encouraging an even skin tone and in reducing skin pigmentation.

  20. Linking incomplete reprogramming to the improved pluripotency of murine embryonal carcinoma cell-derived pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Gang Chang

    Full Text Available Somatic cell nuclear transfer (SCNT has been proved capable of reprogramming various differentiated somatic cells into pluripotent stem cells. Recently, induced pluripotent stem cells (iPS have been successfully derived from mouse and human somatic cells by the over-expression of a combination of transcription factors. However, the molecular mechanisms underlying the reprogramming mediated by either the SCNT or iPS approach are poorly understood. Increasing evidence indicates that many tumor pathways play roles in the derivation of iPS cells. Embryonal carcinoma (EC cells have the characteristics of both stem cells and cancer cells and thus they might be the better candidates for elucidating the details of the reprogramming process. Although previous studies indicate that EC cells cannot be reprogrammed into real pluripotent stem cells, the reasons for this remain unclear. Here, nuclei from mouse EC cells (P19 were transplanted into enucleated oocytes and pluripotent stem cells (P19 NTES cells were subsequently established. Interestingly, P19 NTES cells prolonged the development of tetraploid aggregated embryos compared to EC cells alone. More importantly, we found that the expression recovery of the imprinted H19 gene was dependent on the methylation state in the differential methylation region (DMR. The induction of Nanog expression, however, was independent of the promoter region DNA methylation state in P19 NTES cells. A whole-genome transcriptome analysis further demonstrated that P19 NTES cells were indeed the intermediates between P19 cells and ES cells and many interesting genes were uncovered that may be responsible for the failed reprogramming of P19 cells. To our knowledge, for the first time, we linked incomplete reprogramming to the improved pluripotency of EC cell-derived pluripotent stem cells. The candidate genes we discovered may be useful not only for understanding the mechanisms of reprogramming, but also for deciphering the

  1. Atypical squamous and glandular cells of undetermined significance (ASCUS and AGUS) of the uterine cervix.

    Science.gov (United States)

    Cenci, M; Vecchione, A

    2000-01-01

    ASCUS (Atypical Squamous Cells of Undetermined Significance) and AGUS (Atypical Glandular Cells of Undetermined Significance), or AGCUS, are two acronyms introduced in 1988 by The Bethesda System (TBS) for reporting borderline cytological changes in cervical cytology. ASCUS and AGUS categories should be subclassified. Five ASCUS subgroups were proposed: 1) ASCUS due to processing defects, 2) with "mature" cytoplasm, 3) in post-menopausal women (a--in the setting of atrophy and b--with estrogen stimulation), 4) atypical metaplasia, and 5) ASCUS with keratinized cytoplasm. AGUS subgroups may be subcategorized in endometrial or endocervical on the basis of origin. Endocervical AGUS should be further qualified, but the analysis of atypical glandular cells may be really difficult and the conclusive diagnosis is frequently "AGUS not otherwise specified". The subclassification of ASCUS and AGUS is useful for an appropriate clinical management, but pertinent patient information (such as age, date of last menstrual period, mechanical therapies, tamoxifen therapy, and others) is needed to avoid an overdiagnosis and consequently an overtreatment. In fact various subgroups require different clinical management. Therefore, an effective communication between cytopathologists and referring physicians is essential in the analysis of squamous and glandular atypias.

  2. Improvement in survival of patients with oral cavity squamous cell carcinoma: An international collaborative study.

    Science.gov (United States)

    Amit, Moran; Yen, Tzu-Chen; Liao, Chun-Ta; Chaturvedi, Pankaj; Agarwal, Jai Prakash; Kowalski, Luiz P; Ebrahimi, Ardalan; Clark, Jonathan R; Kreppel, Matthias; Zöller, Joachim; Fridman, Eran; Bolzoni, Villaret A; Shah, Jatin P; Binenbaum, Yoav; Patel, Snehal G; Gil, Ziv

    2013-12-15

    An association between the survival of patients with oral cavity squamous cell carcinoma (OCSCC) and advancements in diagnosis and therapy has not been established. This was a retrospective, longitudinal, international, population-based study of 2738 patients who underwent resection of OCSCC during 2 different decades. Characteristics of patients from 7 international cancer centers who received treatment between 1990 and 2000 (group A; n = 735) were compared with patients who received treatment between 2001 and 2011 (group B; n = 2003). Patients in group B had more advanced tumors and tended to develop distant metastases more frequently than patients in group A (P = .005). More group B patients underwent selective neck dissection and received adjuvant radiotherapy (P < .001). Outcome analysis revealed a significant improvement in 5-year overall survival, from 59% for group A to 70% for group B (P < .001). There was also a significant improvement in disease-specific survival associated with operations performed before and after 2000 (from 69% to 81%, respectively; P < .001). Surgery after 2000, negative margins, adjuvant treatment, and early stage disease were independent predictors of a better outcome in multivariate analysis. The decade of treatment was an independent prognostic factor for cancer-specific mortality (hazard ratio, 0.42; 95% confidence interval, 0.3-0.6). The survival rate of patients with OCSCC improved significantly during the past 2 decades despite older age, more advanced disease stage, and a higher rate of distant metastases. The current results suggest that the prognosis for patients with OCSCC has improved over time, presumably because of advances in imaging and therapy. © 2013 American Cancer Society.

  3. Corrugated round fibers to improve cell adhesion and proliferation in tissue engineering scaffolds

    NARCIS (Netherlands)

    Bettahalli Narasimha, M.S.; Arkesteijn, I.T.M.; Wessling, Matthias; Poot, Andreas A.; Stamatialis, Dimitrios

    2013-01-01

    Optimal cell interaction with biomaterial scaffolds is one of the important requirements for the development of successful in vitro tissue-engineered tissues. Fast, efficient and spatially uniform cell adhesion can improve the clinical potential of engineered tissue. Three-dimensional (3-D) solid

  4. Introducing catalyst in alkaline membrane for improved performance direct borohydride fuel cells

    Science.gov (United States)

    Qin, Haiying; Lin, Longxia; Chu, Wen; Jiang, Wei; He, Yan; Shi, Qiao; Deng, Yonghong; Ji, Zhenguo; Liu, Jiabin; Tao, Shanwen

    2018-01-01

    A catalytic material is introduced into the polymer matrix to prepare a novel polymeric alkaline electrolyte membrane (AEM) which simultaneously increases ionic conductivity, reduces the fuel cross-over. In this work, the hydroxide anion exchange membrane is mainly composed of poly(vinylalcohol) and alkaline exchange resin. CoCl2 is added into the poly(vinylalcohol) and alkaline exchange resin gel before casting the membrane to introduce catalytic materials. CoCl2 is converted into CoOOH after the reaction with KOH solution. The crystallinity of the polymer matrix decreases and the ionic conductivity of the composite membrane is notably improved by the introduction of Co-species. A direct borohydride fuel cell using the composite membrane exhibits an open circuit voltage of 1.11 V at 30 °C, which is notably higher than that of cells using other AEMs. The cell using the composite membrane achieves a maximum power density of 283 mW cm-2 at 60 °C while the cell using the membrane without Co-species only reaches 117 mW cm-2 at the same conditions. The outstanding performance of the cell using the composite membrane benefits from impregnation of the catalytic Co-species in the membrane, which not only increases the ionic conductivity but also reduces electrode polarization thus improves the fuel cell performance. This work provides a new approach to develop high-performance fuel cells through adding catalysts in the electrolyte membrane.

  5. Improved Work Function of Poly(3,4-ethylenedioxythiophene): Poly(styrenesulfonic acid) and its Effect on Hybrid Silicon/Organic Heterojunction Solar Cells

    Science.gov (United States)

    Shen, Xiaojuan; Chen, Ling; Pan, Jianmei; Hu, Yue; Li, Songjun; Zhao, Jie

    2016-11-01

    Hybrid silicon/organic solar cells have been recently extensively investigated due to their simple structure and low-cost fabrication process. However, the efficiency of the solar cells is greatly limited by the barrier height as well as the carrier recombination at the silicon/organic interface. In this work, hydrochloroplatinic acid (H2PtCl6) is employed into the poly(3,4-ethlenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) solution, and the work function (WF) of the PEDOT:PSS layer has been successfully improved. Based on the Pt-modified PEDOT:PSS layer, the efficiency of the silicon/PEDOT:PSS cell can be increased to 11.46%, corresponding to 20% enhancement to the one without platinum (Pt) modification. Theoretical and experimental results show that, when increasing the WF of the PEDO:PSS layer, the barrier height between the silicon/PEDOT:PSS interface can be effectively enhanced. Meanwhile, the carrier recombination at the interface is significantly reduced. These results can contribute to better understanding of the interfacial mechanism of silicon/PEDOT:PSS interface, and further improving the device performance of silicon/organic solar cells.

  6. E4orf1: a novel ligand that improves glucose disposal in cell culture.

    Directory of Open Access Journals (Sweden)

    Emily J Dhurandhar

    Full Text Available Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral treatment of insulin resistance (IR, are marginally successful over the long term. Ad36, a human adenovirus, offers a template to improve IR, independent of dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras-mediated activation of phosphatidyl inositol 3-kinase(PI3K, and improves hyperglycemia in mice, despite a high-fat diet and without reducing adiposity. Ex-vivo studies suggest that Ad36 improves hyperglycemia in mice by increasing glucose uptake by adipose tissue and skeletal muscle, and by reducing hepatic glucose output. It is impractical to use Ad36 for therapeutic action. Instead, we investigated if the E4orf1 protein of Ad36, mediates its anti-hyperglycemic action. Such a candidate protein may offer an attractive template for therapeutic development. Experiment-1 determined that Ad36 'requires' E4orf1 protein to up-regulate cellular glucose uptake. Ad36 significantly increased glucose uptake in 3T3-L1 preadipocytes, which was abrogated by knocking down E4orf1 with siRNA. Experiment-2 identified E4orf1 as 'sufficient' to up-regulate glucose uptake. 3T3-L1 cells that inducibly express E4orf1, increased glucose uptake in an induction-dependent manner, compared to null vector control cells. E4orf1 up-regulated PI3K pathway and increased abundance of Ras--the obligatory molecule in Ad36-induced glucose uptake. Experiment-3: Signaling studies of cells transiently transfected with E4orf1 or a null vector, revealed that E4orf1 may activate Ras/PI3K pathway by binding to Drosophila discs-large (Dlg1 protein. E4orf1 activated total Ras and, particularly the H-Ras isoform. By mutating the PDZ domain binding motif (PBM of E4orf1, Experiment-4 showed that E4orf1 requires its PBM to increase Ras activation or glucose uptake. Experiment-5: In-vitro, a transient transfection by E4orf1 significantly increased glucose uptake in preadipocytes

  7. E4orf1: a novel ligand that improves glucose disposal in cell culture.

    Science.gov (United States)

    Dhurandhar, Emily J; Dubuisson, Olga; Mashtalir, Nazar; Krishnapuram, Rashmi; Hegde, Vijay; Dhurandhar, Nikhil V

    2011-01-01

    Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral treatment of insulin resistance (IR), are marginally successful over the long term. Ad36, a human adenovirus, offers a template to improve IR, independent of dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras-mediated activation of phosphatidyl inositol 3-kinase(PI3K), and improves hyperglycemia in mice, despite a high-fat diet and without reducing adiposity. Ex-vivo studies suggest that Ad36 improves hyperglycemia in mice by increasing glucose uptake by adipose tissue and skeletal muscle, and by reducing hepatic glucose output. It is impractical to use Ad36 for therapeutic action. Instead, we investigated if the E4orf1 protein of Ad36, mediates its anti-hyperglycemic action. Such a candidate protein may offer an attractive template for therapeutic development. Experiment-1 determined that Ad36 'requires' E4orf1 protein to up-regulate cellular glucose uptake. Ad36 significantly increased glucose uptake in 3T3-L1 preadipocytes, which was abrogated by knocking down E4orf1 with siRNA. Experiment-2 identified E4orf1 as 'sufficient' to up-regulate glucose uptake. 3T3-L1 cells that inducibly express E4orf1, increased glucose uptake in an induction-dependent manner, compared to null vector control cells. E4orf1 up-regulated PI3K pathway and increased abundance of Ras--the obligatory molecule in Ad36-induced glucose uptake. Experiment-3: Signaling studies of cells transiently transfected with E4orf1 or a null vector, revealed that E4orf1 may activate Ras/PI3K pathway by binding to Drosophila discs-large (Dlg1) protein. E4orf1 activated total Ras and, particularly the H-Ras isoform. By mutating the PDZ domain binding motif (PBM) of E4orf1, Experiment-4 showed that E4orf1 requires its PBM to increase Ras activation or glucose uptake. Experiment-5: In-vitro, a transient transfection by E4orf1 significantly increased glucose uptake in preadipocytes, adipocytes, or

  8. Expression and Clinicopathological Significance of Mel-18 and Bmi-1 in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Ji, Huaijun; Cao, Ming; Ren, Kunlun; Sun, Ningbo; Wang, Wei; Zhu, Qiang; Zang, Qi; Jiang, Zhongmin

    2017-01-01

    The Polycomb group genes are a general class of regulators that are responsible for maintaining homeotic gene expression throughout cell division. Polycomb group expression plays an important role in oncogenesis of several types of human cancer. Melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 are key Polycomb group proteins. Studies have shown that melanoma nuclear protein 18 is a potential tumor suppression, and B-cell-specific Moloney leukemia virus insert site 1 is overexpressed in several human malignancies. However, the roles of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in esophageal squamous cell carcinoma are still unclear. In this study, we analyzed the expression levels of melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 in 89 esophageal cancer tissues and paired normal mucosal tissues using immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction analyses. We found that the expression of melanoma nuclear protein 18 in the carcinoma tissues was significantly lower than that in the noncancerous mucosal tissues ( P .05). B-cell-specific Moloney leukemia virus insert site 1 expression was strongly correlated with the degree of differentiation, clinical stage, and lymph node metastasis ( P .05). Moreover, there was a negative correlation between melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 expressions in esophageal squamous cell carcinoma ( P < .05). Our study suggests that melanoma nuclear protein 18 and B-cell-specific Moloney leukemia virus insert site 1 may play a crucial role in esophageal squamous cell carcinoma. Melanoma nuclear protein 18 or B-cell-specific Moloney leukemia virus insert site 1 may be a potential biomarker for diagnosis and prognosis of esophageal squamous cell carcinoma.

  9. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

    Science.gov (United States)

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  10. Rac1 selective activation improves retina ganglion cell survival and regeneration.

    Directory of Open Access Journals (Sweden)

    Erika Lorenzetto

    Full Text Available In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role in neuronal survival and regeneration in vivo has not yet been properly investigated. To address this point we intravitreally injected selective cell-penetrating Rac1 mutants after optic nerve crush and studied the effect on RGC survival and axonal regeneration. We injected two well-characterized L61 constitutively active Tat-Rac1 fusion protein mutants, in which a second F37A or Y40C mutation confers selectivity in downstream signaling pathways. Results showed that, 15 days after crush, both mutants were able to improve survival and to prevent dendrite degeneration, while the one harboring the F37A mutation also improved axonal regeneration. The treatment with F37A mutant for one month did not improve the axonal elongation respect to 15 days. Furthermore, we found an increase of Pak1 T212 phosphorylation and ERK1/2 expression in RGCs after F37A treatment, whereas ERK1/2 was more activated in glial cells after Y40C administration. Our data suggest that the selective activation of distinct Rac1-dependent pathways could represent a therapeutic strategy to counteract neuronal degenerative processes in the retina.

  11. Parameter estimation of photovoltaic cells using an improved chaotic whale optimization algorithm

    International Nuclear Information System (INIS)

    Oliva, Diego; Abd El Aziz, Mohamed; Ella Hassanien, Aboul

    2017-01-01

    Highlights: •We modify the whale algorithm using chaotic maps. •We apply a chaotic algorithm to estimate parameter of photovoltaic cells. •We perform a study of chaos in whale algorithm. •Several comparisons and metrics support the experimental results. •We test the method with data from real solar cells. -- Abstract: The using of solar energy has been increased since it is a clean source of energy. In this way, the design of photovoltaic cells has attracted the attention of researchers over the world. There are two main problems in this field: having a useful model to characterize the solar cells and the absence of data about photovoltaic cells. This situation even affects the performance of the photovoltaic modules (panels). The characteristics of the current vs. voltage are used to describe the behavior of solar cells. Considering such values, the design problem involves the solution of the complex non-linear and multi-modal objective functions. Different algorithms have been proposed to identify the parameters of the photovoltaic cells and panels. Most of them commonly fail in finding the optimal solutions. This paper proposes the Chaotic Whale Optimization Algorithm (CWOA) for the parameters estimation of solar cells. The main advantage of the proposed approach is using the chaotic maps to compute and automatically adapt the internal parameters of the optimization algorithm. This situation is beneficial in complex problems, because along the iterative process, the proposed algorithm improves their capabilities to search for the best solution. The modified method is able to optimize complex and multimodal objective functions. For example, the function for the estimation of parameters of solar cells. To illustrate the capabilities of the proposed algorithm in the solar cell design, it is compared with other optimization methods over different datasets. Moreover, the experimental results support the improved performance of the proposed approach

  12. The cytoskeleton of Drosophila-derived Schneider line-1 and Kc23 cells undergoes significant changes during long-term culture

    Science.gov (United States)

    Schatten, H.; Hedrick, J.; Chakrabarti, A.

    1998-01-01

    Insect cell cultures derived from Drosophila melanogaster are increasingly being used as an alternative system to mammalian cell cultures, as they are amenable to genetic manipulation. Although Drosophila cells are an excellent tool for the study of genes and expression of proteins, culture conditions have to be considered in the interpretation of biochemical results. Our studies indicate that significant differences occur in cytoskeletal structure during the long-term culture of the Drosophila-derived cell lines Schneider Line-1 (S1) and Kc23. Scanning, transmission-electron, and immunofluorescence microscopy studies reveal that microfilaments, microtubules, and centrosomes become increasingly different during the culture of these cells from 24 h to 7-14 days. Significant cytoskeletal changes are observed at the cell surface where actin polymerizes into microfilaments, during the elongation of long microvilli. Additionally, long protrusions develop from the cell surface; these protrusions are microtubule-based and establish contact with neighboring cells. In contrast, the microtubule network in the interior of the cells becomes disrupted after four days of culture, resulting in altered transport of mitochondria. Microtubules and centrosomes are also affected in a small percent of cells during cell division, indicating an instability of centrosomes. Thus, the cytoskeletal network of microfilaments, microtubules, and centrosomes is affected in Drosophila cells during long-term culture. This implies that gene regulation and post-translational modifications are probably different under different culture conditions.

  13. A facile template method to synthesize significantly improved LiNi0.5Mn1.5O4 using corn stalk as a bio-template

    International Nuclear Information System (INIS)

    Liu, Guiyang; Kong, Xin; Sun, Hongyan; Wang, Baosen; Yi, Zhongzhou; Wang, Quanbiao

    2014-01-01

    In order to simplify the template method for the synthesis of cathode materials for lithium ion batteries, a facile template method using plant stalks as bio-templates has been introduced. Based on this method, LiNi 0.5 Mn 1.5 O 4 spinel with a significantly improved electrochemical performance has been synthesized using corn stalk as a template. X-ray diffraction (XRD), Fourier transform infrared pectroscopy (FTIR) and scanning electron microscope (SEM) have been used to investigate the phase composition and micro-morphologies of the products. Charge-discharge measurements in lithium cells, cyclic voltammetry (CV) and Electrochemical impedance spectroscopy (EIS) have been used to study the electrochemical performance of the products. The results indicate that the templated product exhibits higher crystallinity than that of non-templated product. Both of the templated product and the non-templated product are combination of the ordered space group P4 3 32 and the disordered Fd-3 m. The specific BET surface area of the templated product is about twice larger than that of the non-templated product. Moreover, the electrochemical performances of the templated product including specific capacity, cycling stability and rate capability are significantly improved as compared with the non-templated product, due to its higher crystallinity, larger Li + diffusion coefficient and lower charge transfer resistance

  14. Functional significance of erythropoietin in renal cell carcinoma

    International Nuclear Information System (INIS)

    Morais, Christudas; Johnson, David W; Vesey, David A; Gobe, Glenda C

    2013-01-01

    One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive hematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma (RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial and sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream molecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression of solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays a critical role in the development and progression of tumours in general, it is of special significance in the case of RCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers, including RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because the rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in RCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current knowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are equivocal and insufficient to draw a definitive conclusion

  15. Immunohistochemical and molecular characteristics with prognostic significance in diffuse large B-cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Carmen Bellas

    Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification was associated with the non-germinal center B subtype (non-GCB. BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of cases. We detected an association between high FOXP1 expression and a high proliferation rate as well as a significant positive correlation between MYC overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were significant predictors of overall survival. The co-expression of MYC and BCL2 confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas cases negative for both markers had the best outcomes. Our study confirms that DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor prognosis and establishes a significant positive correlation with MYC and FOXP1 over-expression in this entity.

  16. Herbal tea extract combined with light-induced significant in vitro cytotoxicity of human bladder cancer cells

    Science.gov (United States)

    Nseyo, Unyime; Kim, Albert; Stavropoulos, Nicholas E.; Skalkos, Dimitris; Nseyo, U. U.; Chung, Theodore D.

    2005-04-01

    The anti-inflammatory, anti-microbial, antiviral, and antidepressant activities of the Greek herb, Hypericum Perforatum L, HP L, have been attributed to the total extract or single constituents. We investigated the use of the extract,specifically of the polar methanolic fraction (PMF) of Epirus"HPL in photodynamic therapy (PDT) alone and in combination with recombinant Interferon-a2b (IFN) and gemcitabine (GCB) in the treatment of human bladder cancer cells. The PMF was extracted from the dry herb with methanol, followed by liquid-liquid extraction with petroleum ether. T-24 bladder cancer cells were plated (105 cells/well) and placed in the incubator (370 C, 5%CO) for 24 hours prior to addition of drugs. PMF 60ug/ml was added and incubation continued. After 24 hours, the cells were subjected to laser light (630nm) treatment with 0, 1, 4 and 8 Joules. After reincubation for 24 hours, IFN, (50,000 IU) or GCB, (2ug/ml) was added to the PDT-treated cells. After this incubation cell survival was assessed by the MTT assay. PMF-PDT alone-induced percent cell kill of 0%, 8%, 44% and 80% versus 31%, 64 and 86 % for PMF-PDT and IFN, versus 63%, 80% and 88% for MPF-PDT plus GCB at 1, 2, 4 and 8 Joules respectively. IFN and GCB induced 20% and 53% cell kill respectively. Our data suggest that MPF may be an effective agent for in vitro photodynamic therapy. PMF-PDT combined with Intron A, or gemcitabine achieved improved kill of cultured bladder cancer cells. Confirmation of these results in preclinical studies may lead to clinical trials.

  17. Induced Human Decidual NK-Like Cells Improve Utero-Placental Perfusion in Mice.

    Directory of Open Access Journals (Sweden)

    Ricardo C Cavalli

    Full Text Available Decidual NK (dNK cells, a distinct type of NK cell, are thought to regulate uterine spiral artery remodeling, a process that allows for increased blood delivery to the fetal-placental unit. Impairment of uterine spiral artery remodeling is associated with decreased placental perfusion, increased uterine artery resistance, and obstetric complications such as preeclampsia and intrauterine growth restriction. Ex vivo manipulation of human peripheral blood NK (pNK cells by a combination of hypoxia, TGFß-1 and 5-aza-2'-deoxycytidine yields cells with phenotypic and in vitro functional similarities to dNK cells, called idNK cells. Here, gene expression profiling shows that CD56Bright idNK cells derived ex vivo from human pNK cells, and to a lesser extent CD56Dim idNK cells, are enriched in the gene expression signature that distinguishes dNK cells from pNK cells. When injected into immunocompromised pregnant mice with elevated uterine artery resistance, idNK cells homed to the uterus and reduced the uterine artery resistance index, suggesting improved placental perfusion.

  18. Giant cell tumor in long bones: the significance of marginal sclerosis for the differential diagnosis

    International Nuclear Information System (INIS)

    Kim, Hee Jin; Suh, Jin Suck; Park, Chang Yun

    1993-01-01

    Plain radiographs of thirty nine patients with giant cell tumor of long bone and CT scans of twenty patients among the thirty patients were reviewed retrospectively to evaluate the frequency and significance of sclerosis of the tumor margin. The sclerosis of the tumor margin was observed on plain radiographs in thirteen patients(33.3%) and they were located either on epiphyseal or on both epiphyseal or metaphyseal portion of the tumor. The authors concluded that the giant cell tumor should not be excluded from the differential entities even though the tumor has the marginal sclerosis

  19. Natalizumab Significantly Improves Cognitive Impairment over Three Years in MS: Pattern of Disability Progression and Preliminary MRI Findings.

    Directory of Open Access Journals (Sweden)

    Flavia Mattioli

    Full Text Available Previous studies reported that Multiple Sclerosis (MS patients treated with natalizumab for one or two years exhibit a significant reduction in relapse rate and in cognitive impairment, but the long term effects on cognitive performance are unknown. This study aimed to evaluate the effects of natalizumab on cognitive impairment in a cohort of 24 consecutive patients with relapsing remitting MS treated for 3 years. The neuropsychological tests, as well as relapse number and EDSS, were assessed at baseline and yearly for three years. The impact on cortical atrophy was also considered in a subgroup of them, and are thus to be considered as preliminary. Results showed a significant reduction in the number of impaired neuropsychological tests after three years, a significant decrease in annualized relapse rate at each time points compared to baseline and a stable EDSS. In the neuropsychological assessment, a significant improvement in memory, attention and executive function test scores was detected. Preliminary MRI data show that, while GM volume did not change at 3 years, a significantly greater parahippocampal and prefrontal gray matter density was noticed, the former correlating with neuropsychological improvement in a memory test. This study showed that therapy with Natalizumab is helpful in improving cognitive performance, and is likely to have a protective role on grey matter, over a three years follow-up.

  20. Dual Functional Capability of Dendritic Cells - Cytokine-Induced Killer Cells in Improving Side Effects of Colorectal Cancer Therapy.

    Science.gov (United States)

    Mosińska, Paula; Gabryelska, Agata; Zasada, Malwina; Fichna, Jakub

    2017-01-01

    The aim of cancer therapy is to eradicate cancer without affecting healthy tissues. Current options available for treating colorectal cancer (CRC), including surgery, chemotherapy or radiotherapy, usually elicit multiple adverse effects and frequently fail to completely remove the tumor cells. Thus, there is a constant need for seeking cancer cell-specific therapeutics to improve the course of cancer therapy and reduce the risk of relapse. In this review we elaborate on the mechanisms underlying the immunotherapy with dendritic cells (DCs) and cytokine-induced killer (CIK) cells, and summarize their effectiveness and tolerability available clinical studies. Finally, we discuss the up-to-date combinatorial adoptive anti-cancer immunotherapy with CIK cells co-cultured with DCs that recently showed encouraging efficacy and usefulness in treating malignant disease, including CRC.

  1. Significant association of inflammation grade with the number of Langerhans cells in odontogenic keratocysts

    Directory of Open Access Journals (Sweden)

    Chun-Han Chang

    2017-10-01

    Conclusion: A significant association of inflammation grade with the number of LCs in OKCs is found. The paucity of finding LCs in the lining epithelia of OKCs without inflammation indicates the loss of immunosurveillance ability against the OKC lining epithelial cells; this can explain why OKCs have aggressive clinical behavior, a great growth potential, and a high recurrence rate.

  2. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro

    NARCIS (Netherlands)

    Smith, Ida M; Baker, Adam; Christensen, Jeffrey E; Boekhout, Teun; Frøkiær, Hanne; Arneborg, Nils; Jespersen, Lene

    2016-01-01

    Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim

  3. Slow-Adhering Stem Cells Derived from Injured Skeletal Muscle Have Improved Regenerative Capacity

    Science.gov (United States)

    2011-08-01

    stress urinary incontinence . Urology 2006, 68:449–454 15. Chermansky CJ, Tarin T, Kwon DD, Jankowski RJ, Cannon TW, de Groat WC, Huard J, Chancellor...from control noninjured muscle. These data suggest that traumatic injury may modify stem cell characteristics through trophic factors and improve the...alter the microenvironment of resident muscle cells (ie, stimu- lating cell dedifferentiation on various trophic factors )20,21 and result in profound

  4. Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats.

    Directory of Open Access Journals (Sweden)

    Anette I Öberg

    Full Text Available BACKGROUND: There is considerable interest in identifying compounds that can improve glucose homeostasis. Skeletal muscle, due to its large mass, is the principal organ for glucose disposal in the body and we have investigated here if shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increases glucose uptake in skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Shikonin increases glucose uptake in L6 skeletal muscle myotubes, but does not phosphorylate Akt, indicating that in skeletal muscle cells its effect is medaited via a pathway distinct from that used for insulin-stimulated uptake. Furthermore we find no evidence for the involvement of AMP-activated protein kinase in shikonin induced glucose uptake. Shikonin increases the intracellular levels of calcium in these cells and this increase is necessary for shikonin-mediated glucose uptake. Furthermore, we found that shikonin stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myoblasts. The beneficial effect of shikonin on glucose uptake was investigated in vivo by measuring plasma glucose levels and insulin sensitivity in spontaneously diabetic Goto-Kakizaki rats. Treatment with shikonin (10 mg/kg intraperitoneally once daily for 4 days significantly decreased plasma glucose levels. In an insulin sensitivity test (s.c. injection of 0.5 U/kg insulin, plasma glucose levels were significantly lower in the shikonin-treated rats. In conclusion, shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium. CONCLUSIONS/SIGNIFICANCE: Shikonin increases glucose uptake in skeletal muscle cells via an insulin-independent pathway dependent on calcium. The beneficial effects of shikonin on glucose metabolism, both in vitro and in vivo, show that the compound possesses properties that make it of considerable interest for developing novel treatment of type 2 diabetes.

  5. Developments for improved direct methanol fuel cell stacks for portable power

    Energy Technology Data Exchange (ETDEWEB)

    Cremers, C.; Stimming, U. [Bavarian Center for Applied Energy Research, ZAE Bayern, Abteilung 1, Walther-Meissner-Str. 6, D-85748 Garching (Germany); Technische Universitaet Muenchen, Department of Physics E19, James-Franck-Str. 1, D-85748 Garching (Germany); Scholz, M.; Seliger, W. [Bavarian Center for Applied Energy Research, ZAE Bayern, Abteilung 1, Walther-Meissner-Str. 6, D-85748 Garching (Germany); Racz, A. [Technische Universitaet Muenchen, Department of Physics E19, James-Franck-Str. 1, D-85748 Garching (Germany); Knechtel, W.; Rittmayr, J.; Grafwallner, F.; Peller, H. [ET EnergieTechnologie GmbH, Eugen-Saenger-Ring 4, D-85649 Brunnthal-Nord (Germany)

    2007-02-15

    Different aspects of the improvement of direct methanol fuel cell (DMFC) systems for portable power generation are investigated, in a project funded by the Bavarian state. The materials research focuses on the development of improved catalysts, in particular for the oxygen reduction reaction. Some recent results on supported ruthenium selenium catalysts are reported. In parallel, tests on other fuel cell materials are performed using MEAs made from industrial unsupported catalysts as the reference. These standard MEAs have catalyst loadings of about 11 mg cm{sup -2} and, at high air flux, can deliver current densities of about 500 mA cm{sup -2} and 100 mA cm{sup -2} at 110 C and 50 C, respectively. At low air flux and 50 C, current densities between 60 and 80 mA cm{sup -2} are possible rate at 500 mV. Using these MEAs, different commercial gas diffusion materials are tested as the cathode backing. Thus, it is found that the Sigracet materials by SGL Carbon are the most suitable for operation at a low air flux. Finally, a demonstration stack, comprised of up to ten cells, is developed using graphite PVDF compound bipolar plates by SGL Carbon. As will be reported, this stack shows a high homogeneity of cell voltages and stable operation under relevant conditions, using standard MEAs. (Abstract Copyright [2007], Wiley Periodicals, Inc.)

