Sample records for conventional dc cdc
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The prolyl isomerase Pin1 modulates development of CD8+ cDC in mice.
Barberi, Theresa J; Dunkle, Alexis; He, You-Wen; Racioppi, Luigi; Means, Anthony R
2012-01-01
Pin1 has previously been described to regulate cells that participate in both innate and adaptive immunity. Thus far, however, no role for Pin1 has been described in modulating conventional dendritic cells, innate antigen presenting cells that potently activate naïve T cells, thereby bridging innate and adaptive immune responses. When challenged with LPS, Pin1-null mice failed to accumulate spleen conventional dendritic cells (cDC). Analysis of steady-state spleen DC populations revealed that Pin1-null mice had fewer CD8+ cDC. This defect was recapitulated by culturing Pin1-null bone marrow with the DC-instructive cytokine Flt3 Ligand. Additionally, injection of Flt3 Ligand for 9 days failed to induce robust expansion of CD8+ cDC in Pin1-null mice. Upon infection with Listeria monocytogenes, Pin1-null mice were defective in stimulating proliferation of adoptively transferred WT CD8+ T cells, suggesting that decreases in Pin1 null CD8+ cDC may affect T cell responses to infection in vivo. Finally, upon analyzing expression of proteins involved in DC development, elevated expression of PU.1 was detected in Pin1-null cells, which resulted from an increase in PU.1 protein half-life. We have identified a novel role for Pin1 as a modulator of CD8+ cDC development. Consistent with reduced numbers of CD8+ cDC in Pin1-null mice, we find that the absence of Pin1 impairs CD8+ T cell proliferation in response to infection with Listeria monocytogenes. These data suggest that, via regulation of CD8+ cDC production, Pin1 may serve as an important modulator of adaptive immunity.
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Li, Yan-Feng; Lee, Koon-Guan; Ou, Xijun; Lam, Kong-Peng
2014-01-01
Stimulation of TLR7/9 by their respective ligands leads to the activation of IκB kinase α (IKKα) and Interferon Regulatory Factor 1 (IRF-1) and results in interferon (IFN)-β production in conventional dendritic cells (cDC). However, which other signaling molecules are involved in IKKα and IRF-1 activation during TLR7/9 signaling pathway are not known. We and others have shown that Bruton's Tyrosine Kinase (BTK) played a part in TLR9-mediated cytokine production in B cells and macrophages. However, it is unclear if BTK participates in TLR7/9-induced IFN-β production in cDC. In this study, we show that BTK is required for IFN-β synthesis in cDC upon TLR7/9 stimulation and that stimulated BTK-deficient cDC are defective in the induction of IKKα/β phosphorylation and IRF-1 activation. In addition, we demonstrate that Protein Kinase C µ (PKCµ) is also required for TLR7/9-induced IRF-1 activation and IFN-β upregulation in cDC and acts downstream of BTK. Taken together, we have uncovered two new molecules, BTK and PKCµ, that are involved in TLR7/9-triggered IFN-β production in cDC.
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Antigen Presenting Properties of a Myeloid Dendritic-Like Cell in Murine Spleen.
Hey, Ying-Ying; O'Neill, Helen C
This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named "L-DC" since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11bhiCD11cloMHCII-CD43+Ly6C-Ly6G-Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross-presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties.
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Gigley, Jason P.; Khan, Imtiaz A.
2011-01-01
Age associated impairment of immune function results in inefficient vaccination, tumor surveillance and increased severity of infections. Several alterations in adaptive immunity have been observed and recent studies report age related declines in innate immune responses to opportunistic pathogens including Encephalitozoon cuniculi. We previously demonstrated that conventional dendritic cells (cDC) from 9-month-old animals exhibit sub-optimal response to E. cuniculi infection, suggesting that age associated immune senescence begins earlier than expected. We focused this study on how age affects plasmacytoid DC (pDC) function. More specifically how aged pDC affect cDC function as we observed that the latter are the predominant activators of CD8 T cells during this infection. Our present study demonstrates that pDC from middle-aged mice (12 months) suppress young (8 week old) cDC driven CD8 T cell priming against E. cuniculi infection. The suppressive effect of pDC from older mice decreased maturation of young cDC via cell contact. Aged mouse pDC exhibited higher expression of PD-L1 and blockade of their interaction with cDC via this molecule restored cDC maturation and T cell priming. Furthermore, the PD-L1 dependent suppression of cDC T cell priming was restricted to effector function of antigen-specific CD8 T cells not their expansion. To the best of our knowledge, the data presented here is the first report highlighting a cell contact dependent, PD-L1 regulated, age associated defect in a DC subpopulation that results in a sub-optimal immune response against E. cuniculi infection. These results have broad implications for design of immunotherapeutic approaches to enhance immunity for aging populations. PMID:21695169
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Gigley, Jason P; Khan, Imtiaz A
2011-01-01
Age associated impairment of immune function results in inefficient vaccination, tumor surveillance and increased severity of infections. Several alterations in adaptive immunity have been observed and recent studies report age related declines in innate immune responses to opportunistic pathogens including Encephalitozoon cuniculi. We previously demonstrated that conventional dendritic cells (cDC) from 9-month-old animals exhibit sub-optimal response to E. cuniculi infection, suggesting that age associated immune senescence begins earlier than expected. We focused this study on how age affects plasmacytoid DC (pDC) function. More specifically how aged pDC affect cDC function as we observed that the latter are the predominant activators of CD8 T cells during this infection. Our present study demonstrates that pDC from middle-aged mice (12 months) suppress young (8 week old) cDC driven CD8 T cell priming against E. cuniculi infection. The suppressive effect of pDC from older mice decreased maturation of young cDC via cell contact. Aged mouse pDC exhibited higher expression of PD-L1 and blockade of their interaction with cDC via this molecule restored cDC maturation and T cell priming. Furthermore, the PD-L1 dependent suppression of cDC T cell priming was restricted to effector function of antigen-specific CD8 T cells not their expansion. To the best of our knowledge, the data presented here is the first report highlighting a cell contact dependent, PD-L1 regulated, age associated defect in a DC subpopulation that results in a sub-optimal immune response against E. cuniculi infection. These results have broad implications for design of immunotherapeutic approaches to enhance immunity for aging populations.
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Sei, Janet J.; Waters, Ryan A.; Kenney, Mary; Barlow, John W.; Golde, William T.
2016-01-01
Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes one of the most devastating diseases in cloven-hoofed animals. Disease symptoms develop within 2 to 3 days of exposure and include fever and vesicular lesions on the tongue and hooves. Dendritic cells (DC) play an essential role in protective immune responses against pathogens. Therefore, investigating their role during FMDV infection would lead to a better understanding of host-pathogen interactions. In this study, following infection of cattle with FMDV, we investigated the frequency and function of conventional (cDC) and plasmacytoid DC (pDC) in blood by using multi-color flow cytometry. We show that the frequency of cDC and pDC increased following FMDV infection and peaked 3 to 4 days post-infection. During peak viremia, the cattle became lymphopenic, the expression of MHC class II molecules on cDC and pDC was dramatically down-regulated, the processing of exogenous antigen by cDC and pDC was impaired, and there was an increase in IL-10 production by DC and monocytes. Notably, after clearance of FMDV from the blood, MHC class II expression returned to pre-infection levels. Altogether, our study demonstrates that in cattle, FMDV inhibits the function of DC, thereby retarding the initiation of adaptive immune responses, potentially enhancing virus shedding during the acute phase of infection. PMID:27008425
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GM-CSF Inhibits c-Kit and SCF Expression by Bone Marrow-Derived Dendritic Cells
Barroeta Seijas, Amairelys Belen; Simonetti, Sonia; Vitale, Sara; Runci, Daniele; Quinci, Angela Caterina; Soriani, Alessandra; Criscuoli, Mattia; Filippi, Irene; Naldini, Antonella; Sacchetti, Federico Maria; Tarantino, Umberto; Oliva, Francesco; Piccirilli, Eleonora; Santoni, Angela; Di Rosa, Francesca
2017-01-01
Stem cell factor (SCF), the ligand of c-kit, is a key cytokine for hematopoiesis. Hematopoietic precursors express c-kit, whereas differentiated cells of hematopoietic lineage are negative for this receptor, with the exception of NK cells, mast cells, and a few others. While it has long been recognized that dendritic cells (DCs) can express c-kit, several questions remain concerning the SCF/c-kit axis in DCs. This is particularly relevant for DCs found in those organs wherein SCF is highly expressed, including the bone marrow (BM). We characterized c-kit expression by conventional DCs (cDCs) from BM and demonstrated a higher proportion of c-kit+ cells among type 1 cDC subsets (cDC1s) than type 2 cDC subsets (cDC2s) in both humans and mice, whereas similar levels of c-kit expression were observed in cDC1s and cDC2s from mouse spleen. To further study c-kit regulation, DCs were generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) from mouse BM, a widely used protocol. CD11c+ cells were purified from pooled non-adherent and slightly adherent cells collected after 7 days of culture, thus obtaining highly purified BM-derived DCs (BMdDCs). BMdDCs contained a small fraction of c-kit+ cells, and by replating them for 2 days with GM-CSF, we obtained a homogeneous population of c-kit+ CD40hi MHCIIhi cells. Not only did BMdDCs express c-kit but they also produced SCF, and both were striking upregulated if GM-CSF was omitted after replating. Furthermore, a small but significant reduction in BMdDC survival was observed upon SCF silencing. Incubation of BMdDCs with SCF did not modulate antigen presentation ability of these cells, nor it did regulate their membrane expression of the chemokine receptor CXCR4. We conclude that the SCF/c-kit-mediated prosurvival circuit may have been overlooked because of the prominent use of GM-CSF in DC cultures in vitro, including those human DC cultures destined for the clinics. We speculate that DCs more prominently rely on SCF in vivo in some microenvironments, with potential implications for graft-versus-host disease and antitumor immunity. PMID:28261209
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Tissue-specific differentiation of a circulating CCR9- pDC-like common dendritic cell precursor.
Schlitzer, Andreas; Heiseke, Alexander F; Einwächter, Henrik; Reindl, Wolfgang; Schiemann, Matthias; Manta, Calin-Petru; See, Peter; Niess, Jan-Hendrik; Suter, Tobias; Ginhoux, Florent; Krug, Anne B
2012-06-21
The ontogenic relationship between the common dendritic cell (DC) progenitor (CDP), the committed conventional DC precursor (pre-cDC), and cDC subpopulations in lymphoid and nonlymphoid tissues has been largely unraveled. In contrast, the sequential steps of plasmacytoid DC (pDC) development are less defined, and it is unknown at which developmental stage and location final commitment to the pDC lineage occurs. Here we show that CCR9(-) pDCs from murine BM which enter the circulation and peripheral tissues have a common DC precursor function in vivo in the steady state, in contrast to CCR9(+) pDCs which are terminally differentiated. On adoptive transfer, the fate of CCR9(-) pDC-like precursors is governed by the tissues they enter. In the BM and liver, most transferred CCR9(-) pDC-like precursors differentiate into CCR9(+) pDCs, whereas in peripheral lymphoid organs, lung, and intestine, they additionally give rise to cDCs. CCR9(-) pDC-like precursors which are distinct from pre-cDCs can be generated from the CDP. Thus, CCR9(-) pDC-like cells are novel CDP-derived circulating DC precursors with pDC and cDC potential. Their final differentiation into functionally distinct pDCs and cDCs depends on tissue-specific factors allowing adaptation to local requirements under homeostatic conditions.
