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  1. Physalis peruviana extract induces apoptosis in human Hep G2 cells through CD95/CD95L system and the mitochondrial signaling transduction pathway.

    Science.gov (United States)

    Wu, Shu-Jing; Ng, Lean-Teik; Lin, Doung-Liang; Huang, Shan-Ney; Wang, Shyh-Shyan; Lin, Chun-Ching

    2004-11-25

    Physalis species is a popular folk medicine used for treating cancer, leukemia, hepatitis and other diseases. Studies have shown that the ethanol extract of Physalis peruviana (EEPP) inhibits growth and induces apoptotic death of human Hep G2 cells in culture, whereas proliferation of the mouse BALB/C normal liver cells was not affected. In this study, we performed detailed studies to define the molecular mechanism of EEPP-induced apoptosis in Hep G2 cells. The results further confirmed that EEPP inhibited cell proliferation in a dose- and time-dependent manner. At 50 microg/ml, EEPP significantly increased the accumulation of the sub-G1 peak (hypoploid) and the portion of apoptotic annexin V positive cells. EEPP was found to trigger apoptosis through the release of cytochrome c, Smac/DIABLO and Omi/HtrA2 from mitochondria to cytosol and consequently resulted in caspase-3 activation. Pre-treatment with a general caspase inhibitor (z-VAD-fmk) prevented cytochrome c release. After 48 h of EEPP treatment, the apoptosis of Hep G2 cells was found to associate with an elevated p53, and CD95 and CD95L proteins expression. Furthermore, a marked down-regulation of the expression of the Bcl-2, Bcl-XL and XIAP, and up-regulation of the Bax and Bad proteins were noted. Taken together, the present results suggest that EEPP-induced Hep G2 cell apoptosis was possibly mediated through the CD95/CD95L system and the mitochondrial signaling transduction pathway.

  2. Bcl-xL acts downstream of caspase-8 activation by the CD95 death-inducing signaling complex

    NARCIS (Netherlands)

    Medema, J. P.; Scaffidi, C.; Krammer, P. H.; Peter, M. E.

    1998-01-01

    The Bcl-2 family member Bcl-xL has often been correlated with apoptosis resistance. We have shown recently that in peripheral human T cells resistance to CD95-mediated apoptosis is characterized by a lack of caspase-8 recruitment to the CD95 death-inducing signaling complex (DISC) and by increased

  3. GSK-3β inhibition by lithium confers resistance to chemotherapy-induced apoptosis through the repression of CD95 (Fas/APO-1) expression

    International Nuclear Information System (INIS)

    Beurel, Eleonore; Kornprobst, Michel; Blivet-Van Eggelpoel, Marie-Jose; Ruiz-Ruiz, Carmen; Cadoret, Axelle; Capeau, Jacqueline; Desbois-Mouthon, Christele

    2004-01-01

    Lithium exerts neuroprotective actions that involve the inhibition of glycogen synthase kinase-3β (GSK-3β). Otherwise, recent studies suggest that sustained GSK-3β inhibition is a hallmark of tumorigenesis. In this context, the present study was undertaken to examine whether lithium modulated cancer cell sensitivity to apoptosis induced by chemotherapy agents. We observed that, in different human cancer cell lines, lithium significantly reduced etoposide- and camptothecin-induced apoptosis. In HepG2 cells, lithium repressed drug induction of CD95 expression and clustering at the cell surface as well as caspase-8 activation. Lithium acted through deregulation of GSK-3β signaling since (1) it provoked a rapid and sustained phosphorylation of GSK-3β on the inhibitory serine 9 residue; (2) the GSK-3β inhibitor SB-415286 mimicked lithium effects by repressing drug-induced apoptosis and CD95 membrane expression; and (3) lithium promoted the disruption of nuclear GSK-3β/p53 complexes. Moreover, the overexpression of an inactivated GSK-3β mutant counteracted the stimulatory effects of etoposide and camptothecin on a luciferase reporter plasmid driven by a p53-responsive sequence from the CD95 gene. In conclusion, we provide the first evidence that lithium confers resistance to apoptosis in cancer cells through GSK-3β inhibition and subsequent repression of CD95 gene expression. Our study also highlights the concerted action of GSK-3β and p53 on CD95 gene expression

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

    International Nuclear Information System (INIS)

    Gill, Randall; Lanni, Lydia; Jen, K.-L. Catherine; McCabe, Michael J.; Rosenspire, Allen

    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 2+ ) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg 2+ intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. 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...... a single dose of UVB irradiation. Normal healthy individuals were irradiated with three minimal erythema doses (MED) of UVB on forearm or buttock skin. Suction blisters from unirradiated and irradiated skin were raised, and Fas, FasL, and apoptosis of epidermal cells quantified by flow cytometry....... Clustering of Fas was from skin biopsied. Soluble FasL in suction blister fluid was quantified by ELISA. Flow cytometric analysis demonstrated increased expression intensity of Fas after irradiation, with 1.6-,2.2- and 2.7-fold increased median expression at 24, 48 and 72 h after irradiation, respectively (n...

  7. Interferon-β-induced activation of c-Jun NH2-terminal kinase mediates apoptosis through up-regulation of CD95 in CH31 B lymphoma cells

    International Nuclear Information System (INIS)

    Takada, Eiko; Shimo, Kuniaki; Hata, Kikumi; Abiake, Maira; Mukai, Yasuo; Moriyama, Masami; Heasley, Lynn; Mizuguchi, Junichiro

    2005-01-01

    Type I interferon (IFN)-induced antitumor action is due in part to apoptosis, but the molecular mechanisms underlying IFN-induced apoptosis remain largely unresolved. In the present study, we demonstrate that IFN-β induced apoptosis and the loss of mitochondrial membrane potential (ΔΨm) in the murine CH31 B lymphoma cell line, and this was accompanied by the up-regulation of CD95, but not CD95-ligand (CD95-L), tumor necrosis factor (TNF), or TNF-related apoptosis-inducing ligand (TRAIL). Pretreatment with anti-CD95-L mAb partially prevented the IFN-β-induced loss of ΔΨm, suggesting that the interaction of IFN-β-up-regulated CD95 with CD95-L plays a crucial role in the induction of fratricide. IFN-β induced a sustained activation of c-Jun NH 2 -terminal kinase 1 (JNK1), but not extracellular signal-regulated kinases (ERKs). The IFN-β-induced apoptosis and loss of ΔΨm were substantially compromised in cells overexpressing a dominant-negative form of JNK1 (dnJNK1), and it was slightly enhanced in cells carrying a constitutively active JNK construct, MKK7-JNK1 fusion protein. The IFN-β-induced up-regulation of CD95 together with caspase-8 activation was also abrogated in the dnJNK1 cells while it was further enhanced in the MKK7-JNK1 cells. The levels of cellular FLIP (c-FLIP), competitively interacting with caspase-8, were down-regulated by stimulation with IFN-β but were reversed by the proteasome inhibitor lactacystin. Collectively, the IFN-β-induced sustained activation of JNK mediates apoptosis, at least in part, through up-regulation of CD95 protein in combination with down-regulation of c-FLIP protein

  8. Dissection of pathways leading to antigen receptor-induced and Fas/CD95-induced apoptosis in human B cells

    NARCIS (Netherlands)

    Lens, S. M.; den Drijver, B. F.; Pötgens, A. J.; Tesselaar, K.; van Oers, M. H.; van Lier, R. A.

    1998-01-01

    To dissect intracellular pathways involved in B cell Ag receptor (BCR)-mediated and Fas-induced human B cell death, we isolated clones of the Burkitt lymphoma cell line Ramos with different apoptosis sensitivities. Selection for sensitivity to Fas-induced apoptosis also selected for clones with

  9. Lack of T-cell receptor-induced signaling is crucial for CD95 ligand up-regulation and protects cutaneous T-cell lymphoma cells from activation-induced cell death.

    Science.gov (United States)

    Klemke, Claus-Detlev; Brenner, Dirk; Weiss, Eva-Maria; Schmidt, Marc; Leverkus, Martin; Gülow, Karsten; Krammer, Peter H

    2009-05-15

    Restimulation of previously activated T cells via the T-cell receptor (TCR) leads to activation-induced cell death (AICD), which is, at least in part, dependent on the death receptor CD95 (APO-1, FAS) and its natural ligand (CD95L). Here, we characterize cutaneous T-cell lymphoma (CTCL) cells (CTCL tumor cell lines and primary CTCL tumor cells from CTCL patients) as AICD resistant. We show that CTCL cells have elevated levels of the CD95-inhibitory protein cFLIP. However, cFLIP is not responsible for CTCL AICD resistance. Instead, our data suggest that reduced TCR-proximal signaling in CTCL cells is responsible for the observed AICD resistance. CTCL cells exhibit no PLC-gamma1 activity, resulting in an impaired Ca(2+)release and reduced generation of reactive oxygen species upon TCR stimulation. Ca(2+) and ROS production are crucial for up-regulation of CD95L and reconstitution of both signals resulted in AICD sensitivity of CTCL cells. In accordance with these data, CTCL tumor cells from patients with Sézary syndrome do not up-regulate CD95L upon TCR-stimulation and are therefore resistant to AICD. These results show a novel mechanism of AICD resistance in CTCL that could have future therapeutic implications to overcome apoptosis resistance in CTCL patients.

  10. 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.

  11. Regulation of CD95 expression and CD95-mediated cell death by interferon-gamma in acute lymphoblastic leukemia with chromosomal translocation t(4;11).

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    Dörrie, J; Schuh, W; Keil, A; Bongards, E; Greil, J; Fey, G H; Zunino, S J

    1999-10-01

    The regulatory effects of IFNgamma on CD95 expression and CD95-mediated cell death were investigated in three high-risk pro-B acute lymphoblastic leukemia (ALL) lines that carry the chromosomal translocation t(4;11)(q21;q23). These leukemias are characteristically refractory to conventional chemotherapeutic treatments operating through the induction of apoptosis. However, the mechanisms leading to increased cell survival and resistance to cell death in these leukemias are largely unknown. Interferon-gamma (IFNgamma), a potent inhibitor of hematopoiesis, acts in part by upregulating CD95 and sensitizing cells to CD95-induced apoptosis. The t(4;11) lines SEM, RS4;11, and MV4;11 expressed low levels of CD95, but were completely resistant to CD95-mediated death. Addition of IFNgamma markedly upregulated CD95 expression in SEM (8-9-fold), RS4;11 (2-3-fold), and MV4;11 (2-3-fold) lines. However, after treatment with IFNgamma, only an 11% increase in sensitivity to CD95-mediated cell death was observed in SEM cells, whereas RS4;11 and MV4;11 cells remained resistant. Cycloheximide, but not actinomycin D or brefeldin A, increased CD95-specific cell death only in IFNgamma-treated RS4;11 cells by approximately 12%. Abundant levels of Bcl-2 and Bcl-XL, known to inhibit CD95-signaling in some cells, were present suggesting a possible role for both molecules in the resistance to CD95-mediated cell death. Resistance of the leukemic blasts to CD95-mediated cell death and the failure of IFNgamma to substantially sensitize the CD95-signaling pathway may contribute to the highly malignant phenotype of pro-B ALL with translocation t(4;11).

  12. Pro- and anti-apoptotic CD95 signaling in T cells

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    Janssen Ottmar

    2011-04-01

    Full Text Available Abstract The TNF receptor superfamily member CD95 (Fas, APO-1, TNFRSF6 is known as the prototypic death receptor in and outside the immune system. In fact, many mechanisms involved in apoptotic signaling cascades were solved by addressing consequences and pathways initiated by CD95 ligation in activated T cells or other "CD95-sensitive" cell populations. As an example, the binding of the inducible CD95 ligand (CD95L to CD95 on activated T lymphocytes results in apoptotic cell death. This activation-induced cell death was implicated in the control of immune cell homeostasis and immune response termination. Over the past years, however, it became evident that CD95 acts as a dual function receptor that also exerts anti-apoptotic effects depending on the cellular context. Early observations of a potential non-apoptotic role of CD95 in the growth control of resting T cells were recently reconsidered and revealed quite unexpected findings regarding the costimulatory capacity of CD95 for primary T cell activation. It turned out that CD95 engagement modulates TCR/CD3-driven signal initiation in a dose-dependent manner. High doses of immobilized CD95 agonists or cellular CD95L almost completely silence T cells by blocking early TCR-induced signaling events. In contrast, under otherwise unchanged conditions, lower amounts of the same agonists dramatically augment TCR/CD3-driven activation and proliferation. In the present overview, we summarize these recent findings with a focus on the costimulatory capacity of CD95 in primary T cells and discuss potential implications for the T cell compartment and the interplay between T cells and CD95L-expressing cells including antigen-presenting cells.

  13. CD95 (FAS) and CD178 (FASL) induce the apoptosis of CD4+ and CD8+ cells isolated from the peripheral blood and spleen of dogs naturally infected with Leishmania spp.

    Science.gov (United States)

    Silva, Kathlenn Liezbeth Oliveira; Melo, Larissa Martins; Perosso, Juliana; Oliveira, Bruna Brito; Santos, Paulo Sérgio Patto Dos; Eugênio, Flávia de Rezende; Lima, Valéria Marçal Felix de

    2013-11-08

    Infected dogs are urban reservoirs of Leishmania chagasi, which is a causative agent of visceral leishmaniasis (VL). Dogs exhibit immune suppression during the course of this disease, and lymphocyte apoptosis is involved in this process. To investigate apoptosis and the expression levels of FAS-FAS-associated death domain protein (CD95 or APO-1), FASL-FAS ligand protein (CD178), and TRAIL-TNF-related apoptosis-inducing ligand (CD253) receptors in peripheral blood mononuclear cells and spleen leukocytes from 38 symptomatic dogs with moderate VL and 25 healthy dogs were evaluated by flow cytometry. The apoptosis rate of blood and splenic CD4+ and CD8+ cells was higher in infected dogs than in healthy dogs. The expression levels of FAS and FASL in blood and splenic CD4+ cells were lower in infected dogs than in healthy dogs. FAS expression in CD8+ cells was higher in infected dogs than in healthy dogs; in contrast, FASL expression was lower in infected dogs. The expression of the TRAIL receptor increased only in splenic CD8+ cells from infected dogs. The FAS and FAS-L blocking antibodies confirmed the importance of these receptors in apoptosis. Our results enhance the current understanding of the immune response in dogs infected with L. chagasi, facilitating the future development of therapeutic interventions to reduce lymphocyte depletion. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    being recognized that CD95 signaling by immune cells mediates effects other than apoptosis, such as cell survival and under inflammatory conditions expression of this protein promotes neural-immune interactions. Both neuroscientists and immunologists can contribute to defining the mechanisms underlying...

  15. The naturally processed CD95L elicits a c-yes/calcium/PI3K-driven cell migration pathway.

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    Sébastien Tauzin

    2011-06-01

    Full Text Available Patients affected by chronic inflammatory disorders display high amounts of soluble CD95L. This homotrimeric ligand arises from the cleavage by metalloproteases of its membrane-bound counterpart, a strong apoptotic inducer. In contrast, the naturally processed CD95L is viewed as an apoptotic antagonist competing with its membrane counterpart for binding to CD95. Recent reports pinpointed that activation of CD95 may attract myeloid and tumoral cells, which display resistance to the CD95-mediated apoptotic signal. However, all these studies were performed using chimeric CD95Ls (oligomerized forms, which behave as the membrane-bound ligand and not as the naturally processed CD95L. Herein, we examine the biological effects of the metalloprotease-cleaved CD95L on CD95-sensitive activated T-lymphocytes. We demonstrate that cleaved CD95L (cl-CD95L, found increased in sera of systemic lupus erythematosus (SLE patients as compared to that of healthy individuals, promotes the formation of migrating pseudopods at the leading edge of which the death receptor CD95 is capped (confocal microscopy. Using different migration assays (wound healing/Boyden Chamber/endothelial transmigration, we uncover that cl-CD95L promotes cell migration through a c-yes/Ca²⁺/PI3K-driven signaling pathway, which relies on the formation of a CD95-containing complex designated the MISC for Motility-Inducing Signaling Complex. These findings revisit the role of the metalloprotease-cleaved CD95L and emphasize that the increase in cl-CD95L observed in patients affected by chronic inflammatory disorders may fuel the local or systemic tissue damage by promoting tissue-filtration of immune cells.

  16. Precise mapping of the CD95 pre-ligand assembly domain.

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    Valérie Edmond

    Full Text Available Pre-association of CD95 at the plasma membrane is mandatory for efficient death receptor signaling. This homotrimerization occurs through self-association of an extracellular domain called the pre-ligand assembly domain (PLAD. Using novel molecular and cellular tools, we confirmed that CD95-PLAD is necessary to promote CD95 multimerization and plays a pivotal role in the transmission of apoptotic signals. However, while a human CD95 mutant deleted of the previously described PLAD domain (amino acids 1 to 66 fails to interact with its wild-type counterpart and trigger autonomous cell death, deletion of amino acids 1 to 42 does not prevent homo- or hetero (human/mouse-oligomerization of CD95, and thus does not alter transmission of the apoptotic signal. Overall, these findings indicate that the region between amino acids 43 to 66 corresponds to the minimal motif involved in CD95 homotypic interaction and is necessary to convey an efficient apoptotic signal. Interfering with this PLAD may represent a new therapeutic strategy for altering CD95-induced apoptotic and non-apoptotic signals.

  17. 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

  18. Solution NMR investigation of the CD95/FADD homotypic death domain complex suggests lack of engagement of the CD95 C terminus.

    Science.gov (United States)

    Esposito, Diego; Sankar, Andrew; Morgner, Nina; Robinson, Carol V; Rittinger, Katrin; Driscoll, Paul C

    2010-10-13

    We have addressed complex formation between the death domain (DD) of the death receptor CD95 (Fas/APO-1) with the DD of immediate adaptor protein FADD using nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and size-exclusion chromatography with in-line light scattering. We find complexation to be independent of the C-terminal 12 residues of CD95 and insensitive to mutation of residues that engage in the high-order clustering of CD95-DD molecules in a recently reported crystal structure obtained at pH 4. Differential NMR linewidths indicate that the C-terminal region of the CD95 chains remains in a disordered state and (13)C-methyl TROSY data are consistent with a lack of high degree of symmetry for the complex. The overall molecular mass of the complex is inconsistent with that in the crystal structure, and the complex dissociates at pH 4. We discuss these findings using sequence analysis of CD95 orthologs and the effect of FADD mutations on the interaction with CD95. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer

    International Nuclear Information System (INIS)

    Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis F; Romero-Ramos, Jose E; Olimon-Andalon, Vicente; Hernandez-Flores, Georgina; Lerma-Diaz, Jose M; Ortiz-Lazareno, Pablo C; Morgan-Villela, Gilberto; Toro-Arreola, Susana del; Bravo-Cuellar, Alejandro

    2008-01-01

    Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95) in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma). The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L) were measured by ELISA kits. We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of the apoptotic rate induced by serum in Jurkat cells and the

  20. Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer

    Directory of Open Access Journals (Sweden)

    Bravo-Cuellar Alejandro

    2008-04-01

    Full Text Available Abstract Background Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95 in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. Methods Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma. The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L were measured by ELISA kits. Results We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. Conclusion Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of

  1. Cutting edge: CD95 maintains effector T cell homeostasis in chronic immune activation

    NARCIS (Netherlands)

    Arens, Ramon; Baars, Paul A.; Jak, Margot; Tesselaar, Kiki; van der Valk, Martin; van Oers, Marinus H. J.; van Lier, René A. W.

    2005-01-01

    The elimination of activated T cells is important to maintain homeostasis and avoid immunopathology. CD95 (Fas/APO-1) has been identified as a death mediator for activated T cells in vitro but the function of CD95 in death of mature T cells in vivo is still controversial. Here we show that

  2. CD95 is part of a let-7/p53/miR-34 regulatory network.

    Directory of Open Access Journals (Sweden)

    Annika Hau

    Full Text Available The death receptor CD95 (APO-1/Fas mediates apoptosis induction upon ligation by its cognate ligand CD95L. Two types of CD95 signaling pathways have been identified, which are characterized by the absence (Type I or presence (Type II of mitochondrial involvement. Micro(miRNAs are small noncoding RNAs that negatively regulate gene expression. They are important regulators of differentiation processes and are found frequently deregulated in many human cancers. We recently showed that Type I cells express less of the differentiation marker miRNA let-7 and, hence, likely represent more advanced tumor cells than the let-7 high expressing Type II cells. We have now identified miR-34a as a selective marker for cells that are sensitive to CD95-mediated apoptosis. Both CD95 and miR-34a are p53 target genes, and consequently, both the sensitivity of cancer cells to CD95-mediated apoptosis and the ability to respond to p53 mediated DNA genotoxic stress are linked. Interestingly, while miR-34a was found to positively correlate with the ability of cells to respond to genotoxic stress, let-7 was negatively correlated. The expression level of CD95 inversely correlated with the expression of let-7 suggesting regulation of let-7 expression by CD95. To test a link between p53 and miR-34a, we altered the expression of CD95. This affected the ability of cells to activate p53 and to regulate miR-34a. Our data point to a novel regulatory network comprising p53, CD95, let-7, and miR-34a that affects cancer cell survival, differentiation, and sensitivity to apoptotic signals. The possible relevance of this regulatory network for cancer stem cells is discussed.

  3. Inorganic mercury dissociates preassembled Fas/CD95 receptor oligomers in T lymphocytes

    International Nuclear Information System (INIS)

    Ziemba, Stamatina E.; McCabe, Michael J.; Rosenspire, Allen J.

    2005-01-01

    Genetically susceptible rodents exposed to low burdens of inorganic mercury (Hg 2+ ) develop autoimmune disease. Previous studies have shown that low, noncytotoxic levels of Hg 2+ inhibit Fas-mediated apoptosis in T cells. These results suggest that inhibition of the Fas death receptor pathway potentially contributes to autoimmune disease after Hg 2+ exposure, as a consequence of disruption of peripheral tolerance. The formation of active death inducing signaling complexes (DISC) following CD95/Fas receptor oligomerization is a primary step in the Fas-mediated apoptotic pathway. Other recent studies have shown that Hg 2+ at concentrations that inhibit apoptosis also inhibit formation of active DISC, suggesting that inhibition of DISC is the mechanism responsible for Hg 2+ -mediated inhibition of apotosis. Preassociated Fas receptors have been implicated as key elements necessary for the production of functional DISC. We present evidence in this study showing that low and nontoxic concentrations of Hg 2+ induce the dissociation of preassembled Fas receptor complexes in Jurkat T cells. Thus, this Hg 2+ -induced event should subsequently decrease the amount of preassembled Fas available for DISC formation, potentially resulting in the attenuation of Fas-mediated apoptosis in T lymphocytes

  4. Immunoexpression of CD95 in chronic gastritis and gastric mucosa-associated lymphomas

    Directory of Open Access Journals (Sweden)

    Vassallo J.

    2004-01-01

    Full Text Available CD95 (Fas/APO-1-mediated apoptosis plays an important role in immunological regulation and is related to the pathogenesis of autoimmune diseases. Immunoexpression of CD95 has been reported to frequently occur in low grade non-Hodgkin lymphomas, especially of post-germinal center histogenesis, among which those originating in mucosa-associated lymphoid tissue (MALT lymphomas. However, there is no report comparing in situ immunoexpression of this marker in lymphomas and the hyperplastic lymphoid reaction (chronic gastritis related to Helicobacter pylori infection. The purpose of the present research was to compare the intensity of lymphoid CD95 immunoexpression in 15 cases of H. pylori-related chronic gastritis and 15 gastric MALT lymphomas. CD95 (anti-CD95 was detected by an immunoperoxidase technique in paraffin sections using the catalyzed amplification system. Graduation of reaction intensity (percentage of CD95-positive cells was semiquantitative, from 1+ to 4+. Nine cases of chronic gastritis were 4+, five 2+ and one 1+. Three lymphomas were 4+, three 3+, four 2+, four 1+, and one was negative. Although 14 of 15 lymphomas were positive for CD95, the intensity of the reaction was significantly weaker compared to that obtained with gastric tissue for patients with gastritis (P = 0.03. The difference in CD95 immunoexpression does not seem to be useful as an isolated criterion in the differential diagnosis between chronic gastritis and MALT lymphomas since there was overlapping of immunostaining patterns. However, it suggests the possibility of a pathogenetic role of this apoptosis-regulating protein in MALT lymphomas.

  5. HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular FLICE-inhibitory protein (c-FLIP).

    Science.gov (United States)

    Krueger, Andreas; Fas, Stefanie C; Giaisi, Marco; Bleumink, Marc; Merling, Anette; Stumpf, Christine; Baumann, Sven; Holtkotte, Denise; Bosch, Valerie; Krammer, Peter H; Li-Weber, Min

    2006-05-15

    The HTLV-1 transactivator protein Tax is essential for malignant transformation of CD4 T cells, ultimately leading to adult T-cell leukemia/lymphoma (ATL). Malignant transformation may involve development of apoptosis resistance. In this study we investigated the molecular mechanisms by which HTLV-1 Tax confers resistance toward CD95-mediated apoptosis. We show that Tax-expressing T-cell lines derived from HTLV-1-infected patients express elevated levels of c-FLIP(L) and c-FLIP(S). The levels of c-FLIP correlated with resistance toward CD95-mediated apoptosis. Using an inducible system we demonstrated that both resistance toward CD95-mediated apoptosis and induction of c-FLIP are dependent on Tax. In addition, analysis of early cleavage of the BH3-only Bcl-2 family member Bid, a direct caspase-8 substrate, revealed that apoptosis is inhibited at a CD95 death receptor proximal level in Tax-expressing cells. Finally, using siRNA we directly showed that c-FLIP confers Tax-mediated resistance toward CD95-mediated apoptosis. In conclusion, our data suggest an important mechanism by which expression of HTLV-1 Tax may lead to immune escape of infected T cells and, thus, to persistent infection and transformation.

  6. 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.

  7. 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

    a single dose of UVB irradiation. Normal healthy individuals were irradiated with three minimal erythema doses (MED) of UVB on forearm or buttock skin. Suction blisters from unirradiated and irradiated skin were raised, and Fas, FasL, and apoptosis of epidermal cells quantified by flow cytometry...

  8. Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain ischemia.

    Science.gov (United States)

    Reich, Arno; Spering, Christopher; Gertz, Karen; Harms, Christoph; Gerhardt, Ellen; Kronenberg, Golo; Nave, Klaus A; Schwab, Markus; Tauber, Simone C; Drinkut, Anja; Harms, Kristian; Beier, Chrstioph P; Voigt, Aaron; Göbbels, Sandra; Endres, Matthias; Schulz, Jörg B

    2011-01-05

    Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia.

  9. 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.

  10. STUDIES IN DYNAMICS OF APOPTOSIS-RELATED SURFACE ANTIGEN (CD95 EXPRESSION ON NEUTROPHILS FROM CERVICAL AND VAGINAL SECRETIONS IN WOMEN WITH CHLAMIDIA INFECTION

    Directory of Open Access Journals (Sweden)

    O. A. Giesinger

    2010-01-01

    Full Text Available CD95 (Fas/APO-1 antigen expression was studied on the surface of neutrophil granulocytes from cervical secretions. Sixty-five female patients with established Chlamydia infection were found to have an increased CD95+ antigen expression following basic therapy. CD95+ receptors on neutrophils in the patients with Chlamydia infection have been shown to return to normal levels following a combined magnetic laser treatment.

  11. Hepatitis C Virus and Disrupted Interferon Signaling Promote Lymphoproliferation via Type II CD95 and Interleukins

    Science.gov (United States)

    MACHIDA, KEIGO; TSUKIYAMA-KOHARA, KYOKO; SEKIGUCH, SATOSHI; SEIKE, EIJI; TÓNE, SHIGENOBU; HAYASHI, YUKIKO; TOBITA, YOSHIMI; KASAMA, YURI; SHIMIZU, MASUMI; TAKAHASHI, HIDEMI; TAYA, CHYOJI; YONEKAWA, HIROMICHI; TANAKA, NOBUYUKI; KOHARA, MICHINORI

    2014-01-01

    BACKGROUND & AIMS The molecular mechanisms of lymphoproliferation associated with the disruption of interferon (IFN) signaling and chronic hepatitis C virus (HCV) infection are poorly understood. Lymphomas are extrahepatic manifestations of HCV infection; we sought to clarify the molecular mechanisms of these processes. METHODS We established interferon regulatory factor-1– null (irf-1−/−) mice with inducible and persistent expression of HCV structural proteins (irf-1/CN2 mice). All the mice (n = 900) were observed for at least 600 days after Cre/loxP switching. Histologic analyses, as well as analyses of lymphoproliferation, sensitivity to Fas-induced apoptosis, colony formation, and cytokine production, were performed. Proteins associated with these processes were also assessed. RESULTS Irf-1/CN2 mice had extremely high incidences of lymphomas and lymphoproliferative disorders and displayed increased mortality. Disruption of irf-1 reduced the sensitivity to Fas-induced apoptosis and decreased the levels of caspases-3/7 and caspase-9 messenger RNA species and enzymatic activities. Furthermore, the irf-1/CN2 mice showed decreased activation of caspases-3/7 and caspase-9 and increased levels of interleukin (IL)-2, IL-10, and Bcl-2, as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes. IL-2 and IL-10 were induced by the HCV core protein in splenocytes. CONCLUSIONS Disruption of IFN signaling resulted in development of lymphoma, indicating that differential signaling occurs in lymphocytes compared with liver. This mouse model, in which HCV expression and disruption of IFN signaling synergize to promote lymphoproliferation, will be an important tool for the development of therapeutic agents that target the lymphoproliferative pathway. PMID:19362089

  12. Prognostic significance of CD95, P53, and BCL2 expression in extranodal non-Hodgkin's lymphoma

    OpenAIRE

    Chatzitolios , Anastasios; Venizelos , Ioannis; Tripsiannis , Gregory; Anastassopoulos , George; Papadopoulos , Nikolaos

    2010-01-01

    Abstract Apoptosis-related proteins play an important role in lymphoma cell death during chemotherapy. In our study, we investigated the prognostic significance of CD95, BCL2, and P53 expression in extranodal non-Hodgkin?s lymphoma (NHL). We examined 71 patients with extranodal NHL [45 diffuse large B-cell lymphomas (DLBCLs) and 26 mucosa-associated lymphoid tissue lymphomas (MALTLs)], 35 male and 36 female, with a median age of 65.8 years. The most common site of origin was the st...

  13. Death receptor Fas (CD95) signaling in the central nervous system: tuning neuroplasticity?

    Science.gov (United States)

    Reich, Arno; Spering, Christopher; Schulz, Jörg B

    2008-09-01

    For over a decade, neuroscientific research has focused on processes of apoptosis and its contribution to the pathophysiology of neurological diseases. In the central nervous system, the degree of intrinsic mitochondrial-mediated apoptotic signaling expresses a cell's individual metabolic stress, whereas activation of the extrinsic death receptor-induced cascade is regarded as a sign of imbalanced cellular networks. Under physiological conditions, most neurons possess death receptors without being sensitive to receptor-mediated apoptosis. This paradox raises two questions: what is the evolutionary advantage of expressing potentially harmful proteins? How is their signaling controlled? This review summarizes the functional relevance of FasL-Fas signaling--a quintessential death ligand/receptor system--in different neurological disease models ranging from traumatic, inflammatory and ischemic to neurodegenerative processes. Furthermore, it outlines alternative non-apoptotic Fas signaling, shedding new light on its neuroplastic capacity. Finally, receptor-proximal regulatory proteins are introduced and identified as potential protagonists of disease-modifying neurological therapies.

  14. Using cluster of differentiation CD 38, CD 45 and CD 95 as a method of primary diagnosis of uterine fibroids

    Directory of Open Access Journals (Sweden)

    I. V. Savytskyi

    2017-07-01

    Full Text Available Uterine myoma is one of the first places among gynecological diseases. There is a rise of the number of pathology diagnoses among young women. Currently inUkrainethere is no single approved laboratory method for screening of uterine myomas. The aim of our work is the studying of the efficiency of CD38, CD45, and CD95 leukocyte differentiation clusters for early detection of uterine myomas. Determination of a subpopulation of lymphocytes in urine with immune complex of peroxidase-antiperoxidase. The features of the number of leukocytes with CD 38, CD 45, CD 95 antigens were analyzed among women with uterine myoma compared with women who did not have gynecological diseases and underwent an appropriate research. Each sample consisted of 50 women aged 30 to 65 years (average age in both samples was 45 years. The Student's test for independent samples was used for statistical methods of comparison. The results we’ve got indicate that the most statistically significant differences were established by SD 95, so it can be assumed that it is the one that is the most informative as a possible marker for the presence of uterine fibroids. At the same time, during the analyzingof  the clusters of CD38 and CD45 differentiation, there were also found highly significant differences between the group of patients with uterine myoma and healthy women.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

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    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Safety and efficacy of the CD95-ligand inhibitor asunercept in transfusion-dependent patients with low and intermediate risk MDS.

    Science.gov (United States)

    Boch, Tobias; Luft, Thomas; Metzgeroth, Georgia; Mossner, Maximilian; Jann, Johann-Christoph; Nowak, Daniel; Meir, Franziska La; Schumann, Christiane; Klemmer, Jennifer; Brendel, Susanne; Fricke, Harald; Kunz, Claudia; Weiß, Christel; Hofmann, Wolf-Karsten; Nolte, Florian

    2018-05-01

    In low risk MDS, increased apoptosis of erythroid progenitors mediated via CD95 (Fas) activation has been described to result in peripheral cytopenia. Blockade of the CD95 system can improve erythropoiesis in MDS. Asunercept (APG101) is a fusion protein consisting of the extracellular domain of human CD95 and the Fc domain of human IgG1 blocking the interaction between CD95 and its ligand. Here we report on results from a phase I study in 20 transfusion-dependent low and intermediate risk MDS patients treated with intravenous asunercept (EudraCT 2012-003027-37). Primary objectives were safety and tolerability as well as pharmacodynamic effects. Secondary objectives were hematologic improvement, incidence and time to leukemic progression as well as overall survival. Frequency and severity of adverse events were in range of what could be expected in a patient cohort comprising of elderly MDS patients. Two patients experienced a serious adverse event with a suspected relationship to asunercept. The incidence of disease progression was low. In the 20 patients a decrease of the transfusion need from a mean of 10,8 (±5,1) pRBCs during the 12 weeks treatment phase to a mean of 10,0 (±4,2) pRBCs at the end of the study was observed. In conclusion, asunercept was well tolerated and showed efficacy in transfusion-dependent low and intermediate risk MDS patients. Further clinical investigation is warranted, particularly in combination with erythropoiesis stimulating agents (ESAs). Copyright © 2018. Published by Elsevier Ltd.

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

    Directory of Open Access Journals (Sweden)

    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

  1. Changing of expression level of fas-antigen (CD95), cytokines synthesis and production after irradiation in low doses

    International Nuclear Information System (INIS)

    Kalinina, N.M.; Solntceva, O.S.; Bytchkova, N.V.; Nikiforov, A.M.

    1997-01-01

    It is known that bone marrow progenitor (CD34+), tymocytes and peripheral blood lymphocytes (PBL) are most radiosensitive than other cell types. Even low doses of radiation induce apoptosis. The investigators suggest that it is possible relationship between synthesis and production of cytokines and apoptotic process. With the purpose to determine correlation between expression of Fas-antigen and synthesis of cytokines after low doses irradiation the experiments by irradiation PBL of healthy persons in vitro were held. Cells were X-irradiated by 12,5, 25 and 50 cGy. In consequence of the experiments increasing of Fas-antigen was revealed. This increasing correlated with changing in synthesis and production of cytokines. Also the Chernobyl's accident liquidators (CAL) were investigated. After comparison data in the group CAL (I) with data in the control group (II) increasing of Fas-antigen expression was revealed. Also in I group was discovered increasing of the cell number sinthesied interleukine-4 (IL-4) and interleukine-6 (IL-6). Interleukine-lβ (IL-1 β) producing pell were decreased. These changes have been correlated with degree of immunodeficiency at CAL. These data allow to consider the apoptosis as cell mechanism included in pathogenesis of diseases, which can be showed later long time after irradiation. (author)

  2. Polyamine-Induced Rapid Root Abscission in Azolla pinnata.

    Science.gov (United States)

    Gurung, Sushma; Cohen, Michael F; Fukuto, Jon; Yamasaki, Hideo

    2012-01-01

    Floating ferns of the genus Azolla detach their roots under stress conditions, a unique adaptive response termed rapid root abscission. We found that Azolla pinnata plants exhibited dose-dependent rapid root abscission in response to the polyamines spermidine and spermine after a substantial time lag (>20 min). The duration of the time lag decreased in response to high pH and high temperature whereas high light intensity increased the time lag and markedly lowered the rate of abscission. The oxidation products of polyamines, 1,3-diaminopropane, β-alanine and hydrogen peroxide all failed to initiate root abscission, and hydroxyethyl hydrazine, an inhibitor of polyamine oxidase, did not inhibit spermine-induced root abscission. Exposure of A. pinnata to the polyamines did not result in detectable release of NO and did not affect nitrite-dependent NO production. The finding of polyamine-induced rapid root abscission provides a facile assay for further study of the mode of action of polyamines in plant stress responses.

  3. Major rapid weight loss induces changes in cardiac repolarization

    DEFF Research Database (Denmark)

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

    2016-01-01

    INTRODUCTION: Obesity is associated with increased all-cause mortality, but weight loss may not decrease cardiovascular events. In fact, very low calorie diets have been linked to arrhythmias and sudden death. The QT interval is the standard marker for cardiac repolarization, but T-wave morphology...... 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......A1c (pweight loss induces changes in cardiac repolarization. Monitoring of MCS during calorie restriction makes it possible to detect repolarization changes with higher discriminative power than the QT-interval during major rapid weight...

  4. Tracking Spinal Cord Injury: Differences in Cytokine Expression of IGF-1, TGF- B1, and sCD95l Can Be Measured in Blood Samples and Correspond to Neurological Remission in a 12-Week Follow-Up.

    Science.gov (United States)

    Ferbert, Thomas; Child, Christopher; Graeser, Viola; Swing, Tyler; Akbar, Michael; Heller, Raban; Biglari, Bahram; Moghaddam, Arash

    2017-02-01

    Neuroinflammation presumably has an important impact on the secondary phase of spinal cord injury and is regulated by pro- and anti-inflammatory cytokines. We analyzed serum levels of three different cytokines (insulin-like-growth-factor [IGF]-1, tumor growth factor [TGF]-β1, and soluble CD 95 ligand [sCD95L]), in blood samples of 23 patients admitted with acute traumatic spinal cord injury between November 2010 and July 2013 with a follow-up period of 12 weeks. Quantification was performed using Human Quantikine Immunoassays, classification of neurological impairment was performed using the American Spinal Cord Injury Impairment Scale at time of admission and after 12 weeks. After an initial drop of all three cytokine serum levels, IGF-1, TGF-β1, and sCD95L showed significantly increased serum levels during the acute and sub-acute phases. For IGF-1 and sCD95L, we could also observe significantly higher serum levels in patients without neurological improvement compared with patients who had improvement after 12 weeks. In this study, we were able to show differences in cytokine serum levels in patients with different neurological outcome. Measuring the serum level patterns of IGF-1, TGF-β1, and sCD95L might be a useful tool for prognosis in patients with neurological improvement and tracking the pathophysiology in further studies. Further, our observations might link promising therapeutic efforts in numerous animal studies and future studies in human patients.

  5. Rapid decompression and desorption induced energetic failure in coal

    Directory of Open Access Journals (Sweden)

    Shugang Wang

    2015-06-01

    Full Text Available In this study, laboratory experiments are conducted to investigate the rapid decompression and desorption induced energetic failure in coal using a shock tube apparatus. Coal specimens are recovered from Colorado at a depth of 610 m. The coal specimens are saturated with the strong sorbing gas CO2 for a certain period and then the rupture disc is suddenly broken on top of the shock tube to generate a shock wave propagating upwards and a rarefaction wave propagating downwards through the specimen. This rapid decompression and desorption has the potential to cause energetic fragmentation in coal. Three types of behaviors in coal after rapid decompression are found, i.e. degassing without fragmentation, horizontal fragmentation, and vertical fragmentation. We speculate that the characteristics of fracture network (e.g. aperture, spacing, orientation and stiffness and gas desorption play a role in this dynamic event as coal can be considered as a dual porosity, dual permeability, dual stiffness sorbing medium. This study has important implications in understanding energetic failure process in underground coal mines such as coal gas outbursts.

  6. Fas (CD95) expression and death-mediating function are induced by CD4 cross-linking on CD4+ T cells.

    OpenAIRE

    Desbarats, J; Freed, J H; Campbell, P A; Newell, M K

    1996-01-01

    The CD4 receptor contributes to T-cell activation by coligating major histocompatibility complex class II on antigen presenting cells with the T-cell receptor (TCR)/CD3 complex, and triggering a cascade of signaling events including tyrosine phosphorylation of intracellular proteins. Paradoxically, CD3 cross-linking prior to TCR stimulation results in apoptotic cell death, as does injection of anti-CD4 antibodies in vivo of CD4 ligation by HIV glycoprotein (gp) 120. In this report we investig...

  7. Clinical meanings of changes of blood expression of CD95 antigen (Fas), Bcl-2 and transforming growth factor-α (TGF-α) in patients with chronic renal failure on hemodialysis

    International Nuclear Information System (INIS)

    Yang Daoli; Luo Nanping; Sun Xiaoming

    2005-01-01

    Objective: To study the changes of expression of blood CD95 antigen (Fas), and anti-apoptosis factor (Bcl-2) and TGF-α after hemodialysis in patients with chronic renal failure. Methods: The percentage of CD95 and Bcl-2 positive cells in peripheral blood monocytes were examined with flow cytometry and serum TGF-α contents were measured with RIA in 40 patients with chronic renal failure both before and after hemodialysis as well as in 25 other patients with chronic renal failure but not on dialysis and 30 controls. Results: Expressions of CD95 were significantly higher and expressions of Bcl-2, TGF-α were significantly lower in all the patients with chronic renal failure than those in the controls (P 0.05). Conclusion: The up-regulation of CD95 expression and increase of serum TGF-α contents after hemodialysis might contribute to induction of apoptosis of mesangial cells, which would be beneficial to the patient. (authors)

  8. Leukocyte function-associated antigen-1-dependent lysis of Fas+ (CD95+/Apo-1+) innocent bystanders by antigen-specific CD8+ CTL.

    Science.gov (United States)

    Kojima, H; Eshima, K; Takayama, H; Sitkovsky, M V

    1997-09-15

    Exquisite specificity toward Ag-bearing cells (cognate targets) is one of the most important properties of CD8+ CTL-mediated cytotoxicity. Using highly Ag-specific CD8+ CTL lines and clones, which spare noncognate, Ag-free targets, we found that in the presence of Ag-bearing targets the CTL acquire the ability to lyse noncognate target cells (bystanders). It is shown that the unexpectedly rapid and efficient lysis of bystanders by Ag-activated CTL is mediated by a Fas ligand (FasL)/Fas-based mechanism and does not depend on perforin. The CTL lysed Fas-expressing bystanders, but spared the Fas-negative or anti-Fas mAb-resistant bystander cells. Accordingly, the FasL-deficient gld/gld CTL did not kill bystanders, while perforin-deficient CTL did. Unlike anti-Fas mAb-induced cell death, the lysis of bystanders was not only FasL/Fas dependent but also required adhesion molecule LFA-1 on the surface of the activated CTL. Lysis of bystanders is viewed as acceptable "collateral" damage, but the persistent presence of activated CTL could result in immunopathologies involving functional Fas-expressing tissues.

  9. Flurbiprofen in rapid eye movement sleep deprivation induced hyperalgesia.

    Science.gov (United States)

    Gürel, Elif Ezgi; Ural, Keremcan; Öztürk, Gülnur; Öztürk, Levent

    2014-04-10

    Rapid eye movement (REM) sleep deprivation induces hyperalgesia in healthy rats. Here, we evaluated the effects of flurbiprofen, an anti-inflammatory and neuroprotective agent, on the increased thermal responses observed in REM sleep deprived rats. Forty female rats were divided into four groups following 96-hour REM sleep deprivation: intraperitoneal injections of placebo, and flurbiprofen 5 mg/kg, 15 mg/kg and 40 mg/kg were made in CONT (n=10), FBP5, FBP15 and FBP40 groups respectively. Pain threshold measurements were performed three times at baseline (0.hour), at the end of REM sleep deprivation (96.hour) and at 1 h after injections (97.hour) by hot plate and tail-flick tests. REM sleep deprivation induced a significant decrease in pain thresholds of all rats (hotplate: 0.hour vs 96.hour, 9.75±2.85 vs 5.10±2.02, pFlurbiprofen in 15 mg/kg and 40 mg/kg doses significantly improved pain tolerance measured by tail flick test (tail flick in FBP15 and FBP40 groups: 96.hour vs 97.hour, 7.01±4.97 vs 8.34±3.61 and 5.06±1.57 vs 7.04±2.49, pFlurbiprofen was used for the first time in a rat model of REM sleep deprivation, and it provided anti-nociceptive effects in 15 mg/kg and 40 mg/kg doses. Flurbiprofen may have the potential for treatment of painful syndromes accompanying insomnia or sleep loss. Copyright © 2014 Elsevier Inc. All rights reserved.

