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  1. Death Induced by CD95 or CD95 Ligand Elimination

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    Abbas Hadji

    2014-04-01

    Full Text Available CD95 (Fas/APO-1, when bound by its cognate ligand CD95L, induces cells to die by apoptosis. We now show that elimination of CD95 or CD95L results in a form of cell death that is independent of caspase-8, RIPK1/MLKL, and p53, is not inhibited by Bcl-xL expression, and preferentially affects cancer cells. All tumors that formed in mouse models of low-grade serous ovarian cancer or chemically induced liver cancer with tissue-specific deletion of CD95 still expressed CD95, suggesting that cancer cannot form in the absence of CD95. Death induced by CD95R/L elimination (DICE is characterized by an increase in cell size, production of mitochondrial ROS, and DNA damage. It resembles a necrotic form of mitotic catastrophe. No single drug was found to completely block this form of cell death, and it could also not be blocked by the knockdown of a single gene, making it a promising way to kill cancer cells.

  2. IL-7 promotes CD95-induced apoptosis in B cells via the IFN-γ/STAT1 pathway.

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    Stefano Sammicheli

    Full Text Available Interleukin-7 (IL-7 concentrations are increased in the blood of CD4+ T cell depleted individuals, including HIV-1 infected patients. High IL-7 levels might stimulate T cell activation and, as we have shown earlier, IL-7 can prime resting T cell to CD95 induced apoptosis as well. HIV-1 infection leads to B cell abnormalities including increased apoptosis via the CD95 (Fas death receptor pathway and loss of memory B cells. Peripheral B cells are not sensitive for IL-7, due to the lack of IL-7Ra expression on their surface; however, here we demonstrate that high IL-7 concentration can prime resting B cells to CD95-mediated apoptosis via an indirect mechanism. T cells cultured with IL-7 induced high CD95 expression on resting B cells together with an increased sensitivity to CD95 mediated apoptosis. As the mediator molecule responsible for B cell priming to CD95 mediated apoptosis we identified the cytokine IFN-γ that T cells secreted in high amounts in response to IL-7. These results suggest that the lymphopenia induced cytokine IL-7 can contribute to the increased B cell apoptosis observed in HIV-1 infected individuals.

  3. Docosahexaenoic acid counteracts attenuation of CD95-induced cell death by inorganic mercury

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    Gill, Randall [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States); Lanni, Lydia; Jen, K.-L. Catherine [Department of Nutrition and Food Science, Wayne State University, Detroit MI (United States); McCabe, Michael J. [Department of Environmental Medicine, University of Rochester, Rochester NY (United States); Rosenspire, Allen, E-mail: arosenspire@wayne.edu [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States)

    2015-01-01

    In the United States the principal environmental exposure to mercury is through dietary consumption of sea food. Although the mechanism by which low levels of mercury affect the nervous system is not well established, epidemiological studies suggest that low level exposure of pregnant women to dietary mercury can adversely impact cognitive development in their children, but that Docosahexaenoic acid (DHA), the most prominent n-polyunsaturated fatty acid (n-PUFA) present in fish may counteract negative effects of mercury on the nervous system. Aside from effects on the nervous system, epidemiological and animal studies have also suggested that low level mercury exposure may be a risk factor for autoimmune disease. However unlike the nervous system where a mechanism linking mercury to impaired cognitive development remains elusive, we have previously suggested a potential mechanism linking low level mercury exposures to immune system dysfunction and autoimmunity. In the immune system it is well established that disruption of CD95 mediated apoptosis leads to autoimmune disease. We have previously shown in vitro as well as in vivo that in lymphocytes burdened with low levels of mercury, CD95 mediated cell death is impaired. In this report we now show that DHA counteracts the negative effect of mercury on CD95 signaling in T lymphocytes. T cells which have been pre-exposed to DHA are able to cleave pro-caspase 3 and efficiently signal programmed cell death through the CD95 signaling pathway, whether or not they are burdened with low levels of mercury. Thus DHA may lower the risk of autoimmune disease after low level mercury exposures. - Highlights: • Inorganic mercury (Hg{sup 2+}) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg{sup 2+} intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3.

  4. Loss of drug-induced activation of the CD95 apoptotic pathway in a cisplatin-resistant testicular germ cell tumor cell line

    NARCIS (Netherlands)

    Spierings, DCJ; de Vries, EGE; Vellenga, E; de Jong, S

    Testicular germ cell tumors (TGCTs) are unusually sensitive to cisplatin. In the present study the role of the CD95 death pathway in cisplatin sensitivity of TGCT cells was studied in Tera and its in vitro acquired cisplatin-resistant subclone Tera-CP. Cisplatin induced an increase in CD95 membrane

  5. In vivo UVB irradiation induces clustering of Fas (CD95) on human epidermal cells

    DEFF Research Database (Denmark)

    Bang, Bo; Gniadecki, Robert; Larsen, Jørgen K

    2003-01-01

    In vitro studies with human cell lines have demonstrated that the death receptor Fas plays a role in ultraviolet (UV)-induced apoptosis. The purpose of the present study was to investigate the relation between Fas expression and apoptosis as well as clustering of Fas in human epidermis after...... clustering has a functional significance. Our results ar in accordance with previous findings from in vitro studies, and suggest that Fas is activated in vivo in human epidermis after UVB exposure....

  6. Inhibitors of XIAP sensitize CD40-activated chronic lymphocytic leukemia cells to CD95-mediated apoptosis

    NARCIS (Netherlands)

    Kater, Arnon P.; Dicker, Frank; Mangiola, Massimo; Welsh, Kate; Houghten, Richard; Ostresh, John; Nefzi, Adel; Reed, John C.; Pinilla, Clemencia; Kipps, Thomas J.

    2005-01-01

    Patients with chronic lymphocytic leukemia (CLL) treated with adenovirus CD154 (Ad-CD154, CD40 ligand [CD40L]) gene therapy experienced rapid reductions in leukemia cell counts and lymph node size associated with the induced expression of Fas (CD95). However, CLL cells initially resist CD95-mediated

  7. Tumor necrosis factor α sensitizes primary murine hepatocytes to Fas/CD95-induced apoptosis in a Bim- and Bid-dependent manner.

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    Schmich, Kathrin; Schlatter, Rebekka; Corazza, Nadia; Sá Ferreira, Karine; Ederer, Michael; Brunner, Thomas; Borner, Christoph; Merfort, Irmgard

    2011-01-01

    Fas/CD95 is a critical mediator of cell death in many chronic and acute liver diseases and induces apoptosis in primary hepatocytes in vitro. In contrast, the proinflammatory cytokine tumor necrosis factor α (TNFα) fails to provoke cell death in isolated hepatocytes but has been implicated in hepatocyte apoptosis during liver diseases associated with chronic inflammation. Here we report that TNFα sensitizes primary murine hepatocytes cultured on collagen to Fas ligand (FasL)-induced apoptosis. This synergism is time-dependent and is specifically mediated by TNFα. Fas itself is essential for the sensitization, but neither Fas up-regulation nor endogenous FasL is responsible for this effect. Although FasL is shown to induce Bid-independent apoptosis in hepatocytes cultured on collagen, the sensitizing effect of TNFα is clearly dependent on Bid. Moreover, both c-Jun N-terminal kinase activation and Bim, another B cell lymphoma 2 homology domain 3 (BH3)-only protein, are crucial mediators of TNFα-induced apoptosis sensitization. Bim and Bid activate the mitochondrial amplification loop and induce cytochrome c release, a hallmark of type II apoptosis. The mechanism of TNFα-induced sensitization is supported by a mathematical model that correctly reproduces the biological findings. Finally, our results are physiologically relevant because TNFα also induces sensitivity to agonistic anti-Fas-induced liver damage. Our data suggest that TNFα can cooperate with FasL to induce hepatocyte apoptosis by activating the BH3-only proteins Bim and Bid. Copyright © 2010 American Association for the Study of Liver Diseases.

  8. Epstein-Barr virus induces Fas (CD95) in T cells and Fas ligand in B cells leading to T-cell apoptosis.

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    Tanner, J E; Alfieri, C

    1999-11-15

    Epstein-Barr virus (EBV) acute infectious mononucleosis (AIM) is characterized by transient immunosuppression in vivo and increased T-cell apoptosis after ex vivo culture of AIM peripheral blood mononuclear cells. We undertook experiments to test whether EBV or purified virion envelope glycoprotein gp350 could contribute to Fas-mediated T-cell apoptosis. Our in vitro results indicate that EBV increased Fas expression in CD4(+) T cells and Fas ligand (FasL) expression in B cells and macrophages. Purified gp350 was also shown to significantly increase CD95 expression in CD4(+) T cells. When T-cell CD95 was cross-linked, EBV-stimulated T cells underwent apoptosis. The induction of T-cell CD95 by EBV followed by CD95 cross-linking with anti-CD95 monoclonal antibody resulted in a loss in the number of T cells responding to the T-cell mitogens, anti-CD3 antibody, and interleukin-2. These results indicate that, in addition to serving as a principal ligand for the attachment of virus to target cells, gp350 may also act as an immunomodulatory molecule that promotes T-cell apoptosis.

  9. Cytoplasmic Overexpression of CD95L in Esophageal Adenocarcinoma Cells Overcomes Resistance to CD95-Mediated Apoptosis

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    Gregory A. Watson

    2011-03-01

    Full Text Available Introduction: The CD95/CD95L pathway plays a critical role in tissue homeostasis and immune system regulation; however, the function of this pathway in malignancy remains poorly understood. We hypothesized that CD95L expression in esophageal adenocarcinoma confers advantages to the neoplasm other than immune privilege. Methods: CD95L expression was characterized in immortalized squamous esophagus (HET-1A and Barrett esophagus (BAR-T cells; adenocarcinoma cell lines FLO-1, SEG-1, and BIC-1, and MDA468 (- control; and KFL cells (+ control. Analyses included reverse transcription-polymerase chain reaction, immunoblots of whole cell and secretory vesicle lysates, FACScan analysis, laser scanning confocal microscopy of native proteins and fluorescent constructs, and assessment of apoptosis and ERK1/2 pathways. Results: Cleaved, soluble CD95L is expressed at both the RNA and protein levels in these cell lines derived from esophageal adenocarcinoma and other human tissues. CD95L was neither trafficked to the cell membrane nor secreted into the media or within vesicles, rather the protein seems to be sequestered in the cytoplasm. CD95 and CD95L colocalize by immunofluorescence, but an interaction was not proven by immunoprecipitation. Overexpression of CD95L in the adenocarcinoma cell lines induced robust apoptosis and, under conditions of pan-caspase inhibition, resulted in activation of ERK signaling. Conclusions: CD95L localization in EA cells is inconsistent with the conference of immune privilege and is more consistent with a function that promotes tumor growth through alternative CD95 signaling. Reduced cell surface expression of CD95 affects cell sensitivity to extracellular apoptotic signals more significantly than alterations in downstream modulators of apoptosis.

  10. Cucurbitacin E Induces G2/M Phase Arrest through STAT3/p53/p21 Signaling and Provokes Apoptosis via Fas/CD95 and Mitochondria-Dependent Pathways in Human Bladder Cancer T24 Cells

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    Wen-Wen Huang

    2012-01-01

    Full Text Available Cucurbitacin E, a tetracyclic triterpenes compound extracted from cucurbitaceous plants, has been shown to exhibit anticancer and anti-inflammatory activities. The purpose of this study was to elucidate whether cucurbitacin E promotes cell cycle arrest and induces apoptosis in T24 cells and further to explore the underlying molecular mechanisms. The effects of cucurbitacin E on T24 cell's growth and accompanied morphological changes were examined by MTT assay and a phase-contrast microscope. DNA content, mitochondrial membrane potential (ΔΨm and annexin V/PI staining were determined by flow cytometry. The protein levels were measured by Western blotting. Our results demonstrated that cucurbitacin E-induced G2/M arrest was associated with a marked increase in the levels of p53, p21 and a decrease in phospho-signal transducer and activator of transcription 3 (STAT3, cyclin-dependent kinase 1 (CDK1 and cyclin B. Cucurbitacin E-triggered apoptosis was accompanied with up-regulation of Fas/CD95, truncated BID (t-BID and a loss of ΔΨm, resulting in the releases of cytochrome c, apoptotic protease activating factor 1 (Apaf-1 and apoptosis-inducing factor (AIF, and sequential activation of caspase-8, caspase-9, and caspase-3. Our findings provided the first evidence that STAT3/p53/p21 signaling, Fas/CD95 and mitochondria-dependent pathways play critical roles in cucurbitacin E-induced G2/M phase arrest and apoptosis of T24 cells.

  11. Cucurbitacin E Induces G2/M Phase Arrest through STAT3/p53/p21 Signaling and Provokes Apoptosis via Fas/CD95 and Mitochondria-Dependent Pathways in Human Bladder Cancer T24 Cells

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    Huang, Wen-Wen; Yang, Jai-Sing; Lin, Meng-Wei; Chen, Po-Yuan; Chiou, Shang-Ming; Chueh, Fu-Shin; Lan, Yu-Hsuan; Pai, Shu-Jen; Tsuzuki, Minoru; Ho, Wai-Jane; Chung, Jing-Gung

    2012-01-01

    Cucurbitacin E, a tetracyclic triterpenes compound extracted from cucurbitaceous plants, has been shown to exhibit anticancer and anti-inflammatory activities. The purpose of this study was to elucidate whether cucurbitacin E promotes cell cycle arrest and induces apoptosis in T24 cells and further to explore the underlying molecular mechanisms. The effects of cucurbitacin E on T24 cell's growth and accompanied morphological changes were examined by MTT assay and a phase-contrast microscope. DNA content, mitochondrial membrane potential (ΔΨm) and annexin V/PI staining were determined by flow cytometry. The protein levels were measured by Western blotting. Our results demonstrated that cucurbitacin E-induced G2/M arrest was associated with a marked increase in the levels of p53, p21 and a decrease in phospho-signal transducer and activator of transcription 3 (STAT3), cyclin-dependent kinase 1 (CDK1) and cyclin B. Cucurbitacin E-triggered apoptosis was accompanied with up-regulation of Fas/CD95, truncated BID (t-BID) and a loss of ΔΨm, resulting in the releases of cytochrome c, apoptotic protease activating factor 1 (Apaf-1) and apoptosis-inducing factor (AIF), and sequential activation of caspase-8, caspase-9, and caspase-3. Our findings provided the first evidence that STAT3/p53/p21 signaling, Fas/CD95 and mitochondria-dependent pathways play critical roles in cucurbitacin E-induced G2/M phase arrest and apoptosis of T24 cells. PMID:22272214

  12. CNS Macrophages Control Neurovascular Development via CD95L

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    Si Chen

    2017-05-01

    Full Text Available The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina. Furthermore, we identify CNS macrophages as the main source of CD95L, and macrophage-specific deletion thereof reduces both neurovascular complexity and synaptic activity in the brain. CD95L-induced neuronal and vascular growth is mediated through src-family kinase (SFK and PI3K signaling. Together, our study highlights a coordinated neurovascular development instructed by CNS macrophage-derived CD95L, and it underlines the importance of macrophages for the establishment of the neurovascular network during CNS development.

  13. CNS Macrophages Control Neurovascular Development via CD95L.

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    Chen, Si; Tisch, Nathalie; Kegel, Marcel; Yerbes, Rosario; Hermann, Robert; Hudalla, Hannes; Zuliani, Cecilia; Gülcüler, Gülce Sila; Zwadlo, Klara; von Engelhardt, Jakob; Ruiz de Almodóvar, Carmen; Martin-Villalba, Ana

    2017-05-16

    The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina. Furthermore, we identify CNS macrophages as the main source of CD95L, and macrophage-specific deletion thereof reduces both neurovascular complexity and synaptic activity in the brain. CD95L-induced neuronal and vascular growth is mediated through src-family kinase (SFK) and PI3K signaling. Together, our study highlights a coordinated neurovascular development instructed by CNS macrophage-derived CD95L, and it underlines the importance of macrophages for the establishment of the neurovascular network during CNS development. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. CD95-CD95L: can the brain learn from the immune system?

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    Becher, B; Barker, P A; Owens, T

    1998-01-01

    Members of the tumor necrosis factor/nerve growth factor receptor superfamily of cell-surface molecules can play the dual role of mediating either cytotoxicity or cell survival, both in the immune system and in the nervous system. A member of this superfamily, CD95 (also known as ApoI or Fas), wa...

  15. Quantification of Bax/Bcl-2 ratios in peripheral blood lymphocytes, monocytes and granulocytes and their relation to susceptibility to anti-Fas (anti-CD95)-induced apoptosis

    NARCIS (Netherlands)

    van der Vliet, H. J.; Wever, P. C.; van Diepen, F. N.; Yong, S. L.; ten Berge, I. J.

    1997-01-01

    Neutrophils have the shortest half-life among circulating leucocytes and rapidly undergo apoptosis in vitro. The homologous Bcl-2 and Bax proteins have opposing effects, with Bcl-2 extending cellular survival and Bax promoting cell death following an apoptotic stimulus. We determined Bcl-2 to Bax

  16. Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95

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    Das, Anindita; Durrant, David; Mitchell, Clint; Dent, Paul; Batra, Surinder K.; Kukreja, Rakesh C.

    2016-01-01

    We previously reported that Sildenafil enhances apoptosis and antitumor efficacy of doxorubicin (DOX) while attenuating its cardiotoxic effect in prostate cancer. In the present study, we investigated the mechanism by which sildenafil sensitizes DOX in killing of prostate cancer (PCa) cells, DU145. The death receptor Fas (APO-1 or CD95) induces apoptosis in many carcinoma cells, which is negatively regulated by anti-apoptotic molecules such as FLIP (Fas-associated death domain (FADD) interleukin-1-converting enzyme (FLICE)-like inhibitory protein). Co-treatment of PCa cells with sildenafil and DOX for 48 hours showed reduced expression of both long and short forms of FLIP (FLIP-L and -S) as compared to individual drug treatment. Over-expression of FLIP-s with an adenoviral vector attentuated the enhanced cell-killing effect of DOX and sildenafil. Colony formation assays also confirmed that FLIP-S over-expression inhibited the DOX and sildenafil-induced synergistic killing effect as compared to the cells infected with an empty vector. Moreover, siRNA knock-down of CD95 abolished the effect of sildenafil in enhancing DOX lethality in cells, but had no effect on cell killing after treatment with a single agent. Sildenafil co-treatment with DOX inhibited DOX-induced NF-κB activity by reducing phosphorylation of IκB and nuclear translocation of the p65 subunit, in addition to down regulation of FAP-1 (Fas associated phosphatase-1, a known inhibitor of CD95-mediated apoptosis) expression. This data provides evidence that the CD95 is a key regulator of sildenafil and DOX mediated enhanced cell death in prostate cancer. PMID:26716643

  17. CD95 is a key mediator of invasion and accelerated outgrowth of mouse colorectal liver metastases following radiofrequency ablation

    NARCIS (Netherlands)

    Nijkamp, Maarten W.; Hoogwater, Frederik J. H.; Steller, Ernst J. A.; Westendorp, B. Florien; van der Meulen, Taco A.; Leenders, Martijn W. H.; Borel Rinkes, Inne H. M.; Kranenburg, Onno

    2010-01-01

    Recently, we have shown that micro-metastases, in the hypoxic transition zone surrounding lesions generated by radiofrequency ablation (RFA), display strongly accelerated outgrowth. CD95 is best known for its ability to induce apoptosis but can also promote tumorigenesis in apoptosis-resistant tumor

  18. Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes.

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    Potestio, M; Pawelec, G; Di Lorenzo, G; Candore, G; D'Anna, C; Gervasi, F; Lio, D; Tranchida, G; Caruso, C; Romano, G C

    1999-08-01

    Aging is associated with alterations of the immune system, thought to be related to an increased susceptibility to infectious diseases, and possibly to cancer and autoimmunity in the elderly. In the present paper we report data obtained on freshly collected blood from 148 healthy subjects of different ages (from cord blood to 102 years old). The subjects were divided into seven age classes (cord blood, 3-11 years, 15-39 years, 41-60 years, 61-74 years, 75-84 years, 85-102 years) and their lymphocyte subsets and the expression of the apoptosis-related molecule CD95 were evaluated. In respect of lymphocyte subsets, the major differences were found in the cord-blood samples compared with the oldest old groups. In the cord-blood group, the absolute number of all the lymphocyte subsets was enhanced, but in the oldest group, an increase of CD16+ lymphocytes was observed, whereas CD19+ lymphocytes, which progressively decrease with age, continue to decrease further in the very old. The data show that the expression of CD95 increases until age 74 years, whereas in the oldest old it tends to decrease again. The trend of CD95 expression seems to be related to the change of expression of CD95 on CD4+ lymphocytes, because the CD8+/CD95+ population rose steadily throughout the entire age range. The evaluation of CD95+/CD45R0+ lymphocytes shows similar results to those observed analyzing CD95 on total lymphocytes. Furthermore, a constant increase of CD95+/CD28+ and a related decline of CD28+ lymphocytes was observed in all age groups. These data suggest that the expression of CD95 on the different subsets of lymphocytes can be considered a good marker for studies of immunosenescence, because it may be predictive of successful aging, and can partially explain the change in lymphocytes subsets in elderly.

  19. Upregulation of Fas-Fas-L (CD95/CD95L)-mediated epithelial apoptosis--a putative role in pouchitis?

    LENUS (Irish Health Repository)

    Coffey, J C

    2012-02-03

    INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.

  20. Expression of Fas (CD95/APO-1) ligand by human breast cancers: significance for tumor immune privilege.

    LENUS (Irish Health Repository)

    O'Connell, J

    2012-02-03

    Breast cancers have been shown to elicit tumor-specific immune responses. As in other types of cancer, the antitumor immune response fails to contain breast tumor growth, and a reduction in both the quantity and cytotoxic effectiveness of tumor-infiltrating lymphocytes (TILs) is associated with a poorer prognosis. Fas ligand (FasL) induces apoptotic death of activated lymphocytes that express its cell surface receptor, FasR (CD95\\/APO-1). FasL-mediated apoptosis of activated lymphocytes contributes to normal immune downregulation through its roles in tolerance acquisition, immune response termination, and maintenance of immune privilege in the eye, testis, and fetus. In this report, we demonstrate that breast carcinomas express FasL. Using in situ hybridization and immunohistochemistry, we show that breast tumors constitutively express FasL at both the mRNA and protein levels, respectively. FasL expression is prevalent in breast cancer: 100% of breast tumors (17 of 17) were found to express FasL, and expression occurred over more than 50% of the tumor area in all cases. By immunohistochemistry, FasR was found to be coexpressed with FasL throughout large areas of all the breast tumors. This suggests that the tumor cells had acquired intracellular defects in FasL-mediated apoptotic signaling. FasL and FasR expression were independent of tumor type or infiltrative capacity. FasL expressed by tumor cells has previously been shown to kill Fas-sensitive lymphoid cells in vitro and has been associated with apoptosis of TILs in vivo. We conclude that mammary carcinomas express FasL in vivo as a potential inhibitor of the antitumor immune response.

  1. Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival

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    Sebastian Horn

    2017-04-01

    Full Text Available Formation of the death-inducing signaling complex (DISC initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD. Utilizing caspase-8-knockout cells, we demonstrate that caspase-8 is required upstream of both cFLIP and caspase-10 and that DISC formation critically depends on the scaffold function of caspase-8. We establish that caspase-10 rewires DISC signaling to NF-κB activation/cell survival and demonstrate that the catalytic activity of caspase-10, and caspase-8, is redundant in gene induction. Thus, our data are consistent with a model in which both caspase-10 and cFLIP coordinately regulate CD95L-mediated signaling for death or survival.

  2. Significant role of Fas ligand-binding but defective Fas receptor (CD95) in lymph node hyperplasia composed of abnormal double-negative T cells

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    Matsuzawa, Akio; Shimizu, Motomu; Takeda, Yasutaka; Nagase, Hisashi; Sayama, Kazutoshi; Kimura, Mikio

    2002-01-01

    The functional differences between two mutations of the Fas (CD95) locus, Faslpr (lpr) and Faslprcg (lprcg), were investigated using bone marrow (BM) transplantation on the C3H mouse background. Both lpr/lpr and lprcg/lprcg BM transferred caused lymph node (LN) hyperplasia in lpr/+ and lprcg/+ recipients, although it was clearly smaller than that in lpr/lpr and lprcg/lprcg recipients of lpr/lpr and lprcg/lprcg BM. In addition, both BM induced significantly larger LN hyperplasia in lprcg/+ than lpr/+ recipients. Appearance of CD4− CD8−[double negative (DN)] T cells in the periphery is the most consistent phenotype of Fas mutations. Importantly, the proportion of DN T cells was higher in larger LN hyperplasia in the order of lpr/+, lprcg/+ and lpr/lpr or lprcg/lprcg recipients. On the other hand, both lpr/lpr and lprcg/lprcg BM transferred into wild-type (+/+) mice caused marked LN atrophy. The former, but not the latter, induced wasting syndrome. Faslg1d (gld)-homozygous lpr/lpr BM transferred into +/+ mice elicited LN hyperplasia of the same extent as that in lpr/lpr mice transferred with lpr/lpr BM, but not wasting syndrome. Taken together with the fact that DN T cells massively express Fas ligand (FasL), this study implied that FasL overexpressed on DN cells may be involved in the accumulation of DN T cells in LN, LN atrophy and wasting syndrome, and that lprcg Fas, which can bind to Fas ligand but not transduce apoptosis signal into cells, may modulate these pathological conditions by interfering with the binding of FasL to Fas. PMID:12153509

  3. CD95 (Fas) ligand expression of Epstein-Barr virus (EBV)-infected lymphocytes: a possible mechanism of immune evasion in chronic active EBV infection.

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    Ohshima, K; Suzumiya, J; Sugihara, M; Nagafuchi, S; Ohga, S; Kikuchi, M

    1999-01-01

    The Epstein-Barr virus (EBV) induces infectious mononucleosis (IM) and can be associated with chronic active EBV infection (CAEBV). Cytotoxic T lymphocytes (CTL) play an important role in excluding EBV-infected cells. Two cytotoxic mechanisms of CTL have been demonstrated: one perforin/granzyme-based and the other Fas (CD95)/Fas ligand (FasL)-based. To clarify these two pathways in CAEBV, we analyzed six patients with CAEBV and four patients with IM using immunohistochemical staining of the lymph nodes. In both CAEBV and IM, CD8+ T-cells increased in number, but CD56+ natural killer cells were rare. In four of six cases with CAEBV, approximately half the lymphocytes were positive for T cell-restricted intracellular antigens (TIA-1), which were recognized by the cytolytic granules of CTL. In IM, the number of TIA-1 positive cells was smaller than that in CAEBV. Fas-positive lymphocytes were frequently encountered in both CAEBV and IM. However, FasL-positive lymphocytes increased in three of six patients with CAEBV, but not in patients with IM. Except for one case with CAEBV, the number of perforin- and/or granzyme-positive cells was small in number in both CAEBV and IM cases. In double-staining FasL and EBV in situ hybridization, FasL-positive EBV-infected lymphocytes were detected in CAEBV but not in IM. In CAEBV, the Fas/FasL pathway and not perforin pathways appears to play an important role in the pathogenesis. The data suggest that EBV-infected lymphocytes may evade immune attack through the expression of FasL.

  4. Levetiracetam differentially alters CD95 expression of neuronal cells and the mitochondrial membrane potential of immune and neuronal cells in vitro

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    Susannah K Rogers

    2014-02-01

    Full Text Available Epilepsy is a neurological seizure disorder that affects over 100 million people worldwide. Levetiracetam, either alone, as monotherapy, or as adjunctive treatment, is widely used to control certain types of seizures. Despite its increasing popularity as a relatively safe and effective anti-convulsive treatment option, its mechanism(s of action are poorly understood. Studies have suggested neuronal, glial, and immune mechanisms of action. Understanding the precise mechanisms of action of Levetiracetam would be extremely beneficial in helping to understand the processes involved in seizure generation and epilepsy. Moreover, a full understanding of these mechanisms would help to create more efficacious treatments while minimizing side effects. The current study examined the effects of Levetiracetam on the mitochondrial membrane potential of neuronal and non-neuronal cells, in vitro, in order to determine if Levetiracetam influences metabolic processes in these cell types. In addition, this study sought to address possible immune-mediated mechanisms by determining if Levetiracetam alters the expression of immune receptor-ligand pairs. The results show that Levetiracetam induces expression of CD95 and CD178 on NGF-treated C17.2 neuronal cells. The results also show that Levetiracetam increases mitochondrial membrane potential on C17.2 neuronal cells in the presence of nerve growth factor. In contrast, Levetiracetam decreases the mitochondrial membrane potential of splenocytes and this effect was dependent on intact invariant chain, thus implicating immune cell interactions. These results suggest that both neuronal and non-neuronal anti-epileptic activities of Levetiracetam involve control over energy metabolism, more specifically, mΔΨ. Future studies are needed to further investigate this potential mechanism of action.

  5. Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Annika Sommerfeld

    2015-05-01

    Full Text Available Background/Aims: Ursodeoxycholic acid, which in vivo is rapidly converted into its taurine conjugate, is frequently used for the treatment of cholestatic liver disease. Apart from its choleretic effects, tauroursodeoxycholate (TUDC can protect hepatocytes from bile acid-induced apoptosis, but the mechanisms underlying its anti-apoptotic effects are poorly understood. Methods: These mechanisms were investigated in perfused rat liver and isolated rat hepatocytes. Results: It was found that TUDC inhibited the glycochenodeoxycholate (GCDC-induced activation of the CD95 death receptor at the level of association between CD95 and the epidermal growth factor receptor. This was due to a rapid TUDC-induced β1-integrin-dependent cyclic AMP (cAMP signal with induction of the dual specificity mitogen-activated protein (MAP kinase phosphatase 1 (MKP-1, which prevented GCDC-induced phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4 and c-jun-NH2-terminal kinase (JNK activation. Furthermore, TUDC induced a protein kinase A (PKA-mediated serine/threonine phosphorylation of the CD95, which was recently identified as an internalization signal for CD95. Furthermore, TUDC inhibited GCDC-induced CD95 targeting to the plasma membrane in a β1-integrin-and PKA-dependent manner. In line with this, the β1-integrin siRNA knockdown in sodium taurocholate cotransporting polypeptide (Ntcp-transfected HepG2 cells abolished the protective effect of TUDC against GCDC-induced apoptosis. Conclusion: TUDC exerts its anti-apoptotic effect via a β1-integrin-mediated formation of cAMP, which prevents CD95 activation by hydrophobic bile acids at the levels of JNK activation and CD95 serine/threonine phosphorylation.

  6. CD95 ligand-dependant endothelial cell death initiates oral mucosa damage in a murine model of acute graft versus host disease.

    Science.gov (United States)

    Deschaumes, Christophe; Verneuil, Laurence; Ertault-Daneshpouy, Marjan; Adle-Biassette, Homa; Galateau, Françoise; Aïnoun, Fadela; Micic-Polianski, Juliette; Janin, Anne; Ameisen, Jean C

    2007-05-01

    Oral mucosa lesions are one of the common pathological consequences of acute graft versus host disease (aGVHD), the major complication of allogeneic bone marrow transplantation caused by mature T lymphocytes of donor origin. Oral mucosa damage in aGVHD is characterized by apoptosis induction in the basal keratinocytes, associated with immune effector T-cell infiltration, but its pathogenesis remains unclear because these lesions might result from the patient conditioning therapy that includes radiation and/or chemotherapy. Here, using a murine model of aGVHD that does not involve any conditioning treatment, we show that the earliest detectable oral mucosa lesion is apoptosis of the endothelial cells from chorion capillaries, which precedes basal keratinocyte apoptosis induction. Neither vascular damage nor epithelial-cell death occurred in recipients of allogeneic lymphocytes from CD95 ligand (CD95L)-defective mice. Our findings indicate that oral mucosa lesions in aGVHD are initiated by endothelial-cell death and require CD95L expression by the allogeneic lymphocytes. This early vascular damage may contribute to the induction of further tissue damage in the oral mucosa, through the induction of hypoxia and vascular leakage of immune cells or soluble proapoptotic mediators.

  7. ROLE OF CD95 AND DR3 RECEPTORS IN NA VE T-LYMPHOCYTES APOPTOSIS IN CHILDREN WITH INFECTIOUS MONONUCLEOSIS DURING CONVALESCENCE

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    E. N. Filatova

    2017-01-01

    Full Text Available Infectious mononucleosis is a widespread disease caused by certain members of Herpesviridae family. Acute infectious mononucleosis develops predominantly in children and is accompanied by an increase of the number of circulating naive CD4+ and naive CD8+ T-lymphocytes in the peripheral blood. The normalization of immunological parameters is achieved within 4–6 months after recovery and that is an indicator of a proper functioning of the immune system. CD95 and DR3 death receptors are involved in the initiation of apoptosis of naive T-lymphocytes in healthy people and in patients with infectious mononucleosis. The aim of the study was to evaluate the ability of CD95 and DR3 receptors to initiate apoptosis of naive CD4+ and naive CD8+ T-lymphocytes in children with infectious mononucleosis during convalescence. The material for the study was the samples of the peripheral blood of children who previously had infectious mononucleosis. The blood sampling was carried out again after 4–6 months after the disease. At the time of the study, children did not display clinical and laboratory signs of infectious mononucleosis. Same children who were examined earlier in the period of the development of acute infectious mononucleosis, as well as relatively healthy children were used as the comparison groups. Isolation of naive CD4+ and naive CD8+ T-lymphocytes was performed by negative magnetic immunoseparation. For specific stimulation of CD95 and DR3 receptors monoclonal antibodies were used. The level of apoptosis and expression of death receptors were evaluated by flow cytometry. Freshly isolated cells were analyzed, as well as cells cultured with the addition of appropriate monoclonal antibodies. It was shown that the recovery period was accompanied by increased apoptosis of freshly isolated naive CD4+ and naive CD8+ T-lymphocytes compared with the acute phase of infectious mononucleosis. Thus in both populations of naive T-cells showed an increase of

  8. Advanced Lung Cancer Is Associated with Decreased Expression of Perforin, CD95, CD38 by Circulating CD3+CD8+ T Lymphocytes.

    Science.gov (United States)

    Xu, Liyun; Chen, Dongdong; Lu, ChangChang; Liu, Xiaoguang; Wu, Guoqing; Zhang, Yongkui

    2015-01-01

    It is known that dysregulation of the immune system is closely related to the development of lung cancer and that CD8+T lymphocytes play a critical role in antitumor immunity. We analyzed the percentage of CD3+CD8+ T cells in peripheral blood, and expressions of the activated molecules, perforin, CD95, CD28, HLA-DR and CD38 in circulating CD3+CD8+ T cells from 68 lung cancer cases with stage I∼II and 61 lung cancer cases with stage III∼IV by flow cytometry. 61 lung cancer cases with stage III∼IV were followed up for more than 6 months and survival time was recorded. The percentages of perforin+ cells, CD95+ cells and CD38+ cells in fresh CD3+CD8+ T lymphocytes of stage III∼IV group were lower than those of stage I∼II group (p=0.021; p=0.043; p=0.036). And an increased percentage of CD3+CD8+perforin+ cells was shown to have a positive effect on the survival time in stage III∼IV lung cancer patients (p=0.043). Advanced lung cancer patients have characteristics of impairment in the cytotoxicity of circulating CD3+CD8+ T lymphocytes and perforin expression in circulating CD3+CD8+ T cells might be used as a prognostic biomarker for the advanced lung cancer. © 2015 by the Association of Clinical Scientists, Inc.

  9. Rapid flow-induced responses in endothelial cells

    Science.gov (United States)

    Stamatas, G. N.; McIntire, L. V.

    2001-01-01

    Endothelial cells alter their morphology, growth rate, and metabolism in response to fluid shear stress. To study rapid flow-induced responses in the 3D endothelial cell morphology and calcium distribution, coupled fluorescence microscopy with optical sectioning, digital imaging, and numerical deconvolution techniques have been utilized. Results demonstrate that within the first minutes of flow application nuclear calcium is increasing. In the same time frame whole cell height and nuclear height are reduced by about 1 microm. Whole cell height changes may facilitate reduction of shear stress gradients on the luminal surface, whereas nuclear structural changes may be important for modulating endothelial growth rate and metabolism. To study the role of the cytoskeleton in these responses, endothelial cells have been treated with specific disrupters (acrylamide, cytochalasin D, and colchicine) of each of the cytoskeleton elements (intermediate filaments, microfilaments, and microtubules, respectively). None of these compounds had any effect on the shear-induced calcium response. Cytochalasin D and acrylamide did not affect the shear-induced nuclear morphology changes. Colchicine, however, completely abrogated the response, indicating that microtubules may be implicated in force transmission from the plasma membrane to the nucleus. A pedagogical model based on tensegrity theory principles is presented that is consistent with the results on the 3D endothelial morphology.

  10. Rapid treatment-induced brain changes in pediatric CRPS.

    Science.gov (United States)

    Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

    2016-03-01

    To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.

  11. Rapid Treatment-Induced Brain Changes in Pediatric CRPS

    Science.gov (United States)

    Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

    2014-01-01

    To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex-and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray (PAG), two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation. PMID:25515312

  12. Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation).

    Science.gov (United States)

    Ostinelli, Edoardo G; Brooke-Powney, Melanie J; Li, Xue; Adams, Clive E

    2017-07-31

    Haloperidol used alone is recommended to help calm situations of aggression or agitation for people with psychosis. It is widely accessible and may be the only antipsychotic medication available in limited-resource areas. To examine whether haloperidol alone is an effective treatment for psychosis-induced aggression or agitation, wherein clinicians are required to intervene to prevent harm to self and others. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (26th May 2016). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. Randomised controlled trials (RCTs) involving people exhibiting aggression and/or agitation thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes of interest included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We included trials meeting our selection criteria and providing useable data. We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR), for continuous data we calculated mean difference (MD), and for cognitive outcomes we derived standardised mean difference (SMD) effect sizes, all with 95% confidence intervals (CI) and using a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce 'Summary of findings' tables which included our pre-specified main outcomes of interest. We found nine new RCTs from the

  13. The Fas/CD95 receptor regulates the death of autoreactive B cells and the selection of antigen-specific B cells

    Directory of Open Access Journals (Sweden)

    Anne-Odile eHUEBER

    2012-07-01

    Full Text Available Cell death receptors have crucial roles in the regulation of immune responses. Here we review recent in vivo data confirming that the Fas death receptor (TNFSR6 on B cells is important for the regulation of autoimmunity since the impairment of only Fas function on B cells results in uncontrolled autoantibody production and autoimmunity. Fas plays a role in the elimination of the non-specific and auto-reactive B cells in germinal center, while during the selection of antigen specific B cells different escape signals ensure the resistance to Fas-mediated apoptosis. Antigen specific survival such as BCR or MHCII signal or coreceptors (CD19 cooperating with BCR inhibits the formation of death inducing signaling complex. Antigen-specific survival can be reinforced by antigen-independent signals of IL4 or CD40 overproducing the anti-apoptotic members of the Bcl-2 family proteins.

  14. Major rapid weight loss induces changes in cardiac repolarization

    DEFF Research Database (Denmark)

    Vedel-Larsen, Esben; Iepsen, Eva Pers Winning; Lundgren, Julie

    2016-01-01

    analysis has been suggested as a more sensitive method to identify changes in cardiac repolarization. We examined the effect of a major and rapid weight loss on T-wave morphology. METHODS AND RESULTS: Twenty-six individuals had electrocardiograms (ECG) taken before and after eight weeks of weight loss...... intervention along with plasma measurements of fasting glucose, HbA1c, and potassium. For assessment of cardiac repolarization changes, T-wave Morphology Combination Score (MCS) and ECG intervals: RR, PR, QT, QTcF (Fridericia-corrected QT-interval), and QRS duration were derived. The participants lost......A1c (pMonitoring of MCS during calorie restriction makes it possible to detect repolarization changes with higher discriminative power than the QT-interval during major rapid weight...

  15. Friction Induced Wear of Rapid Prototyping Generated Materials: A Review

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    A. Tsouknidas

    2011-01-01

    Full Text Available Additive manufacturing has been introduced in the early 80s and has gained importance as a manufacturing process ever since. Even though the inception of the implicated processes predominantly focused on prototyping purposes, during the last years rapid prototyping (RP has emerged as a key enabling technology for the fabrication of highly customized, functionally gradient materials. This paper reviews friction-related wear phenomena and the corresponding deterioration mechanisms of RP-generated components as well as the potential of improving the implicated materials' wear resistance without significantly altering the process itself. The paper briefly introduces the concept of RP technologies and the implicated materials, as a premises to the process-dependent wear progression of the generated components for various degeneration scenarios (dry sliding, fretting, etc..

  16. Perforin rapidly induces plasma membrane phospholipid flip-flop.

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    Sunil S Metkar

    Full Text Available The cytotoxic cell granule secretory pathway is essential for host defense. This pathway is fundamentally a form of intracellular protein delivery where granule proteases (granzymes from cytotoxic lymphocytes are thought to diffuse through barrel stave pores generated in the plasma membrane of the target cell by the pore forming protein perforin (PFN and mediate apoptotic as well as additional biological effects. While recent electron microscopy and structural analyses indicate that recombinant PFN oligomerizes to form pores containing 20 monomers (20 nm when applied to liposomal membranes, these pores are not observed by propidium iodide uptake in target cells. Instead, concentrations of human PFN that encourage granzyme-mediated apoptosis are associated with pore structures that unexpectedly favor phosphatidylserine flip-flop measured by Annexin-V and Lactadherin. Efforts that reduce PFN mediated Ca influx in targets did not reduce Annexin-V reactivity. Antigen specific mouse CD8 cells initiate a similar rapid flip-flop in target cells. A lipid that augments plasma membrane curvature as well as cholesterol depletion in target cells enhance flip-flop. Annexin-V staining highly correlated with apoptosis after Granzyme B (GzmB treatment. We propose the structures that PFN oligomers form in the membrane bilayer may include arcs previously observed by electron microscopy and that these unusual structures represent an incomplete mixture of plasma membrane lipid and PFN oligomers that may act as a flexible gateway for GzmB to translocate across the bilayer to the cytosolic leaflet of target cells.

  17. Rapid detection of radiation-induced hydrocarbons in cooked ham.

    Science.gov (United States)

    Barba, C; Santa-María, G; Herraiz, M; Calvo, M M

    2012-03-01

    Solid phase microextraction (SPME) coupled with either gas chromatography-ionization flame detector (CG-FID) or multidimensional gas chromatography-mass spectrometry (MDGC-MS) was evaluated for its ability to detect volatile hydrocarbons produced during the irradiation of cooked ham. The chromatogram of an irradiated sample obtained using GC-FID showed a complex pattern of peaks, with several co-eluting peaks superimposed, indicating that the method was unlikely to resolve adequately the volatile hydrocarbons formed during irradiation. Using SPME-MDGC-MS 1-tetradecene (C(1-14:1)), n-pentadecane (C(15:0)), 1-hexadecene (C(1-16:1)), n-heptadecane (C(17:0)) and 8-heptadecene (C(8-17:1)) were detected in cooked ham irradiated at 0.5, 2, 4 and 8kGy. This method allows the detection of most n-alkanes and n-alkenes produced during the irradiation of the majority of fatty acids in cooked ham, namely oleic acid, stearic acid and palmitic acid. SPME is rapid and inexpensive and does not require organic solvents. The proposed SPME-MDGC-MS method allows the determination of radiolytic markers in cooked ham in less than 115min. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Oxidative Stress Induced by Polymyxin E Is Involved in Rapid Killing of Paenibacillus polymyxa

    Directory of Open Access Journals (Sweden)

    Zhiliang Yu

    2017-01-01

    Full Text Available Historically, the colistin has been thought to kill bacteria through membrane lysis. Here, we present an alternative mechanism that colistin induces rapid Paenibacillus polymyxa death through reactive oxygen species production. This significantly augments our understanding of the mechanism of colistin action, which is critical knowledge toward the yield development of colistin in the future.

  19. Optogenetic Activation of the Sublaterodorsal (SLD) Nucleus Induces Rapid Muscle Inhibition

    Science.gov (United States)

    2015-09-01

    and neural activity, as measured with electroencephalography ( EEG ). One of the hallmarks of rapid eye movement (REM) sleep is muscle inhibition and is...than the prior studies previously cited that relied on pharmaceuticals to induce REM sleep . Building on this known literature, we have generated pilot... sleep /wake component we may need to alter our experimental paradigm and test whether we can influence EEG activity after the animal is already in SWS

  20. Clozapine-induced myocarditis may be associated with rapid titration: A case report verified with autopsy.

    Science.gov (United States)

    Chopra, Nitin; de Leon, Jose

    Clozapine-induced myocarditis is a poorly understood, rare, potentially fatal adverse drug reaction with absolute risks ranging from 7 to 34 per 1000 in Australia and 0.07-0.6 per 1000 in other countries. Hypersensitivity reactions have been postulated including some cases probably associated with rapid titrations. This case describes a 50-year-old African-American man with schizoaffective disorder, naïve to clozapine, who probably died from clozapine-induced myocarditis. He was started on 25 mg/day of clozapine and received 1625 mg over 14 days, prior to his death on day 15. The autopsy found predominantly lymphocytic infiltrate of the perivascular soft tissue and myocardium of the ventricles, with occasional eosinophils. Using the Liverpool ADR Causality Assessment Tool, it was deemed probable that the patient's death was secondary to myocarditis. The patient had fulminant death with no obvious changes in vital signs. Neither C-reactive protein nor troponin was measured, but it is unlikely that the results would have arrived in time to prevent the patient's death. Age, rapid titration, and concomitant use of valproate contributed to this case, which was probably an idiosyncratic adverse drug reaction associated with rapid titration. Lamotrigine-induced Stevens-Johnson syndrome also appears to be an idiosyncratic adverse drug reaction associated with rapid titration, but its incidence has been remarkably reduced since the recommended starting lamotrigine dose was reduced and corrected by the effect of inhibitors such as valproate. Similarly, clozapine-induced myocarditis incidence probably can be reduced with the use of slow titrations, including even slower titrations for patients with lower ability to metabolize clozapine, such as those taking valproate. © The Author(s) 2015.

  1. Corticosterone induces rapid spinogenesis via synaptic glucocorticoid receptors and kinase networks in hippocampus.

    Directory of Open Access Journals (Sweden)

    Yoshimasa Komatsuzaki

    Full Text Available BACKGROUND: Modulation of dendritic spines under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrated the mechanisms of rapid effect (∼1 h of CORT on the density and morphology of spines by imaging neurons in adult male rat hippocampal slices. The application of CORT at 100-1000 nM induced a rapid increase in the density of spines of CA1 pyramidal neurons. The density of small-head spines (0.2-0.4 µm was increased even at low CORT levels (100-200 nM. The density of middle-head spines (0.4-0.5 µm was increased at high CORT levels between 400-1000 nM. The density of large-head spines (0.5-1.0 µm was increased only at 1000 nM CORT. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR, abolished the effect of CORT. Blocking a single kinase, such as MAPK, PKA, PKC or PI3K, suppressed CORT-induced enhancement of spinogenesis. Blocking NMDA receptors suppressed the CORT effect. CONCLUSIONS/SIGNIFICANCE: These results imply that stress levels of CORT (100-1000 nM drive the spinogenesis via synaptic GR and multiple kinase pathways.

  2. Rapid effects of olopatadine hydrochloride on the histamine-induced skin responses.

    Science.gov (United States)

    Morita, Keisuke; Koga, Tetsuya; Moroi, Yoichi; Urabe, Kazunori; Furue, Masutaka

    2002-11-01

    Olopatadine hydrochloride is one of the second-generation nonsedating antihistamines that are used for treating allergic disorders such as urticaria, rhinitis, and atopic dermatitis. We examined the inhibitory effects of this drug on the flare and wheal responses induced by histamine iontophoresis at 30, 60, and 90 min after oral administration in a double-blind, cross-over, and placebo-controlled study. Olopatadine hydrochloride significantly inhibited the histamine-induced flare and wheal responses as early as 60 min after oral administration when compared with placebo. Significant inihibitory effects of olopatadine hydrochloride on the itch responses were seen at 90 min after administration. Thus, olopatadine hydrochloride exhibited a very rapid and potent antihistamine effect on the histamine-induced skin responses.

  3. Rapid modification of proteins using a rapamycin-inducible tobacco etch virus protease system.

    Directory of Open Access Journals (Sweden)

    Damian J Williams

    2009-10-01

    Full Text Available The ability to disrupt the function of a specific protein on a rapid time scale provides a powerful tool for biomedical research. Specific proteases provide a potential method to selectively cleave a chosen protein, but rapid control of protease activity is difficult.A heterologous expression system for rapid target-directed proteolysis in mammalian cells was developed. The system consists of an inducible NIa protease from the tobacco etch virus (TEVp and a chosen protein into which a TEVp substrate recognition sequence (TRS has been inserted. Inducible activity was conferred to the TEVp using rapamycin-controlled TEVp fragment complementation. TEVp activity was assayed using a FRET-based reporter construct. TEVp expression was well tolerated by mammalian cells and complete cleavage of the substrate was possible. Cleavage at 37 degrees C proceeded exponentially with a time constant of approximately 150 minutes. Attempts to improve cleavage efficiency were hampered by substantial background activity, which was attributed to inherent affinity between the TEVp fragments. A second TEVp assay, based on changes in inactivation of a modified K(V3.4 channel, showed that functional properties of a channel can be using altered using an inducible TEVp system. Similar levels of background activity and variability were observed in both electrophysiological and FRET assays.The results suggested that an optimum level of TEVp expression leading to sufficient inducible activity (with minimal background activity exists but the variability in expression levels between cells makes the present system rather impractical for single cell experiments. The system is likely to be more suitable for experiments in which the cell-to-cell variability is less of an issue; for example, in experiments involving large populations of cells.

  4. [The influence of methylprednisolone on the ability of CD4+CD95+HLA-DR+ T-cells to produce proinflammatory medators in cultures of TCR-activated CD3+CD45RO+ T-lymphocytes from patients with rheumatoid arthritis].

    Science.gov (United States)

    Todosenko, N M; Khaziakhmatova, O G; Yurova, K A; Malinina, I P; Litvinova, L S

    2017-05-01

    The effect of different concentrations of the glucocorticoid (GC) methylprednisolone (MP) on CD4+CD95+HLA-DR+ T-cells and their ability to produce proinflammatory mediators in cultures of TCR-stimulated CD3+CD45RO+ T-lymphocytes in the in vitro system was investigated. T cells were obtained from healthy donors and patients with rheumatoid arthritis (RA).Under conditions of TCR-activation, MP increased the number of CD4+HLA-DR+CD95+ cells in CD3+CD45RO+ cultures obtained from RA patients and did not change their content in the control group. In general, MP decreased production of proinflammatory factors (IFN-, IL-2, IL-17, IL-21 and TNF-) by TCR-activated CD3+CD45RO+ cells from healthy donors and RA, consistent with the overall immunosuppressive mechanism of GC action. The correlation between CD4+CD45RO+HLA-DR+CD95+ T-cell contents and parameters reflecting production of proinflammatory mediators (IL-17, IL-21 and TNF-) in RA patients indicates maintenance of the pro-inflammatory potential of this T-cell population exposed to GC action. We suggest that relative resistance of CD4+CD45RO+CD95+HLA-DR+ T-cells of RA patients to the suppressor effect of GC leads to maintenance and even enhancement in the functional capacities of autoreactive cells in the pathogenesis of RA.

  5. Rapid elemental analysis and provenance study of Blumea balsamifera DC using laser-induced breakdown spectroscopy.

    Science.gov (United States)

    Liu, Xiaona; Zhang, Qiao; Wu, Zhisheng; Shi, Xinyuan; Zhao, Na; Qiao, Yanjiang

    2014-12-31

    Laser-induced breakdown spectroscopy (LIBS) was applied to perform a rapid elemental analysis and provenance study of Blumea balsamifera DC. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were implemented to exploit the multivariate nature of the LIBS data. Scores and loadings of computed principal components visually illustrated the differing spectral data. The PLS-DA algorithm showed good classification performance. The PLS-DA model using complete spectra as input variables had similar discrimination performance to using selected spectral lines as input variables. The down-selection of spectral lines was specifically focused on the major elements of B. balsamifera samples. Results indicated that LIBS could be used to rapidly analyze elements and to perform provenance study of B. balsamifera.

  6. Rapid Elemental Analysis and Provenance Study of Blumea balsamifera DC Using Laser-Induced Breakdown Spectroscopy

    Directory of Open Access Journals (Sweden)

    Xiaona Liu

    2014-12-01

    Full Text Available Laser-induced breakdown spectroscopy (LIBS was applied to perform a rapid elemental analysis and provenance study of Blumea balsamifera DC. Principal component analysis (PCA and partial least squares discriminant analysis (PLS-DA were implemented to exploit the multivariate nature of the LIBS data. Scores and loadings of computed principal components visually illustrated the differing spectral data. The PLS-DA algorithm showed good classification performance. The PLS-DA model using complete spectra as input variables had similar discrimination performance to using selected spectral lines as input variables. The down-selection of spectral lines was specifically focused on the major elements of B. balsamifera samples. Results indicated that LIBS could be used to rapidly analyze elements and to perform provenance study of B. balsamifera.

  7. Far field velocity potential induced by a rapidly decaying vorticity distribution

    Science.gov (United States)

    Klein, Rupert; Ting, LU

    1990-01-01

    The velocity field induced by a vorticity distribution decaying rapidly in the distance from the origin is investigated. It is shown that the sum of vector potentials for the velocity field can be expressed as a linear combination of Mn values, where Mn denotes the number of linearly independent vector functions of nth order. It is then shown that only the linear combinations 2n + 1 of these Mn vector functions contribute to the far field velocity which is irrotational, and that the corresponding scalar potential is then represented by a linear combination of 2n + 1 spherical harmonics of nth order whose coefficients are linear combinations of nth moments of vorticity.

  8. Activation of intracellular angiotensin AT2 receptors induces rapid cell death in human uterine leiomyosarcoma cells

    DEFF Research Database (Denmark)

    Zhao, Yi; Lützen, Ulf; Fritsch, Jürgen

    2015-01-01

    of apoptosis and cell death in cultured human uterine leiomyosarcoma (SK-UT-1) cells and control human uterine smooth muscle cells (HutSMC). The intracellular levels of the AT2 receptor are low in proliferating SK-UT-1 cells but the receptor is substantially up-regulated in quiescent SK-UT-1 cells with high...... densities in mitochondria. Activation of the cell membrane AT2 receptors by a concomitant treatment with angiotensin II and the AT1 receptor antagonist, losartan, induces apoptosis but does not affect the rate of cell death. We demonstrate for the first time that the high-affinity, non-peptide AT2 receptor...... agonist, Compound 21 (C21) penetrates the cell membrane of quiescent SK-UT-1 cells, activates intracellular AT2 receptors and induces rapid cell death; approximately 70% of cells died within 24 h. The cells, which escaped from the cell death, displayed activation of the mitochondrial apoptotic pathway, i...

  9. Neuropeptide S mitigates spatial memory impairment induced by rapid eye movement sleep deprivation in rats.

    Science.gov (United States)

    Zhao, Zhengqing; Huang, Liuqing; Wu, Huijuan; Li, Yanpeng; Zhang, Lin; Yin, You; Xiang, Zhenghua; Zhao, Zhongxin

    2010-06-23

    Rapid eye movement (REM) sleep deprivation causes learning and memory deficits. Neuropeptide S, a newly discovered neuropeptide, has been shown to regulate arousal, anxiety, and may enhance long-term memory formation and spatial memory. However, it is unknown whether neuropeptide S could improve the REM sleep deprivation-induced memory impairment. Here, we report that 72-h REM sleep deprivation in rats resulted in spatial memory impairment and reduced phosphorylation level of cAMP-response element binding protein in the hippocampus, both of which were reversed by central administration of neuropeptide S. The results suggest that neuropeptide S mitigates spatial memory impairment in rats induced by 72-h REM sleep deprivation, possibly through activating cAMP-response element binding protein phosphorylation in the hippocampus.

  10. Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus.

    Science.gov (United States)

    Diaz-San Segundo, Fayna; Dias, Camila C A; Moraes, Mauro P; Weiss, Marcelo; Perez-Martin, Eva; Owens, Gary; Custer, Max; Kamrud, Kurt; de los Santos, Teresa; Grubman, Marvin J

    2013-05-01

    We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach to induce rapid protection against FMDV, we have examined the ability of VRPs containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-α (VRP-poIFN-α) to block FMDV replication in vitro and in vivo. Pretreatment of swine or bovine cell lines with either VRP significantly inhibited subsequent infection with FMDV as early as 6 h after treatment and for at least 120 h posttreatment. Furthermore, mice pretreated with either 10(7) or 10(8) infectious units of VRP-GFP and challenged with a lethal dose of FMDV 24 h later were protected from death. Protection was induced as early as 6 h after treatment and lasted for at least 48 h and correlated with induction of an antiviral response and production of IFN-α. By 6 h after treatment several genes were upregulated, and the number of genes and the level of induction increased at 24 h. Finally, we demonstrated that the chemokine IP-10, which is induced by IFN-α and VRP-GFP, is directly involved in protection against FMDV.

  11. Cortical plasticity induced by rapid Hebbian learning of novel tonal word-forms : Evidence from mismatch negativity

    NARCIS (Netherlands)

    Yue, Jinxing; Bastiaanse, Roelien; Alter, Kai

    2014-01-01

    Although several experiments reported rapid cortical plasticity induced by passive exposure to novel segmental patterns, few studies have devoted attention to the neural dynamics during the rapid learning of novel tonal word-forms in tonal languages, such as Chinese. In the current study, native

  12. Rapid auxin-induced stimulation of cell wall synthesis in pea internodes

    Energy Technology Data Exchange (ETDEWEB)

    Kutschera, U.; Briggs, W.R.

    1987-05-01

    The effect of auxin (indole-3-acetic acid; IAA) on growth and incorporation of myo-(2-/sup 3/H(N)) inositol ((/sup 3/H)Ins) into noncellulosic polysacchharides in the cell walls of third internode sections from red light-grown pea seedlings (Pisum sativum L. cv. Alaska) was investigated. Intact section were incubated on (/sup 3/H)Ins for 4 hr to permit uptake of the tracer and then IAA was added. Growth started after a lag phase of 15 min under these conditions. The sections were removed from the tracer and separated into epidermis and cortical cylinder (cortex plus vascular tissue). In the epidermis, IAA-induced stimulation of (/sup 3/H)Ins incorporation started after a lag of 15 min. The amount of incorporation was 15% higher after 30 min and 24% higher after 2 hr than in the control. In the cortical cylinder, IAA-induced stimulation of (/sup 3/H)Ins incorporation started only approx. = 1 hr after adding IAA. The ionophore monensin (20 ..mu..M) inhibited the IAA-induced growth by 95%. Under these conditions, the IAA-induced stimulation of (/sup 3/H)Ins incorporation and the IAA-induced increase in in vivo extensibility of the sections was almost completely inhibited, although oxygen uptake was unaffected. The authors suggest that wall synthesis (as represented by (/sup 3/H)Ins incorporation) and wall loosening (increase in in vivo extensibility) are related processes. The results support the hypothesis that IAA induces growth by rapid simulation of cell wall synthesis in the growth-limiting epidermal cell layer.

  13. Laser induced breakdown spectroscopy (LIBS) as a rapid tool for material analysis

    Science.gov (United States)

    Hussain, T.; Gondal, M. A.

    2013-06-01

    Laser induced breakdown spectroscopy (LIBS) is a novel technique for elemental analysis based on laser-generated plasma. In this technique, laser pulses are applied for ablation of the sample, resulting in the vaporization and ionization of sample in hot plasma which is finally analyzed by the spectrometer. The elements are identified by their unique spectral signatures. LIBS system was developed for elemental analysis of solid and liquid samples. The developed system was applied for qualitative as well as quantitative measurement of elemental concentration present in iron slag and open pit ore samples. The plasma was generated by focusing a pulsed Nd:YAG laser at 1064 nm on test samples to study the capabilities of LIBS as a rapid tool for material analysis. The concentrations of various elements of environmental significance such as cadmium, calcium, magnesium, chromium, manganese, titanium, barium, phosphorus, copper, iron, zinc etc., in these samples were determined. Optimal experimental conditions were evaluated for improving the sensitivity of developed LIBS system through parametric dependence study. The laser-induced breakdown spectroscopy (LIBS) results were compared with the results obtained using standard analytical technique such as inductively couple plasma emission spectroscopy (ICP). Limit of detection (LOD) of our LIBS system were also estimated for the above mentioned elements. This study demonstrates that LIBS could be highly appropriate for rapid online analysis of iron slag and open pit waste.

  14. Rapid and specific gray matter changes in M1 induced by balance training.

    Science.gov (United States)

    Taubert, Marco; Mehnert, Jan; Pleger, Burkhard; Villringer, Arno

    2016-06-01

    Training-induced changes in cortical structure can be observed non-invasively with magnetic resonance imaging (MRI). While macroscopic changes were found mainly after weeks to several months of training in humans, imaging of motor cortical networks in animals revealed rapid microstructural alterations after a few hours of training. We used MRI to test the hypothesis of immediate and specific training-induced alterations in motor cortical gray matter in humans. We found localized increases in motor cortical thickness after 1h of practice in a complex balancing task. These changes were specific to motor cortical effector representations primarily responsible for balance control in our task (lower limb and trunk) and these effects could be confirmed in a replication study. Cortical thickness changes (i) linearly increased across the training session, (ii) occurred independent of alterations in resting cerebral blood flow and (iii) were not triggered by repetitive use of the lower limbs. Our findings show that motor learning triggers rapid and specific gray matter changes in M1. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Methamphetamine induces a rapid increase of intracellular Ca(++) levels in neurons overexpressing GCaMP5.

    Science.gov (United States)

    Yu, Seong-Jin; Wu, Kou-Jen; Bae, Eun K; Hsu, Man-Jung; Richie, Christopher T; Harvey, Brandon K; Wang, Yun

    2016-03-01

    In this study, methamphetamine (Meth)- and glutamate (Glu)-mediated intracellular Ca(++) (Ca(++) i) signals were examined in real time in primary cortical neurons overexpressing an intracellular Ca(++) probe, GCaMP5, by adeno-associated viral (AAV) serotype 1. Binding of Ca(++) to GCaMP increased green fluorescence intensity in cells. Both Meth and Glu induced a rapid increase in Ca(++) i, which was blocked by MK801, suggesting that Meth enhanced Ca(++) i through Glu receptor in neurons. The Meth-mediated Ca(++) signal was also blocked by Mg(++) , low Ca(++) or the L-type Ca(++) channel inhibitor nifedipine. The ryanodine receptor inhibitor dantrolene did not alter the initial Ca(++) influx but partially reduced the peak of Ca(++) i. These data suggest that Meth enhanced Ca(++) influx through membrane Ca(++) channels, which then triggered the release of Ca(++) from the endoplasmic reticulum in the cytosol. AAV-GCaMP5 was also injected to the parietal cortex of adult rats. Administration of Meth enhanced fluorescence in the ipsilateral cortex. Using immunohistochemistry, Meth-induced green fluorescence was found in the NeuN-containing cells in the cortex, suggesting that Meth increased Ca(++) in neurons in vivo. In conclusion, we have used in vitro and in vivo techniques to demonstrate a rapid increase of Ca(++) i by Meth in cortical neurons through overexpression of GCaMP5. As Meth induces behavioral responses and neurotoxicity through Ca(++) i, modulation of Ca(++) i may be useful to reduce Meth-related reactions. © 2014 Society for the Study of Addiction.

  16. Mechanism of shock train rapid motion induced by variation of attack angle

    Science.gov (United States)

    Xu, Kejing; Chang, Juntao; Zhou, Weixing; Yu, Daren

    2017-11-01

    Numerical simulation was conducted to study the effect of attack angle variation on the quasi-steady motion characteristics of shock train leading edge. Simulation results indicate the motion of shock train has jumping feature, which is mainly caused by the strength changing of the local flow separation. During the process of attack angle decreasing, the reflection points of background wave move downstream, and the one of which approaches the separation zone of shock train. Thus a rapid forward movement is induced by the increasing local adverse pressure gradients. In attack angle increasing case, shock train is not moving back continuously but can be temporarily stabilized at the front part of the reflection point, because of the local adverse pressure gradient that formed by background waves. Once the refection point moves forward and surmounts leading edge of shock train, the pressure boost from background wave to the separation zone is lost, and a suddenly backward jumping will occur.

  17. Rapid and durable response to intravenous immunoglobulin in delayed heparin-induced thrombocytopenia: a case report.

    Science.gov (United States)

    Lei, Brandon Z; Shatzel, Joseph J; Sendowski, Merav

    2017-04-01

    Heparin-induced thrombocytopenia (HIT) results in platelet consumption and a virulent thrombotic state, which generally responds to cessation of heparin and initiation of anticoagulation. Rarely, delayed HIT can occur and/or persist after heparin is discontinued. A 47-year-old male developed delayed HIT with severe thrombocytopenia and thrombosis after cardiac surgery. Thrombocytopenia developed and persisted after heparin cessation and did not improve despite sequential use of argatroban followed by bivalirudin. Treatment with intravenous immunoglobulin (IVIg) was well tolerated and resulted in rapid resolution of thrombocytopenia. There are few case reports on the management of delayed HIT with severe and prolonged thrombocytopenia. The risk for thrombosis and bleeding in the setting of an undefined time course increases uncertainty in management. This case, along with others accumulating in the literature, suggest that IVIg may be effective in treating delayed HIT with persistent thrombocytopenia. © 2016 AABB.

  18. Rapid generation and manipulation of microfluidic vortex flows induced by AC electrokinetics with optical illumination.

    Science.gov (United States)

    Park, Choongbae; Wereley, Steven T

    2013-04-07

    We demonstrate a rapid generation of twin opposing microvortices (TOMVs) induced by non-uniform alternating current (AC) electric fields together with a laser beam on a patterned pair of indium tin oxide (ITO) electrodes. A fast and strong jet flow region between twin microvortices is also generated. Its pattern and direction, such as whether it is symmetric or asymmetric, are controlled mainly by the location of a single laser spot relative to the ITO electrodes. With two laser beams, two separate flows are superposed to give a new one. In situ generation and control of the TOMV flow are tested in suspensions of fluorescent polystyrene particles, as well as in milk emulsions. This technique has great potential for dynamically manipulating micro-fluid flows, functioning as a micro-pump or mixer.

  19. Taser-induced rapid ventricular myocardial capture demonstrated by pacemaker intracardiac electrograms.

    Science.gov (United States)

    Cao, Michael; Shinbane, Jerold S; Gillberg, Jeffrey M; Saxon, Leslie A; Swerdlow, Charles D

    2007-08-01

    A Taser weapon is designed to incapacitate violent individuals by causing temporary neuromuscular paralysis due to current application. We report the first case of a Taser application in a person with a dual-chamber pacemaker demonstrating evidence of Taser-induced myocardial capture. Device interrogation was performed in a 53-year-old man with a dual-chamber pacemaker who had received a Taser shot consisting of two barbs delivered simultaneously. Assessment of pacemaker function after Taser application demonstrated normal sensing, pacing thresholds, and lead impedances. Stored event data revealed two high ventricular rate episodes corresponding to the exact time of the Taser application. This report describes the first human case of ventricular myocardial capture at a rapid rate resulting from a Taser application. This raises the issue as to whether conducted energy devices can cause primary myocardial capture or capture only in association with cardiac devices providing a preferential pathway of conduction to the myocardium.

  20. Rapid response, monitoring, and mitigation of induced seismicity near Greeley, Colorado

    Science.gov (United States)

    Yeck, William; Sheehan, A.F; Benz, Harley M.; Weingarten, Matthew; Nakai, J

    2016-01-01

    On 1 June 2014 (03:35 UTC), an Mw 3.2 earthquake occurred in Weld County, Colorado, a historically aseismic area of the Denver–Julesburg basin. Weld County is a prominent area of oil and gas development, including many high‐rate class II wastewater injection wells. In the days following the earthquake, the University of Colorado, with support from the U.S. Geological Survey and Incorporated Research Institutions for Seismology–Portable Array Seismic Studies of the Continental Lithosphere, rapidly deployed six seismic stations to characterize the seismicity associated with the 1 June earthquake (the Greeley sequence) and to investigate its possible connection to wastewater disposal. The spatial and temporal proximity of earthquakes to a high‐rate wastewater disposal well strongly suggests these earthquakes were induced. Scientific communication between the university, state agencies, and the energy industry led to rapid mitigation strategies to reduce the occurrence of further earthquakes. Mitigation efforts included implementing a temporary moratorium on injection at the well, cementing the bottom portion of the disposal well to minimize hydrologic connectivity between the disposal formation and the underlying crystalline basement, and subsequently allowing injection to resume at lower rates. Following the resumption of wastewater disposal, microseismicity was closely monitored for both increases in earthquake rate and magnitude. Following mitigation efforts, between 13 August 2014 and 29 December 2015, no earthquakes larger than M 1.5 occurred near the Greeley sequence. This study demonstrates that a detailed and rapid characterization of a seismic sequence in space and time relative to disposal, combined with collaboration and communication between scientists, regulators, and industry, can lead to objective and actionable mitigation efforts that potentially reduced the rate of earthquakes and the possible generation of larger earthquakes.

  1. Rapid change in articulatory lip movement induced by preceding auditory feedback during production of bilabial plosives.