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BIM determines the number of merocytic dendritic cells, a cell type that breaks immune tolerance.
Audiger, Cindy; Lesage, Sylvie
2018-05-13
In contrast to conventional dendritic cells (cDC), when merocytic dendritic cells (mcDC) present antigens derived from apoptotic bodies, T-cell anergy is reversed rather than induced, a process that promotes autoimmunity. Interestingly, mcDC are present in higher proportion in type 1 diabetes-prone NOD mice than in autoimmune-resistant B6 and BALB/c mice, and the Insulin-dependent diabetes (Idd)13 locus is linked to mcDC proportion. Therefore, mcDC are notably associated with susceptibility to autoimmune diabetes. To identify which gene determines the proportion and absolute number of mcDC, we undertook a candidate gene approach by selecting relevant candidates within the Idd13 locus. We find that neither β2m nor Sirpa appear to influence the proportion of mcDC. Instead, we show that Bim effectively modulates mcDC number in a hematopoietic-intrinsic manner. We also demonstrate that Bim-deficiency does not impact other cDC subsets and appears to play a specific role in determining the proportion and absolute number of mcDC by promoting their survival. Together, these data demonstrate that Bim specifically modulates the number of mcDC. Identifying factors that facilitate apoptosis of mcDC by increasing BIM activity in a cell type-specific manner may help prevent autoimmunity. © 2018 Australasian Society for Immunology Inc.
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Redefining Myeloid Cell Subsets in Murine Spleen
Hey, Ying-Ying; Tan, Jonathan K. H.; O’Neill, Helen C.
2016-01-01
Spleen is known to contain multiple dendritic and myeloid cell subsets, distinguishable on the basis of phenotype, function and anatomical location. As a result of recent intensive flow cytometric analyses, splenic dendritic cell (DC) subsets are now better characterized than other myeloid subsets. In order to identify and fully characterize a novel splenic subset termed “L-DC” in relation to other myeloid cells, it was necessary to investigate myeloid subsets in more detail. In terms of cell surface phenotype, L-DC were initially characterized as a CD11bhiCD11cloMHCII−Ly6C−Ly6G− subset in murine spleen. Their expression of CD43, lack of MHCII, and a low level of CD11c was shown to best differentiate L-DC by phenotype from conventional DC subsets. A complete analysis of all subsets in spleen led to the classification of CD11bhiCD11cloMHCII−Ly6CloLy6G− cells as monocytes expressing CX3CR1, CD43 and CD115. Siglec-F expression was used to identify a specific eosinophil population, distinguishable from both Ly6Clo and Ly6Chi monocytes, and other DC subsets. L-DC were characterized as a clear subset of CD11bhiCD11cloMHCII−Ly6C−Ly6G− cells, which are CD43+, Siglec-F− and CD115−. Changes in the prevalence of L-DC compared to other subsets in spleens of mutant mice confirmed the phenotypic distinction between L-DC, cDC and monocyte subsets. L-DC development in vivo was shown to occur independently of the BATF3 transcription factor that regulates cDC development, and also independently of the FLT3L and GM-CSF growth factors which drive cDC and monocyte development, so distinguishing L-DC from these commonly defined cell types. PMID:26793192
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Hooper, Kirsten M; Yen, Jui-Hung; Kong, Weimin; Rahbari, Kate M; Kuo, Ping-Chang; Gamero, Ana M; Ganea, Doina
2016-01-01
IL-27, a multifunctional cytokine produced by antigen-presenting cells, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well-studied, much less is known about the factors that negatively impact IL-27 expression. Prostaglandin E2 (PGE2), a major immunomodulatory prostanoid, acts as a pro-inflammatory agent in several models of inflammatory/autoimmune diseases, promoting primarily Th17 development and function. In this study, we report on a novel mechanism which promotes the pro-inflammatory function of PGE2. We showed previously that PGE2 inhibits IL-27 production in murine bone marrow derived DCs. Here, we show that, in addition to BMDCs, PGE2 inhibits IL-27 production in macrophages and in splenic cDC and we identify a novel pathway consisting of signaling through EP2/EP4→induction of cAMP→downregulation of IRF1 expression and binding to the p28 ISRE site. The inhibitory effect of PGE2 on p28 and irf1 expression does not involve endogenous IFNβ, STAT1 or STAT2, and inhibition of IL-27 does not appear to be mediated through PKA, EPAC, PI3K, or MAPKs. We observed similar inhibition of il27p28 expression in vivo in splenic DC following administration of dimethyl PGE2 in conjunction with LPS. Based on the anti-inflammatory role of IL-27 in cDC and through the generation of Tr1 cells, we propose that the PGE2-induced inhibition of IL-27 in activated cDC represents an important additional mechanism for its in vivo pro-inflammatory functions. PMID:28062696
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Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection.
Demiri, M; Müller-Luda, K; Agace, W W; Svensson-Frej, M
2017-10-01
Low- and high-dose infections with the murine large intestinal nematode Trichuris muris are associated with induction of adaptive Th1 and Th2 responses, respectively, in mesenteric lymph nodes (MLN). Classical dendritic cells (cDC) accumulate in the large intestinal mucosa and MLN upon T. muris infection, yet their role in driving adaptive responses to infection remains largely unknown. We performed low- and high-dose T. muris infections of mice deficient in defined cDC subsets to investigate their role in induction of adaptive immune responses. Mice lacking IRF4-dependent cDC failed to clear a high-dose infection and displayed impaired Th2 responses. Conversely, mice lacking IRF8-dependent cDC cleared a low-dose infection and displayed an impaired Th1 response while increased production of Th2 cytokines. Finally, mice lacking both IRF4- and IRF8-dependent cDC were able to generate a Th2 response and clear a low-dose infection. Collectively, these results suggest that IRF4- and IRF8-dependent cDC act antagonistically during T. muris infection, and demonstrate that intestinal Th2 responses can be generated towards T. muris in the absence of IRF4-dependent cDC. © 2017 John Wiley & Sons Ltd.
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Draheim, Marion; Wlodarczyk, Myriam F; Crozat, Karine; Saliou, Jean-Michel; Alayi, Tchilabalo Dilezitoko; Tomavo, Stanislas; Hassan, Ali; Salvioni, Anna; Demarta-Gatsi, Claudia; Sidney, John; Sette, Alessandro; Dalod, Marc; Berry, Antoine; Silvie, Olivier; Blanchard, Nicolas
2017-11-01
In malaria, CD4 Th1 and T follicular helper (T FH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins. Immunodominance is shaped differently whether blood stage is preceded or not by liver stage, but the same ETRAMP-specific dominant response develops in both contexts. In naïve mice and at the onset of cerebral malaria, CD8α + dendritic cells (cDC1) are superior to other DC subsets for MHC II presentation of the ETRAMP epitope. Using in vivo depletion of cDC1, we show that cDC1 promote parasite-specific Th1 cells and inhibit the development of IL-10 + CD4 T cells. This work profiles the P. berghei blood-stage MHC II immunopeptidome, highlights the potency of cDC1 to present malaria antigens on MHC II, and reveals a major role for cDC1 in regulating malaria-specific CD4 T-cell responses. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.
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Humbert, Marion; Guery, Leslie; Brighouse, Dale; Lemeille, Sylvain; Hugues, Stephanie
2018-03-27
Cancer immunotherapies utilize distinct mechanisms to harness the power of the immune system to eradicate cancer cells. Therapeutic vaccines, aimed at inducing active immune responses against an existing cancer, are highly dependent on the immunological microenvironment, where many immune cell types display high levels of plasticity and, depending on the context, promote very different immunological outcomes. Among them, plasmacytoid dendritic cells (pDC), known to be highly immunogenic upon inflammation, are maintained in a tolerogenic state by the tumor microenvironment. Here we report that intratumoral (i.t.) injection of established solid tumors with CpG oligonucleotides-B (CpG-B) inhibits tumor growth. Interestingly, control of tumor growth was independent of tumor-associated (TA) pDC, which remained refractory to CpG-B stimulation and whose depletion did not alter the efficacy of the treatment. Instead, tumor growth inhibition subsequent to i.t. CpG-B injection depended on the recruitment of neutrophils into the milieu, resulting in the activation of conventional dendritic cells (cDC), subsequent increased anti-tumor T cell priming in draining lymph nodes, and enhanced effector T cell infiltration in the tumor microenvironment. These results reinforce the concept that intratumoral delivery of TLR9 agonists alters the tumor microenvironment by improving the anti-tumor activity of both innate and adaptive immune cells. Copyright ©2018, American Association for Cancer Research.
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Briseño, Carlos G.; Gargaro, Marco; Durai, Vivek; Davidson, Jesse T.; Theisen, Derek J.; Anderson, David A.; Novack, Deborah V.; Murphy, Theresa L.; Murphy, Kenneth M.
