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Sample records for cells exert 3-dimensional

  1. A novel solar cell fabricated with spiral photo-electrode for capturing sunlight 3-dimensionally

    Institute of Scientific and Technical Information of China (English)

    LIU Yong; SHEN Hui; DENG Youjun

    2006-01-01

    A novel solar cell fabricated with spiral photo-electrode for capturing sunlight 3-dimensionally (3D-cell) is proposed in this paper. We studied its performance both in solar simulator and in nature sunlight. Spiral photo-electrode of 3D-cell can receive sunlight from all directions and therefore can track the sun passively. And it is much insensitive to solar azimuth angle and shade. In addition, it increases the area to obtain scattered sunlight and reflected light. Compared with the dye-sensitized solar cells using sandwich structure, it would be more advantageous in the sealing technique.

  2. Patterned 3-dimensional metal grid electrodes as alternative electron collectors in dye-sensitized solar cells.

    Science.gov (United States)

    Chua, Julianto; Mathews, Nripan; Jennings, James R; Yang, Guangwu; Wang, Qing; Mhaisalkar, Subodh G

    2011-11-21

    We describe the application of 3-dimensional metal grid electrodes (3D-MGEs) as electron collectors in dye-sensitized solar cells (DSCs) as a replacement for fluorinated tin oxide (FTO) electrodes. Requirements, structure, advantages, and limitations of the metal grid electrodes are discussed. Solar conversion efficiencies of 6.2% have been achieved in 3D-MGE based solar cells, comparable to that fabricated on FTO (7.1%). The charge transport properties and collection efficiencies in these novel solar cells have been studied using electrochemical impedance spectroscopy.

  3. Automatic fabrication of 3-dimensional tissues using cell sheet manipulator technique.

    Science.gov (United States)

    Kikuchi, Tetsutaro; Shimizu, Tatsuya; Wada, Masanori; Yamato, Masayuki; Okano, Teruo

    2014-03-01

    Automated manufacturing is a key for tissue-engineered therapeutic products to become common-place and economical. Here, we developed an automatic cell sheet stacking apparatus to fabricate 3-dimensional tissue-engineered constructs exploiting our cell sheet manipulator technique, where cell sheets harvested from temperature-responsive culture dishes are stacked into a multilayered cell sheet. By optimizing the stacking conditions and cell seeding conditions, the apparatus was eventually capable of reproducibly making five-layer human skeletal muscle myoblast (HSMM) sheets with a thickness of approximately 70-80 μm within 100 min. Histological sections and confocal topographies of the five-layer HSMM sheets revealed a stratified structure with no delamination. In cell counts using trypsinization, the live cell numbers in one-, three- and five-layer HSMM sheets were equivalent to the seeded cell numbers at 1 h after the stacking processes; however, after subsequent 5-day static cultures, the live cell numbers of the five-layered HSMM sheets decreased slightly, while one- and three-layer HSMM sheets maintained their live cell numbers. This suggests that there are thickness limitations in maintaining tissues in a static culture. We concluded that by combining our cell sheet manipulator technique and industrial robot technology we can create a secure, cost-effective manufacturing system able to produce tissue-engineered products from cell sheets. PMID:24370007

  4. Derived vascular endothelial cells induced by mucoepidermoid carcinoma cells: 3-dimensional collagen matrix model*

    OpenAIRE

    Yang, Sen; Guo, Li-Juan; Gao, Qing-hong; Xuan, Ming; Tan, Ke; Zhang, Qiang; Wen, Yu-ming; Wang, Chang-mei; Tang, Xiu-fa; Wang, Xiao-yi

    2010-01-01

    Mucoepidermoid carcinoma undergoes uniquely vigorous angiogenic and neovascularization processes, possibly due to proliferation of vascular endothelial cells (ECs) induced by mucoepidermoid carcinoma cells (MCCs) in their three-dimensional (3D) microenvironment. To date, no studies have dealt with tumor cells and vascular ECs from the same origin of mucoepidermoid carcinoma using the in vitro 3D microenvironment model. In this context, the current research aims to observe neovascularization w...

  5. Targeting FAK Radiosensitizes 3-Dimensional Grown Human HNSCC Cells Through Reduced Akt1 and MEK1/2 Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Hehlgans, Stephanie [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt am Main (Germany); Institute of Radiopharmacy, Helmholtz Center Dresden-Rossendorf, Dresden (Germany); Eke, Iris [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Cordes, Nils, E-mail: Nils.Cordes@OncoRay.de [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Institute of Radiopharmacy, Helmholtz Center Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany)

    2012-08-01

    Purpose: Focal adhesion kinase (FAK), a main regulator of integrin signaling and cell migration, is frequently overexpressed and hyperphosphorylated in human head-and-neck squamous cell carcinoma (HNSCC). We have previously shown that pharmacologic FAK inhibition leads to radiosensitization of 3-dimensionally grown HNSCC cell lines. To further evaluate the role of FAK in radioresistance and as a potential cancer target, we examined FAK and FAK downstream signaling in HNSCC cell lines grown in more physiologic extracellular matrix-based 3-dimensional cell cultures. Methods and Materials: Seven HNSCC cell lines were grown in 3-dimensional extracellular matrix and the clonogenic radiation survival, expression, and phosphorylation of FAK, paxillin, Akt1, extracellular signal-regulated kinase (ERK)1/2, and MEK1/2 were analyzed after siRNA-mediated knockdown of FAK, Akt1, MEK1, FAK+Akt1, or FAK+MEK1 compared with controls or stable overexpression of FAK. The role of MEK1/2 for clonogenic survival and signaling was investigated using the MEK inhibitor U0126 with or without irradiation. Results: FAK knockdown moderately or significantly enhanced the cellular radiosensitivity of 3-dimensionally grown HNSCC cells. The FAK downstream targets paxillin, Akt1, and ERK1/2 were substantially dephosphorylated under FAK depletion. FAK overexpression, in contrast, increased radiation survival and paxillin, Akt1, and ERK1/2 phosphorylation. The degree of radiosensitization upon Akt1, ERK1/2, or MEK1 depletion or U0126 was superimposable to FAK knockdown. Combination knockdown conditions (ie, Akt1/FAK, MEK1/FAK, or U0126/FAK) failed to provide additional radiosensitization. Conclusions: Our data provide further evidence for FAK as important determinant of radiation survival, which acts in the same signaling axis as Akt1 and ERK1/2. These data strongly support our hypothesis that FAK is a relevant molecular target for HNSCC radiotherapy.

  6. Application of optical coherence tomography (OCT) as a 3-dimensional imaging technique for roll-to-roll coated polymer solar cells

    DEFF Research Database (Denmark)

    Thrane, Lars; Jørgensen, Thomas Martini; Jørgensen, Mikkel;

    2012-01-01

    The 3-dimensional imaging of complete polymer solar cells prepared by roll-to-roll coating was carried out using high-resolution 1322 nm optical coherence tomography (OCT) system. We found it possible to image the 3-dimensional structure of the entire solar cell that comprises UV-barrier, barrier...

  7. Micropatterned 3-Dimensional Hydrogel System to Study Human Endothelial-Mesenchymal Stem Cell Interactions

    OpenAIRE

    Trkov, Sasa; Eng, George; Di Liddo, Rosa; Parnigotto, Pier Paolo; Vunjak-Novakovic, Gordana

    2010-01-01

    The creation of vascularized engineered tissues of clinically relevant size is a major challenge of tissue engineering. While it is known that endothelial and mural vascular cells are integral to the formation of stable blood vessels, the specific cell type and optimal conditions for engineered vascular networks are poorly understood. To this end, we investigated the vasculogenic potential of human mesenchymal stem cell (MSC) populations derived from three different sources: (i) bone marrow a...

  8. 3-Dimensional cell-laden nano-hydroxyapatite/protein hydrogels for bone regeneration applications

    Energy Technology Data Exchange (ETDEWEB)

    Sadat-Shojai, Mehdi, E-mail: msadatshojai@gmail.com [Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454 (Iran, Islamic Republic of); Department of Biomaterials, Iran Polymer and Petrochemical Institute, Tehran (Iran, Islamic Republic of); Khorasani, Mohammad-Taghi [Department of Biomaterials, Iran Polymer and Petrochemical Institute, Tehran (Iran, Islamic Republic of); Jamshidi, Ahmad [Department of Novel Drug Delivery Systems, Iran Polymer and Petrochemical Institute, Tehran (Iran, Islamic Republic of)

    2015-04-01

    The ability to encapsulate cells in three-dimensional (3D) protein-based hydrogels is potentially of benefit for tissue engineering and regenerative medicine. However, as a result of their poor mechanical strength, protein-based hydrogels have traditionally been considered for soft tissue engineering only. Hence, in this study we tried to render these hydrogels suitable for hard tissue regeneration, simply by incorporation of bioactive nano-hydroxyapatite (HAp) into a photocrosslinkable gelatin hydrogel. Different cell types were also encapsulated in three dimensions in the resulting composites to prepare cell-laden constructs. According to the results, HAp significantly improves the stiffness of gelatin hydrogels, while it maintains their structural integrity and swelling ratio. It was also found that while the bare hydrogel (control) was completely inert in terms of bioactivity, a homogeneous 3D mineralization occurs throughout the nanocomposites after incubation in simulated body fluid. Moreover, encapsulated cells readily elongated, proliferated, and formed a 3D interconnected network with neighboring cells in the nanocomposite, showing the suitability of the nano-HAp/protein hydrogels for cellular growth in 3D. Therefore, the hydrogel nanocomposites developed in this study may be promising candidates for preparing cell-laden tissue-like structures with enhanced stiffness and increased osteoconductivity to induce bone formation in vivo. - Highlights: • We tried to render protein-based hydrogels suitable for hard tissue regeneration. • We developed a three-component system comprising hydrogel, nano-HAp, and cells. • Nano-HAp significantly improved the mechanical strength of hydrogel. • Encapsulated cells readily elongated and proliferated in 3D cell-laden nanocomposite. • 3D deposition of bone crystals occurred in the hydrogel nanocomposites.

  9. Differences in sensitivity to mTHPC-mediated photodynamic therapy of neurons, glial cells and MCF7 cells in a 3-dimensional cell culture model

    OpenAIRE

    Wright, K E; MacRobert, A J; Phillips, J. B.

    2008-01-01

    The effect of photodynamic therapy (PDT) on the cells of the nervous system is an important consideration in the treatment of tumours that are located within or adjacent to the brain, spinal cord and peripheral nerves. Previous studies have reported the sparing of nerves during PDT using meta-tetrahydroxyphenylchlorin (mTHPC, Foscan®) in patients and in animal models. The aim of this study was to investigate the effects of mTHPC on key nervous system cells using a 3-dimensional cell culture s...

  10. 3 dimensional cell cultures: a comparison between manually and automatically produced alginate beads.

    Science.gov (United States)

    Lehmann, R; Gallert, C; Roddelkopf, T; Junginger, S; Wree, A; Thurow, K

    2016-08-01

    Cancer diseases are a common problem of the population caused by age and increased harmful environmental influences. Herein, new therapeutic strategies and compound screenings are necessary. The regular 2D cultivation has to be replaced by three dimensional cell culturing (3D) for better simulation of in vivo conditions. The 3D cultivation with alginate matrix is an appropriate method for encapsulate cells to form cancer constructs. The automated manufacturing of alginate beads might be an ultimate method for large-scaled manufacturing constructs similar to cancer tissue. The aim of this study was the integration of full automated systems for the production, cultivation and screening of 3D cell cultures. We compared the automated methods with the regular manual processes. Furthermore, we investigated the influence of antibiotics on these 3D cell culture systems. The alginate beads were formed by automated and manual procedures. The automated steps were processes by the Biomek(®) Cell Workstation (celisca, Rostock, Germany). The proliferation and toxicity were manually and automatically evaluated at day 14 and 35 of cultivation. The results visualized an accumulation and expansion of cell aggregates over the period of incubation. However, the proliferation and toxicity were faintly and partly significantly decreased on day 35 compared to day 14. The comparison of the manual and automated methods displayed similar results. We conclude that the manual production process could be replaced by the automation. Using automation, 3D cell cultures can be produced in industrial scale and improve the drug development and screening to treat serious illnesses like cancer.

  11. A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles.

    Science.gov (United States)

    Hoelting, Lisa; Scheinhardt, Benjamin; Bondarenko, Olesja; Schildknecht, Stefan; Kapitza, Marion; Tanavde, Vivek; Tan, Betty; Lee, Qian Yi; Mecking, Stefan; Leist, Marcel; Kadereit, Suzanne

    2013-04-01

    Nanoparticles (NPs) have been shown to accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Here, we developed a human embryonic stem cell (hESC)-derived 3-dimensional (3-D) in vitro model that allows for testing of potential developmental neurotoxicants. Early central nervous system PAX6(+) precursor cells were generated from hESCs and differentiated further within 3-D structures. The 3-D model was characterized for neural marker expression revealing robust differentiation toward neuronal precursor cells, and gene expression profiling suggested a predominantly forebrain-like development. Altered neural gene expression due to exposure to non-cytotoxic concentrations of the known developmental neurotoxicant, methylmercury, indicated that the 3-D model could detect DNT. To test for specific toxicity of NPs, chemically inert polyethylene NPs (PE-NPs) were chosen. They penetrated deep into the 3-D structures and impacted gene expression at non-cytotoxic concentrations. NOTCH pathway genes such as HES5 and NOTCH1 were reduced in expression, as well as downstream neuronal precursor genes such as NEUROD1 and ASCL1. FOXG1, a patterning marker, was also reduced. As loss of function of these genes results in severe nervous system impairments in mice, our data suggest that the 3-D hESC-derived model could be used to test for Nano-DNT.

  12. Chondroregulatory action of prolactin on proliferation and differentiation of mouse chondrogenic ATDC5 cells in 3-dimensional micromass cultures

    Energy Technology Data Exchange (ETDEWEB)

    Seriwatanachai, Dutmanee [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok (Thailand); Krishnamra, Nateetip [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok (Thailand); Department of Physiology, Faculty of Science, Mahidol University, Bangkok (Thailand); Charoenphandhu, Narattaphol, E-mail: naratt@narattsys.com [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok (Thailand); Department of Physiology, Faculty of Science, Mahidol University, Bangkok (Thailand)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Mouse chondrogenic ATDC5 cells expressed PRL receptor mRNAs and proteins. Black-Right-Pointing-Pointer Low PRL concentration (10 ng/mL) increased chondrocyte viability and differentiation. Black-Right-Pointing-Pointer Higher PRL concentrations ( Greater-Than-Or-Slanted-Equal-To 100 ng/mL) decreased viability and increased apoptosis. -- Abstract: A recent investigation in lactating rats has provided evidence that the lactogenic hormone prolactin (PRL) increases endochondral bone growth and bone elongation, presumably by accelerating apoptosis of hypertrophic chondrocytes in the growth plate and/or subsequent chondrogenic matrix mineralization. Herein, we demonstrated the direct chondroregulatory action of PRL on proliferation, differentiation and apoptosis of chondrocytes in 3-dimensional micromass culture of mouse chondrogenic ATDC5 cell line. The results showed that ATDC5 cells expressed PRL receptor (PRLR) transcripts, and responded typically to PRL by downregulating PRLR expression. Exposure to a low PRL concentration of 10 ng/mL, comparable to the normal levels in male and non-pregnant female rats, increased chondrocyte viability, differentiation, proteoglycan accumulation, and mRNA expression of several chondrogenic differentiation markers, such as Sox9, ALP and Hspg2. In contrast, high PRL concentrations of Greater-Than-Or-Slanted-Equal-To 100 ng/mL, comparable to the levels in pregnancy or lactation, decreased chondrocyte viability by inducing apoptosis, with no effect on chondrogenic marker expression. It could be concluded that chondrocytes directly but differentially responded to non-pregnant and pregnant/lactating levels of PRL, thus suggesting the stimulatory effect of PRL on chondrogenesis in young growing individuals, and supporting the hypothesis of hypertrophic chondrocyte apoptosis in the growth plate of lactating rats.

  13. Absence of toxicity with hypofractionated 3-dimensional radiation therapy for inoperable, early stage non-small cell lung cancer

    International Nuclear Information System (INIS)

    Hypofractionated radiotherapy may overcome repopulation in rapidly proliferating tumors such as lung cancer. It is more convenient for the patients and reduces health care costs. This study reports our results on patients with medically inoperable, early stage, non-small cell lung cancer (NSCLC) treated with hypofractionation. Stage T1-2N0 NSCLC patients were treated with hypofractionation alone, 52.5 Gy/15 fractions, in 3 weeks, with 3-dimensional conformal planning. T1-2N1 patients with the hilar lymphnode close to the primary tumor were also eligible for this treatment. We did not use any approach to reduce respiratory motion, but it was monitored in all patients. Elective nodal radiotherapy was not performed. Routine follow up included assessment for acute and late toxicity and radiological tumor response. Median follow up time was 29 months for the surviving patients. Thirty-two patients with a median age of 76 years, T1 = 15 and T2 = 17, were treated. Median planning target volume (PTV) volume was 150cc and median V16 of both lungs was 13%. The most important finding of this study is that toxicity was minimal. Two patients had grade ≤ 2 acute pneumonitis and 3 had mild (grade 1) acute esophagitis. There was no late toxicity. Actuarial 1 and 2-year overall survival rates are 78% and 56%, cancer specific survival rates (CSS) are 90% and 74%, and local relapse free survival rates are 93% and 76% respectively. 3-D planning, involved field hypofractionation at a dose of 52.5 Gy in 15 daily fractions is safe, well tolerated and easy radiation treatment for medically inoperable lung cancer patients. It shortens by half the traditional treatment. Results compare favorably with previously published studies. Further studies are needed to compare similar technique with other treatments such as surgery and stereotactic radiotherapy

  14. Optical coherence tomography (OCT) as a 3-dimensional imaging technique for non-destructive testing of roll-to-roll coated polymer solar cells

    DEFF Research Database (Denmark)

    Thrane, Lars; Jørgensen, Thomas Martini; Jørgensen, Mikkel;

    2013-01-01

    We have recently demonstrated the first application of optical coherence tomography (OCT) as a 3-dimensional (3D) imaging technique to visualize the internal structure of complete multilayered polymer solar cell modules (Thrane et al., Solar Energy Materials & Solar Cells 97, 181-185 (2012)). The 3......D imaging of complete polymer solar cells prepared by roll-to-roll coating was carried out using a high-resolution 1322nm OCT system having a 4.5 microns axial resolution and a 12 microns lateral resolution. It was possible to image the 3-dimensional structure of the entire solar cell that comprise...... UV-barrier, barrier material, adhesive, substrate and active solar cell multilayer structure. In addition, it was found that the OCT technique could be readily employed to identify coating defects in the functional layers, making it a potential technique to enable process control by real...

  15. Transcriptional profiling of radiation damage and preventive treatments in a 3-dimensional (3D) human cell culture model of oral mucositis

    OpenAIRE

    Lambros, Maria P.; DeSalvo, Michael K.; Jonathan Moreno; Hari Chandana Mulamalla; Lavanya Kondapalli

    2015-01-01

    Cancer patients who receive radiation are often afflicted by oral mucositis, a debilitating disease, characterized by mouth sores and difficulty in swallowing. Oftentimes, cancer patients afflicted with mucositis must stop life-saving therapies. Thus it is very important to prevent mucositis before it develops. Using a validated organotypic model of human oral mucosa, a 3-dimensional cell culture model of human oral keratinocytes, it has been shown that a mixture (NAC–QYD) of N-acetyl cystein...

  16. The endoplasmic reticulum exerts control over organelle streaming during cell expansion.

    Science.gov (United States)

    Stefano, Giovanni; Renna, Luciana; Brandizzi, Federica

    2014-03-01

    Cytoplasmic streaming is crucial for cell homeostasis and expansion but the precise driving forces are largely unknown. In plants, partial loss of cytoplasmic streaming due to chemical and genetic ablation of myosins supports the existence of yet-unknown motors for organelle movement. Here we tested a role of the endoplasmic reticulum (ER) as propelling force for cytoplasmic streaming during cell expansion. Through quantitative live-cell analyses in wild-type Arabidopsis thaliana cells and mutants with compromised ER structure and streaming, we demonstrate that cytoplasmic streaming undergoes profound changes during cell expansion and that it depends on motor forces co-exerted by the ER and the cytoskeleton.

  17. Dual Effects Exerted in Vitro by Micromolar Concentrations of Deoxynivalenol on Undifferentiated Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-02-01

    Full Text Available Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON, raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37–1.50 μM, relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

  18. Dual effects exerted in vitro by micromolar concentrations of deoxynivalenol on undifferentiated caco-2 cells.

    Science.gov (United States)

    Manda, Gina; Mocanu, Mihaela Andreea; Marin, Daniela Eliza; Taranu, Ionelia

    2015-02-01

    Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON), raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37-1.50 μM), relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics.

  19. Dual Effects Exerted in Vitro by Micromolar Concentrations of Deoxynivalenol on Undifferentiated Caco-2 Cells

    Science.gov (United States)

    Manda, Gina; Mocanu, Mihaela Andreea; Marin, Daniela Eliza; Taranu, Ionelia

    2015-01-01

    Contamination of crops used for food and feed production with Fusarium mycotoxins, such as deoxynivalenol (DON), raise important health and economic issues all along the food chain. Acute exposure to high DON concentrations can alter the intestinal barrier, while chronic exposure to lower doses may exert more subtle effects on signal transduction pathways, leading to disturbances in cellular homeostasis. Using real-time cellular impedance measurements, we studied the effects exerted in vitro by low concentrations of DON (0.37–1.50 μM), relevant for mycotoxin-contaminated food, on the proliferation of undifferentiated Caco-2 cells presenting a tumorigenic phenotype. A 1.5 μM concentration of DON maintained cell adherence of non-proliferating Caco-2 cells, whilst arresting the growth of actively proliferating cells compared with control Caco-2 cells in vitro. At 0.37 μM, DON enhanced Caco-2 cell metabolism, thereby triggering a moderate increase in cell proliferation. The results of the current study suggested that low concentrations of DON commonly detected in food may either limit or sustain the proliferation of colon cancer cells, depending on their proliferation status and on DON concentration. Soluble factors released by Lactobacillus strains can partially counteract the inhibitory action of DON on actively proliferating colon cancer cells. The study also emphasized that real-time cellular impedance measurements were a valuable tool for investigating the dynamics of cellular responses to xenobiotics. PMID:25690693

  20. Curcumin exerts antitumor effects in retinoblastoma cells by regulating the JNK and p38 MAPK pathways.

    Science.gov (United States)

    Yu, Xiaoming; Zhong, Jingtao; Yan, Li; Li, Jie; Wang, Hui; Wen, Yan; Zhao, Yu

    2016-09-01

    Curcumin, a naturally occurring polyphenolic compound present in turmeric (Curcuma longa), exerts antitumor effects in various types of malignancy. However, the precise mechanisms responsible for the effects of curcumin on retinoblastoma (RB) cells have not been fully explored. In the present study, the molecular mechanisms by which curcumin exerts its anticancer effects in RB Y79 cells were investigated. The results showed that curcumin reduced cell viability in Y79 cells. Curcumin induced G1 phase arrest through downregulating the expression of cyclin D3 and cyclin-dependent kinase (CDK)2/6 and upregulating the expression of CDK inhibitor proteins p21 and p27. Curcumin-induced apoptosis of Y79 cells occurred through the activation of caspases-9/-3. Moreover, flow cytometric analysis showed that curcumin induced mitochondrial membrane potential (∆Ψm) collapse in Y79 cells. We also found that curcumin induced the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). JNK and p38 MAPK inhibitors significantly suppressed curcumin‑induced activation of caspases-9/-3 and inhibited the apoptosis of Y79 cells. Taken together, our results suggest that curcumin induced the apoptosis of Y79 cells through the activation of JNK and p38 MAPK pathways. These findings provide a novel treatment strategy for human RB. PMID:27432244

  1. 3 - Dimensional Body Measurement Technology

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xu-dong; LI Yan-mei

    2002-01-01

    3 - dimensional body measurement technology, the basis of developing high technology in industry, accelerates digital development of aplparel industry. This paper briefly introduces the history of 3 - dimensional body measurement technology, and recounts the principle and primary structure of some types of 3 - dimensional automatic body measurement system. With this understanding, it discusses prospect of 3- dimensional CAD and virtual technology used in apparel industry.

  2. Thrombomodulin exerts cytoprotective effect on low-dose UVB-irradiated HaCaT cells

    International Nuclear Information System (INIS)

    Thrombomodulin (TM) is an endothelial cell surface anticoagulant glycoprotein that performs antimetastatic, angiogenic, adhesive, and anti-inflammatory functions in various tissues. It is also expressed in epidermal keratinocytes. We found that a physiological dose (10 mJ/cm2) of mid-wavelength ultraviolet irradiation (UVB) significantly induced TM expression via the p38mitogen-activated protein kinase (MAPK)/cyclic AMP response element (CRE) signaling pathway in the epidermal keratinocyte cell line HaCaT; this shows that TM regulates the survival of HaCaT cells. SB203580, a p38MAPK inhibitor, significantly decreased TM expression and the viability of cells exposed to UVB. Furthermore, overexpression of TM markedly increased cell viability, and it was abrogated by TM small interfering RNA (siRNA), suggesting that TM may play an important role in exerting cytoprotective effect on epidermal keratinocytes against low-dose UVB.

  3. High- and low-LET Radiation-induced Chromosome Aberrations in Human Epithelial Cells Cultured in 3-dimensional Matrices

    Science.gov (United States)

    Hada, M.; George K.; Cucinotta, F. A.; Wu, H.

    2008-01-01

    Energetic heavy ions pose a great health risk to astronauts who participate in extended ISS missions and will be an even greater concern for future manned lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied low- and high-LET radiation-induced chromosome aberrations in human epithelial cells cultured in 2-dimension (2D) using the multicolor banding fluorescence in situ hybridization (mBAND) technique. However, it has been realized that the biological response to radiation insult in a 2D in vitro cellular environment can differ significantly from the response in 3-dimension (3D) or at the actual tissue level. In this study, we cultured human epithelial cells in 3D to provide a more suitable model for human tissue. Human mammary epithelial cells (CH184B5F5/M10) were grown in Matrigel to form 3D structures, and exposed to Fe-ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory or 137Cs-gamma radiation source at the University of Texas MD Anderson Cancer Center. After exposure, cells were allowed to repair for 16hr before dissociation and subcultured at low density in 2D. G2 and metaphase chromosomes in the first cell cycle were collected in the first cell cycle after irradiation using a chemical-induced premature chromosome condensation (PCC) technique, and chromosome aberrations were analyzed using mBAND technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Our data indicate a significant difference in the

  4. Intensity-Modulated Radiotherapy versus 3-Dimensional Conformal Radiotherapy Strategies for Locally Advanced Non-Small-Cell Lung Cancer

    OpenAIRE

    Selek, Uğur; Bölükbaşı, Yasemin; Welsh, James W.; Topkan, Erkan

    2014-01-01

    Chemoradiotherapy is the current standard of care in patients with advanced inoperable stage IIIA or IIIB non-small cell lung cancer (NSCLC). Three-dimensional radiotherapy (3DCRT) has been a trusted method for a long time and has well-known drawbacks, most of which could be improved by Intensity Modulated Radiotherapy (IMRT). IMRT is not currently the standard treatment of locally advanced NSCLC, but almost all patients could benefit to a degree in organ at risk sparing, dose coverage confor...

  5. Interleukin-1 exerts distinct actions on different cell types of the brain in vitro

    Directory of Open Access Journals (Sweden)

    Ying An

    2011-01-01

    Full Text Available Ying An, Qun Chen, Ning QuanDepartment of Oral Biology, Ohio State University, Columbus, OH, USAAbstract: Interleukin-1 (IL-1 is a critical neuroinflammatory mediator in the central nervous system (CNS. In this study, we investigated the effect of IL-1 on inducing inflammation-related gene expression in three astrocyte, two microglial, and one brain endothelial cell line. Interleukin-1 beta (IL-1β is found to be produced by the two microglial cell lines constitutively, but these cells do not respond to IL-1β stimulation. The three astrocyte cell lines responded to IL-1ß stimulation by expressing MCP-1, CXCL-1, and VCAM-1, but different subtypes of astrocytes exhibited different expression profiles after IL-1β stimulation. The brain endothelial cells showed strongest response to IL-1β by producing MCP-1, CXCL-1, VCAM-1, ICAM-1, IL-6, and COX-2 mRNA. The induction of endothelial COX-2 mRNA is shown to be mediated by p38 MAPK pathway, whereas the induction of other genes is mediated by the NF-κB pathway. These results demonstrate that IL-1 exerts distinct cell type-specific action in CNS cells and suggest that IL-1-mediated neuroinflammation is the result of the summation of multiple responses from different cell types in the CNS to IL-1.Keywords: astrocyte, microglia, endothelial cells, signal transduction pathways, gene expression 

  6. Combining 3-dimensional degradable electrostatic spinning scaffold and dental follicle cells to build peri-implant periodontium

    Directory of Open Access Journals (Sweden)

    Ximu Zhang

    2013-01-01

    Full Text Available Introduction: Some inevitable problems, such as concentrated bite force and lacked ability of self-renewal, are proved to be the major challenge in the management of implants failures. Thus, it is meaningful to find an ideal dental implant harboring its own peri-implant periodontium, just as the natural teeth. Various studies attempted to reconstruct the periodontium around implants, but unfortunately, it was previously revealed that the artificial periodotium around implants was just a wilderness of fibers, while without the physiological function of natural periodontium, like sensory and homeostatic. The Hypothesis: In this paper, we propose a hypothesis that a modified three-dimensional scaffold with reconstructed peri-implant tissues can be a network for stem cells differentiation. After seeded on the scaffold, stem cells produce various growth factors and differentiate to different orientations in places necessary. This hypothesis, if proven to be valid, will offer a novel and effective therapy for the restoration of missing teeth by implant. Evaluation of the Hypothesis: The scaffold involves three different tissues. Though degradation rate of electrospinning scaffold is under control, its degradation rate should be in consistent with the generation of three tissues. Therefore, the relative experiments are necessary to define the best rate of degradation. Further verification is necessary to check whether the rebuilt cementum, bone and periodontium are strong enough to keep the implant stable and maintain its function.

  7. Leading research report for fiscal 1998. Research and study of 3-dimensional cell structure module engineering; 1998 nendo sendo chosa kenkyu hokokusho. Sanjigen saibo soshiki module kogaku chosa kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-03-01

    For the formation of cellular tissues to replace bionic tissues, researches were conducted about technologies of forming bionic tissue modules by culturing various kinds of cells. As for the materials and methods for constructing cellular tissues, researches were conducted about the trends of research and development of 3-dimensional tissue culturing matrices and materials for micromanipulation. As for the development of technologies for the functionalization of 3-dimensionally structured cells, research and study were conducted about the technology of 3-dimensional cell structure organization through application of physical stimulation, the biochemical technology of differentiation inducing, and the differentiation inducing technology for hetero tissue culturing. As for the development of technologies for evaluation using 3-dimensionally structured cells, light CT (computer tomography), analysis and evaluation using spectroscopy and the like, feasibility of the biochemical analysis of the cell state using biosensors, technologies for measuring the secretion of carcinogenic and toxic substances, etc., were studied. In addition, the development of organic models to replace test animals, industrial evolution of 3-dimensional tissue module engineering, etc., were investigated. (NEDO)

  8. Sam68 exerts separable effects on cell cycle progression and apoptosis

    Directory of Open Access Journals (Sweden)

    Resnick Ross J

    2004-01-01

    Full Text Available Abstract Background The RNA-binding protein Sam68 has been implicated in a number of cellular processes, including transcription, RNA splicing and export, translation, signal transduction, cell cycle progression and replication of the human immunodeficiency virus and poliovirus. However, the precise impact it has on essential cellular functions remains largely obscure. Results In this report we show that conditional overexpression of Sam68 in fibroblasts results in both cell cycle arrest and apoptosis. Arrest in G1 phase of the cell cycle is associated with decreased levels of cyclins D1 and E RNA and protein, resulting in dramatically reduced Rb phosphorylation. Interestingly, cell cycle arrest does not require the specific RNA binding ability of Sam68. In marked contrast, induction of apoptosis by Sam68 absolutely requires a fully-functional RNA binding domain. Moreover, the anti-cancer agent trichostatin A potentiates Sam68-driven apoptosis. Conclusions For the first time we have shown that Sam68, an RNA binding protein with multiple apparent functions, exerts functionally separable effects on cell proliferation and survival, dependent on its ability to bind specifically to RNA. These findings shed new light on the ability of signal transducing RNA binding proteins to influence essential cell function. Moreover, the ability of a class of anti-cancer therapeutics to modulate its ability to promote apoptosis suggests that Sam68 status may impact some cancer treatments.

  9. Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid

    Directory of Open Access Journals (Sweden)

    Heidi Wichmann

    2016-05-01

    Full Text Available The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP, produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA, a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2. Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells.

  10. Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid

    Science.gov (United States)

    Wichmann, Heidi; Brinkhoff, Thorsten; Simon, Meinhard; Richter-Landsberg, Christiane

    2016-01-01

    The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP), produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA), a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2). Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells. PMID:27164116

  11. Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

    Directory of Open Access Journals (Sweden)

    Zhang Yawei

    2009-08-01

    Full Text Available Abstract Background Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As2O3 with cisplatin (DDP on A549 and H460 non-small cell lung cancer (NSCLC cells were explored. Methods A549 and H460 human lung cancer cells were treated with As2O3 and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5-dimethylthiahiazo (-z-y1-3,5-di-phenytetrazoliumromide (MTT method, clonogenic assay, and flow cytometry (FCM. Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot. Results MTT and clonogenic assay showed As2O3 within 10-2 μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As2O3 exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As2O3 with DDP. FCM showed As2O3 did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As2O3 and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As2O3 and/or DDP. FCM and TUNEL staining illustrated that the combination of As2O3 and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As2O3 and/or DDP treatments compared with controls. The

  12. Interaction of natural killer cells with neutrophils exerts a significant antitumor immunity in hematopoietic stem cell transplantation recipients.

    Science.gov (United States)

    Ueda, Ryosuke; Narumi, Kenta; Hashimoto, Hisayoshi; Miyakawa, Reina; Okusaka, Takuji; Aoki, Kazunori

    2016-01-01

    Autologous hematopoietic stem cell transplantation (HSCT) can induce a strong antitumor immunity by homeostatic proliferation (HP) of T cells and suppression of regulatory T cells following preconditioning-induced lymphopenia. However, the role of innate immunity including natural killer (NK) cells is still not understood. Here, first, we examined whether NK cells exert an antitumor effect after syngeneic HSCT in a murine colon cancer model. Flow cytometry showed that NK cells as well as T cells rapidly proliferated after HSCT, and the frequency of mature NK cells was increased in tumor during HP. Furthermore, NK cells undergoing HP were highly activated, which contributed to substantial tumor suppression. Then, we found that a large number of neutrophils accumulated in tumor early after syngeneic HSCT. It was recently reported that neutrophil-derived mediators modulate NK cell effector functions, and so we examined whether the neutrophils infiltrated in tumor are associated with NK cell-mediated antitumor effect. The depletion of neutrophils significantly impaired an activation of NK cells in tumor and increased the fraction of proliferative NK cells accompanied by a decrease in NK cell survival. The results suggested that neutrophils in tumor prevent NK cells from activation-induced cell death during HP, thus leading to a significant antitumor effect by NK cells. This study revealed a novel aspect of antitumor immunity induced by HSCT and may contribute to the development of an effective therapeutic strategy for cancer using HSCT.

  13. Epicardial delivery of VEGF and cardiac stem cells guided by 3-dimensional PLLA mat enhancing cardiac regeneration and angiogenesis in acute myocardial infarction.

    Science.gov (United States)

    Chung, Hye-Jin; Kim, Jong-Tae; Kim, Hee-Jung; Kyung, Hei-Won; Katila, Pramila; Lee, Jeong-Han; Yang, Tae-Hyun; Yang, Young-Il; Lee, Seung-Jin

    2015-05-10

    Congestive heart failure is mostly resulted in a consequence of the limited myocardial regeneration capacity after acute myocardial infarction. Targeted delivery of proangiogenic factors and/or stem cells to the ischemic myocardium is a promising strategy for enhancing their local and sustained therapeutic effects. Herein, we designed an epicardial delivery system of vascular endothelial growth factor (VEGF) and cardiac stem cells (CSCs) using poly(l-lactic acid) (PLLA) mat applied to the acutely infarcted myocardium. The fibrous VEGF-loaded PLLA mat was fabricated by an electrospinning method using PLLA solution emulsified VEGF. This mat not only allowed for sustained release of VEGF for 4weeks but boosted migration and proliferation of both endothelial cells and CSCs in vitro. Furthermore, sustained release of VEGF showed a positive effect on in vitro capillary-like network formation of endothelial cells compared with bolus treatment of VEGF. PLLA mat provided a permissive 3-dimensional (3D) substratum that led to spontaneous cardiomyogenic differentiation of CSCs in vitro. Notably, sustained stimulation by VEGF-loaded PLLA mat resulted in a substantial increase in the expression of proangiogenic mRNAs of CSCs in vitro. The epicardially implanted VEGF-loaded PLLA mat showed modest effects on angiogenesis and cardiomyogenesis in the acutely infarcted hearts. However, co-implantation of VEGF and CSCs using the PLLA mat showed meaningful therapeutic effects on angiogenesis and cardiomyogenesis compared with controls, leading to reduced cardiac remodeling and enhanced global cardiac function. Collectively, the PLLA mat allowed a smart cargo that enabled the sustained release of VEGF and the delivery of CSCs, thereby synergistically inducing angiogenesis and cardiomyogenesis in acute myocardial infarction.

  14. Novel D-A-π-A organic dyes based on 3-dimensional triarylamine and benzothiadiazole derivatives for high-performance dye-sensitized solar cells

    Science.gov (United States)

    Huang, Hongli; Chen, Huajie; Long, Jun; Wang, Guo; Tan, Songting

    2016-09-01

    Organic dyes with a 3-dimensional (3D) structure is helpful for retarding dyes aggregation and charge recombination as well as improving the power conversion efficiency (PCE) of dye-sensitized solar cells (DSSCs). In this contribution, a novel 3D triarylamine derivative (IDTTPA) featuring an indenothiophenene unit has been designed, synthesized, and applied to develop a 3D organic dyes. Two novel D-A-π-A organic dyes (CD1 and CD2) based on IDTTPA as the electron donors, 2,1,3-benzothiadiazole derivatives as the auxiliary acceptors, and formic acid as the anchoring groups have been successfully synthesized and applied in DSSCs. The effects of the fluoro substitute groups on the photophysical, electrochemical, and photovoltaic properties are investigated. The results indicate that the fluoro-containing dye CD2 exhibits higher molar extinction coefficient, stronger light-capturing ability, and better photovoltaic performance than those of CD1 dye without fluoro substitute. Investigation of the DSSCs performance shows that CD2-based DSSCs exhibit a high PCE value of 7.91%, higher than that of CD1-based DSSCs (6.29%), even higher than that of the reference DSSCs based on N719 (7.49%). This works has demonstrated that this kind of 3D unit (IDTTPA) is a strong and promising electron donor unit to develop high efficiency metal-free organic dyes.

  15. Nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number.

    Science.gov (United States)

    Targoff, Kimara L; Schell, Thomas; Yelon, Deborah

    2008-10-15

    Heart formation is a complex morphogenetic process, and perturbations in cardiac morphogenesis lead to congenital heart disease. NKX2-5 is a key causative gene associated with cardiac birth defects, presumably because of its essential roles during the early steps of cardiogenesis. Previous studies in model organisms implicate NKX2-5 homologs in numerous processes, including cardiac progenitor specification, progenitor proliferation, and chamber morphogenesis. By inhibiting function of the zebrafish NKX2-5 homologs, nkx2.5 and nkx2.7, we show that nkx genes are essential to establish the original dimensions of the linear heart tube. The nkx-deficient heart tube fails to elongate normally: its ventricular portion is atypically short and wide, and its atrial portion is disorganized and sprawling. This atrial phenotype is associated with a surplus of atrial cardiomyocytes, whereas ventricular cell number is normal at this stage. However, ventricular cell number is decreased in nkx-deficient embryos later in development, when cardiac chambers are emerging. Thus, we conclude that nkx genes regulate heart tube extension and exert differential effects on ventricular and atrial cell number. Our data suggest that morphogenetic errors could originate during early stages of heart tube assembly in patients with NKX2-5 mutations.

  16. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Song Zhang

    Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

  17. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    International Nuclear Information System (INIS)

    Highlights: ► The impact of UCP-2 over expression on mitochondrial function is controversial. ► We tested mitochondrial functions at defined levels of overexpression. ► We find minor increases of fatty acid oxidation and uncoupling. ► Effects were seen only at high level (fourfold) of over expression. ► Hence it is doubtful whether these effects are of importance in diabetes. -- Abstract: Evidence is conflicting as to the impact of elevated levels of uncoupling protein-2 (UCP-2) on insulin-producing beta cells. Here we investigated effects of a fourfold induction of UCP-2 protein primarily on mitochondrial parameters and tested for replication of positive findings at a lower level of induction. We transfected INS-1 cells to obtain a tet-on inducible cell line. A 48 h exposure to 1 μg/ml of doxycycline (dox) induced UCP-2 fourfold (424 ± 113%, mean ± SEM) and 0.1 μg/ml twofold (178 ± 29%, n = 3). Fourfold induced cells displayed normal viability (MTT, apoptosis), normal cellular insulin contents and, glucose-induced insulin secretion (+27 ± 11%) as well as D-[U-14C]-glucose oxidation (+5 ± 9% at 11 mM glucose). Oxidation of [1-14C]-oleate was increased from 4088 to 5797 fmol/μg prot/2 h at 3.3 mM glucose, p 14C(U)]-glutamine was unaffected. Induction of UCP-2 did not significantly affect measures of mitochondrial membrane potential (Rhodamine 123) or mitochondrial mass (Mitotracker Green) and did not affect ATP levels. Oligomycin-inhibited oxygen consumption (a measure of mitochondrial uncoupling) was marginally increased, the effect being significant in comparison with dox-only treated cells, p < 0.05. Oxygen radicals, assessed by dichlorofluorescin diacetate, were decreased by 30%, p < 0.025. Testing for the lower level of UCP-2 induction did not reproduce any of the positive findings. A fourfold induction of UCP-2 was required to exert minor metabolic effects. These findings question an impact of moderately elevated UCP-2 levels in beta cells as

  18. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hals, Ingrid K., E-mail: ingrid.hals@ntnu.no [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ogata, Hirotaka; Pettersen, Elin [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ma, Zuheng; Bjoerklund, Anneli [Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden); Skorpen, Frank [Department of Laboratory Medicine, NTNU, Trondheim (Norway); Egeberg, Kjartan Wollo [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Grill, Valdemar [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden)

    2012-06-29

    positive findings. A fourfold induction of UCP-2 was required to exert minor metabolic effects. These findings question an impact of moderately elevated UCP-2 levels in beta cells as seen in diabetes.

  19. Type I Interferons Exert Anti-tumor Effect via Reversing Immunosuppression Mediated by Mesenchymal Stromal Cells

    Science.gov (United States)

    Shou, Peishun; Chen, Qing; Jiang, Jingting; Xu, Chunliang; Zhang, Jimin; Zheng, Chunxing; Jiang, Menghui; Velletri, Tania; Cao, Wei; Huang, Yin; Yang, Qian; Han, Xiaoyan; Zhang, Liying; Wei, Lixin; Rabson, Arnold B.; Chin, Y. Eugene; Wang, Ying; Shi, Yufang

    2016-01-01

    Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites to promote tumor growth, but the underlying mechanisms remain largely elusive. Here, we found that IFNα-secreting MSCs showed more dramatic inhibition effect on tumor progression than that of IFNα alone. Interestingly, IFNα-primed MSCs could also effectively suppress tumor growth. Mechanistically, we demonstrated that both IFNα and IFNβ (type I IFNs) reversed the immunosuppressive effect of MSCs on splenocyte proliferation. This effect of type I IFNs was exerted through inhibiting iNOS (inducible nitric oxide synthase) expression in IFNγ and TNFα-stimulated MSCs. Notably, only NO production was inhibited by IFNα; production of other cytokines or chemokines tested was not suppressed. Furthermore, IFNα promoted the switch from Stat1 homodimers to Stat1-Stat2 heterodimers. Studies using the luciferase reporter system and chromatin immunoprecipitation assay revealed that IFNα suppressed iNOS transcription through inhibiting the binding of Stat1 to iNOS promoter. Therefore, the synergistic anti-tumor effects of type I IFNs and MSCs were achieved by inhibiting NO production. This study provides essential information for understanding the mechanisms of MSC-mediated immunosuppression and for the development of better clinical strategies using IFNs and MSCs for cancer immunotherapy. PMID:27109100

  20. Superparamagnetic iron oxide nanoparticles exert different cytotoxic effects on cells grown in monolayer cell culture versus as multicellular spheroids

    Energy Technology Data Exchange (ETDEWEB)

    Theumer, Anja; Gräfe, Christine; Bähring, Franziska [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Bergemann, Christian [Chemicell GmbH, Eresburgstrasse 22–23, 12103 Berlin (Germany); Hochhaus, Andreas [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany); Clement, Joachim H., E-mail: joachim.clement@med.uni-jena.de [Department of Hematology and Oncology, Jena University Hospital, Erlanger Allee 101, 07747 Jena (Germany)

    2015-04-15

    The aim of this study was to investigate the interaction of superparamagnetic iron oxide nanoparticles (SPION) with human blood–brain barrier-forming endothelial cells (HBMEC) in two-dimensional cell monolayers as well as in three-dimensional multicellular spheroids. The precise nanoparticle localisation and the influence of the NP on the cellular viability and the intracellular Akt signalling were studied in detail. Long-term effects of different polymer-coated nanoparticles (neutral fluidMAG-D, anionic fluidMAG-CMX and cationic fluidMAG-PEI) and the corresponding free polymers on cellular viability of HBMEC were investigated by real time cell analysis studies. Nanoparticles exert distinct effects on HBMEC depending on the nanoparticles' surface charge and concentration, duration of incubation and cellular context. The most severe effects were caused by PEI-coated nanoparticles. Concentrations above 25 µg/ml led to increased amounts of dead cells in monolayer culture as well as in multicellular spheroids. On the level of intracellular signalling, context-dependent differences were observed. Monolayer cultures responded on nanoparticle incubation with an increase in Akt phosphorylation whereas spheroids on the whole show a decreased Akt activity. This might be due to the differential penetration and distribution of PEI-coated nanoparticles.

  1. Superparamagnetic iron oxide nanoparticles exert different cytotoxic effects on cells grown in monolayer cell culture versus as multicellular spheroids

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the interaction of superparamagnetic iron oxide nanoparticles (SPION) with human blood–brain barrier-forming endothelial cells (HBMEC) in two-dimensional cell monolayers as well as in three-dimensional multicellular spheroids. The precise nanoparticle localisation and the influence of the NP on the cellular viability and the intracellular Akt signalling were studied in detail. Long-term effects of different polymer-coated nanoparticles (neutral fluidMAG-D, anionic fluidMAG-CMX and cationic fluidMAG-PEI) and the corresponding free polymers on cellular viability of HBMEC were investigated by real time cell analysis studies. Nanoparticles exert distinct effects on HBMEC depending on the nanoparticles' surface charge and concentration, duration of incubation and cellular context. The most severe effects were caused by PEI-coated nanoparticles. Concentrations above 25 µg/ml led to increased amounts of dead cells in monolayer culture as well as in multicellular spheroids. On the level of intracellular signalling, context-dependent differences were observed. Monolayer cultures responded on nanoparticle incubation with an increase in Akt phosphorylation whereas spheroids on the whole show a decreased Akt activity. This might be due to the differential penetration and distribution of PEI-coated nanoparticles

  2. Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

    Science.gov (United States)

    Tani, Alessia; Anderloni, Giulia; Pierucci, Federica; Matteini, Francesca; Chellini, Flaminia; Zecchi Orlandini, Sandra; Meacci, Elisabetta

    2014-01-01

    Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P), a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK), blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF) involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration. PMID:25264785

  3. Mesenchymal stromal cell secreted sphingosine 1-phosphate (S1P exerts a stimulatory effect on skeletal myoblast proliferation.

    Directory of Open Access Journals (Sweden)

    Chiara Sassoli

    Full Text Available Bone-marrow-derived mesenchymal stromal cells (MSCs have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P, a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK, blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration.

  4. Ginsenoside Rp1 Exerts Anti-inflammatory Effects via Activation of Dendritic Cells and Regulatory T Cells.

    Science.gov (United States)

    Bae, Jingyu; Koo, Jihye; Kim, Soochan; Park, Tae-Yoon; Kim, Mi-Yeon

    2012-10-01

    Ginsenoside Rp1 (G-Rp1) is a saponin derivate that provides anti-metastatic activities through inhibition of the NF-κB pathway. In this study, we examined the effects of G-Rp1 on regulatory T cell (Treg) activation. After treatment of splenocytes with G-Rp1, Tregs exhibited upregulation of IL-10 expression, and along with dendritic cells (DCs), these Tregs showed increased cell number compared to other cell populations. The effect of G-Rp1 on Treg number was augmented in the presence of lipopolysaccharide (LPS), which mimics pathological changes that occur during inflammation. However, depletion of DCs prevented the increase in Treg number in the presence of G-Rp1 and/or LPS. In addition, G-Rp1 promoted the differentiation of the memory types of CD4(+)Foxp3(+)CD62L(low) Tregs rather than the generation of new Tregs. In vivo experiments also demonstrated that Tregs and DCs from mice that were fed G-Rp1 for 7 d and then injected with LPS exhibited increased activation compared with those from mice that were injected with LPS alone. Expression of TGF-β and CTLA4 in Tregs was increased, and upregulation of IL-2 and CD80/ CD86 expression by DCs affected the suppressive function of Tregs through IL-2 receptors and CTLA4. These data demonstrate that G-Rp1 exerts anti-inflammatory effects by activating Tregs in vitro and in vivo. PMID:23717139

  5. RhoA exerts a permissive effect on volume-regulated anion channels in vascular endothelial cells

    DEFF Research Database (Denmark)

    Carton, Iris; Trouet, Dominique; Hermans, Diane;

    2002-01-01

    pathway reduces the swelling-dependent activation of I(Cl,swell). However, these experiments did not allow us to discriminate between a direct activator role or a permissive effect. We now show that the Rho pathway did not affect VRAC activity if this pathway was activated by transfecting CPAE cells......'-O-(3-thiotriphosphate) or C3 exoenzyme had no effect on VRACs in caveolin-1-expressing Caco-2 cells. We conclude that the Rho pathway exerts a permissive effect on VRACs in CPAE cells, i.e., swelling-induced opening of VRACs requires a functional Rho pathway, but not an activation of the Rho pathway.......Cell swelling triggers in most cell types an outwardly rectifying anion current, I(Cl,swell), via volume-regulated anion channels (VRACs). We have previously demonstrated in calf pulmonary artery endothelial (CPAE) cells that inhibition of the Rho/Rho kinase/myosin light chain phosphorylation...

  6. Non-CpG Oligonucleotides Exert Adjuvant Effects by Enhancing Cognate B Cell-T Cell Interactions, Leading to B Cell Activation, Differentiation, and Isotype Switching

    Directory of Open Access Journals (Sweden)

    Melinda Herbáth

    2015-01-01

    Full Text Available Natural and synthetic nucleic acids are known to exert immunomodulatory properties. Notably, nucleic acids are known to modulate immune function via several different pathways and various cell types, necessitating a complex interpretation of their effects. In this study we set out to compare the effects of a CpG motif containing oligodeoxynucleotide (ODN with those of a control and an inhibitory non-CpG ODN during cognate B cell-T cell interactions. We employed an antigen presentation system using splenocytes from TCR transgenic DO11.10 mice and the ovalbumin peptide recognized by the TCR as model antigen. We followed early activation events by measuring CD69 expression, late activation by MHC class II expression, cell division and antibody production of switched, and nonswitched isotypes. We found that both of the tested non-CpG ODN exerted significant immunomodulatory effects on early T cell and on late B cell activation events. Importantly, a synergism between non-CpG effects and T cell help acting on B cells was observed, resulting in enhanced IgG production following cognate T cell-B cell interactions. We propose that non-CpG ODN may perform as better adjuvants when a strong antigen-independent immune activation, elicited by CpG ODNs, is undesirable.

  7. Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells

    Science.gov (United States)

    Montgomery, Amanda; Adeyeni, Temitope; San, KayKay; Heuertz, Rita M.; Ezekiel, Uthayashanker R.

    2016-01-01

    We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer. PMID:27390600

  8. A numerical analysis of forces exerted by laminar flow on spreading cells in a parallel plate flow chamber assay.

    Science.gov (United States)

    Olivier, L A; Truskey, G A

    1993-10-01

    Exposure of spreading anchorage-dependent cells to laminar flow is a common technique to measure the strength of cell adhesion. Since cells protrude into the flow stream, the force exerted by the fluid on the cells is a function of cell shape. To assess the relationship between cell shape and the hydrodynamic force on adherent cells, we obtained numerical solutions of the velocity and stress fields around bovine aortic endothelial cells during various stages of spreading and calculated the force required to detach the cells. Morphometric parameters were obtained from light and scanning electron microscopy measurements. Cells were assumed to have a constant volume, but the surface area increased during spreading until the membrane was stretched taut. Two-dimensional models of steady flow were generated using the software packages ANSYS (mesh generation) and FIDAP (problem solution). The validity of the numerical results was tested by comparison with published results for a semicircle in contact with the surface. The drag force and torque were greatest for round cells making initial contact with the surface. During spreading, the drag force and torque declined by factors of 2 and 20, respectively. The calculated forces and moments were used in adhesion models to predict the wall shear stress at which the cells detached. Based upon published values for the bond force and receptor number, round cells should detach at shear stresses between 2.5 and 6 dyn/cm(2), whereas substantially higher stresses are needed to detach spreading and fully spread cells. Results from the simulations indicate that (1) the drag force varies little with cell shape whereas the torque is very sensitive to cell shape, and (2) the increase in the strength of adhesion during spreading is due to increased contact area and receptor densities within the contact area.

  9. Ganoderma lucidum polysaccharide exerts anti-tumor activity via MAPK pathways in HL-60 acute leukemia cells.

    Science.gov (United States)

    Yang, Guohua; Yang, Lei; Zhuang, Yun; Qian, Xifeng; Shen, Yunfeng

    2016-01-01

    In this study, we investigated the anti-tumor activity both in vitro and in vivo of a polysaccharide obtained from Ganoderma lucidum on HL-60 acute myeloid leukemia cells, and focused on its targeting effect on mitogen-activated protein kinase (MAPK) pathways. It was found by the methods such as western blot and flow cytometry (FCM), that G. lucidum polysaccharide (GLP) blocked the extracellular signal-regulated kinase/MAPK signaling pathway, simultaneously activated p38 and JNK MAPK pathways, and therefore regulated their downstream genes and proteins, including p53, c-myc, c-fos, c-jun, Bcl-2, Bax, cleaved caspase-3 and cyclin D1. As a result, cycle arrest and apoptosis of HL-60 cells were induced. Therefore, GLP exerted anti-tumor activity via MAPK pathways in HL-60 acute leukemia cells.

  10. Anti-Allergic Drugs Tranilast and Ketotifen Dose-Dependently Exert Mast Cell-Stabilizing Properties

    Directory of Open Access Journals (Sweden)

    Asuka Baba

    2016-01-01

    Full Text Available Background: Anti-allergic drugs, such as tranilast and ketotifen, inhibit the release of chemokines from mast cells. However, we know little about their direct effects on the exocytotic process of mast cells. Since exocytosis in mast cells can be monitored electrophysiologically by changes in the whole-cell membrane capacitance (Cm, the absence of such changes by these drugs indicates their mast cell-stabilizing properties. Methods: Employing the standard patch-clamp whole-cell recording technique in rat peritoneal mast cells, we examined the effects of tranilast and ketotifen on the Cm during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Relatively lower concentrations of tranilast (100, 250 µM and ketotifen (1, 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, higher concentrations of tranilast (500 µM, 1 mM and ketotifen (50, 100 µM almost totally suppressed the increase in the Cm, and washed out the trapping of the dye on the surface of the mast cells. Compared to tranilast, ketotifen required much lower doses to similarly inhibit the degranulation of mast cells or the increase in the Cm. Conclusions: This study provides electrophysiological evidence for the first time that tranilast and ketotifen dose-dependently inhibit the process of exocytosis, and that ketotifen is more potent than tranilast in stabilizing mast cells. The mast cell-stabilizing properties of these drugs may be attributed to their ability to counteract the plasma membrane deformation in degranulating mast cells.

  11. Common Effects on Follicular Thyroid Cancer Cells Exerted by Simulated Microgravity

    DEFF Research Database (Denmark)

    Svejgaard, Benjamin; Grimm, Daniela; Corydon, Thomas Juhl;

    2015-01-01

    This study focuses on gravity-sensitive proteins of two human follicular cancer cell lines (ML-1; RO82-W-1), which were exposed to simulated microgravity (s-μg) on two different machines. Changes in protein cytoskeletal structure, growth patterns and protein expression in response to s-μg were...... investigated. After a three-day (3d) or seven-day (7d) culture grown in s-μg, we found both cell types growing three-dimensionally within multicellular spheroids (MCS) and also cells remaining adherent (AD) to the culture flask, while 1g- control cultures only formed adherent monolayers RO82-W-1 cells released...

  12. Supraphysiological doses of performance enhancing anabolic-androgenic steroids exert direct toxic effects on neuron-like cells.

    Science.gov (United States)

    Basile, John R; Binmadi, Nada O; Zhou, Hua; Yang, Ying-Hua; Paoli, Antonio; Proia, Patrizia

    2013-01-01

    Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose) polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR) in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks. PMID:23675320

  13. Supraphysiological Doses of Performance Enhancing Anabolic-Androgenic Steroids Exert Direct Toxic Effects on Neuron-like Cells

    Directory of Open Access Journals (Sweden)

    John Robert Basile

    2013-05-01

    Full Text Available Anabolic-androgenic steroids (AAS are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

  14. Stem cells can form gap junctions with cardiac myocytes and exert pro-arrhythmic effects

    Directory of Open Access Journals (Sweden)

    Nicoline Willemijn Smit

    2014-10-01

    Full Text Available Stem cell therapy has been suggested to be a promising option for regeneration of injured myocardium, for example following a myocardial infarction. For clinical use cell-based therapies have to be safe and applicable and are aimed to renovate the architecture of the heart. Yet for functional and coordinated activity synchronized with the host myocardium stem cells have to be capable of forming electrical connections with resident cardiomyocytes. In this paper we discuss whether stem cells are capable of establishing functional electrotonic connections with cardiomyocytes and whether these may generate a risk for arrhythmias. Application of stem cells in the clinical setting with outcomes concerning arrhythmogenic safety and future perspectives will also briefly be touched upon.

  15. Cyclamen exerts cytotoxicity in solid tumor cell lines: a step toward new anticancer agents?

    Science.gov (United States)

    Yildiz, Mustafa; Bozcu, Hakan; Tokgun, Onur; Karagur, Ege Riza; Akyurt, Oktay; Akca, Hakan

    2013-01-01

    Cyclamen coum is a traditional medicinal plant in the Turkey. Its anticancer properties and whether cyclamen extract induces any cytotoxicity in solid cancer cell lines have not been thoroughly investigated previously. Therefore we examined cytotoxic effects on cervical cancer, HeLa, and non small cell lung cancer cell, H1299, lines. Cyclamen extract induced cellular death of both HeLa and H1299 cells in a dose dependent manner. We also analyzed the capacity of cyclamen extract to induce apoptosis by the TUNEL method. Here, we for the first time report that the extract of Cyclamen coum, an endemic plant for Turkey, can induce cytotoxicity via apoptosis in HeLa and H1299 cells. These results imply that cyclamen extract can be further analyzed to potentially find novel anticancer compounds.

  16. Laccase purified from Cerrena unicolor exerts antitumor activity against leukemic cells

    Science.gov (United States)

    MATUSZEWSKA, ANNA; KARP, MARTA; JASZEK, MAGDALENA; JANUSZ, GRZEGORZ; OSIŃSKA-JAROSZUK, MONIKA; SULEJ, JUSTYNA; STEFANIUK, DAWID; TOMCZAK, WALDEMAR; GIANNOPOULOS, KRZYSZTOF

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is the most commonly observed adult hematological malignancy in Western countries. Despite the fact that recent improvements in CLL treatment have led to an increased percentage of complete remissions, CLL remains an incurable disease. Cerrena unicolor is a novel fungal source of highly active extracellular laccase (ex-LAC) that is currently used in industry. However, to the best of our knowledge, no reports regarding its anti-leukemic activity have been published thus far. In the present study, it was hypothesized that C. unicolor ex-LAC may possess cytotoxic activity against leukemic cell lines and CLL primary cells. C. unicolor ex-LAC was separated using anion exchange chromatography on diethylaminoethyl cellulose-Sepharose and Sephadex G-50 columns. The cytotoxic effects of ex-LAC upon 24- and 48-h treatment on HL-60, Jurkat, RPMI 8226 and K562 cell lines, as well as CLL primary cells of nine patients with CLL, were evaluated using 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. Annexin V/propidium iodide staining of Jurkat cells treated with ex-LAC was used to investigate apoptosis via flow cytometry. Ex-LAC induced changes in Jurkat and RPMI 8226 cells, as visualized by fluorescence and scanning electron microscopy (SEM). The XTT assay revealed high cytotoxic rates following treatment with various concentrations of ex-LAC on all the cell lines and CLL primary cells analyzed, with a half maximal inhibitory concentration ranging from 0.4 to 1.1 µg/ml. Fluorescence microscopy and SEM observations additionally revealed apoptotic changes in Jurkat and RPMI 8226 cells treated with ex-LAC, compared with control cells. These results were in agreement with the apoptosis analysis of Jurkat cells on flow cytometry. In conclusion, C. unicolor ex-LAC was able to significantly induce cell apoptosis, and may represent a novel therapeutic agent for the treatment of various hematological neoplasms. PMID

  17. Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

    International Nuclear Information System (INIS)

    The JAK2V617F mutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1. Pharmacological inhibition of JAK2/STAT5 signaling in JAK2V617F mutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins. Treatment of JAK2V617F mutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2V617F mutant cell viability and sensitized the cells to JAK2 inhibition. We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2V617F cell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1, besides Bcl-xL, is warranted to assess the therapeutic potential for

  18. Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

    Directory of Open Access Journals (Sweden)

    Guthy Daniel A

    2011-01-01

    Full Text Available Abstract Background The JAK2V617F mutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1. Methods Pharmacological inhibition of JAK2/STAT5 signaling in JAK2V617F mutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins. Results Treatment of JAK2V617F mutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2V617F mutant cell viability and sensitized the cells to JAK2 inhibition. Conclusions We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2V617F cell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1

  19. Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells

    OpenAIRE

    Montgomery, Amanda; Adeyeni, Temitope; San, KayKay; Heuertz, Rita M.; Ezekiel, Uthayashanker R.

    2016-01-01

    We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer ...

  20. Combination of gefitinib and DNA methylation inhibitor decitabine exerts synergistic anti-cancer activity in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Yun-feng Lou

    Full Text Available Despite recent advances in the treatment of human colon cancer, the chemotherapy efficacy against colon cancer is still unsatisfactory. In the present study, effects of concomitant inhibition of the epidermal growth factor receptor (EGFR and DNA methyltransferase were examined in human colon cancer cells. We demonstrated that decitabine (a DNA methyltransferase inhibitor synergized with gefitinib (an EGFR inhibitor to reduce cell viability and colony formation in SW1116 and LOVO cells. However, the combination of the two compounds displayed minimal toxicity to NCM460 cells, a normal human colon mucosal epithelial cell line. The combination was also more effective at inhibiting the AKT/mTOR/S6 kinase pathway. In addition, the combination of decitabine with gefitinib markedly inhibited colon cancer cell migration. Furthermore, gefitinib synergistically enhanced decitabine-induced cytotoxicity was primarily due to apoptosis as shown by Annexin V labeling that was attenuated by z-VAD-fmk, a pan caspase inhibitor. Concomitantly, cell apoptosis resulting from the co-treatment of gefitinib and decitabine was accompanied by induction of BAX, cleaved caspase 3 and cleaved PARP, along with reduction of Bcl-2 compared to treatment with either drug alone. Interestingly, combined treatment with these two drugs increased the expression of XIAP-associated factor 1 (XAF1 which play an important role in cell apoptosis. Moreover, small interfering RNA (siRNA depletion of XAF1 significantly attenuated colon cancer cells apoptosis induced by the combination of the two drugs. Our findings suggested that gefitinib in combination with decitabine exerted enhanced cell apoptosis in colon cancer cells were involved in mitochondrial-mediated pathway and induction of XAF1 expression. In conclusion, based on the observations from our study, we suggested that the combined administration of these two drugs might be considered as a novel therapeutic regimen for treating colon

  1. Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment.

    Science.gov (United States)

    Zuo, Fu-Xing; Bao, Xin-Jie; Sun, Xi-Cai; Wu, Jun; Bai, Qing-Ran; Chen, Guo; Li, Xue-Yuan; Zhou, Qiang-Yi; Yang, Yuan-Fan; Shen, Qin; Wang, Ren-Zhi

    2015-11-05

    Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.

  2. Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction

    Directory of Open Access Journals (Sweden)

    María Roel

    2015-07-01

    Full Text Available The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1 on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities.

  3. Spatially coordinated changes in intracellular rheology and extracellular force exertion during mesenchymal stem cell differentiation

    International Nuclear Information System (INIS)

    The mechanical properties within the cell are regulated by the organization of the actin cytoskeleton, which is linked to the extracellular environment through focal adhesion proteins that transmit force. Chemical and mechanical stimuli alter the organization of cytoskeletal actin, which results in changes in cell shape, adhesion, and differentiation. By combining particle-tracking microrheology and traction force cytometry, we can monitor the mechanical properties of the actin meshwork and determine how changes in the intracellular network contribute to force generation. In this study, we investigated the effects of chemical (differentiation factors) and mechanical (substrate rigidity) stimuli important in mesenchymal stem cell (MSC) differentiation on the intracellular mechanics and traction stress generation. We found the presence of adipogenic factors resulted in stiffening of the actin meshwork regardless of substrate rigidity. In contrast, these factors increased traction stresses on hard substrates, which was associated with increased expression of contractility genes. Furthermore, MSCs cultured on hard substrates expressed both adipogenic and osteogenic markers indicative of mixed differentiation. On hard substrates, heterogeneity in the local elastic modulus-traction stress correlation was also increased in response to adipogenic factors, indicating that these mechanical properties may be reflective of differences in the level of MSC differentiation. These results suggest intracellular rheology and traction stress generation are spatially regulated and contribute insight into how single cell mechanical forces contribute to MSC differentiation. (paper)

  4. Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro

    DEFF Research Database (Denmark)

    Martins, João; Elvas, Filipe; Brudzewsky, Dan;

    2015-01-01

    Neuropeptide Y (NPY) is expressed in mammalian retina but the location and potential modulatory effects of NPY receptor activation remain largely unknown. Retinal ganglion cell (RGC) death is a hallmark of several retinal degenerative diseases, particularly glaucoma. Using purified RGCs and ex vivo...

  5. Various Acylglycerols from Common Oils Exert Different Antitumor Activities on Colorectal Cancer Cells.

    Science.gov (United States)

    Ramos-Bueno, Rebeca P; González-Fernández, María J; Guil-Guerrero, José L

    2016-04-01

    Colorectal cancer is one of the leading causes of death in Western countries; therefore, the implementation of healthy dietary habits in order to prevent its occurrence is a desirable action. We show here that both free fatty acids (FFAs) and some acylglycerols induce antitumoral actions in the colorectal cancer cell line HT-29. We tested several C18 polyunsaturated fatty acid-enriched oils (e.g., sunflower and Echium) as well as other oils, such as arachidonic acid-enriched (Arasco®) and docosahexaenoic acid-enriched (Marinol® and cod liver oil), in addition to coconut and olive oils. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test indicated inhibitory effects on HT-29 cells viability for FFAs, and monoacylglycerol and diacylglycerol (DAG) species, while the lactate dehydrogenase test proved that FFAs were the more effective species to induce membrane injury. Conversely, all species did not exhibit actions on CCD-18 normal human colon cells viability. Furthermore, transmission electron microscopy showed the presence of necrosis and apoptosis, while the monoacylglycerol lipase (MAGL) inhibition test demonstrated high activity for 2-monoacylglycerols derived from Arasco and sunflower oils. However, different monoacylglycerols and DAGs have also the potential for MAGL inhibition. Therefore, checking for activity on colon cancer cells of specifically designed acylglycerol-derivative species would be a suitable way to design functional foods destined to avoid colorectal cancer initiation. PMID:27007804

  6. 3-dimensional polymer gel dosimetry

    International Nuclear Information System (INIS)

    Recently developed techniques in conformal radiotherapy demand special properties of radiation dosimeters. Polymer gel dosimeter evaluated by nuclear magnetic resonance (NMR) is promising tool which can be used for measuring rather complicated 3-dimensional dose distributions with required precision of ± 5 %. This system is based on radiation-induced polymerisation and cross-linking of acrylic monomers which are uniformly dispersed in aqueous gel. The formation of cross-linked polymers in the irradiated regions of the gel increases the NMR relaxation rates of neighbouring water protons. BANG-2 type polymer gel was prepared. The composition of gel dosimeter was as follows: 3 % N,N'-methylene-bisacrylamide, 3 % acrylic acid, 1 % sodium hydroxide, 5 % gelatine, and 88 % water, where all percentages are by weight. The dosimeters in glass vessels were homogeneously irradiated by 60Co gamma photons in a Gammacell 220 unit and by 4 MV, 6 MV and 18 MV X ray photons on Varian Clinac 600C and 2100 C linear accelerators by doses in the range of 0-50 Gy. Evaluation of dosimeters was performed on Siemens EXPERT 1 T and Siemens VISION 1,5 T scanners. Multi-echo CPMG sequence with 16 echoes was used for the evaluation of T2-relaxation times in irradiated gel dosimeters. The dependence of 1/T2 response of dosimeters was studied on following factors: absorbed dose, energy of applied radiation, temperature during NMR evaluation, time since irradiation to NMR evaluation and strength of the magnetic field. An exponential dependence of 1/T2 response on absorbed dose in the range of 0-50 Gy was observed, in the range 0-10 Gy the data could be fitted by a linear function. There was observed no dependence of 1/T2 response on: energy (for three different photon energies used in this study), strength of magnetic field of NMR scanner, time from irradiation of the dosimeters to NMR evaluation. Increase of gel dosimeter 1/T2 response with the decrease of the temperature during NMR evaluation

  7. Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells.