  6. Development of an air bleeding technique and specific duration to improve the CO tolerance of proton-exchange membrane fuel cells

    International Nuclear Information System (INIS)

    Chung, Chen-Chung; Chen, Chiun-Hsun; Weng, De-Zheng

    2009-01-01

    This study investigated transient CO poisoning of a proton-exchange membrane fuel cell under either a fixed cell voltage or fixed current density. During CO poisoning tests, the cell performance decreases over time. Experiments were performed to identify which method yields better performance in CO poisoning tests. The results revealed that a change in cell voltage did not affect the stable polarization behavior after CO poisoning of the cell. On the other hand, a higher fixed current density yielded better tolerance of 52.7 ppm CO. The air bleeding technique was then applied using different timings for air introduction during CO poisoning tests. Air bleeding significantly improved the CO tolerance of the cell and recovered the performance after poisoning, regardless of the timing of air introduction. The effects of different anode catalyst materials on cell performance were also investigated during poisoning tests. Without air bleeding, a Pt-Ru alloy catalyst exhibited better CO tolerance than a pure Pt catalyst. However, the air bleeding technique can effectively increase the CO tolerance of cells regardless of the type of catalyst used.

  7. Improving the efficacy and safety of engineered T cell therapy for cancer.

    Science.gov (United States)

    Shi, Huan; Liu, Lin; Wang, Zhehai

    2013-01-28

    Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a powerful immunotherapeutics approach against metastatic melanoma. The success of TIL therapy has led to novel strategies for redirecting normal T cells to recognize tumor-associated antigens (TAAs) by genetically engineering tumor antigen-specific T cell receptors (TCRs) or chimeric antigen receptor (CAR) genes. In this manner, large numbers of antigen-specific T cells can be rapidly generated compared with the longer term expansion of TILs. Great efforts have been made to improve these approaches. Initial clinical studies have demonstrated that genetically engineered T cells can mediate tumor regression in vivo. In this review, we discuss the development of TCR and CAR gene-engineered T cells and the safety concerns surrounding the use of these T cells in patients. We highlight the importance of judicious selection of TAAs for modified T cell therapy and propose solutions for potential "on-target, off-organ" toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Macrophages improve survival, proliferation and migration of engrafted myogenic precursor cells into MDX skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Pierre-François Lesault

    Full Text Available Transplantation of muscle precursor cells is of therapeutic interest for focal skeletal muscular diseases. However, major limitations of cell transplantation are the poor survival, expansion and migration of the injected cells. The massive and early death of transplanted myoblasts is not fully understood although several mechanisms have been suggested. Various attempts have been made to improve their survival or migration. Taking into account that muscle regeneration is associated with the presence of macrophages, which are helpful in repairing the muscle by both cleansing the debris and deliver trophic cues to myoblasts in a sequential way, we attempted in the present work to improve myoblast transplantation by coinjecting macrophages. The present data showed that in the 5 days following the transplantation, macrophages efficiently improved: i myoblast survival by limiting their massive death, ii myoblast expansion within the tissue and iii myoblast migration in the dystrophic muscle. This was confirmed by in vitro analyses showing that macrophages stimulated myoblast adhesion and migration. As a result, myoblast contribution to regenerating host myofibres was increased by macrophages one month after transplantation. Altogether, these data demonstrate that macrophages are beneficial during the early steps of myoblast transplantation into skeletal muscle, showing that coinjecting these stromal cells may be used as a helper to improve the efficiency of parenchymal cell engraftment.

  9. Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2rγnull mice treated with alogliptin

    Directory of Open Access Journals (Sweden)

    Jurczyk A

    2013-12-01

    Full Text Available Agata Jurczyk,1 Philip diIorio,1 Dean Brostowin,1 Linda Leehy,1 Chaoxing Yang,1 Fumihiko Urano,2 David M Harlan,3 Leonard D Shultz,4 Dale L Greiner,1 Rita Bortell1 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 2Department of Medicine, Washington University School of Medicine, St Louis, MO, 3Department of Medicine, University of Massachusetts Medical School, Worcester, MA, 4The Jackson Laboratory, Bar Harbor, ME, USA Purpose: Dipeptidyl-peptidase-4 (DPP-4 inhibitors are known to increase insulin secretion and beta cell proliferation in rodents. To investigate the effects on human beta cells in vivo, we utilize immunodeficient mice transplanted with human islets. The study goal was to determine the efficacy of alogliptin, a DPP-4 inhibitor, to enhance human beta cell function and proliferation in an in vivo context using diabetic immunodeficient mice engrafted with human pancreatic islets. Methods: Streptozotocin-induced diabetic NOD-scid IL2rγnull (NSG mice were transplanted with adult human islets in three separate trials. Transplanted mice were treated daily by gavage with alogliptin (30 mg/kg/day or vehicle control. Islet graft function was compared using glucose tolerance tests and non-fasting plasma levels of human insulin and C-peptide; beta cell proliferation was determined by bromodeoxyuridine (BrdU incorporation. Results: Glucose tolerance tests were significantly improved by alogliptin treatment for mice transplanted with islets from two of the three human islet donors. Islet-engrafted mice treated with alogliptin also had significantly higher plasma levels of human insulin and C-peptide compared to vehicle controls. The percentage of insulin+BrdU+ cells in human islet grafts from alogliptin-treated mice was approximately 10-fold more than from vehicle control mice, consistent with a significant increase in human beta cell proliferation. Conclusion: Human islet-engrafted immunodeficient mice

  10. Carbon nanotube-incorporated collagen hydrogels improve cell alignment and the performance of cardiac constructs

    Directory of Open Access Journals (Sweden)

    Sun HY

    2017-04-01

    Full Text Available Hongyu Sun,* Jing Zhou,* Zhu Huang,* Linlin Qu,* Ning Lin,* Chengxiao Liang, Ruiwu Dai, Lijun Tang, Fuzhou Tian General Surgery Center, Chengdu Military General Hospital, Chengdu, China *These authors contributed equally to this work Abstract: Carbon nanotubes (CNTs provide an essential 2-D microenvironment for cardiomyocyte growth and function. However, it remains to be elucidated whether CNT nanostructures can promote cell–cell integrity and facilitate the formation of functional tissues in 3-D hydrogels. Here, single-walled CNTs were incorporated into collagen hydrogels to fabricate (CNT/Col hydrogels, which improved mechanical and electrical properties. The incorporation of CNTs (up to 1 wt% exhibited no toxicity to cardiomyocytes and enhanced cell adhesion and elongation. Through the use of immunohistochemical staining, transmission electron microscopy, and intracellular calcium-transient measurement, the incorporation of CNTs was found to improve cell alignment and assembly remarkably, which led to the formation of engineered cardiac tissues with stronger contraction potential. Importantly, cardiac tissues based on CNT/Col hydrogels were noted to have better functionality. Collectively, the incorporation of CNTs into the Col hydrogels improved cell alignment and the performance of cardiac constructs. Our study suggests that CNT/Col hydrogels offer a promising tissue scaffold for cardiac constructs, and might serve as injectable biomaterials to deliver cell or drug molecules for cardiac regeneration following myocardial infarction in the near future. Keywords: carbon nanotubes, collagen hydrogel, cardiac constructs, cell alignment, tissue functionality

  11. Amphoteric Ion-Exchange Membranes with Significantly Improved Vanadium Barrier Properties for All-Vanadium Redox Flow Batteries.

    Science.gov (United States)

    Nibel, Olga; Rojek, Tomasz; Schmidt, Thomas J; Gubler, Lorenz

    2017-07-10

    All-vanadium redox flow batteries (VRBs) have attracted considerable interest as promising energy-storage devices that can allow the efficient utilization of renewable energy sources. The membrane, which separates the porous electrodes in a redox flow cell, is one of the key components in VRBs. High rates of crossover of vanadium ions and water through the membrane impair the efficiency and capacity of a VRB. Thus, membranes with low permeation rate of vanadium species and water are required, also characterized by low resistance and stability in the VRB environment. Here, we present a new design concept for amphoteric ion-exchange membranes, based on radiation-induced grafting of vinylpyridine into an ethylene tetrafluoroethylene base film and a two-step functionalization to introduce cationic and anionic exchange sites, respectively. During long-term cycling, redox flow cells containing these membranes showed higher efficiency, less pronounced electrolyte imbalance, and significantly reduced capacity decay compared to the cells with the benchmark material Nafion 117. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.

    Science.gov (United States)

    Gan, Lu; Duan, Hua; Xu, Qian; Tang, Yi-Qun; Li, Jin-Jiao; Sun, Fu-Qing; Wang, Sha

    2017-05-01

    Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models. Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured. Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri. hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. Use of a clinical pathway to improve the acute management of vaso-occlusive crisis pain in pediatric sickle cell disease.

    Science.gov (United States)

    Ender, Katherine L; Krajewski, Jennifer A; Babineau, John; Tresgallo, Mary; Schechter, William; Saroyan, John M; Kharbanda, Anupam

    2014-04-01

    The most common, debilitating morbidity of sickle cell disease (SCD) is vaso-occlusive crisis (VOC) pain. Although guidelines exist for its management, they are generally not well-followed, and research in other pediatric diseases has shown that clinical pathways improve care. The purpose of our study was to determine whether a clinical pathway improves the acute management of sickle cell vaso-occlusive crisis (VOC) pain in the pediatric emergency department (PED). Pain management practices were prospectively investigated before and after the initiation of a clinical pathway in the PED of an urban, tertiary care center with 50,000 ED visits per year and approximately 200 active sickle cell patients. The pathway included instructions for triage, monitoring, medication administration, and timing of assessments and interventions. Data were eligible from 35 pre-pathway and 33 post-pathway visits. Primary outcome was time interval to administration of first analgesic medication. Statistical analysis was by Student's t-test, using natural-log-transformed data for outcomes with skewed distribution curves. Time interval to first analgesic improved from 74 to 42 minutes (P = 0.012) and to first opioid from 94 to 46 minutes (P = 0.013). The percentage of patients who received ketorolac increased from 57% to 82% (P = 0.03). Decrease in time interval to subsequent pain score assessment was not statistically significant (110 to 72 minutes (P = 0.07)), and change in pain score was not different (P = 0.25). The use of a clinical pathway for sickle cell VOC in the PED can improve important aspects of pain management and merits further investigation and implementation. © 2013 Wiley Periodicals, Inc.

  14. EFFECT SIGNIFICANCE ASSESSMENT OF THE THERMODYNAMICAL FACTORS ON THE SOLID OXIDE FUEL CELL OPERATION

    Directory of Open Access Journals (Sweden)

    V. A. Sednin

    2015-01-01

    Full Text Available Technologies of direct conversion of the fuel energy into electrical power are an upcoming trend in power economy. Over the last decades a number of countries have created industrial prototypes of power plants on fuel elements (cells, while fuel cells themselves became a commercial product on the world energy market. High electrical efficiency of the fuel cells allows predictting their further spread as part of hybrid installations jointly with gas and steam turbines which specifically enables achieving the electrical efficiency greater than 70 %. Nevertheless, investigations in the area of increasing efficiency and reliability of the fuel cells continue. Inter alia, research into the effects of oxidizing reaction thermodynamic parameters, fuel composition and oxidation reaction products on effectiveness of the solid oxide fuel cells (SOFC is of specific scientific interest. The article presents a concise analysis of the fuel type effects on the SOFC efficiency. Based on the open publications experimental data and the data of numerical model studies, the authors adduce results of the statistical analysis of the SOFC thermodynamic parameters effect on the effectiveness of its functioning as well as of the reciprocative factors of these parameters and gas composition at the inlet and at the outlet of the cell. The presented diagrams reflect dimension of the indicated parameters on the SOFC operation effectiveness. The significance levels of the above listed factors are ascertained. Statistical analysis of the effects of the SOFC functionning process thermodynamical, consumption and concentration parameters demonstrates quintessential influence of the reciprocative factors (temperature – flow-rate and pressure – flow-rate and the nitrogen N2 and oxygen O2 concentrations on the operation efficiency in the researched range of its functioning. These are the parameters to be considered on a first-priority basis while developing mathematical models

  15. Deformable Hollow Periodic Mesoporous Organosilica Nanocapsules for Significantly Improved Cellular Uptake.

    Science.gov (United States)

    Teng, Zhaogang; Wang, Chunyan; Tang, Yuxia; Li, Wei; Bao, Lei; Zhang, Xuehua; Su, Xiaodan; Zhang, Fan; Zhang, Junjie; Wang, Shouju; Zhao, Dongyuan; Lu, Guangming

    2018-01-31

    Mesoporous solids have been widely used in various biomedical areas such as drug delivery and tumor therapy. Although deformability has been recognized as a prime important characteristic influencing cellular uptake, the synthesis of deformable mesoporous solids is still a great challenge. Herein, deformable thioether-, benzene-, and ethane-bridged hollow periodic mesoporous organosilica (HPMO) nanocapsules have successfully been synthesized for the first time by a preferential etching approach. The prepared HPMO nanocapsules possess uniform diameters (240-310 nm), high surface areas (up to 878 m 2 ·g -1 ), well-defined mesopores (2.6-3.2 nm), and large pore volumes (0.33-0.75 m 3 ·g -1 ). Most importantly, the HPMO nanocapsules simultaneously have large hollow cavities (164-270 nm), thin shell thicknesses (20-38 nm), and abundant organic moiety in the shells, which endow a lower Young's modulus (E Y ) of 3.95 MPa than that of solid PMO nanoparticles (251 MPa). The HPMOs with low E Y are intrinsically flexible and deformable in the solution, which has been well-characterized by liquid cell electron microscopy. More interestingly, it is found that the deformable HPMOs can easily enter into human breast cancer MCF-7 cells via a spherical-to-oval morphology change, resulting in a 26-fold enhancement in cellular uptake (43.1% cells internalized with nanocapsules versus 1.65% cells with solid counterparts). The deformable HPMO nanocapsules were further loaded with anticancer drug doxorubicin (DOX), which shows high killing effects for MCF-7 cells, demonstrating the promise for biomedical applications.

  16. Human endothelial colony-forming cells expanded with an improved protocol are a useful endothelial cell source for scaffold-based tissue engineering.

    Science.gov (United States)

    Denecke, Bernd; Horsch, Liska D; Radtke, Stefan; Fischer, Johannes C; Horn, Peter A; Giebel, Bernd

    2015-11-01

    One of the major challenges in tissue engineering is to supply larger three-dimensional (3D) bioengineered tissue transplants with sufficient amounts of nutrients and oxygen and to allow metabolite removal. Consequently, artificial vascularization strategies of such transplants are desired. One strategy focuses on endothelial cells capable of initiating new vessel formation, which are settled on scaffolds commonly used in tissue engineering. A bottleneck in this strategy is to obtain sufficient amounts of endothelial cells, as they can be harvested only in small quantities directly from human tissues. Thus, protocols are required to expand appropriate cells in sufficient amounts without interfering with their capability to settle on scaffold materials and to initiate vessel formation. Here, we analysed whether umbilical cord blood (CB)-derived endothelial colony-forming cells (ECFCs) fulfil these requirements. In a first set of experiments, we showed that marginally expanded ECFCs settle and survive on different scaffold biomaterials. Next, we improved ECFC culture conditions and developed a protocol for ECFC expansion compatible with 'Good Manufacturing Practice' (GMP) standards. We replaced animal sera with human platelet lysates and used a novel type of tissue-culture ware. ECFCs cultured under the new conditions revealed significantly lower apoptosis and increased proliferation rates. Simultaneously, their viability was increased. Since extensively expanded ECFCs could still settle on scaffold biomaterials and were able to form tubular structures in Matrigel assays, we conclude that these ex vivo-expanded ECFCs are a novel, very potent cell source for scaffold-based tissue engineering. Copyright © 2013 John Wiley & Sons, Ltd.

  17. Combining G-CSF with a blockade of adhesion strongly improves the reconstitutive capacity of mobilized hematopoietic progenitor cells.

    Science.gov (United States)

    Christ, O; Kronenwett, R; Haas, R; Zöller, M

    2001-03-01

    Mobilization of hematopoietic progenitor cells is achieved mainly by application of growth factors and, more recently, by blockade of adhesion. In this report, we describe the advantages of a combined treatment with granulocyte colony-stimulating factor (G-CSF) and anti-VLA4 (CD49d)/anti-CD44 as compared to treatment with the individual components. Mobilization by intravenous injection of anti-CD44, anti-VLA4, or G-CSF was controlled in spleen and bone marrow with regard to frequencies of multipotential colony-forming unit (C-CFU), marrow repopulating ability, long-term reconstitution, recovery of myelopoiesis, and regain of immunocompetence. Mobilization by anti-CD44 had a strong effect on expansion of early progenitor cells in the bone marrow, while the recovery in the spleen was poor. In anti-CD49d-mobilized noncommitted and committed progenitors, progenitor expansion was less pronounced, but settlement in the spleen was quite efficient. Thus, anti-CD44 and anti-CD49d differently influenced mobilization. Accordingly, mobilization and recovery after transfer were improved by combining anti-CD44 with anti-CD49d treatment. Mobilization by G-CSF was most efficient with respect to recovery of progenitor cells in the spleen. However, when transferring G-CSF-mobilized cells, regain of immunocompetence was strongly delayed. This disadvantage could be overridden when progenitor cells were mobilized via blockade of adhesion and when expansion of these mobilized progenitor cells was supported by low-dose G-CSF only during the last 24 hours before transfer. Mobilization of pluripotent progenitor cells via antibody blockade of CD44 or CD49d or via G-CSF relies on distinct mechanisms. Therefore, the reconstitutive capacity of a transplant can be significantly improved by mobilization regimens combining antibody with low-dose G-CSF treatment.

  18. Spontaneous Resolution of Long-Standing Macular Detachment due to Optic Disc Pit with Significant Visual Improvement.

    Science.gov (United States)

    Parikakis, Efstratios A; Chatziralli, Irini P; Peponis, Vasileios G; Karagiannis, Dimitrios; Stratos, Aimilianos; Tsiotra, Vasileia A; Mitropoulos, Panagiotis G

    2014-01-01

    To report a case of spontaneous resolution of a long-standing serous macular detachment associated with an optic disc pit, leading to significant visual improvement. A 63-year-old female presented with a 6-month history of blurred vision and micropsia in her left eye. Her best-corrected visual acuity was 6/24 in the left eye, and fundoscopy revealed serous macular detachment associated with optic disc pit, which was confirmed by optical coherence tomography (OCT). The patient was offered vitrectomy as a treatment alternative, but she preferred to be reviewed conservatively. Three years after initial presentation, neither macular detachment nor subretinal fluid was evident in OCT, while the inner segment/outer segment (IS/OS) junction line was intact. Her visual acuity was improved from 6/24 to 6/12 in her left eye, remaining stable at the 6-month follow-up after resolution. We present a case of spontaneous resolution of a long-standing macular detachment associated with an optic disc pit with significant visual improvement, postulating that the integrity of the IS/OS junction line may be a prognostic factor for final visual acuity and suggesting OCT as an indicator of visual prognosis and the probable necessity of a surgical management.

  19. Spontaneous Resolution ofLong-Standing Macular Detachment due to Optic Disc Pit with Significant Visual Improvement

    Directory of Open Access Journals (Sweden)

    Efstratios A. Parikakis

    2014-03-01

    Full Text Available Purpose: To report a case of spontaneous resolution of a long-standing serous macular detachment associated with an optic disc pit, leading to significant visual improvement. Case Presentation: A 63-year-old female presented with a 6-month history of blurred vision and micropsia in her left eye. Her best-corrected visual acuity was 6/24 in the left eye, and fundoscopy revealed serous macular detachment associated with optic disc pit, which was confirmed by optical coherence tomography (OCT. The patient was offered vitrectomy as a treatment alternative, but she preferred to be reviewed conservatively. Three years after initial presentation, neither macular detachment nor subretinal fluid was evident in OCT, while the inner segment/outer segment (IS/OS junction line was intact. Her visual acuity was improved from 6/24 to 6/12 in her left eye, remaining stable at the 6-month follow-up after resolution. Conclusion: We present a case of spontaneous resolution of a long-standing macular detachment associated with an optic disc pit with significant visual improvement, postulating that the integrity of the IS/OS junction line may be a prognostic factor for final visual acuity and suggesting OCT as an indicator of visual prognosis and the probable necessity of a surgical management.

  20. Improved Diffuse Fluorescence Flow Cytometer Prototype for High Sensitivity Detection of Rare Circulating Cells In Vivo

    Science.gov (United States)

    Pestana, Noah Benjamin

    Accurate quantification of circulating cell populations is important in many areas of pre-clinical and clinical biomedical research, for example, in the study of cancer metastasis or the immune response following tissue and organ transplants. Normally this is done "ex-vivo" by drawing and purifying a small volume of blood and then analyzing it with flow cytometry, hemocytometry or microfludic devices, but the sensitivity of these techniques are poor and the process of handling samples has been shown to affect cell viability and behavior. More recently "in vivo flow cytometry" (IVFC) techniques have been developed where fluorescently-labeled cells flowing in a small blood vessel in the ear or retina are analyzed, but the sensitivity is generally poor due to the small sampling volume. To address this, our group recently developed a method known as "Diffuse Fluorescence Flow Cytometry" (DFFC) that allows detection and counting of rare circulating cells with diffuse photons, offering extremely high single cell counting sensitivity. In this thesis, an improved DFFC prototype was designed and validated. The chief improvements were three-fold, i) improved optical collection efficiency, ii) improved detection electronics, and iii) development of a method to mitigate motion artifacts during in vivo measurements. In combination, these improvements yielded an overall instrument detection sensitivity better than 1 cell/mL in vivo, which is the most sensitive IVFC system reported to date. Second, development and validation of a low-cost microfluidic device reader for analysis of ocular fluids is described. We demonstrate that this device has equivalent or better sensitivity and accuracy compared a fluorescence microscope, but at an order-of-magnitude reduced cost with simplified operation. Future improvements to both instruments are also discussed.

  1. Natural Killer Cells Improve Hematopoietic Stem Cell Engraftment by Increasing Stem Cell Clonogenicity In Vitro and in a Humanized Mouse Model.

    Science.gov (United States)

    Escobedo-Cousin, Michelle; Jackson, Nicola; Laza-Briviesca, Raquel; Ariza-McNaughton, Linda; Luevano, Martha; Derniame, Sophie; Querol, Sergio; Blundell, Michael; Thrasher, Adrian; Soria, Bernat; Cooper, Nichola; Bonnet, Dominique; Madrigal, Alejandro; Saudemont, Aurore

    2015-01-01

    Cord blood (CB) is increasingly used as a source of hematopoietic stem cells (HSC) for transplantation. Low incidence and severity of graft-versus-host disease (GvHD) and a robust graft-versus-leukemia (GvL) effect are observed following CB transplantation (CBT). However, its main disadvantages are a limited number of HSC per unit, delayed immune reconstitution and a higher incidence of infection. Unmanipulated grafts contain accessory cells that may facilitate HSC engraftment. Therefore, the effects of accessory cells, particularly natural killer (NK) cells, on human CB HSC (CBSC) functions were assessed in vitro and in vivo. CBSC cultured with autologous CB NK cells showed higher levels of CXCR4 expression, a higher migration index and a higher number of colony forming units (CFU) after short-term and long-term cultures. We found that CBSC secreted CXCL9 following interaction with CB NK cells. In addition, recombinant CXCL9 increased CBSC clonogenicity, recapitulating the effect observed of CB NK cells on CBSC. Moreover, the co-infusion of CBSC with CB NK cells led to a higher level of CBSC engraftment in NSG mouse model. The results presented in this work offer the basis for an alternative approach to enhance HSC engraftment that could improve the outcome of CBT.

  2. Cellular targets for improved manufacturing of virus-based biopharmaceuticals in animal cells.

    Science.gov (United States)

    Rodrigues, Ana F; Carrondo, Manuel J T; Alves, Paula M; Coroadinha, Ana S

    2014-12-01

    The past decade witnessed the entry into the market of new virus-based biopharmaceuticals produced in animal cells such as oncolytic vectors, virus-like particle vaccines, and gene transfer vectors. Therefore, increased attention and investment to optimize cell culture processes towards enhanced manufacturing of these bioproducts is anticipated. Herein, we review key findings on virus-host interactions that have been explored in cell culture optimization. Approaches supporting improved productivity or quality of vector preparations are discussed, mainly focusing on medium design and genetic manipulation. This review provides an integrated outline for current and future efforts in exploring cellular targets for the optimization of cell culture manufacturing of virus-based biopharmaceuticals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Expression of Rab25 in non-small cell lung cancer and its clinical significance

    Directory of Open Access Journals (Sweden)

    Pu ZHOU

    2014-03-01

    Full Text Available Objective To assess the expression of Rab25 protein in non-small cell lung cancer (NSCLC, and explore the correlation of its expression with tumor proliferation and metastasis. Methods Sixty-one cases of NSCLC specimens (31 cases of squamous cell carcinoma, 26 cases of adenocarcinoma, and 4 cases of adenosquamous carcinoma undergone surgical treatment, and 40 specimens of adjacent normal lung tissues were obtained from Jan. 2009 to Jun. 2010 at Xingqiao Hospital of Third Military Medical University. Immunochemistry method of MaxVision was used to detect the expression of Rab25 in the specimens, and then the correlation of the expression with the clinicopathological parameters (patients' sex, age, smoking history, tumor type, differentiation, volume, TNM stage, lymph metastasis, etc. was analyzed using statistical software SPSS 21.0. Results  Rab25 protein was mainly expressed in cytoplasm and cell membrane. The positive rate of Rab25 in NSCLC was 93.4%, which was significantly higher than that in adjacent normal tissues (27.5%, P<0.01. The expression of Rab25 protein was significantly associated with the TNM stage and tumor size (P<0.05. Conclusions The expression of Rab25 is obviously higher in NSCLC than in the adjacent normal tissues, and the expression is associated with TNM stage and tumor size. Moreover, the later of the NSCLC stage, the larger of tumor size, and the higher of Rab25 expression will be in the NSCLC tissue. DOI: 10.11855/j.issn.0577-7402.2014.02.16

  4. Improved premises for cell factory development

    DEFF Research Database (Denmark)

    Søgaard, Karina Marie

    The sustainable manufacturing of medicines, materials and chemicals is enabled with biotechnology, and the key to the development of new processes, as well as improvement of existing ones, lies in our fundamental understanding of the biological systems we manipulate. Recombinant protein production...... is at the core of biotechnology and numerous molecular tools and bacterial strains have been developed over the past four decades for this purpose. Understanding of the genetic code and our ability to manipulate genetic material, paves the way for the microbial cell factory development that enables production......, and building a platform for enhanced expression of certain plant genes in bacteria. The relevance of the conducted research to the field of biotechnology is covered, as well as necessary scientific background and history. Specifically, the surprisingly minor effects of tRNA overexpression on the production...

  5. Improved method and apparatus for electrostatically sorting biological cells. [DOE patent application

    Science.gov (United States)

    Merrill, J.T.

    An improved method of sorting biological cells in a conventional cell sorter apparatus includes generating a fluid jet containing cells to be sorted, measuring the distance between the centers of adjacent droplets in a zone thereof defined at the point where the fluid jet separates into descrete droplets, setting the distance between the center of a droplet in said separation zone and the position along said fluid jet at which the cell is optically sensed for specific characteristics to be an integral multiple of said center-to-center distance, and disabling a charger from electrically charging a specific droplet if a cell is detected by the optical sensor in a position wherein it will be in the neck area between droplets during droplet formation rather than within a predetermined distance from the droplet center.

  6. Cell phone-based health education messaging improves health literacy.

    Science.gov (United States)

    Zhuang, Runsen; Xiang, Yueying; Han, Tieguang; Yang, Guo-An; Zhang, Yuan

    2016-03-01

    The ubiquity of cell phones, which allow for short message service (SMS), provides new and innovative opportunities for disease prevention and health education. To explore the use of cell phone-based health education SMS to improve the health literacy of community residents in China. A multi-stage random sampling method was used to select representative study communities and participants ≥ 18 years old. Intervention participants were sent health education SMSs once a week for 1 year and controls were sent conventional, basic health education measures. Health literacy levels of the residents before and after the intervention were evaluated between intervention and control groups. Public health literacy scores increased 1.5 points, from 61.8 to 63.3, after SMS intervention for 1 year (P<0.01); the increase was greater for males than females (2.01 vs. 1.03; P<0.01) and for Shenzhen local residents than non-permanent residents (2.56 vs. 1.14; P<0.01). The frequency of high health literacy scores was greater for the intervention than control group (22.03% to 30.93% vs. 22.07% to 20.82%). With health literacy as a cost-effective index, the cost-effectiveness per intervention was 0.54. SMS may be a useful tool for improving health literacy.

  7. An initiative to improve the management of clinically significant test results in a large health care network.

    Science.gov (United States)

    Roy, Christopher L; Rothschild, Jeffrey M; Dighe, Anand S; Schiff, Gordon D; Graydon-Baker, Erin; Lenoci-Edwards, Jennifer; Dwyer, Cheryl; Khorasani, Ramin; Gandhi, Tejal K

    2013-11-01

    The failure of providers to communicate and follow up clinically significant test results (CSTR) is an important threat to patient safety. The Massachusetts Coalition for the Prevention of Medical Errors has endorsed the creation of systems to ensure that results can be received and acknowledged. In 2008 a task force was convened that represented clinicians, laboratories, radiology, patient safety, risk management, and information systems in a large health care network with the goals of providing recommendations and a road map for improvement in the management of CSTR and of implementing this improvement plan during the sub-force sequent five years. In drafting its charter, the task broadened the scope from "critical" results to "clinically significant" ones; clinically significant was defined as any result that requires further clinical action to avoid morbidity or mortality, regardless of the urgency of that action. The task force recommended four key areas for improvement--(1) standardization of policies and definitions, (2) robust identification of the patient's care team, (3) enhanced results management/tracking systems, and (4) centralized quality reporting and metrics. The task force faced many challenges in implementing these recommendations, including disagreements on definitions of CSTR and on who should have responsibility for CSTR, changes to established work flows, limitations of resources and of existing information systems, and definition of metrics. This large-scale effort to improve the communication and follow-up of CSTR in a health care network continues with ongoing work to address implementation challenges, refine policies, prepare for a new clinical information system platform, and identify new ways to measure the extent of this important safety problem.

  8. Improved performance of silicon-nanoparticle film-coated dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Ravindra Kumar; Bedja, Idriss M. [CRC, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433 (Saudi Arabia); Aldwayyan, Abdullah Saleh [Department of Physics and Astronomy, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia)

    2012-11-15

    Silicon (Si) nanoparticles with average size of 13 nm and orange-red luminescence under UV absorption were synthesized using electrochemical etching of silicon wafers. A film of Si nanoparticles with thickness of 0.75 {mu}m to 2.6 {mu}m was coated on the glass (TiO{sub 2} side) of a dye-sensitized solar cell (DSSC). The cell exhibited nearly 9% enhancement in power conversion efficiency ({eta}) at film thickness of {proportional_to}2.4 {mu}m under solar irradiation of 100 mW/cm{sup 2} (AM 1.5) with improved fill factor and short-circuit current density. This study revealed for the first time that the Si-nanoparticle film converting UV into visible light and helping in homogeneous irradiation, can be utilized for improving the efficiency of the DSSCs. (copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  9. Cell type-dependent induction of DNA damage by 1800 MHz radiofrequency electromagnetic fields does not result in significant cellular dysfunctions.

    Directory of Open Access Journals (Sweden)

    Shanshan Xu

    Full Text Available BACKGROUND: Although IARC clarifies radiofrequency electromagnetic fields (RF-EMF as possible human carcinogen, the debate on its health impact continues due to the inconsistent results. Genotoxic effect has been considered as a golden standard to determine if an environmental factor is a carcinogen, but the currently available data for RF-EMF remain controversial. As an environmental stimulus, the effect of RF-EMF on cellular DNA may be subtle. Therefore, more sensitive method and systematic research strategy are warranted to evaluate its genotoxicity. OBJECTIVES: To determine whether RF-EMF does induce DNA damage and if the effect is cell-type dependent by adopting a more sensitive method γH2AX foci formation; and to investigate the biological consequences if RF-EMF does increase γH2AX foci formation. METHODS: Six different types of cells were intermittently exposed to GSM 1800 MHz RF-EMF at a specific absorption rate of 3.0 W/kg for 1 h or 24 h, then subjected to immunostaining with anti-γH2AX antibody. The biological consequences in γH2AX-elevated cell type were further explored with comet and TUNEL assays, flow cytometry, and cell growth assay. RESULTS: Exposure to RF-EMF for 24 h significantly induced γH2AX foci formation in Chinese hamster lung cells and Human skin fibroblasts (HSFs, but not the other cells. However, RF-EMF-elevated γH2AX foci formation in HSF cells did not result in detectable DNA fragmentation, sustainable cell cycle arrest, cell proliferation or viability change. RF-EMF exposure slightly but not significantly increased the cellular ROS level. CONCLUSIONS: RF-EMF induces DNA damage in a cell type-dependent manner, but the elevated γH2AX foci formation in HSF cells does not result in significant cellular dysfunctions.