2017-01-01
RelB is an NF-κB family transcription factor activated in the noncanonical pathway downstream of NF-κB–inducing kinase (NIK) and TNF receptor family members including lymphotoxin-β receptor (LTβR) and CD40. Early analysis suggested that RelB is required for classical dendritic cell (cDC) development based on a severe reduction of cDCs in Relb−/− mice associated with profound myeloid expansion and perturbations in B and T cells. Subsequent analysis of radiation chimeras generated from wild-type and Relb−/− bone marrow showed that RelB exerts cell-extrinsic actions on some lineages, but it has remained unclear whether the impact of RelB on cDC development is cell-intrinsic or -extrinsic. Here, we reevaluated the role of RelB in cDC and myeloid development using a series of radiation chimeras. We found that there was no cell-intrinsic requirement for RelB for development of most cDC subsets, except for the Notch2- and LTβR-dependent subset of splenic CD4+ cDC2s. These results identify a relatively restricted role of RelB in DC development. Moreover, the myeloid expansion in Relb−/− mice resulted from hematopoietic-extrinsic actions of RelB. This result suggests that there is an unrecognized but critical role for RelB within the nonhematopoietic niche that controls normal myelopoiesis. PMID:28348230
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TCF4-Targeting miR-124 is Differentially Expressed amongst Dendritic Cell Subsets
Han, Sun Murray; Na, Hye Young; Ham, Onju; Choi, Wanho; Sohn, Moah; Ryu, Seul Hye; In, Hyunju; Hwang, Ki-Chul
2016-01-01
Dendritic cells (DCs) are professional antigen-presenting cells that sample their environment and present antigens to naïve T lymphocytes for the subsequent antigen-specific immune responses. DCs exist in a range of distinct subpopulations including plasmacytoid DCs (pDCs) and classical DCs (cDCs), with the latter consisting of the cDC1 and cDC2 lineages. Although the roles of DC-specific transcription factors across the DC subsets have become understood, the posttranscriptional mechanisms that regulate DC development are yet to be elucidated. MicroRNAs (miRNAs) are pivotal posttranscriptional regulators of gene expression in a myriad of biological processes, but their contribution to the immune system is just beginning to surface. In this study, our in-house probe collection was screened to identify miRNAs possibly involved in DC development and function by targeting the transcripts of relevant mouse transcription factors. Examination of DC subsets from the culture of mouse bone marrow with Flt3 ligand identified high expression of miR-124 which was able to target the transcript of TCF4, a transcription factor critical for the development and homeostasis of pDCs. Further expression profiling of mouse DC subsets isolated from in vitro culture as well as via ex vivo purification demonstrated that miR-124 was outstandingly expressed in CD24+ cDC1 cells compared to in pDCs and CD172α+ cDC2 cells. These results imply that miR-124 is likely involved in the processes of DC subset development by posttranscriptional regulation of a transcription factor(s). PMID:26937233
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Sontag, Stephanie; Förster, Malrun; Qin, Jie; Wanek, Paul; Mitzka, Saskia; Schüler, Herdit M; Koschmieder, Steffen; Rose-John, Stefan; Seré, Kristin; Zenke, Martin
2017-04-01
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing. Upon induction of hematopoietic differentiation, we demonstrate that IRF8 is dispensable for iPS cell and ES cell differentiation into hemogenic endothelium and for endothelial-to-hematopoietic transition, and thus development of hematopoietic progenitors. We differentiated iPS cell and ES cell derived progenitors into CD141+ cross-presenting cDC1 and CD1c+ classical cDC2 and CD303+ plasmacytoid DC (pDC). We found that IRF8 deficiency compromised cDC1 and pDC development, while cDC2 development was largely unaffected. Additionally, in an unrestricted differentiation regimen, IRF8-/- iPS cells and ES cells exhibited a clear bias toward granulocytes at the expense of monocytes. IRF8-/- DC showed reduced MHC class II expression and were impaired in cytokine responses, migration, and antigen presentation. Taken together, we engineered a human IRF8 knockout model that allows studying molecular mechanisms of human immunodeficiencies in vitro, including the pathophysiology of IRF8 deficient DC. Stem Cells 2017;35:898-908. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
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Murine CD103+ dendritic cells protect against steatosis progression towards steatohepatitis.
Heier, Eva-Carina; Meier, Anna; Julich-Haertel, Henrike; Djudjaj, Sonja; Rau, Monica; Tschernig, Thomas; Geier, Andreas; Boor, Peter; Lammert, Frank; Lukacs-Kornek, Veronika
2017-06-01
Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can progress to non-alcoholic steatohepatitis (NASH). The identification of molecular and cellular factors that determine the progression of NASH and lead to irreversible hepatocellular damage are crucial. Dendritic cells (DCs) represent a heterogeneous cell population among which CD103 + DCs play a significant role in immunity and tolerance. We aimed to clarify the role of this DC subset in the pathomechanism of NASH. Steatosis progression towards steatohepatitis was analysed using multicolor FACS analyses, cytokine and qPCR array in high sucrose diet (HSD) and methionine and choline deficient diet (MCD) fed wild-type and basic leucine zipper transcription factor, ATF-Like-3 (Batf3) deficient animals, which lack CD103 + DCs (classical type-1 DC, cDC1s). Metabolic challenge of Batf3 -/- animals resulted in the progression of steatosis towards steatohepatitis, manifesting by an increased influx of inflammatory cells into the liver and elevated inflammatory cytokine production of myeloid cells upon innate stimuli. However, the lack of cDC1s did not affect cellular apoptosis and fibrosis progression but altered genes involved in lipid metabolism. The adoptive transfer of CD103 + cDC1s to Batf3 deficient animals reversed these observed changes and more importantly could attenuate cellular damage and inflammation in established murine steatohepatitis. Here, we have identified the murine CD103 + cDC1s as a protective DC subtype that influences the pro-anti-inflammatory balance and protects the liver from metabolic damage. As guardians of liver integrity, they play a key role in the inflammatory process during the development of steatohepatitis in mice. Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can lead to non-alcoholic steatohepatitis (NASH). The current study demonstrated that a specific murine dendritic cell subtype possesses a potent regulatory role to influence the inflammatory milieu of the liver in this process. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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Type I interferon dependence of plasmacytoid dendritic cell activation and migration
Asselin-Paturel, Carine; Brizard, Géraldine; Chemin, Karine; Boonstra, Andre; O'Garra, Anne; Vicari, Alain; Trinchieri, Giorgio
2005-01-01
Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration. PMID:15795237
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Gao, Zhiming; Curran, Scott J.; Parks, James E.; ...
2015-04-06
We present fuel economy and engine-out emissions for light-duty (LD) conventional and hybrid vehicles powered by conventional and high-efficiency combustion engines. Engine technologies include port fuel-injected (PFI), direct gasoline injection (GDI), reactivity controlled compression ignition (RCCI) and conventional diesel combustion (CDC). In the case of RCCI, the engine utilized CDC combustion at speed/load points not feasible with RCCI. The results, without emissions considered, show that the best fuel economies can be achieved with CDC/RCCI, with CDC/RCCI, CDC-only, and lean GDI all surpassing PFI fuel economy significantly. In all cases, hybridization significantly improved fuel economy. The engine-out hydrocarbon (HC), carbon monoxidemore » (CO), nitrogen oxides (NOx), and particulate matter (PM) emissions varied remarkably with combustion mode. The simulated engine-out CO and HC emissions from RCCI are significantly higher than CDC, but RCCI makes less NOx and PM emissions. Hybridization can improve lean GDI and RCCI cases by increasing time percentage for these more fuel efficient modes. Moreover, hybridization can dramatically decreases the lean GDI and RCCI engine out emissions. Importantly, lean GDI and RCCI combustion modes decrease exhaust temperatures, especially for RCCI, which limits aftertreatment performance to control tailpipe emissions. Overall, the combination of engine and hybrid drivetrain selected greatly affects the emissions challenges required to meet emission regulations.« less
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1981-04-01
J AFLC AFSC L~-ATC L_ ESC* N~Q USAF R a ±1MAC [ PACAF SAC TAC USAFA USAPE OTHER UNIT ORt ORGANIZATION (Not wirde, Major CowsnedL. IF "OTHER UNIT...Print Filters 88. Printers Model D, 35= 89. Printers Model J , 16= CODE 99 xiv • CDC ID AFS 233XO/X1 m .CX DC3DC1DC1DCD BACKGROUND INFORMATION (CONTINUED...BACKGROUND INFORMATION (CONTINUED) BLACN CIRCLE (1) TO TH RIGHT OF = EACH RESNS-E YOU ISH TO INDICATE . Tacky oller Cleaners 0IDOMMOD(® 115. Tacoma
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The Cost Growth Problem: A Realistic Diagnosis and Solution.
1983-06-01
access 30 0~ LJ 0 CD 0 ( 4c CD - V2 0 C.2 ~~CD.------ 0.0 4-J V) 0 0.0 C.,I Cdc = CC, 0 0D C2 =I . 31 haua La OC I- c C _g .- C2 n C2 __. 6.34 LIA ca D...Department Navy Military Personnel Command Washington, D.C. 20370 6. Director for HRM Plans and Policy (OP-IS0) 1 Human Resource Management Division...Washington, D.C. 20301 25. Dana French, CAPT, USN HD HRM Plans & Policy Branch Washington, D.C. 20301 26. Robert Aaron 820 Lamberton Drive Silver
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Microscopic diagnosis of the leaf and stem of Piper solmsianum C.DC.
Bertocco, A R P; Migacz, I P; Santos, V L P; Franco, C R C; Silva, R Z; Yunes, R A; Cechinel-Filho, V; Budel, J M
2017-08-01
Piper solmsianum C.DC., which is popularly known as pariparoba, is a shrub that measures 1-3 m in height and it inhabits areas with wet tropical soils. The objective of this study was to analyze the leaf and stem anatomy using light microscopy, scanning electron micrographs, and energy-dispersive X-ray spectroscopy in order to provide information for species identification. The anatomical profile showed the following main microscopic markers: hypostomatic leaf; hypodermis layer on both sides; pearl glands; biconvex midrib shape; five collateral vascular bundles in open arc with the central bundle larger than the others; circular stem shape; collateral vascular bundles arranged in two rings; sinuous sclerenchymatic sheath in the pith; secretory idioblasts; and starch grains in the mesophyll, in the ground parenchyma of the midrib, petiole, and in the stem; and six morphotypes of calcium oxalate crystals (styloids, cuneiform, tabular crystal rosettes, cuneiform crystal rosettes, elongated square dipyramids, as well as very elongated square dipyramids). © 2017 Wiley Periodicals, Inc.
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Aminabadi, Naser Asl; Farahani, Ramin Mostofi Zadeh; Oskouei, Sina Ghertasi
2010-01-01
Clinical and radiographic evaluation of the premedicated direct pulp capping using formocresol (PDC) versus conventional direct pulp capping using calcium hydroxide (CDC) in human carious primary molars. A total of 120 vital primary molars with pinpoint exposure during caries removal in 84 patients aged 4-5 years were selected. In the PDC group (n = 60), 20% Buckley's formocresol solution, and in the CDC group (n = 60), calcium hydroxide powder were applied to the exposure sites followed by placement of zinc oxide-eugenol base. Teeth were restored with preformed stainless steel crowns. Clinical and radiographic evaluations of the treatment outcomes were performed at regular intervals of 6 and 12 months, respectively, for two years post-operatively. The prevalence of spontaneous pain, sensitivity on percussion, and fistula were significantly higher in the CDC group compared to the PDC group (P < 0.05). The number of teeth exhibiting periapical/furcal radiolucency or external/internal root resorption was also higher in the CDC group (P < 0.05). The clinical success rate of the PDC was 90% compared to the 61.7% of the CDC (P < 0.05). The radiographic success rates of the PDC and CDC groups were 85% and 53.3%, respectively (P < 0.05). It seems formocresol premedicated direct pulp capping could safely be used as a substitute for conventional direct pulp capping.
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49 CFR 571.5 - Matter incorporated by reference.
Code of Federal Regulations, 2011 CFR
2011-10-01
...), Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402 Illuminating Engineering... Services, Hyattsville, MD 20782. Phone: 1-800-232-4636; Web: http://www.cdc.gov/nchs National Highway..., Warrendale, Pennsylvania 15096. Phone: 1-724-776-4841; Web: http://www.sae.org Society of Automotive...