    Science.gov (United States)

    Huang, Ou; Zhang, Weili; Zhi, Qiaoming; Xue, Xiaofeng; Liu, Hongchun; Shen, Daoming; Geng, Meiyu; Xie, Zuoquan; Jiang, Min

    2015-04-01

    Triple-negative breast cancer (TNBC) is defined as a group of primary breast cancers lacking expression of estrogen, progesterone, and human epidermal growth factor receptor-2 (HER-2) receptors, characterized by higher relapse rate and lower survival compared with other subtypes. Due to lack of identified targets and molecular heterogeneity, conventional chemotherapy is the only available option for treatment of TNBC, but non-discordant positive therapeutic efficacy could not be achieved. Here, we demonstrated that these TNBC cells were sensitive to teriflunomide, which was a well-known immunomodulatory drug for treatment of relapsing multiple sclerosis (MS). Potent anti-cancer effects in TNBC in vitro, including proliferation inhibition, cell cycle delay, cell apoptosis, and suppression of cell motility and invasiveness, could be achieved with this agent. Of note, we showed that multiple signals involved in TNBC proliferation, survival, migratory, and invasive potential were under regulation by teriflunomide. Among them, we identified down-regulation of growth factor receptors to abolish growth maintenance, suppression of c-Myc, and cyclin D1 to contribute to its anti-proliferative effect, modulation of components of cell cycle to induce S-phase arrest, degradation of Bcl-xL, and up-regulation of BAX via activation of MAPK pathway to induce apoptosis, and inhibition of epithelial-mesenchymal transition (EMT) process, matrix metalloproteinase-9 (MMP9) expression, and inactivation of Src/FAK to reduce TNBC migration and invasion. The results identified teriflunomide may be of therapeutic benefit for the more aggressive and difficult-to-treat breast cancer subtype, indicating the use of teriflunomide for clinical trials for treatment of TNBC patients. PMID:25304315

  8. Ultrahigh Resolution 3-Dimensional Imaging Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Southwest Sciences proposes to develop innovative instrumentation for the rapid, 3-dimensional imaging of biological tissues with cellular resolution. Our approach...

  9. A novel adipocytokine, chemerin exerts anti-inflammatory roles in human vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yamawaki, Hideyuki, E-mail: yamawaki@vmas.kitasato-u.ac.jp [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan); Kameshima, Satoshi; Usui, Tatsuya; Okada, Muneyoshi; Hara, Yukio [Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Aomori 034-8628 (Japan)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Chemerin is a novel adipocytokine with almost unknown function in vasculature. Black-Right-Pointing-Pointer Chemerin activates Akt/eNOS/NO pathways in endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-{alpha}-induced monocyte adhesion to endothelial cells. Black-Right-Pointing-Pointer Chemerin inhibits TNF-induced VCAM-1 via suppressing NF-{kappa}B and p38 signal. Black-Right-Pointing-Pointer Chemerin is anti-inflammatory through producing NO in vascular endothelium. -- Abstract: Chemerin is a recently identified adipocytokine which plays a role on inflammation and adipocytes metabolism. However, its function in vasculature is largely unknown. We examined the effects of chemerin on vascular endothelial inflammatory states. Treatment of human umbilical vein endothelial cells with chemerin (300 ng/ml, 20 min) induced phosphorylation of Akt (Ser473) and endothelial nitric oxide (NO) synthase (eNOS) (Ser1177). Consistently, chemerin increased intracellular cyclic GMP content. Pretreatment with chemerin (1-300 ng/ml, 24 h) significantly inhibited phosphorylation of nuclear factor (NF)-{kappa}B p65 (Ser536) and p38 as well as vascular cell adhesion molecule (VCAM)-1 expression induced by tumor necrosis factor (TNF)-{alpha} (5 ng/ml, 20 min-6 h). Inhibitor of NF-{kappa}B or p38 significantly inhibited the TNF-{alpha}-induced VCAM-1 expression. Chemerin also inhibited TNF-{alpha}-induced VCAM-1 expression in rat isolated aorta. Moreover, chemerin significantly inhibited monocytes adhesion to TNF-{alpha}-stimulated endothelial cells. The inhibitory effect of chemerin on TNF-{alpha}-induced VCAM-1 was reversed by a NOS inhibitor. Conversely, an NO donor, sodium nitroprusside significantly inhibited TNF-{alpha}-induced VCAM-1. The present results for the first time demonstrate that chemerin plays anti-inflammatory roles by preventing TNF-{alpha}-induced VCAM-1 expression and monocytes adhesion in vascular

  10. Hsp40 gene therapy exerts therapeutic effects on polyglutamine disease mice via a non-cell autonomous mechanism.

    Directory of Open Access Journals (Sweden)

    H Akiko Popiel

    Full Text Available The polyglutamine (polyQ diseases such as Huntington's disease (HD, are neurodegenerative diseases caused by proteins with an expanded polyQ stretch, which misfold and aggregate, and eventually accumulate as inclusion bodies within neurons. Molecules that inhibit polyQ protein misfolding/aggregation, such as Polyglutamine Binding Peptide 1 (QBP1 and molecular chaperones, have been shown to exert therapeutic effects in vivo by crossing of transgenic animals. Towards developing a therapy using these aggregation inhibitors, we here investigated the effect of viral vector-mediated gene therapy using QBP1 and molecular chaperones on polyQ disease model mice. We found that injection of adeno-associated virus type 5 (AAV5 expressing QBP1 or Hsp40 into the striatum both dramatically suppresses inclusion body formation in the HD mouse R6/2. AAV5-Hsp40 injection also ameliorated the motor impairment and extended the lifespan of R6/2 mice. Unexpectedly, we found even in virus non-infected cells that AAV5-Hsp40 appreciably suppresses inclusion body formation, suggesting a non-cell autonomous therapeutic effect. We further show that Hsp40 inhibits secretion of the polyQ protein from cultured cells, implying that it inhibits the recently suggested cell-cell transmission of the polyQ protein. Our results demonstrate for the first time the therapeutic effect of Hsp40 gene therapy on the neurological phenotypes of polyQ disease mice.

  11. Both cell substratum regulation and hormonal regulation of milk protein gene expression are exerted primarily at the posttranscriptional level

    Energy Technology Data Exchange (ETDEWEB)

    Eisenstein, R.S.; Rosen, J.M.

    1988-08-01

    The mechanism by which individual peptide and steroid hormones and cell-substratum interactions regulate milk protein gene expression has been studied in the COMMA-D mammary epithelial cell line. In the presence of insulin, hydrocortisone, and prolactin, growth of COMMA-D cells on floating collagen gels in comparison with that on a plastic substratum resulted in a 2.5- to 3-fold increase in the relative rate of ..beta..-casein gene transcription but a 37-fold increase in ..beta..-casein mRNA accumulation. In contrast, whey acidic protein gene transcription was constitutive in COMMA-D cells grown on either substratum, but its mRNA was unstable and little intact mature mRNA was detected. Culturing COMMA-D cells on collagen also promoted increased expression of other genes expressed in differentiated mammary epithelial cells, including those encoding ..cap alpha..- and ..gamma..-casein, transferrin, malic enzyme, and phosphoenolpyruvate carboxykinase but decreased the expression of actin and histone genes. Using COMMA-D cells, the authors defined further the role of individual hormones in influencing ..beta..-casein gene transcription. With insulin alone, a basal level of ..beta..-casein gene transcription was detected in COMMA-D cells grown on floating collagen gels. Addition of prolactin but not hydrocortisone resulted in a 2.5- to 3.0-fold increase in ..beta..-casein gene transcription, but both hormones were required to elicit the maximal 73-fold induction in mRNA accumulation. The posttranscriptional effect of hormones on casein mRNA accummulation preceded any detectable changes in the relative rate of transcription. Thus, regulation by both hormones and cell substratum of casein gene expression is exerted primarily at the post transcriptional level.

  12. Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?

    International Nuclear Information System (INIS)

    Dendritic cells (DCs) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system. Ductal pancreatic adenocarcinoma (PDAC), the most common pancreatic cancer, is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence. We examined the systemic influence ductal pancreatic adenocarcinoma (PDAC) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors, chronic pancreatitis, and age-matched controls. All groups examined, including PDAC, had decreased levels of myeloid DCs (MDC) and plasmacytoid DCs (PDC) and enhanced apoptosis in these cells as compared to controls. We found elevated levels of PGE2 and CXCL8 in subjects with PDAC, and chronic pancreatitis. Levels of these inflammatory factors were in part restored in PDAC after tumor resection, whereas the levels of DCs were impaired in the majority of these patients ~12 weeks after tumor removal. Our results prove that solid pancreatic tumors, including PDAC, systemically affect blood DCs. The impairments do not seem to be tumor-specific, since similar results were obtained in subjects with chronic pancreatitis. Furthermore, we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival. Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs. Furthermore, the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and survival

  13. Interleukin-12 Gene Modification Exerts Anti-Tumor Effects on Murine Mammary Sarcoma Cell Line in vivo

    Institute of Scientific and Technical Information of China (English)

    Dan Li; Hong Yu; Tengfei Xu; Jinghua Li; Yunfang Sun; Wenqing Zhang

    2008-01-01

    The aim of this project was to investigate the anti-tumor effect of an IL-12 gene modified mammary sarcoma murine cell line, EMT6/IL-12, in mouse model. In this study, we transfected the recombinant eukaryotic plasmid encoding IL-12 gene (pcDNA6-p70) into EMT6 and obtained the IL-12 expressing EMT6/IL-12 cell line. Then EMT6/IL-12 cells were s.c. inoculated into mice. The recombinant vector treatment group was set as control. We then evaluated the inhibition of tumor growth and the anti-tumor immunity function in vivo such as cytotoxicity, proliferation of splenocytes and serial IFN-y level. And the percentage of IFN-y producing CD4 or CD8 T cells among splenocytes was also analyzed in tumor bearing mice. Our results showed that the growth of tumors was obviously inhibited in EMT6/IL-12 group. Moreover, the capacities of anti-tumor immunity were all significantly higher in EMT6/IL-12 group compared to the controls. The results of the present investigation support the notion that EMT6/IL-12 could exert gene therapy in tumor model by improving the anti-tumor cellular immunity. Cellular & Molecular Immunology. 2008;5(3):225-230.

  14. Osteogenic potential of human adipose-derived stromal cells on 3-dimensional mesoporous TiO{sub 2} coating with magnesium impregnation

    Energy Technology Data Exchange (ETDEWEB)

    Cecchinato, Francesca, E-mail: francesca.cecchinato@mah.se [Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö (Sweden); Karlsson, Johan [Department of Chemical and Biological Engineering, Applied Surface Chemistry, Chalmers University of Technology, Gothenburg (Sweden); Ferroni, Letizia; Gardin, Chiara [Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Padova (Italy); Galli, Silvia; Wennerberg, Ann [Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö (Sweden); Zavan, Barbara [Department of Histology, Microbiology, and Medical Biotechnologies, University of Padova, Padova (Italy); Andersson, Martin [Department of Chemical and Biological Engineering, Applied Surface Chemistry, Chalmers University of Technology, Gothenburg (Sweden); Jimbo, Ryo [Department of Prosthodontics, Faculty of Odontology, Malmö University, Malmö (Sweden); Department of Applied Prosthodontics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki (Japan)

    2015-07-01

    The aim of this study was to evaluate the osteogenic response of human adipose-derived stromal cells (ADScs) to mesoporous titania (TiO{sub 2}) coatings produced with evaporation-induced self-assembly method (EISA) and loaded with magnesium. Our emphasis with the magnesium release functionality was to modulate progenitor cell osteogenic differentiation under standard culture conditions. Osteogenic properties of the coatings were assessed for stromal cells by means of scanning electron microscopy (SEM) imaging, colorimetric mitochondrial viability assay (MTT), colorimetric alkaline phosphates activity (ALP) assay and real time RT-polymerase chain reaction (PCR). Using atomic force microscopy (AFM) it was shown that the surface expansion area (S{sub dr}) was strongly enhanced by the presence of magnesium. From MTT results it was shown that ADSc viability was significantly increased on mesoporous surfaces compared to the non-porous one at a longer cell culture time. However, no differences were observed between the magnesium impregnated and non-impregnated surfaces. The alkaline phosphatase activity confirmed that ADSc started to differentiate into the osteogenic phenotype after 2 weeks of culturing. The gene expression profile at 2 weeks of cell growth showed that such coatings were capable to incorporate specific osteogenic markers inside their interconnected nano-pores and, at 3 weeks, ADSc differentiated into osteoblasts. Interestingly, magnesium significantly promoted the osteopontin gene expression, which is an essential gene for the early biomaterial–cell osteogenic interaction. - Highlights: • The magnesium loading presents a transitory effect on mesoporous TiO{sub 2} surface topography • The mesoporous structure promotes cellular attachment and spreading • The mesoporous structure activates osteogenesis of mesenchymal stem cells in absence of osteogenic promoters • The physical adsorbed magnesium is suggested to be involved in the expression of

  15. 3-dimensional Griess algebras and Miyamoto involutions

    OpenAIRE

    lam, Ching Hung; Yamauchi, Hiroshi

    2016-01-01

    We consider a series of VOAs generated by 3-dimensional Griess algebras. We will show that these VOAs can be characterized by their 3-dimensional Griess algebras and their structures are uniquely determined. As an application, we will determine the groups generated by the Miyamoto involutions associated to Virasoro vectors of our VOAs.

  16. M-BAND Analysis of Chromosome Aberration Induced by Fe-Ions in Human Epithelial Cells Cultured in 3-Dimensional Matrices

    Science.gov (United States)

    Hada, M.; Cucinotta, F. A.; Wu, H.

    2008-01-01

    Energetic heavy ions pose a great health risk to astronauts in extended ISS and future lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied low- and high-LET radiation-induced chromosome aberrations in human epithelial cells cultured in 2-dimension (2D) using the multicolor banding fluorescence in situ hybridization (mBAND) technique. However, it has been realized that the biological response to radiation insult in a 2D cellular environment in vitro can differ significantly from the response in 3-dimension (3D) or at the actual tissue level. In this study, we cultured human epithelial cells in 3D to provide a more suitable model for human tissue. Human mammary epithelia cells (CH184B5F5/M10) were grown in Matrigel to form 3D structures, and exposed to Fe-ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory or 137Cs-gamma radiation source at the University of Texas MD Anderson Cancer Center. After exposure, cells were allowed to repair for 16hr before dissociation and subcultued at low density in 2D. G2 and metaphase chromosomes in the first cell cycle were collected using a chemical-induced premature chromosome condensation (PCC) technique, and chromosome aberrations were analyzed using mBAND technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Our data indicate a significant difference of the chromosome aberration yield between 2D and 3D cell cultures for gamma exposures, but not for Fe ion exposures

  17. Naringenin exerts anti-angiogenic effects in human endothelial cells: Involvement of ERRα/VEGF/KDR signaling pathway.

    Science.gov (United States)

    Li, Qunyi; Wang, Yi; Zhang, Liudi; Chen, Lu; Du, Yongli; Ye, Ting; Shi, Xiaojin

    2016-06-01

    Naringenin (Nar), most abundant in oranges and tomatoes, are known for the hypocholesterolemic, anti-estrogenic, hypolipidemic, anti-hypertensive, and anti-inflammatory activities. Here, the present study was designed to investigate the in vitro and in vivo anti-angiogenesis of Nar. Inhibition of angiogenesis was determined in vitro by using proliferation, apoptosis, migration, and tube-formation assays in Nar-treated human endothelial cell. Finally, CAM assays were used to assess inhibitory effect of Nar on physiological angiogenesis in vivo. The data suggest that Nar should be a direct ERRα inhibitor capable of inhibiting angiogenesis in vitro and in vivo, including endothelial cell proliferation, survival, migration and capillary-like structures formation of HUVECs, as well as reduced neovascularization of the CAM. Furthermore, the effects exerted by Nar are cell cycle related and mediated by VEGF/KDR signaling pathway along with downregulation of certain proangiogenic inflammatory cytokines. Our data thus provide potential molecular mechanisms through which Nar manifests it as a promising anti-angiogenic and anti-cancer agent. PMID:27105956

  18. 3-Dimensional ZnO/CdS nanocomposite with high mobility as an efficient electron transport layer for inverted polymer solar cells.

    Science.gov (United States)

    Wang, Yilin; Fu, Haiyan; Wang, Ying; Tan, Licheng; Chen, Lie; Chen, Yiwang

    2016-04-28

    The inclusions of solution-processed ZnO electron transport layers (ETLs) of inverted polymer solar cells can lead to various surface defects, which can act as interfacial recombination centers for photogenerated charges and thereby can lead to degradation of the device performance. Three-dimensional (3D) CdS with different morphologies, such as flower-like CdS (F-CdS), branched CdS (B-CdS), and spherical CdS (S-CdS), are synthesized to modify ZnO ETLs, by effectively removing the intragap states of the ZnO nanocrystal films by forming ZnO/F-CdS, ZnO/B-CdS, and ZnO/S-CdS composite ETLs, respectively. Moreover, ZnO/CdS possesses higher electron mobility and provides a larger interface between the ETL and active layer, which is beneficial for enhancing the power conversion efficiency (PCE) of the inverted organic solar cells. In particular, a device based on a ZnO/S-CdS ETL and thieno[3,4-b]-thiophene/benzodithiophene (PTB7):[6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) active layer achieved a PCE of 8.0%, together with better long-term stability. PMID:27074904

  19. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.

    Science.gov (United States)

    Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

    2016-01-01

    Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2-5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer. PMID:26699876

  20. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis

    Science.gov (United States)

    Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

    2016-01-01

    abstract Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2–5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer. PMID:26699876

  1. Transparent, 3-dimensional light-collected, and flexible fiber-type dye-sensitized solar cells based on highly ordered hierarchical anatase TiO2 nanorod arrays

    Science.gov (United States)

    Liang, Jia; Zhang, Gengmin; Yin, Jianbo; Yang, Yingchao

    2014-12-01

    Two kinds of hierarchical anatase TiO2 structures are synthesized by a facile hydrothermal method in this report. A new transparent, 3D light-collected, and flexible fiber-type dye-sensitized solar cell (FF-DSSC) with such hierarchical TiO2 structures is developed. The conversion efficiency of the FF-DSSC based on a TiCl4-treated TiO2 nanorod array (hierarchical structure I) exhibits about 4 times higher than that based on a HCl-treated TiO2 nanorod array, and further rises to 4.4% when the TiCl4-treated TiO2 nanorod array is treated in a mixed solution of (NH4)2TiF6 and H3BO3 three times (hierarchical structure II). The obvious enhancement in conversion efficiency can be ascribed to the dye adsorption promotion benefiting from their hierarchical structures. Beyond the attractive conversion efficiency, the new designed FF-DSSC possesses several advantages including good flexibility, excellent stability, and 3D light-collection. The conversion efficiencies of the FF-DSSCs can still keep 85%-90% even the FF-DSSCs are bent for 1000 times. The maximum power outputs of the FF-DSSCs characterized by Diffuse Illumination Mode using home-made Al reflector exhibit about 3 times higher than that done by Standard Illumination Mode due to 3D light-collections. The FF-DSSCs based on highly ordered hierarchical anatase TiO2 nanorod arrays hold great promise in future energy harvest.

  2. B cell development in the bone marrow is regulated by homeostatic feedback exerted by mature B cells

    Directory of Open Access Journals (Sweden)

    Gitit eShahaf

    2016-03-01

    Full Text Available Cellular homeostasis in the B cell compartment is strictly imposed to balance cell production and cell loss. However, it is not clear whether B cell development in the bone marrow (BM is an autonomous process or subjected to regulation by the peripheral B cell compartment. To specifically address this question, we used mice transgenic for human CD20, where effective depletion of B lineage cells is obtained upon administration of mouse-anti-human CD20 antibodies, in the absence of any effect on other cell lineages and/or tissues. We followed the kinetics of B cell return to equilibrium by BrdU labeling and flow cytometry and analyzed the resulting data by mathematical modeling. Labeling was much faster in depleted mice. Compared to control mice, B cell-depleted mice exhibited a higher proliferation rate in the pro-/pre-B compartment, and higher cell death and lower differentiation in the immature B cell compartment. We validated the first result by analysis of the expression of Ki67, the nuclear protein expressed in proliferating cells, and the second using Annexin-V staining. Collectively, our results suggest that B lymphopoiesis is subjected to homeostatic feedback mechanisms imposed by mature B cells in the peripheral compartment.

  3. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy

    Directory of Open Access Journals (Sweden)

    Min-Jung Bae

    2016-01-01

    Full Text Available The prevalence of allergic disorders including atopic dermatitis (AD and food allergy (FA has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3+CD4+ regulatory T cells (Tregs. The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3+CD4+ Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3+CD4+ Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

  4. Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy.

    Science.gov (United States)

    Bae, Min-Jung; See, Hye-Jeong; Choi, Gyeyoung; Kang, Chang-Yuil; Shon, Dong-Hwa; Shin, Hee Soon

    2016-01-01

    The prevalence of allergic disorders including atopic dermatitis (AD) and food allergy (FA) has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB) extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3(+)CD4(+) regulatory T cells (Tregs). The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3(+)CD4(+) Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3(+)CD4(+) Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs. PMID:27445434

  5. Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models.

    Directory of Open Access Journals (Sweden)

    Shujing Shi

    Full Text Available INTRODUCTION: Cytokine-induced killer cells (CIK cells are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. METHODS: We combined recombinant human endostatin (rh-endostatin and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. RESULTS: Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. CONCLUSIONS: Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells

  6. Combining Antiangiogenic Therapy with Adoptive Cell Immunotherapy Exerts Better Antitumor Effects in Non-Small Cell Lung Cancer Models

    Science.gov (United States)

    Shi, Shujing; Wang, Rui; Chen, Yitian; Song, Haizhu; Chen, Longbang; Huang, Guichun

    2013-01-01

    Introduction Cytokine-induced killer cells (CIK cells) are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. Methods We combined recombinant human endostatin (rh-endostatin) and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. Results Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. Conclusions Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells therapy against lung

  7. Butanol isomers exert distinct effects on voltage-gated calcium channel currents and thus catecholamine secretion in adrenal chromaffin cells.

    Directory of Open Access Journals (Sweden)

    Sarah McDavid

    Full Text Available Butanol (C4H10OH has been used both to dissect the molecular targets of alcohols/general anesthetics and to implicate phospholipase D (PLD signaling in a variety of cellular functions including neurotransmitter and hormone exocytosis. Like other primary alcohols, 1-butanol is a substrate for PLD and thereby disrupts formation of the intracellular signaling lipid phosphatidic acid. Because secondary and tertiary butanols do not undergo this transphosphatidylation, they have been used as controls for 1-butanol to implicate PLD signaling. Recently, selective pharmacological inhibitors of PLD have been developed and, in some cases, fail to block cellular functions previously ascribed to PLD using primary alcohols. For example, exocytosis of insulin and degranulation of mast cells are blocked by primary alcohols, but not by the PLD inhibitor FIPI. In this study we show that 1-butanol reduces catecholamine secretion from adrenal chromaffin cells to a much greater extent than tert-butanol, and that the PLD inhibitor VU0155056 has no effect. Using fluorescent imaging we show the effect of these drugs on depolarization-evoked calcium entry parallel those on secretion. Patch-clamp electrophysiology confirmed the peak amplitude of voltage-gated calcium channel currents (I(Ca is inhibited by 1-butanol, with little or no block by secondary or tert-butanol. Detailed comparison shows for the first time that the different butanol isomers exert distinct, and sometimes opposing, effects on the voltage-dependence and gating kinetics of I(Ca. We discuss these data with regard to PLD signaling in cellular physiology and the molecular targets of general anesthetics.

  8. Butanol isomers exert distinct effects on voltage-gated calcium channel currents and thus catecholamine secretion in adrenal chromaffin cells.

    Science.gov (United States)

    McDavid, Sarah; Bauer, Mary Beth; Brindley, Rebecca L; Jewell, Mark L; Currie, Kevin P M

    2014-01-01

    Butanol (C4H10OH) has been used both to dissect the molecular targets of alcohols/general anesthetics and to implicate phospholipase D (PLD) signaling in a variety of cellular functions including neurotransmitter and hormone exocytosis. Like other primary alcohols, 1-butanol is a substrate for PLD and thereby disrupts formation of the intracellular signaling lipid phosphatidic acid. Because secondary and tertiary butanols do not undergo this transphosphatidylation, they have been used as controls for 1-butanol to implicate PLD signaling. Recently, selective pharmacological inhibitors of PLD have been developed and, in some cases, fail to block cellular functions previously ascribed to PLD using primary alcohols. For example, exocytosis of insulin and degranulation of mast cells are blocked by primary alcohols, but not by the PLD inhibitor FIPI. In this study we show that 1-butanol reduces catecholamine secretion from adrenal chromaffin cells to a much greater extent than tert-butanol, and that the PLD inhibitor VU0155056 has no effect. Using fluorescent imaging we show the effect of these drugs on depolarization-evoked calcium entry parallel those on secretion. Patch-clamp electrophysiology confirmed the peak amplitude of voltage-gated calcium channel currents (I(Ca)) is inhibited by 1-butanol, with little or no block by secondary or tert-butanol. Detailed comparison shows for the first time that the different butanol isomers exert distinct, and sometimes opposing, effects on the voltage-dependence and gating kinetics of I(Ca). We discuss these data with regard to PLD signaling in cellular physiology and the molecular targets of general anesthetics.

  9. Green Tea Catechin Metabolites Exert Immunoregulatory Effects on CD4(+) T Cell and Natural Killer Cell Activities.

    Science.gov (United States)

    Kim, Yoon Hee; Won, Yeong-Seon; Yang, Xue; Kumazoe, Motofumi; Yamashita, Shuya; Hara, Aya; Takagaki, Akiko; Goto, Keiichi; Nanjo, Fumio; Tachibana, Hirofumi

    2016-05-11

    Tea catechins, such as (-)-epigallocatechin-3-O-gallate (EGCG), have been shown to effectively enhance immune activity and prevent cancer, although the underlying mechanism is unclear. Green tea catechins are instead converted to catechin metabolites in the intestine. Here, we show that these green tea catechin metabolites enhance CD4(+) T cell activity as well as natural killer (NK) cell activity. Our data suggest that the absence of a 4'-hydroxyl on this phenyl group (B ring) is important for the effect on immune activity. In particular, 5-(3',5'-dihydroxyphenyl)-γ-valerolactone (EGC-M5), a major metabolite of EGCG, not only increased the activity of CD4(+) T cells but also enhanced the cytotoxic activity of NK cells in vivo. These data suggest that EGC-M5 might show immunostimulatory activity. PMID:27112424

  10. Inhibition of Hypoxia Inducible Factor Alpha and Astrocyte-Elevated Gene-1 Mediates Cryptotanshinone Exerted Antitumor Activity in Hypoxic PC-3 Cells

    Directory of Open Access Journals (Sweden)

    Hyo-Jeong Lee

    2012-01-01

    Full Text Available Although cryptotanshinone (CT was known to exert antitumor activity in several cancers, its molecular mechanism under hypoxia still remains unclear. Here, the roles of AEG-1 and HIF-1α in CT-induced antitumor activity were investigated in hypoxic PC-3 cells. CT exerted cytotoxicity against prostate cancer cells and suppressed HIF-1α accumulation and AEG-1 expression in hypoxic PC-3 cells. Also, AEG-1 was overexpressed in prostate cancer cells. Interestingly, HIF-1α siRNA transfection enhanced the cleavages of caspase-9,3, and PAPR and decreased expression of Bcl-2 and AEG1 induced by CT in hypoxic PC-3 cells. Of note, DMOG enhanced the stability of AEG-1 and HIF-1α during hypoxia. Additionally, CT significantly reduced cellular level of VEGF in PC-3 cells and disturbed tube formation of HUVECs. Consistently, ChIP assay revealed that CT inhibited the binding of HIF-1α to VEGF promoter. Furthermore, CT at 10 mg/kg suppressed the growth of PC-3 cells in BALB/c athymic nude mice by 46.4% compared to untreated control. Consistently, immunohistochemistry revealed decreased expression of Ki-67, CD34, VEGF, carbonic anhydrase IX, and AEG-1 indices in CT-treated group compared to untreated control. Overall, our findings suggest that CT exerts antitumor activity via inhibition of HIF-1α, AEG1, and VEGF as a potent chemotherapeutic agent.

  11. Homological aperiodic tilings of 3-dimensional geometries

    CERN Document Server

    Nowak, Piotr W

    2012-01-01

    We construct the first aperiodic tiles for two amenable 3-dimensional Lie groups: Sol and the Heisenberg group. Our construction relies on the use of higher-dimensional uniformly finite homology. In particular, we settle completely the existence of aperiodic tiles for all of the non-compact geometries of 3-manifolds appearing in the geometrization conjecture.

  12. Expanding exertion gaming

    OpenAIRE

    Marshall, Joe; Mueller, Florian ‘Floyd’; Benford, Steve; Pijnappel, Sebastiaan

    2016-01-01

    While exertion games - digital games where the outcome is determined by physical exertion - are of growing interest in HCI, we believe the current health and fitness focus in the research of exertion games limits the opportunities this field has to offer. In order to broaden the agenda on exertion games, we link the existing fields of sports and interactive entertainment (arguing these fields have much to offer) by presenting four of our own designs as case studies. Using our experiences with...

  13. Hsp40 Gene Therapy Exerts Therapeutic Effects on Polyglutamine Disease Mice via a Non-Cell Autonomous Mechanism

    OpenAIRE

    H. Akiko Popiel; Toshihide Takeuchi; Hiromi Fujita; Kazuhiro Yamamoto; Chiyomi Ito; Hiroshi Yamane; Shin-ichi Muramatsu; Tatsushi Toda; Keiji Wada; Yoshitaka Nagai

    2012-01-01

    The polyglutamine (polyQ) diseases such as Huntington's disease (HD), are neurodegenerative diseases caused by proteins with an expanded polyQ stretch, which misfold and aggregate, and eventually accumulate as inclusion bodies within neurons. Molecules that inhibit polyQ protein misfolding/aggregation, such as Polyglutamine Binding Peptide 1 (QBP1) and molecular chaperones, have been shown to exert therapeutic effects in vivo by crossing of transgenic animals. Towards developing a therapy usi...

  14. Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells.

    Science.gov (United States)

    Lin, Chu-Lun; Hsiao, George; Wang, Ching-Chiung; Lee, Yueh-Lun

    2016-08-01

    Imperatorin is a furanocoumarin compound which exists in many medicinal herbs and possesses various biological activities. Herein, we investigated the antiallergic effects of imperatorin in asthmatic mice and explored the immunomodulatory actions of imperatorin on immune cells. We used a murine model of ovalbumin (OVA)-induced asthma to evaluate the therapeutic potential of imperatorin. Additionally, bone marrow-derived dendritic cells (DCs; BMDCs) were used to clarify whether imperatorin exerts an antiallergic effect through altering the ability of DCs to regulate T cells. Oral administration of imperatorin to OVA-sensitized and -challenged mice decreased serum OVA-specific immunoglobulin E (IgE) production, attenuated the airway hyperresponsiveness (AHR), and alleviated airway inflammation in a dose-dependent manner. Notably, secretions of Th2 cytokines and chemokines were reduced, and numbers of interleukin (IL)-10-producing regulatory T cells (Tregs) increased in imperatorin-treated mice. Imperatorin inhibited proinflammatory cytokines and IL-12 production but enhanced IL-10 secretion by lipopolysaccharide (LPS)-stimulated BMDCs. Compared to fully mature DCs, imperatorin-treated DCs expressed high levels of the inducible costimulatory ligand (ICOSL) and Jagged1 molecules, and had the regulatory capacity to promote the generation of IL-10-producing CD4(+) T cells in vitro. Additionally, imperatorin directly suppressed activated CD4(+) T-cell proliferation and cytokine production. Imperatorin may possess therapeutic potential against Th2-mediated allergic asthma not only via stimulating DC induction of Tregs but also via direct inhibition of Th2 cell activation. These findings provide new insights into how imperatorin affects the Th2 immune response and the development of imperatorin as a Treg-type immunomodulatory agent to treat allergic asthma. PMID:27185659

  15. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Angeliki Tiptiri-Kourpeti

    Full Text Available Probiotic microorganisms such as lactic acid bacteria (LAB exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof on murine (CT26 and human (HT29 colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9 CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells. In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9 CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain.

  16. Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells.

    Science.gov (United States)

    Tiptiri-Kourpeti, Angeliki; Spyridopoulou, Katerina; Santarmaki, Valentina; Aindelis, Georgios; Tompoulidou, Evgenia; Lamprianidou, Eleftheria E; Saxami, Georgia; Ypsilantis, Petros; Lampri, Evangeli S; Simopoulos, Constantinos; Kotsianidis, Ioannis; Galanis, Alex; Kourkoutas, Yiannis; Dimitrellou, Dimitra; Chlichlia, Katerina

    2016-01-01

    Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti-proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis-inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID:26849051

  17. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

    Directory of Open Access Journals (Sweden)

    Tayra Judith

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  18. Hydroelectric structures studies using 3-dimensional methods

    Energy Technology Data Exchange (ETDEWEB)

    Harrell, T.R.; Jones, G.V.; Toner, C.K. (Southern Electric International, Birmingham, AL (USA))

    1989-01-01

    Deterioration and degradation of aged, hydroelectric project structures can significantly affect the operation and safety of a project. In many cases, hydroelectric headworks (in particular) have complicated geometrical configurations, loading patterns and hence, stress conditions. An accurate study of such structures can be performed using 3-dimensional computer models. 3-D computer models can be used for both stability evaluation and for finite element stress analysis. Computer aided engineering processes facilitate the use of 3-D methods in both pre-processing and post-processing of data. Two actual project examples are used to emphasize the authors' points.

  19. A New Approach to 3-Dimensional Fields

    OpenAIRE

    agashe, sadanand

    2016-01-01

    A new approach, using the operator "x d/dx + y d/dy + z d/dz", is introduced for studying 3-dimensional scalar and vector fields. The approach uses a property of the operator which is similar to that of the Laplacian operator, but the operator does not seem to have been used before. Also, the operator requires only once-differentiability of the fields. Using it, a number of new formulas are derived and new proofs given for many classical results such as the Helmholtz theorem, the Poisson form...

  20. 3-dimensional defect TQFTs and their tricategories

    CERN Document Server

    Carqueville, Nils; Schaumann, Gregor

    2016-01-01

    We initiate a systematic study of 3-dimensional `defect' topological quantum field theories, that we introduce as symmetric monoidal functors on stratified and decorated bordisms. For every such functor we construct a tricategory with duals, which is the natural categorification of a pivotal bicategory. This captures the algebraic essence of defect TQFTs, and it gives precise meaning to the fusion of line and surface defects as well as their duality operations. As examples, we discuss how Reshetikhin-Turaev and Turaev-Viro theories embed into our framework, and how they can be extended to defect TQFTs.

  1. Lactobacillus acidophilus (strain LB) from the resident adult human gastrointestinal microflora exerts activity against brush border damage promoted by a diarrhoeagenic Escherichia coli in human enterocyte-like cells

    OpenAIRE

    Liévin-Le Moal, V; Amsellem, R; Servin, A.L.; Coconnier, M-H

    2002-01-01

    Background and aims: The normal gastrointestinal microflora exerts a barrier effect against enteropathogens. The aim of this study was to examine whether lactobacilli, a minor genus of the resident gut microflora, exerts a protective effect against the cellular injuries promoted by the diarrhoeagenic Afa/Dr diffusely adhering Escherichia coli (Afa/Dr DAEC) C1845 strain in human intestinal cells.

  2. Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional Gelfoam® histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging.

    Science.gov (United States)

    Yano, Shuya; Miwa, Shinji; Mii, Sumiyuki; Hiroshima, Yukihiko; Uehara, Fuminaru; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Zhao, Ming; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2015-01-01

    The phase of the cell cycle can determine whether a cancer cell can respond to a given drug. We previously reported monitoring of real-time cell cycle dynamics of cancer cells throughout a live tumor, intravitally in live mice, using a fluorescence ubiquitination-based cell-cycle indicator (FUCCI). Approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after cessation of chemotherapy. These results suggested why most drugs currently in clinical use, which target cancer cells in S/G2/M, are mostly ineffective on solid tumors. In the present report, we used FUCCI imaging and Gelfoam® collagen-sponge-gel histoculture, to demonstrate in real time, that the cell-cycle phase distribution of cancer cells in Gelfoam® and in vivo tumors is highly similar, whereby only the surface cells proliferate and interior cells are quiescent in G0/G1. This is in contrast to 2D culture where most cancer cells cycle. Similarly, the cancer cells responded similarly to toxic chemotherapy in Gelfoam® culture as in vivo, and very differently than cancer cells in 2D culture which were much more chemosensitive. Gelfoam® culture of FUCCI-expressing cancer cells offers the opportunity to image the cell cycle of cancer cells continuously and to screen for novel effective therapies to target quiescent cells, which are the majority in a tumor and which would have a strong probability to be effective in vivo. PMID:25564963

  3. XuefuZhuyu Tang exerts antitumor effects by inhibiting glioma cell metastasis and invasion via regulating tumor microenvironment

    Science.gov (United States)

    Liu, Jianmin; Zhang, Ji; Huang, Liangwen; Zhu, Xuhong; Chen, Wei; Hu, Peng

    2016-01-01

    Background XuefuZhuyu Tang (XZT) is a traditional Chinese herb used for destagnation and is currently being used for oncotherapy. This study was intended to assess the effects of XZT on glioma along with its anticancer mechanism. Materials and methods U251 cells were divided into five groups: CNC (cells were cultured with normal saline), TSC (cells were treated with TaohongSiwu Tang [TST]), XSC (cells were treated with XZT), THC (cells were treated with homogenate of TST), and XHC (cells were treated with homogenate of XZT). The mRNA and protein expression of VEGF/VEGFR, CXCR4/CXCL12, and TIMP1/MMP9/MMP2 were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. Moreover, MTT assay, transwell assay, wound-healing assay, and flow cytometry were conducted to assess the cell viability, cell migration and invasion, cell motility, and cell apoptosis of U251 cells, respectively. In vivo, three mice models (group CNM, gavaging saline; group TSM, gavaging TST; group XZM, gavaging XZT) were constructed after establishing xenograft mice models. Then, models were examined using hematoxylin and eosin staining, RT-PCR, and Western blotting. Results In vitro, XZT significantly upregulated TIMP1 expression and downregulated the expression of VEGF, VEGFR, CXCR4, CXCL12, MMP9, and MMP2 in U251 cells (all Pherb for curing glioma. PMID:27382298

  4. White tea (Camellia sinensis Kuntze) exerts neuroprotection against hydrogen peroxide-induced toxicity in PC12 cells.

    Science.gov (United States)

    López, Víctor; Calvo, Maria Isabel

    2011-03-01

    Tea is a popular beverage whose consumption is associated with prevention of certain disorders. The objective of the study was to investigate the potential neuroprotective effect of white tea extract (WTE) on hydrogen peroxide induced toxicity in PC12 cells. Cells were treated with various doses of WTE (10-250 μg/ml) before exposition to 250 μM hydrogen peroxide and cell survival was determined through the MTT and LDH assays. Oxidative stress was quantified in the cells after treatments as intracellular reactive oxygen species (ROS) production and the antioxidant activity of the extract was assessed in a cell free system in terms of free radical scavenging capacity. Results showed that WTE has a significant protective effect in the PC12 cell line against hydrogen peroxide as cell survival was significantly superior in WTE-treated cells compared to hydrogen peroxide-treated cells. A reduction on intracellular oxidative stress as well as radical scavenging properties were produced by WTE. Results suggest that WTE protects PC12 cells against H(2)O(2)-induced toxicity, and that an antioxidant mechanism through ROS scavenging may be in part responsible for cells neuroprotection. PMID:21271291

  5. 3-dimensional bioprinting for tissue engineering applications.

    Science.gov (United States)

    Gu, Bon Kang; Choi, Dong Jin; Park, Sang Jun; Kim, Min Sup; Kang, Chang Mo; Kim, Chun-Ho

    2016-01-01

    The 3-dimensional (3D) printing technologies, referred to as additive manufacturing (AM) or rapid prototyping (RP), have acquired reputation over the past few years for art, architectural modeling, lightweight machines, and tissue engineering applications. Among these applications, tissue engineering field using 3D printing has attracted the attention from many researchers. 3D bioprinting has an advantage in the manufacture of a scaffold for tissue engineering applications, because of rapid-fabrication, high-precision, and customized-production, etc. In this review, we will introduce the principles and the current state of the 3D bioprinting methods. Focusing on some of studies that are being current application for biomedical and tissue engineering fields using printed 3D scaffolds. PMID:27114828

  6. A dilogarithmic 3-dimensional Ising tetrahedron

    CERN Document Server

    Broadhurst, D J

    1999-01-01

    In 3 dimensions, the Ising model is in the same universality class as unknown analytical nature. In contrast, all single-scale 4-dimensional tetrahedra were reduced, in hep-th/9803091, to special values of exponentially convergent polylogarithms. Combining dispersion relations with the integer-relation finder PSLQ, we find that $C^{Tet}/2^{5/2} = Cl_2(4\\alpha) - Cl_2(2\\alpha)$, with $Cl_2(\\theta):=\\sum_{n>0}\\sin(n\\theta)/n^2$ and 1,000-digit precision and readily yields 50,000 digits of $C^{Tet}$, after transformation to an exponentially convergent sum, akin to those studied in math.CA/9803067. It appears that this 3-dimensional result entails a polylogarithmic ladder beginning with the classical formula for $\\pi/\\sqrt2$, in the manner that 4-dimensional results build on that for $\\pi/\\sqrt3$.

  7. Lentinan exerts synergistic apoptotic effects with paclitaxel in A549 cells via activating ROS-TXNIP-NLRP3 inflammasome

    OpenAIRE

    Liu, Wei; Gu, Jun; Qi, Jun; Zeng, Xiao-Ning; Ji, Juan; Chen, Zheng-Zhen; Sun, Xiu-Lan

    2015-01-01

    Paclitaxel is generally used to treat cancers in clinic as an inhibitor of cell division. However, the acquired resistance in tumours limits its clinical efficacy. Therefore, the aim of this study was to detect whether co-treatment with lentinan enhanced the anti-cancer effects of paclitaxel in A549 cells. We found that the combination of paclitaxel and lentinan resulted in a significantly stronger inhibition on A549 cell proliferation than paclitaxel treatment alone. Co-treatment with paclit...

  8. Silver nanoparticles exert a long-lasting antiproliferative effect on human keratinocyte HaCaT cell line.

    Science.gov (United States)

    Zanette, Caterina; Pelin, Marco; Crosera, Matteo; Adami, Gianpiero; Bovenzi, Massimo; Larese, Francesca Filon; Florio, Chiara

    2011-08-01

    For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products designed to come in direct contact with the skin. In this study we investigated the effects of Ag NPs on skin using the human-derived keratinocyte HaCaT cell line model. Ag NPs caused a concentration- and time-dependent decrease of cell viability, with IC(50) values of 6.8 ± 1.3 μM (MTT assay) and 12 ± 1.2 μM (SRB assay) after 7 days of contact. A 24h treatment, followed by a 6 day recovery period in Ag NPs-free medium, reduced cell viability with almost the same potency (IC(50)s of 15.3 ± 4.6 and 35 ± 20 μM, MTT and SRB assays, respectively). Under these conditions, no evidence of induction of necrotic events (propidium iodide assay) was found. Apocynin, NADPH-oxidase inhibitor, or N(G)-monomethyl-L-argynine, nitric oxide synthase inhibitor, did not prevent NPs-induced reduction of cell viability. TEM analysis of cells exposed to NPs for 24h revealed alteration of nuclear morphology but only a marginal presence of individual NPs inside the cells. These results demonstrate that on HaCaT keratinocytes a relatively short time of contact with Ag NPs causes a long-lasting inhibition of cell growth, not associated with consistent Ag NPs internalization.

  9. Combination of temozolomide and Taxol exerts a synergistic inhibitory effect on Taxol‑resistant glioma cells via inhibition of glucose metabolism.

    Science.gov (United States)

    Guan, Ding-Guo; Chen, Han-Min; Liao, Sheng-Fang; Zhao, Tian-Zhi

    2015-11-01

    Malignant gliomas, which comprise the most common type of primary malignant brain tumor, are associated with a poor prognosis and quality of life. Paclitaxel (Taxol) and temozolomide (TMZ) are Food and Drug Administration‑approved anticancer agents, which are known to have therapeutic applications in various malignancies. However, similar to other chemotherapeutic agents, the development of resistance to TMZ and Taxol is common. The aim of the present study was to investigate the regulation of glucose metabolism by TMZ and Taxol in glioma cells. The results demonstrated that glioma cells exhibit decreased glucose uptake and lactate production in response to treatment with TMZ; however, glucose metabolism was increased in response to Taxol treatment. Following analysis of TMZ‑ and Taxol‑resistant cell lines, it was reported that glucose metabolism was decreased in the TMZ‑resistant cells, but was increased in the Taxol‑resistant cells. Notably, a combination of TMZ and Taxol exerted synergistic inhibitory effects on Taxol‑resistant glioma cells. However, the synergistic phenotype was not observed following treatment with a combination of 5‑fluorouracil and Taxol. Furthermore, restoration of glucose metabolism by overexpression of glucose transporter 1 in Taxol‑resistant cells resulted in regained resistance to Taxol. Therefore, the present study proposes a novel mechanism accounting for the synergistic effects of Taxol and TMZ co‑treatment, which may contribute to the development of therapeutic strategies for overcoming chemoresistance in patients with cancer.

  10. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Directory of Open Access Journals (Sweden)

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  11. AZD-4547 exerts potent cytostatic and cytotoxic activities against fibroblast growth factor receptor (FGFR)-expressing colorectal cancer cells.

    Science.gov (United States)

    Yao, Ting-Jing; Zhu, Jin-Hai; Peng, De-Feng; Cui, Zhen; Zhang, Chao; Lu, Pei-hua

    2015-07-01

    Colorectal cancer (CRC) causes significant mortalities worldwide. Fibroblast growth factor (FGF) receptor (FGFR) signaling is frequently dysregulated and/or constitutively activated in CRCs, contributing to cancer carcinogenesis and progression. Here, we studied the activity of AZD-4547, a novel and potent FGFR kinase inhibitor, on CRC cells. AZD-4547 inhibited CRC cell growth in vitro, and its activity correlated with the FGFR-1/2 expression level. AZD-4547 was cytotoxic and pro-apoptotic in FGFR-1/2-expressed CRC cell lines (NCI-H716 and HCT-116), but not in FGFR-1/2 null HT-29 cells. Further, AZD-4547 inhibited cell cycle progression and attenuated the activation of FGFR1-FGFR substrate 2 (FRS-2), ERK/mitogen-activated protein kinase (MAPK), and AKT/mammalian target of rapamycin (AKT/mTOR) signalings in NCI-H716 and HCT-116 cells. In vivo, AZD-4547 oral administration at effective doses inhibited NCI-H716 (high FGFR-1/2 expression) xenograft growth in nude mice. Phosphorylation of FGFR-1, AKT, and ERK1/2 in xenograft specimens was also inhibited by AZD-4547 administration. Thus, our preclinical studies strongly support possible clinical investigations of AZD-4547 for the treatment of CRCs harboring deregulated FGFR signalings. PMID:25691251

  12. HOXA13 exerts a beneficial effect in albumin-induced epithelial-mesenchymal transition via the glucocorticoid receptor signaling pathway in human renal tubular epithelial cells.

    Science.gov (United States)

    Peng, Li; He, Qingnan; Li, Xiaoyan; Shuai, Lanjun; Chen, Haixia; Li, Yongzhen; Yi, Zhuwen

    2016-07-01

    Previous studies have suggested that albumin-induced renal tubular epithelial cell injury contributes to renal interstitial fibrosis. Epithelial-mesenchymal transition (EMT) is known to be a key mechanism in the pathogenesis and progression of renal interstitial fibrosis. Homeobox protein HOX‑A13 (HOXA13) is a nuclear transcriptional factor that has been reported to be involved in renal fibrosis. However, the mechanism underlying the effect of HOXA13 in human serum albumin (HSA)‑induced EMT in HKC renal tubular epithelial cells remains to be elucidated. Thus, the aim of the present study was to investigate the role of HOXA13 in HSA‑induced EMT in HKC cells and the potential mechanism of the glucocorticoid receptor (GR) signaling pathway. The protein and mRNA expression levels of HOXA13, cytokeratin, and vimentin were determined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction in HKC cells, which were co‑incubated with HSA at different concentrations or for different time periods. The results demonstrated that HOXA13 mRNA and protein expression decreased in a dose‑ and time‑dependent manner when induced by HSA in HCK cells. The liposomal transfection experiment suggested that overexpression of HOXA13 activated the GR signal, which inhibits HSA-induced EMT. HOXA13 is involved in HSA‑induced EMT in HKC cells and upregulation of HOXA13 exerts a beneficial effect in EMT, which may be associated with the GR signaling pathway. PMID:27176855

  13. BRAF kinase inhibitor exerts anti-tumor activity against breast cancer cells via inhibition of FGFR2.

    Science.gov (United States)

    Zhang, Zong Xin; Jin, Wen Jun; Yang, Sheng; Ji, Cun Li

    2016-01-01

    Most anti-angiogenic therapies currently being evaluated in clinical trials targetvascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here we identified BRAF kinase inhibitor, vemurafenibas an agent with potential anti-angiogenic and anti-breast cancer activities. Vemurafenib demonstrated inhibition of endothelial cell proliferation, migration, and tube formation in response to basic fibroblast growth factor (bFGF). In ex vivo and in vivo angiogenesis assays, vemurafenib suppressed bFGF-induced microvessel sprouting of rat aortic rings and angiogenesis in vivo. To understand the underlying molecular basis, we examined the effects of vemurafenib on different molecular components in treated endothelial cell, and found that vemurafenib suppressed bFGF-triggered activation of FGFR2 and protein kinase B (AKT). Moreover, vemurafenib directly inhibited proliferation and blocked the oncogenic signaling pathways in breast cancer cell. In vivo, using xenograft models of breast cancer cells MDA-MB-231, vemurafenib showed growth-inhibitory activity associated with inhibition of tumor angiogenesis. Taken together, our results indicate that vemurafenib targets the FGFR2-mediated AKT signaling pathway in endothelial cells, leading to the suppression of tumor growth and angiogenesis.

  14. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    Science.gov (United States)

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract.

  15. Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.

    Science.gov (United States)

    López, Víctor; Pérez, Sergio; Vinuesa, Arturo; Zorzetto, Christian; Abian, Olga

    2016-04-01

    Steviol glycosides are currently being used as natural sweeteners by the food industry and Stevia rebaudiana has long been used as a sweet plant in South America for patients suffering from diabetes. In this study, a Stevia rebaudiana ethanolic extract (SREE) was prepared, analysed and tested for antioxidant activity in terms of free radical scavenging properties and antiproliferative effects in cervix (HeLa), pancreatic (MiaPaCa-2) and colonic (HCT116) cancer cells. The antiproliferative mechanism was confirmed by testing the effects on cyclin D1-CDK4. Bioassays were also performed for the diterpene glycoside stevioside. Our results demonstrate that the extract acts as an antioxidant being able to scavenge free radicals, but this activity was not due to stevioside. The extract also induced cell death in the three cell lines, being more active against cervix cancer cells (HeLa); however, the concentration of stevioside needed to produce antiproliferative effects was higher than the amount of steviol glycosides found in a lower dose of extract inducing cell death. In addition, the extract clearly inhibited CDK4 whereas stevioside did not, concluding that the antiproliferative activity of stevia may be due to inhibition of cyclin-dependent kinases performed by other compounds of the extract. PMID:27071804

  16. Noni (Morinda citrifolia L.) Fruit Extracts Improve Colon Microflora and Exert Anti-Inflammatory Activities in Caco-2 Cells.

    Science.gov (United States)

    Huang, Hsin-Lun; Liu, Cheng-Tzu; Chou, Ming-Chih; Ko, Chien-Hui; Wang, Chin-Kun

    2015-06-01

    Intestinal microflora and inflammation are associated with the risk of inflammatory bowel diseases. Noni (Morinda citrifolia L.) has various bioactivities, but its effect on colon health remains unknown. This study focused on the effects of fermented noni fruit extracts on colon microflora and inflammation of colon epithelial cells. The anti-inflammatory activities of ethanol and ethyl acetate extracts on Caco-2 cells were evaluated including interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2). The growth of Lactobacillus and Bifidobacterium species was promoted by ethanol extract. Ethyl acetate extract decreased intracellular reactive oxygen species and significantly suppressed COX-2, IL-8, and prostaglandin E2 production and neutrophil chemotaxis by suppressing the translocation of the p65 subunit. Quercetin was the main contributor to the anti-inflammatory activity. The fermented noni fruit promoted probiotic growths and downregulated the intracellular oxidation and inflammation in Caco-2 cells. These results suggest that fermented noni fruit might protect against inflammatory diseases of the colon.

  17. Differential Cytotoxicity of MEX: a Component of Neem Oil Whose Action Is Exerted at the Cell Membrane Level

    Directory of Open Access Journals (Sweden)

    Francesca Ricci

    2008-12-01

    Full Text Available Neem oil is obtained from the seeds of the tree Azadirachta indica. Its chemical composition is very complex, being rich in terpenoids and limonoids, as well as volatile sulphur modified compounds. This work focused on the evaluation of a component of the whole Neem oil obtained by methanolic extraction and defined as MEX. Cytotoxicity was assessed on two different cell populations: a stabilized murine fibroblast line (3T6 and a tumor cell line (HeLa. The data presented here suggest a differential sensitivity of these two populations, the tumor line exhibiting a significantly higher sensitivity to MEX. The data strongly suggest that its toxic target is the cell membrane. In addition the results presented here imply that MEX may contain one or more agents that could find a potential use in anti-proliferative therapy.

  18. Differential Cytotoxicity of MEX: a Component of Neem Oil Whose Action Is Exerted at the Cell Membrane Level

    OpenAIRE

    Francesca Ricci; Valerio Berardi; Gianfranco Risuleo

    2008-01-01

    Neem oil is obtained from the seeds of the tree Azadirachta indica. Its chemical composition is very complex, being rich in terpenoids and limonoids, as well as volatile sulphur modified compounds. This work focused on the evaluation of a component of the whole Neem oil obtained by methanolic extraction and defined as MEX. Cytotoxicity was assessed on two different cell populations: a stabilized murine fibroblast line (3T6) and a tumor cell line (HeLa). The data presented here suggest a diffe...

  19. Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo

    Science.gov (United States)

    MA, WEN-HUI; LIU, YONG-CHAO; XUE, MEI-LAN; ZHENG, ZHENG; GE, YIN-LIN

    2016-01-01

    Metastasis constantly occurs in the majority of cases of primary breast cancer at late stage or following surgical treatment. Survivin, a member of the inhibitor of apoptosis protein family, has long been recognized as a promising anticancer target, but its antitumor effects remain largely unexplored. In order to elucidate the role of survivin in breast cancer metastasis, short interfering RNA (siRNA) was used in the present study to specifically downregulate survivin expression in the murine breast cancer cell line 4T1. The results demonstrated that blocking the expression of survivin by siRNA inhibited the proliferation, migration and invasion abilities of murine breast cancer cells in vitro. Vascular endothelial growth factor (VEGF)-C is a lymphatic endothelial cell-stimulating factor that may lead to the formation of lymphatic vessels in lymph nodes. In the present study, the inhibition of survivin by siRNA was able to reduce the overexpression of VEGF-C in 4T1 cells. Furthermore, intratumoral injections of the survivin-siRNA significantly inhibited the growth of orthotopically transplanted 4T1 tumors in vivo. In addition, the number of pulmonary metastases and the microlymphatic vessel density were significantly reduced in vivo, following transfection with survivin-siRNA. The results of the present study suggested that the Akt/hypoxia-inducible factor-1α signaling pathway participates in the survivin-mediated downregulation of VEGF-C expression observed in breast cancer cells treated with survivin-siRNA. Therefore, the use of siRNA specifically targeting survivin may be a potential anticancer method in the future. PMID:26870183

  20. Exertional Leg Pain.

    Science.gov (United States)

    Rajasekaran, Sathish; Finnoff, Jonathan T

    2016-02-01

    Exertional leg pain is a common condition seen in runners and the general population. Given the broad differential diagnosis of this complaint, this article focuses on the incidence, anatomy, pathophysiology, clinical presentation, diagnostic evaluation, and management of common causes that include medial tibial stress syndrome, tibial bone stress injury, chronic exertional compartment syndrome, arterial endofibrosis, popliteal artery entrapment syndrome, and entrapment of the common peroneal, superficial peroneal, and saphenous nerves. Successful diagnosis of these conditions hinges on performing a thorough history and physical examination followed by proper diagnostic testing and appropriate management. PMID:26616179

  1. Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway.

    Science.gov (United States)

    Wu, Xin; Dou, Yannong; Yang, Yan; Bian, Difei; Luo, Jinque; Tong, Bei; Xia, Yufeng; Dai, Yue

    2015-08-15

    Arctigenin, the main effective constituent of Arctium lappa L. fruit, has previously been proven to dramatically attenuate dextran sulfate sodium (DSS)-induced colitis in mice, a frequently used animal model of inflammatory bowel disease (IBD). As Th1 and Th17 cells play a crucial role in the pathogenesis of IBD, the present study addressed whether and how arctigenin exerted anti-colitis efficacy by interfering with the differentiation and activation of Th1/Th17 cells. In vitro, arctigenin was shown to markedly inhibit the differentiation of Th17 cells from naïve T cells, and moderately inhibit the differentiation of Th1 cells, which was accompanied by lowered phosphorylation of STAT3 and STAT4, respectively. In contrast, arctigenin was lack of marked effect on the differentiation of either Th2 or regulatory T cells. Furthermore, arctigenin was shown to suppress the mammalian target of rapamycin complex 1 (mTORC1) pathway in T cells as demonstrated by down-regulated phosphorylation of the downstream target genes p70S6K and RPS6, and it functioned independent of two well-known upstream kinases PI3K/AKT and ERK. Arctigenin was also able to inhibit the activity of mTORC1 by dissociating raptor from mTOR. Interestingly, the inhibitory effect of arctigenin on T cell differentiation disappeared under a status of mTORC1 overactivation via knockdown of tuberous sclerosis complex 2 (TSC2, a negative regulator of mTORC1) or pretreatment of leucine (an agonist of mTOR). In DSS-induced mice, the inhibition of Th1/Th17 responses and anti-colitis effect of arctigenin were abrogated by leucine treatment. In conclusion, arctigenin ameliorates colitis through down-regulating the differentiation of Th1 and Th17 cells via mTORC1 pathway. PMID:26074264

  2. Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway.

    Science.gov (United States)

    Wu, Xin; Dou, Yannong; Yang, Yan; Bian, Difei; Luo, Jinque; Tong, Bei; Xia, Yufeng; Dai, Yue

    2015-08-15

    Arctigenin, the main effective constituent of Arctium lappa L. fruit, has previously been proven to dramatically attenuate dextran sulfate sodium (DSS)-induced colitis in mice, a frequently used animal model of inflammatory bowel disease (IBD). As Th1 and Th17 cells play a crucial role in the pathogenesis of IBD, the present study addressed whether and how arctigenin exerted anti-colitis efficacy by interfering with the differentiation and activation of Th1/Th17 cells. In vitro, arctigenin was shown to markedly inhibit the differentiation of Th17 cells from naïve T cells, and moderately inhibit the differentiation of Th1 cells, which was accompanied by lowered phosphorylation of STAT3 and STAT4, respectively. In contrast, arctigenin was lack of marked effect on the differentiation of either Th2 or regulatory T cells. Furthermore, arctigenin was shown to suppress the mammalian target of rapamycin complex 1 (mTORC1) pathway in T cells as demonstrated by down-regulated phosphorylation of the downstream target genes p70S6K and RPS6, and it functioned independent of two well-known upstream kinases PI3K/AKT and ERK. Arctigenin was also able to inhibit the activity of mTORC1 by dissociating raptor from mTOR. Interestingly, the inhibitory effect of arctigenin on T cell differentiation disappeared under a status of mTORC1 overactivation via knockdown of tuberous sclerosis complex 2 (TSC2, a negative regulator of mTORC1) or pretreatment of leucine (an agonist of mTOR). In DSS-induced mice, the inhibition of Th1/Th17 responses and anti-colitis effect of arctigenin were abrogated by leucine treatment. In conclusion, arctigenin ameliorates colitis through down-regulating the differentiation of Th1 and Th17 cells via mTORC1 pathway.

  3. Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nicolas G. Azios

    2005-02-01

    Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

  4. Cardiothoracic Applications of 3-dimensional Printing.

    Science.gov (United States)

    Giannopoulos, Andreas A; Steigner, Michael L; George, Elizabeth; Barile, Maria; Hunsaker, Andetta R; Rybicki, Frank J; Mitsouras, Dimitris

    2016-09-01

    Medical 3-dimensional (3D) printing is emerging as a clinically relevant imaging tool in directing preoperative and intraoperative planning in many surgical specialties and will therefore likely lead to interdisciplinary collaboration between engineers, radiologists, and surgeons. Data from standard imaging modalities such as computed tomography, magnetic resonance imaging, echocardiography, and rotational angiography can be used to fabricate life-sized models of human anatomy and pathology, as well as patient-specific implants and surgical guides. Cardiovascular 3D-printed models can improve diagnosis and allow for advanced preoperative planning. The majority of applications reported involve congenital heart diseases and valvular and great vessels pathologies. Printed models are suitable for planning both surgical and minimally invasive procedures. Added value has been reported toward improving outcomes, minimizing perioperative risk, and developing new procedures such as transcatheter mitral valve replacements. Similarly, thoracic surgeons are using 3D printing to assess invasion of vital structures by tumors and to assist in diagnosis and treatment of upper and lower airway diseases. Anatomic models enable surgeons to assimilate information more quickly than image review, choose the optimal surgical approach, and achieve surgery in a shorter time. Patient-specific 3D-printed implants are beginning to appear and may have significant impact on cosmetic and life-saving procedures in the future. In summary, cardiothoracic 3D printing is rapidly evolving and may be a potential game-changer for surgeons. The imager who is equipped with the tools to apply this new imaging science to cardiothoracic care is thus ideally positioned to innovate in this new emerging imaging modality.

  5. Cardiothoracic Applications of 3-dimensional Printing.

    Science.gov (United States)

    Giannopoulos, Andreas A; Steigner, Michael L; George, Elizabeth; Barile, Maria; Hunsaker, Andetta R; Rybicki, Frank J; Mitsouras, Dimitris

    2016-09-01

    Medical 3-dimensional (3D) printing is emerging as a clinically relevant imaging tool in directing preoperative and intraoperative planning in many surgical specialties and will therefore likely lead to interdisciplinary collaboration between engineers, radiologists, and surgeons. Data from standard imaging modalities such as computed tomography, magnetic resonance imaging, echocardiography, and rotational angiography can be used to fabricate life-sized models of human anatomy and pathology, as well as patient-specific implants and surgical guides. Cardiovascular 3D-printed models can improve diagnosis and allow for advanced preoperative planning. The majority of applications reported involve congenital heart diseases and valvular and great vessels pathologies. Printed models are suitable for planning both surgical and minimally invasive procedures. Added value has been reported toward improving outcomes, minimizing perioperative risk, and developing new procedures such as transcatheter mitral valve replacements. Similarly, thoracic surgeons are using 3D printing to assess invasion of vital structures by tumors and to assist in diagnosis and treatment of upper and lower airway diseases. Anatomic models enable surgeons to assimilate information more quickly than image review, choose the optimal surgical approach, and achieve surgery in a shorter time. Patient-specific 3D-printed implants are beginning to appear and may have significant impact on cosmetic and life-saving procedures in the future. In summary, cardiothoracic 3D printing is rapidly evolving and may be a potential game-changer for surgeons. The imager who is equipped with the tools to apply this new imaging science to cardiothoracic care is thus ideally positioned to innovate in this new emerging imaging modality. PMID:27149367

  6. C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression

    Directory of Open Access Journals (Sweden)

    Luque Ana

    2008-09-01

    Full Text Available Abstract Background Formation of haemorrhagic neovessels in the intima of developing atherosclerotic plaques is thought to significantly contribute to plaque instability resulting in thrombosis. C-reactive protein (CRP is an acute phase reactant whose expression in the vascular wall, in particular, in reactive plaque regions, and circulating levels increase in patients at high risk of cardiovascular events. Although CRP is known to induce a pro-inflammatory phenotype in endothelial cells (EC a direct role on modulation of angiogenesis has not been established. Results Here, we show that CRP is a powerful inducer of angiogenesis in bovine aortic EC (BAEC and human coronary artery EC (HCAEC. CRP, at concentrations corresponding to moderate/high risk (1–5 μg/ml, induced a significant increase in proliferation, migration and tube-like structure formation in vitro and stimulated blood vessel formation in the chick chorioallantoic membrane assay (CAM. CRP treated with detoxi-gel columns retained such effects. Western blotting showed that CRP increased activation of early response kinase-1/2 (ERK1/2, a key protein involved in EC mitogenesis. Furthermore, using TaqMan Low-density Arrays we identified key pro-angiogenic genes induced by CRP among them were vascular endothelial cell growth factor receptor-2 (VEGFR2/KDR, platelet-derived growth factor (PDGF-BB, notch family transcription factors (Notch1 and Notch3, cysteine-rich angiogenic inducer 61 (CYR61/CCN1 and inhibitor of DNA binding/differentiation-1 (ID1. Conclusion This data suggests a role for CRP in direct stimulation of angiogenesis and therefore may be a mediator of neovessel formation in the intima of vulnerable plaques.

  7. Points of control exerted along the macrophage-endothelial cell-polymorphonuclear neutrophil axis by PECAM-1 in the innate immune response of acute colonic inflammation.

    Science.gov (United States)

    Sugimoto, Naohito; Rui, Tao; Yang, Min; Bharwani, Sulaiman; Handa, Osamu; Yoshida, Norimasa; Yoshikawa, Toshikazu; Kvietys, Peter R

    2008-08-01

    PECAM-1 is expressed on endothelial cells and leukocytes. Its extracellular domain has been implicated in leukocyte diapedesis. In this study, we used PECAM-1(-/-) mice and relevant cells derived from them to assess the role of PECAM-1 in an experimental model of acute colonic inflammation with a predominant innate immune response, i.e., 2,4,6-trinitrobenzine sulfonic acid (TNBS). Using chimeric approaches, we addressed the points of control exerted by PECAM-1 along the macrophage-endothelial cell-polymorphonuclear neutrophil (PMN) axis. In vivo, TNBS-induced colitis was ameliorated in PECAM-1(-/-) mice, an event attributed to PECAM-1 on hematopoietic cells rather than to PECAM-1 on endothelial cells. The in vivo innate immune response was mimicked in vitro by using a construct of the vascular-interstitial interface, i.e., PMN transendothelial migration was induced by colonic lavage fluid (CLF) from TNBS mice or macrophages (MPhi) challenged with CLF. Using the construct, we confirmed that endothelial cell PECAM-1 does not play a role in PMN transendothelial migration. Although MPhi activation (NF-kappaB nuclear binding) and function (keratinocyte-derived chemokine production) induced by CLF was diminished in PECAM-1(-/-) MPhi, this did not affect their ability to promote PMN transendothelial migration. By contrast, PECAM-1(-/-) PMN did not adhere to or migrate across endothelial cell monolayers in response to CLF. Further, as compared with PECAM-1(+/+) PMN, PECAM-1(-/-) PMN were less effective in orientating their CXCR2 receptors (polarization) in the direction of a chemotactic gradient. Collectively, our findings indicate that PECAM-1 modulation of PMN function (at a step before diapedesis) most likely contributes to the inflammation in a colitis model with a strong innate immune component. PMID:18641353

  8. FTIR Metabolomic Fingerprint Reveals Different Modes of Action Exerted by Structural Variants of N-Alkyltropinium Bromide Surfactants on Escherichia coli and Listeria innocua Cells

    Science.gov (United States)

    Corte, Laura; Tiecco, Matteo; Roscini, Luca; De Vincenzi, Sergio; Colabella, Claudia; Germani, Raimondo; Tascini, Carlo; Cardinali, Gianluigi

    2015-01-01

    Surfactants are extremely important agents to clean and sanitize various environments. Their biocidal activity is a key factor determined by the interactions between amphiphile structure and the target microbial cells. The object of this study was to analyze the interactions between four structural variants of N-alkyltropinium bromide surfactants with the Gram negative Escherichia coli and the Gram positive Listeria innocua bacteria. Microbiological and conductometric methods with a previously described FTIR bioassay were used to assess the metabolomic damage exerted by these compounds. All surfactants tested showed more biocidal activity in L. innocua than in E. coli. N-tetradecyltropinium bromide was the most effective compound against both species, while all the other variants had a reduced efficacy as biocides, mainly against E. coli cells. In general, the most prominent metabolomic response was observed for the constituents of the cell envelope in the fatty acids (W1) and amides (W2) regions and at the wavenumbers referred to peptidoglycan (W2 and W3 regions). This response was particularly strong and negative in L. innocua, when cells were challenged by N-tetradecyltropinium bromide, and by the variant with a smaller head and a 12C tail (N-dodecylquinuclidinium bromide). Tail length was critical for microbial inhibition especially when acting against E. coli, maybe due the complex nature of Gram negative cell envelope. Statistical analysis allowed us to correlate the induced mortality with the metabolomic cell response, highlighting two different modes of action. In general, gaining insights in the interactions between fine structural properties of surfactants and the microbial diversity can allow tailoring these compounds for the various operative conditions. PMID:25588017

  9. Major Components of Energy Drinks (Caffeine, Taurine, and Guarana Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production

    Directory of Open Access Journals (Sweden)

    Fares Zeidán-Chuliá

    2013-01-01

    Full Text Available Scope. To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs. Methods and Results. On human neuronal SH-SY5Y cells, caffeine (0.125–2 mg/mL, taurine (1–16 mg/mL, and guarana (3.125–50 mg/mL showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD and catalase (CAT activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5–50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Conclusion. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or “antioxidative stress”, could be a cause of in vitro toxicity induced by these drugs.