  10. Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement.

    Science.gov (United States)

    Zeng, Bin; Ren, Xiaofeng; Lin, Guosheng; Zhu, Chengang; Chen, Honglei; Yin, Jiechao; Jiang, Hong; Yang, Bo; Ding, Danhua

    2008-10-01

    The aim has been to determine whether the supernatants of mesenchymal stem cells (MSCs) transfected with adenovirus carrying human heme oxygenase-1 (hHO-1) gene protect cardiomyocytes from ischemic injury. We have found that hHO-1 infected MSCs (hHO-1-MSCs) increased expression of hHO-1 protein. Apoptosis of cultured hHO-1-MSCs exposed to hypoxia was suppressed. Several cytokines, including HGF, bFGF, TGF-beta, VEGF and IL-1beta, were produced by hHO-1-MSCs, some being significantly enhanced under hypoxia stimulation. Meanwhile, those cytokines reduced caspase-3 level and activity in cultured adult rat ventricular cardiomyocytes (ARVCs) exposed to hypoxia. Supernatants obtained from hHO-1-MSCs improved left ventricular function, limited myocardial infarct size, increased microvessel density, and inhibited apoptosis of cardiomyocytes in rat myocardial infarction. It can be concluded hHO-1-modified MSCs prevent myocardial cell injury via secretion of paracrine-acting mediators.

  11. Communication: Proper treatment of classically forbidden electronic transitions significantly improves detailed balance in surface hopping

    Energy Technology Data Exchange (ETDEWEB)

    Sifain, Andrew E. [Department of Physics and Astronomy, University of Southern California, Los Angeles, California 90089-0485 (United States); Wang, Linjun [Department of Chemistry, Zhejiang University, Hangzhou 310027 (China); Prezhdo, Oleg V. [Department of Physics and Astronomy, University of Southern California, Los Angeles, California 90089-0485 (United States); Department of Chemistry, University of Southern California, Los Angeles, California 90089-1062 (United States)

    2016-06-07

    Surface hopping is the most popular method for nonadiabatic molecular dynamics. Many have reported that it does not rigorously attain detailed balance at thermal equilibrium, but does so approximately. We show that convergence to the Boltzmann populations is significantly improved when the nuclear velocity is reversed after a classically forbidden hop. The proposed prescription significantly reduces the total number of classically forbidden hops encountered along a trajectory, suggesting that some randomization in nuclear velocity is needed when classically forbidden hops constitute a large fraction of attempted hops. Our results are verified computationally using two- and three-level quantum subsystems, coupled to a classical bath undergoing Langevin dynamics.

  12. [Clinic significance of nm23, collage IV and PCNA expression in non-small cell lung cancer].

    Science.gov (United States)

    Yu, Q; Ma, L; Jing, S; Xu, Y; Geng, D

    2001-12-20

    To study the significance of nm23, collagen IV and PCNA expressions in non-small cell lung cancer. Expressions of the nm23, collagen IV and PCNA in 84 cases of non-small cell lung cancer were examined with SP immunohistochemical technique. Of the 84 cases, there were squamous cell carcinoma 42, adenocarcinoma 42, stage I 27, stage II 24, stage III 24, and stage IV 9. Statistical analysis was performed with Chi-Square test. Expressions of the nm23, collagen IV and PCNA in 84 cases of non-small cell lung cancer were 60. 7% ( 51/ 84) , 75. 0% ( 63/ 84) and 53. 6% ( 45/ 84) respectively. There was negative correlation between the lymph node metastasis and the expressions of nm23 and collagen IV in squamous cell carcinoma, and the expressions of collagen IV and PCNA were associated with tumor differentiation. No correlation was found between TNM stage and expressions of nm23, collagen IV and PCNA. The results indicate that nm23, collagen IV and PCNA participate the modulation of metastasis of non-small cell lung cancer and that they may be used to evaluate the potential of metastasis.

  13. Combined strategy of endothelial cells coating, Sertoli cells coculture and infusion improves vascularization and rejection protection of islet graft.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available Improving islet graft revascularization and inhibiting rejection become crucial tasks for prolonging islet graft survival. Endothelial cells (ECs are the basis of islet vascularization and Sertoli cells (SCs have the talent to provide nutritional support and exert immunosuppressive effects. We construct a combined strategy of ECs coating in the presence of nutritious and immune factors supplied by SCs in a co-culture system to investigate the effect of vascularization and rejection inhibition for islet graft. In vivo, the combined strategy improved the survival and vascularization as well as inhibited lymphocytes and inflammatory cytokines. In vitro, we found the combinatorial strategy improved the function of islets and the effect of ECs-coating on islets. Combined strategy treated islets revealed higher levels of anti-apoptotic signal molecules (Bcl-2 and HSP-32, survival and function related molecules (PDX-1, Ki-67, ERK1/2 and Akt and demonstrated increased vascular endothelial growth factor receptor 2 (KDR and angiogenesis signal molecules (FAk and PLC-γ. SCs effectively inhibited the activation of lymphocyte stimulated by islets and ECs. Predominantly immunosuppressive cytokines could be detected in culture supernatants of the SCs coculture group. These results suggest that ECs-coating and Sertoli cells co-culture or infusion synergistically enhance islet survival and function after transplantation.

  14. Industrial n-type solar cells with >20% cell efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Romijn, I.G.; Anker, J.; Burgers, A.R.; Gutjahr, A.; Koppes, M.; Kossen, E.J.; Lamers, M.W.P.E.; Heurtault, Benoit; Saynova-Oosterling, D.S.; Tool, C.J.J. [ECN Solar Energy, Petten (Netherlands)

    2013-03-15

    To realize high efficiencies at low costs, ECN has developed the n-Pasha solar cell concept. The n-Pasha cell concept is a bifacial solar cell concept on n-Cz base material, with which average efficiencies of above 20% have been demonstrated. In this paper recent developments at ECN to improve the cost of ownership (lower Euro/Wp) of the n-Pasha cell concept are discussed. Two main drivers for the manufacturing costs of n-type solar cells are addressed: the n-type Cz silicon material and the silver consumption. We show that a large resistivity range between 2 and 8 cm can be tolerated for high cell efficiency, and that the costs due to the silver metallization can be significantly reduced while increasing the solar cell efficiency. Combining the improved efficiency and cost reduction makes the n-Pasha cell concept a very cost effective solution to manufacture high efficient solar cells and modules.

  15. Lipofection of insulin-producing RINm5F cells: methodological improvements.

    Science.gov (United States)

    Barbu, Andreea; Welsh, Nils

    2007-01-01

    Cationic lipid/DNA-complexes have been widely used as gene transfer vectors because they are less toxic and immunogenic than viral vectors. The aim of the present study was to improve and characterize lipofection of an insulin-producing cell line. We compared the transfection efficiency of seven commercially available lipid formulations (Lipotaxi, SuperFect, Fugene, TransFast, Dosper, GenePORTER and LipofectAMINE) by flow cytometry analysis of GFP-expression. In addition, we have determined the influences of centrifugation, serum and a nuclear localization signal peptide on the lipofection efficiency. We observed that two lipid formulations, GenePORTER and LipofectAMINE, were able to promote efficient gene transfer in RINm5F cells. However, GenePORTER exhibited the important advantage of being able to transfect cells in the presence of serum and with less cytotoxicity than LipofectAMINE. LipofectAMINE-induced RINm5F cell death could partially be counteracted by TPA, forskolin or fumonisin beta(1). Finally, both centrifugation and a nuclear localization signal peptide increased transfection efficiency.

  16. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Science.gov (United States)

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  17. 16.1% Efficient Hysteresis-Free Mesostructured Perovskite Solar Cells Based on Synergistically Improved ZnO Nanorod Arrays

    KAUST Repository

    Mahmood, Khalid

    2015-06-01

    Significant efficiency improvements are reported in mesoscopic perovskite solar cells based on the development of a low-temperature solution-processed ZnO nanorod (NR) array exhibiting higher NR aspect ratio, enhanced electron density, and substantially reduced work function than conventional ZnO NRs. These features synergistically result in hysteresis-free, scan-independent, and stabilized devices with an efficiency of 16.1%. Electron-rich, nitrogen-doped ZnO (N:ZnO) NR-based electron transporting materials (ETMs) with enhanced electron mobility produced using ammonium acetate show consistently higher efficiencies by one to three power points than undoped ZnO NRs. Additionally, the preferential electrostatic interaction between the -nonpolar facets of N:ZnO and the conjugated polyelectrolyte polyethylenimine (PEI) has been relied on to promote the hydrothermal growth of high aspect ratio NR arrays and substantially improve the infiltration of the perovskite light absorber into the ETM. Using the same interactions, a conformal PEI coating on the electron-rich high aspect ratio N:ZnO NR arrays is -successfully applied, resulting in a favorable work function shift and altogether leading to the significant boost in efficiency from <10% up to >16%. These results largely surpass the state-of-the-art PCE of ZnO-based perovskite solar cells and highlight the benefits of synergistically combining mesoscale control with doping and surface modification. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Kefir exhibits anti‑proliferative and pro‑apoptotic effects on colon adenocarcinoma cells with no significant effects on cell migration and invasion.

    Science.gov (United States)

    Khoury, Nathalie; El-Hayek, Stephany; Tarras, Omayr; El-Sabban, Marwan; El-Sibai, Mirvat; Rizk, Sandra

    2014-11-01

    Kefir, a fermented milk product, exhibits anti‑tumoral activity in vivo; yet its mechanism of action remains elusive. Recent studies have focused on the mechanism of action of kefir on cancer cells in vitro. The current study aims at examining the effect of kefir on cell survival, proliferation, and motility of colorectal cancer (CRC) cells. Kefir's anti‑cancer potential was tested on CRC cell lines, Caco‑2 and HT‑29, through cytotoxicity, proliferation, and apoptotic assays. The expression of certain genes involved in proliferation and apoptosis was measured using reverse transcriptase‑polymerase chain reaction (RT‑PCR) and western blotting. To assess the effect of kefir on cancer metastasis, wound‑healing and time‑lapse movies, in addition to collagen‑based invasion assay, were used. The results show that cell‑free fractions of kefir exhibit an anti‑proliferative effect on Caco‑2 and HT‑29 cells. Analysis of DNA content by flow cytometry revealed the ability of kefir to induce cell cycle arrest at the G1 phase. Kefir was also found to induce apoptosis, as seen by cell death ELISA. Results from RT‑PCR showed that kefir decreases the expression of transforming growth factor α (TGF‑α); and transforming growth factor‑β1 (TGF‑β1) in HT‑29 cells. Western blotting results revealed an upregulation in Bax:Bcl‑2 ratio, confirming the pro‑apoptotic effect of kefir, and an increase in p53 independent‑p21 expression upon kefir treatment. MMP expression was not altered by kefir treatment. Furthermore, results from time‑lapse motility movies, wound‑healing, and invasion assays showed no effect on the motility of colorectal as well as breast (MCF‑7 and MB‑MDA‑231) cancer cells upon kefir treatment. Our data suggest that kefir is able to inhibit the proliferation and induce apoptosis in HT‑29 and Caco‑2 CRC cells, yet it does not exhibit a significant effect on the motility and invasion of these cells in vitro.

  19. Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks.

    Directory of Open Access Journals (Sweden)

    Prasanna Vidyasekar

    Full Text Available Zero gravity causes several changes in metabolic and functional aspects of the human body and experiments in space flight have demonstrated alterations in cancer growth and progression. This study reports the genome wide expression profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell line-MOLT-4, under simulated microgravity in an effort to understand central processes and cellular functions that are dysregulated among both cell lines. Altered cell morphology, reduced cell viability and an aberrant cell cycle profile in comparison to their static controls were observed in both cell lines under microgravity. The process of cell cycle in DLD-1 cells was markedly affected with reduced viability, reduced colony forming ability, an apoptotic population and dysregulation of cell cycle genes, oncogenes, and cancer progression and prognostic markers. DNA microarray analysis revealed 1801 (upregulated and 2542 (downregulated genes (>2 fold in DLD-1 cultures under microgravity while MOLT-4 cultures differentially expressed 349 (upregulated and 444 (downregulated genes (>2 fold under microgravity. The loss in cell proliferative capacity was corroborated with the downregulation of the cell cycle process as demonstrated by functional clustering of DNA microarray data using gene ontology terms. The genome wide expression profile also showed significant dysregulation of post transcriptional gene silencing machinery and multiple microRNA host genes that are potential tumor suppressors and proto-oncogenes including MIR22HG, MIR17HG and MIR21HG. The MIR22HG, a tumor-suppressor gene was one of the highest upregulated genes in the microarray data showing a 4.4 log fold upregulation under microgravity. Real time PCR validated the dysregulation in the host gene by demonstrating a 4.18 log fold upregulation of the miR-22 microRNA. Microarray data also showed dysregulation of direct targets of miR-22, SP1, CDK6 and CCNA2.

  20. Costello Syndrome with Severe Nodulocystic Acne: Unexpected Significant Improvement of Acanthosis Nigricans after Oral Isotretinoin Treatment

    Directory of Open Access Journals (Sweden)

    Leelawadee Sriboonnark

    2015-01-01

    Full Text Available We report the case of 17-year-old female diagnosed with Costello syndrome. Genetic testing provided a proof with G12S mutation in the HRAS gene since 3 years of age with a presentation of severe nodulocystic acne on her face. After 2 months of oral isotretinoin treatment, improvement in her acne was observed. Interestingly, an unexpected significant improvement of acanthosis nigricans on her neck and dorsum of her hands was found as well. We present this case as a successful treatment option by using oral isotretinoin for the treatment of acanthosis nigricans in Costello syndrome patients.

  1. Intradialytic aerobic cycling exercise alleviates inflammation and improves endothelial progenitor cell count and bone density in hemodialysis patients.

    Science.gov (United States)

    Liao, Min-Tser; Liu, Wen-Chih; Lin, Fu-Huang; Huang, Ching-Feng; Chen, Shao-Yuan; Liu, Chuan-Chieh; Lin, Shih-Hua; Lu, Kuo-Cheng; Wu, Chia-Chao

    2016-07-01

    Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients.

  2. Synaptic plasticity and sensory-motor improvement following fibrin sealant dorsal root reimplantation and mononuclear cell therapy

    Science.gov (United States)

    Benitez, Suzana U.; Barbizan, Roberta; Spejo, Aline B.; Ferreira, Rui S.; Barraviera, Benedito; Góes, Alfredo M.; de Oliveira, Alexandre L. R.

    2014-01-01

    Root lesions may affect both dorsal and ventral roots. However, due to the possibility of generating further inflammation and neuropathic pain, surgical procedures do not prioritize the repair of the afferent component. The loss of such sensorial input directly disturbs the spinal circuits thus affecting the functionality of the injuried limb. The present study evaluated the motor and sensory improvement following dorsal root reimplantation with fibrin sealant (FS) plus bone marrow mononuclear cells (MC) after dorsal rhizotomy. MC were used to enhance the repair process. We also analyzed changes in the glial response and synaptic circuits within the spinal cord. Female Lewis rats (6–8 weeks old) were divided in three groups: rhizotomy (RZ group), rhizotomy repaired with FS (RZ+FS group) and rhizotomy repaired with FS and MC (RZ+FS+MC group). The behavioral tests electronic von-Frey and Walking track test were carried out. For immunohistochemistry we used markers to detect different synapse profiles as well as glial reaction. The behavioral results showed a significant decrease in sensory and motor function after lesion. The reimplantation decreased glial reaction and improved synaptic plasticity of afferent inputs. Cell therapy further enhanced the rewiring process. In addition, both reimplanted groups presented twice as much motor control compared to the non-treated group. In conclusion, the reimplantation with FS and MC is efficient and may be considered an approach to improve sensory-motor recovery following dorsal rhizotomy. PMID:25249946

  3. Strategies for improving production performance of probiotic Pediococcus acidilactici viable cell by overcoming lactic acid inhibition.

    Science.gov (United States)

    Othman, Majdiah; Ariff, Arbakariya B; Wasoh, Helmi; Kapri, Mohd Rizal; Halim, Murni

    2017-11-27

    Lactic acid bacteria are industrially important microorganisms recognized for fermentative ability mostly in their probiotic benefits as well as lactic acid production for various applications. Fermentation conditions such as concentration of initial glucose in the culture, concentration of lactic acid accumulated in the culture, types of pH control strategy, types of aeration mode and different agitation speed had influenced the cultivation performance of batch fermentation of Pediococcus acidilactici. The maximum viable cell concentration obtained in constant fed-batch fermentation at a feeding rate of 0.015 L/h was 6.1 times higher with 1.6 times reduction in lactic acid accumulation compared to batch fermentation. Anion exchange resin, IRA 67 was found to have the highest selectivity towards lactic acid compared to other components studied. Fed-batch fermentation of P. acidilactici coupled with lactic acid removal system using IRA 67 resin showed 55.5 and 9.1 times of improvement in maximum viable cell concentration compared to fermentation without resin for batch and fed-batch mode respectively. The improvement of the P. acidilactici growth in the constant fed-batch fermentation indicated the use of minimal and simple process control equipment is an effective approach for reducing by-product inhibition. Further improvement in the cultivation performance of P. acidilactici in fed-bath fermentation with in situ addition of anion-exchange resin significantly helped to enhance the growth of P. acidilactici by reducing the inhibitory effect of lactic acid and thus increasing probiotic production.

  4. Improvement of high voltage cycling performance and thermal stability of lithium-ion cells by use of a thiophene additive

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ki-Soo; Sun, Yang-Kook; Kim, Dong-Won [Department of Chemical Engineering, Hanyang University, Seungdong-gu, Seoul 133-791 (Korea); Noh, Jaegeun [Department of Chemistry, Hanyang University, Seungdong-gu, Seoul 133-791 (Korea); Song, Kwang Soup [Advanced Medical Device Center, Korea Electrotechnology, Research Institute, Ansan, Gyeonggi-do 426-170 (Korea)

    2009-10-15

    This study demonstrates that the addition of thiophene improves the cycle life of lithium-ion cells at high voltage. Electrochemical impedance spectroscopy results suggest that addition of thiophene significantly suppresses the increase of the charge transfer resistance that occurs during cycling up to high voltage. Differential scanning calorimetric studies showed that the thermal stability of fully charged LiCoO{sub 2} cathode was also enhanced in the presence of thiophene. (author)

  5. [Expression of Ki-67 and P53 protein in oral squamous cell carcinoma and its clinical significance].

    Science.gov (United States)

    He, Wei; Xiao, Yan; Chen, Wei-min

    2015-04-01

    To investigate the clinical and pathological features and its relationship with the expression of Ki-67 and p53 protein in oral squamous cell carcinoma. Immunohistochemical SP staining method was used to quantify the protein expression levels of Ki-67 and p53 protein in 10 cases of normal oral mucosa, 16 cases of oral leukoplakia (OLK) tissue, and 48 cases of oral squamous cell carcinoma. The relationship of the expression of Ki-67 and p53 protein to clinical and pathological data was analyzed, and SPSS17.0 software package was used for statistical analysis. The positive expression rate of Ki-67 protein in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma was 30%, 56.3% and 79.2%, respectively; The positive expression rate of p53 was 0%, 43.8%, and 70.8%, respectively; Ki-67 and p53 expression had significant difference among normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma (Poral squamous cell carcinoma (Poral squamous cell carcinoma tissues may play an important role in the development of oral squamous cell carcinoma.

  6. α-Lactose Improves the Survival of Septic Mice by Blockade of TIM-3 Signaling to Prevent NKT Cell Apoptosis and Attenuate Cytokine Storm.

    Science.gov (United States)

    Yao, Yao; Deng, Hai; Li, Pingfei; Zhang, Jian; Zhang, Junbo; Wang, Deping; Li, Songbo; Luo, Yixing; Wei, Zhengping; Bi, Guoyu; Yang, Xiang-Ping; Tang, Zhao-Hui

    2017-03-01

    Sepsis is the leading cause of death among critically ill patients and natural killer T (NKT) cell activation is essential to induce inflammatory cytokine cascade in sepsis. However, little is known about what regulates the NKT cell function during sepsis. Herein, we showed that T-cell immunoglobulin and mucin domain 3 (Tim-3) expression in NKT cells is elevated in experimental mice during sepsis. Tim-3 expression was positively correlated with NKT cell activation and apoptosis. In sepsis, interleukin (IL)-12 secreted by dendritic cell exposure to lipopolysaccharide increased the expression of Tim-3 in NKT cells. Administration of α-lactose to block Tim-3 signaling pathway significantly improved the survival of septic mice, concomitant with reduced IL-12 production by dendritic cells, reduced Tim-3 expression, prevented NKT cell apoptosis, and attenuated production of inflammatory cytokines. Collectively, Tim-3 signaling in NKT cells plays a critical role in the immunopathogenesis of sepsis. Thus, α-lactose could be a promising immunomodulatory agent in the treatment of sepsis.

  7. Clinical significance of T-cell clonality in mycosis fungoides and other cutaneous T-cell lymphomas

    NARCIS (Netherlands)

    Muche, Joachim Marcus

    2010-01-01

    The purpose of this thesis was to obtain more insight into T-cell clonality in blood of mycosis fungoides (MF) patients. Investigation of the frequency of blood T-cell clonality clearly indicated early dissemination of neoplastic T-cells into skin and blood as a sign of physiological recirculation.

  8. Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm

    DEFF Research Database (Denmark)

    Rasmussen, Camilla Holzmann; Petersen, Dorthe Roenn; Møller, Jonas Bech

    2015-01-01

    Human embryonic stem cells have the ability to generate all cell types in the body and can potentially provide an unlimited source of cells for cell replacement therapy to treat degenerative diseases such as diabetes. Current differentiation protocols of human embryonic stem cells towards insulin...... and consistent differentiation of stem cells to definitive endoderm. The results shed light on the importance of extracellular matrix proteins for differentiation and also points to a cost effective and easy method to improve differentiation....... embryonic stem cells to the definitive endoderm lineage. The percentage of definitive endoderm cells after differentiation on collagen I and fibronectin was >85% and 65%, respectively. The cells on collagen I substrates displayed different morphology and gene expression during differentiation as assessed...

  9. Prognostic significance of nuclear factor of activated T-cells 5 expression in non-small cell lung cancer patients who underwent surgical resection.

    Science.gov (United States)

    Cho, Hyun Jin; Yun, Hwan-Jung; Yang, Hee Chul; Kim, Soo Jin; Kang, Shin Kwang; Che, Chengri; Lee, Sang Do; Kang, Min-Woong

    2018-06-01

    Nuclear factor of activated T-cells 5 (NFAT5) is known to be correlated with migration or invasion of tumor cells based on previous in vitro studies. The aim of this study was to analyze the relationship between NFAT5 expression and clinical prognosis in non-small cell lung cancer (NSCLC) patients who underwent surgical resection. A total of 92 NSCLC patients who underwent surgical resection were enrolled. The tissue microarray core was obtained from surgically resected tumor specimens. NFAT5 expression was evaluated by immunohistochemistry. Relationships of NFAT5 expression with disease recurrence, overall survival, and disease-free survival (DFS) were analyzed. The mean age of 92 patients was 63.7 y. The median follow-up duration was 63.3 mo. Fifty-one (55%) patients exhibited positive expression of NFAT5. Disease recurrence in the NFAT5-positive group was significantly (P = 0.022) higher than that in the NFAT5-negative group. NFAT5-positive expression (odds ratio: 2.632, 95% confidence interval: 1.071-6.465, P = 0.035) and pathologic N stage (N1-2 versus N0; odds ratio: 3.174, 95% confidence interval: 1.241-8.123, P = 0.016) were independent and significant risk factors for disease recurrence. DFS of the NFAT5-positive group was significantly worse than that of the NFAT5-negative group (89.7 versus 48.7 mo, P = 0.011). A multivariate analysis identified NFAT5 expression (P < 0.029) as a significant independent risk factor for DFS of patients with postoperative pathologic T and N stages (P < 0.001 and P = 0.017, respectively). NFAT5 expression is a useful prognostic biomarker for NSCLC patients who underwent surgical resection. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

    Directory of Open Access Journals (Sweden)

    Ida M Smith

    Full Text Available Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

  11. Kluyveromyces marxianus and Saccharomyces boulardii Induce Distinct Levels of Dendritic Cell Cytokine Secretion and Significantly Different T Cell Responses In Vitro.

    Science.gov (United States)

    Smith, Ida M; Baker, Adam; Christensen, Jeffrey E; Boekhout, Teun; Frøkiær, Hanne; Arneborg, Nils; Jespersen, Lene

    2016-01-01

    Interactions between members of the intestinal microbiota and the mucosal immune system can significantly impact human health, and in this context, fungi and food-related yeasts are known to influence intestinal inflammation through direct interactions with specialized immune cells in vivo. The aim of the present study was to characterize the immune modulating properties of the food-related yeast Kluyveromyces marxianus in terms of adaptive immune responses indicating inflammation versus tolerance and to explore the mechanisms behind the observed responses. Benchmarking against a Saccharomyces boulardii strain with probiotic effects documented in clinical trials, we evaluated the ability of K. marxianus to modulate human dendritic cell (DC) function in vitro. Further, we assessed yeast induced DC modulation of naive T cells toward effector responses dominated by secretion of IFNγ and IL-17 versus induction of a Treg response characterized by robust IL-10 secretion. In addition, we blocked relevant DC surface receptors and investigated the stimulating properties of β-glucan containing yeast cell wall extracts. K. marxianus and S. boulardii induced distinct levels of DC cytokine secretion, primarily driven by Dectin-1 recognition of β-glucan components in their cell walls. Upon co-incubation of yeast exposed DCs and naive T cells, S. boulardii induced a potent IFNγ response indicating TH1 mobilization. In contrast, K. marxianus induced a response dominated by Foxp3+ Treg cells, a characteristic that may benefit human health in conditions characterized by excessive inflammation and positions K. marxianus as a strong candidate for further development as a novel yeast probiotic.

  12. Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines

    International Nuclear Information System (INIS)

    Mitov, Mihail I.; Harris, Jennifer W.; Alstott, Michael C.; Zaytseva, Yekaterina Y.; Evers, B. Mark; Butterfield, D. Allan

    2017-01-01

    Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, microplate based, label-free detection approach. This study investigates how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32 °C, 37 °C and 42 °C using assay medium conditions and equipment settings adjusted to produce equal oxygen and pH levels ubiquitously at the beginning of all experiments. The results suggest that temperature significantly changes multiple components of glycolytic and mitochondrial function of all cell lines tested. Under hypothermia conditions (32 °C), the extracellular acidification rates (ECAR) of CRC cells were significantly lower compared to the same basal ECAR levels measured at 37 °C. Mitochondrial stress test for SW480 cells at 37 °C vs 42 °C demonstrated increased proton leak while all other OCR components remained unchanged (similar results were detected also for the patient-derived xenograft cells Pt.93). Interestingly, the FCCP dose response at 37 °C vs 42 °C show significant shifts in profiles, suggesting that single dose FCCP experiments might not be sufficient to characterize the mitochondrial metabolic potential when comparing groups, conditions or treatments. These findings provide valuable insights for the metabolic and bioenergetic changes of CRC cells under hypo- and hyperthermia conditions that could potentially lead to development of better targeted and personalized strategies for patients undergoing combined thermotherapy with chemotherapy.

  13. Temperature induces significant changes in both glycolytic reserve and mitochondrial spare respiratory capacity in colorectal cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Mitov, Mihail I., E-mail: m.mitov@uky.edu [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Harris, Jennifer W. [Department of Surgery, University of Kentucky, Lexington, KY 40506 (United States); Alstott, Michael C.; Zaytseva, Yekaterina Y. [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Evers, B. Mark [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Department of Surgery, University of Kentucky, Lexington, KY 40506 (United States); Butterfield, D. Allan [Markey Cancer Center, University of Kentucky, Lexington, KY 40536 (United States); Department of Chemistry, University of Kentucky, Lexington, KY 40506 (United States)

    2017-05-15

    Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, microplate based, label-free detection approach. This study investigates how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32 °C, 37 °C and 42 °C using assay medium conditions and equipment settings adjusted to produce equal oxygen and pH levels ubiquitously at the beginning of all experiments. The results suggest that temperature significantly changes multiple components of glycolytic and mitochondrial function of all cell lines tested. Under hypothermia conditions (32 °C), the extracellular acidification rates (ECAR) of CRC cells were significantly lower compared to the same basal ECAR levels measured at 37 °C. Mitochondrial stress test for SW480 cells at 37 °C vs 42 °C demonstrated increased proton leak while all other OCR components remained unchanged (similar results were detected also for the patient-derived xenograft cells Pt.93). Interestingly, the FCCP dose response at 37 °C vs 42 °C show significant shifts in profiles, suggesting that single dose FCCP experiments might not be sufficient to characterize the mitochondrial metabolic potential when comparing groups, conditions or treatments. These findings provide valuable insights for the metabolic and bioenergetic changes of CRC cells under hypo- and hyperthermia conditions that could potentially lead to development of better targeted and personalized strategies for patients undergoing combined thermotherapy with chemotherapy.

  14. Repression of COUP-TFI Improves Bone Marrow-Derived Mesenchymal Stem Cell Differentiation into Insulin-Producing Cells

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2017-09-01

    Full Text Available Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs, which can be used as a therapeutic approach against type 1 diabetes (T1D. As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2 promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI. Functionally, bmMSCs were reprogrammed into IPCs via COUP-TFI suppression and MafA overexpression. The differentiated cells expressed higher levels of genes specific for islet endocrine cells, and they released C-peptide and insulin in response to glucose stimulation. Transplantation of IPCs into streptozotocin-induced diabetic mice caused a reduction in hyperglycemia. Mechanistically, COUP-TFI bound to the DR1 (direct repeats with 1 spacer element in the Ins2 promoter, thereby negatively regulating promoter activity. Taken together, the data provide a novel mechanism by which COUP-TFI acts as a negative regulator in the Ins2 promoter. The differentiation of bmMSCs into IPCs could be improved by knockdown of COUP-TFI, which may provide a novel stem cell-based therapy for T1D. Keywords: siRNAs, differentiation, stem cell transplantation, diabetes, mesenchymal stem cells

  15. Fast Crystallization and improved Stability of Perovskite Solar Cells with Zn 2 SnO 4 Electron Transporting Layer: Interface Matters

    KAUST Repository

    Bera, Ashok

    2015-12-03

    Here we report that mesoporous ternary oxide Zn2SnO4 can significantly promotes the crystallization of hybrid perovskite layers and serves as an efficient electron transporting material in perovskite solar cells. Such devices exhibit an energy conversion efficiency of 13.34%, which is even higher than that achieved with the commonly used TiO2 in the similar experimental conditions (9.1%). Simple one-step spin coating of CH3NH3PbI3−xClx on Zn2SnO4 is found to lead to rapidly crystalized bilayer perovskite structure without any solvent engineering. Furthermore, ultrafast transient absorption measurement reveals efficient charge transfer at the Zn2SnO4/perovskite interface. Most importantly, solar cells with Zn2SnO4 as the electron-transporting material exhibit negligible electrical hysteresis and exceptionally high stability without encapsulation for over one month. Besides underscoring Zn2SnO4 as a highly promising electron transporting material for perovskite solar cells, our results demonstrate the significant role of interfaces on improving the perovskite crystallization and photovoltaic performance.