  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. 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

  12. Histones induce rapid and profound thrombocytopenia in mice

    Science.gov (United States)

    Bhandari, Ashish A.

    2011-01-01

    Histones are released from dying cells and contribute to antimicrobial defense during infection. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. We studied the interactions of histones with platelets. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Hereby fibrinogen cross-linked histone-bearing platelets and triggered microaggregation. Fibrinogen interactions with αIIbβ3 integrins were not required for this process but were necessary for the formation of large platelet aggregates. Infused histones associated with platelets in vivo and caused a profound thrombocytopenia within minutes after administration. Mice lacking platelets or αIIbβ3 integrins were protected from histone-induced death but not from histone-induced tissue damage. Heparin, at high concentrations, prevented histone interactions with platelets and protected mice from histone-induced thrombocytopenia, tissue damage, and death. Heparin and histones are evolutionary maintained. Histones may combine microbicidal with prothrombotic properties to fight invading microbes and maintain hemostasis after injury. Heparin may provide an innate counter mechanism to neutralize histones and diminish collateral tissue damage. PMID:21700775

  13. Lethal Nipah virus infection induces rapid overexpression of CXCL10.

    Directory of Open Access Journals (Sweden)

    Cyrille Mathieu

    Full Text Available Nipah virus (NiV is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10, an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.

  14. Simulations of rapid pressure-induced solidification in molten metals

    International Nuclear Information System (INIS)

    Patel, Mehul V.; Streitz, Frederick H.

    2004-01-01

    The process of interest in this study is the solidification of a molten metal subjected to rapid pressurization. Most details about solidification occurring when the liquid-solid coexistence line is suddenly transversed along the pressure axis remain unknown. We present preliminary results from an ongoing study of this process for both simple models of metals (Cu) and more sophisticated material models (MGPT potentials for Ta). Atomistic (molecular dynamics) simulations are used to extract details such as the time and length scales that govern these processes. Starting with relatively simple potential models, we demonstrate how molecular dynamics can be used to study solidification. Local and global order parameters that aid in characterizing the phase have been identified, and the dependence of the solidification time on the phase space distance between the final (P,T) state and the coexistence line has been characterized

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Norcantharidin (NCTD) induces mitochondria mediated apoptosis in ...

    African Journals Online (AJOL)

    Administrator

    2011-06-15

    Jun 15, 2011 ... cancer deaths for both sexes being attributable to hepatoma. However ..... Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in ... involvement of the CD95 receptor/ligand. J. Cancer. Res.

  17. 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.

  18. Thrombin induces rapid PAR1-mediated non-classical FGF1 release

    International Nuclear Information System (INIS)

    Duarte, Maria; Kolev, Vihren; Soldi, Raffaella; Kirov, Alexander; Graziani, Irene; Oliveira, Silvia Marta; Kacer, Doreen; Friesel, Robert; Maciag, Thomas; Prudovsky, Igor

    2006-01-01

    Thrombin induces cell proliferation and migration during vascular injury. We report that thrombin rapidly stimulated expression and release of the pro-angiogenic polypeptide fibroblast growth factor 1 (FGF1). Thrombin failed to induce FGF1 release from protease-activated receptor 1 (PAR1) null fibroblasts, indicating that this effect was dependent on PAR1. Similarly to thrombin, FGF1 expression and release were induced by TRAP, a specific oligopeptide agonist of PAR1. These results identify a novel aspect of the crosstalk between FGF and thrombin signaling pathways which both play important roles in tissue repair and angiogenesis

  19. Rapid compression induced solidification of two amorphous phases of poly(ethylene terephthalate)

    Energy Technology Data Exchange (ETDEWEB)

    Hong, S M [Laboratory of High Pressure Physics, Southwest Jiaotong University, Chengdu, 610031 (China); Liu, X R [Laboratory of High Pressure Physics, Southwest Jiaotong University, Chengdu, 610031 (China); Su, L [Laboratory of High Pressure Physics, Southwest Jiaotong University, Chengdu, 610031 (China); Huang, D H [Laboratory of High Pressure Physics, Southwest Jiaotong University, Chengdu, 610031 (China); Li, L B [Foods Research Centre Unilever R and D, Vlaardingen Olivier van Noortlaan, 120, 3133 AT Vlaardingen (Netherlands)

    2006-08-21

    Melts of poly(ethylene terephthalate) were solidified by rapid compression to 2 GPa within 20 ms and by a series of comparative processes including natural cooling, slow compressing and rapid cooling, respectively. By combining XRD and differential scanning calorimetry data of the recovered samples, it is made clear that rapid compression induces two kinds of amorphous phases. One is relatively stable and can also be formed in the slow compression and the cooling processes. Another is metastable and transforms to crystalline phase at 371 K. This metastable amorphous phase cannot be obtained by slow compression or natural cooling, and its crystallization temperature is remarkably different from that of the metastable amorphous phase formed in the rapid cooling sample.

  20. Rapid desensitization induces internalization of antigen-specific IgE on mouse mast cells.

    Science.gov (United States)

    Oka, Tatsuya; Rios, Eon J; Tsai, Mindy; Kalesnikoff, Janet; Galli, Stephen J

    2013-10-01

    Rapid desensitization transiently prevents severe allergic reactions, allowing administration of life-saving therapies in previously sensitized patients. However, the mechanisms underlying successful rapid desensitization are not fully understood. We sought to investigate whether the mast cell (MC) is an important target of rapid desensitization in mice sensitized to exhibit IgE-dependent passive systemic anaphylaxis in vivo and to investigate the antigen specificity and underlying mechanisms of rapid desensitization in our mouse model. C57BL/6 mice (in vivo) or primary isolated C57BL/6 mouse peritoneal mast cells (PMCs; in vitro) were passively sensitized with antigen-specific anti-2,4-dinitrophenyl IgE, anti-ovalbumin IgE, or both. MCs were exposed over a short period of time to increasing amounts of antigen (2,4-dinitrophenyl-human serum albumin or ovalbumin) in the presence of extracellular calcium in vitro or by means of intravenous administration to sensitized mice in vivo before challenging the mice with or exposing the PMCs to optimal amounts of specific or irrelevant antigen. Rapidly exposing mice or PMCs to progressively increasing amounts of specific antigen inhibited the development of antigen-induced hypothermia in sensitized mice in vivo and inhibited antigen-induced PMC degranulation and prostaglandin D2 synthesis in vitro. Such MC hyporesponsiveness was induced antigen-specifically and was associated with a significant reduction in antigen-specific IgE levels on MC surfaces. Rapidly exposing MCs to progressively increasing amounts of antigen can both enhance the internalization of antigen-specific IgE on the MC surface and also desensitize these cells in an antigen-specific manner in vivo and in vitro. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  1. Antimicrobial Peptide Lactoferricin B-Induced Rapid Leakage of Internal Contents from Single Giant Unilamellar Vesicles.

    Science.gov (United States)

    Moniruzzaman, Md; Alam, Jahangir Md; Dohra, Hideo; Yamazaki, Masahito

    2015-09-29

    Enzymatic digestion of bovine lactoferrin generates lactoferricin B (Lfcin B), a 25-mer peptide with strong antimicrobial activity of unknown mechanism. To elucidate the mechanistic basis of Lfcin B bactericidal activity, we investigated the interaction of Lfcin B with Escherichia coli and liposomes of lipid membranes. Lfcin B induced the influx of a membrane-impermeant fluorescent probe, SYTOX green, from the outside of E. coli into its cytoplasm. Lfcin B induced gradual leakage of calcein from large unilamellar vesicles (LUVs) of dioleoylphosphatidylglycerol (DOPG)/dioleoylphosphatidylcholine (DOPC) membranes. To clarify the cause of Lfcin B-induced leakage of calcein from the LUVs, we used the single giant unilamellar vesicle (GUV) method to investigate the interaction of Lfcin B with calcein-containing DOPG/DOPC-GUVs. We observed that a rapid leakage of calcein from a GUV started stochastically; statistical analysis provided a rate constant for Lfcin B-induced pore formation, kp. On the other hand, phase-contrast microscopic images revealed that Lfcin B induced a rapid leakage of sucrose from the single GUVs with concomitant appearance of a spherical GUV of smaller diameter. Because of the very fast leakage, and at the present time resolution of the experiments (33 ms), we could not follow the evolution of pore nor the process of the structural changes of the GUV. Here we used the term "local rupture" to express the rapid leakage of sucrose and determined the rate constant of local rupture, kL. On the basis of the comparison between kp and kL, we concluded that the leakage of calcein from single GUVs occurred as a result of a local rupture in the GUVs and that smaller pores inducing leakage of calcein were not formed before the local rupture. The results of the effect of the surface charge density of lipid membranes and that of salt concentration in buffer on kp clearly show that kp increases with an increase in the extent of electrostatic interactions due to

  2. 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.

  3. Rapid stress-induced transcriptomic changes in the brain depend on beta-adrenergic signaling.

    Science.gov (United States)

    Roszkowski, Martin; Manuella, Francesca; von Ziegler, Lukas; Durán-Pacheco, Gonzalo; Moreau, Jean-Luc; Mansuy, Isabelle M; Bohacek, Johannes

    2016-08-01

    Acute exposure to stressful experiences can rapidly increase anxiety and cause neuropsychiatric disorders. The effects of stress result in part from the release of neurotransmitters and hormones, which regulate gene expression in different brain regions. The fast neuroendocrine response to stress is largely mediated by norepinephrine (NE) and corticotropin releasing hormone (CRH), followed by a slower and more sustained release of corticosterone. While corticosterone is an important regulator of gene expression, it is not clear which stress-signals contribute to the rapid regulation of gene expression observed immediately after stress exposure. Here, we demonstrate in mice that 45 min after an acute swim stress challenge, large changes in gene expression occur across the transcriptome in the hippocampus, a region sensitive to the effects of stress. We identify multiple candidate genes that are rapidly and transiently altered in both males and females. Using a pharmacological approach, we show that most of these rapidly induced genes are regulated by NE through β-adrenergic receptor signaling. We find that CRH and corticosterone can also contribute to rapid changes in gene expression, although these effects appear to be restricted to fewer genes. These results newly reveal a widespread impact of NE on the transcriptome and identify novel genes associated with stress and adrenergic signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Src Kinase Dependent Rapid Non-genomic Modulation of Hippocampal Spinogenesis Induced by Androgen and Estrogen

    Directory of Open Access Journals (Sweden)

    Mika Soma

    2018-05-01

    Full Text Available Dendritic spine is a small membranous protrusion from a neuron's dendrite that typically receives input from an axon terminal at the synapse. Memories are stored in synapses which consist of spines and presynapses. Rapid modulations of dendritic spines induced by hippocampal sex steroids, including dihydrotestosterone (DHT, testosterone (T, and estradiol (E2, are essential for synaptic plasticity. Molecular mechanisms underlying the rapid non-genomic modulation through synaptic receptors of androgen (AR and estrogen (ER as well as its downstream kinase signaling, however, have not been well understood. We investigated the possible involvement of Src tyrosine kinase in rapid changes of dendritic spines in response to androgen and estrogen, including DHT, T, and E2, using hippocampal slices from adult male rats. We found that the treatments with DHT (10 nM, T (10 nM, and E2 (1 nM increased the total density of spines by ~1.22 to 1.26-fold within 2 h using super resolution confocal imaging of Lucifer Yellow-injected CA1 pyramidal neurons. We examined also morphological changes of spines in order to clarify differences between three sex steroids. From spine head diameter analysis, DHT increased middle- and large-head spines, whereas T increased small- and middle-head spines, and E2 increased small-head spines. Upon application of Src tyrosine kinase inhibitor, the spine increases induced through DHT, T, and E2 treatments were completely blocked. These results imply that Src kinase is essentially involved in sex steroid-induced non-genomic modulation of the spine density and morphology. These results also suggest that rapid effects of exogenously applied androgen and estrogen can occur in steroid-depleted conditions, including “acute” hippocampal slices and the hippocampus of gonadectomized animals.

  5. Profound and Rapid Reduction in Body Temperature Induced by the Melanocortin Receptor Agonists

    Science.gov (United States)

    Xu, Yuanzhong; Kim, Eun Ran; Fan, Shengjie; Xia, Yan; Xu, Yong; Huang, Cheng; Tong, Qingchun

    2014-01-01

    The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5′AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII’s effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature. PMID:25065745

  6. Profound and rapid reduction in body temperature induced by the melanocortin receptor agonists.

    Science.gov (United States)

    Xu, Yuanzhong; Kim, Eun Ran; Fan, Shengjie; Xia, Yan; Xu, Yong; Huang, Cheng; Tong, Qingchun

    2014-08-22

    The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5'AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII's effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Helminth antigens counteract a rapid high-fat diet-induced decrease in adipose tissue eosinophils.

    Science.gov (United States)

    van den Berg, Susan M; van Dam, Andrea D; Kusters, Pascal J H; Beckers, Linda; den Toom, Myrthe; van der Velden, Saskia; Van den Bossche, Jan; van Die, Irma; Boon, Mariëtte R; Rensen, Patrick C N; Lutgens, Esther; de Winther, Menno P J

    2017-10-01

    Brown adipose tissue (BAT) activation and white adipose tissue (WAT) beiging can increase energy expenditure and have the potential to reduce obesity and associated diseases. The immune system is a potential target in mediating brown and beige adipocyte activation. Type 2 and anti-inflammatory immune cells contribute to metabolic homeostasis within lean WAT, with a prominent role for eosinophils and interleukin (IL)-4-induced anti-inflammatory macrophages. We determined eosinophil numbers in epididymal WAT (EpAT), subcutaneous WAT (ScAT) and BAT after 1 day, 3 days or 1 week of high-fat diet (HFD) feeding in C57Bl/6 mice. One day of HFD resulted in a rapid drop in eosinophil numbers in EpAT and BAT, and after 3 days, in ScAT. In an attempt to restore this HFD-induced drop in adipose tissue eosinophils, we treated 1-week HFD-fed mice with helminth antigens from Schistosoma mansoni or Trichuris suis and evaluated whether the well-known protective metabolic effects of helminth antigens involves BAT activation or beiging. Indeed, antigens of both helminth species induced high numbers of eosinophils in EpAT, but failed to induce beiging. In ScAT, Schistosoma mansoni antigens induced mild eosinophilia, which was accompanied by slightly more beiging. No effects were observed in BAT. To study type 2 responses on brown adipocytes directly, T37i cells were stimulated with IL-4. This increased Ucp1 expression and strongly induced the production of eosinophil chemoattractant CCL11 (+26-fold), revealing that brown adipocytes themselves can attract eosinophils. Our findings indicate that helminth antigen-induced eosinophilia fails to induce profound beiging of white adipocytes. © 2017 Society for Endocrinology.

  8. Mangrove forest against dyke-break-induced tsunami on rapidly subsiding coasts

    Science.gov (United States)

    Takagi, Hiroshi; Mikami, Takahito; Fujii, Daisuke; Esteban, Miguel; Kurobe, Shota

    2016-07-01

    Thin coastal dykes typically found in developing countries may suddenly collapse due to rapid land subsidence, material ageing, sea-level rise, high wave attack, earthquakes, landslides, or a collision with vessels. Such a failure could trigger dam-break tsunami-type flooding, or "dyke-break-induced tsunami", a possibility which has so far been overlooked in the field of coastal disaster science and management. To analyse the potential consequences of one such flooding event caused by a dyke failure, a hydrodynamic model was constructed based on the authors' field surveys of a vulnerable coastal location in Jakarta, Indonesia. In a 2 m land subsidence scenario - which is expected to take place in the study area after only about 10-20 years - the model results show that the floodwaters rapidly rise to a height of nearly 3 m, resembling the flooding pattern of earthquake-induced tsunamis. The depth-velocity product criterion suggests that many of the narrow pedestrian paths behind the dyke could experience strong flows, which are far greater than the safe limits that would allow pedestrian evacuation. A couple of alternative scenarios were also considered to investigate how such flood impacts could be mitigated by creating a mangrove belt in front of the dyke as an additional safety measure. The dyke-break-induced tsunamis, which in many areas are far more likely than regular earthquake tsunamis, cannot be overlooked and thus should be considered in disaster management and urban planning along the coasts of many developing countries.

  9. The importance of rapid, disturbance-induced losses in carbon management and sequestration

    Science.gov (United States)

    Breshears, D.D.; Allen, Craig D.

    2002-01-01

    Management of terrestrial carbon fluxes is being proposed as a means of increasing the amount of carbon sequestered in the terrestrial biosphere. This approach is generally viewed only as an interim strategy for the coming decades while other longer-term strategies are developed and implemented — the most important being the direct reduction of carbon emissions. We are concerned that the potential for rapid, disturbance-induced losses may be much greater than is currently appreciated, especially by the decision-making community. Here we wish to: (1) highlight the complex and threshold-like nature of disturbances — such as fire and drought, as well as the erosion associated with each — that could lead to carbon losses; (2) note the global extent of ecosystems that are at risk of such disturbance-induced carbon losses; and (3) call for increased consideration of and research on the mechanisms by which large, rapid disturbance-induced losses of terrestrial carbon could occur. Our lack of ability as a scientific community to predict such ecosystem dynamics is precluding the effective consideration of these processes into strategies and policies related to carbon management and sequestration. Consequently, scientists need to do more to improve quantification of these potential losses and to integrate them into sound, sustainable policy options.

  10. Methoxychlor and Vinclozolin Induce Rapid Changes in Intercellular and Intracellular Signaling in Liver Progenitor Cells.

    Science.gov (United States)

    Babica, Pavel; Zurabian, Rimma; Kumar, Esha R; Chopra, Rajus; Mianecki, Maxwell J; Park, Joon-Suk; Jaša, Libor; Trosko, James E; Upham, Brad L

    2016-09-01

    Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 µM for MXC and 126 µM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER- or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Neuronal activity rapidly induces transcription of the CREB-regulated microRNA-132, in vivo

    DEFF Research Database (Denmark)

    Nudelman, Aaron Samuel; DiRocco, Derek P; Lambert, Talley J

    2010-01-01

    Activity-dependent changes in gene-expression are believed to underlie the molecular representation of memory. In this study, we report that in vivo activation of neurons rapidly induces the CREB-regulated microRNA miR-132. To determine if production of miR-132 is regulated by neuronal activity its......, olfactory bulb, and striatum by contextual fear conditioning, odor-exposure, and cocaine-injection, respectively, also increased pri-miR-132. Induction kinetics of pri-miR-132 were monitored and found to parallel those of immediate early genes, peaking at 45 min and returning to basal levels within 2 h...

  12. Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus

    OpenAIRE

    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.

    2013-01-01

    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 a...

  13. 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

    The presence of AT2 receptors in mitochondria and their role in NO generation and cell aging were recently demonstrated in various human and mouse non-tumour cells. We investigated the intracellular distribution of AT2 receptors including their presence in mitochondria and the role in the induction...... 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...

  14. 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

    2013-01-01

    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 107 or 108 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. PMID:23468490

  15. Optimization of microwave-induced chemical etching for rapid development of neutron-induced recoil tracks in CR-39 detectors

    International Nuclear Information System (INIS)

    Sahoo, G.S.; Tripathy, S.P.; Bandyopadhyay, T.

    2014-01-01

    A systematic investigation is carried out to optimize the recently established microwave-induced chemical etching (MICE) parameters for rapid development of neutron-induced recoil tracks in CR-39 detectors. Several combinations of all available microwave powers with different etching durations were analysed to determine the most suitable etching condition. The etching duration was found to reduce with increasing microwave power and the tracks were observed at about 18, 15, 12, and 6 min for 300, 450, 600 and 900 W of microwave powers respectively compared to a few hours in chemical etching (CE) method. However, for complete development of tracks the etching duration of 30, 40, 50 and 60 min were found to be suitable for the microwave powers of 900, 600, 450 and 300 W, respectively. Temperature profiles of the etchant for all the available microwave powers at different etching durations were generated to regulate the etching process in a controlled manner. The bulk etch rates at different microwave powers were determined by 2 methods, viz., gravimetric and removed thickness methods. A logarithmic expression was used to fit the variation of bulk etch rate with microwave power. Neutron detection efficiencies were obtained for all the cases and the results on track parameters obtained with MICE technique were compared with those obtained from another detector processed with chemical etching. - Highlights: • Microwave-induced chemical etching method is optimized for rapid development of recoil tracks due to neutrons in CR-39 detector. • Several combinations of microwave powers and etching durations are investigated to standardize the suitable etching condition. • Bulk-etch rates are determined for all microwave powers by two different methods, viz. gravimetric and removed thickness method. • The method is found to be simple, effective and much faster compared to conventional chemical etching

  16. Visible laser induced positive ion emissions from NaCl nanoparticles prepared by droplet rapid drying

    International Nuclear Information System (INIS)

    Sun, Mao-Xu; Guo, Deng-Zhu; Xing, Ying-Jie; Zhang, Geng-Min

    2012-01-01

    Highlights: ► NaCl nanoparticles were firstly prepared by heat induced explosion on silicon wafer. ► We found that laser induced ion emissions from NaCl nanoparticles are more prominent. ► We found that water adsorption can efficiently enhance laser induced ion emissions. ► The ultra-photothermal effect in NaCl nanoparticles was observed and explained. - Abstract: A novel convenient way for the formation of sodium chloride (NaCl) nanoparticles on silicon wafer is proposed by using a droplet rapid drying method. The laser induced positive ion emissions from NaCl nanoparticles with and without water treatment is demonstrated by using a laser desorption/ionization time-of-flight mass spectrometer, with laser intensity well below the plasma formation threshold. It is found that the positive ion emissions from NaCl nanoparticles are obviously higher than that from microsize NaCl particles under soft 532 nm laser irradiations, and water adsorption can efficiently enhance the ion emissions from NaCl nanoparticles. The initial kinetic energies of the emitted ions are estimated as 16–17 eV. The synergy of the ultra-thermal effect in nanomaterials, the defect-mediated multiphoton processes, and the existence of intermediate states in NaCl-water interfaces are suggested as the mechanisms.

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

    International Nuclear Information System (INIS)

    Hussain, T; Gondal, M A

    2013-01-01

    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.

  18. 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.

  19. Rapid grounding line migration induced by internal variability of a marine-terminating ice stream

    Science.gov (United States)

    Robel, A.; Schoof, C.; Tziperman, E.

    2013-12-01

    Numerous studies have found significant variability in the velocity of ice streams to be a prominent feature of geomorphologic records in the Siple Coast (Catania et al. 2012) and other regions in West Antarctica (Dowdeswell et al. 2008). Observations indicate that grounding line position is strongly influenced by ice stream variability, producing rapid grounding line migration in the recent past (Catania et al. 2006) and the modern (Joughin & Tulaczyk 2002). We analyze the interaction of grounding line mass flux and position in a marine-terminating ice stream using a stretch-coordinate flowline model. This model is based on that described in Schoof (2007), with a mesh refined near the grounding line to ensure accurate resolution of the mechanical transition zone. Here we have added lateral shear stress (Dupont & Alley 2005) and an undrained plastic bed (Tulaczyk et al. 2000). The parameter dependence of ice stream variability seen in this model compares favorably to both simpler (Robel et al. 2013) and more complex (van der Wel et al. 2013) models, though with some key differences. We find that thermally-induced internal ice stream variability can cause very rapid grounding line migration even in the absence of retrograde bed slopes or external forcing. Activation waves propagate along the ice stream length and trigger periods of rapid grounding line migration. We compare the behavior of the grounding line due to internal ice stream variability to changes triggered externally at the grounding line such as the rapid disintegration of buttressing ice shelves. Implications for Heinrich events and the Marine Ice Sheet Instability are discussed.

  20. Rapid Prototyping Amphiphilic Polymer/Hydroxyapatite Composite Scaffolds with Hydration-Induced Self-Fixation Behavior

    Science.gov (United States)

    Kutikov, Artem B.; Gurijala, Anvesh

    2015-01-01

    Two major factors hampering the broad use of rapid prototyped biomaterials for tissue engineering applications are the requirement for custom-designed or expensive research-grade three-dimensional (3D) printers and the limited selection of suitable thermoplastic biomaterials exhibiting physical characteristics desired for facile surgical handling and biological properties encouraging tissue integration. Properly designed thermoplastic biodegradable amphiphilic polymers can exhibit hydration-dependent hydrophilicity changes and stiffening behavior, which may be exploited to facilitate the surgical delivery/self-fixation of the scaffold within a physiological tissue environment. Compared to conventional hydrophobic polyesters, they also present significant advantages in blending with hydrophilic osteoconductive minerals with improved interfacial adhesion for bone tissue engineering applications. Here, we demonstrated the excellent blending of biodegradable, amphiphilic poly(D,L-lactic acid)-poly(ethylene glycol)-poly(D,L-lactic acid) (PLA-PEG-PLA) (PELA) triblock co-polymer with hydroxyapatite (HA) and the fabrication of high-quality rapid prototyped 3D macroporous composite scaffolds using an unmodified consumer-grade 3D printer. The rapid prototyped HA-PELA composite scaffolds and the PELA control (without HA) swelled (66% and 44% volume increases, respectively) and stiffened (1.38-fold and 4-fold increases in compressive modulus, respectively) in water. To test the hypothesis that the hydration-induced physical changes can translate into self-fixation properties of the scaffolds within a confined defect, a straightforward in vitro pull-out test was designed to quantify the peak force required to dislodge these scaffolds from a simulated cylindrical defect at dry versus wet states. Consistent with our hypothesis, the peak fixation force measured for the PELA and HA-PELA scaffolds increased 6-fold and 15-fold upon hydration, respectively. Furthermore, we showed that

  1. Photoelectrochemical Sensors for the Rapid Detection of DNA Damage Induced by Some Nanoparticles

    Directory of Open Access Journals (Sweden)

    M. Jamaluddin Ahmed

    2010-06-01

    Full Text Available Photoelectrochemcal sensors were developed for the rapid detection of oxidative DNA damage induced by titanium dioxide and polystyrene nanoparticles. Each sensor is a multilayer film prepared on a tin oxide nanoparticle electrode using layer- by-layer self assembly and is composed of separate layer of a photoelectrochemical indicator, DNA. The organic compound and heavy metals represent genotoxic chemicals leading two major damaging mechanisms, DNA adduct formation and DNA oxidation. The DNA damage is detected by monitoring the change of photocurrent of the indicator. In one sensor configuration, a DNA intercalator, Ru(bpy2 (dppz2+ [bpy=2, 2′ -bipyridine, dppz=dipyrido( 3, 2-a: 2′ 3′-c phenazine], was employed as the photoelectrochemical indicator. The damaged DNA on the sensor bound lesser Ru(bpy2 (dppz2+ than the intact DNA, resulting in a drop in photocurrent. In another configuration, ruthenium tris(bipyridine was used as the indicator and was immobilized on the electrode underneath the DNA layer. After oxidative damage, the DNA bases became more accessible to photoelectrochemical oxidation than the intact DNA, producing a rise in photocurrent. Both sensors displayed substantial photocurrent change after incubation in titanium dioxide / polystyrene solution in a time – dependent manner. According to the data, damage of the DNA film was completed in 1h in titanium dioxide / polystyrene solution. In addition, the titanium dioxide induced much more sever damage than polysterene. The results were verified independently by gel electrophoresis and UV-Vis absorbance experiments. The photoelectrochemical reaction can be employed as a new and inexpensive screening tool for the rapid assessment of the genotoxicity of existing and new chemicals.

  2. Photoelectrochemical sensors for the rapid detection of DNA damage Induced by some nanoparticles

    International Nuclear Information System (INIS)

    Ahmed, M.J.; Zhang, B.T.; Guo, L.H.

    2010-01-01

    Photoelectrochemical sensors were developed for the rapid detection of oxidative DNA damage induced by titanium dioxide and polystyrene nanoparticles. Each sensor is a multilayer film prepared on a tin oxide nanoparticle electrode using layer- by-layer self assembly and is composed of separate layer of a photoelectrochemical indicator, DNA. The organic compound and heavy metals represent genotoxic chemicals leading two major damaging mechanisms, DNA adduct formation and DNA oxidation. The DNA damage is detected by monitoring the change of photocurrent of the indicator. In one sensor configuration, a DNA intercalator, Ru(bpy)2 (dppz)2+ [bpy=2, 2' -bipyridine, dppz=dipyrido (3, 2-a: 2' 3'-c) phenazine], was employed as the photoelectrochemical indicator. The damaged DNA on the sensor bound lesser Ru(bpy)2 (dppz)2+ than the intact DNA, resulting in a drop in photocurrent. In another configuration, ruthenium tris(bipyridine) was used as the indicator and was immobilized on the electrode underneath the DNA layer. After oxidative damage, the DNA bases became more accessible to photoelectrochemical oxidation than the intact DNA, producing a rise in photocurrent. Both sensors displayed substantial photocurrent change after incubation in titanium dioxide / polystyrene solution in a time . dependent manner. According to the data, damage of the DNA film was completed in 1h in titanium dioxide / polystyrene solution. In addition, the titanium dioxide induced much more sever damage than polystyrene. The results were verified independently by gel electrophoresis and UV-Vis absorbance experiments. The photoelectrochemical reaction can be employed as a new and inexpensive screening tool for the rapid assessment of the genotoxicity of existing and new chemicals. (author)

  3. Synthetic ciguatoxin CTX 3C induces a rapid imbalance in neuronal excitability.

    Science.gov (United States)

    Martín, Victor; Vale, Carmen; Hirama, Masahiro; Yamashita, Shuji; Rubiolo, Juan Andrés; Vieytes, Mercedes R; Botana, Luis M

    2015-06-15

    Ciguatera is a human global disease caused by the consumption of contaminated fish that have accumulated ciguatoxins (CTXs), sodium channel activator toxins. Symptoms of ciguatera include neurological alterations such as paraesthesiae, dysaesthesiae, depression, and heightened nociperception, among others. An important issue to understand these long-term neurological alterations is to establish the role that changes in activity produced by CTX 3C represent to neurons. Here, the effects of synthetic ciguatoxin CTX 3C on membrane potential, spontaneous spiking, and properties of synaptic transmission in cultured cortical neurons of 11-18 days in vitro (DIV) were evaluated using electrophysiological approaches. CTX 3C induced a large depolarization that decreased neuronal firing and caused a rapid inward tonic current that was primarily GABAergic. Moreover, the toxin enhanced the amplitude of miniature postsynaptic inhibitory currents (mIPSCs), whereas it decreased the amplitude of miniature postsynaptic excitatory currents (mEPSCs). The frequency of mIPSCs increased, whereas the frequency of mEPSCs remained unaltered. We describe, for the first time, that a rapid membrane depolarization caused by CTX 3C in cortical neurons activates mechanisms that tend to suppress electrical activity by shifting the balance between excitatory and inhibitory synaptic transmission toward inhibition. Indeed, these results suggest that the acute effects of CTX on synaptic transmission could underlie some of the neurological symptoms caused by ciguatera in humans.

  4. Association of malignancy with rapid growth in early lesions induced by irradiation of rat skin

    International Nuclear Information System (INIS)

    McGregor, J.F.

    1979-01-01

    Epithelial lesions induced by irradiation of rat skin were studied to determine (a) the relationship of malignancy to dose, (b) the types of lesions and circumstances leading to overt malignancy, and (c) the growth rates of lesions progressing to malignancy versus those of lesions remaining benign. High doses of radiation were shown to be associated with the production of epidermal cancers, the maximum yield being obtained at 6,400 rads. Conversely, a peak yield of noncancerous lesions was obtained at 1,600 rads. This association between malignancy and high dose was consistent for cancers evolving from warts, cysts, and chronic ulcers. Although the proportion of warts among the induced lesions was much higher than that of the cysts or chronic ulcers (76, 14, and 10%, respectively), the likelihood of warts becoming cancerous was substantially lower (14, 23, and 21%). The combined data for all doses showed that the latency period of the epidermal cancers was significantly (P = 0.015) shorter than that of the benign tumors. Rapid growth rates were observed for warts, cysts, and chronic ulcers progressing to overt cancer, and these did not overlap at any point on the growth scale with rates for benign tumors. This finding suggested that the potential for malignant development had been established early in the carcinogenic process, very likely at induction

  5. Shock wave and flame front induced detonation in a rapid compression machine

    Science.gov (United States)

    Wang, Y.; Qi, Y.; Xiang, S.; Mével, R.; Wang, Z.

    2018-05-01

    The present study focuses on one mode of detonation initiation observed in a rapid compression machine (RCM). This mode is referred to as shock wave and flame front-induced detonation (SWFID). Experimental high-speed imaging and two-dimensional numerical simulations with skeletal chemistry are combined to unravel the dominant steps of detonation initiation under SWFID conditions. It is shown that the interaction between the shock wave generated by the end-gas auto-ignition and the spherical flame creates a region of high pressure and temperature which enables the acceleration of the flame front and the detonation onset. The experimental observation lacks adequate spatial and temporal resolution despite good reproducibility of the detonation onset. Based on the numerical results, phenomenological interpretation of the event within the framework of shock wave refraction indicates that the formation of a free-precursor shock wave at the transition between regular and irregular refraction may be responsible for detonation onset. The present results along with previous findings on shock wave reflection-induced detonation in the RCM indicate that super-knock occurs after the interaction of the shock wave generated by end-gas auto-ignition with the RCM walls, preignition flame, or another shock wave.

  6. Assessment of a potential rapid condensation induced water hammer in a passive auxiliary feedwater system

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Jong Chull; Shin, Byung Soo; Do, Kyu Sik [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Moody, Frederick J. [General Electric (Retired), CA (United States)

    2012-10-15

    A passive auxiliary feedwater system (PAFS) which is incorporated in the APR+ system is a kind of closed natural circulation loop. The PAFS has no operating functions during normal plant operation, but it has a dedicated safety function of the residual heat removal following initiating events, including the unlikely event of the most limiting single failure occurring coincident with a loss of offsite power, when the feedwater system becomes inoperable or unavailable. Even in the unlikely event of a station blackout, the isolation valves can be opened either by DC power or manual operation and then the PAFS can also provide adequate condensate to the steam generator (SG). The PAFS piping in the vicinity of each of the two SGs is designed to minimize the potential for destructive water hammer during start up operation by setting the stroke time for full close or full open of the condensate isolation valves upon receipt of a passive auxiliary feedwater actuation signal. The temperature of the stagnant condensate water and its surrounding tubes and piping during the reactor normal operation modes may fall to the ambient temperature. A possible concern is the introduction of saturated steam into the PAFS recirculation pipe downstream of the PCHX in the beginning of the PAFS operation. Although the steam introduction rate is expected to be slow, a rapid condensation rate is expected due to the initial cold surrounding temperature in the pipe, which could result in a localized pressure reduction and the propagation of decompression and velocity disturbances into the condensate water leg, which might cause the sudden closure of check valves and associated water hammer. Thus, it is requisite for the licensing review of the PAFS design to confirm if destructive water hammers will not be produced due to such rapid condensation induced decompressions in the system. This paper addresses an assessment of the potential local decompressions which could result from the steam

  7. 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.

  8. Cold exposure rapidly induces virtual saturation of brown adipose tissue nuclear T3 receptors

    International Nuclear Information System (INIS)

    Bianco, A.C.; Silva, J.E.

    1988-01-01

    Cold exposure induces a rapid increase in uncoupling protein (UCP) concentration in the brown adipose tissue (BAT) of euthyroid, but not hypothyroid, rats. To normalize this response with exogenous 3,5,3'-triiodothyronine (T 3 ), it is necessary to cause systemic hyperthyroidism. In contrast, the same result can be obtained with just replacement doses of thyroxine (T 4 ) and, in euthyroid rats, the normal response of UCP to cold occurs without hyperthyroid plasma T 3 levels. Consequently, the authors explored the possibility that the cold-induced activation of the type II 5'-deiodinase resulted in high levels of nuclear T 3 receptor occupancy in euthyroid rats. Studies were performed with pulse injections of tracer T 3 or T 4 in rats exposed to 4 degree C for different lengths of time (1 h-3 wk). Within 4 h of cold exposure, they observed a significant increase in the nuclear [ 125 I]T 3 derived from the tracer [ 125 I]T 4 injections (T 3 [T 4 ]) and a significant reduction in the nuclear [ 125 I]T 3 derived from [ 125 I]T 3 injections (T 3 [T 3 ]). The number of BAT nuclear T 3 receptors did not increase for up to 3 wk of observation at 4 degree C. The mass of nuclear-bound T 3 was calculated from the nuclear tracer [ 125 I]T 3 [T 3 ] and [ 125 I]T 3 [T 4 ] at equilibrium and the specific activity of serum T 3 and T 4 , respectively. By 4 h after the initiation of the cold exposure, the receptors were >95% occupied and remained so for the 3 weeks of observation. They conclude that the simultaneous activation of the deiodinase with adrenergic BAT stimulation serves the purpose of nearly saturating the nuclear T 3 receptors. This makes possible the realization of the full thermogenic potential of the tissue without causing systemic hyperthyroidism

  9. Microstructural modifications induced by rapid thermal annealing in plasma deposited SiOxNyHz films

    International Nuclear Information System (INIS)

    Prado, A. del; San Andres, E.; Martil, I.; Gonzalez-Diaz, G.; Bravo, D.; Lopez, F.J.; Fernandez, M.; Martinez, F.L.

    2003-01-01

    The effect of rapid thermal annealing (RTA) processes on the structural properties of SiO x N y H z films was investigated. The samples were deposited by the electron cyclotron resonance plasma method, using SiH 4 , O 2 and N 2 as precursor gases. For SiO x N y H z films with composition close to that of SiO 2 , which have a very low H content, RTA induces thermal relaxation of the lattice and improvement of the structural order. For films of intermediate composition and of compositions close to SiN y H z , the main effect of RTA is the release of H at high temperatures (T>700 deg. C). This H release is more significant in films containing both Si-H and N-H bonds, due to cooperative reactions between both kinds of bonds. In these films the degradation of structural order associated to H release prevails over thermal relaxation, while in those films with only N-H bonds, thermal relaxation predominates. For annealing temperatures in the 500-700 deg. C range, the passivation of dangling bonds by the nonbonded H in the films and the transition from the paramagnetic state to the diamagnetic state of the K center result in a decrease of the density of paramagnetic defects. The H release observed at high annealing temperatures is accompanied by an increase of density of paramagnetic defects

  10. Rapid detection of soils contaminated with heavy metals and oils by laser induced breakdown spectroscopy (LIBS).

    Science.gov (United States)

    Kim, Gibaek; Kwak, Jihyun; Kim, Ki-Rak; Lee, Heesung; Kim, Kyoung-Woong; Yang, Hyeon; Park, Kihong

    2013-12-15

    A laser induced breakdown spectroscopy (LIBS) coupled with the chemometric method was applied to rapidly discriminate between soils contaminated with heavy metals or oils and clean soils. The effects of the water contents and grain sizes of soil samples on LIBS emissions were also investigated. The LIBS emission lines decreased by 59-75% when the water content increased from 1.2% to 7.8%, and soil samples with a grain size of 75 μm displayed higher LIBS emission lines with lower relative standard deviations than those with a 2mm grain size. The water content was found to have a more pronounced effect on the LIBS emission lines than the grain size. Pelletizing and sieving were conducted for all samples collected from abandoned mining areas and military camp to have similar water contents and grain sizes before being analyzed by the LIBS with the chemometric analysis. The data show that three types of soil samples were clearly discerned by using the first three principal components from the spectral data of soil samples. A blind test was conducted with a 100% correction rate for soil samples contaminated with heavy metals and oil residues. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Spectroscopic sensitivity of real-time, rapidly induced phytochemical change in response to damage.

    Science.gov (United States)

    Couture, John J; Serbin, Shawn P; Townsend, Philip A

    2013-04-01

    An ecological consequence of plant-herbivore interactions is the phytochemical induction of defenses in response to insect damage. Here, we used reflectance spectroscopy to characterize the foliar induction profile of cardenolides in Asclepias syriaca in response to damage, tracked in vivo changes and examined the influence of multiple plant traits on cardenolide concentrations. Foliar cardenolide concentrations were measured at specific time points following damage to capture their induction profile. Partial least-squares regression (PLSR) modeling was employed to calibrate cardenolide concentrations to reflectance spectroscopy. In addition, subsets of plants were either repeatedly sampled to track in vivo changes or modified to reduce latex flow to damaged areas. Cardenolide concentrations and the induction profile of A. syriaca were well predicted using models derived from reflectance spectroscopy, and this held true for repeatedly sampled plants. Correlations between cardenolides and other foliar-related variables were weak or not significant. Plant modification for latex reduction inhibited an induced cardenolide response. Our findings show that reflectance spectroscopy can characterize rapid phytochemical changes in vivo. We used reflectance spectroscopy to identify the mechanisms behind the production of plant secondary metabolites, simultaneously characterizing multiple foliar constituents. In this case, cardenolide induction appears to be largely driven by enhanced latex delivery to leaves following damage. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  12. Cyclic AMP Pathway Activation and Extracellular Zinc Induce Rapid Intracellular Zinc Mobilization in Candida albicans

    Science.gov (United States)

    Kjellerup, Lasse; Winther, Anne-Marie L.; Wilson, Duncan; Fuglsang, Anja T.

    2018-01-01

    Zinc is an essential micronutrient, required for a range of zinc-dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo-5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc-signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However, zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen. PMID:29619016

  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 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.

  15. 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.

  16. Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions

    Directory of Open Access Journals (Sweden)

    Benedito M.A.C.

    2001-01-01

    Full Text Available Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei are involved in the generation of rapid eye movement (REM sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase, the enzyme which inactivates acetylcholine (Ach in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min-1 mg protein-1 were assayed photometrically. The results (mean ± SD obtained showed a statistically significant (Student t-test increase in total Achase activity in the pons (control: 147.8 ± 12.8, REM sleep-deprived: 169.3 ± 17.4, N = 6 for both groups, P<0.025 and thalamus (control: 167.4 ± 29.0, REM sleep-deprived: 191.9 ± 15.4, N = 6 for both groups, P<0.05. Increases in membrane-bound Achase activity in the pons (control: 171.0 ± 14.7, REM sleep-deprived: 189.5 ± 19.5, N = 6 for both groups, P<0.05 and soluble enzyme activity in the medulla oblongata (control: 147.6 ± 16.3, REM sleep-deprived: 163.8 ± 8.3, N = 6 for both groups, P<0.05 were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity

  17. Rapid Myoglobin Aggregation through Glucosamine-Induced α-Dicarbonyl Formation.

    Science.gov (United States)

    Hrynets, Yuliya; Ndagijimana, Maurice; Betti, Mirko

    2015-01-01

    The extent of glycation and conformational changes of horse myoglobin (Mb) upon glycation with N-acetyl-glucosamine (GlcNAc), glucose (Glc) and glucosamine (GlcN) were investigated. Among tested sugars, the rate of glycation with GlcN was the most rapid as shown by MALDI and ESI mass spectrometries. Protein oxidation, as evaluated by the amount of carbonyl groups present on Mb, was found to increase exponentially in Mb-Glc conjugates over time, whereas in Mb-GlcN mixtures the carbonyl groups decreased significantly after maximum at 3 days of the reaction. The reaction between GlcN and Mb resulted in a significantly higher amount of α-dicarbonyl compounds, mostly glucosone and 3-deoxyglucosone, ranging from and 27 to 332 mg/L and from 14 to 304 mg/L, respectively. Already at 0.5 days, tertiary structural changes of Mb-GlcN conjugate were observed by altered tryptophan fluorescence. A reduction of metmyoglobin to deoxy-and oxymyoglobin forms was observed on the first day of reaction, coinciding with the greatest amount of glucosone produced. In contrast to native α-helical myoglobin, 41% of the glycated protein sequence was transformed into a β-sheet conformation, as determined by circular dichroism spectropolarimetry. Transmission electron microscopy demonstrated that Mb glycation with GlcN causes the formation of amorphous or fibrous aggregates, started already at 3 reaction days. These aggregates bind to an amyloid-specific dye thioflavin T. With the aid of α-dicarbonyl compounds and advanced products of reaction, this study suggests that the Mb glycation with GlcN induces the unfolding of an initially globular protein structure into amyloid fibrils comprised of a β-sheet structure.

  18. Rapid reversal of heart failure in a patient with pheochromocytoma and catecholamine-induced myocarditis/cardiomyopathy

    International Nuclear Information System (INIS)

    Ahmed, I.; Sankaran, R.; Al-Addad, A.

    2002-01-01

    Pheochromocytoma is rare and usually presents as paroxysal or sustained hypertension, nonetheless, it can also cause severe acute pulmonary edema in normotensive individuals. We present a case with pheochromocytoma and severe left ventricular failure caused by catecholamine induced myocarditis/cardiomyopathy. Severe left ventricular failure resolved rapidly and left ventricular systolic function became normal within two weeks of medical treatment. Later, patient underwent elective and uneventful surgical removal of pheochromocytoma. (author)

  19. 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.