    Science.gov (United States)

    Mochida, Takemi; Gomi, Hiroaki; Kashino, Makio

    2010-11-08

    There has been plentiful evidence of kinesthetically induced rapid compensation for unanticipated perturbation in speech articulatory movements. However, the role of auditory information in stabilizing articulation has been little studied except for the control of voice fundamental frequency, voice amplitude and vowel formant frequencies. Although the influence of auditory information on the articulatory control process is evident in unintended speech errors caused by delayed auditory feedback, the direct and immediate effect of auditory alteration on the movements of articulators has not been clarified. This work examined whether temporal changes in the auditory feedback of bilabial plosives immediately affects the subsequent lip movement. We conducted experiments with an auditory feedback alteration system that enabled us to replace or block speech sounds in real time. Participants were asked to produce the syllable /pa/ repeatedly at a constant rate. During the repetition, normal auditory feedback was interrupted, and one of three pre-recorded syllables /pa/, /Φa/, or /pi/, spoken by the same participant, was presented once at a different timing from the anticipated production onset, while no feedback was presented for subsequent repetitions. Comparisons of the labial distance trajectories under altered and normal feedback conditions indicated that the movement quickened during the short period immediately after the alteration onset, when /pa/ was presented 50 ms before the expected timing. Such change was not significant under other feedback conditions we tested. The earlier articulation rapidly induced by the progressive auditory input suggests that a compensatory mechanism helps to maintain a constant speech rate by detecting errors between the internally predicted and actually provided auditory information associated with self movement. The timing- and context-dependent effects of feedback alteration suggest that the sensory error detection works in a

  2. Rapid change in articulatory lip movement induced by preceding auditory feedback during production of bilabial plosives.

    Directory of Open Access Journals (Sweden)

    Takemi Mochida

    Full Text Available BACKGROUND: There has been plentiful evidence of kinesthetically induced rapid compensation for unanticipated perturbation in speech articulatory movements. However, the role of auditory information in stabilizing articulation has been little studied except for the control of voice fundamental frequency, voice amplitude and vowel formant frequencies. Although the influence of auditory information on the articulatory control process is evident in unintended speech errors caused by delayed auditory feedback, the direct and immediate effect of auditory alteration on the movements of articulators has not been clarified. METHODOLOGY/PRINCIPAL FINDINGS: This work examined whether temporal changes in the auditory feedback of bilabial plosives immediately affects the subsequent lip movement. We conducted experiments with an auditory feedback alteration system that enabled us to replace or block speech sounds in real time. Participants were asked to produce the syllable /pa/ repeatedly at a constant rate. During the repetition, normal auditory feedback was interrupted, and one of three pre-recorded syllables /pa/, /Φa/, or /pi/, spoken by the same participant, was presented once at a different timing from the anticipated production onset, while no feedback was presented for subsequent repetitions. Comparisons of the labial distance trajectories under altered and normal feedback conditions indicated that the movement quickened during the short period immediately after the alteration onset, when /pa/ was presented 50 ms before the expected timing. Such change was not significant under other feedback conditions we tested. CONCLUSIONS/SIGNIFICANCE: The earlier articulation rapidly induced by the progressive auditory input suggests that a compensatory mechanism helps to maintain a constant speech rate by detecting errors between the internally predicted and actually provided auditory information associated with self movement. The timing- and context

  3. Multimodal imaging documentation of rapid evolution of retinal changes in handheld laser-induced maculopathy.

    Science.gov (United States)

    Dhrami-Gavazi, Elona; Lee, Winston; Balaratnasingam, Chandrakumar; Kayserman, Larisa; Yannuzzi, Lawrence A; Freund, K Bailey

    2015-01-01

    To use multimodal imaging to document the relatively rapid clinical evolution of handheld laser-induced maculopathy (HLIM). To demonstrate that inadvertent ocular injury can result from devices mislabeled with respect to their power specifications. The clinical course of a 17-year-old male who sustained self-inflicted, central macular damage from a 20-25 s direct stare at a red-spectrum, handheld laser pointer ordered from an internet retailer is provided. Retrospective review of multimodal imaging that includes fundus photography, fluorescein angiography, MultiColor reflectance, eye-tracked spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence, and microperimetry is used to describe the evolving clinical manifestations of HLIM in the first 3 months. Curvilinear bands of dense hyperreflectivity extending from the outer retina and following the Henle fibers were seen on SD-OCT immediately after injury. This characteristic appearance had largely resolved by 2 weeks. There was significant non-uniformity in the morphological characteristics of HLIM lesions between autofluorescence and reflectance images. The pattern of lesion evolution was also significantly different between imaging modalities. Analysis of the laser device showed its wavelength to be correctly listed, but the power was found to be 102.5-105 mW, as opposed to the laser -induced maculopathy, this finding can undergo rapid resolution in the span of several days. In the absence of this finding, other multimodal imaging clues and a careful history may aid in recognizing this diagnosis. A greater awareness regarding inaccurate labeling on some of these devices could help reduce the frequency of this preventable entity.

  4. Practical biophysics: Sensors for rapid detection of biological targets utilizing target-induced oligonucleotide annealing.

    Science.gov (United States)

    Heyduk, Tomasz

    2010-10-01

    Detection and quantitation of biomolecules is one of the most commonly performed measurements in biomedical research and clinical diagnostics. There is high demand for convenient, rapid and sensitive biomolecule detection methodologies. In this review we discuss a family of sensors that have been developed in our laboratory that share a common simple biophysical mechanism of action and that are capable of rapid detection of a diverse range of biological targets. The sensors generate fluorescence signal in the presence of the target molecule through target-induced association of short fluorochrome-labeled complementary oligonucleotides that are attached to target recognition elements of the sensors (antibodies, aptamers, etc.) via nanometer scale flexible linkers. This sensor design can be used for detecting proteins, antibodies, nucleic acids and whole cells. The assays using these sensors require only adding a sample to the sensor mix followed by simple fluorescence intensity readout. The simplicity, the speed of detection and the potential for miniaturization are the main assets of these sensors. 2010 Elsevier B.V. All rights reserved.

  5. Virus-associated activation of innate immunity induces rapid disruption of Peyer's patches in mice.

    Science.gov (United States)

    Heidegger, Simon; Anz, David; Stephan, Nicolas; Bohn, Bernadette; Herbst, Tina; Fendler, Wolfgang Peter; Suhartha, Nina; Sandholzer, Nadja; Kobold, Sebastian; Hotz, Christian; Eisenächer, Katharina; Radtke-Schuller, Susanne; Endres, Stefan; Bourquin, Carole

    2013-10-10

    Early in the course of infection, detection of pathogen-associated molecular patterns by innate immune receptors can shape the subsequent adaptive immune response. Here we investigate the influence of virus-associated innate immune activation on lymphocyte distribution in secondary lymphoid organs. We show for the first time that virus infection of mice induces rapid disruption of the Peyer's patches but not of other secondary lymphoid organs. The observed effect was not dependent on an active infectious process, but due to innate immune activation and could be mimicked by virus-associated molecular patterns such as the synthetic double-stranded RNA poly(I:C). Profound histomorphologic changes in Peyer's patches were associated with depletion of organ cellularity, most prominent among the B-cell subset. We demonstrate that the disruption is entirely dependent on type I interferon (IFN). At the cellular level, we show that virus-associated immune activation by IFN-α blocks B-cell trafficking to the Peyer's patches by downregulating expression of the homing molecule α4β7-integrin. In summary, our data identify a mechanism that results in type I IFN-dependent rapid but reversible disruption of intestinal lymphoid organs during systemic viral immune activation. We propose that such rerouted lymphocyte trafficking may impact the development of B-cell immunity to systemic viral pathogens.

  6. Cyclone-induced rapid creation of extreme Antarctic sea ice conditions.

    Science.gov (United States)

    Wang, Zhaomin; Turner, John; Sun, Bo; Li, Bingrui; Liu, Chengyan

    2014-06-17

    Two polar vessels, Akademik Shokalskiy and Xuelong, were trapped by thick sea ice in the Antarctic coastal region just to the west of 144°E and between 66.5°S and 67°S in late December 2013. This event demonstrated the rapid establishment of extreme Antarctic sea ice conditions on synoptic time scales. The event was associated with cyclones that developed at lower latitudes. Near the event site, cyclone-enhanced strong southeasterly katabatic winds drove large westward drifts of ice floes. In addition, the cyclones also gave southward ice drift. The arrival and grounding of Iceberg B9B in Commonwealth Bay in March 2011 led to the growth of fast ice around it, forming a northward protruding barrier. This barrier blocked the westward ice drift and hence aided sea ice consolidation on its eastern side. Similar cyclone-induced events have occurred at this site in the past after the grounding of Iceberg B9B. Future events may be predictable on synoptic time scales, if cyclone-induced strong wind events can be predicted.

  7. Loss of neuron-astroglial interaction rapidly induces protective CNTF expression after stroke in mice

    Science.gov (United States)

    Kang, Seong Su; Keasey, Matthew P.; Cai, Jun; Hagg, Theo

    2012-01-01

    Ciliary neurotrophic factor (CNTF) is a potent neural cytokine with very low expression in the CNS, predominantly by astrocytes. CNTF increases rapidly and greatly following traumatic or ischemic injury. Understanding the underlying mechanisms would help to design pharmacological treatments to increase endogenous CNTF levels for neuroprotection. Here, we show that astroglial CNTF expression in the adult mouse striatum is increased two-fold within 1 hour and increases up to >30 fold over two weeks following a focal stroke caused by a transient middle cerebral artery occlusion (MCAO). Selective neuronal loss caused by intrastriatal injection of quinolinic acid resulted in a comparable increase. Co-cultured neurons reduced CNTF expression in astrocytes which was prevented by light trypsinization. RGD blocking peptides induced CNTF expression which was dependent on transcription. Astroglial CNTF expression was not affected by diffusible neuronal molecules or by neurotransmitters. The transient ischemia does not seem to directly increase CNTF, as intrastriatal injection of an ischemic solution or exposure of naive mice or cultured cells to severe hypoxia had minimal effects. Inflammatory mechanisms were probably also not involved, as intrastriatal injection of pro-inflammatory cytokines (IFNγ, IL6) in naive mice had no or small effects, and anti-inflammatory treatments did not diminish the increase in CNTF after MCAO. CNTF−/− mice had more extensive tissue loss and similar astrocyte activation after MCAO than their wildtype littermates. These data suggest that contact-mediated integrin signaling between neurons and astrocytes normally represses CNTF expression and that neuronal dysfunction causes a rapid protective response by the CNS. PMID:22764235

  8. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

    Science.gov (United States)

    Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

    2015-11-01

    Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. Copyright © 2015 by The American Association of Immunologists, Inc.

  9. Large plasma-membrane depolarization precedes rapid blue-light-induced growth inhibition in cucumber

    Science.gov (United States)

    Spalding, E. P.; Cosgrove, D. J.

    1989-01-01

    Blue-light (BL)-induced suppression of elongation of etiolated Cucumis sativus L. hypocotyls began after a 30-s lag time, which was halved by increasing the fluence rate from 10 to 100 micromoles m-2 s-1. Prior to the growth suppression, the plasma-membrane of the irradiated cells depolarized by as much as 100 mV, then returned within 2-3 min to near its initial value. The potential difference measured with surface electrodes changed with an identical time course but opposite polarity. The lag time for the change in surface potential showed an inverse dependence on fluence rate, similar to the lag for the growth inhibition. Green light and red light caused neither the electrical response nor the rapid inhibition of growth. The depolarization by BL did not propagate to nonirradiated regions and exhibited a refractory period of about 10 min following a BL pulse. Fluence-response relationships for the electrical and growth responses provide correlational evidence that the plasma-membrane depolarization reflects an event in the transduction chain of this light-growth response.

  10. Rapid Analysis of Ash Composition Using Laser-Induced Breakdown Spectroscopy (LIBS)

    Energy Technology Data Exchange (ETDEWEB)

    Tyler L. Westover

    2013-01-01

    Inorganic compounds are known to be problematic in the thermochemical conversion of biomass to syngas and ultimately hydrocarbon fuels. The elements Si, K, Ca, Na, S, P, Cl, Mg, Fe, and Al are particularly problematic and are known to influence reaction pathways, contribute to fouling and corrosion, poison catalysts, and impact waste streams. Substantial quantities of inorganic species can be entrained in the bark of trees during harvest operations. Herbaceous feedstocks often have even greater quantities of inorganic constituents, which can account for as much as one-fifth of the total dry matter. Current methodologies to measure the concentrations of these elements, such as inductively coupled plasma-optical emission spectrometry/mass spectrometry (ICP-OES/MS) are expensive in time and reagents. This study demonstrates that a new methodology employing laser-induced breakdown spectroscopy (LIBS) can rapidly and accurately analyze the inorganic constituents in a wide range of biomass materials, including both woody and herbaceous examples. This technique requires little or no sample preparation, does not consume any reagents, and the analytical data is available immediately. In addition to comparing LIBS data with the results from ICP-OES methods, this work also includes discussions of sample preparation techniques, calibration curves for interpreting LIBS spectra, minimum detection limits, and the use of internal standards and standard reference materials.

  11. Laser-Induced Breakdown Spectroscopy for the Rapid Characterization of Lead-Free Gunshot Residues.

    Science.gov (United States)

    Fambro, Lashaundra A; Vandenbos, Deidre D; Rosenberg, Matthew B; Dockery, Christopher R

    2017-04-01

    This study investigated the use of laser-induced breakdown spectroscopy (LIBS) and scanning electron microscopy energy dispersive X-ray spectroscopy (SEM-EDX) as means of characterizing gunshot residue (GSR) originating from commercially available lead-free rounds. Data from two experiments are presented in this work. One experiment focused on identifying prominent analytical markers present in lead-free GSR by LIBS while the other applied SEM-EDX to determine the degree of evidence preservation after LIBS analysis. Samples of GSR were collected via tape-lift method from the hands of volunteer shooters and instrumental analyses were conducted in triplicate. As a result, the lead-free ammunition analyzed in this work generated GSRs comprising primarily Ba, Al, Si, and/or K. Trace amounts of Ti, Fe, and S were also apparent in some compositions. Through SEM-EDX analysis, a spheroidal geometry consistent with traditional lead-containing GSR was observed. Additionally, it was determined that evidence is preserved after LIBS analysis which supports the implementation of LIBS as a rapid preliminary screening method followed by confirmatory testing via SEM-EDX on the preserved evidence.

  12. Rapid and simple IgG specific test for the exclusion of heparin induced thrombocytopenia (HIT).

    Science.gov (United States)

    Kolde, Hans-Jürgen; Dostatni, Ralf; Mauracher, Susanne

    2011-08-29

    The exclusion of heparin induced thrombocytopenia (HIT) is required for selecting the most appropriate anticoagulation therapy in affected patients. It requires the combination of clinical data with the detection of antibodies directed against platelet factor 4 (PF4) in complex with polyanions (PA) such as heparin. We developed a lateral flow immunoassay (LFIA) for PF4/PA complex specific IgG antibodies based on gold nanoparticles. Unlike most other assays, the initial immune reaction takes place in the liquid phase. The sensitivity of the assay has been adjusted with clinical samples aiming in the reliable detection of sera which are positive in a functional platelet activation assay. Sera from 60 patients with suspected HIT were investigated. LFIA identified correctly all samples (n=20) which were positive in a functional assay (HIPA) and an IgG specific ELISA. It correlated with ELISA, but false positive results were less frequent (7 samples were negative with LFIA and HIPA but positive with ELISA). The LFIA may be a suitable tool for the rapid exclusion of HIT within 10 min.

  13. A specific glycerol kinase induces rapid cold hardening of the diamondback moth, Plutella xylostella.

    Science.gov (United States)

    Park, Youngjin; Kim, Yonggyun

    2014-08-01

    Insects in temperate zones survive low temperatures by migrating or tolerating the cold. The diamondback moth, Plutella xylostella, is a serious insect pest on cabbage and other cruciferous crops worldwide. We showed that P. xylostella became cold-tolerant by expressing rapid cold hardiness (RCH) in response to a brief exposure to moderately low temperature (4°C) for 7h along with glycerol accumulation in hemolymph. Glycerol played a crucial role in the cold-hardening process because exogenously supplying glycerol significantly increased the cold tolerance of P. xylostella larvae without cold acclimation. To determine the genetic factor(s) responsible for RCH and the increase of glycerol, four glycerol kinases (GKs), and glycerol-3-phosphate dehydrogenase (PxGPDH) were predicted from the whole P. xylostella genome and analyzed for their function associated with glycerol biosynthesis. All predicted genes were expressed, but differed in their expression during different developmental stages and in different tissues. Expression of the predicted genes was individually suppressed by RNA interference (RNAi) using double-stranded RNAs specific to target genes. RNAi of PxGPDH expression significantly suppressed RCH and glycerol accumulation. Only PxGK1 among the four GKs was responsible for RCH and glycerol accumulation. Furthermore, PxGK1 expression was significantly enhanced during RCH. These results indicate that a specific GK, the terminal enzyme to produce glycerol, is specifically inducible during RCH to accumulate the main cryoprotectant. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Rapid flow cytometric measurement of cytokine-induced phosphorylation pathways [CIPP] in human peripheral blood leukocytes.

    Science.gov (United States)

    Montag, David T; Lotze, Michael T

    2006-11-01

    Current strategies designed to assess cells in the peripheral blood are limited to evaluation of phenotype or delayed measurement [>6 h] of function, usually quantifying cytokine production, cytolytic activity, or response to antigens. We reasoned that measurable abnormalities in signaling pathways could reflect pathological environs that cells experience in the setting of inflammatory states/cancer and could be represented in the peripheral blood. Two major pathways regulating the immune response are the JAK/STAT and MAPK/ERK pathways. These pathways are initiated by ligand-receptor binding and are rapidly propagated by subsequent protein phosphorylation cascades. We evaluated the brief application of cytokines in vitro to interrogate the early phosphorylation events of these signaling pathways in normal peripheral blood mononuclear cells (PBMC). Individual cytokine doses and time intervals of treatment were assessed to identify conditions useful in a clinical laboratory and as an initial goal to induce maximal phosphorylation. Surprisingly, all of the STAT proteins assessed and ERK1/2 are maximally phosphorylated within 15 min in human PBMC simply following addition of cytokines without preactivation of the cells. At 2 h, cells typically return to their basal phosphorylation states. For most of the cytokines tested, increased phosphorylation directly correlated with increased concentrations of the individual cytokines. These strategies will enable robust development of simple blood analyses to identify normal levels as well as impairments in STAT and MAPK/ERK signaling pathways associated with various human disease states including acute and chronic inflammatory conditions throughout clinical immunology.

  15. Flow induced dispersion analysis rapidly quantifies proteins in human plasma samples.

    Science.gov (United States)

    Poulsen, Nicklas N; Andersen, Nina Z; Østergaard, Jesper; Zhuang, Guisheng; Petersen, Nickolaj J; Jensen, Henrik

    2015-07-07

    Rapid and sensitive quantification of protein based biomarkers and drugs is a substantial challenge in diagnostics and biopharmaceutical drug development. Current technologies, such as ELISA, are characterized by being slow (hours), requiring relatively large amounts of sample and being subject to cumbersome and expensive assay development. In this work a new approach for quantification based on changes in diffusivity is presented. The apparent diffusivity of an indicator molecule interacting with the protein of interest is determined by Taylor Dispersion Analysis (TDA) in a hydrodynamic flow system. In the presence of the analyte the apparent diffusivity of the indicator changes due to complexation. This change in diffusivity is used to quantify the analyte. This approach, termed Flow Induced Dispersion Analysis (FIDA), is characterized by being fast (minutes), selective (quantification is possible in a blood plasma matrix), fully automated, and being subject to a simple assay development. FIDA is demonstrated for quantification of the protein Human Serum Albumin (HSA) in human plasma as well as for quantification of an antibody against HSA. The sensitivity of the FIDA assay depends on the indicator-analyte dissociation constant which in favourable cases is in the sub-nanomolar to picomolar range for antibody-antigen interactions.

  16. Rapid EEG desynchronization and EMG activation induced by intravenous cocaine in freely moving rats: a peripheral, nondopamine neural triggering.

    Science.gov (United States)

    Kiyatkin, Eugene A; Smirnov, Michael S

    2010-02-01

    Many important physiological, behavioral, and psychoemotional effects of intravenous (IV) cocaine (COC) are too fast and transient compared with pharmacokinetic predictions, suggesting a possible involvement of peripheral neural mechanisms in their triggering. In the present study, we examined changes in cortical electroencephalogram (EEG) and neck electromyogram (EMG) induced in freely moving rats by IV COC administration at low, reinforcing doses (0.25-1.0 mg/kg) and compared them with those induced by an auditory stimulus and IV COC methiodide, which cannot cross the blood-brain barrier. We found that COC induces rapid, strong, and prolonged EEG desynchronization, associated with decrease in alpha and increase in beta and gamma activities, and EMG activation and that both begin within 2-6 s following the start of a 10-s injection; immediate components of this effect were dose independent. The rapid COC-induced changes in EEG and EMG resembled those induced by an auditory stimulus; the latter effects had shorter onset latencies and durations and were fully blocked during urethane anesthesia. Although urethane anesthesia completely blocked COC-induced EMG activation and rapid components of EEG response, COC still induced EEG desynchronization that was much weaker, greatly delayed (approximately 60 s), and associated with tonic decreases in delta and increases in alpha, beta, and gamma activities. Surprisingly, IV saline delivered during slow-wave sleep (but not quite wakefulness) also induced a transient EEG desynchronization but without changes in EMG activity; these effects were also fully blocked during anesthesia. Peripherally acting COC methiodide fully mimicked rapid EEG and EMG effects of regular COC, but the effects at an equimolar dose were less prolonged than those with regular COC. These data suggest that in awake animals IV COC, like somato-sensory stimuli, induces cortical activation and a subsequent motor response via its action on peripheral neural

  17. Use of molecular beacons for the rapid analysis of DNA damage induced by exposure to an atmospheric pressure plasma jet

    Energy Technology Data Exchange (ETDEWEB)

    Kurita, Hirofumi, E-mail: kurita@ens.tut.ac.jp, E-mail: mizuno@ens.tut.ac.jp; Miyachika, Saki; Yasuda, Hachiro; Takashima, Kazunori; Mizuno, Akira, E-mail: kurita@ens.tut.ac.jp, E-mail: mizuno@ens.tut.ac.jp [Department of Environmental and Life Sciences, Toyohashi University of Technology, Aichi 441-8580 (Japan)

    2015-12-28

    A rapid method for evaluating the damage caused to DNA molecules upon exposure to plasma is demonstrated. Here, we propose the use of a molecular beacon for rapid detection of DNA strand breaks induced by atmospheric pressure plasma jet (APPJ) irradiation. Scission of the molecular beacon by APPJ irradiation leads to separation of the fluorophore-quencher pair, resulting in an increase in fluorescence that directly correlates with the DNA strand breaks. The results show that the increase in fluorescence intensity is proportional to the exposure time and the rate of fluorescence increase is proportional to the discharge power. This simple and rapid method allows the estimation of DNA damage induced by exposure to a non-thermal plasma.

  18. Speleothem isotopic evidence for rapid human-induced expansion of grasslands in Madagascar at 890 CE

    Science.gov (United States)

    Burns, S. J.; Godfrey, L.; Faina, P.; McGee, D.; Hardt, B. F.; Ranivoharimanana, L.; Randrianasy, J.

    2015-12-01

    The degree to which human activity impacted the landscape, vegetation and fauna of Madagascar remains under debate. Since the early 1920's, the prevailing hypothesis has been that the savannah grasslands that now cover 70% of Madagascar were the result of deforestation, which has also been tied to the disappearance of much of the island's endemic megafauna. Other studies suggest that Madagascar's grasslands are largely natural and that megafaunal extinctions may be climatically induced, leading some authors to question the entire narrative of extensive alteration of the landscape by early human activity. We collected two stalagmites, M14-AB2 and M14-AB3, from Anjohibe Cave in northwestern Madagascar (15.55°S, 46.89°E, 100 masl). Age models were constructed using 8 U/Th age determinations from AB2 and 10 from AB3. The samples began to grow at ~500 CE and were active at the time of collection. Carbon and oxygen stable isotope ratios were measured on 266 samples from AB2 and 173 samples from AB3, yielding sub-decadal temporal resolution. A rapid, more than 10 per mil increase in stalagmite carbon stable isotope ratios documents an almost complete transformation of the landscape from one with a flora dominated by C3 plants to a C4 grassland system. This transformation, well replicated in both stalagmites, occurred at approximately 890 +/- 20 CE and was complete in 100 years. Further, relatively constant oxygen isotope ratios across the carbon isotope transition demonstrate that landscape alteration was not related to changes in climate. We hypothesize that the transformation was caused primarily by expansion of the use of fire by early inhabitants of Madagascar to promote agriculture and the growth of grass as fodder for cattle. The resulting loss of forest habitat very likely increased environmental pressures on Madagascar's megafauna and accelerated their disappearance.

  19. Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice.

    Science.gov (United States)

    Chikamoto, Keita; Misu, Hirofumi; Takayama, Hiroaki; Kikuchi, Akihiro; Ishii, Kiyo-Aki; Lan, Fei; Takata, Noboru; Tajima-Shirasaki, Natsumi; Takeshita, Yumie; Tsugane, Hirohiko; Kaneko, Shuichi; Matsugo, Seiichi; Takamura, Toshinari

    2016-09-23

    Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days. In contrast, a switch from a RD to a HFD rapidly elevated serum LECT2 levels. Serum LECT2 levels showed a positive correlation with liver triglyceride contents but not with adipose tissue weight. This study demonstrates the rapid response of LECT2 preceding body weight alterations during weight cycling in mice and suggests that measurement of serum LECT2 may be clinically useful in the management of obesity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Luminal leptin induces rapid inhibition of active intestinal absorption of glucose mediated by sodium-glucose cotransporter 1.

    Science.gov (United States)

    Ducroc, Robert; Guilmeau, Sandra; Akasbi, Khalil; Devaud, Hélène; Buyse, Marion; Bado, André

    2005-02-01

    The effect of leptin on glucose transport was studied in rat jejunal mucosa in Ussing chambers. Leptin was added in the luminal or the serosal compartment before the tissues were challenged with 1, 10, or 50 mmol/l glucose. In response to 10 mmol/l glucose, the increase in short-circuit current (DeltaIsc) reached 26.8 +/- 2.1 microA/cm(2). Luminal addition of leptin dramatically decreased glucose-induced Isc (90.5% for 10 nmol/l leptin). Inhibition was maximal after 5 min and dose dependent (IC(50) = 0.13 nM). Western blot analysis showed that rapid inhibition of glucose-induced Isc by leptin was associated with a parallel decrease in the abundance of sodium-glucose transporter-1 in brush border membranes. Inhibition by luminal leptin of DeltaIsc was prevented by inhibitor of conventional protein kinase C isoforms. Serosal addition of leptin did not decrease glucose-induced Isc within 5 min and reached maximum after 10 min. The effect of leptin from serosal side was blocked by cholecystokinin (CCK) receptor-2 receptor antagonist YM022. Altogether, these data demonstrate that luminal leptin induces rapid inhibition of glucose entry into enterocyte. The slower action of leptin on the serosal side of mucosa seems indirect and is likely mediated by endogenous CCK. They demonstrate that gut leptin is a major regulator of rapid intestinal glucose transport.

  1. A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness

    Directory of Open Access Journals (Sweden)

    Greinwald John H

    2009-01-01

    Full Text Available Abstract Background South Africa has one of the highest incidences of multidrug-resistant tuberculosis (MDR-TB in the world. Concomitantly, aminoglycosides are commonly used in this country as a treatment against MDR-TB. To date, at least five mutations are known to confer susceptibility to aminoglycoside-induced hearing loss. The aim of the present study was to develop a rapid screening method to determine whether these mutations are present in the South African population. Methods A multiplex method using the SNaPshot technique was used to screen for five mutations in the MT-RNR1 gene: A1555G, C1494T, T1095C, 961delT+C(n and A827G. A total of 204 South African control samples, comprising 98 Mixed ancestry and 106 Black individuals were screened for the presence of the five mutations. Results A robust, cost-effective method was developed that detected the presence of all five sequence variants simultaneously. In this pilot study, the A1555G mutation was identified at a frequency of 0.9% in the Black control samples. The 961delT+C(n variant was present in 6.6% of the Black controls and 2% of the Mixed ancestry controls. The T1095C, C1494T and A827G variants were not identified in any of the study participants. Conclusion The frequency of 0.9% for the A1555G mutation in the Black population in South Africa is of concern given the high incidence of MDR-TB in this particular ethnic group. Future larger studies are warranted to determine the true frequencies of the aminoglycoside deafness mutations in the general South African population. The high frequencies of the 961delT+C(n variant observed in the controls suggest that this change is a common non-pathogenic polymorphism. This genetic method facilitates the identification of individuals at high risk of developing hearing loss prior to the start of aminoglycoside therapy. This is important in a low-resource country like South Africa where, despite their adverse side-effects, aminoglycosides will

  2. A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness.

    Science.gov (United States)

    Bardien, Soraya; Human, Hannique; Harris, Tashneem; Hefke, Gwynneth; Veikondis, Rene; Schaaf, H Simon; van der Merwe, Lize; Greinwald, John H; Fagan, Johan; de Jong, Greetje

    2009-01-13

    South Africa has one of the highest incidences of multidrug-resistant tuberculosis (MDR-TB) in the world. Concomitantly, aminoglycosides are commonly used in this country as a treatment against MDR-TB. To date, at least five mutations are known to confer susceptibility to aminoglycoside-induced hearing loss. The aim of the present study was to develop a rapid screening method to determine whether these mutations are present in the South African population. A multiplex method using the SNaPshot technique was used to screen for five mutations in the MT-RNR1 gene: A1555G, C1494T, T1095C, 961delT+C(n) and A827G. A total of 204 South African control samples, comprising 98 Mixed ancestry and 106 Black individuals were screened for the presence of the five mutations. A robust, cost-effective method was developed that detected the presence of all five sequence variants simultaneously. In this pilot study, the A1555G mutation was identified at a frequency of 0.9% in the Black control samples. The 961delT+C(n) variant was present in 6.6% of the Black controls and 2% of the Mixed ancestry controls. The T1095C, C1494T and A827G variants were not identified in any of the study participants. The frequency of 0.9% for the A1555G mutation in the Black population in South Africa is of concern given the high incidence of MDR-TB in this particular ethnic group. Future larger studies are warranted to determine the true frequencies of the aminoglycoside deafness mutations in the general South African population. The high frequencies of the 961delT+C(n) variant observed in the controls suggest that this change is a common non-pathogenic polymorphism. This genetic method facilitates the identification of individuals at high risk of developing hearing loss prior to the start of aminoglycoside therapy. This is important in a low-resource country like South Africa where, despite their adverse side-effects, aminoglycosides will continue to be used routinely and are accompanied with very

  3. Rapid hardening induced by electric pulse annealing in nanostructured pure aluminum

    DEFF Research Database (Denmark)

    Zeng, Wei; Shen, Yao; Zhang, Ning

    2012-01-01

    source-limited hardening” mechanism. However, the hardening kinetics was substantially faster for the electric pulse annealed material. Detailed microstructural characterization suggested that the rapid hardening during electric pulse annealing is related to an enhanced rate of recovery of dislocation...

  4. Sudden collapse of vacuoles in Saintpaulia sp. palisade cells induced by a rapid temperature decrease.

    Science.gov (United States)

    Kadohama, Noriaki; Goh, Tatsuaki; Ohnishi, Miwa; Fukaki, Hidehiro; Mimura, Tetsuro; Suzuki, Yoshihiro

    2013-01-01

    It is well known that saintpaulia leaf is damaged by the rapid temperature decrease when cold water is irrigated onto the leaf surface. We investigated this temperature sensitivity and the mechanisms of leaf damage in saintpaulia (Saintpaulia sp. cv. 'Iceberg') and other Gesneriaceae plants. Saintpaulia leaves were damaged and discolored when subjected to a rapid decrease in temperature, but not when the temperature was decreased gradually. Sensitivity to rapid temperature decrease increased within 10 to 20 min during pre-incubation at higher temperature. Injury was restricted to the palisade mesophyll cells, where there was an obvious change in the color of the chloroplasts. During a rapid temperature decrease, chlorophyll fluorescence monitored by a pulse amplitude modulated fluorometer diminished and did not recover even after rewarming to the initial temperature. Isolated chloroplasts were not directly affected by the rapid temperature decrease. Intracellular pH was monitored with a pH-dependent fluorescent dye. In palisade mesophyll cells damaged by rapid temperature decrease, the cytosolic pH decreased and the vacuolar membrane collapsed soon after a temperature decrease. In isolated chloroplasts, chlorophyll fluorescence declined when the pH of the medium was lowered. These results suggest that a rapid temperature decrease directly or indirectly affects the vacuolar membrane, resulting in a pH change in the cytosol that subsequently affects the chloroplasts in palisade mesophyll cells. We further confirmed that the same physiological damage occurs in other Gesneriaceae plants. These results strongly suggested that the vacuoles of palisade mesophyll cells collapsed during the initial phase of leaf injury.

  5. Sudden collapse of vacuoles in Saintpaulia sp. palisade cells induced by a rapid temperature decrease.

    Directory of Open Access Journals (Sweden)

    Noriaki Kadohama

    Full Text Available It is well known that saintpaulia leaf is damaged by the rapid temperature decrease when cold water is irrigated onto the leaf surface. We investigated this temperature sensitivity and the mechanisms of leaf damage in saintpaulia (Saintpaulia sp. cv. 'Iceberg' and other Gesneriaceae plants. Saintpaulia leaves were damaged and discolored when subjected to a rapid decrease in temperature, but not when the temperature was decreased gradually. Sensitivity to rapid temperature decrease increased within 10 to 20 min during pre-incubation at higher temperature. Injury was restricted to the palisade mesophyll cells, where there was an obvious change in the color of the chloroplasts. During a rapid temperature decrease, chlorophyll fluorescence monitored by a pulse amplitude modulated fluorometer diminished and did not recover even after rewarming to the initial temperature. Isolated chloroplasts were not directly affected by the rapid temperature decrease. Intracellular pH was monitored with a pH-dependent fluorescent dye. In palisade mesophyll cells damaged by rapid temperature decrease, the cytosolic pH decreased and the vacuolar membrane collapsed soon after a temperature decrease. In isolated chloroplasts, chlorophyll fluorescence declined when the pH of the medium was lowered. These results suggest that a rapid temperature decrease directly or indirectly affects the vacuolar membrane, resulting in a pH change in the cytosol that subsequently affects the chloroplasts in palisade mesophyll cells. We further confirmed that the same physiological damage occurs in other Gesneriaceae plants. These results strongly suggested that the vacuoles of palisade mesophyll cells collapsed during the initial phase of leaf injury.

  6. Yueju Pill Rapidly Induces Antidepressant-Like Effects and Acutely Enhances BDNF Expression in Mouse Brain

    Directory of Open Access Journals (Sweden)

    Wenda Xue

    2013-01-01

    Full Text Available The traditional antidepressants have a major disadvantage in delayed onset of efficacy, and the emerging fast-acting antidepressant ketamine has adverse behavioral and neurotoxic effects. Yueju pill, an herb medicine formulated eight hundred years ago by Doctor Zhu Danxi, has been popularly prescribed in China for alleviation of depression-like symptoms. Although several clinical outcome studies reported the relative short onset of antidepressant effects of Yueju, this has not been scientifically investigated. We, therefore, examined the rapid antidepressant effect of Yueju in mice and tested the underlying molecular mechanisms. We found that acute administration of ethanol extract of Yueju rapidly attenuated depressive-like symptoms in learned helpless paradigm, and the antidepressant-like effects were sustained for at least 24 hours in tail suspension test in ICR mice. Additionally, Yueju, like ketamine, rapidly increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus, whereas the BDNF mRNA expression remained unaltered. Yueju rapidly reduced the phosphorylation of eukaryotic elongation factor 2 (eEF2, leading to desuppression of BDNF synthesis. Unlike ketamine, both the BDNF expression and eEF2 phosphorylation were revered at 24 hours after Yueju administration. This study is the first to demonstrate the rapid antidepressant effects of an herb medicine, offering an opportunity to improve therapy of depression.

  7. Rapid inducible protein displacement in Plasmodium in vivo and in vitro using knocksideways technology [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Katie R. Hughes

    2017-03-01

    Full Text Available A deeper understanding of the biology of the Plasmodium parasite is essential in order to identify targets for interventions, with the ultimate aim of eliminating malaria. Determining the function(s of essential proteins in Plasmodium has, until recently, been hampered by the lack of efficient conditional systems to abrogate proteins. We report the adaptation of a conditional technology, knocksideways (KS, for use in Plasmodium berghei, which can potentially rapidly inactivate proteins of interest through relocalisation. The system is induced using rapamycin, which allows for KS both in vitro and in vivo and is effective more rapidly than any other reported system. KS utilises pairs of fluorescent tags that facilitate live imaging and allows for rapid confirmation of efficient protein redistribution on live parasites, allowing for streamlined workflows. We demonstrate the characteristics of the system using transgenically expressed cytoplasmic GFP and provide proof of principle by inducibly redistributing a number of proteins with different native, subcellular locations.  We also demonstrate that KS can be applied to both mammalian and insect stages of Plasmodium. KS expands the range of (conditional technologies for genetic manipulation of malaria parasites and offers the potential to be further developed for medium throughput phenotype screens.

  8. Calcium ionophore (A-23187 induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo

    Directory of Open Access Journals (Sweden)

    T. S. Rao

    1993-01-01

    Full Text Available The present investigation characterizes calcium ionophore (A-23187 induced peritoneal eicosanoid biosynthesis in the rat. Intraperitoneal injection of A-23187 (20 μg/rat stimulated marked biosynthesis of 6-keto-PGF1α (6-KPA, TxB2, LTC4 and LTB4, with no detectable changes on levels of PGE2. Levels of all eicosanoids decreased rapidly after a peak which was seen as early as 5 min. Enzyme markers of cellular contents of neutrophils and mononuclear cells, MPO and NAG respectively, decreased rapidly after ionophore injection; this was followed by increases after 60 min. Indomethacin, a selective cyclooxygenase inhibitor, and zileuton and ICI D-2138, two selective 5-lipoxygenase inhibitors attenuated prostaglandin and leukotriene pathways respectively. Oral administration of zileuton (20 mg/kg, p.o. inhibited LTB4 biosynthesis for up to 6 h suggesting a long duration of pharmacological activity in the rats consistent with its longer half-life. The rapid onset and the magnitude of increases in levels of eicosanoids render the ionophore induced peritoneal eicosanoid biosynthesis a useful model to evaluate pharmacological profiles of inhibitors of eicosanoid pathways in vivo.

  9. Ultra-rapid microwave variable pressure-induced histoprocessing : Description of a new tissue processor

    NARCIS (Netherlands)

    Visinoni, F; Milios, J; Leong, ASY; Boon, ME; Kok, LP; Malcangi, F

    We describe a new method of ultra-rapid histoprocessing that reduces the processing times for needle and endoscopic biopsies to 30 min and that of other surgical biopsy tissue blocks of up to 4 mm thick to 120 min. The MicroMED U R M Histoprocessor, which combines microwave irradiation with precise

  10. Collision-induced fragmentation accurate mass spectrometric analysis methods to rapidly characterize plant extracts

    Science.gov (United States)

    The rapid advances in analytical chromatography equipment have made the reliable and reproducible measurement of a wide range of plant chemical components possible. Full chemical characterization of a given plant material is possible with the new mass spectrometers currently available. For phytochem...

  11. Collision-induced fragmentation accurate mass spectrometric analysis methods to rapidly characterize phytochemicals in plant extracts

    Science.gov (United States)

    The rapid advances in analytical chromatography equipment have made the reliable and reproducible measurement of a wide range of plant chemical components possible. Full chemical characterization of a given plant material is possible with the new mass spectrometers currently available. New methods a...

  12. Bisphenol A induces a rapid activation of Erk1/2 through GPR30 in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dong, S. [Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566 (Japan); Institute of Urban Environment, Chinese Academy of Sciences, Xiamen (China); Terasaka, S. [Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566 (Japan); Kiyama, R., E-mail: kiyama.r@aist.go.j [Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566 (Japan)

    2011-01-15

    Bisphenol A (BPA) has been considered as an endocrine disruptor due to its ability to interact with estrogen receptors (ERs). While G protein-coupled receptor 30 (GPR30) is a novel estrogen receptor, its role in BPA-induced activation of Erk1/2 remains unknown. Human breast cancer cell lines, MCF-7, MDA-MB-231 and SKBR3, were used as experimental models to discriminate between ERs-dependent, putative ERs-independent and/or GPR30-associated effects. BPA induced a rapid activation of Erk1/2 in both ER{alpha}/{beta}-positive and negative breast cancer cells, and this effect was not blocked with an ER antagonist, ICI 182,780. A small interfering RNA assay revealed that the expression of GPR30 was necessary for BPA-induced activation of Erk1/2 and transcriptional regulation of c-fos. In addition, BPA regulates the expression of c-fos likely through an AP1-mediated pathway. As a conclusion, GPR30 plays an important role in the BPA-induced activation of Erk1/2 in a manner distinguishable from that in ER{alpha}-mediated signaling. - We showed here that the mechanism by which BPA induces the activation of Erk1/2 is distinguishable from the mechanism of ER{alpha}-mediated signaling in human breast cancer cells.

  13. Collateral damage: rapid exposure-induced evolution of pesticide resistance leads to increased susceptibility to parasites.

    Science.gov (United States)

    Jansen, Mieke; Stoks, Robby; Coors, Anja; van Doorslaer, Wendy; de Meester, Luc

    2011-09-01

    Although natural populations may evolve resistance to anthropogenic stressors such as pollutants, this evolved resistance may carry costs. Using an experimental evolution approach, we exposed different Daphnia magna populations in outdoor containers to the carbamate pesticide carbaryl and control conditions, and assessed the resulting populations for both their resistance to carbaryl as well as their susceptibility to infection by the widespread bacterial microparasite Pasteuria ramosa. Our results show that carbaryl selection led to rapid evolution of carbaryl resistance with seemingly no cost when assessed in a benign environment. However, carbaryl-resistant populations were more susceptible to parasite infection than control populations. Exposure to both stressors reveals a synergistic effect on sterilization rate by P. ramosa, but this synergism did not evolve under pesticide selection. Assessing costs of rapid adaptive evolution to anthropogenic stress in a semi-natural context may be crucial to avoid too optimistic predictions for the fitness of the evolving populations. © 2011 The Author(s).

  14. Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: Role of adipokines‡

    OpenAIRE

    Malvi, Parmanand; Chaube, Balkrishna; Pandey, Vimal; Vijayakumar, Maleppillil Vavachan; Boreddy, Purushotham Reddy; Mohammad, Naoshad; Singh, Shivendra Vikram; Bhat, Manoj Kumar

    2014-01-01

    Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric i...

  15. Apnea-Induced Rapid Eye Movement Sleep Disruption Impairs Human Spatial Navigational Memory

    OpenAIRE

    Varga, Andrew W.; Kishi, Akifumi; Mantua, Janna; Lim, Jason; Koushyk, Viachaslau; Leibert, David P.; Osorio, Ricardo S.; Rapoport, David M.; Ayappa, Indu

    2014-01-01

    Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restric...

  16. Phencyclidine false positive induced by lamotrigine (Lamictal®) on a rapid urine toxicology screen

    OpenAIRE

    Geraci, Matthew J.; Peele, James; McCoy, Stacey L.; Elias, Brad

    2010-01-01

    Background This report describes two cases with unexplained positive results for phencyclidine (PCP). Aims This case will correlate lamotrigine (Lamictal®) use with false-positive results for PCP on a rapid urine toxicology screen. Methods Case 1: A 62-year-old male arrived to the emergency department in extreme psychosis. All positive results on the urine drug screen could be accounted for except PCP. A comprehensive drug screen was performed to confirm PCP use, but returned negative. PCP wa...

  17. Rapid and Efficient Collection of Platinum from Karstedt's Catalyst Solution via Ligands-Exchange-Induced Assembly.

    Science.gov (United States)

    Yang, Gonghua; Wei, Yanlong; Huang, Zhenzhu; Hu, Jiwen; Liu, Guojun; Ou, Ming; Lin, Shudong; Tu, Yuanyuan

    2018-02-21

    Reported herein is a novel strategy for the rapid and efficient collection of platinum from Karstedt's catalyst solution. By taking advantage of a ligand-exchange reaction between alkynols and the 1,3-divinyltetramethyldisiloxane ligand (M Vi M Vi ) that coordinated with platinum (Pt(0)), the Karstedt's catalyst particles with a size of approximately 2.5 ± 0.7 nm could be reconstructed and assembled into larger particles with a size of 150 ± 35 nm due to the hydrogen bonding between the hydroxyl groups of the alkynol. In addition, because the silicone-soluble M Vi M Vi ligand of the Karstedt's catalyst was replaced by water-soluble alkynol ligands, the resultant large particles were readily dispersed in water, resulting in rapid, efficient, and complete collection of platinum from the Karstedt's catalyst solutions with platinum concentrations in the range from ∼20 000 to 0.05 ppm. Our current strategy not only was used for the rapid and efficient collection of platinum from the Karstedt's catalyst solutions, but it also enabled the precise evaluation of the platinum content in the Karstedt's catalysts, even if this platinum content was extremely low (i.e., 0.05 ppm). Moreover, these platinum specimens that were efficiently collected from the Karstedt's catalyst solutions could be directly used for the evaluation of platinum without the need for pretreatment processes, such as calcination and digestion with hydrofluoric acid, that were traditionally used prior to testing via inductively coupled plasma mass spectrometry in conventional methods.

  18. A new aggregation-induced emission fluorescent probe for rapid detection of nitroreductase and its application in living cells

    Science.gov (United States)

    Xu, Gaoping; Tang, Yonghe; Ma, Yanyan; Xu, An; Lin, Weiying

    2018-01-01

    The biological activity of nitroreductase (NTR) is closely related to biological hypoxia status in organisms. The development of effective methods for monitoring the activity of NTR is of great significance for medical diagnosis and tumor research. Toward this goal, we have developed a new aggregation-induced emission (AIE) fluorescence NTR probe TPE-HY used the tetraphenylethene as the fluorophore, and used the nitro group as the NTR recognition site. The probe TPE-HY has many excellent properties, including rapid response, AIE characteristics, high sensitivity and selectivity, and low cytotoxicity. Importantly, the probe TPE-HY is successfully applied to monitor endogenous NTR in living HeLa cells.

  19. Delayed ischemic electrocortical suppression during rapid repeated cerebral ischemia and kainate-induced seizures in rat

    DEFF Research Database (Denmark)

    Ilie, Andrei; Spulber, Stefan; Avramescu, Sinziana

    2006-01-01

    Global cerebral ischemia induces, within seconds, suppression of spontaneous electrocortical activity, partly due to alterations in synaptic transmission. In vitro studies have found that repeated brief hypoxic episodes prolong the persistence of synaptic transmission due to weakened adenosine...... hydrate anaesthesia. Repeated episodes of 1 min of ischemia were induced by transiently clamping the carotid arteries in a 'four-vessel occlusion' model. We devised an automatic method of T(ES) estimation based on the decay of the root mean square of two-channel electrocorticographic recordings...... in vitro....

  20. Toward a mechanistic understanding of human-induced rapid environmental change: A case study linking energy development, avian nest predation, and predators

    Science.gov (United States)

    Hethcoat, Matthew G.; Chalfoun, Anna D.

    2015-01-01

    Demographic consequences of human-induced rapid environmental change (HIREC) have been widely documented for many populations. The mechanisms underlying such patterns, however, are rarely investigated and yet are critical to understand for effective conservation and management.

  1. Atrial fibrillation in rats induced by rapid transesophageal atrial pacing during brief episodes of asphyxia: A new in vivo model

    DEFF Research Database (Denmark)

    Haugan, K.; Lam, Henrik Rye; Knudsen, C. B.

    2004-01-01

    in anesthetized male Sprague-Dawley rats. AF was reproducibly induced in 81% of the rats. The presence of AF was associated with an increased heart rate, and a decreased blood pressure. Treatment with amiodarone, D,L-sotalol, flecainide, and propranolol all reduced duration of AF, whereas verapamil treatment...... of verapamil. Relative to existing models of AF in larger animals, this model offers rapid, predictive, and inexpensive testing of antiarrhythmic/profibrillatory effects of new drugs.......Non-pharmacological in vivo models of atrial fibrillation (AF) have been developed in large animals only. We aimed to develop and characterize a new small animal non-pharmacological in vivo model of AF. AF was induced by transesophageal atrial burst pacing during 35 seconds periods of asphyxia...

  2. Rapid reversal of corticosteroid-induced mania with sodium valproate: a case series of 20 patients.

    Science.gov (United States)

    Roxanas, Milton G; Hunt, Glenn E

    2012-01-01

    Glucocorticoids are widely used in medicine and are known to cause psychiatric side effects, including mania. There is anecdotal evidence that sodium valproate is effective for treating psychiatric side effects of glucocorticoids. To describe a case series of 20 patients receiving corticosteroids for various medical conditions who developed manic-like symptoms. They were treated with sodium valproate while continuing on corticosteroids. Patients treated with corticosteroids who reported to their physician subjective distress or who were openly disruptive in the ward were assessed by a consultation-liaison psychiatrist on the same day with the Young Mania Rating Scale. Immediately afterwards, blood was taken to measure the cortisol or dexamethasone level and then started on sodium valproate 500 mg twice daily. Valproate levels were measured on day 3 to adjust the dose. There was a significant, rapid improvement of symptoms within 48 hours after sodium valproate was initiated. Within 72 hours all patients were euthymic and remained so over the ensuing week. The only major side effect was hyperammonemia in 1 case which resolved when valproate was stopped. This case series shows that sodium valproate is a safe medication that rapidly reverses manic-like symptoms within a few days without needing to stop the corticosteroids, thus allowing the medical treatment to continue. The ability to continue treatment while controlling or ameliorating the psychiatric side effects of glucocorticoids with sodium valproate is an advance over previous approaches. The mechanism of this rapid action is unclear and deserves further study. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  3. Vaccinia virus induces rapid necrosis in keratinocytes by a STAT3-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Yong He

    Full Text Available Humans with a dominant negative mutation in STAT3 are susceptible to severe skin infections, suggesting an essential role for STAT3 signaling in defense against cutaneous pathogens.To focus on innate antiviral defenses in keratinocytes, we used a standard model of cutaneous infection of severe combined immunodeficient mice with the current smallpox vaccine, ACAM-2000. In parallel, early events post-infection with the smallpox vaccine ACAM-2000 were investigated in cultured keratinocytes of human and mouse origin.Mice treated topically with a STAT3 inhibitor (Stattic developed larger vaccinia lesions with higher virus titers and died more rapidly than untreated controls. Cultured human and murine keratinocytes infected with ACAM-2000 underwent rapid necrosis, but when treated with Stattic or with inhibitors of RIP1 kinase or caspase-1, they survived longer, produced higher titers of virus, and showed reduced activation of type I interferon responses and inflammatory cytokines release. Treatment with inhibitors of RIP1 kinase and STAT3, but not caspase-1, also reduced the inflammatory response of keratinocytes to TLR ligands. Vaccinia growth properties in Vero cells, which are known to be defective in some antiviral responses, were unaffected by inhibition of RIP1K, caspase-1, or STAT3.Our findings indicate that keratinocytes suppress the replication and spread of vaccinia virus by undergoing rapid programmed cell death, in a process requiring STAT3. These data offer a new framework for understanding susceptibility to skin infection in patients with STAT3 mutations. Interventions which promote prompt necroptosis/pyroptosis of infected keratinocytes may reduce risks associated with vaccination with live vaccinia virus.

  4. Pericytes as Inducers of Rapid, Matrix Metalloproteinase-9-Dependent Capillary Damage during Ischemia.

    Science.gov (United States)

    Underly, Robert G; Levy, Manuel; Hartmann, David A; Grant, Roger I; Watson, Ashley N; Shih, Andy Y

    2017-01-04

    Blood-brain barrier disruption (BBB) and release of toxic blood molecules into the brain contributes to neuronal injury during stroke and other cerebrovascular diseases. While pericytes are builders and custodians of the BBB in the normal brain, their impact on BBB integrity during ischemia remains unclear. We imaged pericyte-labeled transgenic mice with in vivo two-photon microscopy to examine the relationship between pericytes and blood plasma leakage during photothrombotic occlusion of cortical capillaries. Upon cessation of capillary flow, we observed that plasma leakage occurred with three times greater frequency in regions where pericyte somata adjoined the endothelium. Pericyte somata covered only 7% of the total capillary length in cortex, indicating that a disproportionate amount of leakage occurred from a small fraction of the capillary bed. Plasma leakage was preceded by rapid activation of matrix metalloproteinase (MMP) at pericyte somata, which was visualized at high resolution in vivo using a fluorescent probe for matrix metalloproteinase-2/9 activity, fluorescein isothiocyanate (FITC)-gelatin. Coinjection of an MMP-9 inhibitor, but not an MMP-2 inhibitor, reduced pericyte-associated FITC-gelatin fluorescence and plasma leakage. These results suggest that pericytes contribute to rapid and localized proteolytic degradation of the BBB during cerebral ischemia. Pericytes are a key component of the neurovascular unit and are essential for normal BBB function. However, during acute ischemia, we find that pericytes are involved in creating rapid and heterogeneous BBB disruption in the capillary bed. The mechanism by which pericytes contribute to BBB damage warrants further investigation, as it may yield new therapeutic targets for acute stroke injury and other neurological diseases involving capillary flow impairment. Copyright © 2017 the authors 0270-6474/17/370129-12$15.00/0.

  5. Rapid normalization of vasculitis-induced left ventricular dysfunction related with multiple cardiac thrombi.

    Science.gov (United States)

    Ikonomidis, Ignatios; Ntai, Konstantina; Parissis, John; Palios, John; Vrettou, Agathi-Rosa; Paraskevaidis, Ioannis; Lekakis, John

    2015-10-01

    We present a young female patient admitted in the emergency department with pulmonary edema, severely impaired left ventricular function, and simultaneous intracardiac thrombi in left and right ventricle as well as in right atrium, at echocardiography. A magnetic resonance tomography showed excess myocardial tissue edema and diffuse gadolinium enhancement. Blood analysis showed an elevated eosinophils count. The patient showed a rapid normalization of left ventricular function as well as resolution of intracardiac thrombi and myocardial tissue edema 3 months after proper treatment with cyclophosphamide and steroids for Churg-Strauss syndrome.

  6. Rapid and Sustained Nuclear-Cytoplasmic ERK Oscillations Induced by Epidermal Growth Factor

    Energy Technology Data Exchange (ETDEWEB)

    Shankaran, Harish; Ippolito, Danielle L.; Chrisler, William B.; Resat, Haluk; Bollinger, Nikki; Opresko, Lee K.; Wiley, H. S.

    2009-12-01

    Mathematical modeling has predicted that ERK activity should oscillate in response to cell stimulation, but this has never been observed. To explore this inconsistency, we expressed an ERK1-GFP fusion protein in mammary epithelial cells. Following EGF stimulation, we observed rapid and continuous ERK oscillations between the nucleus and cytoplasm with a periodicity of approximately 15 minutes. These oscillations were remarkably persistent (>45 cycles), displayed an asymmetric waveform, and were highly dependent on cell density, essentially disappearing at confluency. We conclude that the ERK pathway is an intrinsic oscillator. Although the functional implications of the observed oscillations are uncertain, this property can be used to continuously monitor ERK activity in single cells.

  7. Internal rupture and rapid bouncing of impacting drops induced by submillimeter-scale textures

    Science.gov (United States)

    Zhang, Rui; Zhang, Xiwen; Hao, Pengfei; He, Feng

    2017-06-01

    We demonstrate an internal breakup mechanism for high Weber number drop impact on superhydrophobic surfaces uniformly patterned with submillimeter-scale textures, in which the liquid film ruptures from both interior and rim. The employment of submillimeter-scale posts could help decrease the critical Weber number of internal rupture, due to the small solid fraction and the large dimension ratio between primary structures and droplets. The internal rupture is found to promote more rapid drop bouncing than conventional rebound and rim breakup on superhydrophobic surfaces with small roughness, with a 10%-50% reduction of contact time. The internal rupture results from the film instability inside and the jet instability outside.

  8. Internal rupture and rapid bouncing of impacting drops induced by submillimeter-scale textures.

    Science.gov (United States)

    Zhang, Rui; Zhang, Xiwen; Hao, Pengfei; He, Feng

    2017-06-01

    We demonstrate an internal breakup mechanism for high Weber number drop impact on superhydrophobic surfaces uniformly patterned with submillimeter-scale textures, in which the liquid film ruptures from both interior and rim. The employment of submillimeter-scale posts could help decrease the critical Weber number of internal rupture, due to the small solid fraction and the large dimension ratio between primary structures and droplets. The internal rupture is found to promote more rapid drop bouncing than conventional rebound and rim breakup on superhydrophobic surfaces with small roughness, with a 10%-50% reduction of contact time. The internal rupture results from the film instability inside and the jet instability outside.

  9. Two genes with similarity to bacterial response regulators are rapidly and specifically induced by cytokinin in Arabidopsis

    Science.gov (United States)

    Brandstatter, I.; Kieber, J. J.; Evans, M. L. (Principal Investigator)

    1998-01-01

    Cytokinins are central regulators of plant growth and development, but little is known about their mode of action. By using differential display, we identified a gene, IBC6 (for induced by cytokinin), from etiolated Arabidopsis seedlings, that is induced rapidly by cytokinin. The steady state level of IBC6 mRNA was elevated within 10 min by the exogenous application of cytokinin, and this induction did not require de novo protein synthesis. IBC6 was not induced by other plant hormones or by light. A second Arabidopsis gene with a sequence highly similar to IBC6 was identified. This IBC7 gene also was induced by cytokinin, although with somewhat slower kinetics and to a lesser extent. The pattern of expression of the two genes was similar, with higher expression in leaves, rachises, and flowers and lower transcript levels in roots and siliques. Sequence analysis revealed that IBC6 and IBC7 are similar to the receiver domain of bacterial two-component response regulators. This homology, coupled with previously published work on the CKI1 histidine kinase homolog, suggests that these proteins may play a role in early cytokinin signaling.

  10. Phencyclidine false positive induced by lamotrigine (Lamictal®) on a rapid urine toxicology screen.

    Science.gov (United States)

    Geraci, Matthew J; Peele, James; McCoy, Stacey L; Elias, Brad

    2010-11-06

    This report describes two cases with unexplained positive results for phencyclidine (PCP). This case will correlate lamotrigine (Lamictal®) use with false-positive results for PCP on a rapid urine toxicology screen. Case 1: A 62-year-old male arrived to the emergency department in extreme psychosis. All positive results on the urine drug screen could be accounted for except PCP. A comprehensive drug screen was performed to confirm PCP use, but returned negative. PCP was ruled out as the causative agent. The reason for the PCP false positive remained unknown. Case 2: A 49-year-old female presented to the ED with a history of seizures and depression. Despite positive PCP results on a rapid urine drug screen, PCP use was ruled out due to patient presentation and comprehensive history. The differential diagnosis in case 1 included PCP abuse until PCP was ruled out by a comprehensive drug screen. A literature search failed to explain a reason for false-positive results. The patient in case 2 was not psychotic, but returned a positive urinalysis result for PCP. Case 2's presentation combined with a comprehensive history at the facility ruled out PCP use. Both patients were taking the anti-seizure medication lamotrigine with nothing else in common. Lamotrigine has the potential to cause false-positive results for PCP on the Bio-Rad TOX/See urine toxicology screen.

  11. Assessing surface albedo change and its induced radiation budget under rapid urbanization with Landsat and GLASS data

    Science.gov (United States)

    Hu, Yonghong; Jia, Gensuo; Pohl, Christine; Zhang, Xiaoxuan; van Genderen, John

    2016-02-01

    Radiative forcing (RF) induced by land use (mainly surface albedo) change is still not well understood in climate change science, especially the effects of changes in urban albedo due to rapid urbanization on the urban radiation budget. In this study, a modified RF derivation approach based on Landsat images was used to quantify changes in the solar radiation budget induced by variations in surface albedo in Beijing from 2001 to 2009. Field radiation records from a Beijing meteorological station were used to identify changes in RF at the local level. There has been rapid urban expansion over the last decade, with the urban land area increasing at about 3.3 % annually from 2001 to 2009. This has modified three-dimensional urban surface properties, resulting in lower albedo due to complex building configurations of urban centers and higher albedo on flat surfaces of suburban areas and cropland. There was greater solar radiation (6.93 × 108 W) in the urban center in 2009 than in 2001. However, large cropland and urban fringe areas caused less solar radiation absorption. RF increased with distance from the urban center (less than 14 km) and with greater urbanization, with the greatest value being 0.41 W/m2. The solar radiation budget in urban areas was believed to be mainly influenced by urban structural changes in the horizontal and vertical directions. Overall, the results presented herein indicate that cumulative urbanization impacts on the natural radiation budget could evolve into an important driver of local climate change.

  12. Rapid, Room-Temperature Formation of Crystalline Calcium Molybdate Phosphor Microparticles via Peptide-Induced Precipitation

    Science.gov (United States)

    2006-01-01

    accomplished by methods based on solid-state reaction, coprecipitation , combustion synthesis , or pyrolysis of organic precursors, such powder processing...lighting applications),[4] as catalysts in petrochemical process- ing (e.g., as an ester-exchange copolymerization catalyst ),[5] and as nontoxic... coprecipitation with low-melting organic or inorganic salts). Furthermore, the identification of peptides that locally induce the precipitation of such

  13. Fluconazole induces rapid high-frequency MTL homozygosis with microbiological polymorphism in Candida albicans

    Directory of Open Access Journals (Sweden)

    Tsong-Yih Ou

    2017-12-01

    Full Text Available Background: Candida albicans, a common fungal pathogen that can cause opportunistic infections, is regarded as an apparently asexual, diploid fungus. A parasexual cycle was previously found between homozygotes with opposite mating type-like loci (MTLa/α. Fluconazole-resistant strains had a higher proportion of MTL homozygotes, whereas MTL homozygous C. albicans was found in only about 3.2% of clinical strains. MTL heterozygotes had a low frequency (1.4 × 10−4 of white–opaque switching to MTL homozygotes in nature. Methods: Here, a reference C. albicans strain (SC5314 was used in a fluconazole-induced assay to obtain standard opaque MTL homozygous strains and first-generation daughter strains from the fluconazole inhibition zone. Further separation methods were employed to produce second- and third-generation daughter strains. Polymerase chain reaction analysis based on MTL genes was used to define MTL genotypes, and microscopic observations, a flow-cytometric assay, and an antifungal E-test were used to compare microbiological characteristics. Results: MTL homozygotes were found at a high frequency (17 of 35; 48.6% in fluconazole-induced first-generation daughter strains, as were morphological polymorphisms, decreased DNA content, and modified antifungal drug susceptibility. High-frequency MTL homozygosity was identified inside the fluconazole inhibition zone within 24 hours. The DNA content of fluconazole-induced daughter strains was reduced compared with their progenitor SC5314 and standard MTL homozygous strains. Conclusion: Treatment with fluconazole, commonly used to treat invasive candidiasis, inhibited the growth of C. albicans and altered its microbiological characteristics. Our results suggest that fluconazole treatment induces the high frequency of loss of heterozygosity and microbiological polymorphism in C. albicans. Keywords: Candida albicans, fluconazole, loss of heterozygosity, mating type-like gene

  14. Elevated levels of TRF2 induce telomeric ultrafine anaphase bridges and rapid telomere deletions.

    Science.gov (United States)

    Nera, Bernadette; Huang, Hui-Shun; Lai, Thao; Xu, Lifeng

    2015-12-07

    The shelterin protein TRF2 is essential for chromosome-end protection. Depletion of TRF2 causes chromosome end-to-end fusions, initiating genomic instability that can be cancer promoting. Paradoxically, significant increased levels of TRF2 are observed in a subset of human cancers. Experimental overexpression of TRF2 has also been shown to induce telomere shortening, through an unknown mechanism. Here we report that TRF2 overexpression results in replication stalling in duplex telomeric repeat tracts and the subsequent formation of telomeric ultrafine anaphase bridges (UFBs), ultimately leading to stochastic loss of telomeric sequences. These TRF2 overexpression-induced telomere deletions generate chromosome fusions resembling those detected in human cancers and in mammalian cells containing critically shortened telomeres. Therefore, our findings have uncovered a second pathway by which altered TRF2 protein levels can induce end-to-end fusions. The observations also provide mechanistic insight into the molecular basis of genomic instability in tumour cells containing significantly increased TRF2 levels.

  15. Rapid detection of radiation-induced chromosomal aberrations in lymphocytes and hematopoietic progenitor cells by mFISH

    Energy Technology Data Exchange (ETDEWEB)

    Greulich, K.M.; Rhein, A.P.; Brueckner, M.; Molls, M. [Department of Radiation Oncology, Technical University of Munich, Ismaninger Strasse 22, D-81675 Munich (Germany); Kreja, L. [Institute for Occupational, Social and Environmental Medicine, University of Ulm, Ulm (Germany); Heinze, B. [Department of Medical Genetics, University of Ulm, Ulm (Germany); Weier, H.-U.G. [Life Sciences Division, E.O. Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Fuchs, P. [Vysis GmbH, Bergisch-Gladbach (Germany)

    2000-07-20

    Structural chromosome aberrations (SCAs) are sensitive indicators of a preceding exposure of the hematopoietic system to ionizing radiation. Cytogenetic investigations have therefore become routine tools for an assessment of absorbed radiation doses and their biological effects after occupational exposure or radiation accidents. Due to its speed and ease of use, fluorescence in situ hybridization (FISH) with whole chromosome painting (WCP) probes has become a method of choice to visualize SCAs. Until recently, this technique was limited to a rather small number of chromosomes, which could be tested simultaneously. As a result, only a fraction of the structural aberrations present in a sample could be detected and the overall dose effect had to be calculated by extrapolation. The recent introduction of two genome-wide screening techniques in tumor research, i.e., Spectral Karyotyping (SKY) and multicolor FISH (mFISH) now allows the detection of translocations involving any two non-homologous chromosomes. The present study was prompted by our desire to bring the power of mFISH to bear for the rapid identification of radiation-induced SCAs. We chose two model systems to investigate the utility of mFISH: lymphocytes that were exposed in vitro to 3 Gy photons and single hematopoietic progenitor cell colonies isolated from a Chernobyl victim 9 years after in vivo exposure to 5.4 Sv. In lymphocytes, we found up to 15 different chromosomes involved in rearrangements indicating complex radiation effects. Stable aberrations detected in hematopoietic cell colonies, on the other hand, showed involvement of up to three different chromosomes. These results demonstrated that mFISH is a rapid and powerful approach to detect and characterize radiation-induced SCAs in the hemopoietic system. The application of mFISH is expected to result in a more detailed and, thus, more informative picture of radiation effects. Eventually, this technique will allow researchers to rapidly delineate

  16. Injury-induced rapid activation of MAPK signaling in dechorionated eggs and larvae of the silkworm Bombyx mori.

    Science.gov (United States)

    Gu, Shi-Hong; Chen, Chien-Hung

    2017-04-01

    Previous study showed that diapause in Bombyx mori eggs can be terminated by dechorionation and that activation in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) in dechorionated cultured eggs is involved in diapause termination. In the present study, the possible mechanism underlying activation of ERK upon dechorionation was further investigated. Results showed that mechanical injury of diapause eggs without medium incubation also resulted in rapid increase in the phospho-ERK levels and that injury increased the phospho-ERK levels at different stages of both diapause eggs and eggs in which diapause initiation was prevented by HCl. Effects of anaerobiosis on dechorionation-stimulated phospho-ERK levels showed that the mechanical injury itself but not the dramatic increase in oxygen uptake upon injury is involved in a rapid activation of ERK. Chemical anaerobiosis on dechorionation-stimulated phospho-ERK levels and the in vivo effect of anaerobiosis showed that the supply of oxygen also plays a role in ERK signaling. In addition, injury induced the phosphorylation of c-jun N-terminal kinases (JNKs) and p38 kinase, components of two parallel MAPK pathways. A kinase assay showed a dramatic increase in JNK kinase activity in egg lysates upon injury. When newly hatched first instar larvae were injured, an increase in the phospho-ERK levels similar to that in dechorionated eggs was observed. From the results, we hypothesize that the injury-induced rapid activation of MAPK signaling, which serves as a natural signal for embryonic development, is related to diapause termination in dechorionated eggs. © 2015 Institute of Zoology, Chinese Academy of Sciences.

  17. Rapid changes in brain structure predict improvements induced by perceptual learning.

    Science.gov (United States)

    Ditye, Thomas; Kanai, Ryota; Bahrami, Bahador; Muggleton, Neil G; Rees, Geraint; Walsh, Vincent

    2013-11-01

    Practice-dependent changes in brain structure can occur in task relevant brain regions as a result of extensive training in complex motor tasks and long-term cognitive training but little is known about the impact of visual perceptual learning on brain structure. Here we studied the effect of five days of visual perceptual learning in a motion-color conjunction search task using anatomical MRI. We found rapid changes in gray matter volume in the right posterior superior temporal sulcus, an area sensitive to coherently moving stimuli, that predicted the degree to which an individual's performance improved with training. Furthermore, behavioral improvements were also predicted by volumetric changes in an extended white matter region underlying the visual cortex. These findings point towards quick and efficient plastic neural mechanisms that enable the visual brain to deal effectively with changing environmental demands. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Standing helicon induced by a rapidly bent magnetic field in plasmas

    Science.gov (United States)

    Takahashi, Kazunori; Takayama, Sho; Komuro, Atsushi; Ando, Akira; Plasma physics Team

    2016-09-01

    An electron energy probability function and an rf magnetic field are measured in an rf hydrogen helicon source, where axial and transverse static magnetic fields are applied to the source by solenoids and to the diffusion chamber by filter magnets, respectively. It is demonstrated that the helicon wave is reflected by the rapidly bent magnetic field and the resultant standing wave heats the electrons between the source and the magnetic filter, while the electron cooling effect by the magnetic filter is maintained. It is interpreted that the standing wave is generated by the presence of spatially localized change of a refractive index. The application to the hydrogen negative ion source used for the neutral beam injection system for fusion plasma heating is discussed. This work is partially supported by grant-in-aid for scientific research (16H04084 and 26247096) from the Japan Society for the Promotion of Science.

  19. Rapid evolutionary responses of life history traits to different experimentally-induced pollutions in Caenorhabditis elegans.