  10. Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    Li-Min Zhang; Cong-Cong Sun; Ming-Shu Mo; Luan Cen; Lei Wei; Fei-Fei Luo; Yi Li

    2015-01-01

    Background:Nurr1 plays an essential role in the development,survival,and function maintenance ofmidbrain dopaminergic (DA) neurons,and it is a potential target for Parkinson's disease (PD).Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs),but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive.This study aimed to measure the Nurrl mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.Methods:The mRNA levels of Nurrl in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured.The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC,as well as the subgroups of PD.Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale,age,and drug treatments.Besides,the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.Results:The relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010),respectively.Furthermore,the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group.Multivariate linear regression showed DA agonists,L-dopa,and DA agonists were independent predictors correlated with Nurrl mRNA expression level in PBMC.In vitro,in the cultured PBMC treated with 10 μmol/L pramipexole,the Nurr1 mRNA levels were significantly increased by 99.61%,71.75%,73.16% in 2,4,and 8 h,respectively (P < 0.001).Conclusions:DA agonists can induce Nurr1 expression in PBMC,and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.

  11. Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

    International Nuclear Information System (INIS)

    Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

  12. Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

    Energy Technology Data Exchange (ETDEWEB)

    Sebastià, N., E-mail: natividad.sebastia@uv.es [Radiation Protection Service, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Montoro, A. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Hervás, D. [Biostatistics Unit, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Pantelias, G.; Hatzi, V.I. [Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Centre for Scientific Research “Demokritos”, Aghia Paraskevi, Athens (Greece); Soriano, J.M. [Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Department of Preventive Medicine and Public Health, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia (Spain); Villaescusa, J.I. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); and others

    2014-08-15

    Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

  13. Fucoxanthin exerts differing effects on 3T3-L1 cells according to differentiation stage and inhibits glucose uptake in mature adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Seong-Il [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Ko, Hee-Chul [Jeju Sasa Industry Development Agency, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Shin, Hye-Sun; Kim, Hyo-Min; Hong, Youn-Suk [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Lee, Nam-Ho [Department of Chemistry, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Kim, Se-Jae, E-mail: sjkim@jejunu.ac.kr [Department of Biology, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of); Jeju Sasa Industry Development Agency, Jeju National University, Jejusi, Jeju 690-756 (Korea, Republic of)

    2011-06-17

    Highlights: {yields} Fucoxanthin enhances 3T3-L1 adipocyte differentiation at an early stage. {yields} Fucoxanthin inhibits 3T3-L1 adipocyte differentiation at intermediate and late stages. {yields} Fucoxanthin attenuates glucose uptake by inhibiting the phosphorylation of IRS in mature 3T3-L1 adipocytes. {yields} Fucoxanthin exerts its anti-obesity effect by inhibiting the differentiation of adipocytes at both intermediate and late stages, as well as glucose uptake in mature adipocytes. -- Abstract: Progression of 3T3-L1 preadipocyte differentiation is divided into early (days 0-2, D0-D2), intermediate (days 2-4, D2-D4), and late stages (day 4 onwards, D4-). In this study, we investigated the effects of fucoxanthin, isolated from the edible brown seaweed Petalonia binghamiae, on adipogenesis during the three differentiation stages of 3T3-L1 preadipocytes. When fucoxanthin was applied during the early stage of differentiation (D0-D2), it promoted 3T3-L1 adipocyte differentiation, as evidenced by increased triglyceride accumulation. At the molecular level, fucoxanthin increased protein expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), CCAAT/enhancer-binding protein {alpha} (C/EBP{alpha}), sterol regulatory element-binding protein 1c (SREBP1c), and aP2, and adiponectin mRNA expression, in a dose-dependent manner. However, it reduced the expression of PPAR{gamma}, C/EBP{alpha}, and SREBP1c during the intermediate (D2-D4) and late stages (D4-D7) of differentiation. It also inhibited the uptake of glucose in mature 3T3-L1 adipocytes by reducing the phosphorylation of insulin receptor substrate 1 (IRS-1). These results suggest that fucoxanthin exerts differing effects on 3T3-L1 cells of different differentiation stages and inhibits glucose uptake in mature adipocytes.

  14. Glycyrrhizin exerts antioxidative effects in H5N1 influenza A virus-infected cells and inhibits virus replication and pro-inflammatory gene expression.

    Directory of Open Access Journals (Sweden)

    Martin Michaelis

    Full Text Available Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549 cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 µg/ml but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/ml or higher. Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn reduced activation of NFκB, JNK, and p38, redox-sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.

  15. Projection printing of 3-dimensional tissue scaffolds.

    Science.gov (United States)

    Lu, Yi; Chen, Shaochen

    2012-01-01

    Our ability to create precise, predesigned, spatially patterned biochemical and physical microenvironments inside polymer scaffolds could provide a powerful tool in studying progenitor cell behavior and differentiation under biomimetic, three-dimensional (3D) culture conditions. The development of freeform fabrication technology has become a promising tool for the manufacturing of biological scaffolds for tissue regeneration and stem cell engineering. Freeform fabrication is a very promising technology due to the efficient and simple process for creating bona fide 3D microstructures, such as closed channels and cavities. It is also capable of encapsulating biomolecules and even living cells. This chapter describes direct projection printing of 3D tissue engineering scaffolds by using a digital micromirror-array device (DMD) in a layer-by-layer process. This simple and fast microstereolithography system consists of an ultraviolet (UV) light source, a digital micromirror masking device, imaging optics, and controlling devices. Images of UV light are projected onto the photocurable resin by creating the "dynamic photomask" design with graphic software. Multilayered scaffolds are microfabricated through a photopolymerization process. PMID:22692617

  16. Is nonangiogenesis a novel pathway for cancer progression? A study using 3-dimensional tumour reconstructions

    OpenAIRE

    Adighibe, O; Micklem, K; Campo, L; Ferguson, M.; Harris, A; Pozos, R; Gatter, K; Pezzella, F.

    2006-01-01

    The nonangiogenic lung tumour is characterized by neoplastic cells co-opting the pre-existent vasculature and filling the alveoli space. 3-Dimensional reconstruction of the tumour reveals that this particular tumour progresses without neovascularization and there is no major destruction of the lung's architectural integrity.

  17. Insulin and insulin-like growth factor I exert different effects on plasminogen activator production or cell growth in the ovine thyroid cell line OVNIS.

    Science.gov (United States)

    Degryse, B; Maisonobe, F; Hovsépian, S; Fayet, G

    1991-11-01

    Insulin and Insulin-like Growth Factor I (IGF-I) are evaluated for their capacity to affect cell proliferation and plasminogen activator (PA) activity production in an ovine thyroid cell line OVNIS. Insulin at physiological and supraphysiological doses induces cell proliferation and increases PA activity. IGF-I, which is also clearly mitogenic for these cells, surprisingly does not modulate PA activity. The results indicate that the growth promoting effect is mediated through the insulin and IGF-I receptors whereas PA activity is solely regulated via the insulin receptors. PMID:1802921

  18. Peripheral blood-derived, γ9δ2 t cell-enriched cell lines from glioblastoma multiforme patients exert anti-tumoral effects in vitro.

    Science.gov (United States)

    Marcu-Malina, V; Garelick, D; Peshes-Yeloz, N; Wohl, A; Zach, L; Nagar, M; Amariglio, N; Besser, M J; Cohen, Z R; Bank, I

    2016-01-01

    The goal of this work was to assess the potential of T cells expressing Vγ9Vδ2+ T cell receptors (TCR, γ9δ2T cells) present in peripheral blood (PB) m ononuclear cells (MC, PBMC) of glioblastoma multiforme (GBM) patients to act as anti-tumoral agents. We found that γ9δ2T cell levels were decreased in patients' PB relative to a cohort of healthy donors (HD) (respectively 0.52±0.55%, n=16, vs 1.12±0.6%, n=14, p=0.008) but did not significantly correlate with postoperative survival (R=0.6, p=0.063). Importantly, however, the γ9δ2T cells could be expanded in vitro to consist 51±23% of the cultured lymphocytes (98% CD3+). This was achieved after 14 days of culture in medium containing the amino-bisphosphonate (ABP) Zoledronate (Zol) and interleukin (IL)-2, resulting in γ9δ2T cell-enriched lines (gdTCEL) similar to those of HD derived gdTCEL (54±19%). Moreover, gdTCEL from patients and HD mediated cytotoxicity to GBM-derived cell lines (GBMDCL), which was abrogated by immune-magnetic removal of the γ9δ2T cells. Furthermore, low level interferon (IFN) γ secretion was induced by gdTCEL briefly co-cultured with GBMDCL or autologous - tumor-derived cells, which was greatly amplified in the presence of Zol. Importantly, IFNγ secretion was inhibited by mevastatin but enhanced by cross-linking of butyrophilin 3A1 (CD277) on a CD277+ GBMDCL (U251MG) or by pretreatment of GBMDCL with temozolomide (TMZ). Taken together, these data suggest that γ9δ2T cells in PB of GBM patients can give rise to gdTCEL that mediate anti-tumoral activities. PMID:27049073

  19. The Cotransplantation of Olfactory Ensheathing Cells with Bone Marrow Mesenchymal Stem Cells Exerts Antiapoptotic Effects in Adult Rats after Spinal Cord Injury

    OpenAIRE

    Shifeng Wu; Guanqun Cui; Hua Shao; Zhongjun Du; Ng, Jack C.; Cheng Peng

    2015-01-01

    The mechanisms behind the repairing effects of the cotransplantation of olfactory ensheathing cells (OECs) with bone marrow mesenchymal stromal cells (BMSCs) have not been fully understood. Therefore, we investigated the effects of the cotransplantation of OECs with BMSCs on antiapoptotic effects in adult rats for which the models of SCI are induced. We examined the changes in body weight, histopathological changes, apoptosis, and the expressions of apoptosis-related proteins after 14 days an...

  20. Deoxycholic acid and selenium metabolite methylselenol exert common and distinct effects on cell cycle, apoptosis, and MAP kinase pathway in HCT116 human colon cancer cells.

    Science.gov (United States)

    Zeng, Huawei; Botnen, James H; Briske-Anderson, Mary

    2010-01-01

    The cell growth inhibition induced by bile acid deoxycholic acid (DCA) may cause compensatory hyperproliferation of colonic epithelial cells and consequently increase colon cancer risk. On the other hand, there is increasing evidence for the efficacy of certain forms of selenium (Se) as anticancer nutrients. Methylselenol has been hypothesized to be a critical Se metabolite for anticancer activity in vivo. In this study, we demonstrated that both DCA (75-300 micromol/l) and submicromolar methylselenol inhibited colon cancer cell proliferation by up to 64% and 63%, respectively. In addition, DCA and methylselenol each increased colon cancer cell apoptosis rate by up to twofold. Cell cycle analyses revealed that DCA induced an increase in only the G1 fraction with a concomitant drop in G2 and S-phase; in contrast, methylselenol led to an increase in the G1 and G2 fractions with a concomitant drop only in the S-phase. Although both DCA and methylselenol significantly promoted apoptosis and inhibited cell growth, examination of mitogen-activated protein kinase (MAPK) pathway activation showed that DCA, but not methylselenol, induced SAPK/JNK1/2, p38 MAPK, ERK1/2 activation. Thus, our data provide, for the first time, the molecular basis for opposite effects of methylselenol and DCA on colon tumorigenesis.

  1. The potential of 3-dimensional construct engineered from poly(lactic-co-glycolic acid)/fibrin hybrid scaffold seeded with bone marrow mesenchymal stem cells for in vitro cartilage tissue engineering.

    Science.gov (United States)

    Abdul Rahman, Rozlin; Mohamad Sukri, Norhamiza; Md Nazir, Noorhidayah; Ahmad Radzi, Muhammad Aa'zamuddin; Zulkifly, Ahmad Hafiz; Che Ahmad, Aminudin; Hashi, Abdurezak Abdulahi; Abdul Rahman, Suzanah; Sha'ban, Munirah

    2015-08-01

    Articular cartilage is well known for its simple uniqueness of avascular and aneural structure that has limited capacity to heal itself when injured. The use of three dimensional construct in tissue engineering holds great potential in regenerating cartilage defects. This study evaluated the in vitro cartilaginous tissue formation using rabbit's bone marrow mesenchymal stem cells (BMSCs)-seeded onto poly(lactic-co-glycolic acid) PLGA/fibrin and PLGA scaffolds. The in vitro cartilaginous engineered constructs were evaluated by gross inspection, histology, cell proliferation, gene expression and sulphated glycosaminoglycan (sGAG) production at week 1, 2 and 3. After 3 weeks of culture, the PLGA/fibrin construct demonstrated gross features similar to the native tissue with smooth, firm and glistening appearance, superior histoarchitectural and better cartilaginous extracellular matrix compound in concert with the positive glycosaminoglycan accumulation on Alcian blue. Significantly higher cell proliferation in PLGA/fibrin construct was noted at day-7, day-14 and day-21 (p<0.05 respectively). Both constructs expressed the accumulation of collagen type II, collagen type IX, aggrecan and sox9, showed down-regulation of collagen type I as well as produced relative sGAG content with PLGA/fibrin construct exhibited better gene expression in all profiles and showed significantly higher relative sGAG content at each time point (p<0.05). This study suggested that with optimum in vitro manipulation, PLGA/fibrin when seeded with pluripotent non-committed BMSCs has the capability to differentiate into chondrogenic lineage and may serve as a prospective construct to be developed as functional tissue engineered cartilage.

  2. 3 dimensional volume MR imaging of intratemporal facial nerve

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Jeong Jin; Kang, Heoung Keun; Kim, Hyun Ju; Kim, Jae Kyu; Jung, Hyun Ung; Moon, Woong Jae [Chonnam University Medical School, Kwangju (Korea, Republic of)

    1994-10-15

    To evaluate the usefulness of 3 dimensional volume MR imaging technique for demonstrating the facial nerves and to describe MR findings in facial palsy patients and evaluate the significance of facial nerve enhancement. We reviewed the MR images of facial nerves obtained with 3 dimensional volume imaging technique before and after intravenous administration of Gadopentetate dimeglumine in 13 cases who had facial paralysis and 33 cases who had no facial palsy. And we analyzed the detectability of ananatomical segments of intratemporal facial nerves and facial nerve enhancement. When the 3 dimensional volume MR images of 46 nerves were analyzed subjectively, the nerve courses of 43(93%) of 46 nerves were effectively demonstrated on 3 dimensional volume MR images. Internal acoustic canal portions and geniculate ganglion of facial nerve were well visualized on axial images and tympanic and mastoid segments were well depicted on oblique sagittal images. 10 of 13 patients(77%) were visibly enhanced along at least one segment of the facial nerve with swelling or thickening, and nerves of 8 of normal 33 cases(24%) were enhanced without thickening or swelling. MR findings of facial nerve parelysis is asymmetrical thickening of facial nerve with contrast enhancement. The 3 dimensional volume MR imaging technique should be a useful study for the evaluation of intratemporal facial nerve disease.

  3. Adipose Tissue-Derived Mesenchymal Stem Cells Exert In Vitro Immunomodulatory and Beta Cell Protective Functions in Streptozotocin-Induced Diabetic Mice Model

    Directory of Open Access Journals (Sweden)

    Hossein Rahavi

    2015-01-01

    Full Text Available Regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs might be applied for type 1 diabetes mellitus (T1DM treatment. Thus, we proposed in vitro assessment of adipose tissue-derived MSCs (AT-MSCs immunomodulation on autoimmune response along with beta cell protection in streptozotocin- (STZ- induced diabetic C57BL/6 mice model. MSCs were extracted from abdominal adipose tissue of normal mice and cultured to proliferate. Diabetic mice were prepared by administration of multiple low-doses of streptozotocin. Pancreatic islets were isolated from normal mice and splenocytes prepared from normal and diabetic mice. Proliferation, cytokine production, and insulin secretion assays were performed in coculture experiments. AT-MSCs inhibited splenocytes proliferative response to specific (islet lysate and nonspecific (PHA triggers in a dose-dependent manner (P<0.05. Decreased production of proinflammatory cytokines, such as IFN-γ, IL-2, and IL-17, and increased secretion of regulatory cytokines such as TGF-β, IL-4, IL-10, and IL-13 by stimulated splenocytes were also shown in response to islet lysate or PHA stimulants (P<0.05. Finally, we demonstrated that AT-MSCs could effectively sustain viability as well as insulin secretion potential of pancreatic islets in the presence of reactive splenocytes (P<0.05. In conclusion, it seems that MSCs may provide a new horizon for T1DM cell therapy and islet transplantation in the future.

  4. Differential Cross Section Kinematics for 3-dimensional Transport Codes

    Science.gov (United States)

    Norbury, John W.; Dick, Frank

    2008-01-01

    In support of the development of 3-dimensional transport codes, this paper derives the relevant relativistic particle kinematic theory. Formulas are given for invariant, spectral and angular distributions in both the lab (spacecraft) and center of momentum frames, for collisions involving 2, 3 and n - body final states.

  5. Interexaminer and intraexaminer reliabilities of 3-dimensional orthodontic digital setups

    NARCIS (Netherlands)

    L.N.J. Fabels; P.G. Nijkamp

    2014-01-01

    Introduction The use of digital orthodontic setups has grown quickly. The purpose of this study was to test the interexaminer and intraexaminer reliabilities of 3-dimensional orthodontic digital setups in OrthoCAD (Align Technology, San Jose, Calif). Methods Six clinicians made digital orthodontic s

  6. 2 and 3-dimensional Hamiltonians with Shape Invariance Symmetry

    OpenAIRE

    Jafarizadeh, M. A.; Panahi-Talemi, H.; Faizi, E.

    2000-01-01

    Via a special dimensional reduction, that is, Fourier transforming over one of the coordinates of Casimir operator of su(2) Lie algebra and 4-oscillator Hamiltonian, we have obtained 2 and 3 dimensional Hamiltonian with shape invariance symmetry. Using this symmetry we have obtained their eigenspectrum. In the mean time we show equivalence of shape invariance symmetry and Lie algebraic symmetry of these Hamiltonians.

  7. Recent Therapeutic Effect of Late Course 3 Dimensional Conformal Therapy Concomitant with Chemotherapy on Stage Ⅲ Non-small-cell Lung Cancer%后程适形放射治疗联合化学疗法治疗Ⅲ期非小细胞肺癌近期疗效观察

    Institute of Scientific and Technical Information of China (English)

    赵彩霞; 任勇军; 文世民; 李光明; 潘荣强

    2011-01-01

    目的 探讨后程适形放射治疗(3 dimensional cornformal radiation therapy,3D-CRT)同步化学疗法治疗Ⅲ期非小细胞肺癌(non-small-cell lung cancer,NS4CLC)的近期疗效.方法 搜集2005年1月-2008年6月NSCLC患者共115例,其中53例行单纯后程3D-CRT(单放组),62例行后程3D-CRT联合同步化学疗法(联合组),所有患者均经病理证实为Ⅲ期NSCLC.两组放射治疗方案均采用常规分割治疗加后程3D-CRT,DT 62~72Gy.联合组化学疗法采用TP(紫杉醇+顺铂)方案.结果 单放组和联合组近期疗效(完全缓解+部分缓解)分别为75.47%、91.94%,差异有统计学意义(P<0.05).单放组和联合组的治疗不良反应主要有白细胞、血小板减少,放射性食管炎,放射性气管炎,恶心、呕吐等胃肠道反应.骨髓抑制和消化道反应,联合组稍高于单放组.经对症治疗后,所有患者均可耐受.结论 后程3D-CRT联合TP方案化学疗法较单纯后程适形放射治疗明显提高Ⅲ期NSCLC近期疗效.患者耐受性尚可.%Objective To observe the recent therapeutic effect of late course 3 dimensional conformal therapy concomitant with chemotherapy on locally advanced stage Ⅲ non-small-cell lung cancer (NSCLC). Methods From January 2005 to June 2008, 115 patients with stage Ⅲ NSCLC were confirmed by pathology, in whom 53 only underwent late course conformal therapy (radiotherapy group), and another 62 underwent late course conformal therapy concomitant with chemotherapy (combined group). The radiotherapy schema of the two groups was routine division plus late course conformal therapy (with DT 62-72 Gy). The chemotherapy schema in the combined group was performed with TP (paclitaxel and DDP). Results The recent curative effect (complete remission plus partial remission) in radiotherapy group and combined group was 75. 47% and 91. 94%, respectively (P<0. 05). The frequent adverse reactions in the two groups included leucocytopenia, thrombocytopenia

  8. 3-Dimensional reconstruction of fluorescent structures in tardigrades

    Directory of Open Access Journals (Sweden)

    Franz BRÜMMER

    2007-09-01

    Full Text Available Tardigrades are microscopic animals, thus brightfield microscopy is a well established method for tardigrade observation. Modern techniques in functional genetics like fluorescence in situ hybridisation or fluorescently labelled expression markers demand high resolution fluorescence microscopy. Nevertheless tardigrades are still considered to be difficult objects for fluorescence techniques as they are covered by an opaque and diffracting cuticle. We show a modern technique of structured light illumination that enables us to acquire thin optical sections and consequently to reconstruct 3-dimensional structures in tardigrades with a high spatial resolution in all 3 dimensions. This technique is evaluated on taxonomically valuable internal as well as external structures of eutardigrades: the bucco-pharyngeal apparatus and the claws. The 3-dimensional reconstructions allow the measurement of distances in all 3 dimensions.

  9. Catalytic carbon deposition on 3-dimensional carbon fibre supports

    OpenAIRE

    Thornton, Matthew James

    2005-01-01

    Catalytic carbon deposition reactions, using methane, ethane or synthetic natural gas (1.8 vol. % propane, 6.7 vol. % ethane and balance methane) as the carbon-containing gas feedstock with or without the addition of hydrogen, have been investigated over nickel, cobalt and iron catalysts supported on 3-dimensional carbon fibre supports, using both a horizontal tube furnace and an isothermal, isobaric induction furnace. The transition metal catalysts were prepared by impregnating 3-dimens...

  10. GLOBAL STABILITY IN TIME-DELAYED 3-DIMENSIONAL RICHARDS MODEL

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    We obtain the global attractivity and global asymptotical stability of positive equilibria to a 3-dimensional Richards model with delays. Our results do not depend on the size-asymmetry parameter which measures the degree of the curvature of size-growth among individuals over the entire growth curve, and the shape parameter which affects the shape of model curve. Lastly, we gave a numerical simulation to verify the feasibility of our main results.

  11. Decay vertex reconstruction and 3-dimensional lifetime determination at BESⅢ

    Institute of Scientific and Technical Information of China (English)

    XU Min; HE Kang-Lin; ZHANG Zi-Ping; WANG Yi-Fang; BIAN Jian-Ming; CAO Guo-Fu; CAO Xue-Xiang; CHEN Shen-Jian; DENG Zi-Yan; FU Cheng-Dong; GAO Yuan-Ning; HAN Lei; NAN Shao-Qing; HE Miao; HU Ji-Feng; HU Xiao-Wei; HUANG Bin; HUANG Xing-Tao; JIA Lu-Kui; JI Xiao-Sin; LI Hai-Bo; LI Wei-Dong; LIANG Yu-Wie; LIU Chun-Xiu; LIU Huai-Min; LIU Ying; LIU Yong; LUO Tao; L(U) Qi-Wen; MA Qiu-Mei; MA Xiang; MAO Ya-Jun; MAO Ze-Pu; MO Xiao-Hu; NING Fei-Peng; PING Rong-Gang; QIU Jin-Fa; SONG Wen-Bo; SUN Sheng-Sen; SUN Xiao-Dong; SUN Yong-Zhao; TIAN Hao-Lai; WANG Ji-Ke; WANG Liang-Liang; WEN Shuo-Pin; WU Ling-Hui; WU Zhi; XIE Yu-Guang; YAN Jie; YAN Liang; YAO Jian; YUAN Chang-Zheng; YUAN Ye; ZHANG Chang-Chun; ZHANG Jian-Yong; ZHANG Lei; ZHANG Xue-Yao; ZHANG Yao; ZHENG Yang-Heng; ZHU Yong-Sheng; ZOU Jia-Heng

    2009-01-01

    This paper focuses mainly on the vertex reconstruction of resonance particles with a relatively long lifetime such as KSO, A, as well as on lifetime measurements using a 3-dimensional fit. The kinematic constraints between the production and decay vertices and the decay vertex fitting algorithm based on the least squares method are both presented. Reconstruction efficiencies including experimental resolutions are discussed. The results and systematic errors are calculated based on a Monte Carlo simulation.

  12. Anti-de Sitter 3-dimensional Gravity with Torsion

    OpenAIRE

    Blagojevic, M; Vasilic, M.

    2004-01-01

    Using the canonical formalism, we study the asymptotic symmetries of the topological 3-dimensional gravity with torsion. In the anti-de Sitter sector, the symmetries are realized by two independent Virasoro algebras with classical central charges. In the simple case of the teleparallel vacuum geometry, the central charges are equal to each other and have the same value as in general relativity, while in the general Riemann-Cartan geometry, they become different.

  13. Ganodermanontriol (GDNT) exerts its effect on growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and uPA

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Jiahua; Jedinak, Andrej [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Sliva, Daniel, E-mail: dsliva@iuhealth.org [Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Medicine, School of Medicine, Indiana University, Indianapolis, IN (United States); Indiana University Simon Cancer Center, School of Medicine, Indiana University, Indianapolis, IN (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Ganodermanontriol (GDNT), a Ganoderma mushroom alcohol, inhibits growth of breast cancer cells. Black-Right-Pointing-Pointer CDC20 is over-expressed in tumors but not in the tumor surrounding tissue in breast cancer patients. Black-Right-Pointing-Pointer GDNT inhibits expression of CDC20 in breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits cell adhesion, cell migration and cell invasion of breast cancer cells. Black-Right-Pointing-Pointer GDNT inhibits secretion of uPA and down-regulates expression of uPAR in breast cancer cells. -- Abstract: Ganoderma lucidum is a medicinal mushroom that has been recognized by Traditional Chinese Medicine (TCM). Although some of the direct anticancer activities are attributed to the presence of triterpenes-ganoderic and lucidenic acids-the activity of other compounds remains elusive. Here we show that ganodermanontriol (GDNT), a Ganoderma alcohol, specifically suppressed proliferation (anchorage-dependent growth) and colony formation (anchorage-independent growth) of highly invasive human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle regulatory protein CDC20, which is over-expressed in precancerous and breast cancer cells compared to normal mammary epithelial cells. Moreover, we found that CDC20 is over-expressed in tumors when compared to the tissue surrounding the tumor in specimens from breast cancer patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA) and inhibited expression of uPA receptor. In conclusion, mushroom GDNT is a natural agent that has potential as a therapy for invasive breast cancers.

  14. Myeloid derived suppressor cells (MDSCs are increased and exert immunosuppressive activity together with polymorphonuclear leukocytes (PMNs in chronic myeloid leukemia patients.

    Directory of Open Access Journals (Sweden)

    Cesarina Giallongo

    Full Text Available Tumor immune tolerance can derive from the recruitment of suppressor cell population, including myeloid derived suppressor cells (MDSCs, able to inhibit T cells activity. We identified a significantly expanded MDSCs population in chronic myeloid leukemia (CML patients at diagnosis that decreased to normal levels after imatinib therapy. In addition, expression of arginase 1 (Arg1 that depletes microenvironment of arginine, an essential aminoacid for T cell function, resulted in an increase in patients at diagnosis. Purified CML CD11b+CD33+CD14-HLADR- cells markedly suppressed normal donor T cell proliferation in vitro. Comparing CML Gr-MDSCs to autologous polymorphonuclear leukocytes (PMNs we observed a higher Arg1 expression and activity in PMNs, together with an inhibitory effect on T cells in vitro. Our data indicate that CML cells create an immuno-tolerant environment associated to MDSCs expansion with immunosuppressive capacity mediated by Arg1. In addition, we demonstrated for the first time also an immunosuppressive activity of CML PMNs, suggesting a strong potential immune escape mechanism created by CML cells, which control the anti-tumor reactive T cells. MDSCs should be monitored in imatinib discontinuation trials to understand their importance in relapsing patients.

  15. Possible Involvement of the Inhibition of NF-κB Factor in Anti-Inflammatory Actions That Melatonin Exerts on Mast Cells.

    Science.gov (United States)

    Maldonado, M D; García-Moreno, H; González-Yanes, C; Calvo, J R

    2016-08-01

    Melatonin is a molecule endogenously produced in a wide variety of immune cells, including mast cells (RBL-2H3). It exhibits immunomodulatory, anti-inflammatory and anti-apoptotic properties. The physiologic mechanisms underlying these activities of melatonin have not been clarified in mast cells. This work is designed to determine the anti-inflammatory effect and mechanism of action of melatonin on activated mast cells. RBL-2H3 were pre-treated with exogenous melatonin (MELx) at physiological (100nM) and pharmacological (1 mM) doses for 30 min, washed and activated with PMACI (phorbol 12-myristate 13-acetate plus calcium ionophore A23187) for 2 h and 12 h. The data shows that pre-treatment of MELx in stimulated mast cells, significantly reduced the levels of endogenous melatonin production (MELn), TNF-α and IL-6. These effects are directly related with the MELx concentration used. MELx also inhibited IKK/NF-κB signal transduction pathway in stimulated mast cells. These results indicate a molecular basis for the ability of melatonin to prevent inflammation and for the treatment of allergic inflammatory diseases through the down-regulation of mast cell activation. J. Cell. Biochem. 117: 1926-1933, 2016. © 2016 Wiley Periodicals, Inc. PMID:26756719

  16. The HDAC inhibitors scriptaid and LBH589 combined with the oncolytic virus Delta24-RGD exert enhanced anti-tumor efficacy in patient-derived glioblastoma cells

    NARCIS (Netherlands)

    Pont, L.M.E.B. (Lotte M. E. Berghauser); A. Kleijn (Anne); J.J. Kloezeman (Jenneke); Van Bossche, W.D. (Wouter Den); Kaufmann, J.K. (Johanna K.); J. Vrij (Jeroen); S. Leenstra (Sieger); C.M.F. Dirven (Clemens); M.L.M. Lamfers (Martine)

    2015-01-01

    textabstractBackground: A phase I/II trial for glioblastoma with the oncolytic adenovirus Delta24-RGD was recently completed. Delta24-RGD conditionally replicates in cells with a disrupted retinoblastomapathway and enters cells via αvβ3/5 integrins. Glioblastomas are differentially sensitive to Delt

  17. Exogenous hydrogen sulfide exerts proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway in PLC/PRF/5 hepatoma cells.

    Science.gov (United States)

    Zhen, Yulan; Pan, Wanying; Hu, Fen; Wu, Hongfu; Feng, Jianqiang; Zhang, Ying; Chen, Jingfu

    2015-05-01

    Hydrogen sulfide (H2S) takes part in a diverse range of intracellular pathways and hss physical and pathological properties in vitro and in vivo. However, the effects of H2S on cancer are controversial and remain unclear. The present study investigates the effects of H2S on liver cancer progression via activating NF-κB pathway in PLC/PRF/5 hepatoma cells. PLC/PRF/5 hepatoma cells were pretreated with 500 µmol/l NaHS (a donor of H2S) for 24 h. The expression levels of CSE, CBS, phosphosphorylate (p)-NF-κB p65, caspase-3, COX-2, p-IκB and MMP-2 were measured by western blot assay. Cell viability was detected by cell counter kit 8 (CCK-8). Apoptotic cells were observed by Hoechst 33258 staining assay. The production level of H2S in cell culture medium was measured by using the sulfur-sensitive electrode method. The production of vascular endothelial growth factor (VEGF) was tested by enzyme-linked immunosorbent assay (ELISA). Our results showed that the production of H2S was dramatically increased in the PLC/PRF/5 hepatoma cells, compared with human LO2 hepatocyte cells group, along with the overexpression levels of CSE and CBS. Treatment of PLC/PRF/5 hepatoma cells with 500 µmol/l NaHS (a donor of H2S) for 24 h markedly increased the expression levels of CSE, CBS, p-IκB and NF-κB activation, leading to COX-2 and MMP-2 overexpression, and decreased caspase-3 production, as well as increased cell viability and decreased number of apoptotic cells. Otherwise, the production level of H2S and VEGF were also significantly increased. Furthermore, co-treatment of PLC/PRF/5 hepatoma cells with 500 µmol/l NaHS and 200 µmol/l PDTC for 24 h significantly overturned these indexes. The findings of the present study provide evidence that the NF-κB is involved in the NaHS-induced cell proliferation, anti-apoptisis, angiogenesis, and migration in PLC/PRF/5 hepatoma cells, and that the PDTC against the NaHS-induced effects were by inhibition of the NF-κB pathway.

  18. Materials applications of an advanced 3-dimensional atom probe

    Energy Technology Data Exchange (ETDEWEB)

    Cerezo, A. [Oxford Univ. (United Kingdom). Dept. of Materials; Gibuoin, D. [Oxford Univ. (United Kingdom). Dept. of Materials; Kim, S. [Oxford Univ. (United Kingdom). Dept. of Materials; Sijbrandij, S.J. [Oxford Univ. (United Kingdom). Dept. of Materials; Venker, F.M. [Oxford Univ. (United Kingdom). Dept. of Materials]|[Rijksuniversiteit Groningen (Netherlands). Dept. of Applied Physics; Warren, P.J. [Oxford Univ. (United Kingdom). Dept. of Materials; Wilde, J. [Oxford Univ. (United Kingdom). Dept. of Materials; Smith, G.D.W. [Oxford Univ. (United Kingdom). Dept. of Materials

    1996-09-01

    An advanced 3-dimensional atom probe system has been constructed, based on an optical position-sensitive atom probe (OPoSAP) detector with energy compensation using a reflectron lens. The multi-hit detection capability of the OPoSAP leads to significant improvements in the efficiency of the instrument over the earlier serial position-sensing system. Further gains in efficiency are obtained by using a biassed grid in front of the detector to collect secondary electrons generated when ions strike the interchannel area. The improvement in detection efficiency gives enhanced performance in the studies of ordered materials and the determination of site occupation. Energy compensation leads to a much improved mass resolution (m/{Delta}m=500 full width at half maximum) making it possible to map out the 3-dimensional spatial distributions of all the elements in complex engineering alloys, even when elements lie close together in the mass spectrum. For example, in the analysis of a maraging steel, this allows separation between the {sup 61}Ni{sup 2+} and {sup 92}Mo{sup 3+} peaks, which are only 1/6 of a mass unit apart. (orig.).

  19. Automated feature extraction for 3-dimensional point clouds

    Science.gov (United States)

    Magruder, Lori A.; Leigh, Holly W.; Soderlund, Alexander; Clymer, Bradley; Baer, Jessica; Neuenschwander, Amy L.

    2016-05-01

    Light detection and ranging (LIDAR) technology offers the capability to rapidly capture high-resolution, 3-dimensional surface data with centimeter-level accuracy for a large variety of applications. Due to the foliage-penetrating properties of LIDAR systems, these geospatial data sets can detect ground surfaces beneath trees, enabling the production of highfidelity bare earth elevation models. Precise characterization of the ground surface allows for identification of terrain and non-terrain points within the point cloud, and facilitates further discernment between natural and man-made objects based solely on structural aspects and relative neighboring parameterizations. A framework is presented here for automated extraction of natural and man-made features that does not rely on coincident ortho-imagery or point RGB attributes. The TEXAS (Terrain EXtraction And Segmentation) algorithm is used first to generate a bare earth surface from a lidar survey, which is then used to classify points as terrain or non-terrain. Further classifications are assigned at the point level by leveraging local spatial information. Similarly classed points are then clustered together into regions to identify individual features. Descriptions of the spatial attributes of each region are generated, resulting in the identification of individual tree locations, forest extents, building footprints, and 3-dimensional building shapes, among others. Results of the fully-automated feature extraction algorithm are then compared to ground truth to assess completeness and accuracy of the methodology.

  20. Ovatodiolide of Anisomeles indica Exerts the Anticancer Potential on Pancreatic Cancer Cell Lines through STAT3 and NF-κB Regulation

    Directory of Open Access Journals (Sweden)

    Ya-Ju Hsieh

    2016-01-01

    Full Text Available Pancreatic cancer is the eighth leading cause of cancer death worldwide. Patients with pancreatic cancer are normally diagnosed at an advanced stage and present poor survival rate. Ovatodiolide (OV, a bioactive macrocyclic diterpenoid isolated from Anisomeles indica, showed cytotoxicity effects in pancreatic cancer cells by inhibiting cell proliferation and inducing apoptosis. Moreover, not only were cell adhesion and invasion markedly suppressed in a dose-dependent manner, but the mRNA expression of matrix metalloproteinase-9 (MMP-9 and focal adhesion kinase (FAK was also significantly decreased. Western blot analysis indicated that OV potently suppressed the phosphorylation of STAT-3 and its upstream kinase including ERK1/2, P38, and AKT Ser473. Meanwhile, OV inactivated the nuclear factor kappa B (NF-κB by inhibiting IκB kinase (IKK α/β activation and the subsequent suppression of inhibitor of kappa B (IκB phosphorylation. These results demonstrated that OV could potentially inhibit Mia-PaCa2 cancer cells proliferation and induce apoptosis through modulation of NF-κB and STAT3 pathway. Moreover, OV suppressed cell invasiveness and interfered with cell-matrix adhesion in Mia-PaCa2 cancer cells by reducing MMP-9 and FAK transcription through suppressing NF-κB and STAT3 pathway. Taken together, our findings reveal a new therapeutic and antimetastatic potential of ovatodiolide for pancreatic cancer remedy.

  1. Cellular and molecular mechanisms underlie the anti-tumor activities exerted by Walterinnesia aegyptia venom combined with silica nanoparticles against multiple myeloma cancer cell types.

    Directory of Open Access Journals (Sweden)

    Gamal Badr

    Full Text Available Multiple myeloma (MM is a clonal disease of plasma cells that remains incurable despite the advent of several novel therapeutics. In this study, we aimed to delineate the impact of snake venom extracted from Walterinnesia aegyptia (WEV alone or in combination with silica nanoparticles (WEV+NP on primary MM cells isolated from patients diagnosed with MM as well as on two MM cell lines, U266 and RPMI 8226. The IC(50 values of WEV and WEV+NP that significantly decreased MM cell viability without affecting the viability of normal peripheral mononuclear cells (PBMCs were determined to be 25 ng/ml and 10 ng/ml, respectively. Although both WEV (25 ng/ml and WEV+NP (10 ng/ml decreased the CD54 surface expression without affecting the expression of CXCR4 (CXCL12 receptor on MM cells, they significantly reduced the ability of CXC chemokine ligand 12 (CXCL12 to induce actin cytoskeleton rearrangement and the subsequent reduction in chemotaxis. It has been established that the binding of CXCL12 to its receptor CXCR4 activates multiple intracellular signal transduction pathways that regulate MM cell chemotaxis, adhesion, and proliferation. We found that WEV and WEV+NP clearly decreased the CXCL12/CXCR4-mediated activation of AKT, ERK, NFκB and Rho-A using western blot analysis; abrogated the CXCL12-mediated proliferation of MM cells using the CFSE assay; and induced apoptosis in MM cell as determined by PI/annexin V double staining followed by flow cytometry analysis. Monitoring the expression of B-cell CCL/Lymphoma 2 (Bcl-2 family members and their role in apoptosis induction after treatment with WEV or WEV+NP revealed that the combination of WEV with NP robustly decreased the expression of the anti-apoptotic effectors Bcl-2, Bcl(XL and Mcl-1; conversely increased the expression of the pro-apoptotic effectors Bak, Bax and Bim; and altered the mitochondrial membrane potential in MM cells. Taken together, our data reveal the biological effects of WEV and WEV

  2. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells

    International Nuclear Information System (INIS)

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5 is

  3. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells.

    Science.gov (United States)

    Weber, Axel; Borghouts, Corina; Brendel, Christian; Moriggl, Richard; Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd

    2015-01-01

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5 is

  4. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F+ HEL Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Axel Weber

    2015-03-01

    Full Text Available Signal transducers and activators of transcription (Stats play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML and Jak2(V617F in other myeloproliferative diseases (MPD. We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL

  5. Acetylation of cell wall is required for structural integrity of the leaf surface and exerts a global impact on plant stress responses

    DEFF Research Database (Denmark)

    Nafisi, Majse; Stranne, Maria; Fimognari, Lorenzo;

    2015-01-01

    The epidermis on leaves protects plants from pathogen invasion and provides a waterproof barrier. It consists of a layer of cells that is surrounded by thick cell walls, which are partially impregnated by highly hydrophobic cuticular components. We show that the Arabidopsis T-DNA insertion mutants...... to abiotic stress, particularly detoxification of reactive oxygen species and defense against microbial pathogens (e.g., lipid transfer proteins, peroxidases). In accordance, peroxidase activities were found to be elevated in rwa2 as compared to the wild type. These results indicate that cell wall...... acetylation is essential for maintaining the structural integrity of leaf epidermis, and that reduction of cell wall acetylation leads to global stress responses in Arabidopsis....

  6. The gastric acid secretagogue gastrin-releasing peptide and the inhibitor oxyntomodulin do not exert their effect directly on the parietal cell in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Holst, J J

    1988-01-01

    Previous studies suggested that gastrin-releasing peptide (a neuropeptide found in rat oxyntic mucosa) and oxyntomodulin (a glucagon-containing peptide of mammalian gut) could directly affect the acid secretion of the parietal cells. We therefore studied their effect on gastric acid production in...... and histamine-stimulated parietal cells confirmed that the cells retained the normal morphology of intracellular organelles and that the cells responded to physiological stimulation by marked expansion of the intracellular canaliculi.......Previous studies suggested that gastrin-releasing peptide (a neuropeptide found in rat oxyntic mucosa) and oxyntomodulin (a glucagon-containing peptide of mammalian gut) could directly affect the acid secretion of the parietal cells. We therefore studied their effect on gastric acid production...... in vitro by measuring [14C]-aminopyrine accumulation, a reliable index of H+ generation, in isolated rat parietal cells. However, neither gastrin-releasing peptide nor oxyntomodulin influenced basal acid secretion or histamine-stimulated gastric acid secretion. Electron-microscopic studies of unstimulated...

  7. Mangiferin exerts antitumor activity in breast cancer cells by regulating matrix metalloproteinases, epithelial to mesenchymal transition, and β-catenin signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hongzhong; Huang, Jing; Yang, Bing; Xiang, Tingxiu; Yin, Xuedong; Peng, Weiyan; Cheng, Wei [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Wan, Jingyuan; Luo, Fuling [Department of Pharmacology, Chongqing Medical University, Chongqing (China); Li, Hongyuan [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China); Ren, Guosheng, E-mail: rgs726@163.com [Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing (China)

    2013-10-01

    Although mangiferin which is a naturally occurring glucosylxanthone has exhibited promising anticancer activities, the detailed molecular mechanism of mangiferin on cancers still remains enigmatic. In this study, the anticancer activity of mangiferin was evaluated in breast cancer cell line-based in vitro and in vivo models. We showed that mangiferin treatment resulted in decreased cell viability and suppression of metastatic potential in breast cancer cells. Further mechanistic investigation revealed that mangiferin induced decreased matrix metalloproteinase (MMP)-7 and -9, and reversal of epithelial–mesenchymal transition (EMT). Moreover, it was demonstrated that mangiferin significantly inhibited the activation of β-catenin pathway. Subsequent experiments showed that inhibiting β-catenin pathway might play a central role in mangiferin-induced anticancer activity through modulation of MMP-7 and -9, and EMT. Consistent with these findings in vitro, the antitumor potential was also verified in mangiferin-treated MDA-MB-231 xenograft mice where significantly decreased tumor volume, weight and proliferation, and increased apoptosis were obtained, with lower expression of MMP-7 and -9, vimentin and active β-catenin, and higher expression of E-cadherin. Taken together, our study suggests that mangiferin might be used as an effective chemopreventive agent against breast cancer. - Highlights: • Mangiferin inhibits growth and metastatic potential in breast cancer cells. • Mangiferin down-regulates MMP-7 and -9 in breast cancer cells. • Mangiferin induces the reversal of EMT in metastatic breast cancer cells. • Mangiferin inhibits the activation of β-catenin pathway in breast cancer cells. • Inhibiting β-catenin is responsible for the antitumor activity of mangiferin.

  8. Piperlongumine exerts cytotoxic effects against cancer cells with mutant p53 proteins at least in part by restoring the biological functions of the tumor suppressor.

    Science.gov (United States)

    Basak, Debasish; Punganuru, Surendra R; Srivenugopal, Kalkunte S

    2016-04-01

    Piperlongumine (PL), a small molecule alkaloid present in black pepper (Piper longum), has been reported to kill tumor cells irrespective of their p53 gene status, however, the mechanisms involved are unknown. Since p53 is a redox-sensitive protein, we hypothesized that the redox imbalance induced by PL may affect the structure and/or function of the mutant p53 protein and promote cell death. We used two human colon cancer cell lines, the HT29 and SW620 which harbor the R273H DNA contact abrogatory mutation in p53. PL treatment induced significant ROS production and protein glutathionylation with a concomitant increase in Nrf-2 expression in both cell lines. Surprisingly, immunoprecipitation with wt-p53 specific antibodies (PAb1620) or direct western blotting showed a progressive generation of wild-type-like p53 protein along with a loss of its mutant counterpart in PL-treated HT29 and SW620 cells. Moreover, the EMSA and DNA-affinity blotting revealed a time-dependent restoration of DNA-binding for the mutant p53, which was accompanied by the induction of p53 target genes, MDM2 and Bax. PL, while cytotoxic by itself, also increased the cell killing by many anticancer drugs. In nude mice bearing the HT29 tumors, PL alone (7.5 mg/kg daily) produced a 40% decrease in tumor volume, which was accompanied by diminished intratumoral mutant p53 protein levels. The antitumor efficacy of BCNU or doxorubicin in HT29 xenografts was highly potentiated by PL, followed by expression of apoptotic proteins. These clinically-relevant findings suggest that PL-induced oxidative milieu facilitates a weak functional restoration of mutant p53 through protein glutathionylation and contributes to the increased drug sensitivity. PMID:26848023

  9. Antibacterial activity and immunomodulatory effects on a bovine mammary epithelial cell line exerted by nisin A-producing Lactococcus lactis strains.

    Science.gov (United States)

    Malvisi, M; Stuknytė, M; Magro, G; Minozzi, G; Giardini, A; De Noni, I; Piccinini, R

    2016-03-01

    Twenty-nine strains of mastitis pathogens were used to study the antibacterial activity of the cell-free supernatants (CFS) of 25 strains of Lactococcus lactis ssp. lactis. Out of the tested strains, only the CFS of L. lactis LL11 and SL153 were active, inhibiting and killing most of the pathogens. By means of ultra-performance liquid chromatography/high resolution mass spectrometry, they were shown to produce nisin A, a class I bacteriocin. A variable sensitivity to nisin A-containing CFS was observed among Streptococcus uberis and Enterococcus faecalis strains. Nonetheless, Streptococcus agalactiae, Strep. uberis, and E. faecalis displayed high minimum inhibitory concentration values, reaching 384 arbitrary units/mL. Interestingly, the minimum inhibitory values and the bactericidal concentrations were almost identical among them for each of the 2 stains, LL11 and SL153. Staphylococci were, on average, less sensitive than streptococci, but the 2 CFS inhibited and killed, at different dilutions, strains of methicillin-resistant Staphylococcus aureus. The immune response to nisin A-containing CFS was tested using the bovine mammary epithelial cell line BME-UV1. Application of CFS did not damage epithelial integrity, as demonstrated by the higher activity of N-acetyl-β-d-glucosaminidase (NAGase) and lysozyme inside the cells, in both treated and control samples. On the other hand, the increase of released NAGase after 15 to 24h of treatment with LL11 or SL153 live cultures demonstrated an inflammatory response of epithelial cells. Similarly, a significantly higher lysozyme activity was detected in the cells treated with LL11 live culture confirming the stimulation of lysosomal activity. The treatment of epithelial cells with SL153 live culture induced a significant tumor necrosis factor-α downregulation in the cells, but did not influence IL-8 expression. The control of tumor necrosis factor-α release could be an interesting approach to reduce the symptoms linked

  10. Hexad Preons and Emergent Gravity in 3-dimensional Complex Spacetime

    CERN Document Server

    Wang, Shun-Zhi

    2010-01-01

    We suggest that at high energy each space dimension has their own time dimension, forming a 3-dimensional complex spacetime. Based on this hypothesis, we propose that the primordial universe is made of six fundamental fermions and their complex conjugate states. These fermions are called Hexad Preons which carry hypercolor degree of freedom transforming under $U(3,3)$ gauge group. The Hermitian metric emerges upon the breakdown of the gauge group from $U(3,3)$ to its maximal compact subgroup $U(3)\\otimes U(3)$. Leptons, quarks, as well as other matter states may be formed from the subsequent condensate of Hexad Preons. Strong and electroweak forces are manifestations of the hypercolor interaction in the corresponding cases. Our framework sheds light on many problems in cosmology and particle physics.

  11. A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Yuan-Wu Chen

    Full Text Available Oral squamous cell carcinoma (OSCC is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared.Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin.The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.

  12. Protalign: a 3-dimensional protein alignment assessment tool.

    Science.gov (United States)

    Meads, D; Hansen, M D; Pang, A

    1999-01-01

    Protein fold recognition (sometimes called threading) is the prediction of a protein's 3-dimensional shape based on its similarity to a protein of known structure. Fold predictions are low resolution; that is, no effort is made to rotate the protein's component amino acid side chains into their correct spatial orientations. The goal is simply to recognize the protein family member that most closely resembles the target sequence of unknown structure and to create a sensible alignment of the target to the known structure (i.e., a structure-sequence alignment). To facilitate this type of structure prediction, we have designed a low resolution molecular graphics tool. ProtAlign introduces the ability to interact with and edit alignments directly in the 3-dimensional structure as well as in the usual 2-dimensional layout. It also contains several functions and features to help the user assess areas within the alignment. ProtAlign implements an open pipe architecture to allow other programs to access its molecular graphics capabilities. In addition, it is capable of "driving" other programs. Because amino acid side chain orientation is not relevant in fold recognition, we represent amino acid residues as abstract shapes or glyphs much like Lego (tm) blocks and we borrow techniques from comparative flow visualization using streamlines to provide clean depictions of the entire protein model. By creating a low resolution representation of protein structure, we are able to at least double the amount of information on the screen. At the same time, we create a view that is not as busy as the corresponding representations using traditional high resolution visualization methods which show detailed atomic structure. This eliminates distracting and possibly misleading visual clutter resulting from the mapping of protein alignment information onto a high resolution display of the known structure. This molecular graphics program is implemented in Open GL to facilitate porting to

  13. Shen-Qi-Jie-Yu-Fang exerts effects on a rat model of postpartum depression by regulating inflammatory cytokines and CD4+CD25+ regulatory T cells

    Science.gov (United States)

    Li, Jingya; Zhao, Ruizhen; Li, Xiaoli; Sun, Wenjun; Qu, Miao; Tang, Qisheng; Yang, Xinke; Zhang, Shujing

    2016-01-01

    Background Shen-Qi-Jie-Yu-Fang (SJF) is composed of eight Chinese medicinal herbs. It is widely used in traditional Chinese medicine for treating postpartum depression (PPD). Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism. Aim To further investigate the effect of SJF on the immune system, including the inflammatory response system and CD4+CD25+ regulatory T (Treg) cells. Materials and methods Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were treated with SJF or fluoxetine for 1, 2, and 4 weeks. Levels of Treg cells in peripheral blood were measured by flow cytometry analysis. Serum interleukin (IL)-1β and IL-6 were evaluated by enzyme-linked immunosorbent assay, and gene and protein expressions of IL-1RI, IL-6Rα, and gp130 in the hippocampus were observed by reverse-transcription polymerase chain reaction and Western blot. Results Serum IL-1β in PPD rats increased at 2 weeks and declined from then on, while serum IL-6 increased at 1, 2, and 4 weeks. Both IL-1β and IL-6 were downregulated by SJF and fluoxetine. Changes in gene and protein expressions of IL-1RI and gp130 in PPD rats were consistent with changes in serum IL-1β, and were able to be regulated by SJF and fluoxetine. The levels of Treg cells were negatively correlated with serum IL-1β and IL-6, and were decreased in PPD rats. The levels of Treg cells were increased by SJF and fluoxetine. Conclusion Dysfunction of proinflammatory cytokines and Tregs in different stages of PPD was attenuated by SJF and fluoxetine through the modulation of serum concentrations of IL-1β and IL-6, expressions of IL-1RI, and gp130 in the hippocampus, and CD4+CD25+ Treg cells in peripheral blood. PMID:27143890

  14. PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo.

    Science.gov (United States)

    Aravantinou, Meropi; Frank, Ines; Hallor, Magnus; Singer, Rachel; Tharinger, Hugo; Kenney, Jessica; Gettie, Agegnehu; Grasperge, Brooke; Blanchard, James; Salazar, Andres; Piatak, Michael; Lifson, Jeffrey D; Robbiani, Melissa; Derby, Nina

    2016-01-01

    Myeloid dendritic cells (mDCs) contribute to both HIV pathogenesis and elicitation of antiviral immunity. Understanding how mDC responses to stimuli shape HIV infection outcomes will inform HIV prevention and treatment strategies. The long double-stranded RNA (dsRNA) viral mimic, polyinosinic polycytidylic acid (polyIC, PIC) potently stimulates DCs to focus Th1 responses, triggers direct antiviral activity in vitro, and boosts anti-HIV responses in vivo. Stabilized polyICLC (PICLC) is being developed for vaccine adjuvant applications in humans, making it critical to understand how mDC sensing of PICLC influences HIV infection. Using the monocyte-derived DC (moDC) model, we sought to describe how PICLC (vs. other dsRNAs) impacts HIV infection within DCs and DC-T cell mixtures. We extended this work to in vivo macaque rectal transmission studies by administering PICLC with or before rectal SIVmac239 (SIVwt) or SIVmac239ΔNef (SIVΔNef) challenge. Like PIC, PICLC activated DCs and T cells, increased expression of α4β7 and CD169, and induced type I IFN responses in vitro. The type of dsRNA and timing of dsRNA exposure differentially impacted in vitro DC-driven HIV infection. Rectal PICLC treatment similarly induced DC and T cell activation and pro- and anti-HIV factors locally and systemically. Importantly, this did not enhance SIV transmission in vivo. Instead, SIV acquisition was marginally reduced after a single high dose challenge. Interestingly, in the PICLC-treated, SIVΔNef-infected animals, SIVΔNef viremia was higher, in line with the importance of DC and T cell activation in SIVΔNef replication. In the right combination anti-HIV strategy, PICLC has the potential to limit HIV infection and boost HIV immunity. PMID:27603520

  15. WJ9708012 exerts anticancer activity through PKC-α related crosstalk of mitochondrial and endoplasmic reticulum stresses in human hormone-refractory prostate cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ting-chun KUO; Wei-jan HUANG; Jih-hwa GUH

    2011-01-01

    Aim: To investigate the anticancer mechanism of a methoxyflavanone derivative,WJ9708012,highlighting its role on a crosstalk between endoplasmic reticulum(ER)and mitochondrial stress.Methods: Cell proliferation was examined using sulforhodamine B assay.Cell-cycle progression,Ca2+mobilization and mitochondrial membrane potential(Δψm)were detected using flow cytometric analysis.Protein expression was detected using Western blot.Results: WJ9708012 displayed an antiproliferative and apoptotic activity in human hormone-refractory prostate cancer cells with IC50values of 6.4 and 5.3 μmol/L in PC-3 and DU-145 cells.WJ9708012 induced a prompt increase of cytosolic Ca2+level and activation of protein kinase C(PKC)-α.The cleavage of p-calpain was also induced by WJ9708012.Furthermore,WJ9708012 induced cell-cycle arrest at G1-phase associated with down-regulation of cyclin D1,cyclin E and cyclin-dependent kinase-4 expressions.It also caused a rapid and time-dependent decrease of phosphorylation level of mTOR(Ser2448),4E-BP1(Thr37/Thr46/Thr70)and p70S6K(Thr389),indicating the inhibition of mTOR-mediated translational pathways.The ER stress was activated by the identification of up-regulated GADD153 and glucose-regulated protein-78 protein levels.The subsequent mitochondrial stress was also identified by the observation of a decreased Bcl-2 and Bcl-xL expressions,an increased truncated Bid and Bad and a loss of Δψm.Conclusion: WJ9708012 induces an increase of cytosolic Ca2+concentration and activation of PKC-α.Subsequently,a crosstalk between ER stress and mitochondrial insult is induced,leading to the inhibition of mTOR pathways and arrest of the cell-cycle at G1phase.The apoptosis is ultimately induced by a severe damage of mitochondrial function.

  16. The HDAC Inhibitors Scriptaid and LBH589 Combined with the Oncolytic Virus Delta24-RGD Exert Enhanced Anti-Tumor Efficacy in Patient-Derived Glioblastoma Cells.

    Directory of Open Access Journals (Sweden)

    Lotte M E Berghauser Pont

    Full Text Available A phase I/II trial for glioblastoma with the oncolytic adenovirus Delta24-RGD was recently completed. Delta24-RGD conditionally replicates in cells with a disrupted retinoblastoma-pathway and enters cells via αvβ3/5 integrins. Glioblastomas are differentially sensitive to Delta24-RGD. HDAC inhibitors (HDACi affect integrins and share common cell death pathways with Delta24-RGD. We studied the combination treatment effects of HDACi and Delta24-RGD in patient-derived glioblastoma stem-like cells (GSC, and we determined the most effective HDACi.SAHA, Valproic Acid, Scriptaid, MS275 and LBH589 were combined with Delta24-RGD in fourteen distinct GSCs. Synergy was determined by Chou Talalay method. Viral infection and replication were assessed using luciferase and GFP encoding vectors and hexon-titration assays. Coxsackie adenovirus receptor and αvβ3 integrin levels were determined by flow cytometry. Oncolysis and mechanisms of cell death were studied by viability, caspase-3/7, LDH and LC3B/p62, phospho-p70S6K. Toxicity was studied on normal human astrocytes. MGMT promotor methylation status, TCGA classification, Rb-pathway and integrin gene expression levels were assessed as markers of responsiveness.Scriptaid and LBH589 acted synergistically with Delta24-RGD in approximately 50% of the GSCs. Both drugs moderately increased αvβ3 integrin levels and viral infection in responding but not in non-responding GSCs. LBH589 moderately increased late viral gene expression, however, virus titration revealed diminished viral progeny production by both HDACi, Scriptaid augmented caspase-3/7 activity, LC3B conversion, p62 and phospho-p70S6K consumption, as well as LDH levels. LBH589 increased LDH and phospho-p70S6K consumption. Responsiveness correlated with expression of various Rb-pathway genes and integrins. Combination treatments induced limited toxicity to human astrocytes.LBH589 and Scriptaid combined with Delta24-RGD revealed synergistic anti

  17. The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

    International Nuclear Information System (INIS)

    The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D1 encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E2 synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on different Hu

  18. The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking

    Energy Technology Data Exchange (ETDEWEB)

    Doller, Anke; Badawi, Amel [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Schmid, Tobias; Brauß, Thilo [Institut für Biochemie I (Pathobiochemie), Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pleli, Thomas [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Meyer zu Heringdorf, Dagmar [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Piiper, Albrecht [Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany); Eberhardt, Wolfgang, E-mail: w.eberhardt@em.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main (Germany)

    2015-01-01

    The impact of the RNA-binding protein HuR for the post-transcriptional deregulation of tumor-relevant genes is well established. Despite of elevations in HuR expression levels, an increase in cytoplasmic HuR abundance in many cases correlates with a high grade of malignancy. Here, we demonstrated that administration of the actin-depolymerizing macrolide latrunculin A, or blebbistatin, an inhibitor of myosin II ATPase activity, caused a dose- and time-dependent reduction in the high cytoplasmic HuR content of HepG2 and Huh7 hepatocellular carcinoma (HCC) cells. Subcellular fractionation revealed that in addition, both inhibitors strongly attenuated cytoskeletal and membrane-bound HuR abundance and conversely increased the HuR amount in nuclear cell fractions. Concomitant with changes in intracellular HuR localization, both cytoskeletal inhibitors markedly decreased the half-lives of cyclooxygenase-2 (COX-2), cyclin A and cyclin D{sub 1} encoding mRNAs resulting in a significant reduction in their expression levels in HepG2 cells. Importantly, a similar reduction in the expression of these HuR targets was achieved by a RNA interference (RNAi)-mediated knockdown of either HuR or nonmuscle myoin IIA. Using polysomal fractionation, we further demonstrate that the decrease in cytoplasmic HuR by latrunculin A or blebbistatin is accompanied by a marked change in the allocation of HuR and its mRNA cargo from polysomes to ribonucleoprotein (RNP) particles. Functionally, the basal migration and prostaglandin E{sub 2} synthesis are similarly impaired in inhibitor-treated and stable HuR-knockdown HepG2 cells. Our data demonstrate that interfering with the actomyosin-dependent HuR trafficking may comprise a valid therapeutic option for antagonizing pathologic posttranscriptional gene expression by HuR and furthermore emphasize the potential benefit of HuR inhibitory strategies for treatment of HCC. - Highlights: • We tested the effects of latrunculin A and blebbistatin on

  19. Parathyroid hormone-mitogen-activated protein kinase axis exerts fibrogenic effect of connective tissue growth factor on human renal proximal tubular cells

    Institute of Scientific and Technical Information of China (English)

    GUO Yun-shan; YUAN Wei-jie; ZHANG Ai-ping; DING Yao-hai; WANG Yan-xia

    2010-01-01

    Background Enhanced and prolonged expression of connective tissue growth factor (CTGF) is associated with kidney fibrosis. Parathyroid hormone (PTH) is involved in the genesis of disturbed calcium/phosphate metabolism and ostitis fibrosa in renal failure. PTH activated mitogen-activated protein kinase (MAPK) signaling pathway is present in renal tubular cells. The aim of this study was to identify the mechanism how the signal is transduced to result in extracellular signal-regulated protein kinase (ERK) activation, leading to upregulation of CTGF.Methods The levels of CTGF mRNA and protein in human kidney proximal tubular cells (HK-2) treated with PTH in the presence or absence of the MAPK inhibitor PD98059 were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) and immunoblotting assay. The activation of the CTGF promoter in HK-2 cells was determined by the dual-luciferase assay. The effects of the protein kinase A (PKA) activator 8-Br-cAMP and protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) on MAPK phosphorylation, and the effects of the PKA inhibitor H89 and PKC inhibitor calphostin C on MAPK phosphorylation and CTGF expression were detected by immunoblotting assay.Results PD98059 inhibited the PTH stimulated expression of CTGF, which strongly suggested that the MAPK signaling pathway plays an important role in the PTH-induced CTGF upregulation in renal tubular cells. A PKA activator as well as PKC activators induced MAPK phosphorylation, and both PKA and PKC inhibitors antagonized PTH-induced MAPK phosphorylation and CTGF expression.Conclusion CTGF expression is upregulated by PTH through a PKC/PKA-ERK-dependent pathway.

  20. Heme oxygenase-1 exerts a protective role in ovalbumin-induced neutrophilic airway inflammation by inhibiting Th17 cell-mediated immune response.

    Science.gov (United States)

    Zhang, Yanjie; Zhang, Liya; Wu, Jinhong; Di, Caixia; Xia, Zhenwei

    2013-11-29

    Allergic asthma is conventionally considered as a Th2 immune response characterized by eosinophilic inflammation. Recent investigations revealed that Th17 cells play an important role in the pathogenesis of non-eosinophilic asthma (NEA), resulting in steroid-resistant neutrophilic airway inflammation. Heme oxygenase-1 (HO-1) has anti-inflammation, anti-oxidation, and anti-apoptosis functions. However, its role in NEA is still unclear. Here, we explore the role of HO-1 in a mouse model of NEA. HO-1 inducer hemin or HO-1 inhibitor tin protoporphyrin IX was injected intraperitoneally into ovalbumin-challenged DO11.10 mice. Small interfering RNA (siRNA) was delivered into mice to knock down HO-1 expression. The results show that induction of HO-1 by hemin attenuated airway inflammation and decreased neutrophil infiltration in bronchial alveolar lavage fluid and was accompanied by a lower proportion of Th17 cells in mediastinal lymph nodes and spleen. More importantly, induction of HO-1 down-regulated Th17-related transcription factor retinoic acid-related orphan receptor γt (RORγt) expression and decreased IL-17A levels, all of which correlated with a decrease in phosphorylated STAT3 (p-STAT3) level and inhibition of Th17 cell differentiation. Consistently, the above events could be reversed by tin protoporphyrin IX. Also, HO-1 siRNA transfection abolished the effect of hemin induced HO-1 in vivo. Meanwhile, the hemin treatment promoted the level of Foxp3 expression and enhanced the proportion of regulatory T cells (Tregs). Collectively, our findings indicate that HO-1 exhibits anti-inflammatory activity in the mouse model of NEA via inhibition of the p-STAT3-RORγt pathway, regulating kinetics of RORγt and Foxp3 expression, thus providing a possible novel therapeutic target in asthmatic patients. PMID:24097973

  1. Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed exert prebiotics and anti-inflammatory activities in Caco-2 cells

    Directory of Open Access Journals (Sweden)

    Pai-An Hwang

    2016-08-01

    Full Text Available Background: The aim of this study is to investigate the anti-inflammatory effects of low-molecular-weight fucoidan (LMF and high-stability fucoxanthin (HS-Fucox in a lipopolysaccharide-induced inflammatory Caco-2 cell line co-culture with B. lactis. Methods: We used various methods such as transepithelial resistance (TER assay, cytokine secretion assay, and tight junction protein mRNA expression assay to examine LMF and HS-Fucox anti-inflammatory properties. Results: LMF and HS-Fucox activated probiotic growth and reduced the inflammation of the intestinal epithelial cells. Moreover, the combination of LMFHS-Fucox dramatically enhanced the intestinal epithelial barrier and immune function against the lipopolysaccharide effect by inhibiting IL-1β and TNF-α and promoting IL-10 and IFN-γ. Conclusion: These findings suggested that LMF and HS-Fucox, alone or in combination, could be the potential natural compounds to enhance the immune system and have an anti-inflammatory effect on the intestinal cells.

  2. Shen-Qi-Jie-Yu-Fang exerts effects on a rat model of postpartum depression by regulating inflammatory cytokines and CD4+CD25+ regulatory T cells

    Directory of Open Access Journals (Sweden)

    Li JY

    2016-04-01

    Full Text Available Jingya Li,1,* Ruizhen Zhao,1,* Xiaoli Li,1 Wenjun Sun,1 Miao Qu,1 Qisheng Tang,1 Xinke Yang,1 Shujing Zhang2 1Third Affiliated Hospital, 2School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Shen-Qi-Jie-Yu-Fang (SJF is composed of eight Chinese medicinal herbs. It is widely used in traditional Chinese medicine for treating postpartum depression (PPD. Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism. Aim: To further investigate the effect of SJF on the immune system, including the inflammatory response system and CD4+CD25+ regulatory T (Treg cells. Materials and methods: Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were treated with SJF or fluoxetine for 1, 2, and 4 weeks. Levels of Treg cells in peripheral blood were measured by flow cytometry analysis. Serum interleukin (IL-1β and IL-6 were evaluated by enzyme-linked immunosorbent assay, and gene and protein expressions of IL-1RI, IL-6Rα, and gp130 in the hippocampus were observed by reverse-transcription polymerase chain reaction and Western blot. Results: Serum IL-1β in PPD rats increased at 2 weeks and declined from then on, while serum IL-6 increased at 1, 2, and 4 weeks. Both IL-1β and IL-6 were downregulated by SJF and fluoxetine. Changes in gene and protein expressions of IL-1RI and gp130 in PPD rats were consistent with changes in serum IL-1β, and were able to be regulated by SJF and fluoxetine. The levels of Treg cells were negatively correlated with serum IL-1β and IL-6, and were decreased in PPD rats. The levels of Treg cells were increased by SJF and fluoxetine. Conclusion: Dysfunction of proinflammatory cytokines and Tregs in different stages of PPD was attenuated by SJF and fluoxetine through

  3. Exertion injuries in female athletes.

    OpenAIRE

    Orava, S.; Hulkko, A; Jormakka, E.