  20. Rapid and Persistent Suppression of Feeding Behavior Induced by Sensitization Training in "Aplysia"

    Science.gov (United States)

    Acheampong, Ama; Kelly, Kathleen; Shields-Johnson, Maria; Hajovsky, Julie; Wainwright, Marcy; Mozzachiodi, Riccardo

    2012-01-01

    In "Aplysia," noxious stimuli induce sensitization of defensive responses. However, it remains largely unknown whether such stimuli also alter nondefensive behaviors. In this study, we examined the effects of noxious stimuli on feeding. Strong electric shocks, capable of inducing sensitization, also led to the suppression of feeding. The use of…

  1. RECOMBINANT HUMAN INTERLEUKIN-6 INDUCES A RAPID AND REVERSIBLE ANEMIA IN CANCER-PATIENTS

    NARCIS (Netherlands)

    NIEKEN, J; MULDER, NH; VELLENGA, E; LIMBURG, PC; PIERS, DA; DEVRIES, EGE

    1995-01-01

    Initial studies have shown that recombinant human interleukin-6 (rhIL-6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II

  2. 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

  3. ER Alpha Rapid Signaling Is Required for Estrogen Induced Proliferation and Migration of Vascular Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Qing Lu

    Full Text Available Estrogen promotes the proliferation and migration of vascular endothelial cells (ECs, which likely underlies its ability to accelerate re-endothelialization and reduce adverse remodeling after vascular injury. In previous studies, we have shown that the protective effects of E2 (the active endogenous form of estrogen in vascular injury require the estrogen receptor alpha (ERα. ERα transduces the effects of estrogen via a classical DNA binding, "genomic" signaling pathway and via a more recently-described "rapid" signaling pathway that is mediated by a subset of ERα localized to the cell membrane. However, which of these pathways mediates the effects of estrogen on endothelial cells is poorly understood. Here we identify a triple point mutant version of ERα (KRR ERα that is specifically defective in rapid signaling, but is competent to regulate transcription through the "genomic" pathway. We find that in ECs expressing wild type ERα, E2 regulates many genes involved in cell migration and proliferation, promotes EC migration and proliferation, and also blocks the adhesion of monocytes to ECs. ECs expressing KRR mutant ERα, however, lack all of these responses. These observations establish KRR ERα as a novel tool that could greatly facilitate future studies into the vascular and non-vascular functions of ERα rapid signaling. Further, they support that rapid signaling through ERα is essential for many of the transcriptional and physiological responses of ECs to E2, and that ERα rapid signaling in ECs, in vivo, may be critical for the vasculoprotective and anti-inflammatory effects of estrogen.

  4. Estrogen induces rapid decrease in dendritic thorns of CA3 pyramidal neurons in adult male rat hippocampus

    International Nuclear Information System (INIS)

    Tsurugizawa, Tomokazu; Mukai, Hideo

    2005-01-01

    Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1 nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2 h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but not by MK-801 (NMDA receptor antagonist). ERα agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ERβ agonist DPN did not affect the density of thorns. Note that a 1 nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ERα was performed using purified RC-19 antibody. The localization of ERα (67 kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ERα and MAP kinase

  5. Rapid induction of dopamine sensitization in the nucleus accumbens shell induced by a single injection of cocaine.

    Science.gov (United States)

    Singer, Bryan F; Bryan, Myranda A; Popov, Pavlo; Robinson, Terry E; Aragona, Brandon J

    2017-05-01

    Repeated intermittent exposure to cocaine results in the neurochemical sensitization of dopamine (DA) transmission within the nucleus accumbens (NAc). Indeed, the excitability of DA neurons in the ventral tegmental area (VTA) is enhanced within hours of initial psychostimulant exposure. However, it is not known if this is accompanied by a comparably rapid change in the ability of cocaine to increase extracellular DA concentrations in the ventral striatum. To address this question we used fast-scan cyclic voltammetry (FSCV) in awake-behaving rats to measure DA responses in the NAc shell following an initial intravenous cocaine injection, and then again 2-h later. Both injections quickly elevated DA levels in the NAc shell, but the second cocaine infusion produced a greater effect than the first, indicating sensitization. This suggests that a single injection of cocaine induces sensitization-related plasticity very rapidly within the mesolimbic DA system. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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).

  7. Rapid thermal and swift heavy ion induced annealing of Co ion implanted GaN films

    International Nuclear Information System (INIS)

    Baranwal, V.; Pandey, A. C.; Gerlach, J. W.; Rauschenbach, B.; Karl, H.; Kanjilal, D.; Avasthi, D. K.

    2008-01-01

    Thin epitaxial GaN films grown on 6H-SiC(0001) substrates were implanted with 180 keV Co ions at three different fluences. As-implanted samples were characterized with secondary ion mass spectrometry and Rutherford backscattering spectrometry to obtain the Co depth profiles and the maximum Co concentrations. As-implanted samples were annealed applying two different techniques: rapid thermal annealing and annealing by swift heavy ion irradiation. Rapid thermal annealing was done at two temperatures: 1150 deg. C for 20 s and 700 deg. C for 5 min. 200 MeV Ag ions at two fluences were used for annealing by irradiation. Crystalline structure of the pristine, as-implanted, and annealed samples was investigated using x-ray diffraction, and the results were compared. Improvement of the crystalline quality was observed for rapid thermal annealed samples at the higher annealing temperature as confirmed with rocking curve measurements. The results indicate the presence of Co clusters in these annealed samples. Swift heavy ion irradiation with the parameters chosen for this study did not lead to a significant annealing

  8. 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.

  9. Pressure-jump induced rapid solidification of melt: a method of preparing amorphous materials

    Science.gov (United States)

    Liu, Xiuru; Jia, Ru; Zhang, Doudou; Yuan, Chaosheng; Shao, Chunguang; Hong, Shiming

    2018-04-01

    By using a self-designed pressure-jump apparatus, we investigated the melt solidification behavior in rapid compression process for several kinds of materials, such as elementary sulfur, polymer polyether-ether-ketone (PEEK) and poly-ethylene-terephthalate, alloy La68Al10Cu20Co2 and Nd60Cu20Ni10Al10. Experimental results clearly show that their melts could be solidified to be amorphous states through the rapid compression process. Bulk amorphous PEEK with 24 mm in diameter and 12 mm in height was prepared, which exceeds the size obtained by melt quenching method. The bulk amorphous sulfur thus obtained exhibited extraordinarily high thermal stability, and an abnormal exothermic transition to liquid sulfur was observed at around 396 K for the first time. Furthermore, it is suggested that the glass transition pressure and critical compression rate exist to form the amorphous phase. This approach of rapid compression is very attractive not only because it is a new technique of make bulk amorphous materials, but also because novel properties are expected in the amorphous materials solidified by the pressure-jump within milliseconds or microseconds.

  10. 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......-4, and eotaxin/CCL11 (88% CD95 and 84% CD95L). We therefore propose that ligation of such newly induced CCR3 on peripheral and germinal B cells by eotaxin/CCL11 leads to the enhanced levels of CD95 and CD95L expression. Ligation of CD95 by its CD95L expressed on neigboring B cells triggers relevant....... Interaction between CCR3 and eotaxin/CCL11 may, besides promoting allergic reactions, drive activated B cells to apoptosis, thereby reducing levels of Ig production, including IgE, and consequently limit the development of the humoral immune response. The apoptotic action of eotaxin/CCL11 suggests...

  11. CD 95 mediated apoptosis in embryogenesis: implication in tooth development.

    Czech Academy of Sciences Publication Activity Database

    Matalová, Eva; Šetková, Jana; Blackburn, J.; Míšek, Ivan; Sharpe, P. T.

    2006-01-01

    Roč. 9, 3 (2006), s. 123-128 ISSN 1397-5927 R&D Projects: GA ČR GA304/04/0101; GA MŠk OC B23.001 Institutional research plan: CEZ:AV0Z50450515 Keywords : fas * embryonic development * odontogenesis Subject RIV: EB - Genetics ; Molecular Biology

  12. Fas-induced apoptosis in malnourished infants

    African Journals Online (AJOL)

    EL-HAKIM

    deprivation in animals, including man11. Factor of apoptosis signal (Fas) induces apoptosis in activated T cells when they are repeatedly stimulated by antigen and functions to maintain T cell tolerance by deleting auto reactive cells12. The functional role of Fas (CD95) in the immune system has been examined in a variety ...

  13. 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

    , the mechanisms whereby TRM cells induce rapid recall responses need further investigation. OBJECTIVES: To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. METHODS: To address these questions, we analysed responses......BACKGROUND: Skin-resident memory T (TRM ) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore......, 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....

  14. 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.

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

    DEFF Research Database (Denmark)

    Zeng, Wei; Shen, Yao; Zhang, Ning

    2012-01-01

    Nanostructured pure aluminum was fabricated by heavy cold-rolling and then subjected to recovery annealing either by applying electric pulse annealing or by traditional air furnace annealing. Both annealing treatments resulted in an increase in yield strength due to the occurrence of a “dislocation...... 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...

  16. 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.

  17. 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.

  18. Rapid, Directed Differentiation of Retinal Pigment Epithelial Cells from Human Embryonic or Induced Pluripotent Stem Cells

    OpenAIRE

    Foltz, LP; Clegg, DO

    2017-01-01

    We describe a robust method to direct the differentiation of pluripotent stem cells into retinal pigment epithelial cells (RPE). The purpose of providing a detailed and thorough protocol is to clearly demonstrate each step and to make this readily available to researchers in the field. This protocol results in a homogenous layer of RPE with minimal or no manual dissection needed. The method presented here has been shown to be effective for induced pluripotent stem cells (iPSC) and human embry...

  19. 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

  20. Estrogens induce rapid cytoskeleton re-organization in human dermal fibroblasts via the non-classical receptor GPR30.

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    Julie Carnesecchi

    Full Text Available The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2 addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation.

  1. Estrogens induce rapid cytoskeleton re-organization in human dermal fibroblasts via the non-classical receptor GPR30.

    Science.gov (United States)

    Carnesecchi, Julie; Malbouyres, Marilyne; de Mets, Richard; Balland, Martial; Beauchef, Gallic; Vié, Katell; Chamot, Christophe; Lionnet, Claire; Ruggiero, Florence; Vanacker, Jean-Marc

    2015-01-01

    The post-menopausal decrease in estrogen circulating levels results in rapid skin deterioration pointing out to a protective effect exerted by these hormones. The identity of the skin cell type responding to estrogens is unclear as are the cellular and molecular processes they elicit. Here, we reported that lack of estrogens induces rapid re-organization of the human dermal fibroblast cytoskeleton resulting in striking cell shape change. This morphological change was accompanied by a spatial re-organization of focal adhesion and a substantial reduction of their number as evidenced by vinculin and actin co-staining. Cell morphology and cytoskeleton organization was fully restored upon 17β-estradiol (E2) addition. Treatment with specific ER antagonists and cycloheximide respectively showed that the E2 acts independently of the classical Estrogen Receptors and that cell shape change is mediated by non-genomic mechanisms. E2 treatment resulted in a rapid and transient activation of ERK1/2 but not Src or PI3K. We show that human fibroblasts express the non-classical E2 receptor GPR30 and that its agonist G-1 phenocopies the effect of E2. Inhibiting GPR30 through treatment with the G-15 antagonist or specific shRNA impaired E2 effects. Altogether, our data reveal a novel mechanism by which estrogens act on skin fibroblast by regulating cell shape through the non-classical G protein-coupled receptor GPR30 and ERK1/2 activation.

  2. Pollination-Induced Corolla Wilting in Petunia hybrida Rapid Transfer through the Style of a Wilting-Inducing Substance.

    Science.gov (United States)

    Gilissen, L J; Hoekstra, F A

    1984-06-01

    Pollination or wounding of the stigma of Petunia hybrida flowers led to the generation of a wilting factor and its transfer to the corolla within 4 hours. This was concluded from the effects of time course removal of whole styles. In this 4-hour period, pollen tubes traversed only a fraction of the total distance to the ovaries. Both pollination and wounding of the stigma immediately resulted in an increase of ethylene evolution. Accelerated wilting, however, occured only when treated styles remained connected with the ovaries, and not when they were detached and left in the flower. A wilting factor was found in eluates collected from the ovarian end of the styles, only in the case of previous pollination or wounding. In such eluates, the level of the ethylene precursor 1-amino-cyclopropane-1-carboxylic acid was below detection.These observations suggest a material nature of the wilting factor in Petunia flowers, which rapidly passes through the style to the corolla, but which is different from 1-aminocyclopropane-1-carboxylic acid.

  3. Inducing a long-term potentiation in the dentate gyrus is sufficient to produce rapid antidepressant-like effects.

    Science.gov (United States)

    Kanzari, A; Bourcier-Lucas, C; Freyssin, A; Abrous, D N; Haddjeri, N; Lucas, G

    2018-03-01

    Recent hypotheses propose that one prerequisite to obtain a rapid antidepressant (AD) effect would reside in processes of synaptic reinforcement occurring within the dentate gyrus (DG) of the hippocampus independently from neurogenesis. However, to date no relationship has been established between an increased DG synaptic plasticity, and rapid AD-like action. To the best of our knowledge, this study shows for the first time that inducing a long-term potentiation (LTP) within the DG by stimulating the perforant pathway (PP) is sufficient to induce such effects. Thus, Sprague-Dawley rats having undergone a successful LTP displayed a significant reduction of immobility when passed acutely 3 days thereafter in the forced swimming test (FST). Further, in a longitudinal paradigm using the pseudo-depressed Wistar-Kyoto rat strain, LTP elicited a decrease of FST immobility after only 2 days, whereas the AD desipramine was not effective before 16 days. In both models, the influence of LTP was transient, as it was no more observed after 8-9 days. No effects were observed on the locomotor activity or on anxiety-related behavior. Theta-burst stimulation of a brain region anatomically adjacent to the PP remained ineffective in the FST. Immunoreactivity of DG cells for phosphorylated histone H3 and doublecortin were not modified three days after LTP, indicating a lack of effect on both cell proliferation and neurogenesis. Finally, depleting brain serotonin contents reduced the success rate of LTP but did not affect its subsequent AD-like effects. These results confirm the 'plastic DG' theory of rapid AD efficacy. Beyond, they point out stimulations of the entorhinal cortex, from which the PP originates, as putative new approaches in AD research.

  4. 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.

  5. Pressure disequilibria induced by rapid valve closure in noble gas extraction lines

    Science.gov (United States)

    Morgan, Leah; Davidheiser-Kroll, Brett

    2015-01-01

    Pressure disequilibria during rapid valve closures can affect calculated molar quantities for a range of gas abundance measurements (e.g., K-Ar geochronology, (U-Th)/He geochronology, noble gas cosmogenic chronology). Modeling indicates this effect in a system with a 10 L reservoir reaches a bias of 1% before 1000 pipette aliquants have been removed from the system, and a bias of 10% before 10,000 aliquants. Herein we explore the causes and effects of this problem, which is the result of volume changes during valve closure. We also present a solution in the form of an electropneumatic pressure regulator that can precisely control valve motion. This solution reduces the effect to ∼0.3% even after 10,000 aliquants have been removed from a 10 L reservoir.

  6. Pressure disequilibria induced by rapid valve closure in noble gas extraction lines

    Science.gov (United States)

    Morgan, Leah E.; Davidheiser-Kroll, Brett

    2015-06-01

    Pressure disequilibria during rapid valve closures can affect calculated molar quantities for a range of gas abundance measurements (e.g., K-Ar geochronology, (U-Th)/He geochronology, noble gas cosmogenic chronology). Modeling indicates this effect in a system with a 10 L reservoir reaches a bias of 1% before 1000 pipette aliquants have been removed from the system, and a bias of 10% before 10,000 aliquants. Herein we explore the causes and effects of this problem, which is the result of volume changes during valve closure. We also present a solution in the form of an electropneumatic pressure regulator that can precisely control valve motion. This solution reduces the effect to ˜0.3% even after 10,000 aliquants have been removed from a 10 L reservoir.

  7. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans

    DEFF Research Database (Denmark)

    Nauck, Michael A; Kemmeries, Guido; Holst, Jens Juul

    2011-01-01

    DESIGN AND METHODS: Nine healthy volunteers (25 ± 4 years old, BMI: 24.6 ± 4.7 kg/m(2)) were examined with intravenous infusion of GLP-1 (0.8 pmol · kg(-1) · min(-1)) or placebo over 8.5 h. Two liquid mixed meals were administered at a 4-h interval. Gastric emptying was determined, and blood samples were...... drawn frequently. RESULTS: GLP-1 decelerated gastric emptying significantly more after the first meal compared with the second meal (P = 0.01). This was associated with reductions in pancreatic polypeptide levels (marker of vagal activation) after the first but not the second meal (P ... but increased after the second test meal (P gastric emptying is subject to rapid tachyphylaxis at the level of vagal nervous activation. As a consequence, postprandial glucose control by GLP-1 is attenuated after its chronic administration...

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

    DEFF Research Database (Denmark)

    Poulsen, Nicklas N; Andersen, Nina Z; Østergaard, Jesper

    2015-01-01

    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 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...

  9. Rapid tissue regeneration induced by intracellular ATP delivery-A preliminary mechanistic study.

    Directory of Open Access Journals (Sweden)

    Harshini Sarojini

    Full Text Available We have reported a new phenomenon in acute wound healing following the use of intracellular ATP delivery-extremely rapid tissue regeneration, which starts less than 24 h after surgery, and is accompanied by massive macrophage trafficking, in situ proliferation, and direct collagen production. This unusual process bypasses the formation of the traditional provisional extracellular matrix and significantly shortens the wound healing process. Although macrophages/monocytes are known to play a critical role in the initiation and progression of wound healing, their in situ proliferation and direct collagen production in wound healing have never been reported previously. We have explored these two very specific pathways during wound healing, while excluding confounding factors in the in vivo environment by analyzing wound samples and performing in vitro studies. The use of immunohistochemical studies enabled the detection of in situ macrophage proliferation in ATP-vesicle treated wounds. Primary human macrophages and Raw 264.7 cells were used for an in vitro study involving treatment with ATP vesicles, free Mg-ATP alone, lipid vesicles alone, Regranex, or culture medium. Collagen type 1α 1, MCP-1, IL-6, and IL-10 levels were determined by ELISA of the culture supernatant. The intracellular collagen type 1α1 localization was determined with immunocytochemistry. ATP-vesicle treated wounds showed high immunoreactivity towards BrdU and PCNA antigens, indicating in situ proliferation. Most of the cultured macrophages treated with ATP-vesicles maintained their classic phenotype and expressed high levels of collagen type 1α1 for a longer duration than was observed with cells treated with Regranex. These studies provide the first clear evidence of in situ macrophage proliferation and direct collagen production during wound healing. These findings provide part of the explanation for the extremely rapid tissue regeneration, and this treatment may hold

  10. 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.

  11. Rescaled Range analysis of Induced Seismicity: rapid classification of clusters in seismic crisis

    Science.gov (United States)

    Bejar-Pizarro, M.; Perez Lopez, R.; Benito-Parejo, M.; Guardiola-Albert, C.; Herraiz, M.

    2017-12-01

    Different underground fluid operations, mainly gas storing, fracking and water pumping, can trigger Induced Seismicity (IS). This seismicity is normally featured by small-sized earthquakes (M<2.5), although particular cases reach magnitude as great as 5. It has been up for debate whether earthquakes greater than 5 can be triggered by IS or this level of magnitude only corresponds to tectonic earthquakes caused by stress change. Whatever the case, the characterization of IS for seismic clusters and seismic series recorded close but not into the gas storage, is still under discussion. Time-series of earthquakes obey non-linear patterns where the Hurst exponent describes the persistency or anti-persistency of the sequence. Natural seismic sequences have an H-exponent close to 0.7, which combined with the b-value time evolution during the time clusters, give us valuable information about the stationarity of the phenomena. Tectonic earthquakes consist in a main shock with a decay of time-occurrence of seismic shocks obeying the Omori's empirical law. On the contrary, IS does not exhibit a main shock and the time occurrence depends on the injection operations instead of on the tectonic energy released. In this context, the H-exponent can give information about the origin of the sequence. In 2013, a seismic crisis was declared from the Castor underground gas storing located off-shore in the Mediterranean Sea, close to the Northeastern Spanish cost. The greatest induced earthquake was 3.7. However, a 4.2 earthquake, probably of tectonic origin, occurred few days after the operations stopped. In this work, we have compared the H-exponent and the b-value time evolution according to the timeline of gas injection. Moreover, we have divided the seismic sequence into two groups: (1) Induced Seismicity and (2) Triggered Seismicity. The rescaled range analysis allows the differentiation between natural and induced seismicity and gives information about the persistency and long

  12. 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

  13. 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

  14. 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.

  15. Dynamic Self-Assembly Induced Rapid Dissolution of Cellulose at Low Temperatures

    International Nuclear Information System (INIS)

    Cai, J.; Zhang, L.; Liu, S.; Liu, Y.; Xu, X.; Chen, X.; Chu, B.; Guo, X.; Xu, J.

    2008-01-01

    Cellulose can be dissolved in precooled (-12 C) 7 wt % NaOH-12 wt % urea aqueous solution within 2 min. This interesting process, to our knowledge, represents the most rapid dissolution of native cellulose. The results from 13C NMR, 15N NMR, 1H NMR, FT-IR, small-angle neutron scattering (SANS), transmission electron microscopy (TEM), and wide-angle X-ray diffraction (WAXD) suggested that NaOH 'hydrates' could be more easily attracted to cellulose chains through the formation of new hydrogen-bonded networks at low temperatures, while the urea hydrates could not be associated directly with cellulose. However, the urea hydrates could possibly be self-assembled at the surface of the NaOH hydrogen-bonded cellulose to form an inclusion complex (IC), leading to the dissolution of cellulose. Scattering experiments, including dynamic and static light scattering, indicated that most cellulose molecules, with limited amounts of aggregation, could exist as extended rigid chains in dilute solution. Further, the cellulose solution was relatively unstable and could be very sensitive to temperature, polymer concentration, and storage time, leading to additional aggregations. TEM images and WAXD provided experimental evidence on the formation of a wormlike cellulose IC being surrounded with urea. Therefore, we propose that the cellulose dissolution at -12 C could arise as a result of a fast dynamic self-assembly process among solvent small molecules (NaOH, urea, and water) and the cellulose macromolecules.

  16. Peptide fragments induce a more rapid immune response than intact proteins in earthworms.

    Science.gov (United States)

    Hanusová, R; Tucková, L; Halada, P; Bezouska, K; Bilej, M

    1999-01-01

    The effect of in vivo proteolytic processing of protein antigen was studied in Eisenia foetida earthworms. Parenteral administration of the protein antigen induces elevated levels of an antigen-binding protein (ABP) which recognizes the protein used for stimulation. When the protein antigen is administered simultaneously with nontoxic serine proteinase inhibitor, ABP levels remain close to background. On the other hand, the in vivo adaptive response of earthworms to peptide fragments obtained by coelomic fluid digestion of the foreign antigen occurs even in the presence of proteinase inhibitor and, moreover, is significantly faster as compared to the response to intact antigen. These findings confirm the role of proteolytic processing in earthworms. MALDI mass spectrometric analysis of the fragments after coelomic fluid digestion has revealed the presence of the peptide fragments with molecular weights in the mass range 700-1100 Da.

  17. 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.

  18. 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.

  19. 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.

  20. Temperature dependent rapid annealing effect induces amorphous aggregation of human serum albumin.

    Science.gov (United States)

    Ishtikhar, Mohd; Ali, Mohd Sajid; Atta, Ayman M; Al-Lohedan, Hammad; Badr, Gamal; Khan, Rizwan Hasan

    2016-01-01

    This study represents an analysis of the thermal aggregation of human serum albumin (HSA) induced by novel rosin modified compounds. The aggregation process causes conformational alterations in the secondary and tertiary structures of the proteins. The conversion of globular protein to amorphous aggregates was carried out by spectroscopic, calorimetric and microscopic techniques to investigate the factors that are responsible for the structural, conformational and morphological alteration in the protein. Our outcome results show that the aggregation of HSA was dependent on the hydrophobicity, charge and temperature, because the formation of amorphous aggregates occurs in the presence of a novel cationic rosin compound, quaternary amine of rosin diethylaminoethyl ester (QRMAE), at 40°C and pH 7.4 (but at 25°C on similar pH value, there was no evidence of aggregate formation). In addition, the parent compound of QRMAE, i.e., abietic acid, and other derivatives such as nonionic rosin compounds [(RMPEG-750) and (RMA-MPEG-750)] do not shows the aggregating property. This work provides precise and necessary information that aid in the understanding the effects of rosin derivative compounds on HSA. This study also restrains important information for athletes, health providers, pharmaceutical companies, industries, and soft drink-processing companies. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. 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.

  2. 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.

  3. Community-based management induces rapid recovery of a high-value tropical freshwater fishery

    Science.gov (United States)

    Campos-Silva, João Vitor; Peres, Carlos A.

    2016-10-01

    Tropical wetlands are highly threatened socio-ecological systems, where local communities rely heavily on aquatic animal protein, such as fish, to meet food security. Here, we quantify how a ‘win-win’ community-based resource management program induced stock recovery of the world’s largest scaled freshwater fish (Arapaima gigas), providing both food and income. We analyzed stock assessment data over eight years and examined the effects of protected areas, community-based management, and landscape and limnological variables across 83 oxbow lakes monitored along a ~500-km section of the Juruá River of Western Brazilian Amazonia. Patterns of community management explained 71.8% of the variation in arapaima population sizes. Annual population counts showed that protected lakes on average contained 304.8 (±332.5) arapaimas, compared to only 9.2 (±9.8) in open-access lakes. Protected lakes have become analogous to a high-interest savings account, ensuring an average annual revenue of US$10,601 per community and US$1046.6 per household, greatly improving socioeconomic welfare. Arapaima management is a superb window of opportunity in harmonizing the co-delivery of sustainable resource management and poverty alleviation. We show that arapaima management deserves greater attention from policy makers across Amazonian countries, and highlight the need to include local stakeholders in conservation planning of Amazonian floodplains.

  4. Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.

    Directory of Open Access Journals (Sweden)

    Jun Hu

    Full Text Available Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+, EPSC(-, and EPSC(+/- based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs, using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+ neurons, but increased it in EPSC(- neurons. Unlike EPSC(+ and EPSC(- neurons, EPSC(+/- neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/- neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.

  5. Glucose Rapidly Induces Different Forms of Excitatory Synaptic Plasticity in Hypothalamic POMC Neurons

    Science.gov (United States)

    Hu, Jun; Jiang, Lin; Low, Malcolm J.; Rui, Liangyou

    2014-01-01

    Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(−), and EPSC(+/−)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(−) neurons. Unlike EPSC(+) and EPSC(−) neurons, EPSC(+/−) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/−) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals. PMID:25127258

  6. Glucose rapidly induces different forms of excitatory synaptic plasticity in hypothalamic POMC neurons.

    Science.gov (United States)

    Hu, Jun; Jiang, Lin; Low, Malcolm J; Rui, Liangyou

    2014-01-01

    Hypothalamic POMC neurons are required for glucose and energy homeostasis. POMC neurons have a wide synaptic connection with neurons both within and outside the hypothalamus, and their activity is controlled by a balance between excitatory and inhibitory synaptic inputs. Brain glucose-sensing plays an essential role in the maintenance of normal body weight and metabolism; however, the effect of glucose on synaptic transmission in POMC neurons is largely unknown. Here we identified three types of POMC neurons (EPSC(+), EPSC(-), and EPSC(+/-)) based on their glucose-regulated spontaneous excitatory postsynaptic currents (sEPSCs), using whole-cell patch-clamp recordings. Lowering extracellular glucose decreased the frequency of sEPSCs in EPSC(+) neurons, but increased it in EPSC(-) neurons. Unlike EPSC(+) and EPSC(-) neurons, EPSC(+/-) neurons displayed a bi-phasic sEPSC response to glucoprivation. In the first phase of glucoprivation, both the frequency and the amplitude of sEPSCs decreased, whereas in the second phase, they increased progressively to the levels above the baseline values. Accordingly, lowering glucose exerted a bi-phasic effect on spontaneous action potentials in EPSC(+/-) neurons. Glucoprivation decreased firing rates in the first phase, but increased them in the second phase. These data indicate that glucose induces distinct excitatory synaptic plasticity in different subpopulations of POMC neurons. This synaptic remodeling is likely to regulate the sensitivity of the melanocortin system to neuronal and hormonal signals.

  7. 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.

  8. Thermally induced dispersion mechanisms for aluminum-based plate-type fuels under rapid transient energy deposition

    International Nuclear Information System (INIS)

    Georgevich, V.; Taleyarkham, R.P.; Navarro-Valenti, S.; Kim, S.H.

    1995-01-01

    A thermally induced dispersion model was developed to analyze for dispersive potential and determine onset of fuel plate dispersion for Al-based research and test reactor fuels. Effect of rapid energy deposition in a fuel plate was simulated. Several data types for Al-based fuels tested in the Nuclear Safety Research Reactor in Japan and in the Transient Reactor Test in Idaho were reviewed. Analyses of experiments show that onset of fuel dispersion is linked to a sharp rise in predicted strain rate, which futher coincides with onset of Al vaporization. Analysis also shows that Al oxidation and exothermal chemical reaction between the fuel and Al can significantly affect the energy deposition characteristics, and therefore dispersion onset connected with Al vaporization, and affect onset of vaporization

  9. A Simple Diet- and Chemical-Induced Murine NASH Model with Rapid Progression of Steatohepatitis, Fibrosis and Liver Cancer.

    Science.gov (United States)

    Tsuchida, Takuma; Lee, Youngmin A; Fujiwara, Naoto; Ybanez, Maria; Allen, Brittany; Martins, Sebastiao; Fiel, M Isabel; Goossens, Nicolas; Chou, Hsin-I; Hoshida, Yujin; Friedman, Scott L

    2018-03-20

    Although the majority of patients with nonalcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24-52 weeks, which makes testing for drug response costly and time consuming. We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low dose weekly intraperitoneal carbon tetrachloride (CCl 4 ), which served as an accelerator. C57BL/6J mice were fed a normal chow diet (ND) ± CCl 4 or WD ± CCl 4 for 12 and 24 weeks. Addition of CCl 4 exacerbated histological features of NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3 fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl 4 mice and immunologic features were closely similar to those of human NASH. Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and mimics histological, immunological and transcriptomic features of human NASH, suggesting that it will be a useful experimental tool for preclinical drug testing. A carefully characterized model has been developed in mice that recapitulates the progressive stages of human fatty liver disease, from simple steatosis, to inflammation, fibrosis and cancer. The functional pathways of gene expression and immune abnormalities in this model closely resemble human disease. The ease and reproducibility of this model makes it ideal to study disease pathogenesis and test new treatments. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  10. Sunlight Induced Rapid Oil Absorption and Passive Room-Temperature Release: An Effective Solution toward Heavy Oil Spill Cleanup

    KAUST Repository

    Wu, Mengchun

    2018-05-18

    Rapid cleanup and easy recovery of spilled heavy oils is always a great challenge due to their high viscosity (>103 mPa s). One of the efficient methods to absorb highly viscous oils is to reduce their viscosity by increasing their temperature. In this work, the authors integrate the sunlight‐induced light‐to‐heat conversion effect of polypyrrole (PPy) and thermoresponsive property of poly(N‐isopropylacrylamide) (PNIPAm) into the melamine sponge, which successfully delivers a fast heavy oil absorption under sunlight and passive oil release underwater at room temperature. Thanks to the rationally designed functionalities, the PNIPAm/PPy functionalized sponges possess oleophilicity and hydrophobicity under sunlight. Due to the photothermal effect of PPy, the sponges locally heat up contacting heavy oil under sunlight and reduce its viscosity to a point where the oil voluntarily flow into the pores of the sponge. The material in this work is able to rapidly absorb the heavy oil with room temperature viscosity as high as ≈1.60 × 105 mPa s. The absorbed oil can be passively forced out the sponge underwater at room temperature due to the hydrophilicity of PNIPAm. The sunlight responsive and multifunctional sponge represents a meaningful attempt in coming up with a sustainable solution toward heavy oil spill.

  11. Sunlight Induced Rapid Oil Absorption and Passive Room-Temperature Release: An Effective Solution toward Heavy Oil Spill Cleanup

    KAUST Repository

    Wu, Mengchun; Shi, Yusuf; Chang, Jian; Li, Renyuan; Ong, Chi Siang; Wang, Peng

    2018-01-01

    Rapid cleanup and easy recovery of spilled heavy oils is always a great challenge due to their high viscosity (>103 mPa s). One of the efficient methods to absorb highly viscous oils is to reduce their viscosity by increasing their temperature. In this work, the authors integrate the sunlight‐induced light‐to‐heat conversion effect of polypyrrole (PPy) and thermoresponsive property of poly(N‐isopropylacrylamide) (PNIPAm) into the melamine sponge, which successfully delivers a fast heavy oil absorption under sunlight and passive oil release underwater at room temperature. Thanks to the rationally designed functionalities, the PNIPAm/PPy functionalized sponges possess oleophilicity and hydrophobicity under sunlight. Due to the photothermal effect of PPy, the sponges locally heat up contacting heavy oil under sunlight and reduce its viscosity to a point where the oil voluntarily flow into the pores of the sponge. The material in this work is able to rapidly absorb the heavy oil with room temperature viscosity as high as ≈1.60 × 105 mPa s. The absorbed oil can be passively forced out the sponge underwater at room temperature due to the hydrophilicity of PNIPAm. The sunlight responsive and multifunctional sponge represents a meaningful attempt in coming up with a sustainable solution toward heavy oil spill.

  12. Dietary Deficiency of Essential Amino Acids Rapidly Induces Cessation of the Rat Estrous Cycle

    Science.gov (United States)

    Bannai, Makoto; Ichimaru, Toru; Nakano, Sayako; Murata, Takuya; Higuchi, Takashi; Takahashi, Michio

    2011-01-01

    Reproductive functions are regulated by the sophisticated coordination between the neuronal and endocrine systems and are sustained by a proper nutritional environment. Female reproductive function is vulnerable to effects from dietary restrictions, suggesting a transient adaptation that prioritizes individual survival over reproduction until a possible future opportunity for satiation. This adaptation could also partially explain the existence of amenorrhea in women with anorexia nervosa. Because amino acid nutritional conditions other than caloric restriction uniquely alters amino acid metabolism and affect the hormonal levels of organisms, we hypothesized that the supply of essential amino acids in the diet plays a pivotal role in the maintenance of the female reproductive system. To test this hypothesis, we examined ovulatory cyclicity in female rats under diets that were deficient in threonine, lysine, tryptophan, methionine or valine. Ovulatory cyclicity was monitored by daily cytological evaluations of vaginal smears. After continuous feeding of the deficient diet, a persistent diestrus or anovulatory state was induced most quickly by the valine-deficient diet and most slowly by the lysine-deficient diet. A decline in the systemic insulin-like growth factor 1 level was associated with a dietary amino acid deficiency. Furthermore, a paired group of rats that were fed an isocaloric diet with balanced amino acids maintained normal estrous cyclicity. These disturbances of the estrous cycle by amino acid deficiency were quickly reversed by the consumption of a normal diet. The continuous anovulatory state in this study is not attributable to a decrease in caloric intake but to an imbalance in the dietary amino acid composition. With a shortage of well-balanced amino acid sources, reproduction becomes risky for both the mother and the fetus. It could be viewed as an adaptation to the diet, diverting resources away from reproduction and reallocating them to

  13. 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 < 0.01) in the HG period compared with the HF period. During the HG period, SARA was diagnosed only during week 1, indicating ruminal adaptation to the HG diet. Microscopic examination of the papillae revealed a reduction (P < 0.01) in the stratum basale, spinosum, and granulosum layers, as well as total depth of the epithelium during the HG period. The highest (P < 0.05) papillae lesion scores were noted during week 1 when SARA occurred. Biopsied papillae exhibited a decline in cellular junctions, extensive sloughing of the stratum corneum, and the appearance of undifferentiated cells near the stratum corneum. Differential mRNA expression of candidate genes, including desmoglein 1 and IGF binding proteins 3, 5, and 6, was detected between diets using qRT-PCR. These results suggest that the structural integrity of the rumen epithelium is compromised during grain feeding and is associated with the differential expression of genes involved in epithelial growth and structure.

  14. Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

    International Nuclear Information System (INIS)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

    1983-01-01

    Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

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

    International Nuclear Information System (INIS)

    Ninomiya, Yuichi; Sugahara-Yamashita, Yzumi; Nakachi, Yutaka; Tokuzawa, Yoshimi; Okazaki, Yasushi; Nishiyama, Masahiko

    2010-01-01

    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 γ 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-β1 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.

  16. Age-associated impairments in contraction-induced rapid-onset vasodilatation within the forearm are independent of mechanical factors.

    Science.gov (United States)

    Hughes, William E; Kruse, Nicholas T; Casey, Darren P

    2018-05-01

    What is the central question of this study? We examined whether the mechanical contribution to contraction-induced rapid-onset vasodilatation (ROV) differed with age and whether ROV is associated with peripheral artery stiffness. Furthermore, we examined how manipulation of perfusion pressure modulates ROV in young and older adults. What is the main finding and its importance? The mechanical contribution to ROV is similar in young and older adults. Conversely, peripheral arterial stiffness is not associated with ROV. Enhancing perfusion pressure augments ROV to a similar extent in young and older adults. These results suggest that age-related attenuations in ROV are not attributable to a mechanical component and that ROV responses are independent of peripheral artery stiffness. Contraction-induced rapid-onset vasodilatation (ROV) is modulated by perfusion and transmural pressure in young adults; however, this effect remains unknown in older adults. The present study examined the mechanical contribution to ROV in young versus older adults, the influence of perfusion pressure and whether these responses are associated with arterial stiffness. Forearm vascular conductance (in millilitres per minute per 100 mmHg) was measured in 12 healthy young (24 ± 4 years old) and 12 older (67 ± 3 years old) adults during: (i) single dynamic contractions at 20% of maximal voluntary contraction; and (ii) single external mechanical compression of the forearm (200 mmHg) positioned above, at and below heart level. Carotid-radial pulse-wave velocity characterized upper limb arterial stiffness. Total ROV responses to single muscle contractions and single external mechanical compressions were attenuated in older adults at heart level (P mechanical contribution to contraction-induced peak (46 ± 14 versus 40 ± 18%; P = 0.21) and total (37 ± 21 versus 32 ± 18%; P = 0.27) responses were not different between young and older adults. Reducing or enhancing perfusion

  17. Mangifera indica L. extract protects T cells from activation-induced cell death.

    Science.gov (United States)

    Hernández, Patricia; Delgado, Rene; Walczak, Henning

    2006-09-01

    The aqueous stem bark extract of Mangifera indica L. (Vimang) has been reported to have antioxidant properties. AIDS is characterized by up-regulation of CD95 ligand (CD95L) expression and enhancement of activation-induced cell death (AICD). Recent studies demonstrate oxidative signals combined with simultaneous calcium (Ca(2+)) influx into the cytosol are required for induction of CD95L expression. In this study we show that M. indica extract attenuated anti-CD3-induced accumulation of reactive oxygen species (ROS) and intracellular free Ca(2+) and consequently, downregulates CD95L mRNA expression and CD95-mediated AICD. In addition, TCR triggering caused an elevation in the antioxidant enzyme manganous superoxide dismutase (Mn-SOD) and the increase in c-Jun N-terminal kinase (JNK) phosphorylation, both effects being prevented by M. indica extract. We provide a number of evidences regarding how M. indica extract enhance T-cell survival by inhibiting AICD, a finding associated with a decrease in oxidative stress generated through the TCR signaling pathway in activated T cells.

  18. High-temperature rapid pyrometamorphism induced by a charcoal pit burning: The case of Ricetto, central Italy

    Science.gov (United States)

    Capitanio, Flavio; Larocca, Francesco; Improta, Salvatore

    Bulk chemistry and mineralogy of the peculiar rock of Ricetto (Carseolani Mts., Central Apennines, Italy) was studied to resolve its controversial origin: igneous dyke or anthropic product. This hybrid rock consists of a colorless, felsic component made up of glass plus quartz, and a brown, femic component made up of fans and spherulites of diopside, calcic plagioclase, wollastonite, and melilite. Textural relationships indicate very rapid cooling and immiscibility phenomena. The bulk chemistry of the rock is the same as that of the surrounding siliciclastic sandstone. The 14C analysis of a coal fragment from bottom of the body yields the conventional age of 227(+/-50) years. The Ricetto occurrence is an example of pyrometamorphism of a siliceous limestone induced by a charcoal pit burning. The small size of the heat source at Ricetto caused an intense but short-lived melting of the country rock. Prograde metamorphism caused a temperature increase up to 1,000-1,100 °C when melilite crystallization conditions were reached at appreciable P(CO2) and high f(O2). Melting occurred in a close system represented by the simplified equation: 3Cal+16.5Qtz+Ms+Bt-->Mel+Melt+2H2O+3CO2+0.5O2. Diopside+calcic plagioclase+wollastonite formed by melilite breakdown during rapid cooling, through the reaction: 6Mel+6Qtz+0.5O2-->3Di+2An+7Wo. Liquid immiscibility caused the separation between the felsic melt component and the femic melilite-bearing component. Immiscibility was characterized by different fractionation of alumina and alkalies between these two phases. Differences in bulk, glass, and mineral chemistry between the Ricetto and other melilite-bearing pyrometamorphic rocks can be attributed mainly to different protoliths.

  19. 3-Bromopyruvate induces rapid human prostate cancer cell death by affecting cell energy metabolism, GSH pool and the glyoxalase system.

    Science.gov (United States)

    Valenti, Daniela; Vacca, Rosa A; de Bari, Lidia

    2015-12-01

    3-bromopyruvate (3-BP) is an anti-tumour drug effective on hepatocellular carcinoma and other tumour cell types, which affects both glycolytic and mitochondrial targets, depleting cellular ATP pool. Here we tested 3-BP on human prostate cancer cells showing, differently from other tumour types, efficient ATP production and functional mitochondrial metabolism. We found that 3-BP rapidly induced cultured androgen-insensitive (PC-3) and androgen-responsive (LNCaP) prostate cancer cell death at low concentrations (IC(50) values of 50 and 70 μM, respectively) with a multimodal mechanism of action. In particular, 3-BP-treated PC-3 cells showed a selective, strong reduction of glyceraldeide 3-phosphate dehydrogenase activity, due to the direct interaction of the drug with the enzyme. Moreover, 3-BP strongly impaired both glutamate/malate- and succinate-dependent mitochondrial respiration, membrane potential generation and ATP synthesis, concomitant with the inhibition of respiratory chain complex I, II and ATP synthase activities. The drastic reduction of cellular ATP levels and depletion of GSH pool, associated with significant increase in cell oxidative stress, were found after 3-BP treatment of PC-3 cells. Interestingly, the activity of both glyoxalase I and II, devoted to the elimination of the cytotoxic methylglyoxal, was strongly inhibited by 3-BP. Both N-acetylcysteine and aminoguanidine, GSH precursor and methylglyoxal scavenger, respectively, prevented 3-BP-induced PC-3 cell death, showing that impaired cell antioxidant and detoxifying capacities are crucial events leading to cell death. The provided information on the multi-target cytotoxic action of 3-BP, finally leading to PC-3 cell necrosis, might be useful for future development of 3-BP as a therapeutic option for prostate cancer treatment.

  20. Rapid detection of hypoxia-inducible factor-1-active tumours: pretargeted imaging with a protein degrading in a mechanism similar to hypoxia-inducible factor-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, Masashi [Kyoto University, Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto (Japan); Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kudo, Takashi; Konishi, Hiroaki; Miyano, Azusa; Ono, Masahiro; Saji, Hideo [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Kuge, Yuji [Kyoto University, Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto (Japan); Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan); Mukai, Takahiro [Kyushu University, Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Fukuoka (Japan); Tanaka, Shotaro; Kizaka-Kondoh, Shinae; Hiraoka, Masahiro [Kyoto University, Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto (Japan)

    2010-08-15

    Hypoxia-inducible factor-1 (HIF-1) plays an important role in malignant tumour progression. For the imaging of HIF-1-active tumours, we previously developed a protein, POS, which is effectively delivered to and selectively stabilized in HIF-1-active cells, and a radioiodinated biotin derivative, (3-{sup 123}I-iodobenzoyl)norbiotinamide ({sup 123}I-IBB), which can bind to the streptavidin moiety of POS. In this study, we aimed to investigate the feasibility of the pretargeting method using POS and {sup 123}I-IBB for rapid imaging of HIF-1-active tumours. Tumour-implanted mice were pretargeted with POS. After 24 h, {sup 125}I-IBB was administered and subsequently, the biodistribution of radioactivity was investigated at several time points. In vivo planar imaging, comparison between {sup 125}I-IBB accumulation and HIF-1 transcriptional activity, and autoradiography were performed at 6 h after the administration of {sup 125}I-IBB. The same sections that were used in autoradiographic analysis were subjected to HIF-1{alpha} immunohistochemistry. {sup 125}I-IBB accumulation was observed in tumours of mice pretargeted with POS (1.6%ID/g at 6 h). This result is comparable to the data derived from {sup 125}I-IBB-conjugated POS-treated mice (1.4%ID/g at 24 h). In vivo planar imaging provided clear tumour images. The tumoral accumulation of {sup 125}I-IBB significantly correlated with HIF-1-dependent luciferase bioluminescence (R=0.84, p<0.01). The intratumoral distribution of {sup 125}I-IBB was heterogeneous and was significantly correlated with HIF-1{alpha}-positive regions (R=0.58, p<0.0001). POS pretargeting with {sup 123}I-IBB is a useful technique in the rapid imaging and detection of HIF-1-active regions in tumours. (orig.)