  16. Serum GRP78 as a Tumor Marker and Its Prognostic Significance in Non-Small Cell Lung Cancers: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Xiao Ma

    2015-01-01

    Full Text Available Introduction. Glucose-regulated protein 78 (78 kDa, GRP78, which is also known as immunoglobulin heavy chain binding protein (BIP, is a major chaperone in the endoplasmic reticulum (ER. The expression and clinical significance of GRP78 in the serum of non-small cell lung cancer patients have not yet been clearly described. The aims of the present study were to investigate the expression of GRP78 in the serum of non-small cell lung cancer patients, the relationships with clinicopathological parameters, and the potential implications for survival. Patients and Methods. A total of 163 peripheral blood samples from non-small cell lung cancer patients were prospectively collected at the Department of Thoracic Surgery, Fudan University Shanghai Cancer, China. Clinical characteristics data, including age, gender, stage, overall survival (OS time, and relapse-free survival (RFS time, were also collected. Serum GRP78 levels were measured using a commercially available ELISA kit. The associations between GRP78 levels and clinicopathological characteristics and survival were examined using Student’s t-test, Kaplan-Meier, or Cox regression analyses. Results. The mean ± standard error (SE value of GRP78 was 326.5 ± 49.77 pg/mL. This level was significantly lower compared with the level in late-stage non-small cell lung cancer patients (1227 ± 223.6, p=0.0001. There were no significant correlations with the clinicopathological parameters. No significant difference was found between high GRP78 expression and low GRP78 expression with regard to RFS (p=0.1585. However, the OS of patients with higher GRP78 expression was significantly poorer (p=0.0334. Conclusions. GRP78 was expressed in non-small cell lung cancer patients and was highly enriched in late-stage lung cancer. GRP78 may have an important role in the carcinogenesis of non-small cell lung cancer and may be a prognostic marker for non-small cell lung cancer.

  17. Haptic shared control improves hot cell remote handling despite controller inaccuracies

    NARCIS (Netherlands)

    van Oosterhout, J.; Abbink, D. A.; Koning, J. F.; Boessenkool, H.; Wildenbeest, J. G. W.; Heemskerk, C. J. M.

    2013-01-01

    A promising solution to improve task performance in ITER hot cell remote handling is the use of haptic shared control. Haptic shared control can assist the human operator along a safe and optimal path with continuous guiding forces from an intelligent autonomous controller. Previous research tested

  18. Expression of S-adenosylmethionine Hydrolase in Tissues Synthesizing Secondary Cell Walls Alters Specific Methylated Cell Wall Fractions and Improves Biomass Digestibility

    Directory of Open Access Journals (Sweden)

    Aymerick Eudes

    2016-07-01

    Full Text Available Plant biomass is a large source of fermentable sugars for the synthesis of bioproducts using engineered microbes. These sugars are stored as cell wall polymers, mainly cellulose and hemicellulose, and are embedded with lignin, which makes their enzymatic hydrolysis challenging. One of the strategies to reduce cell wall recalcitrance is the modification of lignin content and composition. Lignin is a phenolic polymer of methylated aromatic alcohols and its synthesis in tissues developing secondary cell walls is a significant sink for the consumption of the methyl donor S-adenosylmethionine (AdoMet. In this study, we demonstrate in Arabidopsis stems that targeted expression of S-adenosylmethionine hydrolase (AdoMetase, E.C. 3.3.1.2 in secondary cell-wall synthesizing tissues reduces the AdoMet pool and impacts lignin content and composition. In particular, both NMR analysis and pyrolysis gas chromatography mass spectrometry of lignin in engineered biomass showed relative enrichment of non-methylated p-hydroxycinnamyl (H units and a reduction of dimethylated syringyl (S units. This indicates a lower degree of methylation compared to that in wild-type lignin. Quantification of cell wall-bound hydroxycinnamates revealed a reduction of ferulate in AdoMetase transgenic lines. Biomass from transgenic lines, in contrast to that in control plants, exhibits an enrichment of glucose content and a reduction in the degree of hemicellulose glucuronoxylan methylation. We also show that these modifications resulted in a reduction of cell wall recalcitrance, because sugar yield generated by enzymatic biomass saccharification was greater than that of wild type plants. Considering that transgenic plants show no important diminution of biomass yields, and that heterologous expression of AdoMetase protein can be spatiotemporally optimized, this novel approach provides a valuable option for the improvement of lignocellulosic biomass feedstock.

  19. Stem Cell Research: A Novel Boulevard towards Improved Bovine Mastitis Management

    Science.gov (United States)

    Sharma, Neelesh; Jeong, Dong Kee

    2013-01-01

    The dairy industry is a multi-billion dollar industry catering the nutritional needs of all age groups globally through the supply of milk. Clinical mastitis has a severe impact on udder tissue and is also an animal welfare issue. Moreover, it significantly reduces animal value and milk production. Mammary tissue damage reduces the number and activity of epithelial cells and consequently contributes to decreased milk production. The high incidence, low cure rate of this highly economic and sometimes deadly disease is an alarming for dairy sector as well as policy makers. Bovine mammary epithelial cells (MECs) and their stem cells are very important in milk production and bioengineering. The adult mammary epithelium consists of two main cell types; an inner layer of luminal epithelial cells, which produce the milk during lactation, and an outer layer of myoepithelial cells resting on a basement membrane, which are responsible for pushing the milk through the ductal network to the teat cistern. Inner layer of columner/luminal cells of bovine MECs, is characterized by cytokeratin18, 19 (CK18, CK19) and outer layer such as myoepithelial cells which are characterized by CK14, α-smooth muscle actin (α-SMA) and p63. Much work has been done in mouse and human, on mammary gland stem cell research, particularly in cancer therapy, but stem cell research in bovine is still in its infancy. Such stem/progenitor cell discoveries in human and mouse mammary gland bring some hope for application in bovines. These progenitors may be therapeutically adopted to correct the structural/cytological defects in the bovine udder due to mastitis. In the present review we focused on various kinds of stem/progenitor cells which can have therapeutic utility and their possibilities to use as a potential stem cell therapy in the management of bovine post-mastitis damage in orders to restore milk production. The possibilities of bovine mammary stem cell therapy offers significant potential for

  20. Long-term dynamic loading improves the mechanical properties of chondrogenic mesenchymal stem cell-laden hydrogel

    Directory of Open Access Journals (Sweden)

    AH Huang

    2010-02-01

    Full Text Available Mesenchymal stem cells (MSCs are an attractive cell source for cartilage tissue engineering given their ability to undergo chondrogenesis in 3D culture systems. Mechanical forces play an important role in regulating both cartilage development and MSC chondrogenic gene expression, however, mechanical stimulation has yet to enhance the mechanical properties of engineered constructs. In this study, we applied long-term dynamic compression to MSC-seeded constructs and assessed whether varying pre-culture duration, loading regimens and inclusion of TGF-beta3 during loading would influence functional outcomes and these phenotypic transitions. Loading initiated before chondrogenesis decreased functional maturation, although chondrogenic gene expression increased. In contrast, loading initiated after chondrogenesis and matrix elaboration further improved the mechanical properties of MSC-based constructs, but only when TGF-beta3 levels were maintained and under specific loading parameters. Although matrix quantity was not affected by dynamic compression, matrix distribution, assessed histologically and by FT-IRIS analysis, was significantly improved on the micro- (pericellular and macro- (construct expanse scales. Further, whole genome expression profiling revealed marked shifts in the molecular topography with dynamic loading. These results demonstrate, for the first time, that dynamic compressive loading initiated after a sufficient period of chondro-induction and with sustained TGF-beta exposure enhances matrix distribution and the mechanical properties of MSC-seeded constructs.

  1. Trophic significance of solitary cells of the prymnesiophyte Phaeocystis globosa depends on cell type

    DEFF Research Database (Denmark)

    Dutz, Jörg; Koski, Marja

    2006-01-01

    With the use of five different isolates of Phaeocystis globosa solitary cells from the North Sea, we conducted experiments to reveal whether grazing and development of the nauplii of the calanoid copepod Temora longicornis varies in response to the cell type. Two P. globosa strains representing n...

  2. Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice.

    Science.gov (United States)

    Hu, Jingchao; Cao, Yu; Xie, Yilin; Wang, Hua; Fan, Zhipeng; Wang, Jinsong; Zhang, Chunmei; Wang, Jinsong; Wu, Chu-Tse; Wang, Songlin

    2016-09-09

    Periodontitis, one of the most prevalent infectious diseases in humans, results in the destruction of tooth-supporting tissues. The purpose of the present study is to evaluate the effect of cell injection and cell sheet transplantation on periodontal regeneration in a swine model. In the present study, human dental pulp stem cells (hDPSCs) were transplanted into a swine model for periodontal regeneration. Twelve miniature pigs were used to generate periodontitis with bone defects of 5 mm in width, 7 mm in length, and 3 mm in depth. hDPSCs were obtained for bone regeneration using cell injection or cell sheet transplantation. After 12 weeks, clinical, radiological, and histological assessments of regenerated periodontal tissues were performed to compare periodontal regeneration treated with xenogeneic cell injection and cell sheet implantation. Our study showed that translating hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. After 12 weeks, both the hDPSC sheet treatment and hDPSC injection significantly improved periodontal tissue healing clinically in comparison with the control group. The volume of regenerative bone in the hDPSC sheet group (52.7 ± 4.1 mm(3)) was significantly larger than in the hDPSC injection group (32.4 ± 5.1 mm(3)) (P cell sheet transplantation significantly regenerated periodontal bone in swine. The hDPSC sheet had more bone regeneration capacity compared with hDPSC injection.

  3. Stellate-cell lipidosis in liver biopsy specimens. Recognition and significance.

    Science.gov (United States)

    Levine, Pascale Hummel; Delgado, Yara; Theise, Neil D; West, A Brian

    2003-02-01

    Hepatic stellate-cell lipidosis due to hypervitaminosis A can lead to cirrhosis, which can be averted by restricting vitamin A intake. Other causes, including the use of synthetic retinoids, have been postulated. We studied the frequency and etiology of stellate-cell lipidosis in patients undergoing liver biopsy for reasons other than vitamin A abuse. Fourteen cases (1.1%) were identified retrospectively among 1,235 nontransplant liver biopsy specimens examined from January 1995 through December 1999. Diagnostic criteria included the following: lipid-laden cells in the space of Disse; small, dark, crescent-shaped nuclei with inconspicuous nucleoli; and wispy cytoplasmic strands separating fat droplets. Patient details, reason for biopsy, and medication use were studied. Reasons for biopsy included hepatitis C (10 cases), abnormal liver enzyme levels (2 cases), methotrexate use (1 case), and alcohol abuse (1 case). Hypervitaminosis A was not suspected clinically in the 5 patients who used oral vitamin A or 3 who used topical tretinoin (Retin-A). In 6 patients, no cause of stellate-cell lipidosis was discerned. Stellate-cell lipidosis should be reported to alert clinicians to a potentially preventable form of liver injury.

  4. An improved single cell ultrahigh throughput screening method based on in vitro compartmentalization.

    Directory of Open Access Journals (Sweden)

    Fuqiang Ma

    Full Text Available High-throughput screening is a key technique in discovery and engineering of enzymes. In vitro compartmentalization based fluorescence-activated cell sorting (IVC-FACS has recently emerged as a powerful tool for ultrahigh-throughput screening of biocatalysts. However, the accuracy of current IVC-FACS assays is severely limited by the wide polydispersity of micro-reactors generated by homogenizing. Here, an improved protocol based on membrane-extrusion technique was reported to generate the micro-reactors in a more uniform manner. This crucial improvement enables ultrahigh-throughput screening of enzymatic activity at a speed of >10⁸ clones/day with an accuracy that could discriminate as low as two-fold differences in enzymatic activity inside the micro-reactors, which is higher than similar IVC-FACS systems ever have reported. The enzymatic reaction in the micro-reactors has very similar kinetic behavior compared to the bulk reaction system and shows wide dynamic range. By using the modified IVC-FACS, E. coli cells with esterase activity could be enriched 330-fold from large excesses of background cells through a single round of sorting. The utility of this new IVC-FACS system was further illustrated by the directed evolution of thermophilic esterase AFEST. The catalytic activity of the very efficient esterase was further improved by ∼2-fold, resulting in several improved mutants with k(cat/K(M values approaching the diffusion-limited efficiency of ∼10⁸ M⁻¹s⁻¹.

  5. [Expression and clinical significance of BCL6 corepressor-like 1 in non-small cell lung cancer].

    Science.gov (United States)

    Zhao, Xu; Tuo, Hang; Si, Meili; Wang, Lei; Liang, Ping

    2015-12-01

    To detect the expression of BCL6 corepressor-like 1 (BCORL1) in tumor tissues of human non-small cell lung cancer (NSCLC) and determine the effect of BCORL1 on cell migration and invasion in A549 cells by knockdown of BCORL1. Sixty-eight pairs of NSCLC and nontumor tissues were collected and the expressions of BCORL1 and E-cadherin in them were detected using immunohistochemical staining. The expression of BCORL1 was knocked down by siRNA in A549 cells. Transwell(TM) assays were performed to test NSCLC cell migration and invasion in vitro. The expression of BCORL1 in NSCLC was significantly higher than that in paired noncancerous tissues, while E-cadherin was down-regulated in NSCLC as compared with nontumor tissues. Pearson correlation coefficient analysis suggested that BCORL1 was negatively correlated with E-cadherin expression in NSCLC tissues. Clinical association analysis suggested that the elevated expression of BCORL1 was evidently associated with the higher incidence of lymph node metastasis and more advanced TNM stage. When the expression of BCORL1 was down-regulated by a specific siRNA, E-cadherin was up-regulated, and BCORL1 knockdown obviously inhibited cell migration and invasion in A549 cells. BCORL1 is overexpressed in NSCLC tissues and it is negatively correlated with E-cadherin expression. Its high expression is correlated with poor prognostic features. BCORL1 knockdown up-regulates E-cadherin expression and subsequently inhibits cell migration and invasion of lung cancer cells.

  6. Prognostic significance of tissue polypeptidespecific antigen (TPS) in patients with advanced non-small cell lung cancer

    NARCIS (Netherlands)

    A. van der Gaast (Ate); C.H.H. Schoenmakers (Christian); T.C. Kok (Tjebbe); B.G. Blijenberg (Bert); W.C.J. Hop (Wim); T.A.W. Splinter (Ted)

    1994-01-01

    textabstractIn this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate

  7. Lipofectamine and related cationic lipids strongly improve adenoviral infection efficiency of primitive human hematopoietic cells.

    Science.gov (United States)

    Byk, T; Haddada, H; Vainchenker, W; Louache, F

    1998-11-20

    Adenoviral vectors have the potential to infect a large number of cell types including quiescent cells. Their use in hematopoietic cells is limited by the episomal form of their DNA, leading to transgene loss in the progeny cells. However, the use of this vector may be interesting for short-term in vitro modifications of primitive human hematopoietic cells. Therefore, we have investigated the ability of adenovirus to transduce cord blood CD34+ cells. Several promoters were tested using the lacZ reporter gene. The PGK and CMV promoters induced transgene expression in 18-25% of the cells, whereas the HTLV-I and especially the RSV promoter were almost inactive. To improve infection efficiency, adenovirus was complexed with cationic lipids. Lipofectamine, Cellfectin, and RPR120535b, but not Lipofectin, Lipofectace, or DOTAP, markedly improved transgene expression in CD34+ cells (from 19 to 35%). Lipofectamine strongly enhanced infection efficiency of the poorly infectable primitive CD34+CD38low cells (from 11 to 28%) whereas the more mature CD34+CD38+ cells were only slightly affected (from 24 to 31%). Lipofectamine tripled the infection of CFU-GMs and LTC-ICs derived from the CD34+CD38low cell fraction (from 4 to 12% and from 5 to 16%, respectively) and doubled that of BFU-Es (from 13 to 26%). We conclude that cationic lipids can markedly increase the efficiency of adenovirus-mediated gene transfer into primitive hematopoietic cells.

  8. Combined VEGF and CXCR4 antagonism targets the GBM stem cell population and synergistically improves survival in an intracranial mouse model of glioblastoma.

    Science.gov (United States)

    Barone, Amy; Sengupta, Rajarshi; Warrington, Nicole M; Smith, Erin; Wen, Patrick Y; Brekken, Rolf A; Romagnoli, Barbara; Douglas, Garry; Chevalier, Eric; Bauer, Michael P; Dembowsky, Klaus; Piwnica-Worms, David; Rubin, Joshua B

    2014-10-30

    Glioblastoma recurrence involves the persistence of a subpopulation of cells with enhanced tumor-initiating capacity (TIC) that reside within the perivascular space, or niche (PVN). Anti-angiogenic therapies may prevent the formation of new PVN but have not prevented recurrence in clinical trials, suggesting they cannot abrogate TIC activity. We hypothesized that combining anti-angiogenic therapy with blockade of PVN function would have superior anti-tumor activity. We tested this hypothesis in an established intracranial xenograft model of GBM using a monoclonal antibody specific for murine and human VEGF (mcr84) and a Protein Epitope Mimetic (PEM) CXCR4 antagonist, POL5551. When doses of POL5551 were increased to overcome an mcr84-induced improvement in vascular barrier function, combinatorial therapy significantly inhibited intracranial tumor growth and improved survival. Anti-tumor activity was associated with significant changes in tumor cell proliferation and apoptosis, and a reduction in the numbers of perivascular cells expressing the TIC marker nestin. A direct effect on TICs was demonstrated for POL5551, but not mcr84, in three primary patient-derived GBM isolates. These findings indicate that targeting the structure and function of the PVN has superior anti-tumor effect and provide a strong rationale for clinical evaluation of POL5551 and Avastin in patients with GBM.

  9. Effects of the prescription of reinforcing kidney, nourishing blood, improving eyesight on ARPE-19 cells induced by acrolein

    Directory of Open Access Journals (Sweden)

    Man Li

    2015-05-01

    Full Text Available AIM: To explore the effects of the prescription of reinforcing kidney, nourishing blood, improving eyesight on the oxidative stress model of ARPE-19 cells induced by acrolein. METHODS: SD rats serum containing the prescription of reinforcing kidney, nourishing blood, improving eyesight and the content of distilled water in serum were prepared. The effects of the prescription and distilled water in serum at different concentration(2.5%, 5%, 10%, 20% and 40%on cell vitality was observed by cell counting kit(CCK-8assay. the logarithmic phase of ARPE-19 cells were pretreated by different concentrations(1.25%, 2.5% and 5%of the prescription serum and distilled water in serum for 24h. Then it was treated with 75μmol/L acrolein for 24h. Cell vitality was observed by CCK-8 assay. The change of cell nucleus was detected by DAPI staining.RESULTS: 2.5% and 5% serum had no effect on cell viability(P>0.05, while 10%, 20%, 40% serum could inhibit cell viability(PPCONCLUSION: The prescription of reinforcing kidney, nourishing blood, improving eyesight has the protective effect on ARPE-19 cell damage induced by acrolein.

  10. Prognostic significance of interleukin-8 and CD163-positive cell-infiltration in tumor tissues in patients with oral squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Yohei Fujita

    Full Text Available PURPOSE: We investigated whether serum interleukin (IL-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC. EXPERIMENTAL DESIGN: Fifty OSCC patients who received radical resection of their tumor(s were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens. RESULTS: We found that disease-free survival (DFS was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001. The tumor expression of IL-8, i.e., IL-8(T and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF were correlated with the serum IL-8 level (p = 0.033 and p = 0.038, respectively, and they were associated with poor clinical outcome (p = 0.007 and p = 0.002, respectively, in DFS in all patients. A multivariate analysis revealed that N status, IL-8(T and CD163(IF significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T or CD163(IF may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10. CONCLUSIONS: These findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS.

  11. A NIR-remote controlled upconverting nanoparticle: an improved tool for living cell dye-labeling

    International Nuclear Information System (INIS)

    Zheng, Bin; Gong, Xiaoqun; Wang, Hanjie; Wang, Sheng; Chang, Jin; Wang, Huiquan; Li, Wei; Tan, Jian

    2015-01-01

    In living cells, due to the selective permeability and complicated cellular environment, the uptake efficiency and fluorescence decay of organic dyes during dye-labeling may be influenced, which may eventually result in poor fluorescent imaging. In this work, a protocol of UCNs@mSiO_2-(FA and Azo) core–shell nanocarriers was designed and prepared successfully. The core–shell nanocarriers were assembled from two parts, including a mesoporous silica shell surface modified by folate (FA) and azobenzene (Azo), and an upconverting nanocrystal (UCN) core. The mesoporous silica shell is used for loading organic dyes and conjugating folate which helps to enhance the cellular uptake of nanocarriers. The UCN core works as a transducer to convert near infrared (NIR) light to local UV and visible light to activate a back-and-forth wagging motion of azobenzene molecules on the surface, while the azobenzene acts as a molecular impeller for propelling the release of organic dyes. The nanocarriers of loading organic dyes can maintain the stability of the fluorescent imaging effect better than free organic dyes. The experimental results show that with the help of the nanoparticle, cell uptake efficiency of the model dyes of rhodamine and 4′, 6-diamidino-2-phenylindole (DAPI) was significantly improved. The release of dyes can only be triggered by NIR light exposure and their quantity is highly dependent on the duration of NIR light exposure, thus realizing NIR-regulated dye release spatiotemporally. Our work may open a novel avenue for precisely controlling UCN-based living cell imaging in biotechnology and diagnostics, as well as studying cell dynamics, cell–cell interactions, and tissue morphogenesis. (paper)

  12. Design of magnetic flywheel control for performance improvement of fuel cells used in vehicles

    International Nuclear Information System (INIS)

    Huang, Chung-Neng; Chen, Yui-Sung

    2017-01-01

    Because hydrogen can be extracted naturally and stored for a long time, different types of fuel cells have been developed to generate clean power, particularly for use in vehicles. However, the power demand of a running vehicle leads to unstable and irregular loading of fuel cells. This not only reduces fuel cell lifespan and efficiency but also affects driving safety when the slow output response cannot satisfy an abrupt increase in power demand. Magnetic flywheels with characteristics such as high energy density, high-speed charging ability, and low loss have been extensively used in Formula One cars. This study developed a hybrid powertrain in which a magnetic flywheel system (MFS) is integrated with the fuel cells to solve the aforementioned problems. Moreover, an auto-tuning proportional–integral–derivative (PID) controller based on the controls of a multiple adaptive neuro-fuzzy interference system and particle swarm optimization was designed for MFS control. Furthermore, MATLAB/Simulink simulations considering an FTP-75 urban driving cycle were conducted, and a variability improvement of approximately 27.3% in fuel cell output was achieved. - Highlights: • A hybrid powertrain integrating the magnetic flywheel and fuel cells is proposed. • An auto-tuning PID controller is designed for MFS control. • The MIMO-ANFIS and PSO based optimal control is realized. • A 27.3% improvement in the output variability of fuel cell is achieved under control.

  13. Adenoviral vector-mediated GM-CSF gene transfer improves anti-mycobacterial immunity in mice - role of regulatory T cells.

    Science.gov (United States)

    Singpiel, Alena; Kramer, Julia; Maus, Regina; Stolper, Jennifer; Bittersohl, Lara Friederike; Gauldie, Jack; Kolb, Martin; Welte, Tobias; Sparwasser, Tim; Maus, Ulrich A

    2018-03-01

    Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in differentiation, survival and activation of myeloid and non-myeloid cells with important implications for lung antibacterial immunity. Here we examined the effect of pulmonary adenoviral vector-mediated delivery of GM-CSF (AdGM-CSF) on anti-mycobacterial immunity in M. bovis BCG infected mice. Exposure of M. bovis BCG infected mice to AdGM-CSF either applied on 6h, or 6h and 7days post-infection substantially increased alveolar recruitment of iNOS and IL-12 expressing macrophages, and significantly increased accumulation of IFNγ pos T cells and particularly regulatory T cells (Tregs). This was accompanied by significantly reduced mycobacterial loads in the lungs of mice. Importantly, diphtheria toxin-induced depletion of Tregs did not influence mycobacterial loads, but accentuated immunopathology in AdGM-CSF-exposed mice infected with M. bovis BCG. Together, the data demonstrate that AdGM-CSF therapy improves lung protective immunity against M. bovis BCG infection in mice independent of co-recruited Tregs, which however critically contribute to limit lung immunopathology in BCG-infected mice. These data may be relevant to the development of immunomodulatory strategies to limit immunopathology-based lung injury in tuberculosis in humans. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Dopaminergic-like neurons derived from oral mucosa stem cells by developmental cues improve symptoms in the hemi-parkinsonian rat model.

    Directory of Open Access Journals (Sweden)

    Javier Ganz

    Full Text Available Achieving safe and readily accessible sources for cell replacement therapy in Parkinson's disease (PD is still a challenging unresolved issue. Recently, a primitive neural crest stem cell population (hOMSC was isolated from the adult human oral mucosa and characterized in vitro and in vivo. In this study we assessed hOMSC ability to differentiate into dopamine-secreting cells with a neuronal-dopaminergic phenotype in vitro in response to dopaminergic developmental cues and tested their therapeutic potential in the hemi-Parkinsonian rat model. We found that hOMSC express constitutively a repertoire of neuronal and dopaminergic markers and pivotal transcription factors. Soluble developmental factors induced a reproducible neuronal-like morphology in the majority of hOMSC, downregulated stem cells markers, upregulated the expression of the neuronal and dopaminergic markers that resulted in dopamine release capabilities. Transplantation of these dopaminergic-induced hOMSC into the striatum of hemi-Parkinsonian rats improved their behavioral deficits as determined by amphetamine-induced rotational behavior, motor asymmetry and motor coordination tests. Human TH expressing cells and increased levels of dopamine in the transplanted hemispheres were observed 10 weeks after transplantation. These results demonstrate for the first time that soluble factors involved in the development of DA neurons, induced a DA phenotype in hOMSC in vitro that significantly improved the motor function of hemiparkinsonian rats. Based on their neural-related origin, their niche accessibility by minimal-invasive procedures and their propensity for DA differentiation, hOMSC emerge as an attractive tool for autologous cell replacement therapy in PD.

  15. Stem Cells as a Tool to Improve Outcomes of Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Emily Sims

    2012-01-01

    Full Text Available The publication of the promising results of the Edmonton protocol in 2000 generated optimism for islet transplantation as a potential cure for Type 1 Diabetes Mellitus. Unfortunately, follow-up data revealed that less than 10% of patients achieved long-term insulin independence. More recent data from other large trials like the Collaborative Islet Transplant Registry show incremental improvement with 44% of islet transplant recipients maintaining insulin independence at three years of follow-up. Multiple underlying issues have been identified that contribute to islet graft failure, and newer research has attempted to address these problems. Stem cells have been utilized not only as a functional replacement for β cells, but also as companion or supportive cells to address a variety of different obstacles that prevent ideal graft viability and function. In this paper, we outline the manners in which stem cells have been applied to address barriers to the achievement of long-term insulin independence following islet transplantation.

  16. Commonly used bowel preparations have significant and different effects upon cell proliferation in the colon: a pilot study

    Directory of Open Access Journals (Sweden)

    Riley Stuart A

    2008-11-01

    Full Text Available Abstract Background Markers of crypt cell proliferation are frequently employed in studies of the impact of genetic and exogenous factors on human colonic physiology. Human studies often rely on the assessment of tissue acquired at endoscopy. Modulation of cell proliferation by bowel preparation with oral laxatives may confound the findings of such studies, but there is little data on the impact of commonly used bowel preparations on markers of cell proliferation. Methods Crypt length, crypt cellularity and crypt cell proliferation were assessed in biopsies acquired after preparation with either Klean-Prep or Picolax. Crypt cell proliferation was assessed by whole-mount mitotic figure count, and by two different immunohistochemical (IHC labelling methods (Ki-67 and pHH3. Subsequent biopsies were obtained from the same patients without bowel preparation and similarly assessed. Parameters were compared between groups using analysis of variance and paired t-tests. Results There were significant differences in labelling indices (LI between biopsies taken after Klean-prep and those taken after Picolax preparation, for both Ki67 (p = 0.019 and pHH3 (p = 0.017. A similar trend was seen for whole-mount mitotic figure counts. Suppression or elevation of proliferation parameters by bowel preparation may mask any effect due to an intervention or disease. Conclusion Commonly used bowel preparations may have significant and different effects on crypt cell proliferation. This should be taken into account when designing studies and when considering the findings of existing studies.

  17. Interventions for patients and caregivers to improve knowledge of sickle cell disease and recognition of its related complications.

    Science.gov (United States)

    Asnani, Monika R; Quimby, Kim R; Bennett, Nadia R; Francis, Damian K

    2016-10-06

    improved further when a trial with high bias was removed in a sensitivity analysis. Caregiver knowledge, reported in a single trial of 20 families, also showed an improvement, standardised mean difference 0.52 points (95% confidence interval 0.03 to 1.00, moderate quality evidence). The effect on patient knowledge was sustained at longer follow-up periods, whereas the effect on caregiver knowledge was not sustained.There were two primary outcomes related to the effectiveness of educational programs on the recognition of signs and symptoms of disease-related morbidity. No comparative data were reported for patients or caregivers (or both) recognising signs and symptoms leading to self-management. Data from two trials were analysed for the utilization of health services and showed no evidence of an effect, mean difference 0.33 (95% confidence interval -0.57 to 1.23, moderate quality evidence).With regard to the review's secondary outcomes, depression showed a statistically significant decline in intervention groups, standardised mean difference -0.66 points (95% confidence interval -1.18, to -0.14, moderate quality evidence). Adherence to treatment was not assessed in any of the identified trials. No effects of interventions were seen on coping, family relationships or health-related quality of life of patients.The quality of evidence was low for positive coping and moderate for child knowledge, healthcare utilization and depression. This suggests that further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimates. This review identifies important positive effects of educational interventions on improving patient knowledge of sickle cell disease and depression. Effects on patients' knowledge were maintained for longer than for caregivers. The effect on knowledge was significant but small and whether it offers any clinical benefit is uncertain. Significant factors limiting these effects could be trials being

  18. Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia

    Science.gov (United States)

    Liu, Chuan-Bin; Huang, He; Sun, Ping; Ma, Shi-Ze; Liu, An-Heng; Xue, Jian; Fu, Jin-Hui; Liang, Yu-Qian; Liu, Bing; Wu, Dong-Ying

    2016-01-01

    Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC-MSCs originated from Wharton’s jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC-MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC-MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC-MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p UC-MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia. Significance Ischemic heart disease is the leading cause of death worldwide. Many patients with chronic myocardial ischemia are not suitable for surgery and have no effective drug treatment; they are called “no-option” patients. This study finds that umbilical cord-derived mesenchymal stromal cells transplanted by intracoronary delivery combined with two intravenous administrations was safe and could significantly improve left ventricular function, perfusion, and remodeling in a large-animal model of chronic myocardial ischemia, which provides a new choice for the no-option patients. In addition, this study used clinical-grade mesenchymal stem cells with delivery and assessment methods commonly used clinically to facilitate further clinical transformation. PMID

  19. Significance of the proportion of binucleate cells in the micronucleus assay; A methodological study

    Energy Technology Data Exchange (ETDEWEB)

    Imamura, Masahiro; Edgren, M.R. (Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics)

    1994-03-01

    Using treatment with cytochalasin-B (Cyt-B) for the induction of a cytokinetic block, the significance of the proportion of binucleate cells (BNC) in the micronucleus (MN) assay was investigated in a methodological study. A Chinese hamster cell line V79 was used in which MN were induced by radiation. In complementary tests the radiation effect in inducing MN was enhanced by depletion of the cellular glutathione content with buthionine sulfoximine (BSO). The data indicated that the concentration of Cyt-B is the major factor which determines the proportion of BNC. This proportion was shown to be independent of radiation dose and of BSO. Furthermore, the MN frequency was not related to the percentage of BNC. Therefore, a high proportion of BNC may be practical for the MN assay, but may not make the technique more accurate. (author).

  20. Immunophenotyping in leukemia and its diagnostic significance

    Directory of Open Access Journals (Sweden)

    S. B. Kresno

    2004-09-01

    Full Text Available The identification of cell surface markers, defined as clusters of differentiation antigens (CD’s could be used to classify and sub-classify leukemia. Although the same antigens are expressed on normal cells, the phenotype on malignant cells are aberrantly and frequently asynchronously expressed and may be present in combinations not observed in normal blood or bone marrow. Aberrant expression of surface antigens corresponds with poor therapeutic response and short survival. Additional surface marker analysis complementary to morphologic evaluation and cytochemical staining has greatly improved our ability to characterize hematologic malignancies. A review and illustration on the diagnostic significance of immunophenotyping in leukemia will be presented. Data from 225 patients having complete assessments including morphology, cytochemistry and immunophenotyping in the period of 1994-2001 were collected and analyzed. Based on morphologic evaluation and cytochemistry, the diagnosis of acute myeloid leukemia and acute lymphoblastic leukemia were established in 51.1% and 48.9% of cases, respectively. Based on immunophenotyping AML was found in 49.0% of the cases. ALL could be classified into 4.9% pre-B-ALL, 18.7% B-ALL, and 14.7% T-ALL. Cases expressing cross-lineage antigens were found in 12.7%. The prognostic significance of these aberrant expression of antigens for those cases has yet to be established but some of the cases responded poorly to therapy. Immunophenotyping provides the tool to: 1 distinguish normal from clonal populations of leukemic cells; 2 define lineage and reveal the stage of maturation; 3 identify inappropriate expression of lineage associated antigens; 4 provides more informations to establish diagnosis and prognosis compared to standard methods. (Med J Indones 2004; 13: 195-202 Keywords: Immunophenotyping, clusters of differentiation antigens, lineage associated antigens

  1. Improved isolation protocol for equine cord blood-derived mesenchymal stromal cells

    DEFF Research Database (Denmark)

    Koch, Thomas Gadegaard; Thomsen, Preben Dybdahl; Betts, Dean H.