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Vaccination coverage among children in kindergarten - United States, 2012-13 school year.
2013-08-02
State and local school vaccination requirements are implemented to maintain high vaccination coverage and minimize the risk from vaccine preventable diseases. To assess school vaccination coverage and exemptions, CDC annually analyzes school vaccination coverage data from federally funded immunization programs. These awardees include 50 states and the District of Columbia (DC), five cities, and eight U.S.-affiliated jurisdictions. This report summarizes vaccination coverage from 48 states and DC and exemption rates from 49 states and DC for children entering kindergarten for the 2012-13 school year. Forty-eight states and DC reported vaccination coverage, with medians of 94.5% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.1% for local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccination; and 93.8% for 2 doses of varicella vaccine among awardees with a 2-dose requirement. Forty-nine states and DC reported exemption rates, with the median total of 1.8%. Although school entry coverage for most awardees was at or near national Healthy People 2020 targets of maintaining 95% vaccination coverage levels for 2 doses of MMR vaccine, 4 doses of DTaP† vaccine, and 2 doses of varicella vaccine, low vaccination and high exemption levels can cluster within communities, increasing the risk for disease. Reports to CDC are aggregated at the state level; however, local reporting of school vaccination coverage might be accessible by awardees. These local-level data can be used to create evidence-based health communication strategies to help parents understand the risks for vaccine-preventable diseases and the benefits of vaccinations to the health of their children and other kindergarteners.
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1990-11-21
buckled coatings is obtained: G - H(ao-6 c )(do 0/dc-do c/dc)%-( o -0C) 2 (dz/dc)](l-a)h/2c (4) where % is c 2b 2(l+v)+c4 (-v)]/ E (c 2-b 2). To determine...pressure on the fiber, o , that results from a cooling differential of AT Is (9): I 20 q. = [ E 2 .(% - a5 ,) + Er(a - atr)]*AT (9) where a% is the...calculated by rule-of-mixtures, these fracture energies can be expressed in terms of critical stress intensity factors: Go + AGb ( o +AKb) 2 / E (3
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77 FR 50926 - Security Zones; Certain Dangerous Cargo Vessels, Tampa, FL
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-23
... Certain Dangerous Cargo (CDC) vessels, which are vessels carrying anhydrous ammonia, liquefied propane gas... Republican National Convention in Tampa, Florida. A CDC vessel is one carrying anhydrous ammonia, liquefied... vessel carrying Anhydrous Ammonia (NH3), Liquefied Petroleum Gas (LPG), or Ammonium Nitrate (NH4) and...
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For the Record - A History of the Nuclear Test Personnel Review Program, 1978-1986.
1986-08-01
Wash., DC.: DNA. DNA- 6034 . Jun 83. 334 p. (A15)AD/A134 735.*/** 8. Operation BUSTER-JANGLE, 1951. Wash., DC.: DNA. DNA-6023F. Jun 82. 190 p. (A09)AD...veterans was selected from the SMOKY cohort by the CDC to be sent to the Argonne National Laboratory ( ANL ) for special testing. The group was chosen on the...members of the group, however, chose not to w’ participate in the study. 1.8 , , 184 The remaining 16 veterans visited ANL during 1979, when they were
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49 CFR 571.5 - Matter incorporated by reference
Code of Federal Regulations, 2010 CFR
2010-10-01
... Printing Office, Washington, DC 20402 Illuminating Engineering Society of North America (IES), 120 Wall St.... Phone: 1-800-232-4636; Web: http://www.cdc.gov/nchs “Weight, Height, and Selected Body Dimensions of..., Pennsylvania 15096. Phone: 1-724-776-4841; Web: http://www.sae.org Society of Automotive Engineers (SAE...
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78 FR 11886 - Agency Forms Undergoing Paperwork Reduction Act Review
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-20
... (CDC) publishes a list of information collection requests under review by the Office of Management and... Officer, Office of Management and Budget, Washington, DC 20503 or by fax to (202) 395-5806. Written...: Strategies to Promote Healthy Teen Relationships TM (OMB 0920-0941, Expiration 06/30/ 2015)--REVISION...
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77 FR 47074 - Agency Forms Undergoing Paperwork Reduction Act Review
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-07
... (CDC) publishes a list of information collection requests under review by the Office of Management and... Officer, Office of Management and Budget, Washington, DC 20503 or by fax to (202) 395-5806. Written... illnesses among emergency medical services (EMS) workers: A NEISS-Work telephone interview survey (0920...
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White, J H; Johnson, A L; Lowndes, N F; Johnston, L H
1991-01-01
By fusing the CDC9 structural gene to the PGK upstream sequences and the CDC9 upstream to lacZ, we showed that the cell cycle expression of CDC9 is largely due to transcriptional regulation. To investigate the role of six ATGATT upstream repeats in CDC9 regulation, synthetic copies of the sequence were attached to a heterologous gene. The repeats stimulated transcription strongly and additively, but, unlike conventional yeast UAS elements, only when present in one orientation. Transcription driven by the repeats declines in cells held at START of the cell cycle or in stationary phase, as occurs with CDC9. However, the repeats by themselves cannot impart cell cycle regulation to a heterologous gene. CDC9 may therefore be controlled by an activating system operating through the repeats that is sensitive to cellular proliferation and a separate mechanism that governs the periodic expression in the cell cycle. Images PMID:1901644
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Physical activity recommendations: an alternative approach using energy expenditure.
Mudd, Lanay M; Rafferty, Ann P; Reeves, Mathew J; Pivarnik, James M
2008-10-01
Most adults do not meet the American College of Sports Medicine and Centers for Disease Control and Prevention (ACSM/CDC) physical activity recommendations. Even fewer meet the more extreme Institute of Medicine (IOM) physical activity recommendations. Compliance with either recommendation has been conventionally assessed by combining frequencies and durations of self-reported activities. Leisure-time energy expenditure is a cumulative measure of activity that offers an alternative method of defining compliance. To calculate the leisure-time energy expenditure of adults complying with the ACSM/CDC or the IOM physical activity recommendations determined by conventional measures and to reexamine compliance with the IOM recommendation using energy expenditure criteria. National, cross-sectional data from the 2000 Behavioral Risk Factor Surveillance System determined the mode, frequency, and duration of up to two leisure-time activities performed by adults. Four mutually exclusive activity groups (Non-, Low-, ACSM/CDC-, and IOM-Active) were defined on the basis of frequencies and durations of reported activities. Leisure-time energy expenditure (kcal x kg(-1) x wk(-1)) was calculated per respondent. The energy expenditure threshold for meeting the IOM recommendation was calculated as 21 kcal x kg(-1) x wk(-1). Of the 162,669 respondents included in the analyses, 29.9% were Nonactive, whereas 42.3%, 23.3%, and 4.5% were Low-, ACSM/CDC-, and IOM-Active, respectively. Median leisure-time energy expenditure values were 9.0, 27.4, and 63.0 kcal x kg(-1) x wk(-1) for Low-, ACSM/CDC-, and IOM-Active groups, respectively. When using energy expenditure criteria, compliance with the IOM recommendation rose to 27.7% of respondents. Compliance with the IOM physical activity recommendation dramatically increased when assessed by energy expenditure compared with conventional criteria, thereby highlighting the potential bias of conventional methods. A significant proportion of adults meet the intent but not the letter of the IOM activity recommendation.
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Zhu, Feng; Feng, Dengyu; Zhang, Tenghui; Gu, Lili; Zhu, Weiming; Guo, Zhen; Li, Yi; Gong, Jianfeng; Li, Ning; Li, Jieshou
2018-05-15
The comprehensive complication index (CCI) is a novel approach to evaluate complications. However, application of the CCI in inflammatory bowel disease (IBD) population is scarce and the difference between the CCI and the Clavien-Dindo classification (CDC) remains unknown. The aim of this study was to compare the CCI to the conventional CDC by applying the CCI among the IBD patients. The data of 426 IBD patients who underwent surgery between September 1, 2015 and August 31, 2017 were collected. Univariate and multivariate analyses were conducted to identify risk factors for postoperative complications. The efficacy of CCI and CDC was compared using correlation analysis and logistic regression. Cumulative sum control (CUSUM) models were applied to monitor the CCI continuously. Totally, 297 complications occurred in 144 (33.8%) patients. The rate of severe complications (CDC grade ≥ III) was 12.9% and the mean CCI was 9.8 ± 15.5. Preoperative glucocorticoids usage and previous abdominal surgery were related to higher CCI value (p = 0.002, p = 0.006, respectively) but not related to higher incidence of severe complications (CDC grade ≥ III) (p = 0.117, p = 0.177, respectively). In patients with multiple complications, the CCI demonstrated a stronger correlation with hospital stay (ρ = 0.604, p < 0.001) than CDC (ρ = 0.508, p < 0.001). Higher CCI value (p < 0.001, OR 1.161, 95% CI 1.093-1.234) and the CDC grade (p < 0.001, OR 3.811, 95% CI 2.283-6.362) were risk factors for prolonged LOS. In the CUSUM-CCI model of IBD surgery, a gradual decrease was observed over time. The CCI and the CDC are both risk factors for prolonged postoperative LOS after surgery for IBD patients. The CCI is more strongly correlated with postoperative LOS than is the conventional CDC. The CUSUM-CCI model is effective in monitoring surgical quality.
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77 FR 10749 - Agency Forms Undergoing Paperwork Reduction Act Review
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-23
... participate; the data are routinely available in each reporting office as a by-product of ongoing activities... Prevention (CDC) publishes a list of information collection requests under review by the Office of Management... Management and Budget, Washington, DC or by fax to (202) 395-6974. Written comments should be received within...
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Revisions to Conventional Clock Domain Crossing Methodologies in Triple Modular Redundant Circuits
NASA Technical Reports Server (NTRS)
Berg, Melanie D.; LaBel, Kenneth A.
2018-01-01
We present updates to the conventional methodology of triple modular redundancy (TMR) insertion as it pertains to clock domain crossings (CDCs). Three types of TMR schemes and their suggested corresponding CDC revisions are discussed.
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USDA-ARS?s Scientific Manuscript database
Piper sarmentosum Roxb. (synonym, P. lolot C.DC.) is a southeast Asian medicinal plant valued for its medicinal and culinary uses. Hand-sections of the vegetative parts of P. sarmentosum were prepared and the anatomical features were studied by light microscopy and scanning electron microscopy. Th...
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Zuotin, a putative Z-DNA binding protein in Saccharomyces cerevisiae
NASA Technical Reports Server (NTRS)
Zhang, S.; Lockshin, C.; Herbert, A.; Winter, E.; Rich, A.