  1. A sunlight-induced method for rapid biosynthesis of silver nanoparticles using an Andrachnea chordifolia ethanol extract

    Energy Technology Data Exchange (ETDEWEB)

    Karimi Zarchi, A.A.; Faridi Majidi, R. [Tehran University of Medical Sciences, Department of Nanomedicine, School of Advanced Medical Technologies, Tehran (Iran, Islamic Republic of); Mokhtari, N.; Shahverdi, A.R. [Tehran University of Medical Sciences, Department of Pharmaceutical Biotechnology and Medicinal Plants Research Center, Faculty of Pharmacy, Tehran (Iran, Islamic Republic of); Arfan, M.; Rehman, T.; Ali, M. [University of Peshawar, Institute of Chemical Sciences, Peshawar, Khyber Pakhtoonkhwa (Pakistan); Amini, M. [Tehran University of Medical Sciences, Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran (Iran, Islamic Republic of)

    2011-05-15

    In this study a sunlight-induced method for rapid synthesis of silver nanoparticles using an ethanol extract of Andrachnea chordifolia is described. The silver nitrate solutions (1 mM) containing the ethanol extract of Andrachnea chordifolia were irradiated by both sunlight radiation and by sunlight radiation passed through different colored filters (red, yellow or green). The smallest size of silver nanoparticles was obtained when a silver ion solution was irradiated for 5 minutes by direct sunlight radiation. Further examination of the shape and size and of the surface chemistry of these biogenic silver nanoparticles, which were prepared under sunlight radiation, was carried out using transmission electron microscopy and infrared spectroscopy, respectively. Transmission electron microscopy images show spherical particles with an average size of 3.4 nm. Hydroxyl residues were also detected on the surface of these biogenic silver nanoparticles fabricated using plant extract of Andrachnea chordifolia under sunlight radiation. Our study on the reduction of silver ions by this plant extract in darkness shows that the synthesis process can take place under dark conditions at much longer incubations (48 hours). Larger silver polydispersed nanoparticles ranging in size from 3 to 30 nm were obtained when the silver ions were treated with the ethanol extract of Andrachnea chordifolia under dark conditions for 48 hours. (orig.)

  2. Rapid analytical assessment of the mechanical perturbations induced by non-isothermal injection into a subsurface formation.

    Science.gov (United States)

    De Simone, Silvia; Carrera, Jesús; María Gómez Castro, Berta

    2016-04-01

    Fluid injection into geological formations is required for several engineering operations, e.g. geothermal energy production, hydrocarbon production and storage, CO2 storage, wastewater disposal, etc. Non-isothermal fluid injection causes alterations of the pressure and temperature fields, which affect the mechanical stability of the reservoir. This coupled thermo-hydro-mechanical behavior has become a matter of special interest because of public concern about induced seismicity. The response is complex and its evaluation often requires numerical modeling. Nevertheless, analytical solutions are useful in improving our understanding of interactions, identifying the controlling parameters, testing codes and in providing a rapid assessment of the system response to an alteration. We present an easy-to-use solution to the transient advection-conduction heat transfer problem for parallel and radial flow. The solution is then applied to derive analytical expressions for hydraulic and thermal driven displacements and stresses. The validity is verified by comparison with numerical simulations and yields fairly accurate results. The solution is then used to illustrate some features of the poroelastic and thermoelastic response and, in particular, the sensitivity to the external mechanical constraints and to the reservoir dimension.

  3. 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.

  4. 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

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

    International Nuclear Information System (INIS)

    Fukui, Masayuki; Choi, Hye Joung; Zhu, Bao Ting

    2012-01-01

    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 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 ATP

  6. 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.

  7. Rapid shoreline erosion induced by human impacts in a tropical muddy coast context, an example from western French Guiana.

    Science.gov (United States)

    Brunier, Guillaume; Anthony, Edward; Gardel, Antoine

    2015-04-01

    The Guyanas coast (French Guiana, Surinam and Guiana) is the longest muddy coast in the world (1500 km). It is under the influence of mud banks in transit from the Amazon delta in Brazil to the Orinoco delta in Venezuela. This westward mud bank migration induces a strong geomorphic control on the shoreline which can be summarized in terms of "bank" (shoreline advance and wave energy dissipation) and "inter-bank" phases (erosion of shoreline by waves). Our study site, rice polders close to Mana city (western French Guiana), is a fine example of the exacerbation, by human activities, of the erosional dynamics on this muddy coast during an "inter-bank" phase. The polders cover 50,000 ha, in 200 x 600 m compartments flanked by earth dikes and canals. They were built in the muddy Holocene coastal plain in the 1980s and are rapidly eroding. Waves (mean significant height = 1.5 m height) comprise Atlantic swell and local trade wind-waves, and the tidal context is semi-diurnal and meso-tidal. We determined historical shoreline evolution from satellite (Landsat & SPOT) and orthophotography images, and conducted four field campaigns between October 2013 and October 2014, comprising topographic (RTK-DGPS) and hydrodynamic (pressure sensors) measurements. The results show intense erosion of 150 m/year affecting the polders since 2001, and lesser retreat (30 to 100 m/year) of the adjacent sectors colonized by mangrove forests. The erosive shoreface shows the same structure in each polder compartment: a chenier beach which freely retreats backwards under the influence of wave overwash. The chenier retreat rate is 100 m/year and it appears to be more intense (net retreat of 45 m) during the high wave-energy season (December to March), which generates more overwashing. In front of the chenier, we observed a large (50 m) inter-tidal mud bed showing different levels of induration and bioturbation by mangrove roots. The mud shorefaces exhibit an erosion rate of 100 m/year on average

  8. Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.

    Science.gov (United States)

    Fan, Jinqi; Zou, Lili; Cui, Kun; Woo, Kamsang; Du, Huaan; Chen, Shaojie; Ling, Zhiyu; Zhang, Quanjun; Zhang, Bo; Lan, Xianbin; Su, Li; Zrenner, Bernhard; Yin, Yuehui

    2015-01-01

    The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1-7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-β1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin-angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF.

  9. 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

    hyperfibrinolysis, as compared to standard KaolinTEG, is unknown. To investigate this, the ability of RapidTEG, KaolinTEG, and functional fibrinogenTEG (FFTEG) to detect tPA-induced (tissue plasminogen activator) lysis in whole blood from healthy individuals was investigated. Our hypothesis was that the initial...... powerful clot formation in the RapidTEG assay would reduce the sensitivity as compared to the normally used KaolinTEG assay. We also evaluated the FFTEG assay. Methods: In vitro comparison of the sensitivity of RapidTEG, KaolinTEG, and FFTEG to 1.8 nmol/L tPA in citrated whole blood (299 ± 23 ng/mL plasma......) induced hyperfibrinolysis in 10 healthy individuals and duplicate titration of the tPA whole blood (WB) concentration from 0.09 to 7.2 nmol/L (14-1144 ng/mL plasma) in 1 healthy donor. Results: At 1.8 nmol/L tPA, KaolinTEG, RapidTEG, and FFTEG all detected fibrinolysis but with different sensitivities...

  10. Growth hormone preferentially induces the rapid, transient expression of SOCS-3, a novel inhibitor of cytokine receptor signaling

    DEFF Research Database (Denmark)

    Adams, T E; Hansen, J A; Starr, R

    1998-01-01

    Four members (SOCS-1, SOCS-2, SOCS-3, and CIS) of a family of cytokine-inducible, negative regulators of cytokine receptor signaling have recently been identified. To address whether any of these genes are induced in response to growth hormone (GH), serum-starved 3T3-F442A fibroblasts were incuba...

  11. GmWRKY53, a water- and salt-inducible soybean gene for rapid dissection of regulatory elements in BY-2 cell culture

    Science.gov (United States)

    Tripathi, Prateek; Rabara, Roel C.; Lin, Jun; Rushton, Paul J.

    2013-01-01

    Drought is the major cause of crop losses worldwide. Water stress-inducible promoters are important for understanding the mechanisms of water stress responses in crop plants. Here we utilized tobacco (Nicotiana tabacum L.) Bright Yellow 2 (BY-2) cell system in presence of polyethylene glycol, salt and phytohormones. Extension of the system to 85 mM NaCl led to inducibility of up to 10-fold with the water stress and salt responsive soybean GmWRKY53 promoter. Upon ABA and JA treatment fold inducibility was up to 5-fold and 14-fold, respectively. Thus, we hypothesize that GmWRKY53 could be used as potential model candidate for dissecting drought regulatory elements as well as understanding crosstalk utilizing a rapid heterologous system of BY-2 culture. PMID:23511199

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

    Science.gov (United States)

    Fukui, Masayuki; Choi, Hye Joung; Zhu, Bao Ting

    2013-01-01

    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 K3) 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. PMID:22575170

  13. 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.

  14. Rapid localized deactivation of self-assembled monolayers by propagation-controlled laser-induced plasma and its application to self-patterning of electronics and biosensors

    Science.gov (United States)

    Kim, Jongsu; Kwon, Seung-Gab; Back, Seunghyun; Kang, Bongchul

    2018-03-01

    We present a novel laser-induced surface treatment process to rapidly control the spatial wettabilities of various functional solutions with submicron to micron resolutions. Ultrathin hydrophobic self-assembled monolayers (SAMs) that little absorb typical laser lights due to short penetration depth were selectively deactivated by instantaneous interaction with laser-induced metallic plasmas. The spatial region of the deactivated SAM, which corresponds to process resolution, is adjustable by controlling the spatial propagation of the plasma. This method leads to the parallel formation of hydrophilic functional solutions on glass substrates with a minimum resolution on the submicron scale. To show its feasibility in device engineering fields, this method was applied to the cost-effective fabrication of electronics and biosensors. Rapid self-patterning of electronic and biological functional solutions (silver nanoparticle solution and streptavidin protein solution) was successfully realized by selective deactivation of two different SAMs (tridecafluoro-1,1,2,2-tetrahydrooctyltrichlorosilane (FOTS) for electronics and the hetero-hybrid SAM (octadecyltrichlorosilane (OTS)/2-[methoxy(polyethyleneoxy)propyl] trichlorosilane (PEG)) for biosensors). As a result, this method can be exploited for the rapid and low-cost fabrication of various thin film devices such as electronics, biosensors, energy, displays, and photonics.

  15. Comparison between basal and apical dendritic spines in estrogen-induced rapid spinogenesis of CA1 principal neurons in the adult hippocampus

    International Nuclear Information System (INIS)

    Murakami, Gen; Tsurugizawa, Tomokazu; Hatanaka, Yusuke; Komatsuzaki, Yoshimasa; Tanabe, Nobuaki; Mukai, Hideo; Hojo, Yasushi; Kominami, Shiro; Yamazaki, Takeshi; Kimoto, Tetsuya; Kawato, Suguru

    2006-01-01

    Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Here, we demonstrated the rapid effect of 17β-estradiol on the density and morphology of spines in the stratum oriens (s.o., basal side) and in the stratum lacunosum-moleculare (s.l.m., apical side) by imaging Lucifer Yellow-injected CA1 neurons in adult male rat hippocampal slices, because spines in s.o. and s.l.m. have been poorly understood as compared with spines in the stratum radiatum. The application of 1 nM estradiol-induced a rapid increase in the density of spines of pyramidal neurons within 2 h. This increase by estradiol was blocked by Erk MAP kinase inhibitor and estrogen receptor inhibitor in both regions. Effect of blockade by agonists of AMPA receptors and NMDA receptors was different between s.o. and s.l.m. In both regions, ERα agonist PPT induced the same enhancing effect of spinogenesis as that induced by estradiol

  16. 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.

  17. Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via the G-protein-coupled receptor 30 in ovarian cancer cells

    DEFF Research Database (Denmark)

    Henic, Emir; Noskova, Vera; Høyer-Hansen, Gunilla

    2009-01-01

    : rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17beta-estradiol (E(2)) on uPAR expression...... for ERalpha, and quantitative polymerase chain reaction. Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E(2) reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents...... agonist G1, mimicked the effect of E(2) on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates...

  18. Extracellular adenosine initiates rapid arteriolar vasodilation induced by a single skeletal muscle contraction in hamster cremaster muscle.

    Science.gov (United States)

    Ross, G A; Mihok, M L; Murrant, C L

    2013-05-01

    Recent studies suggest that adenosine (ADO) can be produced extracellularly in response to skeletal muscle contraction. We tested the hypothesis that a single muscle contraction produces extracellular ADO rapidly enough and in physiologically relevant concentrations to be able to contribute to the rapid vasodilation that occurs at the onset of muscle contraction. We stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ and measured the change in diameter of arterioles at a site of overlap with the stimulated muscle fibres before and after a single contraction (stimulus frequencies: 4, 20 and 60 Hz; 250 ms train duration). Muscle fibres were stimulated in the absence and presence of non-specific ADO membrane receptor antagonists 8-phenyltheophylline (8-PT, 10(-6) M) or xanthine amine congener (XAC, 10(-6) M) or an inhibitor of an extracellular source of ADO, ecto-5'-nucleotidase inhibitor α,β-methylene adenosine 5'-diphosphate (AMPCP, 10(-5) M). We observed that the dilatory event at 4 s following a single contraction was significantly inhibited at all stimulus frequencies by an average of 63.9 ± 2.6% by 8-PT. The 20-s dilatory event that occurred at 20 and 60 Hz was significantly inhibited by 53.6 ± 2.6 and 73.8 ± 2.3% by 8-PT and XAC respectively. Further, both the 4- and 20-s dilatory events were significantly inhibited by AMPCP by 78.6 ± 6.6 and 67.1 ± 1.5%, respectively, at each stimulus frequency tested. Our data show that ADO is produced extracellularly during a single muscle contraction and that it is produced rapidly enough and in physiologically relevant concentrations to contribute to the rapid vasodilation in response to muscle contraction. © 2013 The Authors Acta Physiologica © 2013 Scandinavian Physiological Society.

  19. Si diffusion in compositional disordering of Si-implanted GaAs/AlGaAs superlattices induced by rapid thermal annealing

    International Nuclear Information System (INIS)

    Uematsu, Masashi; Yanagawa, Fumihiko

    1988-01-01

    The Si diffusion in Si-implanted GaAs/Al 0.5 Ga 0.5 As superlattices intermixed in the disrodering process induced by rapid thermal annealing (RTA), is investigated by means of secondary ion mass spectroscopy (SIMS). The SIMS profiles indicate that no fast Si diffusion occurs during the disordering, and the disordering occurs when the Si concentration exceeds 1 x 10 19 cm -3 , which is about three times larger than the threshold value for the disordering by furnace annealing (FA). The number of Si atoms which are allowed to pass through the heterointerface is considered to be essential for disordering. (author)

  20. 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

    in the dorsal and ventral bladder urothelium, arguing against involvement of urinary solids. Egr-1 induction sometimes occurred in a localized fashion, indicating physiological microheterogeneity in the urothelium. The rapid kinetics supported that Egr-1 induction occurred as a result of pharmacological...... activation of PPAR alpha and PPAR gamma, which are coexpressed at high levels in the rat urothelium. Finally, our demonstration of a nuclear localization supports that the Egr-1 induced by PPAR alpha and PPAR gamma coactivation in the rat urothelium may be biologically active....

  1. Rapid screening of spontaneous and radiation-induced structural changes at the vestigial gene of Drosophila melanogaster by polymerase chain reaction

    International Nuclear Information System (INIS)

    Aleksandrov, I.D.; Lapidus, I.L.; Aleksandrova, M.V.; Karpovskij, A.L.; Korablinova, S.V.; Levkovich, N.V.

    1998-01-01

    A total of 27 independent isolated spontaneous and gamma-ray-induced heritable mutations at the vestigial gene of Drosophila melanogaster were analysed by a rapid deletion screening method with polymerase chain reaction (PCR) amplification. According to the results obtained 36.4% (4 of 11) of spontaneous mutants and 62.5% (10 of 16) of gamma-ray-induced ones have revealed deficiency of one or more fragments studied. The rest of spontaneous and radiation mutants showed no alterations in the PCR patterns, indicating possible small scale changes (point mutations) inside the gene region studied or, probably, the gross lesions situated elsewhere. The distribution of the mutation damages in the gene region studied are discussed

  2. Structure of the gene encoding VGF, a nervous system-specific mRNA that is rapidly and selectively induced by nerve growth factor in PC12 cells.

    Science.gov (United States)

    Salton, S R; Fischberg, D J; Dong, K W

    1991-05-01

    Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nucleic acid and predicted amino acid sequences of the NGF33.1 cDNA clone suggested that this clone corresponded to the NGF-inducible mRNA called VGF (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393-395, 1985; R. Possenti, J. D. Eldridge, B. M. Paterson, A. Grasso, and A. Levi, EMBO J. 8:2217-2223, 1989). We have used the NGF33.1 cDNA clone to isolate and characterize the VGF gene, and in this paper we report the complete sequence of the VGF gene, including 853 bases of 5' flank revealed TATAA and CCAAT elements, several GC boxes, and a consensus cyclic AMP response element-binding protein binding site. The VGF promoter contains sequences homologous to other NGF-inducible, neuronal promoters. We further show that VGF mRNA is induced in PC12 cells to a greater extent by depolarization and by phorbol-12-myristate-13-acetate treatment than by 8-bromo-cyclic AMP treatment. By Northern (RNA) and RNase protection analysis, VGF mRNA is detectable in embryonic and postnatal central and peripheral nervous tissues but not in a number of nonneural tissues. In the cascade of events which ultimately leads to the neural differentiation of NGF-treated PC12 cells, the VGF gene encodes the most rapidly and selectively regulated, nervous-system specific mRNA yet identified.

  3. Mechanism for ion-induced mixing of GaAs-AlGaAs interfaces by rapid thermal annealing

    International Nuclear Information System (INIS)

    Kahen, K.B.; Rajeswaran, G.; Lee, S.T.

    1988-01-01

    A mechanism for the transient-enhanced interdiffusion of GaAs-AlGaAs interfaces during rapid thermal annealing of ion-implanted heterostructures is proposed. The model is based on the solution of the coupled diffusion equations involving the excess vacancies and the post-implantation Al distribution following ion implantation. Both initial distributions are obtained from the solution of a three-dimensional Monte Carlo simulation of ion implantation into a heterostructure sample. In general, the model is valid for time frames within which impurity diffusion does not occur appreciably so that impurity-enhanced diffusion remains a weak effect

  4. Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: a case report

    Directory of Open Access Journals (Sweden)

    Kikkawa Ryuichi

    2004-12-01

    Full Text Available Abstract Background The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high. Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined. Case presentation Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis. He had a history of ventricular septum defect (VSD. A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve. Specimens of blood demonstrated Propionibacterium Acnes. The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days. After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved. Conclusion Although renal function in our case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure. We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully.

  5. Interleukin 1β induces rapid phosphorylation and redistribution of talin: A possible mechanism for modulation of fibroblast focal adhesion

    International Nuclear Information System (INIS)

    Qwarnstroem, E.E.; MacFarlane, S.A.; Page, R.C.; Dower, S.K.

    1991-01-01

    The majority of interleukin 1 (IL-1) receptors in human fibroblasts has been shown to be localized at focal adhesions. This study describes rapid alterations caused by IL-1β/IL-1-receptor interaction at these sites. Fibroblast monolayers, incubated with IL-1β and prepared for electron microscopy, showed successive loss of cell-substratum contact and fewer and less-pronounced processes. Immunocytochemistry revealed loss and redistribution of the talin staining initially observed after 5-15 min of IL-1β incubation. Similarly, the cytoskeleton showed a decrease in staining and a disorganization starting from 15 to 30 min after IL-1 addition, whereas extracellular fibronectin appeared largely unaffected. Prelabeling with [ 32 P]phosphate showed a 2- to 3-fold increase in the level of talin phosphorylation, peaking at 15 min. Phospho amino acid analyses revealed a higher level of serine and threonine phosphorylation. The data suggest that the action of IL-1β on fibroblasts may be partially mediated by direct phosphorylation of talin via activation of a protein serine/threonine kinase, leading to changes in transmembrane linkage proteins and the cytoskeleton. Such alterations at focal adhesions may provide a mechanism by which IL-1 can rapidly modulate cell-matrix interactions during inflammation and wound healing

  6. Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

    International Nuclear Information System (INIS)

    Friesen, Claudia; Lubatschofski, Annelie; Debatin, Klaus-Michael; Kotzerke, Joerg; Buchmann, Inga; Reske, Sven N.

    2003-01-01

    Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-x L , a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies. (orig.)

  7. Recent advances in the use of laser-induced breakdown spectroscopy (LIBS) as a rapid point-of-care pathogen diagnostic

    Science.gov (United States)

    Rehse, Steven; Trojand, Daniel; Putnam, Russell; Gillies, Derek; Woodman, Ryan; Sheikh, Khadija; Daabous, Andrew

    2013-05-01

    There is a well-known and urgent need in the fields of medicine, environmental health and safety, food-processing, and defense/security to develop new 21st Century technologies for the rapid and sensitive identification of bacterial pathogens. In only the last five years, the use of a real-time elemental (atomic) analysis performed with laser-induced breakdown spectroscopy (LIBS) has made tremendous progress in becoming a viable technology for rapid bacterial pathogen detection and identification. In this talk we will show how this laser-based optical emission spectroscopic technique is able to sensitively assay the elemental composition of bacterial cells in situ. We will also present the latest achievements of our lab to fully develop LIBS-based bacterial sensing including simulation of a rapid urinary tract infection diagnosis and investigation of a variety of autonomous multivariate analysis algorithms. Lastly, we will show how this technology is now ready to be transitioned from the laboratory to field-portable and potentially man-portable instrumentation. The introduction of such a technology into popular use could very well transform the field of bacterial biosensing - a market valued at approximately 10 billion/year world-wide. Funding for this project was provided in part by a Natural Sciences and Engineering Research Council of Canada Discovery Grant.

  8. 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.

  9. High-resolution lipidomics coupled with rapid fixation reveals novel ischemia-induced signaling in the rat neurolipidome.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Eiden, Michael; Morin-Rivron, Delphine; Bazinet, Richard P; Masoodi, Mojgan

    2017-03-01

    The field of lipidomics has evolved vastly since its creation 15 years ago. Advancements in mass spectrometry have allowed for the identification of hundreds of intact lipids and lipid mediators. However, because of the release of fatty acids from the phospholipid membrane in the brain caused by ischemia, identifying the neurolipidome has been challenging. Microwave fixation has been shown to reduce the ischemia-induced release of several lipid mediators. Therefore, this study aimed to develop a method combining high-resolution tandem mass spectrometry (MS/MS), high-energy head-focused microwave fixation and statistical modeling, allowing for the measurement of intact lipids and lipid mediators in order to eliminate the ischemia-induced release of fatty acids and identify the rat neurolipidome. In this study, we demonstrated the ischemia-induced production of bioactive lipid mediators, and the reduction in variability using microwave fixation in combination with liquid chromatography (LC)-MS/MS. We have also illustrated for the first time that microwave fixation eliminates the alterations in intact lipid species following ischemia. While many phospholipid species were unchanged by ischemia, other intact lipid classes, such as diacylglycerol, were lower in concentration following microwave fixation compared to ischemia. © 2016 International Society for Neurochemistry.

  10. 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

  11. ERK/CANP rapid signaling mediates 17β-estradiol-induced proliferation of human breast cancer cell line MCF-7 cells.

    Science.gov (United States)

    Wang, Guo-Sheng; Huang, Yan-Gang; Li, Huan; Bi, Shi-Jie; Zhao, Jin-Long

    2014-01-01

    17β-estradiol (E2) exerts its functions through both genomic and non-genomic signaling pathways. Because E2 is important in breast cancer development, we investigated whether its actions in promoting breast cancer cell proliferation occur through the non-genomic signaling pathway via extracellular signal-regulated kinase 1/2 (ERK1/2)/calcium-activated neutral protease (CANP). MCF-7 breast cancer cells were treated with ERKl/2 inhibitor (PD98059) or CANP inhibitor (calpeptin) before exposure to 1×10(-8) M E2. MTT colorimetry and flow cytometry were used to analyze effects on cell proliferation and cell cycle progression, respectively. Expression of phosphorylated-ERK (p-ERK), total ERK, and Capn4 proteins were assessed by Western blotting. Cell proliferation increased in cells treated with E2 for 24 h (P<0.05), and the proportion of cells in G0/G1 was decreased, accompanied by accelerated G1/S. Calpeptin pre-treatment significantly inhibited the E2-induced proliferation of MCF-7 cells (P<0.05), while also ameliorating the effects of E2 on cell cycle progression. Further, expression of p-ERK was rapidly up-regulated (after 10 min) by E2 (P<0.05), an effect that persisted 16 h after E2 exposure but which was significantly inhibited by PD98059 (P<0.05). Finally, expression of Capn4 protein was rapidly up-regulated in E2-exposed cells (P<0.05), but this change was significantly inhibited by PD98059 or calpeptin (P<0.05) pre-treatment. Thus, the rapid, non-genomic ERK/CANP signaling pathway mediates E2-induced proliferation of human breast cancer cells.

  12. Current-induced metal-insulator transition in VO x thin film prepared by rapid-thermal-annealing

    International Nuclear Information System (INIS)

    Cho, Choong-Rae; Cho, SungIl; Vadim, Sidorkin; Jung, Ranju; Yoo, Inkyeong

    2006-01-01

    The phenomenon of metal-insulator transition (MIT) in polycrystalline VO x thin films and their preparations have been studied. The films were prepared by sputtering of vanadium thin films succeeded by Rapid Thermal Annealing (RTA) in oxygen ambient at 500 deg. C. Crystalline, compositional, and morphological characterizations reveal a continuous change of phase from vanadium metal to the highest oxide phase, V 2 O 5 , with the time of annealing. Electrical MIT switching has been observed in these films. Sweeping mode, electrode area, and temperature dependent MIT has been studied in Pt/VO x /Pt vertical structure. The important parameters for MIT in VO x have been found to be the current density and the electric field, which depend on carrier density in the films

  13. Redshift and blueshift of GaNAs/GaAs multiple quantum wells induced by rapid thermal annealing

    Science.gov (United States)

    Sun, Yijun; Cheng, Zhiyuan; Zhou, Qiang; Sun, Ying; Sun, Jiabao; Liu, Yanhua; Wang, Meifang; Cao, Zhen; Ye, Zhi; Xu, Mingsheng; Ding, Yong; Chen, Peng; Heuken, Michael; Egawa, Takashi

    2018-02-01

    The effects of rapid thermal annealing (RTA) on the optical properties of GaNAs/GaAs multiple quantum wells (MQWs) grown by chemical beam epitaxy (CBE) are studied by photoluminescence (PL) at 77 K. The results show that the optical quality of the MQWs improves significantly after RTA. With increasing RTA temperature, PL peak energy of the MQWs redshifts below 1023 K, while it blueshifts above 1023 K. Two competitive processes which occur simultaneously during RTA result in redshift at low temperature and blueshift at high temperature. It is also found that PL peak energy shift can be explained neither by nitrogen diffusion out of quantum wells nor by nitrogen reorganization inside quantum wells. PL peak energy shift can be quantitatively explained by a modified recombination coupling model in which redshift nonradiative recombination and blueshift nonradiative recombination coexist. The results obtained have significant implication on the growth and RTA of GaNAs material for high performance optoelectronic device application.

  14. 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

  15. Photo-isomerization induced rapid photo-degradation of optical nonlinearity in cyano substituted stilbene derivative doped poled polymer

    International Nuclear Information System (INIS)

    Yan Jieyun; Liu Liying; Ji Liyong; Ye Mingxin; Xu Lei; Wang Wencheng

    2004-01-01

    We found that, although alpha'-cyano-4'-nitro-4-N, N-dimethylaminostilbene has larger hyperpolarizability than that of conventional 4'-N, N-dimethylamino-nitrostilbene, the addition of the cyano group makes it much more easy to photo-isomerize, thus destroying the molecular ordering in poled chromophore doped polymers. Experimental evidence was obtained by monitoring the second-harmonic generation intensity, UV-Vis absorption spectrum, and FTIR spectrum. The photo-isomerization reaction process was monitored by optical pump induced absorption anisotropy measurement. Comparisons with the behaviour of a azobenzene dye are also made

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Cohen, Michael F; Gurung, Sushma; Birarda, Giovanni; Holman, Hoi-Ying N; Yamasaki, Hideo

    2015-01-01

    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 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.

  18. Rapid and selective detection of cysteine based on its induced aggregates of cetyltrimethylammonium bromide capped gold nanoparticles

    International Nuclear Information System (INIS)

    Wang Jian; Li Yuanfang; Huang Chengzhi; Wu Tong

    2008-01-01

    A detection method of cysteine is reported in this contribution with water-soluble positively charged gold nanoparticles (Au-NPs) that were prepared by seed-mediated method and capped with cetyltrimethylammonium bromide (CTAB). In aqueous medium of pH 4.2, the CTAB-capped Au-NPs display greatly different features from those of generally prepared citrate-coated Au-NPs. It was found that in a medium of high salt concentration, the presence of cysteine could induce aggregation of CTAB-capped Au-NPs, while citrate-coated Au-NPs could get aggregation soon even if without the presence of cysteine. The cysteine-induced aggregates of CTAB-capped Au-NPs display strong plasmon resonance light scattering (PRLS) signals characterized at 566.0 nm when excited by a light beam, and the PRLS intensities of the aggregates are in proportion to the concentration of cysteine in the range of 0.01-0.40 μg mL -1 with the limit of detection (3σ) being 2.9 ng mL -1 . No amino acids in the samples interfere with the detection, and cysteine in artificial samples could be detected with the recovery between 95.3% and 105.9%, and R.S.D. is less than 3.6%

  19. 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.

  20. Homogeneous (Cu, Ni)6Sn5 intermetallic compound joints rapidly formed in asymmetrical Ni/Sn/Cu system using ultrasound-induced transient liquid phase soldering process.

    Science.gov (United States)

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

    2018-04-01

    Homogeneous (Cu, Ni) 6 Sn 5 intermetallic compound (IMC) joints were rapidly formed in asymmetrical Ni/Sn/Cu system by an ultrasound-induced transient liquid phase (TLP) soldering process. In the traditional TLP soldering process, the intermetallic joints formed in Ni/Sn/Cu system consisted of major (Cu, Ni) 6 Sn 5 and minor Cu 3 Sn IMCs, and the grain morphology of (Cu, Ni) 6 Sn 5 IMCs subsequently exhibited fine rounded, needlelike and coarse rounded shapes from the Ni side to the Cu side, which was highly in accordance with the Ni concentration gradient across the joints. However, in the ultrasound-induced TLP soldering process, the intermetallic joints formed in Ni/Sn/Cu system only consisted of the (Cu, Ni) 6 Sn 5 IMCs which exhibited an uniform grain morphology of rounded shape with a remarkably narrowed Ni concentration gradient. The ultrasound-induced homogeneous intermetallic joints exhibited higher shear strength (61.6 MPa) than the traditional heterogeneous intermetallic joints (49.8 MPa). Copyright © 2017 Elsevier B.V. All rights reserved.

  1. 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

    2016-11-01

    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. 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. 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. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Chemical bonding modifications of tetrahedral amorphous carbon and nitrogenated tetrahedral amorphous carbon films induced by rapid thermal annealing

    International Nuclear Information System (INIS)

    McCann, R.; Roy, S.S.; Papakonstantinou, P.; Bain, M.F.; Gamble, H.S.; McLaughlin, J.A.

    2005-01-01

    Tetrahedral amorphous carbon (ta-C) and nitrogenated tetrahedral amorphous carbon films (ta-CN x ), deposited by double bend off plane Filtered Vacuum Cathodic Arc were annealed up to 1000 deg. C in flowing argon for 2 min. Modifications on the chemical bonding structure of the rapidly annealed films, as a function of temperature, were investigated by NEXAFS, X-ray photoelectron and Raman spectroscopies. The interpretation of these spectra is discussed. The results demonstrate that the structure of undoped ta-C films prepared at floating potential with an arc current of 80 A remains stable up to 900 deg. C, whereas that of ta-CN x containing 12 at.% nitrogen is stable up to 700 deg. C. At higher temperatures, all the spectra indicated the predominant formation of graphitic carbon. Through NEXAFS studies, we clearly observed three π* resonance peaks at the ' N K edge structure. The origin of these three peaks is not well established in the literature. However our temperature-dependant study ascertained that the first peak originates from C=N bonds and the third peak originates from the incorporation of nitrogen into the graphite like domains

  3. 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.

  4. Rapid bacterial mineralization of organic carbon produced during a phytoplankton bloom induced by natural iron fertilization in the Southern Ocean

    Science.gov (United States)

    Obernosterer, Ingrid; Christaki, Urania; Lefèvre, Dominique; Catala, Philippe; Van Wambeke, France; Lebaron, Philippe

    2008-03-01

    The response of heterotrophic bacteria ( Bacteria and Archaea) to the spring phytoplankton bloom that occurs annually above the Kerguelen Plateau (Southern Ocean) due to natural iron fertilization was investigated during the KErguelen Ocean and Plateau compared Study (KEOPS) cruise in January-February 2005. In surface waters (upper 100 m) in the core of the phytoplankton bloom, heterotrophic bacteria were, on an average, 3-fold more abundant and revealed rates of production ([ 3H] leucine incorporation) and respiration (bacterial metabolic activities were attributable to high-nucleic-acid-containing cells that dominated (≈80% of total cell abundance) the heterotrophic bacterial community associated with the phytoplankton bloom. Bacterial growth efficiencies varied between 14% and 20% inside the bloom and were bacterial activity, due to the stimulation by phytoplankton-derived dissolved organic matter. Within the Kerguelen bloom, bacterial carbon demand accounted for roughly 45% of gross community production. These results indicate that heterotrophic bacteria processed a significant portion of primary production, with most of it being rapidly respired.

  5. 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.

  6. 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

  7. Laser-induced breakdown spectroscopy (LIBS) for rapid analysis of ash, potassium and magnesium in gluten free flours.

    Science.gov (United States)

    Markiewicz-Keszycka, Maria; Casado-Gavalda, Maria P; Cama-Moncunill, Xavier; Cama-Moncunill, Raquel; Dixit, Yash; Cullen, Patrick J; Sullivan, Carl

    2018-04-01

    Gluten free (GF) diets are prone to mineral deficiency, thus effective monitoring of the elemental composition of GF products is important to ensure a balanced micronutrient diet. The objective of this study was to test the potential of laser-induced breakdown spectroscopy (LIBS) analysis combined with chemometrics for at-line monitoring of ash, potassium and magnesium content of GF flours: tapioca, potato, maize, buckwheat, brown rice and a GF flour mixture. Concentrations of ash, potassium and magnesium were determined with reference methods and LIBS. PCA analysis was performed and presented the potential for discrimination of the six GF flours. For the quantification analysis PLSR models were developed; R 2 cal were 0.99 for magnesium and potassium and 0.97 for ash. The study revealed that LIBS combined with chemometrics is a convenient method to quantify concentrations of ash, potassium and magnesium and present the potential to classify different types of flours. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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    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. Heavy-metal-induced Inhibition of Aspergillus niger nitrate reductase: Applications for Rapid Contaminant Detection in Aqueous Samples

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William Arnold; Aiken, Abigail Marie; Peyton, Brent Michael; Petersen, James N.

    2003-03-01

    Enzyme inhibition assays have the potential to rapidly screen and identify heavy metals in environmental samples. Inhibition of nitrate reductase (NR) was examined as a method for detecting toxic metals. The activity of NR (EC 1.6.6.2) from Aspergillus niger was assayed as a function of metal concentration in the presence of Cd2+, Cr3+, Cr6+, Cu2+, Ni2+, Pb2+, and Zn2+. NR exhibited sensitivity to these metals at concentrations below 10 µM. Various buffers were screened for their ability to protect NR activity from metal inhibition, and 3-(N-morpholino) propanesulfonic acid (MOPS) was selected as the buffering system for the NR assays as it exhibited the least interference with metal inhibition, thus providing increased assay sensitivity. The hypothesis that chelating agents could prevent the inhibition of NR activity by metal ions was also tested. Results indicated that 10 mM ethylenediaminetetraacetic acid (EDTA) could protect NR activity from inhibition by Cr3+, Cu2+, Cd2+, Ni2+, and Zn2+ at concentrations below 100 µM, but that the EDTA had no effect on NR inhibition by Cr6+. An amount of 10 mM nitrilotriacetic acid (NTA) prevented NR inhibition by Cd2+, Cu2+, Ni2+, Pb2+, and Zn2+ at metal concentrations below 100 µM. However, 10 mM NTA was unable to protect the enzyme from inhibition by either Cr3+ or Cr6+. These results indicated that through specific metal chelation, a NR-based method for individually quantifying Cr3+ and Cr6+ species in aqueous solutions could be developed. The ability to restore activity to NR which been previously inhibited by exposure to 100 µM Pb2+, Cd2+, Zn2+, Cu2+, and Cr3+ was explored to determine whether NR activity could be recovered by EDTA additions for use in consecutive metal inhibition assays. The results showed NR activity could not be regained after exposure to Cr3+ or Cu2+, but did partially recover activity after Cd2+, Pb2+, and Zn2+ exposure.

  10. Recent advances in the use of laser-induced breakdown spectroscopy (LIBS) as a rapid point-of-care pathogen diagnostic

    Science.gov (United States)

    Rehse, Steven J.; Miziolek, Andrzej W.

    2012-06-01

    Laser-induced breakdown spectroscopy (LIBS) has made tremendous progress in becoming a viable technology for rapid bacterial pathogen detection and identification. The significant advantages of LIBS include speed (present the latest advances achieved in LIBS-based bacterial sensing including the ability to uniquely identify species from more than five bacterial genera with high-sensitivity and specificity. Bacterial identifications are completely unaffected by environment, nutrition media, or state of growth and accurate diagnoses can be made on autoclaved or UV-irradiated specimens. Efficient discrimination of bacteria at the strain level has been demonstrated. A rapid urinary tract infection diagnosis has been simulated with no sample preparation and a one second diagnosis of a pathogen surrogate has been demonstrated using advanced chemometric analysis with a simple "stop-light" user interface. Stand-off bacterial identification at a 20-m distance has been demonstrated on a field-portable instrument. This technology could be implemented in doctors' offices, clinics, or hospital laboratories for point-of-care medical specimen analysis; mounted on military medical robotic platforms for in-the- field diagnostics; or used in stand-off configuration for remote sensing and detection.

  11. Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects.

    Science.gov (United States)

    Kechagias, S; Ernersson, A; Dahlqvist, O; Lundberg, P; Lindström, T; Nystrom, F H

    2008-05-01

    To study the effect of fast-food-based hyper-alimentation on liver enzymes and hepatic triglyceride content (HTGC). Prospective interventional study with parallel control group. University Hospital of Linköping, Sweden. 12 healthy men and six healthy women with a mean (SD) age of 26 (6.6) years and a matched control group. Subjects in the intervention group aimed for a body weight increase of 5-15% by eating at least two fast-food-based meals a day with the goal to double the regular caloric intake in combination with adoption of a sedentary lifestyle for 4 weeks. Weekly changes of serum aminotransferases and HTGC measured by proton nuclear magnetic resonance spectroscopy at baseline and after the intervention. Subjects in the intervention group increased from 67.6 (9.1) kg to 74.0 (11) kg in weight (p19 U/l, men >30 U/l) during the intervention. Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio (r = 0.62, p = 0.006). HTGC increased from 1.1 (1.9)% to 2.8 (4.8)%, although this was not related to the increase in ALT levels. ALT levels were unchanged in controls. Hyper-alimentation per se can induce profound ALT elevations in less than 4 weeks. Our study clearly shows that in the evaluation of subjects with elevated ALT the medical history should include not only questions about alcohol intake but also explore whether recent excessive food intake has occurred.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Rapid ultrasound-induced transient-liquid-phase bonding of Al-50Si alloys with Zn interlayer in air for electrical packaging application.

    Science.gov (United States)

    Wang, Qian; Chen, Xiaoguang; Zhu, Lin; Yan, Jiuchun; Lai, Zhiwei; Zhao, Pizhi; Bao, Juncheng; Lv, Guicai; You, Chen; Zhou, Xiaoyu; Zhang, Jian; Li, Yuntao

    2017-01-01

    Al-50Si alloys were joined by rapid ultrasound-induced transient-liquid-phase bonding method using Zn foil as interlayer at 390°C in air, below the melt point of interlayer. The fracture of oxide films along the edge of Si particles led to contact and inter-diffusion between aluminum substrate and Zn interlayer, and liquefied Zn-Al alloys were developed. The width of Zn-Al alloys gradually decreased with increasing the ultrasonic vibration time due to liquid squeezing out and accelerated diffusion. A stage of isothermal solidification existed, and the completion time was significantly shortened. In the liquid metal, the acoustic streaming and ultrasonic cavitations were induced. As the process developed, much more Si particles, which were particulate-reinforced phases of Al-50Si, gradually migrated to the center of soldering seam. The highest average shear strength of joints reached to 94.2MPa, and the fracture mainly occurred at the base metal. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Attenuation of ischemia/reperfusion-induced inhibition of the rapid component of delayed rectifier potassium current by Isosteviol through scavenging reactive oxygen species.

    Science.gov (United States)

    Yin, Chunxia; Chen, Yaoxu; Wu, Huanlin; Xu, Danping; Tan, Wen

    2017-12-01

    Isosteviol has been demonstrated to play a protective role during ischemia reperfusion (I/R) myocardial infarction. However, the underlying electrophysiological mechanisms of isosteviol are still unknown. Our previous study showed that the rapid component of the delayed rectifier potassium channel (I Kr ) plays an important role in the prolongation of I/R-induced QT interval-related arrhythmia. This study aimed to investigate whether isosteviol could attenuate I/R-induced prolongation of the action potential duration (APD) along with inhibition of I Kr , and we aimed to clarify the electrophysiological mechanism of isosteviol to determine its cardioprotective effects in guinea pigs. We observed that the APD 90 were 298.5±41.6ms in control, 528.6±56.7ms during I/R, and reduced to 327.8±40.5ms after 10μmol/L of isosteviol treatment. The I Kr currents were 1.44±0.06 pA·pF -1 in the control group, 0.50±0.07pA·pF -1 during I/R, and recovered to 1.20±0.12pA·pF -1 after 10μmol/L of isoteviol treatment. Moreover, isosteviol reduced the over-production of reactive oxygen species (ROS) during I/R. Importantly, isosteviol does not affect the I Kr and human ether-a-go-go-related gene currents of normal cardiomyocytes. It attenuated the I/R-induced inhibition of I Kr due to reduced over-production of ROS. Furthermore, isosteviol is safe and has no cardiotoxicity, and it might be beneficial for coronary reperfusion therapy. Copyright © 2017. Published by Elsevier B.V.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: a rapid in vivo screening method for nanotoxicity.

    Science.gov (United States)

    Lei, Ronghui; Wu, Chunqi; Yang, Baohua; Ma, Huazhai; Shi, Chang; Wang, Quanjun; Wang, Qingxiu; Yuan, Ye; Liao, Mingyang

    2008-10-15

    Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using (1)H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose of 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid beta-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced

  18. Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid invivo screening method for nanotoxicity

    International Nuclear Information System (INIS)

    Lei Ronghui; Wu Chunqi; Yang Baohua; Ma Huazhai; Shi Chang; Wang Quanjun; Wang Qingxiu; Yuan Ye; Liao Mingyang

    2008-01-01

    Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using 1 H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose of 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid β-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced by

  19. 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

  20. 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

    2011-10-07

    Cardiac repolarization is controlled by the rapidly (I(Kr)) and slowly (I(Ks)) activating delayed rectifier potassium channels. The human ether-a-go-go-related gene (hERG) encodes I(Kr), whereas KCNQ1 and KCNE1 together encode I(Ks). Decreases in I(Kr) or I(Ks) 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 I(Ks) compensates for the reduced I(Kr) 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.

  1. Rapid quantitative analysis of elemental composition and depth profile of Cu(In,Ga)Se{sub 2} thin solar cell film using laser-induced breakdown spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    In, Jung-Hwan; Kim, Chan-Kyu; Lee, Seok-Hee; Choi, Jang-Hee; Jeong, Sungho, E-mail: shjeong@gist.ac.kr

    2015-03-31

    Laser-induced breakdown spectroscopy (LIBS) is reported as a method for rapid quantitative analysis of elemental composition and depth profile of Cu(In,Ga)Se{sub 2} (CIGS) thin film. A calibration model considering compositional grading over depth was developed and verified with test samples. The results from eight test samples showed that the average concentration of Cu, In, Ga and Se could be predicted with a root mean square error of below 1% and a relative standard deviation of also below 1%. The depth profile of each constituent element of CIGS predicted by LIBS was close to those by Auger electron spectroscopy and secondary ion mass spectrometry. The average ablation depth per pulse during depth profiling was about 100 nm. - Highlights: • LIBS was adopted for quantitative analysis of CIGS thin film. • A calibration model considering compositional grading over depth was developed. • Concentration prediction of CIGS thin film was accurate and precise. • Quantitative depth profiling by LIBS was compared with those by AES and SIMS.