    2009-01-01

      BACKGROUND AIMS: A robust methodology for the isolation of cord blood-derived multipotent mesenchymal stromal cells (CB-MSCs) from fresh umbilical cord blood has not been reported in any species. The objective of this study was to improve the isolation procedure for equine CB-MSCs. METHODS: Pre......-culture separation of red and white blood cells was done using either PrepaCyte?-EQ medium or Ficoll-Paque? PREMIUM density medium. Regular FBS and MSC-qualified FBS were compared for their ability to support the establishment of putative primary MSC colonies. RESULTS AND CONCLUSIONS: Our results indicate that Prepa...

  2. Improved mass-measurement accuracy using a PNB Load Cell Scale

    International Nuclear Information System (INIS)

    Suda, S.; Pontius, P.; Schoonover, R.

    1981-08-01

    The PNB Load Cell Scale is a Preloaded, Narrow-Band calibration mass comparator. It consists of (1) a frame and servo-mechanism that maintains a preload tension on the load cell until the load, an unknown mass, is sensed, and (2) a null-balance digital instrument that suppresses the cell response associated with the preload, thereby improving the precision and accuracy of the measurements. Ideally, the objects used to set the preload should be replica mass standards that closely approximate the density and mass of the unknowns. The advantages of the PNB scale are an expanded output signal over the range of interest which increases both the sensitivity and resolution, and minimizes the transient effects associated with loading of load cells. An area of immediate and practical application of this technique to nuclear material safeguards is the weighing of UF 6 cyliners where in-house mass standards are currently available and where the mass values are typically assigned on the basis of comparison weighings. Several prototypical versions of the PNB scale have been assembled at the US National Bureau of Standards. A description of the instrumentation, principles of measurements, and applications are presented in this paper

  3. Hydrophobic Polystyrene Passivation Layer for Simultaneously Improved Efficiency and Stability in Perovskite Solar Cells.

    Science.gov (United States)

    Li, Minghua; Yan, Xiaoqin; Kang, Zhuo; Huan, Yahuan; Li, Yong; Zhang, Ruxiao; Zhang, Yue

    2018-06-06

    The major restraint for the commercialization of the high-performance hybrid metal halide perovskite solar cells is the long-term stability, especially at the infirm interface between the perovskite film and organic charge-transfer layer. Recently, engineering the interface between the perovskite and spiro-OMeTAD becomes an effective strategy to simultaneously improve the efficiency and stability in the perovskite solar cells. In this work, we demonstrated that introducing an interfacial polystyrene layer between the perovskite film and spiro-OMeTAD layer can effectively improve the perovskite solar cells photovoltaic performance. The inserted polystyrene layer can passivate the interface traps and defects effectively and decrease the nonradiative recombination, leading to enhanced photoluminescence intensity and carrier lifetime, without compromising the carrier extraction and transfer. Under the optimized condition, the perovskite solar cells with the polystyrene layer achieve an enhanced average power efficiency of about 19.61% (20.46% of the best efficiency) from about 17.63% with negligible current density-voltage hysteresis. Moreover, the optimized perovskite solar cells with the hydrophobic polystyrene layer can maintain about 85% initial efficiency after 2 months storage in open air conditions without encapsulation.

  4. Insights into significance of combined inhibition of MEK and m-TOR signalling output in KRAS mutant non-small-cell lung cancer.

    Science.gov (United States)

    Broutin, Sophie; Stewart, Adam; Thavasu, Parames; Paci, Angelo; Bidart, Jean-Michel; Banerji, Udai

    2016-08-23

    We aimed to understand the dependence of MEK and m-TOR inhibition in EGFR(WT)/ALK(non-rearranged) NSCLC cell lines. In a panel of KRAS(M) and KRAS(WT) NSCLC cell lines, we determined growth inhibition (GI) following maximal reduction in p-ERK and p-S6RP caused by trametinib (MEK inhibitor) and AZD2014 (m-TOR inhibitor), respectively. GI caused by maximal m-TOR inhibition was significantly greater than GI caused by maximal MEK inhibition in the cell line panel (52% vs 18%, PTOR compared with maximal m-TOR+MEK inhibition. However, GI caused by the combination was significantly greater in the KRAS(M) cell lines (79% vs 61%, P=0.017). m-TOR inhibition was more critical to GI than MEK inhibition in EGFR(WT)/ALK(non-rearranged) NSCLC cells. The combination of MEK and m-TOR inhibition was most effective in KRAS(M) cells.

  5. Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats

    Directory of Open Access Journals (Sweden)

    Wang Yu

    2012-06-01

    Full Text Available Abstract Introduction Adipose derived mesenchymal stem cells (ADMSCs, carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4 in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway. Methods ADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4-induced liver fibrosis rats. Computed tomography (CT perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated. Results CT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein. Conclusions ADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.

  6. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    International Nuclear Information System (INIS)

    Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

    2010-01-01

    Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

  7. Improved methods for binding acma-type protein anchor fusions yo cell-wall material of micro-organisms

    NARCIS (Netherlands)

    Leenhouts, Cornelis; Ramasamy, R.; Steen, Anton; Kok, Jan; Buist, Girbe; Kuipers, Oscar

    2002-01-01

    The invention provides a method for improving binding of a proteinaceous substance to cell-wall material of a Gram-positive bacterium, said substance comprising an AcmA cell wall binding domain or homolog or functional derivative thereof, said method comprising treating said cell-wall material with

  8. Improvement of myocardial perfusion reserve detected by cardiovascular magnetic resonance after direct endomyocardial implantation of autologous bone marrow cells in patients with severe coronary artery disease

    Directory of Open Access Journals (Sweden)

    Lau Chu-Pak

    2010-01-01

    Full Text Available Abstract Background Recent studies suggested that bone marrow (BM cell implantation in patients with severe chronic coronary artery disease (CAD resulted in modest improvement in symptoms and cardiac function. This study sought to investigate the functional changes that occur within the chronic human ischaemic myocardium after direct endomyocardial BM cells implantation by cardiovascular magnetic resonance (CMR. Methods and Results We compared the interval changes of left ventricular ejection fraction (LVEF, myocardial perfusion reserve and the extent of myocardial scar by using late gadolinium enhancement CMR in 12 patients with severe CAD. CMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell (n = 12 injection to viable ischaemic myocardium as guided by electromechanical mapping. In patients randomized to receive BM cell injection, there was significant decrease in percentage area of peri-infarct regions (-23.6%, P = 0.04 and increase in global LVEF (+9.0%, P = 0.02, the percentage of regional wall thickening (+13.1%, P= 0.04 and MPR (+0.25%, P = 0.03 over the target area at 6-months compared with baseline. Conclusions Direct endomyocardial implantation of autologous BM cells significantly improved global LVEF, regional wall thickening and myocardial perfusion reserve, and reduced percentage area of peri-infarct regions in patients with severe CAD.

  9. Clinical impact of atypical squamous cells of undetermined significance. A cytohistologic comparison.

    Science.gov (United States)

    Lousuebsakul, V; Knutsen, S M; Gram, I T; Akin, M R

    2000-01-01

    To assess the percentage of squamous intraepithelial lesions (SILs) in the atypical squamous cells of undetermined significance (ASCUS) cytologic diagnosis. From January 1994 to December 1995, 421 cervical Pap smears with a diagnosis of ASCUS were followed with cervical biopsies within three months. The ASCUS cytologic diagnosis was correlated with the histologic findings and stratified according to age group, previous abnormal history and cell type of ASCUS (squamoid vs. metaplastic). Histologic diagnosis showed that of ASCUS diagnoses, 13% were normal, 34% were reactive, 4.8% were atypical, 43% were low grade SIL, 4% were high grade SIL, 1% were carcinoma in situ, and none were invasive lesions. The patients in the youngest group, up to 25 years, demonstrated the highest percentage of SIL. Patients with a previous abnormal gynecologic history showed a higher percentage of SIL than those without an abnormal history. SILs were observed in 51.5% of squamoid ASCUS and 36.5% of metaplastic ASCUS. Forty-eight percent of females having an ASCUS diagnosis on Pap smears had SIL and thus a preneoplastic lesion. The highest percentage of SIL was found in females 25 years and younger. Our findings suggest that an ASCUS diagnosis warrants ongoing follow-up.

  10. Nanostructural optimization of silicon/PEDOT:PSS hybrid solar cells for performance improvement

    International Nuclear Information System (INIS)

    Wang, Yanzhou; Shao, Pengfei; Li, Yali; Li, Junshuai; He, Deyan; Chen, Qiang

    2017-01-01

    In this paper, an inverted silicon (Si) nanopyramid (iSiNP) surface structure with low aspect ratio and remarkable antireflection is developed through sequential treatments of NaOH and HF/CH 3 COOH/HNO 3 solutions to Si nanowire (SiNW)-textured Si wafers, which are prepared by traditional electroless chemical etching. The iSiNP/PEDOT:PSS hybrid solar cell is fabricated through conformally spin-coating poly(3.4-ethylene dioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) onto the iSiNPs; it exhibits enhanced device performance owing to the improved junction and contact quality as compared to the SiNW/PEDOT:PSS counterpart. A power conversion efficiency (PCE) of 9.6% mainly contributed from an increased fill factor (FF) of 0.61 and improved open circuit voltage ( V oc ) of 0.53 V is delivered by the iSiNP/PEDOT:PSS solar cell. As a comparison, the SiNW/PEDOT:PSS structure delivers a 7.1% PCE with a FF of 0.45 and V oc of 0.46 V. Considering the submicro-scale characteristic dimensions, iSiNPs are expected to be applicable to highly efficient thin film Si/PEDOT:PSS hybrid solar cells. (paper)

  11. Endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma: Is it a significant prognostic factor?

    Science.gov (United States)

    Shin, Hae Jin; Moon, Hee Seok; Kang, Sun Hyung; Sung, Jae Kyu; Jeong, Hyun Yong; Kim, Seok Hyun; Lee, Byung Seok; Kim, Ju Seok; Yun, Gee Young

    2017-12-01

    The purpose of this study was to evaluate the prognostic impact of endoscopic traversability in patients with locally advanced esophageal squamous cell carcinoma.This retrospective study was based on medical records from a single tertiary medical center. The records of 317 patients with esophageal squamous cell carcinoma treated with surgery or definitive chemoradiotherapy (CRT) between January 2009 and March 2016 were reviewed. Finally, we retrieved the data on 168 consecutive patients. These 168 patients were divided into 2 groups based on their endoscopic traversability findings: Group A (the endoscope traversable group), and Group B (the endoscope non-traversable group). We then retrospectively compared the clinical characteristics of these 2 groups.The endoscope non-traversable group (Group B) revealed an advanced clinical stage, a poor Eastern Cooperative Oncology Group (ECOG) score, a lower serum albumin level, a higher rate of requirement for esophageal stent insertion and definitive CRT as initial treatment than the endoscope traversable group (Group A). Patients with endoscope traversable cancer showed a significantly higher 3-year overall survival and 3-year relapse-free survival than patients who were endoscope non-traversable (53.8% vs 17.3%, P squamous cell carcinoma treated with definitive CRT, the serum albumin level squamous cell carcinoma treated with definitive CRT is a significant prognostic factor. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  12. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  13. Protein blend ingestion before allogeneic stem cell transplantation improves protein-energy malnutrition in patients with leukemia.

    Science.gov (United States)

    Ren, Guangxu; Zhang, Jianping; Li, Minghua; Yi, Suqin; Xie, Jin; Zhang, Hongru; Wang, Jing

    2017-10-01

    Severe protein-energy malnutrition (PEM) and skeletal muscle wasting are commonly observed in patients with acute leukemia. Recently, the ingestion of a soy-whey protein blend has been shown to promote muscle protein synthesis (MPS). Thus, we tested the hypothesis that the ingestion of a soy-whey blended protein (BP) may improve the PEM status and muscle mass in acute leukemia patients. In total, 24 patients from the same treatment group were randomly assigned to the natural diet plus soy-whey blended protein (BP) group and the natural diet only (ND) group. Our data showed that protein and energy intake decreased significantly (P protein) were observed in the majority (>50%) of the patients. However, 66% of the patients who ingested the BP before transplantation showed obvious increases in arm muscle area. The gripping power value (△ post-pre or △ post-baseline ) was significantly higher in the BP group than in the ND group (P protein to different extents. Notably, the average time to stem cell engraftment was significantly shorter for patients in the BP group (12.2 ± 2.0 days) than for patients in the ND group (15.1 ± 2.9 days). Collectively, our data supported that soy-whey protein can improve PEM status and muscle mass in leukemia patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Oil and mucilage cells in Annona (Annonaceae) and their systematic significance

    NARCIS (Netherlands)

    Bakker, M.E.; Gerritsen, A.F.

    1992-01-01

    The morphology and distribution patterns of oil and/or mucilage cells, i.e. idioblasts, in the leaf of 37 Annona species are described. Idioblasts are always present in the spongy parenchyma in all species and in most cases also in the palisade parenchyma. Usually both oil cells and mucilage cells

  15. [Expression of thioredoxin-2 in human lens epithelial cells with oxidative damage and its significance].

    Science.gov (United States)

    Che, Xuanyi; Zhao, Qingxia; Li, Di

    2018-03-28

    To explore whether thioredoin-2 (Trx-2) is involved in the development of cataract and to study the effect of Trx-2 on hydrogen peroxide (H2O2)-induced injury in human lens epithelial cells.
 Methods: A total of 10 volunteers (removing the lens due totraumatism) and 30 patients received phacoemulsification (age more than 60 years) were selected. The expression of Trx-2 protein in lens epithelial cells from cataract patients and volunteers were detected by the immunohistochemical streptavidin-peroxidase (SP) method. SRA01/04 cells were cultured and were divided into six groups according to different treatment: a control group, H2O2-treated groups at 20, 50 or 
100 μmol/L, a negative control group (transfected with pCMV6 plasmid plus 100 μmol/L H2O2), and a Trx-2 overexpression group (transfected with pCMV6-Trx-2 plasmid plus 100 μmol/L H2O2). Methyl thiazolyltetrazolium (MTT) assay and flow cytometry was performed to measure the cell viability and apoptosis for SRA01/04 cells, respectively. The activities of superoxide dismutase (SOD) and catalase (CAT), the content of glutathione (GSH) and malondialdehyde (MDA) in human lens epithelial cells were measured via chemical chromatometry. Western blot was used to measure the protein levels of Trx-2, B-cell lymphoma 2 protein (Bcl-2), Bcl-2 associated X protein (Bax) and caspase-3.
 Results: Compared with the volunteers, the expression of Trx-2 was significantly decreased in lens epithelial cells in patients with cataract (PTrx-2 protein in the 20, 50 or 100 μmol/L H2O2 groups was decreased (all PTrx-2 and Bcl-2 expression and up-regulated Bax and caspase-3 expression (all PTrx-2 overexpression group (PTrx-2 and Bcl-2 expression and down-regulated Bax and caspase-3 expression (PTrx-2 might be involved in the apoptosis of lens epithelial cells in patients with cataract. The overexpression of Trx-2 obviously attenuated H2O2-induced injury of human lens epithelial cells, which might be associated with the

  16. PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

    International Nuclear Information System (INIS)

    Ghorai, Atanu; Sarma, Asitikantha; Chowdhury, Priyanka; Ghosh, Utpal

    2016-01-01

    Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was

  17. Expression of Th17 and CD4+ CD25+ T regulatory cells in peripheral blood of acute leukemia patients and their prognostic significance.

    Science.gov (United States)

    Xiang, Mingli; Guo, Li; Ma, Yan; Li, Yi

    2016-11-01

    To discuss the expression of T helper cell 17 (Th17) cells and CD4+ CD25+ Foxp3+ regulatory T cells (Treg) in peripheral blood (PB) of patients with acute leukemia (AL), and to explore the relationship between them and disease prognosis. 40 patients diagnosed with acute leukemia in The First Affiliated Hospital of Zhengzhou University from July 2012 to August 2014 were selected as the observation group. Meanwhile, 40 healthy people were taken as the control group. Flow Cytometry Method (FCM) was used to detect the level of Th17 cells and CD4 + CD25 + Foxp3 + cells in peripheral blood of the two groups, and enzyme-linked immuno sorbent assay (ELISA) method was used to test the level of IL17 and TGF-β in peripheral blood of two groups; reverse transcription-polymerase chain reaction (RT-PCR) was adopted to analyze the mRNA levels of RORγT and Foxp3 in peripheral blood. In addition, we examined the levels of Th17 and CD4 + CD25 + Foxp3 + cells and associated factor levels in patients with remission after AL chemotherapy. the Th17 cells (CD3 + CD4 + IL-17 + ) in acute leukemia patients accounted for (1.51±0.27)%, which was significantly higher than that of control group (0.36±0.23)%, with statistical significance (t=20.51, Pcells in AL patients was (3.37±0.48)%, which was significantly higher than that of control group of (1.26±0.27)%, with statistical significance (t=24.23, Pt=7.83, Pt=7.83, Pt=12.27, Pt=7.89, Pcells and CD4 + CD25 + Foxp3 + cells, and the serum levels of IL-17 and TGF-β in acute leukemia patients all decreased significantly after 6 months of chemotherapy, and the difference was statistically significant (Pcells, CD4+ CD25+ Foxp3 + cells and their secretory proteins IL-17, TGF-β and transcription factors were significantly increased in AL patients. Therefore, regular detection of peripheral blood Th17 and Treg cells, as well as their secretory proteins are useful for monitoring the immune status and prognosis of patients.

  18. Quantify and improve PEM fuel cell durability. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Grahl-Madsen, L.; Odgaard, M.; Munksgaard Nielsen, R. (IRD Fuel Cell A/S, Svendborg (Denmark)); Li, Q.; Jensen, Jens Oluf (Technical Univ. of Denmark, Dept. of Chemistry, Kgs. Lyngby (Denmark)); Andersen, Shuang Ma; Speder, J.; Skou, E. (Syddansk Univ. (SDU), Odense (Denmark))

    2010-07-01

    approx 4,000 hours of operation correspond to a loss of catalytic active area of 58% for the anode and 69% for the cathode respectively, and the MEA can be expected to perform equivalent to MEAs with less than half the catalyst loating. DMFC durability tests were carried out on both Nafion and Hydrocarbon membrane based MEAs using different electrode designs. Several single DMFC cells and stacks have been tested up to 3,000 hours. The degradation rates found for both single cells and stacks were in the range between 10-90 muV/hours per cell, depending on the MEA configuration. Certain performance losses incurred by the cell during the steady-state operation were recovered, fully or in part, after the regular OCV hold. Regeneration of the Pt-catalyst particles include electro-reduction of the surface PtO that gradually forms over time, surface electro-oxidation of adsorbed poisons (namely CO formed from methanol crossover), and chemical reduction of PtO and/or PtOH via crossover methanol. The HT PEM FC results indicate that a degradation rate of approx 5 muV/h for HT PEM FC can be expected under continuous operation with hydrogen and air at 150-160 C, corresponding to a lifetime of 12,000 hours before 10% performance loss. This lifetime is somewhat shorter than aimed at in the national Danish HT PEM Road map (2009: 20,000 h), but it is in this context important to remember the limited knowledge on HT PEM lifetime at the time of the roadmap definition in 2008. The accelerated durability test with potential cycling showed significant catalyst degradation, primarily due to the corrosion of carbon supports, which triggers the platinum sintering/agglomeration. Modified catalyst supports in form of graphite or carbon nanotubes improve the catalyst and therefore the PBI cell durability. (LN)

  19. Cysteine modified polyaniline films improve biocompatibility for two cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Yslas, Edith I., E-mail: eyslas@exa.unrc.edu.ar [Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Agencia Postal Nro3, X580BYA Río Cuarto (Argentina); Cavallo, Pablo; Acevedo, Diego F.; Barbero, César A. [Departamento de Química, Universidad Nacional de Río Cuarto, Agencia Postal Nro3, X580BYA Río Cuarto (Argentina); Rivarola, Viviana A. [Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Agencia Postal Nro3, X580BYA Río Cuarto (Argentina)

    2015-06-01

    This work focuses on one of the most exciting application areas of conjugated conducting polymers, which is cell culture and tissue engineering. To improve the biocompatibility of conducting polymers we present an easy method that involves the modification of the polymer backbone using L-cysteine. In this publication, we show the synthesis of polyaniline (PANI) films supported onto Polyethylene terephthalate (PET) films, and modified using cysteine (PANI-Cys) in order to generate a biocompatible substrate for cell culture. The PANI-Cys films are characterized by Fourier Transform infrared and UV–visible spectroscopy. The changes in the hydrophilicity of the polymer films after and before the modification were tested using contact angle measurements. After modification the contact angle changes from 86° ± 1 to 90° ± 1, suggesting a more hydrophylic surface. The adhesion properties of LM2 and HaCaT cell lines on the surface of PANI-Cys films in comparison with tissue culture plastic (TCP) are studied. The PANI-Cys film shows better biocompatibility than PANI film for both cell lines. The cell morphologies on the TCP and PANI-Cys film were examined by florescence and Atomic Force Microscopy (AFM). Microscopic observations show normal cellular behavior when PANI-Cys is used as a substrate of both cell lines (HaCaT and LM2) as when they are cultured on TCP. The ability of these PANI-Cys films to support cell attachment and growth indicates their potential use as biocompatible surfaces and in tissue engineering. - Highlights: • A new surface PANI-Cys was produced on films of polyethylene terephthalate. • The relationship between surface characteristics and biocompatibility is analyzed. • The PANI-Cys film presents good biocompatibility for two cell lines.

  20. Intrathecal administration of autologous bone marrow stromal cells improves neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    Vaquero, J; Zurita, M; Rico, M A; Aguayo, C; Fernández, C; Gutiérrez, R; Rodríguez-Boto, G; Saab, A; Hassan, R; Ortega, C

    2018-03-23

    Neuropathic pain (NP) is highly disabling, responds poorly to pharmacological treatment, and represents a significant cause of decreased quality of life in patients suffering from spinal cord injury (SCI). In recent years, cell therapy with autologous mesenchymal stromal cells (MSCs) has been considered as a potential therapeutic weapon in this entity. Ten patients suffering chronic SCI received 100 million MSCs into subarachnoid space by lumbar puncture (month 1 of the study) and this procedure was repeated at months 4 and 7 until reaching a total doses of 300 million MSCs. Intensity of NP was measured by standard numerical rating scale (VAS) from 0 to 10, recording scores previous to the first MSCs administration and monthly, until month 10 of follow-up. Months 1, 4, 7 and 10 of the study were selected as time points in order to a statistical analysis by the nonparametric Wilcoxon rank test. Our results showed significant and progressive improvement in NP intensity after the first administration of MSCs (p: 0.003). This study supports the benefit of intrathecal administration of autologous MSCs for the treatment of NP in patients with SCI. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Clinical significance of determination of changes of serum SOD and T-cell subsets distribution type after leukocyte-deduced red blood cell transfusion in patients with lung cancer

    International Nuclear Information System (INIS)

    Yu Zhengqin; Li Keqin; Xiang Hengquan

    2006-01-01

    Objective: To investigate the changes of serum SOD contents and T-cell subsets distribution type after leukocyte-deduced red blood cell transfusion in patients with lung cancer. Methods: Serum SOD levels was measured with RIA and T-cell subsets distribution type was detected with monoclonal antibody technic both before and after leukocyte-deduced red blood cell transfusion in 32 patients with lung cancer and 35 normal controls. Results: Before treatment, the serum levels of SOD and T-cell CIM/ CD8 value were significantly lower in the patients than those in controls (P 0.05). Conclusion: Determination of serum SOD level and T-cell subsets distribution type is clinically useful in the management of patients with lung cancer. (authors)

  2. Improving Performance of CIGS Solar Cells by Annealing ITO Thin Films Electrodes

    Directory of Open Access Journals (Sweden)

    Chuan Lung Chuang

    2015-01-01

    Full Text Available Indium tin oxide (ITO thin films were grown on glass substrates by direct current (DC reactive magnetron sputtering at room temperature. Annealing at the optimal temperature can considerably improve the composition, structure, optical properties, and electrical properties of the ITO film. An ITO sample with a favorable crystalline structure was obtained by annealing in fixed oxygen/argon ratio of 0.03 at 400°C for 30 min. The carrier concentration, mobility, resistivity, band gap, transmission in the visible-light region, and transmission in the near-IR regions of the ITO sample were -1.6E+20 cm−3, 2.7E+01 cm2/Vs, 1.4E-03 Ohm-cm, 3.2 eV, 89.1%, and 94.7%, respectively. Thus, annealing improved the average transmissions (400–1200 nm of the ITO film by 16.36%. Moreover, annealing a copper-indium-gallium-diselenide (CIGS solar cell at 400°C for 30 min in air improved its efficiency by 18.75%. The characteristics of annealing ITO films importantly affect the structural, morphological, electrical, and optical properties of ITO films that are used in solar cells.

  3. Development of improved methods for the LWR lattice physics code EPRI-CELL

    International Nuclear Information System (INIS)

    Williams, M.L.; Wright, R.Q.; Barhen, J.

    1982-07-01

    A number of improvements have been made by ORNL to the lattice physics code EPRI-CELL (E-C) which is widely used by utilities for analysis of power reactors. The code modifications were made mainly in the thermal and epithermal routines and resulted in improved reactor physics approximations and more efficient running times. The improvements in the thermal flux calculation included implementation of a group-dependent rebalance procedure to accelerate the iterative process and a more rigorous calculation of interval-to-interval collision probabilities. The epithermal resonance shielding methods used in the code have been extensively studied to determine its major approximations and to examine the sensitivity of computed results to these approximations. The study has resulted in several improvements in the original methodology

  4. Improving Gene Therapy Efficiency through the Enrichment of Human Hematopoietic Stem Cells.

    Science.gov (United States)

    Masiuk, Katelyn E; Brown, Devin; Laborada, Jennifer; Hollis, Roger P; Urbinati, Fabrizia; Kohn, Donald B

    2017-09-06

    Lentiviral vector (LV)-based hematopoietic stem cell (HSC) gene therapy is becoming a promising clinical strategy for the treatment of genetic blood diseases. However, the current approach of modifying 1 × 10 8 to 1 × 10 9 CD34 + cells per patient requires large amounts of LV, which is expensive and technically challenging to produce at clinical scale. Modification of bulk CD34 + cells uses LV inefficiently, because the majority of CD34 + cells are short-term progenitors with a limited post-transplant lifespan. Here, we utilized a clinically relevant, immunomagnetic bead (IB)-based method to purify CD34 + CD38 - cells from human bone marrow (BM) and mobilized peripheral blood (mPB). IB purification of CD34 + CD38 - cells enriched severe combined immune deficiency (SCID) repopulating cell (SRC) frequency an additional 12-fold beyond standard CD34 + purification and did not affect gene marking of long-term HSCs. Transplant of purified CD34 + CD38 - cells led to delayed myeloid reconstitution, which could be rescued by the addition of non-transduced CD38 + cells. Importantly, LV modification and transplantation of IB-purified CD34 + CD38 - cells/non-modified CD38 + cells into immune-deficient mice achieved long-term gene-marked engraftment comparable with modification of bulk CD34 + cells, while utilizing ∼7-fold less LV. Thus, we demonstrate a translatable method to improve the clinical and commercial viability of gene therapy for genetic blood cell diseases. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  5. Improving the Post-Stroke Therapeutic Potency of Mesenchymal Multipotent Stromal Cells by Cocultivation With Cortical Neurons: The Role of Crosstalk Between Cells.

    Science.gov (United States)

    Babenko, Valentina A; Silachev, Denis N; Zorova, Ljubava D; Pevzner, Irina B; Khutornenko, Anastasia A; Plotnikov, Egor Y; Sukhikh, Gennady T; Zorov, Dmitry B

    2015-09-01

    The goal of the present study was to maximally alleviate the negative impact of stroke by increasing the therapeutic potency of injected mesenchymal multipotent stromal cells (MMSCs). To pursue this goal, the intercellular communications of MMSCs and neuronal cells were studied in vitro. As a result of cocultivation of MMSCs and rat cortical neurons, we proved the existence of intercellular contacts providing transfer of cellular contents from one cell to another. We present evidence of intercellular exchange with fluorescent probes specifically occupied by cytosol with preferential transfer from neurons toward MMSCs. In contrast, we observed a reversed transfer of mitochondria (from MMSCs to neural cells). Intravenous injection of MMSCs in a postischemic period alleviated the pathological indexes of a stroke, expressed as a lower infarct volume in the brain and partial restoration of neurological status. Also, MMSCs after cocultivation with neurons demonstrated more profound neuroprotective effects than did unprimed MMSCs. The production of the brain-derived neurotrophic factor was slightly increased in MMSCs, and the factor itself was redistributed in these cells after cocultivation. The level of Miro1 responsible for intercellular traffic of mitochondria was increased in MMSCs after cocultivation. We conclude that the exchange by cellular compartments between neural and stem cells improves MMSCs' protective abilities for better rehabilitation after stroke. This could be used as an approach to enhance the therapeutic benefits of stem cell therapy to the damaged brain. The idea of priming stem cells before practical use for clinical purposes was applied. Thus, cells were preconditioned by coculturing them with the targeted cells (i.e., neurons for the treatment of brain pathological features) before the transfusion of stem cells to the organism. Such priming improved the capacity of stem cells to treat stroke. Some additional minimal study will be required to

  6. MYC protein expression is detected in plasma cell myeloma but not in monoclonal gammopathy of undetermined significance (MGUS).

    Science.gov (United States)

    Xiao, Ruobing; Cerny, Jan; Devitt, Katherine; Dresser, Karen; Nath, Rajneesh; Ramanathan, Muthalagu; Rodig, Scott J; Chen, Benjamin J; Woda, Bruce A; Yu, Hongbo

    2014-06-01

    It has been recognized that monoclonal gammopathy of undetermined significance (MGUS) precedes a diagnosis of plasma cell myeloma in most patients. Recent gene expression array analysis has revealed that an MYC activation signature is detected in plasma cell myeloma but not in MGUS. In this study, we performed immunohistochemical studies using membrane CD138 and nuclear MYC double staining on bone marrow biopsies from patients who met the diagnostic criteria of plasma cell myeloma or MGUS. Our study demonstrated nuclear MYC expression in CD138-positive plasma cells in 22 of 26 (84%) plasma cell myeloma samples and in none of the 29 bone marrow samples from patients with MGUS. In addition, our data on the follow-up biopsies from plasma cell myeloma patients with high MYC expression demonstrated that evaluation of MYC expression in plasma cells can be useful in detecting residual disease. We also demonstrated that plasma cells gained MYC expression in 5 of 8 patients (62.5%) when progressing from MGUS to plasma cell myeloma. Analysis of additional lymphomas with plasmacytic differentiation, including lymphoplasmacytic lymphoma, marginal zone lymphoma, and plasmablastic lymphoma, reveals that MYC detection can be a useful tool in the diagnosis of plasma cell myeloma.

  7. Durability Improvements Through Degradation Mechanism Studies

    Energy Technology Data Exchange (ETDEWEB)

    Borup, Rodney L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Mukundan, Rangachary [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Spernjak, Dusan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Baker, Andrew M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Lujan, Roger W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Langlois, David Alan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ahluwalia, Rajesh [Argonne National Lab. (ANL), Argonne, IL (United States); Papadia, D. D. [Argonne National Lab. (ANL), Argonne, IL (United States); Weber, Adam Z. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Kusoglu, Ahmet [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Shi, Shouwnen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); More, K. L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Grot, Steve [Ion Power, New Castle, DE (United States)

    2015-08-03

    The durability of polymer electrolyte membrane (PEM) fuel cells is a major barrier to the commercialization of these systems for stationary and transportation power applications. By investigating cell component degradation modes and defining the fundamental degradation mechanisms of components and component interactions, new materials can be designed to improve durability. To achieve a deeper understanding of PEM fuel cell durability and component degradation mechanisms, we utilize a multi-institutional and multi-disciplinary team with significant experience investigating these phenomena.