    Science.gov (United States)

    Dutilleul, Morgan; Bonzom, Jean-Marc; Lecomte, Catherine; Goussen, Benoit; Daian, Fabrice; Galas, Simon; Réale, Denis

    2014-12-10

    Anthropogenic disturbances can lead to intense selection pressures on traits and very rapid evolutionary changes. Evolutionary responses to environmental changes, in turn, reflect changes in the genetic structure of the traits, accompanied by a reduction of evolutionary potential of the populations under selection. Assessing the effects of pollutants on the evolutionary responses and on the genetic structure of populations is thus important to understanding the mechanisms that entail specialization to novel environmental conditions or resistance to novel stressors. Using an experimental evolution approach we exposed Caenorhabditis elegans populations to uranium, salt and alternating uranium-salt environments over 22 generations. We analyzed the changes in the average values of life history traits and the consequences at the demographic level in these populations. We also estimated the phenotypic and genetic (co)variance structure of these traits at different generations. Compared to populations in salt, populations in uranium showed a reduction of the stability of their trait structure and a higher capacity to respond by acclimation. However, the evolutionary responses of traits were generally lower for uranium compared to salt treatment; and the evolutionary responses to the alternating uranium-salt environment were between those of constant environments. Consequently, at the end of the experiment, the population rate of increase was higher in uranium than in salt and intermediate in the alternating environment. Our multigenerational experiment confirmed that rapid adaptation to different polluted environments may involve different evolutionary responses resulting in demographic consequences. These changes are partly explained by the effects of the pollutants on the genetic (co)variance structure of traits and the capacity of acclimation to novel conditions. Finally, our results in the alternating environment may confirm the selection of a generalist type in this

  20. Rapid and label-free separation of Burkitt's lymphoma cells from red blood cells by optically-induced electrokinetics.

    Directory of Open Access Journals (Sweden)

    Wenfeng Liang

    Full Text Available Early stage detection of lymphoma cells is invaluable for providing reliable prognosis to patients. However, the purity of lymphoma cells in extracted samples from human patients' marrow is typically low. To address this issue, we report here our work on using optically-induced dielectrophoresis (ODEP force to rapidly purify Raji cells' (a type of Burkitt's lymphoma cell sample from red blood cells (RBCs with a label-free process. This method utilizes dynamically moving virtual electrodes to induce negative ODEP force of varying magnitudes on the Raji cells and RBCs in an optically-induced electrokinetics (OEK chip. Polarization models for the two types of cells that reflect their discriminate electrical properties were established. Then, the cells' differential velocities caused by a specific ODEP force field were obtained by a finite element simulation model, thereby established the theoretical basis that the two types of cells could be separated using an ODEP force field. To ensure that the ODEP force dominated the separation process, a comparison of the ODEP force with other significant electrokinetics forces was conducted using numerical results. Furthermore, the performance of the ODEP-based approach for separating Raji cells from RBCs was experimentally investigated. The results showed that these two types of cells, with different concentration ratios, could be separated rapidly using externally-applied electrical field at a driven frequency of 50 kHz at 20 Vpp. In addition, we have found that in order to facilitate ODEP-based cell separation, Raji cells' adhesion to the OEK chip's substrate should be minimized. This paper also presents our experimental results of finding the appropriate bovine serum albumin concentration in an isotonic solution to reduce cell adhesion, while maintaining suitable medium conductivity for electrokinetics-based cell separation. In short, we have demonstrated that OEK technology could be a promising tool for

  1. Rapid and label-free separation of Burkitt's lymphoma cells from red blood cells by optically-induced electrokinetics.

    Science.gov (United States)

    Liang, Wenfeng; Zhao, Yuliang; Liu, Lianqing; Wang, Yuechao; Dong, Zaili; Li, Wen Jung; Lee, Gwo-Bin; Xiao, Xiubin; Zhang, Weijing

    2014-01-01

    Early stage detection of lymphoma cells is invaluable for providing reliable prognosis to patients. However, the purity of lymphoma cells in extracted samples from human patients' marrow is typically low. To address this issue, we report here our work on using optically-induced dielectrophoresis (ODEP) force to rapidly purify Raji cells' (a type of Burkitt's lymphoma cell) sample from red blood cells (RBCs) with a label-free process. This method utilizes dynamically moving virtual electrodes to induce negative ODEP force of varying magnitudes on the Raji cells and RBCs in an optically-induced electrokinetics (OEK) chip. Polarization models for the two types of cells that reflect their discriminate electrical properties were established. Then, the cells' differential velocities caused by a specific ODEP force field were obtained by a finite element simulation model, thereby established the theoretical basis that the two types of cells could be separated using an ODEP force field. To ensure that the ODEP force dominated the separation process, a comparison of the ODEP force with other significant electrokinetics forces was conducted using numerical results. Furthermore, the performance of the ODEP-based approach for separating Raji cells from RBCs was experimentally investigated. The results showed that these two types of cells, with different concentration ratios, could be separated rapidly using externally-applied electrical field at a driven frequency of 50 kHz at 20 Vpp. In addition, we have found that in order to facilitate ODEP-based cell separation, Raji cells' adhesion to the OEK chip's substrate should be minimized. This paper also presents our experimental results of finding the appropriate bovine serum albumin concentration in an isotonic solution to reduce cell adhesion, while maintaining suitable medium conductivity for electrokinetics-based cell separation. In short, we have demonstrated that OEK technology could be a promising tool for efficient and

  2. Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plague.

    Science.gov (United States)

    Zauberman, Ayelet; Tidhar, Avital; Levy, Yinon; Bar-Haim, Erez; Halperin, Gideon; Flashner, Yehuda; Cohen, Sara; Shafferman, Avigdor; Mamroud, Emanuelle

    2009-06-16

    An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica Oratio8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 10(7)-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD(50) of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed new light on the

  3. Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plague.

    Directory of Open Access Journals (Sweden)

    Ayelet Zauberman

    Full Text Available An important virulence strategy evolved by bacterial pathogens to overcome host defenses is the modulation of host cell death. Previous observations have indicated that Yersinia pestis, the causative agent of plague disease, exhibits restricted capacity to induce cell death in macrophages due to ineffective translocation of the type III secretion effector YopJ, as opposed to the readily translocated YopP, the YopJ homologue of the enteropathogen Yersinia enterocolitica Oratio8. This led us to suggest that reduced cytotoxic potency may allow pathogen propagation within a shielded niche, leading to increased virulence. To test the relationship between cytotoxic potential and virulence, we replaced Y. pestis YopJ with YopP. The YopP-expressing Y. pestis strain exhibited high cytotoxic activity against macrophages in vitro. Following subcutaneous infection, this strain had reduced ability to colonize internal organs, was unable to induce septicemia and exhibited at least a 10(7-fold reduction in virulence. Yet, upon intravenous or intranasal infection, it was still as virulent as the wild-type strain. The subcutaneous administration of the cytotoxic Y. pestis strain appears to activate a rapid and potent systemic, CTL-independent, immunoprotective response, allowing the organism to overcome simultaneous coinfection with 10,000 LD(50 of virulent Y. pestis. Moreover, three days after subcutaneous administration of this strain, animals were also protected against septicemic or primary pneumonic plague. Our findings indicate that an inverse relationship exists between the cytotoxic potential of Y. pestis and its virulence following subcutaneous infection. This appears to be associated with the ability of the engineered cytotoxic Y. pestis strain to induce very rapid, effective and long-lasting protection against bubonic and pneumonic plague. These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed

  4. Rapidly induced chemical defenses in maize stems and their effects on short-term growth of Ostrinia nubilalis.

    Science.gov (United States)

    Dafoe, Nicole J; Huffaker, Alisa; Vaughan, Martha M; Duehl, Adrian J; Teal, Peter E; Schmelz, Eric A

    2011-09-01

    Plants damaged by insect herbivory often respond by inducing a suite of defenses that can negatively affect an insect's growth and fecundity. Ostrinia nubilalis (European corn borer, ECB) is one of the most devastating insect pests of maize, and in the current study, we examined the early biochemical changes that occur in maize stems in response to ECB herbivory and how these rapidly induced defenses influence the growth of ECB. We measured the quantities of known maize defense compounds, benzoxazinoids and the kauralexin class of diterpenoid phytoalexins. ECB herbivory resulted in decreased levels of the benzoxazinoid, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one)-β-D-glucopyranose (DIMBOA-Glc), and a corresponding increase in 2-(2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one)-β-D-glucopyranose (HDMBOA-Glc). Total quantities of benzoxazinoids and kauralexins were increased as early as 24 h after the initiation of ECB feeding. The plant hormones, jasmonic acid (JA) and ethylene (ET), and the transcripts encoding their key biosynthetic enzymes also accumulated in response to ECB herbivory, consistent with a role in defense regulation. The combined pharmacological application of JA and the ET precursor, 1-aminocyclopropane-1-carboxylic acid to stem internode tissue likewise resulted in changes in benzoxazinoids similar to that observed with ECB damage. Despite the fact that maize actively mounts a defense response to ECB stem feeding, no differences in percent weight gain were observed between ECB larvae that fed upon non-wounded control tissues compared to tissues obtained from plants previously subjected to 24 h ECB stem herbivory. These rapid defense responses in maize stems do not appear to negatively impact ECB growth, thus suggesting that ECB have adapted to these induced biochemical changes.

  5. Abscisic Acid Induces Rapid Reductions in Mesophyll Conductance to Carbon Dioxide.

    Directory of Open Access Journals (Sweden)

    Giuseppe Sorrentino

    Full Text Available The rate of photosynthesis (A of plants exposed to water deficit is a function of stomatal (gs and mesophyll (gm conductance determining the availability of CO2 at the site of carboxylation within the chloroplast. Mesophyll conductance often represents the greatest impediment to photosynthetic uptake of CO2, and a crucial determinant of the photosynthetic effects of drought. Abscisic acid (ABA plays a fundamental role in signalling and co-ordination of plant responses to drought; however, the effect of ABA on gm is not well-defined. Rose, cherry, olive and poplar were exposed to exogenous ABA and their leaf gas exchange parameters recorded over a four hour period. Application with ABA induced reductions in values of A, gs and gm in all four species. Reduced gm occurred within one hour of ABA treatment in three of the four analysed species; indicating that the effect of ABA on gm occurs on a shorter timescale than previously considered. These declines in gm values associated with ABA were not the result of physical changes in leaf properties due to altered turgor affecting movement of CO2, or caused by a reduction in the sub-stomatal concentration of CO2 (Ci. Increased [ABA] likely induces biochemical changes in the properties of the interface between the sub-stomatal air-space and mesophyll layer through the actions of cooporins to regulate the transport of CO2. The results of this study provide further evidence that gm is highly responsive to fluctuations in the external environment, and stress signals such as ABA induce co-ordinated modifications of both gs and gm in the regulation of photosynthesis.

  6. Rapid plasticity at inhibitory and excitatory synapses in the hippocampus induced by ictal epileptiform discharges.

    Science.gov (United States)

    Lopantsev, Valeri; Both, Martin; Draguhn, Andreas

    2009-03-01

    Epileptic seizures can induce pathological processes of plasticity in the brain that tend to promote the generation of further seizures. However, the immediate impact of epileptic seizures on cellular excitability remains poorly understood. In order to unravel such early mechanisms of epilepsy-induced plasticity, we studied synaptic transmission before and shortly after three ictal discharges induced by transient elevation of extracellular K(+) in mouse hippocampal slices. Discharges were initiated in the CA3 region and propagated via the Schaffer collaterals into CA1 where they were associated with sustained membrane depolarization and bursts of action potentials in CA1 pyramidal cells. Subsequently, discharges were followed by long-term potentiation (LTP) of Schaffer collateral-evoked field excitatory post-synaptic potentials (EPSPs) in the CA1. The ability to generate epileptiform activity in response to repetitive stimulation was enhanced during LTP. Changes in both inhibitory and excitatory synaptic transmission contributed to LTP in CA1 pyramidal cells. Discharges reduced gamma-aminobutyric acid-A receptor-mediated hyperpolarizing inhibitory post-synaptic potentials by shifting their reversal potentials in a positive direction. At the same time, the amplitudes of Schaffer collateral-evoked RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated EPSPs and action potential-independent miniature EPSPs were enhanced. However, N-methyl-d-aspartate receptor-mediated EPSPs remained unchanged. Paired-pulse stimulation revealed a reduced probability of glutamate release. Together, these changes in synaptic transmission produce a sustained increase in hippocampal excitability. We conclude that a few seizure-like ictal episodes are sufficient to cause fast and lasting changes in the excitation/inhibition balance in hippocampal networks, and therefore may contribute to early phases of progressive epileptogenesis.

  7. A microfluidic platform for rapid, stress-induced antibiotic susceptibility testing of Staphylococcus aureus.

    Science.gov (United States)

    Kalashnikov, Maxim; Lee, Jean C; Campbell, Jennifer; Sharon, Andre; Sauer-Budge, Alexis F

    2012-11-07

    The emergence and spread of bacterial resistance to ever increasing classes of antibiotics intensifies the need for fast phenotype-based clinical tests for determining antibiotic susceptibility. Standard susceptibility testing relies on the passive observation of bacterial growth inhibition in the presence of antibiotics. In this paper, we present a novel microfluidic platform for antibiotic susceptibility testing based on stress-activation of biosynthetic pathways that are the primary targets of antibiotics. We chose Staphylococcus aureus (S. aureus) as a model system due to its clinical importance, and we selected bacterial cell wall biosynthesis as the primary target of both stress and antibiotic. Enzymatic and mechanical stresses were used to damage the bacterial cell wall, and a β-lactam antibiotic interfered with the repair process, resulting in rapid cell death of strains that harbor no resistance mechanism. In contrast, resistant bacteria remained viable under the assay conditions. Bacteria, covalently-bound to the bottom of the microfluidic channel, were subjected to mechanical shear stress created by flowing culture media through the microfluidic channel and to enzymatic stress with sub-inhibitory concentrations of the bactericidal agent lysostaphin. Bacterial cell death was monitored via fluorescence using the Sytox Green dead cell stain, and rates of killing were measured for the bacterial samples in the presence and absence of oxacillin. Using model susceptible (Sanger 476) and resistant (MW2) S. aureus strains, a metric was established to separate susceptible and resistant staphylococci based on normalized fluorescence values after 60 min of exposure to stress and antibiotic. Because this ground-breaking approach is not based on standard methodology, it circumvents the need for minimum inhibitory concentration (MIC) measurements and long wait times. We demonstrate the successful development of a rapid microfluidic-based and stress

  8. Rapid calculations of susceptibility-induced magnetostatic field perturbations for in vivo magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Kevin M; Papademetris, Xenophon; Rothman, Douglas L; Graaf, Robin A de [Yale University, Magnetic Resonance Research Center, New Haven, CT (United States)

    2006-12-21

    Static magnetic field perturbations generated by variations of magnetic susceptibility within samples reduce the quality and integrity of magnetic resonance measurements. These perturbations are difficult to predict in vivo where wide variations of internal magnetic susceptibility distributions are common. Recent developments have provided rapid computational means of estimating static field inhomogeneity within the small susceptibility limits of materials typically studied using magnetic resonance. Such a predictive mechanism could be a valuable tool for sequence simulation, field shimming and post-acquisition image correction. Here, we explore this calculation protocol and demonstrate its predictive power in estimating in vivo inhomogeneity within the human brain. Furthermore, we quantitatively explore the predictive limits of the computation. For in vivo comparison, a method of magnetic susceptibility registration using MRI and CT data is presented and utilized to carry out subject-specific inhomogeneity estimation. Using this algorithm, direct comparisons in human brain and phantoms are made between field map acquisitions and calculated inhomogeneity. Distortion correction in echo-planar images due to static field inhomogeneity is also demonstrated using the computed field maps.

  9. Meteorite Impact-Induced Rapid NH3 Production on Early Earth: Ab Initio Molecular Dynamics Simulation

    Science.gov (United States)

    Shimamura, Kohei; Shimojo, Fuyuki; Nakano, Aiichiro; Tanaka, Shigenori

    2016-12-01

    NH3 is an essential molecule as a nitrogen source for prebiotic amino acid syntheses such as the Strecker reaction. Previous shock experiments demonstrated that meteorite impacts on ancient oceans would have provided a considerable amount of NH3 from atmospheric N2 and oceanic H2O through reduction by meteoritic iron. However, specific production mechanisms remain unclear, and impact velocities employed in the experiments were substantially lower than typical impact velocities of meteorites on the early Earth. Here, to investigate the issues from the atomistic viewpoint, we performed multi-scale shock technique-based ab initio molecular dynamics simulations. The results revealed a rapid production of NH3 within several picoseconds after the shock, indicating that shocks with greater impact velocities would provide further increase in the yield of NH3. Meanwhile, the picosecond-order production makes one expect that the important nitrogen source precursors of amino acids were obtained immediately after the impact. It was also observed that the reduction of N2 proceeded according to an associative mechanism, rather than a dissociative mechanism as in the Haber-Bosch process.

  10. Meteorite Impact-Induced Rapid NH3 Production on Early Earth: Ab Initio Molecular Dynamics Simulation

    Science.gov (United States)

    Shimamura, Kohei; Shimojo, Fuyuki; Nakano, Aiichiro; Tanaka, Shigenori

    2016-01-01

    NH3 is an essential molecule as a nitrogen source for prebiotic amino acid syntheses such as the Strecker reaction. Previous shock experiments demonstrated that meteorite impacts on ancient oceans would have provided a considerable amount of NH3 from atmospheric N2 and oceanic H2O through reduction by meteoritic iron. However, specific production mechanisms remain unclear, and impact velocities employed in the experiments were substantially lower than typical impact velocities of meteorites on the early Earth. Here, to investigate the issues from the atomistic viewpoint, we performed multi-scale shock technique-based ab initio molecular dynamics simulations. The results revealed a rapid production of NH3 within several picoseconds after the shock, indicating that shocks with greater impact velocities would provide further increase in the yield of NH3. Meanwhile, the picosecond-order production makes one expect that the important nitrogen source precursors of amino acids were obtained immediately after the impact. It was also observed that the reduction of N2 proceeded according to an associative mechanism, rather than a dissociative mechanism as in the Haber-Bosch process. PMID:27966594

  11. Rapid and Orthogonal Logic Gating with a Gibberellin-induced Dimerization System

    Science.gov (United States)

    Miyamoto, Takafumi; DeRose, Robert; Suarez, Allison; Ueno, Tasuku; Chen, Melinda; Sun, Tai-ping; Wolfgang, Michael J.; Mukherjee, Chandrani; Meyers, David J.; Inoue, Takanari

    2012-01-01

    Using a newly synthesized gibberellin analog (GA3-AM) and its binding proteins, we developed a novel and efficient chemically induced dimerization (CID) system, that is completely orthogonal to the existing rapamycin-mediated protein dimerization. Combining the two systems should allow applications that were difficult or impossible with only one CID system. By using both chemical inputs (rapamycin and GA3-AM), we designed and synthesized Boolean logic gates in living mammalian cells. These gates produced output signals such as fluorescence and membrane ruffling on a timescale of seconds, a significant improvement over previous intracellular logic gates. The use of two orthogonal dimerization systems in the same cell also allows for finer modulation of protein perturbations than is possible with a single dimerizer. PMID:22446836

  12. Bovine rumen epithelium undergoes rapid structural adaptations during grain-induced subacute ruminal acidosis.

    Science.gov (United States)

    Steele, Michael A; Croom, Jim; Kahler, Melissa; AlZahal, Ousama; Hook, Sarah E; Plaizier, Kees; McBride, Brian W

    2011-06-01

    Alterations in rumen epithelial structure and function during grain-induced subacute ruminal acidosis (SARA) are largely undescribed. In this study, four mature nonlactating dairy cattle were transitioned from a high-forage diet (HF; 0% grain) to a high-grain diet (HG; 65% grain). After feeding the HG diet for 3 wk, the cattle were transitioned back to the original HF diet, which was fed for an additional 3 wk. Continuous ruminal pH was measured on a weekly basis, and rumen papillae were biopsied during the baseline and at the first and final week of each diet. The mean, minimum, and maximum daily ruminal pH were depressed (P rumen epithelium is compromised during grain feeding and is associated with the differential expression of genes involved in epithelial growth and structure.

  13. Increases in myocardial workload induced by rapid atrial pacing trigger alterations in global metabolism.

    Directory of Open Access Journals (Sweden)

    Aslan T Turer

    Full Text Available To determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis.Nineteen patients referred for cardiac catheterization were enrolled. Peripheral and selective coronary sinus (CS blood sampling was performed at serial timepoints following the initiation of pacing, and metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS.Pacing-stress resulted in a 225% increase in the median rate·pressure product from baseline. Increased myocardial work induced significant changes in the peripheral concentration of 43 of 125 metabolites assayed, including large changes in purine [adenosine (+99%, p = 0.006, ADP (+42%, p = 0.01, AMP (+79%, p = 0.004, GDP (+69%, p = 0.003, GMP (+58%, p = 0.01, IMP (+50%, p = 0.03, xanthine (+61%, p = 0.0006], and several bile acid metabolites. The CS changes in metabolites qualitatively mirrored those in the peripheral blood in both timing and magnitude, suggesting the heart was not the major source of the metabolite release.Isolated increases in myocardial work can induce changes in the plasma metabolome, but these changes do not appear to be directly cardiac in origin. A number of these dynamic metabolites have known signaling functions. Our study provides additional evidence to a growing body of literature on metabolic 'cross-talk' between the heart and other organs.

  14. Surface modification induced phase transformation and structure variation on the rapidly solidified recast layer of titanium

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, Ming-Hung [Department of Mechanical Engineering and Graduate Institute of Mechanical and Precision Engineering, National Kaoshiung University of Applied Sciences, Kaoshiung 807, Taiwan (China); School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Haung, Chiung-Fang [School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Division of Family and Operative Dentistry, Department of Dentistry, Taipei Medical University Hospital, Taipei 110, Taiwan (China); Research Center for Biomedical Devices and Prototyping Production, Taipei Medical University, Taipei 110, Taiwan (China); Shyu, Shih-Shiun [Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan (China); Chou, Yen-Ru [Research Center for Biomedical Devices and Prototyping Production, Taipei Medical University, Taipei 110, Taiwan (China); Graduate Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Research Center for Biomedical Implants and Microsurgery Devices, Taipei Medical University, Taipei 110, Taiwan (China); Lin, Ming-Hong [Department of Mechanical Engineering and Graduate Institute of Mechanical and Precision Engineering, National Kaoshiung University of Applied Sciences, Kaoshiung 807, Taiwan (China); Peng, Pei-Wen, E-mail: apon@tmu.edu.tw [School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan (China); and others

    2015-08-15

    In this study, neodymium-doped yttrium orthovanadate (Nd:YVO{sub 4}) as a laser source with different scanning speeds was used on biomedical Ti surface. The microstructural and biological properties of laser-modified samples were investigated by means of optical microscope, electron microscope, X-ray diffraction, surface roughness instrument, contact angle and cell cytotoxicity assay. After laser modification, the rough volcano-like recast layer with micro-/nanoporous structure and wave-like recast layer with nanoporous structure were generated on the surfaces of laser-modified samples, respectively. It was also found out that, an α → (α + rutile-TiO{sub 2}) phase transition occurred on the recast layers of laser-modified samples. The Ti surface becomes hydrophilic at a high speed laser scanning. Moreover, the cell cytotoxicity assay demonstrated that laser-modified samples did not influence the cell adhesion and proliferation behaviors of osteoblast (MG-63) cell. The laser with 50 mm/s scanning speed induced formation of rough volcano-like recast layer accompanied with micro-/nanoporous structure, which can promote cell adhesion and proliferation of MG-63 cell on Ti surface. The results indicated that the laser treatment was a potential technology to enhance the biocompatibility for titanium. - Highlights: • Laser induced the formation of recast layer with micro-/nanoporous structure on Ti. • An α → (α + rutile-TiO{sub 2}) phase transition was observed within the recast layer. • The Ti surface becomes hydrophilic at a high speed laser scanning. • Laser-modified samples exhibit good biocompatibility to osteoblast (MG-63) cell.

  15. Apnea-induced rapid eye movement sleep disruption impairs human spatial navigational memory.

    Science.gov (United States)

    Varga, Andrew W; Kishi, Akifumi; Mantua, Janna; Lim, Jason; Koushyk, Viachaslau; Leibert, David P; Osorio, Ricardo S; Rapoport, David M; Ayappa, Indu

    2014-10-29

    Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA. Copyright © 2014 the authors 0270-6474/14/3414571-07$15.00/0.

  16. Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role of adipokines.

    Science.gov (United States)

    Malvi, Parmanand; Chaube, Balkrishna; Pandey, Vimal; Vijayakumar, Maleppillil Vavachan; Boreddy, Purushotham Reddy; Mohammad, Naoshad; Singh, Shivendra Vikram; Bhat, Manoj Kumar

    2015-03-01

    Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric intake significantly slows down melanoma progression. The diminished tumor progression was correlated with decreased fat mass (adiposity) in obese mice. Obesity associated factors contributing to tumor progression were decreased in the experimental groups compared to respective controls. In tumors, protein levels of fatty acid synthase (FASN), caveolin (Cav)-1 and pAkt, which are tumor promoting molecules implicated in melanoma growth under obese state, were decreased. In addition, increased necrosis and reduction in angiogenesis as well as proliferative markers PCNA and cyclin D1 were observed in tumors of the orlistat treated and/or calorically restricted obese mice. We observed that growth of melanoma cells cultured in conditioned medium (CM) from orlistat-treated adipocytes was reduced. Adipokines (leptin and resistin), via activating Akt and modulation of FASN as well as Cav-1 respectively, enhanced melanoma cell growth and proliferation. Together, we demonstrate that controlling body weight reduces adipose mass thereby diminishing melanoma progression. Therefore, strategic means of controlling obesity by reduced caloric diet or with antiobesity drugs treatment may render obesity-promoted tumor progression in check and prolong survival of patients. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. Extracellular ATP induces the rapid release of HIV-1 from virus containing compartments of human macrophages.

    Science.gov (United States)

    Graziano, Francesca; Desdouits, Marion; Garzetti, Livia; Podini, Paola; Alfano, Massimo; Rubartelli, Anna; Furlan, Roberto; Benaroch, Philippe; Poli, Guido

    2015-06-23

    HIV type 1 (HIV-1) infects CD4(+) T lymphocytes and tissue macrophages. Infected macrophages differ from T cells in terms of decreased to absent cytopathicity and for active accumulation of new progeny HIV-1 virions in virus-containing compartments (VCC). For these reasons, infected macrophages are believed to act as "Trojan horses" carrying infectious particles to be released on cell necrosis or functional stimulation. Here we explored the hypothesis that extracellular ATP (eATP) could represent a microenvironmental signal potentially affecting virion release from VCC of infected macrophages. Indeed, eATP triggered the rapid release of infectious HIV-1 from primary human monocyte-derived macrophages (MDM) acutely infected with the CCR5-dependent HIV-1 strain. A similar phenomenon was observed in chronically infected promonocytic U1 cells differentiated to macrophage-like cells (D-U1) by costimulation with phorbol esters and urokinase-type plasminogen activator. Worthy of note, eATP did not cause necrotic, apoptotic, or pyroptotic cell death, and its effect on HIV-1 release was suppressed by Imipramine (an antidepressant agent known to inhibit microvesicle formation by interfering with membrane-associated acid sphingomyelinase). Virion release was not triggered by oxidized ATP, whereas the effect of eATP was inhibited by a specific inhibitor of the P2X7 receptor (P2X7R). Thus, eATP triggered the discharge of virions actively accumulating in VCC of infected macrophages via interaction with the P2X7R in the absence of significant cytopathicity. These findings suggest that the microvesicle pathway and P2X7R could represent exploitable targets for interfering with the VCC-associated reservoir of infectious HIV-1 virions in tissue macrophages.

  18. Investigation of Near-Surface Defects Induced by Spike Rapid Thermal Annealing in c-SILICON Solar Cells

    Science.gov (United States)

    Liu, Guodong; Ren, Pan; Zhang, Dayong; Wang, Weiping; Li, Jianfeng

    2016-01-01

    The defects induced by a spike rapid thermal annealing (RTA) process in crystalline silicon (c-Si) solar cells were investigated by the photoluminescence (PL) technique and the transmission electron microscopy (TEM), respectively. Dislocation defects were found to form in the near-surface junction region of the monocrystalline Si solar cell after a spike RTA process was performed at 1100∘C. Photo J-V characteristics were measured on the Si solar cell before and after the spike RTA treatments to reveal the effects of defects on the Si cell performances. In addition, the Silvaco device simulation program was used to study the effects of defects density on the cell performances by fitting the experimental data of RTA-treated cells. The results demonstrate that there was an obvious degradation in the Si solar cell performances when the defect density after the spike RTA treatment was above 1×1013cm-3.

  19. Laser-Induced Breakdown Spectroscopy for Rapid Discrimination of Heavy-Metal-Contaminated Seafood Tegillarca granosa

    Directory of Open Access Journals (Sweden)

    Guoli Ji

    2017-11-01

    Full Text Available Tegillarca granosa samples contaminated artificially by three kinds of toxic heavy metals including zinc (Zn, cadmium (Cd, and lead (Pb were attempted to be distinguished using laser-induced breakdown spectroscopy (LIBS technology and pattern recognition methods in this study. The measured spectra were firstly processed by a wavelet transform algorithm (WTA, then the generated characteristic information was subsequently expressed by an information gain algorithm (IGA. As a result, 30 variables obtained were used as input variables for three classifiers: partial least square discriminant analysis (PLS-DA, support vector machine (SVM, and random forest (RF, among which the RF model exhibited the best performance, with 93.3% discrimination accuracy among those classifiers. Besides, the extracted characteristic information was used to reconstruct the original spectra by inverse WTA, and the corresponding attribution of the reconstructed spectra was then discussed. This work indicates that the healthy shellfish samples of Tegillarca granosa could be distinguished from the toxic heavy-metal-contaminated ones by pattern recognition analysis combined with LIBS technology, which only requires minimal pretreatments.

  20. Rapid nanostructuration of polymer colloid surfaces by nonsolvent induced phase separation.

    Science.gov (United States)

    Zheng, Lu; Ma, Zhaohui; Li, Zhanping; Yan, Qingfeng

    2015-03-01

    We have designed an effective strategy for producing nanostructures on the polymer colloid surfaces within few minutes. The poly(N-vinylpyrrolidone) (PVP)-stabilized polystyrene colloid latex dispersed in ethanol was exposed to a nonsolvent medium of PVP and nanometric droplets formed on the polymer colloid surfaces within few minutes. Surface wettability of the polymer colloids with nanoprotrusions experienced a significant change as compared with the smooth polymer colloids. The formation mechanism was ascribed to the precipitation of PVP phase due to the nonsolvent induced phase separation. To further confirm the proposed mechanism, the material components included in the polymer colloid lattices before the nanostructuration process and surface compositions on the nanostructured polymer colloid surfaces were characterized using gel permeation chromatography (GPC) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) respectively. This new strategy provides an alternative and promising method for patterning curved polymer surfaces. The polymer colloids with different surface textures would be ideal for use as model systems in biomedical research such as targets in phagocytosis and platforms of drug delivery. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Expandable and Rapidly Differentiating Human Induced Neural Stem Cell Lines for Multiple Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Dana M. Cairns

    2016-09-01

    Full Text Available Limited availability of human neurons poses a significant barrier to progress in biological and preclinical studies of the human nervous system. Current stem cell-based approaches of neuron generation are still hindered by prolonged culture requirements, protocol complexity, and variability in neuronal differentiation. Here we establish stable human induced neural stem cell (hiNSC lines through the direct reprogramming of neonatal fibroblasts and adult adipose-derived stem cells. These hiNSCs can be passaged indefinitely and cryopreserved as colonies. Independently of media composition, hiNSCs robustly differentiate into TUJ1-positive neurons within 4 days, making them ideal for innervated co-cultures. In vivo, hiNSCs migrate, engraft, and contribute to both central and peripheral nervous systems. Lastly, we demonstrate utility of hiNSCs in a 3D human brain model. This method provides a valuable interdisciplinary tool that could be used to develop drug screening applications as well as patient-specific disease models related to disorders of innervation and the brain.

  2. Rapid tumor necrosis and massive hemorrhage induced by bevacizumab and paclitaxel combination therapy in a case of advanced breast cancer

    Directory of Open Access Journals (Sweden)

    Ono M

    2013-10-01

    Full Text Available Mayu Ono, Tokiko Ito, Toshiharu Kanai, Koichi Murayama, Hiroshi Koyama, Kazuma Maeno, Yasuhiro Mochizuki, Asumi Iesato, Toru Hanamura, Toshihiro Okada, Takayuki Watanabe, Ken-ichi ItoDivision of Breast and Endocrine Surgery, Department of Surgery (II, Shinshu University School of Medicine, Matsumoto, JapanAbstract: Bevacizumab when combined with chemotherapy exerts significant activity against many solid tumors through tumor angiogenesis inhibition; however, it can induce severe side effects. We report the rare case of a 27-year-old premenopausal woman with locally advanced breast cancer that was marked by rapid tumor necrosis followed by massive hemorrhage shortly after bevacizumab and paclitaxel administration. On the basis of histopathological examination of a biopsy specimen and computed tomography findings, she was diagnosed with stage IV estrogen and progesterone receptor-negative and human epidermal growth factor receptor type 2-positive breast cancer with multiple organ metastases when she had entered gestational week 24. Cyclophosphamide, Adriamycin®, fluorouracil therapy was initiated, but multiple liver metastases continued to progress. A healthy fetus was delivered by induced delivery and trastuzumab-based treatment was initiated. Although the multiple liver metastases were controlled successfully by trastuzumab combined with paclitaxel, the primary tumor continued to expand even after subsequent administration of three other treatment regimens including anti-human epidermal growth factor receptor type 2 agents and cytotoxic drugs. To inhibit primary tumor growth, a combination therapy with paclitaxel and bevacizumab was subsequently initiated. Following therapy initiation, however, the large tumor occupying the patient's entire left breast became necrotic and ulcerated rapidly. Furthermore, massive hemorrhage from the tumor occurred 5 weeks after bevacizumab-based therapy initiation. Although hemostasis was achieved by manual

  3. Laser Induced breakdown spectroscopy: A rapid tool for the identification and quantification of minerals in cucurbit seeds.

    Science.gov (United States)

    Singh, Jyotsana; Kumar, Rohit; Awasthi, Shikha; Singh, Vinti; Rai, A K

    2017-04-15

    Laser-induced breakdown spectroscopy (LIBS) was investigated to estimate the viability as a simple and rapid method for analysis of nutrient elements in seed kernels of cucurbits. LIBS spectra were recorded in the range of 200-975nm by using Q-switched Nd:YAG laser at 532nm (4ns, 10Hz) attached to echelle spectrometer with intensified charged coupled device (ICCD). The spectral analysis revealed the presence of several elements like C, O, N, Mg, Ca, Na and K in seeds. The quantification of elements (Mg, Ca, Na and K) through LIBS was done using calibration curve method in which all calibration curve shows good linearity (r>0.95). The result obtained through LIBS was in reasonable agreement with that obtained through atomic absorption spectroscopy (AAS). Principal Component Analysis (PCA) was also applied to the LIBS data for rapid categorization of seed samples belonging to same species although samples have similar nutrient elements. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Rapid determination of gizzerosine in fish meals using microchip capillary electrophoresis with laser-induced fluorescence detection.

    Science.gov (United States)

    Xiao, Meng-Wei; Bai, Xiao-Lin; Xu, Pei-Li; Zhao, Yan; Yang, Li; Liu, Yi-Ming; Liao, Xun

    2017-05-01

    Sensitive detection of gizzerosine, a causative agent for deadly gizzard erosion in chicken feeds, is very important to the poultry industry. In this work, a new method was developed based on microchip capillary electrophoresis (MCE) with laser-induced fluorescence (LIF) detection for rapid analysis of gizzerosine, a biogenic amine in fish meals. The MCE separation was performed on a glass microchip using sodium dodecyl sulfate (SDS) as dynamic coating modifier. Separation conditions, including running buffer pH and concentration, SDS concentration, and the separation voltage were investigated to achieve fast and sensitive quantification of gizzerosine. The assay proposed was very quick and could be completed within 65 s. A linear calibration curve was obtained in the range from 0.04 to 1.8 μg ml-1 gizzerosine. The detection limit was 0.025 μg ml-1 (0.025 mg kg-1), which was far more sensitive than those previously reported. Gizzerosine was well separated from other endogenous components in fish meal samples. Recovery of gizzerosine from this sample matrix (n = 3) was determined to be 97.2-102.8%. The results from analysing fish meal samples indicated that the present MCE-LIF method might hold the potential for rapid detection of gizzerosine in poultry feeds.

  5. BRODIFACOUM INDUCES EARLY HEMOGLOBINURIA AND LATE HEMATURIA IN RATS: NOVEL RAPID BIOMARKERS OF POISONING

    Science.gov (United States)

    Ware, Kyle M; Feinstein, Douglas L; Rubinstein, Israel; Weinberg, Guy; Rovin, Brad H; Hebert, Lee; Muni, Navin; Cianciolo, Rachel E.; Satoskar, Anjali A; Nadasdy, Tibor; Brodsky, Sergey V

    2015-01-01

    Introduction Brodifacoum (BDF) is a superwarfarin that is used primarily as a rodenticide. There have been increasing number of reports of human cases of accidental or intentional BDF ingestion with high mortality rate. Its broad availability and high lethality suggest that BDF should be considered a potential chemical threat. Currently, there is no biomarker for early detection of BDF ingestion in humans; patients typically present with severe coagulopathy. Since we demonstrated earlier that warfarin can induce acute kidney injury with hematuria, we tested whether BDF would also lead to change in urinary biomarkers. Material and methods BDF was administered to Sprague Dawley rats via oral gavage. N-acetylcysteine (NAC) was given per os in drinking water 24 hours prior to BDF. Urinalysis was performed at different times after BDF administration. Anticoagulation and serum creatinine levels were analyzed in the blood. Results We observed that within a few hours the animals developed BDF-dose-dependent transient hemoglobinuria, which ceased within 24 hours. This was accompanied by a transient decrease in hematocrit, gross hemolysis and an increase in free hemoglobin in the serum. At later times, animals developed true hematuria with red blood cells in the urine, which was associated with BDF anticoagulation. NAC prevented early hemoglobinuria, but not late hematuria associated with BDF. Conclusions We propose that transient early hemoglobinuria (associated with oxidative stress) with consecutive late hematuria (associated with anticoagulation) are novel biomarkers of BDF poisoning and they can be used in clinical setting or in mass-casualty with BDF to identify poisoned patients. PMID:26111556

  6. Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC) - the Hot Start experience.

    Science.gov (United States)

    De Sousa, Paul A; Steeg, Rachel; Wachter, Elisabeth; Bruce, Kevin; King, Jason; Hoeve, Marieke; Khadun, Shalinee; McConnachie, George; Holder, Julie; Kurtz, Andreas; Seltmann, Stefanie; Dewender, Johannes; Reimann, Sascha; Stacey, Glyn; O'Shea, Orla; Chapman, Charlotte; Healy, Lyn; Zimmermann, Heiko; Bolton, Bryan; Rawat, Trisha; Atkin, Isobel; Veiga, Anna; Kuebler, Bernd; Serano, Blanca Miranda; Saric, Tomo; Hescheler, Jürgen; Brüstle, Oliver; Peitz, Michael; Thiele, Cornelia; Geijsen, Niels; Holst, Bjørn; Clausen, Christian; Lako, Majlinda; Armstrong, Lyle; Gupta, Shailesh K; Kvist, Alexander J; Hicks, Ryan; Jonebring, Anna; Brolén, Gabriella; Ebneth, Andreas; Cabrera-Socorro, Alfredo; Foerch, Patrik; Geraerts, Martine; Stummann, Tina C; Harmon, Shawn; George, Carol; Streeter, Ian; Clarke, Laura; Parkinson, Helen; Harrison, Peter W; Faulconbridge, Adam; Cherubin, Luca; Burdett, Tony; Trigueros, Cesar; Patel, Minal J; Lucas, Christa; Hardy, Barry; Predan, Rok; Dokler, Joh; Brajnik, Maja; Keminer, Oliver; Pless, Ole; Gribbon, Philip; Claussen, Carsten; Ringwald, Annette; Kreisel, Beate; Courtney, Aidan; Allsopp, Timothy E

    2017-04-01

    A fast track "Hot Start" process was implemented to launch the European Bank for Induced Pluripotent Stem Cells (EBiSC) to provide early release of a range of established control and disease linked human induced pluripotent stem cell (hiPSC) lines. Established practice amongst consortium members was surveyed to arrive at harmonised and publically accessible Standard Operations Procedures (SOPs) for tissue procurement, bio-sample tracking, iPSC expansion, cryopreservation, qualification and distribution to the research community. These were implemented to create a quality managed foundational collection of lines and associated data made available for distribution. Here we report on the successful outcome of this experience and work flow for banking and facilitating access to an otherwise disparate European resource, with lessons to benefit the international research community. ETOC: The report focuses on the EBiSC experience of rapidly establishing an operational capacity to procure, bank and distribute a foundational collection of established hiPSC lines. It validates the feasibility and defines the challenges of harnessing and integrating the capability and productivity of centres across Europe using commonly available resources currently in the field. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Development of a rapid culture method to induce adipocyte differentiation of human bone marrow-derived mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Ninomiya, Yuichi [Translational Research Center, Saitama International Medical, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298 (Japan); Sugahara-Yamashita, Yzumi; Nakachi, Yutaka; Tokuzawa, Yoshimi; Okazaki, Yasushi [Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Saitama 350-1241 (Japan); Nishiyama, Masahiko, E-mail: yamacho@saitama-med.ac.jp [Translational Research Center, Saitama International Medical, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1298 (Japan)

    2010-04-02

    Human mesenchymal stem cells (hMSCs) derived from bone marrow are multipotent stem cells that can regenerate mesenchymal tissues such as adipose, bone or muscle. It is thought that hMSCs can be utilized as a cell resource for tissue engineering and as human models to study cell differentiation mechanisms, such as adipogenesis, osteoblastogenesis and so on. Since it takes 2-3 weeks for hMSCs to differentiate into adipocytes using conventional culture methods, the development of methods to induce faster differentiation into adipocytes is required. In this study we optimized the culture conditions for adipocyte induction to achieve a shorter cultivation time for the induction of adipocyte differentiation in bone marrow-derived hMSCs. Briefly, we used a cocktail of dexamethasone, insulin, methylisobutylxanthine (DIM) plus a peroxisome proliferator-activated receptor {gamma} agonist, rosiglitazone (DIMRo) as a new adipogenic differentiation medium. We successfully shortened the period of cultivation to 7-8 days from 2-3 weeks. We also found that rosiglitazone alone was unable to induce adipocyte differentiation from hMSCs in vitro. However, rosiglitazone appears to enhance hMSC adipogenesis in the presence of other hormones and/or compounds, such as DIM. Furthermore, the inhibitory activity of TGF-{beta}1 on adipogenesis could be investigated using DIMRo-treated hMSCs. We conclude that our rapid new culture method is very useful in measuring the effect of molecules that affect adipogenesis in hMSCs.

  8. A small molecule with anticancer and antimetastatic activities induces rapid mitochondrial-associated necrosis in breast cancer.

    Science.gov (United States)

    Bastian, Anja; Thorpe, Jessica E; Disch, Bryan C; Bailey-Downs, Lora C; Gangjee, Aleem; Devambatla, Ravi K V; Henthorn, Jim; Humphries, Kenneth M; Vadvalkar, Shraddha S; Ihnat, Michael A

    2015-05-01

    Therapy for treatment-resistant breast cancer provides limited options and the response rates are low. Therefore, the development of therapies with alternative chemotherapeutic strategies is necessary. AG311 (5-[(4-methylphenyl)thio]-9H-pyrimido[4,5-b]indole-2,4-diamine), a small molecule, is being investigated in preclinical and mechanistic studies for treatment of resistant breast cancer through necrosis, an alternative cell death mechanism. In vitro, AG311 induces rapid necrosis in numerous cancer cell lines as evidenced by loss of membrane integrity, ATP depletion, HMGB1 (high-mobility group protein B1) translocation, nuclear swelling, and stable membrane blebbing in breast cancer cells. Within minutes, exposure to AG311 also results in mitochondrial depolarization, superoxide production, and increased intracellular calcium levels. Additionally, upregulation of mitochondrial oxidative phosphorylation results in sensitization to AG311. This AG311-induced cell death can be partially prevented by treatment with the mitochondrial calcium uniporter inhibitor, Ru360 [(μ)[(HCO2)(NH3)4Ru]2OCl3], or an antioxidant, lipoic acid. Additionally, AG311 does not increase apoptotic markers such as cleavage of poly (ADP-ribose) polymerase (PARP) or caspase-3 and -7 activity. Importantly, in vivo studies in two orthotopic breast cancer mouse models (xenograft and allograft) demonstrate that AG311 retards tumor growth and reduces lung metastases better than clinically used agents and has no gross or histopathological toxicity. Together, these data suggest that AG311 is a first-in-class antitumor and antimetastatic agent inducing necrosis in breast cancer tumors, likely through the mitochondria. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  9. A rapid virus-induced gene silencing (VIGS) method for assessing resistance and susceptibility to cassava mosaic disease.

    Science.gov (United States)

    Beyene, Getu; Chauhan, Raj Deepika; Taylor, Nigel J

    2017-03-07

    Cassava mosaic disease (CMD) is a major constraint to cassava production in sub-Saharan Africa. Under field conditions, evaluation for resistance to CMD takes 12-18 months, often conducted across multiple years and locations under pressure from whitefly-mediated transmission. Under greenhouse or laboratory settings, evaluation for resistance or susceptibility to CMD involves transmission of the causal viruses from an infected source to healthy plants through grafting, or by using Agrobacterium-mediated or biolistic delivery of infectious clones. Following inoculation, visual assessment for CMD symptom development and recovery requires 12-22 weeks. Here we report a rapid screening system for determining resistance and susceptibility to CMD based on virus-induced gene silencing (VIGS) of an endogenous cassava gene. A VIGS vector was developed based on an infectious clone of the virulent strain of East African cassava mosaic virus (EACMV-K201). A sequence from the cassava (Manihot esculenta) ortholog of Arabidopsis SPINDLY (SPY) was cloned into the CP position of the DNA-A genomic component and used to inoculate cassava plants by Helios® Gene Gun microparticle bombardment. Silencing of Manihot esculenta SPY (MeSPY) using MeSPY1-VIGS resulted in shoot-tip necrosis followed by death of the whole plant in CMD susceptible cassava plants within 2-4 weeks. CMD resistant cultivars were not affected and remained healthy after challenge with MeSPY1-VIGS. Significantly higher virus titers were detected in CMD-susceptible cassava lines compared to resistant controls and were correlated with a concomitant reduction in MeSPY expression in susceptible plants. A rapid VIGS-based screening system was developed for assessing resistance and susceptibility to CMD. The method is space and resource efficient, reducing the time required to perform CMD screening to as little as 2-4 weeks. It can be employed as a high throughput rapid screening system to assess new cassava cultivars and for

  10. Effects of gadolinium chloride on basal flow and compression-induced rapid hyperemia in the rabbit masseter muscle.

    Science.gov (United States)

    Turturici, M; Roatta, S

    2014-06-01

    Aim of the present study is to investigate the role of mechano-sensitive channels on basal muscle blood flow and on the compression-induced rapid hyperaemia. To this aim, the mechano-sensitive channel blocker Gadolinium (Gd(3+)) is employed, which already proved to reduce the myogenic response in isolated vessels. Muscle blood flow (MaBF) was recorded from the masseteric artery in 8 urethane-anesthetized rabbits. Rapid hyperemic responses were evoked by 1-s lasting compressions of the masseter muscle (MC) delivered before and after close arterial infusion of Gd(3+) in the masseteric artery. Three infusions were performed at 1-h interval, producing estimated plasma concentration (EPC) of 0.045, 0.45 and 4.5 mM, in the masseteric artery. The amplitude of the hyperaemic response to MC, equal to 195±77% of basal flow in control condition, was reduced by 9.5±19.4% (p=0.18) and 45±28% (p<0.01) while basal MaBf increased by 10±3% (p=0.90) and by 68±30% (p<0.01) at EPC of 0.045 and 0.45 mM, respectively. At EPC of 4.5 mM a strong reduction in both MaBF (by 54±13%, p<0.01) and MC response (75±12%, p<0.01) was instead observed. These effects did not depend on time from infusion. At all doses employed Gd(3+) never affected arterial blood pressure, heart rate and contralateral MaBF. While the effects observed at the highest EPC likely result from blood vessel occlusion due to Gd(3+) precipitation, the effects observed at lower concentrations demonstrate that Gd(3+) affects musculo-vascular function by decreasing both resting vascular tone and responsiveness to mechanical stimuli. The results are compatible with a Gd(3+)-induced blockade of vascular mechano-sensitive channels.

  11. Evidence that polyhydroxylated C60 fullerenes (fullerenols) amplify the effect of lipopolysaccharides to induce rapid leukocyte infiltration in vivo.

    Science.gov (United States)

    Gonçalves, D M; Girard, D

    2013-12-16

    Fullerenols C60(OH) have therapeutic potential, but there is debate regarding their toxicity. Here, we tested the hypothesis that C60(OH)n possesses a pro-inflammatory effect in vivo. Kinetic and dose-dependent experiments performed with the murine air pouch model of acute inflammation revealed that, unlike TiO2 used as a positive control in this model, C60(OH)n NPs were not pro-inflammatory in CD-1, C57BL/6, and BALB/c mice. However, after 3 h of treatment, C60(OH)n NPs were found to amplify the effect of lipopolysaccharides (LPS) causing a rapid leukocyte influx in which the major cells observed are neutrophils. The use of an antibody array assay to detect different analytes simultaneously indicates that the amplification effect is, at least partially, explained by an increased local production of several cytokines/chemokines in the exudates, including the pro-inflammatory cytokine IL-6. Using an ELISA to quantify the amount of IL-6 produced into air pouch exudates, we demonstrated that C60(OH)n increases the LPS-induced local production of this cytokine. Therefore, although C60(OH)n NPs alone do not exert proinflammatory activity under certain conditions, they can act in concert with other agents to cause inflammation, a situation that is likely to occur in vivo.

  12. Immediate periodontal bone plate changes induced by rapid maxillary expansion in the early mixed dentition: CT findings

    Directory of Open Access Journals (Sweden)

    Daniela Gamba Garib

    2014-06-01

    Full Text Available OBJECTIVE: This study aimed at evaluating buccal and lingual bone plate changes caused by rapid maxillary expansion (RME in the mixed dentition by means of computed tomography (CT. METHODS: The sample comprised spiral CT exams taken from 22 mixed dentition patients from 6 to 9 years of age (mean age of 8.1 years presenting constricted maxillary arch treated with Haas-type expanders. Patients were submitted to spiral CT scan before expansion and after the screw activation period with a 30-day interval between T1 and T2. Multiplanar reconstruction was used to measure buccal and lingual bone plate thickness and buccal bone crest level of maxillary posterior deciduous and permanent teeth. Changes induced by expansion were evaluated using paired t test (p < 0.05. RESULTS: Thickness of buccal and lingual bone plates of posterior teeth remained unchanged during the expansion period, except for deciduous second molars which showed a slight reduction in bone thickness at the distal region of its buccal aspect. Buccal bone dehiscences were not observed in the supporting teeth after expansion. CONCLUSION: RME performed in mixed dentition did not produce immediate undesirable effects on periodontal bone tissues.

  13. Hydrogen-induced changes in the crystalline structure and mechanical properties of a Zn-Al eutectoid alloy rapidly solidified

    Energy Technology Data Exchange (ETDEWEB)

    Sandoval Jimenez, Alberto; Iturbe Garcia, Jose Luis [Instituto Nacional de Investigaciones Nucleares, Ocoyoacac, Estado de Mexico (Mexico)]. E-mail: alberto.sandoval@inin.gob.mx; asandovalj@correo.unam.mx; Negrete Sanchez, Jesus [Universidad Autonoma de San Luis Potosi, San Luis Potosi (Mexico); Torres Villasenor, Gabriel [Instituto de Investigaciones en Materiales, UNAM, Mexico D.F. (Mexico)

    2009-09-15

    Ribbon fractions of a zinc-aluminum eutectoid (Zn40.8Al%at.) alloy, obtained by rapid solidification using melt spinning technique, were submitted to a thermo-hydrogenation process by periods of 1, 6, 18, 24, 30, and 48 hours, to 200 degrees Celsius and 20 atmospheres. Thermo-hydrogenated samples were analyzed by transmission electron microscopy (TEM). Hydrogen-induced changes were produced, such as microstructure refining, development of crystalline defects, microhardness changes and modification of stable crystalline structures to {alpha}R meta-stable phase at room temperature. [Spanish] Fracciones de tiras de una aleacion eutectoide de zinc-aluminio (Zn40.8Al%at.), obtenidas mediante solidificacion rapida usando la tecnica de melt spinning, se sometieron a un proceso de termohidrogenacion por periodos de 1, 6, 18, 24, 30 y 48 horas, a 200 grados centigrados y 20 atmosferas. Las muestras termohidrogenadas se analizaron por microscopia electronica de transmision (MET). Se produjeron cambios inducidos por hidrogeno, tales como la refinacion de la microestructura, el desarrollo de defectos cristalinos, cambios de microdureza y modificacion de las estructuras cristalinas estables a fase metaestable {alpha}R a temperatura ambiente.

  14. Strategies for rapidly mapping proviral integration sites and assessing cardiogenic potential of nascent human induced pluripotent stem cell clones.

    Science.gov (United States)

    Dambrot, Cheryl; Buermans, Henk P J; Varga, Eszter; Kosmidis, Georgios; Langenberg, Karin; Casini, Simona; Elliott, David A; Dinnyes, Andras; Atsma, Douwe E; Mummery, Christine L; Braam, Stefan R; Davis, Richard P

    2014-10-01

    Recent methodological advances have improved the ease and efficiency of generating human induced pluripotent stem cells (hiPSCs), but this now typically results in a greater number of hiPSC clones being derived than can be wholly characterized. It is therefore imperative that methods are developed which facilitate rapid selection of hiPSC clones most suited for the downstream research aims. Here we describe a combination of procedures enabling the simultaneous screening of multiple clones to determine their genomic integrity as well as their cardiac differentiation potential within two weeks of the putative reprogrammed colonies initially appearing. By coupling splinkerette-PCR with Ion Torrent sequencing, we could ascertain the number and map the proviral integration sites in lentiviral-reprogrammed hiPSCs. In parallel, we developed an effective cardiac differentiation protocol that generated functional cardiomyocytes within 10 days without requiring line-specific optimization for any of the six independent human pluripotent stem cell lines tested. Finally, to demonstrate the scalable potential of these procedures, we picked 20 nascent iPSC clones and performed these independent assays concurrently. Before the clones required passaging, we were able to identify clones with a single integrated copy of the reprogramming vector and robust cardiac differentiation potential for further analysis. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Rapid and efficient conversion of integration-free human induced pluripotent stem cells to GMP-grade culture conditions.

    Directory of Open Access Journals (Sweden)

    Jens Durruthy-Durruthy

    Full Text Available Data suggest that clinical applications of human induced pluripotent stem cells (hiPSCs will be realized. Nonetheless, clinical applications will require hiPSCs that are free of exogenous DNA and that can be manufactured through Good Manufacturing Practice (GMP. Optimally, derivation of hiPSCs should be rapid and efficient in order to minimize manipulations, reduce potential for accumulation of mutations and minimize financial costs. Previous studies reported the use of modified synthetic mRNAs to reprogram fibroblasts to a pluripotent state. Here, we provide an optimized, fully chemically defined and feeder-free protocol for the derivation of hiPSCs using synthetic mRNAs. The protocol results in derivation of fully reprogrammed hiPSC lines from adult dermal fibroblasts in less than two weeks. The hiPSC lines were successfully tested for their identity, purity, stability and safety at a GMP facility and cryopreserved. To our knowledge, as a proof of principle, these are the first integration-free iPSCs lines that were reproducibly generated through synthetic mRNA reprogramming that could be putatively used for clinical purposes.

  16. Rapid reversal of human intestinal ischemia-reperfusion induced damage by shedding of injured enterocytes and reepithelialisation.

    Directory of Open Access Journals (Sweden)

    Joep P M Derikx

    . At the same time, M30 immunoreactivity was absent in intact epithelial lining. CONCLUSIONS: This is the first human study to clarify intestinal IR induced cell damage and repair and its direct consequences. It reveals a unique, endogenous clearing mechanism for injured enterocytes: rapid detachment of damaged apoptotic enterocytes into the lumen. This process is followed by repair of the epithelial continuity within an hour, resulting in a normal epithelial lining.

  17. Rapid generation of mitochondrial superoxide induces mitochondrion-dependent but caspase-independent cell death in hippocampal neuronal cells that morphologically resembles necroptosis

    Energy Technology Data Exchange (ETDEWEB)

    Fukui, Masayuki; Choi, Hye Joung; Zhu, Bao Ting, E-mail: BTZhu@kumc.edu

    2012-07-15

    Studies in recent years have revealed that excess mitochondrial superoxide production is an important etiological factor in neurodegenerative diseases, resulting from oxidative modifications of cellular lipids, proteins, and nucleic acids. Hence, it is important to understand the mechanism by which mitochondrial oxidative stress causes neuronal death. In this study, the immortalized mouse hippocampal neuronal cells (HT22) in culture were used as a model and they were exposed to menadione (also known as vitamin K{sub 3}) to increase intracellular superoxide production. We found that menadione causes preferential accumulation of superoxide in the mitochondria of these cells, along with the rapid development of mitochondrial dysfunction and cellular ATP depletion. Neuronal death induced by menadione is independent of the activation of the MAPK signaling pathways and caspases. The lack of caspase activation is due to the rapid depletion of cellular ATP. It was observed that two ATP-independent mitochondrial nucleases, namely, AIF and Endo G, are released following menadione exposure. Silencing of their expression using specific siRNAs results in transient suppression (for ∼ 12 h) of mitochondrial superoxide-induced neuronal death. While suppression of the mitochondrial superoxide dismutase expression markedly sensitizes neuronal cells to mitochondrial superoxide-induced cytotoxicity, its over-expression confers strong protection. Collectively, these findings showed that many of the observed features associated with mitochondrial superoxide-induced cell death, including caspase independency, rapid depletion of ATP level, mitochondrial release of AIF and Endo G, and mitochondrial swelling, are distinctly different from those of apoptosis; instead they resemble some of the known features of necroptosis. -- Highlights: ► Menadione causes mitochondrial superoxide accumulation and injury. ► Menadione-induced cell death is caspase-independent, due to rapid depletion of

  18. Increased extracellular collagen matrix in myocardial sleeves of pulmonary veins: an additional mechanism facilitating repetitive rapid activities in chronic pacing-induced sustained atrial fibrillation.

    Science.gov (United States)

    Chiu, Yung-Tsung; Wu, Tsu-Juey; Wei, Hao-Ji; Cheng, Ching-Chang; Lin, Nai-Nu; Chen, Ying-Tsung; Ting, Chih-Tai

    2005-07-01

    Increased ECM in canine PVs. Cell uncoupling due to fibrosis or increased extracellular collagen matrix (ECM) affects the formation of ectopic focal activity. Whether or not the increase of ECM also exists in the pulmonary veins (PVs) with rapid atrial pacing is unknown. We sought to test the hypothesis that in chronic atrial pacing dogs with sustained atrial fibrillation (AF), the amount of ECM was increased in both atria and the PVs. We induced sustained AF in dogs by rapid atrial pacing. Computerized mapping techniques were used to map both atria and the PVs. We also used histological assessment to quantify the amount of ECM. After 118+/-24 days of rapid atrial pacing, sustained AF was induced in 7 dogs. Repetitive rapid activities (RRAs) either continuously or intermittently arose from the PVs during sustained AF. Histological study shows that there was no fibrosis in both atrial free walls and the PVs. However, the amount of ECM was increased in these regions. The mean ECM surface area fraction at each region in the dogs with sustained AF was all significantly higher compared to the corresponding region in normal dogs. Similarly, the heterogeneity of the ECM surface area fraction at each region in the dogs with sustained AF was also all significantly higher compared to normal dogs. In chronic atrial pacing-induced sustained AF, structural remodeling (i.e., inhomogeneous increase of ECM) also involves the PVs. Reduced coupling of the myocytes in the PV due to histological changes may provide an additional mechanism facilitating RRAs.

  19. Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner.

    Directory of Open Access Journals (Sweden)

    John Meshki

    Full Text Available U373MG astrocytoma cells endogenously express the full-length neurokinin 1 receptor (NK1R. Substance P (SP, the natural ligand for NK1R, triggers rapid and transient membrane blebbing and we report that these morphological changes have different dynamics and intracellular signaling as compared to the changes that we have previously described in HEK293-NK1R cells. In both cell lines, the SP-induced morphological changes are Gq-independent, and they require the Rho, Rho-associated coiled-coil kinase (ROCK signaling pathway. Using confocal microscopy we have demonstrated that tubulin is phosphorylated subsequent to cell stimulation with SP and that tubulin accumulates inside the blebs. Colchicine, a tubulin polymerization inhibitor, blocked SP-induced blebbing in U373MG but not in HEK293-NK1R cells. Although p21-activated kinase (PAK is expressed in both cell lines, SP induced rapid phosphorylation of PAK in U373MG, but failed to phosphorylate PAK in HEK293-NK1R cells. The cell-permeable Rho inhibitor C3 transferase inhibited SP-induced PAK phosphorylation, but the ROCK inhibitor Y27632 had no effect on PAK phosphorylation, suggesting that Rho activates PAK in a ROCK-independent manner. Our study demonstrates that SP triggers rapid changes in cell morphology mediated by distinct intracellular signaling mechanisms in U373MG versus HEK293-NK1R cells.

  20. Auxin induces exocytosis and the rapid synthesis of a high-turnover pool of plasma-membrane H(+)-ATPase.

    Science.gov (United States)

    Hager, A; Debus, G; Edel, H G; Stransky, H; Serrano, R

    1991-11-01

    Auxin causes elongation growth of plant cells by increasing the plastic extensibility of the cell wall. Putative cellular events involved in this hormone action were studied using maize (Zea mays L.) coleoptiles with the following results: (i) Auxin enhances membrane flow from the endoplasmic reticulum to the plasma membrane (PM). This effect was demonstrated by pulse-labeling of the endoplasmic reticulum with myo-[(3)H]inositol in coleoptile segments and by measuring the distribution of the label within isolated and separated microsomal membrane fractions, (ii) Auxin rapidly increases the amount of antibody-detectable H(+)-ATPase in the PM. This augmentation is already significant 10 min after the addition of indole-3-acetic acid (IAA) and reaches a new higher steady-state level after about 30 min. (iii) Cycloheximide, a potent inhibitor of both protein synthesis and extension growth, quickly diminishes the auxin-enhanced level of the PM H(+)-ATPase, indicating an apparent half-life of the enzyme of around 12 min. (iv) Cordycepin, which blocks the synthesis of mRNAs, reduces the auxin-elevated level of the H(+)-ATPase similar to cycloheximide. (v) Changes in the growth rate of coleoptile segments in response to IAA, cycloheximide, and cordycepin exactly reflect the changes of the H(+)-ATPase level in the PM. (vi) The elongation growth induced by fusicoccin, or ester compounds, or by an elevated CO2 concentration in the incubation medium, is not related to an increased number of H(+)-ATPase molecules within the PM. (vii) The necessity of H(+) for cell-wall-loosening processes is again demonstrated by growth experiments with abraded coleoptile segments. The adjustment of the cell wall to a pH of ≥6.5 completely abolishes the auxin-induced elongation growth; no inhibition occurs with non-abraded segments. Buffer solutions of pH ≤6.0 induce "acid growth" of abraded segments for several hours. It is suggested that auxin activates a cluster of genes responsible (i

  1. An invasive species induces rapid adaptive change in a native predator: cane toads and black snakes in Australia.

    Science.gov (United States)

    Phillips, Ben L; Shine, Richard

    2006-06-22

    Rapid environmental change due to human activities has increased rates of extinction, but some species may be able to adapt rapidly enough to deal with such changes. Our studies of feeding behaviour and physiological resistance to toxins reveal surprisingly rapid adaptive responses in Australian black snakes (Pseudechis porphyriacus) following the invasion of a lethally toxic prey item, the cane toad (Bufo marinus). Snakes from toad-exposed localities showed increased resistance to toad toxin and a decreased preference for toads as prey. Separate laboratory experiments suggest that these changes are not attributable to learning (we were unable to teach naive snakes to avoid toxic prey) or to acquired resistance (repeated sub-lethal doses did not enhance resistance). These results strongly suggest that black snake behaviour and physiology have evolved in response to the presence of toads, and have done so rapidly. Toads were brought to Australia in 1935, so these evolved responses have occurred in fewer than 23 snake generations.

  2. Carbachol induces a rapid and sustained hydrolysis of polyphosphoinositide in bovine tracheal smooth muscle measurements of the mass of polyphosphoinositides, 1,2-diacylglycerol, and phosphatidic acid.

    Science.gov (United States)

    Takuwa, Y; Takuwa, N; Rasmussen, H

    1986-11-05

    The effects of carbachol on polyphosphoinositides and 1,2-diacylglycerol metabolism were investigated in bovine tracheal smooth muscle by measuring both lipid mass and the turnover of [3H]inositol-labeled phosphoinositides. Carbachol induces a rapid reduction in the mass of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate and a rapid increase in the mass of 1,2-diacylglycerol and phosphatidic acid. These changes in lipid mass are sustained for at least 60 min. The level of phosphatidylinositol shows a delayed and progressive decrease during a 60-min period of carbachol stimulation. The addition of atropine reverses these responses completely. Carbachol stimulates a rapid loss in [3H]inositol radioactivity from phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate associated with production of [3H]inositol trisphosphate. The carbachol-induced change in the mass of phosphoinositides and phosphatidic acid is not affected by removal of extracellular Ca2+ and does not appear to be secondary to an increase in intracellular Ca2+. These results indicate that carbachol causes phospholipase C-mediated polyphosphoinositide breakdown, resulting in the production of inositol trisphosphate and a sustained increase in the actual content of 1,2-diacylglycerol. These results strongly suggest that carbachol-induced contraction is mediated by the hydrolysis of polyphosphoinositides with the resulting generation of two messengers: inositol 1,4,5-trisphosphate and 1,2-diacylglycerol.

  3. Carbachol induces a rapid and sustained hydrolysis of polyphosphoinositide in bovine tracheal smooth muscle measurements of the mass of polyphosphoinositides, 1,2-diacylglycerol, and phosphatidic acid

    Energy Technology Data Exchange (ETDEWEB)

    Takuwa, Y.; Takuwa, N.; Rasmussen, H.

    1986-11-05

    The effects of carbachol on polyphosphoinositides and 1,2-diacylglycerol metabolism were investigated in bovine tracheal smooth muscle by measuring both lipid mass and the turnover of (/sup 3/H)inositol-labeled phosphoinositides. Carbachol induces a rapid reduction in the mass of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate and a rapid increase in the mass of 1,2-diacylglycerol and phosphatidic acid. These changes in lipid mass are sustained for at least 60 min. The level of phosphatidylinositol shows a delayed and progressive decrease during a 60-min period of carbachol stimulation. The addition of atropine reverses these responses completely. Carbachol stimulates a rapid loss in (/sup 3/H)inositol radioactivity from phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate associated with production of (/sup 3/H)inositol trisphosphate. The carbachol-induced change in the mass of phosphoinositides and phosphatidic acid is not affected by removal of extracellular Ca/sup 2 +/ and does not appear to be secondary to an increase in intracellular Ca/sup 2 +/. These results indicate that carbachol causes phospholipase C-mediated polyphosphoinositide breakdown, resulting in the production of inositol trisphosphate and a sustained increase in the actual content of 1,2-diacylglycerol. These results strongly suggest that carbachol-induced contraction is mediated by the hydrolysis of polyphosphoinositides with the resulting generation of two messengers: inositol 1,4,5-trisphosphate and 1,2-diacylglycerol.

  4. CCR3 expression induced by IL-2 and IL-4 functioning as a death receptor for B cells

    DEFF Research Database (Denmark)

    Jinquan, Tan; Jacobi, Henrik H; Jing, Chen

    2003-01-01

    We report that CCR3 is not expressed on freshly isolated peripheral and germinal B cells, but is up-regulated after stimulation with IL-2 and IL-4 (approximately 98% CCR3(+)). Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19......(+) (approximately 40% apoptotic cells) B cell cultures as well as B cell lines, but has no effect on chemotaxis or cell adhesion. Freshly isolated B cells express low levels of CD95 and CD95 ligand (CD95L) (19 and 21%, respectively). Expression is up-regulated on culture in the presence of a combination of IL-2, IL...

  5. Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC) - the Hot Start experience

    NARCIS (Netherlands)

    De Sousa, Paul A.; Steeg, Rachel; Wachter, Elisabeth; Bruce, Kevin; King, Jason; Hoeve, Marieke; Khadun, Shalinee; McConnachie, George; Holder, Julie; Kurtz, Andreas; Seltmann, Stefanie; Dewender, Johannes; Reimann, Sascha; Stacey, Glyn; O'Shea, Orla; Chapman, Charlotte; Healy, Lyn; Zimmermann, Heiko; Bolton, Bryan; Rawat, Trisha; Atkin, Isobel; Veiga, Anna; Kuebler, Bernd; Serano, Blanca Miranda; Saric, Tomo; Hescheler, Jürgen; Brüstle, Oliver; Peitz, Michael; Thiele, Cornelia; Geijsen, Niels; Holst, Bjørn; Clausen, Christian; Lako, Majlinda; Armstrong, Lyle; Gupta, Shailesh K.; Kvist, Alexander J.; Hicks, Ryan; Jonebring, Anna; Brolén, Gabriella; Ebneth, Andreas; Cabrera-Socorro, Alfredo; Foerch, Patrik; Geraerts, Martine; Stummann, Tina C.; Harmon, Shawn; George, Carol; Streeter, Ian; Clarke, Laura; Parkinson, Helen; Harrison, Peter W.; Faulconbridge, Adam; Cherubin, Luca; Burdett, Tony; Trigueros, Cesar; Patel, Minal J.; Lucas, Christa; Hardy, Barry; Predan, Rok; Dokler, Joh; Brajnik, Maja; Keminer, Oliver; Pless, Ole; Gribbon, Philip; Claussen, Carsten; Ringwald, Annette; Kreisel, Beate; Courtney, Aidan; Allsopp, Timothy E.