  2. 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.

  3. Accurate and rapid modeling of iron-bleomycin-induced DNA damage using tethered duplex oligonucleotides and electrospray ionization ion trap mass spectrometric analysis.

    Science.gov (United States)

    Harsch, A; Marzilli, L A; Bunt, R C; Stubbe, J; Vouros, P

    2000-05-01

    Bleomycin B(2)(BLM) in the presence of iron [Fe(II)] and O(2)catalyzes single-stranded (ss) and double-stranded (ds) cleavage of DNA. Electrospray ionization ion trap mass spectrometry was used to monitor these cleavage processes. Two duplex oligonucleotides containing an ethylene oxide tether between both strands were used in this investigation, allowing facile monitoring of all ss and ds cleavage events. A sequence for site-specific binding and cleavage by Fe-BLM was incorporated into each analyte. One of these core sequences, GTAC, is a known hot-spot for ds cleavage, while the other sequence, GGCC, is a hot-spot for ss cleavage. Incubation of each oligo-nucleotide under anaerobic conditions with Fe(II)-BLM allowed detection of the non-covalent ternary Fe-BLM/oligonucleotide complex in the gas phase. Cleavage studies were then performed utilizing O(2)-activated Fe(II)-BLM. No work-up or separation steps were required and direct MS and MS/MS analyses of the crude reaction mixtures confirmed sequence-specific Fe-BLM-induced cleavage. Comparison of the cleavage patterns for both oligonucleotides revealed sequence-dependent preferences for ss and ds cleavages in accordance with previously established gel electrophoresis analysis of hairpin oligonucleotides. This novel methodology allowed direct, rapid and accurate determination of cleavage profiles of model duplex oligonucleotides after exposure to activated Fe-BLM.

  4. Effect of Rapid Thermal Processing on Light-Induced Degradation of Carrier Lifetime in Czochralski p-Type Silicon Bare Wafers

    Science.gov (United States)

    Kouhlane, Y.; Bouhafs, D.; Khelifati, N.; Belhousse, S.; Menari, H.; Guenda, A.; Khelfane, A.

    2016-11-01

    The electrical properties of Czochralski silicon (Cz-Si) p-type boron-doped bare wafers have been investigated after rapid thermal processing (RTP) with different peak temperatures. Treated wafers were exposed to light for various illumination times, and the effective carrier lifetime ( τ eff) measured using the quasi-steady-state photoconductance (QSSPC) technique. τ eff values dropped after prolonged illumination exposure due to light-induced degradation (LID) related to electrical activation of boron-oxygen (BO) complexes, except in the sample treated with peak temperature of 785°C, for which the τ eff degradation was less pronounced. Also, a reduction was observed when using the 830°C peak temperature, an effect that was enhanced by alteration of the wafer morphology (roughness). Furthermore, the electrical resistivity presented good stability under light exposure as a function of temperature compared with reference wafers. Additionally, the optical absorption edge shifted to higher wavelength, leading to increased free-carrier absorption by treated wafers. Moreover, a theoretical model is used to understand the lifetime degradation and regeneration behavior as a function of illumination time. We conclude that RTP plays an important role in carrier lifetime regeneration for Cz-Si wafers via modification of optoelectronic and structural properties. The balance between an optimized RTP cycle and the rest of the solar cell elaboration process can overcome the negative effect of LID and contribute to achievement of higher solar cell efficiency and module performance.

  5. 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

    International Nuclear Information System (INIS)

    Pham, Anh; Bortolazzo, Anthony; White, J. Brandon

    2012-01-01

    Highlights: ► Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. ► Quercetin forms a heterodimer through oxidation in media with serum. ► The quercetin heterodimer does not kill MDA-MB-231 cells. ► Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. ► 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.

  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. Thioacetamide-induced cirrhosis in selenium-adequate mice displays rapid and persistent abnormity of hepatic selenoenzymes which are mute to selenium supplementation

    International Nuclear Information System (INIS)

    Zhang Jinsong; Wang Huali; Yu Hanqing

    2007-01-01

    Selenium reduction in cirrhosis is frequently reported. The known beneficial effect of selenium supplementation on cirrhosis is probably obtained from nutritionally selenium-deficient subjects. Whether selenium supplementation truly improves cirrhosis in general needs additional experimental investigation. Thioacetamide was used to induce cirrhosis in selenium-adequate and -deficient mice. Selenoenzyme activity and selenium content were measured and the influence of selenium supplementation was evaluated. In Se-adequate mice, thioacetamide-mediated rapid onset of hepatic oxidative stress resulted in an increase in thioredoxin reductase activity and a decrease in both glutathione peroxidase activity and selenium content. The inverse activity of selenoenzymes (i.e. TrxR activity goes up and GPx activity goes down) was persistent and mute to selenium supplementation during the progress of cirrhosis; accordingly, cirrhosis was not improved by selenium supplementation in any period. On the other hand, selenium supplementation to selenium-deficient mice always more efficiently increased hepatic glutathione peroxidase activity and selenium content compared with those treated with thioacetamide, indicating that thioacetamide impairs the liver bioavailability of selenium. Although thioacetamide profoundly affects hepatic selenium status in selenium-adequate mice, selenium supplementation does not modify the changes. Selenium supplementation to cirrhotic subjects with a background of nutritional selenium deficiency can improve selenium status but cannot restore hepatic glutathione peroxidase and selenium to normal levels

  8. Rapid and Weight-Independent Improvement of Glucose Tolerance Induced by a Peptide Designed to Elicit Apoptosis in Adipose Tissue Endothelium

    Science.gov (United States)

    Kim, Dong-Hoon; Sartor, Maureen A.; Bain, James R.; Sandoval, Darleen; Stevens, Robert D.; Medvedovic, Mario; Newgard, Christopher B.; Woods, Stephen C.; Seeley, Randy J.

    2012-01-01

    A peptide designed to induce apoptosis of endothelium in white adipose tissue (WAT) decreases adiposity. The goal of this work is to determine whether targeting of WAT endothelium results in impaired glucose regulation as a result of impaired WAT function. Glucose tolerance tests were performed on days 2 and 3 of treatment with vehicle (HF-V) or proapoptotic peptide (HF-PP) and mice pair-fed to HF-PP (HF-PF) in obese mice on a high-fat diet (HFD). Serum metabolic variables, including lipid profile, adipokines, individual fatty acids, and acylcarnitines, were measured. Microarray analysis was performed in epididymal fat of lean or obese mice treated with vehicle or proapoptotic peptide (PP). PP rapidly and potently improved glucose tolerance of obese mice in a weight- and food intake–independent manner. Serum insulin and triglycerides were decreased in HF-PP relative to HF-V. Levels of fatty acids and acylcarnitines were distinctive in HF-PP compared with HF-V or HF-PF. Microarray analysis in AT revealed that pathways involved in mitochondrial dysfunction, oxidative phosphorylation, and branched-chain amino acid degradation were changed by exposure to HFD and were reversed by PP administration. These studies suggest a novel role of the AT vasculature in glucose homeostasis and lipid metabolism. PMID:22733798

  9. Rapid Electrical Stimulation Increased Cardiac Apoptosis Through Disturbance of Calcium Homeostasis and Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Le Geng

    2018-06-01

    Full Text Available Background/Aims: Heart failure induced by tachycardia, the most common arrhythmia, is frequently observed in clinical practice. This study was designed to investigate the underlying mechanisms. Methods: Rapid electrical stimulation (RES at a frequency of 3 Hz was applied on human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs for 7 days, with 8 h/day and 24 h/day set to represent short-term and long-term tachycardia, respectively. Age-matched hiPSC-CMs without electrical stimulation or with slow electrical stimulation (1 Hz were set as no electrical stimulation (NES control or low-frequency electrical stimulation (LES control. Following stimulation, JC-1 staining flow cytometry analysis was performed to examine mitochondrial conditions. Apoptosis in hiPSC-CMs was evaluated using Hoechst staining and Annexin V/propidium iodide (AV/PI staining flow cytometry analysis. Calcium transients and L-type calcium currents were recorded to evaluate calcium homeostasis. Western blotting and qPCR were performed to evaluate the protein and mRNA expression levels of apoptosis-related genes and calcium homeostasis-regulated genes. Results: Compared to the controls, hiPSC-CMs following RES presented mitochondrial dysfunction and an increased apoptotic percentage. Amplitudes of calcium transients and L-type calcium currents were significantly decreased in hiPSC-CMs with RES. Molecular analysis demonstrated upregulated expression of Caspase3 and increased Bax/Bcl-2 ratio. Genes related to calcium re-sequence were downregulated, while phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII was significantly upregulated following RES. There was no significant difference between the NES control and LES control groups in these aspects. Inhibition of CaMKII with 1 µM KN93 partly reversed these adverse effects of RES. Conclusion: RES on hiPSC-CMs disturbed calcium homeostasis, which led to mitochondrial stress, promoted cell apoptosis and

  10. 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

  11. 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.

  12. 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

  13. Modelling multi-phase liquid-sediment scour and resuspension induced by rapid flows using Smoothed Particle Hydrodynamics (SPH) accelerated with a Graphics Processing Unit (GPU)

    Science.gov (United States)

    Fourtakas, G.; Rogers, B. D.

    2016-06-01

    A two-phase numerical model using Smoothed Particle Hydrodynamics (SPH) is applied to two-phase liquid-sediments flows. The absence of a mesh in SPH is ideal for interfacial and highly non-linear flows with changing fragmentation of the interface, mixing and resuspension. The rheology of sediment induced under rapid flows undergoes several states which are only partially described by previous research in SPH. This paper attempts to bridge the gap between the geotechnics, non-Newtonian and Newtonian flows by proposing a model that combines the yielding, shear and suspension layer which are needed to predict accurately the global erosion phenomena, from a hydrodynamics prospective. The numerical SPH scheme is based on the explicit treatment of both phases using Newtonian and the non-Newtonian Bingham-type Herschel-Bulkley-Papanastasiou constitutive model. This is supplemented by the Drucker-Prager yield criterion to predict the onset of yielding of the sediment surface and a concentration suspension model. The multi-phase model has been compared with experimental and 2-D reference numerical models for scour following a dry-bed dam break yielding satisfactory results and improvements over well-known SPH multi-phase models. With 3-D simulations requiring a large number of particles, the code is accelerated with a graphics processing unit (GPU) in the open-source DualSPHysics code. The implementation and optimisation of the code achieved a speed up of x58 over an optimised single thread serial code. A 3-D dam break over a non-cohesive erodible bed simulation with over 4 million particles yields close agreement with experimental scour and water surface profiles.

  14. JINR rapid communications

    International Nuclear Information System (INIS)

    1998-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on invisible Z-boson width and restrictions on next-to-minimal supersymmetric standard model, cosmic test of honeycomb drift chambers, fission of 209 Bi, 232 Th, 235 U, 238 U and 237 Np in a spallation neutron field, rapid screening of spontaneous and radiation-induced structural changes at the vestigial gene of Drosophila melanogaster by polymerase chain reaction, gamma-ray multiplicities in sub-barrier fission of 226 Th and the decay constants of the scalar and pseudoscalar mesons in the quark models with quasilocal interaction

  15. 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....

  16. 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...

  17. Spin-selective depopulation of triplet sublevels in rapidly rotating triplet exciplexes detected by a heavy-atom-induced magnetic field effect

    OpenAIRE

    Steiner, Ulrich

    1980-01-01

    A mechanism is presented explaining a reported heavy-atom-induced magnetic field effect as a consequence of non-equilibrium triplet sublevel population in an intermediate exciplex. The triplet exciplex spin polarization is induced by sub-level-selective intersystem crossing from the exciplex triplet to its singlet ground state and is decreased by an external magnetic field. The theory accounts almost quantitatively for the observed influence of magnetic field strength and heavy-atom substitue...

  18. JINR rapid communications

    International Nuclear Information System (INIS)

    1998-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on decays of excited strange mesons in the extended NJL model, production of heavy evaporation residues in the reactions induced by an extracted 48 Ca beam on a 208 Pb target, scaling behaviour of tensor analyzing power (A yy ) in the inelastic scattering or relativistic deuterons,two-photon collisions at very low Q 2 from LEP2: forthcoming results, high magnetic field uniformity superconducting magnet for a movable polarized target, multichannel time-to-digital converter for drift detector and wavelet-analysis: application to Gaussian signals

  19. JINR rapid communications

    International Nuclear Information System (INIS)

    1996-01-01

    The present collection of rapid communications from JINR, Dubna, contains five separate reports on analytic QCD running coupling with finite IR behaviour and universal α bar s (0) value, quark condensate in the interacting pion- nucleon medium at finite temperature and baryon number density, γ-π 0 discrimination with a shower maximum detector using neural networks for the solenoidal tracker at RHIC, off-specular neutron reflection from magnetic media with nondiagonal reflectivity matrices and molecular cytogenetics of radiation-induced gene mutations in Drosophila melanogaster. 21 fig., 1 tab

  20. 3' RNA ligase mediated rapid amplification of cDNA ends for validating viroid induced cleavage at the 3' extremity of the host mRNA.

    Science.gov (United States)

    Adkar-Purushothama, Charith Raj; Bru, Pierrick; Perreault, Jean-Pierre

    2017-12-01

    5' RNA ligase-mediated rapid amplification of cDNA ends (5' RLM-RACE) is a widely-accepted method for the validation of direct cleavage of a target gene by a microRNA (miRNA) and viroid-derived small RNA (vd-sRNA). However, this method cannot be used if cleavage takes place in the 3' extremity of the target RNA, as this gives insufficient sequence length to design nested PCR primers for 5' RLM RACE. To overcome this hurdle, we have developed 3' RNA ligase-mediated rapid amplification of cDNA ends (3' RLM RACE). In this method, an oligonucleotide adapter having 5' adenylated and 3' blocked is ligated to the 3' end of the cleaved RNA followed by PCR amplification using gene specific primers. In other words, in 3' RLM RACE, 3' end is mapped using 5' fragment instead of small 3' fragment. The method developed here was verified by examining the bioinformatics predicted and parallel analysis of RNA ends (PARE) proved cleavage sites of chloride channel protein CLC-b-like mRNA in Potato spindle tuber viroid infected tomato plants. The 3' RLM RACE developed in this study has the potential to validate the miRNA and vd-sRNA mediated cleavage of mRNAs at its 3' untranslated region (3' UTR). Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Characterisation of vaccine-induced, broadly cross-reactive IFN-γ secreting T cell responses that correlate with rapid protection against classical swine fever virus.

    Science.gov (United States)

    Graham, Simon P; Haines, Felicity J; Johns, Helen L; Sosan, Olubukola; La Rocca, S Anna; Lamp, Benjamin; Rümenapf, Till; Everett, Helen E; Crooke, Helen R

    2012-04-05

    Live attenuated C-strain classical swine fever viruses (CSFV) provide a rapid onset of protection, but the lack of a serological test that can differentiate vaccinated from infected animals limits their application in CSF outbreaks. Since immunity may precede antibody responses, we examined the kinetics and specificity of peripheral blood T cell responses from pigs vaccinated with a C-strain vaccine and challenged after five days with a genotypically divergent CSFV isolate. Vaccinated animals displayed virus-specific IFN-γ responses from day 3 post-challenge, whereas, unvaccinated challenge control animals failed to mount a detectable response. Both CD4(+) and cytotoxic CD8(+) T cells were identified as the cellular source of IFN-γ. IFN-γ responses showed extensive cross-reactivity when T cells were stimulated with CSFV isolates spanning the major genotypes. To determine the specificity of these responses, T cells were stimulated with recombinant CSFV proteins and a proteome-wide peptide library from a related virus, BVDV. Major cross-reactive peptides were mapped on the E2 and NS3 proteins. Finally, IFN-γ was shown to exert potent antiviral effects on CSFV in vitro. These data support the involvement of broadly cross-reactive T cell IFN-γ responses in the rapid protection conferred by the C-strain vaccine and this information should aid the development of the next generation of CSFV vaccines. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  2. Large-scale Mass Transport Deposits in the Valencia Basin (Western Mediterranean): slope instability induced by rapid sea-level drawdown?

    Science.gov (United States)

    Cameselle, Alejandra L.; Urgeles, Roger; Llopart, Jaume

    2014-05-01

    The Messinian Salinity Crisis (MSC) strongly affected the physiography of the Mediterranean margins at the end of the Miocene. The sharp sea-level fall gave a new configuration to the Mediterranean basin and created dramatic morphological and sedimentological changes: margins have been largely eroded whereas the deep basins accumulated thick evaporitic and detrital units. Amongst these detrital units, there are evidences on seismic reflection data for major large-scale slope failure of the Mediterranean continental margins. About 2700 km of seismic reflection profiles in the southwestern part of the Valencia Basin (Western Mediterranean) have enabled us the detailed mapping of distinctive Messinian erosional surfaces, evaporites and deep detrital deposits. The detrital deposits occur in a distinct unit that is made of chaotic, roughly-bedded or transparent seismic bodies, which have been mainly mapped in the basin domain. Locally, the seismic unit shows discontinuous high-amplitude reflections and/or an imbricate internal structure. This unit is interpreted to be formed by a series of Mass Transport Deposits (MTDs). Rapid drawdown has long been recognized as one of the most severe loadings conditions that a slope can be subjected to. Several large historical slope failures have been documented to occur due to rapid drawdown in dams, riverbanks and slopes. During drawdown, the stabilizing effect of the water on the upstream face is lost, but the pore-water pressures within the slope may remain high. The dissipation of these pore pressures in the slope is controlled by the permeability and the storage characteristics of the slope sediments. We hypothesize that the MTDs observed in our data formed under similar conditions and represent a large-scale equivalent of this phenomenon. Therefore, these MTDs can be used to put some constraints on the duration of the drawdown phase of the MSC. We have performed a series of slope stability analysis under rapid Messinian sea

  3. Rapid method for detecting base damage in DNA of mammalian cells: assay of U. V. -induced pyrimidine dimers in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, P E [Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit; Jansson, G; Ahnstroem, G

    1978-11-01

    Simple and rapid techniques are described for the detection of pyrimidine dimers in DNA. Human cells derived from embryonic lung tissue were UV-irradiated and subjected to either an osmotic shock procedure or detergent lysis, then treated with UV-endonuclease from Micrococcus luteus and the DNA partially denatured by treatment with weak alkali. Brief sonication reduced the molecular weight of the DNA, and the single- and double-stranded DNA could then be separated by hydroxylapatite chromatography. Approximately 40% of the expected number of pyrimidine dimers were detected by the enzyme treatment technique. The mean value of numbers of strand breaks per 10/sup 9/ dalton per J/m/sup 2/ was approximately 50% of the expected value. The method has advantages of speed and reproducibility and a large reduction in the quantities of materials used, particularly at the scintillation-counting stage.

  4. Rapid agonist-induced loss of sup 125 I-. beta. -endorphin opioid receptor sites in NG108-15, but not SK-N-SH neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Cone, R.I.; Lameh, J.; Sadee, W. (Univ. of California, San Francisco (United States))

    1991-01-01

    The authors have measured {mu} and {delta} opioid receptor sites on intact SK-N-SH and NG108-15 neuroblastoma cells, respectively, in culture. Use of {sup 125}I-{beta}-endorphin ({beta}E) as a tracer, together with {beta}E(6-31) to block high-affinity non-opioid binding in both cell lines, permitted the measurement of cell surface {mu} and {delta} opioid receptor sites. Labeling was at {delta} sites in NG108-15 cells and predominantly at {mu} sites in SK-N-SH cells. Pretreatment with the {mu} and {delta} agonist, DADLE, caused a rapid loss of cell surface {delta} receptor sites in NG108-15 cells, but failed to reduce significantly {mu} receptor density in SK-N-SH cells.

  5. JINR rapid communications

    International Nuclear Information System (INIS)

    1997-01-01

    The present collection of rapid communications from JINR, Dubna, contains nine separate reports on collective energy dissipation and fluctuations in elastoplastic systems, diagnostics system of the circulating beam of the NUCLOTRON based on microchannel plates, time-of-flight detector for WA98 CERN experiment, fractal structure formation on the surfaces of solids subjected to high intensity electron and ion treatment, production of nuclei in 32,34,36 S-induced reactions in the energy range 6-75 MeV/A, rare-earth elements in soil and pine needle from northern terrestrial ecosystems, 'thermal' multifragmentation in p + Au collisions at relativistic energies, search for effects of the OZI rule violation in φ and ω mesons production in polarized deuteron beam interaction with polarized proton target (project DPHE3) and fast detector for triggering on charged particle multiplicity for relativistic nucleus-nucleus collisions

  6. Protein Kinase Cε, Which Is Linked to Ultraviolet Radiation-Induced Development of Squamous Cell Carcinomas, Stimulates Rapid Turnover of Adult Hair Follicle Stem Cells

    International Nuclear Information System (INIS)

    Singh, A.; Singh, A.; Sand, J. M.; Bin Hafeez, B.; Verma, A. K.; Sand, J. M.; Heninger, E.

    2013-01-01

    To find clues about the mechanism by which kinase C epsilon (PKCε) may impart susceptibility to ultraviolet radiation (UVR)-induced development of cutaneous squamous cell carcinomas (SCC), we compared PKCε transgenic (TG) mice and their wild-type (WT) litter mates for (1) the effects of UVR exposures on percent of putative hair follicle stem cells (HSC s ) and (2) HSCs proliferation. The percent of double HSC s (CD34+ andα6-integrin or CD34+/CD49f+) in the isolated keratinocytes were determined by flow cytometric analysis. Both single and chronic UVR treatments (1.8 kJ/m 2 ) resulted in an increase in the frequency of double positive HSCs in PKCεTG mice as compared to their WT litter mates. To determine the rate of proliferation of bulge region stem cells, a 5-bromo-2-deoxyuridine labeling (BrdU) experiment was performed. In the WT mice, the percent of double positive HSC s retaining BrdU label was 28.4±0.6% compared to 4.0±0.06% for the TG mice, an approximately 7-fold decrease. A comparison of gene expression profiles of FACS sorted double positive HSCs showed increased expression of Pes1, Rad21, Tfdp1 and Cks1b genes in TG mice compared to WT mice. Also, PKCεover expression in mice increased the clonogenicity of isolated keratinocytes, a property commonly ascribed to stem cells.

  7. 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.

  8. Dissociation in the Effects of Induced Neonatal Hypoxia-Ischemia on Rapid Auditory Processing and Spatial Working Memory in Male Rats.

    Science.gov (United States)

    Smith, Amanda L; Alexander, Michelle; Chrobak, James J; Rosenkrantz, Ted S; Fitch, R Holly

    2015-01-01

    Infants born prematurely are at risk for cardiovascular events causing hypoxia-ischemia (HI; reduced blood and oxygen to the brain). HI in turn can cause neuropathology, though patterns of damage are sometimes diffuse and often highly variable (with clinical heterogeneity further magnified by rapid development). As a result, though HI injury is associated with long-term behavioral and cognitive impairments in general, pathology indices for specific infants can provide only limited insight into individual prognosis. The current paper addresses this important clinical issue using a rat model that simulates unilateral HI in a late preterm infant coupled with long-term behavioral evaluation in two processing domains - auditory discrimination and spatial learning/memory. We examined the following: (1) whether deficits on one task would predict deficits on the other (suggesting that subjects with more severe injury perform worse across all cognitive domains) or (2) whether domain-specific outcomes among HI-injured subjects would be uncorrelated (suggesting differential damage to orthogonal neural systems). All animals (sham and HI) received initial auditory testing and were assigned to additional auditory testing (group A) or spatial maze testing (group B). This allowed within-task (group A) and between-task (group B) correlation. Anatomic measures of cortical, hippocampal and ventricular volume (indexing HI damage) were also obtained and correlated against behavioral measures. Results showed that auditory discrimination in the juvenile period was not correlated with spatial working memory in adulthood (group B) in either sham or HI rats. Conversely, early auditory processing performance for group A HI animals significantly predicted auditory deficits in adulthood (p = 0.05; no correlation in shams). Anatomic data also revealed significant relationships between the volumes of different brain areas within both HI and shams, but anatomic measures did not correlate with any

  9. Rapid shallow breathing

    Science.gov (United States)

    Tachypnea; Breathing - rapid and shallow; Fast shallow breathing; Respiratory rate - rapid and shallow ... Shallow, rapid breathing has many possible medical causes, including: Asthma Blood clot in an artery in the ...

  10. Rapid determination of triclosan in personal care products using new in-tube based ultrasound-assisted salt-induced liquid-liquid microextraction coupled with high performance liquid chromatography-ultraviolet detection.

    Science.gov (United States)

    Chen, Ming-Jen; Liu, Ya-Ting; Lin, Chiao-Wen; Ponnusamy, Vinoth Kumar; Jen, Jen-Fon

    2013-03-12

    This paper describes the development of a novel, simple and efficient in-tube based ultrasound-assisted salt-induced liquid-liquid microextraction (IT-USA-SI-LLME) technique for the rapid determination of triclosan (TCS) in personal care products by high performance liquid chromatography-ultraviolet (HPLC-UV) detection. IT-USA-SI-LLME method is based on the rapid phase separation of water-miscible organic solvent from the aqueous phase in the presence of high concentration of salt (salting-out phenomena) under ultrasonication. In the present work, an indigenously fabricated home-made glass extraction device (8-mL glass tube inbuilt with a self-scaled capillary tip) was utilized as the phase separation device for USA-SI-LLME. After the extraction, the upper extractant layer was narrowed into the self-scaled capillary tip by pushing the plunger plug; thus, the collection and measurement of the upper organic solvent layer was simple and convenient. The effects of various parameters on the extraction efficiency were thoroughly evaluated and optimized. Under optimal conditions, detection was linear in the concentration range of 0.4-100ngmL(-1) with correlation coefficient of 0.9968. The limit of detection was 0.09ngmL(-1) and the relative standard deviations ranged between 0.8 and 5.3% (n=5). The applicability of the developed method was demonstrated for the analysis of TCS in different commercial personal care products and the relative recoveries ranged from 90.4 to 98.5%. The present method was proven to be a simple, sensitive, less organic solvent consuming, inexpensive and rapid procedure for analysis of TCS in a variety of commercially available personal care products or cosmetic preparations. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. 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.

  12. A slow-releasing form of prostacyclin agonist (ONO1301SR) enhances endogenous secretion of multiple cardiotherapeutic cytokines and improves cardiac function in a rapid-pacing-induced model of canine heart failure.

    Science.gov (United States)

    Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Shiozaki, Motoko; Kawaguchi, Naomasa; Matsuura, Nariaki; Nakatani, Satoshi; Sakai, Yoshiki; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

    2013-08-01

    Cardiac functional deterioration in dilated cardiomyopathy (DCM) is known to be reversed by intramyocardial up-regulation of multiple cardioprotective factors, whereas a prostacyclin analog, ONO1301, has been shown to paracrinally activate interstitial cells to release a variety of protective factors. We here hypothesized that intramyocardial delivery of a slow-releasing form of ONO1301 (ONO1301SR) might activate regional myocardium to up-regulate cardiotherapeutic factors, leading to regional and global functional recovery in DCM. ONO1301 elevated messenger RNA and protein level of hepatocyte growth factor, vascular endothelial growth factor, and stromal-derived factor-1 of normal human dermal fibroblasts in a dose-dependent manner in vitro. Intramyocardial delivery of ONO1301SR, which is ONO1301 mixed with polylactic and glycolic acid polymer (PLGA), but not that of PLGA only, yielded significant global functional recovery in a canine rapid pacing-induced DCM model, assessed by echocardiography and cardiac catheterization (n = 5 each). Importantly, speckle-tracking echocardiography unveiled significant regional functional recovery in the ONO1301-delivered territory, consistent to significantly increased vascular density, reduced interstitial collagen accumulation, attenuated myocyte hypertrophy, and reversed mitochondrial structure in the corresponding area. Intramyocardial delivery of ONO1301SR, which is a PLGA-coated slow-releasing form of ONO1301, up-regulated multiple cardiotherapeutic factors in the injected territory, leading to region-specific reverse left ventricular remodeling and consequently a global functional recovery in a rapid-pacing-induced canine DCM model, warranting a further preclinical study to optimize this novel drug-delivery system to treat DCM. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  13. Rapid identification and recovery of ENU-induced mutations with next-generation sequencing and Paired-End Low-Error analysis.

    Science.gov (United States)

    Pan, Luyuan; Shah, Arish N; Phelps, Ian G; Doherty, Dan; Johnson, Eric A; Moens, Cecilia B

    2015-02-14

    Targeting Induced Local Lesions IN Genomes (TILLING) is a reverse genetics approach to directly identify point mutations in specific genes of interest in genomic DNA from a large chemically mutagenized population. Classical TILLING processes, based on enzymatic detection of mutations in heteroduplex PCR amplicons, are slow and labor intensive. Here we describe a new TILLING strategy in zebrafish using direct next generation sequencing (NGS) of 250 bp amplicons followed by Paired-End Low-Error (PELE) sequence analysis. By pooling a genomic DNA library made from over 9,000 N-ethyl-N-nitrosourea (ENU) mutagenized F1 fish into 32 equal pools of 288 fish, each with a unique Illumina barcode, we reduce the complexity of the template to a level at which we can detect mutations that occur in a single heterozygous fish in the entire library. MiSeq sequencing generates 250 base-pair overlapping paired-end reads, and PELE analysis aligns the overlapping sequences to each other and filters out any imperfect matches, thereby eliminating variants introduced during the sequencing process. We find that this filtering step reduces the number of false positive calls 50-fold without loss of true variant calls. After PELE we were able to validate 61.5% of the mutant calls that occurred at a frequency between 1 mutant call:100 wildtype calls and 1 mutant call:1000 wildtype calls in a pool of 288 fish. We then use high-resolution melt analysis to identify the single heterozygous mutation carrier in the 288-fish pool in which the mutation was identified. Using this NGS-TILLING protocol we validated 28 nonsense or splice site mutations in 20 genes, at a two-fold higher efficiency than using traditional Cel1 screening. We conclude that this approach significantly increases screening efficiency and accuracy at reduced cost and can be applied in a wide range of organisms.

  14. A rapid solution-based method for determining the affinity of heroin hapten-induced antibodies to heroin, its metabolites, and other opioids.

    Science.gov (United States)

    Torres, Oscar B; Duval, Alexander J; Sulima, Agnieszka; Antoline, Joshua F G; Jacobson, Arthur E; Rice, Kenner C; Alving, Carl R; Matyas, Gary R

    2018-06-01

    We describe for the first time a method that utilizes microscale thermophoresis (MST) technology to determine polyclonal antibody affinities to small molecules. Using a novel type of heterologous MST, we have accurately measured a solution-based binding affinity of serum antibodies to heroin which was previously impossible with other currently available methods. Moreover, this mismatch approach (i.e., using a cross-reactive hapten tracer) has never been reported in the literature. When compared with equilibrium dialysis combined with ultra-performance liquid chromatography/tandem mass spectrometry (ED-UPLC/MS/MS), this novel MST method yields similar binding affinity values for polyclonal antibodies to the major heroin metabolites 6-AM and morphine. Additionally, we herein report the method of synthesis of this novel cross-reactive hapten, MorHap-acetamide-a useful analog for the study of heroin hapten-antibody interactions. Using heterologous MST, we were able to determine the affinities, down to nanomolar accuracies, of polyclonal antibodies to various abused opioids. While optimizing this method, we further discovered that heroin is protected from serum esterase degradation by the presence of these antibodies in a concentration-dependent manner. Lastly, using affinity data for a number of structurally different opioids, we were able to dissect the moieties that are crucial to antibody binding. The novel MST method that is presented herein can be extended to the analysis of any ligand that is prone to degradation and can be applied not only to the development of vaccines to substances of abuse but also to the analysis of small molecule/protein interactions in the presence of serum. Graphical abstract Strategy for the determination of hapten-induced antibody affinities using Microscale thermophoresis.

  15. Extensin network formation in Vitis vinifera callus cells is an essential and causal event in rapid and H2O2-induced reduction in primary cell wall hydration

    Science.gov (United States)

    2011-01-01

    Background Extensin deposition is considered important for the correct assembly and biophysical properties of primary cell walls, with consequences to plant resistance to pathogens, tissue morphology, cell adhesion and extension growth. However, evidence for a direct and causal role for the extensin network formation in changes to cell wall properties has been lacking. Results Hydrogen peroxide treatment of grapevine (Vitis vinifera cv. Touriga) callus cell walls was seen to induce a marked reduction in their hydration and thickness. An analysis of matrix proteins demonstrated this occurs with the insolubilisation of an abundant protein, GvP1, which displays a primary structure and post-translational modifications typical of dicotyledon extensins. The hydration of callus cell walls free from saline-soluble proteins did not change in response to H2O2, but fully regained this capacity after addition of extensin-rich saline extracts. To assay the specific contribution of GvP1 cross-linking and other wall matrix proteins to the reduction in hydration, GvP1 levels in cell walls were manipulated in vitro by binding selected fractions of extracellular proteins and their effect on wall hydration during H2O2 incubation assayed. Conclusions This approach allowed us to conclude that a peroxidase-mediated formation of a covalently linked network of GvP1 is essential and causal in the reduction of grapevine callus wall hydration in response to H2O2. Importantly, this approach also indicated that extensin network effects on hydration was only partially irreversible and remained sensitive to changes in matrix charge. We discuss this mechanism and the importance of these changes to primary wall properties in the light of extensin distribution in dicotyledons. PMID:21672244

  16. 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.

  17. 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.

  18. Microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse-transcription polymerase chain reaction for the rapid detection of Enterovirus 71 and Coxsackievirus A16 in throat swab specimens.

    Science.gov (United States)

    Jia, Ruan; Chengjun, Sun; Heng, Chen; Chen, Zhou; Yuanqian, Li; Yongxin, Li

    2015-07-01

    Enterovirus 71 and Coxsackievirus A16 are the main pathogens causing hand-foot-mouth disease. In this paper, microchip capillary electrophoresis with laser-induced fluorescence combined with one-step duplex reverse transcript-polymerase chain reaction has been developed for the detection of Enterovirus 71 and Coxsackievirus A16 in throat swab specimens. The specific reverse transcription-polymerase chain reaction amplicons labeled with SYBR Orange were separated by microchip capillary electrophoresis and detected by laser induced fluorescence detector within 7 min. The intraday and interday relative standard deviation of migration time for DNA Marker was in the range of 1.36-2.94 and 2.78-3.96%, respectively. The detection limits were as low as 2.06 × 10(3) copies/mL for Enterovirus 71 and 5 × 10(3) copies/mL for Coxsackievirus A16. No cross-reactivity was observed with rotavirus, astrovirus, norovirus, and adenovirus, which showed good specificity of the method. This assay was validated using 100 throat swab specimens that were detected by real-time reverse-transcript polymerase chain reaction in parallel and the two methods produced the same results. This study provided a rapid, sensitive and specific method for the detection of Enterovirus 71 and Coxsackievirus A16, which make a contribution to significant time and cost saving for the identification and treatment of patients. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. On the mechanism of rapid postirradiation recovery of yeast

    International Nuclear Information System (INIS)

    Glazunov, A.V.; Kapul'tsevich, Yu.G.

    1983-01-01

    Rapid postirradiation recovery of diploid yeast Saccharomyces cerevisiae is equally effective both in water and in a liquid nutrition medium. In the haploid strains, rapid recovery occurs more readily in the log phase than in the stationary phase of growth. In the diploid strains, rapid recovery is more effective in the log phase than in the stationary phase. Rapid recovery of yeast does not require an additional protein synthesis. Damages induced by UV-light are not sub ected to rapid recovery

  20. DHT inhibits the Aβ25-35-induced apoptosis by regulation of seladin-1, survivin, XIAP, bax, and bcl-xl expression through a rapid PI3-K/Akt signaling in C6 glial cell lines.

    Science.gov (United States)

    Bing, Lelin; Wu, Junfeng; Zhang, Jianfeng; Chen, Yinghui; Hong, Zhen; Zu, Hengbing

    2015-01-01

    Previous evidences indicate that androgen is neuroprotective in the brain. However, the underling mechanisms remain to be fully elucidated. Moreover, it is controversial whether dihydrotestosterone (DHT) modulates the expression of apoptosis-related effectors, such as survivin, XIAP, bax, and bcl-xl proteins mediated by the PI3-K/Akt pathway, which contributes to androgen neuroprotection. In this study using a C6 glial cell model, apoptotic cells were detected by flow cytometry. Akt, seladin-1, survivin, XIAP, bcl-xl, and bax protein expression is investigated by Western blot. After amyloid β-protein fragment (Aβ25-35) treatment, apoptotic cells at early (annexin V+, PI-) and late (annexin V+, PI+) stages were significantly increased. Apoptosis at early and late was obviously inhibited in the presence of DHT. The effect of DHT was markedly blocked by PI3-K inhibitor LY294002.To elicit the mechanism of DHT protection, the expression of seladin-1, survivin, XIAP, bax, and bcl-xl protein was determined in C6 cells treated with Aβ25-35, DHT, or LY294002. Aβ25-35 significantly downregulated the expression of seladin-1, survivin, XIAP, bcl-xl protein and upregulated the expression of bax protein. DHT significantly inhibited the expression of bax, seladin-1, survivin, XIAP, and bcl-xl protein induced by Aβ25-35. Further, we found the effect of DHT was significantly inhibited by LY294002. Collectively, in a C6 glial cell model, we firstly found that DHT inhibits Aβ25-35-induced apoptosis by a rapid nongenic PI-3K/Akt activation as well as regulation of seladin-1, survivin, XIAP, bcl-xl, and bax proteins.

  1. Rapid in vivo Taxotere quantitative chemosensitivity response by 4.23 Tesla sodium MRI and histo-immunostaining features in N-Methyl-N-Nitrosourea induced breast tumors in rats

    Directory of Open Access Journals (Sweden)

    Wu Ed X

    2005-08-01

    Full Text Available Abstract Background Sodium weighted images can indicate sodium signal intensities from different features in the tumor before and 24 hours following administration of Taxotere. Aim To evaluate the association of in vivo intracellular sodium magnetic resonance image intensities with immuno-biomarkers and histopathological features to monitor the early tumor response to Taxotere chemotherapy in Methyl-Nitroso-Urea induced rat xenograft breast tumors. Methods and Materials Methyl-Nitroso-Urea (MNU induced rat xenograft breast tumors were imaged for sodium MRI and compared with tumor histology, immunostaining after 24 hours chemotherapy. Results Sodium MRI signal intensities represented sodium concentrations. Excised tumor histological sections showed different in vitro histological end points i.e. single strand DNA content of cell nuclei during cell cycle (G1/S-G2/M, distinct S or M histograms (Feulgen labeling to nuclear DNA content by CAS 200, mitotic figures and apoptosis at different locations of breast tumors. Necrosis and cystic fluid appeared gray on intracellular (IC sodium images while apoptosis rich regions appeared brighter on IC sodium images. After 24 hours Taxotere-treated tumors showed lower 'IC/EC ratio' of viable cells (65–76% with higher mitotic index; apoptotic tumor cells at high risk due to cytotoxicity (>70% with high apoptotic index; reduced proliferation index (270 vs 120 per high power field associated with enhanced IC sodium in vivo MR image intensities and decreased tumor size (3%; p in vivo associated with apoptosis and different pre-malignant features within 24 hours of exposure of cancer cells to anti-neoplastic Taxotere drug. Conclusion Sodium MRI imaging may be used as in vivo rapid drug monitoring method to evaluate Taxotere chemosensitivity response associated with neoplasia, apoptosis and tumor histology features.

  2. 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

  3. Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling*

    Science.gov (United States)

    Liu, Rui; Kenney, Justin W.; Manousopoulou, Antigoni; Johnston, Harvey E.; Kamei, Makoto; Woelk, Christopher H.; Xie, Jianling; Schwarzer, Michael; Proud, Christopher G.

    2016-01-01

    Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. In the former, myocardial growth is a risk factor for cardiac failure and faster protein synthesis is a major factor driving cardiomyocyte growth. Our goal was to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are caused by alterations on mRNA abundance or the translation of specific mRNAs. Cardiomyocytes have very low rates of protein synthesis, posing a challenging problem in terms of studying changes in the synthesis of specific proteins, which also applies to other nondividing primary cells. To study the rates of accumulation of specific proteins in these cells, we developed an optimized version of the Quantitative Noncanonical Amino acid Tagging LC/MS proteomic method to label and selectively enrich newly synthesized proteins in these primary cells while eliminating the suppressive effects of pre-existing and highly abundant nonisotope-tagged polypeptides. Our data revealed that a classical pathologic (phenylephrine; PE) and the recently identified insulin stimulus that also contributes to the development of pathological cardiac hypertrophy (insulin), both increased the synthesis of proteins involved in, e.g. glycolysis, the Krebs cycle and beta-oxidation, and sarcomeric components. However, insulin increased synthesis of many metabolic enzymes to a greater extent than PE. Using a novel validation method, we confirmed that synthesis of selected candidates is indeed up-regulated by PE and insulin. Synthesis of all proteins studied was up-regulated by signaling through mammalian target of rapamycin complex 1 without changes in their mRNA levels, showing the key importance of translational control in the rapid effects of hypertrophic stimuli. Expression of PKM2 was up-regulated in rat hearts following TAC. This isoform possesses specific regulatory

  4. Immunization of chickens with an agonistic monoclonal anti-chicken CD40 antibody-hapten complex: rapid and robust IgG response induced by a single subcutaneous injection.

    Science.gov (United States)

    Chen, Chang-Hsin; Abi-Ghanem, Daad; Waghela, Suryakant D; Chou, Wen-Ko; Farnell, Morgan B; Mwangi, Waithaka; Berghman, Luc R

    2012-04-30

    Producing diagnostic antibodies in chicken egg yolk represents an alternate animal system that offers many advantages including high productivity at low cost. Despite being an excellent counterpart to mammalian antibodies, chicken IgG from yolk still represents an underused resource. The potential of agonistic monoclonal anti-CD40 antibodies (mAb) as a powerful immunological adjuvant has been demonstrated in mammals, but not in chickens. We recently reported an agonistic anti-chicken CD40 mAb (designated mAb 2C5) and showed that it may have potential as an immunological adjuvant. In this study, we examined the efficacy of targeting a short peptide to chicken CD40 [expressed by the antigen-presenting cells (APCs)] in enhancing an effective IgG response in chickens. For this purpose, an immune complex consisting of one streptavidin molecule, two directionally biotinylated mAb 2C5 molecules, and two biotinylated peptide molecules was produced. Chickens were immunized subcutaneously with doses of this complex ranging from 10 to 90 μg per injection once, and relative quantification of the peptide-specific IgG response showed that the mAb 2C5-based complex was able to elicit a strong IgG response as early as four days post-immunization. This demonstrates that CD40-targeting antigen to chicken APCs can significantly enhance antibody responses and induce immunoglobulin isotype-switching. This immunization strategy holds promise for rapid production of hapten-specific IgG in chickens. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. 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,...

  6. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  7. Rapid Tooling via Stereolithography

    OpenAIRE

    Montgomery, Eva

    2006-01-01

    Approximately three years ago, composite stereolithography (SL) resins were introduced to the marketplace, offering performance features beyond what traditional SL resins could offer. In particular, the high heat deflection temperatures and high stiffness of these highly filled resins have opened the door to several new rapid prototyping (RP) applications, including wind tunnel test modelling and, more recently, rapid tooling.

  8. HIV-1 subtype C unproductively infects human cardiomyocytes in vitro and induces apoptosis mitigated by an anti-Gp120 aptamer

    CSIR Research Space (South Africa)

    Rangel Lopes de Campos, W

    2014-10-01

    Full Text Available - surface receptors, the CXCR4 chemokine receptor and the TNF- R1 death receptor. The predominant apoptotic pathway varied from CXCR4-triggered, mitochondrion-initiated to CD95/Fas- ligand initiated, depending on the culture conditions as previously reported... virus type 1 gp120 to CXCR4 induces mitochondrial transmembrane depolarization and cytochrome c- mediated apoptosis independently of Fas signaling. J Virol 75: 7637–7650. 26. Bottarel F, Feito MJ, Bragardo M, Bonissoni S, Buonfiglio D, et al. (1999...