    1981-01-01

    Because sports injuries in men form most of the available statistics, the reportage of injuries in female athletes is sparse. We describe exertion injuries and disorders in 281 women athletes, all of which hampered athletic training or performances. Sixty per cent of the injuries occurred to girls ages between 12-19 years, and about forty-eight per cent were track and field athletes. The most common sites of injury were the ankle, foot, heel and leg. Osteochondritic disorders were the most ty...

  4. N‑trans‑ρ‑caffeoyl tyramine isolated from Tribulus terrestris exerts anti‑inflammatory effects in lipopolysaccharide‑stimulated RAW 264.7 cells.

    Science.gov (United States)

    Ko, Han-Jik; Ahn, Eun-Kyung; Oh, Joa Sub

    2015-10-01

    Inflammation is induced by the expression of cyclooxygenase‑2 (COX‑2), which is an important mediator of chronic inflammatory diseases, such as rheumatoid arthritis, asthma and inflammatory bowel disease. Tribulus terrestris (T. terrestris) is known to have a beneficial effect on inflammatory diseases. In this study, we investigated the effects of N‑trans‑ρ‑caffeoyl tyramine (CT) isolated from T. terrestris on the production of nitric oxide (NO), and the expression of pro‑inflammatory cytokines and COX‑2 in lipopolysaccharide (LPS)‑stimulated RAW 264.7 cells. We also aimed to elucidate the molecular mechanisms involved. We found that the ethanolic extract of T. terrestris (EETT) and CT inhibited the production of NO, tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6 and IL‑10 in the LPS‑stimulated RAW 264.7 cells in a dose‑dependent manner. They were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, CT markedly suppressed the expression of COX‑2 and the production of prostaglandin E2 (PGE2) in response to LPS stimulation. Furthermore, CT markedly decreased p‑c‑Jun N‑terminal kinase (p‑JNK) protein expression in LPS‑stimulated RAW 264.7 cells. COX-2 and p-JNK were measured by western blot analysis. Taken together, these findings indicate that CT isolated from T. terrestris is a novel and potent modulator of inflammatory responses. Thus, it may prove benefiical to further evaluate CT as a possible treatment for chronic inflammatory diseases. PMID:26239676

  5. Phyllanthin of Standardized Phyllanthus amarus Extract Attenuates Liver Oxidative Stress in Mice and Exerts Cytoprotective Activity on Human Hepatoma Cell Line

    Science.gov (United States)

    Krithika, Rajesh; Verma, Ramtej J; Shrivastav, Pranav S; Suguna, Lonchin

    2011-01-01

    Background Phyllanthus amarus, a traditional herbal liver-protecting medicine, is known to contain an active ingredient phyllanthin. Many research studies and clinical trials performed in the past using this plant have given contentious results which clearly accentuates the need for the standardization of the extracts. Aim In this study, P. amarus extract was standardized for phyllanthin content by high performance thin layer chromatography (HPTLC) and high performance liquid chromatography (HPLC) analysis. The preventive role of a standardized extract of P. amarus against CC14-induced hepatotoxicity in vivo and in vitro using mice model and human hepatoma HepG2 cell line, respectively, was investigated. Methods Phyllanthin was used as a marker phytochemical for the standardization of P. amarus extract. The extracts were verified for phyllanthin content by HPTLC and HPLC. Female mice were orally administered with CCl4 either with or without standardized P. amarus extract in three different doses. Similarly, the cytoprotective role of the standardized extract in vitro was studied in HepG2 cell line. Results Oral administration of CCl4 resulted in increased oxidative stress, decreased antioxidative defense, and liver injury. Treatment with P. amarus along with CCl4 significantly mitigated the increase in activities of liver marker enzymes, lipid peroxidation, and bilirubin content. It also increased the antioxidant enzymatic and non-enzymatic defense parameter levels. The results of the in vitro study conducted in HepG2 cells indicated that the hepatotoxin lowered 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (Mil) metabolism and increased the release of transaminases which were corrected with co-incubation with P. amarus. Conclusion: The study established a significant liver-protecting role of standardized P. amarus extract due to the presence of active ingredient phyllanthin. PMID:25755316

  6. Progesterone and estradiol exert an inhibitory effect on the production of anti-inflammatory cytokine IL-10 by activated MZ B cells.

    Science.gov (United States)

    Bommer, I; Muzzio, D O; Zygmunt, M; Jensen, F

    2016-08-01

    The main message of this work is the fact that female sex hormones, progesterone and estradiol, whose levels significantly rise during pregnancy, inhibit the production of anti-inflammatory cytokine IL-10 with no apparent effect on pro-inflammatory cytokine TNF-α by activated MZ B cells. This is an important piece of information and helps to better understand how the maternal immune system controls the balance between immune tolerance and immune activation during pregnancy leading to the simultaneously acceptance of the semi-allogeneic fetus and the proper defense of the mother against pathogens during this critical period of time. PMID:27317920

  7. Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells

    International Nuclear Information System (INIS)

    Endostar, a novel recombinant human endostatin expressed and purified in Escherichia coli with an additional nine-amino acid sequence and forming another his-tag structure, was approved by the SFDA in 2005 for the treatment of non-small-cell lung cancer. But its mechanism of action has not been illustrated before. In this study, we examined the antiangiogenic activities of endostar in vitro and in vivo. The results showed that endostar suppressed the VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Endostar blocked microvessel sprouting from rat aortic rings in vitro. Moreover, it could inhibit the formation of new capillaries from pre-existing vessels in the chicken chorioallantoic membrane (CAM) assay and affect the growth of vessels in tumor. We further found the antiangiogenic effects of endostar were correlated with the VEGF-triggered signaling. Endostar suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1(VEGFR-2) as well as the overall VEGFR-2 expression and the activation of ERK, p38 MAPK, and AKT in HUVECs. Collectively, these data indicated the relationship between endostar and VEGF signal pathways and provided a molecular basis for the antiangiogenic effects of endostar

  8. LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p.

    Science.gov (United States)

    Nie, Wei; Ge, Hui-juan; Yang, Xiao-qun; Sun, Xiangjie; Huang, Hai; Tao, Xia; Chen, Wan-sheng; Li, Bing

    2016-02-01

    Recently, the long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified as an oncogenic gene in multiple human tumor entitles, and dysregulation of UCA1 was tightly linked to carcinogenesis and cancer progression. However, whether the aberrant expression of UCA1 in non-small cell lung cancer (NSCLC) is associated with malignancy, metastasis or prognosis has not been characterized. In this study, we found that UCA1 was upregulated in NSCLC tissues. Higher expression of UCA1 led to a significantly poorer survival time, and multivariate analysis revealed that UCA1 was an independent risk factor of prognosis. UCA1 overexpression enhanced, whereas UCA1 silencing impaired the proliferation and colony formation of NSCLC cells. Moreover, mechanistic investigations showed that UCA1 upregulated the expression of miR-193a-3p target gene ERBB4 through competitively 'spongeing' miR-193a-3p. Overall, we concluded that UCA1 functions as an oncogene in NSCLC, acting mechanistically by upregulating ERBB4 in part through 'spongeing' miR-193a-3p.

  9. miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221.

    Science.gov (United States)

    Kotani, Ai; Ha, Daon; Hsieh, James; Rao, Prakash K; Schotte, Diana; den Boer, Monique L; Armstrong, Scott A; Lodish, Harvey F

    2009-11-01

    MLL-AF4 acute lymphocytic leukemia (ALL) has a poor prognosis. MicroRNAs (miRNA) are small noncoding RNAs that posttranscriptionally regulate expression of target mRNAs. Our analysis of previously published data showed that expression of miR-128b and miR-221 is down-regulated in MLL-rearranged ALL relative to other types of ALL. Reexpression of these miRNAs cooperatively sensitizes 2 cultured lines of MLL-AF4 ALL cells to glucocorticoids. Target genes down-regulated by miR-128b include MLL, AF4, and both MLL-AF4 and AF4-MLL fusion genes; miR-221 down-regulates CDKN1B. These results demonstrate that down-regulation of miR-128b and miR-221 is implicated in glucocorticoid resistance and that restoration of their levels is a potentially promising therapeutic in MLL-AF4 ALL.

  10. Dioxin exerts anti-estrogenic actions in a novel dioxin-responsive telomerase-immortalized epithelial cell line of the porcine oviduct (TERT-OPEC).

    Science.gov (United States)

    Hombach-Klonisch, Sabine; Pocar, Paola; Kauffold, Johannes; Klonisch, Thomas

    2006-04-01

    Oviduct epithelial cells are important for the nourishment and survival of ovulated oocytes and early embryos, and they respond to the steroid hormones estrogen and progesterone. Endocrine-disrupting polyhalogenated aromatic hydrocarbons (PHAH) are environmental toxins that act in part through the ligand-activated transcription factor arylhydrocarbon receptor (AhR; dioxin receptor), and exposure to PHAH has been shown to decrease fertility. To investigate effects of PHAHs on the oviduct epithelium as a potential target tissue of dioxin-type endocrine disruptors, we have established a novel telomerase-immortalized oviduct porcine epithelial cell line (TERT-OPEC). TERT-OPEC exhibited active telomerase and the immunoreactive epithelial marker cytokeratin but lacked the stromal marker vimentin. TERT-OPEC contained functional estrogen receptor (ER)-alpha and AhR, as determined by the detection of ER-alpha- and AhR-specific target molecules. Treatment of TERT-OPEC with the AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a significant increase in the production of the cytochrome P-450 microsomal enzyme CYP1A1. Activated AhR caused a downregulation of ER nuclear protein fraction and significantly decreased ER-signaling in TERT-OPEC as determined by ERE-luciferase transient transfection assays. In summary, the TCDD-induced and AhR-mediated anti-estrogenic responses by TERT-OPEC suggest that PHAH affect the predominantly estrogen-dependent differentiation of the oviduct epithelium within the fallopian tube. This action then alters the local endocrine milieu, potentially resulting in a largely unexplored cause of impaired embryonic development and female infertility. PMID:16431846

  11. Exenatide exerts direct protective effects on endothelial cells through the AMPK/Akt/eNOS pathway in a GLP-1 receptor-dependent manner.

    Science.gov (United States)

    Wei, Rui; Ma, Shifeng; Wang, Chen; Ke, Jing; Yang, Jin; Li, Weihong; Liu, Ye; Hou, Wenfang; Feng, Xinheng; Wang, Guang; Hong, Tianpei

    2016-06-01

    Glucagon-like peptide-1 (GLP-1) may have direct favorable effects on cardiovascular system. The aim of this study was to investigate the effects of the GLP-1 analog exenatide on improving coronary endothelial function in patients with type 2 diabetes and to investigate the underlying mechanisms. The newly diagnosed type 2 diabetic subjects were enrolled and given either lifestyle intervention or lifestyle intervention plus exenatide treatment. After 12-wk treatment, coronary flow velocity reserve (CFVR), an important indicator of coronary endothelial function, was improved significantly, and serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were remarkably decreased in the exenatide treatment group compared with the baseline and the control group. Notably, CFVR was correlated inversely with hemoglobin A1c (Hb A1c) and positively with high-density lipoprotein cholesterol (HDL-C). In human umbilical vein endothelial cells, exendin-4 (a form of exenatide) significantly increased NO production, endothelial NO synthase (eNOS) phosphorylation, and GTP cyclohydrolase 1 (GTPCH1) level in a dose-dependent manner. The GLP-1 receptor (GLP-1R) antagonist exendin (9-39) or GLP-1R siRNA, adenylyl cyclase inhibitor SQ-22536, AMPK inhibitor compound C, and PI3K inhibitor LY-294002 abolished the effects of exendin-4. Furthermore, exendin-4 reversed homocysteine-induced endothelial dysfunction by decreasing sICAM-1 and reactive oxygen species (ROS) levels and upregulating NO production and eNOS phosphorylation. Likewise, exendin (9-39) diminished the protective effects of exendin-4 on the homocysteine-induced endothelial dysfunction. In conclusion, exenatide significantly improves coronary endothelial function in patients with newly diagnosed type 2 diabetes. The effect may be mediated through activation of AMPK/PI3K-Akt/eNOS pathway via a GLP-1R/cAMP-dependent mechanism. PMID:27072494

  12. PWR core safety analysis with 3-dimensional methods

    International Nuclear Information System (INIS)

    Highlights: • An overview of AREVA’s safety analysis codes their coupling is provided. • The validation base and licensing applications of these codes are summarized. • Coupled codes and methods provide improved margins and non-conservative results. • Examples for REA and inadvertent opening of the pressurizer safety valve are given. - Abstract: The main focus of safety analysis is to demonstrate the required safety level of the reactor core. Because of the demanding requirements, the quality of the safety analysis strongly affects the confidence in the operational safety of a reactor. To ensure the highest quality, it is essential that the methodology consists of appropriate analysis tools, an extensive validation base, and last but not least highly educated engineers applying the methodology. The sophisticated 3-dimensional core models applied by AREVA ensure that all physical effects relevant for safety are treated and the results are reliable and conservative. Presently AREVA employs SCIENCE, CASMO/NEMO and CASCADE-3D for pressurized water reactors. These codes are currently being consolidated into the next generation 3D code system ARCADIA®. AREVA continuously extends the validation base, including measurement campaigns in test facilities and comparisons of the predictions of steady state and transient measured data gathered from plants during many years of operation. Thus, the core models provide reliable and comprehensive results for a wide range of applications. For the application of these powerful tools, AREVA is taking benefit of its interdisciplinary know-how and international teamwork. Experienced engineers of different technical backgrounds are working together to ensure an appropriate interpretation of the calculation results, uncertainty analysis, along with continuously maintaining and enhancing the quality of the analysis methodologies. In this paper, an overview of AREVA’s broad application experience as well as the broad validation

  13. Human placental extract exerts hair growth-promoting effects through the GSK-3β signaling pathway in human dermal papilla cells.

    Science.gov (United States)

    Kwon, Tae-Rin; Oh, Chang Taek; Choi, Eun Ja; Park, Hye Min; Han, Hae Jung; Ji, Hyi Jeong; Kim, Beom Joon

    2015-10-01

    Human placental extract (HPE) is widely used in Korea to relieve fatigue. However, its effects on human dermal papilla cells (hDPCs) remain unknown. In the present study, in an effort to develop novel therapies to promote hair growth, we screened HPE. We demonstrate that HPE has hair growth‑promoting activities and induces β‑catenin expression through the inhibition of glycogen synthase kinase‑3β (GSK‑3β) by phosphorylation in hDPCs. Treatment with HPE significantly increased the viability of the hDPCs in a concentration‑dependent manner, as shown by bromodeoxyuridine (BrdU) assay. HPE also significantly increased the alkaline phosphatase (ALP) expression levels. The increased β‑catenin levels and the inhibition of GSK‑3β (Ser9) by phosphorylation suggested that HPE promoted the hair-inductive capacity of hDPCs. We compared the effects of treatment with HPE alone and treatment with HPE in conjunction with minoxidil (MXD). We found that HPE plus MXD effectively inhibited GSK‑3β by phosphorylation (Ser9) in the hDPCs. Moreover, we demonstrated that HPE was effective in inducing root hair elongation in rat vibrissa hair follicles, and that treatment with HPE led to a delay in catagen progression. Overall, our findings suggest that HPE promotes hair growth and may thus provide the basis of a novel therapeutic strategy for the clinical treatment of hair loss. PMID:26311045

  14. Tracking Error analysis of Concentrator Photovoltaic Module Using Total 3-Dimensional Simulator

    Science.gov (United States)

    Ota, Yasuyuki; Nishioka, Kensuke

    2011-12-01

    A 3-dimensional (3D) operating simulator for concentrator photovoltaic (CPV) module using triple-junction solar cell was developed. By connecting 3D equivalent circuit simulation for triple-junction solar cell and ray-trace simulation for optics model, the operating characteristics of CPV module were calculated. A typical flat Fresnel lens and homogenizer were adapted to the optics model. The influence of tracking error on the performance of CPV module was calculated. There was the correlation between the optical efficiency and Isc. However, Pm was not correlated with these values, and was strongly dependent on FF. We can use this total simulator for the evaluation and optimization from the light incidence to operating characteristic of CPV modules.

  15. Exertion injuries in female athletes.

    Science.gov (United States)

    Orava, S; Hulkko, A; Jormakka, E

    1981-12-01

    Because sports injuries in men form most of the available statistics, the reportage of injuries in female athletes is sparse. We describe exertion injuries and disorders in 281 women athletes, all of which hampered athletic training or performances. Sixty per cent of the injuries occurred to girls ages between 12-19 years, and about forty-eight per cent were track and field athletes. The most common sites of injury were the ankle, foot, heel and leg. Osteochondritic disorders were the most typical injuries in the series, and the chronic medical tibial syndrome was the injury that needed surgical treatment most frequently. Overuse injuries seem to differ very little from each other in the events included in this survey. PMID:6797496

  16. Palmitic acid exerts pro-inflammatory effects on vascular smooth muscle cells by inducing the expression of C-reactive protein, inducible nitric oxide synthase and tumor necrosis factor-α.

    Science.gov (United States)

    Wu, Di; Liu, Juntian; Pang, Xiaoming; Wang, Shuyue; Zhao, Jingjing; Zhang, Xiaolu; Feng, Liuxin

    2014-12-01

    Atherosclerosis is a chronic inflammatory disease in the vessel, and inflammatory cytokines play an important role in the inflammatory process of atherosclerosis. A high level of free fatty acids (FFAs) produced in lipid metabolism disorders are known to participate in the formation of atherosclerosis through multiple bioactivities. As the main saturated fatty acid in FFAs, palmitic acid stimulates the expression of inflammatory cytokines in macrophages. However, it is unclear whether palmitic acid exerts a pro-inflammatory effect on vascular smooth muscle cells (VSMCs). The purpose of the present study was to observe the effect of palmitic acid on the expression of C-reactive protein (CRP), tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in VSMCs. Rat VSMCs were cultured, and palmitic acid was used as a stimulant for CRP, TNF-α and iNOS expression. mRNA expression was assayed with reverse transcription-polymerase chain reaction, and protein expression was detected with western blot analysis and immunocytochemistry. The results showed that palmitic acid significantly stimulated mRNA and protein expression of CRP, TNF-α and iNOS in VSMCs in time- and concentration-dependent manners, and therefore, palmitic acid is able to exert a pro-inflammatory effect on VSMCs via stimulating CRP, TNF-α and iNOS expression. The findings provide a novel explanation for the direct pro-inflammatory and atherogenic effects of palmitic acid, and for the association with metabolic syndrome, such as type 2 diabetes mellitus, obesity and atherosclerosis. Therefore, the intervention with anti-inflammatory agents may effectively delay the formation and progression of atherosclerosis in patients with metabolic syndrome.

  17. The 3-dimensional construction of the Rae craton, central Canada

    Science.gov (United States)

    Snyder, David B.; Craven, James A.; Pilkington, Mark; Hillier, Michael J.

    2015-10-01

    Reconstruction of the 3-dimensional tectonic assembly of early continents, first as Archean cratons and then Proterozoic shields, remains poorly understood. In this paper, all readily available geophysical and geochemical data are assembled in a 3-D model with the most accurate bedrock geology in order to understand better the geometry of major structures within the Rae craton of central Canada. Analysis of geophysical observations of gravity and seismic wave speed variations revealed several lithospheric-scale discontinuities in physical properties. Where these discontinuities project upward to correlate with mapped upper crustal geological structures, the discontinuities can be interpreted as shear zones. Radiometric dating of xenoliths provides estimates of rock types and ages at depth beneath sparse kimberlite occurrences. These ages can also be correlated to surface rocks. The 3.6-2.6 Ga Rae craton comprises at least three smaller continental terranes, which "cratonized" during a granitic bloom. Cratonization probably represents final differentiation of early crust into a relatively homogeneous, uniformly thin (35-42 km), tonalite-trondhjemite-granodiorite crust with pyroxenite layers near the Moho. The peak thermotectonic event at 1.86-1.7 Ga was associated with the Hudsonian orogeny that assembled several cratons and lesser continental blocks into the Canadian Shield using a number of southeast-dipping megathrusts. This orogeny metasomatized, mineralized, and recrystallized mantle and lower crustal rocks, apparently making them more conductive by introducing or concentrating sulfides or graphite. Little evidence exists of thin slabs similar to modern oceanic lithosphere in this Precambrian construction history whereas underthrusting and wedging of continental lithosphere is inferred from multiple dipping discontinuities.

  18. Development and Validation of a 3-Dimensional CFB Furnace Model

    Science.gov (United States)

    Vepsäläinen, Arl; Myöhänen, Karl; Hyppäneni, Timo; Leino, Timo; Tourunen, Antti

    At Foster Wheeler, a three-dimensional CFB furnace model is essential part of knowledge development of CFB furnace process regarding solid mixing, combustion, emission formation and heat transfer. Results of laboratory and pilot scale phenomenon research are utilized in development of sub-models. Analyses of field-test results in industrial-scale CFB boilers including furnace profile measurements are simultaneously carried out with development of 3-dimensional process modeling, which provides a chain of knowledge that is utilized as feedback for phenomenon research. Knowledge gathered by model validation studies and up-to-date parameter databases are utilized in performance prediction and design development of CFB boiler furnaces. This paper reports recent development steps related to modeling of combustion and formation of char and volatiles of various fuel types in CFB conditions. Also a new model for predicting the formation of nitrogen oxides is presented. Validation of mixing and combustion parameters for solids and gases are based on test balances at several large-scale CFB boilers combusting coal, peat and bio-fuels. Field-tests including lateral and vertical furnace profile measurements and characterization of solid materials provides a window for characterization of fuel specific mixing and combustion behavior in CFB furnace at different loads and operation conditions. Measured horizontal gas profiles are projection of balance between fuel mixing and reactions at lower part of furnace and are used together with both lateral temperature profiles at bed and upper parts of furnace for determination of solid mixing and combustion model parameters. Modeling of char and volatile based formation of NO profiles is followed by analysis of oxidizing and reducing regions formed due lower furnace design and mixing characteristics of fuel and combustion airs effecting to formation ofNO furnace profile by reduction and volatile-nitrogen reactions. This paper presents

  19. The Design of Networked Exertion Games

    Directory of Open Access Journals (Sweden)

    Frank Vetere

    2009-01-01

    Full Text Available Incorporating physical activity and exertion into pervasive gaming applications can provide health and social benefits. Prior research has resulted in several prototypes of pervasive games that encourage exertion as interaction form; however, no detailed critical account of the various approaches exists. We focus on networked exertion games and detail some of our work while identifying the remaining issues towards providing a coherent framework. We outline common lessons learned and use them as the basis for generalizations for the design of networked exertion games. We propose possible directions of further investigation, hoping to provide guidance for future work to facilitate greater awareness and exposure of exertion games and their benefits.

  20. Automated image analysis reveals the dynamic 3-dimensional organization of multi-ciliary arrays

    Directory of Open Access Journals (Sweden)

    Domenico F. Galati

    2016-01-01

    Full Text Available Multi-ciliated cells (MCCs use polarized fields of undulating cilia (ciliary array to produce fluid flow that is essential for many biological processes. Cilia are positioned by microtubule scaffolds called basal bodies (BBs that are arranged within a spatially complex 3-dimensional geometry (3D. Here, we develop a robust and automated computational image analysis routine to quantify 3D BB organization in the ciliate, Tetrahymena thermophila. Using this routine, we generate the first morphologically constrained 3D reconstructions of Tetrahymena cells and elucidate rules that govern the kinetics of MCC organization. We demonstrate the interplay between BB duplication and cell size expansion through the cell cycle. In mutant cells, we identify a potential BB surveillance mechanism that balances large gaps in BB spacing by increasing the frequency of closely spaced BBs in other regions of the cell. Finally, by taking advantage of a mutant predisposed to BB disorganization, we locate the spatial domains that are most prone to disorganization by environmental stimuli. Collectively, our analyses reveal the importance of quantitative image analysis to understand the principles that guide the 3D organization of MCCs.

  1. Epigenetic and 3-dimensional regulation of V(D)J rearrangement of immunoglobulin genes.

    Science.gov (United States)

    Degner-Leisso, Stephanie C; Feeney, Ann J

    2010-12-01

    V(D)J recombination is a crucial component of the adaptive immune response, allowing for the production of a diverse antigen receptor repertoire (Ig and TCR). This review will focus on how epigenetic regulation and 3-dimensional (3D) interactions may control V(D)J recombination at Ig loci. The interplay between transcription factors and post-translational modifications at the Igh, Igκ, and Igλ loci will be highlighted. Furthermore, we propose that the spatial organization and epigenetic boundaries of each Ig loci before and during V(D)J recombination may be influenced in part by the CTCF/cohesin complex. Taken together, the many epigenetic and 3D layers of control ensure that Ig loci are only rearranged at appropriate stages of B cell development.

  2. A method for generating information of a 3-dimensional molecular structure of a molecule

    NARCIS (Netherlands)

    Flohil, J.A.; Wolf, M.G.; De Leeuw, S.W.

    2009-01-01

    The present invention relates to a method for generating information of a 3 -dimensional molecular structure of a molecule, said method being executable by a computer under the control of a program stored in the computer, said method comprising the steps of : (a) receiving a 3 -dimensional represent

  3. Topological Entropy and Renormalization group flow in 3-dimensional spherical spaces

    CERN Document Server

    Asorey, M; Cavero-Peláez, I; D'Ascanio, D; Santangelo, E M

    2015-01-01

    We analyze the renormalization group flow of the temperature independent term of the entropy in the high temperature limit \\beta/a S^IR_top between the topological entropies of the conformal field theories connected by such flow. From a 3-dimensional viewpoint the same term arises in the 3-dimensional Euclidean effective action and has the same monotone behavior under the RG group flow. We conjecture that such monotonic behavior is generic, which would give rise to a 3-dimensional generalization of the c-theorem, along the lines of the 2-dimensional c-theorem and the 4-dimensional a-theorem.

  4. SOME PROBLEMS ON JUMP CONDITIONS OF SHOCK WAVES IN 3-DIMENSIONAL SOLIDS

    Institute of Scientific and Technical Information of China (English)

    LI Yong-chi; YAO Lei; HU Xiu-zhang; CAO Jie-dong; DONG Jie

    2006-01-01

    Based on the general conservation laws in continuum mechanics, the Eulerian and Lagrangian descriptions of the jump conditions of shock waves in 3-dimensional solids were presented respectively. The implication of the jump conditions and their relations between each other, particularly the relation between the mass conservation and the displacement continuity, were discussed. Meanwhile the shock wave response curves in 3-dimensional solids, i.e. the Hugoniot curves were analysed, which provide the foundation for studying the coupling effects of shock waves in 3-dimensional solids.

  5. On an asymptotic distribution of dependent random variables on a 3-dimensional lattice.

    Science.gov (United States)

    Harvey, Danielle J; Weng, Qian; Beckett, Laurel A

    2010-06-15

    We define conditions under which sums of dependent spatial data will be approximately normally distributed. A theorem on the asymptotic distribution of a sum of dependent random variables defined on a 3-dimensional lattice is presented. Examples are also presented.

  6. 25-Hydroxycholesterol exerts both a cox-2-dependent transient proliferative effect and cox-2-independent cytotoxic effect on bovine endothelial cells in a time- and cell-type-dependent manner

    Directory of Open Access Journals (Sweden)

    Cantarutti Alyssa

    2010-11-01

    Full Text Available Abstract Background 25-hydroxycholesterol (25-OHC is a product of oxidation of dietary cholesterol present in human plasma. 25-OHC and other oxidized forms of cholesterol are implicated in modulating inflammatory responses involved in development of atherosclerosis and colon carcinogenesis. Methods Primary lymphatic, venous and arterial endothelial cells isolated from bovine mesentery (bmLEC, bmVEC, bmAEC were treated with 25-OHC and tested for several different cellular parameters. Results We found 25-OHC to be a potent inducer of cyclooxygenase-2 (Cox-2, prostaglandin G-H synthase-2 expression in bovine mesenteric lymphatic, venous, and arterial endothelial cells. The induction of Cox-2 expression in endothelial cells by 25-OHC led to an initial increase in cellular proliferation that was inhibited by the Cox-2 selective inhibitor celecoxib (Celebrex. Prolonged exposure to 25-OHC was cytotoxic. Furthermore, endothelial cells induced to express Cox-2 by 25-OHC were more sensitive to the effects of the Cox-2 selective inhibitor celecoxib (Celebrex. These results suggest that some effects of 25-OHC on cells may be dependent on Cox-2 enzymatic activity. Conclusions Cox-2 dependent elevating effects of 25-OHC on endothelial cell proliferation was transient. Prolonged exposure to 25-OHC caused cell death and enhanced celecoxib-induced cell death in a cell-type dependent manner. The lack of uniform response by the three endothelial cell types examined suggests that our model system of primary cultures of bmLECs, bmVECs, and bmAECs may aid the evaluation of celecoxib in inhibiting proliferation of different types of tumour-associated endothelial cells.

  7. Monolithically integrated Helmholtz coils by 3-dimensional printing

    International Nuclear Information System (INIS)

    3D printing technology is of great interest for the monolithic fabrication of integrated systems; however, it is a challenge to introduce metallic components into 3D printed molds to enable broader device functionality. Here, we develop a technique for constructing a multi-axial Helmholtz coil by injecting a eutectic liquid metal Gallium Indium alloy (EGaIn) into helically shaped orthogonal cavities constructed in a 3D printed block. The tri-axial solenoids each carry up to 3.6 A of electrical current and produce magnetic field up to 70 G. Within the central section of the coil, the field variation is less than 1% and is in agreement with theory. The flow rates and critical pressures required to fill the 3D cavities with liquid metal also agree with theoretical predictions and provide scaling trends for filling the 3D printed parts. These monolithically integrated solenoids may find future applications in electronic cell culture platforms, atomic traps, and miniaturized chemical analysis systems based on nuclear magnetic resonance.

  8. Initial magnetic field configurations for 3-dimensional simulations of astrophysical jets

    OpenAIRE

    Jorgensen, M.; R. Ouyed; Christensen, M.

    2001-01-01

    We solve, and provide analytical expressions, for current-free magnetic configurations in the context of initial setups of 3-dimensional simulations of astrophysical jets involving an accretion disk corona in hydrostatic balance around a central object. These configurations which thread through the accretion disk and its corona preserve the initial hydrostatic state. This work sets stage for future 3-dimensional jet simulations (including disk rotation and mass-load) where launching, accelera...

  9. Gender and contraction mode on perceived exertion.

    Science.gov (United States)

    Pincivero, D M; Polen, R R; Byrd, B N

    2010-05-01

    The purpose of this study was to examine perceived exertion responses during concentric and eccentric elbow flexor contractions between young adult men and women. Thirty healthy young adults participated in two experimental sessions. During the first session, subjects performed five concentric isokinetic maximal voluntary contractions (MVC) of elbow flexion, followed by nine, randomly-ordered sub-maximal contractions (10-90% MVC). The same procedures were repeated during the second session, with the exception that eccentric contractions were performed. Subjects rated their perceived exertion following the sub-maximal contractions with the Borg category-ratio scale. Perceived exertion was significantly (p<0.05) less than equivalent values on the CR-10 scale at intensities greater than, and equal to, 30% MVC. A three-factor interaction between 30-40% MVC indicated that perceived exertion increased more during the eccentric, than concentric, contractions in women, while the opposite pattern was evident for the men. There were no significant contraction mode or gender differences. Power function modeling revealed that perceived exertion increased in a negatively accelerating manner, except for the men performing eccentric exercise. Perceived exertion increases in a similar non-linear manner between men and women during concentric contractions, while men exhibited a statistically linear pattern during eccentric contractions. PMID:20148376

  10. FTY720 and two novel butterfly derivatives exert a general anti-inflammatory potential by reducing immune cell adhesion to endothelial cells through activation of S1P(3) and phosphoinositide 3-kinase.

    Science.gov (United States)

    Imeri, Faik; Blanchard, Olivier; Jenni, Aurelio; Schwalm, Stephanie; Wünsche, Christin; Zivkovic, Aleksandra; Stark, Holger; Pfeilschifter, Josef; Huwiler, Andrea

    2015-12-01

    Sphingosine-1-phosphate (S1P) is a key lipid regulator of a variety of cellular responses including cell proliferation and survival, cell migration, and inflammatory reactions. Here, we investigated the effect of S1P receptor activation on immune cell adhesion to endothelial cells under inflammatory conditions. We show that S1P reduces both tumor necrosis factor (TNF)-α- and lipopolysaccharide (LPS)-stimulated adhesion of Jurkat and U937 cells to an endothelial monolayer. The reducing effect of S1P was reversed by the S1P1+3 antagonist VPC23019 but not by the S1P1 antagonist W146. Additionally, knockdown of S1P3, but not S1P1, by short hairpin RNA (shRNA) abolished the reducing effect of S1P, suggesting the involvement of S1P3. A suppression of immune cell adhesion was also seen with the immunomodulatory drug FTY720 and two novel butterfly derivatives ST-968 and ST-1071. On the molecular level, S1P and all FTY720 derivatives reduced the mRNA expression of LPS- and TNF-α-induced adhesion molecules including ICAM-1, VCAM-1, E-selectin, and CD44 which was reversed by the PI3K inhibitor LY294002, but not by the MEK inhibitor U0126.In summary, our data demonstrate a novel molecular mechanism by which S1P, FTY720, and two novel butterfly derivatives acted anti-inflammatory that is by suppressing gene transcription of various endothelial adhesion molecules and thereby preventing adhesion of immune cells to endothelial cells and subsequent extravasation. PMID:26267293

  11. TAF4 inactivation reveals the 3 dimensional growth promoting activities of collagen 6A3.

    Directory of Open Access Journals (Sweden)

    Igor Martianov

    Full Text Available Collagen 6A3 (Col6a3, a component of extracellular matrix, is often up-regulated in tumours and is believed to play a pro-oncogenic role. However the mechanisms of its tumorigenic activity are poorly understood. We show here that Col6a3 is highly expressed in densely growing mouse embryonic fibroblasts (MEFs. In MEFs where the TAF4 subunit of general transcription factor IID (TFIID has been inactivated, elevated Col6a3 expression prevents contact inhibition promoting their 3 dimensional growth as foci and fibrospheres. Analyses of gene expression in densely growing Taf4(-/- MEFs revealed repression of the Hippo pathway and activation of Wnt signalling. The Hippo activator Kibra/Wwc1 is repressed under dense conditions in Taf4(-/- MEFs, leading to nuclear accumulation of the proliferation factor YAP1 in the cells forming 3D foci. At the same time, Wnt9a is activated and the Sfrp2 antagonist of Wnt signalling is repressed. Surprisingly, treatment of Taf4(-/- MEFs with all-trans retinoic acid (ATRA restores contact inhibition suppressing 3D growth. ATRA represses Col6a3 expression independently of TAF4 expression and Col6a3 silencing is sufficient to restore contact inhibition in Taf4(-/- MEFs and to suppress 3D growth by reactivating Kibra expression to induce Hippo signalling and by inducing Sfrp2 expression to antagonize Wnt signalling. All together, these results reveal a critical role for Col6a3 in regulating both Hippo and Wnt signalling to promote 3D growth, and show that the TFIID subunit TAF4 is essential to restrain the growth promoting properties of Col6a3. Our data provide new insight into the role of extra cellular matrix components in regulating cell growth.

  12. Does heavy physical exertion trigger myocardial infarction?

    DEFF Research Database (Denmark)

    Hallqvist, J; Möller, J; Ahlbom, A;

    2000-01-01

    To study possible triggering of first events of acute myocardial infarction by heavy physical exertion, the authors conducted a case-crossover analysis (1993-1994) within a population-based case-referent study in Stockholm County, Sweden (the Stockholm Heart Epidemiology Program). Interviews were...... carried out with 699 myocardial infarction patients after onset of the disease. These cases represented 47 percent of all cases in the study base, and 70 percent of all nonfatal cases. The relative risk from vigorous exertion was 6.1 (95% confidence interval: 4.2, 9.0). The rate difference was 1.5 per...

  13. Methylprednisolone exerts neuroprotective effects by regulating autophagy and apoptosis

    Institute of Scientific and Technical Information of China (English)

    Wei Gao; Shu-rui Chen; Meng-yao Wu; Kai Gao; Yuan-long Li; Hong-yu Wang; Chen-yuan Li; Hong Li

    2016-01-01

    Methylprednisolone markedly reduces autophagy and apoptosis after secondary spinal cord injury. Here, we investigated whether pretreat-ment of cells with methylprednisolone would protect neuron-like cells from subsequent oxidative damagevia suppression of autophagy and apoptosis. Cultured N2a cells were pretreated with 10 µM methylprednisolone for 30 minutes, then exposed to 100 µM H2O2 for 24 hours. Inverted phase contrast microscope images, MTT assay, lfow cytometry and western blot results showed that, compared to cells ex-posed to 100 µM H2O2 alone, cells pretreated with methylprednisolone had a signiifcantly lower percentage of apoptotic cells, maintained a healthy morphology, and showed downregulation of autophagic protein light chain 3B and Beclin-1 protein expression. These ifndings indicate that methylprednisolone exerted neuroprotective effects against oxidative damage by suppressing autophagy and apoptosis.

  14. The 3-Dimensional q-Deformed Harmonic Oscillator and Magic Numbers of Alkali Metal Clusters

    CERN Document Server

    Bonatsos, Dennis; Raychev, P P; Roussev, R P; Terziev, P A; Bonatsos, Dennis

    1999-01-01

    Magic numbers predicted by a 3-dimensional q-deformed harmonic oscillator with Uq(3) > SOq(3) symmetry are compared to experimental data for alkali metal clusters, as well as to theoretical predictions of jellium models, Woods--Saxon and wine bottle potentials, and to the classification scheme using the 3n+l pseudo quantum number. The 3-dimensional q-deformed harmonic oscillator correctly predicts all experimentally observed magic numbers up to 1500 (which is the expected limit of validity for theories based on the filling of electronic shells), thus indicating that Uq(3), which is a nonlinear extension of the U(3) symmetry of the spherical (3-dimensional isotropic) harmonic oscillator, is a good candidate for being the symmetry of systems of alkali metal clusters.

  15. Exertion and acute coronary artery injury.

    Science.gov (United States)

    Black, A; Black, M M; Gensini, G

    1975-12-01

    Twelve cases of myocardial infarction as related to strenuous exertion are presented with the pathological findings in several of these cases. Three cases with coronary arteriography are also presented. The pathology of coronary arteriosclerotic plaques and the vulnerability to acute injury is reviewed and discussed. It is concluded that strenuous exertion can cause acute injury to coronary artery plaques due to the unusual stressful whip-like action to which coronary arteries are subject. These injuries may initiate as cracks in the plaques or subintimal hemorrhages and proceed to coronary occlusion and ultimate myocardial infarction. With this concept in mind we use the term of "crack in the plaque" (Black's Crack in the Plaque) to account for the sudden appearance of clinical coronary artery disease appearing during or shortly after exertion, or other stressful situations in patients without previous existing evidence of clinical coronary artery disease. This could also account for exacerbation of symptoms or death occurring after exertion in previously quiescent asymptomatic known coronary artery disease subjects. This concept may explain some of the puzzling features of coronary disease.

  16. Physical exertion may cause high troponin levels.

    Science.gov (United States)

    Agewall, Stefan; Tjora, Solve

    2011-11-15

    It is important to measure troponin levels when acute myocardial infarct is suspected. Many other factors that affect the heart can cause an increase in troponin levels, for example extreme physical exertion. Recent studies have shown that more normal physical activity can also lead to increase in troponin levels in healthy individuals.

  17. Regenerative material for aneurysm embolization A 3-dimensional culture system of fibroblasts and calcium alginate gel

    Institute of Scientific and Technical Information of China (English)

    Jingdong Zhang; Kan Xu; Jinlu Yu; Jun Wang; Qi Luo

    2011-01-01

    Calcium alginate gel (CAG) has been shown to successfully model aneurysm embolization within a short period of time. However, gradually degrading CAG potentially results in aneurysm recanalization.In the present study, a regenerative embolic material was designed by seeding rat fibroblasts in a CAG. The study investigated the feasibility of constructing a 3-dimensional culture system. The fibroblasts grew well and firmly attached to the CAG. CAG was conducive for fibroblast growth, and resulted in a 3-dimensional culture system. Results show that CAG can be used theoretically as a vascular, regenerative, embolic material.

  18. 3-dimensional orthodontics visualization system with dental study models and orthopantomograms

    Science.gov (United States)

    Zhang, Hua; Ong, S. H.; Foong, K. W. C.; Dhar, T.

    2005-04-01

    The aim of this study is to develop a system that provides 3-dimensional visualization of orthodontic treatments. Dental plaster models and corresponding orthopantomogram (dental panoramic tomogram) are first digitized and fed into the system. A semi-auto segmentation technique is applied to the plaster models to detect the dental arches, tooth interstices and gum margins, which are used to extract individual crown models. 3-dimensional representation of roots, generated by deforming generic tooth models with orthopantomogram using radial basis functions, is attached to corresponding crowns to enable visualization of complete teeth. An optional algorithm to close the gaps between deformed roots and actual crowns by using multi-quadratic radial basis functions is also presented, which is capable of generating smooth mesh representation of complete 3-dimensional teeth. User interface is carefully designed to achieve a flexible system with as much user friendliness as possible. Manual calibration and correction is possible throughout the data processing steps to compensate occasional misbehaviors of automatic procedures. By allowing the users to move and re-arrange individual teeth (with their roots) on a full dentition, this orthodontic visualization system provides an easy and accurate way of simulation and planning of orthodontic treatment. Its capability of presenting 3-dimensional root information with only study models and orthopantomogram is especially useful for patients who do not undergo CT scanning, which is not a routine procedure in most orthodontic cases.

  19. Dynamics of large scale 3-dimensional circulation of the Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Swapna, P.

    -diagnostic calculation (ii) To simulate the climatic 3-dimensional circulation of Indian Ocean using the state of art sigma co-ordinate model. (iii) To study the sensitivity of Indian Ocean circulation to different wind fields (iv) To compare the model results...

  20. Study of new chaotic flows on a family of 3-dimensional systems with quadratic nonlinearities

    International Nuclear Information System (INIS)

    Based on a wider systematic search on a family of 3-dimensional systems with quadratic nonlinearities, three new simple chaotic systems were found. One of them has the unusual feature of having a stable equilibrium point, and it is the simplest one of other chaotic flows with this property. The others have some interesting special properties

  1. Reproducibility of a 3-dimensional gyroscope in measuring shoulder anteflexion and abduction

    NARCIS (Netherlands)

    Penning, L.I.F.; Guldemond, N.A.; De Bie, R.A.; Walenkamp, G.H.I.M.

    2012-01-01

    Background: Few studies have investigated the use of a 3-dimensional gyroscope for measuring the range of motion (ROM) in the impaired shoulder. Reproducibility of digital inclinometer and visual estimation is poor. This study aims to investigate the reproducibility of a tri axial gyroscope in measu

  2. 3-Dimensional and Interactive Istanbul University Virtual Laboratory Based on Active Learning Methods

    Science.gov (United States)

    Ince, Elif; Kirbaslar, Fatma Gulay; Yolcu, Ergun; Aslan, Ayse Esra; Kayacan, Zeynep Cigdem; Alkan Olsson, Johanna; Akbasli, Ayse Ceylan; Aytekin, Mesut; Bauer, Thomas; Charalambis, Dimitris; Gunes, Zeliha Ozsoy; Kandemir, Ceyhan; Sari, Umit; Turkoglu, Suleyman; Yaman, Yavuz; Yolcu, Ozgu

    2014-01-01

    The purpose of this study is to develop a 3-dimensional interactive multi-user and multi-admin IUVIRLAB featuring active learning methods and techniques for university students and to introduce the Virtual Laboratory of Istanbul University and to show effects of IUVIRLAB on students' attitudes on communication skills and IUVIRLAB. Although…

  3. 3-Dimensional Cahn-Hilliard Equation with Concentration Dependent Mobility and Gradient Dependent Potential

    Institute of Scientific and Technical Information of China (English)

    Rui HUANG; Yang CAO

    2011-01-01

    In this paper we investigate the initial boundary value problem of Cahn-Hilliard equation with concentration dependent mobility and gradient dependent potential. By the energy method and the theory of Campanato spaces, we prove the existence and the uniqueness of classical solutions in 3-dimensional space.

  4. Full 3-dimensional digital workflow for multicomponent dental appliances : A proof of concept

    NARCIS (Netherlands)

    van der Meer, W. Joerd; Vissink, Arjan; Ren, Yijin

    2016-01-01

    BACKGROUND: The authors used a 3-dimensional (3D) printer and a bending robot to produce a multicomponent dental appliance to assess whether 3D digital models of the dentition are applicable for a full digital workflow. METHODS: The authors scanned a volunteer's dentition with an intraoral scanner (

  5. An application of the 3-dimensional q-deformed harmonic oscillator to the nuclear shell model

    CERN Document Server

    Raychev, P P; Lo-Iudice, N; Terziev, P A

    1998-01-01

    An analysis of the construction of a q-deformed version of the 3-dimensional harmonic oscillator, which is based on the application of q-deformed algebras, is presented. The results together with their applicability to the shell model are compared with the predictions of the modified harmonic oscillator.

  6. On an asymptotic distribution of dependent random variables on a 3-dimensional lattice✩

    Science.gov (United States)

    Harvey, Danielle J.; Weng, Qian; Beckett, Laurel A.

    2010-01-01

    We define conditions under which sums of dependent spatial data will be approximately normally distributed. A theorem on the asymptotic distribution of a sum of dependent random variables defined on a 3-dimensional lattice is presented. Examples are also presented. PMID:20436940

  7. Estimating 3-Dimensional Structure of Tropical Forests from Radar Interferometry / Estimativa da Estrutura 3-Dimensional das Florestas Tropicais Através de Interferometria de Radar

    Directory of Open Access Journals (Sweden)

    Robert Treuhaft

    2006-10-01

    Full Text Available This paper describes the retrieval of 3-dimensional vegetation density profiles from interferometric synthetic aperture radar (InSAR using physical models. InSAR’s sensitivity to vertical structure is generally regarded as less direct and more difficult to understand than that of lidar. But InSAR’s coverage is superior to that of lidar, suggesting InSAR is more promising as an important component of a global 3-dimensional forest monitoring technique. The goal of this paper is to introduce, simplify and demystify the use of simple physical models to understand InSAR. A general equation expressing the InSAR observation in terms of density is described heuristically, along with the approximations in its development. The information content of the equation leads to the estimation of density parameters. Preliminary results are shown from a multibaseline C-band (wavelength=0.056 m vertical-polarization interferometer, realized with AirSAR flown at multiple altitudes over primary, secondary, and selectively logged tropical forests, as well as abandoned pastures at La Selva Biological Station in Costa Rica.

  8. DCP-LA Exerts an Antiaging Action on the Skin.

    Science.gov (United States)

    Nishizaki, Tomoyuki

    2016-01-01

    The present study assessed the possibility for the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) as an antiaging compound for the skin by assaying senescence-associated β-galactosidase (SA-β-Gal), a biomarker of senescence and cell viability. The nitric oxide (NO) donor sodium nitroprusside (SNP) increased in SA-β-Gal-positive cells in cultured human fibroblasts and mouse keratinocytes, and DCP-LA significantly inhibited the effect of SNP. Moreover, SNP induced cell death in cultured mouse keratinocytes, and DCP-LA significantly prevented NO stress-induced death of keratinocytes. Taken together, these results indicate that DCP-LA exerts an antiaging action on the skin. PMID:27310436

  9. DCP-LA Exerts an Antiaging Action on the Skin.

    Science.gov (United States)

    Nishizaki, Tomoyuki

    2016-01-01

    The present study assessed the possibility for the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) as an antiaging compound for the skin by assaying senescence-associated β-galactosidase (SA-β-Gal), a biomarker of senescence and cell viability. The nitric oxide (NO) donor sodium nitroprusside (SNP) increased in SA-β-Gal-positive cells in cultured human fibroblasts and mouse keratinocytes, and DCP-LA significantly inhibited the effect of SNP. Moreover, SNP induced cell death in cultured mouse keratinocytes, and DCP-LA significantly prevented NO stress-induced death of keratinocytes. Taken together, these results indicate that DCP-LA exerts an antiaging action on the skin.

  10. 3-dimensional slope stability analyses using non-associative stress-strain relationships

    Institute of Scientific and Technical Information of China (English)

    CHEN ZuYu; SUN Ping; WANG YuJie; ZHANG HongTao

    2009-01-01

    The research work presented in this paper refers to a new slope stability analysis method used for landslide risk evaluations. It is an extension of the 3-dimensional upper-bound slope stability analysis method proposed by Chen et sl. in 2001, which employs the Mohr-Coulomb's associative flow rule. It has been found that in a 3-dimensional area, a prism may not be able to move at friction angles to all its surrounding interfaces, as required by this associative rule, and convergence problems may occa-sionally arise. The new method establishes two velocity fields: (i) The plastic one that represents a non-associative and the best representative dilation behavior, and (ii) the virtual one that permits the solution for factor of safety in the work and energy balance equation. The new method can then allow any input value of dilation angle and thus solve the convergence problem. A practical application to a concrete dam foundation is illustrated.

  11. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    Energy Technology Data Exchange (ETDEWEB)

    Salama, Joseph K., E-mail: joseph.salama@duke.edu [Duke University Medical Center, Durham, NC (United States); Stinchcombe, Thomas E. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Gu Lin; Wang Xiaofei [CALGB Statistical Center, Duke University Medical Center, Durham, NC (United States); Morano, Karen [Quality Assurance Review Center, Lincoln, RI (United States); Bogart, Jeffrey A. [State University of New York Upstate Medical University, Syracuse, NY (United States); Crawford, Jeffrey C. [Duke University Medical Center, Durham, NC (United States); Socinski, Mark A. [University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Blackstock, A. William [Wake Forest University School of Medicine, Winston-Salem, NC (United States); Vokes, Everett E. [University of Chicago, Chicago, IL (United States)

    2011-11-15

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non-small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  12. Pulmonary Toxicity in Stage III Non-Small Cell Lung Cancer Patients Treated With High-Dose (74 Gy) 3-Dimensional Conformal Thoracic Radiotherapy and Concurrent Chemotherapy Following Induction Chemotherapy: A Secondary Analysis of Cancer and Leukemia Group B (CALGB) Trial 30105

    International Nuclear Information System (INIS)

    Purpose: Cancer and Leukemia Group B (CALGB) 30105 tested two different concurrent chemoradiotherapy platforms with high-dose (74 Gy) three-dimensional conformal radiotherapy (3D-CRT) after two cycles of induction chemotherapy for Stage IIIA/IIIB non–small cell lung cancer (NSCLC) patients to determine if either could achieve a primary endpoint of >18-month median survival. Final results of 30105 demonstrated that induction carboplatin and gemcitabine and concurrent gemcitabine 3D-CRT was not feasible because of treatment-related toxicity. However, induction and concurrent carboplatin/paclitaxel with 74 Gy 3D-CRT had a median survival of 24 months, and is the basis for the experimental arm in CALGB 30610/RTOG 0617/N0628. We conducted a secondary analysis of all patients to determine predictors of treatment-related pulmonary toxicity. Methods and Materials: Patient, tumor, and treatment-related variables were analyzed to determine their relation with treatment-related pulmonary toxicity. Results: Older age, higher N stage, larger planning target volume (PTV)1, smaller total lung volume/PTV1 ratio, larger V20, and larger mean lung dose were associated with increasing pulmonary toxicity on univariate analysis. Multivariate analysis confirmed that V20 and nodal stage as well as treatment with concurrent gemcitabine were associated with treatment-related toxicity. A high-risk group comprising patients with N3 disease and V20 >38% was associated with 80% of Grades 3-5 pulmonary toxicity cases. Conclusions: Elevated V20 and N3 disease status are important predictors of treatment related pulmonary toxicity in patients treated with high-dose 3D-CRT and concurrent chemotherapy. Further studies may use these metrics in considering patients for these treatments.

  13. BPS operators from the Wilson loop in the 3-dimensional supersymmetric Chern-Simons theory

    OpenAIRE

    Fujita, Mitsutoshi

    2009-01-01

    We consider the small deformation of the pointlike Wilson loop in the 3-dimensional N=6 superconformal Chern-Simons theory. By Taylor expansion of the pointlike Wilson loop in powers of the loop variables, we obtain the BPS operators that correspond to the excited string states of the dual IIA string theory on the pp wave background. The BPS conditions of the Wilson loop constrain both the loop variables and the forms of the operators obtained in the Taylor expansion.

  14. Perfect fluid space-times admitting a 3-dimensional conformal group acting on null orbits

    CERN Document Server

    Sintes, A M

    1997-01-01

    Space-times admitting a 3-dimensional Lie group of conformal motions $C_3$ acting on null orbits are studied. Coordinate expressions for the metric and the conformal Killing vectors (CKV) are then provided (irrespectively of the matter content) and all possible perfect fluid solutions are found, although none of them verifies the weak and dominant energy conditions over the whole space-time manifold.

  15. DYNAMICAL CONSISTENCE IN 3-DIMENSIONAL TYPE-K COMPETITIVE LOTKA-VOLTERRA SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    A 3-dimensional type-K competitive Lotka-Volterra system is considered in this paper. Two discretization schemes are applied to the system with an positive interior fixed point, and two corresponding discrete systems are obtained. By analyzing the local dynamics of the corresponding discrete system near the interior fixed point, it is showed that this system is not dynamically consistent with the continuous counterpart system.

  16. The Preoperative Evaluation of Infective Endocarditis via 3-Dimensional Transesophageal Echocardiography.

    Science.gov (United States)

    Yong, Matthew S; Saxena, Pankaj; Killu, Ammar M; Coffey, Sean; Burkhart, Harold M; Wan, Siu-Hin; Malouf, Joseph F

    2015-08-01

    Transesophageal echocardiography continues to have a central role in the diagnosis of infective endocarditis and its sequelae. Recent technological advances offer the option of 3-dimensional imaging in the evaluation of patients with infective endocarditis. We present an illustrative case and review the literature regarding the potential advantages and limitations of 3-dimensional transesophageal echocardiography in the diagnosis of complicated infective endocarditis. A 51-year-old man, an intravenous drug user who had undergone bioprosthetic aortic valve replacement 5 months earlier, presented with prosthetic valve endocarditis. Preoperative transesophageal echocardiography with 3D rendition revealed a large abscess involving the mitral aortic intervalvular fibrosa, together with a mycotic aneurysm that had ruptured into the left atrium, resulting in a left ventricle-to-left atrium fistula. Three-dimensional transesophageal echocardiography enabled superior preoperative anatomic delineation and surgical planning. We conclude that 3-dimensional transesophageal echocardiography can be a useful adjunct to traditional 2-dimensional transesophageal echocardiography as a tool in the diagnosis of infective endocarditis.

  17. Down-regulation of 14-3-3β exerts anti-cancer effects through inducing ER stress in human glioma U87 cells: Involvement of CHOP–Wnt pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Lei; Lei, Hui; Chang, Ming-Ze; Liu, Zhi-Qin [Department of Neurological Disease, Xi' an Central Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710000 (China); Bie, Xiao-Hua, E-mail: biexiaohua_xjtu@126.com [Department of Functional Neurosurgery, Xi' an Red Cross Hospital, Xi' an Jiaotong University, Xi' an, Shaanxi 710054 (China)

    2015-07-10

    We previously identified 14-3-3β as a tumor-specific isoform of 14-3-3 protein in astrocytoma, but its functional role in glioma cells and underlying mechanisms are poorly understood. In the present study, we investigated the effects of 14-3-3β inhibition in human glioma U87 cells using specific targeted small interfering RNA (siRNA). The results showed that 14-3-3β is highly expressed in U87 cells but not in normal astrocyte SVGp12 cells. Knockdown of 14-3-3β by Si-14-3-3β transfection significantly decreased the cell viability but increased the LDH release in a time-dependent fashion in U87 cells, and these effects were accompanied with G0/G1 cell cycle arrest and apoptosis. In addition, 14-3-3β knockdown induced ER stress in U87 cells, as evidenced by ER calcium release, increased expression of XBP1S mRNA and induction of ER related pro-apoptotic factors. Down-regulation of 14-3-3β significantly decreased the nuclear localization of β-catenin and inhibited Topflash activity, which was shown to be reversely correlated with CHOP. Furthermore, Si-CHOP and sFRP were used to inhibit CHOP and Wnt, respectively. The results showed that the anti-cancer effects of 14-3-3β knockdown in U87 cells were mediated by increased expression of CHOP and followed inhibition of Wnt/β-catenin pathway. In summary, the remarkable efficiency of 14-3-3β knockdown to induce apoptotic cell death in U87 cells may find therapeutic application for the treatment of glioma patients. - Highlights: • Knockdown of 14-3-3β leads to cytotoxicity in human glioma U87 cells. • Knockdown of 14-3-3β induces cell cycle arrest and apoptosis in U87 cells. • Knockdown of 14-3-3β results in ER stress in U87 cells. • Knockdown of 14-3-3β inhibits Wnt/β-catenin pathway via CHOP activation.

  18. Functional analysis of Peutz-Jeghers mutations reveals that the LKB1 C-terminal region exerts a crucial role in regulating both the AMPK pathway and the cell polarity.

    NARCIS (Netherlands)

    Forcet, C.; Etienne-Manneville, S.; Gaude, H.; Fournier, L.; Debilly, S.; Salmi, M.; Baas, A.; Olschwang, S.; Clevers, J.C.; Billaud, M.

    2005-01-01

    Germline mutations of the LKB1 gene are responsible for the cancer-prone Peutz-Jeghers syndrome (PJS). LKB1 encodes a serine-threonine kinase that acts as a regulator of cell cycle, metabolism and cell polarity. The majority of PJS missense mutations abolish LKB1 enzymatic activity and thereby impai

  19. A New Approach of In Vivo Musculoskeletal Tissue Engineering Using the Epigastric Artery as Central Core Vessel of a 3-Dimensional Construct

    Directory of Open Access Journals (Sweden)

    Sebastian E. Dunda

    2012-01-01

    Full Text Available The creation of musculoskeletal tissue represents an alternative for the replacement of soft tissue in reconstructive surgery. However, most of the approaches of creating artificial tissue have their limitations in the size as the maximally obtainable dimension of bioartificial tissue (BAT is limited due to the lack of supporting vessels within the 3-dimensional construct. The seeded myoblasts require high amounts of perfusion, oxygen, and nutrients to survive. To achieve this, we developed a 3-dimensional scaffold which features the epigastric artery as macroscopic core vessel inside the BAT in a rat model (perfused group, =4 and a control group (=3 without the epigastric vessels and, therefore, without perfusion. The in vivo monitoring of the transplanted myoblasts was assessed by bioluminescence imaging and showed both the viability of the epigastric artery within the 3-dimensional construct and again that cell survival in vivo is highly depending on the blood supply with the beginning of capillarization within the BAT seven days after transplantation in the perfused group. However, further studies focussing on the matrix improvement will be necessary to create a transplantable BAT with the epigastric artery as anastomosable vessel.

  20. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl{sup +} K562 and Jak2(V617F){sup +} HEL Leukemia Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Axel [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany); Borghouts, Corina [Ganymed Pharmaceuticals AG, Mainz 55131 (Germany); Brendel, Christian [Boston Children’s Hospital, Division of Hematology/Oncology, Boston, MA 02115 (United States); Moriggl, Richard [Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna 1090 (Austria); Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd, E-mail: Groner@em.uni-frankfurt.de [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany)

    2015-03-19

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl{sup +} K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells

  1. The 3-dimensional play of human parechovirus infection; Cell, virus and antibody

    NARCIS (Netherlands)

    B.M. Westerhuis

    2014-01-01

    HPeV3 has been shown to be the ‘odd one out’ compared to the other genotypes; HPeV3 is more often associated with severe disease, infects significantly younger infants, seems to be more difficult to culture, and does not recombine with other HPeV types. The aim of this thesis is to study whether the

  2. Gemcitabine resistance in breast cancer cells regulated by PI3K/AKT-mediated cellular proliferation exerts negative feedback via the MEK/MAPK and mTOR pathways

    Directory of Open Access Journals (Sweden)

    Yang XL

    2014-06-01

    Full Text Available Xiao Li Yang, Feng Juan Lin, Ya Jie Guo, Zhi Min Shao, Zhou Luo Ou Key Laboratory of Breast Cancer in Shanghai, Breast Cancer Institute, Cancer Hospital, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Abstract: Chemoresistance is a major cause of cancer treatment failure and leads to a reduction in the survival rate of cancer patients. Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR and mitogen-activated protein kinase (MAPK pathways are aberrantly activated in many malignant tumors, including breast cancer, which may indicate an association with breast cancer chemoresistance. In this study, we generated a chemoresistant human breast cancer cell line, MDA-MB-231/gemcitabine (simplified hereafter as “231/Gem”, from MDA-MB-231 human breast cancer cells. Flow cytometry studies revealed that with the same treatment concentration of gemcitabine, 231/Gem cells displayed more robust resistance to gemcitabine, which was reflected by fewer apoptotic cells and enhanced percentage of S-phase cells. Through the use of inverted microscopy, Cell Counting Kit-8, and Transwell assays, we found that compared with parental 231 cells, 231/Gem cells displayed more morphologic projections, enhanced cell proliferative ability, and improved cell migration and invasion. Mechanistic studies revealed that the PI3K/AKT/mTOR and mitogen-activated protein kinase kinase (MEK/MAPK signaling pathways were activated through elevated expression of phosphorylated (p-extracellular signal-regulated kinase (ERK, p-AKT, mTOR, p-mTOR, p-P70S6K, and reduced expression of p-P38 and LC3-II (the marker of autophagy in 231/Gem in comparison to control cells. However, there was no change in the expression of Cyclin D1 and p-adenosine monophosphate-activated protein kinase (AMPK. In culture, inhibitors of PI3K/AKT and mTOR, but not of MEK/MAPK, could reverse the enhanced proliferative

  3. Study on evaluation of a linear cross section model in 3-dimensional core analysis method

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Goo; Yang, Chae Yong; Jang, Chang Sun; Jung, Hoon Young; Kim, Hho Jung

    2005-02-15

    The previous studies provided that the ejection rod worth and enthalpy rise have a significant error due to a linear approximation of the cross sections in the analysis of rod ejection accident using a 3-dimensional core kinetics method. This study undertakes the validations of a linear approximation model for the cross sections used in the 3-dimensional core kinetics method. The linear approximation model for the cross sections consists of several parameters related with boron concentration, fuel temperature, coolant temperature and density, etc., but this study examines for the parameter related with boron concentration. At first, a reference boron concentration set are selected, and the corresponding linear parameter are calculated by CASMO-3 code. Another two sets are selected, and their parameters are also calculated. The relative errors are calculated form the cross sections for these 3 cases. For their study, 3 types of fuel are chosen, which are representative of fresh fuel, medium burnup and high burnup. Also, 9 cross sections of 2 energy groups are evaluated. The results shows that the relative error of the cross sections for high burnup fuel are more than low burnup, and the error are large in absorption cross section and fission cross section, the maximum of which is more than 3%. It is concluded that in the analysis of accident using 3-dimensional core kinetics model the cross section model has a significant influence on their result, and the results are largely dependent on how to select parameters in a cross section model. Hence, regulatory reviewer needs to evaluate the validation of cross section model proposed by designer.

  4. Development of a 3-dimensional seismic isolation floor for computer systems

    International Nuclear Information System (INIS)

    In this paper, we investigated the applicability of a seismic isolation floor as a method for protecting computer systems from strong earthquakes, such as computer systems in nuclear power plants. Assuming that the computer system is guaranteed for 250 cm/s2 of input acceleration in the horizontal and vertical directions as the seismic performance, the basic design specification of the seismic isolation floor is considered as follows. Against S1 level earthquakes, the maximum acceleration response of the seismic isolation floor in the horizontal and vertical directions is kept less than 250 cm/s2 to maintain continuous computer operation. Against S2 level earthquakes, the isolation floor allows large horizontal movement and large displacement of the isolation devices to reduce the acceleration response, although it is not guaranteed to be less than 250 cm/s2. By reducing the acceleration response, however, serious damage to the computer systems is reduced, so that they can be restarted after an earthquake. Usually, seismic isolation floor systems permit 2-dimensional (horizontal) isolation. However, in the case of just-under-seated earthquakes, which have large vertical components, the vertical acceleration response of this system is amplified by the lateral vibration of the frame of the isolation floor. Therefore, in this study a 3-dimensional seismic isolation floor, including vertical isolation, was developed. This paper describes 1) the experimental results of the response characteristics of the 3-dimensional seismic isolation floor built as a trial using a 3-dimensional shaking table, and 2) comparison of a 2-dimensional analytical model, for motion in one horizontal direction and the vertical direction, to experimental results. (J.P.N.)

  5. 3-Dimensional quantitative detection of nanoparticle content in biological tissue samples after local cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Rahn, Helene, E-mail: helene.rahn@gmail.com [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany); Alexiou, Christoph [ENT-Department, Section for Experimental Oncology and Nanomedicine (Else Kröner-Fresenius-Stiftungsprofessur), University Hospital Erlangen, Waldstraße 1, Erlangen 91054 (Germany); Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Abbestraße 2-12, Berlin 10587 (Germany); Odenbach, Stefan [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany)

    2014-06-01

    X-ray computed tomography is nowadays used for a wide range of applications in medicine, science and technology. X-ray microcomputed tomography (XµCT) follows the same principles used for conventional medical CT scanners, but improves the spatial resolution to a few micrometers. We present an example of an application of X-ray microtomography, a study of 3-dimensional biodistribution, as along with the quantification of nanoparticle content in tumoral tissue after minimally invasive cancer therapy. One of these minimal invasive cancer treatments is magnetic drug targeting, where the magnetic nanoparticles are used as controllable drug carriers. The quantification is based on a calibration of the XµCT-equipment. The developed calibration procedure of the X-ray-µCT-equipment is based on a phantom system which allows the discrimination between the various gray values of the data set. These phantoms consist of a biological tissue substitute and magnetic nanoparticles. The phantoms have been studied with XµCT and have been examined magnetically. The obtained gray values and nanoparticle concentration lead to a calibration curve. This curve can be applied to tomographic data sets. Accordingly, this calibration enables a voxel-wise assignment of gray values in the digital tomographic data set to nanoparticle content. Thus, the calibration procedure enables a 3-dimensional study of nanoparticle distribution as well as concentration. - Highlights: • Local cancer treatments are promising in reducing negative side effects occurring during conventional chemotherapy. • The nanoparticles play an important role in delivering drugs to the designated area during local cancer treatments as magnetic drug targeting. • We study the nanoparticles distribution in tumor tissue after magnetic drug targeting with X-ray computed tomography. • We achieved a 3-dimensional quantification of the nanoparticles content in tumor tissue out of digital tomographic data.

  6. Formation and microstructural analysis of 3-dimensional titanium oxide structures via large surface electron beam irradiation

    International Nuclear Information System (INIS)

    Recently, in photo electronic devices industry, titanium oxide which was known to have good optical and electrical characteristic's been studied in the microstructural aspect to increase the conversion efficiency, such as making variable architecture, coating the titanium oxide nano-tube with the quantum dots which have higher band gap materials than this, etc. However, the process of making 3-dimensional titanium oxide structure with general deposition system such as hydrothermal growth, CVO, PVD and ALD had more variables and longer time consumption to make nano structures than electron beam irradiation case. Herein, we proceed with making new titanium oxide nano-screen-testing electron beam irradiation. The metal alkoxide composed of the 1 mol of titanium iso-propoxide and the 1 mol of acetylation reacted with water in propylene glycol methyl ether acetate and isopropyl alcohol solvent. After this process which made the bonding among Ti, O and other organics, the polymer solution was deposited on various types of substrate, such as anodized aluminum oxide mail. Kist. ac., Ag nano dots on SiO2 thin film, Au nano dots on SiO2 thin film, etc. The electron beam irradiation was progressed with the vertical accelerator facility of EB tech which was the company in Dijon, Korea The shape, microstructure and chemical composition of the irradiated polymers were characterized using TEM, XRD, Sem and EDS. The three types of Ti-Ox 3-dimensional structure were made; nano dot cluster, spike-like structure and dendrite structure. Each type of these structures was composed of different mircrostructures. Especially, the formation the 3-dimensional structures via electron beam irradiation was not only effected by the electron beam irradiation conditions but also effected by solution concentrate, conductivity and surface energy of substrate

  7. BPS operators from the Wilson loop in the 3-dimensional supersymmetric Chern-Simons theory

    OpenAIRE

    Fujita, Mitsutoshi

    2009-01-01

    We consider the small deformation of the point-like Wilson loop in the 3-dimensional $\\mathcal{N}=6$ superconformal Chern-Simons theory. By Taylor expansion of the point-like Wilson loop in powers of the loop variables, we obtain the BPS operators that correspond to the excited string states of the dual IIA string theory on the pp wave background. The BPS conditions of the Wilson loop constrain both the loop variables and the forms of the operators obtained in the Taylor expansion.

  8. Towards a mathematical definition of Coulomb branches of $3$-dimensional $\\mathcal N=4$ gauge theories, II

    CERN Document Server

    Braverman, Alexander; Nakajima, Hiraku

    2016-01-01

    Consider the $3$-dimensional $\\mathcal N=4$ supersymmetric gauge theory associated with a compact Lie group $G_c$ and its quaternionic representation $\\mathbf M$. Physicists study its Coulomb branch, which is a noncompact hyper-K\\"ahler manifold with an $\\mathrm{SU}(2)$-action, possibly with singularities. We give a mathematical definition of the Coulomb branch as an affine algebraic variety with $\\mathbb C^\\times$-action when $\\mathbf M$ is of a form $\\mathbf N\\oplus\\mathbf N^*$, as the second step of the proposal given in arXiv:1503.03676.