  8. Improving photovoltaic performance of silicon solar cells using a combination of plasmonic and luminescent downshifting effects

    Science.gov (United States)

    Ho, Wen-Jeng; Feng, Sheng-Kai; Liu, Jheng-Jie; Yang, Yun-Chie; Ho, Chun-Hung

    2018-05-01

    This paper reports on efforts to improve the photovoltaic performance of crystalline silicon solar cells by combining the plasmonic scattering of silver nanoparticles (Ag NPs) with the luminescent downshifting (LDS) effects of Eu-doped phosphors. The surface morphology was examined using a scanning electron microscope in conjunction with ImageJ software. Raman scattering and absorbance measurements were used to examine the surface plasmon resonance of Ag NPs of various dimensions in various dielectric environments. The fluorescence emission of the Eu-doped phosphors was characterized via photoluminescence measurements at room temperature. We examined the combination of plasmonic and LDS effects by measuring the optical reflectance and external quantum efficiency. Improvements in the photovoltaic performance of the solar cells were determined by photovoltaic current density-voltage under AM 1.5G illumination. A combination of plasmonic and LDS effects led to an impressive 26.17% improvement in efficiency, whereas plasmonic effects resulted in a 22.63% improvement compared to the cell with a SiO2 ARC of 17.33%.

  9. The cell agglutination agent, phytohemagglutinin-L, improves the efficiency of somatic nuclear transfer cloning in cattle (Bos taurus).

    Science.gov (United States)

    Du, Fuliang; Shen, Perng-Chih; Xu, Jie; Sung, Li-Ying; Jeong, B-Seon; Lucky Nedambale, Tshimangadzo; Riesen, John; Cindy Tian, X; Cheng, Winston T K; Lee, Shan-Nan; Yang, Xiangzhong

    2006-02-01

    One of the several factors that contribute to the low efficiency of mammalian somatic cloning is poor fusion between the small somatic donor cell and the large recipient oocyte. This study was designed to test phytohemagglutinin (PHA) agglutination activity on fusion rate, and subsequent developmental potential of cloned bovine embryos. The toxicity of PHA was established by examining its effects on the development of parthenogenetic bovine oocytes treated with different doses (Experiment 1), and for different durations (Experiment 2). The effective dose and duration of PHA treatment (150 microg/mL, 20 min incubation) was selected and used to compare membrane fusion efficiency and embryo development following somatic cell nuclear transfer (Experiment 3). Cloning with somatic donor fibroblasts versus cumulus cells was also compared, both with and without PHA treatment (150 microg/mL, 20 min). Fusion rate of nuclear donor fibroblasts, after phytohemagglutinin treatment, was increased from 33 to 61% (P cell nuclear donors. The nuclear transfer (NT) efficiency per oocyte used was improved following PHA treatment, for both fibroblast (13% versus 22%) as well as cumulus cells (17% versus 34%; P cloned embryos, both with and without PHA treatment, were subjected to vitrification and embryo transfer testing, and resulted in similar survival (approximately 90% hatching) and pregnancy rates (17-25%). Three calves were born following vitrification and embryo transfer of these embryos; two from the PHA-treated group, and one from non-PHA control group. We concluded that PHA treatment significantly improved the fusion efficiency of somatic NT in cattle, and therefore, increased the development of cloned blastocysts. Furthermore, within a determined range of dose and duration, PHA had no detrimental effect on embryo survival post-vitrification, nor on pregnancy or calving rates following embryo transfer.

  10. Adenovirus-mediated transfer of hepatocyte growth factor gene to human dental pulp stem cells under good manufacturing practice improves their potential for periodontal regeneration in swine.

    Science.gov (United States)

    Cao, Yu; Liu, Zhenhai; Xie, Yilin; Hu, Jingchao; Wang, Hua; Fan, Zhipeng; Zhang, Chunmei; Wang, Jingsong; Wu, Chu-Tse; Wang, Songlin

    2015-12-15

    Periodontitis is one of the most widespread infectious diseases in humans. We previously promoted significant periodontal tissue regeneration in swine models with the transplantation of autologous periodontal ligament stem cells (PDLSCs) and PDLSC sheet. We also promoted periodontal tissue regeneration in a rat model with a local injection of allogeneic bone marrow mesenchymal stem cells. The purpose of the present study is to investigate the roles of the hepatocyte growth factor (HGF) and human dental pulp stem cells (DPSCs) in periodontal tissue regeneration in swine. In the present study, we transferred an adenovirus that carried HGF gene into human DPSCs (HGF-hDPSCs) under good manufacturing practice (GMP) conditions. These cells were then transplanted into a swine model for periodontal regeneration. Twenty miniature pigs were used to generate periodontitis with bone defect of 5 mm in width, 7 mm in length, and 3 mm in depth. After 12 weeks, clinical, radiological, quantitative and histological assessment of regenerated periodontal tissues was performed to compare periodontal regeneration in swine treated with cell implantation. Our study showed that injecting HGF-hDPSCs into this large animal model could significantly improve periodontal bone regeneration and soft tissue healing. A hDPSC or HGF-hDPSC sheet showed superior periodontal tissue regeneration compared to the injection of dissociated cells. However, the sheets required surgical placement; thus, they were suitable for surgically-managed periodontitis treatments. The adenovirus-mediated transfer of the HGF gene markedly decreased hDPSC apoptosis in a hypoxic environment or in serum-free medium, and it increased blood vessel regeneration. This study indicated that HGF-hDPSCs produced under GMP conditions significantly improved periodontal bone regeneration in swine; thus, this method represents a potential clinical application for periodontal regeneration.

  11. Prognostic significance of IgG4+ plasma cell infiltrates following neoadjuvant chemoradiation therapy for esophageal adenocarcinoma.

    Science.gov (United States)

    Yakirevich, Evgeny; Lu, Shaolei; Allen, Danisha; Mangray, Shamlal; Fanion, Jacqueline R; Lombardo, Kara A; Safran, Howard; Resnick, Murray B

    2017-08-01

    Lymphoplasmacytic infiltrates in esophageal adenocarcinoma (EAC) tissue following chemoradiotherapy (CRT) reflect alterations in the tumor immunoenvironment. The presence and role of plasma cells in this process are poorly understood. Our aim was to characterize the IgG4+ plasma cell population in EAC following CRT. Seventy-one esophagectomy specimens post-CRT were compared with a surgery-only group of 31 EACs. The distribution, density, and ratio of IgG4+ and IgG+ plasma cells were evaluated by immunohistochemistry and correlated with clinicopathologic features, treatment response, and survival. In the CRT group, the presence of higher numbers of IgG4+ (≥ median of 94/high-power field) and IgG+ (≥ median of 225/high-power field) plasma cells and increased IgG4+/IgG+ ratio (≥ median of 41%) within ulcers was associated with complete or near-complete treatment response (P = .0077, P = .0503, and P = .0063, respectively). Lower tumor grade, smaller tumor size, and higher levels of IgG4+ plasma cells in posttherapy ulcers significantly correlated with better overall survival, whereas pretherapy clinical stage, posttherapy pathologic stage, smaller tumor size, and lower tumor grade were associated with longer recurrence-free survival. Multivariate analysis revealed that both posttherapy pathologic stage and high IgG4+ plasma cells in ulcers were independent predictors of overall survival (P = .05 and P = .01), whereas only posttherapy pathologic stage was associated with recurrence-free survival (P IgG4+ plasma cell infiltrate in EAC following CRT. The presence of increased IgG4+ plasma cells may be a novel reliable factor to predict prognosis of EAC patients following CRT. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. An improved model for nucleation-limited ice formation in living cells during freezing.

    Directory of Open Access Journals (Sweden)

    Jingru Yi

    Full Text Available Ice formation in living cells is a lethal event during freezing and its characterization is important to the development of optimal protocols for not only cryopreservation but also cryotherapy applications. Although the model for probability of ice formation (PIF in cells developed by Toner et al. has been widely used to predict nucleation-limited intracellular ice formation (IIF, our data of freezing Hela cells suggest that this model could give misleading prediction of PIF when the maximum PIF in cells during freezing is less than 1 (PIF ranges from 0 to 1. We introduce a new model to overcome this problem by incorporating a critical cell volume to modify the Toner's original model. We further reveal that this critical cell volume is dependent on the mechanisms of ice nucleation in cells during freezing, i.e., surface-catalyzed nucleation (SCN and volume-catalyzed nucleation (VCN. Taken together, the improved PIF model may be valuable for better understanding of the mechanisms of ice nucleation in cells during freezing and more accurate prediction of PIF for cryopreservation and cryotherapy applications.

  13. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

    Science.gov (United States)

    Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

    2016-09-01

    The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. © 2016 by The American Society of Hematology.

  14. Surface modification of hydrophobic polymers for improvement of endothelial cell-surface interactions

    NARCIS (Netherlands)

    Dekker, A.; Dekker, A.; Reitsma, K.; Beugeling, T.; Beugeling, T.; Bantjes, A.; Bantjes, A.; Feijen, Jan; Kirkpatrick, C.J.; van Aken, W.G.

    1992-01-01

    The aim of this study is to improve the interaction of endothelial cells with polymers used in vascular prostheses. Polytetrafluoroethylene (PTFE; Teflon) films were treated by means of nitrogen and oxygen plasmas. Depending on the plasma exposure time, modified PTFE surfaces showed water-contact

  15. Local Xenotransplantation of Bone Marrow Derived Mast Cells (BMMCs) Improves Functional Recovery of Transected Sciatic Nerve in Cat: A Novel Approach in Cell Therapy.

    Science.gov (United States)

    Mohammadi, Rahim; Anousheh, Dana; Alaei, Mohammad-Hazhir; Nikpasand, Amin; Rostami, Hawdam; Shahrooz, Rasoul

    2018-04-01

    To determine the effects of bone marrow derived mast cells (BMMCs) on functional recovery of transected sciatic nerve in animal model of cat. A 20-mm sciatic nerve defect was bridged using a silicone nerve guide filled with BMMCs in BMMC group. In Sham-surgery group (SHAM), the sciatic nerve was only exposed and manipulated. In control group (SILOCONE) the gap was repaired with a silicone nerve guide and both ends were sealed using sterile Vaseline to avoid leakage and the nerve guide was filled with 100 μL of phosphate-buffered saline alone. In cell treated group ([SILOCONE/BMMC) the nerve guide was filled with 100 μL BMMCs (2× 106 cells/100 μL). The regenerated nerve fibers were studied, biomechanically, histologically and immunohiscochemically 6 months later. Biomechanical studies confirmed faster recovery of regenerated axons in BMMCs transplanted animals compared to control group ( p <0.05). Morphometric indices of the regenerated fibers showed that the number and diameter of the myelinated fibers were significantly higher in BMMCs transplanted animals than in control group ( p <0.05). In immunohistochemistry, location of reactions to S-100 in BMMCs transplanted animals was clearly more positive than that in control group. BMMCs xenotransplantation could be considered as a readily accessible source of cells that could improve recovery of transected sciatic nerve.

  16. Use of a small molecule cell cycle inhibitor to control cell growth and improve specific productivity and product quality of recombinant proteins in CHO cell cultures.

    Science.gov (United States)

    Du, Zhimei; Treiber, David; McCarter, John D; Fomina-Yadlin, Dina; Saleem, Ramsey A; McCoy, Rebecca E; Zhang, Yuling; Tharmalingam, Tharmala; Leith, Matthew; Follstad, Brian D; Dell, Brad; Grisim, Brent; Zupke, Craig; Heath, Carole; Morris, Arvia E; Reddy, Pranhitha

    2015-01-01

    The continued need to improve therapeutic recombinant protein productivity has led to ongoing assessment of appropriate strategies in the biopharmaceutical industry to establish robust processes with optimized critical variables, that is, viable cell density (VCD) and specific productivity (product per cell, qP). Even though high VCD is a positive factor for titer, uncontrolled proliferation beyond a certain cell mass is also undesirable. To enable efficient process development to achieve consistent and predictable growth arrest while maintaining VCD, as well as improving qP, without negative impacts on product quality from clone to clone, we identified an approach that directly targets the cell cycle G1-checkpoint by selectively inhibiting the function of cyclin dependent kinases (CDK) 4/6 with a small molecule compound. Results from studies on multiple recombinant Chinese hamster ovary (CHO) cell lines demonstrate that the selective inhibitor can mediate a complete and sustained G0/G1 arrest without impacting G2/M phase. Cell proliferation is consistently and rapidly controlled in all recombinant cell lines at one concentration of this inhibitor throughout the production processes with specific productivities increased up to 110 pg/cell/day. Additionally, the product quality attributes of the mAb, with regard to high molecular weight (HMW) and glycan profile, are not negatively impacted. In fact, high mannose is decreased after treatment, which is in contrast to other established growth control methods such as reducing culture temperature. Microarray analysis showed major differences in expression of regulatory genes of the glycosylation and cell cycle signaling pathways between these different growth control methods. Overall, our observations showed that cell cycle arrest by directly targeting CDK4/6 using selective inhibitor compound can be utilized consistently and rapidly to optimize process parameters, such as cell growth, qP, and glycosylation profile in

  17. A pilot study of parent education intervention improves early childhood development among toddlers with sickle cell disease.

    Science.gov (United States)

    Fields, Melanie E; Hoyt-Drazen, Catherine; Abel, Regina; Rodeghier, Mark J; Yarboi, Janet M; Compas, Bruce E; King, Allison A

    2016-12-01

    Young children with sickle cell disease (SCD) are at risk for cognitive delay. In addition to biologic risk factors associated with SCD, environmental factors contribute to cognitive dysfunction within this cohort. We completed a single-arm, prospective cohort study. Children with SCD between the ages of 3 and 36 months and their caregivers were followed between October 2010 and December 2013. The aim was to describe the role of a home visitation model, the home environment, and socioeconomic status in the development of young children with SCD. Primary outcome measures were the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and the Home Observation for Measurement of the Environment (HOME). We hypothesized that the home visitation model, Parents as Teachers ® (PAT), would encourage positive parent-child interactions and improve cognitive outcomes. Thirty-five participants had at least two PAT visits and BSID-III assessments. Mean scores within all five subtests of the BSID-III improved between enrollment and exit, with significant changes within cognitive (P = 0.016) and expressive language (EL) domains (P = 0.002). Multivariate modeling found the HOME score associated with the exit results of the cognitive domain. We report longitudinal results of the first home visitation program within the early childhood SCD population and show significant improvement in cognitive and EL development. Additionally, home environment was a significant predictor of cognitive development. Randomized controlled trials to test the impact of interventions targeting the home environment are warranted for this vulnerable population. © 2016 Wiley Periodicals, Inc.

  18. Improved Power Conversion Efficiency of Inverted Organic Solar Cells by Incorporating Au Nanorods into Active Layer.

    Science.gov (United States)

    He, Yeyuan; Liu, Chunyu; Li, Jinfeng; Zhang, Xinyuan; Li, Zhiqi; Shen, Liang; Guo, Wenbin; Ruan, Shengping

    2015-07-29

    This Research Article describes a cooperative plasmonic effect on improving the performance of organic solar cells. When Au nanorods(NRs) are incorporated into the active layers, the designed project shows superior enhanced light absorption behavior comparing with control devices, which leads to the realization of organic solar cell with power conversion efficiency of 6.83%, accounting for 18.9% improvement. Further investigations unravel the influence of plasmonic nanostructures on light trapping, exciton generation, dissociation, and charge recombination and transport inside the thin films devices. Moreover, the introduction of high-conductivity Au NRs improves electrical conductivity of the whole device, which contributes to the enhanced fill factor.

  19. Thermal and mechanical improvement of aluminum open-cells foams through electrodeposition of copper and graphene

    Directory of Open Access Journals (Sweden)

    Simoncini Alessandro

    2016-01-01

    Full Text Available Thanks to its planar structure, graphene is characterized by unique properties, such as excellent chemical inactivity, high electrical and thermal conductivity, high optical transparency, extraordinary flexibility and high mechanical resistance, which make it suitable in a very wide range of applications. This paper details the state of the art in graphene coating applied to aluminum open-cells foams for the improvement of their mechanical and thermal behavior. Metallic foams are highly porous materials with extremely high convective heat transfer coefficients, thanks to their complex structure of three-dimensional open-cells. Graphene nanoplatelets have been used to improve thermal conductivity of aluminum foams, to make them better suitable during heat transfer in transient state. Also, an improvement of mechanical resistance has been observed. Before electrodeposition, all the samples have been subjected to sandblasting process, to eliminate the oxide layer on the surface, enabling a better adhesion of the coating. Different nanoparticles of graphene have been used. The experimental findings revealed a higher thermal conductivity for aluminum open cells foams electroplated with graphene. Considered the relatively low process costs and the improvements obtainable, these materials are very promising in many technological fields. The topics covered include surface modification, electrochemical plating, thermo-graphic analysis.

  20. [Significance of the alteration of Th17 cells in patients with chronic lymphocytic thyroiditis].

    Science.gov (United States)

    Song, Jin-Zhan; Wu, Han-Ni; Qian, Wei

    2009-10-01

    To investigate the alteration and its significance of T help 17 cells (Th17) in patients with chronic lymphocytic thyroiditis (CLT). Patients were divided into 3 groups: CLT patients with euthyroidism (n=15), CLT patients with hypothyroidism (n=30) and healthy control group (n=20). The ratio of Th17 lymphocytes subpopulations in the peripheral blood were evaluated by technique of flow cytometry. Production of thyroid autoantibody (TPO-Ab, TG-Ab) were measured by electro-chemiluminescence immunoassay (ECLIA). Compared with the healthy control group, in CLT group: The frequencies of Th17 in peripheral blood were found to be significantly higher in patients with CLT than healthy control group (PCLT patients than healthy control group (PCLT which may suggest a potential role for Th17 in the progression and happen of CLT.

  1. Compression stockings significantly improve hemodynamic performance in post-thrombotic syndrome irrespective of class or length.

    Science.gov (United States)

    Lattimer, Christopher R; Azzam, Mustapha; Kalodiki, Evi; Makris, Gregory C; Geroulakos, George

    2013-07-01

    Graduated elastic compression (GEC) stockings have been demonstrated to reduce the morbidity associated with post-thrombotic syndrome. The ideal length or compression strength required to achieve this is speculative and related to physician preference and patient compliance. The aim of this study was to evaluate the hemodynamic performance of four different stockings and determine the patient's preference. Thirty-four consecutive patients (40 legs, 34 male) with post-thrombotic syndrome were tested with four different stockings (Mediven plus open toe, Bayreuth, Germany) of their size in random order: class 1 (18-21 mm Hg) and class II (23-32 mm Hg), below-knee (BK) and above-knee thigh-length (AK). The median age, Venous Clinical Severity Score, Venous Segmental Disease Score, and Villalta scale were 62 years (range, 31-81 years), 8 (range, 1-21), 5 (range, 2-10), and 10 (range, 2-22), respectively. The C of C0-6EsAs,d,pPr,o was C0 = 2, C2 = 1, C3 = 3, C4a = 12, C4b = 7, C5 = 12, C6 = 3. Obstruction and reflux was observed on duplex in 47.5% legs, with deep venous reflux alone in 45%. Air plethysmography was used to measure the venous filling index (VFI), venous volume, and time to fill 90% of the venous volume. Direct pressure measurements were obtained while lying and standing using the PicoPress device (Microlab Elettronica, Nicolò, Italy). The pressure sensor was placed underneath the test stocking 5 cm above and 2 cm posterior to the medial malleolus. At the end of the study session, patients stated their preferred stocking based on comfort. The VFI, venous volume, and time to fill 90% of the venous volume improved significantly with all types of stocking versus no compression. In class I, the VFI (mL/s) improved from a median of 4.9 (range, 1.7-16.3) without compression to 3.7 (range, 0-14) BK (24.5%) and 3.6 (range, 0.6-14.5) AK (26.5%). With class II, the corresponding improvement was to 4.0 (range, 0.3-16.2) BK (18.8%) and 3.7 (range, 0.5-14.2) AK (24

  2. New mounting improves solar-cell efficiency

    Science.gov (United States)

    Shepard, N. F., Jr.

    1980-01-01

    Method boosts output by about 20 percent by trapping and redirecting solar radiation without increasing module depth. Mounted solar-cell array is covered with internally reflecting plate. Plate is attached to each cell by transparent adhesive, and space between cells is covered with layer of diffusely reflecting material. Solar energy falling on space between cells is diffused and reflected internally by plate until it is reflected onto solar cell.

  3. Intra-myocardial injection of both growth factors and heart derived Sca-1+/CD31- cells attenuates post-MI LV remodeling more than does cell transplantation alone: neither intervention enhances functionally significant cardiomyocyte regeneration.

    Science.gov (United States)

    Wang, Xiaohong; Li, Qinglu; Hu, Qingsong; Suntharalingam, Piradeep; From, Arthur H L; Zhang, Jianyi

    2014-01-01

    Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival and regenerative factors in response to myocardial injury (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31- cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31- cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD) ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV) function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31- cells formed viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/-2.4; MI, 17.6+/-3.1; Cell, 28.2+/-4.2, n = 9, Pcell transplantation as evidenced by increased EF (38.8+/-2.2; n = 9, Pcell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31- cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31- cells revealed that Sca-1+/CD31- cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

  4. Improvement of adipose tissue-derived cells by low-energy extracorporeal shock wave therapy.

    Science.gov (United States)

    Priglinger, Eleni; Schuh, Christina M A P; Steffenhagen, Carolin; Wurzer, Christoph; Maier, Julia; Nuernberger, Sylvia; Holnthoner, Wolfgang; Fuchs, Christiane; Suessner, Susanne; Rünzler, Dominik; Redl, Heinz; Wolbank, Susanne

    2017-09-01

    Cell-based therapies with autologous adipose tissue-derived cells have shown great potential in several clinical studies in the last decades. The majority of these studies have been using the stromal vascular fraction (SVF), a heterogeneous mixture of fibroblasts, lymphocytes, monocytes/macrophages, endothelial cells, endothelial progenitor cells, pericytes and adipose-derived stromal/stem cells (ASC) among others. Although possible clinical applications of autologous adipose tissue-derived cells are manifold, they are limited by insufficient uniformity in cell identity and regenerative potency. In our experimental set-up, low-energy extracorporeal shock wave therapy (ESWT) was performed on freshly obtained human adipose tissue and isolated adipose tissue SVF cells aiming to equalize and enhance stem cell properties and functionality. After ESWT on adipose tissue we could achieve higher cellular adenosine triphosphate (ATP) levels compared with ESWT on the isolated SVF as well as the control. ESWT on adipose tissue resulted in a significantly higher expression of single mesenchymal and vascular marker compared with untreated control. Analysis of SVF protein secretome revealed a significant enhancement in insulin-like growth factor (IGF)-1 and placental growth factor (PLGF) after ESWT on adipose tissue. Summarizing we could show that ESWT on adipose tissue enhanced the cellular ATP content and modified the expression of single mesenchymal and vascular marker, and thus potentially provides a more regenerative cell population. Because the effectiveness of autologous cell therapy is dependent on the therapeutic potency of the patient's cells, this technology might raise the number of patients eligible for autologous cell transplantation. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  5. Bone marrow stem cells delivered into the subarachnoid space via cisterna magna improve repair of injured rat spinal cord white matter

    Science.gov (United States)

    Marcol, Wiesław; Slusarczyk, Wojciech; Sieroń, Aleksander L; Koryciak-Komarska, Halina; Lewin-Kowalik, Joanna

    2015-01-01

    The influence of bone marrow stem cells on regeneration of spinal cord in rats was investigated. Young adult male Wistar rats were used (n=22). Focal injury of spinal cord white matter at Th10 level was produced using our original non-laminectomy method by means of high-pressured air stream. Cells from tibial and femoral bone marrow of 1-month old rats (n=3) were cultured, labeled with BrdU/Hoechst and injected into cisterna magna (experimental group) three times: immediately after spinal cord injury and 3 as well as 7 days later. Neurons in brain stem and motor cortex were labeled with FluoroGold (FG) delivered caudally from the injury site a week before the end of experiment. Functional outcome and morphological features of regeneration were analyzed during 12-week follow-up. The lesions were characterized by means of MRI. Maximal distance of expansion of implanted cells in the spinal cord was measured and the number of FG-positive neurons in the brain was counted. Rats treated with stem cells presented significant improvement of locomotor performance and spinal cord morphology when compared to the control group. Distance covered by stem cells was 7 mm from the epicenter of the injury. Number of brain stem and motor cortex FG-positive neurons in experimental group was significantly higher than in control. Obtained data showed that bone marrow stem cells are able to induce the repair of injured spinal cord white matter. The route of cells application via cisterna magna appeared to be useful for their delivery in spinal cord injury therapy. PMID:26628950

  6. Expressions and clinical significance of autophagy-related markers Beclin1, LC3, and EGFR in human cervical squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hu YF

    2015-08-01

    Full Text Available Yun-Feng Hu,1 Xia Lei,2 Hong-Yi Zhang,3 Jun-wei Ma,1 Wei-wei Yang,1 Min-lin Chen,1 Jie Cui,1,4 Hong Zhao1 1Department of Oncology, 2Department of Gynecology, 3Department of Urology, Yan’an University Affiliated Hospital, Yan’an, Shaanxi Province, People’s Republic of China; 4Department of Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China Purpose: We aimed to investigate the expression of EGFR and the autophagy-related markers Beclin1 and LC3 in cervical cancer.Methods: Beclin1, LC3, and EGFR expression were analyzed in 80 samples of cervical squamous cell carcinoma (SCC, 40 samples of high-grade cervical intraepithelial neoplasia (CIN, and 40 samples of normal cervical tissues by immunohistochemistry. The protein expression rates were analyzed with χ2 and Fisher’s exact tests. Differences in overall survival (OS were determined using the Kaplan–Meier method and log-rank tests.Results: Cervical cancer, high-grade CIN, and normal cervical epithelial cells expressed Beclin1 in 26.2%, 77.5%, and 82.5% of patients, respectively, and expressed LC3 in 28.8%, 70.0%, and 75.0% of patients, respectively. There was a significant difference between cervical SCC and high-grade CIN or normal cervical epithelial cells (P=0.000. Cervical cancer cells, high-grade CIN cells, and normal cervical epithelial cells expressed EGFR in 68.8%, 62.5%, and 12.5% of patients, respectively. There was a significant difference between cervical SCC or high-grade CIN and normal cervical epithelial cells (P=0.000. No significant association between Beclin1 or LC3 or EGFR expression and various clinicopathological parameters was observed in cervical SCC. There was no significant correlation between Beclin1, LC3, EGFR expression, and 5-year OS rates of cervical SCC patients. Beclin1- or LC3-negativity with EGFR-positivity in cervical SCC was associated with a higher Federation International of

  7. Improving Efficiency of Evaporated Cu2ZnSnS4 Thin Film Solar Cells by a Thin Ag Intermediate Layer between Absorber and Back Contact

    Directory of Open Access Journals (Sweden)

    Hongtao Cui

    2015-01-01

    Full Text Available A 20 nm Ag coating on Mo back contact was adopted to improve the back contact of evaporated Cu2ZnSnS4 (CZTS solar cells. The Ag layer helped reduce the thickness of MoS2 which improves fill factor (FF significantly; additionally, it reduced secondary phases ZnS and SnS2−x, which may help carrier transport; it was also involved in the doping of the absorber layer, which compensated the intrinsic p-type doping and therefore drags down the doping level. The doping involvement may enlarge the depletion region and improve lifetime of the absorber, which led to enhancing open circuit voltage (VOC, short circuit current density (JSC, and efficiency significantly. However, it degrades the crystallinity of the material slightly.

  8. Millisecond photo-thermal process on significant improvement of supercapacitor’s performance

    International Nuclear Information System (INIS)

    Wang, Kui; Wang, Jixiao; Wu, Ying; Zhao, Song; Wang, Zhi; Wang, Shichang

    2016-01-01

    Graphical abstract: A high way for charge transfer is created by a millisecond photo-thermal process which could decrease contact resistance among nanomaterials and improve the electrochemical performances. - Highlights: • Improve conductivity among nanomaterials with a millisecond photo-thermal process. • The specific capacitance can increase about 25% with an photo-thermal process. • The circle stability and rate capability can be improved above 10% with photo-thermal process. • Provide a new way that create electron path to improve electrochemical performance. - Abstract: Supercapacitors fabricated with nanomaterials usually have high specific capacitance and excellent performance. However, the small size of nanomaterials renders a considerable limitation of the contact area among nanomaterials, which is harmful to charge carrier transfer. This fact may hinder the development and application of nanomaterials in electrochemical storage systems. Here, a millisecond photo-thermal process was introduced to create a charge carries transfer path to decrease the contact resistance among nanomaterials, and enhance the electrochemical performance of supercapacitors. Polyaniline (PANI) nanowire, as a model nanomaterial, was used to modify electrodes under different photo-thermal process conditions. The modified electrodes were characterized by scanning electronic microscopy (SEM), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and the results were analysed by equivalent circuit simulation. These results demonstrate that the photo-thermal process can alter the morphology of PANI nanowires, lower the charge transfer resistances and thus improve the performance of electrodes. The specific capacitance increase of the modified electrodes is about 25%. The improvement of the circle stability and rate capability are above 10%. To the best of our knowledge, this is the first attempt on research the effect of photo-thermal process on the conductivity

  9. Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Cong-Fa Huang

    Full Text Available Oxidative stress has been reported to play an important role in progression and prognostication in various kinds of cancers. However, the role and clinical significance of oxidative stress markers Keap1 and Nrf2 in oral squamous cell carcinoma (OSCC has not been elucidated. This study aimed to investigate the correlation of oxidative stress markers Keap1 and Nrf2 expression and pathological features in OSCC by using tissue microarray. Tissue microarrays containing 17 normal oral mucosa, 7 oral epithelial dysplasia and 43 OSCC specimens were studied by immunohistochemistry. The association among these proteins and pathological features were analyzed. Expression of oxidative stress markers Keap1, Nrf2, and antioxidants PPIA, Prdx6, as well as CD147 was found to increase consecutively from normal oral mucosa to OSCC, and the Keap1, Nrf2, PPIA, Prdx6, CD147 expression in OSCC were significantly higher when compared to normal oral mucosa. Expression of Keap1, Nrf2 in tumors was not found to be significantly associated with T category, lymph node metastases, and pathological grade. Furthermore, we checked the relationship among these oxidative stress markers and found that Keap1 was significantly correlated with Nrf2, Prdx6 and CD147. Significant relationship between Nrf2 and Prdx6 was also detected. Finally, we found patients with overexpression of Keap1 and Nrf2 had not significantly worse overall survival by Kaplan-Meier analysis. These findings suggest that ROS markers are associated with carcinogenesis and progression of OSCC, which may have prognostic value and could be regarded as potential therapeutic targets in OSCC.

  10. The significance of the host inflammatory response on the therapeutic efficacy of cell therapies utilising human adult stem cells

    International Nuclear Information System (INIS)

    Navarro, Melba; Pu, Fanrong; Hunt, John A.

    2012-01-01

    Controlling the fate of implanted hMSCs is one of the major drawbacks to be overcome to realize tissue engineering strategies. In particular, the effect of the inflammatory environment on hMSCs behaviour is poorly understood. Studying and mimicking the inflammatory process in vitro is a very complex and challenging task that involves multiple variables. This research addressed the questions using in vitro co-cultures of primary derived hMSCs together with human peripheral blood mononucleated cells (PBMCs); the latter are key agents in the inflammatory process. This work explored the in vitro phenotypic changes of hMSCs in co-culture direct contact with monocytes and lymphocytes isolated from blood using both basal and osteogenic medium. Our findings indicated that hMSCs maintained their undifferentiated phenotype and pluripotency despite the contact with PBMCs. Moreover, hMSCs demonstrated increased proliferation and were able to differentiate specifically down the osteogenic lineage pathway. Providing significant crucial evidence to support the hypothesis that inflammation and host defence mechanisms could be utilised rather than avoided and combated to provide for the successful therapeutic application of stem cell therapies.