    2017-01-01

    A fast track “Hot Start” process was implemented to launch the European Bank for Induced Pluripotent Stem Cells (EBiSC) to provide early release of a range of established control and disease linked human induced pluripotent stem cell (hiPSC) lines. Established practice amongst consortium members was

  6. Rapid establishment of the European Bank for induced Pluripotent Stem Cells (EBiSC - the Hot Start experience

    Directory of Open Access Journals (Sweden)

    Paul A. De Sousa

    2017-04-01

    eTOC: The report focuses on the EBiSC experience of rapidly establishing an operational capacity to procure, bank and distribute a foundational collection of established hiPSC lines. It validates the feasibility and defines the challenges of harnessing and integrating the capability and productivity of centres across Europe using commonly available resources currently in the field.

  7. Equivalence of biomechanical changes induced by rapid and standard corneal cross-linking, using riboflavin and ultraviolet radiation.

    Science.gov (United States)

    Schumacher, Silvia; Oeftiger, Lydia; Mrochen, Michael

    2011-11-25

    Ultraviolet (UV) corneal cross-linking is an accepted method for treating corneal ecstatic disorders. The authors evaluated whether a rapid treatment protocol (higher intensity and shorter irradiation time) could achieve the same increase in corneal stiffness as the currently used standard protocol. Stress-strain measurements were performed on porcine corneal strips. The corneas (n = 72) were cut into three strips, each randomly receiving a different treatment: rapid (10 mW/cm(2), 9 minutes), standard (3 mW/cm(2), 30 minutes), or no (control, 0 mW/cm(2)) irradiation. After irradiation, the Young's modulus of each strip was determined. The results of the stress-strain measurements were analyzed statistically. Statistical analysis showed that, after irradiation, the median value of Young's modulus from both active treatment groups (rapid, 3.83 N/mm(2); standard, 3.88 N/mm(2)) was significantly higher (P cross-linking treatment can be regarded as equivalent to the standard procedure in terms of increase in corneal stiffness. The new rapid protocol shortens the treatment duration by more than two thirds, from 30 to 9 minutes. The safety of the higher intensities must be addressed in further clinical studies.

  8. Synthetic Toll-like receptor 4 (TLR4) and TLR7 ligands as influenza virus vaccine adjuvants induce rapid, sustained, and broadly protective responses.

    Science.gov (United States)

    Goff, Peter H; Hayashi, Tomoko; Martínez-Gil, Luis; Corr, Maripat; Crain, Brian; Yao, Shiyin; Cottam, Howard B; Chan, Michael; Ramos, Irene; Eggink, Dirk; Heshmati, Mitra; Krammer, Florian; Messer, Karen; Pu, Minya; Fernandez-Sesma, Ana; Palese, Peter; Carson, Dennis A

    2015-03-01

    Current vaccines against influenza virus infection rely on the induction of neutralizing antibodies targeting the globular head of the viral hemagglutinin (HA). Protection against seasonal antigenic drift or sporadic pandemic outbreaks requires further vaccine development to induce cross-protective humoral responses, potentially to the more conserved HA stalk region. Here, we present a novel viral vaccine adjuvant comprised of two synthetic ligands for Toll-like receptor 4 (TLR4) and TLR7. 1Z105 is a substituted pyrimido[5,4-b]indole specific for the TLR4-MD2 complex, and 1V270 is a phospholipid-conjugated TLR7 agonist. Separately, 1Z105 induces rapid Th2-associated IgG1 responses, and 1V270 potently generates Th1 cellular immunity. 1Z105 and 1V270 in combination with recombinant HA from the A/Puerto Rico/8/1934 strain (rPR/8 HA) effectively induces rapid and sustained humoral immunity that is protective against lethal challenge with a homologous virus. More importantly, immunization with the combined adjuvant and rPR/8 HA, a commercially available split vaccine, or chimeric rHA antigens significantly improves protection against both heterologous and heterosubtypic challenge viruses. Heterosubtypic protection is associated with broadly reactive antibodies to HA stalk epitopes. Histological examination and cytokine profiling reveal that intramuscular (i.m.) administration of 1Z105 and 1V270 is less reactogenic than a squalene-based adjuvant, AddaVax. In summary, the combination of 1Z105 and 1V270 with a recombinant HA induces rapid, long-lasting, and balanced Th1- and Th2-type immunity; demonstrates efficacy in a variety of murine influenza virus vaccine models assaying homologous, heterologous, and heterosubtypic challenge viruses; and has an excellent safety profile. Novel adjuvants are needed to enhance immunogenicity and increase the protective breadth of influenza virus vaccines to reduce the seasonal disease burden and ensure pandemic preparedness. We show

  9. Rapid long-wave infrared laser-induced breakdown spectroscopy measurements using a mercury-cadmium-telluride linear array detection system.

    Science.gov (United States)

    Yang, Clayton S-C; Brown, Eiei; Kumi-Barimah, Eric; Hommerich, Uwe; Jin, Feng; Jia, Yingqing; Trivedi, Sudhir; D'souza, Arvind I; Decuir, Eric A; Wijewarnasuriya, Priyalal S; Samuels, Alan C

    2015-11-20

    In this work, we develop a mercury-cadmium-telluride linear array detection system that is capable of rapidly capturing (∼1-5  s) a broad spectrum of atomic and molecular laser-induced breakdown spectroscopy (LIBS) emissions in the long-wave infrared (LWIR) region (∼5.6-10  μm). Similar to the conventional UV-Vis LIBS, a broadband emission spectrum of condensed phase samples covering the whole 5.6-10 μm region can be acquired from just a single laser-induced microplasma or averaging a few single laser-induced microplasmas. Atomic and molecular signature emission spectra of solid inorganic and organic tablets and thin liquid films deposited on a rough asphalt surface are observed. This setup is capable of rapidly probing samples "as is" without the need of elaborate sample preparation and also offers the possibility of a simultaneous UV-Vis and LWIR LIBS measurement.

  10. Rapid and controllable a-Si:H-to-nc-Si:H transition induced by a high-density plasma route

    Science.gov (United States)

    Zhou, H. P.; Xu, M.; Xu, S.; Xu, L. X.; Ji, H.; Xiao, S. Q.; Feng, Y. Y.

    2017-09-01

    The low-temperature rapid solid phase crystallization route of amorphous silicon is fundamentally and technologically significant. Micrometer thick hydrogenated amorphous silicon (a-Si:H) films were exposed to a low-frequency inductively coupled hydrogen plasma under a low substrate temperature of 300 °C. The plasma treated a-Si:H was completely crystallized within half an hour. The evolution of microstructures, optical and electric properties with respect to plasma exposure duration deterministically demonstrates that the present low-temperature rapid crystallization process enables the controllable phase transition from amorphous to nanocrystalline (nc) silicon. The crystallization mechanism is discussed in terms of the unique characteristics of low-frequency inductively coupled plasma (LFICP) and the LFICP-grown precursor a-Si:H film itself. The crucial role of hydrogen atoms in the phase transition is also discussed.

  11. Cytokine-induced proapoptotic gene expression in insulin-producing cells is related to rapid, sustained, and nonoscillatory nuclear factor-kappaB activation

    DEFF Research Database (Denmark)

    Ortis, Fernanda; Cardozo, Alessandra K; Crispim, Daisy

    2006-01-01

    Cytokines, such as IL-1beta and TNF-alpha, contribute to pancreatic beta-cell death in type 1 diabetes mellitus. The transcription factor nuclear factor-kappaB (NF-kappaB) mediates cytokine-induced beta-cell apoptosis. Paradoxically, NF-kappaB has mostly antiapoptotic effects in other cell types......-kappaB activation in insulin-producing cells is more rapid, marked, and sustained than in fibroblasts, which correlates with a more pronounced activation of downstream genes and a proapoptotic outcome....

  12. Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil.

    Science.gov (United States)

    Wuo-Silva, Raphael; Fukushiro, Daniela F; Hollais, André W; Santos-Baldaia, Renan; Mári-Kawamoto, Elisa; Berro, Laís F; Yokoyama, Thaís S; Lopes-Silva, Leonardo B; Bizerra, Carolina S; Procópio-Souza, Roberta; Hashiguchi, Debora; Figueiredo, Lilian A; Costa, Jose L; Frussa-Filho, Roberto; Longo, Beatriz M

    2016-01-01

    There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross-sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg) induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4 h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.

  13. MODAFINIL INDUCES RAPID-ONSET BEHAVIORAL SENSITIZATION AND CROSS-SENSTIZATION WITH COCAINE IN MICE: IMPLICATIONS FOR THE ADDICTIVE POTENTIAL OF MODAFINIL

    Directory of Open Access Journals (Sweden)

    Raphael Wuo-Silva

    2016-11-01

    Full Text Available There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration has been emerged as a valuable tool to study binge-like patterns of drug abuse and the neuroplastic changes that occur quickly after drug administration that ultimately lead to drug abuse. Our aim was to investigate the possible development of rapid-onset behavioral sensitization to modafinil and bidirectional rapid-onset cross-sensitization with cocaine in male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg induced rapid-onset behavioral sensitization to challenge injections of modafinil at the doses of 16 mg/kg, 32 mg/kg, and 64 mg/kg, administered 4h later. Furthermore, rapid-onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg modafinil and 20 mg/kg cocaine, in a bidirectional way. These results were not due to residual levels of modafinil as the behavioral effects of the priming injection of modafinil were no longer present and modafinil plasma concentration was reduced at 4h post-administration. Taken together, the present findings provide preclinical evidence that modafinil can be reinforcing per se and can enhance the reinforcing effects of stimulants like cocaine within hours after administration.

  14. Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8(+) T cells

    DEFF Research Database (Denmark)

    Schmidt, Jonas D; Ahlström, Malin G; Johansen, Jeanne D

    2017-01-01

    of the challenge response correlated with the epidermal accumulation of interleukin (IL)-17A-producing and interferon (IFN)-γ-producing TRM cells. Moreover, IL-17A and IFN-γ enhanced allergen-induced IL-1β production in keratinocytes. CONCLUSIONS: We show that sensitization with contact allergens induces a strong......, long-lasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN-γ-producing CD8(+) TRM cells....

  15. The NLP toxin family in Phytophthora sojae includes rapidly evolving groups that lack necrosis-inducing activity.

    Science.gov (United States)

    Dong, Suomeng; Kong, Guanghui; Qutob, Dinah; Yu, Xiaoli; Tang, Junli; Kang, Jixiong; Dai, Tingting; Wang, Hai; Gijzen, Mark; Wang, Yuanchao

    2012-07-01

    Necrosis- and ethylene-inducing-like proteins (NLP) are widely distributed in eukaryotic and prokaryotic plant pathogens and are considered to be important virulence factors. We identified, in total, 70 potential Phytophthora sojae NLP genes but 37 were designated as pseudogenes. Sequence alignment of the remaining 33 NLP delineated six groups. Three of these groups include proteins with an intact heptapeptide (Gly-His-Arg-His-Asp-Trp-Glu) motif, which is important for necrosis-inducing activity, whereas the motif is not conserved in the other groups. In total, 19 representative NLP genes were assessed for necrosis-inducing activity by heterologous expression in Nicotiana benthamiana. Surprisingly, only eight genes triggered cell death. The expression of the NLP genes in P. sojae was examined, distinguishing 20 expressed and 13 nonexpressed NLP genes. Real-time reverse-transcriptase polymerase chain reaction results indicate that most NLP are highly expressed during cyst germination and infection stages. Amino acid substitution ratios (Ka/Ks) of 33 NLP sequences from four different P. sojae strains resulted in identification of positive selection sites in a distinct NLP group. Overall, our study indicates that expansion and pseudogenization of the P. sojae NLP family results from an ongoing birth-and-death process, and that varying patterns of expression, necrosis-inducing activity, and positive selection suggest that NLP have diversified in function.

  16. Negatively charged food additive dye "Allura Red" rapidly induces SDS-soluble amyloid fibril in beta-lactoglobulin protein.

    Science.gov (United States)

    Al-Shabib, Nasser Abdulatif; Khan, Javed Masood; Malik, Ajamaluddin; Alsenaidy, Abdulrahman M; Alsenaidy, Mohammad A; Husain, Fohad Mabood; Shamsi, Monis Bilal; Hidayathulla, Syed; Khan, Rizwan Hasan

    2018-02-01

    Recent studies have led to an increased interest to categorize small molecular inhibitors of protein fibrillation. In this study, we used spectroscopy, microscopy and gel electrophoresis techniques that provides an elaborated description of the Allura Red-induced amyloid fibrillation in the β-LG protein at two pHs (7.4 and 3.5). The spectroscopy results show that β-LG protein form aggregates in the presence of Allura Red (0.04-15.0mM) at pH 3.5 due to electrostatic and hydrophobic interactions. However, at pH 7.4, the β-LG does not interact electrostatically with Allura Red and therefore no aggregation occurred. The Allura Red-induced aggregates have an amyloid-like structure that was confirmed by far-UV CD, Congo Red and transmission electron microscopy (TEM). The CD spectrum of β-LG contains single minima at ∼218nm, which shifts towards higher wavelength minima at ∼225nm in the presence of Allura Red, characteristics of the cross β-sheet structure. The TEM results suggest that β-LG form long straight fibril when exposed to Allura Red at pH 3.5. The Allura Red-induced amyloid fibril is SDS-soluble confirmed by SDS-PAGE techniques. A far UV CD result shows the conversion of Allura Red induced cross β-sheet structure into alpha-helical structure in the presence of increasing concentration of SDS. The results of this study suggest that the electrostatic, as well as hydrophobic interactions play an important role during Allura Red-induced β-LG fibrillation. Copyright © 2017. Published by Elsevier B.V.

  17. The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway.

    Science.gov (United States)

    Eidet, J R; Reppe, S; Pasovic, L; Olstad, O K; Lyberg, T; Khan, A Z; Fostad, I G; Chen, D F; Utheim, T P

    2016-03-04

    Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients with age-related macular degeneration represents a promising novel treatment modality. Development of RPE transplants, however, requires up to 3 months of cell differentiation. We explored whether the silk protein sericin can induce maturation of primary human retinal pigment epithelial (hRPE) cells. Microarray analysis demonstrated that sericin up-regulated RPE-associated transcripts (RPE65 and CRALBP). Upstream analysis identified the NF-κB pathway as one of the top sericin-induced regulators. ELISA confirmed that sericin stimulates the main NF-κB pathway. Increased levels of RPE-associated proteins (RPE65 and the pigment melanin) in the sericin-supplemented cultures were confirmed by western blot, spectrophotometry and transmission electron microscopy. Sericin also increased cell density and reduced cell death following serum starvation in culture. Inclusion of NF-κB agonists and antagonists in the culture medium showed that activation of the NF-κB pathway appears to be necessary, but not sufficient, for sericin-induced RPE pigmentation. We conclude that sericin promotes pigmentation of cultured primary hRPE cells by activating the main NF-κB pathway. Sericin's potential role in culture protocols for rapid differentiation of hRPE cells derived from embryonic or induced pluripotent stem cells should be investigated.

  18. Toxicant induced changes on delayed fluorescence decay kinetics of cyanobacteria and green algae: a rapid and sensitive biotest.

    Directory of Open Access Journals (Sweden)

    Franziska Leunert

    Full Text Available Algal tests have developed into routine tools for testing toxicity of pollutants in aquatic environments. Meanwhile, in addition to algal growth rates, an increasing number of fluorescence based methods are used for rapid and sensitive toxicity measures. The present study stresses the suitability of delayed fluorescence (DF as a promising parameter for biotests. DF is based on the recombination fluorescence at the reaction centre of photosystem II, which is emitted only by photosynthetically active cells. We analyzed the effects of three chemicals (3-(3,4-dichlorophenyl-1,1-dimethylurea (DCMU, 3,5 Dichlorophenol (3,5 DCP and copper on the shape of the DF decay kinetics for potential use in phytoplankton toxicity tests. The short incubation tests were done with four phytoplankton species, with special emphasis on the cyanobacterium Microcystis aeruginosa. All species exhibited a high sensitivity to DCMU, but cyanobacteria were more affected by copper and less by 3,5 DCP than the tested green algae. Analyses of changes in the DF decay curve in response to the added chemicals indicated the feasibility of the DF decay approach as a rapid and sensitive testing tool.

  19. Induced unilateral vocal fold paralysis and recovery rapidly modulate brain areas related to phonatory behavior: a case study.

    Science.gov (United States)

    Joshi, Ashwini; Jiang, Yang; Stemple, Joseph C; Archer, Sanford M; Andreatta, Richard D

    2011-03-01

    Peripheral and behavioral effects of voice disorders are well documented in the literature; yet, there is little information regarding the central neural biomarkers and mechanisms underlying these disorders. Understanding the details of brain function changes in disordered voice production is a critical factor for developing better treatment strategies that result in more robust patient outcomes. To examine a model of induced unilateral vocal fold paralysis (iUVFP) to demonstrate and characterize the form of activity changes within central mappings of the larynx to the induced paralysis. The induced paralysis model allowed the participant to serve as his or her own control when comparing baseline results of normal voice with results during the paralysis and subsequent recovery. Prospective, case-study design. Functional magnetic resonance imaging was used to examine central laryngeal representations during three time points: pre-iUVFP, during iUVFP, and postrecovery from iUVFP. iUVFP was induced using a lidocaine with epinephrine nerve block unilaterally. Percent changes in blood oxygenation level-dependent (BOLD) activity served as the dependent variable. Results indicated an overall reduced activity level in sensorimotor, subcortical, and cerebellar regions during paralysis. Recovery from paralysis led to augmented responses, particularly in sensory, association, and cerebellar zones. The decrease in activity during iUVFP and the significantly increased activity during the recovery phase likely represent immediate neuroplastic events occurring within minutes of nerve blockade. Recovery-related changes in the BOLD response are hypothesized to be associated with a recalibration of the system after return of normal laryngeal function. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  20. Salmonella enterica serovar Choleraesuis infection of the porcine jejunal Peyer's patch rapidly induces IL-1beta and IL-8 expression.

    Science.gov (United States)

    Hyland, Kendra A; Brown, David R; Murtaugh, Michael P

    2006-01-15

    Salmonella enterica serovar Choleraesuis is an enteric pathogen of swine, producing septicemia, enterocolitis, pneumonia, and hepatitis. The initial molecular events at the site of Salmonella infection are hypothesized to be critical in the initiation of innate and adaptive immune responses; however, the acute immune response elicited by porcine intestinal tissues is not well understood. To address this need, we employed explants of jejunal Peyer's patch (JPP) mucosa from pigs to examine Salmonella-induced immune responses under controlled conditions as well as to overcome limitations of whole animal approaches. JPP explants mounted in Ussing chambers maintained normal histological structure for 2 h and stable short-circuit current and electrical conductance for 2.5 h. After ex vivo luminal exposure to Salmonella serovar Choleraesuis, JPP responded with an increase in mRNA expression of IL-1beta and IL-8, but not TNFalpha. Increased IL-1beta and IL-8 expression were dependent on efficient Salmonella adhesion and internalization, whereas mutant Salmonella did not induce inflammatory cytokine expression. Commensal enteric bacteria, present in some experiments, also did not induce inflammatory cytokine expression. These findings indicate that Salmonella uptake by Peyer's patch is important in the induction of an innate response involving expression of IL-1beta and IL-8, and that ex vivo intestinal immune tissue explants provide an intact tissue model that will facilitate investigation of mucosal immunity in swine.

  1. Low-Temperature Rapid Fabrication of ZnO Nanowire UV Sensor Array by Laser-Induced Local Hydrothermal Growth

    Directory of Open Access Journals (Sweden)

    Sukjoon Hong

    2013-01-01

    Full Text Available We demonstrate ZnO nanowire based UV sensor by laser-induced hydrothermal growth of ZnO nanowire. By inducing a localized temperature rise using focused laser, ZnO nanowire array at ~15 μm size consists of individual nanowires with ~8 μm length and 200~400 nm diameter is readily synthesized on gold electrode within 30 min at the desired position. The laser-induced growth process is consecutively applied on two different points to bridge the micron gap between the electrodes. The resultant photoconductive ZnO NW interconnections display 2~3 orders increase in the current upon the UV exposure at a fixed voltage bias. It is also confirmed that the amount of photocurrent can be easily adjusted by changing the number of ZnO NW array junctions. The device exhibits clear response to the repeated UV illumination, suggesting that this process can be usefully applied for the facile fabrication of low-cost UV sensor array.

  2. Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation

    Science.gov (United States)

    Lenoir, Magalie

    2012-01-01

    Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2–6 s) increased (30–70 μM or 6–14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (−20–40 μM or 5–10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

  3. Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation.

    Science.gov (United States)

    Kiyatkin, Eugene A; Lenoir, Magalie

    2012-09-01

    Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2-6 s) increased (30-70 μM or 6-14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (-20-40 μM or 5-10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

  4. Rabbit antithymocyte globulin induces rapid expansion of effector memory CD8 T cells without accelerating acute graft versus host disease.

    Science.gov (United States)

    Wittenbecher, Friedrich; Rieger, Kathrin; Dziubianau, Mikalai; Herholz, Anne; Mensen, Angela; Blau, Igor Wolfgang; Uharek, Lutz; Dörken, Bernd; Thiel, Andreas; Na, Il-Kang

    2013-01-01

    Rabbit antithymocyte globulin (Thymoglobulin(®)) is commonly used as graft-versus-host disease (GvHD) prophylaxis. Since we found similar total CD8 T cell numbers in patients with and without Thymoglobulin(®) therapy within the first six months after allogeneic hematopoietic stem cell transplantation, we have analyzed the reconstitution of the CD8 T cell compartment in detail. After T cell-depletion, higher and more sustained proliferative capacity of memory CD8 T cells resulted in their rapid expansion, whereas the fraction of naive CD8 T cells decreased. Importantly, this shift towards effector memory CD8 T cells did not accelerate the incidence of GvHD.

  5. The Rapidity Distributions and the Thermalization Induced Transverse Momentum Distributions in Au-Au Collisions at RHIC Energies

    Directory of Open Access Journals (Sweden)

    Zhi-Jin Jiang

    2017-01-01

    Full Text Available It is widely believed that the quark-gluon plasma (QGP might be formed in the current heavy ion collisions. It is also widely recognized that the relativistic hydrodynamics is one of the best tools for describing the process of expansion and hadronization of QGP. In this paper, by taking into account the effects of thermalization, a hydrodynamic model including phase transition from QGP state to hadronic state is used to analyze the rapidity and transverse momentum distributions of identified charged particles produced in heavy ion collisions. A comparison is made between the theoretical results and experimental data. The theoretical model gives a good description of the corresponding measurements made in Au-Au collisions at RHIC energies.

  6. An alphavirus vector-based tetravalent dengue vaccine induces a rapid and protective immune response in macaques that differs qualitatively from immunity induced by live virus infection.

    Science.gov (United States)

    White, Laura J; Sariol, Carlos A; Mattocks, Melissa D; Wahala M P B, Wahala; Yingsiwaphat, Vorraphun; Collier, Martha L; Whitley, Jill; Mikkelsen, Rochelle; Rodriguez, Idia V; Martinez, Melween I; de Silva, Aravinda; Johnston, Robert E

    2013-03-01

    Despite many years of research, a dengue vaccine is not available, and the more advanced live attenuated vaccine candidate in clinical trials requires multiple immunizations with long interdose periods and provides low protective efficacy. Here, we report important contributions to the development of a second-generation dengue vaccine. First, we demonstrate that a nonpropagating vaccine vector based on Venezuelan equine encephalitis virus replicon particles (VRP) expressing two configurations of dengue virus E antigen (subviral particles [prME] and soluble E dimers [E85]) successfully immunized and protected macaques against dengue virus, while antivector antibodies did not interfere with a booster immunization. Second, compared to prME-VRP, E85-VRP induced neutralizing antibodies faster, to higher titers, and with improved protective efficacy. Third, this study is the first to map antigenic domains and specificities targeted by vaccination versus natural infection, revealing that, unlike prME-VRP and live virus, E85-VRP induced only serotype-specific antibodies, which predominantly targeted EDIII, suggesting a protective mechanism different from that induced by live virus and possibly live attenuated vaccines. Fourth, a tetravalent E85-VRP dengue vaccine induced a simultaneous and protective response to all 4 serotypes after 2 doses given 6 weeks apart. Balanced responses and protection in macaques provided further support for exploring the immunogenicity and safety of this vaccine candidate in humans.

  7. An insert-based enzymatic cell culture system to rapidly and reversibly induce hypoxia: investigations of hypoxia-induced cell damage, protein expression and phosphorylation in neuronal IMR-32 cells

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2013-11-01

    Ischemia-reperfusion injury and tissue hypoxia are of high clinical relevance because they are associated with various pathophysiological conditions such as myocardial infarction and stroke. Nevertheless, the underlying mechanisms causing cell damage are still not fully understood, which is at least partially due to the lack of cell culture systems for the induction of rapid and transient hypoxic conditions. The aim of the study was to establish a model that is suitable for the investigation of cellular and molecular effects associated with transient and long-term hypoxia and to gain insights into hypoxia-mediated mechanisms employing a neuronal culture system. A semipermeable membrane insert system in combination with the hypoxia-inducing enzymes glucose oxidase and catalase was employed to rapidly and reversibly generate hypoxic conditions in the culture medium. Hydrogen peroxide assays, glucose measurements and western blotting were performed to validate the system and to evaluate the effects of the generated hypoxia on neuronal IMR-32 cells. Using the insert-based two-enzyme model, hypoxic conditions were rapidly induced in the culture medium. Glucose concentrations gradually decreased, whereas levels of hydrogen peroxide were not altered. Moreover, a rapid and reversible (onoff generation of hypoxia could be performed by the addition and subsequent removal of the enzyme-containing inserts. Employing neuronal IMR-32 cells, we showed that 3 hours of hypoxia led to morphological signs of cellular damage and significantly increased levels of lactate dehydrogenase (a biochemical marker of cell damage. Hypoxic conditions also increased the amounts of cellular procaspase-3 and catalase as well as phosphorylation of the pro-survival kinase Akt, but not Erk1/2 or STAT5. In summary, we present a novel framework for investigating hypoxia-mediated mechanisms at the cellular level. We claim that the model, the first of its kind, enables researchers to rapidly and

  8. Bimodal effect of hydrogen peroxide and oxidative events in nitrite-induced rapid root abscission by the water fern Azolla pinnata

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    Michael F Cohen

    2015-07-01

    Full Text Available In the genus Azolla rapid abscission of roots from floating fronds occurs within minutes in response to a variety of stresses, including exposure to nitrite. We found that hydrogen peroxide, though itself not an inducer of root abscission, modulates nitrite-induced root abscission by Azolla pinnata in a dose-dependent manner, with 2 mM H2O2 significantly diminishing the responsiveness to 2 mM NaNO2, and 10 mM H2O2 slightly enhancing it. Hypoxia, which has been found in other plants to result in autogenic production of H2O2, dramatically stimulated root abscission of A. pinnata in response to nitrite, especially for plants previously cultivated in medium containing 5 mM KNO3 compared to plants cultivated under N2-fixing conditions without combined nitrogen. Plants, including Azolla, produce the small signaling molecule nitric oxide (NO from nitrite using nitrate reductase. We found Azolla plants to display dose-dependent root abscission in response to the NO donor spermine NONOate. Treatment of plants with the thiol-modifying agents S-methyl methanethiosulfonate or glutathione inhibited the nitrite-induced root abscission response. Synchrotron radiation-based Fourier transform infrared (SR-FTIR spectromicroscopy revealed higher levels of carbonylation in the abscission zone of dropped roots, indicative of reaction products of polysaccharides with potent free radical oxidants. We hypothesize that metabolic products of nitrite and NO react with H2O2 in the apoplast leading to free-radical-mediated cleavage of structural polysaccharides and consequent rapid root abscission.

  9. Rapid negative inotropic effect induced by TNF-α in rat heart perfused related to PKC activation.

    Science.gov (United States)

    Jude, B; Vetel, S; Giroux-Metges, M A; Pennec, J P

    2017-11-29

    Myocardial depression, frequently observed in septic shock, is mediated by circulating molecules such as cytokines. TNF-α appears to be the most important pro-inflammatory cytokine released during the early phase of a septic shock. It was previously shown that TNF-α had a negative inotropic effect on myocardium. Now, the aim of this study was to investigate the effects of the activation of PKC by TNF-α on heart function, and to determine if this cytokine could induce a decrease of membrane excitability. Isolated rat hearts (n = 6) were perfused with Tyrode solution containing TNF-α at 20 ng/ml during 30 min by using a Langendorff technique. Expressions of PKC-α and PKC-ε were analysed by western blot on membrane and cytosol proteins extracted from ventricular myocardium. Patch clamp was performed on freshly isolated cardiomyocytes (n = 8). Compared to control situation, 30 min of TNF-α perfusion led to cardiac dysfunction with a decrease of the heart rate (-83%), the force (-20%) and speed of relaxation (-18%) and the coronary flow (-25%). This is associated with an activation and a membrane targeting of both PKC-α and PKC-ε isoforms in ventricle with respectively +123% and +54% compared to control hearts. Nevertheless, TNF-α had no significant effect on voltage-gated sodium current (109.0%+/- 12.5) after addition of the cytokine when compared to control. These results showed that TNF-α had a negative inotropic effect on the isolated rat heart and can induce PKC activation leading to an impaired contractility of the heart. However the early heart dysfunction induced by the cytokine was not associated to a decrease of cardiomyocytes membrane excitability as it has been evidenced in skeletal muscle fibres. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments

    Science.gov (United States)

    Richter, David; Moraga, Ignacio; Winkelmann, Hauke; Birkholz, Oliver; Wilmes, Stephan; Schulte, Markos; Kraich, Michael; Kenneweg, Hella; Beutel, Oliver; Selenschik, Philipp; Paterok, Dirk; Gavutis, Martynas; Schmidt, Thomas; Garcia, K. Christopher; Müller, Thomas D.; Piehler, Jacob

    2017-07-01

    The spatiotemporal organization of cytokine receptors in the plasma membrane is still debated with models ranging from ligand-independent receptor pre-dimerization to ligand-induced receptor dimerization occurring only after receptor uptake into endosomes. Here, we explore the molecular and cellular determinants governing the assembly of the type II interleukin-4 receptor, taking advantage of various agonists binding the receptor subunits with different affinities and rate constants. Quantitative kinetic studies using artificial membranes confirm that receptor dimerization is governed by the two-dimensional ligand-receptor interactions and identify a critical role of the transmembrane domain in receptor dimerization. Single molecule localization microscopy at physiological cell surface expression levels, however, reveals efficient ligand-induced receptor dimerization by all ligands, largely independent of receptor binding affinities, in line with the similar STAT6 activation potencies observed for all IL-4 variants. Detailed spatiotemporal analyses suggest that kinetic trapping of receptor dimers in actin-dependent microcompartments sustains robust receptor dimerization and signalling.

  11. Rapid review on the use of new age induced breeding agent ‘LHRHa’ in Indian finfish seed production sector

    Directory of Open Access Journals (Sweden)

    Koushik Roy

    2016-08-01

    Full Text Available A focused review on the use of LHRHa in induced breeding of fishes in India was made. Use of LHRHa is mainly restricted to high value brackish water and marine fish species whose market value generally exceeds INR 300-400/kg (USD 4.5-6/kg. Published information on use of LHRHa in induced breeding of fishes in India could document only twelve species out of which nine were brackishwater or marine fish. Besides length and weight, the egg diameter of female fishes (>0.45–0.7 mm is an important criterion for treating the fishes with LHRHa. LHRHa is either used alone or in combination with HCG (most popular, PGE, 17α-MT and Pimozide. Dosage of 20-70 µg/kg body weight for females and 10-40 µg/kg body weight for males with a latency period of 24-36 hours is most common in India. Experiments with LHRHa are being carried out mainly by ICAR-CIBA, Chennai (dominant and ICAR-CMFRI, Kochi. Standardization and optimization of LHRHa dosage has been attained in Asian Seabass (Lates calcarifer, Cobia (Rachycentron canadum, Grey mullet (Mugil cephalus and Spotted scat (Scatophagus argus while in Grouper (Epinephelus tauvina, Moonfish (Monodactylus argenteus, Milk fish (Chanos chanos, Crescent Bass (Terapon jarbua and Silver Pompano (Trachinotus blochii, it is under progress.

  12. Rapidly progressive course of Trypanosoma cruzi infection in mice heterozygous for hexamethylene bis-acetamide inducible 1 (Hexim1) gene.

    Science.gov (United States)

    Mascareno, Eduardo; Gupta, Raavi; Martello, Laura A; Dhar-Mascareno, Manya; Salciccioli, Louis; Beckles, Daniel; Walsh, Michael G; Machado, Fabiana S; Tanowitz, Herbert B; Haseeb, M A

    2018-01-01

    Infection with Trypanosoma cruzi causes Chagas disease and results in myocardial inflammation and cardiomyopathy. Downregulated Hexim1 expression, as in Hexim1 +/- mice, reduces cardiac inflammation and fibrosis following ischemic stress. We asked whether reduced expression of Hexim1 would also afford protection against T. cruzi-induced cardiomyopathy. C57BL/6J (wild type - WT) and Hexim1 +/- mice were infected with sub-lethal doses of T. cruzi (Brazil strain), and cardiac function, serologic markers of inflammation and tissue pathology were examined. Infected Hexim1 +/- mice had compromised cardiac function, altered expression of both pro- and anti-inflammatory cytokines, and increased inflammation and fibrosis. Cardiac failure was evidenced by severely diminished heart rate, compensatory increase in respiratory rate, and abnormally high left ventricular mass with severe transmural inflammation. Lungs displayed intense peribronchial inflammation and fibrosis extending into the parenchyma. We also observed Smad3-serine 208 phosphorylation in hearts and lungs of infected mice, suggesting increased TGF-β signaling pathway activity. This was more pronounced in Hexim1 +/- mice and correlated with increased fibrosis in these tissues. Conspicuous splenomegaly in the Hexim1 +/- mice most likely resulted from the observed extensive white pulp expansion. T. cruzi infection induced colonic dilatation and marked villous atrophy in both the WT and Hexim1 +/- mice but more so in the latter. The profound exacerbation of pathologic findings suggests a protective role for Hexim1 in T. cruzi infection. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  13. Rapid glycation with D-ribose induces globular amyloid-like aggregations of BSA with high cytotoxicity to SH-SY5Y cells

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    Ge Lin

    2009-02-01

    Full Text Available Abstract Background D-ribose in cells and human serum participates in glycation of proteins resulting in advanced glycation end products (AGEs that affect cell metabolism and induce cell death. However, the mechanism by which D-ribose-glycated proteins induce cell death is still unclear. Results Here, we incubated D-ribose with bovine serum albumin (BSA and observed changes in the intensity of fluorescence at 410 nm and 425 nm to monitor the formation of D-ribose-glycated BSA. Comparing glycation of BSA with xylose (a control for furanose, glucose and fructose (controls for pyranose, the rate of glycation with D-ribose was the most rapid. Protein intrinsic fluorescence (335 nm, Nitroblue tetrazolium (NBT assays and Western blotting with anti-AGEs showed that glycation of BSA incubated with D-ribose occurred faster than for the other reducing sugars. Protein intrinsic fluorescence showed marked conformational changes when BSA was incubated with D-ribose. Importantly, observations with atomic force microscopy showed that D-ribose-glycated BSA appeared in globular polymers. Furthermore, a fluorescent assay with Thioflavin T (ThT showed a remarkable increase in fluorescence at 485 nm in the presence of D-ribose-glycated BSA. However, ThT fluorescence did not show the same marked increase in the presence of xylose or glucose. This suggests that glycation with D-ribose induced BSA to aggregate into globular amyloid-like deposits. As observed by Hoechst 33258 staining, 3-(4, 5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT and cell counting kit-8 (CCK-8 assay, lactate dehydrogenase (LDH activity assay, flow cytometry using Annexin V and Propidium Iodide staining and reactive oxygen species (ROS measurements, the amyloid-like aggregation of glycated BSA induced apoptosis in the neurotypic cell line SH-SY5Y. Conclusion Glycation with D-ribose induces BSA to misfold rapidly and form globular amyloid-like aggregations which play an important

  14. Inducing magnetic anisotropy and optimized microstructure in rapidly solidified Nd-Fe-B based magnets by thermal gradient, magnetic field and hot deformation

    Science.gov (United States)

    Zhao, L. Z.; Li, W.; Wu, X. H.; Hussain, M.; Liu, Z. W.; Zhang, G. Q.; Greneche, J. M.

    2016-10-01

    Direct preparation of Nd-Fe-B alloys by rapid solidification of copper mold casting is a very simple and low cost process for mini-magnets, but these magnets are generally magnetically isotropic. In this work, high coercivity Nd24Co20Fe41B11Al4 rods were produced by injection casting. To induce magnetic anisotropy, temperature gradient, assisted magnetic field, and hot deformation (HD) procedures were employed. As-cast samples showed non-uniform microstructure due to the melt convection. The thermal gradient during solidification led to the formation of radially distributed acicular hard magnetic grains, which gives the magnetic anisotropy. The growth of the oriented grains was confirmed by phase field simulation. A magnetic field up to 1 T applied along the casting direction could not induce significant magnetic anisotropy, but it improved the magnetic properties by reducing the non-uniformity and forming a uniform microstructure. The annealed alloys exhibited high intrinsic coercivity but disappeared anisotropy. HD was demonstrated to be a good approach for inducing magnetic anisotropy and enhanced coercivity by deforming and refining the grains. This work provides an alternative approach for preparing fully dense Nd-rich anisotropic bulk Nd-Fe-B magnets.

  15. Investigations of rapid thermal annealing induced structural evolution of ZnO: Ge nanocomposite thin films via GISAXS

    Energy Technology Data Exchange (ETDEWEB)

    Ceylan, Abdullah, E-mail: aceylanabd@yahoo.com [Department of Physics Eng., Hacettepe University, Beytepe, 06800 Ankara (Turkey); Ozcan, Yusuf [Department of Electricity and Energy, Pamukkale University, Denizli (Turkey); Orujalipoor, Ilghar [Department of Nanotechnology and Nanomedicine, Hacettepe University, Beytepe, 06800 Ankara (Turkey); Huang, Yen-Chih; Jeng, U-Ser [National Synchrotron Radiation Research Center, 101 Hsin-Ann Road, Hsinchu Science Park, Hsinchu, Taiwan (China); Ide, Semra [Department of Physics Eng., Hacettepe University, Beytepe, 06800 Ankara (Turkey); Department of Nanotechnology and Nanomedicine, Hacettepe University, Beytepe, 06800 Ankara (Turkey)

    2016-06-07

    In this work, we present in depth structural investigations of nanocomposite ZnO: Ge thin films by utilizing a state of the art grazing incidence small angle x-ray spectroscopy (GISAXS) technique. The samples have been deposited by sequential r.f. and d.c. sputtering of ZnO and Ge thin film layers, respectively, on single crystal Si(100) substrates. Transformation of Ge layers into Ge nanoparticles (Ge-np) has been initiated by ex-situ rapid thermal annealing of asprepared thin film samples at 600 °C for 30, 60, and 90 s under forming gas atmosphere. A special attention has been paid on the effects of reactive and nonreactive growth of ZnO layers on the structural evolution of Ge-np. GISAXS analyses have been performed via cylindrical and spherical form factor calculations for different nanostructure types. Variations of the size, shape, and distributions of both ZnO and Ge nanostructures have been determined. It has been realized that GISAXS results are not only remarkably consistent with the electron microscopy observations but also provide additional information on the large scale size and shape distribution of the nanostructured components.

  16. Regeneration in bipinnaria larvae of the bat star Patiria miniata induces rapid and broad new gene expression

    Science.gov (United States)

    Oulhen, Nathalie; Heyland, Andreas; Carrier, Tyler J.; Zazueta-Novoa, Vanesa; Fresques, Tara; Laird, Jessica; Onorato, Thomas M.; Janies, Daniel; Wessel, Gary

    2016-01-01

    Background Some metazoa have the capacity to regenerate lost body parts. This phenomenon in adults has been classically described in echinoderms, especially in sea stars (Asteroidea). Sea star bipinnaria larvae can also rapidly and effectively regenerate a complete larva after surgical bisection. Understanding the capacity to reverse cell fates in the larva is important from both a developmental and biomedical perspective; yet, the mechanisms underlying regeneration in echinoderms are poorly understood. Results Here, we describe the process of bipinnaria regeneration after bisection in the bat star Patiria miniata. We tested transcriptional, translational, and cell proliferation activity after bisection in anterior and posterior bipinnaria halves as well as expression of SRAP, reported as a sea star regeneration associated protease (Vickery et al., 2001b). Moreover, we found several genes whose transcripts increased in abundance following bisection, including: vasa, dysferlin, vitellogenin 1 and vitellogenin 2. Conclusion These results show a transformation following bisection, especially in the anterior halves, of cell fate reassignment in all three germ layers, with clear and predictable changes. These results define molecular events that accompany the cell fate changes coincident to the regenerative response in echinoderm larvae. PMID:27555501

  17. Rapid prototyping of all-solution-processed multi-lengthscale electrodes using polymer-induced thin film wrinkling.

    Science.gov (United States)

    Gabardo, Christine M; Adams-McGavin, Robert C; Fung, Barnabas C; Mahoney, Eric J; Fang, Qiyin; Soleymani, Leyla

    2017-02-13

    Three-dimensional electrodes that are controllable over multiple lengthscales are very important for use in bioanalytical systems that integrate solid-phase devices with solution-phase samples. Here we present a fabrication method based on all-solution-processing and thin film wrinkling using smart polymers that is ideal for rapid prototyping of tunable three-dimensional electrodes and is extendable to large volume manufacturing. Although all-solution-processing is an attractive alternative to vapor-based techniques for low-cost manufacturing of electrodes, it often results in films suffering from low conductivity and poor substrate adhesion. These limitations are addressed here by using a smart polymer to create a conformal layer of overlapping wrinkles on the substrate to shorten the current path and embed the conductor onto the polymer layer. The structural evolution of these wrinkled electrodes, deposited by electroless deposition onto a nanoparticle seed layer, is studied at varying deposition times to understand its effects on structural parameters such as porosity, wrinkle wavelength and height. Furthermore, the effect of structural parameters on functional properties such as electro-active surface area and surface-enhanced Raman scattering is investigated. It is found that wrinkling of electroless-deposited thin films can be used to reduce sheet resistance, increase surface area, and enhance the surface-enhanced Raman scattering signal.

  18. Rapid prototyping of all-solution-processed multi-lengthscale electrodes using polymer-induced thin film wrinkling

    Science.gov (United States)

    Gabardo, Christine M.; Adams-McGavin, Robert C.; Fung, Barnabas C.; Mahoney, Eric J.; Fang, Qiyin; Soleymani, Leyla

    2017-02-01

    Three-dimensional electrodes that are controllable over multiple lengthscales are very important for use in bioanalytical systems that integrate solid-phase devices with solution-phase samples. Here we present a fabrication method based on all-solution-processing and thin film wrinkling using smart polymers that is ideal for rapid prototyping of tunable three-dimensional electrodes and is extendable to large volume manufacturing. Although all-solution-processing is an attractive alternative to vapor-based techniques for low-cost manufacturing of electrodes, it often results in films suffering from low conductivity and poor substrate adhesion. These limitations are addressed here by using a smart polymer to create a conformal layer of overlapping wrinkles on the substrate to shorten the current path and embed the conductor onto the polymer layer. The structural evolution of these wrinkled electrodes, deposited by electroless deposition onto a nanoparticle seed layer, is studied at varying deposition times to understand its effects on structural parameters such as porosity, wrinkle wavelength and height. Furthermore, the effect of structural parameters on functional properties such as electro-active surface area and surface-enhanced Raman scattering is investigated. It is found that wrinkling of electroless-deposited thin films can be used to reduce sheet resistance, increase surface area, and enhance the surface-enhanced Raman scattering signal.

  19. High glucose induced alteration of SIRTs in endothelial cells causes rapid aging in a p300 and FOXO regulated pathway.

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    Rokhsana Mortuza

    Full Text Available In diabetes, some of the cellular changes are similar to aging. We hypothesized that hyperglycemia accelerates aging-like changes in the endothelial cells (ECs and tissues leading to structural and functional damage. We investigated glucose-induced aging in 3 types of ECs using senescence associated β-gal (SA β-gal staining and cell morphology. Alterations of sirtuins (SIRTs and their downstream mediator FOXO and oxidative stress were investigated. Relationship of such alteration with histone acetylase (HAT p300 was examined. Similar examinations were performed in tissues of diabetic animals. ECs in high glucose (HG showed evidence of early senescence as demonstrated by increased SA β-gal positivity and reduced replicative capacities. These alterations were pronounced in microvascular ECs. They developed an irregular and hypertrophic phenotype. Such changes were associated with decreased SIRT (1-7 mRNA expressions. We also found that p300 and SIRT1 regulate each other in such process, as silencing one led to increase of the others' expression. Furthermore, HG caused reduction in FOXO1's DNA binding ability and antioxidant target gene expressions. Chemically induced increased SIRT1 activity and p300 knockdown corrected these abnormalities slowing aging-like changes. Diabetic animals showed increased cellular senescence in renal glomerulus and retinal blood vessels along with reduced SIRT1 mRNA expressions in these tissues. Data from this study demonstrated that hyperglycemia accelerates aging-like process in the vascular ECs and such process is mediated via downregulation of SIRT1, causing reduction of mitochondrial antioxidant enzyme in a p300 and FOXO1 mediated pathway.

  20. SLCO1B1 and SLC19A1 gene variants and irinotecan-induced rapid response and survival: a prospective multicenter pharmacogenetics study of metastatic colorectal cancer.

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    Liu Huang

    Full Text Available Rapid response to chemotherapy in metastatic colorectal cancer (mCRC patients (response within 12 weeks of chemotherapy may increase the chance of complete resection and improved survival. Few molecular markers predict irinotecan-induced rapid response and survival. Single-nucleotide polymorphisms (SNPs in solute carrier genes are reported to correlate with the variable pharmacokinetics of irinotecan and folate in cancer patients. This study aims to evaluate the predictive role of 3 SNPs in mCRC patients treated with irinotecan and fluoropyrimidine-containing regimens.Three SNPs were selected and genotyped in 137 mCRC patients from a Chinese prospective multicenter trial (NCT01282658. The chi-squared test, univariate and multivariable logistic regression model, and receiver operating characteristic analysis were used to evaluate correlations between the genotypes and rapid response. Kaplan-Meier survival analysis and Cox proportional hazard models were used to evaluate the associations between genotypes and survival outcomes. Benjamini and Hochberg False Discovery Rate correction was used in multiple testing.Genotype GA/AA of SNP rs2306283 of the gene SLCO1B1 and genotype GG of SNP rs1051266 of the gene SLC19A1 were associated with a higher rapid response rate (odds ratio [OR] =3.583 and 3.521, 95%CI =1.301-9.871 and 1.271-9.804, p=0.011 and p=0.013, respectively. The response rate was 70% in patients with both genotypes, compared with only 19.7% in the remaining patients (OR = 9.489, 95%CI = 2.191-41.093, Fisher's exact test p=0.002. Their significances were all maintained even after multiple testing (all p c < 0.05. The rs2306283 GA/AA genotype was also an independent prognostic factor of longer progression-free survival (PFS (hazard ratio = 0.402, 95%CI = 0.171-0.945, p=0.037. None of the SNPs predicted overall survival.Polymorphisms of solute carriers' may be useful to predict rapid response to irinotecan plus fluoropyrimidine and PFS in m

  1. Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response

    Science.gov (United States)

    Schauer, Dominic; Starlinger, Patrick; Alidzanovic, Lejla; Zajc, Philipp; Maier, Thomas; Feldman, Alexandra; Padickakudy, Robin; Buchberger, Elisabeth; Elleder, Vanessa; Spittler, Andreas; Stift, Judith; Pop, Lorand; Gruenberger, Birgit; Gruenberger, Thomas; Brostjan, Christine

    2016-01-01

    ABSTRACT We have previously reported that intermediate monocytes (CD14++/CD16+) were increased in colorectal cancer (CRC) patients, while the subset of pro-angiogenic TIE2-expressing monocytes (TEMs) was not significantly elevated. This study was designed to evaluate changes in frequency and function of intermediate monocytes and TEMs during chemotherapy and anti-angiogenic cancer treatment and their relation to treatment response. Monocyte populations were determined by flow cytometry in 60 metastasized CRC (mCRC) patients who received neoadjuvant chemotherapy with or without bevacizumab. Blood samples were taken before treatment, after two therapy cycles, at the end of neoadjuvant therapy and immediately before surgical resection of liver metastases. Neoadjuvant treatment resulted in a significant increase in circulating intermediate monocytes which was most pronounced after two cycles and positively predicted tumor response (AUC = 0.875, p = 0.005). With a cut-off value set to 1% intermediate monocytes of leukocytes, this parameter showed a predictive sensitivity and specificity of 75% and 88%. Anti-angiogenic therapy with bevacizumab had no impact on monocyte populations including TEMs. In 15 patients and six healthy controls, the gene expression profile and the migratory behavior of monocyte subsets was evaluated. The profile of intermediate monocytes suggested functions in antigen presentation, inflammatory cytokine production, chemotaxis and was remarkably stable during chemotherapy. Intermediate monocytes showed a preferential migratory response to tumor-derived signals in vitro and correlated with the level of CD14+/CD16+ monocytic infiltrates in the resected tumor tissue. In conclusion, the rapid rise of intermediate monocytes during chemotherapy may offer a simple marker for response prediction and a timely change in regimen. PMID:27471631

  2. Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Sudipta Das

    2016-05-01

    Full Text Available Among the several new antimalarials discovered over the past decade are at least three clinical candidate drugs, each with a distinct chemical structure, that disrupt Na+ homeostasis resulting in a rapid increase in intracellular Na+ concentration ([Na+]i within the erythrocytic stages of Plasmodium falciparum. At present, events triggered by Na+ influx that result in parasite demise are not well-understood. Here we report effects of two such drugs, a pyrazoleamide and a spiroindolone, on intraerythrocytic P. falciparum. Within minutes following the exposure to these drugs, the trophozoite stage parasite, which normally contains little cholesterol, was made permeant by cholesterol-dependent detergents, suggesting it acquired a substantial amount of the lipid. Consistently, the merozoite surface protein 1 and 2 (MSP1 and MSP2, glycosylphosphotidylinositol (GPI-anchored proteins normally uniformly distributed in the parasite plasma membrane, coalesced into clusters. These alterations were not observed following drug treatment of P. falciparum parasites adapted to grow in a low [Na+] growth medium. Both cholesterol acquisition and MSP1 coalescence were reversible upon the removal of the drugs, implicating an active process of cholesterol exclusion from trophozoites that we hypothesize is inhibited by high [Na+]i. Electron microscopy of drug-treated trophozoites revealed substantial morphological changes normally seen at the later schizont stage including the appearance of partial inner membrane complexes, dense organelles that resemble "rhoptries" and apparent nuclear division. Together these results suggest that [Na+]i disruptor drugs by altering levels of cholesterol in the parasite, dysregulate trophozoite to schizont development and cause parasite demise.

  3. Chemical-Induced Read-Through at Premature Termination Codons Determined by a Rapid Dual-Fluorescence System Based on S. cerevisiae.

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    Emiliano Altamura

    Full Text Available Nonsense mutations generate in-frame stop codons in mRNA leading to a premature arrest of translation. Functional consequences of premature termination codons (PTCs include the synthesis of truncated proteins with loss of protein function causing severe inherited or acquired diseases. A therapeutic approach has been recently developed that is based on the use of chemical agents with the ability to suppress PTCs (read-through restoring the synthesis of a functional full-length protein. Research interest for compounds able to induce read-through requires an efficient high throughput large scale screening system. We present a rapid, sensitive and quantitative method based on a dual-fluorescence reporter expressed in the yeast Saccharomyces cerevisiae to monitor and quantitate read-through at PTCs. We have shown that our novel system works equally well in detecting read-through at all three PTCs UGA, UAG and UAA.

  4. Rapidly induced, T-cell independent xenoantibody production is mediated by marginal zone B cells and requires help from NK cells.

    Science.gov (United States)

    Li, Shengqiao; Yan, Yehong; Lin, Yuan; Bullens, Dominique M; Rutgeerts, Omer; Goebels, Jozef; Segers, Constant; Boon, Louis; Kasran, Ahmad; De Vos, Rita; Dewolf-Peeters, Christiane; Waer, Mark; Billiau, An D

    2007-12-01

    Xenoantibody production directed at a wide variety of T lymphocyte-dependent and T lymphocyte-independent xenoantigens remains the major immunologic obstacle for successful xenotransplantation. The B lymphocyte subpopulations and their helper factors, involved in T-cell-independent xenoantibody production are only partially understood, and their identification will contribute to the clinical applicability of xenotransplantation. Here we show, using models involving T-cell-deficient athymic recipient mice, that rapidly induced, T-cell-independent xenoantibody production is mediated by marginal zone B lymphocytes and requires help from natural killer (NK) cells. This collaboration neither required NK-cell-mediated IFN-gamma production, nor NK-cell-mediated cytolytic killing of xenogeneic target cells. The T-cell-independent IgM xenoantibody response could be partially suppressed by CD40L blockade.

  5. Coilin is rapidly recruited to UVA-induced DNA lesions and γ-radiation affects localized movement of Cajal bodies.

    Science.gov (United States)

    Bártová, Eva; Foltánková, Veronika; Legartová, Soňa; Sehnalová, Petra; Sorokin, Dmitry V; Suchánková, Jana; Kozubek, Stanislav

    2014-01-01

    Cajal bodies are important nuclear structures containing proteins that preferentially regulate RNA-related metabolism. We investigated the cell-type specific nuclear distribution of Cajal bodies and the level of coilin, a protein of Cajal bodies, in non-irradiated and irradiated human tumor cell lines and embryonic stem (ES) cells. Cajal bodies were localized in different nuclear compartments, including DAPI-poor regions, in the proximity of chromocenters, and adjacent to nucleoli. The number of Cajal bodies per nucleus was cell cycle-dependent, with higher numbers occurring during G2 phase. Human ES cells contained a high coilin level in the nucleoplasm, but coilin-positive Cajal bodies were also identified in nuclei of mouse and human ES cells. Coilin, but not SMN, recognized UVA-induced DNA lesions, which was cell cycle-independent. Treatment with γ-radiation reduced the localized movement of Cajal bodies in many cell types and GFP-coilin fluorescence recovery after photobleaching was very fast in nucleoplasm in comparison with GFP-coilin recovery in DNA lesions. By contrast, nucleolus-localized coilin displayed very slow fluorescence recovery after photobleaching, which indicates very slow rates of protein diffusion, especially in nucleoli of mouse ES cells.

  6. Salivary glucose oxidase from caterpillars mediates the induction of rapid and delayed-induced defenses in the tomato plant.

    Directory of Open Access Journals (Sweden)

    Donglan Tian

    Full Text Available Caterpillars produce oral secretions that may serve as cues to elicit plant defenses, but in other cases these secretions have been shown to suppress plant defenses. Ongoing work in our laboratory has focused on the salivary secretions of the tomato fruitworm, Helicoverpa zea. In previous studies we have shown that saliva and its principal component glucose oxidase acts as an effector by suppressing defenses in tobacco. In this current study, we report that saliva elicits a burst of jasmonic acid (JA and the induction of late responding defense genes such as proteinase inhibitor 2 (Pin2. Transcripts encoding early response genes associated with the JA pathway were not affected by saliva. We also observed a delayed response to saliva with increased densities of Type VI glandular trichomes in newly emerged leaves. Proteomic analysis of saliva revealed glucose oxidase (GOX was the most abundant protein identified and we confirmed that it plays a primary role in the induction of defenses in tomato. These results suggest that the recognition of GOX in tomato may represent a case for effector-triggered immunity. Examination of saliva from other caterpillar species indicates that saliva from the noctuids Spodoptera exigua and Heliothis virescens also induced Pin2 transcripts.

  7. Salivary glucose oxidase from caterpillars mediates the induction of rapid and delayed-induced defenses in the tomato plant.

    Science.gov (United States)

    Tian, Donglan; Peiffer, Michelle; Shoemaker, Erica; Tooker, John; Haubruge, Eric; Francis, Frederic; Luthe, Dawn S; Felton, Gary W

    2012-01-01

    Caterpillars produce oral secretions that may serve as cues to elicit plant defenses, but in other cases these secretions have been shown to suppress plant defenses. Ongoing work in our laboratory has focused on the salivary secretions of the tomato fruitworm, Helicoverpa zea. In previous studies we have shown that saliva and its principal component glucose oxidase acts as an effector by suppressing defenses in tobacco. In this current study, we report that saliva elicits a burst of jasmonic acid (JA) and the induction of late responding defense genes such as proteinase inhibitor 2 (Pin2). Transcripts encoding early response genes associated with the JA pathway were not affected by saliva. We also observed a delayed response to saliva with increased densities of Type VI glandular trichomes in newly emerged leaves. Proteomic analysis of saliva revealed glucose oxidase (GOX) was the most abundant protein identified and we confirmed that it plays a primary role in the induction of defenses in tomato. These results suggest that the recognition of GOX in tomato may represent a case for effector-triggered immunity. Examination of saliva from other caterpillar species indicates that saliva from the noctuids Spodoptera exigua and Heliothis virescens also induced Pin2 transcripts.

  8. The Impact of Traffic-Induced Bridge Vibration on Rapid Repairing High-Performance Concrete for Bridge Deck Pavement Repairs

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2014-01-01

    Full Text Available Based on forced vibration tests for high-performance concrete (HPC, the influence of bridge vibration induced by traveling vehicle on compressive strength and durability of HPC has been studied. It is concluded that 1 d and 2 d compressive strength of HPC decreased significantly, and the maximum reduction rate is 9.1%, while 28 d compressive strength of HPC had a slight lower with a 3% maximal drop under the action of two simple harmonic vibrations with 2 Hz, 3 mm amplitude, and 4 Hz, 3 mm amplitude. Moreover, the vibration had a slight effect on the compressive strength of HPC when the simple harmonic vibration had 4 Hz and 1 mm amplitude; it is indicated that the amplitude exerts a more prominent influence on the earlier compressive strength with the comparison of the frequency. In addition, the impact of simple harmonic vibration on durability of HPC can be ignored; this shows the self-healing function of concrete resulting from later hydration reaction. Thus, the research achievements mentioned above can contribute to learning the laws by which bridge vibration affects the properties of concrete and provide technical support for the design and construction of the bridge deck pavement maintenance.

  9. Simultaneous measurements of velocity, temperature, and pressure using rapid CW wavelength-modulation laser-induced fluorescence of OH

    Science.gov (United States)

    Chang, A. Y.; Battles, B. E.; Hanson, R. K.

    1990-01-01

    In high speed flows, laser induced fluorescence (LIF) on Doppler shifted transitions is an attractive technique for velocity measurement. LIF velocimetry was applied to combined single-point measurements of velocity, temperature, and pressure and 2-D imaging of velocity and pressure. Prior to recent research using NO, LIF velocimetry in combustion related flows relied largely on the use of seed molecules. Simultaneous, single-point LIF measurements is reported of velocity, temperature, and pressure using the naturally occurring combustion species OH. This experiment is an extension of earlier research in which a modified ring dye laser was used to make time resolved temperature measurements behind reflected shock waves by using OH absorption an in postflame gases by using OH LIF. A pair of fused-silica rhombs mounted on a single galvanonmeter in an intracavity-doubled Spectra-Physics 380 ring laser permit the UV output to be swept continuously over a few wave numbers at an effective frequency of 3kHz.

  10. Rapid changes in key ruminal microbial populations during the induction of and recovery from diet-induced milk fat depression in dairy cows.

    Science.gov (United States)

    Rico, D E; Preston, S H; Risser, J M; Harvatine, K J

    2015-08-14

    The ruminant provides a powerful model for understanding the temporal dynamics of gastrointestinal microbial communities. Diet-induced milk fat depression (MFD) in the dairy cow is caused by rumen-derived bioactive fatty acids, and is commonly attributed to the changes in the microbial population. The aim of the present study was to determine the changes occurring in nine ruminal bacterial taxa with well-characterised functions, and abundance of total fungi, ciliate protozoa and bacteria during the induction of and recovery from MFD. Interactions between treatment and time were observed for ten of the twelve populations. The total number of both fungi and ciliate protozoa decreased rapidly (days 4 and 8, respectively) by more than 90% during the induction period and increased during the recovery period. The abundance of Streptococcus bovis (amylolytic) peaked at 350% of control levels on day 4 of induction and rapidly decreased during the recovery period. The abundance of Prevotella bryantii (amylolytic) decreased by 66% from day 8 to 20 of the induction period and increased to the control levels on day 12 of the recovery period. The abundance of Megasphaera elsdenii and Selenomonas ruminantium (lactate-utilising bacteria) increased progressively until day 12 of induction (>170%) and decreased during the recovery period. The abundance of Fibrobacter succinogenes (fibrolytic) decreased by 97% on day 4 of induction and increased progressively to an equal extent during the recovery period, although smaller changes were observed for other fibrolytic bacteria. The abundance of the Butyrivibrio fibrisolvens/Pseudobutyrivibrio group decreased progressively during the induction period and increased during the recovery period, whereas the abundance of Butyrivibrio hungatei was not affected by treatment. Responsive taxa were modified rapidly, with the majority of changes occurring within 8 d and their time course was similar to the time course of the induction of MFD

  11. Rapid generation of mature hepatocyte-like cells from human induced pluripotent stem cells by an efficient three-step protocol.

    Science.gov (United States)

    Chen, Yu-Fan; Tseng, Chien-Yu; Wang, Hsei-Wei; Kuo, Hung-Chih; Yang, Vincent W; Lee, Oscar K

    2012-04-01

    Liver transplantation is the only definitive treatment for end-stage cirrhosis and fulminant liver failure, but the lack of available donor livers is a major obstacle to liver transplantation. Recently, induced pluripotent stem cells (iPSCs) derived from the reprogramming of somatic fibroblasts, have been shown to resemble embryonic stem (ES) cells in that they have pluripotent properties and the potential to differentiate into all cell lineages in vitro, including hepatocytes. Thus, iPSCs could serve as a favorable cell source for a wide range of applications, including drug toxicity testing, cell transplantation, and patient-specific disease modeling. Here, we describe an efficient and rapid three-step protocol that is able to rapidly generate hepatocyte-like cells from human iPSCs. This occurs because the endodermal induction step allows for more efficient and definitive endoderm cell formation. We show that hepatocyte growth factor (HGF), which synergizes with activin A and Wnt3a, elevates the expression of the endodermal marker Foxa2 (forkhead box a2) by 39.3% compared to when HGF is absent (14.2%) during the endodermal induction step. In addition, iPSC-derived hepatocytes had a similar gene expression profile to mature hepatocytes. Importantly, the hepatocyte-like cells exhibited cytochrome P450 3A4 (CYP3A4) enzyme activity, secreted urea, uptake of low-density lipoprotein (LDL), and possessed the ability to store glycogen. Moreover, the hepatocyte-like cells rescued lethal fulminant hepatic failure in a nonobese diabetic severe combined immunodeficient mouse model. We have established a rapid and efficient differentiation protocol that is able to generate functional hepatocyte-like cells from human iPSCs. This may offer an alternative option for treatment of liver diseases. Copyright © 2011 American Association for the Study of Liver Diseases.

  12. Evidence that the contraction-induced rapid hyperemia in rabbit masseter muscle is based on a mechanosensitive mechanism, not shared by cutaneous vascular beds.

    Science.gov (United States)

    Turturici, Marco; Mohammed, Mazher; Roatta, Silvestro

    2012-08-15

    Several mechanisms have been hypothesized to contribute to the rapid hyperemia at the onset of exercise. The aim of the present study was to investigate the role played by the mechanosensitivity of the vascular network. In 12 anesthetized rabbits blood flow was recorded from the exclusively muscular masseteric artery in response to brief spontaneous contractions (BSC) of the masseter muscle, artery occlusion (AO), muscle compression (MC), and muscle stretch (MS). Activation of masseter muscle was monitored by electromyography (EMG). Responses to AO were also recorded from the mostly cutaneous facial and the central ear arteries. Five animals were also tested in the awake condition. The hyperemic response to BSC (peak amplitude of 394 ± 82%; time to peak of 1.8 ± 0.8 s) developed with a latency of 300-400 ms from the beginning of the EMG burst and 200-300 ms from the contraction-induced transient flow reduction. This response was neither different from the response to AO (peak amplitude = 426 ± 158%), MC, and MS (P = 0.23), nor from the BSC response in the awake condition. Compared with the masseteric artery, the response to AO was markedly smaller both in the facial (83 ± 18%,) and in the central ear artery (68 ± 20%) (P < 0.01). In conclusion, the rapid contraction-induced hyperemia can be replicated by a variety of stimuli affecting transmural pressure in muscle blood vessels and is thus compatible with the Bayliss effect. This prominent mechanosensitivity appears to be a characteristic of muscle and not cutaneous vascular beds.

  13. Wideband arrhythmia-Insensitive-rapid (AIR) pulse sequence for cardiac T1 mapping without image artifacts induced by an implantable-cardioverter-defibrillator.

    Science.gov (United States)

    Hong, KyungPyo; Jeong, Eun-Kee; Wall, T Scott; Drakos, Stavros G; Kim, Daniel

    2015-08-01

    To develop and evaluate a wideband arrhythmia-insensitive-rapid (AIR) pulse sequence for cardiac T1 mapping without image artifacts induced by implantable-cardioverter-defibrillator (ICD). We developed a wideband AIR pulse sequence by incorporating a saturation pulse with wide frequency bandwidth (8.9 kHz) to achieve uniform T1 weighting in the heart with ICD. We tested the performance of original and "wideband" AIR cardiac T1 mapping pulse sequences in phantom and human experiments at 1.5 Tesla. In five phantoms representing native myocardium and blood and postcontrast blood/tissue T1 values, compared with the control T1 values measured with an inversion-recovery pulse sequence without ICD, T1 values measured with original AIR with ICD were considerably lower (absolute percent error > 29%), whereas T1 values measured with wideband AIR with ICD were similar (absolute percent error T1 values measured with original AIR without ICD, T1 measured with original AIR with ICD was significantly lower (absolute percent error > 10.1%), whereas T1 measured with wideband AIR with ICD was similar (absolute percent error T1 mapping without significant image artifacts induced by ICD. © 2015 Wiley Periodicals, Inc.

  14. Rapid Exercise-Induced Mobilization of Dendritic Cells Is Potentially Mediated by a Flt3L- and MMP-9-Dependent Process in Multiple Sclerosis

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    Nathalie Deckx

    2015-01-01

    Full Text Available In healthy individuals, one exercise bout induces a substantial increase in the number of circulating leukocytes, while their function is transiently suppressed. The effect of one exercise bout in multiple sclerosis (MS is less studied. Since recent evidence suggests a role of dendritic cells (DC in the pathogenesis of MS, we investigated the effect of one combined endurance/resistance exercise bout on the number and function of DC in MS patients and healthy controls. Our results show a rapid increase in the number of DC in response to physical exercise in both MS patients and controls. Further investigation revealed that in particular DC expressing the migratory molecules CCR5 and CD62L were increased upon acute physical activity. This may be mediated by Flt3L- and MMP-9-dependent mobilization of DC, as demonstrated by increased circulating levels of Flt3L and MMP-9 following one exercise bout. Circulating DC display reduced TLR responsiveness after acute exercise, as evidenced by a less pronounced upregulation of activation markers, HLA-DR and CD86, on plasmacytoid DC and conventional DC, respectively. Our results indicate mobilization of DC, which may be less prone to drive inflammatory processes, following exercise. This may present a negative feedback mechanism for exercise-induced tissue damage and inflammation.

  15. Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies.

    Science.gov (United States)

    Axell, Richard G; Giblett, Joel P; White, Paul A; Klein, Andrew; Hampton-Til, James; O'Sullivan, Michael; Braganza, Denise; Davies, William R; West, Nick E J; Densem, Cameron G; Hoole, Stephen P

    2017-06-06

    We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  16. Detection of tPA-Induced Hyperfibrinolysis in Whole Blood by RapidTEG, KaolinTEG, and Functional FibrinogenTEG in Healthy Individuals

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Ostrowski, Sisse Rye; Sørensen, Anne Marie

    2012-01-01

    Background: Rapid identification of clinically relevant coagulopathies in, acute coagulopathy of trauma shock (ACOTS) has led to the development of faster point-of-care viscoelastic whole-blood-based tests like rapid thrombelastography (RapidTEG). The sensitivity of RapidTEG to detect hyperfibrin...

  17. Rapid Response to a Typhoon-Induced Flood with an SAR-Derived Map of Inundated Areas: Case Study and Validation

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    Hsiao-Wei Chung

    2015-09-01

    Full Text Available We report the successful case of a rapid response to a flash flood in I-Lan County of Taiwan with a map of inundated areas derived from COSMO-SkyMed 1 radar satellite imagery within 24 hours. The flood was caused by the intensive precipitation brought by Typhoon Soulik in July 2013. Based on the ensemble forecasts of trajectory, an urgent request of spaceborne SAR imagery was made 24 hours before Typhoon Soulik made landfall. Two COSMO-SkyMed images were successfully acquired when the center of Typhoon Soulik had just crossed the northern part of Taiwan. The standard level-1b product (radiometric-corrected, geometric-calibrated and orthorectified image was generated by using the off-the-shelf SARscape software. Following the same approach used with the Expert Landslide and Shadow Area Delineating System, the regional threshold of each tile image was determined to delineate still water surface and quasi-inundated areas in a fully-automatic manner. The results were overlaid on a digital elevation model, and the same tile was visually compared to an optical image taken by Formosat-2 before this event. With this ancillary information, the inundated areas were accurately and quickly identified. The SAR-derived map of inundated areas was published on a web-based platform powered by Google Earth within 24 hours, with the aim of supporting the decision-making process of disaster prevention and mitigation. A detailed validation was made afterwards by comparing the map with in situ data of the water levels at 17 stations. The results demonstrate the feasibility of rapidly responding to a typhoon-induced flood with a spaceborne SAR-derived map of inundated areas. A standard operating procedure was derived from this work and followed by the Water Hazard Mitigation Center of the Water Resources Agency, Taiwan, in subsequent typhoon seasons, such as Typhoon Trami (August, 2013 and Typhoon Soudelor (August, 2015.