  9. Incorporating a 3-dimensional printer into the management of early-stage cervical cancer.

    Science.gov (United States)

    Baek, Min-Hyun; Kim, Dae-Yeon; Kim, Namkug; Rhim, Chae Chun; Kim, Jong-Hyeok; Nam, Joo-Hyun

    2016-08-01

    We used a 3-dimensional (3D) printer to create anatomical replicas of real lesions and tested its application in cervical cancer. Our study patient decided to undergo radical hysterectomy after seeing her 3D model which was then used to plan and simulate this surgery. Using 3D printers to create patient-specific 3D tumor models may aid cervical cancer patients make treatment decisions. This technology will lead to better surgical and oncological outcomes for cervical cancer patients. J. Surg. Oncol. 2016;114:150-152. © 2016 Wiley Periodicals, Inc. PMID:27222318

  10. Hamiltonian Analysis of 3-Dimensional Connection Dynamics in Bondi-like Coordinates

    CERN Document Server

    Huang, Chao-Guang

    2016-01-01

    The Hamiltonian analysis for a 3-dimensional $SO(1,1)\\times T_+$-connection dynamics is conducted in a Bondi-like coordinate system.A null coframe with 5 independent variables and 9 connection coefficients are treated as basic configuration variables.All constraints and their consistency conditions, as well as the equations of motion,for the system are presented.There is no physical degree of freedom in the system as expected.The Ba\\~nados-Teitelboim-Zanelli spacetime as an example is used to check the analysis.

  11. Development of a 3-Dimensional Dosimetry System for Leksell Gamma Knife-Perfexion

    OpenAIRE

    Yoon, KyoungJun; Kwak, Jungwon; Lee, DoHeui; Cho, Byungchul; Lee, Sangwook; Ahn, SeungDo

    2015-01-01

    The purpose of our study is to develop a new, 3-dimensional dosimetry system to verify the accuracy of dose deliveries in Leksell Gamma Knife-Perfexion TM (LGKP) (Elekta, Norcross, GA, USA). The instrument consists of a moving head phantom, an embedded thin active layer and a CCD camera system and was designed to be mounted to LGKP. As an active material concentrically located in the hemispheric head phantom, we choose Gafchromic EBT3 films and Gd2O2S;Tb phosphor sheets for dosimetric measure...

  12. Development of water packing mitigation scheme for MARS 3- dimensional thermal-hydraulic module

    International Nuclear Information System (INIS)

    Water packing mitigation scheme was developed to enhance the numerical stability and calculational efficiency of MARS 3-dimensional thermal-hydraulic module. The water packing phenomena is unphysical pressure spike which occurs in a two-phase system thermal-hydraulic code using Eulerian finite difference method. Great velocities developed from large pressure spike slow down the calculation efficiency due to the stability limit. Also, large pressure spike and subsequent low pressure can make errors in thermodynamic state table search. The developed water packing mitigation scheme was implemented in MARS3D module. It is shown from the results of some benchmark problema that numerical stability and calculational efficiency were improved

  13. Quantum Computing - A new Implementation of Simon Algorithm for 3-Dimensional Registers

    Directory of Open Access Journals (Sweden)

    Adina Bărîlă

    2015-03-01

    Full Text Available Quantum computing is a new field of science aiming to use quantum phenomena in order to perform operations on data. The Simon algorithm is one of the quantum algorithms which solves a certain problem exponentially faster than any classical algorithm solving the same problem. Simulating of quantum algorithms is very important since quantum hardware is not available outside of the research labs. QCL (Quantum Computation Language is the most advanced implemented quantum computer simulator and was conceived by Bernhard Ömer. The paper presents an implementation in QCL of the Simon algorithm in the case of 3-dimensional registers.

  14. The study of 3-dimensional structures of IgG with atomic force microscopy

    Institute of Scientific and Technical Information of China (English)

    YU Yi-gang; XU Ru-xiang; JIANG Xiao-dan; KE Yi-quan

    2005-01-01

    Objective: To detect 3-dimensional images of anti-N-methyl-D-aspartate receptor Nr1 (NMDAr1) polycolonal IgG affixed on mica in physiological environment. Methods: The images and data were obtained from a contact mode and commercial Si3N4 probed tip by using atomic force microscope (AFM). Conclusions: Using AFM to investigate biomacromolecule can make us deeply understand the structure of IgG, which will instruct us to detect the membrane receptor protein as a labelling agent.

  15. The definition of exertion-related cardiac events.

    Science.gov (United States)

    Rai, M; Thompson, P D

    2011-02-01

    Vigorous physical activity increases the risk of sudden cardiac death (SCD) and acute myocardial infarction (AMI) but there is no standard definition as to what constitutes an exertion-related cardiac event, specifically the time interval between physical exertion and cardiac event. A systematic review of studies related to exertion-related cardiac events was performed and the time interval between exertion and the event or the symptoms leading to the event was looked for in all the articles selected for inclusion. A total of 12 of 26 articles "suggested" or "defined" exertion-related events as those events whose symptoms started during or within 1 h of exertion. Others used definitions of 0.5 h, 2 h, "during exertion", "during or immediately post exertion" and "during or within several hours after exertion". It is suggested, therefore, that the definition of an exertion-related cardiac event be established as a cardiac event in which symptoms started during or within 1 h of physical exertion.

  16. Acute leg compartment syndrome after exertion

    Directory of Open Access Journals (Sweden)

    Mišović Sidor

    2005-01-01

    Full Text Available A case of a 22-year old soldier, with a history of pain in the leg during heavy exercise, which desisted at rest, was presented. One day before admission, the patient had felt an extreme exertion-induced pain in his right leg which had not lessened at rest. At the same time, the patient noticed persistent severe leg edema. On physical examination, the intracompartmental pressure was 62 mmHg (>30 mmHg. The patient was urgently operated on, and fasciotomy according to Mubarak was used. At second surgery, the debridement of the muscles of the posterior group of the leg, and the evacuation of hemathoma from the anterior and lateral group of the right leg muscles were perfomed. Postoperative recovery was uneventful. Fasciotomy wounds were closed within 14 days of the surgery. The complete physical treatment was done. Follow-up examinations 1, 3, and 6 months afterwards were satisfactory. The soldier completed his compulsory military service without any sequelae. Laboratory results were normal. Overlooked, unrecognized or surgically untreated compartment syndrome can cause severe damage, including even the loss of the extremity.

  17. 5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone, a polymethoxyflavone, exerts antitumor effect on PI3K/Akt signaling pathway in human gastric cancer cell BGC-7901.

    Science.gov (United States)

    Wang, Xinjian; Xia, Min

    2016-10-01

    5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5HHMF), a polymethoxyflavone (PMF) mainly found in citrus plants, exhibits excellent physiological functions. In this study, we aimed to investigate the anticancer activity of 5HHMF against human gastric cancer cell BGC-7901 both in vitro and in vivo and illustrate the potential mechanisms. The proliferation of BGC-7901 cells was assessed by MTT assay. Reactive oxygen species (ROS) level was determined by ELISA kit. The protein expression was determined by western blot analysis. Antitumor activity of 5HHMF in vivo was evaluated in BALB/c nude mice. The results showed that treatment with 5HHMF significantly suppressed BGC-7901 cells proliferation, increased ROS generation, and upregulated cytochrome c release from the mitochondria to the cytosol. Western blot analysis demonstrated that 5HHMF significantly downregulated the expression of procaspase-3, procaspase-9, and PARP and upregulated cleaved caspase-3, cleaved caspase-9, cleaved PARP, and Bax/Bcl-2 ratio. Meanwhile, 5HHMF treatment markedly decreased the expression of PI3K and p-Akt. In addition, 5HHMF effectively inhibited tumor growth in xenograft models in BALB/c nude mice without major side action. In summary, 5HHMF-induced apoptosis via targeting PI3K/Akt, indicating 5HHMF is a potential antitumor agent for gastric cancer. PMID:26671739

  18. Unobservable Problem of Target Tracking with Bearing-only Measurements in 3-dimensional Space

    Institute of Scientific and Technical Information of China (English)

    XU Zhi-gang; SHENG An-dong

    2008-01-01

    The bearings-only tracking (BOT) system is said to be observability if and only if the target motion parameters can be uniquely determined by noise-free bearing measurements. By utilizing the method of orthogonal vectors and characteristic of linear matrix equation, the problem of observability for BOT in noise-free bearings measurements from single observer is discussed based on the target and observer traveling in the 3-dimensional space. A proposition that BOT for target and observer traveling in the 3-dimensional space with constant acceleration remains unsolvable is presented and proved. By proving the proposition, it is also shown that some motion parameter ratios of target can be estimated under certain condition satisfied by measurements and time samples. The proposition is extended to arbitrary rank of manoeuvre for the observer and the target, which BOT remains unobservable property while the rank of target manoeuvre is higher than that of the observer manoeuvre. The theoretical analysis of this paper provides the guidelines for how the observer trajectory should be formulated to avoid unobservable state for BOT in practice application.

  19. 3-dimensional slope stability analyses using non-associative stress-strain relationships

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The research work presented in this paper refers to a new slope stability analysis method used for landslide risk evaluations. It is an extension of the 3-dimensional upper-bound slope stability analysis method proposed by Chen et al. in 2001,which employs the Mohr-Coulomb’s associative flow rule. It has been found that in a 3-dimensional area,a prism may not be able to move at friction angles to all its surrounding interfaces,as required by this associative rule,and convergence problems may occasionally arise. The new method establishes two velocity fields:(i) The plastic one that represents a non-associative and the best representative dilation behavior,and (ii) the virtual one that permits the solution for factor of safety in the work and energy balance equation. The new method can then allow any input value of dilation angle and thus solve the convergence problem. A practical application to a concrete dam foundation is illustrated.

  20. Contactless 2-dimensional laser sensor for 3-dimensional wire position and tension measurements

    CERN Document Server

    Prall, Matthias; Joehren, R; Ortjohann, H W; Reinhardt, M; Weinheimer, Ch

    2009-01-01

    We have developed a contact-free 2-dimensional laser sensor with which the position of wires can be measured in 3 dimensions with an accuracy of better than 10 micrometer and with which the tension of the wires can be determined with an accuracy of 0.04 N. These measurements can be made from a distance of 15 cm. The sensor consists of commercially available laser pointers, lenses, color filters and photodiodes. In our application we have used this laser sensor together with an automated 3 dimensional coordinate table. For a single position measurement, the laser sensor is moved by the 3-dimensional coordinate table in a plane and determines the coordinates at which the wires intersect with this plane. The position of the plane itself (the third coordinate) is given by the third axis of the measurement table which is perpendicular to this plane. The control and readout of the table and the readout of the laser sensor were realized with LabVIEW. The precision of the position measurement in the plane was determi...

  1. MR imaging of the knee joint with 3-dimensional gradient echo

    Energy Technology Data Exchange (ETDEWEB)

    Shimagaki, Hajime; Matsubara, T.; Narisawa, Hiroko; Yamazaki, Yukio [Tsubame Rosai Hospital, Niigata (Japan)

    1996-11-01

    Authors considered and discussed whether various lesions of the knee joint can be diagnosed under the MR imaging condition with a pulse sequence of 3-dimensional fourier transformed gradient recalled acquisition in the steady state and what advantages the method has. The apparatus was 1.5T Signa (General Electric) equipped with surface coil for the knee. The consecutive 124 sagittal images of 0.8 mm thickness taken primarily for 3-dimensional reconstruction were processed to give any cross sections of coronary, horizontal, sagittal or further additional ones. Subjects were 243 knees (138 internal derangement and 105 osteoarthritis) whose lesions were confirmed by arthroscope or by arthrostomy after the MR imaging. Comparison of the MR imaging and surgical finding revealed that accuracy, specificity and sensitivity of the present MR imaging method were all >90% for diagnosis of internal derangement of anterior cruciate ligament and meniscus. For osteoarthritis, the method was thought useful for evaluation of the depth of cartilage deficit. (K.H.)

  2. Comparison of nonnavigated and 3-dimensional image-based computer navigated balloon kyphoplasty.

    Science.gov (United States)

    Sembrano, Jonathan N; Yson, Sharon C; Polly, David W; Ledonio, Charles Gerald T; Nuckley, David J; Santos, Edward R G

    2015-01-01

    Balloon kyphoplasty is a common treatment for osteoporotic and pathologic compression fractures. Advantages include minimal tissue disruption, quick recovery, pain relief, and in some cases prevention of progressive sagittal deformity. The benefit of image-based navigation in kyphoplasty has not been established. The goal of this study was to determine whether there is a difference between fluoroscopy-guided balloon kyphoplasty and 3-dimensional image-based navigation in terms of needle malposition rate, cement leakage rate, and radiation exposure time. The authors compared navigated and nonnavigated needle placement in 30 balloon kyphoplasty procedures (47 levels). Intraoperative 3-dimensional image-based navigation was used for needle placement in 21 cases (36 levels); conventional 2-dimensional fluoroscopy was used in the other 9 cases (11 levels). The 2 groups were compared for rates of needle malposition and cement leakage as well as radiation exposure time. Three of 11 (27%) nonnavigated cases were complicated by a malpositioned needle, and 2 of these had to be repositioned. The navigated group had a significantly lower malposition rate (1 of 36; 3%; P=.04). The overall rate of cement leakage was also similar in both groups (P=.29). Radiation exposure time was similar in both groups (navigated, 98 s/level; nonnavigated, 125 s/level; P=.10). Navigated kyphoplasty procedures did not differ significantly from nonnavigated procedures except in terms of needle malposition rate, where navigation may have decreased the need for needle repositioning.

  3. Crossover from 2-dimensional to 3-dimensional aggregations of clusters on square lattice substrates

    Science.gov (United States)

    Cheng, Yi; Zhu, Yu-Hong; Pan, Qi-Fa; Yang, Bo; Tao, Xiang-Ming; Ye, Gao-Xiang

    2015-11-01

    A Monte Carlo study on the crossover from 2-dimensional to 3-dimensional aggregations of clusters is presented. Based on the traditional cluster-cluster aggregation (CCA) simulation, a modified growth model is proposed. The clusters (including single particles and their aggregates) diffuse with diffusion step length l (1 ≤ l ≤ 7) and aggregate on a square lattice substrate. If the number of particles contained in a cluster is larger than a critical size sc, the particles at the edge of the cluster have a possibility to jump onto the upper layer, which results in the crossover from 2-dimensional to 3-dimensional aggregations. Our simulation results are in good agreement with the experimental findings. Project supported by the National Natural Science Foundation of China (Grant Nos. 11374082 and 11074215), the Science Foundation of Zhejiang Province Department of Education, China (Grant No. Y201018280), the Fundamental Research Funds for Central Universities, China (Grant No. 2012QNA3010), and the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20100101110005).

  4. SECOND-ORDER OPTIMALITY CONDITIONS FOR OPTIMAL CONTROL PROBLEMS GOVERNED BY 3-DIMENSIONAL NEVIER-STOKES EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This article is concerned with second-order necessary and sufficient optimality conditions for optimal control problems governed by 3-dimensional Navier-Stokes equations. The periodic state constraint is considered.

  5. Biomechanical 3-Dimensional Finite Element Analysis of Obturator Protheses Retained with Zygomatic and Dental Implants in Maxillary Defects

    OpenAIRE

    Akay, Canan; Yaluğ, Suat

    2015-01-01

    Background The objective of this study was to investigate the stress distribution in the bone around zygomatic and dental implants for 3 different implant-retained obturator prostheses designs in a Aramany class IV maxillary defect using 3-dimensional finite element analysis (FEA). Material\\Methods A 3-dimensional finite element model of an Aramany class IV defect was created. Three different implant-retained obturator prostheses were modeled: model 1 with 1 zygomatic implant and 1 dental imp...

  6. Simple computer program to model 3-dimensional underground heat flow with realistic boundary conditions

    Science.gov (United States)

    Metz, P. D.

    A FORTRAN computer program called GROCS (GRound Coupled Systems) has been developed to study 3-dimensional underground heat flow. Features include the use of up to 30 finite elements or blocks of Earth which interact via finite difference heat flow equations and a subprogram which sets realistic time and depth dependent boundary conditions. No explicit consideration of mositure movement or freezing is given. GROCS has been used to model the thermal behavior of buried solar heat storage tanks (with and without insulation) and serpentine pipe fields for solar heat pump space conditioning systems. The program is available independently or in a form compatible with specially written TRNSYS component TYPE subroutines. The approach taken in the design of GROCS, the mathematics contained and the program architecture, are described. Then, the operation of the stand-alone version is explained. Finally, the validity of GROCS is discussed.

  7. Large-eddy-simulation of 3-dimensional Rayleigh-Taylor instability in incompressible fluids

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 3-dimensional incompressible Rayleigh-Taylor instability is numerically studied through the large-eddy-simulation (LES) approach based on the passive scalar transport model. Both the instantaneous velocity and the passive scalar fields excited by sinusoidal perturbation and random perturbation are simulated. A full treatment of the whole evolution process of the instability is addressed. To verify the reliability of the LES code, the averaged turbulent energy as well as the flux of passive scalar are calculated at both the resolved scale and the subgrid scale. Our results show good agreement with the experimental and other numerical work. The LES method has proved to be an effective approach to the Rayleigh-Taylor instability.

  8. Reference Trajectory Generation for 3-Dimensional Walking of a Humanoid Robot

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Humanoid walking planning is a complicated task because of the high number of degrees of freedom (DOFs) and the variable mechanical structure during walking. In this paper, a planning method for 3-dimensional (3-D) walking movements was developed based on a model of a typical humanoid robot with 12 DOFs on the lower body. The planning process includes trajectory generation for the hip, ankle, and knee joints in the Cartesian space. The balance of the robot was ensured by adjusting the hip motion. The angles for each DOF were obtained from 3-D kinematics calculation. The calculation gave reference trajectories of all the DOFs on the humanoid robot which were used to control the real robot. The simulation results show that the method is effective.

  9. 3-dimensional numerical modelling of rolling of superconducting Ag/BSCCO tape

    DEFF Research Database (Denmark)

    Eriksen, Morten; Bech, Jakob Ilsted; Seifi, Behrouz;

    2000-01-01

    Numerical simulation of the deformation process during flat rolling of multifilament HTS tapes has been investigated using a commercial FEM program, ELFEN. The numerical models were built up in 2D and 3D using a Drucker-Prager/Cap model for the powder. Three different roll diameters (Ø24 mm, Ø85 mm...... and Ø126 mm) have been investigated. It is found that it is possible to perform numerical simulation with 3D models of flat rolling of multifilament wire. Two 3D models have been used; 3D pressing with rolls and 3D rolling. 3D pressing with rolls have the advance that the simulation time is lower than...... in the 3D rolling. The 3D models have the advantage compared to 2D pressing that they can predict the 3 dimensional flow in the flat rolling, which has been showed to be very imported for the super conduction properties...

  10. Application and Program Composition of the Virtual Laminated 3 Dimensional Degenerated Element in the Bridge Structure

    Institute of Scientific and Technical Information of China (English)

    YAN Xing-fei; He Shuan-hai; SUN limin

    2003-01-01

    The text include two aspects, one is the general finite element method (FEM), the other is bridge special FEM. And two viewpoints are used in it, one is the theory of FEM, the other is the practical program-making. The virtual laminated 3 dimensional degenerated element with vivid character is introduced in this paper and a large-scale computer program of FEM is manufactured. 1In addition, some current advantaged computer technology is used to make simple pre- and post processing program in order to exemplify and calculate easily in the process of researching. By using a factual example, the text also prove the method simply and resultful for analyze of bridge.

  11. Towards a mathematical definition of Coulomb branches of $3$-dimensional $\\mathcal N=4$ gauge theories, I

    CERN Document Server

    Nakajima, Hiraku

    2015-01-01

    Consider the $3$-dimensional $\\mathcal N=4$ supersymmetric gauge theory associated with a compact Lie group $G$ and its quaternionic representation $\\mathbf M$. Physicists study its Coulomb branch, which is a noncompact hyper-K\\"ahler manifold, such as instanton moduli spaces on $\\mathbb R^4$, $SU(2)$-monopole moduli spaces on $\\mathbb R^3$, etc. In this paper and its sequel, we propose a mathematical definition of the coordinate ring of the Coulomb branch, using the vanishing cycle cohomology group of a certain moduli space for a gauged $\\sigma$-model on the $2$-sphere associated with $(G,\\mathbf M)$. In this first part, we check that the cohomology group has the correct graded dimensions expected from the monopole formula proposed by Cremonesi, Hanany and Zaffaroni arXiv:1309.2657. A ring structure (on the cohomology of a modified moduli space) will be introduced in the sequel of this paper.

  12. Generation and Active Absorption of 2- and 3-Dimensional Linear Water Waves in Physical Models

    DEFF Research Database (Denmark)

    Christensen, Morten

    in the wave channel in front of the wave generator. The results of physical model tests performed with an absorbing wave maker based on this principle show that the problem of rereflection is reduced significantly when active absorption is performed. Finally, an absorbing directional wave generator for 3-D......Methods for mechanical generation of 2-dimensional (2-D) and 3-dimensional (3-D) linear water waves in physical models are presented. The results of a series of laboratory 3-D wave generation tests are presented and discussed. The tests preformed involve reproduction of wave fields characterised...... by different directional wave spectra. The wave generator displacement signals applied in the tests are generated by means of linear digital filtering of Gaussian white noise in the time domain. An absorbing wave generator for 2-D wave facilities (wave channels) is developed. The absorbing wave generator...

  13. Using 3-dimensional printing to create presurgical models for endodontic surgery.

    Science.gov (United States)

    Bahcall, James K

    2014-09-01

    Advances in endodontic surgery--from both a technological and procedural perspective-have been significant over the last 18 years. Although these technologies and procedural enhancements have significantly improved endodontic surgical treatment outcomes, there is still an ongoing challenge of overcoming the limitations of interpreting preoperative 2-dimensional (2-D) radiographic representation of a 3-dimensional (3-D) in vivo surgical field. Cone-beam Computed Tomography (CBCT) has helped to address this issue by providing a 3-D enhancement of the 2-D radiograph. The next logical step to further improve a presurgical case 3-D assessment is to create a surgical model from the CBCT scan. The purpose of this article is to introduce 3-D printing of CBCT scans for creating presurgical models for endodontic surgery. PMID:25197746

  14. NOVEL 6-SPS PARALLEL 3-DIMENSIONAL PLATFORM MANIPULATOR AND ITS FORCE/MOTION TRANSMISSION ANALYSIS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The unique design for a novel 6-SPS parallel 3-dimensional platform manipulator with an orthogonal configu-ration is investigated. The layout feature of the parallel manipulator is described. Its force/motion transmission capabilityevaluation criteria are presented. At the orthogonal configuration, the criteria and the relationships between the criteriaand the link lengths are analyzed, which is important since it can provide designer a piece of valuable information abouthow to choose the linear actuators. From the analysis of the results it is shown that the force/motion transmission capabil-ities of the parallel manipulator are characterized by isotropy at the orthogonal configuration. The manipulator is particu-larly suitable for certain applications in 6-DOF micromanipulators and 6-axis force/moment transducers.

  15. Using Ratings of Perceived Exertion in Physical Education

    Science.gov (United States)

    Lagally, Kristen M.

    2013-01-01

    Ratings of perceived exertion have been shown to be a valid method of monitoring physical activity intensity for both adults and children. As such, this subjective method may serve as an alternative to objective measurements for assessing students' performance on national standards 2 and 4. The OMNI-Child perceived exertion scales were…

  16. Exercise exerts neuroprotective effects on Parkinson's disease model of rats.

    Science.gov (United States)

    Tajiri, Naoki; Yasuhara, Takao; Shingo, Tetsuro; Kondo, Akihiko; Yuan, Wenji; Kadota, Tomohito; Wang, Feifei; Baba, Tanefumi; Tayra, Judith Thomas; Morimoto, Takamasa; Jing, Meng; Kikuchi, Yoichiro; Kuramoto, Satoshi; Agari, Takashi; Miyoshi, Yasuyuki; Fujino, Hidemi; Obata, Futoshi; Takeda, Isao; Furuta, Tomohisa; Date, Isao

    2010-01-15

    Recent studies demonstrate that rehabilitation ameliorates physical and cognitive impairments of patients with stroke, spinal cord injury, and other neurological diseases and that rehabilitation also has potencies to modulate brain plasticity. Here we examined the effects of compulsive exercise on Parkinson's disease model of rats. Before 6-hydroxydopamine (6-OHDA, 20 microg) lesion into the right striatum of female SD rats, bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Subsequently, at 24 h after the lesion, the rats were forced to run on the treadmill (5 days/week, 30 min/day, 11 m/min). As behavioral evaluations, cylinder test was performed at 1, 2, 3, and 4 weeks and amphetamine-induced rotational test was performed at 2 and 4 weeks with consequent euthanasia for immunohistochemical investigations. The exercise group showed better behavioral recovery in cylinder test and significant decrease in the number of amphetamine-induced rotations, compared to the non-exercise group. Correspondingly, significant preservation of tyrosine hydroxylase (TH)-positive fibers in the striatum and TH-positive neurons in the substantia nigra pars compacta (SNc) was demonstrated, compared to the non-exercise group. Additionally, the number of migrated BrdU- and Doublecortin-positive cells toward the lesioned striatum was increased in the exercise group. Furthermore, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the striatum by exercise. The results suggest that exercise exerts neuroprotective effects or enhances the neuronal differentiation in Parkinson's disease model of rats with subsequent improvement in deteriorated motor function. PMID:19900418

  17. Embedding and publishing interactive, 3-dimensional, scientific figures in Portable Document Format (PDF files.

    Directory of Open Access Journals (Sweden)

    David G Barnes

    Full Text Available With the latest release of the S2PLOT graphics library, embedding interactive, 3-dimensional (3-d scientific figures in Adobe Portable Document Format (PDF files is simple, and can be accomplished without commercial software. In this paper, we motivate the need for embedding 3-d figures in scholarly articles. We explain how 3-d figures can be created using the S2PLOT graphics library, exported to Product Representation Compact (PRC format, and included as fully interactive, 3-d figures in PDF files using the movie15 LaTeX package. We present new examples of 3-d PDF figures, explain how they have been made, validate them, and comment on their advantages over traditional, static 2-dimensional (2-d figures. With the judicious use of 3-d rather than 2-d figures, scientists can now publish, share and archive more useful, flexible and faithful representations of their study outcomes. The article you are reading does not have embedded 3-d figures. The full paper, with embedded 3-d figures, is recommended and is available as a supplementary download from PLoS ONE (File S2.

  18. A Novel Method of Orbital Floor Reconstruction Using Virtual Planning, 3-Dimensional Printing, and Autologous Bone.

    Science.gov (United States)

    Vehmeijer, Maarten; van Eijnatten, Maureen; Liberton, Niels; Wolff, Jan

    2016-08-01

    Fractures of the orbital floor are often a result of traffic accidents or interpersonal violence. To date, numerous materials and methods have been used to reconstruct the orbital floor. However, simple and cost-effective 3-dimensional (3D) printing technologies for the treatment of orbital floor fractures are still sought. This study describes a simple, precise, cost-effective method of treating orbital fractures using 3D printing technologies in combination with autologous bone. Enophthalmos and diplopia developed in a 64-year-old female patient with an orbital floor fracture. A virtual 3D model of the fracture site was generated from computed tomography images of the patient. The fracture was virtually closed using spline interpolation. Furthermore, a virtual individualized mold of the defect site was created, which was manufactured using an inkjet printer. The tangible mold was subsequently used during surgery to sculpture an individualized autologous orbital floor implant. Virtual reconstruction of the orbital floor and the resulting mold enhanced the overall accuracy and efficiency of the surgical procedure. The sculptured autologous orbital floor implant showed an excellent fit in vivo. The combination of virtual planning and 3D printing offers an accurate and cost-effective treatment method for orbital floor fractures. PMID:27137437

  19. Using Interior Point Method Optimization Techniques to Improve 2- and 3-Dimensional Models of Earth Structures

    Science.gov (United States)

    Zamora, A.; Gutierrez, A. E.; Velasco, A. A.

    2014-12-01

    2- and 3-Dimensional models obtained from the inversion of geophysical data are widely used to represent the structural composition of the Earth and to constrain independent models obtained from other geological data (e.g. core samples, seismic surveys, etc.). However, inverse modeling of gravity data presents a very unstable and ill-posed mathematical problem, given that solutions are non-unique and small changes in parameters (position and density contrast of an anomalous body) can highly impact the resulting model. Through the implementation of an interior-point method constrained optimization technique, we improve the 2-D and 3-D models of Earth structures representing known density contrasts mapping anomalous bodies in uniform regions and boundaries between layers in layered environments. The proposed techniques are applied to synthetic data and gravitational data obtained from the Rio Grande Rift and the Cooper Flat Mine region located in Sierra County, New Mexico. Specifically, we improve the 2- and 3-D Earth models by getting rid of unacceptable solutions (those that do not satisfy the required constraints or are geologically unfeasible) given the reduction of the solution space.

  20. 3-dimensional conformal radiotherapy for cervical and upper-thoracic esophageal cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect of 3-dimensional conformal radiotherapy (3D CRT) and prognostic factors for cervical and upper-thoracic esophageal cancer. Methods: Between July 1998 and July 2001, 33 patients with cervical and upper-thoracic esophageal cancer were treated with 3D CRT(2 Gy per day, 5 sessions a week to a total dose of 66-68 Gy over 6-7 weeks). Acute toxicities and survival rates were evaluated by Kaplan-Meier method and prognostic factors were analyzed by Cox proportional hazard model. Results: The 1-, 2-, 3-year local control rates were 87.9%, 75.8%, 45.5% respectively. The 1-, 2-, 3-year disease-free and overall survival rates were 72.7%, 60.6%, 30.3% and 78.8%, 66.8%, 44.2% respectively. GradeI- II acute esophagitis and bronchitis were the most common radiation side effects. Multivariate analysis revealed that the depth of primary tumor invasion, regional lymph node metastasis and tumor length were independent prognostic factors (P<0.05). Conclusions: 3D CRT can be considered as an effective and feasible approach to cervical and upper-thoracic esophageal cancer treatment. The depth of primary tumor invasion, regional lymph node status and tumor length are important prognostic indicators for cervical and upper-thoracic esophageal cancer. (authors)

  1. The Usefulness of 3-Dimensional Virtual Simulation Using Haptics in Training Orotracheal Intubation

    Directory of Open Access Journals (Sweden)

    Dong Hoon Lee

    2013-01-01

    Full Text Available Objectives. Airway control is the most critical treatment. The most common and basic method of endotracheal intubation is orotracheal intubation. To perform accurate and rapid tracheal intubation, appropriate education and training are required. We developed the virtual simulation program utilizing the 3-dimensional display and haptic device to exercise orotracheal intubation, and the educational effect of this program was compared with that of the mannequin method. Method. The control group used airway mannequin and virtual intubation group was trained with new program. We videotaped both groups during objective structured clinical examination (OSCE with airway mannequin. The video was reviewed and scored, and the rate of success and time were calculated. Result. The success rate was 78.6% in virtual intubation group and 93.3% in control group (P=0.273. There was no difference in overall score of OSCE (21.14 ± 4.28 in virtual intubation group and 23.33 ± 4.45 in control group, P=0.188, the time spent in successful intubation (P=0.432, and the number of trials (P>0.101. Conclusion. The virtual simulation with haptics had a similar effect compared with mannequin, but it could be more cost effective and convenient than mannequin training in time and space.

  2. Research on the method of cavitations resistance in a piezoelectric pump with 3-dimensional mesh structure

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian-hui; XIA Qi-xiao; Bai Heng-jun; NING Hong-gang; ONUKI Akiyoshi

    2006-01-01

    The volume valve piezoelectric pump has received increasing attention from many areas because of its different characteristics such as the absence of chemical pollution and electromagnetic pollution.However,when the pump is working,it produces cavitations and the air bubbles that originate from these will flow out of the pump.Cavitations occurring in the pump will bring out noise and shorten the life of the pump.Furthermore,air bubbles flowing out of the pump will hinder its application in areas such as medical treatment and health care where blood transfusion and infusion are concerned.As a solution to this disadvantage,the CR3DMS (cavitations resistance with 3-dimensional mesh structure) method is developed,which is tested and verified to be effective on not only reducing the occurrence of cavitations and eliminating cavitations' flowing out,but also restraining the emission of noise.In conclusion,the pump with CR3DMS,on the relationship between flow and driving frequency and the relationship between flow and the number of Resistant-Layers in both theory and test,are analyzed.

  3. Optimal iodine dose for 3-dimensional multidetector-row CT angiography of the liver

    International Nuclear Information System (INIS)

    Purpose: To clarify the optimal iodine dose of contrast material for 3-dimensional multidetector-row CT angiography (3D-MDCTA) of the venous vasculature of the liver using volume rendering technique. Materials and methods: This study included 103 patients who were randomly assigned to 5 contrast-enhanced MDCT protocol groups with different body-weight-tailored doses of contrast material: 500, 600, 630, 650, and 700 mgI/kg body weight. The arterial, portal, and hepatic parenchymal phases were obtained to evaluate enhancement values of the aorta, portal vein, and hepatic vein. Visualization of the portal and hepatic veins on the volume-rendering images of 3D-MDCTA was evaluated using a 5-point grade. Dunnett's test was used to compare the mean enhancement value and mean grades of image quality (700 mgI/kg dose group was control). Results: The mean enhancement values of portal and hepatic vein in the group with 500 and 600 mgI/kg were significantly lower than those of the control group. During visual assessment, a significantly lower mean grades were observed in 500 mgI/kg groups for the portal vein, and 500 and 600 mgI/kg groups for hepatic vein. There were no significant intergroup differences in mean enhancement values and visual assessment among the groups using 630 mgI/kg or more. Conclusion: Iodine doses of 630 mgI/kg was recommended for 3D-MDCTA

  4. SBNCT plan: A 3-dimensional treatment planning system for boron neutron capture therapy

    International Nuclear Information System (INIS)

    The need for accurate and comprehensive 3-dimensional treatment planning for boron neutron capture therapy (BNCT) has been debated for the past several years. Although many argue against the need for elaborate and expensive treatment planning programs which mimic conventional radiotherapy planning systems, it is clear that in order to realize significant gains over conventional fractionated radiation therapy, patients must be treated to the edge of normal tissue tolerance. Just how close to this edge is dictated by the uncertainties in dosimetry. Hence the focus of BNCT planning is the determination of dose distribution throughout normal tissue volumes. Although precise geometric manipulation of the epithermal neutron beam is not achievable, the following variables play an important role in BNCT optimization: patient orientation, dose fractionation, number of fields, megawatt-minutes per fraction, use of surface bolus, and use of collimation. Other variables which are not as easily adjustable and would not, therefore, be part of treatment planning optimization, include external patient contour, internal patient heterogeneities, boron compound distributions, and RBE's. The boron neutron capture therapy planning system developed at SUNY Stony Brook (SBNCT-Plan) was designed as an interactive graphic tool to assist the radiation oncologist in generating the optimum plan for a neutron capture treatment

  5. PAMELA positron and electron spectra are reproduced by 3-dimensional cosmic-ray modeling

    CERN Document Server

    Gaggero, Daniele; Maccione, Luca; Di Bernardo, Giuseppe; Evoli, Carmelo

    2013-01-01

    The PAMELA collaboration recently released the $e^+$ absolute spectrum between 1 and 300 GeV in addition to the positron fraction and $e^-$ spectrum previously measured in the same time period. We use the newly developed 3-dimensional upgrade of the DRAGON code and the charge dependent solar modulation HelioProp code to consistently describe those data. We obtain very good fits of all data sets if a $e^+$ + $e^-$ hard extra-component peaked at 1 TeV is added to a softer $e^-$ background and the secondary $e^\\pm$ produced by the spallation of cosmic ray proton and helium nuclei. All sources are assumed to follow a realistic spiral arm spatial distribution. Remarkably, PAMELA data do not display any need of charge asymmetric extra-component. Finally, plain diffusion, or low re-acceleration, propagation models which are tuned against nuclear data, nicely describe PAMELA lepton data with no need to introduce a low energy break in the proton and Helium spectra.

  6. 3-DIMENSIONAL Numerical Modeling on the Combustion and Emission Characteristics of Biodiesel in Diesel Engines

    Science.gov (United States)

    Yang, Wenming; An, Hui; Amin, Maghbouli; Li, Jing

    2014-11-01

    A 3-dimensional computational fluid dynamics modeling is conducted on a direct injection diesel engine fueled by biodiesel using multi-dimensional software KIVA4 coupled with CHEMKIN. To accurately predict the oxidation of saturated and unsaturated agents of the biodiesel fuel, a multicomponent advanced combustion model consisting of 69 species and 204 reactions combined with detailed oxidation pathways of methyl decenoate (C11H22O2), methyl-9-decenoate (C11H20O2) and n-heptane (C7H16) is employed in this work. In order to better represent the real fuel properties, the detailed chemical and thermo-physical properties of biodiesel such as vapor pressure, latent heat of vaporization, liquid viscosity and surface tension were calculated and compiled into the KIVA4 fuel library. The nitrogen monoxide (NO) and carbon monoxide (CO) formation mechanisms were also embedded. After validating the numerical simulation model by comparing the in-cylinder pressure and heat release rate curves with experimental results, further studies have been carried out to investigate the effect of combustion chamber design on flow field, subsequently on the combustion process and performance of diesel engine fueled by biodiesel. Research has also been done to investigate the impact of fuel injector location on the performance and emissions formation of diesel engine.

  7. A Novel Method of Orbital Floor Reconstruction Using Virtual Planning, 3-Dimensional Printing, and Autologous Bone.

    Science.gov (United States)

    Vehmeijer, Maarten; van Eijnatten, Maureen; Liberton, Niels; Wolff, Jan

    2016-08-01

    Fractures of the orbital floor are often a result of traffic accidents or interpersonal violence. To date, numerous materials and methods have been used to reconstruct the orbital floor. However, simple and cost-effective 3-dimensional (3D) printing technologies for the treatment of orbital floor fractures are still sought. This study describes a simple, precise, cost-effective method of treating orbital fractures using 3D printing technologies in combination with autologous bone. Enophthalmos and diplopia developed in a 64-year-old female patient with an orbital floor fracture. A virtual 3D model of the fracture site was generated from computed tomography images of the patient. The fracture was virtually closed using spline interpolation. Furthermore, a virtual individualized mold of the defect site was created, which was manufactured using an inkjet printer. The tangible mold was subsequently used during surgery to sculpture an individualized autologous orbital floor implant. Virtual reconstruction of the orbital floor and the resulting mold enhanced the overall accuracy and efficiency of the surgical procedure. The sculptured autologous orbital floor implant showed an excellent fit in vivo. The combination of virtual planning and 3D printing offers an accurate and cost-effective treatment method for orbital floor fractures.

  8. A 60GHz-Band 3-Dimensional System-in-Package Transmitter Module with Integrated Antenna

    Science.gov (United States)

    Suematsu, Noriharu; Yoshida, Satoshi; Tanifuji, Shoichi; Kameda, Suguru; Takagi, Tadashi; Tsubouchi, Kazuo

    A low cost, ultra small Radio Frequency (RF) transceiver module with integrated antenna is one of the key technologies for short range millimeter-wave wireless communication. This paper describes a 60GHz-band transmitter module with integrated dipole antenna. The module consists of three pieces of low-cost organic resin substrate. These substrates are vertically stacked by employing Cu ball bonding 3-dimensional (3-D) system-in-package (SiP) technology and the MMIC's are mounted on each organic substrates by using Au-stud bump bonding (SBB) technique. The planer dipole antenna is fabricated on the top of the stacked organic substrate to avoid the influence of the grounding metal on the base substrate. At 63GHz, maximum actual gain of 6.0dBi is obtained for fabricated planar dipole antenna. The measured radiation patterns are agreed with the electro-magnetic (EM) simulated result, therefore the other RF portion of the 3-D front-end module, such as flip chip mounted IC's on the top surface of the module, does not affect the antenna characteristics. The results show the feasibility of millimeter-wave low cost, ultra small antenna integrated module using stacked organic substrates.

  9. Development of a 3-Dimensional Dosimetry System for Leksell Gamma Knife-Perfexion

    CERN Document Server

    Yoon, KyoungJun; Lee, DoHeui; Cho, ByungChul; Lee, SangWook; Ahn, SeungDo

    2015-01-01

    The purpose of our study is to develop a new, 3-dimensional dosimetry system to verify the accuracy of dose deliveries in Leksell Gamma Knife-Perfexion TM (LGKP) (Elekta, Norcross, GA, USA). The instrument consists of a moving head phantom, an embedded thin active layer and a CCD camera system and was designed to be mounted to LGKP. As an active material concentrically located in the hemispheric head phantom, we choose Gafchromic EBT3 films and Gd2O2S;Tb phosphor sheets for dosimetric measurements. Also, to compensate the lack of backscatter, we located a 1 cm thick PMMA plate downstream of the active layer. The PMMA plate was transparent for scintillation lights to reach the CCD with 1200x1200 pixels by a 5.2 um pitch. Using this system, three hundred images by a 0.2 mm slice gap were acquired under each of three collimator setups, i.e. 4 mm, 8 mm, and 16 mm, respectively. The 2D projected images taken by CCD camera were compared with the dose distributions measured by EBT3 films in the same conditions. All ...

  10. A 3-dimensional rigid cluster thorax model for kinematic measurements during gait.

    Science.gov (United States)

    Kiernan, D; Malone, A; O'Brien, T; Simms, C K

    2014-04-11

    The trunk has been shown to work as an active segment rather than a passenger unit during gait and it is felt that trunk kinematics should be given more consideration during gait assessment. While 3-dimensional assessment of the thorax with respect to the pelvis and laboratory can provide a comprehensive description of trunk movement, the majority of existing 3-D thorax models demonstrate shortcomings such as the need for multiple skin marker configurations, difficult landmark identification and practical issues for assessment on female subjects. A small number of studies have used rigid cluster models to quantify thorax movement, however the models and points of attachment are not well described and validation rarely considered. The aim of this study was to propose an alternative rigid cluster 3-D thorax model to quantify movement during gait and provide validation of this model. A rigid mount utilising active markers was developed and applied over the 3rd thoracic vertebra, previously reported as an area of least skin movement artefact on the trunk. The model was compared to two reference thorax models through simultaneous recording during gait on 15 healthy subjects. Excellent waveform similarity was demonstrated between the proposed model and the two reference models (CMC range 0.962-0.997). Agreement of discrete parameters was very-good to excellent. In addition, ensemble average graphs demonstrated almost identical curve displacement between models. The results suggest that the proposed model can be confidently used as an alternative to other thorax models in the clinical setting.

  11. A 3-Dimensional discrete fracture network generator to examine fracture-matrix interaction using TOUGH2

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Kazumasa; Yongkoo, Seol

    2003-04-09

    Water fluxes in unsaturated, fractured rock involve the physical processes occurring at fracture-matrix interfaces within fracture networks. Modeling these water fluxes using a discrete fracture network model is a complicated effort. Existing preprocessors for TOUGH2 are not suitable to generate grids for fracture networks with various orientations and inclinations. There are several 3-D discrete-fracture-network simulators for flow and transport, but most of them do not capture fracture-matrix interaction. We have developed a new 3-D discrete-fracture-network mesh generator, FRACMESH, to provide TOUGH2 with information about the fracture network configuration and fracture-matrix interactions. FRACMESH transforms a discrete fracture network into a 3 dimensional uniform mesh, in which fractures are considered as elements with unique rock material properties and connected to surrounding matrix elements. Using FRACMESH, individual fractures may have uniform or random aperture distributions to consider heterogeneity. Fracture element volumes and interfacial areas are calculated from fracture geometry within individual elements. By using FRACMESH and TOUGH2, fractures with various inclinations and orientations, and fracture-matrix interaction, can be incorporated. In this paper, results of flow and transport simulations in a fractured rock block utilizing FRACMESH are presented.

  12. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-07-01

    Full Text Available Astaxanthin (ATX is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and peroxisome proliferator-activated receptor gamma (PPARγ. Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  13. A customized bolus produced using a 3-dimensional printer for radiotherapy.

    Directory of Open Access Journals (Sweden)

    Shin-Wook Kim

    Full Text Available OBJECTIVE: Boluses are used in high-energy radiotherapy in order to overcome the skin sparing effect. In practice though, commonly used flat boluses fail to make a perfect contact with the irregular surface of the patient's skin, resulting in air gaps. Hence, we fabricated a customized bolus using a 3-dimensional (3D printer and evaluated its feasibility for radiotherapy. METHODS: We designed two kinds of bolus for production on a 3D printer, one of which was the 3D printed flat bolus for the Blue water phantom and the other was a 3D printed customized bolus for the RANDO phantom. The 3D printed flat bolus was fabricated to verify its physical quality. The resulting 3D printed flat bolus was evaluated by assessing dosimetric parameters such as D1.5 cm, D5 cm, and D10 cm. The 3D printed customized bolus was then fabricated, and its quality and clinical feasibility were evaluated by visual inspection and by assessing dosimetric parameters such as Dmax, Dmin, Dmean, D90%, and V90%. RESULTS: The dosimetric parameters of the resulting 3D printed flat bolus showed that it was a useful dose escalating material, equivalent to a commercially available flat bolus. Analysis of the dosimetric parameters of the 3D printed customized bolus demonstrated that it is provided good dose escalation and good contact with the irregular surface of the RANDO phantom. CONCLUSIONS: A customized bolus produced using a 3D printer could potentially replace commercially available flat boluses.

  14. Estimating the costs of intensity-modulated and 3-dimensional conformal radiotherapy in Ontario

    Science.gov (United States)

    Yong, J.H.E.; McGowan, T.; Redmond-Misner, R.; Beca, J.; Warde, P.; Gutierrez, E.; Hoch, J.S.

    2016-01-01

    Background Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (imrt) and 3-dimensional conformal radiotherapy (3D-crt) in Ontario. Methods An activity-based costing model was developed to estimate the costs of imrt and 3D-crt in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (vmat) alongside imrt. Results From the perspective of the health care system, treating prostate cancer with imrt and 3D-crt respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although imrt was more costly than 3D-crt, its cost will likely decline over time as programs mature and vmat is incorporated. Conclusions Our costing model can be modified to estimate the costs of 3D-crt and imrt for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of imrt cost to consider how vmat affects time consumption. PMID:27330359

  15. Evaluation of xerostomia following 3 dimensional conformal radiotherapy for nasopharyngeal cancer patients

    International Nuclear Information System (INIS)

    This study is to evaluate the xerostomia following 3-dimensional conformal radiation therapy (3D CRT) in nasopharynx cancer patients using the xerostomia questionnaire score (XQS). Questionnaire study was done on 51 patients with nasopharynx cancer who received 3D CRT from Dec. 2000 to Aug. 2005. 3D CRT technique is based on 'serial shrinking field' concept by 3 times of computed tomography (CT) simulation. Total target dose to the primary tumor was 72 Gy with 1.8 Gy daily fractions. Xerostomia was assessed with 4-questions XQS, and the associations between XQS and time elapsed after RT, age, sex, stage, concurrent chemotherapy, an parotid dose were analyzed. Concurrent chemotherapy was given to 40 patients and RT alone was given to 11 patients. The median time elapsed after 3D CRT was 20 (1 ∼ 58) months and the mean XQS of all 51 patients was 8.4 ± 1.9 (6 ∼ 14). XQS continuously and significantly decreased over time after 3D CRT (χ 2 -0.484, ρ < 0.05). There was no significant difference in XQS according to sex, age, and stag. However, XQS of concurrent chemotherapy patients was significantly higher than RT alone patients (ρ = 0.001). XQS of patients receiving total mean parotid dose ≥ 35 Gy was significantly higher than < 35 Gy (ρ = 0.05). Decreasing tendency of XQS over time after 3D CRT was observed. Concurrent chemotherapy and total mean parotid dose ≥ 35 Gy were suggested to adversely affect radiation-induced xerostomia

  16. Development of a 3-dimensional dosimetry system for Leksell Gamma Knife Perfexion

    Science.gov (United States)

    Yoon, KyoungJun; Kwak, JungWon; Lee, DoHeui; Cho, ByungChul; Lee, SangWook; Ahn, SeungDo

    2015-07-01

    The purpose of our study is to develop a new, 3-dimensional dosimetry system to verify the accuracy of dose deliveries in Leksell Gamma Knife Perfexion (LGKP) (Elekta, Norcross, GA, USA). The instrument consists of a moving head phantom, an embedded thin active layer and a CCD camera system and was designed to be mounted to LGKP. As an active material concentrically located in the hemispheric head phantom, we choose Gafchromic EBT3 films and Gd2O2S:Tb phosphor sheets for dosimetric measurements. Also, to compensate for the lack of backscatter, we located a 1-cm-thick poly methyl methacrylate (PMMA) plate downstream of the active layer. The PMMA plate was transparent to scintillation light to reach the CCD with 1200 × 1200 pixels and a 5.2 µm pitch. With this system, 300 images with a 0.2-mm slice gap were acquired under each of three collimator setups, i.e. 4-mm, 8-mm, and 16-mm, respectively. The 2D projected images taken by the CCD camera were compared with the dose distributions measured by the EBT3 films under the same conditions. All 2D distributions were normalized to the maximum values derived by fitting peaks for each collimator setup. The differences in the full widths at half maximum (FWHM) of 2D profiles between CCD images and film doses were measured to be less than 0.3-mm. The scanning task for all peak regions took less than three minutes with the new instrument. So it can be utilized as a QA tool for the Gamma knife radiosurgery system instead of film dosimetry, the use of which requires much more time and many more resources.

  17. SU-E-T-104: Development of 3 Dimensional Dosimetry System for Gamma Knife

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, K; Kwak, J; Cho, B; Lee, D; Ahn, S [Asan Medical Center, Seoul (Korea, Republic of)

    2014-06-01

    Purpose: The aim of this study was to develop a new 3 dimensional dosimetry system to verify the dosimetric accuracy of Leksell Gamma Knife-Perfexion™ (LGK) (Elekta, Norcross, GA). Methods: We designed and manufactured a lightweight dosimetry instrument to be equipped with the head frame to LGK. It consists of a head phantom, a scintillator, a CCD camera and a step motor. The 10×10 cm2 sheet of Gd2O3;Tb phosphor or Gafchromic EBT3 film was located at the center of the 16 cm diameter hemispherical PMMA, the head phantom. The additional backscatter compensating material of 1 cm thick PMMA plate was placed downstream of the phosphor sheet. The backscatter plate was transparent for scintillation lights to reach the CCD camera with 1200×1200 pixels by 5.2 um pitch. With This equipment, 300 images with 0.2 mm of slice gap were acquired under three collimator setups (4mm, 8mm and 16mm), respectively. The 2D projected doses from 3D distributions were compared with the exposured film dose. Results: As all doses normalized by the maximum dose value in 16 mm setup, the relative differences between the equipment dose and film dose were 0.2% for 4mm collimator and 0.5% for 8mm. The acquisition of 300 images by the equipment took less than 3 minutes. Conclusion: The new equipment was verified to be a good substitute to radiochromic film, with which required more time and resources. Especially, the new methods was considered to provide much convenient and faster solution in the 3D dose acquisition for LGK.

  18. Reproducibility of a 3-dimensional gyroscope in measuring shoulder anteflexion and abduction

    Directory of Open Access Journals (Sweden)

    Penning Ludo I F

    2012-07-01

    Full Text Available Abstract Background Few studies have investigated the use of a 3-dimensional gyroscope for measuring the range of motion (ROM in the impaired shoulder. Reproducibility of digital inclinometer and visual estimation is poor. This study aims to investigate the reproducibility of a tri axial gyroscope in measurement of anteflexion, abduction and related rotations in the impaired shoulder. Methods Fifty-eight patients with either subacromial impingement (27 or osteoarthritis of the shoulder (31 participated. Active anteflexion, abduction and related rotations were measured with a tri axial gyroscope according to a test retest protocol. Severity of shoulder impairment and patient perceived pain were assessed by the Disability of Arm Shoulder and Hand score (DASH and the Visual Analogue Scale (VAS. VAS scores were recorded before and after testing. Results In two out of three hospitals patients with osteoarthritis (n = 31 were measured, in the third hospital patients with subacromial impingement (n = 27. There were significant differences among hospitals for the VAS and DASH scores measured before and after testing. The mean differences between the test and retest means for anteflexion were −6 degrees (affected side, 9 (contralateral side and for abduction 15 degrees (affected side and 10 degrees (contralateral side. Bland & Altman plots showed that the confidence intervals for the mean differences fall within −6 up to 15 degrees, individual test - retest differences could exceed these limits. A simulation according to ‘Generalizability Theory’ produces very good coefficients for anteflexion and related rotation as a comprehensive measure of reproducibility. Optimal reproducibility is achieved with 2 repetitions for anteflexion. Conclusions Measurements were influenced by patient perceived pain. Differences in VAS and DASH might be explained by different underlying pathology. These differences in shoulder pathology however did not alter

  19. Oxidation behavior of ammonium in a 3-dimensional biofilm-electrode reactor.

    Science.gov (United States)

    Tang, Jinjing; Guo, Jinsong; Fang, Fang; Chen, Youpeng; Lei, Lijing; Yang, Lin

    2013-12-01

    Excess nitrogenous compounds are detrimental to natural water systems and to human health. To completely realize autohydrogenotrophic nitrogen removal, a novel 3-dimensional biofilm-electrode reactor was designed. Titanium was electroplated with ruthenium and used as the anode. Activated carbon fiber felt was used as the cathode. The reactor was separated into two chambers by a permeable membrane. The cathode chamber was filled with granular graphite and glass beads. The cathode and cathode chamber were inhabited with domesticated biofilm. In the absence of organic substances, a nitrogen removal efficiency of up to 91% was achieved at DO levels of 3.42 +/- 0.37 mg/L when the applied current density was only 0.02 mA/cm2. The oxidation of ammonium in biofilm-electrode reactors was also investigated. It was found that ammonium could be oxidized not only on the anode but also on particle electrodes in the cathode chamber of the biofilm-electrode reactor. Oxidation rates of ammonium and nitrogen removal efficiency were found to be affected by the electric current loading on the biofilm-electrode reactor. The kinetic model of ammonium at different electric currents was analyzed by a first-order reaction kinetics equation. The regression analysis implied that when the current density was less than 0.02 mA/cm2, ammonium removal was positively correlated to the current density. However, when the current density was more than 0.02 mA/cm2, the electric current became a limiting factor for the oxidation rate of ammonium and nitrogen removal efficiency. PMID:24649670

  20. Albedo and heat transport in 3-dimensional model simulations of the early Archean climate

    Directory of Open Access Journals (Sweden)

    H. Kienert

    2013-01-01

    Full Text Available At the beginning of the Archean eon (ca. 3.8 billion yr ago, the Earth's climate state was significantly different from today due to the lower solar luminosity, smaller continental fraction, higher rotation rate and, presumably, significantly larger greenhouse gas concentrations. All these aspects play a role in solutions to the "faint young Sun problem" which must explain why the ocean surface was not fully frozen at that time. Here, we present 3-dimensional model simulations of climate states that are consistent with early Archean boundary conditions and have different CO2 concentrations, aiming at an understanding of the fundamental characteristics of the early Archean climate system. We focus on three states: one of them is ice-free, one has the same mean surface air temperature of 288 K as today's Earth and the third one is the coldest stable state in which there is still an area with liquid surface water (i.e. the critical state at the transition to a "snowball Earth". We find a reduction in meridional heat transport compared to today which leads to a steeper latitudinal temperature profile and has atmospheric as well as oceanic contributions. Ocean surface velocities are largely zonal, and the strength of the atmospheric meridional circulation is significantly reduced in all three states. These aspects contribute to the observed relation between global mean temperature and albedo, which we suggest as a parameterisation of the ice-albedo feedback for 1-dimensional model simulations of the early Archean and thus the faint young Sun problem.

  1. Realization of masticatory movement by 3-dimensional simulation of the temporomandibular joint and the masticatory muscles.

    Science.gov (United States)

    Park, Jong-Tae; Lee, Jae-Gi; Won, Sung-Yoon; Lee, Sang-Hee; Cha, Jung-Yul; Kim, Hee-Jin

    2013-07-01

    Masticatory muscles are closely involved in mastication, pronunciation, and swallowing, and it is therefore important to study the specific functions and dynamics of the mandibular and masticatory muscles. However, the shortness of muscle fibers and the diversity of movement directions make it difficult to study and simplify the dynamics of mastication. The purpose of this study was to use 3-dimensional (3D) simulation to observe the functions and movements of each of the masticatory muscles and the mandible while chewing. To simulate the masticatory movement, computed tomographic images were taken from a single Korean volunteer (30-year-old man), and skull image data were reconstructed in 3D (Mimics; Materialise, Leuven, Belgium). The 3D-reconstructed masticatory muscles were then attached to the 3D skull model. The masticatory movements were animated using Maya (Autodesk, San Rafael, CA) based on the mandibular motion path. During unilateral chewing, the mandible was found to move laterally toward the functional side by contracting the contralateral lateral pterygoid and ipsilateral temporalis muscles. During the initial mouth opening, only hinge movement was observed at the temporomandibular joint. During this period, the entire mandible rotated approximately 13 degrees toward the bicondylar horizontal plane. Continued movement of the mandible to full mouth opening occurred simultaneously with sliding and hinge movements, and the mandible rotated approximately 17 degrees toward the center of the mandibular ramus. The described approach can yield data for use in face animation and other simulation systems and for elucidating the functional components related to contraction and relaxation of muscles during mastication.

  2. Using a clinical protocol for orthognathic surgery and assessing a 3-dimensional virtual approach: current therapy.

    Science.gov (United States)

    Quevedo, Luis A; Ruiz, Jessica V; Quevedo, Cristobal A

    2011-03-01

    Oral and maxillofacial surgeons who perform orthognathic surgery face major changes in their practices, and these challenges will increase in the near future, because the extraordinary advances in technology applied to our profession are not only amazing but are becoming the standard of care as they promote improved outcomes for our patients. Orthognathic surgery is one of the favorite areas of practicing within the scope of practice of an oral and maxillofacial surgeon. Our own practice in orthognathic surgery has completed over 1,000 surgeries of this type. Success is directly related to the consistency and capability of the surgical-orthodontic team to achieve predictable, stable results, and our hypothesis is that a successful result is directly related to the way we take our records and perform diagnosis and treatment planning following basic general principles. Now that we have the opportunity to plan and treat 3-dimensional (3D) problems with 3D technology, we should enter into this new era with appropriate standards to ensure better results, instead of simply enjoying these new tools, which will clearly show not only us but everyone what we do when we perform orthognathic surgery. Appropriate principles need to be taken into account when implementing this new technology. In other words, new technology is welcome, but we do not have to reinvent the wheel. The purpose of this article is to review the current protocol that we use for orthognathic surgery and compare it with published protocols that incorporate new 3D and virtual technology. This report also describes our approach to this new technology.

  3. Novel Radiobiological Gamma Index for Evaluation of 3-Dimensional Predicted Dose Distribution

    Energy Technology Data Exchange (ETDEWEB)

    Sumida, Iori, E-mail: sumida@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Yamaguchi, Hajime; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yoshikawa, Nobuhiko; Yamada, Yuji [Department of Radiation Oncology, NTT West Osaka Hospital, Osaka (Japan); Suzuki, Osamu; Seo, Yuji [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Isohashi, Fumiaki [Department of Radiation Oncology, NTT West Osaka Hospital, Osaka (Japan); Yoshioka, Yasuo [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Ogawa, Kazuhiko [Department of Radiation Oncology, NTT West Osaka Hospital, Osaka (Japan)

    2015-07-15

    Purpose: To propose a gamma index-based dose evaluation index that integrates the radiobiological parameters of tumor control (TCP) and normal tissue complication probabilities (NTCP). Methods and Materials: Fifteen prostate and head and neck (H&N) cancer patients received intensity modulated radiation therapy. Before treatment, patient-specific quality assurance was conducted via beam-by-beam analysis, and beam-specific dose error distributions were generated. The predicted 3-dimensional (3D) dose distribution was calculated by back-projection of relative dose error distribution per beam. A 3D gamma analysis of different organs (prostate: clinical [CTV] and planned target volumes [PTV], rectum, bladder, femoral heads; H&N: gross tumor volume [GTV], CTV, spinal cord, brain stem, both parotids) was performed using predicted and planned dose distributions under 2%/2 mm tolerance and physical gamma passing rate was calculated. TCP and NTCP values were calculated for voxels with physical gamma indices (PGI) >1. We propose a new radiobiological gamma index (RGI) to quantify the radiobiological effects of TCP and NTCP and calculate radiobiological gamma passing rates. Results: The mean RGI gamma passing rates for prostate cases were significantly different compared with those of PGI (P<.03–.001). The mean RGI gamma passing rates for H&N cases (except for GTV) were significantly different compared with those of PGI (P<.001). Differences in gamma passing rates between PGI and RGI were due to dose differences between the planned and predicted dose distributions. Radiobiological gamma distribution was visualized to identify areas where the dose was radiobiologically important. Conclusions: RGI was proposed to integrate radiobiological effects into PGI. This index would assist physicians and medical physicists not only in physical evaluations of treatment delivery accuracy, but also in clinical evaluations of predicted dose distribution.

  4. Characterization of the 3-dimensional microstructure of a graphite negative electrode from a Li-ion battery

    DEFF Research Database (Denmark)

    Shearing, P.R.; Howard, L.E.; Jørgensen, Peter Stanley;

    2010-01-01

    The 3-dimensional microstructure of a porous electrode from a lithium-ion battery has been characterized for the first time. We use X-ray tomography to reconstruct a 43 × 348 × 478 μm sample volume with voxel dimensions of 480 nm, subsequent division of the reconstructed volumes into sub-volumes ...

  5. Reliability and the smallest detectable difference of measurements on 3-dimensional cone-beam computed tomography images

    NARCIS (Netherlands)

    Damstra, Janalt; Fourie, Zacharias; Huddleston Slater, James J R; Ren, Yijin

    2011-01-01

    INTRODUCTION: The aim of this study was to determine the reliability and the measurement error (by means of the smallest detectable error) of 17 commonly used cephalometric measurements made on 3-dimensional (3D) cone-beam computed tomography images. METHODS: Twenty-five cone-beam computed tomograph

  6. 3-Dimensional modelling of chick embryo eye development and growth using high resolution magnetic resonance imaging.

    Science.gov (United States)

    Goodall, Nicola; Kisiswa, Lilian; Prashar, Ankush; Faulkner, Stuart; Tokarczuk, Paweł; Singh, Krish; Erichsen, Jonathan T; Guggenheim, Jez; Halfter, Willi; Wride, Michael A

    2009-10-01

    Magnetic resonance imaging (MRI) is a powerful tool for generating 3-dimensional structural and functional image data. MRI has already proven valuable in creating atlases of mouse and quail development. Here, we have exploited high resolution MRI to determine the parameters necessary to acquire images of the chick embryo eye. Using a 9.4 Tesla (400 MHz) high field ultra-shielded and refrigerated magnet (Bruker), MRI was carried out on paraformaldehyde-fixed chick embryos or heads at E4, E6, E8, and E10. Image data were processed using established and custom packages (MRICro, ImageJ, ParaVision, Bruker and mri3dX). Voxel dimensions ranged from 62.5 microm to 117.2 microm. We subsequently used the images obtained from the MRI data in order to make precise measurements of chick embryo eye surface area, volume and axial length from E4 to E10. MRI was validated for accurate sizing of ocular tissue features by direct comparison with previously published literature. Furthermore, we demonstrate the utility of high resolution MRI for making accurate measurements of morphological changes due to experimental manipulation of chick eye development, thereby facilitating a better understanding of the effects on chick embryo eye development and growth of such manipulations. Chondroitin sulphate or heparin were microinjected into the vitreous cavity of the right eyes of each of 3 embryos at E5. At E10, embryos were fixed and various eye parameters (volume, surface area, axial length and equatorial diameter) were determined using MRI and normalised with respect to the un-injected left eyes. Statistically significant alterations in eye volume (p < 0.05; increases with chondroitin sulphate and decreases with heparin) and changes in vitreous homogeneity were observed in embryos following microinjection of glycosaminoglycans. Furthermore, in the heparin-injected eyes, significant disturbances at the vitreo-retinal boundary were observed as well as retinal folding and detachment

  7. New Technique for Developing a Proton Range Compensator With Use of a 3-Dimensional Printer

    Energy Technology Data Exchange (ETDEWEB)

    Ju, Sang Gyu, E-mail: sg.ju@samsung.com [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Min Kyu; Hong, Chae-Seon; Kim, Jin Sung; Han, Youngyih; Choi, Doo Ho [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Shin, Dongho; Lee, Se Byeong [Proton Therapy Center, National Cancer Center, Gyeonggi-do (Korea, Republic of)

    2014-02-01

    Purpose: A new system for manufacturing a proton range compensator (RC) was developed by using a 3-dimensional printer (3DP). The physical accuracy and dosimetric characteristics of the new RC manufactured by 3DP (RC{sub 3}DP) were compared with those of a conventional RC (RC{sub C}MM) manufactured by a computerized milling machine (CMM). Methods and Materials: An RC for brain tumor treatment with a scattered proton beam was calculated with a treatment planning system, and the resulting data were converted into a new format for 3DP using in-house software. The RC{sub 3}DP was printed with ultraviolet curable acrylic plastic, and an RC{sub C}MM was milled into polymethylmethacrylate using a CMM. The inner shape of both RCs was scanned by using a 3D scanner and compared with TPS data by applying composite analysis (CA; with 1-mm depth difference and 1 mm distance-to-agreement criteria) to verify their geometric accuracy. The position and distal penumbra of distal dose falloff at the central axis and field width of the dose profile at the midline depth of spread-out Bragg peak were measured for the 2 RCs to evaluate their dosimetric characteristics. Both RCs were imaged on a computed tomography scanner to evaluate uniformity of internal density. The manufacturing times for both RCs were compared to evaluate the production efficiency. Results: The pass rates for the CA test were 99.5% and 92.5% for RC{sub 3}DP and RC{sub C}MM, respectively. There was no significant difference in dosimetric characteristics and uniformity of internal density between the 2 RCs. The net fabrication times of RC{sub 3}DP and RC{sub C}MM were about 18 and 3 hours, respectively. Conclusions: The physical accuracy and dosimetric characteristics of RC{sub 3}DP were comparable with those of the conventional RC{sub C}MM, and significant system minimization was provided.

  8. Fucoxanthin: A Marine Carotenoid Exerting Anti-Cancer Effects by Affecting Multiple Mechanisms

    OpenAIRE

    Sangeetha Ravi Kumar; Masashi Hosokawa; Kazuo Miyashita

    2013-01-01

    Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing ...

  9. n-3 Polyunsaturated fatty acids exert immunomodulatory effects on lymphocytes by targeting plasma membrane molecular organization

    OpenAIRE

    Shaikh, Saame Raza; Jolly, Christopher A.; Chapkin, Robert S.

    2011-01-01

    Fish oil, enriched in bioactive n-3 polyunsaturated fatty acids (PUFA), has therapeutic value for the treatment of inflammation-associated disorders. The effects of n-3 PUFAs are pleiotropic and complex; hence, an understanding of their cellular targets and molecular mechanisms of action remains incomplete. Here we focus on recent data indicating n-3 PUFAs exert immunosuppressive effects on the function of effector and regulatory CD4+ T cells. In addition, we also present emerging evidence th...

  10. Persulfate activation during exertion of total oxidant demand.

    Science.gov (United States)

    Teel, Amy L; Elloy, Farah C; Watts, Richard J

    2016-09-01

    Total oxidant demand (TOD) is a parameter that is often measured during in situ chemical oxidation (ISCO) treatability studies. The importance of TOD is based on the concept that the oxidant demand created by soil organic matter and other reduced species must be overcome before contaminant oxidation can proceed. TOD testing was originally designed for permanganate ISCO, but has also recently been applied to activated persulfate ISCO. Recent studies have documented that phenoxides activate persulfate; because soil organic matter is rich in phenolic moieties, it may activate persulfate rather than simply exerting TOD. Therefore, the generation of reactive oxygen species was investigated in three soil horizons of varied soil organic carbon content over 5-day TOD testing. Hydroxyl radical may have been generated during TOD exertion, but was likely scavenged by soil organic matter. A high flux of reductants + nucleophiles (e.g. alkyl radicals + superoxide) was generated as TOD was exerted, resulting in the rapid destruction of the probe compound hexachloroethane and the common groundwater contaminant trichloroethylene (TCE). The results of this research document that, unlike permanganate TOD, contaminant destruction does occur as TOD is exerted in persulfate ISCO systems and is promoted by the activation of persulfate by soil organic matter. Future treatability studies for persulfate ISCO should consider contaminant destruction as TOD is exerted, and the potential for persulfate activation by soil organic matter. PMID:27269993

  11. Editorial Commentary: Single-Image Slice Magnetic Resonance Imaging Assessments Do Not Predict 3-Dimensional Muscle Volume.

    Science.gov (United States)

    Brand, Jefferson C

    2016-01-01

    No single-image magnetic resonance imaging (MRI) assessment-Goutallier classification, Fuchs classification, or cross-sectional area-is predictive of whole-muscle volume or fatty atrophy of the supraspinatus or infraspinatus. Rather, 3-dimensional MRI measurement of whole-muscle volume and fat-free muscle volume is required and is associated with shoulder strength, which is clinically relevant. Three-dimensional MRI may represent a new gold standard for assessment of the rotator cuff musculature using imaging and may help to predict the feasibility of repair of a rotator cuff tear as well as the postoperative outcome. Unfortunately, 3-dimensional MRI assessment of muscle volume is labor intensive and is not widely available for clinical use.