1992-01-01
A putative Z-DNA binding protein, named zuotin, was purified from a yeast nuclear extract by means of a Z-DNA binding assay using [32P]poly(dG-m5dC) and [32P]oligo(dG-Br5dC)22 in the presence of B-DNA competitor. Poly(dG-Br5dC) in the Z-form competed well for the binding of a zuotin containing fraction, but salmon sperm DNA, poly(dG-dC) and poly(dA-dT) were not effective. Negatively supercoiled plasmid pUC19 did not compete, whereas an otherwise identical plasmid pUC19(CG), which contained a (dG-dC)7 segment in the Z-form was an excellent competitor. A Southwestern blot using [32P]poly(dG-m5dC) as a probe in the presence of MgCl2 identified a protein having a molecular weight of 51 kDa. The 51 kDa zuotin was partially sequenced at the N-terminal and the gene, ZUO1, was cloned, sequenced and expressed in Escherichia coli; the expressed zuotin showed similar Z-DNA binding activity, but with lower affinity than zuotin that had been partially purified from yeast. Zuotin was deduced to have a number of potential phosphorylation sites including two CDC28 (homologous to the human and Schizosaccharomyces pombe cdc2) phosphorylation sites. The hexapeptide motif KYHPDK was found in zuotin as well as in several yeast proteins, DnaJ of E.coli, csp29 and csp32 proteins of Drosophila and the small t and large T antigens of the polyoma virus. A 60 amino acid segment of zuotin has similarity to several histone H1 sequences. Disruption of ZUO1 in yeast resulted in a slow growth phenotype.
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Prostaglandin E2 inhibits Tr1 cell differentiation through suppression of c-Maf
Hooper, Kirsten Mary; Kong, Weimin
2017-01-01
Prostaglandin E2 (PGE2), a major lipid mediator abundant at inflammatory sites, acts as a proinflammatory agent in models of inflammatory/autoimmune diseases by promoting CD4 Th1/Th17 differentiation. Regulatory T cells, including the IL-10 producing Tr1 cells counterbalance the proinflammatory activity of effector Th1/Th17 cells. Tr1 cell differentiation and function are induced by IL-27, and depend primarily on sustained expression of c-Maf in addition to AhR and Blimp-1. In agreement with the in vivo proinflammatory role of PGE2, here we report for the first time that PGE2 inhibits IL-27-induced differentiation and IL-10 production of murine CD4+CD49b+LAG-3+Foxp3- Tr1 cells. The inhibitory effect of PGE2 was mediated through EP4 receptors and induction of cAMP, leading to a significant reduction in c-Maf expression. Although PGE2 reduced IL-21 production in differentiating Tr1 cells, its inhibitory effect on Tr1 differentiation and c-Maf expression also occurred independent of IL-21 signaling. PGE2 did not affect STAT1/3 activation, AhR expression and only marginally reduced Egr-2/Blimp-1 expression. The effect of PGE2 on CD4+CD49b+LAG-3+ Tr1 differentiation was not associated with either induction of Foxp3 or IL-17 production, suggesting a lack of transdifferentiation into Foxp3+ Treg or effector Th17 cells. We recently reported that PGE2 inhibits the expression and production of IL-27 from activated conventional dendritic cells (cDC) in vivo and in vitro. The present study indicates that PGE2 also reduces murine Tr1 differentiation and function directly by acting on IL-27-differentiating Tr1 cells. Together, the ability of PGE2 to inhibit IL-27 production by cDC, and the direct inhibitory effect on Tr1 differentiation mediated through reduction in c-Maf expression, represent a new mechanistic perspective for the proinflammatory activity of PGE2. PMID:28604806
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Jiang, Bo; Grage-Griebenow, Evelin; Csernok, Elena; Butherus, Kristine; Ehlers, Stefan; Gross, Wolfgang L; Holle, Julia U
2010-01-01
The aim of the study was to assess PAR-2 expression on dendritic cell (DC) subsets and other immune cells of Wegener's granulomatosis (WG) patients and healthy controls (HC) and to investigate whether Proteinase 3 (PR3, a serine protease which can activate PAR2) induces maturation of human DC-like monocytes and murine Flt-3 ligand- and GM-CSF-generated DC. Human peripheral blood cells including DC subsets and Flt-3l- and GM-CSF-generated mouse DC were analysed for expression of PAR-2 and DC maturation markers by flow cytometry before and after stimulation with PR3, trypsin, PAR-2 agonist or LPS for 24 h. There was no difference of PAR-2 expression on PMNs, monocytes, lymphocytes and DC between all WG samples and HC. However, in inactive WG, expression of PAR-2 was downregulated on the cell surface of PMNs, monocytes, lymphocytes, and CD11c+DC compared to active WG and HC. PR3 and PAR2-agonists did not induce upregulation of PAR-2 or maturation markers of human DC-like monocytes in WG and HC. Likewise, murine PR3 did not induce upregulation of PAR-2 or maturation markers in murine DC. PAR-2 expression is downregulated on human peripheral blood cells including CD11c+ DC in inactive WG compared to active WG and HC, possibly reflecting a non-activated status of these cells in inactive disease. PR3 and PAR-2- agonists did not induce maturation of human ex vivo DC-like monocytes in WG and HC and of murine DC, suggesting this pathway is not singularly involved in the maturation of these cell subsets.
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In vitro and in vivo comparisons of constant resistance AC iontophoresis and DC iontophoresis.
Li, S Kevin; Higuchi, William I; Zhu, Honggang; Kern, Steven E; Miller, David J; Hastings, Matthew S
2003-09-04
A previous in vitro constant electrical resistance alternating current (AC) iontophoresis study with human epidermal membrane (HEM) and a model neutral permeant has shown less inter- and intra-sample variability in iontophoretic transport relative to conventional constant direct current (DC) iontophoresis. The objectives of the present study were to address the following questions. (1) Can the skin electrical resistance be maintained at a constant level by AC in humans in vivo? (2) Are the in vitro data with HEM representative of those in vivo? (3) Does constant skin resistance AC iontophoresis have less inter- and intra-sample variability than conventional constant current DC iontophoresis in vivo? (4) What are the electrical and the barrier properties of skin during iontophoresis in vivo? In the present study, in vitro HEM experiments were carried out with the constant resistance AC and the conventional constant current DC methods using mannitol and glucose as the neutral model permeants. In vivo human experiments were performed using glucose as the permeant with a constant skin resistance AC only protocol and two conventional constant current DC methods (continuous constant current DC and constant current DC with its polarity alternated every 10 min with a 3:7 on:off duty cycle). Constant current DC iontophoresis was conducted with commercial constant current DC devices, and constant resistance AC iontophoresis was carried out by reducing and maintaining the skin resistance at a constant target value with AC supplied from a function generator. This study shows that (1) skin electrical resistance can be maintained at a constant level during AC iontophoresis in vivo; (2) HEM in vitro and human skin in vivo demonstrate similar electrical and barrier properties, and these properties are consistent with our previous findings; (3) there is general qualitative and semi-quantitative agreement between the HEM data in vitro and human skin data in vivo; and (4) constant skin resistance AC iontophoresis generally provides less inter- and intra-subject variability than conventional constant current DC.
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CDC's Emergency Management Program activities - worldwide, 2003-2012.
2013-09-06
In 2003, recognizing the increasing frequency and complexity of disease outbreaks and disasters and a greater risk for terrorism, CDC established the Emergency Operations Center (EOC), bringing together CDC staff members who respond to public health emergencies to enhance communication and coordination. To complement the physical EOC environment, CDC implemented the Incident Management System (IMS), a staffing structure and set of standard operational protocols and services to support and monitor CDC program-led responses to complex public health emergencies. The EOC and IMS are key components of CDC's Emergency Management Program (EMP), which applies emergency management principles to public health practice. To enumerate activities conducted by the EMP during 2003-2012, CDC analyzed data from daily reports and activity logs. The results of this analysis determined that, during 2003-2012, the EMP fully activated the EOC and IMS on 55 occasions to support responses to infectious disease outbreaks, natural disasters, national security events (e.g., conventions, presidential addresses, and international summits), mass gatherings (e.g., large sports and social events), and man-made disasters. On 109 other occasions, the EMP was used to support emergency responses that did not require full EOC activation, and the EMP also conducted 30 exercises and drills. This report provides an overview of those 194 EMP activities.
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The Analysis Phase of MITHRAS.
1986-06-23
o •% •% • " + ". " . _.% .+. + , + •’. .’ .’ % ..’ ,’ -. • + , .... "...."....................-.. . % - . - rr.tr-e. n-.,~,.-~ w w X- C W- W, WU- I...v- 1? HLI 12 HL T ~ ~~0 a. .- - cc cc CD u 8 A DC Cj 0NJ o’u o .21 0 S cDc 00 CO LU Z. -j z4 CD - cow m 0 /~~ W "~~ ZZ~ C w Nŕ*\\ co Li. 46~ Between...electrons. 75 1,6’ S 2 - =0 N E’ 0 z CD (D z 0 D E C E -z 2 ZO -U.1’ C4 Euc CD o LJo E
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2014-01-15
in a Light Duty Engine Under Conventional Diesel, Homogeneous Charge Compression Ignition , and Reactivity Controlled Compression Ignition ...Conventional Diesel (CDC), Homogeneous Charge Compression Ignition (HCCI), and Reactivity Controlled Compression Ignition (RCCI) combustion...LTC) regimes, including reactivity controlled compression ignition (RCCI), partially premixed combustion (PPC), and homogenous charge compression
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A Study of 4-level DC-DC Boost Inverter with Passive Component Reduction Consideration
NASA Astrophysics Data System (ADS)
Kasiran, A. N.; Ponniran, A.; Harimon, M. A.; Hamzah, H. H.
2018-04-01
This study is to analyze design principles of boost inductor and capacitor used in the 4-level DC-DC boost converter to realize size reduction of passive component referring to their attributes. The important feature of this circuit is that most of the boost-up energy is transferred from the capacitor-clamped to the output side which the small inductance can be used at the input side. The inductance of the boost inductor is designed by referring the inductor current ripple. On the other hand, the capacitance of the capacitor-clamped is designed by considering voltage stress on semiconductor devices and also the used switching frequency. Besides that, according to the design specifications, the required inductance in 4-level DC-DC boost converter is decreased compared to a conventional conventional DC-DC boost converter. Meanwhile, voltage stress on semiconductor device is depending on the maximum voltage ripple of the capacitor-clamped. A 50 W 4-level DC-DC boost converter prototype has been constructed. The results show that the inductor current ripple was 1.15 A when the inductors, 1 mH and 0.11 mH were used in the conventional and 4-level DC-DC boost converters, respectively. Thus, based on the experimental results, it shows that the reduction of passive components by referring to their attributes in 4-level DC-DC boost converter is achieved. Moreover, the decreasing of voltage stress on the semiconductor devices is an advantage for the selection of low ON-resistance of the devices which will contribute to the reduction of the semiconductor conduction loss. The integration result of boost converter and H-bridge inverter is also shown.
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NASA Astrophysics Data System (ADS)
Dehkordi, N. Mahdian; Sadati, N.; Hamzeh, M.