  18. Simultaneous gene transfer of bone morphogenetic protein (BMP -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression

    Directory of Open Access Journals (Sweden)

    Miyazaki Jun-ichi

    2006-08-01

    Full Text Available Abstract Background Transcutaneous in vivo electroporation is expected to be an effective gene-transfer method for promoting bone regeneration using the BMP-2 plasmid vector. To promote enhanced osteoinduction using this method, we simultaneously transferred cDNAs for BMP-2 and BMP-7, as inserts in the non-viral vector pCAGGS. Methods First, an in vitro study was carried out to confirm the expression of BMP-2 and BMP-7 following the double-gene transfer. Next, the individual BMP-2 and BMP-7 plasmids or both together were injected into rat calf muscles, and transcutaneous electroporation was applied 8 times at 100 V, 50 msec. Results In the culture system, the simultaneous transfer of the BMP-2 and BMP-7 genes led to a much higher ALP activity in C2C12 cells than did the transfer of either gene alone. In vivo, ten days after the treatment, soft X-ray analysis showed that muscles that received both pCAGGS-BMP-2 and pCAGGS-BMP-7 had better-defined opacities than those receiving a single gene. Histological examination showed advanced ossification in calf muscles that received the double-gene transfer. BMP-4 mRNA was also expressed, and RT-PCR showed that its level increased for 3 days in a time-dependent manner in the double-gene transfer group. Immunohistochemistry confirmed that BMP-4-expressing cells resided in the matrix between muscle fibers. Conclusion The simultaneous transfer of BMP-2 and BMP-7 genes using in vivo electroporation induces more rapid bone formation than the transfer of either gene alone, and the increased expression of endogenous BMP-4 suggests that the rapid ossification is related to the induction of BMP-4.

  19. A moderate dose of propofol and rapidly induced mild hypothermia with extracorporeal lung and heart assist (ECLHA) improve the neurological outcome after prolonged cardiac arrest in dogs.

    Science.gov (United States)

    Ichinose, Keisuke; Okamoto, Taisuke; Tanimoto, Hironari; Taguchi, Hiroyuki; Tashiro, Masafumi; Sugita, Michiko; Takeya, Motohiro; Terasaki, Hidenori

    2006-08-01

    Propofol has been shown to protect against neuronal damage induced by brain ischaemia in small animal models. We reported previously that mild hypothermia (33 degrees C) in combination with extracorporeal lung and heart assist (ECLHA) improved the neurological outcome in dogs with cardiac arrest (CA) of 15 min induced during normothermia. In the present study, we investigated the neuroprotective effect of propofol infusion under mild hypothermia with ECLHA in this model. Twenty-one female dogs (15 mongrel dogs and 6 beagles) were divided into three groups: Midazolam 0.1 mg/(kg h) infusion group (M, n=7), Propofol 2 mg/(kg h) infusion group (P2, n=7), Propofol 4 mg/(kg h) infusion group (P4, n=7). Normothermic ventricular fibrillation (VF) was induced in all dogs for 15 min, followed by brief ECLHA and 168 h of intensive care. The drug infusion was initiated at a constant rate after the restoration of spontaneous circulation (ROSC) to 24 h. Mild hypothermia (33 degrees C) was maintained for 20 h. Neurological deficit scores (NDS: 0%=normal, 100%=brain death) were evaluated for neurological function from 33 to 168 h. One dog in the M group died, and the remaining dogs survived for 168 h. The P4 group showed better neurological recovery compared with the M group (48 h, 21+/-16% versus 32+/-15%; 72 h, 7+/-6% versus 25+/-11%; 96 h, 6+/-6% versus 21+/-6%; 120 h, 5+/-5% versus 20+/-6%; 144 h, 4+/-4% versus 20+/-6%; 168 h, 4+/-4% versus 20+/-6%, pdog in the P2 and three dogs in the P4 group achieved full neurological recovery (NDS: 0%). The number of intact pyramidal cells in the hippocampal CA1 was greater in the propofol groups than midazolam group (p<0.05). The combination of propofol infusion at a rate of 4 mg/(kg h), 24h and rapidly induced mild hypothermia (33 degrees C) with ECLHA might provide a successful means of cerebral resuscitation from CA.

  20. Asexual reproduction induces a rapid and permanent loss of sexual reproduction capacity in the rice fungal pathogen Magnaporthe oryzae: results of in vitro experimental evolution assays

    Directory of Open Access Journals (Sweden)

    Saleh Dounia

    2012-03-01

    Full Text Available Abstract Background Sexual reproduction is common in eukaryotic microorganisms, with few species reproducing exclusively asexually. However, in some organisms, such as fungi, asexual reproduction alternates with episodic sexual reproduction events. Fungi are thus appropriate organisms for studies of the reasons for the selection of sexuality or clonality and of the mechanisms underlying this selection. Magnaporthe oryzae, an Ascomycete causing blast disease on rice, reproduces mostly asexually in natura. Sexual reproduction is possible in vitro and requires (i two strains of opposite mating types including (ii at least one female-fertile strain (i.e. a strain able to produce perithecia, the female organs in which meiosis occurs. Female-fertile strains are found only in limited areas of Asia, in which evidence for contemporary recombination has recently been obtained. We induced the forced evolution of four Chinese female-fertile strains in vitro by the weekly transfer of asexual spores (conidia between Petri dishes. We aimed to determine whether female fertility was rapidly lost in the absence of sexual reproduction and whether this loss was controlled genetically or epigenetically. Results All the strains became female-sterile after 10 to 19 rounds of selection under asexual conditions. As no single-spore isolation was carried out, the observed decrease in the production of perithecia reflected the emergence and the invasion of female-sterile mutants. The female-sterile phenotype segregated in the offspring of crosses between female-sterile evolved strains and female-fertile wild-type strains. This segregation was maintained in the second generation in backcrosses. Female-sterile evolved strains were subjected to several stresses, but none induced the restoration of female fertility. This loss of fertility was therefore probably due to genetic rather than epigenetic mechanisms. In competition experiments, female-sterile mutants produced similar

  1. Coral mortality induced by the 2015-2016 El-Niño in Indonesia: the effect of rapid sea level fall

    Science.gov (United States)

    Elvan Ampou, Eghbert; Johan, Ofri; Menkes, Christophe E.; Niño, Fernando; Birol, Florence; Ouillon, Sylvain; Andréfouët, Serge

    2017-02-01

    The 2015-2016 El-Niño and related ocean warming has generated significant coral bleaching and mortality worldwide. In Indonesia, the first signs of bleaching were reported in April 2016. However, this El Niño has impacted Indonesian coral reefs since 2015 through a different process than temperature-induced bleaching. In September 2015, altimetry data show that sea level was at its lowest in the past 12 years, affecting corals living in the bathymetric range exposed to unusual emersion. In March 2016, Bunaken Island (North Sulawesi) displayed up to 85 % mortality on reef flats dominated by Porites, Heliopora and Goniastrea corals with differential mortality rates by coral genus. Almost all reef flats showed evidence of mortality, representing 30 % of Bunaken reefs. For reef flat communities which were living at a depth close to the pre-El Niño mean low sea level, the fall induced substantial mortality likely by higher daily aerial exposure, at least during low tide periods. Altimetry data were used to map sea level fall throughout Indonesia, suggesting that similar mortality could be widespread for shallow reef flat communities, which accounts for a vast percent of the total extent of coral reefs in Indonesia. The altimetry historical records also suggest that such an event was not unique in the past two decades, therefore rapid sea level fall could be more important in the dynamics and resilience of Indonesian reef flat communities than previously thought. The clear link between mortality and sea level fall also calls for a refinement of the hierarchy of El Niño impacts and their consequences on coral reefs.

  2. A rapid, non-destructive methodology to monitor activity of sulfide-induced corrosion of concrete based on H2S uptake rate.

    Science.gov (United States)

    Sun, Xiaoyan; Jiang, Guangming; Bond, Philip L; Wells, Tony; Keller, Jurg

    2014-08-01

    Many existing methods to monitor the corrosion of concrete in sewers are either very slow or destructive measurements. To overcome these limitations, a rapid, non-invasive methodology was developed to monitor the sulfide-induced corrosion process on concrete through the measurement of the H2S uptake rates of concrete at various corrosion stages. The H2S uptake rate for a concrete coupon was determined by measuring the gaseous H2S concentrations over time in a temperature- and humidity-controlled gas-tight reactor. The reliability of this method was evaluated by carrying out repeated tests on different concrete coupons previously exposed to 50 ppm of H2S, at 30 °C and 100% relative humidity for over 32 months. The H2S uptake measurements showed good reproducibility. It was also shown that a severely corroded coupon exhibited higher sulfide uptake rates than a less corroded coupon. This could be explained by the corrosion layer in the more corroded coupon having a higher biological sulfide oxidation activity than the less corroded coupon. Additionally, temperature changes had a stronger effect on the uptake rate of the heavily corroded coupon compared to the less corroded coupon. A corrosion rate of 8.9 ± 0.5 mm/year, estimated from the H2S uptake results, agreed well with the corrosion rate observed in real sewers under similar conditions. The method could be applied to investigate important factors affecting sulfide-induced concrete corrosion, particularly temperature, fluctuating gaseous H2S concentrations, oxygen concentrations, surface pH and relative humidity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Intranasal administration of CpG induces a rapid and transient cytokine response followed by dendritic and natural killer cell activation and recruitment in the mouse lung.

    Science.gov (United States)

    Pesce, Isabella; Monaci, Elisabetta; Muzzi, Alessandro; Tritto, Elaine; Tavarini, Simona; Nuti, Sandra; De Gregorio, Ennio; Wack, Andreas

    2010-01-01

    CpG-containing oligodeoxynucleotides are potent mucosal adjuvants and effective as stand-alone treatment of respiratory infections in mice. Although CpG is also used as a type 1 helper immunomodulator in the treatment of asthma and allergic disease, immune modulation following intranasal application has not been fully characterized yet. Using a B-type CpG, we monitored RNA expression profiles, cytokine production and cellular activation in lung tissue and bronchoalveolar lavages ex vivo and cytokine production of purified cell populations in vitro. CpG triggered the upregulation of many transcripts, including interferon response genes and proinflammatory cytokine genes, between 3 h and 4 days. Overlapping subsets of these cytokine proteins were induced in vitro in purified CD11c+ cells, B cells and alveolar macrophages from the lung, thus identifying these cells as direct targets of CpG. While lung B cells strongly respond to CpG in vitro, less activation is found ex vivo, suggesting efficient CpG sequestering or rapid B cell migration after activation. In contrast, a type II alveolar epithelial cell line did not respond to CpG in vitro. We noted selective recruitment of plasmacytoid dendritic cells (DCs) into the lung tissue, and of conventional DCs and natural killer (NK) cells into the lung tissue and bronchoalveolar space. Furthermore, CpG induced activation of intrapulmonary DCs, NK and T cells. We hypothesize that CpG-linked adjuvanticity and clearance of respiratory pathogens are mediated by two major mechanisms: transient induction of the interferon pathway limiting microbial survival and selective recruitment of DCs and NK cells, which allows for better adaptive responses.

  4. Interaction between the Cardiac Rapidly (IKr) and Slowly (IKs) Activating Delayed Rectifier Potassium Channels Revealed by Low K+-induced hERG Endocytic Degradation*

    Science.gov (United States)

    Guo, Jun; Wang, Tingzhong; Yang, Tonghua; Xu, Jianmin; Li, Wentao; Fridman, Michael D.; Fisher, John T.; Zhang, Shetuan

    2011-01-01

    Cardiac repolarization is controlled by the rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels. The human ether-a-go-go-related gene (hERG) encodes IKr, whereas KCNQ1 and KCNE1 together encode IKs. Decreases in IKr or IKs cause long QT syndrome (LQTS), a cardiac disorder with a high risk of sudden death. A reduction in extracellular K+ concentration ([K+]o) induces LQTS and selectively causes endocytic degradation of mature hERG channels from the plasma membrane. In the present study, we investigated whether IKs compensates for the reduced IKr under low K+ conditions. Our data show that when hERG and KCNQ1 were expressed separately in human embryonic kidney (HEK) cells, exposure to 0 mm K+ for 6 h completely eliminated the mature hERG channel expression but had no effect on KCNQ1. When hERG and KCNQ1 were co-expressed, KCNQ1 significantly delayed 0 mm K+-induced hERG reduction. Also, hERG degradation led to a significant reduction in KCNQ1 in 0 mm K+ conditions. An interaction between hERG and KCNQ1 was identified in hERG+KCNQ1-expressing HEK cells. Furthermore, KCNQ1 preferentially co-immunoprecipitated with mature hERG channels that are localized in the plasma membrane. Biophysical and pharmacological analyses indicate that although hERG and KCNQ1 closely interact with each other, they form distinct hERG and KCNQ1 channels. These data extend our understanding of delayed rectifier potassium channel trafficking and regulation, as well as the pathology of LQTS. PMID:21844197

  5. Activation of phasic pontine-wave generator prevents rapid eye movement sleep deprivation-induced learning impairment in the rat: a mechanism for sleep-dependent plasticity.

    Science.gov (United States)

    Datta, Subimal; Mavanji, Vijayakumar; Ulloor, Jagadish; Patterson, Elissa H

    2004-02-11

    Animal and human studies of sleep and learning have demonstrated that training on various tasks increases subsequent rapid eye movement (REM) sleep and phasic pontine-wave (P-wave) activity, followed by improvement in performance on the learned task. It is well documented that REM sleep deprivation after learning trials blocks the expected improvement in performance on subsequent retesting. Our aim was to test whether experimentally induced P-wave generator activation could eliminate the learning impairment produced by post-training REM sleep deprivation. Rats were trained on a two-way active avoidance-learning task. Immediately thereafter, two groups of those rats received a control vehicle (100 nl saline) microinjection and one group received a carbachol (50 ng in 100 nl saline) microinjection into the P-wave generator. The carbachol-injected group and one of the two control saline microinjected groups were selectively deprived of REM sleep during a 6 hr polygraphic recording session. All rats were then tested on the avoidance-learning task. The rats that received both the control saline injection and REM sleep deprivation showed learning deficits compared with the control saline-injected rats that were allowed to sleep normally. In contrast, the rats that received the carbachol microinjection and REM sleep deprivation demonstrated normal learning. These results demonstrate, for the first time, that carbachol-induced activation of the P-wave generator prevents the memory-impairing effects of post-training REM sleep deprivation. This evidence supports our hypothesis that the activation of the P-wave generator during REM sleep deprivation enhances a physiological process of memory, which occurs naturally during post-training REM sleep.

  6. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Anh; Bortolazzo, Anthony [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States); White, J. Brandon, E-mail: Brandon.White@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

  7. Characteristics of the calibration curves of copper for the rapid sorting of steel scrap by means of laser-induced breakdown spectroscopy under ambient air atmospheres.

    Science.gov (United States)

    Kashiwakura, Shunsuke; Wagatsuma, Kazuaki

    2013-01-01

    For the rapid and precise sorting of steel scrap with relatively high contents of copper, laser-induced breakdown spectroscopy (LIBS) is a promising method. It has several advantages such that it can work under ambient air atmospheres, and specimens can be tested without any pretreatment, such as acid digestion, polishing of the surface of the specimens, etc. For the application of LIBS for actual steel scrap, we obtained emission spectra by an LIBS system, which was mainly comprised of an Nd:YAG laser, an Echelle-type spectrometer, and an ICCD detector. The standard reference materials (SRMs) of JISF FXS 350-352, which are Fe-Cu binary alloy and have certified concentrations of copper, were employed for making calibration lines. Considering spectral interferences from the emission lines of the iron matrix in the alloys, Cu I lines having wavelengths of 324.754 and 327.396 nm could be chosen. In five replicate measurements of each SRM, shorter delay times after laser irradiation and longer gate widths for detecting the transient emission signal are suggested to be the optimal experiment parameters. In the determination process, utilizing the calibration line from Cu I 327.396 nm was better because of less spectral interference. By using 200 pulsed laser shots for the measurement sequence, a limit of detection of 0.004 Cu at% could be obtained.

  8. Rapid and sensitive detection of Cronobacter spp. (previously Enterobacter sakazakii) in food by duplex PCR combined with capillary electrophoresis-laser-induced fluorescence detector.

    Science.gov (United States)

    Ruan, Jia; Li, Ming; Liu, Ya-Pan; Li, Yuan-Qian; Li, Yong-Xin

    2013-03-15

    Cronobacter spp. (Enterobacter sakazakii) is an emerging opportunistic pathogen with a 40-80% mortality rate in infants and immunocompromised crowd resulting from the consumption of contaminated food. A novel method for detecting Cronobacter spp. in food samples by duplex polymerase chain reaction (PCR) in combination with capillary electrophoresis-laser induced fluorescence (CE-LIF) detector has been developed. The specific gene sequences of 16S-23S rDNA internal transcribed spacer (ITS) and the outer membrane protein A (OmpA) of Cronobacter spp. were amplified by duplex PCR. The PCR products were separated and determined sensitively by CE-LIF within 12min. The relative standard deviations of migration time for the detected DNA fragments were 2.01-2.91%. The detection limit was as low as 1.6×10(1)cfu/mL of Cronobacter spp. Besides, the specificity of the method was verified by 24 non-Cronobacter bacterial strains. A total of 120 commercial infant food formula were tested for the presence of Cronobacter spp. by using the proposed method. This current study demonstrates that the combination of CE-LIF method with duplex PCR is rapid, sensitive and environmental friendly, and has the potential to be adapted for the routine detection of Cronobacter spp. in food samples. To the best of our knowledge, this is the first use of CE-LIF for the detection of Cronobacter spp. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  9. Prospective evaluation of a rapid nanoparticle-based lateral flow immunoassay (STic Expert(®) HIT) for the diagnosis of heparin-induced thrombocytopenia.

    Science.gov (United States)

    Leroux, Dorothée; Hezard, Nathalie; Lebreton, Aurélien; Bauters, Anne; Suchon, Pierre; de Maistre, Emmanuel; Biron, Christine; Huisse, Marie-Genevieve; Ternisien, Catherine; Voisin, Sophie; Gruel, Yves; Pouplard, Claire

    2014-09-01

    A rapid lateral flow immunoassay (LFIA) (STic Expert(®) HIT), recently developed for the diagnosis of heparin-induced thrombocytopenia (HIT), was evaluated in a prospective multicentre cohort of 334 consecutive patients. The risk of HIT was estimated by the 4Ts score as low, intermediate and high in 28·7%, 61·7% and 9·6% of patients, respectively. Definite HIT was diagnosed in 40 patients (12·0%) with positive results on both enzyme-linked immunosorbent assay (Asserachrom(®) HPIA IgG) and serotonin release assay. The inter-reader reproducibility of results obtained was excellent (kappa ratio > 0·9). The negative predictive value of LFIA with plasma samples was 99·6% with a negative likelihood ratio (LR) of 0·03, and was comparable to those of the particle gel immunoassay (H/PF4-PaGIA(®) ) performed in 124 cases. Positive predictive value and positive LR were 44·4% and 5·87, respectively, and the results were similar for serum samples. The probability of HIT in intermediate risk patients decreased from 11·2% to 0·4% when the LFIA result was negative and increased to 42·5% when it was positive. In conclusion, the STic Expert(®) HIT combined with the 4Ts score is a reliable tool to rule out the diagnosis of HIT. © 2014 John Wiley & Sons Ltd.

  10. Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

    Science.gov (United States)

    Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

    2012-01-01

    Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

  11. Rapid eye movement sleep loss induces neuronal apoptosis in the rat brain by noradrenaline acting on alpha 1-adrenoceptor and by triggering mitochondrial intrinsic pathway

    Directory of Open Access Journals (Sweden)

    Bindu I Somarajan

    2016-03-01

    Full Text Available Many neurodegenerative disorders are associated with rapid eye movement sleep (REMS-loss, however the mechanism was unknown. As REMS-loss elevates noradrenaline (NA level in the brain as well as induces neuronal apoptosis and degeneration, in this study we have delineated the intracellular molecular pathway involved in REMS deprivation (REMSD associated NA-induced neuronal apoptosis. Rats were REMS deprived for 6 days by the classical flower-pot method, suitable controls were conducted and the effects on apoptosis markers evaluated. Further, the role of NA was studied by one, intraperitoneal (i.p. injection of NA-ergic alpha1-adrenoceptor antagonist prazosin (PRZ and two, by down-regulation of NA synthesis in locus coeruleus (LC neurons by local microinjection of tyrosine hydroxylase siRNA (TH-siRNA. Immunoblot estimates showed that the expressions of pro-apoptotic proteins viz. Bcl2-associated death promoter (BAD protein, apoptotic protease activating factor-1 (Apaf-1, cytochrome c, caspase9, caspase3 were elevated in the REMS-deprived rat brains, while caspase8 level remained unaffected; PRZ treatment did not allow elevation of these pro-apoptotic factors. Further, REMSD increased cytochrome c expression, which was prevented if the NA synthesis from the LC neurons was blocked by microinjection of TH-siRNA in vivo into the LC during REMSD in freely moving normal rats. Mitochondrial damage was re-confirmed by transmission electron microscopy (TEM, which showed distinctly swollen mitochondria with disintegrated cristae, chromosomal condensation and clumping along the nuclear membrane and all these changes were prevented in PRZ treated rats. Combining findings of this study along with earlier reports we propose that upon REMSD NA level increases in the brain as the LC NA-ergic REM-OFF neurons do not cease firing and TH is up-regulated in those neurons. This elevated NA acting on alpha1-adrenoceptors damages mitochondria causing release of

  12. A mouse model for inducible overexpression of Prdm14 results in rapid-onset and highly penetrant T-cell acute lymphoblastic leukemia (T-ALL

    Directory of Open Access Journals (Sweden)

    Brandi L. Carofino

    2013-11-01

    PRDM14 functions in embryonic stem cell (ESC maintenance to promote the expression of pluripotency-associated genes while suppressing differentiation genes. Expression of PRDM14 is tightly regulated and typically limited to ESCs and primordial germ cells; however, aberrant expression is associated with tumor initiation in a wide variety of human cancers, including breast cancer and leukemia. Here, we describe the generation of a Cre-recombinase-inducible mouse model for the spatial and temporal control of Prdm14 misexpression [ROSA26 floxed-stop Prdm14 (R26PR]. When R26PR is mated to either of two Cre lines, Mx1-cre or MMTV-cre, mice develop early-onset T-cell acute lymphoblastic leukemia (T-ALL with median overall survival of 41 and 64 days for R26PR;Mx1-cre and R26PR;MMTV-cre, respectively. T-ALL is characterized by the accumulation of immature single-positive CD8 cells and their widespread infiltration. Leukemia is preceded by a dramatic expansion of cells resembling hematopoietic stem cells and lymphoid-committed progenitors prior to disease onset, accompanied by a blockage in B-cell differentiation at the early pro-B stage. Rapid-onset PRDM14-induced T-ALL requires factors that are present in stem and progenitor cells: R26PR;dLck-cre animals, which express Prdm14 starting at the double-positive stage of thymocyte development, do not develop disease. PRDM14-induced leukemic cells contain high levels of activated NOTCH1 and downstream NOTCH1 targets, including MYC and HES1, and are sensitive to pharmacological inhibition of NOTCH1 with the γ-secretase inhibitor DAPT. Greater than 50% of human T-ALLs harbor activating mutations in NOTCH1; thus, our model carries clinically relevant molecular aberrations. The penetrance, short latency and involvement of the NOTCH1 pathway will make this hematopoietic R26PR mouse model ideal for future studies on disease initiation, relapse and novel therapeutic drug combinations. Furthermore, breeding R26PR to additional Cre

  13. Expression of FAS/APO 1/CD 95 in thyroid tumors.

    Directory of Open Access Journals (Sweden)

    Waldemar Balcerzak

    2007-06-01

    Full Text Available Using immunohistochemistry, Fas/Apo-1 protein expression was investigated in thyroid cancers of 67 patients. Thyroid biopsies from twenty eight patients with benign thyroid diseases were also examined. The patients with thyroid cancer manifested a variable histology of the cancer, including 14 patients with follicular carcinoma, 48 with papillary carcinoma, 5 patients with medullary carcinoma. The benign thyroid disease involved nodular goitre in 11 patients and follicular adenoma in other 17 patients. The study aimed at examining immunohistochemical expression of Fas protein in order to determine whether the level of its expression correlated with histological diagnosis. In individual patients Fas expression was more prevalent in thyroid carcinomas as compared to benign tumors (p=0.001. A marked increase in Fas expression was found in papillary carcinoma, as compared to follicular and medullary carcinomas (p=0.02. In conclusion, Fas was significantly more frequently overexpressed in thyroid cancer, indicating its role in thyroid tumorigenesis.

  14. Using EarthScope magnetotelluric data to improve the resilience of the US power grid: rapid predictions of geomagnetically induced currents

    Science.gov (United States)

    Schultz, A.; Bonner, L. R., IV

    2016-12-01

    Existing methods to predict Geomagnetically Induced Currents (GICs) in power grids, such as the North American Electric Reliability Corporation standard adopted by the power industry, require explicit knowledge of the electrical resistivity structure of the crust and mantle to solve for ground level electric fields along transmission lines. The current standard is to apply regional 1-D resistivity models to this problem, which facilitates rapid solution of the governing equations. The systematic mapping of continental resistivity structure from projects such as EarthScope reveals several orders of magnitude of lateral variations in resistivity on local, regional and continental scales, resulting in electric field intensifications relative to existing 1-D solutions that can impact GICs to first order. The computational burden on the ground resistivity/GIC problem of coupled 3-D solutions inhibits the prediction of GICs in a timeframe useful to protecting power grids. In this work we reduce the problem to applying a set of filters, recognizing that the magnetotelluric impedance tensors implicitly contain all known information about the resistivity structure beneath a given site, and thus provides the required relationship between electric and magnetic fields at each site. We project real-time magnetic field data from distant magnetic observatories through a robustly calculated multivariate transfer function to locations where magnetotelluric impedance tensors had previously been obtained. This provides a real-time prediction of the magnetic field at each of those points. We then project the predicted magnetic fields through the impedance tensors to obtain predictions of electric fields induced at ground level. Thus, electric field predictions can be generated in real-time for an entire array from real-time observatory data, then interpolated onto points representing a power transmission line contained within the array to produce a combined electric field prediction

  15. Eating ‘Junk-Food' Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction

    Science.gov (United States)

    Oginsky, Max F; Goforth, Paulette B; Nobile, Cameron W; Lopez-Santiago, Luis F; Ferrario, Carrie R

    2016-01-01

    Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals. Motivational responses are mediated in part by NAc AMPA receptor (AMPAR) transmission, and recent work shows that cue-triggered motivation is enhanced in obesity-susceptible rats after ‘junk-food' diet consumption. Therefore, here we determined whether NAc AMPAR expression and function is increased by ‘junk-food' diet consumption in obesity-susceptible vs -resistant populations using both outbred and selectively bred models of susceptibility. In addition, cocaine-induced locomotor activity was used as a general ‘read out' of mesolimbic function after ‘junk-food' consumption. We found a sensitized locomotor response to cocaine in rats that gained weight on a ‘junk-food' diet, consistent with greater responsivity of mesolimbic circuits in obesity-susceptible groups. In addition, eating ‘junk-food' increased NAc calcium-permeable-AMPAR (CP-AMPAR) function only in obesity-susceptible rats. This increase occurred rapidly, persisted for weeks after ‘junk-food' consumption ceased, and preceded the development of obesity. These data are considered in light of enhanced cue-triggered motivation and striatal function in obesity-susceptible rats and the role of NAc CP-AMPARs in enhanced motivation and addiction. PMID:27383008

  16. Eating 'Junk-Food' Produces Rapid and Long-Lasting Increases in NAc CP-AMPA Receptors: Implications for Enhanced Cue-Induced Motivation and Food Addiction.

    Science.gov (United States)

    Oginsky, Max F; Goforth, Paulette B; Nobile, Cameron W; Lopez-Santiago, Luis F; Ferrario, Carrie R

    2016-12-01

    Urges to eat are influenced by stimuli in the environment that are associated with food (food cues). Obese people are more sensitive to food cues, reporting stronger craving and consuming larger portions after food cue exposure. The nucleus accumbens (NAc) mediates cue-triggered motivational responses, and activations in the NAc triggered by food cues are stronger in people who are susceptible to obesity. This has led to the idea that alterations in NAc function similar to those underlying drug addiction may contribute to obesity, particularly in obesity-susceptible individuals. Motivational responses are mediated in part by NAc AMPA receptor (AMPAR) transmission, and recent work shows that cue-triggered motivation is enhanced in obesity-susceptible rats after 'junk-food' diet consumption. Therefore, here we determined whether NAc AMPAR expression and function is increased by 'junk-food' diet consumption in obesity-susceptible vs -resistant populations using both outbred and selectively bred models of susceptibility. In addition, cocaine-induced locomotor activity was used as a general 'read out' of mesolimbic function after 'junk-food' consumption. We found a sensitized locomotor response to cocaine in rats that gained weight on a 'junk-food' diet, consistent with greater responsivity of mesolimbic circuits in obesity-susceptible groups. In addition, eating 'junk-food' increased NAc calcium-permeable-AMPAR (CP-AMPAR) function only in obesity-susceptible rats. This increase occurred rapidly, persisted for weeks after 'junk-food' consumption ceased, and preceded the development of obesity. These data are considered in light of enhanced cue-triggered motivation and striatal function in obesity-susceptible rats and the role of NAc CP-AMPARs in enhanced motivation and addiction.

  17. Conditional Inducible Triple-Transgenic Mouse Model for Rapid Real-Time Detection of HCV NS3/4A Protease Activity

    Science.gov (United States)

    Yang, Jing; Zhao, Haiwei; Qiao, Qinghua; Han, Peijun; Xu, Zhikai; Yin, Wen

    2016-01-01

    Hepatitis C virus (HCV) frequently establishes persistent infections that can develop into severe liver disease. The HCV NS3/4A serine protease is not only essential for viral replication but also cleaves multiple cellular targets that block downstream interferon activation. Therefore, NS3/4A is an ideal target for the development of anti-HCV drugs and inhibitors. In the current study, we generated a novel NS3/4A/Lap/LC-1 triple-transgenic mouse model that can be used to evaluate and screen NS3/4A protease inhibitors. The NS3/4A protease could be conditionally inducibly expressed in the livers of the triple-transgenic mice using a dual Tet-On and Cre/loxP system. In this system, doxycycline (Dox) induction resulted in the secretion of Gaussia luciferase (Gluc) into the blood, and this secretion was dependent on NS3/4A protease-mediated cleavage at the 4B5A junction. Accordingly, NS3/4A protease activity could be quickly assessed in real time simply by monitoring Gluc activity in plasma. The results from such monitoring showed a 70-fold increase in Gluc activity levels in plasma samples collected from the triple-transgenic mice after Dox induction. Additionally, this enhanced plasma Gluc activity was well correlated with the induction of NS3/4A protease expression in the liver. Following oral administration of the commercial NS3/4A-specific inhibitors telaprevir and boceprevir, plasma Gluc activity was reduced by 50% and 65%, respectively. Overall, our novel transgenic mouse model offers a rapid real-time method to evaluate and screen potential NS3/4A protease inhibitors. PMID:26943641

  18. Rapid assessment of high-dose radiation exposures through scoring of cell-fusion-induced premature chromosome condensation and ring chromosomes.

    Science.gov (United States)

    Lamadrid Boada, A I; Romero Aguilera, I; Terzoudi, G I; González Mesa, J E; Pantelias, G; García, O

    2013-09-18

    Analysis of premature chromosome condensation (PCC) mediated by fusion of G0-lymphocytes with mitotic CHO cells in combination with rapid visualization and quantification of rings (PCC-Rf) is proposed as an alternative technique for dose assessment of radiation-exposed individuals. Isolated lymphocytes or whole blood from six individuals were γ-irradiated with 5, 10, 15 and 20Gy at a dose rate of 0.5Gy/min. Following either 8- or 24-h post-exposure incubation of irradiated samples at 37°C, chromosome spreads were prepared by standard PCC cytogenetic procedures. The protocol for PCC fusion proved to be effective at doses as high as 20Gy, enabling the analysis of ring chromosomes and excess PCC fragments. The ring frequencies remained constant during the 8-24-h repair time; the pooled dose relationship between ring frequency (Y) and dose (D) was linear: Y=(0.088±0.005)×D. During the repair time, excess fragments decreased from 0.91 to 0.59 chromatid pieces per Gy, revealing the importance of information about the exact time of exposure for dose assessment on the basis of fragments. Compared with other cytogenetic assays to estimate radiation dose, the PCC-Rf method has the following benefits: a 48-h culture time is not required, allowing a much faster assessment of dose in comparison with conventional scoring of dicentrics and rings in assays for chemically-induced premature chromosome condensation (PCC-Rch), and it allows the analysis of heavily irradiated lymphocytes that are delayed or never reach mitosis, thus avoiding the problem of saturation at high doses. In conclusion, the use of the PCC fusion assay in conjunction with scoring of rings in G0-lymphocytes offers a suitable alternative for fast dose estimation following accidental exposure to high radiation doses. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Sunlight-induced rapid and efficient biogenic synthesis of silver nanoparticles using aqueous leaf extract of Ocimum sanctum Linn. with enhanced antibacterial activity.

    Science.gov (United States)

    Brahmachari, Goutam; Sarkar, Sajal; Ghosh, Ranjan; Barman, Soma; Mandal, Narayan C; Jash, Shyamal K; Banerjee, Bubun; Roy, Rajiv

    2014-12-01

    , thus offers a cost-effective and environmentally benign route for their large-scale commercial production. The nanoparticles dispersed in the mother solution showed promising antibacterial efficacy. Graphical AbstractSunlight-induced rapid and efficient biogenic synthesis of silver nanoparticles using aqueous leaf extract of Ocimum sanctum Linn. with enhanced antibacterial activity.

  20. Rapid Prototyping

    Science.gov (United States)

    1999-01-01

    Javelin, a Lone Peak Engineering Inc. Company has introduced the SteamRoller(TM) System as a commercial product. The system was designed by Javelin during a Phase II NASA funded small commercial product. The purpose of the invention was to allow automated-feed of flexible ceramic tapes to the Laminated Object Manufacturing rapid prototyping equipment. The ceramic material that Javelin was working with during the Phase II project is silicon nitride. This engineered ceramic material is of interest for space-based component.

  1. Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of atorvastatin using multivariate data analysis

    DEFF Research Database (Denmark)

    Christensen, Niels Peter Aae; Van Eerdenbrugh, Bernard; Kwok, Kaho

    2013-01-01

    To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin.......To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin....

  2. Detecting mortality induced structural and functional changes in a pinon-juniper woodland using Landsat and RapidEye time series

    Science.gov (United States)

    Dan J. Krofcheck; Jan U. H. Eitel; Lee A. Vierling; Urs Schulthess; Timothy M. Hilton; Eva Dettweiler-Robinson; Rosemary Pendleton; Marcy E. Litvak

    2014-01-01

    Pinon-juniper (PJ) woodlands have recently undergone dramatic drought-induced mortality, triggering broad scale structural changes in this extensive Southwestern US biome. Given that climate projections for the region suggest widespread conifer mortality is likely to continue into the next century, it is critical to better understand how this climate-induced change in...

  3. No synergy between ATG induction and costimulation blockade induced kidney allograft survival in rhesus monkeys.

    Science.gov (United States)

    Haanstra, Krista G; Sick, Ella A; Ringers, Jan; Wubben, Jacqueline A M; Kuhn, Eva-Maria; 't Hart, Bert A; Boon, Louis; Jonker, Margreet

    2006-11-15

    Costimulation blockade with antibodies directed against human CD40 and CD86 leads to prolonged kidney allograft survival in rhesus monkeys, but fails to induce permanent graft acceptance. We have tested whether costimulation blockade is more effective after peripheral T-cell ablation with antithymocyte globulin (ATG), with the aim to remove already primed autoreactive cells present in the normal repertoire. Rhesus monkeys were transplanted with a mismatched kidney allograft. ATG was given around the time of transplantation (day -1 and 0). Costimulation blockade with anti-CD40+anti-CD86 was given at tapering dosages from day -1 to 56. Cyclosporin A (CsA) was given from day 42 onwards and first rejections occurring after day 42 were treated with prednisone. We observed accelerated rejection in ATG-treated monkeys, compared to animals receiving only costimulation blockade. The accelerated rejection of the kidney allograft occurred despite the application of rejection therapy with steroids and CsA. Three of the five ATG-treated animals were found seropositive for donor-specific alloantibodies. Early biopsies (day 21) from animals treated with ATG and anti-CD40+anti-CD86 show substantially reduced expression of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and forkhead box P3 (FOXP3) in focal infiltrates as compared to animals treated with only costimulation blockade. Furthermore, we observed the rapid reappearance of CD8 T-cells with a memory phenotype (disappearance of naive CD95/CD11a T-cells) in peripheral blood. We conclude that (subtotal) T-cell depletion using ATG does not add to costimulation blockade induced kidney allograft survival.

  4. Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization with Cocaine in Mice: Implications for the Addictive Potential of Modafinil

    OpenAIRE

    Raphael Wuo-Silva; Daniela Fukushiro; André Hollais; Renan Baldaia; Elisa Kawamoto; Berro, Lais F. [UNIFESP; Thais Yokoyama; Leonardo Lopes-Silva; Carolina Bizerra; Roberta Procópio-Souza; Debora Hashiguchi; Lilian Figueiredo; Costa,José L.; Roberto Frussa-Filho; Beatriz Monteiro Longo

    2016-01-01

    There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for cocaine abuse, and used indiscriminately by healthy individuals due to its positive effects on arousal and cognition. The rapid-onset type of behavioral sensitization (i.e., a type of sensitization that develops within a few hours from the drug priming administration) has been emerged as a valuable tool to study binge-like patterns of dru...

  5. Rapid formation of Ni3Sn4 joints for die attachment of SiC-based high temperature power devices using ultrasound-induced transient liquid phase bonding process.

    Science.gov (United States)

    Li, Z L; Dong, H J; Song, X G; Zhao, H Y; Feng, J C; Liu, J H; Tian, H; Wang, S J

    2017-05-01

    High melting point Ni3Sn4 joints for the die attachment of SiC-based high temperature power devices was successfully achieved using an ultrasound-induced transient liquid phase (TLP) bonding process within a remarkably short bonding time of 8s. The formed intermetallic joints, which are completely composed of the refined equiaxial Ni3Sn4 grains with the average diameter of 2μm, perform the average shear strength of 26.7MPa. The sonochemical effects of ultrasonic waves dominate the mechanism and kinetics of the rapid formation of Ni3Sn4 joints. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. PPARa and PPAR¿ coactivation rapidly induces Egr-1 in the nuclei of the dorsal and ventral urinary bladder and kidney pelvis urothelium of rats

    DEFF Research Database (Denmark)

    Egerod, Frederikke Lihme; Svendsen, Jette Eldrup; Hinley, Jennifer

    2009-01-01

    and PPAR gamma agonists. Immunohistochemistry for Egr-1 with a rabbit monoclonal antibody demonstrated that male vehicle-treated rats exhibited minimal urothelial expression and specifically, no nuclear signal. In contrast, Egr-1 was induced in the nuclei of bladder, as well as kidney pelvis, urothelia...

  7. Rapid mitochondrial DNA typing using restriction enzyme digestion of polymerase chain reaction amplicons followed by capillary electrophoresis separation with laser-induced fluorescence detection.

    Science.gov (United States)

    Butler, J M; Wilson, M R; Reeder, D J

    1998-01-01

    The polymorphic control region of mitochondrial DNA (mtDNA) is becoming more commonly used in forensic applications to differentiate among individuals in a population. Two hypervariable regions (HV1 and HV2) are often sequenced following amplification of the mtDNA via the polymerase chain reaction (PCR). More rapid screening assays would reduce both the effort and the expense of comparing two samples. A methodology has been developed that first uses restriction endonuclease digestion of the PCR-amplified mtDNA using RsaI and MnlI and then capillary electrophoresis (CE) to separate and size the PCR-RFLP fragments. This rapid procedure offers an alternative method for screening of polymorphisms in amplified mtDNA samples. In addition, the presence of a T-->C transition at position 16189, which gives rise to the so-called "C-stretch" in HV1, may be predicted from the presence of nonspecific PCR products in the CE results.

  8. Rapid and Effective Electrical Conductivity Improvement of the Ag NW-Based Conductor by Using the Laser-Induced Nano-Welding Process

    Directory of Open Access Journals (Sweden)

    Phillip Lee

    2017-05-01

    Full Text Available To date, the silver nanowire-based conductor has been widely used for flexible/stretchable electronics due to its several advantages. The optical nanowire annealing process has also received interest as an alternative annealing process to the Ag nanowire (NW-based conductor. In this study, we present an analytical investigation on the phenomena of the Ag NWs’ junction and welding properties under laser exposure. The two different laser-induced welding processes (nanosecond (ns pulse laser-induced nano-welding (LINW and continuous wave (cw scanning LINW are applied to the Ag NW percolation networks. The Ag NWs are selectively melted and merged at the junction of Ag NWs under very short laser exposure; these results are confirmed by scanning electron microscope (SEM, focused-ion beam (FIB, electrical measurement, and finite difference time domain (FDTD simulation.

  9. The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway

    OpenAIRE

    J. R. Eidet; Reppe, S.; Pasovic, L.; Olstad, O K; Lyberg, T; Khan, A. Z.; Fostad, I. G.; D. F. Chen; Utheim, T. P.

    2016-01-01

    Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients with age-related macular degeneration represents a promising novel treatment modality. Development of RPE transplants, however, requires up to 3 months of cell differentiation. We explored whether the silk protein sericin can induce maturation of primary human retinal pigment epithelial (hRPE) cells. Microarray analysis demonstrated that sericin up-regulated RPE-associated transcripts (RPE6...

  10. Salmonella enterica serovar Choleraesuis infection of the porcine jejunal Peyer’s patch rapidly induces IL-1β and IL-8 expression

    Science.gov (United States)

    Hyland, Kendra A.; Brown, David R.; Murtaugh, Michael P.

    2008-01-01

    Salmonella enterica serovar Choleraesuis is an enteric pathogen of swine, producing septicemia, enterocolitis, pneumonia, and hepatitis. The initial molecular events at the site of Salmonella infection are hypothesized to be critical in the initiation of innate and adaptive immune responses; however the acute immune response elicited by porcine intestinal tissues is not well understood. To address this need, we employed explants of jejunal Peyer’s patch (JPP) mucosa from pigs to examine Salmonella-induced immune responses under controlled conditions as well as to overcome limitations of whole animal approaches. JPP explants mounted in Ussing chambers maintained normal histological structure for 2 h and stable short-circuit current and electrical conductance for 2.5 h. After ex vivo luminal exposure to Salmonella serovar Choleraesuis, JPP responded with an increase in mRNA expression of IL-1β and IL-8, but not TNFα. Increased IL-1β and IL-8 expression were dependent on efficient Salmonella adhesion and internalization, whereas mutant Salmonella did not induce inflammatory cytokine expression. Commensal enteric bacteria, present in some experiments, also did not induce inflammatory cytokine expression. These findings indicate that Salmonella uptake by Peyer’s patch is important in the induction of an innate response involving expression of IL-1β and IL-8, and that ex vivo intestinal immune tissue explants provide an intact tissue model that will facilitate investigation of mucosal immunity in swine. PMID:16115691

  11. Infection with host-range mutant adenovirus 5 suppresses innate immunity and induces systemic CD4+ T cell activation in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Huma Qureshi

    Full Text Available Ad5 is a common cause of respiratory disease and an occasional cause of gastroenteritis and conjunctivitis, and seroconversion before adolescence is common in humans. To gain some insight into how Ad5 infection affects the immune system of rhesus macaques (RM 18 RM were infected with a host-range mutant Ad5 (Ad5hr by 3 mucosal inoculations. There was a delay of 2 to 6 weeks after the first inoculation before plasmacytoid dendritic cell (pDC frequency and function increased in peripheral blood. Primary Ad5hr infection suppressed IFN-γ mRNA expression, but the second Ad5hr exposure induced a rapid increase in IFN-gamma mRNA in peripheral blood mononuclear cells (PBMC. Primary Ad5hr infection suppressed CCL20, TNF and IL-1 mRNA expression in PBMC, and subsequent virus exposures further dampened expression of these pro-inflammatory cytokines. Primary, but not secondary, Ad5hr inoculation increased the frequency of CXCR3+ CD4+ T cells in blood, while secondary, but not primary, Ad5hr infection transiently increased the frequencies of Ki67+, HLADR+ and CD95+/CCR5+ CD4+ T cells in blood. Ad5hr infection induced polyfunctional CD4 and CD8+ T cells specific for the Ad5 hexon protein in all of the animals. Thus, infection with Ad5hr induced a complex pattern of innate and adaptive immunity in RM that included transient systemic CD4+ T cell activation and suppressed innate immunity on re-exposure to the virus. The complex effects of adenovirus infection on the immune system may help to explain the unexpected results of testing Ad5 vector expressing HIV antigens in Ad5 seropositive people.

  12. Actin filament-associated protein 1 (AFAP-1) is a key mediator in inflammatory signaling-induced rapid attenuation of intrinsic P-gp function in human brain capillary endothelial cells.

    Science.gov (United States)

    Hoshi, Yutaro; Uchida, Yasuo; Tachikawa, Masanori; Ohtsuki, Sumio; Terasaki, Tetsuya

    2017-04-01

    The purpose of this study was to identify regulatory molecule(s) involved in the inflammatory signaling-induced decrease in P-glycoprotein (P-gp) efflux function at the blood-brain barrier (BBB) that may occur in brain diseases. We confirmed that in vivo P-gp efflux activity at the BBB was decreased without any change in P-gp protein expression level in a mouse model of acute inflammation induced by 3 mg/kg lipopolysaccharide. In a human BBB model cell line (human brain capillary endothelial cells; hCMEC/D3), 1-h treatment with 10 ng/mL tumor necrosis factor-α (TNF-α; an inflammatory mediator) rapidly reduced P-gp efflux activity, but had no effect on P-gp protein expression level. To clarify the non-transcriptional mechanism that causes the decrease in intrinsic efflux activity of P-gp in acute inflammation, we applied comprehensive quantitative phosphoproteomics to compare hCMEC/D3 cells treated with TNF-α and vehicle (control). Actin filament-associated protein-1 (AFAP-1), MAPK1, and transcription factor AP-1 (AP-1) were significantly phosphorylated in TNF-α-treated cells, and were selected as candidate proteins. In validation experiments, knockdown of AFAP-1 expression blocked the reduction in P-gp efflux activity by TNF-α treatment, whereas inhibition of MAPK function or knockdown of AP-1 expression did not. Quantitative targeted absolute proteomics revealed that the reduction in P-gp activity by TNF-α did not require any change in P-gp protein expression levels in the plasma membrane. Our results demonstrate that AFAP-1 is a key mediator in the inflammatory signaling-induced, translocation-independent rapid attenuation of P-gp efflux activity in human brain capillary endothelial cells. © 2017 International Society for Neurochemistry.

  13. Rosmarinic Acid Potentiates Pentobarbital-Induced Sleep Behaviors and Non-Rapid Eye Movement (NREM) Sleep through the Activation of GABAA-ergic Systems.

    Science.gov (United States)

    Kwon, Yeong Ok; Hong, Jin Tae; Oh, Ki-Wan

    2017-03-01

    It has been known that RA, one of major constituents of Perilla frutescens which has been used as a traditional folk remedy for sedation in oriental countries, shows the anxiolytic-like and sedative effects. This study was performed to know whether RA may enhance pentobarbital-induced sleep through γ-aminobutyric acid (GABA)A-ergic systems in rodents. RA (0.5, 1.0 and 2.0 mg/ kg, p.o.) reduced the locomotor activity in mice. RA decreased sleep latency and increased the total sleep time in pentobarbital (42 mg/kg, i.p.)-induced sleeping mice. RA also increased sleeping time and number of falling sleep mice after treatment with sub-hypnotic pentobarbital (28 mg/kg, i.p.). In electroencephalogram (EEG) recording, RA (2.0 mg/kg) not only decreased the counts of sleep/wake cycles and REM sleep, but also increased the total and NREM sleep in rats. The power density of NREM sleep showed the increase in δ-waves and the decrease in α-waves. On the other hand, RA (0.1, 1.0 and 10 μg/ml) increased intracellular Cl- influx in the primary cultured hypothalamic cells of rats. RA (p.o.) increased the protein expression of glutamic acid decarboxylase (GAD65/67) and GABAA receptors subunits except β1 subunit. In conclusion, RA augmented pentobarbital-induced sleeping behaviors through GABAA-ergic transmission. Thus, it is suggested that RA may be useful for the treatment of insomnia.

  14. The endocytosis gene END3 is essential for the glucose-induced rapid decline of small vesicles in the extracellular fraction in Saccharomyces cerevisiae.

    Science.gov (United States)

    Giardina, Bennett J; Stein, Kathryn; Chiang, Hui-Ling

    2014-01-01

    Protein secretion is a fundamental process in all living cells. Gluconeogenic enzymes are secreted when Saccharomyces cerevisiae are grown in media containing low glucose. However, when cells are transferred to media containing high glucose, they are internalized. We investigated whether or not gluconeogenic enzymes were associated with extracellular vesicles in glucose-starved cells. We also examined the role that the endocytosis gene END3 plays in the internalization of extracellular proteins/vesicles in response to glucose addition. Transmission electron microscopy was performed to determine the presence of extracellular vesicles in glucose-starved wild-type cells and the dynamics of vesicle transport in cells lacking the END3 gene. Proteomics was used to identify extracellular proteins that associated with these vesicles. Total extracts prepared from glucose-starved cells consisted of about 95% small vesicles (30-50 nm) and 5% large structures (100-300 nm). The addition of glucose caused a rapid decline in small extracellular vesicles in wild-type cells. However, most of the extracellular vesicles were still observed in cells lacking the END3 gene following glucose replenishment. Proteomics was used to identify 72 extracellular proteins that may be associated with these vesicles. Gluconeogenic enzymes fructose-1,6-bisphosphatase, malate dehydrogenase, isocitrate lyase, and phosphoenolpyruvate carboxykinase, as well as non-gluconeogenic enzymes glyceraldehyde-3-phosphate dehydrogenase and cyclophilin A, were distributed in the vesicle-enriched fraction in total extracts prepared from cells grown in low glucose. Distribution of these proteins in the vesicle-enriched fraction required the integrity of the membranes. When glucose was added to glucose-starved wild-type cells, levels of extracellular fructose-1,6-bisphosphatase, malate dehydrogenase, isocitrate lyase, phosphoenolpyruvate carboxykinase, glyceraldehyde-3-phosphate dehydrogenase, and cyclophilin A were

  15. Naegleria fowleri That Induces Primary Amoebic Meningoencephalitis: Rapid Diagnosis and Rare Case of Survival in a 12-Year-Old Caucasian Girl.

    Science.gov (United States)

    Dunn, Andrew L; Reed, Tameika; Stewart, Charlotte; Levy, Rebecca A

    2016-05-01

    Primary amoebic meningoencephalitis (PAM) is a rare and almost always fatal disease that is caused by Naegleria fowleri, a freshwater thermophilic amoeba. Our case involves an adolescent female who presented with fever of unknown origin. A lumbar puncture was performed, and the Wright-Giemsa and Gram stained cerebrospinal fluid (CSF) cytospin slides showed numerous organisms. Experienced medical technologists in the microbiology and hematology laboratories identified the organisms as morphologically consistent with Naegleria species. The laboratory made a rapid diagnosis and alerted emergency department care providers within 75 minutes. The patient was treated for PAM with amphotericin, rifampin, azithromycin, fluconazole and aggressive supportive therapy including dexamethasone. The Centers for Disease Control and Prevention (CDC) was contacted, and miltefosine, an investigational medication, was started. Additional treatment included an intraventricular shunt and controlled hypothermia in order to mitigate potential cerebral edema. Our patient is a rare success story, as she was diagnosed swiftly, successfully treated, and survived PAM. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. A Facile and Microwave-assisted Rapid Synthesis of 2-Arylamino-4-(3'-indolyl)- thiazoles as Apoptosis Inducing Cytotoxic Agents.

    Science.gov (United States)

    Tantak, Mukund P; Mukherjee, Dipanwita Das; Kumar, Anil; Chakrabarti, Gopal; Kumar, Dalip

    2017-01-01

    The clinical success of the chemotherapeutic drugs is restricted by the nonspecific toxicity-related adverse side effects. The diverse implication of indoles and thiazoles in medicinal chemistry prompted us to develop a new series of novel 2-aryl-amino-4-(3'-indolyl)thiazoles as more effective and less toxic anti-cancer compounds. One-pot microwave-assisted rapid and high yielding synthesis of 2-arylamino-4-(3'- indolyl)thiazoles involved the reaction of easily available α-tosyloxy-ketones with N-arylthioureas in polyethylene glycol-400 (PEG-400). In vitro cytotoxicity study of 2-arylamino-4-(3'-indolyl)thiazoles against a panel of human cancer cell lines by MTT assay revealed IC50 values in the low micromolar range. Of the fifteen synthesized arylaminothiazoles, compounds 17b, 17d, 17g and 17il showed significant anti-proliferative activity against the selected cancer cell lines with IC50 synthesis for 2-arylamino-4-(3'-indolyl)thiazoles, and their in vitro cytotoxicity studies demonstrate that compound 17b exhibits significant anti-proliferative activity against MCF-7 (breast cancer) cells by activating ROS-mediated apoptosis through the mitochondrial apoptosis pathway. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Rapid 'on-line' image processing as a tool in the evaluation of kinetic and morphological aspects of receptor-induced cell activation.

    Science.gov (United States)

    Theler, J M; Wollheim, C B; Schlegel, W

    1991-01-01

    Transmembrane signalling involves rapid and spatially well defined changes in cytosolic free Ca2+, [Ca2+]i. Specific technologies involving image processing permit the analysis of kinetic and morphological aspects of [Ca2+]i at the subcellular level with the fluorescent Ca2+ probe fura-2. Fluorescence excitation wavelengths (340 nm or 380 nm) are alternated in synchrony with the acquisition at video rate of images captured with an intensified CCD camera. Images are digitized, recursively filtered, divided, and displayed after calibration of the 'ratio' image into a numerical [Ca2+]i scale. The image processor IMAGINE (Synoptics Ltd., UK) permits these operations at video rate. This produces 'on-line' [Ca2+]i images in real time which are stored on video tapes for subsequent analysis. The present communication summarizes the rationale for the selection of our current technologies. A comparison with alternative solutions should highlight the particular advantages and drawbacks of our approach. The present text thus should serve as a help for investigators who try to assemble image processing tools for work in the receptor and cellular signalling field.

  18. Mechanical stress rapidly induces E-resveratrol and E-piceatannol biosynthesis in grape canes stored as a freshly-pruned byproduct.

    Science.gov (United States)

    Billet, Kévin; Houillé, Benjamin; Besseau, Sébastien; Mélin, Céline; Oudin, Audrey; Papon, Nicolas; Courdavault, Vincent; Clastre, Marc; Giglioli-Guivarc'h, Nathalie; Lanoue, Arnaud

    2018-02-01

    Grape canes represent a promising source of bioactive phytochemicals. However the stabilization of the raw material after pruning remains challenging. We recently reported the induction of stilbenoid metabolism after winter pruning including a strong accumulation of E-resveratrol and E-piceatannol during the first six weeks of storage. In the present study, the effect of mechanical wounding on freshly-pruned canes was tested to increase the induction of stilbenoid metabolism. Cutting the grape canes in short segments immediately after pruning triggered a transient expression of phenylalanine ammonia-lyase (PAL) and stilbene synthase (STS) genes, followed by a rapid accumulation of E-resveratrol and E-piceatannol. The degree of stilbenoid induction was related to the intensity of mechanical wounding. Data suggest that a global defense response is triggered involving jasmonate signaling, PR proteins and stilbenoid metabolism. Mechanical wounding of freshly-pruned canes drastically shortens the time required to reach maximal stilbenoid accumulation from 6 to 2weeks. Copyright © 2017. Published by Elsevier Ltd.

  19. Rapid proteasomal degradation of posttranscriptional regulators of the TIS11/tristetraprolin family is induced by an intrinsically unstructured region independently of ubiquitination.

    Science.gov (United States)

    Ngoc, Long Vo; Wauquier, Corinne; Soin, Romuald; Bousbata, Sabrina; Twyffels, Laure; Kruys, Véronique; Gueydan, Cyril

    2014-12-01

    The TIS11/tristetraprolin (TTP) CCCH tandem zinc finger proteins are major effectors in the destabilization of mRNAs bearing AU-rich elements (ARE) in their 3' untranslated regions. In this report, we demonstrate that the Drosophila melanogaster dTIS11 protein is short-lived due to its rapid ubiquitin-independent degradation by the proteasome. Our data indicate that this mechanism is tightly associated with the intrinsically unstructured, disordered N- and C-terminal domains of the protein. Furthermore, we show that TTP, the mammalian TIS11/TTP protein prototype, shares the same three-dimensional characteristics and is degraded by the same proteolytic pathway as dTIS11, thereby indicating that this mechanism has been conserved across evolution. Finally, we observed a phosphorylation-dependent inhibition of dTIS11 and TTP degradation by the proteasome in vitro, raising the possibility that such modifications directly affect proteasomal recognition for these proteins. As a group, RNA-binding proteins (RNA-BPs) have been described as enriched in intrinsically disordered regions, thus raising the possibility that the mechanism that we uncovered for TIS11/TTP turnover is widespread among other RNA-BPs. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  20. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors.

    Science.gov (United States)

    Linge, Raquel; Jiménez-Sánchez, Laura; Campa, Leticia; Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Pazos, Angel; Adell, Albert; Díaz, Álvaro

    2016-04-01

    Cannabidiol (CBD), the main non-psychotomimetic component of marihuana, exhibits anxiolytic-like properties in many behavioural tests, although its potential for treating major depression has been poorly explored. Moreover, the mechanism of action of CBD remains unclear. Herein, we have evaluated the effects of CBD following acute and chronic administration in the olfactory bulbectomy mouse model of depression (OBX), and investigated the underlying mechanism. For this purpose, we conducted behavioural (open field and sucrose preference tests) and neurochemical (microdialysis and autoradiography of 5-HT1A receptor functionality) studies following treatment with CBD. We also assayed the pharmacological antagonism of the effects of CBD to dissect out the mechanism of action. Our results demonstrate that CBD exerts fast and maintained antidepressant-like effects as evidenced by the reversal of the OBX-induced hyperactivity and anhedonia. In vivo microdialysis revealed that the administration of CBD significantly enhanced serotonin and glutamate levels in vmPFCx in a different manner depending on the emotional state and the duration of the treatment. The potentiating effect upon neurotransmitters levels occurring immediately after the first injection of CBD might underlie the fast antidepressant-like actions in OBX mice. Both antidepressant-like effect and enhanced cortical 5-HT/glutamate neurotransmission induced by CBD were prevented by 5-HT1A receptor blockade. Moreover, adaptive changes in pre- and post-synaptic 5-HT1A receptor functionality were also found after chronic CBD. In conclusion, our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signalling through a 5-HT1A receptor-dependent mechanism. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Release of GTP Exchange Factor Mediated Down-Regulation of Abscisic Acid Signal Transduction through ABA-Induced Rapid Degradation of RopGEFs

    Science.gov (United States)

    Waadt, Rainer; Schroeder, Julian I.

    2016-01-01

    The phytohormone abscisic acid (ABA) is critical to plant development and stress responses. Abiotic stress triggers an ABA signal transduction cascade, which is comprised of the core components PYL/RCAR ABA receptors, PP2C-type protein phosphatases, and protein kinases. Small GTPases of the ROP/RAC family act as negative regulators of ABA signal transduction. However, the mechanisms by which ABA controls the behavior of ROP/RACs have remained unclear. Here, we show that an Arabidopsis guanine nucleotide exchange factor protein RopGEF1 is rapidly sequestered to intracellular particles in response to ABA. GFP-RopGEF1 is sequestered via the endosome-prevacuolar compartment pathway and is degraded. RopGEF1 directly interacts with several clade A PP2C protein phosphatases, including ABI1. Interestingly, RopGEF1 undergoes constitutive degradation in pp2c quadruple abi1/abi2/hab1/pp2ca mutant plants, revealing that active PP2C protein phosphatases protect and stabilize RopGEF1 from ABA-mediated degradation. Interestingly, ABA-mediated degradation of RopGEF1 also plays an important role in ABA-mediated inhibition of lateral root growth. The presented findings point to a PP2C-RopGEF-ROP/RAC control loop model that is proposed to aid in shutting off ABA signal transduction, to counteract leaky ABA signal transduction caused by “monomeric” PYL/RCAR ABA receptors in the absence of stress, and facilitate signaling in response to ABA. PMID:27192441

  2. Aircraft borne combined measurements of the Fukushima radionuclide Xe-133 and fossil fuel combustion generated pollutants in the TIL - implications for cyclone induced rapid lift and TIL physico-chemical processes

    Energy Technology Data Exchange (ETDEWEB)

    Schlager, Hans; Aufmhoff, Heinfried; Baumann, Robert; Schumann, Ulrich [DLR IPA, Oberpfaffenhofen (Germany); Arnold, Frank [MPI Kernphysik, Heidelberg (Germany); DLR IPA, Oberpfaffenhofen (Germany); Simgen, Hardy; Lindemann, Siegfried; Rauch, Ludwig; Kaether, Frank [MPI Kernphysik, Heidelberg (Germany); Pirjola, Liisa [University of Helsinki, Helsinki (Finland)

    2013-07-01

    The radionuclide Xe-133, released by the March 2011 nuclear disaster at Fukushima/Daiichi (hereafter FD), represents an ideal tracer for atmospheric transport. We report the, to our best knowledge, only aircraft borne measurements of FD Xe-133 in the Tropopause Inversion Layer (TIL), indicating rapid lift of polluted planetary boundary layer air to the TIL. On the same research aircraft (FALCON), we have also conducted on-line measurements of fossil fuel combustion generated pollutant gases (SO{sub 2} and other species), which had increased concentrations in the TIL. In addition, we have conducted supporting model simulations of transport, chemical processes, and aerosol processes. Our investigations reveal a potentially important impact of East-Asian cyclone induced pollutants transport to the TIL. This impact includes particularly aerosol formation.

  3. Positive selection drives rapid evolution of certain amino acid residues in an evolutionarily highly conserved interferon-inducible antiviral protein of fishes.

    Science.gov (United States)

    Padhi, Abinash

    2013-01-01

    Viperin, an evolutionarily highly conserved interferon-inducible multifunctional protein, has previously been reported to exhibit antiviral activity against a wide range of DNA and RNA viruses. Utilizing the complete nucleotide coding sequence data of fish viperin antiviral genes, and employing the maximum likelihood-based codon substitution models, the present study reports the pervasive role of positive selection in the evolution of viperin antiviral protein in fishes. The overall rate of nonsynonymous (dN) to synonymous (dS) substitutions (dN/dS) for the three functional domains of viperin (N-terminal, central domain and C-terminal) were 1.1, 0.12, and 0.24, respectively. Codon-by-codon substitution analyses have revealed that while most of the positively selected sites were located at the N-terminal amphipathic α-helix domain, few amino acid residues at the C-terminal domain were under positive selection. However, none of the sites in the central domain were under positive selection. These results indicate that, although viperin is evolutionarily highly conserved, the three functional domains experienced differential selection pressures. Taken together with the results of previous studies, the present study suggests that the persistent antagonistic nature of surrounding infectious viral pathogens might be the likely cause for such adaptive evolutionary changes of certain amino acids in fish viperin antiviral protein.

  4. Raman spectroscopic detection of rapid, reversible, early-stage inflammatory cytokine-induced apoptosis of adult hippocampal progenitors/stem cells

    CERN Document Server

    Ladiwala, Uma; Thakur, Bhushan; Santhosh, Chidangil; Mathur, Deepak

    2014-01-01

    The role of neuro-inflammation in diverse, acute and chronic brain pathologies is being increasingly recognized. Neuro-inflammation is accompanied by increased levels of both pro- and anti-inflammatory cytokines; these have deleterious as well as protective/reparative effects. Inflammation has varying effects on neurogenesis and is a subject of intense contemporary interest. We show that TNF-alpha and IFN-gamma, used concomitantly, cause apoptosis of adult rat hippocampal progenitor/stem cells in vitro as detected by the TUNEL and MTT assays on time scales of several hours. We have coupled Raman spectroscopy to an optical trap to probe early changes of apoptosis in single, live neural stem cells that have been treated with pro-inflammatory cytokines, TNF-alpha and IFN-gamma. Changes caused by inflammation-induced denaturation of DNA are observed in the Raman spectra that correspond to very early stages of apoptosis, occurring on very fast time scales: as short as 10 minutes. Addition of the anti-inflammatory ...

  5. H3N2 influenza A virus replicates in immortalized human first trimester trophoblast cell lines and induces their rapid apoptosis.

    Science.gov (United States)

    Trinh, Quang Duy; Izumi, Yasuyuki; Komine-Aizawa, Shihoko; Shibata, Toshikatsu; Shimotai, Yoshitaka; Kuroda, Kazumichi; Mizuguchi, Masashi; Ushijima, Hiroshi; Mor, Gil; Hayakawa, Satoshi

    2009-09-01

    Epidemiological data suggested that pandemic influenza increased the risks of spontaneous abortion and premature labor, while seasonal influenza also increased the risk of schizophrenia in adolescence. However, their pathogenesis is so far unknown. The first trimester trophoblast cell lines, namely, Swan71 and HTR8 cells were challenged with A/Udorn/72 influenza virus (H3N2). At indicated time points, cells were examined for expression of influenza proteins. Viral replication in culture media, apoptosis and the expression of human leukocyte antigen (HLA)-G were also examined. Intracellular localization of viral proteins was observed. Twenty-four hours after inoculation, virus was detected in culture media while most cells fell into apoptosis. During apoptosis, expression of HLA-G was unchanged. We revealed replication of low pathogenic influenza virus in the first trimester trophoblast cell lines. Placental damages are likely to be induced by direct cytopathic effects of influenza virus and subsequent apoptosis rather than down regulation of HLA-G expression and subsequent rejection by maternal immune system.

  6. Rapid generation of functional dopaminergic neurons from human induced pluripotent stem cells through a single-step procedure using cell lineage transcription factors.

    Science.gov (United States)

    Theka, Ilda; Caiazzo, Massimiliano; Dvoretskova, Elena; Leo, Damiana; Ungaro, Federica; Curreli, Sebastiano; Managò, Francesca; Dell'Anno, Maria Teresa; Pezzoli, Gianni; Gainetdinov, Raul R; Dityatev, Alexander; Broccoli, Vania

    2013-06-01

    Current protocols for in vitro differentiation of human induced pluripotent stem cells (hiPSCs) to generate dopamine (DA) neurons are laborious and time-expensive. In order to accelerate the overall process, we have established a fast protocol by expressing the developmental transcription factors ASCL1, NURR1, and LMX1A. With this method, we were able to generate mature and functional dopaminergic neurons in as few as 21 days, skipping all the intermediate steps for inducting and selecting embryoid bodies and rosette-neural precursors. Strikingly, the resulting neuronal conversion process was very proficient, with an overall efficiency that was more than 93% of all the coinfected cells. hiPSC-derived DA neurons expressed all the critical molecular markers of the DA molecular machinery and exhibited sophisticated functional features including spontaneous electrical activity and dopamine release. This one-step protocol holds important implications for in vitro disease modeling and is particularly amenable for exploitation in high-throughput screening protocols.

  7. Simultaneous separation of five major ribonucleic acids by capillary electrophoresis with laser-induced fluorescence in the presence of electroosmotic flow: application to the rapid screening of 5S rRNA from ovarian cancer cells.

    Science.gov (United States)

    Shih, Ya-Chu; Liao, Ching-Ru; Chung, I-Che; Chang, Yu-Sun; Chang, Po-Ling

    2014-10-17

    RNA integrity is important in RNA studies because poor RNA quality may impact downstream methodologies. This study proposes a rapid and cost-effective method for the determination of RNA integrity based on CE-LIF in the presence of electroosmotic flow. The proposed method uses poly(ethylene) oxide (Mavg=4,000,000 Da) as a sieving matrix for total RNA separation. Ethidium bromide (μg mL(-1)) was dissolved in a polymer solution as an interchelating dye for on-column fluorescent labeling. The 28S rRNA, 18S rRNA, 5.8S rRNA, 5S rRNA and tRNA from the total human RNA extracted from the cells were fully separated using the proposed method. The lowest detectable concentration of total RNA achieved was 100 pg μL(-1) with a 6 min sample injection followed by on-column concentration. In addition, the temperature-induced degradation of total RNA was observed by CE-LIF. The electropherograms revealed more fragmentation of 28S and 18S rRNAs by temperature-induced hydrolysis compared with the 5.8S rRNA, 5S rRNA and tRNA. Therefore, the results indicated that RNA degradation should be considered for long-term, high-temperature incubations in RNA-related experiments involving RNA hybridization. The proposed method is furthermore, applied to the determination of 5S rRNA overexpressed in ovarian cancer cells as compared to the cervical cancer cells. Overall, CE-LIF is highly promising for rapid screening of ovarian cancers without tedious pre-amplification steps. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Novel lineage- and stage-selective effects of retinoic acid on mouse granulopoiesis: Blockade by dexamethasone or inducible NO synthase inactivation.