  11. Improving the long-term stability of PBDTTPD polymer solar cells through material purification aimed at removing organic impurities

    KAUST Repository

    Mateker, William R.; Douglas, Jessica D.; Cabanetos, Clement; Sachs-Quintana, I. T.; Bartelt, Jonathan A.; Hoke, Eric T.; El Labban, Abdulrahman; Beaujuge, Pierre; Frechet, Jean; McGehee, Michael D.

    2013-01-01

    While bulk heterojunction (BHJ) solar cells fabricated from high M n PBDTTPD achieve power conversion efficiencies (PCE) as high as 7.3%, the short-circuit current density (JSC) of these devices can drop by 20% after seven days of storage in the dark and under inert conditions. This degradation is characterized by the appearance of S-shape features in the reverse bias region of current-voltage (J-V) curves that increase in amplitude over time. Conversely, BHJ solar cells fabricated from low Mn PBDTTPD do not develop S-shaped J-V curves. However, S-shapes identical to those observed in high Mn PBDTTPD solar cells can be induced in low M n devices through intentional contamination with the TPD monomer. Furthermore, when high Mn PBDTTPD is purified via size exclusion chromatography (SEC) to reduce the content of low molecular weight species, the JSC of polymer devices is significantly more stable over time. After 111 days of storage in the dark under inert conditions, the J-V curves do not develop S-shapes and the JSC degrades by only 6%. The S-shape degradation feature, symptomatic of low device lifetimes, appears to be linked to the presence of low molecular weight contaminants, which may be trapped within samples of high Mn polymer that have not been purified by SEC. Although these impurities do not affect initial device PCE, they significantly reduce device lifetime, and solar cell stability is improved by increasing the purity of the polymer materials. © 2013 The Royal Society of Chemistry.

  12. Improving Efficiency of Multicrystalline Silicon and CIGS Solar Cells by Incorporating Metal Nanoparticles

    Directory of Open Access Journals (Sweden)

    Ming-Jer Jeng

    2015-10-01

    Full Text Available This work studies the use of gold (Au and silver (Ag nanoparticles in multicrystalline silicon (mc-Si and copper-indium-gallium-diselenide (CIGS solar cells. Au and Ag nanoparticles are deposited by spin-coating method, which is a simple and low cost process. The random distribution of nanoparticles by spin coating broadens the resonance wavelength of the transmittance. This broadening favors solar cell applications. Metal shadowing competes with light scattering in a manner that varies with nanoparticle concentration. Experimental results reveal that the mc-Si solar cells that incorporate Au nanoparticles outperform those with Ag nanoparticles. The incorporation of suitable concentration of Au and Ag nanoparticles into mc-Si solar cells increases their efficiency enhancement by 5.6% and 4.8%, respectively. Incorporating Au and Ag nanoparticles into CIGS solar cells improve their efficiency enhancement by 1.2% and 1.4%, respectively. The enhancement of the photocurrent in mc-Si solar cells is lower than that in CIGS solar cells, owing to their different light scattering behaviors and material absorption coefficients.

  13. Berkeley Lab Sheds Light on Improving Solar Cell Efficiency

    International Nuclear Information System (INIS)

    Lawrence Berkeley National Laboratory

    2007-01-01

    Typical manufacturing methods produce solar cells with an efficiency of 12-15%; and 14% efficiency is the bare minimum for achieving a profit. In work performed at the Ernest Orlando Lawrence Berkeley National Laboratory (Berkeley, CA, 5 10-486-577 1)--a US Department of Energy national laboratory that conducts unclassified scientific research and is managed by the University of California--scientist Scott McHugo has obtained keen insights into the impaired performance of solar cells manufactured from polycrystalline silicon. The solar cell market is potentially vast, according to Berkeley Lab. Lightweight solar panels are highly beneficial for providing electrical power to remote locations in developing nations, since there is no need to build transmission lines or truck-in generator fuel. Moreover, industrial nations confronted with diminishing resources have active programs aimed at producing improved, less expensive solar cells. 'In a solar cell, there is a junction between p-type silicon and an n-type layer, such as diffused-in phosphorous', explained McHugo, who is now with Berkeley Lab's Accelerator and Fusion Research Division. 'When sunlight is absorbed, it frees electrons, which start migrating in a random-walk fashion toward that junction. If the electrons make it to the junction; they contribute to the cell's output of electric current. Often, however, before they reach the junction, they recombine at specific sites in the crystal' (and, therefore, cannot contribute to current output). McHugo scrutinized a map of a silicon wafer in which sites of high recombination appeared as dark regions. Previously, researchers had shown that such phenomena occurred not primarily at grain boundaries in the polycrystalline material, as might be expected, but more often at dislocations in the crystal. However, the dislocations themselves were not the problem. Using a unique heat treatment technique, McHugo performed electrical measurements to investigate the material

  14. Expression and Clinical Significance of CD147 and MMP-2 
in Squamous Cell Carcinoma and Adenocarcinoma of the Lungs

    Directory of Open Access Journals (Sweden)

    Siwen WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that CD147 was an extracellular matrix metalloproteinase inducer reportedly involved in the invasion and metastasis of malignancies. The aim of this study is to investigate CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs and to analyze their clinical significance. Methods Tissue samples from 55 patients with squamous cell carcinoma and adenocarcinoma of the lungs and their corresponding non-cancerous tissues were examined for CD147 and MMP-2 expression using immunohistochemistry. Results The positive expression rates of CD147 and MMP-2 in the squamous cell carcinoma and adenocarcinoma among the lung tissues were significantly higher than those in the corresponding normal lung tissues. Moreover, the CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs were related to lymph node metastasis and TNM stages (P<0.05, but not to age, gender and histologic type (P>0.05. MMP-2 expression was highly correlated with CD147 expression. Conclusion CD147 and MMP-2 expression is correlated with the invasion and metastasis of squamous cell carcinoma and adenocarcinoma of the lungs and may be used as objective markers for predicting the behavior of squamous cell carcinoma and adenocarcinoma of the lungs.

  15. Defibrotide in combination with granulocyte colony-stimulating factor significantly enhances the mobilization of primitive and committed peripheral blood progenitor cells in mice.

    Science.gov (United States)

    Carlo-Stella, Carmelo; Di Nicola, Massimo; Magni, Michele; Longoni, Paolo; Milanesi, Marco; Stucchi, Claudio; Cleris, Loredana; Formelli, Franca; Gianni, Massimo A

    2002-11-01

    Defibrotide is a polydeoxyribonucleotide, which significantly reduces the expression of adhesion molecules on endothelial cells. We investigated the activity of Defibrotide alone or in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) to mobilize peripheral blood progenitor cells (PBPCs) in BALB/c mice. A 5-day treatment with Defibrotide alone (1-15 mg/mouse/day) had no effect on WBC counts, frequencies and absolute numbers of total circulating colony-forming cells (CFCs), i.e., granulocyte-macrophage colony-forming units, erythroid burst-forming units, and multilineage colony-forming units. As compared with mock-injected mice, administration of rhG-CSF alone (5 micro g/mouse/day) for 5 days significantly (P Defibrotide (15 mg/mouse/day) and rhG-CSF significantly (P Defibrotide plus rhG-CSF resulted in a significant increase (P Defibrotide/rhG-CSF-mobilized mononuclear cells rescued 43% and 71% of recipient mice, respectively. Experiments of CFC homing performed in lethally irradiated or nonirradiated recipients showed that marrow homing of transplanted PBPCs was reduced by 3-fold in Defibrotide-treated animals as compared with mock-injected mice (P Defibrotide might be because of an effect on PBPC trafficking. In conclusion, our data demonstrate that Defibrotide synergizes with rhG-CSF and significantly increases the mobilization of a broad spectrum of PBPCs, including primitive and committed progenitor cells. These data might have relevant implications for autologous and allogeneic anticancer therapy in humans.

  16. Improved performance of colloidal CdSe quantum dot-sensitized solar cells by hybrid passivation.

    Science.gov (United States)

    Huang, Jing; Xu, Bo; Yuan, Chunze; Chen, Hong; Sun, Junliang; Sun, Licheng; Agren, Hans

    2014-11-12

    A hybrid passivation strategy is employed to modify the surface of colloidal CdSe quantum dots (QDs) for quantum dot-sensitized solar cells (QDSCs), by using mercaptopropionic acid (MPA) and iodide anions through a ligand exchange reaction in solution. This is found to be an effective way to improve the performance of QDSCs based on colloidal QDs. The results show that MPA can increase the coverage of the QDs on TiO2 electrodes and facilitate the hole extraction from the photoxidized QDs, and simultaneously, that the iodide anions can remedy the surface defects of the CdSe QDs and thus reduce the recombination loss in the device. This hybrid passivation treatment leads to a significant enhancement of the power conversion efficiency of the QDSCs by 41%. Furthermore, an optimal ratio of iodide ions to MPA was determined for favorable hybrid passivation; results show that excessive iodine anions are detrimental to the loading of the QDs. This study demonstrates that the improvement in QDSC performance can be realized by using a combination of different functional ligands to passivate the QDs, and that ligand exchange in solution can be an effective approach to introduce different ligands.

  17. Further Improvement and System Integration of High Temperature Polymer Electrolyte Membrane Fuel Cells

    DEFF Research Database (Denmark)

    Li, Qingfeng; Jensen, Jens Oluf

    The strategic developments of the FURIM are in three steps: (1) further improvement of the high temperature polymer membranes and related materials; (2) development of technological units including fuel cell stack, hydrocarbon reformer and afterburner, that are compatible with the HT-PEMFC; and (3......) integration of the HT-PEMFC stack with these compatible subunits. The main goal of the project is a 2kWel HT-PEMFC stack operating in a temperature range of 150-200°C, with a single cell performance target of 0.7 A/cm² at a cell voltage around 0.6 V. The target durability is more than 5,000 hours...

  18. Low-dose vaporized cannabis significantly improves neuropathic pain.

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-02-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

  19. Expression of transcription factor Pokemon in non-small cell lung cancer and its clinical significance.

    Science.gov (United States)

    Zhao, Zhi-hong; Wang, Sheng-fa; Yu, Liang; Wang, Ju; Chang, Hao; Yan, Wei-li; Fu, Kai; Zhang, Jian

    2008-03-05

    Transcription factor Pokemon, a central regulation gene of the important tumor suppressor ARF gene, exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in NSCLC and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis. Fifty-five cases of NSCLC were involved in this study. The expression of Pokemon in the tumor tissue, the corresponding tumor adjacent tissue and the surrounding tissue was detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, with the aim of investigating the correlation between the expression of Pokemon in tumor tissue of NSCLC and its clinical pathological characteristics. Moreover, a prognostic analysis was carried out based upon the immunohistochemical (IHC) detection of the expression of Pokemon gene in archival tumor specimens (5 years ago) of 62 cases of NSCLC. Statistical significance of the expression of Pokemon mRNA and protein was determined in the tumor tissue, the tumor adjacent tissue and the surrounding tissue (PPokemon was determined not to be associated with the patients' sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (PPokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034). Pokemon was over-expressed in NSCLC tissue and the expression of Pokemon might be of clinical significance in non-small cell lung cancer prognostic evaluation.

  20. Fusion-Expressed CTB Improves Both Systemic and Mucosal T-Cell Responses Elicited by an Intranasal DNA Priming/Intramuscular Recombinant Vaccinia Boosting Regimen

    Directory of Open Access Journals (Sweden)

    Sugan Qiu

    2014-01-01

    Full Text Available Previous study showed that CTB (Cholera toxin subunit B can be used as a genetic adjuvant to enhance the systemic immune responses. To further investigate whether it can also be used as a genetic adjuvant to improve mucosal immune responses, we constructed DNA and recombinant Tiantan vaccinia (rTTV vaccines expressing OVA-CTB fusion antigen. Female C57BL/6 mice were immunized with an intranasal DNA priming/intramuscular rTTV boosting regimen. OVA specific T-cell responses were measured by IFN-γ ELISPOT and specific antibody responses were determined by ELISA. Compared to the nonadjuvant group (pSV-OVA intranasal priming/rTTV-OVA intramuscular boosting, pSV-OVA-CTB intranasal priming/rTTV-OVA-CTB intramuscular boosting group significantly improved the magnitudes of T-cell responses at spleen (1562±567 SFCs/106 splenocytes versus 330±182 SFCs/106 splenocytes, P<0.01, mesenteric LN (96±83 SFCs/106 lymphocytes versus 1±2 SFCs/106 lymphocytes, P<0.05, draining LNs of respiratory tract (109±60 SFCs/106 lymphocytes versus 2±2 SFCs/106 lymphocytes, P<0.01 and female genital tract (89±48 SFCs/106 lymphocytes versus 23±21 SFCs/106 lymphocytes, P<0.01. These results collectively demonstrated that fusion-expressed CTB could act as a potent adjuvant to improve both systemic and mucosal T-cell responses.

  1. Bone Marrow-Derived Stem Cell (BMDSC transplantation improves fertility in a murine model of Asherman's syndrome.

    Directory of Open Access Journals (Sweden)

    Feryal Alawadhi

    Full Text Available Asherman's Syndrome is characterized by intrauterine adhesions or fibrosis resulting as a consequence of damage to the basal layer of endometrium and is associated with infertility due to loss of normal endometrium. We have previously shown that bone marrow derived stem cells (BMDSCs engraft the endometrium in mice and humans and Ischemia/reperfusion injury of uterus promoted BMDSCs migration to the endometrium; however, the role of BMDSCs in Asherman's syndrome has not been characterized. Here a murine model of Asherman's syndrome was created by traumatizing the uterus. We evaluate stem cell recruitment and pregnancy after BMDSCs transplantation in a model of Asherman's syndrome. In the Asheman's syndrome model, after BMDSC transplant, the Y chromosome bearing CD45-cells represented less than 0.1% of total endometrial cells. Twice the number of Y+CD45- cells was identified in the damaged uterus compared to the uninjured controls. There was no significant difference between the damaged and undamaged uterine horns in mice that received injury to a single horn. In the BMDSC transplant group, 9 of the 10 mice conceived, while only 3 of 10 in the non-transplanted group conceived (Chi-Square p = 0.0225; all mice in an uninjured control group conceived. The time to conception and mean litter size were not different between groups. Taken together, BMDSCs are recruited to endometrium in response to injury. Fertility improves after BMDSC transplant in Asherman's Syndrome mice, demonstrating a functional role for these cells in uterine repair. BMDSC transplantation is a potential novel treatment for Asherman's Syndrome and may also be useful to prevent Asherman's syndrome after uterine injury.

  2. Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats.

    Science.gov (United States)

    Mao, Chenggang; Hou, Xu; Wang, Benzhen; Chi, Jingwei; Jiang, Yanjie; Zhang, Caining; Li, Zipu

    2017-01-28

    Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model. A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy. Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity. Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.

  3. Electron spin resonance studies on the detectability of radiation damage and radiosensitization of neoplastic cells. Coordinated programme on improvement of radiotherapy of cancer using modifiers of radiosensitivity of cells

    International Nuclear Information System (INIS)

    Lukiewicz, S.

    1982-01-01

    The comparison of direct and indirect ESR methods applicable for the examination of radiation damage to melanoma cells leads to the conclusion that only the indirect ones appear to be useful for its detection. The new results of animal experiments and clinical trials carried out according to the rules of radio-chelation therapy are briefly discussed. Selective incorporation of 35 S-labelled compounds by pigmented hamster melanoma cells was found to be followed by a depression of their proliferative activity in vitro and in situ, which may suggest the possible therapeutic value of endo-irradiation. The ESR measurements performed with the use of newly elaborated indirect methods revealed that pigmented and non-pigmented cells consume oxygen at significantly different rates, which means that oxygen utilization may contribute to the overall level of radioresistance of melanoma cells. This assumption has been confirmed by comparing the radiosensitivity of melanotic and amelanotic cells to fast neutrons. Pigment-containing hamster melanoma cells which are twice as resistant to low LET radiation as their non-pigmented counterparts, proved to be equally susceptible to neutrons. The chance of improving the efficiency of radiotherapy of malignant melanomas does not appear unlikely in the light of new experimental data and clinical trials

  4. A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

    Directory of Open Access Journals (Sweden)

    Deanna M Schmitt

    Full Text Available Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS, does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of the same gene in LVS displayed similar in vitro characteristics, but vaccination with this strain did not improve survival after challenge with a virulent Francisella strain. In vivo, this mutant was attenuated for growth and did not stimulate T cell responses in the lung comparable to wild type. Therefore, stimulation of antigen-presenting cells in vitro was improved by genetic modification of LVS, but did not correlate with efficacy against challenge in vivo within this model system.

  5. REMOTE IN-CELL SAMPLING IMPROVEMENTS PROGRAM AT THESAVANNAH RIVER SITE (SRS) DEFENSE WASTE PROCESSING FACILITY (DWPF)

    International Nuclear Information System (INIS)

    Marzolf, A

    2007-01-01

    Remote Systems Engineering (RSE) of the Savannah River National Lab (SRNL) in combination with the Defense Waste Processing Facility(DWPF) Engineering and Operations has evaluated the existing equipment and processes used in the facility sample cells for 'pulling' samples from the radioactive waste stream and performing equipment in-cell repairs/replacements. RSE has designed and tested equipment for improving remote in-cell sampling evolutions and reducing the time required for in-cell maintenance of existing equipment. The equipment within the present process tank sampling system has been in constant use since the facility start-up over 17 years ago. At present, the method for taking samples within the sample cells produces excessive maintenance and downtime due to frequent failures relative to the sampling station equipment and manipulator. Location and orientation of many sampling stations within the sample cells is not conducive to manipulator operation. The overextension of manipulators required to perform many in-cell operations is a major cause of manipulator failures. To improve sampling operations and reduce downtime due to equipment maintenance, a Portable Sampling Station (PSS), wireless in-cell cameras, and new commercially available sampling technology has been designed, developed and/or adapted and tested. The uniqueness of the design(s), the results of the scoping tests, and the benefits relative to in-cell operation and reduction of waste are presented

  6. Complete Au@ZnO core-shell nanoparticles with enhanced plasmonic absorption enabling significantly improved photocatalysis

    Science.gov (United States)

    Sun, Yiqiang; Sun, Yugang; Zhang, Tao; Chen, Guozhu; Zhang, Fengshou; Liu, Dilong; Cai, Weiping; Li, Yue; Yang, Xianfeng; Li, Cuncheng

    2016-05-01

    Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic absorption in the visible range due to the Au NP cores. They also show a significantly improved photocatalytic performance in comparison with their single-component counterparts, i.e., the Au NPs and ZnO NPs. Moreover, the high catalytic activity of the as-synthesized Au@ZnO core-shell NPs can be maintained even after many cycles of photocatalytic reaction. Our results shed light on the fact that the Au@ZnO core-shell NPs represent a promising class of candidates for applications in plasmonics, surface-enhanced spectroscopy, light harvest devices, solar energy conversion, and degradation of organic pollutants.Nanostructured ZnO exhibits high chemical stability and unique optical properties, representing a promising candidate among photocatalysts in the field of environmental remediation and solar energy conversion. However, ZnO only absorbs the UV light, which accounts for less than 5% of total solar irradiation, significantly limiting its applications. In this article, we report a facile and efficient approach to overcome the poor wettability between ZnO and Au by carefully modulating the surface charge density on Au nanoparticles (NPs), enabling rapid synthesis of Au@ZnO core-shell NPs at room temperature. The resulting Au@ZnO core-shell NPs exhibit a significantly enhanced plasmonic

  7. Tailoring of TiO2 films by H2SO4 treatment and UV irradiation to improve anticoagulant ability and endothelial cell compatibility.

    Science.gov (United States)

    Liao, Yuzhen; Li, Linhua; Chen, Jiang; Yang, Ping; Zhao, Ansha; Sun, Hong; Huang, Nan

    2017-07-01

    Surfaces with dual functions that simultaneously exhibit good anticoagulant ability and endothelial cell (EC) compatibility are desirable for blood contact materials. However, these dual functions have rarely been achieved by inorganic materials. In this study, titanium dioxide (TiO 2 ) films were treated by sulphuric acid (H 2 SO 4 ) and ultraviolet (UV) irradiation successively (TiO 2 H 2 SO 4 -UV), resulting in good anticoagulant ability and EC compatibility simultaneously. We found that UV irradiation improved the anticoagulant ability of TiO 2 films significantly while enhancing EC compatibility, though not significantly. The enhanced anticoagulant ability could be related to the oxidation of surface-adsorbed hydrocarbons and increased hydrophilicity. The H 2 SO 4 treatment improved the anticoagulant ability of TiO 2 films slightly, while UV irradiation improved the anticoagulant ability strongly. The enhanced EC compatibility could be related to the increased surface roughness and positive charges on the surface of the TiO 2 films. Furthermore, the time-dependent degradation of the enhanced EC compatibility and anticoagulant ability of TiO 2 H 2 SO 4 -UV was observed. In summary, TiO 2 H 2 SO 4 -UV expressed both excellent anticoagulant ability and good EC compatibility at the same time, which could be desirable for blood contact materials. However, the compatibility of TiO 2 H 2 SO 4 -UV with smooth muscle cells (SMCs) and macrophages was also improved. More effort is still needed to selectively improve EC compatibility on TiO 2 films for better re-endothelialization. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Mulberry anthocyanins improves thyroid cancer progression mainly by inducing apoptosis and autophagy cell death

    Directory of Open Access Journals (Sweden)

    Hou-Long Long

    2018-05-01

    Full Text Available Dietary anthocyanin compounds have multiple biological effects, including antioxidant, anti-inflammatory, and anti-atherosclerotic characteristics. The present study evaluated the anti-tumor capacity of mulberry anthocyanins (MA in thyroid cancer cells. Our data showed that MA suppressed SW1736 and HTh-7 cell proliferation in a time- and dose-dependent manner. Meanwhile, flow cytometry results indicated that MA significantly increased SW1736 and HTh-7 cell apoptosis. We additionally observed that SW1736 and HTh-7 cell autophagy was markedly enhanced after MA treatment. Importantly, anthocyanin-induced cell death was largely abolished by 3-methyladenine (3-MA or chloroquine diphosphate salt (CQ treatment, suggesting that MA-induced SW1736 and HTh-7 cell death was partially dependent on autophagy. In addition, activation of protein kinase B (Akt, mammalian target of rapamycin (mTOR, and ribosomal protein S6 (S6 were significantly suppressed by anthocyanin exposure. In summary, MA may serve as an adjunctive therapy for thyroid cancer patients through induction of apoptosis and autophagy-dependent cell death. Keywords: Mulberry anthocyanins, Thyroid cancer, Apoptosis, Autophagic death

  9. Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.

    Science.gov (United States)

    Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

    2014-07-01

    Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy.

  10. Improving washing strategies of human mesenchymal stem cells using negative mode expanded bed chromatography.

    Science.gov (United States)

    Cunha, Bárbara; Silva, Ricardo J S; Aguiar, Tiago; Serra, Margarida; Daicic, John; Maloisel, Jean-Luc; Clachan, John; Åkerblom, Anna; Carrondo, Manuel J T; Peixoto, Cristina; Alves, Paula M

    2016-01-15

    The use of human mesenchymal stem cells (hMSC) in clinical applications has been increasing over the last decade. However, to be applied in a clinical setting hMSC need to comply with specific requirements in terms of identity, potency and purity. This study reports the improvement of established tangential flow filtration (TFF)-based washing strategies, further increasing hMSC purity, using negative mode expanded bed adsorption (EBA) chromatography with a new multimodal prototype matrix based on core-shell bead technology. The matrix was characterized and a stable, expanded bed could be obtained using standard equipment adapted from what is used for conventional packed bed chromatography processes. The effect of different expansion rates on cell recovery yield and protein removal capacity was assessed. The best trade-off between cell recovery (89%) and protein clearance (67%) was achieved using an intermediate expansion bed rate (1.4). Furthermore, we also showed that EBA chromatography can be efficiently integrated on the already established process for the downstream processing (DSP) of hMSC, where it improved the washing efficiency more than 10-fold, recovering approximately 70% of cells after global processing. This strategy showed not to impact cell viability (>95%), neither hMSC's characteristics in terms of morphology, immunophenotype, proliferation, adhesion capacity and multipotent differentiation potential. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Clinical significance of atypical squamous cells of undetermined significance in detecting preinvasive cervical lesions in post- menopausal Turkish women.

    Science.gov (United States)

    Tokmak, Aytekin; Guzel, Ali Irfan; Ozgu, Emre; Oz, Murat; Akbay, Serap; Erkaya, Salim; Gungor, Tayfun

    2014-01-01

    To evaluate the clinical significance of atypical squamous cells of undetermined significance (ASCUS) in PAP test in post-menopausal women and compare with reproductive age women. A total of 367 patients who referred to our gynecologic oncology clinic were included to the study between September 2012 and August 2013. Data for 164 post-menopausal (group 1) and 203 pre-menopausal (group 2) women with ASCUS cytology were evaluated retrospectively. Immediate colposcopy and endocervical curettage was performed for both groups and conization for all women with a result suggestive of CIN2-3. Histopathological results and demographic features of patients were compared between the two groups. Mean age of the patients was 54.6±6.5 years in group 1 and 38±6.6 years in group 2. Some 14 (8.5%) of post- menopausal women and 36 (17.7%) of pre-menopausal women were current smokers (p=011). Totals of 38 (23.2%) post-menopausal and 64 (31.5%) pre-menopausal women were assessed for HPV-DNA. High risk HPV was detected in 7 (4.3%) and 21 (10.3%), respectively (p=0.029). Final histopathological results recorded were normal cervix, low grade cervical intra-epithelial neoplasia (CIN 1), and high grade cervical intra-epithelial neoplasia (CIN2-3). In group 1 results were 84.8%, 12.2% and 1.8%, respectively, and in group 2 were 71.9%, 23.2% and 4.9%. There were no cases of micro invasive or invasive cervical carcinoma in either group. Two cases were detected as endometrial carcinoma in the menopausal group (1.2%). In current study we found that preinvasive lesions were statistically significantly higher in pre-menopausal women than post- menopausal women with ASCUS. Cervicitis was more common in menopausal women. Therefore, we think that in case of ASCUS in a post-menopausal woman there is no need for radical management.

  12. Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury.

    Directory of Open Access Journals (Sweden)

    Jianqin Ye

    Full Text Available BACKGROUND: Endogenous cardiac progenitor cells are a promising option for cell-therapy for myocardial infarction (MI. However, obtaining adequate numbers of cardiac progenitors after MI remains a challenge. Cardiospheres (CSs have been proposed to have cardiac regenerative properties; however, their cellular composition and how they may be influenced by the tissue milieu remains unclear. METHODOLOGY/PRINCIPAL FINDING: Using "middle aged" mice as CSs donors, we found that acute MI induced a dramatic increase in the number of CSs in a mouse model of MI, and this increase was attenuated back to baseline over time. We also observed that CSs from post-MI hearts engrafted in ischemic myocardium induced angiogenesis and restored cardiac function. To determine the role of Sca-1(+CD45(- cells within CSs, we cloned these from single cell isolates. Expression of Islet-1 (Isl1 in Sca-1(+CD45(- cells from CSs was 3-fold higher than in whole CSs. Cloned Sca-1(+CD45(- cells had the ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. We also observed that cloned cells engrafted in ischemic myocardium induced angiogenesis, differentiated into endothelial and smooth muscle cells and improved cardiac function in post-MI hearts. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate that cloned Sca-1(+CD45(- cells derived from CSs from infarcted "middle aged" hearts are enriched for second heart field (i.e., Isl-1(+ precursors that give rise to both myocardial and vascular tissues, and may be an appropriate source of progenitor cells for autologous cell-therapy post-MI.

  13. Optimizing autologous cell grafts to improve stem cell gene therapy.

    Science.gov (United States)

    Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

    2016-07-01

    Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  14. Improving the Safety of Cell Therapy Products by Suicide Gene Transfer

    Directory of Open Access Journals (Sweden)

    Antonio eDi Stasi

    2014-11-01

    Full Text Available Adoptive T-cell therapy can involve donor lymphocyte infusion (DLI after allogeneic hematopoietic stem cell transplantation, the administration of tumor infiltrating lymphocyte (TILs expanded ex-vivo, or more recently the use of T cell receptor (TCR or chimeric antigen receptor (CAR redirected T cells. However cellular therapies can pose significant risks, including graft-versus-host-disease and other on and off-target effects, and therefore strategies need to be implemented to permanently reverse any sign of toxicity. A suicide gene is a genetically encoded molecule that allows selective destruction of adoptively transferred cells. Suicide gene addition to cellular therapeutic products can lead to selective ablation of gene-modified cells, preventing collateral damage to contiguous cells and/or tissues. The ‘ideal’ suicide gene would ensure the safety of gene modified cellular applications by granting irreversible elimination of ‘all’ and ‘only’ the cells responsible for the unwanted toxicity. This review presents the suicide gene safety systems reported to date, with a focus on the state-of-the-art and potential applications regarding two of the most extensively validated suicide genes, including the clinical setting: herpes-simplex-thymidine-kinase (HSV-TK and inducible-caspase-9 (iCasp9.

  15. Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra.

    Science.gov (United States)

    Cannon, Tracy W; Lee, Ji Youl; Somogyi, George; Pruchnic, Ryan; Smith, Christopher P; Huard, Johnny; Chancellor, Michael B

    2003-11-01

    To study the physiologic outcome of allogenic transplant of muscle-derived progenitor cells (MDPCs) in the denervated female rat urethra. MDPCs were isolated from muscle biopsies of normal 6-week-old Sprague-Dawley rats and purified using the preplate technique. Sciatic nerve-transected rats were used as a model of stress urinary incontinence. The experimental group was divided into three subgroups: control, denervated plus 20 microL saline injection, and denervated plus allogenic MDPCs (1 to 1.5 x 10(6) cells) injection. Two weeks after injection, urethral muscle strips were prepared and underwent electrical field stimulation. The pharmacologic effects of d-tubocurare, phentolamine, and tetrodotoxin on the urethral strips were assessed by contractions induced by electrical field stimulation. The urethral tissues also underwent immunohistochemical staining for fast myosin heavy chain and CD4-activated lymphocytes. Urethral denervation resulted in a significant decrease of the maximal fast-twitch muscle contraction amplitude to only 8.77% of the normal urethra and partial impairment of smooth muscle contractility. Injection of MDPCs into the denervated sphincter significantly improved the fast-twitch muscle contraction amplitude to 87.02% of normal animals. Immunohistochemistry revealed a large amount of new skeletal muscle fiber formation at the injection site of the urethra with minimal inflammation. CD4 staining showed minimal lymphocyte infiltration around the MDPC injection sites. Urethral denervation resulted in near-total abolishment of the skeletal muscle and partial impairment of smooth muscle contractility. Allogenic MDPCs survived 2 weeks in sciatic nerve-transected urethra with minimal inflammation. This is the first report of the restoration of deficient urethral sphincter function through muscle-derived progenitor cell tissue engineering. MDPC-mediated cellular urethral myoplasty warrants additional investigation as a new method to treat stress urinary

  16. Exogenous DNA internalisation by sperm cells is improved by combining lipofection and restriction enzyme mediated integration.

    Science.gov (United States)

    Churchil, R R; Gupta, J; Singh, A; Sharma, D

    2011-06-01

    1. Three types of exogenous DNA inserts, i.e. complete linearised pVIVO2-GFP/LacZ vector (9620 bp), the LacZ gene (5317 bp) and the GFP gene (2152 bp) were used to transfect chicken spermatozoa through simple incubation of sperm cells with insert. 2. PCR assay, Dot Blot hybridisation and Southern hybridisation showed the successful internalisation of exogenous DNA by chicken sperm cells. 3. Lipofection and Restriction Enzyme Mediated Integration (REMI) were used to improve the rate of internalisation of exogenous DNA by sperm cells. 4. Results from dot blot as well as Southern hybridisation were semi-quantified and improved exogenous DNA uptake by sperm cells through lipofection and REMI. Stronger signals were observed from hybridisation of LacZ as well as GFP specific probe with the DNA from lipofected exogenous DNA transfected sperm DNA in comparison with those transfected with nude exogenous DNA.