2017-09-01
This paper presents a robust dc-link voltage as well as a current control strategy for a bidirectional interlink converter (BIC) in a hybrid ac/dc microgrid. To enhance the dc-bus voltage control, conventional methods strive to measure and feedforward the load or source power in the dc-bus control scheme. However, the conventional feedforward-based approaches require remote measurement with communications. Moreover, conventional methods suffer from stability and performance issues, mainly due to the use of the small-signal-based control design method. To overcome these issues, in this paper, the power from DG units of the dc subgrid imposed on the BIC is considered an unmeasurable disturbance signal. In the proposed method, in contrast to existing methods, using the nonlinear model of BIC, a robust controller that does not need the remote measurement with communications effectively rejects the impact of the disturbance signal imposed on the BIC's dc-link voltage. To avoid communication links, the robust controller has a plug-and-play feature that makes it possible to add a DG/load to or remove it from the dc subgrid without distorting the hybrid microgrid stability. Finally, Monte Carlo simulations are conducted to confirm the effectiveness of the proposed control strategy in MATLAB/SimPowerSystems software environment.
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Marynak, Kristy; Kenemer, Brandon; King, Brian A; Tynan, Michael A; MacNeil, Allison; Reimels, Elizabeth
2017-12-15
Electronic cigarettes (e-cigarettes) are the most frequently used tobacco product among U.S. youths, and past 30-day e-cigarette use is more prevalent among high school students than among adults (1,2). E-cigarettes typically deliver nicotine, and the U.S. Surgeon General has concluded that nicotine exposure during adolescence can cause addiction and can harm the developing adolescent brain (2). Through authority granted by the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration (FDA) prohibits e-cigarette sales to minors, free samples, and vending machine sales, except in adult-only facilities (3). States, localities, territories, and tribes maintain broad authority to adopt additional or more stringent requirements regarding tobacco product use, sales, marketing, and other topics (2,4). To understand the current e-cigarette policy landscape in the United States, CDC assessed state and territorial laws that 1) prohibit e-cigarette use and conventional tobacco smoking indoors in restaurants, bars, and worksites; 2) require a retail license to sell e-cigarettes; 3) prohibit e-cigarette self-service displays (e.g., requirement that products be kept behind the counter or in a locked box); 4) establish 21 years as the minimum age of purchase for all tobacco products, including e-cigarettes (tobacco-21); and 5) apply an excise tax to e-cigarettes. As of September 30, 2017, eight states, the District of Columbia (DC), and Puerto Rico prohibited indoor e-cigarette use and smoking in indoor areas of restaurants, bars, and worksites; 16 states, DC, and the U.S. Virgin Islands required a retail license to sell e-cigarettes; 26 states prohibited e-cigarette self-service displays; five states, DC, and Guam had tobacco-21 laws; and eight states, DC, Puerto Rico, and the U.S. Virgin Islands taxed e-cigarettes. Sixteen states had none of the assessed laws. A comprehensive approach that combines state-level strategies to reduce youths' initiation of e-cigarettes and population exposure to e-cigarette aerosol, coupled with federal regulation, could help reduce health risks posed by e-cigarettes among youths (2,5).
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Sawada, Yu; Hanakawa, Sho; Nakamizo, Satoshi; Murata, Teruasa; Ueharaguchi-Tanada, Yuri; Ono, Sachiko; Amano, Wataru; Nakajima, Saeko; Egawa, Gyohei; Tanizaki, Hideaki; Otsuka, Atsushi; Kitoh, Akihiko; Dainichi, Teruki; Ogawa, Narihito; Kobayashi, Yuichi; Yokomizo, Takehiko; Arita, Makoto; Nakamura, Motonobu; Miyachi, Yoshiki
2015-01-01
Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade. PMID:26438363
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Degree of conversion of two lingual retainer adhesives cured with different light sources.
Usümez, Serdar; Büyükyilmaz, Tamer; Karaman, Ali Ihya; Gündüz, Beniz
2005-04-01
The aim of this study was to evaluate the degree of conversion (DC) of two lingual retainer adhesives, Transbond Lingual Retainer (TLR) and Light Cure Retainer (LCR), cured with a fast halogen light, a plasma arc light and a light-emitting diode (LED) at various curing times. A conventional halogen light served as the control. One hundred adhesive samples (five per group) were cured for 5, 10 or 15 seconds with an Optilux 501 (fast halogen light), for 3, 6 or 9 seconds with a Power Pac (plasma arc light), or for 10, 20 or 40 seconds with an Elipar Freelight (LED). Samples cured for 40 seconds with the conventional halogen lamp were used as the controls. Absorbance peaks were recorded using Fourier transform infrared (FT-IR) spectroscopy. DC values were calculated. Data were analysed using Kruskal-Wallis and Mann-Whitney U-tests. For the TLR, the highest DC values were achieved in 6 and 9 seconds with the plasma arc light. Curing with the fast halogen light for 15 seconds and with the LED for 40 seconds produced statistically similar DC values, but these were lower than those with the plasma arc light. All of these light exposures yielded a statistically significantly higher DC than 40 seconds of conventional halogen light curing. The highest DC value for the LCR was achieved in 15 seconds with the fast halogen light, then the plasma arc light curing for 6 seconds. These two combinations produced a statistically significantly higher DC when compared with the 40 seconds of conventional halogen light curing. The lowest DC for the LCR was achieved with 10 seconds of LED curing. The overall DC of the LCR was significantly higher than that of the TLR. The results suggest that a similar or higher DC than the control values could be achieved in 6-9 seconds by plasma arc curing, in 10-15 seconds by fast halogen curing or in 20 seconds by LED curing.
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Simultaneous DC and three phase output using hybrid converter
NASA Astrophysics Data System (ADS)
Surenderanath, S.; Rathnavel, P.; Prakash, G.; Rayavel, P.
2018-04-01
This Paper introduces new hybrid converter topologies which can supply simultaneously three phase AC as well as DC from a single DC source. The new Hybrid Converter is derived from the single switch controlled Boost converter by replacing the controlled switch with voltage source inverter (VSI). This new hybrid converter has the advantages like reduced number of switches as compared with conventional design having separate converter for supplying three phase AC and DC loads, provide DC and three AC outputs with an increased reliability, resulting from the inherent shoot through protection in the inverter stage. The proposed converter, studied in this paper, is called Boost-Derived Hybrid Converter (BDHC) as it is obtained from the conventional boost topology. A DSPIC based feedback controller is designed to regulate the DC as well as AC outputs. The proposed Converter can supply DC and AC loads at 95 V and 35 V (line to ground) respectively from a 48 V DC source.
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Dendritic Cells Promote Pancreatic Viability in Mice with Acute Pancreatitis
Bedrosian, Andrea S.; Nguyen, Andrew H.; Hackman, Michael; Connolly, Michael K.; Malhotra, Ashim; Ibrahim, Junaid; Cieza-Rubio, Napoleon E.; Henning, Justin R.; Barilla, Rocky; Rehman, Adeel; Pachter, H. Leon; Medina-Zea, Marco V.; Cohen, Steven M.; Frey, Alan B.; Acehan, Devrim; Miller, George
2011-01-01
Background & Aims Acute pancreatitis increases morbidity and mortality from organ necrosis by mechanisms that are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. Methods Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier analysis. Results Numbers of MHC II+CD11c+DC increased 100-fold in pancreas of mice with acute pancreatitis, to account for nearly 15% of intra-pancreatic leukocytes. Intra-pancreatic DC acquired an immune phenotype in mice with acute pancreatitis; they expressed higher levels of MHC II and CD86 and increased production of interleukin-6, membrane cofactor protein (MCP)-1, and tumor necrosis factor (TNF)-α. However, rather than inducing an organ-destructive inflammatory process, DC were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DC and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DC died from acinar cell death within 4 days. Depletion of DC from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DC did not require infiltrating neutrophils, activation of NF-κB, or signaling by mitogen-activated protein kinase or TNF-α. Conclusions DC are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress. PMID:21801698
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Dąbrowski, Michał; Jakimiuk, Ewa; Baranowski, Mirosław; Gajęcka, Magdalena; Zielonka, Łukasz; Gajęcki, Maciej Tadeusz
2017-04-26
Deoxynivalenol (DON) is one of the most prevalent mycotoxins in Europe. Pigs are an animal species that is most susceptible to this mycotoxin. Deoxynivalenol causes significant losses in pig production by lowering feed intake, decreasing daily weight gains, disrupting immune responses, and increasing susceptibility to diseases. The aim of this experiment was to determine the influence of feed contaminated with DON at concentrations insignificantly higher than recommended by the European Commission (900 µg/kg). The experimental feed contained 1008 μg DON/kg. The experiment was performed on eight weaners from the same litter. The animals were randomly divided into two groups: an experimental group (M, n = 4) fed contaminated feed and a control group (C, n = 4) administered feed free of mycotoxins. The experiment lasted for six weeks, and peripheral blood samples were collected from the animals for analyses of selected morphological parameters and changes in the percentages of CD4⁺8 - , CD4 - 8⁺, and CD4⁺8⁺ lymphocytes and antigen-presenting cells (APC) with CD14⁺172⁺ (monocytes), CD172a high 4 - 14 - (conventional dendritic cells, cDC), and CD172a dim 4⁺14 - (plasmacytoid dendritic cells, pDC) phenotypes. The morphological parameters of porcine blood samples were determined by flow cytometry with non-fluorescent particle-size calibration standards, and no differences were observed between groups M and C. An immunophenotyping analysis of lymphocytes and dendritic cells (DC) revealed an increase in the percentage of CD4⁺8 - , CD172a high 4 - 14 - , and CD172a dim 4⁺14 - cells, and a decrease in the number of CD4 - 8⁺ cells in group M. The results of this experiment suggest that prolonged exposure to low doses of DON can change the proportions of immunocompetent cells (a shift towards humoral immunity), without affecting their overall counts.
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A Single-Phase Embedded Z-Source DC-AC Inverter
Kim, Se-Jin; Lim, Young-Cheol
2014-01-01
In the conventional DC-AC inverter consisting of two DC-DC converters with unipolar output capacitors, the output capacitor voltages of the DC-DC converters must be higher than the DC input voltage. To overcome this weakness, this paper proposes a single-phase DC-AC inverter consisting of two embedded Z-source converters with bipolar output capacitors. The proposed inverter is composed of two embedded Z-source converters with a common DC source and output AC load. Though the output capacitor voltages of the converters are relatively low compared to those of a conventional inverter, an equivalent level of AC output voltages can be obtained. Moreover, by controlling the output capacitor voltages asymmetrically, the AC output voltage of the proposed inverter can be higher than the DC input voltage. To verify the validity of the proposed inverter, experiments were performed with a DC source voltage of 38 V. By controlling the output capacitor voltages of the converters symmetrically or asymmetrically, the proposed inverter can produce sinusoidal AC output voltages. The experiments show that efficiencies of up to 95% and 97% can be achieved with the proposed inverter using symmetric and asymmetric control, respectively. PMID:25133241
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A single-phase embedded Z-source DC-AC inverter.