  9. Rapid improvement teams.

    Science.gov (United States)

    Alemi, F; Moore, S; Headrick, L; Neuhauser, D; Hekelman, F; Kizys, N

    1998-03-01

    Suggestions, most of which are supported by empirical studies, are provided on how total quality management (TQM) teams can be used to bring about faster organizationwide improvements. Ideas are offered on how to identify the right problem, have rapid meetings, plan rapidly, collect data rapidly, and make rapid whole-system changes. Suggestions for identifying the right problem include (1) postpone benchmarking when problems are obvious, (2) define the problem in terms of customer experience so as not to blame employees nor embed a solution in the problem statement, (3) communicate with the rest of the organization from the start, (4) state the problem from different perspectives, and (5) break large problems into smaller units. Suggestions for having rapid meetings include (1) choose a nonparticipating facilitator to expedite meetings, (2) meet with each team member before the team meeting, (3) postpone evaluation of ideas, and (4) rethink conclusions of a meeting before acting on them. Suggestions for rapid planning include reducing time spent on flowcharting by focusing on the future, not the present. Suggestions for rapid data collection include (1) sample patients for surveys, (2) rely on numerical estimates by process owners, and (3) plan for rapid data collection. Suggestions for rapid organizationwide implementation include (1) change membership on cross-functional teams, (2) get outside perspectives, (3) use unfolding storyboards, and (4) go beyond self-interest to motivate lasting change in the organization. Additional empirical investigations of time saved as a consequence of the strategies provided are needed. If organizations solve their problems rapidly, fewer unresolved problems may remain.

  10. Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder.

    Science.gov (United States)

    McKenna, Dillon; Peever, John

    2017-05-01

    During healthy rapid eye movement sleep, skeletal muscles are actively forced into a state of motor paralysis. However, in rapid eye movement sleep behavior disorder-a relatively common neurological disorder-this natural process is lost. A lack of motor paralysis (atonia) in rapid eye movement sleep behavior disorder allows individuals to actively move, which at times can be excessive and violent. At first glance this may sound harmless, but it is not because rapid eye movement sleep behavior disorder patients frequently injure themselves or the person they sleep with. It is hypothesized that the degeneration or dysfunction of the brain stem circuits that control rapid eye movement sleep paralysis is an underlying cause of rapid eye movement sleep behavior disorder. The link between brain stem degeneration and rapid eye movement sleep behavior disorder stems from the fact that rapid eye movement sleep behavior disorder precedes, in the majority (∼80%) of cases, the development of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, which are known to initially cause degeneration in the caudal brain stem structures where rapid eye movement sleep circuits are located. Furthermore, basic science and clinical evidence demonstrate that lesions within the rapid eye movement sleep circuits can induce rapid eye movement sleep-specific motor deficits that are virtually identical to those observed in rapid eye movement sleep behavior disorder. This review examines the evidence that rapid eye movement sleep behavior disorder is caused by synucleinopathic neurodegeneration of the core brain stem circuits that control healthy rapid eye movement sleep and concludes that rapid eye movement sleep behavior disorder is not a separate clinical entity from synucleinopathies but, rather, it is the earliest symptom of these disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and

  11. Rapid response systems.

    Science.gov (United States)

    Lyons, Patrick G; Edelson, Dana P; Churpek, Matthew M

    2018-07-01

    Rapid response systems are commonly employed by hospitals to identify and respond to deteriorating patients outside of the intensive care unit. Controversy exists about the benefits of rapid response systems. We aimed to review the current state of the rapid response literature, including evolving aspects of afferent (risk detection) and efferent (intervention) arms, outcome measurement, process improvement, and implementation. Articles written in English and published in PubMed. Rapid response systems are heterogeneous, with important differences among afferent and efferent arms. Clinically meaningful outcomes may include unexpected mortality, in-hospital cardiac arrest, length of stay, cost, and processes of care at end of life. Both positive and negative interventional studies have been published, although the two largest randomized trials involving rapid response systems - the Medical Early Response and Intervention Trial (MERIT) and the Effect of a Pediatric Early Warning System on All-Cause Mortality in Hospitalized Pediatric Patients (EPOCH) trial - did not find a mortality benefit with these systems, albeit with important limitations. Advances in monitoring technologies, risk assessment strategies, and behavioral ergonomics may offer opportunities for improvement. Rapid responses may improve some meaningful outcomes, although these findings remain controversial. These systems may also improve care for patients at the end of life. Rapid response systems are expected to continue evolving with novel developments in monitoring technologies, risk prediction informatics, and work in human factors. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. 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.

  13. Rapid world modeling

    International Nuclear Information System (INIS)

    Little, Charles; Jensen, Ken

    2002-01-01

    Sandia National Laboratories has designed and developed systems capable of large-scale, three-dimensional mapping of unstructured environments in near real time. This mapping technique is called rapid world modeling and has proven invaluable when used by prototype systems consisting of sensory detection devices mounted on mobile platforms. These systems can be deployed into previously unmapped environments and transmit real-time 3-D visual images to operators located remotely. This paper covers a brief history of the rapid world modeling system, its implementation on mobile platforms, and the current state of the technology. Applications to the nuclear power industry are discussed. (author)

  14. JINR rapid communications

    International Nuclear Information System (INIS)

    1998-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on relativistic multiparticle processes in the central rapidity region at asymptotically high energies, a new experimental study of charged K→3π decays, pre-Cherenkov radiation as a phenomenon of 'light barrier', stable S=-2 H dibaryon found in Dubna, calculation of Green functions and gluon top in some unambiguous gauges, a method of a fast selection of inelastic nucleus-nucleus collisions for the CMS experiment and the manifestation of jet quenching in differential distributions of the total transverse energy in nucleus-nucleus collisions

  15. Rapid microbiology - raising awareness.

    Science.gov (United States)

    Bailie, Jonathan

    2016-01-01

    A 'high-level overview' of some of the emerging rapid microbiology technologies designed to help healthcare engineering and infection control teams working in hospitals and other healthcare facilities more rapidly identify potentially hazardous levels of waterborne microorganisms in their water systems, enabling them to take prompt remedial action, and a look at the some of the 'pros and cons' of such testing techniques, was given by Nalco technical director, Howard Barnes, the vice-chair of the Legionella Control Association (LCA), at a recent LCA open day. HEJ editor, Jonathan Bailie, reports.

  16. Navigate the Digital Rapids

    Science.gov (United States)

    Lindsay, Julie; Davis, Vicki

    2010-01-01

    How can teachers teach digital citizenship when the digital landscape is changing so rapidly? How can teachers teach proper online social interactions when the students are outside their classroom and thus outside their control? Will encouraging students to engage in global collaborative environments land teachers in hot water? These are the…

  17. Isoflurane Damages the Developing Brain of Mice and Induces Subsequent Learning and Memory Deficits through FASL-FAS Signaling

    Directory of Open Access Journals (Sweden)

    Xiuwen Yi

    2015-01-01

    Full Text Available Background. Isoflurane disrupts brain development of neonatal mice, but its mechanism is unclear. We explored whether isoflurane damaged developing hippocampi through FASL-FAS signaling pathway, which is a well-known pathway of apoptosis. Method. Wild type and FAS- or FASL-gene-knockout mice aged 7 days were exposed to either isoflurane or pure oxygen. We used western blotting to study expressions of caspase-3, FAS (CD95, and FAS ligand (FASL or CD95L proteins, TUNEL staining to count apoptotic cells in hippocampus, and Morris water maze (MWM to evaluate learning and memory. Result. Isoflurane increased expression of FAS and FASL proteins in wild type mice. Compared to isoflurane-treated FAS- and FASL-knockout mice, isoflurane-treated wild type mice had higher expression of caspase-3 and more TUNEL-positive hippocampal cells. Expression of caspase-3 in wild isoflurane group, wild control group, FAS/FASL-gene-knockout control group, and FAS/FASL-gene-knockout isoflurane group showed FAS or FASL gene knockout might attenuate increase of caspase-3 caused by isoflurane. MWM showed isoflurane treatment of wild type mice significantly prolonged escape latency and reduced platform crossing times compared with gene-knockout isoflurane-treated groups. Conclusion. Isoflurane induces apoptosis in developing hippocampi of wild type mice but not in FAS- and FASL-knockout mice and damages brain development through FASL-FAS signaling.

  18. Rapid road repair vehicle

    Science.gov (United States)

    Mara, Leo M.

    1998-01-01

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.

  19. Rapidly processable radiographic material

    International Nuclear Information System (INIS)

    Brabandere, L.A. de; Borginon, H.A.; Pattyn, H.A.; Pollet, R.J.

    1981-01-01

    A new rapidly processable radiographic silver halide material is described for use in mammography and non-destructive testing of industrial materials. The radiographic material is used for direct exposure to penetrating radiation without the use of fluorescent-intensifying screens. It consists of a transparent support with a layer of hydrophilic colloid silver halide emulsion on one or both sides. Examples of the preparation of three different silver halide emulsions are given including the use of different chemical sensitizers. These new radiographic materials have good resistance to the formation of pressure marks in rapid processing apparatus and they have improved sensitivity for direct exposure to penetrating radiation compared to conventional radiographic emulsions. (U.K.)

  20. Rapid manufacturing for microfluidics

    CSIR Research Space (South Africa)

    Land, K

    2012-10-01

    Full Text Available for microfluidics K. LAND, S. HUGO, M MBANJWA, L FOURIE CSIR Materials Science and Manufacturing P O Box 395, Pretoria 0001, SOUTH AFRICA Email: kland@csir.co.za INTRODUCTION Microfluidics refers to the manipulation of very small volumes of fluid.... 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...

  1. 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.

  2. Rapid MR imaging

    International Nuclear Information System (INIS)

    Edelman, R.R.; Buxton, R.B.; Brady, T.J.

    1988-01-01

    Conventional magnetic resonance (MR) imaging methods typically require several minutes to produce an image, but the periods of respiration, cardiac motion and peristalsis are on the order of seconds or less. The need to reduce motion artifact, as well as the need to reduce imaging time for patient comfort and efficiency, have provided a strong impetus for the development of rapid imaging methods. For abdominal imaging, motion artifacts due to respiration can be significantly reduced by collecting the entire image during one breath hold. For other applications, such as following the kinetics of administered contrast agents, rapid imaging is essential to achieve adequate time resolution. A shorter imaging time entails a cost in image signal/noise (S/N), but improvements in recent years in magnet homogeneity, gradient and radiofrequency coil design have led to steady improvements in S/N and consequently in image quality. For many chemical applications the available S/N is greater than needed, and a trade-off of lower S/N for a shorter imaging time is acceptable. In this chapter, the authors consider the underlying principles of rapid imaging as well as clinical applications of these methods. The bulk of this review concentrates on short TR imaging, but methods that provide for a more modest decrease in imaging time as well as or those that dramatically shorten the imaging time to tens of milliseconds are also discussed

  3. 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.

  4. JINR rapid communications

    International Nuclear Information System (INIS)

    1995-01-01

    The present collection of rapid communications from JINR, Dubna, contains eight separate reports on the measurement of charge radii for Ti nuclei, spectroscopy of 13 Be, concentrations of hadrons and quark-gluon plasma in mixed phase, experimental results on one-spin pion asymmetry in the d↑ + A → π±(90 0 ) + X process, new results on cumulative pion and proton production in p-D collisions, investigation of charge exchange reactions, the study of the tensor analyzing power in cumulative particle production on a deuteron beam and an evidence for the excited states of the S = -2 stable light dibaryon. 32 figs., 6 tabs

  5. JINR rapid communications

    International Nuclear Information System (INIS)

    1999-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on additional conditions on eigenvectors in solving inverse problem for two-dimensional Schroedinger equation, on an absolute calibration of deuteron beam polarization at LHE, determination of the vector component of the polarization of the JINR synchrophasotron deuteron beam, wavelet-analysis: criterion of reliable signal selection, on asymptotics in inclusive production of antinuclei and nuclear fragments, use of neutron activation analysis at the IBR-2 reactor for atmospheric monitoring and impulse method for temperature measurement of silicon detectors

  6. JINR rapid communications

    International Nuclear Information System (INIS)

    1995-01-01

    The present collection of rapid communications from JINR, Dubna, contains six separate reports on Monte Carlo simulation of silicon detectors for the ALICE experiment at LHC, a study of single tagged multihadronic γγ* events at an average Q 2 of 90 GeV 2 , epithermal neutron activation analysis of moss, lichen and pine needles in atmospheric deposition monitoring, the theory of neutrino oscillation, coupled quadrupole and monopole vibrations of large amplitude and test of the Ellis-Jaffe sum rule using parametrization of the measured lepton-proton asymmetry. 21 figs., 18 tabs

  7. 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.

  8. 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

  9. Exposure of Human CD8+ T Cells to Type-2 Cytokines Impairs Division and Differentiation and Induces Limited Polarization

    Directory of Open Access Journals (Sweden)

    Annette Fox

    2018-05-01

    Full Text Available Effector CD8+ T cells generally produce type-1 cytokines and mediators of the perforin/granzyme cytolytic pathway, yet type-2-polarized CD8+ cells (Tc2 are detected in type-2 (T2 cytokine-driven diseases such as asthma. It is unclear whether T2 cytokine exposure during activation is sufficient to polarize human CD8+ T cells. To address this question, a protocol was developed for high-efficiency activation of human CD8+ T cells in which purified single cells or populations were stimulated with plate-bound anti-CD3 and anti-CD11a mAb for up to 8 days in T2 polarizing or neutral conditions, before functional analysis. Activation of CD8+ naïve T cells (TN in T2 compared with neutral conditions decreased the size of single-cell clones, although early division kinetics were equivalent, indicating an effect on overall division number. Activation of TN in T2 conditions followed by brief anti-CD3 mAb restimulation favored expression of T2 cytokines, GATA3 and Eomes, and lowered expression of type-1 cytokines, Prf1, Gzmb, T-BET, and Prdm1. However, IL-4 was only weakly expressed, and PMA and ionomycin restimulation favored IFN-γ over IL-4 expression. Activation of TN in T2 compared with neutral conditions prevented downregulation of costimulatory (CD27, CD28 and lymph-node homing receptors (CCR7 and CD95 acquisition, which typically occur during differentiation into effector phenotypes. CD3 was rapidly and substantially induced after activation in neutral, but not T2 conditions, potentially contributing to greater division and differentiation in neutral conditions. CD8+ central memory T cells (TCM were less able to enter division upon reactivation in T2 compared with neutral conditions, and were more refractory to modulating IFN-γ and IL-4 production than CD8+ TN. In summary, while activation of TN in T2 conditions can generate T2 cytokine-biased cells, IL-4 expression is weak, T2 bias is lost upon strong restimulation, differentiation, and division

  10. Rapid Geophysical Surveyor

    International Nuclear Information System (INIS)

    Roybal, L.G.; Carpenter, G.S.; Josten, N.E.

    1993-01-01

    The Rapid Geophysical Surveyor (RGS) is a system designed to rapidly and economically collect closely-spaced geophysical data used for characterization of US Department of Energy waste sites. Geophysical surveys of waste sites are an important first step in the remediation and closure of these sites; especially older sites where historical records are inaccurate and survey benchmarks have changed because of refinements in coordinate controls and datum changes. Closely-spaced data are required to adequately differentiate pits, trenches, and soil vault rows whose edges may be only a few feet from each other. A prototype vehicle designed to collect magnetic field data was built at the Idaho National Engineering Laboratory (INEL) during the summer of 1992. The RGS was funded by the Buried Waste Integrated Demonstration program. This vehicle was demonstrated at the Subsurface Disposal Area (SDA) within the Radioactive Waste Management Complex at the INEL in September 1992. Magnetic data were collected over two areas in the SDA, with a total survey area of about 1.7 acres. Data were collected at a nominal density of 2 1/2 in. along survey lines spaced 1-ft apart. Over 350,000 data points were collected over a 6 day period corresponding to about 185 worker-days using conventional ground survey techniques

  11. Rapid automated nuclear chemistry

    International Nuclear Information System (INIS)

    Meyer, R.A.

    1979-01-01

    Rapid Automated Nuclear Chemistry (RANC) can be thought of as the Z-separation of Neutron-rich Isotopes by Automated Methods. The range of RANC studies of fission and its products is large. In a sense, the studies can be categorized into various energy ranges from the highest where the fission process and particle emission are considered, to low energies where nuclear dynamics are being explored. This paper presents a table which gives examples of current research using RANC on fission and fission products. The remainder of this text is divided into three parts. The first contains a discussion of the chemical methods available for the fission product elements, the second describes the major techniques, and in the last section, examples of recent results are discussed as illustrations of the use of RANC

  12. JINR rapid communications

    International Nuclear Information System (INIS)

    1999-01-01

    The present collection of rapid communications from JINR, DUBNA, contains eight separate records on symmetry in modern physics (dedicated to the 100th anniversary of the birth of academician V.A.Fock), the double φ-meson production investigation on the Serpukhov accelerator, two-leptonic η-meson decays and SUSY without R parity, charge form factors and alpha-cluster internal structure of 12 C, increasing of muon-track reconstruction efficiency in ME1/1 Dubna prototype for the CMS/LHC, study of photon-structure function F 2 γ in the reaction e + e - → e + e - + hadrons at LEP2, jets reconstruction possibility in pAu and AuAu interactions at STAR RHIC and high-vacuum nondispersable gas absorber

  13. Rapid thermal pulse annealing

    International Nuclear Information System (INIS)

    Miller, M.G.; Koehn, B.W.; Chaplin, R.L.

    1976-01-01

    Characteristics of recovery processes have been investigated for cases of heating a sample to successively higher temperatures by means of isochronal annealing or by using a rapid pulse annealing. A recovery spectra shows the same features independent of which annealing procedure is used. In order to determine which technique provides the best resolution, a study was made of how two independent first-order processes are separated for different heating rates and time increments of the annealing pulses. It is shown that the pulse anneal method offers definite advantages over isochronal annealing when annealing for short time increments. Experimental data by means of the pulse anneal techniques are given for the various substages of stage I of aluminium. (author)

  14. JINR rapid communications

    International Nuclear Information System (INIS)

    1996-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate reports on the identification of events with a secondary vertex in the experiment EXCHARM, the zero degree calorimeter for CERN WA-98 experiment, a new approach to increase the resource of installation elements for super-high energy physics, a method of the in-flight production of exotic systems in the charge-exchange reactions, the neutron activation analysis for monitoring northern terrestrial ecosystems, a search for 28 O and study of the neutron-rich nuclei near the neutron closure N=20, a search for new neutron-rich nuclei with a 70A MeV 48 Ca beam. 33 figs., 4 tabs

  15. JINR Rapid Communications. Collection

    International Nuclear Information System (INIS)

    1994-01-01

    The present collection of rapid communications from JINR, Dubna, contains nine separate reports on quasi-classical description of one-nucleon transfer reactions with heavy ions, elastic and inelastic scattering in the high energy approximation, experimental study of fission and evaporation cross sections for 6 He + 209 Bi reaction, d ↑ + 12 C → p + X at Θ p = 0 o in the region of high internal momenta in the deuteron, the Nuclotron internal targets, actively screened superconducting magnets, using of polarized target in backward elastic dp scattering, application of transputers in the data acquisition system of the INESS-ALPHA spectrometer, narrow dibaryon resonances with isotopic spin I=2. 93 refs., 27 figs., 4 tabs

  16. JINR Rapid Communications. Collection

    International Nuclear Information System (INIS)

    1994-01-01

    The present collection of rapid communications from JINR, Dubna, contains eight separate reports on Lorentz transformations with superluminal velocities, photo chromic effect in HTSC films, the investigation of hypernuclei in the Nuclotron accelerator, a new hadron jets finding algorithm in the four-dimensional velocity space, investigations of neutral particle production by relativistic nuclei on the LHE 90-channel γ-spectrometer (results and perspectives), coherent meson production in the dp → 3 HeX reaction, the relativistic projectile nuclei fragmentation and A-dependence of nucleon Fermi-momenta, energy spectra of γ-quanta from d-propane interactions at momentum P d = 1.25 GeV/c per nucleon. 86 refs., 26 figs., 4 tabs

  17. JINR rapid communications

    International Nuclear Information System (INIS)

    1999-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on measurements of the total cross section difference Δσ L (np) at 1.59, 1.79, and 2.20 GeV, to the estimation of angular distributions of double charged spectator fragments in nucleus-nucleus interactions at superhigh energies, simulation dE/dx analysis results for silicon inner tracking system of ALICE set-up at LHC accelerator, high-multiplicity processes, triggering of high-multiplicity events using calorimetry, ORBIT-3.0 - a computer code for simulation and correction of the closed orbit and first turn in synchrotrons and determination of memory performance

  18. JINR rapid communications

    International Nuclear Information System (INIS)

    1999-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate records on yields of the rare-earth neutron-deficient isotopes in the reactions of Mo isotopes with 40 Ca ions, observations of slow components of solitonic-type wave structure excited by e-beam in massive copper sample, development and investigation of low-mass multilayer drift chambers (MDC-2) for inner part of the HADES spectrometer, temperature measurement of the uranium sample irradiated with secondary neutrons, edge effects in multiwire proportional chambers, the influence of the dielectric frame, an object-oriented framework for the hadronic Monte-Carlo event generators and uranium-238 as a source for electronuclear power production. 32 figs., 3 tabs

  19. JINR rapid communications

    International Nuclear Information System (INIS)

    1997-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate reports on observation of transversal handedness in the diffractive production of pion triples, a possible experiment on the research of dibaryon states, Cherenkov beam counter system of the CERES/NA45 spectrometer for investigation with 160 GeV/n. lead ions, a profile-based gaseous detector with capacitive pad readout as the prototype of the shower maximum detector for the end-cap electromagnetic calorimeter for the STAR experiment, what DELPHI can get with an upgraded position for the very small angle tagger, estimation of the radiation environment and the shielding aspect for the point 2 area of the LHC and the orthopositronium decay puzzle

  20. 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).

  1. JINR rapid communications

    International Nuclear Information System (INIS)

    1997-01-01

    The present collection of rapid communications from JINR, Dubna, contains seven separate reports on investigation of the tensor analyzing power A yy in the reaction A(d polarized, p)X at large transverse momenta of proton, double-differential ionization cross section calculations for fast collisions of ions and atoms, a study of the two-photon interactions tagged at an average 2 > of 90 GeV 2 , cluster and single-particle distributions in nucleus-nucleus interactions, the Coulomb interaction of charged pions in CC-and CTa-collisions at 4.2 A GeV/c, influence of nitrogen and oxygen gas admixtures on the response of the DELPHI HCAL and MUS detectors and an automation of physics research on base of open standards

  2. JINR rapid communications

    International Nuclear Information System (INIS)

    1997-01-01

    The present collection of rapid communications from JINR, Dubna, contains nine separate reports on effects arising from charged particles overcoming of the light velocity barrier, deformable templates for circle recognition, scintillation detectors for precise time measurements, atomic form factors and incoherent scattering functions of atoms and ions with the number of electrons N ≤ 10, experimental set-up ANOMALON for measurement of relativistic nuclear fragmentation cross sections, superconducting dipole magnet for ALICE dimuon arm spectrometer, analysis of transverse mass dependence of Bose-Einstein correlation radii using the DELPHI data, low-energy theorem in softly broken supersymmetry and study of the characteristics of particles in reactions π - , p, d, He, C + C with the total disintegration on carbon nucleus

  3. JINR rapid communications

    International Nuclear Information System (INIS)

    1998-01-01

    The present collection of rapid communications from JINR, Dubna, contains six separate records on test of a threshold aerogel Cherenkov counter on cosmic particles, first results of study of transversal dimension of region of cumulative particles production in d + C and d + Cu reactions for energy 2 GeV/nucleon, the evidence of σ[0 + (0 ++ 0)] meson at a mass of M π + π - = 750 ± 5 MeV/c 2 observed in π + π - combinations from the reaction np → npπ + π - at an incident momentum of P n (5.20 ± 0.16 GeV/c, inclusive spectra of protons and π - mesons emitted in 4 HeC and 12 CC interactions with total disintegration of nuclei, heavy quark-antiquark pair production by double pomeron exchange in pp and AA collisions on the CMS and global features of nucleus-nucleus collisions in ultrarelativistic domain

  4. 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...

  5. 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...

  6. Rapid population growth.

    Science.gov (United States)

    1972-01-01

    At the current rate of population growth, world population by 2000 is expected to reach 7 billion or more, with developing countries accounting for some 5.4 billion, and economically advanced nations accounting for 1.6 billion. 'Population explosion' is the result of falling mortality rates and continuing high birth rates. Many European countries, and Japan, have already completed what is termed as demographic transition, that is, birth rates have fallen to below 20 births per 1000 population, death rates to 10/1000 population, and annual growth rates are 1% or less; annual growth rates for less developed countries ranged from 2 to 3.5%. Less developed countries can be divided into 3 groups: 1) countries with both high birth and death rates; 2) countries with high birth rates and low death rates; and 3) countries with intermediate and declining birth rates and low death rates. Rapid population growth has serious economic consequences. It encourages inequities in income distribution; it limits rate of growth of gross national product by holding down level of savings and capital investments; it exerts pressure on agricultural production and land; and it creates unemployment problems. In addition, the quality of education for increasing number of chidren is adversely affected, as high proportions of children reduce the amount that can be spent for the education of each child out of the educational budget; the cost and adequacy of health and welfare services are affected in a similar way. Other serious consequences of rapid population growth are maternal death and illness, and physical and mental retardation of children of very poor families. It is very urgent that over a billion births be prevented in the next 30 years to reduce annual population growth rate from the current 2% to 1% per year.

  7. Rapid geophysical surveyor

    International Nuclear Information System (INIS)

    Roybal, L.G.; Carpenter, G.S.; Josten, N.E.

    1993-01-01

    The Rapid Geophysical Surveyor (RGS) is a system designed to rapidly and economically collect closely-spaced geophysical data used for characterization of Department of Energy (DOE) waste sites. Geophysical surveys of waste sites are an important first step in the remediation and closure of these sites; especially older sties where historical records are inaccurate and survey benchmarks have changed due to refinements in coordinate controls and datum changes. Closely-spaced data are required to adequately differentiate pits, trenches, and soil vault rows whose edges may be only a few feet from each other. A prototype vehicle designed to collect magnetic field data was built at the Idaho national Engineering Laboratory (INEL) during the summer of 1992. The RGS was one of several projects funded by the Buried Waste Integrated Demonstration (BWID) program. This vehicle was demonstrated at the Subsurface Disposal Area (SDA) within the Radioactive Waste Management Complex (RWMC) on the INEL in September of 1992. Magnetic data were collected over two areas in the SDA, with a total survey area of about 1.7 acres. Data were collected at a nominal density of 2 1/2 inches along survey lines spaced 1 foot apart. Over 350,000 data points were collected over a 6 day period corresponding to about 185 man-days using conventional ground survey techniques. This report documents the design and demonstration of the RGS concept including the presentation of magnetic data collected at the SDA. The surveys were able to show pit and trench boundaries and determine details of their spatial orientation never before achieved

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

    Directory of Open Access Journals (Sweden)

    Kanikkai Raja Aseer

    Full Text Available 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.

  9. 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

  10. 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)

  11. 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.

  12. Rapid Evaporation of microbubbles

    Science.gov (United States)

    Gautam, Jitendra; Esmaeeli, Asghar

    2008-11-01

    When a liquid is heated to a temperature far above its boiling point, it evaporates abruptly. Boiling of liquid at high temperatures can be explosive and destructive, and poses a potential hazard for a host of industrial processes. Explosive boiling may occur if a cold and volatile liquid is brought into contact with a hot and non-volatile liquid, or if a liquid is superheated or depressurized rapidly. Such possibilities are realized, for example, in the depressurization of low boiling point liquefied natural gas (LNG) in the pipelines or storage tanks as a result of a leak. While boiling of highly heated liquids can be destructive at macroscale, the (nearly) instantaneous pace of the process and the release of large amount of kinetic energy make the phenomena extremely attractive at microscale where it is possible to utilize the released energy to derive micromechanical systems. For instance, there is currently a growing interest in micro-explosion of liquid for generation of micro bubbles for actuation purposes. The aim of the current study is to gain a fundamental understanding of the subject using direct numerical simulations. In particular, we seek to investigate the boundary between stable and unstable nucleus growth in terms of the degree of liquid superheat and to compare the dynamics of unstable and stable growth.

  13. Rapid flow imaging method

    International Nuclear Information System (INIS)

    Pelc, N.J.; Spritzer, C.E.; Lee, J.N.

    1988-01-01

    A rapid, phase-contrast, MR imaging method of imaging flow has been implemented. The method, called VIGRE (velocity imaging with gradient recalled echoes), consists of two interleaved, narrow flip angle, gradient-recalled acquisitions. One is flow compensated while the second has a specified flow encoding (both peak velocity and direction) that causes signals to contain additional phase in proportion to velocity in the specified direction. Complex image data from the first acquisition are used as a phase reference for the second, yielding immunity from phase accumulation due to causes other than motion. Images with pixel values equal to MΔΘ where M is the magnitude of the flow compensated image and ΔΘ is the phase difference at the pixel, are produced. The magnitude weighting provides additional vessel contrast, suppresses background noise, maintains the flow direction information, and still allows quantitative data to be retrieved. The method has been validated with phantoms and is undergoing initial clinical evaluation. Early results are extremely encouraging

  14. JINR rapid communications

    International Nuclear Information System (INIS)

    1995-01-01

    The present collection of rapid communications from JINR, Dubna, contains twelve separate reports on an estimation of the possibility of fusion reactions in water molecules, an analysis of pion spectra of the charge-exchange reaction Mg(t, 3 He), the results of simulation of e + e - pair production and detection in the ALICE experiment, the data on the edge effects in multiwire proportional chambers, standard and nonstandard applications of wavelet analysis, the design and study of light readout system for scintillator shower maximum detector for the endcap electromagnetic calorimeter for the STAR experiment at RHIC, a study of multiparticle azimuthal correlations in high energy interactions, coherent multifragmentation of relativistic nuclei, superposition of neutrino eigenstates and neutrino oscillation, simulation results and suggestions for possible design of gaseous shower maximum detector for the endcap electromagnetic calorimeter for the STAR experiment at RHIC, determination of the sizes of the pion emission region in np-interactions at P n =(5.2±0.16)GeV/c using the interference correlation method for identical particles, inelasticity of nucleus-nucleus collisions in the CMS experiment. 65 figs., 19 tabs

  15. 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.

  16. JINR rapid communications

    International Nuclear Information System (INIS)

    1993-01-01

    The possibility of observation of the heavy fermion band magnet state in rare-earth alloys Ce(Ru 1-x Rh x ) 2 B 2 and Ce(Cu 1-x N x ) 2 Ge 2 using inelastic neutron scattering has been discussed. The idea of new mechanism of induced coherent radiation by the atoms of a gas under the Cherenkov threshold is suggested. The reduced probabilities of delayed fission channels for 188 Bi and 196 At are determined. 4.5 x A x Gev/C deuteron and carbon nucleus fragmentation into cumulative pions has been measured on various target nuclei. The present states and future development of data acquisition system for the magnetic spectrometer SPHERE are described

  17. A Complicated Case of Tacrolimus-Induced Rapid Remission after Cesarean Section in the Early Third Trimester for Refractory Severe Ulcerative Colitis Flaring in the Initial Period of Gestation

    Directory of Open Access Journals (Sweden)

    Takashi Mizushima

    2011-04-01

    Full Text Available A 36-year-old woman who had been diagnosed with ulcerative colitis at the age of 17 years was referred to our hospital because of severe abdominal pain and repeated bloody diarrhea that persisted during pregnancy despite combination therapy with high-dose corticosteroids and weekly granulocyte and monocyte adsorptive apheresis (GMA. She underwent combination therapy consisting of high-dose corticosteroids, intensive GMA (two sessions per week and vancomycin, which was used to eradicate Clostridium difficile, under total parenteral nutrition control until the estimated weight of her fetus reached 1,000 g. This combination therapy was partially successful, resulting in almost complete disappearance of abdominal pain and a marked decrease in stool frequency. However bloody diarrhea persisted and the patient developed anemia and hypoalbuminemia and was unable to prolong her gestation time. Cesarean section was conducted at 28 weeks of gestation without any congenital abnormalities or neurological defects. Oral administration of tacrolimus was begun 7 days after cesarean section, which was followed by rapid induction of remission. Corticosteroids were then gradually tapered off. Tacrolimus is one therapeutic option after cesarean section in pregnant patients who do not respond well to GMA and high-dose corticosteroids for persistent active ulcerative colitis.

  18. 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)

  19. 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

  20. Dasatinib rapidly induces deep molecular response in chronic-phase chronic myeloid leukemia patients who achieved major molecular response with detectable levels of BCR-ABL1 transcripts by imatinib therapy.

    Science.gov (United States)

    Shiseki, Masayuki; Yoshida, Chikashi; Takezako, Naoki; Ohwada, Akira; Kumagai, Takashi; Nishiwaki, Kaichi; Horikoshi, Akira; Fukuda, Tetsuya; Takano, Hina; Kouzai, Yasuji; Tanaka, Junji; Morita, Satoshi; Sakamoto, Junichi; Sakamaki, Hisashi; Inokuchi, Koiti

    2017-10-01

    With the introduction of imatinib, a first-generation tyrosine kinase inhibitor (TKI) to inhibit BCR-ABL1 kinase, the outcome of chronic-phase chronic myeloid leukemia (CP-CML) has improved dramatically. However, only a small proportion of CP-CML patients subsequently achieve a deep molecular response (DMR) with imatinib. Dasatinib, a second-generation TKI, is more potent than imatinib in the inhibition of BCR-ABL1 tyrosine kinase in vitro and more effective in CP-CML patients who do not achieve an optimal response with imatinib treatment. In the present study, we attempted to investigate whether switching the treatment from imatinib to dasatinib can induce DMR in 16 CP-CML patients treated with imatinib for at least two years who achieved a major molecular response (MMR) with detectable levels of BCR-ABL1 transcripts. The rates of achievement of DMR at 1, 3, 6 and 12 months after switching to dasatinib treatment in the 16 patients were 44% (7/16), 56% (9/16), 63% (10/16) and 75% (12/16), respectively. The cumulative rate of achieving DMR at 12 months from initiation of dasatinib therapy was 93.8% (15/16). The proportion of natural killer cells and cytotoxic T cells in peripheral lymphocytes increased after switching to dasatinib. In contrast, the proportion of regulatory T cells decreased during treatment. The safety profile of dasatinib was consistent with previous studies. Switching to dasatinib would be a therapeutic option for CP-CML patients who achieved MMR but not DMR by imatinib, especially for patients who wish to discontinue TKI therapy.

  1. Rapid prototyping: een veelbelovende methode

    NARCIS (Netherlands)

    Haverman, T.M.; Karagozoglu, K.H.; Prins, H.; Schulten, E.A.J.M.; Forouzanfar, T.

    2013-01-01

    Rapid prototyping is a method which makes it possible to produce a three-dimensional model based on two-dimensional imaging. Various rapid prototyping methods are available for modelling, such as stereolithography, selective laser sintering, direct laser metal sintering, two-photon polymerization,

  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. Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells

    Czech Academy of Sciences Publication Activity Database

    Mertlíková-Kaiserová, Helena; Votruba, Ivan; Matoušová, Marika; Holý, Antonín; Hájek, Miroslav

    2010-01-01

    Roč. 30, č. 7 (2010), s. 2791-2798 ISSN 0250-7005 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : acyclic nucleoside phosphonate * programmed cell death * CCRF-CEM cells * cell cycle Subject RIV: CC - Organic Chemistry Impact factor: 1.656, year: 2010

  4. Rapid deployment intrusion detection system

    International Nuclear Information System (INIS)

    Graham, R.H.

    1997-01-01

    A rapidly deployable security system is one that provides intrusion detection, assessment, communications, and annunciation capabilities; is easy to install and configure; can be rapidly deployed, and is reusable. A rapidly deployable intrusion detection system (RADIDS) has many potential applications within the DOE Complex: back-up protection for failed zones in a perimeter intrusion detection and assessment system, intrusion detection and assessment capabilities in temporary locations, protection of assets during Complex reconfiguration, and protection in hazardous locations, protection of assets during Complex reconfiguration, and protection in hazardous locations. Many DOE user-need documents have indicated an interest in a rapidly deployable intrusion detection system. The purpose of the RADIDS project is to design, develop, and implement such a system. 2 figs

  5. Rapid Continuous Multimaterial Extrusion Bioprinting

    NARCIS (Netherlands)

    Liu, Wanjun; Zhang, Yu Shrike; Heinrich, Marcel A.; De Ferrari, F; Jang, HL; Bakht, SM; Alvarez, MM; Yang, J; Li, YC; Trujillo-de Stantiago, G; Miri, AK; Zhu, K; Khoshakhlagh, P; Prakash, G; Cheng, H; Guan, X; Zhong, Z; Ju, J; Zhu, GH; Jin, X; Ryon Shin, Su; Dokmeci, M.R.; Khademhosseini, Ali

    The development of a multimaterial extrusion bioprinting platform is reported. This platform is capable of depositing multiple coded bioinks in a continuous manner with fast and smooth switching among different reservoirs for rapid fabrication of complex constructs, through digitally controlled

  6. Colour reconnections and rapidity gaps

    International Nuclear Information System (INIS)

    Loennblad, Leif

    1996-01-01

    I argue that the success of recently proposed models describing events with large rapidity gaps in DIS at HERA in terms of non-perturbative colour exchange is heavily reliant on suppression of perturbative gluon emission in the proton direction. There is little or no physical motivation for such suppression and I show that a model without this suppression cannot describe the rapidity gap events at HERA. (author)

  7. Dilepton distributions at backward rapidities

    International Nuclear Information System (INIS)

    Betemps, M. A.; Ducati, M. B. Gay; Oliveira, E. G. de

    2006-01-01

    The dilepton production at backward rapidities in pAu and pp collisions at RHIC and LHC energies is investigated in the dipole approach. The results are shown through the nuclear modification ratio R pA considering transverse momentum and rapidity spectra. The dilepton modification ratio presents interesting behavior at the backward rapidities when compared with the already known forward ones, since it is related with the large x kinematical region that is being probed. The rapidity dependence of the nuclear modification ratio in the dilepton production is strongly dependent on the Bjorken x behavior of the nuclear structure function ratio R F 2 =F 2 A /F 2 p . The R pA transverse momentum dependence at backward rapidities is modified due to the large x nuclear effects: at RHIC energies, for instance, the ratio R pA is reduced as p T increases, presenting an opposite behavior when compared with the forward one. It implies that the dilepton production at backward rapidities should carry information of the nuclear effects at large Bjorken x, as well as that it is useful to investigate the p T dependence of the observables in this kinematical regime

  8. Rapid

    Directory of Open Access Journals (Sweden)

    Nahla M. Wassim

    2013-01-01

    Full Text Available Members of Aedes caspius mosquitoes are incriminated to be a potential reservoir of “Rift Valley Fever Virus” (RVF during interepizootic periods in Egypt. Ae. caspius contains two distinct forms which are morphologically indistinguishable but differ in physiology and behavior; Ae. caspius form (a requires a blood meal for each egg batch(anautogeny, is unable to mate in confined spaces(eurygamous. The second form (b lays egg batch without blood meal (autogenous and can mate in confined spaces (stenogamous. In this work, we collected the autogenous and anautogenous forms of Ae. caspius from two different breeding habitats in the Qalyubia Governorate. Analysis of the Drosophila ace-Orthologous acetylecholinesterase gene revealed that a single polymorphic region characterized each species. Based on this region, specific primers were used to amplify the entire section of intron II, sections of Exon 2 and Exon 3 of ace-2 gene for differentiating the complex species of mosquitoes. The amplicons of anautogenous form sized 441 pb and increase 116 bp than autogenous form of Ae. caspius. High rates of point mutations were addressed; deletion/insertion events are 120 bases. The transversion mutations were 44 bases and were relatively close to the transtion mutations 43 base. The genetic distance was 0.01 between the two forms.

  9. Rapid Modulation of Aromatase Activity in the Vertebrate Brain

    Directory of Open Access Journals (Sweden)

    Thierry D. Charlier

    2013-01-01

    Full Text Available Numerous steroid hormones, including 17β-estradiol (E2, activate rapid and transient cellular, physiological, and behavioral changes in addition to their well-described genomic effects. Aromatase is the key-limiting enzyme in the production of estrogens, and the rapid modulation of this enzymatic activity could produce rapid changes in local E2 concentrations. The mechanisms that might mediate such rapid enzymatic changes are not fully understood but are currently under intense scrutiny. Recent studies in our laboratory indicate that brain aromatase activity is rapidly inhibited by an increase in intracellular calcium concentration resulting from potassium-induced depolarization or from the activation of glutamatergic receptors. Phosphorylating conditions also reduce aromatase activity within minutes, and this inhibition is blocked by the addition of multiple protein kinase inhibitors. This rapid modulation of aromatase activity by phosphorylating conditions is a general mechanism observed in different cell types and tissues derived from a variety of species, including human aromatase expressed in various cell lines. Phosphorylation processes affect aromatase itself and do not involve changes in aromatase protein concentration. The control of aromatase activity by multiple kinases suggests that several amino acids must be concomitantly phosphorylated to modify enzymatic activity but site-directed mutagenesis of several amino acids alone or in combination has not to date revealed the identity of the targeted residue(s. Altogether, the phosphorylation processes affecting aromatase activity provide a new general mechanism by which the concentration of estrogens can be rapidly altered in the brain.

  10. A rapid and sensitive method for diagnosis of dermatophyte induced

    African Journals Online (AJOL)

    Sherin M. Emam

    2015-08-29

    10.1016/j.ajme.2015.05.001 ... C. guilliermondii, C. tropicalis and Blastoschizomyces capitatus ... contaminants, Scrapings were taken with a sterile scalpel blade ... shape, consistency, margins, color of the colony both in recto.

  11. Hard diffraction and rapidity gaps

    International Nuclear Information System (INIS)

    Brandt, A.

    1995-09-01

    The field of hard diffraction, which studies events with a rapidity gap and a hard scattering, has expanded dramatically recently. A review of new results from CDF, D OE, H1 and ZEUS will be given. These results include diffractive jet production, deep-inelastic scattering in large rapidity gap events, rapidity gaps between high transverse energy jets, and a search for diffractive W-boson production. The combination of these results gives new insight into the exchanged object, believed to be the pomeron. The results axe consistent with factorization and with a hard pomeron that contains both quarks and gluons. There is also evidence for the exchange of a strongly interacting color singlet in high momentum transfer (36 2 ) events

  12. 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.

  13. On the rapid melt quenching

    International Nuclear Information System (INIS)

    Usatyuk, I.I.; Novokhatskij, I.A.; Kaverin, Yu.F.

    1994-01-01

    Specific features of instrumentation of traditionally employed method of melt spinning (rapid quenching), its disadvantages being discussed, were analyzed. The necessity of the method upgrading as applied to the problems of studying fine structure of molten metals and glasses was substantiated. The principle flowsheet of experimental facility for extremely rapid quenching of the melts of metals is described, specificity of its original functional units being considered. The sequence and character of all the principal stages of the method developed were discussed. 18 refs.; 3 figs

  14. Global Landslides on Rapidly Spinning Spheroids

    Science.gov (United States)

    Scheeres, Daniel J.; Sanchez, P.

    2013-10-01

    The angle of repose and conditions for global landslides on the surfaces of small, rapidly spinning, spheroidal asteroids are studied. Applying techniques of soil mechanics, we develop a theory for, and examples of, how regolith will fail and flow in this microgravity environment. Our motivation is to develop an understanding of the "top-shaped" class of asteroids based on analytical soil mechanics. Our analysis transforms the entire asteroid surface into a local frame where we can model it as a conventional granular pile with a surface slope, acceleration and height variations as a function of the body's spin rate, shape and density. A general finding is that the lowest point on a rapidly spinning spheroid is at the equator with the effective height of surface material monotonically increasing towards the polar regions, where the height can be larger than the physical radius of the body. We study the failure conditions of both cohesionless and cohesive regolith, and develop specific predictions of the surface profile as a function of the regolith angle of friction and the maximum spin rate experienced by the body. The theory also provides simple guidelines on what the shape may look like, although we do not analyze gravitationally self-consistent evolution of the body shape. The theory is tested with soft-sphere discrete element method granular mechanics simulations to better understand the dynamical aspects of global asteroid landslides. We find significant differences between failure conditions for cohesive and cohesionless regolith. In the case of cohesive regolith, we show that extremely small values of strength (much less than that found in lunar regolith) can stabilize a surface even at very rapid spin rates. Cohesionless surfaces, as expected, fail whenever their surface slopes exceed the angle of friction. Based on our analysis we propose that global landslides and the flow of material towards the equator on spheroidal bodies are precipitated by exogenous

  15. Program for rapid dose assessment in criticality accident, RADAPAS

    International Nuclear Information System (INIS)

    Takahashi, Fumiaki

    2006-09-01

    In a criticality accident, a person near fissile material can receive extremely high dose which can cause acute health effect. For such a case, medical treatment should be carried out for the exposed person, according to severity of the exposure. Then, radiation dose should be rapidly assessed soon after an outbreak of an accident. Dose assessment based upon the quantity of induced 24 Na in human body through neutron exposure is expected as one of useful dosimetry techniques in a criticality accident. A dose assessment program, called RADAPAS (RApid Dose Assessment Program from Activated Sodium in Criticality Accidents), was therefore developed to assess rapidly radiation dose to exposed persons from activity of induced 24 Na. RADAPAS consists of two parts; one is a database part and the other is a part for execution of dose calculation. The database contains data compendiums of energy spectra and dose conversion coefficients from specific activity of 24 Na induced in human body, which had been derived in a previous analysis using Monte Carlo calculation code. Information for criticality configuration or characteristics of radiation in the accident field is to be interactively given with interface displays in the dose calculation. RADAPAS can rapidly derive radiation dose to the exposed person from the given information and measured 24 Na specific activity by using the conversion coefficient in database. This report describes data for dose conversions and dose calculation in RADAPAS and explains how to use the program. (author)

  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 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

  18. Rapid general microdetermination of fluorine

    NARCIS (Netherlands)

    Leuven, H.C.E. van; Rotscheid, G.J.; Buis, W.J.