  12. Editorial Commentary: Single-Image Slice Magnetic Resonance Imaging Assessments Do Not Predict 3-Dimensional Muscle Volume.

    Science.gov (United States)

    Brand, Jefferson C

    2016-01-01

    No single-image magnetic resonance imaging (MRI) assessment-Goutallier classification, Fuchs classification, or cross-sectional area-is predictive of whole-muscle volume or fatty atrophy of the supraspinatus or infraspinatus. Rather, 3-dimensional MRI measurement of whole-muscle volume and fat-free muscle volume is required and is associated with shoulder strength, which is clinically relevant. Three-dimensional MRI may represent a new gold standard for assessment of the rotator cuff musculature using imaging and may help to predict the feasibility of repair of a rotator cuff tear as well as the postoperative outcome. Unfortunately, 3-dimensional MRI assessment of muscle volume is labor intensive and is not widely available for clinical use. PMID:26743416

  13. Going beyond 2D: following membrane diffusion and topography in the IgE-Fc[epsilon]RI system using 3-dimensional tracking microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Wells, Nathan P [Los Alamos National Laboratory; Lessard, Guillaume A [Los Alamos National Laboratory; Phipps, Marry E [Los Alamos National Laboratory; Goodwin, Peter M [Los Alamos National Laboratory; Werner, James H [Los Alamos National Laboratory; Lidke, Diane S [UNM; Wilson, Bridget S [UNM

    2008-01-01

    The ability to follow and observe single molecules as they function in live cells would represent a major milestone for molecular-cellular biology. Here we present a tracking microscope that is able to track quantum dots in 3 dimensions and simultaneously record time-resolved emission statistics from a single dot. This innovative microscopy approach is based on four spatial filters and closed loop feedback to constantly keep a single quantum dot in the focal spot. Using this microscope, we demonstrate the ability to follow quantum dot-labeled IgE antibodies bound to Fc{epsilon}Rl membrane receptors in live RBL-2H3 cells. The results are consistent with prior studies of 2 dimensional membrane diffusion (Andrews et al., Nat. Cell Biol., 10, 955, 2008). In addition, the microscope captures motion in the axial (Z) direction, which permits tracking of diffusing receptors relative the 'hills and valley' of the dynamically changing membrane landscape. Our novel approach is uniquely capable of following single-molecule dynamics on live cells with 3 dimensional spatial resolution.

  14. Intelligent Layout Method of the Powerhouse for Tank & Armored Vehicles Based on 3-Dimensional Rectangular Packing Theory

    Institute of Scientific and Technical Information of China (English)

    WANG Yan-long; MAO Ming; LU Yi-ping; BIE Jie-min

    2005-01-01

    Probes into a new and effective method in arranging the powerhouses of tank & armored vehicles. Theory and method of 3-dimensional rectangular packing are adapted to arrange effectively almost all the systems and components in the powerhouse of the vehicle, thus the study can be regarded as an attempt for the theory's engineering applications in the field of tank & armored vehicle design. It is proved that most parts of the solutions attained are reasonable, and some of the solutions are innovative.

  15. Study on the stability and 3-dimensional character for natural convection in a rectangular cavity heated from below

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Natural convection of air is numerically simulated in a 3-dimensional rectangular cavity heated from below using SIMPLE algorithm with a QUICK scheme.The results suggest that when all lateral walls are adiabatic,the fluid rolls occur along the long axis.When the Rayleigh number is smaller,the flow is of 2-dimensional character,and the rolls shapes are similar.The average Nusselt numbers in the central part of the cavity are similar.The average Nusselt numbers in the part near by the cavity are different.According to the comparison of 3-dimensional results with 2-dimensional results,the flow patterns and heat transfer in the central part of the cavity can be assumed as a 2-dimensional flow,While those in the part near by the cavity can not.With increasing Rayleigh number,the flow is 3-dimensional characteristic.The 3-dimensional result accords with the experimental result.When all lateral walls are adiabatic,the ten rolls occur along the long axis.But when lateral walls are heated or cooled,the rolls disappear along the long axis and two rolls occur along the short axis.The rotation direction of the rolls is reversed.When Rayleigh number is over some critical value,flow and heat transfer will be asymmetry,indicating unsteady oscillation occurs.By nonlinear analyses,it is shown that with increasing Rayleigh number,flow and heat transfer will change from steady state to unsteady state through HOPF bifurcation,and transition to chaos will occur through multi-periodical oscillation.

  16. Accuracy of 3-Dimensional Transoesophageal Echocardiography in Assessment of Prosthetic Mitral Valve Dehiscence with Comparison to Anatomical Specimens

    Directory of Open Access Journals (Sweden)

    Martin R. Brown

    2010-01-01

    Full Text Available The evolution of echocardiography from 2-Dimensional Transthoracic Echo through to real time 3-Dimensional Transoesophageal Echo has enabled more accurate visualisation and quantification of valvular disorders especially prosthetic mitral valve paravalvular regurgitation. However, validation of accuracy is rarely confirmed by surgical or post-mortem specimens. We present a case directly comparing different echocardiographic modality images to post mortem specimens in a patient with prosthetic mitral valve paravalvular regurgitation.

  17. Unified description of magic numbers of metal clusters in terms of the 3-dimensional q-deformed harmonic oscillator

    CERN Document Server

    Bonatsos, Dennis; Lenis, D; Raychev, P P; Roussev, R P; Terziev, P A

    2000-01-01

    Magic numbers predicted by a 3-dimensional q-deformed harmonic oscillator with Uq(3)>SOq(3) symmetry are compared to experimental data for atomic clusters of alkali metals (Li, Na, K, Rb, Cs), noble metals (Cu, Ag, Au), divalent metals (Zn, Cd), and trivalent metals (Al, In), as well as to theoretical predictions of jellium models, Woods-Saxon and wine bottle potentials, and to the classification scheme using the 3n+l pseudo quantum number. In alkali metal clusters and noble metal clusters the 3-dimensional q-deformed harmonic oscillator correctly predicts all experimentally observed magic numbers up to 1500 (which is the expected limit of validity for theories based on the filling of electronic shells), while in addition it gives satisfactory results for the magic numbers of clusters of divalent metals and trivalent metals, thus indicating that Uq(3), which is a nonlinear extension of the U(3) symmetry of the spherical (3-dimensional isotropic) harmonic oscillator, is a good candidate for being the symmetry ...

  18. Intracellular trafficking of superparamagnetic iron oxide nanoparticles conjugated with TAT peptide: 3-dimensional electron tomography analysis

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Baiju G.; Fukuda, Takahiro; Mizuki, Toru; Hanajiri, Tatsuro [Bio-Nano Electronics Research Centre, Toyo University, Saitama 350-8585 (Japan); Maekawa, Toru, E-mail: maekawa@toyo.jp [Bio-Nano Electronics Research Centre, Toyo University, Saitama 350-8585 (Japan)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer We study the intracellular localisation of TAT-SPIONs using 3-D electron tomography. Black-Right-Pointing-Pointer 3-D images of TAT-SPIONs in a cell are clearly shown. Black-Right-Pointing-Pointer Release of TAT-SPIONs from endocytic vesicles into the cytoplasm is clearly shown. -- Abstract: Internalisation of nanoparticles conjugated with cell penetrating peptides is a promising approach to various drug delivery applications. Cell penetrating peptides such as transactivating transcriptional activator (TAT) peptides derived from HIV-1 proteins are effective intracellular delivery vectors for a wide range of nanoparticles and pharmaceutical agents thanks to their amicable ability to enter cells and minimum cytotoxicity. Although different mechanisms of intracellular uptake and localisation have been proposed for TAT conjugated nanoparticles, it is necessary to visualise the particles on a 3-D plane in order to investigate the actual intracellular uptake and localisation. Here, we study the intracellular localisation and trafficking of TAT peptide conjugated superparamagnetic ion oxide nanoparticles (TAT-SPIONs) using 3-D electron tomography. 3-D tomograms clearly show the location of TAT-SPIONs in a cell and their slow release from the endocytic vesicles into the cytoplasm. The present methodology may well be utilised for further investigations of the behaviours of nanoparticles in cells and eventually for the development of nano drug delivery systems.

  19. Forces exerted by jumping children: A pilot study

    NARCIS (Netherlands)

    Moes, C.C.M.; Bakker, H.E.

    1998-01-01

    This article reports on a pilot study of the loads exerted vertically by children when jumping. The subjects of the study were 17 children, aged from two to twelve years. Measurements were made using video recordings and a force-plate. The influence of the stiffness of the base and of jumping with a

  20. Muscle localization of Tc-99m MDP after exertion

    Energy Technology Data Exchange (ETDEWEB)

    Valk, P.

    1984-09-01

    Very high muscle uptake of Tc-99m MDP was seen two days after the start of a program of vigorous weight-lifting exercises. Localization of Tc-99m bone tracer in muscle that has been damaged by exertion may be a more common phenomenon than is recognized at present.

  1. 3-dimensional local field polarization vector mapping of a focused radially polarized beam using gold nanoparticle functionalized tips.

    Science.gov (United States)

    Ahn, J S; Kihm, H W; Kihm, J E; Kim, D S; Lee, K G

    2009-02-16

    We have measured local electric field polarization vectors in 3-dimensional space on the nanoscale. A radial polarized light is generated by using a radial polarization converter and focused by an objective lens. Gold nanoparticle functionalized tips are used to scatter the focused field into the far-field region. Two different methods, rotational analyzer ellipsometry and Stokes parameters, are used in determining the polarization state of the scattered light. Two methods give consistent results with each other. Three dimensional local polarization vectors could be reconstructed by applying back transformation of the fully characterized polarizability tensor of the tip. PMID:19219131

  2. Numerical study of certain 3-dimensional effects in a sectioned MHD generator channel with successive inclusion of electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Ovchinnikov, V.L.

    1982-01-01

    In a 3-dimensional statement, a study is made of the effect of finite sectioning, shapes of electrodes and heterogeneity of the plasma parameters on the characteristics of the diagonal MHD generator. It is indicated that increase in specific electrical conductance of the plasma at the insulator wall results in a monotonic decrease in the voltage idling. There is an optimal specific electrical conductance of plasma at the electrode wall in which the voltage idling is the maximum. The expediency is shown of making channels with external commutation. There is an optimal ratio between the lengths of the electrode and the insulator.

  3. Experimental Validation of Plastic Mandible Models Produced by a “Low-Cost” 3-Dimensional Fused Deposition Modeling Printer

    OpenAIRE

    Maschio, Federico; Pandya, Mirali; Olszewski, Raphael

    2016-01-01

    Background The objective of this study was to investigate the accuracy of 3-dimensional (3D) plastic (ABS) models generated using a low-cost 3D fused deposition modelling printer. Material/Methods Two human dry mandibles were scanned with a cone beam computed tomography (CBCT) Accuitomo device. Preprocessing consisted of 3D reconstruction with Maxilim software and STL file repair with Netfabb software. Then, the data were used to print 2 plastic replicas with a low-cost 3D fused deposition mo...

  4. Measurement and Relation between Received and Exerted Violence against Partner

    OpenAIRE

    Moral de la Rubia, José; López Rosales, Fuensanta

    2014-01-01

    A female victimization model is often assumed in the study of couple violence, even in general population. In Mexico, a questionnaire of couple violence has been developed. This instrument evaluates suffered and exerted violence. The aims of this paper were to contrast the factor structure of this questionnaire, calculate its internal consistency, describe its distributions, compare means of violence between both sexes and between persons who live or not with their partners, and study the rel...

  5. Stereotactic Ablative Body Radiation Therapy for Primary Kidney Cancer: A 3-Dimensional Conformal Technique Associated With Low Rates of Early Toxicity

    International Nuclear Information System (INIS)

    Purpose: To describe our 3-dimensional conformal planning approaches and report early toxicities with stereotactic body radiation therapy for the management of primary renal cell carcinoma. Methods and Materials: This is an analysis of a phase 1 trial of stereotactic body radiation therapy for primary inoperable renal cell carcinoma. A dose of 42 Gy/3 fractions was prescribed to targets ≥5 cm, whereas for <5 cm 26 Gy/1 fraction was used. All patients underwent a planning 4-dimensional CT to generate a planning target volume (PTV) from a 5-mm isotropic expansion of the internal target volume. Planning required a minimum of 8 fields prescribing to the minimum isodose surrounding the PTV. Intermediate dose spillage at 50% of the prescription dose (R50%) was measured to describe the dose gradient. Early toxicity (<6 months) was scored using the Common Terminology Criteria for Adverse Events (v4.0). Results: From July 2012 to August 2013 a total of 20 patients (median age, 77 years) were recruited into a prospective clinical trial. Eleven patients underwent fractionated treatment and 9 patients a single fraction. For PTV targets <100 cm3 the median number of beams used was 8 (2 noncoplanar) to achieve an average R50% of 3.7. For PTV targets >100 cm3 the median beam number used was 10 (4 noncoplanar) for an average R50% value of 4.3. The R50% was inversely proportional to decreasing PTV volume (r=−0.62, P=.003) and increasing total beams used (r=−0.51, P=.022). Twelve of 20 patients (60%) suffered grade ≤2 early toxicity, whereas 8 of 20 patients (40%) were asymptomatic. Nausea, chest wall pain, and fatigue were the most common toxicities reported. Conclusion: A 3-dimensional conformal planning technique of 8-10 beams can be used to deliver highly tolerable stereotactic ablation to primary kidney targets with minimal early toxicities. Ongoing follow-up is currently in place to assess long-term toxicities and cancer control

  6. Stereotactic Ablative Body Radiation Therapy for Primary Kidney Cancer: A 3-Dimensional Conformal Technique Associated With Low Rates of Early Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Daniel, E-mail: daniel.pham@petermac.org [Department of Radiotherapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Department of Medical Imaging and Radiation Sciences, Monash University, Melbourne, Victoria (Australia); Thompson, Ann [Department of Radiotherapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Kron, Tomas [Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Sir Peter MacCallum Department of Oncology, Melbourne University, Melbourne, Victoria (Australia); Foroudi, Farshad [Sir Peter MacCallum Department of Oncology, Melbourne University, Melbourne, Victoria (Australia); Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Kolsky, Michal Schneider [Department of Medical Imaging and Radiation Sciences, Monash University, Melbourne, Victoria (Australia); Devereux, Thomas; Lim, Andrew [Department of Radiotherapy Services, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia); Siva, Shankar [Sir Peter MacCallum Department of Oncology, Melbourne University, Melbourne, Victoria (Australia); Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria (Australia)

    2014-12-01

    Purpose: To describe our 3-dimensional conformal planning approaches and report early toxicities with stereotactic body radiation therapy for the management of primary renal cell carcinoma. Methods and Materials: This is an analysis of a phase 1 trial of stereotactic body radiation therapy for primary inoperable renal cell carcinoma. A dose of 42 Gy/3 fractions was prescribed to targets ≥5 cm, whereas for <5 cm 26 Gy/1 fraction was used. All patients underwent a planning 4-dimensional CT to generate a planning target volume (PTV) from a 5-mm isotropic expansion of the internal target volume. Planning required a minimum of 8 fields prescribing to the minimum isodose surrounding the PTV. Intermediate dose spillage at 50% of the prescription dose (R50%) was measured to describe the dose gradient. Early toxicity (<6 months) was scored using the Common Terminology Criteria for Adverse Events (v4.0). Results: From July 2012 to August 2013 a total of 20 patients (median age, 77 years) were recruited into a prospective clinical trial. Eleven patients underwent fractionated treatment and 9 patients a single fraction. For PTV targets <100 cm{sup 3} the median number of beams used was 8 (2 noncoplanar) to achieve an average R50% of 3.7. For PTV targets >100 cm{sup 3} the median beam number used was 10 (4 noncoplanar) for an average R50% value of 4.3. The R50% was inversely proportional to decreasing PTV volume (r=−0.62, P=.003) and increasing total beams used (r=−0.51, P=.022). Twelve of 20 patients (60%) suffered grade ≤2 early toxicity, whereas 8 of 20 patients (40%) were asymptomatic. Nausea, chest wall pain, and fatigue were the most common toxicities reported. Conclusion: A 3-dimensional conformal planning technique of 8-10 beams can be used to deliver highly tolerable stereotactic ablation to primary kidney targets with minimal early toxicities. Ongoing follow-up is currently in place to assess long-term toxicities and cancer control.

  7. Cleft posterior mitral valve leaflet in an adult with Turner syndrome diagnosed with the use of 3-dimensional transesophageal echocardiography.

    Science.gov (United States)

    Negrea, Stefania Luminita; Alexandrescu, Clara; Sabatier, Michel; Dreyfus, Gilles D

    2012-01-01

    Turner syndrome is a monosomy (45,X karyotype) in which the prevalence of cardiovascular anomalies is high. However, this aspect of Turner syndrome has received little attention outside of the pediatric medical literature, and the entire spectrum of cardiovascular conditions in adults remains unknown. We present the case of a 34-year-old woman who had Turner syndrome. When she was a teenager, her native bicuspid aortic valve was replaced with a mechanical prosthesis. Fifteen years later, during preoperative examination for prosthesis-patient mismatch, severe mitral regurgitation was detected, and a congenital cleft in the posterior leaflet of the mitral valve was diagnosed with use of 3-dimensional transesophageal echocardiography. The patient underwent concurrent mitral valve repair and aortic valve replacement. To our knowledge, this is the first report of a cleft in the posterior mitral valve leaflet as a cardiovascular defect observed in Turner syndrome, and the first such instance to have been diagnosed with the use of 3-dimensional echocardiography.

  8. Influence of slice thickness of computed tomography and type of rapid protyping on the accuracy of 3-dimensional medical model

    International Nuclear Information System (INIS)

    This study was to evaluate the influence of slice thickness of computed tomography (CT) and rapid protyping (RP) type on the accuracy of 3-dimensional medical model. Transaxial CT data of human dry skull were taken from multi-detector spiral CT. Slice thickness were 1, 2, 3 and 4 mm respectively. Three-dimensional image model reconstruction using 3-D visualization medical software (V-works 3.0) and RP model fabrication were followed. 2-RP models were 3D printing (Z402, Z Corp., Burlington, USA) and Stereolithographic Apparatus model. Linear measurements of anatomical landmarks on dry skull, 3-D image model, and 2-RP models were done and compared according to slice thickness and RP model type. There were relative error percentage in absolute value of 0.97, 1.98, 3.83 between linear measurements of dry skull and image models of 1, 2, 3 mm slice thickness respectively. There was relative error percentage in absolute value of 0.79 between linear measurements of dry skull and SLA model. There was relative error difference in absolute value of 2.52 between linear measurements of dry skull and 3D printing model. These results indicated that 3-dimensional image model of thin slice thickness and stereolithographic RP model showed relative high accuracy.

  9. A 3-dimensional in vitro model of epithelioid granulomas induced by high aspect ratio nanomaterials

    Directory of Open Access Journals (Sweden)

    Hurt Robert H

    2011-05-01

    Full Text Available Abstract Background The most common causes of granulomatous inflammation are persistent pathogens and poorly-degradable irritating materials. A characteristic pathological reaction to intratracheal instillation, pharyngeal aspiration, or inhalation of carbon nanotubes is formation of epithelioid granulomas accompanied by interstitial fibrosis in the lungs. In the mesothelium, a similar response is induced by high aspect ratio nanomaterials, including asbestos fibers, following intraperitoneal injection. This asbestos-like behaviour of some engineered nanomaterials is a concern for their potential adverse health effects in the lungs and mesothelium. We hypothesize that high aspect ratio nanomaterials will induce epithelioid granulomas in nonadherent macrophages in 3D cultures. Results Carbon black particles (Printex 90 and crocidolite asbestos fibers were used as well-characterized reference materials and compared with three commercial samples of multiwalled carbon nanotubes (MWCNTs. Doses were identified in 2D and 3D cultures in order to minimize acute toxicity and to reflect realistic occupational exposures in humans and in previous inhalation studies in rodents. Under serum-free conditions, exposure of nonadherent primary murine bone marrow-derived macrophages to 0.5 μg/ml (0.38 μg/cm2 of crocidolite asbestos fibers or MWCNTs, but not carbon black, induced macrophage differentiation into epithelioid cells and formation of stable aggregates with the characteristic morphology of granulomas. Formation of multinucleated giant cells was also induced by asbestos fibers or MWCNTs in this 3D in vitro model. After 7-14 days, macrophages exposed to high aspect ratio nanomaterials co-expressed proinflammatory (M1 as well as profibrotic (M2 phenotypic markers. Conclusions Induction of epithelioid granulomas appears to correlate with high aspect ratio and complex 3D structure of carbon nanotubes, not with their iron content or surface area. This model

  10. Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation.

    Directory of Open Access Journals (Sweden)

    Ying Li

    Full Text Available Candida albicans, which is the most common human fungal pathogen, causes high mortality among immunocompromised patients. Antifungal drug resistance becomes a major challenge for the management of Candida infection. Diorcinol D (DD, a diphenyl ether derivative isolated from an endolichenic fungus, exerted fungicidal action against Candida species. In this study, we investigated the possible mechanism of its antifungal activity. The change of membrane dynamics and permeability suggested that the cell membrane was disrupted by the treatment of DD. This was further supported by the evidences of intracellular glycerol accumulation, alteration of cell ultrastructure, and down-regulation of genes involved in cell membrane synthesis. In addition, the treatment of C. albicans with DD resulted in the elevation of reactive oxygen species (ROS, which caused the dysfunction of mitochondria. These altogether suggested that DD exerted its antifungal activity through cytoplasmic membrane destruction and ROS accumulation. This finding is helpful to uncover the underlying mechanisms for the diphenyl ether derivatives and provides a potential application in fighting clinical fungal infections.

  11. Polymer lattices as mechanically tunable 3-dimensional photonic crystals operating in the infrared

    Energy Technology Data Exchange (ETDEWEB)

    Chernow, V. F., E-mail: vchernow@caltech.edu [Division of Engineering and Applied Sciences, California Institute of Technology, Pasadena, California 91125 (United States); Alaeian, H. [Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Department of Materials Science and Engineering, Stanford University, Stanford, California 94305 (United States); Dionne, J. A. [Department of Materials Science and Engineering, Stanford University, Stanford, California 94305 (United States); Greer, J. R. [Division of Engineering and Applied Sciences, California Institute of Technology, Pasadena, California 91125 (United States); The Kavli Nanoscience Institute, California Institute of Technology, Pasadena, California 91125 (United States)

    2015-09-07

    Broadly tunable photonic crystals in the near- to mid-infrared region could find use in spectroscopy, non-invasive medical diagnosis, chemical and biological sensing, and military applications, but so far have not been widely realized. We report the fabrication and characterization of three-dimensional tunable photonic crystals composed of polymer nanolattices with an octahedron unit-cell geometry. These photonic crystals exhibit a strong peak in reflection in the mid-infrared that shifts substantially and reversibly with application of compressive uniaxial strain. A strain of ∼40% results in a 2.2 μm wavelength shift in the pseudo-stop band, from 7.3 μm for the as-fabricated nanolattice to 5.1 μm when strained. We found a linear relationship between the overall compressive strain in the photonic crystal and the resulting stopband shift, with a ∼50 nm blueshift in the reflection peak position per percent increase in strain. These results suggest that architected nanolattices can serve as efficient three-dimensional mechanically tunable photonic crystals, providing a foundation for new opto-mechanical components and devices across infrared and possibly visible frequencies.

  12. Polymer lattices as mechanically tunable 3-dimensional photonic crystals operating in the infrared

    International Nuclear Information System (INIS)

    Broadly tunable photonic crystals in the near- to mid-infrared region could find use in spectroscopy, non-invasive medical diagnosis, chemical and biological sensing, and military applications, but so far have not been widely realized. We report the fabrication and characterization of three-dimensional tunable photonic crystals composed of polymer nanolattices with an octahedron unit-cell geometry. These photonic crystals exhibit a strong peak in reflection in the mid-infrared that shifts substantially and reversibly with application of compressive uniaxial strain. A strain of ∼40% results in a 2.2 μm wavelength shift in the pseudo-stop band, from 7.3 μm for the as-fabricated nanolattice to 5.1 μm when strained. We found a linear relationship between the overall compressive strain in the photonic crystal and the resulting stopband shift, with a ∼50 nm blueshift in the reflection peak position per percent increase in strain. These results suggest that architected nanolattices can serve as efficient three-dimensional mechanically tunable photonic crystals, providing a foundation for new opto-mechanical components and devices across infrared and possibly visible frequencies

  13. An active 3-dimensional localization scheme for femtocell subscribers using E-UTRAN

    KAUST Repository

    Mohammed, Aquil Mirza

    2012-05-01

    Femtocells provide an efficient solution to overcome the indoor coverage problems and also to deal with the traffic within Macro cells. The possibility of localizing femtocell subscriber stations based on the timing ranging advance parameter (TRAP), obtained from E-UTRAN (Evolved UMTS Terrestrial Radio Access Network), within the network signal internals is challenging and is studied throughout in this paper. The principle approach to localization based on Euclidean distances from multiple base stations is outlined.We investigate the specifications of the timing parameters or TRAP used for air interface of 4G network as they relate to calculating the subscriber distances. Computer simulation is used to demonstrate the localization accuracy using multiple base station networks when estimating likely locations of femtocell subscribers stations on a twodimensional coordinate mapping system. However, we further extend our simulations to demonstrate expected location accuracy of subscriber stations, for multiple base station networks, on a three dimensional coordinate mapping scheme. The possibility of of error-fixes shows eight times greater accuracy than in previous results is expected to achieve by applying timing advance techniques to Global System for Mobile communications networks, by using a two-dimensional coordinate mapping scheme. We later compare our study with the effect of global positioning system (GPS) by using a three-dimensional coordinate mapping scheme, which is predicted to give an 72.4 cms accuracy of subscriber station location. © 2012 IEEE.

  14. Microencapsulated 3-dimensional sensor for the measurement of oxygen in single isolated pancreatic islets.

    Directory of Open Access Journals (Sweden)

    Wanyu Chen

    approach should be applicable to other cell types and dyes sensitive to other biologically important molecules.

  15. PolySac3DB: an annotated data base of 3 dimensional structures of polysaccharides

    Directory of Open Access Journals (Sweden)

    Sarkar Anita

    2012-11-01

    Full Text Available Abstract Background Polysaccharides are ubiquitously present in the living world. Their structural versatility makes them important and interesting components in numerous biological and technological processes ranging from structural stabilization to a variety of immunologically important molecular recognition events. The knowledge of polysaccharide three-dimensional (3D structure is important in studying carbohydrate-mediated host-pathogen interactions, interactions with other bio-macromolecules, drug design and vaccine development as well as material science applications or production of bio-ethanol. Description PolySac3DB is an annotated database that contains the 3D structural information of 157 polysaccharide entries that have been collected from an extensive screening of scientific literature. They have been systematically organized using standard names in the field of carbohydrate research into 18 categories representing polysaccharide families. Structure-related information includes the saccharides making up the repeat unit(s and their glycosidic linkages, the expanded 3D representation of the repeat unit, unit cell dimensions and space group, helix type, diffraction diagram(s (when applicable, experimental and/or simulation methods used for structure description, link to the abstract of the publication, reference and the atomic coordinate files for visualization and download. The database is accompanied by a user-friendly graphical user interface (GUI. It features interactive displays of polysaccharide structures and customized search options for beginners and experts, respectively. The site also serves as an information portal for polysaccharide structure determination techniques. The web-interface also references external links where other carbohydrate-related resources are available. Conclusion PolySac3DB is established to maintain information on the detailed 3D structures of polysaccharides. All the data and features are available

  16. A comparison of VRML and animation of rotation for teaching 3-dimensional crystal lattice structures

    Science.gov (United States)

    Sauls, Barbara Lynn

    Chemistry students often have difficulty visualizing abstract concepts of molecules and atoms, which may lead to misconceptions. The three-dimensionality of these structures presents a challenge to educators. Typical methods of teaching include text with two-dimensional graphics and structural models. Improved methods to allow visualization of 3D structures may improve learning of these concepts. This research compared the use of Virtual Reality Modeling Language (VRML) and animation of rotation for teaching three-dimensional structures. VRML allows full control of objects by altering angle, size, rotation, and provides the ability to zoom into and through objects. Animations may only be stopped, restarted and replayed. A web-based lesson teaching basic concepts of crystals, which requires comprehension of their three-dimensional structure was given to 100 freshmen chemistry students. Students were stratified by gender then randomly to one of two lessons, which were identical except for the multimedia method used to show the lattices and unit cells. One method required exploration of the structures using VRML, the other provided animations of the same structures rotating. The students worked through an examination as the lesson progressed. A Welch t' test was used to compare differences between groups. No significant difference in mean achievement was found between the two methods, between genders, or within gender. There was no significant difference in mean total SAT in the animation and VRML group. Total time on task had no significant difference nor did enjoyment of the lesson. Students, however, spent 14% less time maneuvering VRML structures than viewing the animations of rotation. Neither method proved superior for presenting three-dimensional information. The students spent less time maneuvering the VRML structures with no difference in mean score so the use of VRML may be more efficient. The investigator noted some manipulation difficulties using VRML to

  17. Open reduction and internal fixation aided by intraoperative 3-dimensional imaging improved the articular reduction in 72 displaced acetabular fractures

    DEFF Research Database (Denmark)

    Eckardt, Henrik; Lind, Dennis; Toendevold, Erik

    2015-01-01

    Background and purpose - During acetabular fracture surgery, the acetabular roof is difficult to visualize with 2-dimensional fluoroscopic views. We assessed whether intraoperative 3-dimensional (3D) imaging can aid the surgeon to achieve better articular reduction and improve implant fixation....... Patients and methods - We operated on 72 acetabular fractures using intraoperative 3D imaging and compared the operative results, duration of surgery, and complications with those for 42 consecutive acetabular fracture operations conducted using conventional fluoroscopic imaging. Postoperative reduction...... was evaluated on reconstructed coronal and sagittal images of the acetabulum. Results - The fracture severity and patient characteristics were similar in the 2 groups. In the 3D group, 46 of 72 patients (0.6) had a perfect result after open reduction and internal fixation, and in the control group, 17 of 42 (0...

  18. Preoperative evaluation of vertebral and posterior communicating arteries using 3-dimensional CT angiography before cervical posterior instrumentation surgery

    International Nuclear Information System (INIS)

    We preoperatively examined 45 patients to investigate the frequency of an anomalous vertebral artery (VA) and the presence of a posterior communicating artery (PCOM) using 3-dimensional CT angiography (3D-CTA). Asymmetry of the VAs was detected in eight patients (18%). Anomalous VAs in the intra- or extraosseous region, including a high-riding VA, persistent 1st intersegmental artery, and ponticulus posticus, were found in a total of 8 patients (18%). Nineteen patients (42%) did not have a PCOM on either side. When a VA, especially the VA on the dominant side, is injured during cervical instrumentation, catastrophic vascular complications occur in approximately 7% of patients who have asymmetrical VAs without collateral circulation. Preoperative 3D-CTA provides information on anomalous VAs and collateral circulation that is crucial to preventing vascular complications. (author)

  19. Numerical simulation of recalescence of 3-dimensional isothermal solidification for binary alloy using phase-field approach

    Institute of Scientific and Technical Information of China (English)

    ZHU Chang-sheng; XIAO Rong-zhen; WANG Zhi-ping; FENG Li

    2009-01-01

    A accelerated arithmetic algorithm of the dynamic computing regions was designed, and 3-dimensional numerical simulation of isothermal solidification for a binary alloy was implemented. The dendritic growth and the recalescence of Ni-Cu binary alloy during the solidification at different cooling rates were investigated. The effects of cooling rate on dendritic patterns and microsegregation patterns were studied. The computed results indicate that, with the increment of the cooling rate, the dendritic growth velocity increases, both the main branch and side-branches become slender, the secondary dendrite arm spacing becomes smaller, the inadequate solute diffusion in solid aggravates, and the severity of microsegregation ahead of interface aggravates. At a higher cooling rate, the binary alloy presents recalescence; while the cooling rate is small, no recalescence occurs.

  20. Comparison of Ground-Based 3-Dimensional Lightning Mapping Observation with Satellite-Based LIS Observations in Oklahoma

    Science.gov (United States)

    Thomas, Ronald J.; Krehbiel, Paul R.; Rison, William; Hamlin, Timothy; Boccippio, Dennis J.; Goodman, Steven J.; Christian, Hugh J.

    1999-01-01

    3-dimensional lightning mapping observations were obtained in central Oklahoma during June 1998, using New Mexico Tech's Lightning Mapping Array (LMA). The results have been compared with observations of the discharges from space obtained by NASA's Lightning Imaging Sensor (LIS) on the Tropical Rainfall Measuring Mission (TRMM) spacecraft. Excellent spatial and temporal correlations were obtained between the two sets of observations. All discharges seen by LIS were mapped by the LMA. Most of the detected optical events were associated with lightning channels that extended into the upper part of the storm. Cloud-to-ground discharges that were confined to mid- and lower-altitudes tended to be detected by LIS at the time of late-stage return strokes. Extensive illumination tended to occur in impulsive bursts toward the end or part way through intracloud discharges and appeared to be produced by energetic K-changes that typically occur at these times.

  1. 3-dimensional organic Dirac-line material due to non-symmorphic symmetry: a data mining approach

    CERN Document Server

    Geilhufe, R Matthias; Borysov, Stanislav S; Balatsky, Alexander V

    2016-01-01

    A data mining study of electronic Kohn-Sham band structures was performed to identify Dirac materials within the Organic Materials Database (OMDB). Out of that, the 3-dimensional organic crystal 5,6-Bis(trifluoromethyl)-2-methoxy-1H-1,3-diazepine was found to host different Dirac line-nodes within the band structure. From a group theoretical analysis, it is possible to distinguish between Dirac line-nodes occurring due to 2-fold degenerate energy levels protected by the monoclinic crystalline symmetry and 2-fold degenerate accidental crossings protected by the topology of the electronic band structure. The obtained results can be generalized to all materials having the space group $P2_1/c$ ($\\#14$, $C^5_{2h}$) by introducing three distinct topological classes.

  2. Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting RAGE Signaling in Diabetic Atherosclerosis.

    Science.gov (United States)

    Chung, Jihwa; An, Shung Hyun; Kang, Sang Won; Kwon, Kihwan

    2016-01-01

    A naturally occurring bile acid, ursodeoxycholic acid (UDCA), is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, the detailed action mechanisms of UDCA in atherosclerosis are not fully understood. In this study, we demonstrated whether UDCA exerts anti-atherogenic activity in diabetic atherosclerosis by targeting ER stress and "receptor for advanced glycation endproduct" (RAGE) signaling. UDCA markedly reduced ER stress, RAGE expression, and pro-inflammatory responses [including NF-κB activation and reactive oxygen species (ROS) production] induced in endothelial cells (ECs) by high glucose (HG). In particular, UDCA inhibited HG-induced ROS production by increasing the Nrf2 level. In macrophages, UDCA also blocked HG-induced RAGE and pro-inflammatory cytokine expression and inhibited foam cell formation via upregulation of the ATP-binding cassette (ABC) transporters, ABCA1 and ABCG1. In the diabetic mouse model, UDCA inhibited atheromatous plaque formation by decreasing ER stress, and the levels of RAGE and adhesion molecules. In conclusion, UDCA exerts an anti-atherogenic activity in diabetic atherosclerosis by targeting both ER stress and RAGE signaling. Our work implicates UDCA as a potential therapeutic agent for prevention or treatment of diabetic atherosclerosis. PMID:26807573

  3. Bilateral flight muscle activity predicts wing kinematics and 3-dimensional body orientation of locusts responding to looming objects.

    Science.gov (United States)

    McMillan, Glyn A; Loessin, Vicky; Gray, John R

    2013-09-01

    We placed locusts in a wind tunnel using a loose tether design that allowed for motion in all three rotational degrees of freedom during presentation of a computer-generated looming disc. High-speed video allowed us to extract wing kinematics, abdomen position and 3-dimensional body orientation. Concurrent electromyographic (EMG) recordings monitored bilateral activity from the first basalar depressor muscles (m97) of the forewings, which are implicated in flight steering. Behavioural responses to a looming disc included cessation of flight (wings folded over the body), glides and active steering during sustained flight in addition to a decrease and increase in wingbeat frequency prior to and during, respectively, an evasive turn. Active steering involved shifts in bilateral m97 timing, wing asymmetries and whole-body rotations in the yaw (ψ), pitch (χ) and roll (η) planes. Changes in abdomen position and hindwing asymmetries occurred after turns were initiated. Forewing asymmetry and changes in η were most highly correlated with m97 spike latency. Correlations also increased as the disc approached, peaking prior to collision. On the inside of a turn, m97 spikes occurred earlier relative to forewing stroke reversal and bilateral timing corresponded to forewing asymmetry as well as changes in whole-body rotation. Double spikes in each m97 occurred most frequently at or immediately prior to the time the locusts turned, suggesting a behavioural significance. These data provide information on mechanisms underlying 3-dimensional flight manoeuvres and will be used to drive a closed loop flight simulator to study responses of motion-sensitive visual neurons during production of realistic behaviours.

  4. NEBIVOLOL IN TREATMENT OF STABLE EXERTIONAL ANGINA PECTORIS

    Directory of Open Access Journals (Sweden)

    Y. V. Gavrilov

    2015-12-01

    Full Text Available Aim. To evaluate antianginal and antiischemic efficiency of nebivolol in patients with stable angina pectoris.Material and methods. 100 patients with ischemic heart disease showing stable exertional angina pectoris and having no contraindications to beta-blockers were studied. After 5-7 days of control period 50 randomly selected patients began to take nebivolol in initial dose of 5mg once daily and 50 patients started to take metoprolol in initial dose of 50 mg twice daily. Duration of treatment was 8 weeks. Efficiency of treatment was assessed according to the results of control treadmill assessment and control daily ECG monitoring.Results. 56-day therapy with nebivolol at a dose of 7,5 mg per day results in increase in duration of treadmill test before angina or ST depression (p<0.05. Antianginal and antiischemic effect of nebivolol 7.5 mg once daily is rather similar with that of metoprolol in average daily dose of 175 mg. Nebivolol compared to metoprolol significantly (p<0.05 more effectively reduces the number of silent myocardial ischemia.Conclusion. Nebivolol is an efficient antianginal and antiischemic drug for patients with stable exertional angina pectoris.

  5. Physical exertion and working efficiency of reforestation workers

    Directory of Open Access Journals (Sweden)

    Kennedy Michael D

    2011-06-01

    Full Text Available Abstract Background The purpose of this study was to quantify the physical exertion during tree planting work and to examine the relationships between exertion, task efficiency, and productivity. Methods Heart rate (HR was monitored on 34 tree planters while they worked. HR data was collected for a complete working day on 19 subjects and for shorter periods of time on 15 subjects. Video of work tasks was recorded on 22 subjects (video was recorded on 7 of the subjects for whom HR was monitored through a full working day and analyzed for working pace and proportion of time spent on each task. Results HR during a full day (9.0 ± 1.2 hours of tree planting work was 115.2 ± 8.8 beats.min-1, and working HR was 128.2 ± 15.6 beats.min-1 for 82.5 ± 6.8% of the work day. Mean work pace was 452 ± 174 trees.h-1, and the proportion of time spent planting each tree was 53 ± 8% of the working time. Significant (P Conclusions Tree planters work at approximately 65% of age-predicted HRmax, and maintain HR at approximately 59% of HRmax throughout the entire working day. Productivity in these workers appears to be related to effort rather than to experience or task efficiency per se.

  6. Chronic Exertional Compartment Syndrome in a High School Soccer Player

    Directory of Open Access Journals (Sweden)

    James J. Bresnahan

    2015-01-01

    Full Text Available Chronic exertional compartment syndrome (CECS is a relatively rare condition that affects young adult athletes and often causes them to present to the emergency department. If left untreated, those who continue to compete at high levels may experience debilitating leg pain. Physicians may have difficulty differentiating CECS from other syndromes of the lower leg such as medial tibial stress syndrome, stress fractures, and popliteal artery entrapment. The gold standard for diagnosing CECS is intramuscular compartment pressure monitoring before and/or after 10 minutes of exercise. Some patients may choose to stop participation in sports in order to relieve their pain, which otherwise does not respond well to nonoperative treatments. In patients who wish to continue to participate in sports and live an active life, fasciotomy provides relief in 80% or more. The typical athlete can return to training in about 8 weeks. This is a case of a high school soccer player who stopped competing due to chronic exertional compartment syndrome. She had a fascial hernia, resting intramuscular pressure of 30 mmHg, and postexercise intramuscular pressure of 99 mmHg. Following fasciotomy she experienced considerable life improvement and is once again training and playing soccer without symptoms.

  7. Spinal cord stimulation exerts neuroprotective effects against experimental Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Aiko Shinko

    Full Text Available In clinical practice, deep brain stimulation (DBS is effective for treatment of motor symptoms in Parkinson's disease (PD. However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS. We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the

  8. Probabilistic Analysis on Fault Tolerance of 3-Dimensional Mesh Networks%3-维Mesh网络容错性的概率分析研究

    Institute of Scientific and Technical Information of China (English)

    王高才; 陈建二; 王国军; 陈松乔

    2003-01-01

    Mesh network is very popualr and important topological structure in parallel computing. In this paper,we focus on the fault tolerance of 3-dimensional mesh. We use the probability model to analyze the fault tolerance of mesh. To simplify our analysis, we assume the failure probability of each node is independent. We partition a 3-dimensional mesh into smaller submeshes and compute the probability with which each submesh satisfies the condition we define. If each submesh satisfies the condition, then the whole mesh is connected. We then compute the probability that a 3-dimensional mesh is connected assuming each node has a failure probability p. We use mathematical methods to derive a relationship between network node failure probability and network connectivity probability. Our simulations show that 3-dimensional mesh networks can remain connected with very high probability in practice. For example, the paper formally proves that when the network node failure probability is bounded by 0.05%, 3-dimensional mesh network of more than two hundred thousand nodes remain connected with probability larger than 99%. Theoretical and experimental results show that our method is powderful technique to calculate the lower bound of the connectivity probability of mesh network.

  9. Progesterone exerts neuroprotective effects against Aβ-induced neuroinflammation by attenuating ER stress in astrocytes.

    Science.gov (United States)

    Hong, Yang; Wang, Xiaomin; Sun, Shuang; Xue, Gai; Li, Jianli; Hou, Yanning

    2016-04-01

    The deposition of amyloid-β (Aβ) and neuroinflammation are critical pathological features of Alzheimer's disease (AD). Astrocytes are considered the principal immunoregulatory cells in the brain. Neurosteroid progesterone (PG) exerts neuromodulatory properties, particularly its potential therapeutic function in ameliorating AD. However, the role of PG and the neuroprotective mechanism involving in the regulation of neuroinflammation in astrocytes warrant further investigation. In this study, we found that Aβ significantly increased the processing of neuroinflammatory responses in astrocytes. The processing is induced by an increase activity of PERK/elF2ɑ-dependent endoplasmic reticulum (ER) stress. Additionally, the inhibition of ER stress activation by Salubrinal significantly suppressed the Aβ-induced neuroinflammatory responses in astrocytes. While the treatment of astrocytes with Aβ caused an increase of neuroinflammatory responses, PG significantly inhibited Aβ-induced neuroinflammatory cytokine production by suppressing ER stress activation together with attenuating PERK/elF2ɑ signalling. Taken together, these results indicate that PG exerts a neuroprotective effect against Aβ-induced neuroinflammatory responses, and significantly suppresses ER stress activation, which is an important mediator of the neurotoxic events occurring in Aβ-induced neuroinflammatory responses in astrocytes. These neuroprotective mechanisms may facilitate the development of therapies to ameliorate AD. PMID:26878478

  10. Fucoxanthin: A Marine Carotenoid Exerting Anti-Cancer Effects by Affecting Multiple Mechanisms

    Directory of Open Access Journals (Sweden)

    Sangeetha Ravi Kumar

    2013-12-01

    Full Text Available Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing influence via different molecules and pathways including the Bcl-2 proteins, MAPK, NFκB, Caspases, GADD45, and several other molecules that are involved in either cell cycle arrest, apoptosis, or metastasis. Thus, in addition to decreasing the frequency of occurrence and growth of tumours, fucoxanthin has a cytotoxic effect on cancer cells. Some studies show that this effect is selective, i.e., fucoxanthin has the capability to target cancer cells only, leaving normal physiological cells unaffected/less affected. Hence, fucoxanthin and its metabolites show great promise as chemotherapeutic agents in cancer.

  11. DNA damage intensity in fibroblasts in a 3-dimensional collagen matrix correlates with the Bragg curve energy distribution of a high LET particle

    Science.gov (United States)

    Roig, Andres I.; Hight, Suzie K.; Minna, John D.; Shay, Jerry W.; Rusek, Adam; Story, Michael D.

    2012-01-01

    Purpose The DNA double-strand break (DSB) damage response induced by high energy charged particles on lung fibroblast cells embedded in a 3-dimensional (3-D) collagen tissue equivalents was investigated using antibodies to the DNA damage response proteins gamma-histone 2AX (γ-H2AX) and phosphorylated DNA-PKcs (p-DNA-PKcs). Materials and methods 3-D tissue equivalents were irradiated in positions across the linear distribution of the Bragg curve profiles of 307.7 MeV/nucleon, 556.9 MeV/nucleon, or 967.0 MeV/nucleon 56Fe ions at a dose of 0.30 Gy. Results Patterns of discrete DNA damage streaks across nuclei or saturated nuclear damage were observed, with saturated nuclear damage being more predominant as samples were positioned closer to the physical Bragg peak. Quantification of the DNA damage signal intensities at each distance for each of the examined energies revealed a biological Bragg curve profile with a pattern of DNA damage intensity similar to the physical Bragg curve for the particular energy. Deconvolution microscopy of nuclei with streaked or saturated nuclear damage pattern revealed more details of the damage, with evidence of double-strand breaks radially distributed from the main particle track as well as multiple discrete tracks within saturated damage nuclei. Conclusions These 3-D culture systems can be used as a biological substrate to better understand the interaction of heavy charged particles of different energies with tissue and could serve as a basis to model space-radiation-induced cancer initiation and progression. PMID:20201648

  12. Evaluation of the Zone of Influence and Entrainment Impacts for an Intake Using a 3-Dimensional Hydrodynamic and Transport Model

    Directory of Open Access Journals (Sweden)

    Shwet Prakash

    2014-04-01

    Full Text Available Ballast water systems in large LNG carriers are essential for proper operations and stability. Water withdrawn from the surrounding environment to supply to the ballast can pose entrainment and impingement risk to the resident fish population. Quantification of these risks and the net effect on population is usually quite challenging and complex. Various methods over the last several decades have been developed and are available in the literature for quantification of entrainment of mobile and immobile lifestages of resident fish. In this study, a detailed 3-dimensional model was developed to estimate the entrainment of ichthyoplankton (fish eggs and larvae and fish from an estuarine environment during the repeated short-term operation of a ballast water intake for an LNG carrier. It was also used to develop a zone of influence to determine the ability of mobile life stages to avoid impingement. The ichthyoplankton model is an Equivalent Adult Model (EAM and assesses the number of breeding adults lost to the population. The EAM incorporates four different methods developed between 1978 and 2005. The study also considers the uncertainty in estimates for the lifestage data and, as such, performs sensitivity analyses to evaluate the confidence level achievable in such quantitative estimates for entrainment.

  13. The Use of Biofiltration Technology and 3-dimensional Cubical Bamboo Shelter for Nursery Phase Productivity Improvement of Giant Freshwater Prawn

    Directory of Open Access Journals (Sweden)

    Gede Suantika

    2012-07-01

    Full Text Available This experiment aimed to know the effect of nitrifying bacteria and Chlorellasp. addition and different number of 3-dimensional cubical bamboo shelter in enhancing growth performance of Giant Freshwater Prawn (Macrobrachium rosenbergii de Man during nursery phase in indoor system. During28 days of culture, treatment II (4 shelters addition~40% culture volume occupation resulted in better prawn growth and culture performance compared to control (no shelter addition (p<0,05. At the end of experiment, treatment II shown the highest biomass, SGR, mean body weight and length of the prawn with (1.96+0.05 g.cage-1, 8.24%BW.day-1, (2.18 +0,89 g and (6.50 +0.91 cm, respectively. However, the results were not significantly different compared to treatment I (2 shelters addition~20%culture volume occupation. Survival rate the two treatments (treatment I="90"%, and treatment II="92"% was significantly higher compared to control (78%. During the experiments, increase of ammonium concentration and nitrate can be controlled and maintained by addition of nitrifying bacteria and microalgae which can keep the microbial loop between ammonium reduction by bacteria and nitrate uptake by microalgae in balance. Addition of nitrifying bacteria and microalgae and also availability of 40% bamboo shelter occupation in the culture can enhance prawn culture productivity.

  14. Heating-Rate-Triggered Carbon-Nanotube-based 3-Dimensional Conducting Networks for a Highly Sensitive Noncontact Sensing Device

    KAUST Repository

    Tai, Yanlong

    2016-01-28

    Recently, flexible and transparent conductive films (TCFs) are drawing more attention for their central role in future applications of flexible electronics. Here, we report the controllable fabrication of TCFs for moisture-sensing applications based on heating-rate-triggered, 3-dimensional porous conducting networks through drop casting lithography of single-walled carbon nanotube (SWCNT)/poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS) ink. How ink formula and baking conditions influence the self-assembled microstructure of the TCFs is discussed. The sensor presents high-performance properties, including a reasonable sheet resistance (2.1 kohm/sq), a high visible-range transmittance (>69%, PET = 90%), and good stability when subjected to cyclic loading (>1000 cycles, better than indium tin oxide film) during processing, when formulation parameters are well optimized (weight ratio of SWCNT to PEDOT:PSS: 1:0.5, SWCNT concentration: 0.3 mg/ml, and heating rate: 36 °C/minute). Moreover, the benefits of these kinds of TCFs were verified through a fully transparent, highly sensitive, rapid response, noncontact moisture-sensing device (5 × 5 sensing pixels).

  15. Cognitive functions and stereopsis in patients with Parkinson's disease and Alzheimer's disease using 3-dimensional television: a case controlled trial.

    Directory of Open Access Journals (Sweden)

    Chan-Nyoung Lee

    Full Text Available Stereopsis or depth perception is an awareness of the distances of objects from the observer, and binocular disparity is a necessary component of recognizing objects through stereopsis. In the past studies, patients with neurodegenerative disease (Alzheimer dementia, AD; Parkinson's disease IPD have problems of stereopsis but they did not have actual stimulation of stereopsis. Therefore in this study, we used a 3-dimensional (3D movie on 3D television (TV for actual stereopsis stimulation. We propose research through analyzing differences between the three groups (AD, IPD, and Controls, and identified relations between the results from the Titmus Stereo Fly Test, and the 3D TV test. The study also looked into factors that affect the 3D TV test. Before allowing the patients to watch TV, we examined Titmus stereo Fly Test and cognitive test. We used the 3D version of a movie, of 17 minutes 1 second duration, and carried out a questionnaire about stereopsis. The scores of the stereopsis questionnaire were decreased in AD patients, compared with in IPD and controls, although they did not have any difference of Titmus Stereo Fly Test scores. In IPD patients, cognitive function (Montreal cognitive assessment, MoCA scores were correlated with the scores of the stereopsis questionnaire. We could conclude that Titmus fly test could not distinguish between the three groups and cognitive dysfunction contributes to actual stereopsis perception in IPD patients. Therefore the 3D TV test of AD and IPD patients was more effective than Titmus fly test.

  16. Morphological analysis and preoperative simulation of a double-chambered right ventricle using 3-dimensional printing technology.

    Science.gov (United States)

    Shirakawa, Takashi; Koyama, Yasushi; Mizoguchi, Hiroki; Yoshitatsu, Masao

    2016-05-01

    We present a case of a double-chambered right ventricle in adulthood, in which we tried a detailed morphological assessment and preoperative simulation using 3-dimensional (3D) heart models for improved surgical planning. Polygonal object data for the heart were constructed from computed tomography images of this patient, and transferred to a desktop 3D printer to print out models in actual size. Medical staff completed all of the work processes. Because the 3D heart models were examined by hand, observed from various viewpoints and measured by callipers with ease, we were able to create an image of the complete form of the heart. The anatomical structure of an anomalous bundle was clearly observed, and surgical approaches to the lesion were simulated accurately. During surgery, we used an incision on the pulmonary infundibulum and resected three muscular components of the stenosis. The similarity between the models and the actual heart was excellent. As a result, the operation for this rare defect was performed safely and successfully. We concluded that the custom-made model was useful for morphological analysis and preoperative simulation. PMID:26860990

  17. Heating-Rate-Triggered Carbon-Nanotube-based 3-Dimensional Conducting Networks for a Highly Sensitive Noncontact Sensing Device

    Science.gov (United States)

    Tai, Yanlong; Lubineau, Gilles

    2016-01-01

    Recently, flexible and transparent conductive films (TCFs) are drawing more attention for their central role in future applications of flexible electronics. Here, we report the controllable fabrication of TCFs for moisture-sensing applications based on heating-rate-triggered, 3-dimensional porous conducting networks through drop casting lithography of single-walled carbon nanotube (SWCNT)/poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS) ink. How ink formula and baking conditions influence the self-assembled microstructure of the TCFs is discussed. The sensor presents high-performance properties, including a reasonable sheet resistance (2.1 kohm/sq), a high visible-range transmittance (>69%, PET = 90%), and good stability when subjected to cyclic loading (>1000 cycles, better than indium tin oxide film) during processing, when formulation parameters are well optimized (weight ratio of SWCNT to PEDOT:PSS: 1:0.5, SWCNT concentration: 0.3 mg/ml, and heating rate: 36 °C/minute). Moreover, the benefits of these kinds of TCFs were verified through a fully transparent, highly sensitive, rapid response, noncontact moisture-sensing device (5 × 5 sensing pixels). PMID:26818091

  18. Metal organic framework derived magnetically separable 3-dimensional hierarchical Ni@C nanocomposites: Synthesis and adsorption properties

    Science.gov (United States)

    Song, Yixuan; Qiang, Tingting; Ye, Ming; Ma, Qiuyang; Fang, Zhen

    2015-12-01

    Design an effective absorbent that has high surface area, and perfect recyclable is imperative for pollution elimination. Herein, we report a facile two-step strategy to fabricate magnetically separable 3-dimensional (3D) hierarchical carbon-coated nickel (Ni@C) nanocomposites by calcinating nickel based metal organic framework (Ni3(OH)2(C8H4O4)2(H2O)4). SEM and TEM images illuminate that the nanocomposites were constructed by 8 nm nickel nanoparticle encapsulated in 3D flake like carbon. The specific surface area of the obtained nanocomposites is up to 120.38 m2 g-1. Room temperature magnetic measurement indicates the nanocomposites show soft magnetism property, which endows the nanocomposites with an ideal fast magnetic separable property. The maximum adsorption capacity of the nanocomposites for rhodamine B is 84.5 mg g-1. Furthermore, the nanocomposites also exhibit a high adsorption capacity for heavy metal ions. The adsorbent can be very easily separated from the solution by using a common magnet without exterior energy. The as-prepared Ni@C nanocomposites can apply in waste water treatment on a large-scale as a new adsorbent with high efficiency and excellent recyclability.

  19. Evaluation of Temperature and Stress Distribution on 2 Different Post Systems Using 3-Dimensional Finite Element Analysis

    Science.gov (United States)

    Değer, Yalçın; Adigüzel, Özkan; Özer, Senem Yiğit; Kaya, Sadullah; Polat, Zelal Seyfioğlu; Bozyel, Bejna

    2015-01-01

    Background The mouth is exposed to thermal irritation from hot and cold food and drinks. Thermal changes in the oral cavity produce expansions and contractions in tooth structures and restorative materials. The aim of this study was to investigate the effect of temperature and stress distribution on 2 different post systems using the 3-dimensional (3D) finite element method. Material/Methods The 3D finite element model shows a labio-lingual cross-sectional view of the endodontically treated upper right central incisor and supporting periodontal ligament with bone structures. Stainless steel and glass fiber post systems with different physical and thermal properties were modelled in the tooth restored with composite core and ceramic crown. We placed 100 N static vertical occlusal loading onto the center of the incisal surface of the tooth. Thermal loads of 0°C and 65°C were applied on the model for 5 s. Temperature and thermal stresses were determined on the labio-lingual section of the model at 6 different points. Results The distribution of stress, including thermal stress values, was calculated using 3D finite element analysis. The stainless steel post system produced more temperature and thermal stresses on the restorative materials, tooth structures, and posts than did the glass fiber reinforced composite posts. Conclusions Thermal changes generated stresses in the restorative materials, tooth, and supporting structures. PMID:26615495

  20. The Accuracy of Prostate Cancer Localization Diagnosed on Transrectal Ultrasound-Guided Biopsy Compared to 3-Dimensional Transperineal Approach

    Directory of Open Access Journals (Sweden)

    Kevin Krughoff

    2013-01-01

    Full Text Available Background. Prostate cancer is often understaged following 12-core transrectal ultrasound- (TRUS- guided biopsies. Our goal is to understand where cancers are typically missed by this method. Methods. Transperineal 3-dimensional mapping biopsy (3DMB provides a more accurate depiction of disease status than transrectal ultrasound- (TRUS- guided biopsy. We compared 3DMB findings in men with prior TRUS-guided biopsies to determine grade and location of missed cancer. Results were evaluated for 161 men with low-risk organ confined prostate cancer. Results. The number of cancer-positive biopsy zones per patient with TRUS was 1.38 ± 1.21 compared to 3.33 ± 4.06 with 3DMB, with most newly discovered cancers originating from the middle lobe and apex. Approximately half of all newly discovered cancerous zones resulted from anterior 3DMB sampling. Gleason upgrade was recognized in 56 patients using 3DMB. When both biopsy methods found positive cores in a given zone, Gleason upgrades occurred most frequently in the middle left and right zones. TRUS cancer-positive zones not confirmed by 3DMB were most often the basal zones. Conclusion. Most cancer upgrades and cancers missed from TRUS biopsy originated in the middle left zone of the prostate, specifically in anterior regions. Anterior sampling may lead to more accurate diagnosis and appropriate followup.

  1. Quantitative analysis of 3-dimensional rootarchitecture based on image reconstruction and itsapplication to research on phosphorus uptake in soybean

    Institute of Scientific and Technical Information of China (English)

    ZHU Tonglin; FANG Suqin; LI Zhiyuan; LIU Yutao; LIAO Hong; YAN Xiaolong

    2006-01-01

    Quantification of 3-dimensional (3-D) plant root architecture is one of the most important approaches to investigating plant root growth and its function in nutrient acquisition and utilization. However, no effective methods have been reported hitherto to quantify 3-D root architecture parameters, making it difficult to further study the 3-D characteristics of the root system and its function. In the present study, we created a rapid algorithm to reconstruct 3-D root system images based on the basic structural features of such linear objects as roots, using 2-D root images taken by digital CCD cameras at multi- viewing angles. This method is very effective in the reconstruction of plant root system images, thus enabling us to obtain the digital model of 3-D root architecture and its 3-D skeleton, based on which some major root architecture parameters can be calculated. Using this method, we were able to acquire 3-D parameters of soybean root architecture whose root diameter was more than 0.3 mm, including tap root length, total root length, average basal root angle, ratio of root width to root depth, percentage distribution of root length in different layers and root distribution in different 3-D regions of the growth medium. We also quantitatively analyzed the relationship between different root architecture parame-ters and such plant nutrition parameters as soybean biomass and phosphorus (P) uptake. Our study may provide a new tool in studying the growth and nutritional functions of plant root systems.

  2. Image Quality of the 3 Dimensional Phase-Contrast Technique in an Intracranial Magnetic Resonance Angiography with Artifacts Caused by Orthodontic Devices: A Comparison with 3 Dimensional Time-of-Flight Technique

    International Nuclear Information System (INIS)

    To evaluate the degree of image distortion caused by orthodontic devices during a intracranial magnetic resonance angiography (MRA), and to determine the effectiveness of the 3 dimensional phase-contrast (3D PC). Subjects were divided into group A (n = 20) wearing a home-made orthodontic device, and group B (n = 10) with an actual orthodontic device. A 3.0T MR scanner was used, applying 3D time-of-flight (TOF) and 3D PC. Two board-certified radiologists evaluated images independently based on a four point scale classifying segments of the circle of Willis. Magnetic susceptibility variations and contrast-to-noise ratio (CNR) on maximum intensity projection images were measured. In group A, scores of the 3D TOF and 3D PC were 2.84 ± 0.1 vs. 2.88 ± 0.1 (before) and 1.8 ± 0.4 vs 2.83 ± 0.1 (after wearing device), respectively. In group B, the scores of 3D TOF and 3D PC were 1.86 ± 0.43 and 2.81 ± 0.15 (p = 0.005), respectively. Magnetic susceptibility variations showed meaningful results after wearing the device (p = 0.0001). CNRs of the 3D PC before and after wearing device were 142.9 ± 6.6 vs. 140.8 ± 7.2 (p = 0.7507), respectively. In the 3D TOF, CNRs were 324.8 ± 25.4 vs. 466.3 ± 41.7 (p = 0.0001). The 3D PC may be a solution method for distorted images by magnetic susceptibility in the intracranial MRA compared with 3D TOF.

  3. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.

    Directory of Open Access Journals (Sweden)

    Pushpa Hegde

    Full Text Available Viscum album (VA preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2 and prostaglandin E2 (PGE2 play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2.

  4. Effect of radiation exerted to creep rate of resin

    International Nuclear Information System (INIS)

    One of the high performance composite materials which became to be manufactured by the progress of working techniques and the improvement of material performance is fiber-reinforced plastics (FRP). Carbon fiber-reinforced plastics (CFRP) are used as space and aircraft material, and glass fiber-reinforced plastics (GFRP) are expected as the structural material for superconducting magnets in nuclear fusion. In these materials, the use for long term must be considered, and the creep characteristics, of resin should be taken as one of the design factors. Therefore, the effect that radiation exerted to the stress relaxation of epoxy resin was measured, and its mechanism was investigated. The sample was bisphenol F system epoxy. The measurements of DSC, dynamic viscoelasticity and stress relaxation were carried out. The stress relaxation in bisphenol F system epoxy resin occurred down to 10 % of the initial stress only at 3 MGy. This is the dose far lower than the life in the radiation resistance of this resin. It is considered that the stress relaxation of the resin was caused by the change in molecular structure instead of the cut of molecular chain, as energy was given to the microscopic region by the interaction with radiation. (K.I.)

  5. Selective Mitochondrial Targeting Exerts Anxiolytic Effects In Vivo.

    Science.gov (United States)

    Nussbaumer, Markus; Asara, John M; Teplytska, Larysa; Murphy, Michael P; Logan, Angela; Turck, Christoph W; Filiou, Michaela D

    2016-06-01

    Current treatment strategies for anxiety disorders are predominantly symptom-based. However, a third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress. In this work, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. We treated high anxiety-related behavior (HAB) mice with MitoQ, an antioxidant that selectively targets mitochondria. MitoQ administration resulted in decreased anxiety-related behavior in HAB mice. This anxiolytic effect was specific for high anxiety as MitoQ treatment did not affect the anxiety phenotype of C57BL/6N and DBA/2J mouse strains. We furthermore investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found that MitoQ treatment alters the brain metabolome and that the response to MitoQ treatment is characterized by distinct molecular signatures. These results indicate that a mechanism-driven approach based on selective mitochondrial targeting has the potential to attenuate the high anxiety phenotype in vivo, thus paving the way for translational implementation as long-term MitoQ administration is well-tolerated with no reported side effects in mice and humans. PMID:26567514

  6. Formwork pressure exerted by self-consolidating concrete

    Science.gov (United States)

    Omran, Ahmed Fathy

    Self-consolidating concrete (SCC) is an emerging technology that utilizes flowable concrete that eliminates the need for consolidation. The advantages of SCC lie in a remarkable reduction of the casting time, facilitating the casting of congested and complex structural elements, possibility to reduce labor demand, elimination of mechanical vibrations and noise, improvement of surface appearance, producing a better and premium concrete product. The research focussed on capturing existing knowledge and making recommendations for current practice. An experimental program was undertaken at the Universite de Sherbrooke to evaluate the lateral pressure developed by SCC mixtures. A portable devise (UofS2 pressure column) for measuring and predicting lateral pressure and its rate of decay of SCC was developed and validated. The UofS2 pressure column is cast with 0.5 m high fresh concrete and air pressure is introduced from the top to simulate casting depth up to 13 m. Then, develop and implement test method for field evaluation of relevant plastic and thixotropic properties of SCC that affect formwork pressure were done. Portable vane (PV) test based on the hand-held vane test method used to determine the undrained shear strength property of clay soil was the first setup as well as the inclined plane (IP) test. The IP device involves slumping a small concrete cylinder on a horizontal plate and then lifting up the plate at different durations of rest until the slumped sample starts to move. Identifying role of material constituents, mix design, concrete placement characteristics (casting rate, waiting periods between lifts, and casting depth), temperature, and formwork characteristics that have major influence on formwork pressure exerted by SCC were evaluated in laboratory and validated by actual field measurements. Relating the maximum lateral pressure and its rate of decay to the plastic properties of SCC were established. In the analytical part of the research

  7. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    DEFF Research Database (Denmark)

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H;

    2015-01-01

    BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number...... endogenous IFN-β signaling did not affect the infarct volume. CONCLUSIONS: We conclude that endogenous IFN-β signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome....

  8. Fgf8-Related Secondary Organizers Exert Different Polarizing Planar Instructions along the Mouse Anterior Neural Tube

    Science.gov (United States)

    Crespo-Enriquez, Ivan; Partanen, Juha; Martinez, Salvador; Echevarria, Diego

    2012-01-01

    Early brain patterning depends on proper arrangement of positional information. This information is given by gradients of secreted signaling molecules (morphogens) detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical location of the secondary organizers: the isthmic organizer (IsO) and the anterior neural ridge (anr) but not on zona limitans intrathalamica (zli). Our results suggest that Sprouty2, a negative modulator of RAS/ERK pathway, is important for regulating Fgf8 morphogenetic signal activity by controlling Fgf8-induced signaling pathways and positional information during early brain development. PMID:22792203

  9. Fgf8-related secondary organizers exert different polarizing planar instructions along the mouse anterior neural tube.

    Directory of Open Access Journals (Sweden)

    Ivan Crespo-Enriquez

    Full Text Available Early brain patterning depends on proper arrangement of positional information. This information is given by gradients of secreted signaling molecules (morphogens detected by individual cells within the responding tissue, leading to specific fate decisions. Here we report that the morphogen FGF8 exerts initially a differential signal activity along the E9.5 mouse neural tube. We demonstrate that this polarizing activity codes by RAS-regulated ERK1/2 signaling and depends on the topographical location of the secondary organizers: the isthmic organizer (IsO and the anterior neural ridge (anr but not on zona limitans intrathalamica (zli. Our results suggest that Sprouty2, a negative modulator of RAS/ERK pathway, is important for regulating Fgf8 morphogenetic signal activity by controlling Fgf8-induced signaling pathways and positional information during early brain development.

  10. BDNF-secreting capsule exerts neuroprotective effects on epilepsy model of rats.

    Science.gov (United States)

    Kuramoto, Satoshi; Yasuhara, Takao; Agari, Takashi; Kondo, Akihiko; Jing, Meng; Kikuchi, Yoichiro; Shinko, Aiko; Wakamori, Takaaki; Kameda, Masahiro; Wang, Feifei; Kin, Kyohei; Edahiro, Satoru; Miyoshi, Yasuyuki; Date, Isao

    2011-01-12

    Brain-derived neurotrophic factor (BDNF) is a well neurotrophic factor with neuroprotective potentials for various diseases in the central nervous system. However several previous studies demonstrated that BDNF might deteriorate symptoms for epilepsy model of animals by progression of abnormal neurogenesis. We hypothesized that continuous administration of BDNF at low dose might be more effective for epilepsy model of animals because high dose of BDNF was used in many studies. BDNF-secreting cells were genetically made and encapsulated for transplantation. Rats receiving BDNF capsule showed significant amelioration of seizure stage and reduction of the number of abnormal spikes at 7 days after kainic acid administration, compared to those of control group. The number of BrdU and BrdU/doublecortin positive cells in the hippocampus of BDNF group significantly increased, compared to that of control group. NeuN positive cells in the CA1 and CA3 of BDNF group were significantly preserved, compared to control group. In conclusion, low dose administration using encapsulated BDNF-secreting cells exerted neuroprotective effects with enhanced neurogenesis on epilepsy model of rats. These results might suggest the importance of the dose and administrative way of this neurotrophic factor to the epilepsy model of animals.

  11. Comparison of 3-dimensional dose reconstruction system between fluence-based system and dose measurement-guided system.