Kim, Se-Jin; Lim, Young-Cheol
2014-01-01
In the conventional DC-AC inverter consisting of two DC-DC converters with unipolar output capacitors, the output capacitor voltages of the DC-DC converters must be higher than the DC input voltage. To overcome this weakness, this paper proposes a single-phase DC-AC inverter consisting of two embedded Z-source converters with bipolar output capacitors. The proposed inverter is composed of two embedded Z-source converters with a common DC source and output AC load. Though the output capacitor voltages of the converters are relatively low compared to those of a conventional inverter, an equivalent level of AC output voltages can be obtained. Moreover, by controlling the output capacitor voltages asymmetrically, the AC output voltage of the proposed inverter can be higher than the DC input voltage. To verify the validity of the proposed inverter, experiments were performed with a DC source voltage of 38 V. By controlling the output capacitor voltages of the converters symmetrically or asymmetrically, the proposed inverter can produce sinusoidal AC output voltages. The experiments show that efficiencies of up to 95% and 97% can be achieved with the proposed inverter using symmetric and asymmetric control, respectively.
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Rajan, Bhargavi; Zerrouki, Kamelia; Karnell, Jodi L; Sagar, Divya; Vainshtein, Inna; Farmer, Erika; Rosenthal, Kimberly; Morehouse, Chris; de los Reyes, Melissa; Schifferli, Kevin; Liang, Meina; Sanjuan, Miguel A; Sims, Gary P; Kolbeck, Roland
2018-01-01
Objective We investigated the mechanistic and pharmacological properties of anifrolumab, a fully human, effector-null, anti-type I interferon (IFN) alpha receptor 1 (IFNAR1) monoclonal antibody in development for SLE. Methods IFNAR1 surface expression and internalisation on human monocytes before and after exposure to anifrolumab were assessed using confocal microscopy and flow cytometry. The effects of anifrolumab on type I IFN pathway activation were assessed using signal transducer and activator of transcription 1 (STAT1) phosphorylation, IFN-stimulated response element–luciferase reporter cell assays and type I IFN gene signature induction. The ability of anifrolumab to inhibit plasmacytoid dendritic cell (pDC) function and plasma cell differentiation was assessed by flow cytometry and ELISA. Effector-null properties of anifrolumab were assessed in antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays with B cells. Results Anifrolumab reduced cell surface IFNAR1 by eliciting IFNAR1 internalisation. Anifrolumab blocked type I IFN-dependent STAT1 phosphorylation and IFN-dependent signalling induced by recombinant and pDC-derived type I IFNs and serum of patients with SLE. Anifrolumab suppressed type I IFN production by blocking the type I IFN autoamplification loop and inhibited proinflammatory cytokine induction and the upregulation of costimulatory molecules on stimulated pDCs. Blockade of IFNAR1 suppressed plasma cell differentiation in pDC/B cell co-cultures. Anifrolumab did not exhibit CDC or ADCC activity. Conclusions Anifrolumab potently inhibits type I IFN-dependent signalling, including the type I IFN autoamplification loop, and is a promising therapeutic for patients with SLE and other diseases that exhibit chronic dysfunctional type I IFN signalling. PMID:29644082
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Kost, Gerald J; Ferguson, William J; Hoe, Jackie; Truong, Anh-Thu; Banpavichit, Arirat; Kongpila, Surin
2015-01-01
To present a vision where point-of-care testing (POCT) accelerates an Ebola Spatial Care Path™ (SCP) and future molecular diagnostics enable facilitated-access self-testing (FAST POC); to design an alternate care facility (ACF) for the SCP; to innovate an Ebola diagnostic center (DC); and to propel rapid POCT to the frontline to create resilience that stops future outbreaks. PubMed, literature, and web searches. Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), Medicine Without Frontiers, and World Health Organization (WHO) document analyses. Investigations in China, the Philippines, Thailand, and the United States. Review of SE Asia, US, and West Africa isolation-treatment centers. Innovation of a SCP, ACF, and DC suitable for American and other communities. The authors designed an ACF and DC to integrate SCP principles for urgent Ebola care. FDA emergency use authorizations for Ebola molecular diagnostics were discovered, but no portable, handheld, or self-contained molecular POC instruments are yet available, although feasible. The WHO initiated design criteria and an acceptance protocol for testing. Financial investment in POCT will downsize Ebola outbreaks. POCT is facilitating global health. Now, global health problems are elevating POCT to new levels of importance for accelerating diagnosis and evidence-based decision making during disease outbreaks. Authorities concur that rapid diagnosis has potential to stop disease spread. With embedded POCT, strategic SCPs planned by communities fulfill CDC recommendations. POC devices should consolidate multiplex test clusters supporting patients with Ebola in isolation. The ultimate future solution is FAST POC. New technologies offer minimally significant risks. Diagnostic centers in ACFs and transportable formats also will optimize Ebola SCPs.
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Molecular-Based Detection Systems for Cryptosporidium Oocysts
The presentation describes on-going studies in collaboration with US EPA Region 2, 3, and the CDC on identifying sources of Cryptosporidium oocyst contamination in source waters using conventional and real-time PCR approaches.
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Jia, Guang; O'Dell, Craig; Heverhagen, Johannes T; Yang, Xiangyu; Liang, Jiachao; Jacko, Richard V; Sammet, Steffen; Pellas, Theodore; Cole, Patricia; Knopp, Michael V
2008-09-01
To describe and determine the reproducibility of a simplified model to quantitatively measure heterogeneous intralesion contrast agent diffusion in colorectal liver metastases. This HIPAA-compliant retrospective study received institutional review board approval, and written informed consent was obtained from 14 patients (mean age, 61 years +/- 9 [standard deviation]; range, 41-78 years), including 10 men (mean age, 65 years +/- 8; range, 47-78 years) and four women (mean age, 54 years +/- 9; range, 41-59 years), with colorectal liver metastases. Magnetic resonance (MR) imaging was performed twice (first baseline MR image [B(1)] and second baseline MR image [B(2)]) in a single target lesion prior to therapy. Dynamic contrast material-enhanced MR imaging was performed by using a saturation-recovery fast gradient-echo sequence. A simplified contrast agent diffusion model was proposed, and a contrast agent diffusion coefficient (CDC) was calculated. The reproducibility of the CDC measurement was evaluated by using the Bland-Altman plot and a linear regression model. The mean CDC was 0.22 mm(2)/sec (range, 0.01-0.73 mm(2)/sec) on B(1) and 0.24 mm(2)/sec (range, 0.01-0.71 mm(2)/sec) on B(2), with an intraclass correlation coefficient of 0.91 (P < .0001). Bland-Altman plot showed good agreement, with a mean difference in measurement pairs of 0.017 mm(2)/sec +/- 0.096. The slope from the linear regression model was 0.89 (95% confidence interval: 0.63, 1.15) and the intercept was 0.01 (95% confidence interval: -0.08, 0.09). The CDC enables a quantitative description of contrast enhancement heterogeneity in lesions. Given the high reproducibility of the CDC metric, CDC appears promising for further qualification as an imaging biomarker of change measurement in response assessment. http://radiology.rsnajnls.org/cgi/content/full/248/3/901/DC1. RSNA, 2008
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Daud, Muhamad Zalani; Mohamed, Azah; Hannan, M. A.
2014-01-01
This paper presents an evaluation of an optimal DC bus voltage regulation strategy for grid-connected photovoltaic (PV) system with battery energy storage (BES). The BES is connected to the PV system DC bus using a DC/DC buck-boost converter. The converter facilitates the BES power charge/discharge to compensate for the DC bus voltage deviation during severe disturbance conditions. In this way, the regulation of DC bus voltage of the PV/BES system can be enhanced as compared to the conventional regulation that is solely based on the voltage-sourced converter (VSC). For the grid side VSC (G-VSC), two control methods, namely, the voltage-mode and current-mode controls, are applied. For control parameter optimization, the simplex optimization technique is applied for the G-VSC voltage- and current-mode controls, including the BES DC/DC buck-boost converter controllers. A new set of optimized parameters are obtained for each of the power converters for comparison purposes. The PSCAD/EMTDC-based simulation case studies are presented to evaluate the performance of the proposed optimized control scheme in comparison to the conventional methods. PMID:24883374
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Daud, Muhamad Zalani; Mohamed, Azah; Hannan, M A
2014-01-01
This paper presents an evaluation of an optimal DC bus voltage regulation strategy for grid-connected photovoltaic (PV) system with battery energy storage (BES). The BES is connected to the PV system DC bus using a DC/DC buck-boost converter. The converter facilitates the BES power charge/discharge to compensate for the DC bus voltage deviation during severe disturbance conditions. In this way, the regulation of DC bus voltage of the PV/BES system can be enhanced as compared to the conventional regulation that is solely based on the voltage-sourced converter (VSC). For the grid side VSC (G-VSC), two control methods, namely, the voltage-mode and current-mode controls, are applied. For control parameter optimization, the simplex optimization technique is applied for the G-VSC voltage- and current-mode controls, including the BES DC/DC buck-boost converter controllers. A new set of optimized parameters are obtained for each of the power converters for comparison purposes. The PSCAD/EMTDC-based simulation case studies are presented to evaluate the performance of the proposed optimized control scheme in comparison to the conventional methods.
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State laws on tobacco control--United States, 1998.
Fishman, J A; Allison, H; Knowles, S B; Fishburn, B A; Woollery, T A; Marx, W T; Shelton, D M; Husten, C G; Eriksen, M P
1999-06-25
State laws addressing tobacco use, the leading preventable cause of death in the United States, are summarized. Laws address smoke-free indoor air, minors' access to tobacco products, advertising of tobacco products, and excise taxes on tobacco products. Legislation effective through December 31, 1998. CDC identified laws addressing tobacco control by using an on-line legal research database. CDC's findings were verified with the National Cancer Institute's State Cancer Legislative Database. Since a previous surveillance summary on state tobacco-control laws published in November 1995 (covering legislation effective through June 30, 1995), several states have enacted new restrictions or strengthened existing legislation that addresses smoke-free indoor air, minors' access to tobacco, tobacco advertising, and tobacco taxes. Five states strengthened their smoke-free indoor air legislation. All states and Washington, D.C., continued to prohibit the sale and distribution of tobacco products to minors; however, 21 states expanded minors' access laws by designating enforcement authorities, adding license suspension or revocation for sale to minors, or requiring signage. Since the 1995 report, eight additional states (a total of 19 states and Washington, D.C.) now ban vending machines from areas accessible to minors. Thirteen states restrict advertising of tobacco products, an increase of four states since the 1995 report. Although the number of states that tax cigarettes and smokeless tobacco did not change, 13 states increased excise taxes on cigarettes, and five states increased excise taxes on smokeless tobacco products. The average state excise tax on cigarettes is 38.9 cents per pack, an increase of 7.4 cents compared with the average tax in the 1995 report. State laws addressing tobacco control vary in relation to restrictiveness, enforcement and penalties, preemptions, and exceptions. The data summarizing state tobacco-control laws are available through CDC's State Tobacco Activities Tracking and Evaluation (STATE) System; the laws are collected and updated every quarter. The STATE System also contains state-specific data on the prevalence of tobacco use, tobacco-related deaths, and the costs of tobacco use. Information from the STATE System is available for use by policy makers at the state and local levels to plan and implement initiatives to prevent and reduce tobacco use. In addition, CDC is using this information to assess the ongoing impact of tobacco-control programs and policies on tobacco use.