    1979-01-01

    A rapid micromethod for the determination of fluorine in a wide variety of materials has been developed. The method is based on the liberation of the fluorine (as HF) from the sample by means of pyrohydrolysis with steam at 1120?? C, The amount of fluoride in the condensate is subsequently measured

  19. Rapid Prototyping Enters Mainstream Manufacturing.

    Science.gov (United States)

    Winek, Gary

    1996-01-01

    Explains rapid prototyping, a process that uses computer-assisted design files to create a three-dimensional object automatically, speeding the industrial design process. Five commercially available systems and two emerging types--the 3-D printing process and repetitive masking and depositing--are described. (SK)

  20. 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.

  1. 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.

  2. Rapid-scan EPR imaging.

    Science.gov (United States)

    Eaton, Sandra S; Shi, Yilin; Woodcock, Lukas; Buchanan, Laura A; McPeak, Joseph; Quine, Richard W; Rinard, George A; Epel, Boris; Halpern, Howard J; Eaton, Gareth R

    2017-07-01

    In rapid-scan EPR the magnetic field or frequency is repeatedly scanned through the spectrum at rates that are much faster than in conventional continuous wave EPR. The signal is directly-detected with a mixer at the source frequency. Rapid-scan EPR is particularly advantageous when the scan rate through resonance is fast relative to electron spin relaxation rates. In such scans, there may be oscillations on the trailing edge of the spectrum. These oscillations can be removed by mathematical deconvolution to recover the slow-scan absorption spectrum. In cases of inhomogeneous broadening, the oscillations may interfere destructively to the extent that they are not visible. The deconvolution can be used even when it is not required, so spectra can be obtained in which some portions of the spectrum are in the rapid-scan regime and some are not. The technology developed for rapid-scan EPR can be applied generally so long as spectra are obtained in the linear response region. The detection of the full spectrum in each scan, the ability to use higher microwave power without saturation, and the noise filtering inherent in coherent averaging results in substantial improvement in signal-to-noise relative to conventional continuous wave spectroscopy, which is particularly advantageous for low-frequency EPR imaging. This overview describes the principles of rapid-scan EPR and the hardware used to generate the spectra. Examples are provided of its application to imaging of nitroxide radicals, diradicals, and spin-trapped radicals at a Larmor frequency of ca. 250MHz. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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 ...

  4. 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...

  5. Rapid and sustained cost management

    International Nuclear Information System (INIS)

    Hanson, D.

    2009-01-01

    Accenture helps clients develop comprehensive, process-driven strategies for rapid and sustained cost management that leverage deep insights and analytics. This approach enables companies to gain operating cost advantages by rationalizing, simplifying and automating current operating capabilities. It drives structural cost advantages by optimizing business mix, capital structure, organizational structure and geographic presence. This paper discussed how successful companies achieve high performance during times of economic turmoil. It also discussed the value of the winner's strategy in terms of rapid and sustained cost management (RSCM). It discussed how Accenture operates and its leveraged capabilities, improved efficiency, margins and cash flow while maintaining customer service levels. Building structural advantage and the Accenture difference were also discussed. It was concluded that RSCM is one vital way that Accenture can help companies achieve success. 4 figs

  6. Rapidly Progressive Quadriplegia and Encephalopathy.

    Science.gov (United States)

    Wynn, DonRaphael; McCorquodale, Donald; Peters, Angela; Juster-Switlyk, Kelsey; Smith, Gordon; Ansari, Safdar

    2016-11-01

    A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

  7. Rapid mask prototyping for microfluidics.

    Science.gov (United States)

    Maisonneuve, B G C; Honegger, T; Cordeiro, J; Lecarme, O; Thiry, T; Fuard, D; Berton, K; Picard, E; Zelsmann, M; Peyrade, D

    2016-03-01

    With the rise of microfluidics for the past decade, there has come an ever more pressing need for a low-cost and rapid prototyping technology, especially for research and education purposes. In this article, we report a rapid prototyping process of chromed masks for various microfluidic applications. The process takes place out of a clean room, uses a commercially available video-projector, and can be completed in less than half an hour. We quantify the ranges of fields of view and of resolutions accessible through this video-projection system and report the fabrication of critical microfluidic components (junctions, straight channels, and curved channels). To exemplify the process, three common devices are produced using this method: a droplet generation device, a gradient generation device, and a neuro-engineering oriented device. The neuro-engineering oriented device is a compartmentalized microfluidic chip, and therefore, required the production and the precise alignment of two different masks.

  8. Rapidity correlations test stochastic hydrodynamics

    International Nuclear Information System (INIS)

    Zin, C; Gavin, S; Moschelli, G

    2017-01-01

    We show that measurements of the rapidity dependence of transverse momentum correlations can be used to determine the characteristic time τ π that dictates the rate of isotropization of the stress energy tensor, as well as the shear viscosity ν = η/sT . We formulate methods for computing these correlations using second order dissipative hydrodynamics with noise. Current data are consistent with τ π /ν ∼ 10 but targeted measurements can improve this precision. (paper)

  9. Rapid duodenal and jejunal intubation

    International Nuclear Information System (INIS)

    Nolan, D.J.

    1979-01-01

    A size 12 French radiopaque catheter, 135 cm long, suitable for rapid duodenal and jejunal intubation, is described. Its size and flexibility enable it to be passed with ease through the nose, stomach and duodenum. A guide wire is used to act as a stiffener as the catheter is passed through the stomach. The catheter is suitable for infusing barium directly into the small intestine and for performing hypotonic duodenography. The technique for duodenal and jejunal intubation is discussed. (author)

  10. 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.

  11. Rapid reconnection of flux lines

    International Nuclear Information System (INIS)

    Samain, A.

    1982-01-01

    The rapid reconnection of flux lines in an incompressible fluid through a singular layer of the current density is discussed. It is shown that the liberated magnetic energy must partially appear in the form of plasma kinetic energy. A laminar structure of the flow is possible, but Alfven velocity must be achieved in eddies of growing size at the ends of the layer. The gross structure of the flow and the magnetic configuration may be obtained from variational principles. (author)

  12. Single wafer rapid thermal multiprocessing

    International Nuclear Information System (INIS)

    Saraswat, K.C.; Moslehi, M.M.; Grossman, D.D.; Wood, S.; Wright, P.; Booth, L.

    1989-01-01

    Future success in microelectronics will demand rapid innovation, rapid product introduction and ability to react to a change in technological and business climate quickly. These technological advances in integrated electronics will require development of flexible manufacturing technology for VLSI systems. However, the current approach of establishing factories for mass manufacturing of chips at a cost of more than 200 million dollars is detrimental to flexible manufacturing. The authors propose concepts of a micro factory which may be characterized by more economical small scale production, higher flexibility to accommodate many products on several processes, and faster turnaround and learning. In-situ multiprocessing equipment where several process steps can be done in sequence may be a key ingredient in this approach. For this environment to be flexible, the equipment must have ability to change processing environment, requiring extensive in-situ measurements and real time control. This paper describes the development of a novel single wafer rapid thermal multiprocessing (RTM) reactor for next generation flexible VLSI manufacturing. This reactor will combine lamp heating, remote microwave plasma and photo processing in a single cold-wall chamber, with applications for multilayer in-situ growth and deposition of dielectrics, semiconductors and metals

  13. Rapid Sampling from Sealed Containers

    International Nuclear Information System (INIS)

    Johnston, R.G.; Garcia, A.R.E.; Martinez, R.K.; Baca, E.T.

    1999-01-01

    The authors have developed several different types of tools for sampling from sealed containers. These tools allow the user to rapidly drill into a closed container, extract a sample of its contents (gas, liquid, or free-flowing powder), and permanently reseal the point of entry. This is accomplished without exposing the user or the environment to the container contents, even while drilling. The entire process is completed in less than 15 seconds for a 55 gallon drum. Almost any kind of container can be sampled (regardless of the materials) with wall thicknesses up to 1.3 cm and internal pressures up to 8 atm. Samples can be taken from the top, sides, or bottom of a container. The sampling tools are inexpensive, small, and easy to use. They work with any battery-powered hand drill. This allows considerable safety, speed, flexibility, and maneuverability. The tools also permit the user to rapidly attach plumbing, a pressure relief valve, alarms, or other instrumentation to a container. Possible applications include drum venting, liquid transfer, container flushing, waste characterization, monitoring, sampling for archival or quality control purposes, emergency sampling by rapid response teams, counter-terrorism, non-proliferation and treaty verification, and use by law enforcement personnel during drug or environmental raids

  14. Rapid Adaptation in Digital Transformation

    DEFF Research Database (Denmark)

    Hansen, Anne Mette; Kræmmergaard, Pernille; Mathiassen, Lars

    2011-01-01

    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...... 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....

  15. Rapid thermal processing by stamping

    Science.gov (United States)

    Stradins, Pauls; Wang, Qi

    2013-03-05

    A rapid thermal processing device and methods are provided for thermal processing of samples such as semiconductor wafers. The device has components including a stamp (35) having a stamping surface and a heater or cooler (40) to bring it to a selected processing temperature, a sample holder (20) for holding a sample (10) in position for intimate contact with the stamping surface; and positioning components (25) for moving the stamping surface and the stamp (35) in and away from intimate, substantially non-pressured contact. Methods for using and making such devices are also provided. These devices and methods allow inexpensive, efficient, easily controllable thermal processing.

  16. Rapidly Adaptable Instrumentation Tester (RAIT)

    International Nuclear Information System (INIS)

    Vargo, Timothy D.

    1999-01-01

    Emerging technologies in the field of ''Test ampersand Measurement'' have recently enabled the development of the Rapidly Adaptable Instrumentation Tester (RAIT). Based on software developed with LabVIEW, the RAIT design enables quick reconfiguration to test and calibrate a wide variety of telemetry systems. The consequences of inadequate testing could be devastating if a telemetry system were to fail during an expensive flight mission. Supporting both open-bench testing as well as automated test sequences, the RAIT has significantly lowered total time required to test and calibrate a system. This has resulted in an overall lower per unit testing cost than has been achievable in the past

  17. 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.

  18. 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.

  19. Direct, rapid RNA sequence analysis

    International Nuclear Information System (INIS)

    Peattie, D.A.

    1987-01-01

    The original methods of RNA sequence analysis were based on enzymatic production and chromatographic separation of overlapping oligonucleotide fragments from within an RNA molecule followed by identification of the mononucleotides comprising the oligomer. Over the past decade the field of nucleic acid sequencing has changed dramatically, however, and RNA molecules now can be sequenced in a variety of more streamlined fashions. Most of the more recent advances in RNA sequencing have involved one-dimensional electrophoretic separation of 32 P-end-labeled oligoribonucleotides on polyacrylamide gels. In this chapter the author discusses two of these methods for determining the nucleotide sequences of RNA molecules rapidly: the chemical method and the enzymatic method. Both methods are direct and degradative, i.e., they rely on fragmatic and chemical approaches should be utilized. The single-strand-specific ribonucleases (A, T 1 , T 2 , and S 1 ) provide an efficient means to locate double-helical regions rapidly, and the chemical reactions provide a means to determine the RNA sequence within these regions. In addition, the chemical reactions allow one to assign interactions to specific atoms and to distinguish secondary interactions from tertiary ones. If the RNA molecule is small enough to be sequenced directly by the enzymatic or chemical method, the probing reactions can be done easily at the same time as sequencing reactions

  20. Rapid learning: a breakthrough agenda.

    Science.gov (United States)

    Etheredge, Lynn M

    2014-07-01

    A "rapid-learning health system" was proposed in a 2007 thematic issue of Health Affairs. The system was envisioned as one that uses evidence-based medicine to quickly determine the best possible treatments for patients. It does so by drawing on electronic health records and the power of big data to access large volumes of information from a variety of sources at high speed. The foundation for a rapid-learning health system was laid during 2007-13 by workshops, policy papers, large public investments in databases and research programs, and developing learning systems. Challenges now include implementing a new clinical research system with several hundred million patients, modernizing clinical trials and registries, devising and funding research on national priorities, and analyzing genetic and other factors that influence diseases and responses to treatment. Next steps also should aim to improve comparative effectiveness research; build on investments in health information technology to standardize handling of genetic information and support information exchange through apps and software modules; and develop new tools, data, and information for clinical decision support. Further advances will require commitment, leadership, and public-private and global collaboration. Project HOPE—The People-to-People Health Foundation, Inc.

  1. Rapid chemical analysis of allanite

    International Nuclear Information System (INIS)

    Nishiyama, Goro; Hayashi, Hiroshi

    1981-01-01

    Rapid chemical analysis of allanite was studied by atomic absorption spectrophotometry. Powdered sample was fused with mixture of sodium carbonate anhydrous and borax (4 : 1 weight) in platinum crucible and sample solution was prepared. SiO 2 , Fe 2 O 3 , Al 2 O 3 , MnO and rare earth metals were determined by atomic absorption spectrophotometry, CaO, MgO and Ce 2 O 3 by titration, ThO 2 by colorimetry, and La 2 O 3 by flame photometry respectively. For sample solution treated with hydrofluoric acid and sulfuric acid. Na 2 O and K 2 O were determined by atomic absorption spectrophotometry, TiO 2 and P 2 O 5 by colorimetry. Chemical analyses for four samples were carried out and gave consistent results. (author)

  2. Rapid world modelling for robotics

    International Nuclear Information System (INIS)

    Littile, C.Q.; Wilson, C.W.

    1996-01-01

    The ability to use an interactive world model, whether it is for robotics simulation or most other virtual graphical environments, relies on the users ability to create an accurate world model. Typically this is a tedious process, requiring many hours to create 3-D CAD models of the surfaces within a workspace. The goal of this ongoing project is to develop usable methods to rapidly build world models of real world workspaces. This brings structure to an unstructured environment and allows graphical based robotics control to be accomplished in a reasonable time frame when traditional CAD modelling is not enough. To accomplish this, 3D range sensors are deployed to capture surface data within the workspace. This data is then transformed into surface maps, or models. A 3D world model of the workspace is built quickly and accurately, without ever having to put people in the environment

  3. On rapid rotation in stellarators

    International Nuclear Information System (INIS)

    Helander, Per

    2008-01-01

    The conditions under which rapid plasma rotation may occur in a three-dimensional magnetic field, such as that of a stellarator, are investigated. Rotation velocities comparable to the ion thermal speed are found to be attainable only in magnetic fields which are approximately isometric. In an isometric magnetic field the dependence of the magnetic field strength B on the arc length l along the field is the same for all field lines on each flux surface ψ. Only in fields where the departure from exact isometry, B=B(ψ,l), is of the order of the ion gyroradius divided by the macroscopic length scale are rotation speeds comparable to the ion thermal speed possible. Moreover, it is shown that the rotation must be in the direction of the vector ∇ψx∇B. (author)

  4. Microstructure of rapidly solidified materials

    Science.gov (United States)

    Jones, H.

    1984-07-01

    The basic features of rapidly solidified microstructures are described and differences arising from alternative processing strategies are discussed. The possibility of achieving substantial undercooling prior to solidification in processes such as quench atomization and chill block melt spinning can give rise to striking microstructural transitions even when external heat extraction is nominally Newtonian. The increased opportunity in laser and electron beam surface melting for epitaxial growth on the parent solid at an accelerating rate, however, does not exclude the formation of nonequilibrium phases since the required undercooling can be locally attained at the solidification front which is itself advancing at a sufficiently high velocity. The effects of fluid flow indicated particularly in melt spinning and surface melting are additional to the transformational and heat flow considerations that form the present basis for interpretation of such microstructural effects.

  5. Rapid iconic erasure without masking.

    Science.gov (United States)

    Tijus, Charles Albert; Reeves, Adam

    2004-01-01

    We report on the erasure of the iconic memory of an array of 12 black letters flashed on a continuously- present white field. Erasure is accomplished by replacing the 16 ms letter array (frame 1) with a blank white frame for 16 ms (frame 2). The letter array returns in frame 3, with from one to six letters missing. Report of the missing letters is accurate without the blank white frame but is impoverished with it, as if interposing the blank erases the icon. Erasure occurs without any obvious luminance masking, 'mud splashes', pattern masking (backward, forward, or metacontrast), lateral masking, or masking by object substitution. Erasure is greatly decreased if the blank is presented one frame earlier or later. We speculate that erasure is due to a rapid reset of the icon produced by an informational mis-match.

  6. Rapid onset aggressive vertebral haemangioma.

    Science.gov (United States)

    Cheung, Nicholas K; Doorenbosch, Xenia; Christie, John G

    2011-03-01

    Vertebral haemangiomas are generally benign asymptomatic vascular tumours seen commonly in the adult population. Presentations in paediatric populations are extremely rare, which can result in rapid onset of neurological symptoms. We present a highly unusual case of an aggressive paediatric vertebral haemangioma causing significant cord compression. A 13-year-old boy presented with only 2 weeks duration of progressive gait disturbance, truncal ataxia and loss of bladder control. Magnetic resonance imaging (MRI) of the spine revealed a large vascular epidural mass extending between T6 and T8 vertebral bodies. Associated displacement and compression of the spinal cord was present. A highly vascular bony lesion was found during surgery. Histopathology identified this tumour to be a vertebral haemangioma. We present an extremely unusual acute presentation of a paediatric vertebral haemangioma. This study highlights the need for early diagnosis, MRI for investigation and urgent surgical management. © Springer-Verlag 2011

  7. Customer-experienced rapid prototyping

    Science.gov (United States)

    Zhang, Lijuan; Zhang, Fu; Li, Anbo

    2008-12-01

    In order to describe accurately and comprehend quickly the perfect GIS requirements, this article will integrate the ideas of QFD (Quality Function Deployment) and UML (Unified Modeling Language), and analyze the deficiency of prototype development model, and will propose the idea of the Customer-Experienced Rapid Prototyping (CE-RP) and describe in detail the process and framework of the CE-RP, from the angle of the characteristics of Modern-GIS. The CE-RP is mainly composed of Customer Tool-Sets (CTS), Developer Tool-Sets (DTS) and Barrier-Free Semantic Interpreter (BF-SI) and performed by two roles of customer and developer. The main purpose of the CE-RP is to produce the unified and authorized requirements data models between customer and software developer.

  8. 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…

  9. Rapid charging of nickel-cadmium accumulators

    Energy Technology Data Exchange (ETDEWEB)

    Bruck, F

    1972-01-01

    Four types of charging of gas-tight Ni-Cd accumulators (a) normal; (b) accelerated; (c) rapid; and (d) ultra-rapid are described. For rapid charging, a built-in temperature sensor cuts off charging current at a prescribed point. In ultra-rapid charging, 50% charge can be attained in 3.5 min. and 25% charge within 50 sec. In the second phase of ultra-rapid charging, a surplus of oxygen is released at the positive electrode and a safety valve is provided for pressure reduction. Characteristic curves are given for various rates of charging and some data on discharge rates is also given.

  10. Resummation improved rapidity spectrum for gluon fusion Higgs production

    International Nuclear Information System (INIS)

    Ebert, Markus A.; Tackmann, Frank J.; Michel, Johannes K.L.; Muenster Univ.

    2017-02-01

    Gluon-induced processes such as Higgs production typically exhibit large perturbative corrections. These partially arise from large virtual corrections to the gluon form factor, which at timelike momentum transfer contains Sudakov logarithms evaluated at negative arguments ln 2 (-1)=-π 2 . It has been observed that resumming these terms in the timelike form factor leads to a much improved perturbative convergence for the total cross section. We discuss how to consistently incorporate the resummed form factor into the perturbative predictions for generic cross sections differential in the Born kinematics, including in particular the Higgs rapidity spectrum. We verify that this indeed improves the perturbative convergence, leading to smaller and more reliable perturbative uncertainties, and that this is not affected by cancellations between resummed and unresummed contributions. Combining both fixed-order and resummation uncertainties, the perturbative uncertainty for the total cross section at N 3 LO+N 3 LL φ ' is about a factor of two smaller than at N 3 LO. The perturbative uncertainty of the rapidity spectrum at NNLO+NNLL φ ' is similarly reduced compared to NNLO. We also study the analogous resummation for quark-induced processes, namely Higgs production through bottom quark annihilation and the Drell-Yan rapidity spectrum. For the former the resummation leads to a small improvement, while for the latter it confirms the already small uncertainties of the fixed-order predictions.

  11. 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.

  12. Rapid contextual conditioning in autoshaping.

    Science.gov (United States)

    Balsam, P D; Schwartz, A L

    1981-10-01

    Two experiments are reported which investigate the speed of contextual conditioning in autoshaping. In both experiments, a procedure was employed in which ring doves were magazine trained in one context prior to the manipulation of background values in a second context. In Experiment 1, subjects were exposed to 4, 8, 64, 128, or 256 US-only presentations prior to autoshaping. Acquisition speed and maintained response measures were monotonically related to the number of pretraining trials. Subjects in Group 4 acquired the key-peck response fastest, and retardation was maximal within 64 pretraining trials. In Experiment 2, subjects given 20 pretraining trials were significantly more retarded than subjects given 2 pretraining trials, but only when pretraining and testing were conducted in the same context. Overall, the results of these experiments show that in autoshaping, contextual conditioning is very rapid; this demonstrates the plausibility of theoretical accounts of Pavlovian conditioning which assert that the development of the conditioned response depends on the associative values of both the CS and background stimuli.

  13. Rapid Gradient-Echo Imaging

    Science.gov (United States)

    Hargreaves, Brian

    2012-01-01

    Gradient echo sequences are widely used in magnetic resonance imaging (MRI) for numerous applications ranging from angiography to perfusion to functional MRI. Compared with spin-echo techniques, the very short repetition times of gradient-echo methods enable very rapid 2D and 3D imaging, but also lead to complicated “steady states.” Signal and contrast behavior can be described graphically and mathematically, and depends strongly on the type of spoiling: fully balanced (no spoiling), gradient spoiling, or RF-spoiling. These spoiling options trade off between high signal and pure T1 contrast while the flip angle also affects image contrast in all cases, both of which can be demonstrated theoretically and in image examples. As with spin-echo sequences, magnetization preparation can be added to gradient-echo sequences to alter image contrast. Gradient echo sequences are widely used for numerous applications such as 3D perfusion imaging, functional MRI, cardiac imaging and MR angiography. PMID:23097185

  14. Rapidly developing market regions : Brazil

    International Nuclear Information System (INIS)

    Britto, A.

    1997-01-01

    Brazil and the State of Rio Grande do Sul are experiencing a period of rapid industrial development. Global investment has been forecast to reach $240 billion over the next five to seven years. This level of development is likely to result in a sharp increase in the consumption of plastic products made from olefins and from aromatic products. Accordingly, Copesul, the centre of raw materials for the State complex, is expected to increase its production of ethane from 685 tonnes to 1.13 million tonnes after 1999. The government has established a program of incentives to stimulate investment in third generation industries. Also, the State petrochemical industry has been rendered more competitive as a result of the purchase of the latest generation equipment. The principal challenges that exist for the petrochemical industry in Brazil and for that matter, around the world, are to reduce production costs and to preserve the natural environment. Another challenge, also world-wide, is to address the issue of plastic residues and to eliminate such residues through plastic recycling programs

  15. Rapidly Progressive Corticobasal Degeneration Syndrome

    Directory of Open Access Journals (Sweden)

    Ana Herrero Valverde

    2011-08-01

    Full Text Available Introduction: Corticobasal syndrome (CBS has a heterogeneous clinical presentation with no specific pathologic substratum. Its accurate diagnosis is a challenge for neurologists; in order to establish CBS definitively, postmortem confirmation is required. Some clinical and radiological features can help to distinguish it from other neurodegenerative conditions, such as Creutzfeldt-Jakob disease (CJD. Clinical Case: A 74-year-old woman presented with language impairment, difficulty in walking and poor attentiveness that had begun 10 days before. Other symptoms, such as asymmetrical extra-pyramidal dysfunction, limb dystonia and ‘alien limb’ phenomena, were established over the next 2 months, with rapid progression. Death occurred 3 months after symptom onset. Laboratory results were normal. Initially, imaging only showed restricted diffusion with bilateral parieto-occipital gyri involvement on DWI-MRI, with unspecific EEG changes. An autopsy was performed. Brain neuropathology confirmed sporadic CJD (sCJD. Conclusions: CBS is a heterogeneous clinical syndrome whose differential diagnosis is extensive. CJD can occasionally present with clinical characteristics resembling CBS. MRI detection of abnormalities in some sequences (FLAIR, DWI, as previously reported, has high diagnostic utility for sCJD diagnosis – especially in early stages – when other tests can still appear normal. Abnormalities on DWI sequencing may not correlate with neuropathological findings, suggesting a functional basis to explain the changes found.

  16. Rapid purification of recombinant histones.

    Science.gov (United States)

    Klinker, Henrike; Haas, Caroline; Harrer, Nadine; Becker, Peter B; Mueller-Planitz, Felix

    2014-01-01

    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.

  17. 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.

  18. The rapid identification for the unaware radioactive material

    International Nuclear Information System (INIS)

    Jin Yuren; Cheng Zhiwei; Xu Hui; Wang Jiang; Han Xiaoyuan; Long Bin

    2010-01-01

    The unaware radioactive material(URM) appeared in the society may induce serious deterministic effect, even result in havoc and instability of the society. The rapid and accurate identification for URM is the premise for its reasonable treatment. In this paper, an identification procedure for URM was developed and which was successfully implemented in the identification of an URM. The In-situ HPGe gamma spectrometry etc was employed for the rapid preliminary identification, and the laboratory HPGe gamma spectrometry and ICP-MS as well as the density measurement were used for its final identification. One unaware radioactive material was assayed, and the results indicate that it is a kind of high pure depleted uranium metal with the 235 U/ 238 U atomic ratio of 0.454%. (authors)

  19. RAPID TRANSFER ALIGNMENT USING FEDERATED KALMAN FILTER

    Institute of Scientific and Technical Information of China (English)

    GUDong-qing; QINYong-yuan; PENGRong; LIXin

    2005-01-01

    The dimension number of the centralized Kalman filter (CKF) for the rapid transfer alignment (TA) is as high as 21 if the aircraft wing flexure motion is considered in the rapid TA. The 21-dimensional CKF brings the calculation burden on the computer and the difficulty to meet a high filtering updating rate desired by rapid TA. The federated Kalman filter (FKF) for the rapid TA is proposed to solve the dilemma. The structure and the algorithm of the FKF, which can perform parallel computation and has less calculation burden, are designed.The wing flexure motion is modeled, and then the 12-order velocity matching local filter and the 15-order attitud ematching local filter are devised. Simulation results show that the proposed EKE for the rapid TA almost has the same performance as the CKF. Thus the calculation burden of the proposed FKF for the rapid TA is markedly decreased.

  20. Effects of amifostine on radiation-induced apoptosis in mouse ovary

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Lee, Kyoung Hee; Yoon Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

    2002-07-01

    The present study was designed to assess the radioprotective effects of amifostine on ovarian follicles. Three week-old female mice with or without pretreatment of amifostine were irradiated with 6.42 Gy of {gamma} -ray. Ovaries were collected 0 and 6h after irradiation. DNA fragmentation pattern and expression of genes and activity of proteins related with apoptosis were investigated by means of RT-PCR and Western blot. Proliferation of granulosa cells was reduced and incidence rate of follicular atresia was increased in ovarian follicles in {gamma} -ray irradiated mice compared to those in control or amifostine-treated group. DNA fragmentation was increased in time-dependent manner in granulosa cells of all irradiated groups. However, no difference between amifostine pre-treated group and irradiated groups was found and the expression of p53 as tumor suppressor gene and Bax as one of pro-apoptotic Bcl-2 family was increased in irradiated mice ovaries. PARP as DNA damage sensor was cleaved and its upstream regulator, Caspase-3 was activated. Fas (CD95), one of membrane bound receptor which initiated apoptosis pathway was expressed by {gamma} -ray. Pretreatment of amifostine before irradiation, however, inhibited the expression of p53 and Bax, the cleavage of PARP and the activation of Caspase-3. In conclusion, amifostine has an inhibitory effect on gonadal cell apoptosis induced by {gamma} -ray irradiation, through lowering the expression of apoptotic signaling peptide and the activation of DNA repair enzymes.

  1. Theory of hard diffraction and rapidity gaps

    International Nuclear Information System (INIS)

    Del Duca, V.

    1995-06-01

    In this talk we review the models describing the hard diffractive production of jets or more generally high-mass states in presence of rapidity gaps in hadron-hadron and lepton-hadron collisions. By rapidity gaps we mean regions on the lego plot in (pseudo)-rapidity and azimuthal angle where no hadrons are produced, between the jet(s) and an elastically scattered hadron (single hard diffraction) or between two jets (double hard diffraction). (orig.)

  2. Theory of hard diffraction and rapidity gaps

    International Nuclear Information System (INIS)

    Del Duca, V.

    1996-01-01

    In this talk we review the models describing the hard diffractive production of jets or more generally high-mass states in presence of rapidity gaps in hadron-hadron and lepton-hadron collisions. By rapidity gaps we mean regions on the lego plot in (pseudo)-rapidity and azimuthal angle where no hadrons are produced, between the jet(s) and an elastically scattered hadron (single hard diffraction) or between two jets (double hard diffraction). copyright 1996 American Institute of Physics

  3. The consequences of rapid deforestation: A North African example

    International Nuclear Information System (INIS)

    Zaimeche, S.E.

    1994-01-01

    This paper discusses some of the consequences of deforestation in Algeria. It focuses on the Wilaya region of Jijel, in the eastern part of the country, which has some of the last, dense, sub-humid Mediterranean forests. The issue of a possible connection between the recent widespread deforestation and the drier conditions affecting the region is discussed. It is also shown how rapid social and economic changes have induced deforestation on such a large scale that erosion and soil losses are reaching unprecedented levels. The paper also points to the loss of economic potential for Algeria's forests. 38 refs, 2 figs, 3 tabs, 3 photos

  4. Parallel, Rapid Diffuse Optical Tomography of Breast

    National Research Council Canada - National Science Library

    Yodh, Arjun

    2001-01-01

    During the last year we have experimentally and computationally investigated rapid acquisition and analysis of informationally dense diffuse optical data sets in the parallel plate compressed breast geometry...

  5. Parallel, Rapid Diffuse Optical Tomography of Breast

    National Research Council Canada - National Science Library

    Yodh, Arjun

    2002-01-01

    During the last year we have experimentally and computationally investigated rapid acquisition and analysis of informationally dense diffuse optical data sets in the parallel plate compressed breast geometry...

  6. Numerology on pion and proton rapidity

    International Nuclear Information System (INIS)

    Gugelot, P.C.

    1987-01-01

    The pseudo-rapidity of pion jets which were measured for 50 GeV and 150 GeV incident pions and protons on carbon, copper and lead targets is analysed. The shape of the rapidity distribution for a ''fireball'' which emits particles isotropically in its center of mass is a cosh -2 y distribution. It is possible to unfold all measured distributions into three groups which correspond to a low rapidity originating from the target fragmentation, a middle group which is a function of the center of mass of the projectile and target rapidity and a fast group which is due to the projectile. 11 refs., 8 figs. (author)

  7. Rapid Automated Mission Planning System, Phase II

    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...

  8. Rapid Robot Design Validation, Phase II

    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...

  9. [Drug induced diarrhea].

    Science.gov (United States)

    Morard, Isabelle; Hadengue, Antoine

    2008-09-03

    Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

  10. 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.

  11. JS-K, a GST-activated nitric oxide generator, induces DNA double-strand breaks, activates DNA damage response pathways, and induces apoptosis in vitro and in vivo in human multiple myeloma cells.

    Science.gov (United States)

    Kiziltepe, Tanyel; Hideshima, Teru; Ishitsuka, Kenji; Ocio, Enrique M; Raje, Noopur; Catley, Laurence; Li, Chun-Qi; Trudel, Laura J; Yasui, Hiroshi; Vallet, Sonia; Kutok, Jeffery L; Chauhan, Dharminder; Mitsiades, Constantine S; Saavedra, Joseph E; Wogan, Gerald N; Keefer, Larry K; Shami, Paul J; Anderson, Kenneth C

    2007-07-15

    Here we investigated the cytotoxicity of JS-K, a prodrug designed to release nitric oxide (NO(*)) following reaction with glutathione S-transferases, in multiple myeloma (MM). JS-K showed significant cytotoxicity in both conventional therapy-sensitive and -resistant MM cell lines, as well as patient-derived MM cells. JS-K induced apoptosis in MM cells, which was associated with PARP, caspase-8, and caspase-9 cleavage; increased Fas/CD95 expression; Mcl-1 cleavage; and Bcl-2 phosphorylation, as well as cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G (EndoG) release. Moreover, JS-K overcame the survival advantages conferred by interleukin-6 (IL-6) and insulin-like growth factor 1 (IGF-1), or by adherence of MM cells to bone marrow stromal cells. Mechanistic studies revealed that JS-K-induced cytotoxicity was mediated via NO(*) in MM cells. Furthermore, JS-K induced DNA double-strand breaks (DSBs) and activated DNA damage responses, as evidenced by neutral comet assay, as well as H2AX, Chk2 and p53 phosphorylation. JS-K also activated c-Jun NH(2)-terminal kinase (JNK) in MM cells; conversely, inhibition of JNK markedly decreased JS-K-induced cytotoxicity. Importantly, bortezomib significantly enhanced JS-K-induced cytotoxicity. Finally, JS-K is well tolerated, inhibits tumor growth, and prolongs survival in a human MM xenograft mouse model. Taken together, these data provide the preclinical rationale for the clinical evaluation of JS-K to improve patient outcome in MM.

  12. 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...

  13. 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...

  14. Rapid 3-D analysis of rockfalls

    Science.gov (United States)

    Stock, Greg M.; Guerin, A.; Avdievitch, Nikita N.; Collins, Brian D.; Jaboyedoff, Michel

    2018-01-01

    Recent fatal and damaging rockfalls in Yosemite National Park indicate the need for rapid response data collection methods to inform public safety and assist with management response. Here we show the use of multiple-platform remote sensing methods to rapidly capture pertinent data needed to inform management and the public following a several large rockfalls from El Capitan cliff in Yosemite Valley, California.

  15. Rapid Prototyping: An Alternative Instructional Design Strategy.

    Science.gov (United States)

    Tripp, Steven D.; Bichelmeyer, Barbara

    1990-01-01

    Discusses the nature of instructional design and describes rapid prototyping as a feasible model for instructional system design (ISD). The use of prototyping in software engineering is described, similarities between software design and instructional design are discussed, and an example is given which uses rapid prototyping in designing a…

  16. A Systems Approach to Rapid School Improvement

    Science.gov (United States)

    McCauley, Carlas

    2018-01-01

    To support systemic thinking about school improvement, the Center on School Turnaround at WestEd developed a framework to assist states, districts, and schools in leading and managing rapid improvement efforts. The framework, which is presented in this article, has four domains that have proved central to rapid, significant improvement: (1)…

  17. Ionizing radiation and nitric oxide donor sensitize Fas-induced apoptosis via up-regulation of Fas in human cervical cancer cells

    International Nuclear Information System (INIS)

    Park, In Chul; Woo, Sang Hyeok; Park, Myung Jin; Lee, Hyung Chahn; Lee Su Jae; Hong, Young Joon; Lee, Seung Hoon; Hong, Seok II; Rhee, Chang Hun

    2004-01-01

    Fas/CD95/Apo1 is a transmembrane receptor known to trigger apoptotic cell death in several cell types. In the present study, we showed that ionizing radiation (IR) and NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), sensitized Fas-induced apoptotic cell death of HeLa human cervical cancers. Suboptimal dose of IR and SNAP up-regulated cell-surface Fas antigen, detected by FACScan using FITC-anti-Fas antibody. When combined with IR or SNAP, agonistic anti-Fas antibody CH-11 resulted in marked enhancement of apoptosis. This sensitization was completely abrogated by anti-Fas neutralizing antibody ZB4. During the IR and SNAP sensitized Fas-induced apoptosis, mitochondria permeabilization, cytochrome c release, and DNA fragmentation were detected. Furthermore, combined treatment of IR and SNAP additively up-regulated the surface Fas protein expression and sensitized Fas-induced apoptosis. Our finding demonstrate that sensitization of HeLa cervical cells to Fas-mediated apoptosis by IR and NO donor is most likely due to the up-regulation of Fas expression and also provides a means with which to sensitize tumors to the killing effects of cancer therapy via the Fas receptor

  18. A fluorescence-based rapid screening assay for cytotoxic compounds

    International Nuclear Information System (INIS)

    Montoya, Jessica; Varela-Ramirez, Armando; Estrada, Abril; Martinez, Luis E.; Garza, Kristine; Aguilera, Renato J.

    2004-01-01

    A simple fluorescence-based assay was developed for the rapid screening of potential cytotoxic compounds generated by combinatorial chemistry. The assay is based on detection of nuclear green fluorescent protein (GFP) staining of a human cervical cancer cell line (HeLa) carrying an integrated histone H2B-GFP fusion gene. Addition of a cytotoxic compound to the HeLa-GFP cells results in the eventual degradation of DNA and loss of the GFP nuclear fluorescence. Using this assay, we screened 11 distinct quinone derivatives and found that several of these compounds were cytotoxic. These compounds are structurally related to plumbagin an apoptosis-inducing naphthoquinone isolated from Black Walnut. In order to determine the mechanism by which cell death was induced, we performed additional experiments with the most cytotoxic quinones. These compounds were found to induce morphological changes (blebbing and nuclear condensation) consistent with induction of apoptosis. Additional tests revealed that the cytotoxic compounds induce both necrotic and apoptotic modes of death

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Economic analyses of rapid population growth.

    Science.gov (United States)

    Birdsall, N

    1989-01-01

    "Discussion of the macroeconomic consequences of rapid population growth is organized into three schools: pessimists, optimists, and the recent revisionists. For the revisionists, differing views are presented about the pervasiveness and relevance of market failures, such as the negative externalities of childbearing, and about the ability of families and institutions to adjust rapidly to changes brought on by rapid population growth. A welfare economics approach is used to review the merits of various public policies to reduce fertility, including public financing of family planning services and taxes and incentives associated with childbearing." The focus is on developing countries. excerpt

  6. Cation distributions on rapidly solidified cobalt ferrite

    Science.gov (United States)

    De Guire, Mark R.; Kalonji, Gretchen; O'Handley, Robert C.

    1990-01-01

    The cation distributions in two rapidly solidified cobalt ferrites have been determined using Moessbauer spectroscopy at 4.2 K in an 8-T magnetic field. The samples were obtained by gas atomization of a Co0-Fe2O3-P2O5 melt. The degree of cation disorder in both cases was greater than is obtainable by cooling unmelted cobalt ferrite. The more rapidly cooled sample exhibited a smaller departure from the equilibrium cation distribution than did the more slowly cooled sample. This result is explained on the basis of two competing effects of rapid solidification: high cooling rate of the solid, and large undercooling.

  7. [Rapid prototyping: a very promising method].

    Science.gov (United States)

    Haverman, T M; Karagozoglu, K H; Prins, H-J; Schulten, E A J M; Forouzanfar, T

    2013-03-01

    Rapid prototyping is a method which makes it possible to produce a three-dimensional model based on two-dimensional imaging. Various rapid prototyping methods are available for modelling, such as stereolithography, selective laser sintering, direct laser metal sintering, two-photon polymerization, laminated object manufacturing, three-dimensional printing, three-dimensional plotting, polyjet inkjet technology,fused deposition modelling, vacuum casting and milling. The various methods currently being used in the biomedical sector differ in production, materials and properties of the three-dimensional model which is produced. Rapid prototyping is mainly usedforpreoperative planning, simulation, education, and research into and development of bioengineering possibilities.

  8. Rapid Multiplex Microbial Detector, Phase I

    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...

  9. simple and rapid spectrophotometric assay of levocetirizine

    African Journals Online (AJOL)

    Preferred Customer

    Simple, rapid, selective and fairly sensitive method is described for the ... Determination of small amounts of LCTZ in pharmaceutical preparations is important for .... sodium hydroxide and extraction of HCl-free-amine into chloroform followed ...

  10. 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...

  11. Mars Sample Return Orbiter Rapid Architecture Study

    Science.gov (United States)

    Godfrey, A.; Johnson, M.; Stroud, C.

    2018-04-01

    An overview of rapid systems analysis (mass, risk, and schedule) on 1000s of MSRO configurations to understand key technologies and feasible options. Can we generate enough power? Can we aerobrake in time? Are some technology elements just too risky?

  12. 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...

  13. A Rapid Coliform Detector, Phase I

    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...

  14. 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.

  15. Clan structure analysis and rapidity gap probability

    International Nuclear Information System (INIS)

    Lupia, S.; Giovannini, A.; Ugoccioni, R.

    1995-01-01

    Clan structure analysis in rapidity intervals is generalized from negative binomial multiplicity distribution to the wide class of compound Poisson distributions. The link of generalized clan structure analysis with correlation functions is also established. These theoretical results are then applied to minimum bias events and evidentiate new interesting features, which can be inspiring and useful in order to discuss data on rapidity gap probability at TEVATRON and HERA. (orig.)

  16. Clan structure analysis and rapidity gap probability

    Energy Technology Data Exchange (ETDEWEB)

    Lupia, S. [Turin Univ. (Italy). Ist. di Fisica Teorica]|[Istituto Nazionale di Fisica Nucleare, Turin (Italy); Giovannini, A. [Turin Univ. (Italy). Ist. di Fisica Teorica]|[Istituto Nazionale di Fisica Nucleare, Turin (Italy); Ugoccioni, R. [Turin Univ. (Italy). Ist. di Fisica Teorica]|[Istituto Nazionale di Fisica Nucleare, Turin (Italy)

    1995-03-01

    Clan structure analysis in rapidity intervals is generalized from negative binomial multiplicity distribution to the wide class of compound Poisson distributions. The link of generalized clan structure analysis with correlation functions is also established. These theoretical results are then applied to minimum bias events and evidentiate new interesting features, which can be inspiring and useful in order to discuss data on rapidity gap probability at TEVATRON and HERA. (orig.)

  17. Characterization of aluminium alloys rapidly solidified

    International Nuclear Information System (INIS)

    Monteiro, W.A.

    1988-01-01

    This paper discussed the investigation of the microstructural and mechanical properties of the aluminium alloys (3003; 7050; Al-9% Mg) rapidly solidified by melt spinning process (cooling rate 10 4 - 10 6 K/s). The rapidly solidification process of the studied aluminium alloys brought a microcrystallinity, a minimum presence of coarse precipitation and, also, better mechanical properties of them comparing to the same alloys using ingot process. (author) [pt

  18. 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.

  19. Rapid modification of retroviruses using lipid conjugates

    International Nuclear Information System (INIS)

    Mukherjee, Nimisha G; Le Doux, Joseph M; Andrew Lyon, L

    2009-01-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  20. Radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Ohyama, Harumi

    1995-01-01

    Apoptosis is an active process of gene-directed cellular self-destruction that can be induced in many cell types via numerous physiological and pathological stimuli. We found that interphasedeath of thymocytes is a typical apoptosis showing the characteristic features of apoptosis including cell shrinkage, chromatin condensation and DNA degradation. Moderate dose of radiation induces extensive apoptosis in rapidly proliferating cell population such as the epithelium of intestinal crypt. Recent reports indicate that the ultimate form of radiation-induced mitotic death in several cells is also apoptosis. One of the hallmarks of apoptosis is the enzymatic internucleosomal degradation of chromatin DNA. We identified an endonuclease responsible for the radiation-induced DNA degradation in rat thymocytes. The death-sparing effects of interrupting RNA and protein synthesis suggested a cell genetic program for apoptosis. Apoptosis of thymocytes initiated by DNA damage, such as radiation and radio mimetic substance, absolutely requires the protein of p53 cancer suppresser gene. The cell death induced by glucocorticoid, or aging, has no such requirement. Expression of oncogene bcl-2 rescues cells from the apoptosis. Massive apoptosis in radiosensitive cells induced by higher dose radiation may be fatal. It is suggested that selective apoptotic elimination of cells would play an important role for protection against carcinogenesis and malformation through removal of cells with unrepaired radiation-induced DNA damages. Data to evaluate the significance of apoptosis in the radiation risk are still poor. Further research should be done in order to clarify the roles of the cell death on the acute and late effects of irradiation. (author)

  1. Review on CNC-Rapid Prototyping

    International Nuclear Information System (INIS)

    M Nafis O Z; Nafrizuan M Y; Munira M A; Kartina J

    2012-01-01

    This article reviewed developments of Computerized Numerical Control (CNC) technology in rapid prototyping process. Rapid prototyping (RP) can be classified into three major groups; subtractive, additive and virtual. CNC rapid prototyping is grouped under the subtractive category which involves material removal from the workpiece that is larger than the final part. Richard Wysk established the use of CNC machines for rapid prototyping using sets of 2½-D tool paths from various orientations about a rotary axis to machine parts without refixturing. Since then, there are few developments on this process mainly aimed to optimized the operation and increase the process capabilities to stand equal with common additive type of RP. These developments include the integration between machining and deposition process (hybrid RP), adoption of RP to the conventional machine and optimization of the CNC rapid prototyping process based on controlled parameters. The article ended by concluding that the CNC rapid prototyping research area has a vast space for improvement as in the conventional machining processes. Further developments and findings will enhance the usage of this method and minimize the limitation of current approach in building a prototype.