  17. Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model

    Science.gov (United States)

    Song, Juhyun; Hur, Bo Eun; Bokara, Kiran Kumar; Yang, Wonsuk; Cho, Hyun Jin; Park, Kyung Ah; Lee, Won Taek; Lee, Kyoung Min

    2014-01-01

    Purpose Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. Materials and Methods We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 µL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. Results Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and γ-glutamyl cysteine synthetase, in the STZ-Agm group. Conclusion Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD. PMID:24719136

  18. Chronic inflammation-elicited liver progenitor cell conversion to liver cancer stem cell with clinical significance.

    Science.gov (United States)

    Li, Xiao-Feng; Chen, Cheng; Xiang, Dai-Min; Qu, Le; Sun, Wen; Lu, Xin-Yuan; Zhou, Teng-Fei; Chen, Shu-Zhen; Ning, Bei-Fang; Cheng, Zhuo; Xia, Ming-Yang; Shen, Wei-Feng; Yang, Wen; Wen, Wen; Lee, Terence Kin Wah; Cong, Wen-Ming; Wang, Hong-Yang; Ding, Jin

    2017-12-01

    The substantial heterogeneity and hierarchical organization in liver cancer support the theory of liver cancer stem cells (LCSCs). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here, we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in nonobese diabetic/severe combined immunodeficient mice, suggesting the malignant transformation of LPCs toward LCSCs. Interestingly, depletion of Kupffer cells in vivo attenuated the LCSC properties of transformed LPCs and suppressed cytokeratin 19/Oval cell 6-positive tumor occurrence. Conversely, LPCs cocultured with macrophages exhibited enhanced LCSC properties. We further demonstrated that macrophage-secreted tumor necrosis factor-α triggered chromosomal instability in LPCs through the deregulation of ubiquitin D and checkpoint kinase 2 and enhanced the self-renewal of LPCs through the tumor necrosis factor receptor 1/Src/signal transducer and activator of transcription 3 pathway, which synergistically contributed to the conversion of LPCs to LCSCs. Clinical investigation revealed that cytokeratin 19/Oval cell 6-positive liver cancer patients displayed a worse prognosis and exhibited superior response to sorafenib treatment. Our results not only clarify the cellular and molecular mechanisms underlying the inflammation-mediated LCSC generation but also provide a molecular classification for the individualized treatment of liver cancer. (Hepatology 2017;66:1934-1951). © 2017 by the American Association for the Study of Liver Diseases.

  19. Targeting myeloid cells using nanoparticles to improve cancer immunotherapy.

    Science.gov (United States)

    Amoozgar, Zohreh; Goldberg, Michael S

    2015-08-30

    While nanoparticles have traditionally been used to deliver cytotoxic drugs directly to tumors to induce cancer cell death, emerging data suggest that nanoparticles are likely to generate a larger impact on oncology through the delivery of agents that can stimulate antitumor immunity. Tumor-targeted nanocarriers have generally been used to localize chemotherapeutics to tumors and thus decrease off-target toxicity while enhancing efficacy. Challengingly, tumor heterogeneity and evolution render tumor-intrinsic approaches likely to succumb to relapse. The immune system offers exquisite specificity, cytocidal potency, and long-term activity that leverage an adaptive memory response. For this reason, the ability to manipulate immune cell specificity and function would be desirable, and nanoparticles represent an exciting means by which to perform such manipulation. Dendritic cells and tumor-associated macrophages are cells of the myeloid lineage that function as natural phagocytes, so they naturally take up nanoparticles. Dendritic cells direct the specificity and potency of cellular immune responses that can be targeted for cancer vaccines. Herein, we discuss the specific criteria needed for efficient vaccine design, including but not limited to the route of administration, size, morphology, surface charge, targeting ligands, and nanoparticle composition. In contrast, tumor-associated macrophages are critical mediators of immunosuppression whose trans-migratory abilities can be exploited to localize therapeutics to the tumor core and which can be directly targeted for elimination or for repolarization to a tumor suppressive phenotype. It is likely that a combination of targeting dendritic cells to stimulate antitumor immunity and tumor-associated macrophages to reduce immune suppression will impart significant benefits and result in durable antitumor responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Efficiency improvements by Metal Wrap Through technology for n-type Si solar cells and modules

    Energy Technology Data Exchange (ETDEWEB)

    Wenchao, Zhao; Jianming, Wang; Yanlong, Shen; Ziqian, Wang; Yingle, Chen; Shuquan, Tian; Zhiliang, Wan; Bo, Yu; Gaofei, Li; Zhiyan, Hu; Jingfeng, Xiong [Yingli Green Energy Holding Co., Ltd, 3399 North Chaoyang Avenue, Baoding (China); Guillevin, N.; Heurtault, B.; Aken, B.B. van; Bennett, I.J.; Geerligs, L.J.; Weeber, A.W.; Bultman, J.H. [ECN Solar Energy, Petten (Netherlands)

    2012-09-15

    N-type Metal Wrap Through (n-MWT) is presented as an industrially promising back-contact technology to reach high performance of silicon solar cells and modules. It can combine benefits from both n-type base and MWT metallization. In this paper, the efficiency improvements of commercial industrial n-type bifacial Si solar cells (239 cm{sup 2}) and modules (60 cells) by the integration of the MWT technique are described. For the cell, after the optimization of integration, over 0.3% absolute efficiency gain was achieved over the similar non-MWT technology, and Voc gain and Isc gain up to 0.9% and 3.5%, respectively. These gains are mainly attributed to reduced shading loss and surface recombination. Besides the front pattern optimization, a 0.1m{Omega} reduction of Rs in via part will induce further 0.06% absolute efficiency improvement. For the module part, a power output of n-MWT module up to 279W was achieved, corresponding to a module efficiency of about 17.7%.

  1. Cell cycle gene expression networks discovered using systems biology: Significance in carcinogenesis

    Science.gov (United States)

    Scott, RE; Ghule, PN; Stein, JL; Stein, GS

    2015-01-01

    The early stages of carcinogenesis are linked to defects in the cell cycle. A series of cell cycle checkpoints are involved in this process. The G1/S checkpoint that serves to integrate the control of cell proliferation and differentiation is linked to carcinogenesis and the mitotic spindle checkpoint with the development of chromosomal instability. This paper presents the outcome of systems biology studies designed to evaluate if networks of covariate cell cycle gene transcripts exist in proliferative mammalian tissues including mice, rats and humans. The GeneNetwork website that contains numerous gene expression datasets from different species, sexes and tissues represents the foundational resource for these studies (www.genenetwork.org). In addition, WebGestalt, a gene ontology tool, facilitated the identification of expression networks of genes that co-vary with key cell cycle targets, especially Cdc20 and Plk1 (www.bioinfo.vanderbilt.edu/webgestalt). Cell cycle expression networks of such covariate mRNAs exist in multiple proliferative tissues including liver, lung, pituitary, adipose and lymphoid tissues among others but not in brain or retina that have low proliferative potential. Sixty-three covariate cell cycle gene transcripts (mRNAs) compose the average cell cycle network with p = e−13 to e−36. Cell cycle expression networks show species, sex and tissue variability and they are enriched in mRNA transcripts associated with mitosis many of which are associated with chromosomal instability. PMID:25808367

  2. Amrubicin therapy improves patients with refractory small-cell lung cancer: A single-arm confirmatory Chinese clinical study

    Directory of Open Access Journals (Sweden)

    Mengli Zheng

    2016-09-01

    Full Text Available Our objective was to evaluate an open-label, multicenter, single-arm study to appraise whether amrubicin therapy improves patients with refractory small-cell lung cancer in Chinese clinical study. Patients (n=95 with refractory small-cell lung cancer received 3 consecutive days amrubicin therapy for 21 days. Overall response rate of response to amrubicin was 39%. Anemia, febrile neutropenia, thrombocytopenia, hyperglycemia, hyponatremia, infection, elevated serum transaminases levels were appeared, but the incidences of adverse events were very few. Our results suggest amrubicin therapy can improve patients with refractory small-cell lung cancer and may be an effective and safe treatment option.

  3. Ibrutinib treatment improves T cell number and function in CLL patients.

    Science.gov (United States)

    Long, Meixiao; Beckwith, Kyle; Do, Priscilla; Mundy, Bethany L; Gordon, Amber; Lehman, Amy M; Maddocks, Kami J; Cheney, Carolyn; Jones, Jeffrey A; Flynn, Joseph M; Andritsos, Leslie A; Awan, Farrukh; Fraietta, Joseph A; June, Carl H; Maus, Marcela V; Woyach, Jennifer A; Caligiuri, Michael A; Johnson, Amy J; Muthusamy, Natarajan; Byrd, John C

    2017-08-01

    Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially. T cell phenotype, immune function, and CLL cell immunosuppressive capacity were evaluated. Ibrutinib markedly increased CD4+ and CD8+ T cell numbers in CLL patients. This effect was more prominent in effector/effector memory subsets and was not observed with acalabrutinib. Ex vivo studies demonstrated that this may be due to diminished activation-induced cell death through ITK inhibition. PD-1 and CTLA-4 expression was significantly markedly reduced in T cells by both agents. While the number of Treg cells remained unchanged, the ratio of these to conventional CD4+ T cells was reduced with ibrutinib, but not acalabrutinib. Both agents reduced expression of the immunosuppressive molecules CD200 and BTLA as well as IL-10 production by CLL cells. Ibrutinib treatment increased the in vivo persistence of activated T cells, decreased the Treg/CD4+ T cell ratio, and diminished the immune-suppressive properties of CLL cells through BTK-dependent and -independent mechanisms. These features provide a strong rationale for combination immunotherapy approaches with ibrutinib in CLL and other cancers. ClinicalTrials.gov NCT01589302 and NCT02029443. Samples described here were collected per OSU-0025. The National Cancer Institute.

  4. Can the outcomes of mesenchymal stem cell-based therapy for myocardial infarction be improved? Providing weapons and armour to cells.

    Science.gov (United States)

    Karpov, Andrey A; Udalova, Daria V; Pliss, Michael G; Galagudza, Michael M

    2017-04-01

    Use of mesenchymal stem cell (MSC) transplantation after myocardial infarction (MI) has been found to have infarct-limiting effects in numerous experimental and clinical studies. However, recent meta-analyses of randomized clinical trials on MSC-based MI therapy have highlighted the need for improving its efficacy. There are two principal approaches for increasing therapeutic effect of MSCs: (i) preventing massive MSC death in ischaemic tissue and (ii) increasing production of cardioreparative growth factors and cytokines with transplanted MSCs. In this review, we aim to integrate our current understanding of genetic approaches that are used for modification of MSCs to enable their improved survival, engraftment, integration, proliferation and differentiation in the ischaemic heart. Genetic modification of MSCs resulting in increased secretion of paracrine factors has also been discussed. In addition, data on MSC preconditioning with physical, chemical and pharmacological factors prior to transplantation are summarized. MSC seeding on three-dimensional polymeric scaffolds facilitates formation of both intercellular connections and contacts between cells and the extracellular matrix, thereby enhancing cell viability and function. Use of genetic and non-genetic approaches to modify MSC function holds great promise for regenerative therapy of myocardial ischaemic injury. © 2016 John Wiley & Sons Ltd.

  5. Risk and prognostic significance of metachronous contralateral testicular germ cell tumours

    NARCIS (Netherlands)

    Schaapveld, M.; van den Belt-Dusebout, A. W.; Gietema, J. A.; de Wit, R.; Horenblas, S.; Witjes, J. A.; Hoekstra, H. J.; Kiemeney, L. A. L. M.; Louwman, W. J.; Ouwens, G. M.; Aleman, B. M. P.; van Leeuwen, F. E.

    2012-01-01

    BACKGROUND: Testicular germ cell tumour (TGCT) patients are at increased risk of developing a contralateral testicular germ cell tumour (CTGCT). It is unclear whether TGCT treatment affects CTGCT risk. METHODS: The risk of developing a metachronous CTGCT (a CTGCT diagnosed >= 6 months after a

  6. Anion-Exchange Membrane Fuel Cells with Improved CO2 Tolerance: Impact of Chemically Induced Bicarbonate Ion Consumption.

    Science.gov (United States)

    Katayama, Yu; Yamauchi, Kosuke; Hayashi, Kohei; Okanishi, Takeou; Muroyama, Hiroki; Matsui, Toshiaki; Kikkawa, Yuuki; Negishi, Takayuki; Watanabe, Shin; Isomura, Takenori; Eguchi, Koichi

    2017-08-30

    Over the last few decades, because of the significant development of anion exchange membranes, increasing efforts have been devoted the realization of anion exchange membrane fuel cells (AEMFCs) that operate with the supply of hydrogen generated on-site. In this paper, ammonia was selected as a hydrogen source, following which the effect of conceivable impurities, unreacted NH 3 and atmospheric CO 2 , on the performance of AEMFCs was established. As expected, we show that these impurities worsen the performance of AEMFCs significantly. Furthermore, with the help of in situ attenuated total reflection infrared (ATR-IR) spectroscopy, it was revealed that the degradation of the cell performance was primarily due to the inhibition of the hydrogen oxidation reaction (HOR). This is attributed to the active site occupation by CO-related adspecies derived from (bi)carbonate adspecies. Interestingly, this degradation in the HOR activity is suppressed in the presence of both NH 3 and HCO 3 - because of the bicarbonate ion consumption reaction induced by the existence of NH 3 . Further analysis using in situ ATR-IR and electrochemical methods revealed that the poisonous CO-related adspecies were completely removed under NH 3 -HCO 3 - conditions, accompanied by the improvement in HOR activity. Finally, a fuel cell test was conducted by using the practical AEMFC with the supply of NH 3 -contained H 2 gas to the anode and ambient air to the cathode. The result confirmed the validity of this positive effect of NH 3 -HCO 3 - coexistence on CO 2 -tolerence of AEMFCs. The cell performance achieved nearly 95% of that without any impurity in the fuels. These results clearly show the impact of the chemically induced bicarbonate ion consumption reaction on the realization of highly CO 2 -tolerent AEMFCs.

  7. Improved cell viability and hydroxyapatite growth on nitrogen ion-implanted surfaces

    Science.gov (United States)

    Shafique, Muhammad Ahsan; Murtaza, G.; Saadat, Shahzad; Uddin, Muhammad K. H.; Ahmad, Riaz

    2017-08-01

    Stainless steel 306 is implanted with various doses of nitrogen ions using a 2 MV pelletron accelerator for the improvement of its surface biomedical properties. Raman spectroscopy reveals incubation of hydroxyapatite (HA) on all the samples and it is found that the growth of incubated HA is greater in higher ion dose samples. SEM profiles depict uniform growth and greater spread of HA with higher ion implantation. Human oral fibroblast response is also found consistent with Raman spectroscopy and SEM results; the cell viability is found maximum in samples treated with the highest (more than 300%) dose. XRD profiles signified greater peak intensity of HA with ion implantation; a contact angle study revealed hydrophilic behavior of all the samples but the treated samples were found to be lesser hydrophilic compared to the control samples. Nitrogen implantation yields greater bioactivity, improved surface affinity for HA incubation and improved hardness of the surface.

  8. Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation.

    Science.gov (United States)

    Wen, Di; Peng, Yang; Liu, Di; Weizmann, Yossi; Mahato, Ram I

    2016-09-28

    Human bone marrow mesenchymal stem cells (hBMSCs) and their exosomes can suppress immune reaction and deliver small RNAs. Thus, they may improve islet transplantation by delivering small RNAs for promoting islet function and inhibiting immune rejection. Here, we proposed an hBMSC and its exosome-based therapy to overcome immune rejection and poor islet function, both of which hinder the success of islet transplantation. We found overexpressed siFas and anti-miR-375 in plasmid encoding shFas and anti-miR-375 transfected hBMSC-derived exosomes, which silenced Fas and miR-375 of human islets and improved their viability and function against inflammatory cytokines. This plasmid transfected hBMSCs downregulated Fas and miR-375 of human islets in a humanized NOD scid gamma (NSG) mouse model, whose immune reaction was inhibited by injecting hBMSC and peripheral blood mononuclear cell (PBMC) co-cultured exosomes. These exosomes suppressed immune reaction by inhibiting PBMC proliferation and enhancing regulatory T cell (Treg) function. Collectively, our studies elucidated the mechanisms of RNA delivery from hBMSCs to human islets and the immunosuppressive effect of hBMSC and peripheral blood mononuclear cell co-cultured exosomes for improving islet transplantation. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Embryo aggregation does not improve the development of interspecies somatic cell nuclear transfer embryos in the horse.

    Science.gov (United States)

    Gambini, Andrés; De Stéfano, Adrián; Jarazo, Javier; Buemo, Carla; Karlanian, Florencia; Salamone, Daniel Felipe

    2016-09-01

    The low efficiency of interspecies somatic cell nuclear transfer (iSCNT) makes it necessary to investigate new strategies to improve embryonic developmental competence. Embryo aggregation has been successfully applied to improve cloning efficiency in mammals, but it remains unclear whether it could also be beneficial for iSCNT. In this study, we first compared the effect of embryo aggregation over in vitro development and blastocyst quality of porcine, bovine, and feline zona-free (ZF) parthenogenetic (PA) embryos to test the effects of embryo aggregation on species that were later used as enucleated oocytes donors in our iSCNT study. We then assessed whether embryo aggregation could improve the in vitro development of ZF equine iSCNT embryos after reconstruction with porcine, bovine, and feline ooplasm. Bovine- and porcine-aggregated PA blastocysts had significantly larger diameters compared with nonaggregated embryos. On the other hand, feline- and bovine-aggregated PA embryos had higher blastocyst cell number. Embryo aggregation of equine-equine SCNT was found to be beneficial for embryo development as we have previously reported, but the aggregation of three ZF reconstructed embryos did not improve embryo developmental rates on iSCNT. In vitro embryo development of nonaggregated iSCNT was predominantly arrested around the stage when transcriptional activation of the embryonic genome is reported to start on the embryo of the donor species. Nevertheless, independent of embryo aggregation, equine blastocyst-like structures could be obtained in our study using domestic feline-enucleated oocytes. Taken together, these results reported that embryo aggregation enhance in vitro PA embryo development and embryo quality but effects vary depending on the species. Embryo aggregation also improves, as expected, the in vitro embryo development of equine-equine SCNT embryos; however, we did not observe positive effects on equine iSCNT embryo development. Among oocytes

  10. Improved cell for water-vapor electrolysis

    Science.gov (United States)

    Aylward, J. R.

    1981-01-01

    Continuous-flow electrolytic cells decompose water vapor in steam and room air into hydrogen and oxygen. Sintered iridium oxide catalytic anode coating yields dissociation rates hundredfold greater than those obtained using platinum black. Cell consists of two mirror-image cells, with dual cathode sandwiched between two anodes. Gas traverses serpentine channels within cell and is dissociated at anode. Oxygen mingles with gas stream, while hydrogen migrates through porous matrix and is liberated as gas at cathode.

  11. Creating Significant Learning Experiences across Disciplines

    Science.gov (United States)

    Levine, Laura E.; Fallahi, Carolyn R.; Nicoll-Senft, Joan M.; Tessier, Jack T.; Watson, Cheryl L.; Wood, Rebecca M.

    2008-01-01

    The purpose of this study was to use Fink's (2003) taxonomy of significant learning to redesign courses and assess student learning. Significant improvements were found across the semester for students in the six courses, but there were differences in which taxa showed improvement in each course. The meta-analysis showed significant, positive…

  12. Improvement of ionic conductivity and performance of quasi-solid-state dye sensitized solar cell using PEO/PMMA gel electrolyte

    International Nuclear Information System (INIS)

    Aram, E.; Ehsani, M.; Khonakdar, H.A.

    2015-01-01

    Graphical abstract: Reduced interfacial resistance of a quasi-solid-state dye sensitized solar cell with PEO/PMMA blend gel electrolytes. - Highlights: • A new polymer gel electrolyte containing PEO/PMMA was developed for DSSCs. • Optimization of polymer gel electrolyte was done for dye sensitized solar cell. • The best ionic conductivity was found in PEO/PMMA blend with 10/90 w/w composition. • The DSSC with the PEO/PMMA based electrolyte showed good photovoltaic performance. • Significant stability improvement for quasi-solid state DSSC was obtained. - Abstract: Polymer blend gel electrolytes based on polyethylene oxide (PEO) and poly(methyl methacrylate) (PMMA) as host polymers with various weight ratios, LiI/I 2 as redox couple in electrolyte and 4-tert-butyl pyridine as additive were prepared by solution method. The introduction of PMMA in the PEO gel electrolyte reduced the degree of crystallinity of PEO, which was confirmed by differential scanning calorimetry (DSC). Complexation and ionic conductivity as a function of temperature were investigated with Fourier transform infrared and ionic conductometry, respectively. A good correlation was found between the degree of crystallinity and ionic conductivity. The reduction in crystallinity, governed by blending ratio, led to improvement of ionic conductivity. The best ionic conductivity was attained in PEO/PMMA blend with 10/90 w/w composition. The performance of a quasi-solid-state dye sensitized solar cell using the optimized polymer gel electrolyte was investigated. The optimized system of high ionic conductivity of 7 mS cm −1 , with fill factor of 0.59, short-circuit density of 11.11 mA cm −2 , open-circuit voltage of 0.75 V and the conversion efficiency of 4.9% under air mass 1.5 irradiation (100 mW cm −2 ) was obtained. The long-term stability of the dye-sensitized solar cell (DSSC) during 600 h was improved by using PEO/PMMA gel electrolyte relative to a liquid type electrolyte

  13. Improvement of ionic conductivity and performance of quasi-solid-state dye sensitized solar cell using PEO/PMMA gel electrolyte

    Energy Technology Data Exchange (ETDEWEB)

    Aram, E. [Iran Polymer and Petrochemical Institute, 14965/115 Tehran (Iran, Islamic Republic of); Ehsani, M., E-mail: m.ehsani@ippi.ac.ir [Iran Polymer and Petrochemical Institute, 14965/115 Tehran (Iran, Islamic Republic of); Khonakdar, H.A. [Iran Polymer and Petrochemical Institute, 14965/115 Tehran (Iran, Islamic Republic of); Leibniz Institute of Polymer Research, D-01067 Dresden (Germany)

    2015-09-10

    Graphical abstract: Reduced interfacial resistance of a quasi-solid-state dye sensitized solar cell with PEO/PMMA blend gel electrolytes. - Highlights: • A new polymer gel electrolyte containing PEO/PMMA was developed for DSSCs. • Optimization of polymer gel electrolyte was done for dye sensitized solar cell. • The best ionic conductivity was found in PEO/PMMA blend with 10/90 w/w composition. • The DSSC with the PEO/PMMA based electrolyte showed good photovoltaic performance. • Significant stability improvement for quasi-solid state DSSC was obtained. - Abstract: Polymer blend gel electrolytes based on polyethylene oxide (PEO) and poly(methyl methacrylate) (PMMA) as host polymers with various weight ratios, LiI/I{sub 2} as redox couple in electrolyte and 4-tert-butyl pyridine as additive were prepared by solution method. The introduction of PMMA in the PEO gel electrolyte reduced the degree of crystallinity of PEO, which was confirmed by differential scanning calorimetry (DSC). Complexation and ionic conductivity as a function of temperature were investigated with Fourier transform infrared and ionic conductometry, respectively. A good correlation was found between the degree of crystallinity and ionic conductivity. The reduction in crystallinity, governed by blending ratio, led to improvement of ionic conductivity. The best ionic conductivity was attained in PEO/PMMA blend with 10/90 w/w composition. The performance of a quasi-solid-state dye sensitized solar cell using the optimized polymer gel electrolyte was investigated. The optimized system of high ionic conductivity of 7 mS cm{sup −1}, with fill factor of 0.59, short-circuit density of 11.11 mA cm{sup −2}, open-circuit voltage of 0.75 V and the conversion efficiency of 4.9% under air mass 1.5 irradiation (100 mW cm{sup −2}) was obtained. The long-term stability of the dye-sensitized solar cell (DSSC) during 600 h was improved by using PEO/PMMA gel electrolyte relative to a liquid type

  14. Accelerated and Improved Differentiation of Retinal Organoids from Pluripotent Stem Cells in Rotating-Wall Vessel Bioreactors

    Directory of Open Access Journals (Sweden)

    Tyler DiStefano

    2018-01-01

    Full Text Available Pluripotent stem cells can be differentiated into 3D retinal organoids, with major cell types self-patterning into a polarized, laminated architecture. In static cultures, organoid development may be hindered by limitations in diffusion of oxygen and nutrients. Herein, we report a bioprocess using rotating-wall vessel (RWV bioreactors to culture retinal organoids derived from mouse pluripotent stem cells. Organoids in RWV demonstrate enhanced proliferation, with well-defined morphology and improved differentiation of neurons including ganglion cells and S-cone photoreceptors. Furthermore, RWV organoids at day 25 (D25 reveal similar maturation and transcriptome profile as those at D32 in static culture, closely recapitulating spatiotemporal development of postnatal day 6 mouse retina in vivo. Interestingly, however, retinal organoids do not differentiate further under any in vitro condition tested here, suggesting additional requirements for functional maturation. Our studies demonstrate that bioreactors can accelerate and improve organoid growth and differentiation for modeling retinal disease and evaluation of therapies.

  15. Methylphenidate significantly improves declarative memory functioning of adults with ADHD.

    NARCIS (Netherlands)

    Verster, J.C.; Bekker, E.M.; Kooij, J.J.; Buitelaar, J.K.; Verbaten, M.N.; Volkerts, E.R.; Olivier, B.

    2010-01-01

    BACKGROUND: Declarative memory deficits are common in untreated adults with attention-deficit hyperactivity disorder (ADHD), but limited evidence exists to support improvement after treatment with methylphenidate. The objective of this study was to examine the effects of methylphenidate on memory

  16. The SGLT2 Inhibitor Dapagliflozin Significantly Improves the Peripheral Microvascular Endothelial Function in Patients with Uncontrolled Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Sugiyama, Seigo; Jinnouchi, Hideaki; Kurinami, Noboru; Hieshima, Kunio; Yoshida, Akira; Jinnouchi, Katsunori; Nishimura, Hiroyuki; Suzuki, Tomoko; Miyamoto, Fumio; Kajiwara, Keizo; Jinnouchi, Tomio

    2018-03-30

    Objective Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce cardiovascular events and decrease the body fat mass in patients with type 2 diabetes mellitus (T2DM). We examined whether or not the SGLT2-inhibitor dapagliflozin can improve the endothelial function associated with a reduction in abdominal fat mass. Methods We prospectively recruited patients with uncontrolled (hemoglobin A1c [HbA1c] >7.0%) T2DM who were not being treated by SGLT2 inhibitors. Patients were treated with add-on dapagliflozin (5 mg/day) or non-SGLT2 inhibitor medicines for 6 months to improve their HbA1c. We measured the peripheral microvascular endothelial function as assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and calculated the natural logarithmic transformed value of the RH-PAT index (LnRHI). We then investigated changes in the LnRHI and abdominal fat area using computed tomography (CT). Results The subjects were 54 patients with uncontrolled T2DM (72.2% men) with a mean HbA1c of 8.1%. The HbA1c was significantly decreased in both groups, with no significant difference between the groups. Dapagliflozin treatment, but not non-SGLT2 inhibitor treatment, significantly increased the LnRHI. The changes in the LnRHI were significantly greater in the dapagliflozin group than in the non-SGLT2 inhibitor group. Dapagliflozin treatment, but not non-SGLT2 inhibitor treatment, significantly decreased the abdominal visceral fat area, subcutaneous fat area (SFA), and total fat area (TFA) as assessed by CT and significantly increased the plasma adiponectin levels. The percentage changes in the LnRHI were significantly correlated with changes in the SFA, TFA, systolic blood pressure, and adiponectin. Conclusion Add-on treatment with dapagliflozin significantly improves the glycemic control and endothelial function associated with a reduction in the abdominal fat mass in patients with uncontrolled T2DM.

  17. Changes in T-cell subpopulations and cytokine network during early period of ibrutinib therapy in chronic lymphocytic leukemia patients: the significant decrease in T regulatory cells number.

    Science.gov (United States)

    Podhorecka, Monika; Goracy, Aneta; Szymczyk, Agnieszka; Kowal, Malgorzata; Ibanez, Blanca; Jankowska-Lecka, Olga; Macheta, Arkadiusz; Nowaczynska, Aleksandra; Drab-Urbanek, Elzbieta; Chocholska, Sylwia; Jawniak, Dariusz; Hus, Marek

    2017-05-23

    B cell receptor (BCR) stimulation signal plays an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and kinase inhibitors directed toward the BCR pathway are now the promising anti-leukemic drugs. Ibrutinib, a Bruton tyrosine kinase inhibitor, demonstrates promising clinical activity in CLL. It is reported that ibrutinib, additionally to directly targeting leukemic cells, also inhibits the interactions of these cells with T cells, macrophages and accessory cells. Assessment of these mechanisms is important because of their non -direct anti-leukemic effects and to identify possible side effects connected with long-term drug administration.The aim of this study was to assess the in vivo effects of ibrutinib on T-cell subpopulations and cytokine network in CLL. The analysis was performed on a group of 19 patients during first month of ibrutinib therapy. The standard multicolor flow cytometry and cytometric bead array methods were used for assessment of T-cell subsets and cytokines/chemokines, respectively.The data obtained indicates that Ibrutinib treatment results in changes in T-cell subpopulations and cytokine network in CLL patients. Particularly, a significant reduction of T regulatory cells in peripheral blood was observed. By targeting these populations of T cells Ibrutinib can stimulate rejection of tumor cells by the immune system.

  18. Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF?

    Science.gov (United States)

    Cashen, A F; Lazarus, H M; Devine, S M

    2007-05-01

    Currently, granulocyte colony stimulating factor (G-CSF) remains the standard mobilizing agent for peripheral blood stem cell (PBSC) donors, allowing the safe collection of adequate PBSCs from the vast majority of donors. However, G-CSF mobilization can be associated with some significant side effects and requires a multi-day dosing regimen. The other cytokine approved for stem cell mobilization, granulocyte-macrophage colony stimulating factor (GM-CSF), alters graft composition and may reduce the development of graft-versus-host disease, but a significant minority of donors fails to provide sufficient CD34+ cells with GM-CSF and some experience unacceptable toxicity. AMD3100 is a promising new mobilizing agent, which may have several advantages over G-CSF for donor mobilization. As it is a direct antagonist of the interaction between the chemokine stromal-derived factor-1 and its receptor CXCR4, AMD3100 mobilizes PBSCs within hours rather than days. It is also well tolerated, with no significant side effects reported in any of the clinical trials to date. Studies of autologous and allogeneic transplantation of AMD3100 mobilized grafts have demonstrated prompt and stable engraftment. Here, we review the current state of stem cell mobilization in normal donors and discuss novel strategies for donor stem cell mobilization.

  19. The prognostic significance and relationship with body composition of CCR7-positive cells in colorectal cancer.

    Science.gov (United States)

    Malietzis, George; Lee, Gui Han; Bernardo, David; Blakemore, Alexandra I F; Knight, Stella C; Moorghen, Morgan; Al-Hassi, Hafid O; Jenkins, John T

    2015-07-01

    The host local immune response (LIR) to cancer is a determinant of cancer outcome. Regulation of this local response is largely achieved through chemokine synthesis from the tumor microenvironment such as C-Chemokine-Receptor-7 (CCR7). We examined the LIR measured as CCR7 expression, in colorectal cancers (CRC) and explored relationships with body composition (BC) and survival. A study of paraffin-embedded tissue specimens was carried out in 116 patients with non-metastatic CRC. CCR7 expression was determined by immunohistochemistry. Analysis of computer tomography scans was used to calculate BC parameters. Survival analyses and multivariate regression models were used. High CCR7(+) cell density within the tumor stroma and at the margin was significantly associated with increased age, the presence of lymphovascular invasion, higher tumor stage, lymph node metastasis, high Klintrup-Makinen immune score, and myosteatosis. High CCR7(+) cell density in the tumor margin was significantly associated with shorter disease-free (DFS) and overall survival (OS) (P < 0.001). This was also significantly associated with shorter survival in multivariate analysis (HR = 8.87; 95%CI [2.51-31.3]; P < 0.01 for OS and HR = 4.72; 95%CI (1.24-12.9); P = 0.02 for DFS). Our results suggest that a specific immune microenvironment may be associated with altered host's BC and tumor behavior, and that CCR7 may serve as a novel prognostic biomarker. © 2015 Wiley Periodicals, Inc.

  20. Improving startup performance with carbon mesh anodes in separator electrode assembly microbial fuel cells

    KAUST Repository

    Zhang, Fang; Xia, Xue; Luo, Yong; Sun, Dan; Call, Douglas F.; Logan, Bruce E.

    2013-01-01

    In a separator electrode assembly microbial fuel cell, oxygen crossover from the cathode inhibits current generation by exoelectrogenic bacteria, resulting in poor reactor startup and performance. To determine the best approach for improving startup