    Science.gov (United States)

    Nakaguchi, Yuji; Ono, Takeshi; Onitsuka, Ryota; Maruyama, Masato; Shimohigashi, Yoshinobu; Kai, Yudai

    2016-01-01

    COMPASS system (IBA Dosimetry, Schwarzenbruck, Germany) and ArcCHECK with 3DVH software (Sun Nuclear Corp., Melbourne, FL) are commercial quasi-3-dimensional (3D) dosimetry arrays. Cross-validation to compare them under the same conditions, such as a treatment plan, allows for clear evaluation of such measurement devices. In this study, we evaluated the accuracy of reconstructed dose distributions from the COMPASS system and ArcCHECK with 3DVH software using Monte Carlo simulation (MC) for multi-leaf collimator (MLC) test patterns and clinical VMAT plans. In a phantom study, ArcCHECK 3DVH showed clear differences from COMPASS, measurement and MC due to the detector resolution and the dose reconstruction method. Especially, ArcCHECK 3DVH showed 7% difference from MC for the heterogeneous phantom. ArcCHECK 3DVH only corrects the 3D dose distribution of treatment planning system (TPS) using ArcCHECK measurement, and therefore the accuracy of ArcCHECK 3DVH depends on TPS. In contrast, COMPASS showed good agreement with MC for all cases. However, the COMPASS system requires many complicated installation procedures such as beam modeling, and appropriate commissioning is needed. In terms of clinical cases, there were no large differences for each QA device. The accuracy of the compass and ArcCHECK 3DVH systems for phantoms and clinical cases was compared. Both systems have advantages and disadvantages for clinical use, and consideration of the operating environment is important. The QA system selection is depending on the purpose and workflow in each hospital. PMID:27179708

  12. Joint environmental assessment for western NPR-1 3-dimensional seismic project at Naval Petroleum Reserve No. 1, Kern County, California

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-05-01

    The Department of Energy (DOE), in conjunction with the Bureau of Land Management (BLM), has prepared an Environmental Assessment (DOE/EA-1124) to identify and evaluate the potential environmental impacts of the proposed geophysical seismic survey on and adjacent to the Naval Petroleum Reserve No.1 (NPR-1), located approximately 35 miles west of Bakersfield, California. NPR-1 is jointly owned and operated by the federal government and Chevron U.S.A. Production Company. The federal government owns about 78 percent of NPR-1, while Chevron owns the remaining 22 percent. The government`s interest is under the jurisdiction of DOE, which has contracted with Bechtel Petroleum Operations, Inc. (BPOI) for the operation and management of the reserve. The 3-dimensional seismic survey would take place on NPR-1 lands and on public and private lands adjacent to NPR-1. This project would involve lands owned by BLM, California Department of Fish and Game (CDFG), California Energy Commission (CEC), The Nature Conservancy, the Center for Natural Lands Management, oil companies (Chevron, Texaco, and Mobil), and several private individuals. The proposed action is designed to provide seismic data for the analysis of the subsurface geology extant in western NPR-1 with the goal of better defining the commercial limits of a currently producing reservoir (Northwest Stevens) and three prospective hydrocarbon bearing zones: the {open_quotes}A Fan{close_quotes} in Section 7R, the 19R Structure in Section 19R, and the 13Z Structure in Section 13Z. Interpreting the data is expected to provide NPR-1 owners with more accurate locations of structural highs, faults, and pinchouts to maximize the recovery of the available hydrocarbon resources in western NPR-1. Completion of this project is expected to increase NPR-1 recoverable reserves, and reduce the risks and costs associated with further exploration and development in the area.

  13. Impact of the difference in power frequency on diamond-like carbon thin film coating over 3-dimensional objects

    International Nuclear Information System (INIS)

    With a type of capacitatively coupled plasma enhanced chemical vapor deposition (PECVD) technique, where two specially designed electrodes face to each other, the inner surface of hollow 3-dimensional objects such as poly(ethylene terephthalate) (PET) bottles can be coated with diamond-like carbon (DLC) thin film. DLC-coated PET bottles obtained with this technique have an enhanced gas barrier property, and therefore are applicable to industrial use such as for the extension of the shelf-life of contents sensitive to gas permeation. In this paper, the impact of power frequency ranging from 2.5 to 13.56 MHz was studied in order to research the behavior of plasma inside PET bottles and resultant properties. Different power frequency turned out to be influential on gas barrier property, the overall and distribution of tint, and adhesion between DLC and PET substrate. In addition, positron annihilation turned out to be powerful tool for the comparison of different coating conditions because it clarifies the homogeneity of DLC thin films through providing information on overall structure and thickness of them. These findings can be used for the optimization not only in the beverage PET bottle application, but also in other capacitatively coupled PECVD devices. - Highlights: • We demonstrated an effective methodology for the homogeneity of thin films. • We described the influence of power frequency on plasma and resultant thin film. • Diamond-like carbon coated on poly(ethylene terephthalate) bottles was used. • Different frequency provided homogenous thin films based on the above methodology. • For the industrial performance of the bottles, optimization was found at 6 MHz

  14. Impact of the difference in power frequency on diamond-like carbon thin film coating over 3-dimensional objects

    Energy Technology Data Exchange (ETDEWEB)

    Nakaya, Masaki, E-mail: m-nakaya@kirin.co.jp [Packaging Technology Development Center, Technology Development Department, Kirin Brewery Co., Ltd., 1-17-1 Namamugi, Tsurumi-ku, Yokohama, Kanagawa 230-8682 (Japan); Shimizu, Mari [Packaging Technology Development Center, Technology Development Department, Kirin Brewery Co., Ltd., 1-17-1 Namamugi, Tsurumi-ku, Yokohama, Kanagawa 230-8682 (Japan); Uedono, Akira [Division of Applied Physics, Faculty of Pure and Applied Science, University of Tsukuba, Tsukuba, Ibaraki 305-8573 (Japan)

    2014-08-01

    With a type of capacitatively coupled plasma enhanced chemical vapor deposition (PECVD) technique, where two specially designed electrodes face to each other, the inner surface of hollow 3-dimensional objects such as poly(ethylene terephthalate) (PET) bottles can be coated with diamond-like carbon (DLC) thin film. DLC-coated PET bottles obtained with this technique have an enhanced gas barrier property, and therefore are applicable to industrial use such as for the extension of the shelf-life of contents sensitive to gas permeation. In this paper, the impact of power frequency ranging from 2.5 to 13.56 MHz was studied in order to research the behavior of plasma inside PET bottles and resultant properties. Different power frequency turned out to be influential on gas barrier property, the overall and distribution of tint, and adhesion between DLC and PET substrate. In addition, positron annihilation turned out to be powerful tool for the comparison of different coating conditions because it clarifies the homogeneity of DLC thin films through providing information on overall structure and thickness of them. These findings can be used for the optimization not only in the beverage PET bottle application, but also in other capacitatively coupled PECVD devices. - Highlights: • We demonstrated an effective methodology for the homogeneity of thin films. • We described the influence of power frequency on plasma and resultant thin film. • Diamond-like carbon coated on poly(ethylene terephthalate) bottles was used. • Different frequency provided homogenous thin films based on the above methodology. • For the industrial performance of the bottles, optimization was found at 6 MHz.

  15. Effects of Non-Uniform Wall Heating on Thermal and Momentum Fields in a 3-Dimensional Urban Environment

    Science.gov (United States)

    Nazarian, N.; Kleissl, J. P.

    2014-12-01

    As urbanization progresses, microclimate modifications are also aggravated and the increasing environmental concerns call for more sophisticated methods of urban microclimate analysis. Comprehensive numerical simulations for a clear summer day in southern California are performed in a compact low-rise urban environment. The effect of realistic unsteady, non-uniform thermal forcing, that is caused by solar insolation and inter-building shadowing on thermal and flow conditions are analyzed based on Algebraic Wall-Modeled Large Eddy Simulation (LES) model. The urban thermal field is influenced by urban density, material properties and local weather conditions, as well as urban canyon flow. Urban canyon conditions are translated into vertical and horizontal bulk Richardson numbers indicating atmospheric instability and solar tilt with respect to the momentum forcing of the canyon vortex, respectively. The effect of roof heating is found to be critical on the vortex formation between buildings when the vertical bulk Richardson number is low. Variations of Convective Heat Transfer Coefficients (CHTCs) along building walls are studied and the street canyon ventilation performance is characterized by the mean of air exchange rate (ACH). It is found that volumetric air exchange from street canyons, as well as the distribution of heat transfer along the wall depends strongly on the three-dimensional orientation of the heated wall in relation to wind direction. For example, air removal increases by surface heating and is larger when the leeward wall is heated. In summary, we demonstrate the importance of considering complex realistic conditions on 3-dimensional thermal and momentum fields in Urban Environments.

  16. Automorphosis of higher plants in space is simulated by using a 3-dimensional clinostat or by application of chemicals

    Science.gov (United States)

    Miyamoto, K.; Hoshino, T.; Hitotsubashi, R.; Yamashita, M.; Ueda, J.

    In STS-95 space experiments, etiolated pea seedlings grown under microgravity conditions in space have shown to be automorphosis. Epicotyls were almost straight but the most oriented toward the direction far from their cotyledons with ca. 45 degrees from the vertical line as compared with that on earth. In order to know the mechanism of microgravity conditions in space to induce automorphosis, we introduced simulated microgravity conditions on a 3-dimensional clinostat, resulting in the successful induction of automorphosis-like growth and development. Kinetic studies revealed that epicotyls bent at their basal region or near cotyledonary node toward the direction far from the cotyledons with about 45 degrees in both seedlings grown on 1 g and under simulated microgravity conditions on the clinostat within 48 hrs after watering. Thereafter epicotyls grew keeping this orientation under simulated microgravity conditions on the clinostat, whereas those grown on 1 g changed the growth direction to vertical direction by negative gravitropic response. Automorphosis-like growth and development was induced by the application of auxin polar transport inhibitors (2,3,5-triiodobenzoic acid, N-(1-naphtyl)phthalamic acid, 9-hydroxyfluorene-9-carboxylic acid), but not an anti-auxin, p-chlorophenoxyisobutyric acid. Automorphosis-like epicotyl bending was also phenocopied by the application of inhibitors of stretch-activated channel, LaCl3 and GdCl3, and by the application of an inhibitor of protein kinase, cantharidin. These results suggest that automorphosis-like growth in epicotyls of etiolated pea seedlings is due to suppression of negative gravitropic responses on 1 g, and the growth and development of etiolated pea seedlings under 1 g conditions requires for normal activities of auxin polar transport and the gravisensing system relating to calcium channels. Possible mechanisms of perception and transduction of gravity signals to induce automorphosis are discussed.

  17. Accuracy Evaluation of a 3-Dimensional Surface Imaging System for Guidance in Deep-Inspiration Breath-Hold Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Alderliesten, Tanja; Sonke, Jan-Jakob; Betgen, Anja; Honnef, Joeri; Vliet-Vroegindeweij, Corine van [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Remeijer, Peter, E-mail: p.remeijer@nki.nl [Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

    2013-02-01

    Purpose: To investigate the applicability of 3-dimensional (3D) surface imaging for image guidance in deep-inspiration breath-hold radiation therapy (DIBH-RT) for patients with left-sided breast cancer. For this purpose, setup data based on captured 3D surfaces was compared with setup data based on cone beam computed tomography (CBCT). Methods and Materials: Twenty patients treated with DIBH-RT after breast-conserving surgery (BCS) were included. Before the start of treatment, each patient underwent a breath-hold CT scan for planning purposes. During treatment, dose delivery was preceded by setup verification using CBCT of the left breast. 3D surfaces were captured by a surface imaging system concurrently with the CBCT scan. Retrospectively, surface registrations were performed for CBCT to CT and for a captured 3D surface to CT. The resulting setup errors were compared with linear regression analysis. For the differences between setup errors, group mean, systematic error, random error, and 95% limits of agreement were calculated. Furthermore, receiver operating characteristic (ROC) analysis was performed. Results: Good correlation between setup errors was found: R{sup 2}=0.70, 0.90, 0.82 in left-right, craniocaudal, and anterior-posterior directions, respectively. Systematic errors were {<=}0.17 cm in all directions. Random errors were {<=}0.15 cm. The limits of agreement were -0.34-0.48, -0.42-0.39, and -0.52-0.23 cm in left-right, craniocaudal, and anterior-posterior directions, respectively. ROC analysis showed that a threshold between 0.4 and 0.8 cm corresponds to promising true positive rates (0.78-0.95) and false positive rates (0.12-0.28). Conclusions: The results support the application of 3D surface imaging for image guidance in DIBH-RT after BCS.

  18. Nanostructural evolution of Cr-rich precipitates in a Cu-Cr-Zr alloy during heat treatment studied by 3 dimensional atom probe

    DEFF Research Database (Denmark)

    Hatakeyama, Masahiko; Toyama, Takeshi; Nagai, Yasuyoshi;

    2008-01-01

    Nanostructural evolution of Cr (Cr-rich) precipitates in a Cu-0.78%Cr-0.13%Zr alloy has been studied after aging and overaging (reaging) by laser assisted local electrode 3 dimensional atom probe (Laser-LEAP). This material is a candidate for the first wall and divertor components of future fusion...

  19. Application of a parallel 3-dimensional hydrogeochemistry HPF code to a proposed waste disposal site at the Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    The objectives of this study are (1) to parallelize a 3-dimensional hydrogeochemistry code and (2) to apply the parallel code to a proposed waste disposal site at the Oak Ridge National Laboratory (ORNL). The 2-dimensional hydrogeochemistry code HYDROGEOCHEM, developed at the Pennsylvania State University for coupled subsurface solute transport and chemical equilibrium processes, was first modified to accommodate 3-dimensional problem domains. A bi-conjugate gradient stabilized linear matrix solver was then incorporated to solve the matrix equation. We chose to parallelize the 3-dimensional code on the Intel Paragons at ORNL by using an HPF (high performance FORTRAN) compiler developed at PGI. The data- and task-parallel algorithms available in the HPF compiler proved to be highly efficient for the geochemistry calculation. This calculation can be easily implemented in HPF formats and is perfectly parallel because the chemical speciation on one finite-element node is virtually independent of those on the others. The parallel code was applied to a subwatershed of the Melton Branch at ORNL. Chemical heterogeneity, in addition to physical heterogeneities of the geological formations, has been identified as one of the major factors that affect the fate and transport of contaminants at ORNL. This study demonstrated an application of the 3-dimensional hydrogeochemistry code on the Melton Branch site. A uranium tailing problem that involved in aqueous complexation and precipitation-dissolution was tested. Performance statistics was collected on the Intel Paragons at ORNL. Implications of these results on the further optimization of the code were discussed

  20. Initial results of 3-dimensional 1H-magnetic resonance spectroscopic imaging in the localization of prostate cancer at 3 Tesla: should we use an endorectal coil?

    NARCIS (Netherlands)

    Yakar, D.; Heijmink, S.W.T.P.J.; Hulsbergen- van de Kaa, C.A.; Huisman, H.J.; Barentsz, J.O.; Futterer, J.J.; Scheenen, T.W.J.

    2011-01-01

    PURPOSE: The purpose of this study was to compare the diagnostic performance of 3 Tesla, 3-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) in the localization of prostate cancer (PCa) with and without the use of an endorectal coil (ERC). MATERIALS AND METHODS: Our prospective study

  1. Qualitative dimensions of exertional dyspnea in adults with cystic fibrosis.

    Science.gov (United States)

    Quon, Bradley S; Wilkie, Sabrina S; Ramsook, Andrew H; Schaeffer, Michele R; Puyat, Joseph H; Wilcox, Pearce G; Guenette, Jordan A

    2016-08-01

    No studies of cystic fibrosis (CF) have systematically characterized the evolution of the qualitative dimensions of exertional dyspnea. Adults with CF (n = 25) and control individuals matched for sex, age, and body mass index (n = 25) underwent cardiopulmonary cycle exercise testing with a detailed evaluation of ventilatory and dyspnea responses. The qualitative dimensions of dyspnea were examined during each exercise stage by having subjects select phrases that best described their breathing (i.e., "work/effort," "unsatisfied inspiration," and "unsatisfied expiration"). Subjects also selected phrases that described the quality of their breathing at peak exercise using an established 15-item questionnaire, which was then clustered into different categories. Subjects with CF had greater ventilatory requirements, higher end-inspiratory and end-expiratory lung volumes (% total lung capacity), and an earlier inflection/plateau in tidal volume during exercise compared with control subjects. Increased work/effort was the dominant qualitative descriptor in both groups throughout exercise. Unsatisfied inspiration was selected by 48% of subjects with CF and 40% of controls at some point during exercise. The onset of unsatisfied inspiration in these subjects occurred at a significantly lower relative exercise intensity in subjects with CF vs. controls (72 ± 21 vs. 94 ± 11% Wmax, P < 0.01). Chest tightness was the only qualitative descriptor cluster that was selected more frequently by subjects with CF vs. controls (36 vs. 0%, respectively, P < 0.05) at peak exercise. Therapeutic interventions that reduce ventilatory requirements and improve lung volumes may delay the onset of distressing sensations such as unsatisfied inspiration and chest tightness in adults with CF. PMID:27311438

  2. Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

    Directory of Open Access Journals (Sweden)

    Keisuke Ishizawa

    Full Text Available Diabetic nephropathy (DN is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice, NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

  3. VALIDATION OF ADULT OMNI PERCEIVED EXERTION SCALES FOR ELLIPTICAL ERGOMETRY12

    Science.gov (United States)

    MAYS, RYAN J.; GOSS, FREDRIC L.; SCHAFER, MARK A.; KIM, KEVIN H.; NAGLE-STILLEY, ELIZABETH F.; ROBERTSON, ROBERT J.

    2012-01-01

    Summary This investigation examined the validity of newly developed Adult OMNI Elliptical Ergometer Ratings of Perceived Exertion Scales. Sixty men and women performed a graded exercise test on an elliptical ergometer. Oxygen consumption (VO2), heart rate (HR) and ratings of perceived exertion were recorded each stage from the Borg 15 Category Scale and two different OMNI scales. One scale employed an elliptical ergometer format of the OMNI Picture System of Perceived Exertion. The second scale modified verbal, numerical, and pictorial descriptors at the low end of the response range. Concurrent and construct validity were established by the positive relation between ratings of perceived exertion from each OMNI scale with VO2, HR and Borg Scale ratings of perceived exertion (men, r = .94–.97; women, r = .93–.98). Validity was established for both OMNI scales, indicating either metric can be used to estimate ratings of perceived exertion during partial weight bearing exercise. PMID:21319623

  4. Exertional heat stroke in a young military trainee: is it preventable?

    OpenAIRE

    Wijerathne, Buddhika T. B.; Pilapitiya, Senaka D.; Vijitharan, Vadivel; Farah, Mohammed M. F.; Wimalasooriya, Yashodhara V. M.; Siribaddana, Sisira H.

    2016-01-01

    Background Heat stroke is a life-threatening condition with exertional heat stroke occurring frequently among soldiers and athletes. Because of its common occurrence, many military trainees practice preventive measures prior to any activity requiring severe exertion. Although it is said to be common in practice, different presentations of heat stroke are scarcely described in literature. Case Presentation We describe a case of an exertional heat stroke in a 23-year-old male Sinhalese soldier ...

  5. Camphene, a Plant Derived Monoterpene, Exerts Its Hypolipidemic Action by Affecting SREBP-1 and MTP Expression.

    Directory of Open Access Journals (Sweden)

    Ioanna Vallianou

    Full Text Available The control of hyperlipidemia plays a central role in cardiovascular disease. Previously, we have shown that camphene, a constituent of mastic gum oil, lowers cholesterol and triglycerides (TG in the plasma of hyperlipidemic rats without affecting HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. In the present study, we examine the mechanism by which camphene exerts its hypolipidemic action. We evaluated the effect of camphene on the de novo synthesis of cholesterol and TG from [14C]-acetate in HepG2 cells, along with the statin mevinolin. Camphene inhibited the biosynthesis of cholesterol in a concentration-dependent manner, and a maximal inhibition of 39% was observed at 100 μM while mevinolin nearly abolished cholesterol biosynthesis. Moreover, treatment with camphene reduced TG by 34% and increased apolipoprotein AI expression. In contrast, mevinolin increased TG by 26% and had a modest effect on apolipoprotein AI expression. To evaluate the mode of action of camphene, we examined its effects on the expression of SREBP-1, which affects TG biosynthesis and SREBP-2, which mostly affects sterol synthesis. Interestingly, camphene increased the nuclear translocation of the mature form of SREBP-1 while mevinolin was found to increase the amount of the mature form of SREBP-2. The effect of camphene is most likely regulated through SREBP-1 by affecting MTP levels in response to a decrease in the intracellular cholesterol. We propose that camphene upregulates SREBP-1 expression and MTP inhibition is likely to be a probable mechanism whereby camphene exerts its hypolipidemic effect.

  6. The effectiveness and user perception of 3-dimensional digital human anatomy in an online undergraduate anatomy laboratory

    Science.gov (United States)

    Hilbelink, Amy Joanne

    2007-12-01

    The primary purpose of this study was to determine the effectiveness of implementing desktop 3-dimensional (3D) stereo images of human anatomy into an undergraduate human anatomy distance laboratory. User perceptions of 2D and 3D images were gathered via questionnaire in order to determine ease of use and level of satisfaction associated with the 3D software in the online learning environment. Mayer's (2001, p. 184) principles of design were used to develop the study materials that consisted of PowerPoint presentations and AVI files accessed via Blackboard. The research design employed a mixed-methods approach. Volunteers each were administered a demographic survey and were then stratified into groups based upon pre-test scores. A total sample size of 62 pairs was available for combined data analysis. Quantitative research questions regarding the effectiveness of 2D versus the 3D treatment were analyzed using a doubly-multivariate repeated measures (Doubly-MANOVA) design. Paired test scores achieved by undergraduates on a laboratory practical of identification and spatial relationships of the bones and features of a human skull were used in the analysis. The questionnaire designed to gather user perceptions consisted of quantitative and qualitative questions. Response frequencies were analyzed for the two groups and common themes were noted. Results revealed a statistically significant difference in group means for the main effect of the treatment groups 2D and 3D and for the variables of identification and relationship with the 3D group outperforming the 2D group on both dependent variables. Effect sizes were determined to be small, 0.215 for the identification variable and 0.359 for the relationship variable. Overall, all students liked the convenience of using PowerPoint and AVI files online. The 3D group felt their PowerPoint was more realistic than did the 2D group and both groups appreciated the detailed labeling of the online images. One third of the

  7. Use of 3-Dimensional Volumetric Modeling of Adrenal Gland Size in Patients with Primary Pigmented Nodular Adrenocortical Disease.

    Science.gov (United States)

    Chrysostomou, P P; Lodish, M B; Turkbey, E B; Papadakis, G Z; Stratakis, C A

    2016-04-01

    Primary pigmented nodular adrenocortical disease (PPNAD) is a rare type of bilateral adrenal hyperplasia leading to hypercortisolemia. Adrenal nodularity is often appreciable with computed tomography (CT); however, accurate radiologic characterization of adrenal size in PPNAD has not been studied well. We used 3-dimensional (3D) volumetric analysis to characterize and compare adrenal size in PPNAD patients, with and without Cushing's syndrome (CS). Patients diagnosed with PPNAD and their family members with known mutations in PRKAR1A were screened. CT scans were used to create 3D models of each adrenal. Criteria for biochemical diagnosis of CS included loss of diurnal variation and/or elevated midnight cortisol levels, and paradoxical increase in urinary free cortisol and/or urinary 17-hydroxysteroids after dexamethasone administration. Forty-five patients with PPNAD (24 females, 27.8±17.6 years) and 8 controls (19±3 years) were evaluated. 3D volumetric modeling of adrenal glands was performed in all. Thirty-eight patients out of 45 (84.4%) had CS. Their mean adrenal volume was 8.1 cc±4.1, 7.2 cc±4.5 (p=0.643) for non-CS, and 8.0cc±1.6 for controls. Mean values were corrected for body surface area; 4.7 cc/kg/m(2)±2.2 for CS, and 3.9 cc/kg/m(2)±1.3 for non-CS (p=0.189). Adrenal volume and midnight cortisol in both groups was positively correlated, r=0.35, p=0.03. We conclude that adrenal volume measured by 3D CT in patients with PPNAD and CS was similar to those without CS, confirming empirical CT imaging-based observations. However, the association between adrenal volume and midnight cortisol levels may be used as a marker of who among patients with PPNAD may develop CS, something that routine CT cannot do. PMID:27065461

  8. Hydrogel Based 3-Dimensional (3D System for Toxicity and High-Throughput (HTP Analysis for Cultured Murine Ovarian Follicles.

    Directory of Open Access Journals (Sweden)

    Hong Zhou

    Full Text Available Various toxicants, drugs and their metabolites carry potential ovarian toxicity. Ovarian follicles, the functional unit of the ovary, are susceptible to this type of damage at all stages of their development. However, despite of the large scale of potential negative impacts, assays that study ovarian toxicity are limited. Exposure of cultured ovarian follicles to toxicants of interest served as an important tool for evaluation of toxic effects for decades. Mouse follicles cultured on the bottom of a culture dish continue to serve an important approach for mechanistic studies. In this paper, we demonstrated the usefulness of a hydrogel based 3-dimensional (3D mouse ovarian follicle culture as a tool to study ovarian toxicity in a different setup. The 3D in vitro culture, based on fibrin alginate interpenetrating network (FA-IPN, preserves the architecture of the ovarian follicle and physiological structure-function relationship. We applied the novel 3D high-throughput (HTP in vitro ovarian follicle culture system to study the ovotoxic effects of an anti-cancer drug, Doxorobucin (DXR. The fibrin component in the system is degraded by plasmin and appears as a clear circle around the encapsulated follicle. The degradation area of the follicle is strongly correlated with follicle survival and growth. To analyze fibrin degradation in a high throughput manner, we created a custom MATLAB® code that converts brightfield micrographs of follicles encapsulated in FA-IPN to binary images, followed by image analysis. We did not observe any significant difference between manually processed images to the automated MATLAB® method, thereby confirming that the automated program is suitable to measure fibrin degradation to evaluate follicle health. The cultured follicles were treated with DXR at concentrations ranging from 0.005 nM to 200 nM, corresponding to the therapeutic plasma levels of DXR in patients. Follicles treated with DXR demonstrated decreased

  9. A 3-Dimensional Model of Water-Bearing Sequences in the Dominguez Gap Region, Long Beach, California

    Science.gov (United States)

    Ponti, Daniel J.; Ehman, Kenneth D.; Edwards, Brian D.; Tinsley, John C.; Hildenbrand, Thomas; Hillhouse, John W.; Hanson, Randall T.; McDougall, Kristen; Powell, Charles L.; Wan, Elmira; Land, Michael; Mahan, Shannon; Sarna-Wojcicki, Andrei M.

    2007-01-01

    A 3-dimensional computer model of the Quaternary sequence stratigraphy in the Dominguez gap region of Long Beach, California has been developed to provide a robust chronostratigraphic framework for hydrologic and tectonic studies. The model consists of 13 layers within a 16.5 by 16.1 km (10.25 by 10 mile) square area and extends downward to an altitude of -900 meters (-2952.76 feet). Ten sequences of late Pliocene to Holocene age are identified and correlated within the model. Primary data to build the model comes from five reference core holes, extensive high-resolution seismic data obtained in San Pedro Bay, and logs from several hundred water and oil wells drilled in the region. The model is best constrained in the vicinity of the Dominguez gap seawater intrusion barrier where a dense network of subsurface data exist. The resultant stratigraphic framework and geologic structure differs significantly from what has been proposed in earlier studies. An important new discovery from this approach is the recognition of ongoing tectonic deformation throughout nearly all of Quaternary time that has impacted the geometry and character of the sequences. Anticlinal folding along a NW-SE trend, probably associated with Quaternary reactivation of the Wilmington anticline, has uplifted and thinned deposits along the fold crest, which intersects the Dominguez gap seawater barrier near Pacific Coast Highway. A W-NW trending fault system that approximately parallels the fold crest has also been identified. This fault progressively displaces all but the youngest sequences down to the north and serves as the southern termination of the classic Silverado aquifer. Uplift and erosion of fining-upward paralic sequences along the crest of the young fold has removed or thinned many of the fine-grained beds that serve to protect the underlying Silverado aquifer from seawater contaminated shallow groundwater. As a result of this process, the potential exists for vertical migration of

  10. Human soluble delta-like 1 homolog exerts antitumor effects in vitro and in vivo.

    Science.gov (United States)

    Lee, Donghee; Yoon, Sun Ha; Lee, Hyun Ju; Jo, Ki Won; Park, Bum-Chan; Kim, In Seop; Choi, Yunseon; Lim, Jung Chae; Park, Young Woo

    2016-06-24

    Proteolysis of delta-like 1 homolog (DLK1), a cell-surface transmembrane protein, produces an active soluble form of DLK1 (sDLK1). Both membrane-bound DLK1 and sDLK1 modulate multiple developmental processes including adipogenesis, osteogenesis, chondrogenesis and myogenesis. However, cancer-related functions of DLK1 have not yet been established. We thus evaluated the roles of extracellular sDLK1, comprising six EGF-like domains and juxtamembrane regions, in human pancreatic cancer MIA PaCa-2 cells in vitro and in vivo. We observed that sDLK1 exerted antitumor effects not only in cancer cell migration and anchorage-independent cell growth but also in in vivo tumor growth. PMID:27191393

  11. The Effect of Exertion and Sex on Vertical Ground Reaction Force Variables and Landing Mechanics.

    Science.gov (United States)

    Bell, David R; Pennuto, Anthony P; Trigsted, Stephanie M

    2016-06-01

    Bell, DR, Pennuto, AP, and Trigsted, SM. The effect of exertion and sex on vertical ground reaction force variables and landing mechanics. J Strength Cond Res 30(6): 1661-1669, 2016-The purpose of this investigation was to determine how exertion and sex affected a variety of vertical ground reaction force (VGRF) parameters during a jump-landing task, including peak VGRF, peak VGRF asymmetry, loading rate, and loading rate asymmetry. Additionally, we wanted to determine whether landing mechanics changed after exertion as measured by the Landing Error Scoring System (LESS). Forty recreationally active participants (20 men and 20 women) completed jump landings from a 30-cm-high box onto force plates before and after repeated bouts of an exercise circuit until a specific rating of perceived exertion was achieved. Three-way (sex × time × limb) analyses of variance were used to analyze variables pre-exertion to postexertion. No significant 3-way interactions were observed for peak VGRF (p = 0.31) or loading rate (p = 0.14). Time by sex interactions were observed for peak VGRF (p = 0.02) and loading rate (p = 0.008). Post hoc analysis revealed that men increased landing force and loading rate after exertion while women did not. Landing mechanics, as assessed by total LESS score, were worse after exertion (p errors for knee flexion landing. Women may be more resistant to exertion compared with men and use different joint controls' strategies to cope with VGRF after exertion. However, VGRF asymmetry is not affected by sex and exertion. Limiting peak VGRF and addressing landing postures, especially after exertion, should be components of injury prevention strategies. PMID:26562710

  12. “Non-Toxic” Proteins of the Botulinum Toxin Complex Exert In-vivo Toxicity

    Science.gov (United States)

    Miyashita, Shin-Ichiro; Sagane, Yoshimasa; Suzuki, Tomonori; Matsumoto, Takashi; Niwa, Koichi; Watanabe, Toshihiro

    2016-01-01

    The botulinum neurotoxin (BoNT) causes muscle paralysis and is the most potent toxin in nature. BoNT is associated with a complex of auxiliary “Non-Toxic” proteins, which constitute a large-sized toxin complex (L-TC). However, here we report that the “Non-Toxic” complex of serotype D botulinum L-TC, when administered to rats, exerts in-vivo toxicity on small-intestinal villi. Moreover, Serotype C and D of the “Non-Toxic” complex, but not BoNT, induced vacuole-formation in a rat intestinal epithelial cell line (IEC-6), resulting in cell death. Our results suggest that the vacuole was formed in a manner distinct from the mechanism by which Helicobacter pylori vacuolating toxin (VacA) and Vibrio cholerae haemolysin induce vacuolation. We therefore hypothesise that the serotype C and D botulinum toxin complex is a functional hybrid of the neurotoxin and vacuolating toxin (VT) which arose from horizontal gene transfer from an ancestral BoNT-producing bacterium to a hypothetical VT-producing bacterium. PMID:27507612

  13. "Non-Toxic" Proteins of the Botulinum Toxin Complex Exert In-vivo Toxicity.

    Science.gov (United States)

    Miyashita, Shin-Ichiro; Sagane, Yoshimasa; Suzuki, Tomonori; Matsumoto, Takashi; Niwa, Koichi; Watanabe, Toshihiro

    2016-01-01

    The botulinum neurotoxin (BoNT) causes muscle paralysis and is the most potent toxin in nature. BoNT is associated with a complex of auxiliary "Non-Toxic" proteins, which constitute a large-sized toxin complex (L-TC). However, here we report that the "Non-Toxic" complex of serotype D botulinum L-TC, when administered to rats, exerts in-vivo toxicity on small-intestinal villi. Moreover, Serotype C and D of the "Non-Toxic" complex, but not BoNT, induced vacuole-formation in a rat intestinal epithelial cell line (IEC-6), resulting in cell death. Our results suggest that the vacuole was formed in a manner distinct from the mechanism by which Helicobacter pylori vacuolating toxin (VacA) and Vibrio cholerae haemolysin induce vacuolation. We therefore hypothesise that the serotype C and D botulinum toxin complex is a functional hybrid of the neurotoxin and vacuolating toxin (VT) which arose from horizontal gene transfer from an ancestral BoNT-producing bacterium to a hypothetical VT-producing bacterium. PMID:27507612

  14. Oral administration of Brazilian propolis exerts estrogenic effect in ovariectomized rats.

    Science.gov (United States)

    Okamoto, Yoshinori; Tobe, Takao; Ueda, Koji; Takada, Tatsuyuki; Kojima, Nakao

    2015-04-01

    Propolis, a natural product derived from plants by honeybees, is a mixture of several hundred chemicals, including flavonoids, coumaric acids, and caffeic acids, some of which show estrogen-like activity. In this study, the estrogenic activity of crude ethanolic extract of Brazilian propolis was determined using several in vitro and in vivo assays. Propolis was found to bind to human estrogen receptors (ERs). Furthermore, propolis induced the expression of estrogen-responsive genes in ER-positive MCF-7 and Ishikawa cells. These in vitro assays suggest that propolis exerts estrogenic activity; therefore, in vivo experiments were conducted using ovariectomized rats. Oral administration of propolis (55 or 550 mg/kg/day for 3 days) significantly increased uterine wet weight and luminal epithelium thickness in comparison with the corresponding values in the corn oil-treated control group. Moreover, propolis induced ductal cell proliferation in the mammary glands. These effects were completely inhibited by full ER antagonist ICI 182,780, confirming that the effects of propolis are mediated by the ER. Our data show that oral intake of propolis induces estrogenic activity in ER-expressing organs in vivo and suggest that Brazilian propolis is a useful dietary source of phytoestrogens and a promising treatment for postmenopausal symptoms. PMID:25786527

  15. Proof of confinement of static quarks in 3-dimensional U(1) lattice gauge theory for all values of the coupling constant

    International Nuclear Information System (INIS)

    We study the 3-dimensional pure U(1) lattice gauge theory with Villain action which is related to the 3-dimensional Z-ferro-magnet by an exact duality transformation (and also to a Coulomb system). We show that its string tension α is nonzero for all values of the coupling constant g2, and obeys and bound α >= const x msub(D)β-1 for small ag2, with β = 4π2/g2 and m2sub(D) = (2β/a3)esup(-βupsiloncb(0)/2) (a = lattice spacing). A continuum limit a → 0, msub(D) fixed, exists and represents a scalar free field theory of mass msub(D). The string tension αmsub(D)-2 in physical units tends to infinite in this limit. Characteristic differences in the behavior of the model for large and small coupling constant ag2 are found. Renormalization group aspects are discussed. (orig.)

  16. Phenolcarboxylic acids from medicinal herbs exert anticancer effects through disruption of COX-2 activity.

    Science.gov (United States)

    Tao, Li; Wang, Sheng; Zhao, Yang; Sheng, Xiaobo; Wang, Aiyun; Zheng, Shizhong; Lu, Yin

    2014-09-25

    Integrated research of herbs and formulas characterized by functions of promoting blood circulation and removing blood stasis is one of the most active fields in traditional Chinese medicine. This paper strives to demonstrate the roles of a homologous series of phenolcarboxylic acids from these medicinal herbs in cancer treatment via targeting cyclooxygenase-2 (COX-2), a well-recognized mediator in tumorigenesis. We selected thirteen typical phenolcarboxylic acids (benzoic acid derivatives, cinnamic acid derivatives and their dehydration-condensation products), and found gallic acid, caffeic acid, danshensu, rosmarinic acid and salvianolic acid B showed 50% inhibitory effects on hCOX-2 activity and A549 cells proliferation. 2D-quantitative method was introduced to describe the potential structural features that contributed to certain bioactivities. We also found these compounds underwent responsible hydrogen bonding to Arg120 and Ser353 in COX-2 active site residues. We further extensively focused on danshensu [d-(+)-β-(3,4-dihydoxy-phenylalanine)] or DSS, which exerted COX-2 dependent anticancer manner. Both genetic and pharmacological inhibition of COX-2 could enhance the ability of DSS inhibiting A549 cells growth. Additionally, COX-2/PGE2/ERK signaling axis was essential for the anticancer effect of DSS. Furthermore, combined treatment with DSS and celecoxib could produce stronger anticancer effects in experimental lung metastasis of A549 cells in vivo. All these findings indicated that phenolcarboxylic acids might possess anticancer effects through jointly targeting COX-2 activity in cancer cells and provided strong evidence in cancer prevention and therapy for the herbs characterized by blood-activating and stasis-resolving functions in clinic. PMID:24916702

  17. Self-Regulating Cycling Using the Children's OMNI Scale of Perceived Exertion.

    Science.gov (United States)

    Robertson, Robert J.; Goss, Fredric L.; Bell, Jill A.; Dixon, Curt B.; Gallagher, Kara I.; Lagally, Kristen M.; Timmer, Jeffrey M.; Abt, Kristie L.; Gallagher, Jere D.; Thompkins, Taylor

    2002-01-01

    Investigated whether normal children could self-regulate intermittent cycle ergometer exercise using a prescribed target rating of perceived exertion (RPE), discriminate between target RPEs, and produce intermittent target RPEs in ascending and descending sequences. RPE was estimated using the Children's OMNI Scale of Perceived Exertion. Overall,…

  18. A New Approach of In Vivo Musculoskeletal Tissue Engineering Using the Epigastric Artery as Central Core Vessel of a 3-Dimensional Construct

    OpenAIRE

    Dunda, Sebastian E.; Schriever, T.; Rosen, C; C. Opländer; Tolba, R.H.; Diamantouros, S.; Jockenhoevel, S.; Pallua, N

    2012-01-01

    The creation of musculoskeletal tissue represents an alternative for the replacement of soft tissue in reconstructive surgery. However, most of the approaches of creating artificial tissue have their limitations in the size as the maximally obtainable dimension of bioartificial tissue (BAT) is limited due to the lack of supporting vessels within the 3-dimensional construct. The seeded myoblasts require high amounts of perfusion, oxygen, and nutrients to survive. To achieve this, we developed ...

  19. Comparative Effectiveness of 3-Dimensional vs 2-Dimensional and High-Definition vs Standard-Definition Neuroendoscopy: A Preclinical Randomized Crossover Study

    OpenAIRE

    Marcus, Hani J; Hughes-Hallett, Archie; Cundy, Thomas P.; Di Marco, Aimee; Pratt, Philip; Nandi, Dipankar; Darzi, Ara; Yang, Guang-Zhong

    2013-01-01

    BACKGROUND: Although the potential benefits of 3-dimensional (3-D) vs 2-dimensional (2-D) and high-definition (HD) vs standard-definition (SD) endoscopic visualization have long been recognized in other surgical fields, such endoscopes are generally considered too large and bulky for use within the brain. The recent development of 3-D and HD neuroendoscopes may therefore herald improved depth perception, better appreciation of anatomic details, and improved overall surgical performance. OBJEC...

  20. Implementation of new echocardiographic modalities in routine practice in a general hospital – Pocket-size cardiac ultrasound and 3 dimensional echocardiography. Studies on feasibility and diagnostic accuracy

    OpenAIRE

    2015-01-01

    This thesis is based upon the implementation of pocket-size cardiac ultrasound (PCU) among medical students and residents in internal medicine and 3 dimensional echocardiography (3DE) in routine care at a general hospital. The introduction of widely available and handy ultrasound devices has represented a challenge to the medical community as implementation in clinical practice can be made by non-specialists. In view of favorable results from the non-expert use of the larger laptop-sized d...

  1. Reconstruction 3-dimensional image from 2-dimensional image of status optical coherence tomography (OCT) for analysis of changes in retinal thickness

    Energy Technology Data Exchange (ETDEWEB)

    Arinilhaq,; Widita, Rena [Department of Physics, Nuclear Physics and Biophysics Research Group, Institut Teknologi Bandung (Indonesia)

    2014-09-30

    Optical Coherence Tomography is often used in medical image acquisition to diagnose that change due easy to use and low price. Unfortunately, this type of examination produces a two-dimensional retinal image of the point of acquisition. Therefore, this study developed a method that combines and reconstruct 2-dimensional retinal images into three-dimensional images to display volumetric macular accurately. The system is built with three main stages: data acquisition, data extraction and 3-dimensional reconstruction. At data acquisition step, Optical Coherence Tomography produced six *.jpg images of each patient were further extracted with MATLAB 2010a software into six one-dimensional arrays. The six arrays are combined into a 3-dimensional matrix using a kriging interpolation method with SURFER9 resulting 3-dimensional graphics of macula. Finally, system provides three-dimensional color graphs based on the data distribution normal macula. The reconstruction system which has been designed produces three-dimensional images with size of 481 × 481 × h (retinal thickness) pixels.

  2. Stress changes of lateral collateral ligament at different knee flexion with or without displaced movements: a 3-dimensional finite element analysis

    Institute of Scientific and Technical Information of China (English)

    ZHONG Yan-lin; WANG You; WANG Hai-peng; RONG Ke; XIE Le

    2011-01-01

    Objective: To create a 3-dimensional finite element model of knee ligaments and to analyse the stress changes of lateral collateral ligament (LCL) with or without displaced movements at different knee flexion conditions.Methods: A four-major-ligament contained knee specimen from an adult died of skull injury was prepared for CT scanning with the detectable ligament insertion footprints,locations and orientations precisely marked in advance. The CT scanning images were converted to a 3-dimensional model of the knee with the 3-dimensional reconstruction technique and transformed into finite element model by the software of ANSYS. The model was validated using experimental and numerical results obtained by other scientists.The natural stress changes of LCL at five different knee flexion angles (0°, 30°, 60°, 90°, 120°) and under various motions of anterior-posterior tibial translation, tibial varus rotation and internal-external tibial rotation were measured.Results: The maximum stress reached to 87%-113%versus natural stress in varus motion at early 30° of knee flexions. The stress values were smaller than the peak value of natural stress at 0° (knee full extension) when knee bending was over 60° of flexion in anterior-posterior tibial translation and internal-external rotation.Conclusion: LCL is vulnerable to varus motion in almost all knee bending positions and susceptible to anterlor-posterior tibial translation or internal-external rotation at early 30° of knee flexions.

  3. Nanoliposomal Nitroglycerin Exerts Potent Anti-Inflammatory Effects

    Science.gov (United States)

    Ardekani, Soroush; Scott, Harry A.; Gupta, Sharad; Eum, Shane; Yang, Xiao; Brunelle, Alexander R.; Wilson, Sean M.; Mohideen, Umar; Ghosh, Kaustabh

    2015-11-01

    Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory properties of NO remains unknown. Here, we examined whether NTG can suppress endothelial cell (EC) activation during inflammation and developed NTG nanoformulation to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with high-dose NTG administration. Our findings reveal that NTG significantly inhibits human U937 cell adhesion to NO-deficient human microvascular ECs in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering, as determined by NO analyzer, microfluorimetry, and immunofluorescence staining. Nanoliposomal NTG (NTG-NL) was formulated by encapsulating NTG within unilamellar lipid vesicles (DPhPC, POPC, Cholesterol, DHPE-Texas Red at molar ratio of 6:2:2:0.2) that were ~155 nm in diameter and readily uptaken by ECs, as determined by dynamic light scattering and quantitative fluorescence microscopy, respectively. More importantly, NTG-NL produced a 70-fold increase in NTG therapeutic efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production associated with high NTG doses. Thus, these findings, which are the first to reveal the superior therapeutic effects of an NTG nanoformulation, provide the rationale for their detailed investigation for potentially superior vascular normalization therapies.

  4. 3,6-O-[N-(2-Aminoethyl)-acetamide-yl]-chitosan exerts antibacterial activity by a membrane damage mechanism.

    Science.gov (United States)

    Yan, Feilong; Dang, Qifeng; Liu, Chengsheng; Yan, Jingquan; Wang, Teng; Fan, Bing; Cha, Dongsu; Li, Xiaoli; Liang, Shengnan; Zhang, Zhenzhen

    2016-09-20

    A novel chitosan derivative, 3,6-O-[N-(2-aminoethyl)-acetamide-yl]-chitosan (AACS), was successfully prepared to improve water solubility and antibacterial activity of chitosan. AACS had good antibacterial activity, with minimum inhibitory concentrations of 0.25mg/mL, against Escherichia coli and Staphylococcus aureus. Cell membrane integrity, electric conductivity and NPN uptake tests showed that AACS caused quickly increasing the release of intracellular nucleic acids, the uptake of NPN, and the electric conductivity by damaging membrane integrity. On the other hand, hydrophobicity, cell viability and SDS-PAGE experiments indicated that AACS was able to reduce the surface hydrophobicity, the cell viability and the intracellular proteins through increasing membrane permeability. SEM observation further confirmed that AACS could kill bacteria via disrupting their membranes. All results above verified that AACS mainly exerted antibacterial activity by a membrane damage mechanism, and it was expected to be a new food preservative. PMID:27261735

  5. Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

    KAUST Repository

    Arsenescu, Violeta

    2011-04-11

    Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

  6. Subtilase SprP exerts pleiotropic effects in Pseudomonas aeruginosa.

    Science.gov (United States)

    Pelzer, Alexander; Polen, Tino; Funken, Horst; Rosenau, Frank; Wilhelm, Susanne; Bott, Michael; Jaeger, Karl-Erich

    2014-02-01

    The open reading frame PA1242 in the genome of Pseudomonas aeruginosa PAO1 encodes a putative protease belonging to the peptidase S8 family of subtilases. The respective enzyme termed SprP consists of an N-terminal signal peptide and a so-called S8 domain linked by a domain of unknown function (DUF). Presumably, this DUF domain defines a discrete class of Pseudomonas proteins as homologous domains can be identified almost exclusively in proteins of the genus Pseudomonas. The sprP gene was expressed in Escherichia coli and proteolytic activity was demonstrated. A P. aeruginosa ∆sprP mutant was constructed and its gene expression pattern compared to the wild-type strain by genome microarray analysis revealing altered expression levels of 218 genes. Apparently, SprP is involved in regulation of a variety of different cellular processes in P. aeruginosa including pyoverdine synthesis, denitrification, the formation of cell aggregates, and of biofilms. PMID:24376018

  7. Heritability of Recurrent Exertional Rhabdomyolysis in Standardbred and Thoroughbred Racehorses Derived From SNP Genotyping Data.

    Science.gov (United States)

    Norton, Elaine M; Mickelson, James R; Binns, Matthew M; Blott, Sarah C; Caputo, Paul; Isgren, Cajsa M; McCoy, Annette M; Moore, Alison; Piercy, Richard J; Swinburne, June E; Vaudin, Mark; McCue, Molly E

    2016-11-01

    Recurrent exertional rhabdomyolysis (RER) in Thoroughbred and Standardbred racehorses is characterized by episodes of muscle rigidity and cell damage that often recur upon strenuous exercise. The objective was to evaluate the importance of genetic factors in RER by obtaining an unbiased estimate of heritability in cohorts of unrelated Thoroughbred and Standardbred racehorses. Four hundred ninety-one Thoroughbred and 196 Standardbred racehorses were genotyped with the 54K or 74K SNP genotyping arrays. Heritability was calculated from genome-wide SNP data with a mixed linear and Bayesian model, utilizing the standard genetic relationship matrix (GRM). Both the mixed linear and Bayesian models estimated heritability of RER in Thoroughbreds to be approximately 0.34 and in Standardbred racehorses to be approximately 0.45 after adjusting for disease prevalence and sex. To account for potential differences in the genetic architecture of the underlying causal variants, heritability estimates were adjusted based on linkage disequilibrium weighted kinship matrix, minor allele frequency and variant effect size, yielding heritability estimates that ranged between 0.41-0.46 (Thoroughbreds) and 0.39-0.49 (Standardbreds). In conclusion, between 34-46% and 39-49% of the variance in RER susceptibility in Thoroughbred and Standardbred racehorses, respectively, can be explained by the SNPs present on these 2 genotyping arrays, indicating that RER is moderately heritable. These data provide further rationale for the investigation of genetic mutations associated with RER susceptibility. PMID:27489252

  8. Fenugreek powder exerts protective effects on alcoholised rats' kidney, highlighted using ultrastructural studies.

    Science.gov (United States)

    Pribac, George Ciprian; Sferdian, Mircea Florin; Neamţu, Carmen; Crăciun, Constantin; Roşioru, Corina Luminiţa; Ardelean, Aurel; Totolici, Bogdan Dan

    2015-01-01

    Trigonella foenum-graecum (TFG) seeds exert a protective antioxidant effect and membrane protector through their rich content in polyphenolic flavonoids. The previous research focused on the hypoglycemic action of the seeds, with scarce studies on the preventive effects in the pathology of the kidney. Our work was conducted on an experimental in vivo model; the animals were given two different concentrations of TFG seeds, consequently to alcohol intoxication. Transmission electron microscopy (TEM) analysis showed vacuolation in cytoplasm, edemas at the apical pole of the nephrocytes, diffusion of the cytoplasmic and mitochondrial matrix and the increase in number of the lysozymes and especially peroxisomes, as well as the congestion of blood capillaries. In the case of the groups T5R and T10R, which received Trigonella powder together with ethanol, the structural and ultrastructural changes produced by the ethylic intoxication were more reduced, being somewhat improved in the T5R group. Therefore, the majority of the cells nuclei have retained their spherical shape, being at the same time predominantly euchromatic, with little heterochromatin and evenly dispersed. Our results suggest the use of Trigonella seeds as a food supplement to prevent cellular deterioration and improve renal morphology and function. PMID:26193212

  9. Heparin exerts anti-apoptotic effects on uterine explants by targeting the endocannabinoid system.

    Science.gov (United States)

    Salazar, Ana Inés; Vercelli, Claudia; Schiariti, Victoria; Davio, Carlos; Correa, Fernando; Franchi, Ana María

    2016-09-01

    Miscarriage caused by Gram-negative bacteria infecting the female genital tract is one of the most common complications of human pregnancy. Intraperitoneal administration of LPS to 7-days pregnant mice induces embryo resorption after 24 h. Here, we show that LPS induced apoptosis on uterine explants from 7-days pregnant mice and that CB1 receptor was involved in this effect. On the other hand, heparin has been widely used for the prevention of pregnancy loss in women with frequent miscarriage with or without thrombophilia. Besides its anticoagulant properties, heparin exerts anti-inflammatory, immunomodulatory and anti-apoptotic effects. Here, we sought to investigate whether the administration of heparin prevented LPS-induced apoptosis in uterine explants from 7-days pregnant mice. We found that heparin enhanced cell survival in LPS-treated uterine explants and that this effect was mediated by increasing uterine FAAH activity. Taken together, our results point towards a novel mechanism involved in the protective effects of heparin. PMID:27364950

  10. Synchrony and exertion during dance independently raise pain threshold and encourage social bonding.

    Science.gov (United States)

    Tarr, Bronwyn; Launay, Jacques; Cohen, Emma; Dunbar, Robin

    2015-10-01

    Group dancing is a ubiquitous human activity that involves exertive synchronized movement to music. It is hypothesized to play a role in social bonding, potentially via the release of endorphins, which are analgesic and reward-inducing, and have been implicated in primate social bonding. We used a 2 × 2 experimental design to examine effects of exertion and synchrony on bonding. Both demonstrated significant independent positive effects on pain threshold (a proxy for endorphin activation) and in-group bonding. This suggests that dance which involves both exertive and synchronized movement may be an effective group bonding activity. PMID:26510676

  11. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya, E-mail: jyli@mail.shcnc.ac.cn; Nan, Fa-Jun, E-mail: fjnan@mail.shcnc.ac.cn; Li, Jia, E-mail: jli@mail.shcnc.ac.cn

    2013-12-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome.

  12. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    International Nuclear Information System (INIS)

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome

  13. High Lithium Transference Number Electrolytes via Creation of 3-Dimensional, Charged, Nanoporous Networks from Dense Functionalized Nanoparticle Composites

    KAUST Repository

    Schaefer, Jennifer L.

    2013-03-26

    High lithium transference number, tLi+, electrolytes are desired for use in both lithium-ion and lithium metal rechargeable battery technologies. Historically, low tLi+ electrolytes have hindered device performance by allowing ion concentration gradients within the cell, leading to high internal resistances that ultimately limit cell lifetime, charging rates, and energy density. Herein, we report on the synthesis and electrochemical features of electrolytes based on nanoparticle salts designed to provide high tLi+. The salts are created by cofunctionalization of metal oxide nanoparticles with neutral organic ligands and tethered lithium salts. When dispersed in a conducting fluid such as tetraglyme, they spontaneously form a charged, nanoporous network of particles at moderate nanoparticle loadings. Modification of the tethered anion chemistry from -SO3 - to -SO3BF3 - is shown to enhance ionic conductivity of the electrolytes by facilitating ion pair dissociation. At a particle volume fraction of 0.15, the electrolyte exists as a self-supported, nanoporous gel with an optimum ionic conductivity of 10 -4 S/cm at room temperature. Galvanostatic polarization measurements on symmetric lithium metal cells containing the electrolyte show that the cell short circuit time, tSC, is inversely proportional to the square of the applied current density tSC ∼ J-2, consistent with previously predicted results for traditional polymer-in-salt electrolytes with low tLi+. Our findings suggest that electrolytes with tLi+ ≈ 1 and good ion-pair dissociation delay lithium dendrite nucleation and may lead to improved lithium plating in rechargeable batteries with metallic lithium anodes. © 2013 American Chemical Society.

  14. A 3-DIMENSIONAL MATRIX ASSAY THAT MAY HELP PREDICT TREATMENT RESPONSE TO TEMOZOLOMIDE IN PATIENTS WITH GLIOBASTOMA: SUBGROUP ANALYSIS OF PATIENTS UNDERGOING MGMT TESTING

    Science.gov (United States)

    Megyesi, Joseph F.; Costello, Penny; McDonald, Warren; Macdonald, David; Easaw, Jay

    2014-01-01

    BACKGROUND: (blind field). METHODS: Records for patients treated for newly diagnosed or recurrent glioblastoma were analyzed. All patients had undergone surgical resection and tumor specimens at time of surgery were available for culture in a 3-dimensional matrix assay and observed for growth and invasion. Drug effects on mean invasion and growth were expressed as a ratio relative to control conditions. Length of survival was compared between temozolomide treated patients whose screening results had predicted a positive or negative response to temozolomide. The MGMT status of a subgroup of these patients was analyzed and correlated with the response of tumor tissue in the assay to temozolomide. RESULTS: Fifty-eight patients with glioblastoma were assessed. Each patient's tumor displayed a unique invasion and response profile. We looked in particular at the correlation between the outcome of a patient with glioblastoma treated with temozolomide and the response of that patient's tumor tissue to temozolomide in the 3-dimensional assay. Mean survival time for patients whose tumors were not significantly sensitive to temozolomide in the assay was 181.7 +/- 43 days. Mean survival time for patients whose tumors were significantly sensitive to temozolomide in the assay was 290.0 +/- 33 days. Twelve patients underwent MGMT testing. In 10 of the 12 patients there was a correlation between tumor response in the assay and MGMT status. CONCLUSIONS: The 3-dimensional assay may help predict glioblastoma patients who will show a treatment response to temozolomide. There appears to be a positive correlation between the response profiles in the assay to the MGMT status of the patient's tumor. SECONDARY CATEGORY: n/a.

  15. Physical exercise at the workplace reduces perceived physical exertion during healthcare work

    DEFF Research Database (Denmark)

    Jakobsen, Markus Due; Sundstrup, Emil; Brandt, Mikkel;

    2015-01-01

    BACKGROUND: High physical exertion during work is a risk factor for musculoskeletal pain and long-term sickness absence. Physical exertion (RPE) reflects the balance between physical work demands and physical capacity of the individual. Thus, increasing the physical capacity through physical...... exercise may decrease physical exertion during work. This study investigates the effect of workplace-based versus home-based physical exercise on physical exertion during work (WRPE) among healthcare workers. METHODS: 200 female healthcare workers (age: 42.0, body mass index: 24.1, average pain intensity......: 3.1 on a scale of 0 to 10, average WRPE: 3.6 on a scale of 0 to 10) from 18 departments at three participating hospitals. Participants were randomly allocated at the cluster level to 10 weeks of: (1) workplace physical exercise (WORK) performed in groups during working hours for 5×10 minutes per...

  16. Stiffness and thickness of fascia do not explain chronic exertional compartment syndrome

    DEFF Research Database (Denmark)

    Dahl, Morten; Hansen, Philip; Stål, Per;

    2011-01-01

    Chronic exertional compartment syndrome is diagnosed based on symptoms and elevated intramuscular pressure and often is treated with fasciotomy. However, what contributes to the increased intramuscular pressure remains unknown....

  17. Integration of 3-dimensional surgical and orthodontic technologies with orthognathic "surgery-first" approach in the management of unilateral condylar hyperplasia.

    Science.gov (United States)

    Janakiraman, Nandakumar; Feinberg, Mark; Vishwanath, Meenakshi; Nalaka Jayaratne, Yasas Shri; Steinbacher, Derek M; Nanda, Ravindra; Uribe, Flavio

    2015-12-01

    Recent innovations in technology and techniques in both surgical and orthodontic fields can be integrated, especially when treating subjects with facial asymmetry. In this article, we present a treatment method consisting of 3-dimensional computer-aided surgical and orthodontic planning, which was implemented with the orthognathic surgery-first approach. Virtual surgical planning, fabrication of surgical splints using the computer-aided design/computer-aided manufacturing technique, and prediction of final orthodontic occlusion using virtual planning with robotically assisted customized archwires were integrated for this patient. Excellent esthetic and occlusal outcomes were obtained in a short period of 5.5 months. PMID:26672712

  18. Accidents leading to over-exertion back injuries among nursing personnel

    OpenAIRE

    Engkvist, Inga-Lill

    1999-01-01

    The overall aim of the present thesis was to contribute to the knowledge of occupational accidents leading to over-exertion back injuries among nursing personnel, which can be used for developing effective preventive strategies. Different combinations of factors and events were assumed to determine the type of accident process leading to an over-exertion injury. The first study used the Swedish Occupational Injury Register (ISA) to investigate the occurrence of reported ...

  19. Synchrony and exertion during dance independently raise pain threshold and encourage social bonding.

    OpenAIRE

    Tarr, B; Launay, JP; Cohen, EEA; Dunbar, RIM

    2015-01-01

    Group dancing is a ubiquitous human activity that involves exertive synchronized movement to music. It is hypothesized to play a role in social bonding, potentially via the release of endorphins, which are analgesic and reward-inducing, and have been implicated in primate social bonding. We used a 2 × 2 experimental design to examine effects of exertion and synchrony on bonding. Both demonstrated significant independent positive effects on pain threshold (a proxy for endorphin activation) and...

  20. Prolonged mental exertion does not alter neuromuscular function of the knee extensors

    OpenAIRE

    Pageaux, Benjamin; Marcora, Samuele; Lepers, Romuald

    2013-01-01

    International audience; Purpose: The aim of this study was to test the hypotheses that prolonged mental exertion i) reduces maximal muscle activation and ii) increases the extent of central fatigue induced by subsequent endurance exercise. Methods: Neuromuscular function of the knee extensor muscles was assessed in 10 male subjects in two different conditions: i) before and after prolonged mental exertion leading to mental fatigue; ii) before and after an easy cognitive task (control). Both c...

  1. Vaticaffinol, a resveratrol tetramer, exerts more preferable immunosuppressive activity than its precursor in vitro and in vivo through multiple aspects against activated T lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Li-Li; Wu, Xue-Feng; Liu, Hai-Liang; Guo, Wen-Jie; Luo, Qiong; Tao, Fei-Fei; Ge, Hui-Ming; Shen, Yan; Tan, Ren-Xiang; Xu, Qiang, E-mail: molpharm@163.com; Sun, Yang, E-mail: yangsun@nju.edu.cn

    2013-03-01

    In the present study, we aimed to investigate the immunosuppressive activity of vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, on T lymphocytes both in vitro and in vivo, and further explored its potential molecular mechanism. Resveratrol had a wide spectrum of healthy beneficial effects with multiple targets. Interestingly, its tetramer, vaticaffinol, exerted more intensive immunosuppressive activity than resveratrol. Vaticaffinol significantly inhibited T cells proliferation activated by concanavalin A (Con A) or anti-CD3 plus anti-CD28 in a dose- and time-dependent manner. It also induced Con A-activated T cells undergoing apoptosis through mitochondrial pathway. Moreover, this compound prevented cells from entering S phase and G2/M phase during T cells activation. In addition, vaticaffinol inhibited ERK and AKT signaling pathways in Con A-activated T cells. Furthermore, vaticaffinol significantly ameliorated ear swelling in a mouse model of picryl chloride-induced ear contact dermatitis in vivo. In most of the aforementioned experiments, however, resveratrol had only slight effects on the inhibition of T lymphocytes compared with vaticaffinol. Taken together, our findings suggest that vaticaffinol exerts more preferable immunosuppressive activity than its precursor resveratrol both in vitro and in vivo by affecting multiple targets against activated T cells. - Graphical abstract: Vaticaffinol, a resveratrol tetramer isolated from Vatica mangachapoi, exerts more intensive immunosuppressive activity than its precursor resveratrol does in vitro and in vivo. Its mechanism may involve multiple effects against activated T cells: regulation of signalings involved in cell proliferation, G0/G1 arrest of T cells, as well as an apoptosis induction in activated effector T cells. Highlights: ► Vaticaffinol, a resveratrol tetramer, exerts more potent activity than its precursor. ► It inhibited T cells proliferation and prevented them from entering

  2. 4-dimethylamino-3',4'-dimethoxychalcone downregulates iNOS expression and exerts anti-inflammatory effects.

    Science.gov (United States)

    Herencia, F; Ferrándiz, M L; Ubeda, A; Guillén, I; Dominguez, J N; Charris, J E; Lobo, G M; Alcaraz, M J

    2001-01-01

    Reactive oxygen and nitrogen species contribute to the pathophysiology of inflammatory conditions. We have studied the effects of a novel superoxide scavenger, 4-dimethylamino-3', 4'-dimethoxychalcone (CH11) in macrophages and in vivo. CH11 has been shown to inhibit the chemiluminescence induced by zymosan in mouse peritoneal macrophages and the cytotoxic effects of superoxide. In the same cells, the modulation by superoxide of nitric oxide (NO) production in response to zymosan was investigated. CH11 was more effective than the membrane-permeable scavenger Tiron for inhibition of inducible nitric oxide synthase (iNOS) protein expression and nitrite production. We have shown that CH11 inhibited chemiluminescence in vivo, as well as cell migration, and eicosanoid and tumor necrosis factor-alpha (TNF-alpha) levels in the mouse air pouch injected with zymosan. This chalcone derivative also exerted anti-inflammatory effects in the carrageenan paw oedema.

  3. α-MSH exerts direct postsynaptic excitatory effects on NTS neurons and enhances GABAergic signaling in the NTS.

    Science.gov (United States)

    Mimee, A; Kuksis, M; Ferguson, A V

    2014-03-14

    The central melanocortin system plays an essential role in the regulation of energy balance. While anorexigenic effects of α-melanocyte-stimulating hormone (α-MSH) acting in the nucleus of the solitary tract (NTS), a critical medullary autonomic control center, have been established, the cellular events underlying these effects are less well characterized. In this study, we used whole-cell patch-clamp electrophysiology to examine firstly whether α-MSH exerts direct postsynaptic effects on the membrane potential of rat NTS neurons in slice preparation, and secondly whether α-MSH influences GABAergic signaling in the NTS. In normal artificial cerebrospinal fluid, perfusion of α-MSH (500 nM) resulted in a depolarization in 39% of cells (n=16, mean 6.14±0.54 mV), and a hyperpolarization in 22% of cells (n=9, -6.79±1.02 mV). Studies using tetrodotoxin to block neuronal communication revealed α-MSH exerts direct depolarizing effects on some NTS neurons, and indirect inhibitory effects on others. A third subset of neurons is simultaneously directly depolarized and indirectly hyperpolarized by α-MSH, resulting in a net lack of effect on membrane potential. The inhibitory inputs influenced by α-MSH were identified as GABAergic, as α-MSH increased the frequency, but not amplitude, of inhibitory postsynaptic currents (IPSCs) in 50% of NTS neurons. α-MSH had no effect on the frequency or amplitude of miniature IPSCs. Furthermore, pharmacological blockade of GABAA and GABAB receptors, and physical removal of all synaptic inputs via cellular dissociation, abolished hyperpolarizations induced by α-MSH. We conclude α-MSH exerts direct, postsynaptic excitatory effects on a subset of NTS neurons. By exciting GABAergic NTS neurons and presynaptically enhancing GABAergic signaling, α-MSH also indirectly inhibits other NTS cells. These findings provide critical insight into the cellular events underlying medullary melanocortin anorexigenic effects, and expand the

  4. Methodology for Using 3-Dimensional Sonography to Measure Fetal Adrenal Gland Volumes in Pregnant Women With and Without Early Life Stress.

    Science.gov (United States)

    Kim, Deborah; Epperson, C Neill; Ewing, Grace; Appleby, Dina; Sammel, Mary D; Wang, Eileen

    2016-09-01

    Fetal adrenal gland volumes on 3-dimensional sonography have been studied as potential predictors of preterm birth. However, no consistent methodology has been published. This article describes the methodology used in a study that is evaluating the effects of maternal early life stress on fetal adrenal growth to allow other researchers to compare methodologies across studies. Fetal volumetric data were obtained in 36 women at 20 to 22 and 28 to 30 weeks' gestation. Two independent examiners measured multiple images of a single fetal adrenal gland from each sonogram. Intra- and inter-rater consistency was examined. In addition, fetal adrenal volumes between male and female fetuses were reported. The intra- and inter-rater reliability was satisfactory when the mean of 3 measurements from each rater was used. At 20 weeks' gestation, male fetuses had larger average adjusted adrenal volumes than female fetuses (mean, 0.897 versus 0.638; P = .004). At 28 weeks' gestation, the fetal weight was more influential in determining values for adjusted fetal adrenal volume (0.672 for male fetuses versus 0.526 for female fetuses; P = .034). This article presents a methodology for assessing fetal adrenal volume using 3-dimensional sonography that can be used by other researchers to provide more consistency across studies.

  5. Development of an Autonomous, Dual Chamber Bioreactor for the Growth of 3-Dimensional Epithelial-Stromal Tissues in Microgravity

    Science.gov (United States)

    Patel, Zarana S.; Wettergreen, Matthew A.; Huff, Janice L.

    2014-01-01

    We are developing a novel, autonomous bioreactor that can provide for the growth and maintenance in microgravity of 3-D organotypic epithelial-stromal cultures that require an air-liquid interface. These complex 3-D tissue models accurately represent the morphological features, differentiation markers, and growth characteristics observed in normal human epithelial tissues, including the skin, esophagus, lung, breast, pancreas, and colon. However, because of their precise and complex culture requirements, including that of an air-liquid interface, these 3-D models have yet to be utilized for life sciences research aboard the International Space Station. The development of a bioreactor for these cultures will provide the capability to perform biological research on the ISS using these realistic, tissue-like human epithelial-stromal cell models and will contribute significantly to advances in fundamental space biology research on questions regarding microgravity effects on normal tissue development, aging, cancer, and other disease processes. It will also allow for the study of how combined stressors, such as microgravity with radiation and nutritional deficiencies, affect multiple biological processes and will provide a platform for conducting countermeasure investigations on the ISS without the use of animal models. The technology will be autonomous and consist of a cell culture chamber that provides for air-liquid, liquid-liquid, and liquid-air exchanges within the chambers while maintaining the growth and development of the biological samples. The bioreactor will support multiple tissue types and its modular design will provide for incorporation of add-on capabilities such as microfluidics drug delivery, media sampling, and in situ biomarker analysis. Preliminary flight testing of the hardware will be conducted on a parabolic platform through NASA's Flight Opportunities Program.

  6. 3-Bromopyruvate antagonizes effects of lactate and pyruvate, synergizes with citrate and exerts novel anti-glioma effects.