    Science.gov (United States)

    Xavier-Elsas, Pedro; Vieira, Bruno Marques; Masid-de-Brito, Daniela; Santos, Juliana; Barradas, Monica Gomes; de Luca, Bianca; Gaspar-Elsas, Maria Ignez

    2017-04-01

    Despite the close relationship of eosinophils and neutrophils, these granulocyte lineages respond to distinct cytokines and play unique roles in immune responses. They nevertheless respond to shared physiological/pharmacological regulators, including glucocorticoids and retinoids, and to ubiquitous mediators, including NO. Others showed that, in humans, all-trans retinoic acid (ATRA) suppresses eosinophil differentiation, but promotes neutrophil differentiation. Mechanisms of dual co-regulation of physiological granulopoiesis were here examined in murine bone-marrow, a model system suitable for exploration of immunopharmacological mechanisms, given the availability of experimental resources, including mutant/knockout mouse strains. We examined the effects of ATRA on mouse eosinophil and neutrophil production, using wild-type (BALB/c, C57BL/6) and mutant (iNOS-, CD95L-, or CD95-KO) bone-marrow cultures, further assessing the modification of ATRA activity by dexamethasone and iNOS blockade. ATRA (10(-6)-10(-8)M) significantly decreased eosinophil production relative to IL-5 controls. This effect was iNOS-independent, but CD95L- and caspase-dependent, and prevented by dexamethasone (10(-7)M in vitro; 1-20mg·kg(-1) in vivo). In myeloid colony formation assays, ATRA markedly suppressed GM-CSF-responsive progenitors, through an iNOS-dependent, CD95-independent, dexamethasone-sensitive mechanism. By contrast, ATRA potently enhanced GM-CSF-dependent neutropoiesis in liquid culture from BALB/c or C57BL/6 bone-marrow. This novel stimulatory effect was resistant to dexamethasone and abolished in iNOS-KO bone-marrow. ATRA injections also induced lineage- and stage-selective effects on granulopoiesis in vivo. ATRA therefore co-regulates eosinophil and neutrophil production in murine bone-marrow through multiple lineage- and stage-selective mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Rapid Induction of Cerebral Organoids From Human Induced Pluripotent Stem Cells Using a Chemically Defined Hydrogel and Defined Cell Culture Medium.

    Science.gov (United States)

    Lindborg, Beth A; Brekke, John H; Vegoe, Amanda L; Ulrich, Connor B; Haider, Kerri T; Subramaniam, Sandhya; Venhuizen, Scott L; Eide, Cindy R; Orchard, Paul J; Chen, Weili; Wang, Qi; Pelaez, Francisco; Scott, Carolyn M; Kokkoli, Efrosini; Keirstead, Susan A; Dutton, James R; Tolar, Jakub; O'Brien, Timothy D

    2016-07-01

    Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. By using no additional neural induction components, cOrgs appeared on the hydrogel surface within 10-14 days, and under static culture conditions, they attained sizes up to 3 mm in greatest dimension by day 28. Histologically, the organoids showed neural rosette and neural tube-like structures and evidence of early corticogenesis. Immunostaining and quantitative reverse-transcription polymerase chain reaction demonstrated protein and gene expression representative of forebrain, midbrain, and hindbrain development. Physiologic studies showed responses to glutamate and depolarization in many cells, consistent with neural behavior. The method of cerebral organoid generation described here facilitates access to this technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. Tissue organoids are a promising technology with many potential applications, such as pharmaceutical screens and development of in vitro disease models, particularly for human polygenic conditions where animal models are insufficient. This work describes a robust and simple method for generating cerebral organoids from human induced pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. This method, by virtue of its simplicity and use of defined materials, greatly facilitates access to cerebral organoid technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. ©AlphaMed Press.

  10. Rapid stalk elongation in tulip (Tulipa gesneriana L. cv. Apeldoorn) and the combined action of cold-induced invertase and the water-channel protein gammaTIP.

    Science.gov (United States)

    Balk, P A; de Boer, A D

    1999-09-01

    Many bulbous plants need a low-temperature treatment for flowering. Cold, for example, affects the elongation of the stalk, thereby influencing the quality of the cut flower. How the elongation of the stalk is promoted by cold and which physiological and biochemical mechanisms are involved have remained obscure. As invertase has been shown to be involved in the cold-induced elongation of the flower stalks of tulips (Lambrechts et al., 1994, Plant Physiol 104: 515-520), we further characterized this enzyme by cloning the cDNA and analysing its expression in various tissues of the tulip (Tulipa gesneriana L. cv. Apeldoorn) stalk. In addition, the role of sucrose synthase was investigated. Since turgor pressure is an important force driving cell elongation, the role of a water-channel protein (gammaTIP) was studied in relation to these two enzymes. The mRNA level of the invertase found was substantially up-regulated as a result of cold treatment. Analysis of the amino acid sequence of this invertase revealed the presence of a vacuolar targeting signal. Two different forms of sucrose synthase were found, the expression of one of them appeared to be restricted to the vascular tissue while the other form was present in the surrounding tissue. Both sucrose synthases were present in the stalk during the entire period of bulb storage and after planting, but their activities declined during stalk elongation. The expression of the gammaTIP gene was restricted mainly to the vascular tissue and its expression profile was identical to that of invertase. Simultaneous expression of invertase and gammaTIP possibly leads to an increase in osmotic potential and vacuolar water uptake, thus providing a driving force for stretching the stalk cells.

  11. XIAP acts as a switch between type I and type II FAS-induced apoptosis signalling

    OpenAIRE

    Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D.; Nachbur, Ueli; Huang, David C.S; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2009-01-01

    FAS (APO-1/CD95) and its physiological ligand, FASL, regulate apoptotic death of unwanted or dangerous cells in many tissues, functioning as a guardian against autoimmunity and cancer development1-4. Distinct cell types differ in the mechanisms by which the ‘death receptor’ FAS triggers their apoptosis1-4. In type I cells, such as lymphocytes, activation of ‘effector caspases’ by FAS-induced activation of caspase-8 suffices for cell killing whereas in type II cells, including hepatocytes and ...

  12. N-acetyl cysteine protects anti-melanoma cytotoxic T cells from exhaustion induced by rapid expansion via the downmodulation of Foxo1 in an Akt-dependent manner.

    Science.gov (United States)

    Scheffel, Matthew J; Scurti, Gina; Wyatt, Megan M; Garrett-Mayer, Elizabeth; Paulos, Chrystal M; Nishimura, Michael I; Voelkel-Johnson, Christina

    2018-02-02

    Therapeutic outcomes for adoptive cell transfer (ACT) therapy are constrained by the quality of the infused T cells. The rapid expansion necessary to obtain large numbers of cells results in a more terminally differentiated phenotype with decreased durability and functionality. N-acetyl cysteine (NAC) protects against activation-induced cell death (AICD) and improves anti-tumor efficacy of Pmel-1 T cells in vivo. Here, we show that these benefits of NAC can be extended to engineered T cells and significantly increases T-cell survival within the tumor microenvironment. The addition of NAC to the expansion protocol of human TIL13838I TCR-transduced T cells that are under evaluation in a Phase I clinical trial, demonstrated that findings in murine cells extend to human cells. Expansion of TIL13838I TCR-transduced T cells in NAC also increased their ability to kill target cells in vitro. Interestingly, NAC did not affect memory subsets, but diminished up-regulation of senescence (CD57) and exhaustion (PD-1) markers and significantly decreased expression of the transcription factors EOMES and Foxo1. Pharmacological inhibition of the PI3K/Akt pathway ablates the decrease in Foxo1 induced by NAC treatment of activated T cells. This suggests a model in which NAC through PI3K/Akt activation suppresses Foxo1 expression, thereby impacting its transcriptional targets EOMES, PD-1, and granzyme B. Taken together, our results indicate that NAC exerts pleiotropic effects that impact the quality of TCR-transduced T cells and suggest that the addition of NAC to current clinical protocols should be considered.

  13. Highly active microbial phosphoantigen induces rapid yet sustained MEK/Erk- and PI-3K/Akt-mediated signal transduction in anti-tumor human gammadelta T-cells.

    Directory of Open Access Journals (Sweden)

    Daniel V Correia

    Full Text Available BACKGROUND: The unique responsiveness of Vgamma9Vdelta2 T-cells, the major gammadelta subset of human peripheral blood, to non-peptidic prenyl pyrophosphate antigens constitutes the basis of current gammadelta T-cell-based cancer immunotherapy strategies. However, the molecular mechanisms responsible for phosphoantigen-mediated activation of human gammadelta T-cells remain unclear. In particular, previous reports have described a very slow kinetics of activation of T-cell receptor (TCR-associated signal transduction pathways by isopentenyl pyrophosphate and bromohydrin pyrophosphate, seemingly incompatible with direct binding of these antigens to the Vgamma9Vdelta2 TCR. Here we have studied the most potent natural phosphoantigen yet identified, (E-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP, produced by Eubacteria and Protozoa, and examined its gammadelta T-cell activation and anti-tumor properties. METHODOLOGY/PRINCIPAL FINDINGS: We have performed a comparative study between HMB-PP and the anti-CD3epsilon monoclonal antibody OKT3, used as a reference inducer of bona fide TCR signaling, and followed multiple cellular and molecular gammadelta T-cell activation events. We show that HMB-PP activates MEK/Erk and PI-3K/Akt pathways as rapidly as OKT3, and induces an almost identical transcriptional profile in Vgamma9(+ T-cells. Moreover, MEK/Erk and PI-3K/Akt activities are indispensable for the cellular effects of HMB-PP, including gammadelta T-cell activation, proliferation and anti-tumor cytotoxicity, which are also abolished upon antibody blockade of the Vgamma9(+ TCR Surprisingly, HMB-PP treatment does not induce down-modulation of surface TCR levels, and thereby sustains gammadelta T-cell activation upon re-stimulation. This ultimately translates in potent human gammadelta T-cell anti-tumor function both in vitro and in vivo upon transplantation of human leukemia cells into lymphopenic mice, CONCLUSIONS/SIGNIFICANCE: The development of

  14. Rapid Prototyping Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  15. The transmembrane domains of TNF-related apoptosis-inducing ligand (TRAIL receptors 1 and 2 co-regulate apoptotic signaling capacity.

    Directory of Open Access Journals (Sweden)

    Simon Neumann

    Full Text Available TNF-related apoptosis-inducing ligand (TRAIL is a member of the tumor necrosis factor (TNF ligand family that exerts its apoptotic activity in human cells by binding to two transmembrane receptors, TRAILR1 and TRAILR2. In cells co-expressing both receptors the particular contribution of either protein to the overall cellular response is not well defined. Here we have investigated whether differences in the signaling capacities of TRAILR1 and TRAILR2 can be attributed to certain functional molecular subdomains. We generated and characterized various chimeric receptors comprising TRAIL receptor domains fused with parts from other members of the TNF death receptor family. This allowed us to compare the contribution of particular domains of the two TRAIL receptors to the overall apoptotic response and to identify elements that regulate apoptotic signaling. Our results show that the TRAIL receptor death domains are weak apoptosis inducers compared to those of CD95/Fas, because TRAILR-derived constructs containing the CD95/Fas death domain possessed strongly enhanced apoptotic capabilities. Importantly, major differences in the signaling strengths of the two TRAIL receptors were linked to their transmembrane domains in combination with the adjacent extracellular stalk regions. This was evident from receptor chimeras comprising the extracellular part of TNFR1 and the intracellular signaling part of CD95/Fas. Both receptor chimeras showed comparable ligand binding affinities and internalization kinetics. However, the respective TRAILR2-derived molecule more efficiently induced apoptosis. It also activated caspase-8 and caspase-3 more strongly and more quickly, albeit being expressed at lower levels. These results suggest that the transmembrane domains together with their adjacent stalk regions can play a major role in control of death receptor activation thereby contributing to cell type specific differences in TRAILR1 and TRAILR2 signaling.

  16. The transmembrane domains of TNF-related apoptosis-inducing ligand (TRAIL) receptors 1 and 2 co-regulate apoptotic signaling capacity.

    Science.gov (United States)

    Neumann, Simon; Bidon, Tobias; Branschädel, Marcus; Krippner-Heidenreich, Anja; Scheurich, Peter; Doszczak, Malgorzata

    2012-01-01

    TNF-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) ligand family that exerts its apoptotic activity in human cells by binding to two transmembrane receptors, TRAILR1 and TRAILR2. In cells co-expressing both receptors the particular contribution of either protein to the overall cellular response is not well defined. Here we have investigated whether differences in the signaling capacities of TRAILR1 and TRAILR2 can be attributed to certain functional molecular subdomains. We generated and characterized various chimeric receptors comprising TRAIL receptor domains fused with parts from other members of the TNF death receptor family. This allowed us to compare the contribution of particular domains of the two TRAIL receptors to the overall apoptotic response and to identify elements that regulate apoptotic signaling. Our results show that the TRAIL receptor death domains are weak apoptosis inducers compared to those of CD95/Fas, because TRAILR-derived constructs containing the CD95/Fas death domain possessed strongly enhanced apoptotic capabilities. Importantly, major differences in the signaling strengths of the two TRAIL receptors were linked to their transmembrane domains in combination with the adjacent extracellular stalk regions. This was evident from receptor chimeras comprising the extracellular part of TNFR1 and the intracellular signaling part of CD95/Fas. Both receptor chimeras showed comparable ligand binding affinities and internalization kinetics. However, the respective TRAILR2-derived molecule more efficiently induced apoptosis. It also activated caspase-8 and caspase-3 more strongly and more quickly, albeit being expressed at lower levels. These results suggest that the transmembrane domains together with their adjacent stalk regions can play a major role in control of death receptor activation thereby contributing to cell type specific differences in TRAILR1 and TRAILR2 signaling.

  17. Rapid Airplane Parametric Input Design (RAPID)

    Science.gov (United States)

    Smith, Robert E.

    1995-01-01

    RAPID is a methodology and software system to define a class of airplane configurations and directly evaluate surface grids, volume grids, and grid sensitivity on and about the configurations. A distinguishing characteristic which separates RAPID from other airplane surface modellers is that the output grids and grid sensitivity are directly applicable in CFD analysis. A small set of design parameters and grid control parameters govern the process which is incorporated into interactive software for 'real time' visual analysis and into batch software for the application of optimization technology. The computed surface grids and volume grids are suitable for a wide range of Computational Fluid Dynamics (CFD) simulation. The general airplane configuration has wing, fuselage, horizontal tail, and vertical tail components. The double-delta wing and tail components are manifested by solving a fourth order partial differential equation (PDE) subject to Dirichlet and Neumann boundary conditions. The design parameters are incorporated into the boundary conditions and therefore govern the shapes of the surfaces. The PDE solution yields a smooth transition between boundaries. Surface grids suitable for CFD calculation are created by establishing an H-type topology about the configuration and incorporating grid spacing functions in the PDE equation for the lifting components and the fuselage definition equations. User specified grid parameters govern the location and degree of grid concentration. A two-block volume grid about a configuration is calculated using the Control Point Form (CPF) technique. The interactive software, which runs on Silicon Graphics IRIS workstations, allows design parameters to be continuously varied and the resulting surface grid to be observed in real time. The batch software computes both the surface and volume grids and also computes the sensitivity of the output grid with respect to the input design parameters by applying the precompiler tool

  18. Rapid shallow breathing

    Science.gov (United States)

    ... the smallest air passages of the lungs in children ( bronchiolitis ) Pneumonia or other lung infection Transient tachypnea of the newborn Anxiety and panic Other serious lung disease Home Care Rapid, shallow breathing should not be treated at home. It is ...

  19. Rapid Strep Test

    Science.gov (United States)

    ... worse than normal. Your first thoughts turn to strep throat. A rapid strep test in your doctor’s office ... your suspicions.Viruses cause most sore throats. However, strep throat is an infection caused by the Group A ...

  20. RAPID3? Aptly named!

    Science.gov (United States)

    Berthelot, J-M

    2014-01-01

    The RAPID3 score is the sum of three 0-10 patient self-report scores: pain, functional impairment on MDHAQ, and patient global estimate. It requires 5 seconds for scoring and can be used in all rheumatologic conditions, although it has mostly been used in rheumatoid arthritis where cutoffs for low disease activity (12/30) have been set. A RAPID3 score of ≤ 3/30 with 1 or 0 swollen joints (RAPID3 ≤ 3 + ≤ SJ1) provides remission criteria comparable to Boolean, SDAI, CDAI, and DAS28 remission criteria, in far less time than a formal joint count. RAPID3 performs as well as the DAS28 in separating active drugs from placebos in clinical trials. RAPID3 also predicts subsequent structural disease progression. RAPID3 can be determined at short intervals at home, allowing the determination of the area under the curve of disease activity between two visits and flare detection. However, RAPID3 should not be seen as a substitute for DAS28 and face to face visits in routine care. Monitoring patient status with only self-report information without a rheumatologist's advice (including joints and physical examination, and consideration of imaging and laboratory tests) may indeed be as undesirable for most patients than joint examination without a patient questionnaire. Conversely, combining the RAPID3 and the DAS28 may consist in faster or more sensitive confirmation that a medication is effective. Similarly, better enquiring of most important concerns of patients (pain, functional status and overall opinion on their disorder) should reinforces patients' confidence in their rheumatologist and treatments.

  1. Thymoquinone inhibits the CXCL12-induced chemotaxis of multiple myeloma cells and increases their susceptibility to Fas-mediated apoptosis.

    Directory of Open Access Journals (Sweden)

    Gamal Badr

    Full Text Available In multiple myeloma (MM, malignant plasma cells reside in the bone marrow, where they accumulate in close contact with stromal cells. The mechanisms responsible for the chemotaxis of malignant plasma cells are still poorly understood. Thus, we investigated the mechanisms involved in the chemotaxis of MDN and XG2 MM cell lines. Both cell lines strongly expressed CCR9, CXCR3 and CXCR4 chemokine receptors but only migrated toward CXCL12. Activation of CXCR4 by CXCL12 resulted in the association of CXCR4 with CD45 and activation of PLCβ3, AKT, RhoA, IκBα and ERK1/2. Using siRNA-silencing techniques, we showed CD45/CXCR4 association is essential for CXCL12-induced migration of MM cells. Thymoquinone (TQ, the major active component of the medicinal herb Nigella sativa Linn, has been described as a chemopreventive and chemotherapeutic compound. TQ treatment strongly inhibited CXCL12-mediated chemotaxis in MM cell lines as well as primary cells isolated from MM patients, but not normal PBMCs. Moreover, TQ significantly down-regulated CXCR4 expression and CXCL12-mediated CXCR4/CD45 association in MM cells. Finally, TQ also induced the relocalization of cytoplasmic Fas/CD95 to the membrane of MM cells and increased CD95-mediated apoptosis by 80%. In conclusion, we demonstrate the potent anti-myeloma activity of TQ, providing a rationale for further clinical evaluation.

  2. The Rapid Perceptual Impact of Emotional Distractors.

    Directory of Open Access Journals (Sweden)

    Briana L Kennedy

    Full Text Available The brief presentation of an emotional distractor can temporarily impair perception of a subsequent, rapidly presented target, an effect known as emotion-induced blindness (EIB. How rapidly does this impairment unfold? To probe this question, we examined EIB for targets that immediately succeeded ("lag-1" emotional distractors in a rapid stream of items relative to EIB for targets at later serial positions. Experiments 1 and 2 suggested that emotional distractors interfere with items presented very soon after them, with impaired target perception emerging as early as lag-1. Experiment 3 included an exploratory examination of individual differences, which suggested that EIB onsets more rapidly among participants scoring high in measures linked to negative affect.

  3. Rapid small lot manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Harrigan, R.W.

    1998-05-09

    The direct connection of information, captured in forms such as CAD databases, to the factory floor is enabling a revolution in manufacturing. Rapid response to very dynamic market conditions is becoming the norm rather than the exception. In order to provide economical rapid fabrication of small numbers of variable products, one must design with manufacturing constraints in mind. In addition, flexible manufacturing systems must be programmed automatically to reduce the time for product change over in the factory and eliminate human errors. Sensor based machine control is needed to adapt idealized, model based machine programs to uncontrolled variables such as the condition of raw materials and fabrication tolerances.

  4. Rapidly Developing Toxic Epidermal Necrolysis

    Directory of Open Access Journals (Sweden)

    Viktoria Oline Barrios Poulsen

    2013-01-01

    Full Text Available Severe cutaneous reactions with potentially fatal outcomes can have many different causes. The Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are rare. They are characterized by a low incidence but high mortality, and drugs are most commonly implicated. Urgent active therapy is required. Prompt recognition and withdrawal of suspect drug and rapid intervention can result in favourable outcome. No further international guidelines for treatment exist, and much of the treatment relies on old or experimental concepts with no scientific evidence. We report on a 54-year-old man experiencing rapidly developing drug-induced severe TEN and presented multiorgan failure involving the respiratory and circulatory system, coagulopathy, and renal insufficiency. Detachment counted 30% of total body surface area (TBSA. SCORTEN = 5, indicating a mortality rate >90%. The patient was sedated and mechanically ventilated, supported with fluids and inotropes to maintain a stable circulation. Component therapy was guided by thromboelastography (TEG. The patient received plasmapheresis, and shock reversal treatment was initiated. He was transferred to a specialized intensive care burn unit within 24 hours from admittance. The initial care was continued, and hemodialysis was started. Pulmonary, circulatory, and renal sequelae resolved with intensive care, and re-epithelialization progressed slowly. The patient was discharged home on hospital day 19.

  5. Rapid Cycling and Its Treatment

    Science.gov (United States)

    ... Announcements Public Service Announcements Partnering with DBSA Rapid Cycling and its Treatment What is bipolar disorder? Bipolar ... to Depression and Manic Depression . What is rapid cycling? Rapid cycling is defined as four or more ...

  6. Rapid manufacturing for microfluidics

    CSIR Research Space (South Africa)

    Land, K

    2012-10-01

    Full Text Available . Microfluidics is at the forefront of developing solutions for drug discovery, diagnostics (from glucose tests to malaria and TB testing) and environmental diagnostics (E-coli monitoring of drinking water). In order to quickly implement new designs, a rapid...

  7. Rapid Prototyping in PVS

    Science.gov (United States)

    Munoz, Cesar A.; Butler, Ricky (Technical Monitor)

    2003-01-01

    PVSio is a conservative extension to the PVS prelude library that provides basic input/output capabilities to the PVS ground evaluator. It supports rapid prototyping in PVS by enhancing the specification language with built-in constructs for string manipulation, floating point arithmetic, and input/output operations.

  8. Rapid Prototyping Reconsidered

    Science.gov (United States)

    Desrosier, James

    2011-01-01

    Continuing educators need additional strategies for developing new programming that can both reduce the time to market and lower the cost of development. Rapid prototyping, a time-compression technique adapted from the high technology industry, represents one such strategy that merits renewed evaluation. Although in higher education rapid…

  9. Rapid manufacturing facilitated customisation

    OpenAIRE

    Tuck, Christopher John; Hague, Richard; Ruffo, Massimiliano; Ransley, Michelle; Adams, Paul Russell

    2008-01-01

    Abstract This paper describes the production of body-fitting customised seat profiles utilising the following digital methods: three dimensional laser scanning, reverse engineering and Rapid Manufacturing (RM). The seat profiles have been manufactured in order to influence the comfort characteristics of an existing ejector seat manufactured by Martin Baker Aircraft Ltd. The seat, known as Navy Aircrew Common Ejection Seat (NACES), was originally designed with a generic profile. ...

  10. Rapid Detection of Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    David Perlin

    2005-08-14

    Pathogen identification is a crucial first defense against bioterrorism. A major emphasis of our national biodefense strategy is to establish fast, accurate and sensitive assays for diagnosis of infectious diseases agents. Such assays will ensure early and appropriate treatment of infected patients. Rapid diagnostics can also support infection control measures, which monitor and limit the spread of infectious diseases agents. Many select agents are highly transmissible in the early stages of disease, and it is critical to identify infected patients and limit the risk to the remainder of the population and to stem potential panic in the general population. Nucleic acid-based molecular approaches for identification overcome many of the deficiencies associated with conventional culture methods by exploiting both large- and small-scale genomic differences between organisms. PCR-based amplification of highly conserved ribosomal RNA (rRNA) genes, intergenic sequences, and specific toxin genes is currently the most reliable approach for bacterial, fungal and many viral pathogenic agents. When combined with fluorescence-based oligonucleotide detection systems, this approach provides real-time, quantitative, high fidelity analysis capable of single nucleotide allelic discrimination (4). These probe systems offer rapid turn around time (<2 h) and are suitable for high throughput, automated multiplex operations that are critical for clinical diagnostic laboratories. In this pilot program, we have used molecular beacon technology invented at the Public health Research Institute to develop a new generation of molecular probes to rapidly detect important agents of infectious diseases. We have also developed protocols to rapidly extract nucleic acids from a variety of clinical specimen including and blood and tissue to for detection in the molecular assays. This work represented a cooperative research development program between the Kramer-Tyagi/Perlin labs on probe development

  11. Tiber Personal Rapid Transit

    Directory of Open Access Journals (Sweden)

    Diego Carlo D'agostino

    2011-02-01

    Full Text Available The project “Tiber Personal Rapid Transit” have been presented by the author at the Rome City Vision Competition1 2010, an ideas competition, which challenges architects, engineers, designers, students and creatives individuals to develop visionary urban proposals with the intention of stimulating and supporting the contemporary city, in this case Rome. The Tiber PRT proposal tries to answer the competition questions with the definition of a provocative idea: a Personal Rapid transit System on the Tiber river banks. The project is located in the central section of the Tiber river and aims at the renewal of the river banks with the insertion of a Personal Rapid Transit infrastructure. The project area include the riverbank of Tiber from Rome Transtevere RFI station to Piazza del Popolo, an area where main touristic and leisure attractions are located. The intervention area is actually no used by the city users and residents and constitute itself a strong barrier in the heart of the historic city.

  12. Rapid development of fasting-induced hepatic lipidosis in the American mink (Neovison vison): effects of food deprivation and re-alimentation on body fat depots, tissue fatty acid profiles, hematology and endocrinology.

    Science.gov (United States)

    Rouvinen-Watt, Kirsti; Mustonen, Anne-Mari; Conway, Rebecca; Pal, Catherine; Harris, Lora; Saarela, Seppo; Strandberg, Ursula; Nieminen, Petteri

    2010-02-01

    Hepatic lipidosis is a common pathological finding in the American mink (Neovison vison) and can be caused by nutritional imbalance due to obesity or rapid body weight loss. The objectives of the present study were to investigate the timeline and characterize the development of hepatic lipidosis in mink in response to 0-7 days of food deprivation and liver recovery after 28 days of re-feeding. We report here the effects on hematological and endocrine variables, body fat mobilization, the development of hepatic lipidosis and the alterations in the liver lipid classes and tissue fatty acid (FA) sums. Food deprivation resulted in the rapid mobilization of body fat, most notably visceral, causing elevated hepatosomatic index and increased liver triacylglycerol content. The increased absolute amounts of liver total phospholipids and phosphatidylcholine suggested endoplasmic reticulum stress. The hepatic lipid infiltration and the altered liver lipid profiles were associated with a significantly reduced proportion of n-3 polyunsaturated FA (PUFA) in the livers and the decrease was more evident in the females. Likewise, re-feeding of the female mink resulted in a more pronounced recovery of the liver n-3 PUFA. The rapid decrease in the n-3/n-6 PUFA ratio in response to food deprivation could trigger an inflammatory response in the liver. This could be a key contributor to the pathophysiology of fatty liver disease in mink influencing disease progression.

  13. Rapidly variable relatvistic absorption

    Science.gov (United States)

    Parker, M.; Pinto, C.; Fabian, A.; Lohfink, A.; Buisson, D.; Alston, W.; Jiang, J.

    2017-10-01

    I will present results from the 1.5Ms XMM-Newton observing campaign on the most X-ray variable AGN, IRAS 13224-3809. We find a series of nine absorption lines with a velocity of 0.24c from an ultra-fast outflow. For the first time, we are able to see extremely rapid variability of the UFO features, and can link this to the X-ray variability from the inner accretion disk. We find a clear flux dependence of the outflow features, suggesting that the wind is ionized by increasing X-ray emission.

  14. Rapid prototype and test

    Energy Technology Data Exchange (ETDEWEB)

    Gregory, D.L.; Hansche, B.D.

    1996-06-01

    In order to support advanced manufacturing, Sandia has acquired the capability to produce plastic prototypes using stereolithography. Currently, these prototypes are used mainly to verify part geometry and ``fit and form`` checks. This project investigates methods for rapidly testing these plastic prototypes, and inferring from prototype test data actual metal part performance and behavior. Performances examined include static load/stress response, and structural dynamic (modal) and vibration behavior. The integration of advanced non-contacting measurement techniques including scanning laser velocimetry, laser holography, and thermoelasticity into testing of these prototypes is described. Photoelastic properties of the epoxy prototypes to reveal full field stress/strain fields are also explored.

  15. Right-Rapid-Rough

    Science.gov (United States)

    Lawrence, Craig

    2003-01-01

    IDEO (pronounced 'eye-dee-oh') is an international design, engineering, and innovation firm that has developed thousands of products and services for clients across a wide range of industries. Its process and culture attracted the attention of academics, businesses, and journalists around the world, and are the subject of a bestselling book, The Art of Innovation by Tom Kelley. One of the keys to IDEO's success is its use of prototyping as a tool for rapid innovation. This story covers some of IDEO's projects, and gives reasons for why they were successful.

  16. Reinfusion of autologous lymphocytes with granulocyte-macrophage colony-stimulating factor induces rapid recovery of CD4+ and CD8+ T cells after high-dose chemotherapy for metastatic breast cancer

    NARCIS (Netherlands)

    de Gast, G. C.; Vyth-Dreese, F. A.; Nooijen, W.; van den Bogaard, C. J. C.; Sein, J.; Holtkamp, M. M. J.; Linthorst, G. A. M.; Baars, J. W.; Schornagel, J. H.; Rodenhuis, S.

    2002-01-01

    PURPOSE: Repeated high-dose chemotherapy (HDCT) followed by peripheral-blood progenitor cell (PBPC) transplantation can induce a complete remission in patients with metastatic breast cancer sensitive to standard chemotherapy (CT), but the majority of patients relapse within 1 to 2 years. The immune

  17. Rapid mineralocorticoid receptor trafficking.

    Science.gov (United States)

    Gekle, M; Bretschneider, M; Meinel, S; Ruhs, S; Grossmann, C

    2014-03-01

    The mineralocorticoid receptor (MR) is a ligand-dependent transcription factor that physiologically regulates water-electrolyte homeostasis and controls blood pressure. The MR can also elicit inflammatory and remodeling processes in the cardiovascular system and the kidneys, which require the presence of additional pathological factors like for example nitrosative stress. However, the underlying molecular mechanism(s) for pathophysiological MR effects remain(s) elusive. The inactive MR is located in the cytosol associated with chaperone molecules including HSP90. After ligand binding, the MR monomer rapidly translocates into the nucleus while still being associated to HSP90 and after dissociation from HSP90 binds to hormone-response-elements called glucocorticoid response elements (GREs) as a dimer. There are indications that rapid MR trafficking is modulated in the presence of high salt, oxidative or nitrosative stress, hypothetically by induction or posttranslational modifications. Additionally, glucocorticoids and the enzyme 11beta hydroxysteroid dehydrogenase may also influence MR activation. Because MR trafficking and its modulation by micro-milieu factors influence MR cellular localization, it is not only relevant for genomic but also for nongenomic MR effects. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Rapid response manufacturing (RRM)

    Energy Technology Data Exchange (ETDEWEB)

    Cain, W.D. [Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States); Waddell, W.L. [National Centers for Manufacturing Sciences, Ann Arbor, MI (United States)

    1997-02-18

    US industry is fighting to maintain its competitive edge in the global market place. Today markets fluctuate rapidly. Companies, to survive, have to be able to respond with quick-to-market, improved, high quality, cost efficient products. The way products are developed and brought to market can be improved and made more efficient through the proper incorporation of emerging technologies. The RRM project was established to leverage the expertise and resources of US private industries and federal agencies to develop, integrate, and deploy new technologies that meet critical needs for effective product realization. The RRM program addressed a needed change in the US Manufacturing infrastructure that will ensure US competitiveness in world market typified by mass customization. This project provided the effort needed to define, develop and establish a customizable infrastructure for rapid response product development design and manufacturing. A major project achievement was the development of a broad-based framework for automating and integrating the product and process design and manufacturing activities involved with machined parts. This was accomplished by coordinating and extending the application of feature-based product modeling, knowledge-based systems, integrated data management, and direct manufacturing technologies in a cooperative integrated computing environment. Key technological advancements include a product model that integrates product and process data in a consistent, minimally redundant manner, an advanced computer-aided engineering environment, knowledge-based software aids for design and process planning, and new production technologies to make products directly from design application software.

  19. Evidence that generation of inositol 1,4,5-trisphosphate and hydrolysis of phosphatidylinositol 4,5-bisphosphate are rapid responses following addition of fungal elicitor which induces phytoalexin synthesis in lucerne (Medicago sativa) suspension culture cells.

    Science.gov (United States)

    Walton, T J; Cooke, C J; Newton, R P; Smith, C J

    1993-05-01

    Treatment of lucerne suspension culture cells with glycoprotein elicitor from the phytopathogenic fungus Verticillium albo-atrum R & B triggers Ca(2+)-mediated induction of antimicrobial secondary metabolites termed phytoalexins. The present study investigated the possible role of polyphosphoinositide signal transduction in phytoalexin elicitation. Within 1 min of addition of elicitor to lucerne suspension culture cells we found a 100-160% (15-25 pmol/g fresh wt) increase in the level of compound with chromatographic and electrophoretic properties expected for an inositol trisphosphate (InsP3) and which was strongly bound by an inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-specific binding protein; after 3 min the level of this compound had fallen below that observed prior to elicitor challenge. In 32P-prelabelled cells, the relative proportion of radioactivity which cochromatographed with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) was found to have decreased by 48% 1 min after elicitor addition and that rapid depletion of membrane lipid radioactivity was specific to this lipid fraction. The rapid, transient increase in level of Ins(1,4,5)P3 and concomitant fall in PtdIns(4,5)P2 suggests that Ins(1,4,5)P3 generated by hydrolysis of PtdIns(4,5)P2 may provide a Ca(2+)-mobilizing signal in phytoalexin elicitation in lucerne.

  20. Rapid Refresh (RAP) [13 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

  1. Rapid Refresh (RAP) [20 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

  2. Rapid chemical separations

    CERN Document Server

    Trautmann, N

    1976-01-01

    A survey is given on the progress of fast chemical separation procedures during the last few years. Fast, discontinuous separation techniques are illustrated by a procedure for niobium. The use of such techniques for the chemical characterization of the heaviest known elements is described. Other rapid separation methods from aqueous solutions are summarized. The application of the high speed liquid chromatography to the separation of chemically similar elements is outlined. The use of the gas jet recoil transport method for nuclear reaction products and its combination with a continuous solvent extraction technique and with a thermochromatographic separation is presented. Different separation methods in the gas phase are briefly discussed and the attachment of a thermochromatographic technique to an on-line mass separator is shown. (45 refs).

  3. Comprehensive study of solid pharmaceutical tablets in visible, near infrared (NIR), and longwave infrared (LWIR) spectral regions using a rapid simultaneous ultraviolet/visible/NIR (UVN) + LWIR laser-induced breakdown spectroscopy linear arrays detection system and a fast acousto-optic tunable filter NIR spectrometer.

    Science.gov (United States)

    Yang, Clayton S C; Jin, Feng; Swaminathan, Siva R; Patel, Sita; Ramer, Evan D; Trivedi, Sudhir B; Brown, Ei E; Hommerich, Uwe; Samuels, Alan C

    2017-10-30

    This is the first report of a simultaneous ultraviolet/visible/NIR and longwave infrared laser-induced breakdown spectroscopy (UVN + LWIR LIBS) measurement. In our attempt to study the feasibility of combining the newly developed rapid LWIR LIBS linear array detection system to existing rapid analytical techniques for a wide range of chemical analysis applications, two different solid pharmaceutical tablets, Tylenol arthritis pain and Bufferin, were studied using both a recently designed simultaneous UVN + LWIR LIBS detection system and a fast AOTF NIR (1200 to 2200 nm) spectrometer. Every simultaneous UVN + LWIR LIBS emission spectrum in this work was initiated by one single laser pulse-induced micro-plasma in the ambient air atmosphere. Distinct atomic and molecular LIBS emission signatures of the target compounds measured simultaneously in UVN (200 to 1100 nm) and LWIR (5.6 to 10 µm) spectral regions are readily detected and identified without the need to employ complex data processing. In depth profiling studies of these two pharmaceutical tablets without any sample preparation, one can easily monitor the transition of the dominant LWIR emission signatures from coating ingredients gradually to the pharmaceutical ingredients underneath the coating. The observed LWIR LIBS emission signatures provide complementary molecular information to the UVN LIBS signatures, thus adding robustness to identification procedures. LIBS techniques are more surface specific while NIR spectroscopy has the capability to probe more bulk materials with its greater penetration depth. Both UVN + LWIR LIBS and NIR absorption spectroscopy have shown the capabilities of acquiring useful target analyte spectral signatures in comparable short time scales. The addition of a rapid LWIR spectroscopic probe to these widely used optical analytical methods, such as NIR spectroscopy and UVN LIBS, may greatly enhance the capability and accuracy of the combined system for a comprehensive analysis.

  4. Opposite Expression of SPARC between the Liver and Pancreas in Streptozotocin-Induced Diabetic Rats

    Science.gov (United States)

    Aseer, Kanikkai Raja; Kim, Sang Woo; Choi, Myung-Sook; Yun, Jong Won

    2015-01-01

    Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates several cellular events, including inflammation and tissue remodelling. In this study, we investigated the tissue-specific expression of SPARC in streptozotocin (STZ)-induced diabetes, and found that SPARC was significantly up-regulated in the liver while down-regulated in the pancreas of STZ-induced diabetic rats. Chronic inflammation occurred in the diabetic pancreas accompanied by up-regulation of CCAAT/enhancer-binding protein beta (C/EBPβ) and its targets (TNFα, Il6, CRP, and Fn1) as well as myeloperoxidase (Mpo) and C-X-C chemokine receptor type 2 (Cxcr2). Diabetic liver showed significant up-regulation of Tgfb1 as well as moderately less up-regulated TNFα and reduced Fn1, resulting in elevated fibrogenesis. PARP-1 was not up-regulated during CD95-mediated apoptosis, resulting in restoration of high ATP levels in the diabetic liver. On the contrary, CD95-dependent apoptosis was not observed in the diabetic pancreas due to up-regulation of PARP-1 and ATP depletion, resulting in necrosis. The cytoprotective machinery was damaged by pancreatic inflammation, whereas adequate antioxidant capacity indicates low oxidative stress in the diabetic liver. High and low cellular insulin content was found in the diabetic liver and pancreas, respectively. Furthermore, we identified six novel interacting partner proteins of SPARC by co-immunoprecipitation in the diabetic liver and pancreas, and their interactions with SPARC were predicted by bioinformatics tools. Taken together, opposite expression of SPARC in the diabetic liver and pancreas may be related to inflammation and immune cell infiltration, degrees of apoptosis and fibrosis, cytoprotective machinery, and cellular insulin levels. PMID:26110898

  5. Building a rapid response team.

    Science.gov (United States)

    Halvorsen, Lisa; Garolis, Salomeja; Wallace-Scroggs, Allyson; Stenstrom, Judy; Maunder, Richard

    2007-01-01

    The use of rapid response teams is a relatively new approach for decreasing or eliminating codes in acute care hospitals. Based on the principles of a code team for cardiac and/or respiratory arrest in non-critical care units, the rapid response teams have specially trained nursing, respiratory, and medical personnel to respond to calls from general care units to assess and manage decompensating or rapidly changing patients before their conditions escalate to a full code situation. This article describes the processes used to develop a rapid response team, clinical indicators for triggering a rapid response team call, topics addressed in an educational program for the rapid response team members, and methods for evaluating effectiveness of the rapid response team.

  6. Ionisation and dissociation of water induced by swift multicharged ions; Etude de l'ionisation et de la dissociation d'H{sub 2}O induites par collision avec des ions multicharges rapides

    Energy Technology Data Exchange (ETDEWEB)

    Legendre, S

    2006-02-15

    Ionization and dissociation of water molecules and water clusters induced by 11.7 MeV/A Ni{sup 25+} ions were carried out by imaging techniques. Branching ratios, ionisation cross sections and Kinetic Energy Released distributions have been measured together with fragmentation dynamics studies. Multiple ionization represents approximately 30% of the ionizing events. Double ionization produces in significant way atomic oxygen, considered as a possible precursor of the large production of HO{sub 2} radical in liquid water radiolysis by ions of high Linear Energy Transfer. We evidence a strong selectivity of bond breakage in the case of ion-induced HOD fragmentation. Once the molecule doubly ionized, the breakage of the O-H bond is found 6.5 times more probable than that of the O-D bond. A semi-classical calculation simulating the fragmentation dynamics on the potential energy surface of the ground-state of di-cation H{sub 2}O{sup 2+} makes possible to as well reproduce the preferential nature of the breakage of the O-H bond as the position and the shift of the kinetic energy distributions. First results concerning interaction with water clusters are also reported. Measurements in coincidence are carried out giving access to correlation, with the distributions in energy and angle of the emitted fragments. Mass spectrum points fast intra-cluster proton transfer, leading to the emission of protonated clusters. (author)

  7. Study of the production of neutron-rich isotope beams issuing from fissions induced by fast neutrons; Etude de la production de faisceaux riches en neutrons par fission induite par neutrons rapides

    Energy Technology Data Exchange (ETDEWEB)

    Lau, Ch

    2000-09-15

    This work is a contribution to the PARRNe project (production of radioactive neutron-rich isotopes). This project is based on the fission fragments coming from the fission of 238-uranium induced by fast neutrons. The fast neutron flux is produced by the collisions of deutons in a converter. Thick targets of uranium carbide and liquid uranium targets have been designed in order to allow a quick release of fission fragments. A device, able to trap on a cryogenic thimble rare gas released by the target, has allowed the production of radioactive nuclei whose half-life is about 1 second. This installation has been settled to different deuton accelerators in the framework of the European collaboration SPIRAL-2. A calibration experiment has proved the feasibility of fixing an ISOL-type isotope separator to a 15 MV tandem accelerator, this installation can provide 500 nA deutons beams whose energy is 26 MeV and be a valuable tool for studying fast-neutron induced fission. Zinc, krypton, rubidium, cadmium, iodine, xenon and cesium beams have been produced in this installation. The most intense beams reach 10000 nuclei by micro-coulomb for 26 MeV deutons. An extra gain of 2 magnitude orders can be obtained by using a more specific ion source and by increasing the thickness of the target. Another extra gain of 2 magnitude orders involves 100 MeV deutons.

  8. Problems of rapid growth.

    Science.gov (United States)

    Kim, T D

    1980-01-01

    South Korea's export-oriented development strategy has achieved a remarkable growth record, but it has also brought 2 different problems: 1) since the country's exports accounted for about 1% of total world export volume, the 1st world has become fearful about Korea's aggressive export drive; and 2) the fact that exports account for over 30% of its total gross national product (GNP) exposes the vulnerability of South Korea's economy itself. South Korea continues to be a poor nation, although it is rated as 1 of the most rapidly growing middle income economies. A World Bank 1978 report shows Korea to be 28th of 58 middle income countries in terms of per capita GNP in 1976. Of 11 newly industrializing countries (NIC), 5 in the European continent are more advanced than the others. A recent emphasis on the basic human needs approach has tended to downgrade the concept of GNP. Korea has only an abundant labor force and is without any natural resources. Consequently, Korea utilized an export-oriented development strategy. Oil requirements are met with imports, and almost all raw materials to be processed into exportable products must be imported. To pay import bills Korea must export and earn foreign exchange. It must be emphasized that foreign trade must always be 2-way traffic. In order to export more to middle income countries like Korea, the countries of the 1st world need to ease their protectionist measures against imports from developing countries.

  9. Rapid Polymer Sequencer

    Science.gov (United States)

    Stolc, Viktor (Inventor); Brock, Matthew W (Inventor)

    2013-01-01

    Method and system for rapid and accurate determination of each of a sequence of unknown polymer components, such as nucleic acid components. A self-assembling monolayer of a selected substance is optionally provided on an interior surface of a pipette tip, and the interior surface is immersed in a selected liquid. A selected electrical field is impressed in a longitudinal direction, or in a transverse direction, in the tip region, a polymer sequence is passed through the tip region, and a change in an electrical current signal is measured as each polymer component passes through the tip region. Each of the measured changes in electrical current signals is compared with a database of reference electrical change signals, with each reference signal corresponding to an identified polymer component, to identify the unknown polymer component with a reference polymer component. The nanopore preferably has a pore inner diameter of no more than about 40 nm and is prepared by heating and pulling a very small section of a glass tubing.

  10. Rapidly rotating red giants

    Science.gov (United States)

    Gehan, Charlotte; Mosser, Benoît; Michel, Eric

    2017-10-01

    Stellar oscillations give seismic information on the internal properties of stars. Red giants are targets of interest since they present mixed modes, wich behave as pressure modes in the convective envelope and as gravity modes in the radiative core. Mixed modes thus directly probe red giant cores, and allow in particular the study of their mean core rotation. The high-quality data obtained by CoRoT and Kepler satellites represent an unprecedented perspective to obtain thousands of measurements of red giant core rotation, in order to improve our understanding of stellar physics in deep stellar interiors. We developed an automated method to obtain such core rotation measurements and validated it for stars on the red giant branch. In this work, we particularly focus on the specific application of this method to red giants having a rapid core rotation. They show complex spectra where it is tricky to disentangle rotational splittings from mixed-mode period spacings. We demonstrate that the method based on the identification of mode crossings is precise and efficient. The determination of the mean core rotation directly derives from the precise measurement of the asymptotic period spacing ΔΠ1 and of the frequency at which the crossing of the rotational components is observed.

  11. Rapid mixing kinetic techniques.

    Science.gov (United States)

    Martin, Stephen R; Schilstra, Maria J

    2013-01-01

    Almost all of the elementary steps in a biochemical reaction scheme are either unimolecular or bimolecular processes that frequently occur on sub-second, often sub-millisecond, time scales. The traditional approach in kinetic studies is to mix two or more reagents and monitor the changes in concentrations with time. Conventional spectrophotometers cannot generally be used to study reactions that are complete within less than about 20 s, as it takes that amount of time to manually mix the reagents and activate the instrument. Rapid mixing techniques, which generally achieve mixing in less than 2 ms, overcome this limitation. This chapter is concerned with the use of these techniques in the study of reactions which reach equilibrium; the application of these methods to the study of enzyme kinetics is described in several excellent texts (Cornish-Bowden, Fundamentals of enzyme kinetics. Portland Press, 1995; Gutfreund, Kinetics for the life sciences. Receptors, transmitters and catalysis. Cambridge University Press, 1995).There are various ways to monitor changes in concentration of reactants, intermediates and products after mixing, but the most common way is to use changes in optical signals (absorbance or fluorescence) which often accompany reactions. Although absorbance can sometimes be used, fluorescence is often preferred because of its greater sensitivity, particularly in monitoring conformational changes. Such methods are continuous with good time resolution but they seldom permit the direct determination of the concentrations of individual species. Alternatively, samples may be taken from the reaction volume, mixed with a chemical quenching agent to stop the reaction, and their contents assessed by techniques such as HPLC. These methods can directly determine the concentrations of different species, but are discontinuous and have a limited time resolution.

  12. Investigation of the fission yields of the fast neutron-induced fission of {sup 233}U; Mesure de la distribution en masse et en charge des produits de la fission rapide de l'{sup 233}U

    Energy Technology Data Exchange (ETDEWEB)

    Galy, J

    1999-09-01

    As a stars, a survey of the different methods of investigations of the fission product yields and the experimental data status have been studied, showing advantages and shortcomings for the different approaches. An overview of the existing models for the fission product distributions has been as well intended. The main part of this thesis was the measurement of the independent yields of the fast neutron-induced fission of{sup 233}U, never investigated before this work. The experiment has been carried out using the mass separator OSIRIS (Isotope Separator On-Line). Its integrated ion-source and its specific properties required an analysis of the delay-parameter and ionisation efficiency for each chemical species. On the other hand, this technique allows measurement of independent yields and cumulative yields for elements from Cu to Ba, covering most of the fission yield distribution. Thus, we measured about 180 independent yields from Zn (Z=30) to Sr (Z=38) in the mass range A=74-99 and from Pd (Z=46) to Ba (Z=56) in the mass range A=113-147, including many isomeric states. An additional experiment using direct {gamma}-spectroscopy of aggregates of fission products was used to determine more than 50 cumulative yields of element with half-life from 15 min to a several days. All experimental data have been compared to estimates from a semi-empirical model, to calculated values and to evaluated values from the European library JEF 2.2. Furthermore, a study of both thermal and fast neutron-induced fission of {sup 233}U measured at Studsvik, the comparison of the OSIRIS and LOHENGRIN facilities and the trends in new data for the Reactors Physics have been discussed. (author)

  13. The photon PDF in events with rapidity gaps

    Energy Technology Data Exchange (ETDEWEB)

    Harland-Lang, L.A. [University College London, Department of Physics and Astronomy, London (United Kingdom); Khoze, V.A. [Durham University, Institute for Particle Physics Phenomenology, Durham (United Kingdom); NRC Kurchatov Institute, Petersburg Nuclear Physics Institute, Moscow (Russian Federation); Ryskin, M.G. [NRC Kurchatov Institute, Petersburg Nuclear Physics Institute, Moscow (Russian Federation)

    2016-05-15

    We consider photon-initiated events with large rapidity gaps in proton-proton collisions, where one or both protons may break up. We formulate a modified photon PDF that accounts for the specific experimental rapidity gap veto, and demonstrate how the soft survival probability for these gaps may be implemented consistently. Finally, we present some phenomenological results for the two-photon induced production of lepton and W boson pairs. (orig.)

  14. MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression.

    Directory of Open Access Journals (Sweden)

    Christopher R Shaler

    2017-06-01

    Full Text Available Superantigens (SAgs are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS. Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections. Unlike in mouse models, the mechanisms underlying SAg-associated immunosuppression in humans are ill-defined. In this work, we have identified a population of innate-like T cells, called mucosa-associated invariant T (MAIT cells, as the most powerful source of pro-inflammatory cytokines after exposure to SAgs. We have utilized primary human peripheral blood and hepatic mononuclear cells, mouse MAIT hybridoma lines, HLA-DR4-transgenic mice, MAIThighHLA-DR4+ bone marrow chimeras, and humanized NOD-scid IL-2Rγnull mice to demonstrate for the first time that: i mouse and human MAIT cells are hyperresponsive to SAgs, typified by staphylococcal enterotoxin B (SEB; ii the human MAIT cell response to SEB is rapid and far greater in magnitude than that launched by unfractionated conventional T, invariant natural killer T (iNKT or γδ T cells, and is characterized by production of interferon (IFN-γ, tumor necrosis factor (TNF-α and interleukin (IL-2, but not IL-17A; iii high-affinity MHC class II interaction with SAgs, but not MHC-related protein 1 (MR1 participation, is required for MAIT cell activation; iv MAIT cell responses to SEB can occur in a T cell receptor (TCR Vβ-specific manner but are largely contributed by IL-12 and IL-18; v as MAIT cells are primed by SAgs, they also begin to

  15. Chaotic Maps Dynamics, Fractals, and Rapid Fluctuations

    CERN Document Server

    Chen, Goong

    2011-01-01

    This book consists of lecture notes for a semester-long introductory graduate course on dynamical systems and chaos taught by the authors at Texas A&M University and Zhongshan University, China. There are ten chapters in the main body of the book, covering an elementary theory of chaotic maps in finite-dimensional spaces. The topics include one-dimensional dynamical systems (interval maps), bifurcations, general topological, symbolic dynamical systems, fractals and a class of infinite-dimensional dynamical systems which are induced by interval maps, plus rapid fluctuations of chaotic maps as a

  16. Rapid Active Sampling Package

    Science.gov (United States)

    Peters, Gregory

    2010-01-01

    A field-deployable, battery-powered Rapid Active Sampling Package (RASP), originally designed for sampling strong materials during lunar and planetary missions, shows strong utility for terrestrial geological use. The technology is proving to be simple and effective for sampling and processing materials of strength. Although this originally was intended for planetary and lunar applications, the RASP is very useful as a powered hand tool for geologists and the mining industry to quickly sample and process rocks in the field on Earth. The RASP allows geologists to surgically acquire samples of rock for later laboratory analysis. This tool, roughly the size of a wrench, allows the user to cut away swaths of weathering rinds, revealing pristine rock surfaces for observation and subsequent sampling with the same tool. RASPing deeper (.3.5 cm) exposes single rock strata in-situ. Where a geologist fs hammer can only expose unweathered layers of rock, the RASP can do the same, and then has the added ability to capture and process samples into powder with particle sizes less than 150 microns, making it easier for XRD/XRF (x-ray diffraction/x-ray fluorescence). The tool uses a rotating rasp bit (or two counter-rotating bits) that resides inside or above the catch container. The container has an open slot to allow the bit to extend outside the container and to allow cuttings to enter and be caught. When the slot and rasp bit are in contact with a substrate, the bit is plunged into it in a matter of seconds to reach pristine rock. A user in the field may sample a rock multiple times at multiple depths in minutes, instead of having to cut out huge, heavy rock samples for transport back to a lab for analysis. Because of the speed and accuracy of the RASP, hundreds of samples can be taken in one day. RASP-acquired samples are small and easily carried. A user can characterize more area in less time than by using conventional methods. The field-deployable RASP used a Ni

  17. Rapid Robot Design Validation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Energid Technologies will create a comprehensive software infrastructure for rapid validation of robotic designs. The software will support push-button validation...

  18. Rapid Robot Design Validation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Energid Technologies will create a comprehensive software infrastructure for rapid validation of robot designs. The software will support push-button validation...

  19. Rapid prediction of electric fields associated with geomagnetically induced currents in the presence of three-dimensional ground structure: Projection of remote magnetic observatory data through magnetotelluric impedance tensors

    Science.gov (United States)

    Bonner, L. R.; Schultz, Adam

    2017-01-01

    Ground level electric fields arising from geomagnetic disturbances (GMDs) are used by the electric power industry to calculate geomagnetically induced currents (GICs) in the power grid. Current industry practice is limited to electric fields associated with 1-D ground electrical conductivity structure, yet at any given depth in the crust and mantle lateral (3-D) variations in conductivity can span at least 3 orders of magnitude, resulting in large deviations in electric fields relative to 1-D models. Solving Maxwell's equations for electric fields associated with GMDs above a 3-D Earth is computationally burdensome and currently impractical for industrial applications. A computationally light algorithm is proposed as an alternative. Real-time data from magnetic observatories are projected through multivariate transfer functions to locations of previously occupied magnetotelluric (MT) stations. MT time series and impedance tensors, such as those publically available from the NSF EarthScope Program, are used to scale the projected magnetic observatory data into local electric field predictions that can then be interpolated onto points along power grid transmission lines to actively improve resilience through GIC modeling. Preliminary electric field predictions are tested against previously recorded time series, idealized transfer function cases, and existing industry methods to assess the validity of the algorithm for potential adoption by the power industry. Some limitations such as long-period diurnal drift are addressed, and solutions are suggested to further improve the method before direct comparisons with actual GIC measurements are made.

  20. Reliability of a rapid hematology stain for sputum cytology

    OpenAIRE

    Gonçalves, Jéssica; Pizzichini, Emilio; Pizzichini, Marcia Margaret Menezes; Steidle, Leila John Marques; Rocha, Cristiane Cinara; Ferreira, Samira Cardoso; Zimmermann, Célia Tânia

    2014-01-01

    Objective: To determine the reliability of a rapid hematology stain for the cytological analysis of induced sputum samples. Methods: This was a cross-sectional study comparing the standard technique (May-Grünwald-Giemsa stain) with a rapid hematology stain (Diff-Quik). Of the 50 subjects included in the study, 21 had asthma, 19 had COPD, and 10 were healthy (controls). From the induced sputum samples collected, we prepared four slides: two were stained with May-Grünwald-Giemsa, and two w...

  1. Rapid prototyping in medical sciences

    Directory of Open Access Journals (Sweden)

    Ákos Márk Horváth

    2015-09-01

    Full Text Available Even if it sound a bit incredible rapid prototyping (RPT as production method has been used for decades in other professions. Nevertheless medical science just started discover the possibilities of this technology and use the offered benefits of 3D printing. In this paper authors have investigated the pharmaceutical usage of rapid prototyping.

  2. How Rapid is Rapid Prototyping? Analysis of ESPADON Programme Results

    Directory of Open Access Journals (Sweden)

    Ian D. Alston

    2003-05-01

    Full Text Available New methodologies, engineering processes, and support environments are beginning to emerge for embedded signal processing systems. The main objectives are to enable defence industry to field state-of-the-art products in less time and with lower costs, including retrofits and upgrades, based predominately on commercial off the shelf (COTS components and the model-year concept. One of the cornerstones of the new methodologies is the concept of rapid prototyping. This is the ability to rapidly and seamlessly move from functional design to the architectural design to the implementation, through automatic code generation tools, onto real-time COTS test beds. In this paper, we try to quantify the term “rapid” and provide results, the metrics, from two independent benchmarks, a radar and sonar beamforming application subset. The metrics show that the rapid prototyping process may be sixteen times faster than a conventional process.

  3. Fas-ligand (CD178) and TRAIL synergistically induce apoptosis of CD40-activated chronic lymphocytic leukemia B cells

    NARCIS (Netherlands)

    Dicker, Frank; Kater, Arnon P.; Fukuda, Tetsuya; Kipps, Thomas J.

    2005-01-01

    Chronic lymphocytic leukemia (CLL) B cells become sensitive to Fas (CD95)-mediated apoptosis 3 to 5 days after CD40 ligation. However, CD4+ cytotoxic T lymphocytes (CTLs) can kill CLL B cells via a Fas-ligand (CD178)-dependent process within 24 hours after CD40 cross-linking, when ligation of CD95

  4. Human embryonic and induced pluripotent stem cells express TRAIL receptors and can be sensitized to TRAIL-induced apoptosis.

    Science.gov (United States)

    Vinarsky, Vladimir; Krivanek, Jan; Rankel, Liina; Nahacka, Zuzana; Barta, Tomas; Jaros, Josef; Andera, Ladislav; Hampl, Ales

    2013-11-15

    Death ligands and their tumor necrosis factor receptor (TNFR) family receptors are the best-characterized and most efficient inducers of apoptotic signaling in somatic cells. In this study, we analyzed whether these prototypic activators of apoptosis are also expressed and able to be activated in human pluripotent stem cells. We examined human embryonic stem cells (hESC) and human-induced pluripotent stem cells (hiPSC) and found that both cell types express primarily TNF-related apoptosis-inducing ligand (TRAIL) receptors and TNFR1, but very low levels of Fas/CD95. We also found that although hESC and hiPSC contain all the proteins required for efficient induction and progression of extrinsic apoptotic signaling, they are resistant to TRAIL-induced apoptosis. However, both hESC and hiPSC can be sensitized to TRAIL-induced apoptosis by co-treatment with protein synthesis inhibitors such as the anti-leukemia drug homoharringtonine (HHT). HHT treatment led to suppression of cellular FLICE inhibitory protein (cFLIP) and Mcl-1 expression and, in combination with TRAIL, enhanced processing of caspase-8 and full activation of caspase-3. cFLIP likely represents an important regulatory node, as its shRNA-mediated down-regulation significantly sensitized hESC to TRAIL-induced apoptosis. Thus, we provide the first evidence that, irrespective of their origin, human pluripotent stem cells express canonical components of the extrinsic apoptotic system and on stress can activate death receptor-mediated apoptosis.

  5. A Rapid Coliform Detector Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC, in collaboration with Lucigen, proposes a rapid genetic detector for spaceflight water systems to enable real-time detection of E-coli with minimal...

  6. Rapid Multiplex Microbial Detector Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC, in collaboration with Lucigen, proposes a rapid nucleic acid-based detector for spaceflight water systems to enable simultaneous quantification of multiple...

  7. A rapid and sensitive method for diagnosis of dermatophyte induced ...

    African Journals Online (AJOL)

    Sherin M. Emam

    2015-08-29

    Aug 29, 2015 ... Sa˜o Paulo 1999;41:147–9. 34. Va´squez-del Mercado E, Arenas R. Onychomycosis among · children. A retrospective study of 233 Mexican cases. Gac Med · Mex 2008;144:7–10. 35. Ng KP, Soo Hoo TS, Nik SL, Ang LS. Dermatophytes isolated · from patients in University Hospital, Kuala Lumpur, Malaysia ...

  8. Agrobacteria lacking ornithine lipids induce more rapid tumour formation

    Science.gov (United States)

    Vences-Guzmán, Miguel Ángel; Guan, Ziqiang; Bermúdez-Barrientos, José Roberto; Geiger, Otto; Sohlenkamp, Christian

    2013-01-01

    Summary Ornithine lipids (OLs) are phosphorus-free membrane lipids that are widespread among Gram-negative bacteria. Their basic structure consists of a 3-hydroxy fatty acyl group attached in amide linkage to the α-amino group of ornithine and a second fatty acyl group ester-linked to the 3-hydroxy position of the first fatty acid. It has been shown that OLs can be hydroxylated within the amide-linked fatty acyl moiety, the secondary fatty acyl moiety or within the ornithine moiety. These modifications have been related to increased stress tolerance and symbiotic proficiency in different organisms such as Rhizobium tropici or Burkholderia cenocepacia. Analysing the membrane lipid composition of the plant pathogen Agrobacterium tumefaciens we noticed that it forms two different OLs. In the present work we studied if OLs play a role in stress tolerance and pathogenicity in A. tumefaciens. Mutants deficient in the OLs biosynthesis genes olsB or olsE were constructed and characterized. They either completely lack OLs (ΔolsB) or only form the unmodified OL (ΔolsE). Here we present a characterization of both OL mutants under stress conditions and in a plant transformation assay using potato tuber discs. Surprisingly, the lack of agrobacterial OLs promotes earlier tumour formation on the plant host. PMID:22958119

  9. A rapid and sensitive method for diagnosis of dermatophyte induced ...

    African Journals Online (AJOL)

    Sherin M. Emam

    2015-08-29

    Aug 29, 2015 ... b Dermatology & Andrology Departments, Faculty of Medicine, Benha University, Benha, Egypt1. Received 29 November 2014; accepted 21 May ..... they attributed to the suggestion that ''men exercise more'' and so more liable to trauma. ... often or for cosmetic reasons. Also Sais et al.26 found that females ...

  10. Dysfunction of Rapid Neural Adaptation in Dyslexia.

    Science.gov (United States)

    Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

    2016-12-21

    Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Composites by rapid prototyping technology

    CSIR Research Space (South Africa)

    Kumar, S

    2010-02-01

    Full Text Available powder is a fiber, problems of manufacturing occur. The method has also been used to make Metal Matrix Composite (MMC), e.g Fe and graphite [17], WC-Co [18,19], WC-Co and Cu [20,21], Fe, Ni and TiC [22] etc and Ceramic Matrix Composite (CMC) e.g. Si... of various materials used. Key words: : Rapid Prototyping (RP), Laser, Composites 1 Introduction Rapid Prototyping (RP) initially focussed on polymers. These were later re- placed/supplemented by ceramics, metals and composites. Composites are used in RP...

  12. Effects of Bepridil on Atrial Electrical Remodeling in Short-Term Rapid Pacing

    Directory of Open Access Journals (Sweden)

    Hiroto Tsuchiya, MD

    2009-01-01

    Conclusions: Bepridil prevented the shortening of the ERP and MAPD90 induced by rapid atrial pacing in the acute phase. The results of this study might explain the efficacy of bepridil for preventing the recurrence of paroxysmal AF.

  13. Developmental evolution facilitates rapid adaptation.

    Science.gov (United States)

    Lin, Hui; Kazlauskas, Romas J; Travisano, Michael

    2017-11-21

    Developmental evolution has frequently been identified as a mode for rapid adaptation, but direct observations of the selective benefits and associated mechanisms of developmental evolution are necessarily challenging to obtain. Here we show rapid evolution of greatly increased rates of dispersal by developmental changes when populations experience stringent selection. Replicate populations of the filamentous fungus Trichoderma citrinoviride underwent 85 serial transfers, under conditions initially favoring growth but not dispersal. T. citrinoviride populations shifted away from multicellular growth toward increased dispersal by producing one thousand times more single-celled asexual conidial spores, three times sooner than the ancestral genotype. Conidia of selected lines also germinated fifty percent faster. Gene expression changed substantially between the ancestral and selected fungi, especially for spore production and growth, demonstrating rapid evolution of tight regulatory control for down-regulation of growth and up-regulation of conidia production between 18 and 24 hours of growth. These changes involved both developmentally fixed and plastic changes in gene expression, showing that complex developmental changes can serve as a mechanism for rapid adaptation.

  14. Multigrade Teaching Rapid Appraisal Procedure.

    Science.gov (United States)

    Nielsen, Dean

    Multigrade classes have been recognized as part of elementary education for many years, but their special needs have been largely ignored. This manual focuses on the survey research that should predate the design of instructional management strategies in multigrade classrooms. It describes rapid and reliable ways to collect information about the…

  15. Rapid thermal processing of semiconductors

    CERN Document Server

    Borisenko, Victor E

    1997-01-01

    Rapid thermal processing has contributed to the development of single wafer cluster processing tools and other innovations in integrated circuit manufacturing environments Borisenko and Hesketh review theoretical and experimental progress in the field, discussing a wide range of materials, processes, and conditions They thoroughly cover the work of international investigators in the field

  16. Furnace for rapid thermal processing

    NARCIS (Netherlands)

    Roozeboom, F.; Duine, P.A.; Sluis, P. van der

    2001-01-01

    A Method (1) for Rapid Thermal Processing of a wafer (7), wherein the wafer (7) is heated by lamps (9), and the heat radiation is reflected by an optical switching device (15,17) which is in the reflecting state during the heating stage. During the cooling stage of the wafer (7), the heat is

  17. Rapid Energy Modeling Workflow Demonstration

    Science.gov (United States)

    2013-10-31

    BIM Building Information Modeling BPA Building Performance Analysis BTU British Thermal Unit CBECS Commercial Building ...geometry, orientation, weather, and materials, generates 3D Building Information Models ( BIM ) guided by satellite views of building footprints and...Rapid Energy Modeling (REM) workflows that employed building information modeling ( BIM ) approaches and conceptual energy analysis.

  18. Portable Diagnostics and Rapid Germination

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, Zachary Spencer [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-12-01

    In the Bioenergy and Defense Department of Sandia National Laboratories, characterization of the BaDx (Bacillus anthracis diagnostic cartridge) was performed and rapid germination chemistry was investigated. BaDx was tested with complex sample matrixes inoculated with Bacillus anthracis, and the trials proved that BaDx will detect Bacillus anthracis in a variety of the medium, such as dirt, serum, blood, milk, and horse fluids. The dimensions of the device were altered to accommodate an E. coli or Listeria lateral flow immunoassay, and using a laser printer, BaDx devices were manufactured to identify E. coli and Listeria. Initial testing with E. coli versions of BaDx indicate that the device will be viable as a portable diagnostic cartridge. The device would be more effective with faster bacteria germination; hence studies were performed the use of rapid germination chemistry. Trials with calcium dipicolinic acid displayed increased cell germination, as shown by control studies using a microplate reader. Upon lyophilization the rapid germination chemistry failed to change growth patterns, indicating that the calcium dipicolinic acid was not solubilized under the conditions tested. Although incompatible with the portable diagnostic device, the experiments proved that the rapid germination chemistry was effective in increasing cell germination.

  19. Pyrazinamide induced thrombocytopenia

    Science.gov (United States)

    Kant, Surya; Verma, Sanjay Kumar; Gupta, Vaibhav; Anand, Sunish C.; Prasad, Rajendra

    2010-01-01

    Thrombocytopenia is an uncommon but potentially life-threatening complication of certain antitubercular drugs and is characterized by rapid destruction of platelets whenever offending drug is taken by a susceptible person. We report a case of pyrazinamide-induced thrombocytopenia in a patient receiving anti tubercular drugs. PMID:20711377

  20. A rapid mitochondrial toxicity assay utilizing rapidly changing cell energy metabolism.

    Science.gov (United States)

    Sanuki, Yosuke; Araki, Tetsuro; Nakazono, Osamu; Tsurui, Kazuyuki

    2017-01-01

    Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay. Here, we report a rapid version of this method with the same predictability as the original method. We found that replacing the glucose in the medium with galactose resulted in HepG2 cells immediately shifting their energy metabolism from glycolysis to oxidative phosphorylation due to drastic energy starvation; in addition, the intracellular concentration of ATP was reduced by mitotoxicants when glucose in the medium was replaced with galactose. Using our proposed rapid method, mitochondrial dysfunction in HepG2 cells can be evaluated by drug exposure for one hour without a pre-culture step. This rapid assay for mitochondrial toxicity may be more suitable for high-throughput screening than the original method at an early stage of drug development.

  1. Lab-on-a-chip for rapid electrochemical detection of nerve agent Sarin

    DEFF Research Database (Denmark)

    Tan, Hsih-Yin; Loke, Weng Keong; Nguyen, Nam-Trung

    2014-01-01

    This paper reports a lab-on-a-chip for the detection of Sarin nerve agent based on rapid electrochemical detection. The chemical warfare agent Sarin (C4H10FO2P, O-isopropyl methylphosphonofluoridate) is a highly toxic organophosphate that induces rapid respiratory depression, seizures and death w...

  2. Induced Abortion

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Induced Abortion Home For Patients Search FAQs Induced Abortion Page ... Induced Abortion FAQ043, May 2015 PDF Format Induced Abortion Special Procedures What is an induced abortion? What ...

  3. Rapid scenarios and observed intensities

    OpenAIRE

    Franco Pettenati; Livio Sirovich

    2012-01-01

    After a destructive earthquake, national Governments need to know the approximate amount of damage, the number of casualties, and the financial losses as soon as possible. Rapid scenarios are also used to inform the general public; see the widely used Shakemap package [Wald et al. 1999, 2006] of the US Geological Survey (USGS) and the one modified by the Istituto Nazionale di Geofisica e Vulcanologia (INGV; National Institute of Geophysics and Volcanology), which is reproduced for Figure 1. T...