  2. Induced Seismicity

    Science.gov (United States)

    Keranen, Katie M.; Weingarten, Matthew

    2018-05-01

    The ability of fluid-generated subsurface stress changes to trigger earthquakes has long been recognized. However, the dramatic rise in the rate of human-induced earthquakes in the past decade has created abundant opportunities to study induced earthquakes and triggering processes. This review briefly summarizes early studies but focuses on results from induced earthquakes during the past 10 years related to fluid injection in petroleum fields. Study of these earthquakes has resulted in insights into physical processes and has identified knowledge gaps and future research directions. Induced earthquakes are challenging to identify using seismological methods, and faults and reefs strongly modulate spatial and temporal patterns of induced seismicity. However, the similarity of induced and natural seismicity provides an effective tool for studying earthquake processes. With continuing development of energy resources, increased interest in carbon sequestration, and construction of large dams, induced seismicity will continue to pose a hazard in coming years.

  3. 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

    2018-04-01

    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

  4. 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.

  5. Rapid-Sequence Serial Sexual Homicides.

    Science.gov (United States)

    Schlesinger, Louis B; Ramirez, Stephanie; Tusa, Brittany; Jarvis, John P; Erdberg, Philip

    2017-03-01

    Serial sexual murderers have been described as committing homicides in a methodical manner, taking substantial time between offenses to elude the authorities. The results of our study of the temporal patterns (i.e., the length of time between homicides) of a nonrandom national sample of 44 serial sexual murderers and their 201 victims indicate that this representation may not always be accurate. Although 25 offenders (56.8%) killed with longer than a 14-day period between homicides, a sizeable subgroup was identified: 19 offenders (43.2%) who committed homicides in rapid-sequence fashion, with fewer than 14 days between all or some of the murders. Six offenders (13.6%) killed all their victims in one rapid-sequence, spree-like episode, with homicides just days apart or sometimes two murders in the same day. Thirteen offenders (29.5%) killed in one or two rapid-sequence clusters (i.e., more than one murder within a 14-day period, as well as additional homicides with greater than 14 days between each). The purpose of our study was to describe this subgroup of rapid-sequence offenders who have not been identified until now. These findings argue for accelerated forensic assessments of dangerousness and public safety when a sexual murder is detected. Psychiatric disorders with rapidly occurring symptom patterns, or even atypical mania or mood dysregulation, may serve as exemplars for understanding this extraordinary group of offenders. © 2017 American Academy of Psychiatry and the Law.

  6. 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.

  7. 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

  8. 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.

  9. Rapidity gap survival in enhanced Pomeron scheme

    Energy Technology Data Exchange (ETDEWEB)

    Ostapchenko, Sergey [Frankfurt Institute for Advanced Studies, Frankfurt am Main (Germany); Moscow State University, D.V. Skobeltsyn Institute of Nuclear Physics, Moscow (Russian Federation); Bleicher, Marcus [Frankfurt Institute for Advanced Studies, Frankfurt am Main (Germany); Goethe-Universitat, Institute for Theoretical Physics, Frankfurt am Main (Germany)

    2018-01-15

    We apply the phenomenological Reggeon field theory framework to investigate rapidity gap survival (RGS) probability for diffractive dijet production in proton-proton collisions. In particular, we study in some detail rapidity gap suppression due to elastic rescatterings of intermediate partons in the underlying parton cascades, described by enhanced (Pomeron-Pomeron interaction) diagrams. We demonstrate that such contributions play a subdominant role, compared to the usual, so-called ''eikonal'', rapidity gap suppression due to elastic rescatterings of constituent partons of the colliding protons. On the other hand, the overall RGS factor proves to be sensitive to color fluctuations in the proton. Hence, experimental data on diffractive dijet production can be used to constrain the respective model approaches. (orig.)

  10. Rapid Quench in an Electrostatic Levitator

    Science.gov (United States)

    SanSoucie, Michael P.; Rogers, Jan R.; Matson, Douglas M.

    2016-01-01

    The Electrostatic Levitation (ESL) Laboratory at the NASA Marshall Space Flight Center (MSFC) is a unique facility for investigators studying high-temperature materials. The ESL laboratory's main chamber has been upgraded with the addition of a rapid quench system. This system allows samples to be dropped into a quench vessel that can be filled with a low melting point material, such as a gallium or indium alloy, as a quench medium. Thereby allowing rapid quenching of undercooled liquid metals. Up to eight quench vessels can be loaded into a wheel inside the chamber that is indexed with control software. The system has been tested successfully with samples of zirconium, iron-cobalt alloys, titanium-zirconium-nickel alloys, and a silicon-cobalt alloy. This new rapid quench system will allow materials science studies of undercooled materials and new materials development. In this presentation, the system is described and some initial results are presented.

  11. Rapid monitoring of gaseous radionuclides using a portable spectrometer

    International Nuclear Information System (INIS)

    Chung, C.; Tsai, C.H.

    1995-01-01

    A field gamma ray spectrometer, consisting of a portable high purity germanium detector, portable multichannel analyser, and a notebook computer, was used to conduct in situ rapid scanning of radioactive Ar, Kr and Xe isotopes in the air around a nuclear facility. The portable gamma ray spectrometer was calibrated using Ar, Kr, and Xe radioisotopes, activated in a research reactor and released in a sealed chamber. The unit was further tested inside the reactor containment to monitor the concentration of 41 Ar. In a typical one hour field measurement, the detection limits for some rare gas radionuclides corresponded to dose rates around 0.1 nSv.h -1 , which is far less than the dose rate induced by derived air concentrations imposed by the authority. The dose rate due to ground level concentrations of gaseous radionuclides dispersed from a source, such a nuclear facility or nuclear test, can be monitored in a short period using the portable unit. (Author)

  12. Rapid web development using AJAX and Python

    Energy Technology Data Exchange (ETDEWEB)

    Dolgert, A; Gibbons, L; Kuznetsov, V [Cornell University, Ithaca, NY 14853 (United States)], E-mail: vkuznet@gmail.com

    2008-07-15

    We discuss the rapid development of a large scale data discovery service for the CMS experiment using modern AJAX techniques and the Python language. To implement a flexible interface capable of accommodating several different versions of the DBS database, we used a 'stack' approach. Asynchronous JavaScript and XML (AJAX) together with an SQL abstraction layer, template engine, code generation tool and dynamic queries provide powerful tools for constructing interactive interfaces to large amounts of data. We show how the use of these tools, with rapid development in a modern scripting language, improved the scalability and usability of the the search interface for different user communities.

  13. Rapid web development using AJAX and Python

    International Nuclear Information System (INIS)

    Dolgert, A; Gibbons, L; Kuznetsov, V

    2008-01-01

    We discuss the rapid development of a large scale data discovery service for the CMS experiment using modern AJAX techniques and the Python language. To implement a flexible interface capable of accommodating several different versions of the DBS database, we used a 'stack' approach. Asynchronous JavaScript and XML (AJAX) together with an SQL abstraction layer, template engine, code generation tool and dynamic queries provide powerful tools for constructing interactive interfaces to large amounts of data. We show how the use of these tools, with rapid development in a modern scripting language, improved the scalability and usability of the the search interface for different user communities

  14. Rapid prototyping using robot welding : process description

    OpenAIRE

    Ribeiro, António Fernando; Norrish, John

    1997-01-01

    Rapid Prototyping is a relatively recent technique to produce component prototypes for industry in a much shorter period of time, since the time to market a product is essential to its success. A new Rapid Prototyping process which uses metal as the raw material had been under development at Cranfield University in the last few years. The process uses a Gas Metal Arc fusion welding robot which deposits successive layers of metal in such way that it forms a 3D solid component. Firstly, a CAD s...

  15. 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

  16. Interplay between estrogen receptor and AKT in estradiol-induced alternative splicing.

    Science.gov (United States)

    Bhat-Nakshatri, Poornima; Song, Eun-Kyung; Collins, Nikail R; Uversky, Vladimir N; Dunker, A Keith; O'Malley, Bert W; Geistlinger, Tim R; Carroll, Jason S; Brown, Myles; Nakshatri, Harikrishna

    2013-06-11

    Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown. MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction was performed to verify alternative splicing. ERα binding to alternatively spliced genes was verified by chromatin immunoprecipitation assay. Bromodeoxyuridine incorporation-ELISA and Annexin V labeling assays were done to measure cell proliferation and apoptosis, respectively. We identified the targets of E2-induced alternative splicing and deconstructed some of the mechanisms surrounding E2-induced splicing by combining splice array with ERα cistrome and gene expression array. E2-induced alternatively spliced genes fall into at least two subgroups: coupled to E2-regulated transcription and ERα binding to the gene without an effect on rate of transcription. Further, AKT, which phosphorylates both ERα and splicing factors, influenced ERα:E2 dependent splicing in a gene-specific manner. Genes that are alternatively spliced include FAS/CD95, FGFR2, and AXIN-1. E2 increased the expression of FGFR2 C1 isoform but reduced C3 isoform at mRNA level. E2-induced alternative splicing of FAS and FGFR2 in MCF-7 cells correlated with resistance to FAS activation-induced apoptosis and response to keratinocyte growth factor (KGF), respectively. Resistance of MCF-7 breast cancer cells to the anti-estrogen tamoxifen was associated with ER

  17. 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

  18. 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.

  19. 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).

  20. 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.

  1. Ceramic microfabrication by rapid prototyping process chains

    Indian Academy of Sciences (India)

    Ceramic microfabrication by rapid prototyping process chains ... is nearly impossible, shaping has to be done by a replication step in the green, unfired state. ... This process chain combines the fast and inexpensive supply of master models by ...

  2. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie; Danquah, Agyemang; Zé licourt, Axel de; Hirt, Heribert; Colcombet, Jean

    2015-01-01

    rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests

  3. 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,…

  4. Rapid City Native American Population Needs Assessment.

    Science.gov (United States)

    Farrokhi, Abdollah

    1993-01-01

    Interviews with 301 Native American households in Rapid City, South Dakota, examined demographic variables and attitudes and needs in the areas of education, housing, transportation, health care, recreation, and employment. The ultimate goals for Native American people are achieving empowerment and group determination through greater cultural…

  5. High precision, rapid laser hole drilling

    Science.gov (United States)

    Chang, Jim J.; Friedman, Herbert W.; Comaskey, Brian J.

    2013-04-02

    A laser system produces a first laser beam for rapidly removing the bulk of material in an area to form a ragged hole. The laser system produces a second laser beam for accurately cleaning up the ragged hole so that the final hole has dimensions of high precision.

  6. Utilizing Rapid Prototyping for Architectural Modeling

    Science.gov (United States)

    Kirton, E. F.; Lavoie, S. D.

    2006-01-01

    This paper will discuss our approach to, success with and future direction in rapid prototyping for architectural modeling. The premise that this emerging technology has broad and exciting applications in the building design and construction industry will be supported by visual and physical evidence. This evidence will be presented in the form of…

  7. 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.

  8. Rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Jennum, Poul

    2009-01-01

    Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by loss of REM sleep and related electromyographic atonia with marked muscular activity and dream enactment behaviour. RBD is seen in 0.5% of the population. It occurs in an idiopathic form and secondarily to medical...

  9. Rapid arc - clinical rationale and results

    International Nuclear Information System (INIS)

    Cozzi, Lucca

    2008-01-01

    The presentation will focus on the background of Intensity modulation volumetric arc therapy Rapid Arc from Varian Medical Systems aiming to highlight the technical and clinical rational also from an historical perspective to the founding pillars of fast delivery with a minimum number of arcs and a minimum number of monitor units

  10. Rapid thermal annealing of phosphorus implanted silicon

    International Nuclear Information System (INIS)

    Lee, Y.H.; Pogany, A.; Harrison, H.B.; Williams, J.S.

    1985-01-01

    Rapid thermal annealing (RTA) of phosphorus-implanted silicon has been investigated by four point probe, Van der Pauw methods and transmission electron microscopy. The results have been compared to furnace annealing. Experiments show that RTA, even at temperatures as low as 605 deg C, results in good electrical properties with little remnant damage and compares favourably with furnace annealing

  11. Utilizing Information Technology to Facilitate Rapid Acquisition

    Science.gov (United States)

    2006-06-01

    PAGES 109 14. SUBJECT TERMS Rapid Acquisition, eCommerce , eProcurement, Information Technology, Contracting, Global Information Network...Agency. 5 eCommerce and eProcurement, and possess an adequate knowledge of information technology. D. RESEARCH QUESTIONS 1. Primary Research... eCommerce , Information Technology, and eProcurement knowledge, and government and private industry reports utilizing numerous library and Internet

  12. 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…

  13. Rapidly solidified aluminium for optical applications

    NARCIS (Netherlands)

    Gubbels, G.P.H.; Venrooy, B.W.H. van; Bosch, A.J.; Senden, R.

    2008-01-01

    This paper present the results of a diamond turning study of a rapidly solidified aluminium 6061 alloy grade, known as RSA6061. It is shown that this small grain material can be diamond turned to smaller roughness values than standard AA6061 aluminium grades. Also, the results are nearly as good as

  14. The Health Penalty of China's Rapid Urbanization

    NARCIS (Netherlands)

    E. Van de Poel (Ellen); O.A. O'Donnell (Owen); E.K.A. van Doorslaer (Eddy)

    2009-01-01

    textabstractRapid urbanization could have positive and negative health effects, such that the net impact on population health is not obvious. It is, however, highly pertinent to the human welfare consequences of development. This paper uses community and individual level longitudinal data from the

  15. Analysis of the Rapid Chloride Migration test

    NARCIS (Netherlands)

    Spiesz, P.R.; Ballari, M.; Brouwers, H.J.H.; Ferreira, R. M.; Gulikers, J.; Andrade, C.

    2009-01-01

    In this study the Rapid Chloride Migration test (RCM) standardized as NT Build 492 and BAW-Merkblatt is reviewed. Since the traditional natural diffusion tests are laborious, time consuming and costly, they are not always preferred from a practical point of view. To overcome these disadvantages,

  16. Rapid pasteurization of shell eggs using RF

    Science.gov (United States)

    A novel method for rapidly pasteurizing eggs in the shell could enhance the safety of the United States’ food supply. Current federal regulations do not require eggs sold in stores to be pasteurized, yet these eggs are often consumed raw or undercooked and cause untold cases of salmonella illness ea...

  17. Classroom Evaluation of a Rapid Prototyping System.

    Science.gov (United States)

    Tennyson, Stephen A.; Krueger, Thomas J.

    2001-01-01

    Introduces rapid prototyping which creates virtual models through a variety of automated material additive processes. Relates experiences using JP System 5 in freshman and sophomore engineering design graphics courses. Analyzes strengths and limitations of the JP System 5 and discusses how to use it effectively. (Contains 15 references.)…

  18. Rapid restoration after lignite mining in Hungary

    Energy Technology Data Exchange (ETDEWEB)

    1988-06-01

    The 30th anniversary of the commencement of large scale lignite production by opencast mining in Hungary was celebrated in 1987. A process of rapid technical and biological reclamation without the use of humus has now been developed. The costs involved are only 5-10% of those of conventional methods and reclamation cycle is four years compared to ten years for conventional methods.

  19. Implementing RapidArc into clinical routine

    DEFF Research Database (Denmark)

    Van Esch, Ann; Huyskens, Dominique P; Behrens, Claus F

    2011-01-01

    With the increased commercial availability of intensity modulated arc therapy (IMAT) comes the need for comprehensive QA programs, covering the different aspects of this newly available technology. This manuscript proposes such a program for the RapidArc (RA) (Varian Medical Systems, Palo Alto...

  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

    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....

  1. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells

    KAUST Repository

    Ren, Jian; Wu, Junhua

    2012-01-01

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E 2) induces rapid non-genomic responses

  2. 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

  3. Rapid polyclonal desensitization with antibodies to IgE and FcεRIα.

    Science.gov (United States)

    Khodoun, Marat V; Kucuk, Zeynep Yesim; Strait, Richard T; Krishnamurthy, Durga; Janek, Kevin; Lewkowich, Ian; Morris, Suzanne C; Finkelman, Fred D

    2013-06-01

    Rapid desensitization, a procedure in which persons allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky, way to induce temporary tolerance. We wanted to determine whether this approach can be adapted to suppress all IgE-mediated allergies in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or FcεRIα. Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-FcεRIα mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and FcεRI and IgE expression were evaluated. Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through FcεRI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer lasting than rapid desensitization with antigen. A rapid desensitization approach with anti-FcεRIα mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later removing all mast cell IgE. Rapid desensitization with an anti-human FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  4. Rapid acceleration leads to rapid weakening in earthquake-like laboratory experiments

    Science.gov (United States)

    Chang, J. C.; Lockner, D. A.; Reches, Z.

    2012-12-01

    acceleration (up to 25 m/s2 during ~0.1 s). Thus, the weakening distance, dc, is reached within the initial acceleration spike. These observations are not unique, and similar weakening-acceleration associations were reported in stick-slip, rotary shear, and impact shear experiments. These studies greatly differ from each other in slip distance, normal stress, acceleration, and slip-velocities with the outstanding commonality of abrupt loading and intense acceleration. We propose that impact loading induces extremely high strain-rates that significantly increase rock brittleness, fracture tendency, and fragmentation. We envision that these processes intensify fault wear as manifested in ELSE experiments by extremely high initial wear-rates. This intense, early wear generates a layer of fine-grain gouge that reduces the fault strength by powder-lubrication. Our analysis indicates that rapid acceleration associated with earthquake rupture accelerates fault weakening and shortens the weakening-distance.

  5. Smac Mimetic Bypasses Apoptosis Resistance in FADD- or Caspase-8-Deficient Cells by Priming for Tumor Necrosis Factor α-Induced Necroptosis

    Directory of Open Access Journals (Sweden)

    Bram Laukens

    2011-10-01

    Full Text Available Searching for new strategies to bypass apoptosis resistance, we investigated the potential of the Smac mimetic BV6 in Jurkat leukemia cells deficient in key molecules of the death receptor pathway. Here, we demonstrate for the first time that Smac mimetic primes apoptosis-resistant, FADD- or caspase-8-deficient leukemia cells for TNFα-induced necroptosis in a synergistic manner. In contrast to TNFα, Smac mimetic significantly enhances CD95-induced apoptosis in wild-type but not in FADD-deficient cells. Interestingly, Smac mimetic- and TNFα-mediated cell death occurs without characteristic features of apoptosis (i.e., caspase activation, DNA fragmentation in FADD-deficient cells. By comparison, Smac mimetic and TNFα trigger activation of caspase-8, -9, and -3 and DNA fragmentation in wild-type cells. Consistently, the caspase inhibitor zVAD.fmk fails to block Smac mimetic- and TNFα-triggered cell death in FADD- or caspase-8-deficient cells, while it confers protection in wild-type cells. By comparison, necrostatin-1, an RIP1 kinase inhibitor, abolishes Smac mimetic- and TNFα-induced cell death in FADD- or caspase-8-deficient. Thus, Smac mimetic enhances TNFα-induced cell death in leukemia cells via two distinct pathways in a context-dependent manner: it primes apoptosis-resistant cells lacking FADD or caspase-8 to TNFα-induced, RIP1-dependent and caspase-independent necroptosis, whereas it sensitizes apoptosis-proficient cells to TNFα-mediated, caspase-dependent apoptosis. These findings have important implications for the therapeutic exploitation of necroptosis as an alternative cell death program to overcome apoptosis resistance.

  6. 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.

  7. Radiographic and computed tomographic demonstration of pseudotumor cerebri due to rapid weight gain in a child with pelvic rhabdomyosarcoma

    International Nuclear Information System (INIS)

    Berdon, W.E.; Barker, D.H.; Barash, F.S.

    1982-01-01

    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

  8. JPSS CGS Tools For Rapid Algorithm Updates

    Science.gov (United States)

    Smith, D. C.; Grant, K. D.

    2011-12-01

    The National Oceanic and Atmospheric Administration (NOAA) and National Aeronautics and Space Administration (NASA) are jointly acquiring the next-generation civilian weather and environmental satellite system: the Joint Polar Satellite System (JPSS). JPSS will contribute the afternoon orbit component and ground processing system of the restructured National Polar-orbiting Operational Environmental Satellite System (NPOESS). As such, JPSS replaces the current Polar-orbiting Operational Environmental Satellites (POES) managed by NOAA and the ground processing component of both POES and the Defense Meteorological Satellite Program (DMSP) replacement known as the Defense Weather Satellite System (DWSS), managed by the Department of Defense (DoD). The JPSS satellites will carry a suite of sensors designed to collect meteorological, oceanographic, climatological, and solar-geophysical observations of the earth, atmosphere, and space. The ground processing system for JPSS is known as the JPSS Common Ground System (JPSS CGS), and consists of a Command, Control, and Communications Segment (C3S) and the Interface Data Processing Segment (IDPS). Both are developed by Raytheon Intelligence and Information Systems (IIS). The Interface Data Processing Segment will process NPOESS Preparatory Project, Joint Polar Satellite System and Defense Weather Satellite System satellite data to provide environmental data products to NOAA and DoD processing centers operated by the United States government. Under NPOESS, Northrop Grumman Aerospace Systems Algorithms and Data Products (A&DP) organization was responsible for the algorithms that produce the EDRs, including their quality aspects. For JPSS, that responsibility has transferred to NOAA's Center for Satellite Applications & Research (STAR). As the Calibration and Validation (Cal/Val) activities move forward following both the NPP launch and subsequent JPSS and DWSS launches, rapid algorithm updates may be required. Raytheon and

  9. Laser induced energy transfer

    International Nuclear Information System (INIS)

    Falcone, R.W.

    1979-01-01

    Two related methods of rapidly transferring stored energy from one excited chemical species to another are described. The first of these, called a laser induced collision, involves a reaction in which the energy balance is met by photons from an intense laser beam. A collision cross section of ca 10 - 17 cm 2 was induced in an experiment which demonstrated the predicted dependence of the cross section on wavelength and power density of the applied laser. A second type of laser induced energy transfer involves the inelastic scattering of laser radiation from energetically excited atoms, and subsequent absorption of the scattered light by a second species. The technique of producing the light, ''anti-Stokes Raman'' scattering of visible and infrared wavelength laser photons, is shown to be an efficient source of narrow bandwidth, high brightness, tunable radiation at vacuum ultraviolet wavelengths by using it to excite a rare gas transition at 583.7 A. In addition, this light source was used to make the first measurement of the isotopic shift of the helium metastable level at 601 A. Applications in laser controlled chemistry and spectroscopy, and proposals for new types of lasers using these two energy transfer methods are discussed

  10. Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

    Science.gov (United States)

    2016-01-01

    Myers AC, Kajekar R, Undem BJ. Allergic inflammation-induced neuropeptide production in rapidly adapting afferent nerves in guinea pig airways. Am J...induced neuro- peptide production in rapidly adapting afferent nerves in guinea pig airways. Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L775–L781...co-localization of transient receptor po- tential vanilloid (trpv)1 and sensory neuropeptides in the guinea - pig respiratory system. Neuroscience

  11. Rapid ion-exchange separations of actinides

    International Nuclear Information System (INIS)

    Usuda, Shigekazu

    1988-01-01

    For the purpose of studying short-lived actinide nuclides, three methods for rapid ion exchange separation of actinide elements with mineral acid-alcohol mixed media were developed: anion exchange with nitric acid-methyl alcohol mixed media to separate the transplutonium and rare earth elements from target material, U or Pu and Al catcher foils; anion exchange with hydrochloric acid-methyl alcohol media to separate Am+Cm, Bk and Cf+Fm from the target, catcher foils and major fission products; and cation exchange with hydrochloric acid-methyl alcohol media and with concentrated hydrochloric acid to separate the transplutonium elements as a group from the rare earths after eliminating the large amounts of U, Al, Cu, Fe etc. The methods enable one to perform rapid and effective separation at elevated temperature (90 deg C) and immediate source preparation for alpha-ray spectrometry. (author) 47 refs.; 10 figs

  12. 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.

  13. Surgically assisted rapid maxillary expansion in adults.

    Science.gov (United States)

    Pogrel, M A; Kaban, L B; Vargervik, K; Baumrind, S

    1992-01-01

    Twelve adults with maxillary width discrepancy of greater than 5 mm were treated by surgically assisted rapid maxillary expansion. The procedure consisted of bilateral zygomatic buttress and midpalatal osteotomies combined with the use of a tooth-borne orthopedic device postoperatively. Mean palatal expansion of 7.5 mm (range of 6 to 13 mm), measured in the first molar region, was achieved within 3 weeks in all patients. Expansion remained stable during the 12-month study period, with a mean relapse for the entire group of 0.88 +/- 0.48 mm. Morbidity was limited to mild postoperative discomfort. The results of this preliminary study indicated that surgically assisted rapid maxillary expansion is a safe, simple, and reliable procedure for achieving a permanent increase in skeletal maxillary width in adults. Further study is necessary to document the three-dimensional movements of the maxillary segments and long-term stability of the skeletal and dental changes.

  14. 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.

  15. Relatively Inexpensive Rapid Prototyping of Small Parts

    Science.gov (United States)

    Swan, Scott A.

    2003-01-01

    Parts with complex three-dimensional shapes and with dimensions up to 8 by 8 by 10 in. (20.3 by 20.3 by 25.4 cm) can be made as unitary pieces of a room-temperature-curing polymer, with relatively little investment in time and money, by a process now in use at Johnson Space Center. The process is one of a growing number of processes and techniques that are known collectively as the art of rapid prototyping. The main advantages of this process over other rapid-prototyping processes are greater speed and lower cost: There is no need to make paper drawings and take them to a shop for fabrication, and thus no need for the attendant paperwork and organizational delays. Instead, molds for desired parts are made automatically on a machine that is guided by data from a computer-aided design (CAD) system and can reside in an engineering office.

  16. Rapid scanning system for fuel drawers

    International Nuclear Information System (INIS)

    Caldwell, J.T.; Fehlau, P.E.; France, S.W.

    1981-01-01

    A nondestructive method for uniqely distinguishing among and quantifying the mass of individual fuel plates in situ in fuel drawers utilized in nuclear reactors is described. The method is both rapid and passive, eliminating the personnel hazard of the commonly used irradiation techniques which require that the analysis be performed in proximity to an intense neutron source such as a reactor. In the present technique, only normally decaying nuclei are observed. This allows the analysis to be performed anywhere. This feature, combined with rapid scanning of a given fuel drawer (in approximately 30 s), and the computer data analysis allows the processing of large numbers of fuel drawers efficiently in the event of a loss alert

  17. Automated rapid chemistry in heavy element research

    International Nuclear Information System (INIS)

    Schaedel, M.

    1994-01-01

    With the increasingly short half-lives of the heavy element isotopes in the transition region from the heaviest actinides to the transactinide elements the demand for automated rapid chemistry techniques is also increasing. Separation times of significantly less than one minute, high chemical yields, high repetition rates, and an adequate detection system are prerequisites for many successful experiments in this field. The development of techniques for separations in the gas phase and in the aqueous phase for applications of chemical or nuclear studies of the heaviest elements are briefly outlined. Typical examples of results obtained with automated techniques are presented for studies up to element 105, especially those obtained with the Automated Rapid Chemistry Apparatus, ARCA. The prospects to investigate the properties of even heavier elements with chemical techniques are discussed

  18. 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.

  19. 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.

  20. A rapid stereoselective synthesis of fluorinated carbohydrates

    International Nuclear Information System (INIS)

    Adam, M.J.; Neeser, J-R.; Hall, L.D.; Pate, B.D.

    1983-01-01

    Acetyl hypofluorite has been added to six unsaturated carbohydrates which contain the vinyl ether moiety. All reactions were rapid (less than 5 min.) at -78 degrees C and gave, with one exception, high yields of isomerically pure products. The hypofluorite was shown to add exclusively in a cis mode and with a strong preference for a particular 'face' of the double bond. As well as the syntheses, NMR data and preferred conformations for the fluorinated products are also discussed

  1. Rapid depressurization of a compressible fluid

    International Nuclear Information System (INIS)

    Dang, M.; Dupont, J.F.; Weber, H.

    1978-08-01

    The rapid depressurization of a plenum is a situation frequently encountered in the dynamical analysis of nuclear gas cycles of the HHT type. Various methods of numerical analyses for a 1-dimensional flow model are examined: finite difference method; control volume method; method of characteristics. Based on the shallow water analogy to compressible flow, the numerical results are compared with those from a water table set up to simulate a standard problem. (Auth.)

  2. Rapid quality assurance with requirements smells

    OpenAIRE

    Femmer, Henning; Méndez Fernández, Daniel; Wagner, Stefan; Eder, Sebastian

    2016-01-01

    Context: Bad requirements quality can cause expensive consequences during the software development lifecycle, especially if iterations are long and feedback comes late. Objectives: We aim at a light-weight static requirements analysis approach that allows for rapid checks immediately when requirements are written down. Method: We transfer the concept of code smells to Requirements Engineering as Requirements Smells. To evaluate the benefits and limitations, we define Requirements Smells, real...

  3. Rapid quality assurance with Requirements Smells

    OpenAIRE

    Femmer, H.; Fernández, D. Méndez; Wagner, S.; Eder, S.

    2016-01-01

    Bad requirements quality can cause expensive consequences during the software development lifecycle, especially if iterations are long and feedback comes late. %-- the faster a problem is found, the cheaper it is to fix. This makes explicit the need of a lightweight detection mechanism of requirements quality violations. We aim at a light-weight static requirements analysis approach that allows for rapid checks immediately when requirements are written down. We transfer the concept of code sm...

  4. Rapid hydrolysis of celluloses in homogeneous solution

    Energy Technology Data Exchange (ETDEWEB)

    Garves, K

    1979-01-01

    Dissolution of cellulose (I), cotton, and cotton linters in a mixture of Ac0H, Ac/sub 2/O, H/sub 2/SO/sub 4/, and DMF at 120 to 160 degrees resulted in rapid and complete hydrolysis of I with decomposition of the cellulose acetatesulfate formed by gradual addition of aqueous acid. Highly crystalline I is quickly decomposed to glucose with minimum byproduct formation. Carbohydrate products containing sugar units other than glucose are hydrolyzed with destruction of monosaccharides.

  5. Rapid prototyping using CBCT: an initial experience

    International Nuclear Information System (INIS)

    Yovchev, D.; Deliverska, E.; Indjova, J.; Ugrinov, R.

    2011-01-01

    This report presents a case of fibrous dysplasia in the left lower jaw of a 12-year-old girl, scanned with CBCT. On the basis of CBCT scan a model of affected jaw was produced using a rapid-prototyping three-dimensional printer. The case demonstrates the possibility to get a prototype by CBCT data. Prototypes can be used to support the diagnosis, planning, training (students and postgraduates) and to obtain informed consent from the patient.

  6. An Analysis of Army Rapid Acquisition

    Science.gov (United States)

    2015-09-01

    measuring its bottom-line impacts enables managers to increase the productivity of these critical assets.”16 If we determine that the current rapid...readiness-requirements/. 111 William Beaver , “Mantech Awarded $61M for Contractor Logistics Sustainment Support Services,” Danger Zone Jobs (blog...could be quickly produced and fielded.”120  Stable and Available Funding. MRAP “was able to avoid negative cost and schedule impacts that are

  7. Rapidly solidified long-range-ordered alloys

    International Nuclear Information System (INIS)

    Lee, E.H.; Koch, C.C.; Liu, C.T.

    1981-01-01

    The influence of rapid solidification processing on the microstructure of long-range-ordered alloys in the (Fe, Co, Ni) 3 V system has been studied by transmission electron microscopy. The main microstructural feature of the as-quenched alloys was a fine cell structure (approx. 300 nm diameter) decorated with carbide particles. This structure was maintained aftr annealing treatments which develop the ordered crystal structure. Other features of the microstructures both before and after annealing are presented and discussed. 6 figures

  8. Software testing for evolutionary iterative rapid prototyping

    OpenAIRE

    Davis, Edward V., Jr.

    1990-01-01

    Approved for public release; distribution unlimited. Rapid prototyping is emerging as a promising software development paradigm. It provides a systematic and automatable means of developing a software system under circumstances where initial requirements are not well known or where requirements change frequently during development. To provide high software quality assurance requires sufficient software testing. The unique nature of evolutionary iterative prototyping is not well-suited for ...

  9. 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.

  10. Rapid Spontaneously Resolving Acute Subdural Hematoma

    Science.gov (United States)

    Gan, Qi; Zhao, Hexiang; Zhang, Hanmei; You, Chao

    2017-01-01

    Introduction: This study reports a rare patient of a rapid spontaneously resolving acute subdural hematoma. In addition, an analysis of potential clues for the phenomenon is presented with a review of the literature. Patient Presentation: A 1-year-and-2-month-old boy fell from a height of approximately 2 m. The patient was in a superficial coma with a Glasgow Coma Scale of 8 when he was transferred to the authors’ hospital. Computed tomography revealed the presence of an acute subdural hematoma with a midline shift beyond 1 cm. His guardians refused invasive interventions and chose conservative treatment. Repeat imaging after 15 hours showed the evident resolution of the hematoma and midline reversion. Progressive magnetic resonance imaging demonstrated the complete resolution of the hematoma, without redistribution to a remote site. Conclusions: Even though this phenomenon has a low incidence, the probability of a rapid spontaneously resolving acute subdural hematoma should be considered when patients present with the following characteristics: children or elderly individuals suffering from mild to moderate head trauma; stable or rapidly recovered consciousness; and simple acute subdural hematoma with a moderate thickness and a particularly low-density band in computed tomography scans. PMID:28468224

  11. Survey of methods for rapid spin reversal

    International Nuclear Information System (INIS)

    McKibben, J.L.

    1980-01-01

    The need for rapid spin reversal technique in polarization experiments is discussed. The ground-state atomic-beam source equipped with two rf transitions for hydrogen can be reversed rapidly, and is now in use on several accelerators. It is the optimum choice provided the accelerator can accept H + ions. At present all rapid reversal experiments using H - ions are done with Lamb-shift sources; however, this is not a unique choice. Three methods for the reversal of the spin of the atomic beam within the Lamb-shift source are discussed in order of development. Coherent intensity and perhaps focus modulation seem to be the biggest problems in both types of sources. Methods for reducing these modulations in the Lamb-shift source are discussed. The same Lamb-shift apparatus is easily modified to provide information on the atomic physics of quenching of the 2S/sub 1/2/ states versus spin orientation, and this is also discussed. 2 figures

  12. Rapid prototyping model for percutaneous nephrolithotomy training.

    Science.gov (United States)

    Bruyère, Franck; Leroux, Cecile; Brunereau, Laurent; Lermusiaux, Patrick

    2008-01-01

    Rapid prototyping is a technique used for creating computer images in three dimensions more efficiently than classic techniques. Percutaneous nephrolithotomy (PCNL) is a popular method to remove kidney stones; however, broader use by the urologic community has been hampered by the morbidity associated with needle puncture to gain access to the renal calix (bleeding, pneumothorax, hydrothorax, inadvertent colon injury). A training model to improve technique and understanding of renal anatomy could improve complications related to renal puncture; however, no model currently exists for resident training. We created a training model using the rapid prototyping technique based on abdominal CT images of a patient scheduled to undergo PCNL. This allowed our staff and residents to train on the model before performing the operation. This model allowed anticipation of particular difficulties inherent to the patient's anatomy. After training, the procedure proceeded without complication, and the patient was discharged at postoperative day 1 without problems. We hypothesize that rapid prototyping could be useful for resident education, allowing the creation of numerous models for research and surgical training. In addition, we anticipate that experienced urologists could find this technique helpful in preparation for difficult PCNL operations.

  13. NPOESS Tools for Rapid Algorithm Updates

    Science.gov (United States)

    Route, G.; Grant, K. D.; Hughes, B.; Reed, B.

    2009-12-01

    The National Oceanic and Atmospheric Administration (NOAA), Department of Defense (DoD), and National Aeronautics and Space Administration (NASA) are jointly acquiring the next-generation weather and environmental satellite system; the National Polar-orbiting Operational Environmental Satellite System (NPOESS). NPOESS replaces the current Polar-orbiting Operational Environmental Satellites (POES) managed by NOAA and the Defense Meteorological Satellite Program (DMSP) managed by the DoD. The NPOESS satellites carry a suite of sensors that collect meteorological, oceanographic, climatological, and solar-geophysical observations of the earth, atmosphere, and space. The ground data processing segment for NPOESS is the Interface Data Processing Segment (IDPS), developed by Raytheon Intelligence and Information Systems. The IDPS processes both NPP and NPOESS satellite data to provide environmental data products to NOAA and DoD processing centers operated by the United States government. Northrop Grumman Aerospace Systems Algorithms and Data Products (A&DP) organization is responsible for the algorithms that produce the EDRs, including their quality aspects. As the Calibration and Validation activities move forward following both the NPP launch and subsequent NPOESS launches, rapid algorithm updates may be required. Raytheon and Northrop Grumman have developed tools and processes to enable changes to be evaluated, tested, and moved into the operational baseline in a rapid and efficient manner. This presentation will provide an overview of the tools available to the Cal/Val teams to ensure rapid and accurate assessment of algorithm changes, along with the processes in place to ensure baseline integrity.

  14. 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.

  15. Rapid Thermal Processing to Enhance Steel Toughness.

    Science.gov (United States)

    Judge, V K; Speer, J G; Clarke, K D; Findley, K O; Clarke, A J

    2018-01-11

    Quenching and Tempering (Q&T) has been utilized for decades to alter steel mechanical properties, particularly strength and toughness. While tempering typically increases toughness, a well-established phenomenon called tempered martensite embrittlement (TME) is known to occur during conventional Q&T. Here we show that short-time, rapid tempering can overcome TME to produce unprecedented property combinations that cannot be attained by conventional Q&T. Toughness is enhanced over 43% at a strength level of 1.7 GPa and strength is improved over 0.5 GPa at an impact toughness of 30 J. We also show that hardness and the tempering parameter (TP), developed by Holloman and Jaffe in 1945 and ubiquitous within the field, is insufficient for characterizing measured strengths, toughnesses, and microstructural conditions after rapid processing. Rapid tempering by energy-saving manufacturing processes like induction heating creates the opportunity for new Q&T steels for energy, defense, and transportation applications.

  16. MSFC Electrostatic Levitator (ESL) Rapid Quench System

    Science.gov (United States)

    SanSoucie, Michael P.; Craven, Paul D.; Rogers, Jan R.

    2014-01-01

    The NASA Marshall Space Flight Center (MSFC) Electrostatic Levitator (ESL) Laboratory is a unique facility for investigators studying high-temperature materials. The laboratory boasts two levitators in which samples can be levitated, heated, melted, undercooled, and resolidified, all without the interference of a container or data-gathering instrument. The ESL main chamber has been upgraded with the addition of a rapid quench system. This system allows samples to be dropped into a quench vessel that can be filled with a low melting point material, such as a gallium or indium alloy. Thereby allowing rapid quenching of undercooled liquid metals. Up to 8 quench vessels can be loaded into the quench wheel, which is indexed with LabVIEW control software. This allows up to 8 samples to be rapidly quenched before having to open the chamber. The system has been tested successfully on several zirconium samples. Future work will be done with other materials using different quench mediums. Microstructural analysis will also be done on successfully quench samples.

  17. Rapid Radiochemical Methods for Asphalt Paving Material ...

    Science.gov (United States)

    Technical Brief Validated rapid radiochemical methods for alpha and beta emitters in solid matrices that are commonly encountered in urban environments were previously unavailable for public use by responding laboratories. A lack of tested rapid methods would delay the quick determination of contamination levels and the assessment of acceptable site-specific exposure levels. Of special concern are matrices with rough and porous surfaces, which allow the movement of radioactive material deep into the building material making it difficult to detect. This research focuses on methods that address preparation, radiochemical separation, and analysis of asphalt paving materials and asphalt roofing shingles. These matrices, common to outdoor environments, challenge the capability and capacity of very experienced radiochemistry laboratories. Generally, routine sample preparation and dissolution techniques produce liquid samples (representative of the original sample material) that can be processed using available radiochemical methods. The asphalt materials are especially difficult because they do not readily lend themselves to these routine sample preparation and dissolution techniques. The HSRP and ORIA coordinate radiological reference laboratory priorities and activities in conjunction with HSRP’s Partner Process. As part of the collaboration, the HSRP worked with ORIA to publish rapid radioanalytical methods for selected radionuclides in building material matrice

  18. Rapid determination of actinides in seawater samples

    International Nuclear Information System (INIS)

    Maxwell, S.L.; Culligan, B.K.; Hutchison, J.B.; Utsey, R.C.; McAlister, D.R.

    2014-01-01

    A new rapid method for the determination of actinides in seawater samples has been developed at the Savannah River National Laboratory. The actinides can be measured by alpha spectrometry or inductively-coupled plasma mass spectrometry. The new method employs novel pre-concentration steps to collect the actinide isotopes quickly from 80 L or more of seawater. Actinides are co-precipitated using an iron hydroxide co-precipitation step enhanced with Ti +3 reductant, followed by lanthanum fluoride co-precipitation. Stacked TEVA Resin and TRU Resin cartridges are used to rapidly separate Pu, U, and Np isotopes from seawater samples. TEVA Resin and DGA Resin were used to separate and measure Pu, Am and Cm isotopes in seawater volumes up to 80 L. This robust method is ideal for emergency seawater samples following a radiological incident. It can also be used, however, for the routine analysis of seawater samples for oceanographic studies to enhance efficiency and productivity. In contrast, many current methods to determine actinides in seawater can take 1-2 weeks and provide chemical yields of ∼30-60 %. This new sample preparation method can be performed in 4-8 h with tracer yields of ∼85-95 %. By employing a rapid, robust sample preparation method with high chemical yields, less seawater is needed to achieve lower or comparable detection limits for actinide isotopes with less time and effort. (author)

  19. Rapid maxillary expansion in contemporary orthodontic literature

    Directory of Open Access Journals (Sweden)

    Sabrina Mutinelli

    2016-01-01

    Full Text Available We have reviewed our retrospective research about rapid maxillary expansion performed in the early mixed dentition to summarize the results of different studies regarding maxillary dental arch width variation and crowding improvement in light of contemporary literature. The aim is to define the effects of treatments followed until the end of dental arch growth. In all studies, a Haas expander anchored to the deciduous dentition was used. The samples consisted of treated patients with and without a lateral crossbite and homogeneous untreated individuals as controls. Two additional control groups of adolescents and adults in dental Class 1 were also compared. As a result of the analysis, rapid maxillary expansion with anchorage to the deciduous dentition was found to be effective in increasing transverse width in intermolar and intercanine areas, and the change was preserved until the full permanent dentition stage. When performed before maxillary lateral incisors have fully erupted, this procedure allows for a rapid increase in the arch length in the anterior area and consequently, in the space available for permanent incisors with a stable reduction in crowding over time.

  20. Motion-insensitive rapid configuration relaxometry.

    Science.gov (United States)

    Nguyen, Damien; Bieri, Oliver

    2017-08-01

    Triple echo steady state (TESS) uses the lowest steady state configuration modes for rapid relaxometry. Due to its unbalanced gradient scheme, however, TESS is inherently motion-sensitive. The purpose of this work is to merge TESS with a balanced acquisition scheme for motion-insensitive rapid configuration relaxometry, termed MIRACLE. The lowest order steady state free precession (SSFP) configurations are retrieved by Fourier transformation of the frequency response of N frequency-shifted balanced SSFP (bSSFP) scans and subsequently processed for relaxometry, as proposed with TESS. Accuracy of MIRACLE is evaluated from simulations, phantom studies as well as in vivo brain and cartilage imaging at 3T. Simulations and phantom results revealed no conceptual flaw, and artifact-free configuration imaging was achieved in vivo. Overall, relaxometry results were accurate in phantoms and in good agreement for cartilage and for T2 in the brain, but apparent low T1 values were observed for brain white matter; reflecting asymmetries in the bSSFP profile. Rapid T1 and T2 mapping with MIRACLE offers analogous properties as TESS while successfully mitigating its motion-sensitivity. As a result of the Fourier transformation, relaxometry becomes sensitive to the voxel frequency distribution, which may contain useful physiologic information, such as structural brain integrity. © 2016 International Society for Magnetic Resonance in Medicine. Magn Reson Med 78:518-526, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.