    Science.gov (United States)

    El Sayed, S M; El-Magd, R M Abou; Shishido, Y; Chung, S P; Diem, T H; Sakai, T; Watanabe, H; Kagami, S; Fukui, K

    2012-02-01

    Oxidative stress-energy depletion therapy using oxidative stress induced by D-amino acid oxidase (DAO) and energy depletion induced by 3-bromopyruvate (3BP) was reported recently (El Sayed et al., Cancer Gene Ther., 19, 1-18, 2012). Even in the presence of oxygen, cancer cells oxidize glucose preferentially to produce lactate (Warburg effect) which seems vital for cancer microenvironment and progression. 3BP is a closely related structure to lactate and pyruvate and may antagonize their effects as a novel mechanism of its action. Pyruvate exerted a potent H(2)O(2) scavenging effect to exogenous H(2)O(2), while lactate had no scavenging effect. 3BP induced H(2)O(2) production. Pyruvate protected against H(2)O(2)-induced C6 glioma cell death, 3BP-induced C6 glioma cell death but not against DAO/D-serine-induced cell death, while lactate had no protecting effect. Lactate and pyruvate protected against 3BP-induced C6 glioma cell death and energy depletion which were overcome with higher doses of 3BP. Lactate and pyruvate enhanced migratory power of C6 glioma which was blocked by 3BP. Pyruvate and lactate did not protect against C6 glioma cell death induced by other glycolytic inhibitors e.g. citrate (inhibitor of phosphofructokinase) and sodium fluoride (inhibitor of enolase). Serial doses of 3BP were synergistic with citrate in decreasing viability of C6 glioma cells and spheroids. Glycolysis subjected to double inhibition using 3BP with citrate depleted ATP, clonogenic power and migratory power of C6 glioma cells. 3BP induced a caspase-dependent cell death in C6 glioma. 3BP was powerful in decreasing viability of human glioblastoma multiforme cells (U373MG) and C6 glioma in a dose- and time-dependent manner. PMID:22318356

  7. Withaferin A: a proteasomal inhibitor promotes healing after injury and exerts anabolic effect on osteoporotic bone.

    Science.gov (United States)

    Khedgikar, V; Kushwaha, P; Gautam, J; Verma, A; Changkija, B; Kumar, A; Sharma, S; Nagar, G K; Singh, D; Trivedi, P K; Sangwan, N S; Mishra, P R; Trivedi, R

    2013-01-01

    Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic β subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation. WFA increased expression of osteoblast-specific transcription factor and mineralizing genes, promoted osteoblast survival and suppressed inflammatory cytokines. In osteoclast, WFA treatment decreased osteoclast number directly by decreasing expression of tartarate-resistant acid phosphatase and receptor activator of nuclear factor kappa-B (RANK) and indirectly by decreasing osteoprotegrin/RANK ligand ratio. Our data show that in vitro treatment of WFA to calvarial osteoblast cells decreased expression of E3 ubiquitin ligase, Smad ubiquitin regulatory factor 2 (Smurf2), preventing degradation of Runt-related transcription factor 2 (RunX2) and relevant Smad proteins, which are phosphorylated by bone morphogenetic protein 2. Increased Smurf2 expression due to exogenous treatment of tumor necrosis factor α (TNFα) to primary osteoblast cells was decreased by WFA treatment. This was corroborated by using small interfering RNA against Smurf2. Further, WFA also blocked nuclear factor kappa-B (NF-kB) signaling as assessed by tumor necrosis factor stimulated nuclear translocation of p65-subunit of NF-kB. Overall data show that in vitro proteasome inhibition by WFA simultaneously promoted osteoblastogenesis by stabilizing RunX2 and suppressed osteoclast differentiation, by inhibiting osteoclastogenesis. Oral administration of WFA to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased expression of osteogenic genes. WFA

  8. Methotrexate and 5-aminoimidazole-4-carboxamide riboside exert synergistic anticancer action against human breast cancer and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-liang CHENG; Tian-yan ZHOU; Bo LI; Meng-yao LI; Liang LI; Zai-quan LI; Wei LU

    2013-01-01

    Aim:To investigate the influences of methotrexate (MTX) on the anticancer actions and pharmacokinetics of 5-aminoimidazole-4-carboxamide riboside (AICA riboside) in human breast cancer and hepatocellular carcinoma.Methods:Human breast cancer cell line MCF-7 and human hepatocellular carcinoma cell line HepG2 were examined.The cell proliferation was assessed using a sulforhodamine B assay.Western blotting and radioactivity assays were used to analyze the phosphorylation of AMPK.The DNA synthesis was analyzed with BrdU incorporation.Nude mice bearing MCF-7 cell xenografts were used to for in vivo study.MTX (50 mg/kg,ip,per week) and AICA riboside (200 mg/kg,ip,every other day) were administered the animals for 2 weeks.The concentrations of AICA riboside and its active metabolite AICA ribotide in the plasma and tumors were measured with HPLC.Results:Synergistic cytotoxicity in vitro was observed with MTX (0.1,0.5,and 1 μmol/L) combined with AICA riboside (0.25-1 mmol/L)in MCF-7 cells,and with MTX (0.5 and 1 μmol/L) combined with AICA riboside (0.5 and 1 mmol/L) in HepG2 cells.MTX (1 μmol/L) significantly enhanced the AICA riboside-induced AMPK activation and BrdU incorporation in both MCF-7 and HepG2 cells.Co-treatment with MTX and AICA riboside exerted more potent inhibition on the tumor growth in nude mice than either drug alone.After injection of AICA riboside (200 mg/kg,iv) in nude mice bearing MCF-7 xenografts,MTX (50 mg/kg,iv) significantly increased the concentrations of AICA riboside and its active metabolite AICA ribotide in tumors.Conclusion:MTX and AICA riboside exert synergistic anticancer action against MCF-7 and HepG2 cells in vitro and in vivo.MTX increases the concentration of AICA riboside and its active metabolite AICA ribotide in tumors in vivo.

  9. Enzyme-treated asparagus extract promotes expression of heat shock protein and exerts antistress effects.

    Science.gov (United States)

    Ito, Tomohiro; Maeda, Takahiro; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Sato, Atsuya

    2014-03-01

    A novel enzyme-treated asparagus extract (ETAS) has been developed as a functional material produced from asparagus stem. Studies were conducted to determine the effect of ETAS on heat shock protein 70 (HSP70) expression and alleviation of stress. HeLa cells were treated with ETAS, and HSP70 mRNA and protein levels were measured using a reverse transcription-polymerase chain reaction (RT-PCR) assay and an enzyme-linked immunosorbent assay (ELISA), respectively. ETAS showed significant increases in HSP70 mRNA at more than 0.125 mg/mL and the protein at more than 1.0 mg/mL. The antistress effect was evaluated in a murine sleep-deprivation model. A sleep-deprivation stress load resulted in elevation of blood corticosterone and lipid peroxide concentrations, while supplementation with ETAS at 200 and 1000 mg/kg body weight was associated with significantly reduced levels of both stress markers, which were in the normal range. The HSP70 protein expression level in mice subjected to sleep-deprivation stress and supplemented with ETAS was significantly enhanced in stomach, liver, and kidney, compared to ETAS-untreated mice. A preliminary and small-sized human study was conducted among healthy volunteers consuming up to 150 mg/d of ETAS daily for 7 d. The mRNA expression of HSP70 in peripheral leukocytes was significantly elevated at intakes of 100 or 150 mg/d, compared to their baseline levels. Since HSP70 is known to be a stress-related protein and its induction leads to cytoprotection, the present results suggest that ETAS might exert antistress effects under stressful conditions, resulting from enhancement of HSP70 expression.

  10. Interferon Regulatory Factor-1 Exerts Inhibitory Effect on Neointimal Formation after Vascular Injury

    Institute of Scientific and Technical Information of China (English)

    Zhen Li; Zhong-gao Wang; Ce Bian; Xiao-dong Chen; Jian-wen Li; Xiu Chen; Bing Han; Gao-feng Hou; Jian Chu; Qi Cui

    2009-01-01

    To investigate the effect of interferon regulatory factors (IRFs) on neointimal formation after vascular injury in the mouse, and its possible mechanism.Methods Vascular injury was induced by polyethylene cuff placement around the left femoral artery of IRF-1-deficient mice and C57BL/6J mice. The mRNA expressions of IRF-1, IRF-2, angiotensin Ⅱ type 2 (AT) receptor, interleukin-1β converting enzyme (ICE), inducible nitric oxide synthase (iNOS) were detected by RT-PCR and immunohistochemical staining.Results Neointimal formation after vascular injury was significantly greater in IRF-1-deficient mice than that in C57BL/6J mice (P<0.05). In contrast, TUNEL-positive nuclei to total nuclei in the neointima and media in vascular smooth muscle cell (VSMC) in the injured artery significantly attenuated in IRF-1-deficient mice compared to C57BL/6J mice (P<0.05). The expressions of AT2 receptor as well as pro-apoptotic genes such as ICE and iNOS in C57BL/6J mice were up-regulated in response to vascular injury, but this upregulation was attenuated in IRF-1-deficient mice.Conclusions Our results suggest that IRF-1 induces VSMC apoptosis and inhibits neointimal formation after vascular injury at least partly due to the upregulation of AT2 receptor, ICE and iNOS expressions. These results indicate that IRF-1 exerts an inhibitory effect on neointimal formation through the induction of apoptosis inVSMCs.

  11. Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.

    Science.gov (United States)

    Russmann, Vera; Goc, Joanna; Boes, Katharina; Ongerth, Tanja; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

    2016-01-15

    The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies.

  12. Minocycline fails to exert antiepileptogenic effects in a rat status epilepticus model.

    Science.gov (United States)

    Russmann, Vera; Goc, Joanna; Boes, Katharina; Ongerth, Tanja; Salvamoser, Josephine D; Siegl, Claudia; Potschka, Heidrun

    2016-01-15

    The tetracycline antibiotic minocycline can exert strong anti-inflammatory, antioxidant, and antiapoptotic effects. There is cumulating evidence that epileptogenic brain insults trigger neuroinflammation and anti-inflammatory concepts can modulate the process of epileptogenesis. Based on the mechanisms of action discussed for minocycline, the compound is of interest for intervention studies as it can prevent the polarization of microglia into a pro-inflammatory state. Here, we assessed the efficacy of sub-chronic minocycline administration initiated immediately following an electrically-induced status epilepticus in rats. The treatment did not affect the development of spontaneous seizures. However, minocycline attenuated behavioral long-term consequences of status epilepticus with a reduction in hyperactivity and hyperlocomotion. Furthermore, the compound limited the spatial learning deficits observed in the post-status epilepticus model. The typical status epilepticus-induced neuronal cell loss was evident in the hippocampus and the piriform cortex. Minocycline exposure selectively protected neurons in the piriform cortex and the hilus, but not in the hippocampal pyramidal layer. In conclusion, the data argue against an antiepileptogenic effect of minocycline in adult rats. However, the findings suggest a disease-modifying impact of the tetracycline affecting the development of behavioral co-morbidities, as well as long-term consequences on spatial learning. In addition, minocycline administration resulted in a selective neuroprotective effect. Although strong anti-inflammatory effects have been proposed for minocycline, we could not verify these effects in our experimental model. Considering the multitude of mechanisms claimed to contribute to minocycline's effects, it is of interest to further explore the exact mechanisms underlying the beneficial effects in future studies. PMID:26681545

  13. Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus.

    Science.gov (United States)

    Feduchi, E; Alonso, M A; Carrasco, L

    1989-03-01

    The replication of herpes simplex virus type 1 (HSV-1) is not inhibited in either HeLa or HEp-2 cells treated with human alpha interferon (HuIFN-alpha), particularly when high multiplicities of infection are used. However, HuIFN-gamma partially inhibits HSV-1 translation in HEp-2 cells infected at low multiplicities. Under these conditions, the transcription of genes alpha 22, TK, and gamma 0 is greatly diminished. The combined addition of human tumor necrosis factor (TNF) and HuIFN-gamma to HEp-2 cells exerts a synergistic inhibition of HSV-1 translation. Cells treated with both cytokines continue synthesizing cellular proteins, even 20 h after HSV-1 infection. As little as 10 U of IFN-gamma per ml blocked HSV-1 DNA replication, provided that TNF was also present in the medium. Analyses of HSV-1 gene transcription suggest that the action of both TNF and IFN-gamma blocked a step that comes at or prior to early HSV-1 gene expression. This early step in HSV-1 replication inhibited by TNF and IFN-gamma occurs after virus attachment and entry into cells, since the internalization of radioactive HSV-1 virion particles was not blocked by the presence of the two cytokines. Therefore, we conclude that the synergistic action of TNF plus IFN-gamma affects a step in HSV-1 replication that comes after virus entry but before or at the transcription of immediate-early genes.

  14. Physical exertion as a trigger of myocardial infarction and sudden cardiac death.

    Science.gov (United States)

    Mittleman, M A; Siscovick, D S

    1996-05-01

    The data reviewed in this article indicate that physical exertion can trigger the onset of nonfatal myocardial infarction and sudden cardiac death. In addition, it is clear that although the relative risk associated with heavy exertion may be high, the absolute risk is actually quite small. It also is clear that regular exercise reduces the risk of triggering of myocardial infarction and sudden cardiac death by isolated bouts of exertion. Thus, these data provide further support for encouragement of regular exercise, as recommended by the American Heart Association. Such a program is likely to lower the overall risk of myocardial infarction and sudden cardiac death because it may lower the baseline risk and also decrease the relative risk that an episode of exertion will trigger a myocardial infarction or sudden cardiac death. Specific recommendations for patients with a history of myocardial infarction or angina are complex. Patients with coronary artery disease have the same relative risk of myocardial infarction and sudden cardiac death as those with no such history. Because of their elevated and variable baseline risk, however, specific recommendations regarding the risks and benefits of heavy physical exertion must be provided by their individual physicians, acting on recommended guidelines for exercise in such patients.

  15. Relationships between recall of perceived exertion and blood lactate concentration in a judo competition.

    Science.gov (United States)

    Serrano, M A; Salvador, A; González-Bono, E G; Sanchís, C; Suay, F

    2001-06-01

    Relationships between perceived exertion and blood lactate have usually been studied in laboratory or training contexts but not in competition, the most important setting in which sports performance is evaluated. The purpose of this study was to examine the relationships between psychological and physiological indices of the physical effort in a competition setting, taking into account the duration of effort. For this, we employed two Ratings of Perceived Exertion (RPE and CR-10) and lactic acid plasma concentration as a biological marker of the effort performed. 13 male judo fighters who participated in a sports club competition provided capillary blood samples to assay lactate concentrations and indicated on scale their Recall of Perceived Exertion in the total competition and again in just the Last Fight to compare the usefulness of RPE and CR-10 in assessing discrete bouts of effort and a whole session. Analysis showed that perceived exertion or the effort made during the whole competition was positively and significantly related to maximal lactate concentration and lactate increase in competition, thus extending the validity of this scale to sports contests. The Recall of Perceived Exertion scores were not significantly correlated with the duration of effort.

  16. Exertional responses to sprint interval training: a comparison of 30-sec. and 60-sec. conditions.

    Science.gov (United States)

    Kilpatrick, Marcus W; Greeley, Samuel J

    2014-06-01

    The purpose of this study was to assess the effect of sprint interval training on rating of perceived exertion. 20 healthy participants (11 men, 9 women; M age = 23 yr.) completed a maximal cycle ergometer test and two high-intensity interval training cycling sessions. Each session utilized the same work-to-rest ratio (1:1), work intensity (90% max), recovery intensity (10% work intensity), and session duration (16 min.). Trials differed on duration of the interval segment, with a 30-sec. trial and a 60-sec. trial. Sessions required the same amount of total work over the duration of the trial. Rating of perceived exertion assessed before, during, and after exercise were higher for the 60-sec. trial than the 30-sec. trial despite no difference in total work. High intensity interval training trials utilizing the same total external work but differing in interval length produced different ratings of perceived exertion. Perceived exertion is significantly higher for sessions of exercise that utilize longer work intervals. These findings suggest that shorter intervals may produce more favorable exertional responses that could positively affect future behavior.

  17. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection

    NARCIS (Netherlands)

    Bartfeld, Sina; Bayram, Tülay; van de Wetering, Marc; Huch, Meritxell; Begthel, Harry; Kujala, Pekka; Vries, Robert; Peters, Peter J; Clevers, Hans

    2015-01-01

    BACKGROUND & AIMS: We previously established long-term, 3-dimensional culture of organoids from mouse tissues (intestine, stomach, pancreas, and liver) and human intestine and pancreas. Here we describe conditions required for long-term 3-dimensional culture of human gastric stem cells. The technolo

  18. Glucocorticoids exert context-dependent effects on cells of the joint in vitro

    DEFF Research Database (Denmark)

    Madsen, Suzi H; Andreassen, Kim V; Christensen, Søren T;

    2011-01-01

    Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthritis. This st....... This study aimed at characterizing the effect of glucocorticoids on chondrocytes, osteoclasts, and osteoblasts....

  19. Galacto-oligosaccharides exert a protective effect against heat stress in a Caco-2 cell model

    NARCIS (Netherlands)

    Varasteh, Soheil; Braber, Saskia; Garssen, Johan; Fink-Gremmels, Johanna

    2015-01-01

    Thermal stress can evoke a stress response and enhance the synthesis of heat shock proteins, while gut barrier dysfunction is considered as an important adverse effect of thermal stress. Considering the previously described effects of galacto-oligosaccharides, nowadays mainly used in infant formulas

  20. Design Strategies for Balancing Exertion Games: A Study of Three Approaches

    DEFF Research Database (Denmark)

    Jensen, Mads Møller; Grønbæk, Kaj

    2016-01-01

    In sports, if players' physical and technical abilities are mismatched, the competition is often uninteresting for them. With the emergence of exertion games, this could be changing. Player balancing, known from video games, allows players with different skill levels to compete, however, it is un......In sports, if players' physical and technical abilities are mismatched, the competition is often uninteresting for them. With the emergence of exertion games, this could be changing. Player balancing, known from video games, allows players with different skill levels to compete, however...... these three approaches is used to investigate the qualities and challenges within each approach and explore how the player experience is affected by them. Based on these findings, we suggest four design strategies for balancing exertion games, so that players will stay engaged in the game and contain...... the feeling of a fair competition, even if they have mismatched skills....

  1. Prediction of radiation pressure force exerted on moving particles by the two-level skeletonization.

    Science.gov (United States)

    Pan, Xiao-Min; Gou, Ming-Jiang; Sheng, Xin-Qing

    2014-04-21

    A fast full-wave method for computing radiation pressure force (RPF) exerted by shaped light beams on moving particles is presented. The problem of evaluating RPF exerted on a moving particle by a single excitation beam is converted into that of computing RPF's exerted on a static particle by multiple beams. The discretization of different beams leads to distinct right hand sides (RHS's) for the matrix system. To avoid solving each RHS by the brute-force manner, the algorithm conducts low-rank decomposition on the excitation matrix consisting of all RHS's to figure out the so-called skeleton light beams by interpolative decomposition (ID). The peak memory requirement of the skeletonization is a bottle-neck if the particle is large. A two-level skeletonization scheme is proposed to solve this problem. Some numerical experiments on arbitrarily shaped homogeneous particles are performed to illustrate the performance and capability of the developed method. PMID:24787885

  2. Acute liver failure due to non-exertional heatstroke after sauna.

    Science.gov (United States)

    Erarslan, Elife; Yüksel, Ilhami; Haznedaroglu, Serap

    2012-01-01

    Acute liver failure is defined as rapid loss of liver function that patients without previously recognized liver disease sustain a liver damage. Acute liver failure due to non-exertional heatstroke has rarely been reported. We reported here an unusual case of heat stroke induced acute liver failure (ALF) after sauna. A 63 year old man without previously recognized liver and other systemic disease was admitted for loss of consciousness and impaired liver function after sauna. Despite intensive supportive care, ALF developed. Liver transplantation was planned but the patient died on the sixth day of hospitalization. Non-exertional heatstroke induced ALF is a rare and serious condition. ALF caused by non-exertional heatstroke which requires liver transplantation for definitive solution should be kept in mind in early period.

  3. Grouper TRIM13 exerts negative regulation of antiviral immune response against nodavirus.

    Science.gov (United States)

    Huang, Youhua; Yang, Min; Yu, Yepin; Yang, Ying; Zhou, Linli; Huang, Xiaohong; Qin, Qiwei

    2016-08-01

    The tripartite motif (TRIM)-containing proteins have attracted particular attention to their multiple functions in different biological processes. TRIM13, a member of the TRIM family, is a RING domain-containing E3 ubiquitin ligase which plays critical roles in diverse cellular processes including cell death, cancer and antiviral immunity. In this study, a TRIM13 homolog from orange spotted grouper, Epinephelus coioides (EcTRIM13) was cloned and characterized. The full-length of EcTRIM13 cDNA encoded a polypeptide of 399 amino acids which shared 81% identity with TRIM13 homolog from large yellow croaker (Larimichthys crocea). Amino acid alignment analysis showed that EcTRIM13 contained conserved RING finger and B-box domain. Expression patterns analysis indicated that EcTRIM13 was abundant in liver, spleen, kidney, intestine and gill. Moreover, the transcript of EcTRIM13 in grouper spleen was differently regulated after injection with Singapore grouper iridovirus (SGIV) or polyinosin-polycytidylic acid (poly I:C). Under fluorescence microscopy, we observed the tubular structure in wild type EcTRIM13 transfected cells, but the RING domain mutant resulted in the fluorescence distribution was changed and the bright punctate fluorescence was evenly situated throughout the cytoplasm, suggesting that the RING domain was essential for its accurate localization. Overexpression of EcTRIM13 in vitro obviously increased the replication of red spotted grouper nervous necrosis virus (RGNNV), and the enhancing effect of EcTRIM13 on virus replication was affected by the RING domain. Furthermore, the ectopic expression of EcTRIM13 not only negatively regulated the interferon promoter activity induced by interferon regulator factor (IRF) 3, IRF7, and melanoma differentiation-associated protein 5 (MDA5), but also decreased the expression of several interferon related factors. In addition, the overexpression of EcTRIM13 also differently regulated the transcription of pro

  4. Effects of fitness and self-confidence on time perception during exertion

    Directory of Open Access Journals (Sweden)

    2015-09-01

    Full Text Available Aims: Human physical and psychological features influence perceptions of the environment during activity. If during exercise an individual over-estimates time, they may interpret this as spending longer than necessary under a potentially aversive state of exertion. This may in turn decrease one’s sense of exercise success and tendency to persevere with exercise. We tested if experimentally manipulating sense of exercise self-efficacy would affect time perception during standardised physical exertion. Method: Exercise Self-Efficacy (ESE of 18 -73 year olds (N=51 was measured before and after an exercise challenge of moderate intensity. Height, weight and body fat composition were measured before participants were randomly allocated to one of three groups. After a 4-minute treadmill fitness test, participants were presented with either bogus feedback about their performance (positive or negative or no feedback (control. Before and during exercise, participants estimated a prescribed 2-minute time interval. Ratings of perceived exertion were also measured periodically. Results: Feedback on performance had no significant effect on time perception, even when controlling for individual exertion level. Reported ESE was also unaffected by whether someone received positive, negative or no feedback. Age was again found to be significantly correlated with VO2max, r(51 = .62, p < .001, but in contrast to prior findings, estimates of general fitness such as VO2max, BMI and waist circumference were unrelated to changes in time perception due to exertion. Conclusions: These findings failed to support prior findings and anecdotal evidence suggesting that exertion might alter one’s perception of time. We also failed to find any support for effects on ESE when participants were given explicit performance feedback. Finally, participants’ physical characteristics appear to be unrelated to time perception whilst exercising at moderate intensity.

  5. Comparison of Ground-Based 3-Dimensional Lightning Mapping Observations with Satellite-Based LIS Observations in Oklahoma: Comparison of LMS and LIS Lightning Mapping

    Science.gov (United States)

    Thomas, Ronald J.; Krehbiel, Paul R.; Rison, William; Hamlin, Timothy; Boccippio, Dennis J.; Goodman, Steven J.; Christian, Hugh J.

    1999-01-01

    3-dimensional lightning mapping observations obtained during the MEaPRS program in central Oklahoma during June, 1998 have been compared with observations of the discharges from space, obtained by NASA's Lightning Imaging Sensor (LIS) on the TRMM satellite. Excellent spatial and temporal correlations were observed between the two sets of observations. Most of the detected optical events were associated with intracloud discharges that developed into the upper part of the storm. Cloud-to-ground discharges that were confined to mid- and lower-altitudes tended not to be detected by LIS. Extensive illumination tended to occur in impulsive bursts toward the end or part way through intracloud flashes and appeared to be produced by energetic K-changes that typically occur at these times.

  6. Cardiac risk of coronary patients after reintegration into occupations with heavy physical exertion.

    Science.gov (United States)

    Wolf, R; Habel, F; Heiermann, M; Jäkel, R; Sinn, R

    2005-04-01

    The job related reintegration of patients with coronary artery disease (CAD) is a central part of cardiac rehabilitation. However, specific occupational demands like jobs with heavy physical exertion (> 6 METs) could increase the cardiovascular risk because the relative risk for acute myocardial infarction (MI) and cardiac death is temporarily elevated after vigorous exertion ("hazard period"). Thus, in 2001 any male patient with proven CAD who performed a job with heavy exertion until the occurrence of an index event (MI/ACS, any interventional or surgical revascularization measure) received a questionnaire after an average of 20 months. Complete data were available in 108 from 119 included patients (90.8%), aged 51.8+/-7.8 years. Ejection fraction was 61.5+/-13.1% and the functional capacity at the time of hospital discharge averaged 130.1+/-31.2 W. 75% of the patients had a previous MI and 59.3% underwent bypass surgery. During follow-up the previous job with heavy exertion was performed over a cumulated time of 74 years. The aim of the study was to compare the observed and the expected incidence of MI and cardiac death with and without job performance. The expected ("basal") risk for MI and cardiac death without heavy physical exertion was determined from pooled study results and assumed to be 5.2% per year. The combined risk due to performing an occupation with strenuous exertion can be calculated from time periods with and without working hours and amounts to 11.9%. There could be expected 0.119 . 74=8.8 cardiac events related to the job. In contrast, 5 MIs (4 NSTEMI, 1 STEMI) were observed (6.8%). The relative risk for an expected event compared to the basal risk without heavy exertion was 2.3 (95% CI: 0.7-7.4). The relative risk for the observed cardiac events amounts to 1.3 (95% CI: 0.4-4.8). The lower observed risk is probably due to the high grade of physical fitness in this patient group. In spite of several limitations, our study showed no convincing

  7. Complications after liver transplantation: evaluation with magnetic resonance imaging, magnetic resonance cholangiography, and 3-dimensional contrast-enhanced magnetic resonance angiography in a single session

    International Nuclear Information System (INIS)

    To evaluate a comprehensive magnetic resonance imaging (MRI) protocol as noninvasive diagnostic modality for simultaneous detection of parenchymal, biliary, and vascular complications after liver transplantation. Fifty-two liver transplant recipients suspected to have parenchymal, biliary, and (or) vascular complications underwent our MRI protocol at 1.5T unit using a phased array coil. After preliminary acquisition of axial T1w and T2w sequences, magnetic resonance cholangiography (MRC) was performed through a breath-hold, thin- and thick-slab, single-shot T2w sequence in the coronal plane. Contrast-enhanced magnetic resonance angiography (CEMRA) was obtained using a 3-dimensional coronal spoiled gradient-echo sequence, which enabled acquisition of 32 partitions 2.0 mm thick. A fixed dose of 20 ml gadobenate dimeglumine was administered at 2 mL/s. A post-contrast T1w sequence was also performed. Two observers in conference reviewed source images and 3-dimensional reconstructions to determine the presence of parenchymal, biliary, and vascular complications. MRI findings were correlated with surgery, endoscopic retrograde cholangiography (ERC), biopsy, digital subtraction angiography (DSA), and imaging follow-up. MRI revealed abnormal findings in 32 out of 52 patients (61%), including biliary complications (anastomotic and nonanastomotic strictures, and lithiasis) in 31, vascular disease (hepatic artery stenosis and thrombosis) in 9, and evidence of hepatic abscess and hematoma in 2. ERC confirmed findings of MRC in 30 cases, but suggested disease underestimation in 2. DSA confirmed 7 magnetic resonance angiogram (MRA) findings, but suggested disease overestimation in 2. MRI combined with MRC and CEMRA can provide a comprehensive assessment of parenchymal, biliary, and vascular complications in most recipients of liver transplantation. (author)

  8. Complications after liver transplantation: evaluation with magnetic resonance imaging, magnetic resonance cholangiography, and 3-dimensional contrast-enhanced magnetic resonance angiography in a single session

    Energy Technology Data Exchange (ETDEWEB)

    Boraschi, P.; Donati, F.; Gigoni, R. [Pisa Univ. Hospital, Second Dept. of Radiology, Pisa (Italy)], E-mail: p.boraschi@do.med.unipi.it; Salemi, S. [Univ. of Pisa, Diagnostic and Interventional Radiology, Pisa (Italy); Urbani, L.; Filipponi, F. [Univ. of Pisa, Liver Transplant Unit of the Dept. of Oncology, Transplants and Advanced Technologies in Medicine, Pisa (Italy); Falaschi, F. [Pisa Univ. Hospital, Second Dept. of Radiology, Pisa (Italy); Bartolozzi, C. [Univ. of Pisa, Diagnostic and Interventional Radiology, Pisa (Italy)

    2008-12-15

    To evaluate a comprehensive magnetic resonance imaging (MRI) protocol as noninvasive diagnostic modality for simultaneous detection of parenchymal, biliary, and vascular complications after liver transplantation. Fifty-two liver transplant recipients suspected to have parenchymal, biliary, and (or) vascular complications underwent our MRI protocol at 1.5T unit using a phased array coil. After preliminary acquisition of axial T{sub 1}w and T{sub 2}w sequences, magnetic resonance cholangiography (MRC) was performed through a breath-hold, thin- and thick-slab, single-shot T{sub 2}w sequence in the coronal plane. Contrast-enhanced magnetic resonance angiography (CEMRA) was obtained using a 3-dimensional coronal spoiled gradient-echo sequence, which enabled acquisition of 32 partitions 2.0 mm thick. A fixed dose of 20 ml gadobenate dimeglumine was administered at 2 mL/s. A post-contrast T{sub 1}w sequence was also performed. Two observers in conference reviewed source images and 3-dimensional reconstructions to determine the presence of parenchymal, biliary, and vascular complications. MRI findings were correlated with surgery, endoscopic retrograde cholangiography (ERC), biopsy, digital subtraction angiography (DSA), and imaging follow-up. MRI revealed abnormal findings in 32 out of 52 patients (61%), including biliary complications (anastomotic and nonanastomotic strictures, and lithiasis) in 31, vascular disease (hepatic artery stenosis and thrombosis) in 9, and evidence of hepatic abscess and hematoma in 2. ERC confirmed findings of MRC in 30 cases, but suggested disease underestimation in 2. DSA confirmed 7 magnetic resonance angiogram (MRA) findings, but suggested disease overestimation in 2. MRI combined with MRC and CEMRA can provide a comprehensive assessment of parenchymal, biliary, and vascular complications in most recipients of liver transplantation. (author)

  9. Long-term Cosmetic Outcomes and Toxicities of Proton Beam Therapy Compared With Photon-Based 3-Dimensional Conformal Accelerated Partial-Breast Irradiation: A Phase 1 Trial

    International Nuclear Information System (INIS)

    Purpose: To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. Methods and Materials: From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. Results: At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Conclusions: Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity

  10. Long-term Cosmetic Outcomes and Toxicities of Proton Beam Therapy Compared With Photon-Based 3-Dimensional Conformal Accelerated Partial-Breast Irradiation: A Phase 1 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Galland-Girodet, Sigolène; Pashtan, Itai; MacDonald, Shannon M.; Ancukiewicz, Marek [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Hirsch, Ariel E.; Kachnic, Lisa A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts (United States); Specht, Michelle; Gadd, Michele; Smith, Barbara L. [Department of Surgical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Powell, Simon N. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Taghian, Alphonse G., E-mail: ataghian@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-11-01

    Purpose: To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. Methods and Materials: From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. Results: At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Conclusions: Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity.

  11. Functional glass slides for in vitro evaluation of interactions between osteosarcoma TE85 cells and mineral-binding ligands

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jie; Chen, Julia; Klapperich, Catherine M.; Eng, Vincent; Bertozzi, Carolyn R.

    2004-07-20

    Primary amine-functionalized glass slides obtained through a multi-step plasma treatment were conjugated with anionic amino acids that are frequently found as mineral binding elements in acidic extracellular matrix components of natural bone. The modified glass surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. Human osteosarcoma TE85 cells were cultured on these functionalized slides and analyses on both protein and gene expression levels were performed to probe the ''biocompatibility'' of the surface ligands. Cell attachment and proliferation on anionic surfaces were either better than or comparable to those of cells cultured on tissue culture polystyrene (TCPS). The modified glass surfaces promoted the expression of osteocalcin, alkaline phosphatase activity and ECM proteins such as fibronectin and vitronectin under differentiation culture conditions. Transcript analysis using gene chip microarrays confirmed that culturing TE85 cells on anionic surfaces did not activate apoptotic pathways. Collectively, these results suggest that the potential mineral-binding anionic ligands examined here do not exert significant adverse effects on the expression of important osteogenic markers of TE85 cells. This work paves the way for the incorporation of these ligands into 3-dimensional artificial bone-like scaffolds.

  12. Combination of miRNA499 and miRNA133 exerts a synergic effect on cardiac differentiation.

    Science.gov (United States)

    Pisano, Federica; Altomare, Claudia; Cervio, Elisabetta; Barile, Lucio; Rocchetti, Marcella; Ciuffreda, Maria Chiara; Malpasso, Giuseppe; Copes, Francesco; Mura, Manuela; Danieli, Patrizia; Viarengo, Gianluca; Zaza, Antonio; Gnecchi, Massimiliano

    2015-04-01

    Several studies have demonstrated that miRNA are involved in cardiac development, stem cell maintenance, and differentiation. In particular, it has been shown that miRNA133, miRNA1, and miRNA499 are involved in progenitor cell differentiation into cardiomyocytes. However, it is unknown whether different miRNA may act synergistically to improve cardiac differentiation. We used mouse P19 cells as a cardiogenic differentiation model. miRNA499, miRNA1, or miRNA133 were transiently over-expressed in P19 cells individually or in different combinations. The over-expression of miRNA499 alone increased the number of beating cells and the association of miRNA499 with miRNA133 exerted a synergistic effect, further increasing the number of beating cells. Real-time polymerase chain reaction showed that the combination of miRNA499 + 133 enhanced the expression of cardiac genes compared with controls. Western blot and immunocytochemistry for connexin43 and cardiac troponin T confirmed these findings. Importantly, caffeine responsiveness, a clear functional parameter of cardiac differentiation, was increased by miRNA499 in association with miRNA133 and was directly correlated with the activation of the cardiac troponin I isoform promoter. Cyclic contractions were reversibly abolished by extracellular calcium depletion, nifedipine, ryanodine, and IP3R blockade. Finally, we demonstrated that the use of miRNA499 + 133 induced cardiac differentiation even in the absence of dimethyl sulfoxide. Our results show that the areas spontaneously contracting possess electrophysiological and pharmacological characteristics compatible with true cardiac excitation-contraction coupling. The translational relevance of our findings was reinforced by the demonstration that the over-expression of miRNA499 and miRNA133 was also able to induce the differentiation of human mesenchymal stromal cells toward the cardiac lineage. PMID:25534971

  13. Pheromones from males of different familiarity exert divergent effects on adult neurogenesis in the female accessory olfactory bulb.

    Science.gov (United States)

    Wu, Jyun-Han; Han, Yueh-Ting; Yu, Jenn-Yah; Wang, Tsu-Wei

    2013-08-01

    Pheromones from urine of unfamiliar conspecific male animals can reinitiate a female's estrus cycle to cause pregnancy block through the vomeronasal organ (VNO)-accessory olfactory bulb (AOB)-hypothalamic pathway. This phenomenon is called the Bruce effect. Pheromones from the mate of the female, however, do not trigger re-entrance of the estrus cycle because an olfactory memory toward its mate is formed. The activity of the VNO-AOB-hypothalamic pathway is negatively modulated by GABAergic granule cells in the AOB. Since these cells are constantly replenished by neural stem cells in the subventricular zone (SVZ) of the lateral ventricle throughout adulthood and adult neurogenesis is required for mate recognition and fertility, we tested the hypothesis that pheromones from familiar and unfamiliar males may have different effects on adult AOB neurogenesis in female mice. When female mice were exposed to bedding used by a male or lived with one, cell proliferation and neuroblast production in the SVZ were increased. Furthermore, survival of newly generated cells in the AOB was enhanced. This survival effect was transient and mediated by norepinephrine. Interestingly, male bedding-induced newborn cell survival in the AOB but not cell proliferation in the SVZ was attenuated when females were subjected to bedding from an unfamiliar male. Our results indicate that male pheromones from familiar and unfamiliar males exert different effects on neurogenesis in the adult female AOB. Given that adult neurogenesis is required for reproductive behaviors, these divergent pheromonal effects may provide a mechanism for the Bruce effect. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 632-645, 2013. PMID:23696538

  14. [Characteristics of non-exertional heat-related illness in Japan].

    Science.gov (United States)

    Miyake, Yasufumi

    2012-06-01

    This report shows characteristics of non-exertional heat-related illness in Japan. The findings are similar to those of previous reports in heatwaves of Europe and The United States. Eldery people with pre-existing diseases, homeless, living alone, poverty are independent risk factors of heatstoke and are strongly associated with severity and mortality. PMID:22690607

  15. Saving the Seneca Outdoor Recreation Program: A Case Study in Exerting Political Influence.

    Science.gov (United States)

    Magee, Clare

    1998-01-01

    This case study demonstrates the process of exerting political influence in faculty's systematic efforts to save the outdoor recreation program at Seneca College (Ontario). A chart and explanatory list present a seven-stage plan for influencing political decision-making. (SAS)

  16. Effect of Carbohydrate Ingestion on Ratings of Perceived Exertion during a Marathon.

    Science.gov (United States)

    Utter, Alan C.; Kang, Jie; Robertson, Robert J.; Nieman, David C.; Chaloupka, Edward C.; Suminski, Richard R.; Piccinni, Cristiana R.

    2002-01-01

    Investigated the effects of carbohydrate substrate availability on ratings of perceived exertion (RPE) and hormonal regulation during a competitive marathon. Data on marathon runners randomly assigned to receive carbohydrate or placebo indicated that those who ingested carbohydrate rather than placebo beverages were able to run at a higher…

  17. Coordination of strength exertion during the chair-rise movement in very old people

    NARCIS (Netherlands)

    Lindemann, Ulrich; Muche, Rainer; Stuber, Michael; Zijlstra, Wiebren; Hauer, Klaus; Becker, Clemens

    2007-01-01

    Background. Changes in performance of standing up from a chair have been related to measures of strength or power. However, the sit-to-stand (STS) transfer requires that the individual exerts forces with appropriate magnitude and timing. These coordinative aspects have received less attention. This

  18. Implicit theories about willpower predict the activation of a rest goal following self-control exertion.

    Science.gov (United States)

    Job, Veronika; Bernecker, Katharina; Miketta, Stefanie; Friese, Malte

    2015-10-01

    Past research indicates that peoples' implicit theories about the nature of willpower moderate the ego-depletion effect. Only people who believe or were led to believe that willpower is a limited resource (limited-resource theory) showed lower self-control performance after an initial demanding task. As of yet, the underlying processes explaining this moderating effect by theories about willpower remain unknown. Here, we propose that the exertion of self-control activates the goal to preserve and replenish mental resources (rest goal) in people with a limited-resource theory. Five studies tested this hypothesis. In Study 1, individual differences in implicit theories about willpower predicted increased accessibility of a rest goal after self-control exertion. Furthermore, measured (Study 2) and manipulated (Study 3) willpower theories predicted an increased preference for rest-conducive objects. Finally, Studies 4 and 5 provide evidence that theories about willpower predict actual resting behavior: In Study 4, participants who held a limited-resource theory took a longer break following self-control exertion than participants with a nonlimited-resource theory. Longer resting time predicted decreased rest goal accessibility afterward. In Study 5, participants with an induced limited-resource theory sat longer on chairs in an ostensible product-testing task when they had engaged in a task requiring self-control beforehand. This research provides consistent support for a motivational shift toward rest after self-control exertion in people holding a limited-resource theory about willpower. PMID:26075793

  19. Exertional dyspnoea in chronic heart failure: the role of the lung and respiratory mechanical factors.

    Science.gov (United States)

    Dubé, Bruno-Pierre; Agostoni, Piergiuseppe; Laveneziana, Pierantonio

    2016-09-01

    Exertional dyspnoea is among the dominant symptoms in patients with chronic heart failure and progresses relentlessly as the disease advances, leading to reduced ability to function and engage in activities of daily living. Effective management of this disabling symptom awaits a better understanding of its underlying physiology.Cardiovascular factors are believed to play a major role in dyspnoea in heart failure patients. However, despite pharmacological interventions, such as vasodilators or inotropes that improve central haemodynamics, patients with heart failure still complain of exertional dyspnoea. Clearly, dyspnoea is not determined by cardiac factors alone, but likely depends on complex, integrated cardio-pulmonary interactions.A growing body of evidence suggests that excessively increased ventilatory demand and abnormal "restrictive" constraints on tidal volume expansion with development of critical mechanical limitation of ventilation, contribute to exertional dyspnoea in heart failure. This article will offer new insights into the pathophysiological mechanisms of exertional dyspnoea in patients with chronic heart failure by exploring the potential role of the various constituents of the physiological response to exercise and particularly the role of abnormal ventilatory and respiratory mechanics responses to exercise in the perception of dyspnoea in patients with heart failure. PMID:27581831

  20. Exertion of forces by children performing a free-style jump

    NARCIS (Netherlands)

    Moes, C.C.M.; Visser, R.J.

    1998-01-01

    This research project focuses on the force characteristics and force/time relationships of loads exerted by jumping children. The current study is an experimental research into children jumping on both hard and soft substrates. The hard substrate is obtained by using a force plate. For the soft subs

  1. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    NARCIS (Netherlands)

    J.R. Homberg; J.D.A. Olivier; T. Blom; T. Arentsen; C. van Brunschot; P. Schipper; G. Korte-Bouws; G. van Luijtelaar; L. Reneman

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac (R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and there

  2. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac(R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereb

  3. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat

    NARCIS (Netherlands)

    Homberg, Judith R; Olivier, Jocelien D A; Blom, Tom; Arentsen, Tim; van Brunschot, Chantal; Schipper, Pieter; Korte-Bouws, Gerdien; van Luijtelaar, Gilles; Reneman, Liesbeth

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby

  4. Implicit theories about willpower predict the activation of a rest goal following self-control exertion.

    Science.gov (United States)

    Job, Veronika; Bernecker, Katharina; Miketta, Stefanie; Friese, Malte

    2015-10-01

    Past research indicates that peoples' implicit theories about the nature of willpower moderate the ego-depletion effect. Only people who believe or were led to believe that willpower is a limited resource (limited-resource theory) showed lower self-control performance after an initial demanding task. As of yet, the underlying processes explaining this moderating effect by theories about willpower remain unknown. Here, we propose that the exertion of self-control activates the goal to preserve and replenish mental resources (rest goal) in people with a limited-resource theory. Five studies tested this hypothesis. In Study 1, individual differences in implicit theories about willpower predicted increased accessibility of a rest goal after self-control exertion. Furthermore, measured (Study 2) and manipulated (Study 3) willpower theories predicted an increased preference for rest-conducive objects. Finally, Studies 4 and 5 provide evidence that theories about willpower predict actual resting behavior: In Study 4, participants who held a limited-resource theory took a longer break following self-control exertion than participants with a nonlimited-resource theory. Longer resting time predicted decreased rest goal accessibility afterward. In Study 5, participants with an induced limited-resource theory sat longer on chairs in an ostensible product-testing task when they had engaged in a task requiring self-control beforehand. This research provides consistent support for a motivational shift toward rest after self-control exertion in people holding a limited-resource theory about willpower.

  5. Citrus-derived flavonoid naringenin exerts uterotrophic effects in female mice at human relevant doses

    DEFF Research Database (Denmark)

    Breinholt, Vibeke Miller; Svendsen, Gitte Winkel; Dragsted, Lars Ove;

    2004-01-01

    ingestion of 400-760 ml of orange juice (Erlund et al. 2001). This could be taken to suggests that ingestion of orange juice and other citrus fruits and juices may give rise to sufficiently high tissue levels of naringenin in man to exert a biological effect....

  6. Hydrocortisone Infusion Exerts Dose- and Sex-Dependent Effects on Attention to Emotional Stimuli

    Science.gov (United States)

    Breitberg, Alaina; Drevets, Wayne C.; Wood, Suzanne E.; Mah, Linda; Schulkin, Jay; Sahakian, Barbara J.; Erickson, Kristine

    2013-01-01

    Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to…

  7. Respiratory and immune response to maximal physical exertion following exposure to secondhand smoke in healthy adults.

    Directory of Open Access Journals (Sweden)

    Andreas D Flouris

    Full Text Available We assessed the cardiorespiratory and immune response to physical exertion following secondhand smoke (SHS exposure through a randomized crossover experiment. Data were obtained from 16 (8 women non-smoking adults during and following a maximal oxygen uptake cycling protocol administered at baseline and at 0-, 1-, and 3- hours following 1-hour of SHS set at bar/restaurant carbon monoxide levels. We found that SHS was associated with a 12% decrease in maximum power output, an 8.2% reduction in maximal oxygen consumption, a 6% increase in perceived exertion, and a 6.7% decrease in time to exhaustion (P<0.05. Moreover, at 0-hours almost all respiratory and immune variables measured were adversely affected (P<0.05. For instance, FEV(1 values at 0-hours dropped by 17.4%, while TNF-α increased by 90.1% (P<0.05. At 3-hours mean values of cotinine, perceived exertion and recovery systolic blood pressure in both sexes, IL4, TNF-α and IFN-γ in men, as well as FEV(1/FVC, percent predicted FEV(1, respiratory rate, and tidal volume in women remained different compared to baseline (P<0.05. It is concluded that a 1-hour of SHS at bar/restaurant levels adversely affects the cardiorespiratory and immune response to maximal physical exertion in healthy nonsmokers for at least three hours following SHS.

  8. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby

  9. Physiological responses and perceptions of exertion in a step aerobics session.

    Science.gov (United States)

    Sutherland, R; Wilson, J; Aitchison, T; Grant, S

    1999-06-01

    The aims of this study were to establish the cardiovascular and metabolic demands of a university step aerobics session entitled 'Uni-Step' performed at three step heights, and to evaluate the use of heart rate and ratings of perceived exertion for the estimation of exercise intensity during this mode. Ten female participants in step aerobics (mean VO2max = 47.7, s = 6.8 ml.kg-1.min-1) performed a 40-min Uni-Step routine on steps of height 6, 8 and 10 inches (15.2, 20.3 and 25.4 cm). Oxygen uptake, heart rate and ratings of perceived exertion were recorded throughout each test. Maximum oxygen uptake (VO2max) and maximum heart rate were measured using a continuous treadmill protocol. The mean intensities were 45.6%, 51.6% and 56.2% VO2max for the 6-, 8- and 10-inch steps respectively. The mean percent heart rate reserves were 57.2%, 63.6% and 70.1% at these three heights respectively. Correlations indicated a weak relationship between %VO2max and ratings of perceived exertion for the 6- and 8-inch steps (r = 0.61 and 0.66 respectively) but a stronger one for the 10-inch step (r = 0.79). Uni-Step performed on the two highest steps was of a sufficient relative intensity to improve or maintain the cardiovascular fitness of participants in this study. The lowest step may be useful for participants of lower fitness. Heart rate overestimated the metabolic cost of Uni-Step at all three step heights and therefore caution is advised if used to predict intensity. Low correlations between %VO2max and ratings of perceived exertion at the two lower step heights indicate that ratings of perceived exertion may have limited utility in prescribing training intensity. PMID:10404498

  10. Mapping and Morphometric Analysis of Synapses and Spines on Fusiform Cells in the Dorsal Cochlear Nucleus.

    Directory of Open Access Journals (Sweden)

    Rony H. Salloum

    2014-09-01

    Full Text Available Fusiform cells are the main integrative units of the mammalian dorsal cochlear nucleus (DCN, collecting and processing inputs from auditory and other sources before transmitting information to higher levels of the auditory system. Despite much previous work describing these cells and the sources and pharmacological identity of their synaptic inputs, information on the 3- dimensional organization and utltrastructure of synapses on these cells is currently very limited. This information is essential since an understanding of synaptic plasticity and remodeling and pathologies underlying disease states and hearing disorders must begin with knowledge of the normal characteristics of synapses on these cells, particularly those features that determine the strength of their influence on the various compartments of the cell. Here, we employed serial block face scanning electron microscopy (SBFSEM followed by 3D reconstructions to map and quantitatively characterize synaptic features on DCN fusiform cells. Our results reveal a relative sparseness of synapses on the somata of fusiform cells but a dense distribution of synapses on apical and basal dendrites. Synapses on apical dendrites were smaller and more numerous than on basal dendrites. The vast majority of axosomatic terminals were found to be linked to other terminals connected by the same axon or different branches of the same axon, suggesting a high degree of divergent input to fusiform cells. The size of terminals was correlated with the number of mitochondria and with the number of active zones, which was highly correlated with the number of postsynaptic densities, suggesting that larger terminals exert more powerful influence on the cell than smaller terminals. These size differences suggest that the input to basal dendrites, most likely those from the auditory nerve, provide the most powerful sources of input to fusiform cells, while those to apical dendrites (e.g., parallel fiber are weaker

  11. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bishayee, Anupam, E-mail: abishayee@auhs.edu [Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA 90755 (United States); Mandal, Animesh [Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272 (United States)

    2014-10-15

    Highlights: • Dietary administration of an ethanolic extract of aerial parts of T. portulacastrum (TPE) exhibits a striking chemopreventive effect in an experimentally induced classical animal model of breast cancer. • The mammary tumor-inhibitory effect of TPE could be achieved, at least in part, though intervention of key hallmark capabilities of tumor cells, such as abnormal cell proliferation and evasion of apoptosis. • TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during this early-stage mammary carcinoma. • These results coupled with a safety profile of T. portulacastrum may encourage further studies to understand the full potential of this dietary plant for chemoprevention of breast cancer. - Abstract: Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight

  12. Prior physical exertion modulates allocentric distance perception: a demonstration of task-irrelevant cross-modal transfer

    OpenAIRE

    Clark, E. V.; Ward, N.S.; Kuppuswamy, A.

    2016-01-01

    Physical exertion has been previously shown to influence distance perception in the egocentric framework. In this study, we show that physical exertion influences allocentric distance perception. Twenty healthy volunteers made allocentric line length estimates following varying levels of physical exertion. Each participant was presented with 30 different line lengths ranging from 1 to 12 cm, and each length was presented three times. Each line presentation was preceded by the participant exer...

  13. Assessment value of 3-dimensional speckle tracking imaging for changes of early left ventricular longitudinal systolic function in patients with primary hypertension

    Institute of Scientific and Technical Information of China (English)

    Jing Yu; Yun-Jian Huang

    2016-01-01

    Objective:To study the assessment value of 3-dimensional speckle tracking imaging for changes of early left ventricular longitudinal systolic function in patients with primary hypertension.Methods:Patients with primary hypertension who were treated in our hospital from May 2012 to October 2015 were selected, and 40 patients with left ventricular normal (LVN) primary hypertension and 40 patients with left ventricular remodeling (LVR) primary hypertension were screened according to Ganau typing and enrolled in the LVN group and LVR group of the study respectively; 40 cases of healthy volunteers who received physical examination in our hospital during the same period were selected as control group. Ultrasonic testing was conducted to determine conventional ultrasonic indicators and 3D-STI parameters, and serum was collected to determine AngII, ALD, TGF-β1 and Ang1-7 levels.Results:LVEDd, LVPWT and LVEF of LVN group were not significantly different from those of control group, LVEF of LVR group was not significantly different from those of LVN group and control group, and LVEDd and LVPWT of LVR group were significantly higher than those of LVN group and control group; absolute values of GLS, GCS, GRS and GAS as well as serum Ang1-7 level of LVN group was significantly lower than those of control group, serum AngII, ALD and TGF-β1 levels were higher than those of control group, absolute values of GLS, GCS, GRS and GAS as well as serum Ang1-7 level of LVR group was significantly lower than those of LVN group and control group, and serum AngII, ALD and TGF-β1 levels were higher than those of LVN group and control group; absolute values of GLS, GCS, GRS and GAS were negatively correlated with serum AngII, ALD and TGF-β1 levels, and positively correlated with serum Ang1-7 level.Conclusion:3-dimensional speckle tracking imaging can be used for early evaluation of left ventricular longitudinal systolic function in patients with primary hypertension, and it also has high

  14. Mimicking Stem Cell Niches to Increase Stem Cell Expansion

    OpenAIRE

    Dellatore, Shara M.; Garcia, A. Sofia; Miller, William M.

    2008-01-01

    Niches regulate lineage-specific stem cell self-renewal vs. differentiation in vivo and are comprised of supportive cells and extracellular matrix components arranged in a 3-dimensional topography of controlled stiffness in the presence of oxygen and growth factor gradients. Mimicking stem cell niches in a defined manner will facilitate production of the large numbers of stem cells needed to realize the promise of regenerative medicine and gene therapy. Progress has been made in mimicking com...

  15. FEM Pre-Processing for 3-Dimensional Complicated Welded Structure%三维复杂焊接结构有限元分析前处理

    Institute of Scientific and Technical Information of China (English)

    蔡洪能; 张国栋; 王雅生

    2001-01-01

    For the finite element analysis of 3-dimensional complicated welded structure,modeling of the structure including tne weld is difficult.In this research,isoparametric mapping principle is used to model the complicated structure.Software is complied in Turbo C2.0 and AutoLisp progamming.Virtual example is demonstrated to show its practical engineering value.%针对有限元分析前处理中,三维复杂结构的单元网格较难生成的问题,采用Turbo C2.0和AUTOLISP语言联合编程,利用等参数单元映射原理对复杂结构进行建模和网格剖分,并通过一个具体焊接结构的应用,说明程序具有较强的实用性和工程价值。

  16. New 3-dimensional CFD modeling of CO2 and H2S simultaneous stripping from water within PVDF hollow fiber membrane contactor

    Science.gov (United States)

    Bahlake, Ahmad; Farivar, Foad; Dabir, Bahram

    2016-07-01

    In this paper a 3-dimensional modeling of simultaneous stripping of carbon dioxide (CO2) and hydrogen sulfide (H2S) from water using hollow fiber membrane made of polyvinylidene fluoride is developed. The water, containing CO2 and H2S enters to the membrane as feed. At the same time, pure nitrogen flow in the shell side of a shell and tube hollow fiber as the solvent. In the previous methods of modeling hollow fiber membranes just one of the membranes was modeled and the results expand to whole shell and tube system. In this research the whole hollow fiber shell and tube module is modeled to reduce the errors. Simulation results showed that increasing the velocity of solvent flow and decreasing the velocity of the feed are leads to increase in the system yield. However the effect of the feed velocity on the process is likely more than the influence of changing the velocity of the gaseous solvent. In addition H2S stripping has higher yield in comparison with CO2 stripping. This model is compared to the previous modeling methods and shows that the new model is more accurate. Finally, the effect of feed temperature is studied using response surface method and the operating conditions of feed temperature, feed velocity, and solvent velocity is optimized according to synergistic effects. Simulation results show that, in the optimum operating conditions the removal percentage of H2S and CO2 are 27 and 21 % respectively.

  17. Reconstruction of Typhoon Structure Using 3-Dimensional Doppler Radar Radial Velocity Data with the Multigrid Analysis: A Case Study in an Idealized Simulation Context

    Directory of Open Access Journals (Sweden)

    Hongli Fu

    2016-01-01

    Full Text Available Extracting multiple-scale observational information is critical for accurately reconstructing the structure of mesoscale circulation systems such as typhoon. The Space and Time Mesoscale Analysis System (STMAS with multigrid data assimilation developed in Earth System Research Laboratory (ESRL in National Oceanic and Atmospheric Administration (NOAA has addressed this issue. Previous studies have shown the capability of STMAS to retrieve multiscale information in 2-dimensional Doppler radar radial velocity observations. This study explores the application of 3-dimensional (3D Doppler radar radial velocities with STMAS for reconstructing a 3D typhoon structure. As for the first step, here, we use an idealized simulation framework. A two-scale simulated “typhoon” field is constructed and referred to as “truth,” from which randomly distributed conventional wind data and 3D Doppler radar radial wind data are generated. These data are used to reconstruct the synthetic 3D “typhoon” structure by the STMAS and the traditional 3D variational (3D-Var analysis. The degree by which the “truth” 3D typhoon structure is recovered is an assessment of the impact of the data type or analysis scheme being evaluated. We also examine the effects of weak constraint and strong constraint on STMAS analyses. Results show that while the STMAS is superior to the traditional 3D-Var for reconstructing the 3D typhoon structure, the strong constraint STMAS can produce better analyses on both horizontal and vertical velocities.

  18. Quantitative 2- and 3-dimensional analysis of pharmacokinetic model-derived variables for breast lesions in dynamic, contrast-enhanced MR mammography

    International Nuclear Information System (INIS)

    Purpose: 2- and 3-dimensional evaluation of quantitative pharmacokinetic parameters derived from the Tofts model modeling dynamic contrast enhancement of lesions in MR mammography. Materials and methods: In 95 patients, MR mammography revealed 127 suspicious lesions. The initial rate of enhancement was coded by color intensity, the post-initial enhancement change is coded by color hue. 2D and 3D analysis of distribution of color hue and intensity, vascular permeability and extracellular volume were performed. Results: In 2D, malignant lesions showed significant higher number of bright red, medium red, dark red, bright green, medium green, dark green and bright blue pixels than benign lesions. In 3D, statistical significant differences between malignant and benign lesions was found for all this parameters. Vascular permeability was significant higher in malignant lesions than in benign lesions. Regression model using the 3D data found that the best discriminator between malignant and benign lesions was combined number of voxels and medium green pixels, with a sensitivity of 79.4% and a specificity of 83.1%. Conclusions: Quantitative analysis of pharmacokinetic variables of contrast kinetics showed significant differences between malignant and benign lesions. 3D analysis showed superior diagnostic differentiation between malignant and benign lesions than 2D analysis. The parametric analysis using a pharmacokinetic model allows objective analysis of contrast enhancement in breast lesions

  19. Comparison of Isocentric C-Arm 3-Dimensional Navigation and Conventional Fluoroscopy for Percutaneous Retrograde Screwing for Anterior Column Fracture of Acetabulum: An Observational Study.

    Science.gov (United States)

    He, Jiliang; Tan, Guoqing; Zhou, Dongsheng; Sun, Liang; Li, Qinghu; Yang, Yongliang; Liu, Ping

    2016-01-01

    Percutaneous screw insertion for minimally displaced or reducible acetabular fracture using x-ray fluoroscopy and computer-assisted navigation system has been advocated by some authors. The purpose of this study was to compare intraoperative conditions and clinical results between isocentric C-arm 3-dimensional (Iso-C 3D) fluoroscopy and conventional fluoroscopy for percutaneous retrograde screwing of acetabular anterior column fracture.A prospective cohort study was conducted. A total of 22 patients were assigned to 2 different groups: 10 patients in the Iso-C 3D navigation group and 12 patients in the conventional group. The operative time, fluoroscopic time, time of screw insertion, blood loss, and accuracy were analyzed between the 2 groups.There were significant differences in operative time, screw insertion time, fluoroscopy time, and mean blood loss between the 2 groups. Totally 2 of 12 (16.7%) screws were misplaced in the conventional fluoroscopy group, and all 10 screws were in safe zones in the navigation group. Percutaneous screw fixation using the Iso-C 3D computer-assisted navigation system significantly reduced the intraoperative fluoroscopy time and blood loss in percutaneous screwing for acetabular anterior column fracture.The Iso-C 3D computer-assisted navigation system provided a reliable and effective method for percutaneous screw insertion in acetabular anterior column fractures compared to conventional fluoroscopy.

  20. Radiation pressure cross section exerted on homogenous dielectric spherical particle by zeroth order Mathieu beams

    Science.gov (United States)

    Chafiq, A.; Belafhal, A.

    2016-08-01

    In this paper, we present a full calculation of radiation pressure cross section and optical forces exerted by linearly polarized zeroth order Mathieu beams on homogenous dielectric spherical particle in the framework of generalized Lorenz-Mie theory (GLMT). In this theory, the scattered fields are dependent upon the Mie scattering coefficients and the beam shape coefficients. So a new optical property such as force and torque appears by changing the beam profile and the nature of particle. In this way, this work is devoted to the analysis of both transverse and longitudinal optical forces exerted on a simple dielectric spherical particle by zeroth order Mathieu beams and zeroth order Bessel (which is a particular case of the first beam). Thus, through numerical simulations, we show that zeroth order Mathieu beams can't trap this particle but Bessel beam presents some dimensional stable equilibrium points.

  1. Incidental Finding of Inferior Vena Cava Atresia Presenting with Deep Venous Thrombosis following Physical Exertion

    Directory of Open Access Journals (Sweden)

    Shalini Koppisetty

    2015-01-01

    Full Text Available Inferior vena cava atresia (IVCA is a rare but well described vascular anomaly. It is a rare risk factor for deep venous thrombosis (DVT, found in approximately 5% of cases of unprovoked lower extremity (LE DVT in patients <30 years of age. Affected population is in the early thirties, predominantly male, often with a history of major physical exertion and presents with extensive or bilateral DVTs. Patients with IVC anomalies usually develop compensatory circulation through the collateral veins with enlarged azygous/hemizygous veins. Despite the compensatory circulation, the venous drainage of the lower limbs is often insufficient leading to venous stasis and thrombosis. We describe a case of extensive and bilateral deep venous thrombosis following physical exertion in a thirty-six-year-old male patient with incidental finding of IVCA on imaging.

  2. Angina and exertional myocardial ischemia in diabetic and nondiabetic patients: assessment by exercise thallium scintigraphy

    International Nuclear Information System (INIS)

    Patients with diabetes mellitus and coronary artery disease are thought to have painless myocardial ischemia more often than patients without diabetes. We studied 50 consecutive patients with diabetes and 50 consecutive patients without diabetes, all with ischemia, on exercise thallium scintigraphy to show the reliability of angina as a marker for exertional ischemia. The two groups had similar clinical characteristics, treadmill test results, and extent of infarction and ischemia, but only 7 patients with diabetes compared with 17 patients without diabetes had angina during exertional ischemia. In diabetic patients the extent of retinopathy, nephropathy, or peripheral neuropathy was similar in patients with and without angina. Angina is an unreliable index of myocardial ischemia in diabetic patients with coronary artery disease. Given the increased cardiac morbidity and mortality in such patients, periodic objective assessments of the extent of ischemia are warranted

  3. Fostering body movement in children through an exertion interface as an educational tool

    OpenAIRE

    Casta??er Balcells, Marta; Camerino Foguet, Oleguer; Landry, Pascal; Par??s, Narc??s, 1966-

    2011-01-01

    We present an exertion interface called the Interactive Slide (Soler, Ferrer, Par??s, 2009), a large inflatable slide augmented with virtual reality technology that offers the possibility to children to move freely in a large and diverse spatial area. Diversity of motor skills actions that children do while playing were analyzed with observational methodology and sequential analysis through temporal pattern detection (T-patterns) to obtain behavior motor responses. The results reveal that the...

  4. Acute exertional medial compartment syndrome of the foot in a teenager

    Directory of Open Access Journals (Sweden)

    Nathan R. Kelsey, MD

    2015-01-01

    Full Text Available Acute compartment syndrome is an emergent condition characterized by increased pressure in a noncompliant fascial compartment, resulting in ischemia of the muscles and nerves. It is most commonly caused by a traumatic etiology but rarely can be caused by an atraumatic etiology, resulting in a confusing clinical scenario. We present a case of a 15-year-old sedentary teenager diagnosed with acute exertional medial compartment syndrome of the foot, initially diagnosed with MRI, following two days of rugby practice.

  5. Acute Hepatic Failure as a Leading Manifestation in Exertional Heat Stroke

    OpenAIRE

    Qi Jin; Erzhen Chen; Jie Jiang; Yiming Lu

    2012-01-01

    Background. Acute hepatic failure (AHF) is uncommon as a leading symptom in patients with exertional heat stroke (EHS). Which stage to perform the liver transplantation for severe hepatic failure in EHS is still obscure at clinical setting. The conservative management has been reported to be successful in treating heat-stroke-associated AHF even in the presence of accepted criteria for emergency liver transplantation. Case Presentation. Here, we reported a 35-year-old male who presented with ...

  6. Defining the Focus of Attention: Effects of Attention on Perceived Exertion and Fatigue.

    OpenAIRE

    Keith eLohse; SHERWOOD, DAVID E.

    2011-01-01

    This manuscript presents two experiments designed to explore the effects of attention on perceived exertion and time to failure in a fatiguing athletic task. There were two major motivating factors for these experiments. First, there are few studies evaluating attentional focus effects in endurance tasks and, second, there is a lack of integration between studies of attentional focus as external/internal (e.g., Wulf, 2007a) compared to associative/dissociative (e.g., Stevinson and Biddle, 199...

  7. Acute Exertional Rhabdomyolysis and Triceps Compartment Syndrome During a High School Football Camp

    OpenAIRE

    Oh, John Y.; Laidler, Matthew; Fiala, Steven C.; Hedberg, Katrina

    2012-01-01

    Background: Acute exertional rhabdomyolysis has been infrequently reported among adolescents. In August 2010, several high school football players from one team developed rhabdomyolysis and triceps compartment syndrome following an upper arm exercise held in a non-air-conditioned wrestling room. Purpose: To confirm the diagnoses, characterize the spectrum of illnesses, and determine the factors contributing to rhabdomyolysis and triceps compartment syndromes. Study Design: Descriptive epidemi...

  8. Neuropathogenic Escherichia coli K1 does not exhibit proteolytic activities to exert its pathogenicity

    OpenAIRE

    Iqbal, Junaid; Rajani, Mehak; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2013-01-01

    Background Proteases are well-known virulence factors that promote survival, pathogenesis and immune evasion of many pathogens. Several lines of evidence suggest that the blood–brain barrier permeability is a prerequisite in microbial invasion of the central nervous system. Because proteases are frequently associated with vascular permeability by targeting junctional proteins, here it is hypothesized that neuropathogenic Escherichia coli K1 exhibit proteolytic activities to exert its pathogen...

  9. Unexplained exertional dyspnea caused by low ventricular filling pressures: results from clinical invasive cardiopulmonary exercise testing

    OpenAIRE

    Oldham, William M.; Lewis, Gregory D.; Opotowsky, Alexander R.; Waxman, Aaron B.; Systrom, David M.

    2016-01-01

    To determine whether low ventricular filling pressures are a clinically relevant etiology of unexplained dyspnea on exertion, a database of 619 consecutive, clinically indicated invasive cardiopulmonary exercise tests (iCPETs) was reviewed to identify patients with low maximum aerobic capacity (V̇o2max) due to inadequate peak cardiac output (Qtmax) with normal biventricular ejection fractions and without pulmonary hypertension (impaired: n = 49, V̇o2max = 53% predicted [interquartile range (I...

  10. Effect of Stimulant Medication Use by Children with ADHD on Heart Rate and Perceived Exertion

    Science.gov (United States)

    Mahon, Anthony D.; Woodruff, Megan E.; Horn, Mary P.; Marjerrison, Andrea D.; Cole, Andrew S.

    2012-01-01

    The effect of stimulant medication use by children with attention deficit/hyperactivity disorder (ADHD) on the rating of perceived exertion (RPE)--heart rate (HR) relationship was examined. Children with ADHD (n = 20; 11.3 [plus or minus] 1.8 yrs) and children without ADHD (n = 25; 11.2 [plus or minus] 2.1 yrs) were studied. Children with ADHD…

  11. Exertional dyspnoea in chronic heart failure: the role of the lung and respiratory mechanical factors

    OpenAIRE

    Bruno-Pierre Dubé; Piergiuseppe Agostoni; Pierantonio Laveneziana

    2016-01-01

    Exertional dyspnoea is among the dominant symptoms in patients with chronic heart failure and progresses relentlessly as the disease advances, leading to reduced ability to function and engage in activities of daily living. Effective management of this disabling symptom awaits a better understanding of its underlying physiology. Cardiovascular factors are believed to play a major role in dyspnoea in heart failure patients. However, despite pharmacological interventions, such as vasodilators o...

  12. The effects of exertion on the postural stability in young soccer players

    OpenAIRE

    Arliani, Gustavo Gonçalves; Almeida, Gabriel Peixoto Leão; dos Santos, Ciro Veronese; Venturini, André Manrique; Astur, Diego da Costa; Cohen, Moises

    2013-01-01

    OBJECTIVE : Analyze the effects of physical exertion during a soccer match on the functional capacity and stability of the lower limbs of young soccer players. METHODS : We analyzed 10 soccer players who underwent functional capacity assessment of the lower limbs by a Hop Test protocol and evaluation of the level of postural stability in the Biodex Stability System (Biodex, Inc., Shirley, NY) before and immediately after a friendly game lasting 45 minutes. RESULTS : After the match, there was...

  13. Validity of Borg Ratings of Perceived Exertion During Active Video Game Play

    OpenAIRE

    Pollock, Brandon S; Jacob E. Barkley; POTENZINI, NICK; DESALVO, RENEE M.; BUSER, STACEY L.; OTTERSTETTER, RONALD; JUVANCIC-HELTZEL, JUDITH A.

    2013-01-01

    During physically interactive video game play (e.g., Nintendo Wii), users are exposed to potential distracters (e.g., video, music), which may decrease their ratings of perceived exertion (RPE) throughout game play. The purpose of this investigation was to determine the association between RPE scores and heart rate while playing the Nintendo Wii. Healthy adults (N = 13, 53.5 ± 5.4 years old) participated in two exercise sessions using the Nintendo Wii Fit Plus. During each session participant...

  14. Matrix stiffness exerts biphasic control over monocyte-endothelial adhesion via Rho-mediated ICAM-1 clustering.

    Science.gov (United States)

    Scott, Harry A; Quach, Boi; Yang, Xiao; Ardekani, Soroush; Cabrera, Andrea P; Wilson, Randall; Messaoudi-Powers, Ilhem; Ghosh, Kaustabh

    2016-08-01

    Leukocyte-endothelial adhesion is a critical early step in chronic vascular inflammation associated with diabetes, emphysema, and aging. Importantly, these conditions are also marked by abnormal subendothelial matrix crosslinking (stiffness). Yet, whether and how abnormal matrix stiffness contributes to leukocyte-endothelial adhesion remains poorly understood. Using a co-culture of human monocytic cells and human microvascular endothelial cells (ECs) grown on matrices of tunable stiffness, we demonstrate that matrix stiffness exerts biphasic control over