  4. Rapid synthesis of beta zeolites

    Science.gov (United States)

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  5. Rapid scenarios and observed intensities

    Directory of Open Access Journals (Sweden)

    Franco Pettenati

    2012-10-01

    Full Text Available After a destructive earthquake, national Governments need to know the approximate amount of damage, the number of casualties, and the financial losses as soon as possible. Rapid scenarios are also used to inform the general public; see the widely used Shakemap package [Wald et al. 1999, 2006] of the US Geological Survey (USGS and the one modified by the Istituto Nazionale di Geofisica e Vulcanologia (INGV; National Institute of Geophysics and Volcanology, which is reproduced for Figure 1. The general matter of the use of intensities in damage scenarios was discussed in a special session at the 2008 Annual Meeting of the Seismological Society of America (http://www.seismosoc.org/meetings/2008/specialsessions.html, and was also discussed in the NIS-1 session of the European Congress in Moscow, in August 2012 (http://www.esc2012-moscow.org/esc_thematicareas.html. The purposes of the present report are to: (i compare different types of intensities; (ii check two rapid scenarios of intensity; and (iii understand whether the KF formula [Sirovich 1996, Sirovich et al. 2009] can be used as a new 'attenuation' relationship to improve rapid scenarios. […

  6. Rapid diagnosis of mycobacterial infections

    Directory of Open Access Journals (Sweden)

    Michel Drancourt

    2015-01-01

    Full Text Available While pulmonary tuberculosis (PTB remains an important public health issue worldwide, there is an emerging interest in non-tuberculous mycobacteria (NTM which is responsible for opportunistic infections of the respiratory tract as well as other anatomical sites in both developed and developing countries. In this context the one goal of the clinical mycobacteriology laboratories is to provide physicians with an accurate identification of the mycobacterium as rapidly as possible. During the last ten years, several lines of laboratory tools have been developed in order to speed the isolation and identification of mycobacteria from clinical specimens. Chiefly, the composition of culture medium was renewed along with the protocol of incubation in order to recover Mycobacterium tuberculosis (MTB micro-colonies as soon as 48 h after the inoculation of the specimen. MALDI-TOF rapid identification is clearly the tool to be implemented in the laboratory for the rapid identification of the micro-colonies. Also, molecular tools and genomics are necessary in order to depict new mycobacteria species, including those of the Mycobacterium abscessus complex and the Mycobacterium avium complex. All these tools and their connections will be presented during this conference.

  7. Abrupt tectonics and rapid slab detachment with grain damage.

    Science.gov (United States)

    Bercovici, David; Schubert, Gerald; Ricard, Yanick

    2015-02-03

    A simple model for necking and detachment of subducting slabs is developed to include the coupling between grain-sensitive rheology and grain-size evolution with damage. Necking is triggered by thickened buoyant crust entrained into a subduction zone, in which case grain damage accelerates necking and allows for relatively rapid slab detachment, i.e., within 1 My, depending on the size of the crustal plug. Thick continental crustal plugs can cause rapid necking while smaller plugs characteristic of ocean plateaux cause slower necking; oceanic lithosphere with normal or slightly thickened crust subducts without necking. The model potentially explains how large plateaux or continental crust drawn into subduction zones can cause slab loss and rapid changes in plate motion and/or induce abrupt continental rebound.

  8. Interleukin-1β Converting Enzyme–like Protease Involvement in Fas-induced and Activation-induced Peripheral Blood T Cell Apoptosis in HIV Infection. TNF-related Apoptosis-inducing Ligand Can Mediate Activation-induced T Cell Death in HIV Infection

    Science.gov (United States)

    Katsikis, Peter D.; Garcia-Ojeda, Marcos E.; Torres-Roca, Javier F.; Tijoe, Iwan M.; Smith, Craig A.; Herzenberg, Leonore A.; Herzenberg, Leonard A.

    1997-01-01

    Apoptosis of peripheral blood T cells has been suggested to play an important role in the pathogenesis of human immunodeficiency virus (HIV) infection. Spontaneous, Fas (CD95)–induced and activation-induced T cell apoptosis have all been described in peripheral blood mononuclear cell cultures of HIV-infected individuals. We have previously shown that activation-induced T cell apoptosis is Fas independent in peripheral blood T cells from HIV+ individuals. In this study, we extend and confirm these observations by using an inhibitor of interleukin-1β converting enzyme (ICE) homologues. We show that z-VAD-fmk, a tripeptide inhibitor of ICE homologues, can inhibit Fas-induced apoptosis of peripheral blood CD4+ and CD8+ T cells from asymptomatic HIV+ individuals. z-VAD-fmk also inhibited activation (anti-CD3)– induced CD4+ and CD8+ T cell apoptosis (AICD) in some but not all asymptomatic HIV+ individuals. Apoptosis was measured by multiparameter flow cytometry. The z-VAD-fmk inhibitor also enhanced survival of T cells in anti-Fas or anti-CD3 antibody-treated cultures and inhibited DNA fragmentation. AICD that could be inhibited by z-VAD-fmk was Fas independent and could be inhibited with a blocking monoclonal antibody to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), a recently described member of the TNF/nerve growth factor ligand family. The above findings show that Fas-induced T cell apoptosis is ICE dependent in HIV infection. AICD can be blocked by ICE inhibitors in some patients, and this AICD is mediated by TRAIL. These results show that TRAIL can be a mediator of AICD in T cells. These different mechanisms of peripheral blood T cell apoptosis may play different roles in the pathogenesis of HIV infection. PMID:9334376

  9. Rapidity resummation for B-meson wave functions

    Directory of Open Access Journals (Sweden)

    Shen Yue-Long

    2014-01-01

    Full Text Available Transverse-momentum dependent (TMD hadronic wave functions develop light-cone divergences under QCD corrections, which are commonly regularized by the rapidity ζ of gauge vector defining the non-light-like Wilson lines. The yielding rapidity logarithms from infrared enhancement need to be resummed for both hadronic wave functions and short-distance functions, to achieve scheme-independent calculations of physical quantities. We briefly review the recent progress on the rapidity resummation for B-meson wave functions which are the key ingredients of TMD factorization formulae for radiative-leptonic, semi-leptonic and non-leptonic B-meson decays. The crucial observation is that rapidity resummation induces a strong suppression of B-meson wave functions at small light-quark momentum, strengthening the applicability of TMD factorization in exclusive B-meson decays. The phenomenological consequence of rapidity-resummation improved B-meson wave functions is further discussed in the context of B → π transition form factors at large hadronic recoil.

  10. Rapid exocytosis and endocytosis in nerve terminals of the rat posterior pituitary.

    Science.gov (United States)

    Hsu, S F; Jackson, M B

    1996-07-15

    1. Ca(2+)-induced exocytosis and endocytosis were studied by measuring the membrane capacitance of voltage-clamped peptidergic nerve terminals in slices prepared from the rat posterior pituitary. 2. Depolarizing pulses produced rapid increases in capacitance. These increases varied in parallel with Ca2+ current as voltage was varied. Elimination of Ca2+ current blocked depolarization-induced capacitance changes. 3. Depolarization-induced capacitance changes increased with pulse duration. Capacitance changes also increased with integrated Ca2+ influx, but saturated at high levels of Ca2+ entry. This saturation allowed us to estimate a pool size of 190 vesicles, assuming each vesicle has a capacitance of 1 fF. Vesicles from this pool fused with a time constant of 0.43 s. The capacitance change increased with the first power of integrated Ca2+ influx. 4. Experiments with briefer pulses revealed a rapid component of exocytosis comprising a pool of forty vesicles that fuse with a time constant of 14 ms. This rapid process may reflect a final Ca(2+)-regulated triggering step, which is distinct from the slower kinetic step revealed by longer duration pulses. The slower step may reflect a priming of vesicles prior to exocytosis. 5. Depolarization-induced capacitance increases in most cases were followed by a rapid decay in capacitance, reflecting membrane reuptake tightly coupled to exocytosis. A variable amount of rapid endocytosis followed depolarization-induced capacitance increases. The time constant for rapid endocytosis to baseline was 0.44 s. Excess endocytosis was occasionally observed, with capacitance decaying below the pre-stimulus baseline with a time constant of 2.1 s. 6. Rapid endocytosis was slower after pulses that produced greater increases in intracellular Ca2+, consistent with the hypothesis that intracellular Ca2+ inhibits rapid endocytosis. 7. Exocytosis follows depolarization with no detectable delay, indicating that Ca2+ triggers neuropeptide

  11. Wyoming Basin Rapid Ecoregional Assessment

    Science.gov (United States)

    Carr, Natasha B.; Melcher, Cynthia P.

    2015-08-28

    The Wyoming Basin Rapid Ecoregional Assessment was conducted in partnership with the Bureau of Land Management (BLM). The overall goals of the BLM Rapid Ecoregional Assessments (REAs) are to identify important ecosystems and wildlife habitats at broad spatial scales; identify where these resources are at risk from Change Agents, including development, wildfire, invasive species, disease and climate change; quantify cumulative effects of anthropogenic stressors; and assess current levels of risk to ecological resources across a range of spatial scales and jurisdictional boundaries by assessing all lands within an ecoregion. There are several components of the REAs. Management Questions, developed by the BLM and stakeholders for the ecoregion, identify the regionally significant information needed for addressing land-management responsibilities. Conservation Elements represent regionally significant species and ecological communities that are of management concern. Change Agents that currently affect or are likely to affect the condition of species and communities in the future are identified and assessed. REAs also identify areas that have high conservation potential that are referred to as “large intact areas.” At the ecoregion level, the ecological value of large intact areas is based on the assumption that because these areas have not been greatly altered by human activities (such as development), they are more likely to contain a variety of plant and animal communities and to be resilient and resistant to changes resulting from natural disturbances such as fire, insect outbreaks, and disease.

  12. Rapid self-healing hydrogels

    Science.gov (United States)

    Phadke, Ameya; Zhang, Chao; Arman, Bedri; Hsu, Cheng-Chih; Mashelkar, Raghunath A.; Lele, Ashish K.; Tauber, Michael J.; Arya, Gaurav; Varghese, Shyni

    2012-01-01

    Synthetic materials that are capable of autonomous healing upon damage are being developed at a rapid pace because of their many potential applications. Despite these advancements, achieving self-healing in permanently cross-linked hydrogels has remained elusive because of the presence of water and irreversible cross-links. Here, we demonstrate that permanently cross-linked hydrogels can be engineered to exhibit self-healing in an aqueous environment. We achieve this feature by arming the hydrogel network with flexible-pendant side chains carrying an optimal balance of hydrophilic and hydrophobic moieties that allows the side chains to mediate hydrogen bonds across the hydrogel interfaces with minimal steric hindrance and hydrophobic collapse. The self-healing reported here is rapid, occurring within seconds of the insertion of a crack into the hydrogel or juxtaposition of two separate hydrogel pieces. The healing is reversible and can be switched on and off via changes in pH, allowing external control over the healing process. Moreover, the hydrogels can sustain multiple cycles of healing and separation without compromising their mechanical properties and healing kinetics. Beyond revealing how secondary interactions could be harnessed to introduce new functions to chemically cross-linked polymeric systems, we also demonstrate various potential applications of such easy-to-synthesize, smart, self-healing hydrogels. PMID:22392977

  13. Rapid generalization in phonotactic learning

    Directory of Open Access Journals (Sweden)

    Tal Linzen

    2017-10-01

    Full Text Available Speakers judge novel strings to be better potential words of their language if those strings consist of sound sequences that are attested in the language. These intuitions are often generalized to new sequences that share some properties with attested ones: Participants exposed to an artificial language where all words start with the voiced stops [b] and [d] will prefer words that start with other voiced stops (e.g., [g] to words that start with vowels or nasals. The current study tracks the evolution of generalization across sounds during the early stages of artificial language learning. In Experiments 1 and 2, participants received varying amounts of exposure to an artificial language. Learners rapidly generalized to new sounds: In fact, following short exposure to the language, attested patterns were not distinguished from unattested patterns that were similar in their phonological properties to the attested ones. Following additional exposure, participants showed an increasing preference for attested sounds, alongside sustained generalization to unattested ones. Finally, Experiment 3 tested whether participants can rapidly generalize to new sounds based on a single type of sound. We discuss the implications of our results for computational models of phonotactic learning.

  14. Rapid ISS Power Availability Simulator

    Science.gov (United States)

    Downing, Nicholas

    2011-01-01

    The ISS (International Space Station) Power Resource Officers (PROs) needed a tool to automate the calculation of thousands of ISS power availability simulations used to generate power constraint matrices. Each matrix contains 864 cells, and each cell represents a single power simulation that must be run. The tools available to the flight controllers were very operator intensive and not conducive to rapidly running the thousands of simulations necessary to generate the power constraint data. SOLAR is a Java-based tool that leverages commercial-off-the-shelf software (Satellite Toolkit) and an existing in-house ISS EPS model (SPEED) to rapidly perform thousands of power availability simulations. SOLAR has a very modular architecture and consists of a series of plug-ins that are loosely coupled. The modular architecture of the software allows for the easy replacement of the ISS power system model simulator, re-use of the Satellite Toolkit integration code, and separation of the user interface from the core logic. Satellite Toolkit (STK) is used to generate ISS eclipse and insulation times, solar beta angle, position of the solar arrays over time, and the amount of shadowing on the solar arrays, which is then provided to SPEED to calculate power generation forecasts. The power planning turn-around time is reduced from three months to two weeks (83-percent decrease) using SOLAR, and the amount of PRO power planning support effort is reduced by an estimated 30 percent.

  15. KEPLER RAPIDLY ROTATING GIANT STARS

    Energy Technology Data Exchange (ETDEWEB)

    Costa, A. D.; Martins, B. L. Canto; Bravo, J. P.; Paz-Chinchón, F.; Chagas, M. L. das; Leão, I. C.; Oliveira, G. Pereira de; Silva, R. Rodrigues da; Roque, S.; Oliveira, L. L. A. de; Silva, D. Freire da; De Medeiros, J. R., E-mail: renan@dfte.ufrn.br [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, Campus Universitário, Natal RN (Brazil)

    2015-07-10

    Rapidly rotating giant stars are relatively rare and may represent important stages of stellar evolution, resulting from stellar coalescence of close binary systems or accretion of substellar companions by their hosting stars. In the present Letter, we report 17 giant stars observed in the scope of the Kepler space mission exhibiting rapid rotation behavior. For the first time, the abnormal rotational behavior for this puzzling family of stars is revealed by direct measurements of rotation, namely from photometric rotation period, exhibiting a very short rotation period with values ranging from 13 to 55 days. This finding points to remarkable surface rotation rates, up to 18 times the rotation of the Sun. These giants are combined with six others recently listed in the literature for mid-infrared (IR) diagnostics based on Wide-field Infrared Survey Explorer information, from which a trend for an IR excess is revealed for at least one-half of the stars, but at a level far lower than the dust excess emission shown by planet-bearing main-sequence stars.

  16. Rapid starting methanol reactor system

    Science.gov (United States)

    Chludzinski, Paul J.; Dantowitz, Philip; McElroy, James F.

    1984-01-01

    The invention relates to a methanol-to-hydrogen cracking reactor for use with a fuel cell vehicular power plant. The system is particularly designed for rapid start-up of the catalytic methanol cracking reactor after an extended shut-down period, i.e., after the vehicular fuel cell power plant has been inoperative overnight. Rapid system start-up is accomplished by a combination of direct and indirect heating of the cracking catalyst. Initially, liquid methanol is burned with a stoichiometric or slightly lean air mixture in the combustion chamber of the reactor assembly. The hot combustion gas travels down a flue gas chamber in heat exchange relationship with the catalytic cracking chamber transferring heat across the catalyst chamber wall to heat the catalyst indirectly. The combustion gas is then diverted back through the catalyst bed to heat the catalyst pellets directly. When the cracking reactor temperature reaches operating temperature, methanol combustion is stopped and a hot gas valve is switched to route the flue gas overboard, with methanol being fed directly to the catalytic cracking reactor. Thereafter, the burner operates on excess hydrogen from the fuel cells.

  17. XIAP discriminates between type I and type II FAS-induced apoptosis.

    Science.gov (United States)

    Jost, Philipp J; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D; Nachbur, Ueli; Huang, David C S; Bouillet, Philippe; Thomas, Helen E; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2009-08-20

    FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.

  18. XIAP acts as a switch between type I and type II FAS-induced apoptosis signalling

    Science.gov (United States)

    Jost, Philipp J.; Grabow, Stephanie; Gray, Daniel; McKenzie, Mark D.; Nachbur, Ueli; Huang, David C.S.; Bouillet, Philippe; Thomas, Helen E.; Borner, Christoph; Silke, John; Strasser, Andreas; Kaufmann, Thomas

    2010-01-01

    FAS (APO-1/CD95) and its physiological ligand, FASL, regulate apoptotic death of unwanted or dangerous cells in many tissues, functioning as a guardian against autoimmunity and cancer development1-4. Distinct cell types differ in the mechanisms by which the ‘death receptor’ FAS triggers their apoptosis1-4. In type I cells, such as lymphocytes, activation of ‘effector caspases’ by FAS-induced activation of caspase-8 suffices for cell killing whereas in type II cells, including hepatocytes and pancreatic β-cells, amplification of the caspase cascade through caspase-8 mediated activation of the pro-apoptotic BCL-2 family member BID5 is essential6-8. Here we show, that loss of X-chromosome linked inhibitor of apoptosis (XIAP)9,10 function by gene-targeting or treatment with a second mitochondria-derived activator of caspases (SMAC11, also called DIABLO12: direct IAP binding protein with low pI) mimetic drug rendered hepatocytes independent of BID for FAS-induced apoptosis signalling. These results show that XIAP is the critical discriminator between type I versus type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions. PMID:19626005

  19. Rapid Adaptation in Digital Transformation

    DEFF Research Database (Denmark)

    Hansen, Anne Mette; Kræmmergaard, Pernille; Mathiassen, Lars

    2011-01-01

    the organization’s digitization approach. We demonstrate in detail how the leaders within these two organizations were engaged and offer recommendations for how other organizations can use the PPM to rapidly adapt their approaches to digital transformation through more effective IS leadership roles.......In today’s highly dynamic environments, organizational leaders need to quickly adapt existing approaches to digital transformation. However, without a shared mindset between IS and business leaders, it is difficult to adopt new approaches in response to changes in the competitive and technology...... landscape. In this article, we share insights gained from two public sector organizations in which IS and business leaders used the Participatory Process Model (PPM) designed by the authors to share their assumptions about IS leadership, challenge existing IT strategies and collaboration patterns and adapt...

  20. Moved by a Rapid Transit

    Science.gov (United States)

    Bueter, C.

    2013-04-01

    Enticing by virtue of its predictability, historical utility, and spectacle, the transit of Venus is a niche event among astronomical phenomena. Though the value of a transit for scientific purposes is now diminished, the brief appearance of Venus silhouetted against the background of the Sun in 2004 moved the artistic community to celebrate the rare alignment. Artists of all ages combined old traditions with fresh technology to create a 21st-century tapestry of music, sculpture, paintings, glasswork, quilts, sky shows, and digital imagery. A full catalog of transit-related art generated over the centuries would feature the sampling of entries presented here and at the Moved by a Rapid Transit website.

  1. [Rapid diagnostic test for malaria].

    Science.gov (United States)

    Houzé, S

    2017-02-01

    The rapid diagnostic tests (RDTs) whose main interest lies in their implementation without special equipment by unskilled personnel have grown significantly over the past fifteen years to diagnose malaria. They rely on the detection of specific Plasmodium proteins, PfHRP2, pLDH and aldolase. If the detection of PfHRP2 has very good sensitivity for the diagnosis of Plasmodium falciparum malaria, the detection of pLDH or aldolase is less efficient for other species, leaving its place to the reference microscopic diagnosis. RDT could not generally be used to monitor therapeutic efficacy because they can remain positive after clinical and parasitological cure. Furthermore, the development of the use of these tests has highlighted the need for quality assurance programs to monitor their production as their use.

  2. Rapid Solidification of Magnetic Oxides

    Science.gov (United States)

    Kalonji, G.; Deguire, M. R.

    1985-01-01

    The enhanced control over microstructural evolution inherent in rapid solidification processing techniques are exploited to create novel ceramic magnetic materials. The great sensitivity of magnetic properties to local structure provides a powerful probe both for the study of structure and of microscopic solidification mechanisms. The first system studied is the SrO-Fe2O3 binary, which contains the commercially important hard magnetic compound strontium hexaferrite. The products were analyzed by transmission electron microscopy, Mossbauer spectroscopy, magnetic measurements, and differential thermal analysis. As-quenched ribbons contain high concentrations of super-paramagnetic particles, 80 to 250 Angstroms in diameter, in a glassy matrix. This suggests the possibility of crystallizing monodomain strontium hexaferrite during subsequent heat treatment, with a resulting increase in coercivity over conventionally processed ferrite magnets. That magnetic properties can be controlled in solidification processing by varying the quench rate is demonstrated.

  3. Ceramic microfabrication by rapid prototyping process chains

    Indian Academy of Sciences (India)

    To avoid high tooling costs in product development, a rapid prototyping process chain has been established that enables rapid manufacturing of ceramic microcomponents from functional models to small lot series within a short time. This process chain combines the fast and inexpensive supply of master models by rapid ...

  4. Rapid Prototyping in Instructional Design: Creating Competencies

    Science.gov (United States)

    Fulton, Carolyn D.

    2010-01-01

    Instructional designers working in rapid prototyping environments currently do not have a list of competencies that help to identify the knowledge, skills, and attitudes (KSAs) required in these workplaces. This qualitative case study used multiple cases in an attempt to identify rapid prototyping competencies required in a rapid prototyping…

  5. Rapid Tooling via Investment Casting and Rapid Prototype Patterns

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, Michael D.

    1999-06-01

    The objective of this work to develop the materials processing and design technologies required to reduce the die development time for metal mold processes from 12 months to 3 months, using die casting of Al and Mg as the example process. Sandia demonstrated that investment casting, using rapid prototype patterns produced from Stereo lithography or Selective laser Sintering, was a viable alternative/supplement to the current technology of machining form wrought stock. A demonstration die insert (ejector halt) was investment cast and subsequently tested in the die casting environment. The stationary half of the die insert was machined from wrought material to benchmark the cast half. The two inserts were run in a die casting machine for 3,100 shots of aluminum and at the end of the run no visible difference could be detected between the cast and machined inserts. Inspection concluded that the cast insert performed identically to the machined insert. Both inserts had no indications of heat checking or degradation.

  6. Rapid local anesthesia in humans using minimally invasive microneedles.

    Science.gov (United States)

    Gupta, Jyoti; Denson, Donald D; Felner, Eric I; Prausnitz, Mark R

    2012-02-01

    This study tested the hypothesis that minimally invasive microneedles cause less pain during injection of lidocaine, but induce local anesthesia in humans with the same rapid onset and efficacy as intradermal lidocaine injection using hypodermic needles. This study was a randomized, single-blinded, within participants, controlled design. Hollow, 500-μm long microneedles were used to inject lidocaine to the forearm of 15 human participants. The associated pain was recorded using a visual analog (VAS) scale. The area and depth of numbness were determined at 0, 7.5, and 15 minutes after injection. Lidocaine was also injected to the dorsum of the hand near a vein, followed by placement of an intravenous catheter and measurement of associated pain. A 26-gauge intradermal bevel hypodermic needle similarly administered lidocaine on the opposite forearm/hand to serve as the positive control. VAS pain scores revealed that injection using microneedles was significantly less painful than hypodermic needles for both the forearm and dorsum of the hand injections. However, there was no significant difference in the area or depth of the resulting numbness between the 2 treatment methods at any time point (0, 7.5, and 15 min) indicating that microneedles had immediate onset and were as effective as hypodermic needles in inducing dermal anesthesia. Moreover, insertion of an intravenous catheter immediately after lidocaine injection on the dorsum of the hand led to comparable pain scores for the microneedle and hypodermic needle treated sites, further confirming efficacy of microneedles in inducing rapid local anesthesia. Lastly, 77% of the participants preferred microneedles and 80% indicated that they did not consider microneedles to be painful. This study demonstrates for the first time that microneedle-based lidocaine injection is as rapid and as effective as hypodermic injection in inducing local anesthesia while resulting in significantly less pain during injection.

  7. Food-induced anaphylaxis.

    Science.gov (United States)

    Cianferoni, Antonella; Muraro, Antonella

    2012-02-01

    Food-induced anaphylaxis (FIA) is a serious allergic reaction that may cause death rapidly in otherwise healthy individuals. There is no universal agreement on its definition or criteria for diagnosis. Hospital admissions for FIA have more than doubled in the last decade. Food is one of the most common causes of anaphylaxis, with most surveys indicating that food-induced reactions account for 30% to 50% of cases. The most commonly implicated foods are peanut, tree nuts, milk, eggs, sesame seeds, fish, and shellfish. The only life-saving treatment for anaphylaxis is allergen avoidance, and epinephrine injection if an anaphylactic event occurs. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Wyoming Basin Rapid Ecoregional Assessment

    Science.gov (United States)

    Carr, Natasha B.; Means, Robert E.

    2013-01-01

    The overall goal of the Wyoming Basin Rapid Ecoregional Assessment (REA) is to provide information that supports regional planning and analysis for the management of ecological resources. The REA provides an assessment of baseline ecological conditions, an evaluation of current risks from drivers of ecosystem change (including energy development, fire, and invasive species), and a predictive capacity for evaluating future risks (including climate change). Additionally, the REA may be used for identifying priority areas for conservation or restoration and for assessing cumulative effects of multiple land uses. The Wyoming Basin REA will address Management Questions developed by the Bureau of Land Management and other agency partners for 8 major biomes and 19 species or species assemblages. The maps developed for addressing Management Questions will be integrated into overall maps of landscape-level ecological values and risks. The maps can be used to address the goals of the REA at a number of levels: for individual species, species assemblages, aquatic and terrestrial systems, and for the entire ecoregion. This allows flexibility in how the products of the REA are compiled to inform planning and management actions across a broad range of spatial scales.

  9. Rapid purification of recombinant histones.

    Directory of Open Access Journals (Sweden)

    Henrike Klinker

    Full Text Available The development of methods to assemble nucleosomes from recombinant histones decades ago has transformed chromatin research. Nevertheless, nucleosome reconstitution remains time consuming to this day, not least because the four individual histones must be purified first. Here, we present a streamlined purification protocol of recombinant histones from bacteria. We termed this method "rapid histone purification" (RHP as it circumvents isolation of inclusion bodies and thereby cuts out the most time-consuming step of traditional purification protocols. Instead of inclusion body isolation, whole cell extracts are prepared under strongly denaturing conditions that directly solubilize inclusion bodies. By ion exchange chromatography, the histones are purified from the extracts. The protocol has been successfully applied to all four canonical Drosophila and human histones. RHP histones and histones that were purified from isolated inclusion bodies had similar purities. The different purification strategies also did not impact the quality of octamers reconstituted from these histones. We expect that the RHP protocol can be readily applied to the purification of canonical histones from other species as well as the numerous histone variants.

  10. Rapid typing of Coxiella burnetii.

    Directory of Open Access Journals (Sweden)

    Heidie M Hornstra

    Full Text Available Coxiella burnetii has the potential to cause serious disease and is highly prevalent in the environment. Despite this, epidemiological data are sparse and isolate collections are typically small, rare, and difficult to share among laboratories as this pathogen is governed by select agent rules and fastidious to culture. With the advent of whole genome sequencing, some of this knowledge gap has been overcome by the development of genotyping schemes, however many of these methods are cumbersome and not readily transferable between institutions. As comparisons of the few existing collections can dramatically increase our knowledge of the evolution and phylogeography of the species, we aimed to facilitate such comparisons by extracting SNP signatures from past genotyping efforts and then incorporated these signatures into assays that quickly and easily define genotypes and phylogenetic groups. We found 91 polymorphisms (SNPs and indels among multispacer sequence typing (MST loci and designed 14 SNP-based assays that could be used to type samples based on previously established phylogenetic groups. These assays are rapid, inexpensive, real-time PCR assays whose results are unambiguous. Data from these assays allowed us to assign 43 previously untyped isolates to established genotypes and genomic groups. Furthermore, genotyping results based on assays from the signatures provided here are easily transferred between institutions, readily interpreted phylogenetically and simple to adapt to new genotyping technologies.

  11. Rapid Response Flood Water Mapping

    Science.gov (United States)

    Policelli, Fritz; Brakenridge, G. R.; Coplin, A.; Bunnell, M.; Wu, L.; Habib, Shahid; Farah, H.

    2010-01-01

    Since the beginning of operation of the MODIS instrument on the NASA Terra satellite at the end of 1999, an exceptionally useful sensor and public data stream have been available for many applications including the rapid and precise characterization of terrestrial surface water changes. One practical application of such capability is the near-real time mapping of river flood inundation. We have developed a surface water mapping methodology based on using only bands 1 (620-672 nm) and 2 (841-890 nm). These are the two bands at 250 m, and the use of only these bands maximizes the resulting map detail. In this regard, most water bodies are strong absorbers of incoming solar radiation at the band 2 wavelength: it could be used alone, via a thresholding procedure, to separate water (dark, low radiance or reflectance pixels) from land (much brighter pixels) (1, 2). Some previous water mapping procedures have in fact used such single band data from this and other sensors that include similar wavelength channels. Adding the second channel of data (band 1), however, allows a band ratio approach which permits sediment-laden water, often relatively light at band 2 wavelengths, to still be discriminated, and, as well, provides some removal of error by reducing the number of cloud shadow pixels that would otherwise be misclassified as water.

  12. Asymmetric core collapse of rapidly rotating massive star

    Science.gov (United States)

    Gilkis, Avishai

    2018-02-01

    Non-axisymmetric features are found in the core collapse of a rapidly rotating massive star, which might have important implications for magnetic field amplification and production of a bipolar outflow that can explode the star, as well as for r-process nucleosynthesis and natal kicks. The collapse of an evolved rapidly rotating MZAMS = 54 M⊙ star is followed in three-dimensional hydrodynamic simulations using the FLASH code with neutrino leakage. A rotating proto-neutron star (PNS) forms with a non-zero linear velocity. This can contribute to the natal kick of the remnant compact object. The PNS is surrounded by a turbulent medium, where high shearing is likely to amplify magnetic fields, which in turn can drive a bipolar outflow. Neutron-rich material in the PNS vicinity might induce strong r-process nucleosynthesis. The rapidly rotating PNS possesses a rotational energy of E_rot ≳ 10^{52} erg. Magnetar formation proceeding in a similar fashion will be able to deposit a portion of this energy later on in the supernova ejecta through a spin-down mechanism. These processes can be important for rare supernovae generated by rapidly rotating progenitors, even though a complete explosion is not simulated in the present study.

  13. Rapidly Progressive Atrioventricular Block in a Patient with Sarcoidosis

    Directory of Open Access Journals (Sweden)

    Nagham Saeed Jafar

    2014-01-01

    Full Text Available Cardiac sarcoidosis is a major cause of death in patients with systemic sarcoidosis. Cardiac manifestations are seen in 2.3% of the patients. Atrioventricular (AV block is one of the common manifestations of cardiac sarcoidosis. Other presentations of cardiac involvement include congestive heart failure, ventricular arrhythmias, and sudden cardiac death. The presence of AV block in young patients should raise the suspicion of sarcoidosis. AV block may be the only manifestation and patients may not have clinical evidence of pulmonary involvement. Here we describe a young male presented with exercise induced AV block rapidly progressing to complete heart block with recurrent syncope needing urgent pacemaker implantation. Factors that suggested an infiltrative process included his young age, rapidly progressive conduction abnormalities in the ECG in the absence of coronary disease, and previous history of cutaneous sarcoidosis.

  14. Rapid onsite assessment of spore viability.

    Energy Technology Data Exchange (ETDEWEB)

    Branda, Steven; Lane, Todd W.; VanderNoot, Victoria A.; Gaucher, Sara P.; Jokerst, Amanda S.

    2005-12-01

    This one year LDRD addresses problems of threat assessment and restoration of facilities following a bioterror incident like the incident that closed down mail facilities in late 2001. Facilities that are contaminated with pathogenic spores such as B. anthracis spores must be shut down while they are treated with a sporicidal agent and the effectiveness of the treatment is ascertained. This process involves measuring the viability of spore test strips, laid out in a grid throughout the facility; the CDC accepted methodologies require transporting the samples to a laboratory and carrying out a 48 hr outgrowth experiment. We proposed developing a technique that will ultimately lead to a fieldable microfluidic device that can rapidly assess (ideally less than 30 min) spore viability and effectiveness of sporicidal treatment, returning facilities to use in hours not days. The proposed method will determine viability of spores by detecting early protein synthesis after chemical germination. During this year, we established the feasibility of this approach and gathered preliminary results that should fuel a future more comprehensive effort. Such a proposal is currently under review with the NIH. Proteomic signatures of Bacillus spores and vegetative cells were assessed by both slab gel electrophoresis as well as microchip based gel electrophoresis employing sensitive laser-induced fluorescence detection. The conditions for germination using a number of chemical germinants were evaluated and optimized and the time course of protein synthesis was ascertained. Microseparations were carried out using both viable spores and spores inactivated by two different methods. A select number of the early synthesis proteins were digested into peptides for analysis by mass spectrometry.

  15. Transiently increased glutamate cycling in rat PFC is associated with rapid onset of antidepressant-like effects

    OpenAIRE

    Chowdhury, Golam M.I.; Zhang, Jie; Thomas, Monique; Banasr, Mounira; Ma, Xiaoxian; Pittman, Brian; Bristow, Linda; Schaeffer, Eric; Duman, Ronald; Rothman, Douglas; Behar, Kevin; Sanacora, Gerard

    2016-01-01

    Several drugs have recently been reported to induce rapid antidepressant effects in clinical trials and rodent models. Although the cellular mechanisms involved remain unclear, reports suggest that increased glutamate transmission contributes to these effects. Here, we demonstrate that the antidepressant-like efficacy of three unique drugs, with reported rapid onset antidepressant properties, is coupled with a rapid transient rise in glutamate cycling in medial prefronal cortex (mPFC) of awak...

  16. The Application Trends of Rapid Prototyping Manufacturing

    Directory of Open Access Journals (Sweden)

    Qiu Xiao Lin

    2016-01-01

    characteristics of laser stero lithography (LSL selective laser sintering (SLS, three-dimensional printing (DP, fused deposition modeling (FDM, computer numerical control (CNC and other rapid prototyping technologies. After discussed these five rapid prototyping technology materials, we presented the hotspot and direction of rapid prototyping technology and look forward to the development of its technique, the expansion of its field and the progress of its academic ideology.

  17. Diapiric flow at subduction zones: a recipe for rapid transport.

    Science.gov (United States)

    Hall, P S; Kincaid, C

    2001-06-29

    Recent geochemical studies of uranium-thorium series disequilibrium in rocks from subduction zones require magmas to be transported through the mantle from just above the subducting slab to the surface in as little as approximately 30,000 years. We present a series of laboratory experiments that investigate the characteristic time scales and flow patterns of the diapiric upwelling model of subduction zone magmatism. Results indicate that the interaction between buoyantly upwelling diapirs and subduction-induced flow in the mantle creates a network of low-density, low-viscosity conduits through which buoyant flow is rapid, yielding transport times commensurate with those indicated by uranium-thorium studies.

  18. Rapidly fluctuating anosmia: A clinical sign for unilateral smell impairment.

    Science.gov (United States)

    Negoias, Simona; Friedrich, Hergen; Caversaccio, Marco D; Landis, Basile N

    2016-02-01

    Reports about fluctuating olfactory deficits are rare, as are reports of unilateral olfactory loss. We present a case of unilateral anosmia with contralateral normosmia, presenting as rapidly fluctuating anosmia. The olfactory fluctuation occurred in sync with the average nasal cycle duration. Examination after nasal decongestion, formal smell testing, and imaging revealed unilateral, left-sided anosmia of sinonasal cause, with right-sided normosmia. We hypothesize that the nasal cycle induced transient anosmia when blocking the normosmic side. Fluctuating olfactory deficits might hide a unilateral olfactory loss and require additional unilateral testing and thorough workup. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  19. Rapid recovery from sevoflurane and desflurane with hypercapnia and hyperventilation.

    Science.gov (United States)

    Sakata, Derek J; Gopalakrishnan, Nishant A; Orr, Joseph A; White, Julia L; Westenskow, Dwayne R

    2007-07-01

    Hypercapnia with hyperventilation shortens the time between turning off the vaporizer (1 MAC) and when patients open their eyes after isoflurane anesthesia by 62%. In the present study we tested whether a proportional shortening occurs with sevoflurane and desflurane. Consistent with a proportional shortening, we found that hypercapnia with hyperventilation decreased recovery times by 52% for sevoflurane and 64% for desflurane (when compared with normal ventilation with normocapnia). Concurrent hyperventilation to rapidly remove the anesthetic from the lungs and rebreathing to induce hypercapnia can significantly shorten recovery times and produce the same proportionate decrease for anesthetics that differ in solubility.

  20. Rapid Automated Mission Planning System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is an automated UAS mission planning system that will rapidly identify emergency (contingency) landing sites, manage contingency routing, and...

  1. WIST: toolkit for rapid, customized LIMS development

    National Research Council Canada - National Science Library

    Huang, Y Wayne; Arkin, Adam P; Chandonia, John-Marc

    2011-01-01

    Workflow Information Storage Toolkit (WIST) is a set of application programming interfaces and web applications that allow for the rapid development of customized laboratory information management systems (LIMS...

  2. JIEDDO Experience Provides Rapid Acquisition Insights

    National Research Council Canada - National Science Library

    James P Craft

    2015-01-01

    .... JIDA's rapid acquisition capabilities were preserved by transitioning the expedient organization that received supplemental funding into the Defense Department's newest combat support agency (CSA...

  3. Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

    Science.gov (United States)

    Ramsay, D A; Drachman, D B; Pestronk, A

    1988-10-11

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  4. Treatment of nephrotic syndrome associated with idiopathic rapidly progressive glomerulonephritis and cyclosporin A.

    Science.gov (United States)

    Maduell, F; Sánchez-Alcaraz, A; Sigüenza, F; Caridad, A; Sangrador, G

    1993-02-01

    Recent reports suggest that cyclosporin A is beneficial in inducing remission of idiopathic nephrotic syndrome. Nephrotic syndrome is seen in 10-30% of patients with rapidly progressive glomerulonephritis. We report a case of a 69-year-old man with nephrotic syndrome, associated with idiopathic rapidly progressive glomerulonephritis, who was treated initially with corticosteroid and cyclophosphamide. Three months later he developed thrombophlebitis and leucopenia and cyclophosphamide was suspended. Relapse of nephrotic syndrome associated with rapidly progressive glomerulonephritis developed and therapy with cyclosporin A was used with a good response.

  5. Test plan for the Rapid Geophysical Surveyor

    Energy Technology Data Exchange (ETDEWEB)

    Roybal, L.G.

    1993-06-01

    This document describes the test plant for demonstrating and testing a set of optically pumped cesium-based total field magnetometers using the Rapid Geophysical Surveyor platform. The proposed testing will be used to assess the function of these magnetometers as deployed on the Rapid Geophysical Surveyor and evaluate the practical utility of high resolution magnetic data for supporting waste retrieval efforts.

  6. Rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Schenck, C H; Montplaisir, J Y; Frauscher, B

    2013-01-01

    We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD...

  7. Rapid Prototyping of Mobile Learning Games

    Science.gov (United States)

    Federley, Maija; Sorsa, Timo; Paavilainen, Janne; Boissonnier, Kimo; Seisto, Anu

    2014-01-01

    This position paper presents the first results of an on-going project, in which we explore rapid prototyping method to efficiently produce digital learning solutions that are commercially viable. In this first phase, rapid game prototyping and an iterative approach was tested as a quick and efficient way to create learning games and to evaluate…

  8. Rapid methods for detection of bacteria

    DEFF Research Database (Denmark)

    Corfitzen, Charlotte B.; Andersen, B.Ø.; Miller, M.

    2006-01-01

    Traditional methods for detection of bacteria in drinking water e.g. Heterotrophic Plate Counts (HPC) or Most Probable Number (MNP) take 48-72 hours to give the result. New rapid methods for detection of bacteria are needed to protect the consumers against contaminations. Two rapid methods...

  9. Effect of rapid maxillary expansion on sleep characteristics in children

    Directory of Open Access Journals (Sweden)

    Navya Ashok

    2014-01-01

    Full Text Available Introduction: Rapid maxillary expansion (RME is an orthopedic treatment procedure routinely used to treat constricted maxillary arches and also a potential additional treatment in children presenting with sleep-disordered breathing (SDB. Aims and Objectives: The main objective of this study was to evaluate the effects of RME on sleep characteristics in children. Materials and Methods: Polysomnography was done on children of 8-13 years of age before expansion (T0, after expansion (T1 and after a period of 3 months after retention (T2. Bonded rapid maxillary expander was cemented in all children. Inter-molar distance was also measured at T0 and T2. Statistical Analysis: Nonparametric Friedman test was used for comparing the averages of sleep parameters at different time period (T0, T1, T2. Wilcoxon signed ranks test was used for comparing the averages of inter-molar width (T0-T2. P < 0.05 were considered as significant. Results: All children showed an improvement in sleep parameters with an increase in sleep efficiency, decreased in arousal and desaturation index after expansion. Total sleep time showed a statistically significant increase after expansion. A statistically significant increase in inter-molar distance was obtained after expansion. Conclusions: Rapid maxillary expansion is a useful treatment option for improving quality of sleep even in normal children without SDB. It also induces widening of the maxilla, corrects posterior crossbites and improves maxillary and mandibular dental arch coordination.

  10. Effect of rapid maxillary expansion on sleep characteristics in children.

    Science.gov (United States)

    Ashok, Navya; Varma, N K Sapna; Ajith, V V; Gopinath, Siby

    2014-10-01

    Rapid maxillary expansion (RME) is an orthopedic treatment procedure routinely used to treat constricted maxillary arches and also a potential additional treatment in children presenting with sleep-disordered breathing (SDB). The main objective of this study was to evaluate the effects of RME on sleep characteristics in children. Polysomnography was done on children of 8-13 years of age before expansion (T0), after expansion (T1) and after a period of 3 months after retention (T2). Bonded rapid maxillary expander was cemented in all children. Inter-molar distance was also measured at T0 and T2. Nonparametric Friedman test was used for comparing the averages of sleep parameters at different time period (T0, T1, T2). Wilcoxon signed ranks test was used for comparing the averages of inter-molar width (T0-T2). P children showed an improvement in sleep parameters with an increase in sleep efficiency, decreased in arousal and desaturation index after expansion. Total sleep time showed a statistically significant increase after expansion. A statistically significant increase in inter-molar distance was obtained after expansion. Rapid maxillary expansion is a useful treatment option for improving quality of sleep even in normal children without SDB. It also induces widening of the maxilla, corrects posterior crossbites and improves maxillary and mandibular dental arch coordination.

  11. Rapid neurogenesis through transcriptional activation in human stem cells.

    Science.gov (United States)

    Busskamp, Volker; Lewis, Nathan E; Guye, Patrick; Ng, Alex H M; Shipman, Seth L; Byrne, Susan M; Sanjana, Neville E; Murn, Jernej; Li, Yinqing; Li, Shangzhong; Stadler, Michael; Weiss, Ron; Church, George M

    2014-11-17

    Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two Neurogenin transcription factors in human-induced pluripotent stem cells and obtained neurons with bipolar morphology in 4 days, at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the rapid transition from stem cell to neuron. The resulting cells exhibited transcriptional, morphological and functional signatures of differentiated neurons, with greatest transcriptional similarity to prenatal human brain samples. Our analysis revealed a network of key transcription factors and microRNAs that promoted loss of pluripotency and rapid neurogenesis via progenitor states. Perturbations of key transcription factors affected homogeneity and phenotypic properties of the resulting neurons, suggesting that a systems-level view of the molecular biology of differentiation may guide subsequent manipulation of human stem cells to rapidly obtain diverse neuronal types. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  12. Small acid soluble proteins for rapid spore identification.

    Energy Technology Data Exchange (ETDEWEB)

    Branda, Steven S.; Lane, Todd W.; VanderNoot, Victoria A.; Jokerst, Amanda S.

    2006-12-01

    This one year LDRD addressed the problem of rapid characterization of bacterial spores such as those from the genus Bacillus, the group that contains pathogenic spores such as B. anthracis. In this effort we addressed the feasibility of using a proteomics based approach to spore characterization using a subset of conserved spore proteins known as the small acid soluble proteins or SASPs. We proposed developing techniques that built on our previous expertise in microseparations to rapidly characterize or identify spores. An alternative SASP extraction method was developed that was amenable to both the subsequent fluorescent labeling required for laser-induced fluorescence detection and the low ionic strength requirements for isoelectric focusing. For the microseparations, both capillary isoelectric focusing and chip gel electrophoresis were employed. A variety of methods were evaluated to improve the molecular weight resolution for the SASPs, which are in a molecular weight range that is not well resolved by the current methods. Isoelectric focusing was optimized and employed to resolve the SASPs using UV absorbance detection. Proteomic signatures of native wild type Bacillus spores and clones genetically engineered to produce altered SASP patterns were assessed by slab gel electrophoresis, capillary isoelectric focusing with absorbance detection as well as microchip based gel electrophoresis employing sensitive laser-induced fluorescence detection.

  13. Rapid and reversible epigenome editing by endogenous chromatin regulators.

    Science.gov (United States)

    Braun, Simon M G; Kirkland, Jacob G; Chory, Emma J; Husmann, Dylan; Calarco, Joseph P; Crabtree, Gerald R

    2017-09-15

    Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells. Furthermore, Hp1/Suv39h1 heterochromatin complex recruitment to active promoters deposits H3K9me3 domains, resulting in gene silencing that can be reversed upon washout of the chemical dimerizer. This inducible recruitment strategy provides precise kinetic information to model epigenetic memory and plasticity. It is broadly applicable to mechanistic studies of chromatin in mammalian cells and is particularly suited to the analysis of endogenous multi-subunit chromatin regulator complexes.Understanding the link between epigenetic marks and gene regulation requires the development of new tools to directly manipulate chromatin. Here the authors demonstrate a Cas9-based system to recruit chromatin remodelers to loci of interest, allowing rapid, reversible manipulation of epigenetic states.

  14. Rapid adaptation of harmful cyanobacteria to rising CO2.

    Science.gov (United States)

    Sandrini, Giovanni; Ji, Xing; Verspagen, Jolanda M H; Tann, Robert P; Slot, Pieter C; Luimstra, Veerle M; Schuurmans, J Merijn; Matthijs, Hans C P; Huisman, Jef

    2016-08-16

    Rising atmospheric CO2 concentrations are likely to affect many ecosystems worldwide. However, to what extent elevated CO2 will induce evolutionary changes in photosynthetic organisms is still a major open question. Here, we show rapid microevolutionary adaptation of a harmful cyanobacterium to changes in inorganic carbon (Ci) availability. We studied the cyanobacterium Microcystis, a notorious genus that can develop toxic cyanobacterial blooms in many eutrophic lakes and reservoirs worldwide. Microcystis displays genetic variation in the Ci uptake systems BicA and SbtA, where BicA has a low affinity for bicarbonate but high flux rate, and SbtA has a high affinity but low flux rate. Our laboratory competition experiments show that bicA + sbtA genotypes were favored by natural selection at low CO2 levels, but were partially replaced by the bicA genotype at elevated CO2 Similarly, in a eutrophic lake, bicA + sbtA strains were dominant when Ci concentrations were depleted during a dense cyanobacterial bloom, but were replaced by strains with only the high-flux bicA gene when Ci concentrations increased later in the season. Hence, our results provide both laboratory and field evidence that increasing carbon concentrations induce rapid adaptive changes in the genotype composition of harmful cyanobacterial blooms.

  15. A new method for rapid Canine retraction

    Directory of Open Access Journals (Sweden)

    "Khavari A

    2001-06-01

    Full Text Available Distraction osteogenesis method (Do in bone lengthening and rapid midpalatal expansion have shown the great ability of osteognic tissues for rapid bone formation under distraction force and special protocol with optimum rate of one millimeter per day. Periodontal membrane of teeth (PDM is the extension of periostium in the alveolar socked. Orthodontic force distracts PDM fibers in the tension side and then bone formation will begin.Objects: Rapid retraction of canine tooth into extraction space of first premolar by DO protocol in order to show the ability of the PDM in rapid bone formation. The other objective was reducing total orthodontic treatment time of extraction cases.Patients and Methods: Tweleve maxillary canines in six patients were retracted rapidly in three weeks by a custom-made tooth-born appliance. Radiographic records were taken to evaluate the effects of heavy applied force on canine and anchorage teeth.Results: Average retraction was 7.05 mm in three weeks (2.35 mm/week. Canines rotated distal- in by mean 3.5 degrees.Anchorage loss was from 0 to 0.8 mm with average of 0.3 mm.Root resorption of canines was negligible, and was not significant clinically. Periodontium was normal after rapid retraction. No hazard for pulp vitality was observed.Discussion: PDM responded well to heavy distraction force by Do protocol. Rapid canine retraction seems to be a safe method and can considerabely reduce orthodontic time.

  16. Risks and Benefits of Rapid Clozapine Titration.

    Science.gov (United States)

    Lochhead, Jeannie D; Nelson, Michele A; Schneider, Alan L

    2016-05-18

    Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS) during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

  17. Risks and benefits of rapid clozapine titration

    Directory of Open Access Journals (Sweden)

    Jeannie D. Lochhead

    2016-05-01

    Full Text Available Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

  18. Rapid stimulus-evoked astrocyte Ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo

    DEFF Research Database (Denmark)

    Lind, Barbara Lykke; Brazhe, Alexey; Jessen, Sanne Barsballe

    2013-01-01

    Increased neuron and astrocyte activity triggers increased brain blood flow, but controversy exists over whether stimulation-induced changes in astrocyte activity are rapid and widespread enough to contribute to brain blood flow control. Here, we provide evidence for stimulus-evoked Ca(2+) elevat...... brief Ca(2+) responses with a rapid onset in vivo, fast enough to initiate hemodynamic responses or influence synaptic activity.......Increased neuron and astrocyte activity triggers increased brain blood flow, but controversy exists over whether stimulation-induced changes in astrocyte activity are rapid and widespread enough to contribute to brain blood flow control. Here, we provide evidence for stimulus-evoked Ca(2......+) elevations with rapid onset and short duration in a large proportion of cortical astrocytes in the adult mouse somatosensory cortex. Our improved detection of the fast Ca(2+) signals is due to a signal-enhancing analysis of the Ca(2+) activity. The rapid stimulation-evoked Ca(2+) increases identified...

  19. Rapid response to changing environments during biological invasions: DNA methylation perspectives.

    Science.gov (United States)

    Huang, Xuena; Li, Shiguo; Ni, Ping; Gao, Yangchun; Jiang, Bei; Zhou, Zunchun; Zhan, Aibin

    2017-12-01

    Dissecting complex interactions between species and their environments has long been a research hot spot in the fields of ecology and evolutionary biology. The well-recognized Darwinian evolution has well-explained long-term adaptation scenarios; however, "rapid" processes of biological responses to environmental changes remain largely unexplored, particularly molecular mechanisms such as DNA methylation that have recently been proposed to play crucial roles in rapid environmental adaptation. Invasive species, which have capacities to successfully survive rapidly changing environments during biological invasions, provide great opportunities to study molecular mechanisms of rapid environmental adaptation. Here, we used the methylation-sensitive amplified polymorphism (MSAP) technique in an invasive model ascidian, Ciona savignyi, to investigate how species interact with rapidly changing environments at the whole-genome level. We detected quite rapid DNA methylation response: significant changes of DNA methylation frequency and epigenetic differentiation between treatment and control groups occurred only after 1 hr of high-temperature exposure or after 3 hr of low-salinity challenge. In addition, we detected time-dependent hemimethylation changes and increased intragroup epigenetic divergence induced by environmental stresses. Interestingly, we found evidence of DNA methylation resilience, as most stress-induced DNA methylation variation maintained shortly (~48 hr) and quickly returned back to the control levels. Our findings clearly showed that invasive species could rapidly respond to acute environmental changes through DNA methylation modifications, and rapid environmental changes left significant epigenetic signatures at the whole-genome level. All these results provide fundamental background to deeply investigate the contribution of DNA methylation mechanisms to rapid contemporary environmental adaptation. © 2017 John Wiley & Sons Ltd.

  20. A scoping review of rapid review methods.

    Science.gov (United States)

    Tricco, Andrea C; Antony, Jesmin; Zarin, Wasifa; Strifler, Lisa; Ghassemi, Marco; Ivory, John; Perrier, Laure; Hutton, Brian; Moher, David; Straus, Sharon E

    2015-09-16

    Rapid reviews are a form of knowledge synthesis in which components of the systematic review process are simplified or omitted to produce information in a timely manner. Although numerous centers are conducting rapid reviews internationally, few studies have examined the methodological characteristics of rapid reviews. We aimed to examine articles, books, and reports that evaluated, compared, used or described rapid reviews or methods through a scoping review. MEDLINE, EMBASE, the Cochrane Library, internet websites of rapid review producers, and reference lists were searched to identify articles for inclusion. Two reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted. We included 100 articles plus one companion report that were published between 1997 and 2013. The studies were categorized as 84 application papers, seven development papers, six impact papers, and four comparison papers (one was included in two categories). The rapid reviews were conducted between 1 and 12 months, predominantly in Europe (58 %) and North America (20 %). The included studies failed to report 6 % to 73 % of the specific systematic review steps examined. Fifty unique rapid review methods were identified; 16 methods occurred more than once. Streamlined methods that were used in the 82 rapid reviews included limiting the literature search to published literature (24 %) or one database (2 %), limiting inclusion criteria by date (68 %) or language (49 %), having one person screen and another verify or screen excluded studies (6 %), having one person abstract data and another verify (23 %), not conducting risk of bias/quality appraisal (7 %) or having only one reviewer conduct the quality appraisal (7 %), and presenting results as a narrative summary (78 %). Four case studies were identified that compared the results of rapid reviews to systematic reviews. Three studies found that the conclusions between

  1. New developments in rapidly solidified magnesium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Das, S.K. [Allied-Signal, Inc., Morristown, NJ (United States); Chang, C.F. [Allied-Signal, Inc., Morristown, NJ (United States); Raybould, D. [Allied-Signal, Inc., Morristown, NJ (United States); King, J.F. [Magnesium Elektron Ltd., Manchester (United Kingdom); Thistlethwaite, S. [Magnesium Elektron Ltd., Manchester (United Kingdom)

    1992-12-31

    In the present paper, we will examine the new developments in the rapidly solidified Mg-Al-Zn-Nd (EA55RS) alloy. We shall first briefly review the process scale-up currently employed for producing rapidly solidified magnesium alloys in large quantities, and then discuss the effect of billet size and processing parameters on the mechanical properties of various mill product forms such as extrusions and sheets. The superplastic behavior of EA55RS extrusions and rolled sheets are also discussed. Finally, some results on magnesium metal-matrix composites using rapidly solidified EA55RS matrix powders and SiC particulates are presented. (orig.)

  2. Hypothyroidism and its rapid correction alter cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Georges Hajje

    Full Text Available The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10 group and a group treated with 6-propyl-2-thiouracil (PTU (n = 20 to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL6 and pro-fibrotic transforming growth factor beta 1 (TGF-β1, were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP and cardiac troponin T (cTnT were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

  3. Hypothyroidism and its rapid correction alter cardiac remodeling.

    Science.gov (United States)

    Hajje, Georges; Saliba, Youakim; Itani, Tarek; Moubarak, Majed; Aftimos, Georges; Farès, Nassim

    2014-01-01

    The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10) group and a group treated with 6-propyl-2-thiouracil (PTU) (n = 20) to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL6) and pro-fibrotic transforming growth factor beta 1 (TGF-β1), were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

  4. HIV-Selectest enzyme immunoassay and rapid test: ability to detect seroconversion following HIV-1 infection.

    Science.gov (United States)

    Khurana, Surender; Norris, Philip J; Busch, Michael P; Haynes, Barton F; Park, Susan; Sasono, Pretty; Mlisana, Koleka; Salim, Abdool Karim; Hecht, Frederick M; Mulenga, Joseph; Chomba, Elwyn; Hunter, Eric; Allen, Susan; Nemo, George; Rodriguez-Chavez, Isaac R; Margolick, Joseph B; Golding, Hana

    2010-01-01

    HIV-Selectest is a serodiagnostic enzyme immunoassay (EIA), containing p6 and gp41 peptides, designed to differentiate between vaccine-induced antibodies and true infections. A rapid test version of the HIV-Selectest was developed. Both assays detected HIV antibodies in men and women within 2 to 4 weeks of infection, with sensitivity similar to third-generation EIAs.

  5. The rapid cold hardening response of Collembola is influenced by thermal variability of the habitat

    DEFF Research Database (Denmark)

    Bahrndorff, Simon; Loeschcke, Volker; Pertoldi, Cino

    2009-01-01

    exposure to a range of temperatures from 1 ° C to –12 ° C. Rapid cold-hardening (RCH) was induced by cooling individuals from 20 ° C to a temperature 7 ° C above the LT 50 during 80 min, followed by 1 h at the specific cold shock temperature, which was close to the LT 50 of the particular species. 5...

  6. Viral infection causes rapid sensitization to lipopolysaccharide: central role of IFN-alpha beta

    DEFF Research Database (Denmark)

    Nansen, A; Randrup Thomsen, A

    2001-01-01

    hyperproduction of TNF-alpha was completely abrogated in IFN-alphabetaR-deficient mice, indicating that the principal mechanism underlying rapid virus-induced sensitization to LPS is an IFN-alphabeta-mediated priming of mice for an augmented production of TNF-alpha in response to LPS. This conclusion was further...

  7. Implementation of rapid diagnostics with antimicrobial stewardship.

    Science.gov (United States)

    Minejima, Emi; Wong-Beringer, Annie

    2016-11-01

    Antimicrobial stewardship (ASP) is an intervention-based program to improve patient outcomes to infection while limiting spread of resistance and unintended consequences. Many rapid diagnostic tools are now FDA cleared for clinical use, with three evaluated across multiple settings: Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry, Verigene, and FilmArray. Areas covered: This review will focus on studies published that evaluated ASP intervention with rapid diagnostic implementation on outcomes of infection. A description of the key ASP personnel, rapid diagnostic notification methods, hours of notification, and scope of ASP intervention is summarized. Expert commentary: It is critical that ASPs continually re-evaluate and evolve with technological advances. Rapid diagnostic tools are powerful in their ability to identify organisms quickly. A trained clinician is needed to evaluate the results and interact with the providers to educate them on result interpretation and optimal antimicrobial selection to maximize treatment success.

  8. Rapid Update Cycle (RUC) [20 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Update Cycle (RUC) weather forecast model was developed by the National Centers for Environmental Prediction (NCEP). On May 1, 2012, the RUC was replaced...

  9. Rapid Update Cycle (RUC) [13 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Update Cycle (RUC) weather forecast model was developed by the National Centers for Environmental Prediction (NCEP). On May 1, 2012, the RUC was replaced...

  10. Rapid Chemical Exposure and Dose Research

    Science.gov (United States)

    EPA evaluates the potential risks of the manufacture and use of thousands of chemicals. To assist with this evaluation, EPA scientists developed a rapid, automated model using off the shelf technology that predicts exposures for thousands of chemicals.

  11. Innovative rapid construction/reconstruction methods.

    Science.gov (United States)

    2005-07-01

    Innovative construction and reconstruction methods provide the opportunity to significantly reduce the time of roadway projects while maintaining the necessary quality of workmanship. The need for these rapid methods stems from the increase in ...

  12. Colorado Plateau Rapid Ecoregion Assessment Data Catalog

    Data.gov (United States)

    Bureau of Land Management, Department of the Interior — Datasets used in the analysis of the Colorado Plateau (COP) Rapid Ecoregion Assessment (REA).They can be downloaded via a layer package (lpk, similar to a zip file...

  13. Development of a Rapid Thermoplastic Impregnation Device

    NARCIS (Netherlands)

    Weustink, A.P.D.

    2007-01-01

    A melt impregnation device for rapid thermoplastic impregnation of fiber bundles has been developed through modeling and experiments. The basic principles behind the thermoplastic impregnation process are investigated and the properties needed for a successful thermoplastic impregnation device are

  14. Practical implications of rapid development methodologies

    CSIR Research Space (South Africa)

    Gerber, A

    2007-11-01

    Full Text Available Rapid development methodologies are popular approaches for the development of modern software systems. The goals of these methodologies are the inclusion of the client into the analysis, design and implementation activities, as well...

  15. Rapidly curable electrically conductive clear coatings

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, Mark P.; Anderson, Lawrence G.; Post, Gordon L.

    2018-01-16

    Rapidly curable electrically conductive clear coatings are applied to substrates. The electrically conductive clear coating includes to clear layer having a resinous binder with ultrafine non-stoichiometric tungsten oxide particles dispersed therein. The clear coating may be rapidly cured by subjecting the coating to infrared radiation that heats the tungsten oxide particles and surrounding resinous binder. Localized heating increases the temperature of the coating to thereby thermally cure the coating, while avoiding unwanted heating of the underlying substrate.

  16. Rapidly separating microneedles for transdermal drug delivery.

    Science.gov (United States)

    Zhu, Dan Dan; Wang, Qi Lei; Liu, Xu Bo; Guo, Xin Dong

    2016-09-01

    The applications of polymer microneedles (MNs) into human skin emerged as an alternative of the conventional hypodermic needles. However, dissolving MNs require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin, which may lead to the low drug delivery efficiency. To address these issues, we introduce rapidly separating MNs that can rapidly deliver drugs into the skin in a minimally invasive way. For the rapidly separating MNs, drug loaded dissolving MNs are mounted on the top of solid MNs, which are made of biodegradable polylactic acid which eliminate the biohazardous waste. These MNs have sufficient mechanical strength to be inserted into the skin with the drug loaded tips fully embedded for subsequent dissolution. Compared with the traditional MNs, rapidly separating MNs achieve over 90% of drug delivery efficiency in 30s while the traditional MNs needs 2min to achieve the same efficiency. With the in vivo test in mice, the micro-holes caused by rapidly separating MNs can heal in 1h, indicating that the rapidly separating MNs are safe for future applications. These results indicate that the design of rapidly separating dissolvable MNs can offer a quick, high efficient, convenient, safe and potentially self-administered method of drug delivery. Polymer microneedles offer an attractive, painless and minimally invasive approach for transdermal drug delivery. However, dissolving microneedles require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin due to the skin deformation, which may lead to the low drug delivery efficiency. In this work we proposed rapidly separating microneedles which can deliver over 90% of drug into the skin in 30s. The in vitro and in vivo results indicate that the new design of these microneedles can offer a quick, high efficient, convenient and safe method for transdermal drug delivery. Copyright © 2016 Acta Materialia Inc

  17. Exploring data with RapidMiner

    CERN Document Server

    Chisholm, Andrew

    2013-01-01

    A step-by-step tutorial style using examples so that users of different levels will benefit from the facilities offered by RapidMiner.If you are a computer scientist or an engineer who has real data from which you want to extract value, this book is ideal for you. You will need to have at least a basic awareness of data mining techniques and some exposure to RapidMiner.

  18. [Trauma-induced coagulopathy].

    Science.gov (United States)

    Hanke, A A; Rahe-Meyer, N

    2014-02-01

    The main cause of death in the patient group less than 45 years is trauma. Beside severe traumatic brain injury, bleeding remains a leading cause of death in this group. For a causal therapy, it is necessary to understand the pathophysiology of trauma-induced coagulopathy (TIC). Beside the well-known lethal triad of trauma (hypothermia, acidosis, and coagulopathy), dilution and hypoperfusion with activation of the protein C pathway play a crucial role. TIC is a complex independent syndrome which may be present without initial hypercoagulopathy. A rapid and differentiated diagnosis and goal-directed therapy is crucial for causal therapy.

  19. Bid participates in genotoxic drug-induced apoptosis of HeLa cells and is essential for death receptor ligands' apoptotic and synergistic effects.

    Science.gov (United States)

    Köhler, Barbara; Anguissola, Sergio; Concannon, Caoimhin G; Rehm, Markus; Kögel, Donat; Prehn, Jochen H M

    2008-07-30

    The BH3-only protein Bid is an important component of death receptor-mediated caspase activation. Bid is cleaved by caspase-8 or -10 into t-Bid, which translocates to mitochondria and triggers the release of caspase-activating factors. Bid has also been reported to be cleaved by other proteases. To test the hypothesis that Bid is a central mediator of stress-induced apoptosis, we investigated the effects of a small molecule Bid inhibitor on stress-induced apoptosis, and generated HeLa cells deficient for Bid. Stable knockdown of bid lead to a pronounced resistance to Fas/CD95- and TRAIL-induced caspase activation and apoptosis, and significantly increased clonogenic survival. While Bid-deficient cells were equally sensitive to ER stress-induced apoptosis, they showed moderate, but significantly reduced levels of apoptosis, as well as increased clonogenic survival in response to the genotoxic drugs Etoposide, Oxaliplatin, and Doxorubicin. Similar effects were observed using the Bid inhibitor BI6C9. Interestingly, Bid-deficient cells were dramatically protected from apoptosis when subtoxic concentrations of ER stressors, Etoposide or Oxaliplatin were combined with subtoxic TRAIL concentrations. Our data demonstrate that Bid is central for death receptor-induced cell death and participates in anti-cancer drug-induced apoptosis in human cervical cancer HeLa cells. They also show that the synergistic effects of TRAIL in combination with either ER stressors or genotoxic anti-cancer drugs are nearly exclusively mediated via an increased activation of Bid-induced apoptosis signalling.

  20. Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights.

    Science.gov (United States)

    Heeley, Nicholas; Kirwan, Peter; Darwish, Tamana; Arnaud, Marion; Evans, Mark L; Merkle, Florian T; Reimann, Frank; Gribble, Fiona M; Blouet, Clemence

    2018-02-07

    Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration. A neurochemically diverse subset of both mouse and human hypothalamic neurons responded rapidly to l-leucine. Consistent with l-leucine's anorexigenic role, we found that 25% of mouse MBH POMC neurons were activated by l-leucine. 10% of MBH NPY neurons were inhibited by l-leucine, and leucine rapidly reduced AGRP secretion, providing a mechanism for the rapid leucine-induced inhibition of foraging behavior in rodents. Surprisingly, none of the candidate mechanisms previously implicated in hypothalamic leucine sensing (K ATP channels, mTORC1 signaling, amino-acid decarboxylation) were involved in the acute activity changes produced by l-leucine. Instead, our data indicate that leucine-induced neuronal activation involves a plasma membrane Ca 2+ channel, whereas leucine-induced neuronal inhibition is mediated by inhibition of a store-operated Ca 2+ current. A subset of neurons in the mediobasal hypothalamus rapidly respond to physiological changes in extracellular leucine concentration. Leucine can produce both increases and decreases in neuronal Ca 2+ concentrations in a neurochemically-diverse group of neurons, including some POMC and NPY/AGRP neurons. Our data reveal that leucine can signal through novel mechanisms to rapidly

  1. Rapid antimicrobial susceptibility testing with electrokinetics enhanced biosensors for diagnosis of acute bacterial infections.

    Science.gov (United States)

    Liu, Tingting; Lu, Yi; Gau, Vincent; Liao, Joseph C; Wong, Pak Kin

    2014-11-01

    Rapid pathogen detection and antimicrobial susceptibility testing (AST) are required in diagnosis of acute bacterial infections to determine the appropriate antibiotic treatment. Molecular approaches for AST are often based on the detection of known antibiotic resistance genes. Phenotypic culture analysis requires several days from sample collection to result reporting. Toward rapid diagnosis of bacterial infection in non-traditional healthcare settings, we have developed a rapid AST approach that combines phenotypic culture of bacterial pathogens in physiological samples and electrochemical sensing of bacterial 16S rRNA. The assay determines the susceptibility of pathogens by detecting bacterial growth under various antibiotic conditions. AC electrokinetic fluid motion and Joule heating induced temperature elevation are optimized to enhance the sensor signal and minimize the matrix effect, which improve the overall sensitivity of the assay. The electrokinetics enhanced biosensor directly detects the bacterial pathogens in blood culture without prior purification. Rapid determination of the antibiotic resistance profile of Escherichia coli clinical isolates is demonstrated.

  2. Hypoxia-Inducible Hydrogels

    Science.gov (United States)

    Park, Kyung Min; Gerecht, Sharon

    2014-01-01

    Oxygen is vital for the existence of all multicellular organisms, acting as a signaling molecule regulating cellular activities. Specifically, hypoxia, which occurs when the partial pressure of oxygen falls below 5%, plays a pivotal role during development, regeneration, and cancer. Here we report a novel hypoxia-inducible (HI) hydrogel composed of gelatin and ferulic acid that can form hydrogel networks via oxygen consumption in a laccase-mediated reaction. Oxygen levels and gradients within the hydrogels can be accurately controlled and precisely predicted. We demonstrate that HI hydrogels guide vascular morphogenesis in vitro via hypoxia-inducible factors activation of matrix metalloproteinases and promote rapid neovascularization from the host tissue during subcutaneous wound healing. The HI hydrogel is a new class of biomaterials that may prove useful in many applications, ranging from fundamental studies of developmental, regenerative and disease processes through the engineering of healthy and diseased tissue models towards the treatment of hypoxia-regulated disorders. PMID:24909742

  3. Induced Charge Capacitive Deionization

    CERN Document Server

    Rubin, S; Biesheuvel, P M; Bercovici, M

    2016-01-01

    We demonstrate the phenomenon of induced-charge capacitive deionization (ICCDI) that occurs around a porous and conducting particle immersed in an electrolyte, under the action of an external electrostatic field. The external electric field induces an electric dipole in the porous particle, leading to capacitive charging of its volume by both cations and anions at opposite poles. This regime is characterized both by a large RC charging time and a small electrochemical charge relaxation time, which leads to rapid and significant deionization of ionic species from a volume which is on the scale of the particle. We show by theory and experiment that the transient response around a cylindrical particle results in spatially non-uniform charging and non-steady growth of depletion regions which emerge around the particle's poles. Potentially, ICCDI can be useful in applications where fast concentration changes of ionic species are required over large volumes.

  4. Perforin-dependent apoptosis functionally compensates Fas deficiency in activation-induced cell death of human T lymphocytes.

    Science.gov (United States)

    Mateo, Véronique; Ménager, Michael; de Saint-Basile, Geneviève; Stolzenberg, Marie-Claude; Roquelaure, Bertrand; André, Nicolas; Florkin, Benoit; le Deist, Françoise; Picard, Capucine; Fischer, Alain; Rieux-Laucat, Frédéric

    2007-12-15

    Activation-induced cell death (AICD) is involved in peripheral tolerance by controlling the expansion of repeatedly stimulated T cells via an apoptotic Fas (CD95; APO-1)-dependent pathway. The TNFRSF-6 gene encoding Fas is mutated in children suffering from autoimmune lymphoproliferative syndrome (ALPS), which is characterized by lymphoproliferation and autoimmunity. We examined AICD in Fas-deficient T cells from ALPS patients. We showed that primary activated Fas-deficient T cells die by apoptosis after repeated T cell antigen receptor (TCR) stimulation despite resistance to Fas-mediated cell death. This Fas-independent AICD was found to be mediated through a cytotoxic granules-dependent pathway. Cytotoxic granules-mediated AICD was also detected in normal T lymphocytes though to a lesser extent. As expected, the cytotoxic granules-dependent AICD was abolished in T cells from Rab27a- or perforin-deficient patients who exhibited defective granules-dependent cytotoxicity. Supporting an in vivo relevance of the cytotoxic granules-dependent AICD in ALPS patients, we detected an increased number of circulating T lymphocytes expressing granzymes A and B. Altogether, these data indicated that the cytotoxic granules-dependent cell death in ALPS may compensate for Fas deficiency in T lymphocytes. Furthermore, they identified a novel AICD pathway as a unique alternative to Fas apoptosis in human peripheral T lymphocytes.

  5. Transverse vetoes with rapidity cutoff in SCET

    Science.gov (United States)

    Hornig, Andrew; Kang, Daekyoung; Makris, Yiannis; Mehen, Thomas

    2017-12-01

    We consider di-jet production in hadron collisions where a transverse veto is imposed on radiation for (pseudo-)rapidities in the central region only, where this central region is defined with rapidity cutoff. For the case where the transverse measurement (e.g., transverse energy or min p T for jet veto) is parametrically larger relative to the typical transverse momentum beyond the cutoff, the cross section is insensitive to the cutoff parameter and is factorized in terms of collinear and soft degrees of freedom. The virtuality for these degrees of freedom is set by the transverse measurement, as in typical transverse-momentum dependent observables such as Drell-Yan, Higgs production, and the event shape broadening. This paper focuses on the other region, where the typical transverse momentum below and beyond the cutoff is of similar size. In this region the rapidity cutoff further resolves soft radiation into (u)soft and soft-collinear radiation with different rapidities but identical virtuality. This gives rise to rapidity logarithms of the rapidity cutoff parameter which we resum using renormalization group methods. We factorize the cross section in this region in terms of soft and collinear functions in the framework of soft-collinear effective theory, then further refactorize the soft function as a convolution of the (u)soft and soft-collinear functions. All these functions are calculated at one-loop order. As an example, we calculate a differential cross section for a specific partonic channel, qq ' → qq ' , for the jet shape angularities and show that the refactorization allows us to resum the rapidity logarithms and significantly reduce theoretical uncertainties in the jet shape spectrum.

  6. Prostate treatments, 1MRT o RapidArc; Tratamiento de prostata, IMART o RapidArc?

    Energy Technology Data Exchange (ETDEWEB)

    Castro novais, J.; Ruiz Maqueda, S.; Pardo Perez, E.; Molina Lopez, M. Y.; Cerro Penalver, E.

    2015-07-01

    Techniques that modulate the dose (as IMRT or RapidArcTM) improve dose homogeneity within the target volume decreasing the dose in healthy organs. The aim of this work is to study the dosimetric differences in prostate radiotherapy treatments with IMRT and RapidArcTM. The results of the 109 patients studied show that plans to RapidArcTM have better coverage, compliance and dose gradient outside the target volume. (Author)

  7. An Exponential Regulator for Rapidity Divergences

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ye [Fermilab; Neill, Duff [MIT, Cambridge, CTP; Zhu, Hua Xing [MIT, Cambridge, CTP

    2016-04-01

    Finding an efficient and compelling regularization of soft and collinear degrees of freedom at the same invariant mass scale, but separated in rapidity is a persistent problem in high-energy factorization. In the course of a calculation, one encounters divergences unregulated by dimensional regularization, often called rapidity divergences. Once regulated, a general framework exists for their renormalization, the rapidity renormalization group (RRG), leading to fully resummed calculations of transverse momentum (to the jet axis) sensitive quantities. We examine how this regularization can be implemented via a multi-differential factorization of the soft-collinear phase-space, leading to an (in principle) alternative non-perturbative regularization of rapidity divergences. As an example, we examine the fully-differential factorization of a color singlet's momentum spectrum in a hadron-hadron collision at threshold. We show how this factorization acts as a mother theory to both traditional threshold and transverse momentum resummation, recovering the classical results for both resummations. Examining the refactorization of the transverse momentum beam functions in the threshold region, we show that one can directly calculate the rapidity renormalized function, while shedding light on the structure of joint resummation. Finally, we show how using modern bootstrap techniques, the transverse momentum spectrum is determined by an expansion about the threshold factorization, leading to a viable higher loop scheme for calculating the relevant anomalous dimensions for the transverse momentum spectrum.

  8. Rapid, generalized adaptation to asynchronous audiovisual speech.

    Science.gov (United States)

    Van der Burg, Erik; Goodbourn, Patrick T

    2015-04-07

    The brain is adaptive. The speed of propagation through air, and of low-level sensory processing, differs markedly between auditory and visual stimuli; yet the brain can adapt to compensate for the resulting cross-modal delays. Studies investigating temporal recalibration to audiovisual speech have used prolonged adaptation procedures, suggesting that adaptation is sluggish. Here, we show that adaptation to asynchronous audiovisual speech occurs rapidly. Participants viewed a brief clip of an actor pronouncing a single syllable. The voice was either advanced or delayed relative to the corresponding lip movements, and participants were asked to make a synchrony judgement. Although we did not use an explicit adaptation procedure, we demonstrate rapid recalibration based on a single audiovisual event. We find that the point of subjective simultaneity on each trial is highly contingent upon the modality order of the preceding trial. We find compelling evidence that rapid recalibration generalizes across different stimuli, and different actors. Finally, we demonstrate that rapid recalibration occurs even when auditory and visual events clearly belong to different actors. These results suggest that rapid temporal recalibration to audiovisual speech is primarily mediated by basic temporal factors, rather than higher-order factors such as perceived simultaneity and source identity. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  9. Geoengineering and the Risk of Rapid Climate Change

    Science.gov (United States)

    Ross, A. J.; Matthews, D.

    2008-12-01

    Many scientists have proposed that geoengineering could be used to artificially cool the planet as a means of reducing CO2-induced climate warming. However, several recent studies have shown some of the potential risks of geoengineering, including negative impacts on stratospheric ozone, the hydrologic cycle and the possibility of rapid climate change in the case of abrupt failure, or rapid decommissioning of geoengineering technology. In this study, we have emulated a geoengineering scenario in the MAGICC climate model, by counteracting the radiative forcing from greenhouse gases. We have used a hypothetical scenario of business-as-usual greenhouse gas emissions, in which geoengineering is implemented at the year 2020, and is removed abruptly after 40 years. By varying the climate sensitivity of the MAGICC model, and using previously published estimates of climate sensitivity likelihoods, we are able to derive a probabilistic prediction of the rate of temperature change following the removal of geoengineering. In a simulation without geoengineering (considering only the A1B AIM emissions scenario) the maximum annual rate of temperature change (in the highest climate sensitivity simulation) was 0.5° C per decade. In the geoengineering simulations the maximum annual rate of temperature change, occurring in the year after geoengineering was stopped, varied from 0.22° C per decade for a climate sensitivity of 0.5° C to nearly 8° C per decade for a climate sensitivity of 10° C. The most likely maximum rate of change (corresponding to a climate sensitivity of 2.5° C) was just over 5° C per decade. There is a 99.8 percent probability that the rate of temperature change following the stoppage of geoengineering in this scenario would exceed 3° C per decade. This risk of rapid climate change associated with the use of planetary-scale geoengineering is highly relevant to discussion of climate policies aimed at avoiding "dangerous anthropogenic interference" in the

  10. Rapid penetration into granular media visualizing the fundamental physics of rapid earth penetration

    CERN Document Server

    Iskander, Magued

    2015-01-01

    Rapid Penetration into Granular Media: Visualizing the Fundamental Physics of Rapid Earth Penetration introduces readers to the variety of methods and techniques used to visualize, observe, and model the rapid penetration of natural and man-made projectiles into earth materials. It provides seasoned practitioners with a standard reference that showcases the topic's most recent developments in research and application. The text compiles the findings of new research developments on the subject, outlines the fundamental physics of rapid penetration into granular media, and assembles a com

  11. Rapid spheroid clearing on a microfluidic chip.

    Science.gov (United States)

    Silva Santisteban, Tomas; Rabajania, Omid; Kalinina, Iana; Robinson, Stephen; Meier, Matthias

    2017-12-19

    Spheroids are three-dimensional (3D) cell cultures that aim to bridge the gap between the use of whole animals and cellular monolayers. Microfluidics is regarded as an enabling technology to actively control the chemical environment of 3D cell cultures. Although a wide variety of platforms have been developed to handle spheroid cultures, the development of analytical systems for spheroids remains a major challenge. In this study, we engineered a microfluidic large-scale integration (mLSI) chip platform for tissue-clearing and imaging. To enable handling and culturing of spheroids on mLSI chips, with diameters within hundreds of microns, we first developed a general rapid prototyping procedure, which allows scaling up of the size of pneumatic membrane valves (PMV). The presented prototyping method makes use of milled poly(methylmethacrylate) (PMMA) molds for obtaining semi-circular microchannels with heights up to 750 μm. Semi-circular channel profiles are required for the functioning of the commonly used PMVs in normally open configuration. Height limits to tens of microns for this channel profile on photolithographic molds have hampered the application of 3D tissue models on mLSI chips. The prototyping technique was applied to produce an mLSI chip for miniaturization, automation, and integration of the steps involved in the tissue clearing method CLARITY, including spheroid fixation, acrylamide hydrogel infiltration, temperature-initiated hydrogel polymerization, lipid extraction, and immuno-fluorescence staining of the mitochondrial protein COX-IV, and metabolic enzyme GAPDH. Precise fluidic control over the liquids in the spheroid culturing chambers allowed implementation of a local hydrogel polymerization reaction, exclusively within the spheroid tissue. Hydrogel-embedded spheroids undergo swelling and shrinkage depending on the pH of the surrounding buffer solution. A pH-jump from 8.5 to 5.5 shrinks the hydrogel-embedded spheroid volume by 108% with a rate

  12. Polyjet technology applications for rapid tooling

    Directory of Open Access Journals (Sweden)

    Udroiu Razvan

    2017-01-01

    Full Text Available Polymer Jetting (PolyJet has proved to be one of the most accurate additive manufacturing technologies, in order to manufacture rapid tools. Rapid Tooling (RT is different from conventional tooling as follow: manufacturing time is shorter, the cost is much less, but the tool life is shorter and tolerances are wider. The purpose of this paper is to make a comparative study between the soft tools (silicon moulds and hard tools (acrylic thermoplastic moulds based on the Polymer Jetting technology. Thus, two types of moulds have been made in order to manufacture a test part. Reaction injection moulding (RIM and casting techniques were used to fill these moulds with resins that simulate the plastic injection materials. Rapid tooling applications, such as indirect tooling and direct tooling, based on PolyJet technology were experimentally investigated.

  13. Rapid Hepatitis B Vaccination in Adults

    Directory of Open Access Journals (Sweden)

    Mansur Özcan

    2004-01-01

    Full Text Available Vaccination is a very important method in prevention of HBV.Especially rapid immunization takes an important place in subjects at highrisk. We have injected HBV vaccine to health workers who are attending inour hospital by rapid immunisation programme (at 0, 1 and 2 months andaimed to identify it’s efficiacy. Eighty seven subjects (69% male, 31%female were included to our study. Median age was 34 for male and 32 forwomen. We obtained 90% achievement of immunity rate after theprogramme finished. There were no significant difference between maleend female groups, and age groups. The non-responder rate was 11.6% inmale, and 7.4% in female. This rate was 6% in under 40 years old group,and 22.7% in 40 or older group. This difference was significant in twogroups statistically (p=0.02. The rapid immunization programme, weperformed has nearly the same success results as in standard programme.

  14. Rapid solidification of Nb-base alloys

    Science.gov (United States)

    Gokhale, A. B.; Javed, K. R.; Abbaschian, G. J.; Lewis, R. E.

    1988-01-01

    New Nb-base alloys are of interest for aerospace structural applications at high temperatures, viz, 800 to 1650 C. Fundamental information regarding the effects of rapid solidification in achieving greatly refined microstructures, extended solid solubility, suppression of embrittling equilibrium phases, and formation of new phases is desired in a number of Nb-X alloys. The microstructures and selected properties of Nb-Si and other Nb-base alloys are presented for materials both rapidly quenched from the equilibrium liquidus and rapidly solidified following deep supercooling. Electromagnetic levitation was used to achieve melting and supercooling in a containerless inert gas environment. A variety of solidification conditions were employed including splatting or drop casting of supercooled samples. The morphology and composition of phases formed are discussed in terms of both solidification history and bulk composition.

  15. MiR-133b targets antiapoptotic genes and enhances death receptor-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Juan P Patron

    Full Text Available Despite the importance of microRNAs (miRs for regulation of the delicate balance between cell proliferation and death, evidence for their specific involvement during death receptor (DR-mediated apoptosis is scarce. Transfection with miR-133b rendered resistant HeLa cells sensitive to tumor necrosis factor-alpha (TNFα-induced cell death. Similarly, miR-133b caused exacerbated proapoptotic responses to TNF-related apoptosis-inducing ligand (TRAIL or an activating antibody to Fas/CD95. Comprehensive analysis, encompassing global RNA or protein expression profiling performed by microarray experiments and pulsed stable isotope labeling with amino acids in cell culture (pSILAC, led to the discovery of the antiapoptotic protein Fas apoptosis inhibitory molecule (FAIM as immediate miR-133b target. Moreover, miR-133b impaired the expression of the detoxifying protein glutathione-S-transferase pi (GSTP1. Expression of miR-133b in tumor specimens of prostate cancer patients was significantly downregulated in 75% of the cases, when compared with matched healthy tissue. Furthermore, introduction of synthetic miR-133b into an ex-vivo model of prostate cancer resulted in impaired proliferation and cellular metabolic activity. PC3 cells were also sensitized to apoptotic stimuli after transfection with miR-133b similar to HeLa cells. These data reveal the ability of a single miR to influence major apoptosis pathways, suggesting an essential role for this molecule during cellular transformation, tumorigenesis and tissue homeostasis.

  16. Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis.

    LENUS (Irish Health Repository)

    O'Connell, J

    2012-02-03

    Homeostasis in the colonic epithelium is achieved by a continuous cycle of proliferation and apoptosis, in which imbalances are associated with disease. Inflammatory bowel disease (IBD) and colon cancer are associated with either excessive or insufficient apoptosis of colonic epithelial cells, respectively. By using two colonic epithelial cell lines, HT29 and SW620, we investigated how the epithelial cell\\'s sensitivity to apoptosis was regulated by the proinflammatory cytokine interferon-gamma (IFN-gamma). We found that IFN-gamma sensitized HT29 cells, and to a lesser extent SW620, to diverse inducers of apoptosis of physiologic or therapeutic relevance to the colon. These apoptosis inducers included Fas (CD95\\/APO-1) ligand (FasL), short-chain fatty acids, and chemotherapeutic drugs. The extent of IFN-gamma-mediated apoptosis sensitization in these two cell lines correlated well with the degree of IFN-gamma-mediated upregulation of the proapoptotic protease caspase-1. Although IFN-gamma alone effectively sensitized HT29 cells to apoptosis, inclusion of the protein synthesis inhibitor cyclohexamide (CHX) during apoptotic challenge was necessary for maximal sensitization of SW620. The requirement of CHX to sensitize SW620 cells to apoptosis implies a need to inhibit translation of antiapoptotic proteins absent from HT29. In particular, the antiapoptotic protein Bcl-2 was strongly expressed in SW620 cells but absent from HT29. Our results indicate that IFN-gamma increases the sensitivity of colonic epithelial cells to diverse apoptotic stimuli in concert, via upregulation of caspase-1. Our findings implicate caspase-1 and Bcl-2 as important central points of control determining the general sensitivity of colonic epithelial cells to apoptosis.

  17. Osmotic Challenge Drives Rapid and Reversible Chromatin Condensation in Chondrocytes

    Science.gov (United States)

    Irianto, Jerome; Swift, Joe; Martins, Rui P.; McPhail, Graham D.; Knight, Martin M.; Discher, Dennis E.; Lee, David A.

    2013-01-01

    Changes in extracellular osmolality have been shown to alter gene expression patterns and metabolic activity of various cell types, including chondrocytes. However, mechanisms by which physiological or pathological changes in osmolality impact chondrocyte function remain unclear. Here we use quantitative image analysis, electron microscopy, and a DNase I assay to show that hyperosmotic conditions (>400 mOsm/kg) induce chromatin condensation, while hypoosmotic conditions (100 mOsm/kg) cause decondensation. Large density changes (p condensation and decondensation during a daily loading cycle. The effect of changes in osmolality on nuclear morphology (p condensation (p condensation and osmolality was accurately modeled by a polymer gel model which, along with the rapid nature of the chromatin condensation (<20 s), reveals the basic physicochemical nature of the process. Alterations in chromatin structure are expected to influence gene expression and thereby regulate chondrocyte activity in response to osmotic changes. PMID:23442954

  18. Rapid serial visual presentation design for cognition

    CERN Document Server

    Spence, Robert

    2013-01-01

    A powerful new image presentation technique has evolved over the last twenty years, and its value demonstrated through its support of many and varied common tasks. Conceptually, Rapid Serial Visual Presentation (RSVP) is basically simple, exemplified in the physical world by the rapid riffling of the pages of a book in order to locate a known image. Advances in computation and graphics processing allow RSVP to be applied flexibly and effectively to a huge variety of common tasks such as window shopping, video fast-forward and rewind, TV channel selection and product browsing. At its heart is a

  19. Accuracy of rapid disposition by emergency clinicians.

    Science.gov (United States)

    Backay, Andrew; Bystrzycki, Adam; Smit, De Villiers; Keogh, Martin; O'Reilly, Gerard; Mitra, Biswadev

    2017-05-01

    Objectives Rapid disposition protocols are increasingly being considered for implementation in emergency departments (EDs). Among patients presenting to an adult tertiary referral hospital, this study aimed to compare prediction accuracy of a rapid disposition decision at the conclusion of history and examination, compared with disposition following standard assessment. Methods Prospective observational data were collected for 1 month between October and November 2012. Emergency clinicians (including physicians, registrars, hospital medical officers, interns and nurse practitioners) filled out a questionnaire within 5min of obtaining a history and clinical examination for eligible patients. Predicted patient disposition (representing 'rapid disposition') was compared with final disposition (determined by 'standard assessment'). Results There were 301 patient episodes included in the study. Predicted disposition was correct in 249 (82.7%, 95% confidence interval (CI) 78.0-86.8) cases. Accuracy of predicting discharge to home appeared highest among emergency physicians at 95.8% (95% CI 78.9-99.9). Overall accuracy at predicting admission was 79.7% (95% CI 67.2-89.0). The remaining 20.3% (95% CI 11.0-32.8) were not admitted following standard assessment. Conclusion Rapid disposition by ED clinicians can predict patient destination accurately but was associated with a potential increase in admission rates. Any model of care using rapid disposition decision making should involve establishment of inpatient systems for further assessment, and a culture of timely inpatient team transfer of patients to the most appropriate treating team for ongoing patient management. What is known about the topic? In response to the National Emergency Access Targets, there has been widespread adoption of rapid-disposition-themed care models across Australia. Although there is emerging data that clinicians can predict disposition accurately, this data is currently limited. What does this

  20. Rapidly destructive osteoarthritis can mimic infection

    Directory of Open Access Journals (Sweden)

    Gavin Hart, MD

    2016-03-01

    Full Text Available The intraoperative appearance of rapidly destructive osteoarthritis and septic arthritis can be similar. Three patients at our institution demonstrated preoperative or intraoperative findings potentially consistent with infection during primary total hip arthroplasty; however, none of these patients were found to have an actual infection. One of these patients underwent an unnecessary 2-stage total hip arthroplasty secondary to the intraoperative appearance of their joint fluid. We advocate performing an infection workup preoperatively when patients present with rapid degenerative changes of their hip joint to diminish the uncertainty of proceeding with arthroplasty.

  1. Drug-coated microneedles for rapid and painless local anesthesia.

    Science.gov (United States)

    Baek, Sung-Hyun; Shin, Ju-Hyung; Kim, Yeu-Chun

    2017-03-01

    This study showed that drug-coated PLLA (Poly (L-lactide)) microneedle arrays can induce rapid and painless local anesthesia. Microneedle arrays were fabricated using a micro-molding technique, and the needle tips were coated with 290.6 ± 45.9 μg of lidocaine, the most widely used local anesthetic worldwide. A dip-coating device was newly designed for the coating step using an optimized coating formulation. Lidocaine coated on the arrays was released rapidly into PBS within 2 min, and its stability in storage lasted 3 weeks at 4, 25, and 37°C. Furthermore, the microneedle arrays showed consistent in vitro skin penetration and delivered 200.8 ± 43.9, 224.2 ± 39.3, and 244.1 ± 19.6 μg of lidocaine into the skin 1, 2, and 5 min after application with a high delivery efficiency of 69, 77, and 84%. Compared to a commercially available topical anesthetic EMLA® cream, a 22.0, 13.6, and 14.0-fold higher amount of lidocaine was delivered into the skin. Note, in vitro skin permeation of Lidocaine was also notably enhanced by a 2-min-application of the lidocaine-coated microneedle arrays. Altogether, these results suggest that the biocompatible lidocaine-coated PLLA microneedle arrays could provide significantly rapid local anesthesia in a painless manner without any of the issues from topical applications or hypodermic injections of local anesthetics.

  2. Controlled cooling versus rapid freezing of teratozoospermic semen samples: Impact on sperm chromatin integrity

    Directory of Open Access Journals (Sweden)

    Shivananda N Kalludi

    2011-01-01

    Full Text Available Aim: The present study evaluates the impact of controlled slow cooling and rapid freezing techniques on the sperm chromatin integrity in teratozoospermic and normozoospermic samples. Setting: The study was done in a university infertility clinic, which is a tertiary healthcare center serving the general population. Design: It was a prospective study designed in vitro. Materials and Methods: Semen samples from normozoospermic (N=16 and teratozoospermic (N=13 infertile men were cryopreserved using controlled cooling and rapid freezing techniques. The sperm chromatin integrity was analyzed in fresh and frozen-thawed samples. Statistical Analysis Used: Data were reported as mean and standard error (mean ± SEM of mean. The difference between two techniques was determined by a paired t-test. Results: The freeze-thaw induced chromatin denaturation was significantly (P<0.01 elevated in the post-thaw samples of normozoospermic and teratozoospermic groups. Compared to rapid freezing, there was no difference in the number of red sperms (with DNA damage by the controlled slow cooling method in both normozoospermic and teratozoospermic groups. Freeze-thaw induced sperm chromatin denaturation in teratozoospermic samples did not vary between controlled slow cooling and rapid freezing techniques. Conclusions: Since the controlled slow cooling technique involves the use of expensive instrument and is a time consuming protocol, rapid freezing can be a good alternative technique for teratozoospermic and normozoospermic samples when sperm DNA damage is a concern.

  3. Rapid glutamate receptor 2 trafficking during retinal degeneration

    Directory of Open Access Journals (Sweden)

    Lin Yanhua

    2012-02-01

    Full Text Available Abstract Background Retinal degenerations, such as age-related macular degeneration (AMD and retinitis pigmentosa (RP, are characterized by photoreceptor loss and anomalous remodeling of the surviving retina that corrupts visual processing and poses a barrier to late-stage therapeutic interventions in particular. However, the molecular events associated with retinal remodeling remain largely unknown. Given our prior evidence of ionotropic glutamate receptor (iGluR reprogramming in retinal degenerations, we hypothesized that the edited glutamate receptor 2 (GluR2 subunit and its trafficking may be modulated in retinal degenerations. Results Adult albino Balb/C mice were exposed to intense light for 24 h to induce light-induced retinal degeneration (LIRD. We found that prior to the onset of photoreceptor loss, protein levels of GluR2 and related trafficking proteins, including glutamate receptor-interacting protein 1 (GRIP1 and postsynaptic density protein 95 (PSD-95, were rapidly increased. LIRD triggered neuritogenesis in photoreceptor survival regions, where GluR2 and its trafficking proteins were expressed in the anomalous dendrites. Immunoprecipitation analysis showed interaction between KIF3A and GRIP1 as well as PSD-95, suggesting that KIF3A may mediate transport of GluR2 and its trafficking proteins to the novel dendrites. However, in areas of photoreceptor loss, GluR2 along with its trafficking proteins nearly vanished in retracted retinal neurites. Conclusions All together, LIRD rapidly triggers GluR2 plasticity, which is a potential mechanism behind functionally phenotypic revisions of retinal neurons and neuritogenesis during retinal degenerations.

  4. Rapid identification of Mycobacterium species by lectin agglutination.

    Science.gov (United States)

    Athamna, Abed; Cohen, Dani; Athamna, Muhammad; Ofek, Itzhak; Stavri, Henriette

    2006-05-01

    The purpose of the present study is to explore the possibility that plant lectins can be used for the development of rapid and inexpensive technique for differentiation of mycobacterial species. The method is based on interaction between mycobacteria and lectins as visualized by agglutination in a microtiter plate. We employed 18 mycobacterium species and determined the minimal lectin concentration (MLC) of 23 different lectins. For some of the bacteria as a high as 1000 microg/ml of one or more lectins were required to induce agglutination, while for other strains as low as 1.95 microg/ml of the lectin were needed. A unique pattern of agglutination was observed for each species over a range of 62-1000 microg/ml lectin concentrations. There were little or no variations in MLC within strains (intraspecies) of each of two species tested. In contrast, there were marked interspecies variations in MLC. Analysis of the MLC showed that the highest score of interspecies differences with 23 lectins was obtained at 125 microg/ml lectin concentration. At this concentration it was found that the pattern of agglutinations with only two lectins was sufficient to differentiate mycobacterium species from each other. Because the bacteria-lectin interaction is adaptable to various methods of visualization, our findings may set the stage for developing a rapid and reliable tool to differentiate mycobacterium species.

  5. Biofilm streamers cause rapid clogging of flow systems

    Science.gov (United States)

    Shen, Yi; Drescher, Knut; Wingreen, Ned; Bassler, Bonnie; Stone, Howard

    2012-11-01

    Biofilms are antibiotic-resistant, sessile bacterial communities that are found on most surfaces on Earth. In addition to constituting the most abundant form of bacterial life, biofilms also cause chronic and medical device-associated infections. Despite their importance, basic information about how biofilms behave in common ecological environments is lacking. Here we demonstrate that flow through soil-like porous materials, industrial filters, and medical stents dramatically modifies the morphology of Pseudomonas aeruginosa biofilms to form streamers which over time bridge the space between obstacles and corners in non-uniform environments. Using a microfluidic model system we find that, contrary to the accepted paradigm, the accumulation of surface-attached bacterial biofilm has little effect on flow resistance whereas the formation of biofilm streamers causes sudden and rapid clogging. The time at which clogging happens depends on bacterial growth, while the duration of the clogging transition is driven by flow-mediated transport of bacteria to the clogging site. Flow-induced shedding of extracellular matrix from the resident biofilm generates a sieve-like network that catches bacteria flowing by, which add to the network of extracellular matrix, to cause exponentially rapid clogging. We expect these biofilm streamers to be ubiquitous in nature, and to have profound effects on flow through porous materials in environmental, industrial, and medical environments.

  6. Rapid opiate detoxication in outpatient treatment: relationship with naltrexone compliance.

    Science.gov (United States)

    Gerra, G; Zaimovic, A; Rustichelli, P; Fontanesi, B; Zambelli, U; Timpano, M; Bocchi, C; Delsignore, R

    2000-03-01

    A variety of detoxification methods have been utilized for the treatment of heroin withdrawal before individuals begin long-term opiate-free and naltrexone programs. While methadone in decreasing doses is still widely used for detoxication procedures, rapid and ultrarapid protocols including clonidine and opiate receptors antagonists have been proposed. This study compares the efficacy of different detoxification methods and investigates possible changes in naltrexone compliance. Ninety-eight heroin-addicted individuals were studied to evaluate withdrawal symptoms, craving, mood, urine toxicologic screens, and drop-out rate during therapy with: Group A: clonidine only (5 days); Group B: clonidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone (2 days); and Group C: methadone in decreasing doses (10 days). Naltrexone compliance and relapse rates were evaluated during a 6-month follow-up period. Rapid detoxification with opiate antagonists (Group B) induced slight and transient withdrawal symptoms, and resulted in a significantly lower percentage of heroin catabolites in urine controls during the detoxification procedure, lower negative and positive craving, less mood problems, and higher compliance in extended naltrexone treatment. In comparison with clonidine only (Group A) and methadone (Group C), the early use of naltrexone during detoxification in combination with benzodiazepines and clonidine facilitated extended naltrexone acceptance and improved the recovery outcome in outpatients.

  7. Continuous-Flow Detector for Rapid Pathogen Identification

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, Louise M. [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Microfluidics; Skulan, Andrew J. [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Microfluidics; Singh, Anup K. [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Microfluidics; Cummings, Eric B. [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Microfluidics; Fiechtner, Gregory J. [Sandia National Lab. (SNL-CA), Livermore, CA (United States). Microfluidics

    2006-09-01

    This report describes the continued development of a low-power, portable detector for the rapid identification of pathogens such as B. anthracis and smallpox. Based on our successful demonstration of the continuous filter/concentrator inlet, we believe strongly that the inlet section will enable differentiation between viable and non-viable populations, between types of cells, and between pathogens and background contamination. Selective, continuous focusing of particles in a microstream enables highly selective and sensitive identification using fluorescently labeled antibodies and other receptors such as peptides, aptamers, or small ligands to minimize false positives. Processes such as mixing and lysing will also benefit from the highly localized particle streams. The concentrator is based on faceted prisms to contract microfluidic flows while maintaining uniform flowfields. The resulting interfaces, capable of high throughput, serve as high-, low-, and band-pass filters to direct selected bioparticles to a rapid, affinity-based detection system. The proposed device is superior to existing array-based detectors as antibody-pathogen binding can be accomplished in seconds rather than tens of minutes or even hours. The system is being designed to interface with aerosol collectors under development by the National Laboratories or commercial systems. The focused stream is designed to be interrogated using diode lasers to differentiate pathogens by light scattering. Identification of particles is done using fluorescently labeled antibodies to tag the particles, followed by multiplexed laser-induced fluorescence (LIF) detection (achieved by labeling each antibody with a different dye).

  8. Rapidly dissolvable microneedle patches for transdermal delivery of exenatide.

    Science.gov (United States)

    Zhu, Zhuangzhi; Luo, Huafei; Lu, Wangding; Luan, Hansen; Wu, Yubo; Luo, Jing; Wang, Youjie; Pi, Jiaxin; Lim, Chee Yen; Wang, Hao

    2014-12-01

    To assess the feasibility of transdermal delivery of exenatide (EXT) using low-molecular-weight sodium hyaluronate (HA) dissolving microneedles (MNs) patches for type 2 diabetes mellitus therapy. Micromold casting method was used to fabricate EXT-loaded dissolving MNs. The characteristics of prepared MNs including mechanical strength, in vitro/in vivo insertion capacity, dissolution profile and storage stability were then investigated. Finally, the in vivo pharmacokinetics and hypoglycemic effects were compared with traditional subcutaneous (SC) injection. EXT-loaded dissolving MNs made of HA possessed sufficient mechanical strength and the strength could be weakened as the water content increases. The EXT preserved its pharmacological activity during fabrication and one-month storage. With the aid of spring-operated applicator, dissolving MNs could be readily penetrated into the skin in vitro/in vivo, and then rapidly dissolved to release encapsulated drug within 2 min. Additionally, transepidermal water loss (TEWL) determinations showed that skin's barrier properties disrupted by MNs recovered within 10-12 h. Transdermal pharmacokinetics and antidiabetic effects studies demonstrated that fabricated EXT MNs induced comparable efficacy to SC injection. Our rapidly dissolving MNs patch appears to an excellent, painless alternative to conventional SC injection of EXT, and this minimally invasive device might also be suitable for other biotherapeutics.

  9. [Responses of tomato leaf photosynthesis to rapid water stress].

    Science.gov (United States)

    Han, Guo-Jun; Chen, Nian-lai; Huang, Hai-xia; Zhang, Ping; Zhang, Kai; Guo, Yan-hong

    2013-04-01

    By using polyethylene glycol (PEG-6000) solution to regulate the water potential of tomato (Lycopersicon esculentum) rhizosphere to simulate water stress, this paper studied the dynamic changes of net photosynthetic rate, dark respiratory rate and CO2 compensatory concentration of detached tomato leaves in the process of photosynthetic induction. Under 1000 micromol m-2 s-1 of light induction, the time required to reach the maximum net photosynthetic rate of water-stressed tomato leaves was shortened by 1/3, while the stomatal conductance was increased by 1.5 times, as compared to the non-stress control. Also, the light saturation point (LSP) of water-stressed tomato leaves was lowered by 65% to 85%, and the light compensation point (LCP) was increased by 75% to 100%, suggesting that the effective range of light utilized by tomato leaves was reduced. Furthermore, water stress decreased the maximum photosynthetic capacity of tomato leaves by 40%, but increased the dark respiration rate by about 45% . It was suggested that rapid water stress made the stomata of tomato leaves quickly opened, without initial photosynthetic induction stage. In conclusion, water stress could induce the decrease of plant light-energy use efficiency and potential, being the main reason for the decrease of plant productivity, and stomatal regulation could be the main physiological mechanism of tomato plants to adapt to rapid water stress.

  10. A kinetic model of rapidly reversible nonphotochemical quenching

    Science.gov (United States)

    Zaks, Julia; Amarnath, Kapil; Kramer, David M.; Niyogi, Krishna K.; Fleming, Graham R.

    2012-01-01

    Oxygen-evolving photosynthetic organisms possess nonphotochemical quenching (NPQ) pathways that protect against photo-induced damage. The majority of NPQ in plants is regulated on a rapid timescale by changes in the pH of the thylakoid lumen. In order to quantify the rapidly reversible component of NPQ, called qE, we developed a mathematical model of pH-dependent quenching of chlorophyll excitations in Photosystem II. Our expression for qE depends on the protonation of PsbS and the deepoxidation of violaxanthin by violaxanthin deepoxidase. The model is able to simulate the kinetics of qE at low and high light intensities. The simulations suggest that the pH of the lumen, which activates qE, is not itself affected by qE. Our model provides a framework for testing hypothesized qE mechanisms and for assessing the role of qE in improving plant fitness in variable light intensity. PMID:22891305

  11. Generalization of prior information for rapid Bayesian time estimation.

    Science.gov (United States)

    Roach, Neil W; McGraw, Paul V; Whitaker, David J; Heron, James

    2017-01-10

    To enable effective interaction with the environment, the brain combines noisy sensory information with expectations based on prior experience. There is ample evidence showing that humans can learn statistical regularities in sensory input and exploit this knowledge to improve perceptual decisions and actions. However, fundamental questions remain regarding how priors are learned and how they generalize to different sensory and behavioral contexts. In principle, maintaining a large set of highly specific priors may be inefficient and restrict the speed at which expectations can be formed and updated in response to changes in the environment. However, priors formed by generalizing across varying contexts may not be accurate. Here, we exploit rapidly induced contextual biases in duration reproduction to reveal how these competing demands are resolved during the early stages of prior acquisition. We show that observers initially form a single prior by generalizing across duration distributions coupled with distinct sensory signals. In contrast, they form multiple priors if distributions are coupled with distinct motor outputs. Together, our findings suggest that rapid prior acquisition is facilitated by generalization across experiences of different sensory inputs but organized according to how that sensory information is acted on.

  12. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140.

    Science.gov (United States)

    Geng, J G; Bevilacqua, M P; Moore, K L; McIntyre, T M; Prescott, S M; Kim, J M; Bliss, G A; Zimmerman, G A; McEver, R P

    1990-02-22

    Granule membrane protein-140 (GMP-140), a membrane glycoprotein of platelet and endothelial cell secretory granules, is rapidly redistributed to the plasma membrane during cellular activation and degranulation. Also known as PADGEM protein, GMP-140 is structurally related to two molecules involved in leukocyte adhesion to vascular endothelium: ELAM-1, a cytokine-inducible endothelial cell receptor for neutrophils, and the MEL-14 lymphocyte homing receptor. These three proteins define a new gene family, termed selectins, each of which contains an N-terminal lectin domain, followed by an epidermal growth factor-like module, a variable number of repeating units related to those in complement-binding proteins, a transmembrane domain, and a short cytoplasmic tail. Here we demonstrate that GMP-140 can mediate leukocyte adhesion, thus establishing a functional similarity with the other selectins. Human neutrophils and promyelocytic HL-60 cells bind specifically to COS cells transfected with GMP-140 complementary DNA and to microtitre wells coated with purified GMP-140. Cell binding does not require active neutrophil metabolism but is dependent on extracellular Ca2+. Within minutes after stimulation with phorbol esters or histamine, human endothelial cells become adhesive for neutrophils; this interaction is inhibited by antibodies to GMP-140. Thus, GMP-140 expressed by activated endothelium might promote rapid neutrophil targeting to sites of acute inflammation.

  13. The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Barilla, Rocky; Daley, Donnele; Greco, Stephanie H; Torres-Hernandez, Alejandro; Pergamo, Matthew; Ochi, Atsuo; Zambirinis, Constantinos P; Pansari, Mridul; Rendon, Mauricio; Tippens, Daniel; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Engle, Dannielle; Miller, George

    2016-04-14

    Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells

  14. Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile : a retrospective observational study

    NARCIS (Netherlands)

    Valayannopoulos, Vassili; Baruteau, Julien; Delgado, Maria Bueno; Cano, Aline; Couce, Maria L; Del Toro, Mireia; Donati, Maria Alice; Garcia-Cazorla, Angeles; Gil-Ortega, David; Gomez-de Quero, Pedro; Guffon, Nathalie; Hofstede, Floris C; Kalkan-Ucar, Sema; Coker, Mahmut; Lama-More, Rosa; Martinez-Pardo Casanova, Mercedes; Molina, Agustin; Pichard, Samia; Papadia, Francesco; Rosello, Patricia; Plisson, Celine; Le Mouhaer, Jeannie; Chakrapani, Anupam

    2016-01-01

    BACKGROUND: Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic acid metabolism induces hyperammonaemia arising partly from secondary deficiency of N-acetylglutamate (NAG) synthase. Rapid reduction in

  15. Corrosion of metal samples rapidly measured

    Science.gov (United States)

    Maskell, C. E.

    1966-01-01

    Corrosion of a large number of metal samples that have been exposed to controlled environment is accurately and rapidly measured. Wire samples of the metal are embedded in clear plastic and sectioned for microexamination. Unexposed wire can be included in the matrix as a reference.

  16. Morphological Transition in Rapidly Expanding Magmas

    Science.gov (United States)

    Kolinski, J.; Chakraborty, P.; Gioia, G.; Kieffer, S. W.

    2008-12-01

    Many explosive eruptions are initiated by rapid decompression of bubbly magma, which behaves as an elastic material during the decompression and fragments into discrete pieces following the decompression. To emulate the rapid decompression of bubbly magma, we subject a two-dimensional foam of soap bubbles to quasi-static expansion. A recent theory predicts that where a two-dimensional foam of soap bubbles is first subjected to expansion, the foam expands homogeneously. After a critical value of expansion is attained, the foam undergoes a morphological transition and separates into a large number of small bubbles immersed in a background of a few large bubbles [Vainchtein and Aref, Physics of Fluids 13, 2001]. In our experiments we verify the phenomenon of morphological transition under area expansion. We verity the predictions of Vainchtein and Aref, compare our results with the experimental results on rapidly expanding bubble-bearing viscoelastic fluids reported by [Namiki and Manga, Earth and Planetary Science Letters 236, 2005], and discuss the implications of our results for the rapid decompression of magmas.

  17. Rapid resistome mapping using nanopore sequencing

    DEFF Research Database (Denmark)

    van der Helm, Eric; Imamovic, Lejla; Ellabaan, Mostafa M Hashim

    2017-01-01

    of bacterial infections. Yet, rapid workflows for resistome characterization are lacking. To address this challenge we developed the poreFUME workflow that deploys functional metagenomic selections and nanopore sequencing to resistome mapping. We demonstrate the approach by functionally characterizing the gut...

  18. Rapid Targeted Genomics in Critically Ill Newborns

    NARCIS (Netherlands)

    van Diemen, Cleo C; Kerstjens-Frederikse, Wilhelmina S; Bergman, Klasien A; de Koning, Tom J; Sikkema-Raddatz, Birgit; van der Velde, Joeri K; Abbott, Kristin M; Herkert, Johanna C; Löhner, Katharina; Rump, Patrick; Meems-Veldhuis, Martine T; Neerincx, Pieter B T; Jongbloed, Jan D H; van Ravenswaaij-Arts, Conny M; Swertz, Morris A; Sinke, Richard J; van Langen, Irene M; Wijmenga, Cisca

    2017-01-01

    BACKGROUND: Rapid diagnostic whole-genome sequencing has been explored in critically ill newborns, hoping to improve their clinical care and replace time-consuming and/ or invasive diagnostic testing. A previous retrospective study in a research setting showed promising results with diagnoses in

  19. Cognitive Predictors of Rapid Picture Naming

    Science.gov (United States)

    Decker, Scott L.; Roberts, Alycia M.; Englund, Julia A.

    2013-01-01

    Deficits in rapid automatized naming (RAN) have been found to be a sensitive cognitive marker for children with dyslexia. However, there is a lack of consensus regarding the construct validity and theoretical neuro-cognitive processes involved in RAN. Additionally, most studies investigating RAN include a narrow range of cognitive measures. The…

  20. Utilizing Information Technology to Facilitate Rapid Acquisition

    Science.gov (United States)

    2006-06-01

    ordering systems to facilitate streamlined commercial item acquisitions that reap the benefits of improved efficiency, reduced overall costs, and...PAGES 109 14. SUBJECT TERMS Rapid Acquisition, eCommerce , eProcurement, Information Technology, Contracting, Global Information Network...streamlined commercial item acquisitions that reap the benefits of improved efficiency, reduced overall costs, and timeliness. This thesis

  1. A rapidly enlarging cutaneous hemangioma in pregnancy

    Directory of Open Access Journals (Sweden)

    Marwan Ma’ayeh

    2014-10-01

    Full Text Available This is a case of a rapidly enlarging cutaneous pedunculated tumor on a patient’s thumb during her pregnancy. This was excised and identified as a hemangioma. A literature search identified a possible hormonal factor in causing an accelerated growth of this tumor.

  2. Preparation, Evaluation and Optimization of Rapidly Disintegrating ...

    African Journals Online (AJOL)

    The unit dose content uniformity, dissolution rate, assay values and other tablet characteristics evaluated were all within the acceptable limits. Thus, it was possible to formulate an RDT of artemether-lumefantrine FDC using CPVP as a disintegrant and camphor as a pore forming agent. Keywords: rapidly disintegrating tablet ...

  3. Ceramic microfabrication by rapid prototyping process chains

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    fast and inexpensive supply for polymer master models and a ceramic shaping method that enables the replication of the RP model into multiple ceramic materials within a short time. (Knitter et al 1999). 2. Rapid prototyping process chains. The manufacturing of ceramic microparts presented here set out with the 3D-CAD ...

  4. RESEARCH NOTE Rapid isolation and characterization of ...

    Indian Academy of Sciences (India)

    fraser c

    2017-10-25

    Oct 25, 2017 ... Rapid isolation and characterization of microsatellites in the critically endangered Mountain Bongo (Tragelaphus eurycerus isaaci). Authors: Fraser J Combe1, Evelyn Taylor-Cox1, Graeme Fox1, Tommy Sandri1,3, Nick Davis2, Martin J Jones1, Bradly Cain1, David. Mallon1, W Edwin Harris1*. 1. Division of ...

  5. A rapidly enlarging cutaneous hemangioma in pregnancy.

    LENUS (Irish Health Repository)

    Ma'ayeh, Marwan

    2014-06-18

    This is a case of a rapidly enlarging cutaneous pedunculated tumor on a patient\\'s thumb during her pregnancy. This was excised and identified as a hemangioma. A literature search identified a possible hormonal factor in causing an accelerated growth of this tumor.

  6. Short Communication: Rapid Visual Assessment of Fish ...

    African Journals Online (AJOL)

    Short Communication: Rapid Visual Assessment of Fish Communities on Selected Reefs in the Bazaruto Archipelago. ... the Bazaruto reef types to provide a basis for their sound management and conservation. Keywords: Bazaruto Archipelago, Mozambique, ichthyofauna, fish surveys, underwater visual census, coral reefs.

  7. Rapid response systems in The Netherlands

    NARCIS (Netherlands)

    Ludikhuize, Jeroen; Hamming, Annette; de Jonge, Evert; Fikkers, Bernard G.

    2011-01-01

    Sixty-three (approximately 80%) of the 81 hospitals that responded to a survey sent to all hospitals in The Netherlands with nonpediatric intensive care units had a rapid response system (RRS) in place or were in the final process of starting one. Among many other findings regarding RRS

  8. Rapid micropropagation of three elite Sugarcane (Saccharum ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-07-04

    Jul 4, 2008 ... For rapid multiplication the regenerated shoots were transferred on liquid Murashige and Skoog medium containing 2% sucrose, supplemented with. BAP in combinations with GA3. Optimum multiplication was observed at 1 mg/l BAP in combination with. 0.1 mg/l GA3 for variety HSF-240. Best response of ...

  9. Rapid micropropagation of Boesenbergia rotunda (L.) Mansf ...

    African Journals Online (AJOL)

    user

    2011-02-14

    Feb 14, 2011 ... A rapid multiplication method is required to supply sufficient disease-free plant material for large scale cultivation using in vitro propa- gation. In vitro propagation of Zingiberaceae has already been reported, for example Alpinia galanga (Inden and. Asahir, 1988) and Zingiber officinale (Hosoki and Sagawa,.

  10. The RapidEye mission design

    Science.gov (United States)

    Tyc, George; Tulip, John; Schulten, Daniel; Krischke, Manfred; Oxfort, Michael

    2005-01-01

    The RapidEye mission is a commercial remote sensing mission by the German Company RapidEye AG. The RapidEye mission will deliver information products for various customers in the agricultural insurance market, large producers, international institutions and cartography. The mission consists of a constellation of five identical small satellites and a sophisticated ground infrastructure based on proven systems. The five satellites will be placed in a single sun-synchronous orbit of approximately 620 km, with the satellites equally spaced over the orbit. The RapidEye system has the unique ability to image any area on earth once per day and can also provide large area coverage within 5 days. The satellites will each carry a 5 band multi-spectral optical imager with a ground sampling distance of 6.5 m at nadir and a swath width of 80 km. These capabilities along with the processing throughput of the ground segment allows the system to deliver the information products needed by the customers reliably and in a time frame that meets their specific needs.

  11. Integrating Rapid Prototyping into Graphic Communications

    Science.gov (United States)

    Xu, Renmei; Flowers, Jim

    2015-01-01

    Integrating different science, technology, engineering, and mathematics (STEM) areas can help students learn and leverage both the equipment and expertise at a single school. In comparing graphic communications classes with classes that involve rapid prototyping (RP) technologies like 3D printing, there are sufficient similarities between goals,…

  12. Rapid Energy Modeling Workflow Demonstration Project

    Science.gov (United States)

    2014-01-01

    BIM Building Information Model BLCC building life cycle costs BPA Building Performance Analysis CAD computer assisted...utilizes information on operations, geometry, orientation, weather, and materials, generating Three-Dimensional (3D) Building Information Models ( BIM ...executed a demonstration of Rapid Energy Modeling (REM) workflows that employed building information modeling ( BIM ) approaches and

  13. Rapid high performance liquid chromatographic determination of ...

    African Journals Online (AJOL)

    Rapid high performance liquid chromatographic determination of chlorpropamide in human plasma. MTB Odunola, IS Enemali, M Garba, OO Obodozie. Abstract. Samples were extracted with dichloromethane and the organic layer evaporated to dryness. The residue was dissolved in methanol, and 25 ìl aliquot injected ...

  14. Rapidly progressive post-transplant lymphoproliferative disease ...

    African Journals Online (AJOL)

    Sirolimus, a potent inhibitor of B- and T-cell activation, is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus ...

  15. Radiographic and computed tomographic demonstration of pseudotumor cerebri due to rapid weight gain in a child with pelvic rhabdomyosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Berdon, W.E.; Barker, D.H.; Barash, F.S.

    1982-06-01

    Rapid weight gain in a malnourished child can be associated with suture diastasis in the pattern of pseudotumor cerebri; this has been previously reported in deprivational dwarfism and cystic fibrosis. In a child with pelvic rhabdomyosarcoma, skull radiographs and cranial computed tomographic (CT) scans were available prior to a period of rapid weight gain induced by hyperalimentation. Suture diastasis developed and repeat CT scans showed this to be accompanied by smaller ventricles.

  16. Energy considerations in accelerating rapid shear granular flows

    Directory of Open Access Journals (Sweden)

    S. P. Pudasaini

    2009-05-01

    Full Text Available We present a complete expression for the total energy associated with a rapid frictional granular shear flow down an inclined surface. This expression reduces to the often used energy for a non-accelerating flow of an isotropic, ideal fluid in a horizontal channel, or to the energy for a vertically falling mass. We utilize thickness-averaged mass and momentum conservation laws written in a slope-defined coordinate system. Both the enhanced gravity and friction are taken into account in addition to the bulk motion and deformation. The total energy of the flow at a given spatial position and time is defined as the sum of four energy components: the kinetic energy, gravity, pressure and the friction energy. Total energy is conserved for stationary flow, but for non-stationary flow the non-conservative force induced by the free-surface gradient means that energy is not conserved. Simulations and experimental results are used to sketch the total energy of non-stationary flows. Comparison between the total energy and the sum of the kinetic and pressure energy shows that the contribution due to gravity acceleration and frictional resistance can be of the same order of magnitude, and that the geometric deformation plays an important role in the total energy budget of the cascading mass. Relative importance of the different constituents in the total energy expression is explored. We also introduce an extended Froude number that takes into account the apparent potential energy induced by gravity and pressure.

  17. Diffraction and rapidity gap measurements with ATLAS

    CERN Document Server

    Kus, V; The ATLAS collaboration

    2014-01-01

    Two diffraction related measurements of proton-proton collisions in the ATLAS experiment of the Large Hadron Collider at $\\surd s$ = 7 TeV centre-of-mass energy are reviewed. First of them is a fraction of diffractive contribution to the inelastic cross section. Second measurement is dedicated to the identification of Single Diffractive interactions with large pseudo-rapidity gaps using early 2010 data sample of integrated luminosity 7.1 $\\mu b^{-1}$. Differential cross sections of largest forward areas of the ATLAS detector starting at its most forward edges $\\eta = \\pm 4.9$ without any particle activity above different transverse momentum thresholds are measured. Results are compared to several distinctive Monte Carlo models resulting in constraint of Pomeron intercept value in triple Pomeron based approach. Furthermore, proton-proton interactions in small pseudo-rapidity gap region test qualitatively a description of different hadronisation models as well as statistical fluctuations during hadronisation pr...

  18. To Internationalize Rapidly from Inception: Crowdsource

    Directory of Open Access Journals (Sweden)

    Nirosh Kannangara

    2012-10-01

    Full Text Available Technology entrepreneurs continuously search for tools to accelerate the internationalization of their startups. For the purpose of internationalizing rapidly from inception, we propose that technology startups use crowdsourcing to internalize the tacit knowledge embodied in members of a crowd distributed across various geographies. For example, a technology startup can outsource to a large crowd the definition of a customer problem that occurs across various geographies, the development of the best solution to the problem, and the identification of attractive business expansion opportunities. In this article, we analyze how three small firms use crowdsourcing, discuss the benefits of crowdsourcing, and offer six recommendations to technology entrepreneurs interested in using crowdsourcing to rapidly internationalize their startups from inception.

  19. Rapid-Cycling Bubble-Chamber, details

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    Parts of the hydraulic expansion system of the Rapid-Cycling Bubble-Chamber (RCBC). RCBC was the largest of 3 rapid-cycling bubble-chambers (the others were LEBC and HOLEBC), used as target- and vertex-detectors within the European Hybrid Spectrometer (EHS) in the SPS North Area (EHN1). RCBC contained 250 l of liquid hydrogen and was located inside a 3 T superconducting magnet. It was designed for 30 expansions/s (100 times faster than BEBC), the system shown here allowed 50 expansions/s. RCBC operated from 1981 to 1983 for experiments NA21, NA22 and NA23 at a rate of 15 expansions/s, clocking up a total of over 4 million. In the rear, at left, is bearded Lucien Veillet; Augustin Didona is at the right. See also 8001009. The installation of the piston assembly in the RCBC chamber body is shown in the Annual Report 1980, p.65.

  20. Rapid quenching effects in PVC films

    Science.gov (United States)

    Lee, H. D.; Mandell, J. F.; Mcgarry, F. J.

    1981-01-01

    Using a specially constructed microbalance for hydrostatic weighing, density changes in PVC thin films (with no additives, 30-100 micrometers thick), due to rapid quenching (approximately 300 C/sec) through the glass transition temperature, have been observed. The more severe the quench, the greater is the free volume content. Isobaric volume recovery of PVC has also been studied by volume dilatometry. Both show aging of relaxing molecular rearrangements takes place as a linear function of logarithmic aging time at room temperature. Distribution of retardation times and Primak's distributed activation energy spectra have been applied to the volume recovery data. The concomitant changes in mechanical properties of PVC after quenching have been monitored by tensile creep and stress-strain to failure. All reflect the presence of excess free volume content, due to rapid quenching.

  1. Rapid parapatric speciation on holey adaptive landscapes

    CERN Document Server

    Gavrilets, S; Vose, M D; Gavrilets, Sergey; Li, Hai; Vose, Michael D.

    1998-01-01

    A classical view of speciation is that reproductive isolation arises as a by-product of genetic divergence. Here, individual-based simulations are used to evaluate whether the mechanisms implied by this view may result in rapid speciation if the only source of genetic divergence are mutation and random genetic drift. Distinctive features of the simulations are the consideration of the complete process of speciation (from initiation until completion), and of a large number of loci, which was only one order of magnitude smaller than that of bacteria. It is demonstrated that rapid speciation on the time scale of hundreds of generations is plausible without the need for extreme founder events, complete geographic isolation, the existence of distinct adaptive peaks or selection for local adaptation. The plausibility of speciation is enhanced by population subdivision. Simultaneous emergence of more than two new species from a subdivided population is highly probable. Numerical examples relevant to the theory of ce...

  2. Rapid prototyping: An innovative technique in dentistry

    Directory of Open Access Journals (Sweden)

    Shakeba Quadri

    2017-01-01

    Full Text Available Emergence of advanced digital technology has opened up new perspectives for design and production in the field of dentistry. Rapid prototyping (RP is a technique to quickly and automatically construct a three-dimensional (3D model of a part or product using 3D printers or stereolithography machines. RP has various dental applications, such as fabrication of implant surgical guides, zirconia prosthesis and molds for metal castings, maxillofacial prosthesis and frameworks for fixed and removable partial dentures, wax patterns for the dental prosthesis and complete denture. Rapid prototyping presents fascinating opportunities, but the process is difficult as it demands a high level of artistic skill, which means that the dental technicians should be able to work with the models obtained after impression to form a mirror image and achieve good esthetics. This review aims to focus on various RP methods and its application in dentistry.

  3. Rapid eye movement sleep in breath holders.

    Science.gov (United States)

    Kohyama, J; Hasegawa, T; Shimohira, M; Fukumizu, M; Iwakawa, Y

    2000-07-01

    One-night polysomnography was performed on seven subjects suffering from breath-holding spells, including one whose death was suggested to be a consequence of a breath-holding spell. The fatal case showed no rapid eye movements (REMs) during REM sleep, although he exhibited REMs during wakefulness. The average numbers of both REMs and bursts of REMs in REM sleep in the other six breath holders were significantly lower than those in age-matched controls. The breath holders showed no airway obstruction, desaturation, or sleep fragmentation. Since the rapid ocular activity in REM sleep is generated in the brain stem, we hypothesized that a functional brainstem disturbance is involved in the occurrence of breath-holding spells.

  4. Rapidly moving contact lines and damping contributions

    Science.gov (United States)

    Xia, Yi; Daniel, Susan; Steen, Paul

    2017-11-01

    Contact angle varies dynamically with contact line (CL) speed when a liquid moves across a solid support, as when a liquid spreads rapidly. For sufficiently rapid spreading, inertia competes with capillarity to influence the interface shape near the support. We use resonant-mode plane-normal support oscillations of droplets to drive lateral contact-line motion. Reynolds numbers based on CL speeds are high and capillary numbers are low. These are inertial-capillary motions. By scanning the driving frequency, we locate the frequency at peak amplification (resonance), obtain the scaled peak height (amplification factor) and a measure of band-width (damping ratio). We report how a parameter for CL mobility depends on these scanning metrics, with the goal of distinguishing contributions from the bulk- and CL-dissipation to overall damping.

  5. Inducing labor

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000625.htm Inducing labor To use the sharing features on this page, ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  6. Organizational Design for USSOCOM Rapid Acquisition

    Science.gov (United States)

    2017-03-31

    2 Ibid., 249. 25 of the programs.3 In rapid innovation , it is important for Program Executive Officers to ensure that technical...organizational learning is what the company does in order to create innovative products and survive. They note that, “interviewees emphasized the importance ...14. ABSTRACT USSOCOM Special Operations Forces (SOF) Acquisition, Technology and Logistics (AT&L) struggles to keep pace with technology innovation

  7. Rapid determination of capsaicinoids by colorimetric method

    OpenAIRE

    Ryu, Wang-Kyun; Kim, Hee-Woong; Kim, Geun-Dong; Rhee, Hae-Ik

    2016-01-01

    Capsaicinoids, the pungent component of chili peppers, are generally analyzed by precise analytical techniques, such as gas chromatography and high-performance liquid chromatography (HPLC), but these are not practical for the mass analyses of samples. To analyze mass samples rapidly, a colorimetric method was suggested. In this work, pigments and capsaicinoids were efficiently separated from chili pepper extract by sequential solid–liquid extraction and liquid–liquid extraction in test tubes ...

  8. Rapid Set Materials for Advanced Spall Repair

    Science.gov (United States)

    2010-08-01

    compressive strength, tensile strength, modulus of rupture, and the coefficient of thermal expansion. pavement , spall repair, airfield damage repair...expediency and quality. Rapid repairs extend the life of a pavement using more forgiving methods than those used in traditional repairs, but...cement-based polymer -cement mortar and concrete • Magnesium-ammonium-phosphate-cement mortar and concrete • Polymer -based mortar and concrete

  9. Rapid Hydraulic Assessment for Stream Restoration

    Science.gov (United States)

    2016-02-01

    governing equations are often used in conjunction with each other to define the flow characteristics of a given hydraulic phenomenon. The energy equation...Approved for public release; distribution is unlimited. ERDC TN-EMRRP-SR-48 February 2016 Rapid Hydraulic Assessment for Stream Restoration...account the hydraulic conditions of the stream being restored. This is true whether the project involves a few feet of bank stabilization or several

  10. Development and tendency of rapid prototyping technology

    Science.gov (United States)

    Yan, Yongnian; Hong, Guodong

    1998-08-01

    The definition of the rapid prototyping is given in this paper. Various RP processes, which build the prototypes with 2.5 or 3 dimensional layers, are introduced. The relative techniques of RP and the differences between RP technique and CNC manufacturing are analyzed. The paper discusses the RP's applied fields and methods and presents the RP development in the world. According to the idea that requirements determine the developing, the RP's tendency is discussed.

  11. Rapid and highly fieldable viral diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    McKnight, Timothy E.

    2016-12-20

    The present invention relates to a rapid, highly fieldable, nearly reagentless diagnostic to identify active RNA viral replication in a live, infected cells, and more particularly in leukocytes and tissue samples (including biopsies and nasal swabs) using an array of a plurality of vertically-aligned nanostructures that impale the cells and introduce a DNA reporter construct that is expressed and amplified in the presence of active viral replication.

  12. Removable partial dentures: use of rapid prototyping.

    Science.gov (United States)

    Lima, Julia Magalhaes Costa; Anami, Lilian Costa; Araujo, Rodrigo Maximo; Pavanelli, Carlos A

    2014-10-01

    The CAD/CAM technology associated with rapid prototyping (RP) is already widely used in the fabrication of all-ceramic fixed prostheses and in the biomedical area; however, the use of this technology for the manufacture of metal frames for removable dentures is new. This work reports the results of a literature review conducted on the use of CAD/CAM and RP in the manufacture of removable partial dentures. © 2014 by the American College of Prosthodontists.

  13. Diffraction and rapidity gap measurements in ATLAS

    CERN Document Server

    Bernat, P; The ATLAS collaboration

    2012-01-01

    The early data recorded by the ATLAS detector during 2010 presents a great opportunity to study diffraction cross section in proton-proton collision. The differential cross section of diffractive dissociation is studied as a function of the maximum rapidity gap, up to 8 in rapidity units. Data are compared to different models of diffractive dynamics in standard event generators. A rise at large rapidity gaps is interpreted with a triple pomeron based approach, using Pythia 8 prediction (with a Donnachie-Landshoff model). A pomeron intercept of 1.058 ± 0.003(stat) +0.034-0.039 (syst) is found. A measurement of the dijet production with a jet veto on additional central activity using 2010 data is also presented. The use of a veto scale at 20 GeV allows to measure the jet activity in dijet events. As the veto scale is much larger than Lambda_s different QCD phenomena can be studied. Moreover, ATLAS data explores regions of the phase space for the first time. The main observable in this analysis is the fraction ...

  14. Rapidly progressive young-onset dementia.

    Science.gov (United States)

    Kelley, Brendan J; Boeve, Bradley F; Josephs, Keith A

    2009-03-01

    To characterize a cohort of individuals who have experienced rapidly progressive dementia with onset before age 45. Very little data regarding the clinical features or clinical spectrum of rapidly progressive young-onset dementia (RP-YOD) is available, primarily consisting of case reports or small series. A search of the Mayo Clinic medical record was employed to identify patients who had onset before age 45 of rapidly progressive dementia. All available medical records, laboratory data, neuroimaging studies, and pathologic data were reviewed. Twenty-two patients met the predefined inclusion and exclusion criteria. Behavioral and affective disorders, cerebellar dysfunction, and visual and/or oculomotor dysfunction were common early clinical features within the cohort, as were clinical features often associated with Creutzfeldt-Jakob disease. Diagnostic testing identified an etiology in most patients. Presentations of RP-YOD result from a variety of etiologies and significant overlap in clinical features is observed. Clinical features often associated with Creutzfeldt-Jakob disease seem to be common within the entire cohort of RP-YOD patients. Diagnostic studies aided in establishing a diagnosis in most patients, however 5 had uncertain diagnoses despite exhaustive evaluation.

  15. Rapid Prototyping and its Application in Dentistry

    Directory of Open Access Journals (Sweden)

    V. N. V. Madhav

    2013-01-01

    Full Text Available Medical implants and biological models have three main characteristics: low volume, complex shape, and can be customized. These characteristics suit very well with Rapid Prototyping (RP and Rapid Manufacturing (RM processes. RP/RM processes are fabricated part layer- by-layer until complete shape finished from 3D model. Biocompatible materials, such as Titanium and Titanium alloy, Zirconium, Cobalt Chromium, PEEK, etc, are used for fabrication process. Reverse Engineering (RE technology greatly affects RP/RM processes. RE is used to capture or scan image of the limb, cranium, tooth, and other biological objects. Three common methods to get the image are 3D laser scanning, Computer Tomography (CT, and Magnetic Resonance Imaging (MRI. Main RP/RM techniques used in Dentistry are Stereotype Lithography Apparatus (SLA, Fused Deposition Modeling (FDM, Selective Laser Sintering (SLS, and ink jet printing. This article reviews the changing scenario of technology in dentistry with special emphasis on Rapid Prototyping and its various applications in Dentistry.

  16. The genomic landscape of rapid repeated evolutionary ...

    Science.gov (United States)

    Atlantic killifish populations have rapidly adapted to normally lethal levels of pollution in four urban estuaries. Through analysis of 384 whole killifish genome sequences and comparative transcriptomics in four pairs of sensitive and tolerant populations, we identify the aryl hydrocarbon receptor–based signaling pathway as a shared target of selection. This suggests evolutionary constraint on adaptive solutions to complex toxicant mixtures at each site. However, distinct molecular variants apparently contribute to adaptive pathway modification among tolerant populations. Selection also targets other toxicity-mediatinggenes and genes of connected signaling pathways; this indicates complex tolerance phenotypes and potentially compensatory adaptations. Molecular changes are consistent with selection on standing genetic variation. In killifish, high nucleotide diversityhas likely been a crucial substrate for selective sweeps to propel rapid adaptation. This manuscript describes genomic evaluations that contribute to our understanding of the ecological and evolutionary risks associated with chronic contaminant exposures to wildlife populations. Here, we assessed genetic patterns associated with long-term response to an important class of highly toxic environmental pollutants. Specifically, chemical-specific tolerance has rapidly and repeatedly evolved in an estuarine fish species resident to estuaries of the Atlantic U.S. coast. We used laboratory studies to ch

  17. Management of Infections with Rapidly Growing

    Directory of Open Access Journals (Sweden)

    Jong Hwan Kim

    2012-01-01

    Full Text Available Background Infection caused by rapidly growing mycobacteria (RGM is not uncommon, andthe prevalence of RGM infection has been increasing. Clinical diagnosis is difficult becausethere are no characteristic clinical features. There is also no standard antibiotic regimenfor treating RGM infection. A small series of patients with RGM infections was studied toexamine their treatments and outcomes.Methods A total of 5 patients who had developed postoperative infections from January2009 to December 2010 were retrospectively reviewed. Patients were initially screened using amycobacteria rapid screening test (polymerase chain reaction [PCR]-reverse blot hybridizationassay. To confirm mycobacterial infection, specimens were cultured for nontuberculousmycobacteria and analyzed by 16 S ribosomal RNA and rpoB gene PCR.Results The patients were treated with intravenous antibiotics during hospitalization,and oral antibiotics were administered after discharge. The mean duration of follow-upwas 9 months, and all patients were completely cured of infection with a regimen of acombination of antibiotics plus surgical treatment. Although none of the patients developedrecurrence, there were complications at the site of infection, including hypertrophic scarring,pigmentation, and disfigurement.Conclusions Combination antibiotic therapy plus drainage of surgical abscesses appeared tobe effective for the RGM infections seen in our patients. Although neither the exact dosagenor a standardized regimen has been firmly established, we propose that our treatment canprovide an option for the management of rapidly growing mycobacterial infection.

  18. Rapid Column Extraction method for SoilRapid Column Extraction method for Soil

    Energy Technology Data Exchange (ETDEWEB)

    Maxwell, Sherrod, L. III; Culligan, Brian K.

    2005-11-07

    The analysis of actinides in environmental soil and sediment samples is very important for environmental monitoring as well as for emergency preparedness. A new, rapid actinide separation method has been developed and implemented that provides total dissolution of large soil samples, high chemical recoveries and effective removal of matrix interferences. This method uses stacked TEVA Resin{reg_sign}, TRU Resin{reg_sign} and DGA-Resin{reg_sign} cartridges from Eichrom Technologies (Darien, IL, USA) that allows the rapid separation of plutonium (Pu) neptunium (Np), uranium (U), americium (Am), and curium (Cm) using a single multi-stage column combined with alpha spectrometry. The method combines a rapid fusion step for total dissolution to dissolve refractory analytes and matrix removal using cerium fluoride precipitation to remove the difficult soil matrix. By using vacuum box cartridge technology with rapid flow rates, sample preparation time is minimized.

  19. Hyperkalemia caused by rapid red cell transfusion and the potassium absorption filter

    Directory of Open Access Journals (Sweden)

    Yasuhiko Imashuku

    2017-01-01

    Full Text Available We report a case of transient hyperkalemia during hysterectomy after cesarean section, due to preoperatively undiagnosed placenta accreta that caused unforeseen massive hemorrhage and required rapid red cell transfusion. Hyperkalemia-induced by rapid red cell transfusion is a well-known severe complication of transfusion; however, in patients with sudden massive hemorrhage, rapid red cell transfusion is necessary to save their life. In such cases, it is extremely important to monitor serum potassium levels. For an emergency situation, a system should be developed to ensure sufficient preparation for immediate transfusion and laboratory tests. Furthermore, sufficient stock of preparations to treat hyperkalemia, such as calcium preparations, diuretics, glucose, and insulin is required. Moreover, a transfusion filter that absorbs potassium has been developed and is now available for clinical use in Japan. The filter is easy to use and beneficial, and should be prepared when it is available.

  20. Elastic uplift in southeast Greenland due to rapid ice mass loss

    DEFF Research Database (Denmark)

    Khan, Shfaqat Abbas; Van dam, Tonie; Hamilton, Gordon S.

    2007-01-01

    , calculated from sequential digital elevation models, contributes about 16 mm of the observed uplift, with an additional 5 mm from volume loss of Kangerdlugssuaq Glacier. The remaining uplift signal is attributed to significant melt-induced ice volume loss from the ice sheet margin along the southeast coast......The rapid unloading of ice from the southeastern sector of the Greenland ice sheet between 2001 and 2006 caused an elastic uplift of 35 mm at a GPS site in Kulusuk. Most of the uplift results from ice dynamic-induced volume losses on two nearby outlet glaciers. Volume loss from Helheim Glacier...... between 62N and 66N. Citation: Khan, S. A., J. Wahr, L. A. Stearns, G. S. Hamilton, T. van Dam, K. M. Larson, and O. Francis (2007), Elastic uplift in southeast Greenland due to rapid ice mass loss....