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Halbach array DC motor/generator
Merritt, B.T.; Dreifuerst, G.R.; Post, R.F.
1998-01-06
A new configuration of DC motor/generator is based on a Halbach array of permanent magnets. This motor does not use ferrous materials so that the only losses are winding losses and losses due to bearings and windage. An ``inside-out`` design is used as compared to a conventional motor/generator design. The rotating portion, i.e., the rotor, is on the outside of the machine. The stationary portion, i.e., the stator, is formed by the inside of the machine. The rotor contains an array of permanent magnets that provide a uniform field. The windings of the motor are placed in or on the stator. The stator windings are then ``switched`` or ``commutated`` to provide a DC motor/generator much the same as in a conventional DC motor. The commutation can be performed by mechanical means using brushes or by electronic means using switching circuits. The invention is useful in electric vehicles and adjustable speed DC drives. 17 figs.
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Halbach array DC motor/generator
Merritt, Bernard T.; Dreifuerst, Gary R.; Post, Richard F.
1998-01-01
A new configuration of DC motor/generator is based on a Halbach array of permanent magnets. This motor does not use ferrous materials so that the only losses are winding losses and losses due to bearings and windage. An "inside-out" design is used as compared to a conventional motor/generator design. The rotating portion, i.e., the rotor, is on the outside of the machine. The stationary portion, i.e., the stator, is formed by the inside of the machine. The rotor contains an array of permanent magnets that provide a uniform field. The windings of the motor are placed in or on the stator. The stator windings are then "switched" or "commutated" to provide a DC motor/generator much the same as in a conventional DC motor. The commutation can be performed by mechanical means using brushes or by electronic means using switching circuits. The invention is useful in electric vehicles and adjustable speed DC drives.
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Human spleen contains different subsets of dendritic cells and regulatory T lymphocytes
Velásquez-Lopera, M M; Correa, L A; García, L F
2008-01-01
Most knowledge about dendritic cells (DCs) and regulatory T cells in humans has been gathered from circulating cells but little is known about their frequency and distribution in lymphoid organs. This report shows the frequency, phenotype and location of DCs and regulatory T cells in deceased organ donors' spleens. As determined by flow cytometry, conventional/myeloid DCs (cDCs) CD11chighHLA-DR+CD123−/low were 2·3 ± 0·9% and LIN- HLA-DR+CD11chigh 2·1 ± 0·3% of total spleen cells. Mature CD11chighHLA-DR+CD83+ were 1·5 ± 0·8% and 1·0 ± 1·6% immature CD11chighHLA-DR+CD83- cDC. There were 0·3 ± 0·3% plasmacytoid DCs (pDC) CD11c−/lowHLA-DR+CD123high and 0·3 ± 0·1% LIN-HLA-DR+CD123high. Cells expressing cDCs markers, BDCA-1 and BDCA-3, and pDCs markers BDCA-2 and BDCA-4 were observed in higher frequencies than DCs with other phenotypes evaluated. CD11c+, CD123+ and CD83+ cells were located in subcapsular zone, T cells areas and B-cell follicles. CD4+CD25high Tregs were 0·2 ± 0·2% and CD8+CD28- comprised 11·5 ± 8·1% of spleen lymphocytes. FOXP3+ cells were found in T- and B-cell areas. The improvement in cell separation, manipulation and expansion techniques, will facilitate the manipulation of donor spleen cells as a part of protocols for induction and maintenance of allograft tolerance or treatment of autoimmune diseases. PMID:18727627
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NASA Astrophysics Data System (ADS)
Tanaka, S.; Ozaki, S.; Sakamoto, Y.; Tanuma, R.; Yoshida, T.; Murata, J.
2014-07-01
A new type of a trigger-scintillation counter array designed for the MTV experiment at TRIUMF-ISAC has been developed, which uses aluminum-metallized film tape for wrapping to achieve the required assembling precision of ±0.5 mm. The MTV experiment uses a cylindrical drift chamber (CDC) as the main electron-tracking detector. The barrel-type trigger counter is placed inside the CDC to generate a trigger signal using 1 mm thick, 300 mm long thin plastic scintillation counters. Detection efficiency and light attenuation compared with conventional wrapping materials are studied.
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Yan, Li; Hu, Rui; Tu, Song; Cheng, Wen-Jun; Zheng, Qiong; Wang, Jun-Wen; Kan, Wu-Sheng; Ren, Yi-Jun
2015-01-01
TNFα played a dominant role in the development and progression of rheumatoid arthritis (RA). Clinical trials proved the efficacies of anti-TNFα agents for curing RA. However, most researchers were concentrating on their abilities of neutralizing TNFα, the potencies of different anti-TNFα agents varied a lot due to the antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). For better understanding and differentiating the potentiality of various candidate anti-TNF reagents at the stage of new drug research and development, present study established a cell model expressing the transmembrane TNFα for usage in in vitro ADCC or CDC assay, meanwhile, the assay protocol described here could provide guidelines for screening macromolecular antibody drugs. A stable cell subline bearing transmembrane TNFα was first established by conventional transfection method, the expression of transmembrane TNFα was approved by flow cytometer, and the performance of the stable subline in ADCC and CDC assay was evaluated, using human peripheral blood mononuclear cells as effector cells, and Adalimumab as the anti-TNFα reagent. The stable cell subline demonstrated high level of surface expression of transmembrane TNFα, and Adalimumab exerted both ADCC and CDC effects on this cell model. In conclusion, the stable cell line we established in present research could be used in ADCC or CDC assay for screening antibody drugs, which would provide in-depth understanding of the potencies of candidate antibody drugs in addition to the traditional TNFα neutralizing assay.
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NASA Astrophysics Data System (ADS)
Pedersen, F.
2008-09-01
The presented bidirectional DC/DC converter design concept is a further development of an already existing converter used for low battery voltage operation.For low battery voltage operation a high efficient low parts count DC/DC converter was developed, and used in a satellite for the battery charge and battery discharge function.The converter consists in a bidirectional, non regulating DC/DC converter connected to a discharge regulating Buck converter and a charge regulating Buck converter.The Bidirectional non regulating DC/DC converter performs with relatively high efficiency even at relatively high currents, which here means up to 35Amps.This performance was obtained through the use of power MOSFET's with on- resistances of only a few mille Ohms connected to a special transformer allowing paralleling several transistor stages on the low voltage side of the transformer. The design is patent protected. Synchronous rectification leads to high efficiency at the low battery voltages considered, which was in the range 2,7- 4,3 Volt DC.The converter performs with low switching losses as zero voltage zero current switching is implemented in all switching positions of the converter.Now, the drive power needed, to switch a relatively large number of low Ohm , hence high drive capacitance, power MOSFET's using conventional drive techniques would limit the overall conversion efficiency.Therefore a resonant drive consuming considerable less power than a conventional drive circuit was implemented in the converter.To the originally built and patent protected bidirectional non regulating DC/DC converter, is added the functionality of regulation.Hereby the need for additional converter stages in form of a Charge Buck regulator and a Discharge Buck regulator is eliminated.The bidirectional DC/DC converter can be used in connection with batteries, motors, etc, where the bidirectional feature, simple design and high performance may be useful.
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Hardware Evolution of Analog Speed Controllers for a DC Motor
NASA Technical Reports Server (NTRS)
Gwaltney, David A.; Ferguson, Michael I.
2003-01-01
Evolvable hardware provides the capability to evolve analog circuits to produce amplifier and filter functions. Conventional analog controller designs employ these same functions. Analog controllers for the control of the shaft speed of a DC motor are evolved on an evolvable hardware platform utilizing a Field Programmable Transistor Array (FPTA). The performance of these evolved controllers is compared to that of a conventional proportional-integral (PI) controller.
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Optimized efficiency of all-electric ships by dc hybrid power systems
NASA Astrophysics Data System (ADS)
Zahedi, Bijan; Norum, Lars E.; Ludvigsen, Kristine B.
2014-06-01
Hybrid power systems with dc distribution are being considered for commercial marine vessels to comply with new stringent environmental regulations, and to achieve higher fuel economy. In this paper, detailed efficiency analysis of a shipboard dc hybrid power system is carried out. An optimization algorithm is proposed to minimize fuel consumption under various loading conditions. The studied system includes diesel engines, synchronous generator-rectifier units, a full-bridge bidirectional converter, and a Li-Ion battery bank as energy storage. In order to evaluate potential fuel saving provided by such a system, an online optimization strategy for fuel consumption is implemented. An Offshore Support Vessel (OSV) is simulated over different operating modes using the online control strategy. The resulted consumed fuel in the simulation is compared to that of a conventional ac power system, and also a dc power system without energy storage. The results show that while the dc system without energy storage provides noticeable fuel saving compared to the conventional ac system, optimal utilization of the energy storage in the dc system results in twice as much fuel saving.
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Conversion degrees of resin composites using different light sources.
Ozturk, Bora; Cobanoglu, Nevin; Cetin, Ali Rıza; Gunduz, Beniz
2013-01-01
The objective of this study was to compare the conversion degree of six different composite materials (Filtek Z 250, Filtek P60, Spectrum TPH, Pertac II, Clearfil AP-X, and Clearfil Photo Posterior) using three different light sources (blue light-emitting diode [LED], plasma arc curing [PAC], and conventional halogen lamp [QTH]). Composites were placed in a 2 mm thick and 5 mm diameter Teflon molds and light cured from the top using three methods: LED for 40 s, PAC for 10 s, and QTH for 40 s. A Fourier Transform Infrared Spectroscopy (FTIR) was used to evaluate the degree of conversion (DC) (n=5). The results were analyzed with two-way analysis of variance and Tukey HSD test. DC was significantly influenced by two variables, light source and composite (P<.05). QTH revealed significantly higher DC values than LED (P<.05). However, there were no significant differences between DC values of QTH and PAC or between DC values of LED and PAC (P>.05). The highest DC was observed in the Z 250 composite specimens following photopolymerization with QTH (70%). The lowest DC was observed in Clearfil Photo Posterior composite specimens following photo-polymerization with LED (43%). The DC was found to be changing according to both light sources and composite materials used. Conventional light halogen (QTH) from light sources and Filtek Z 250 and Filtek P 60 among composite materials showed the most DC performance.
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NASA Technical Reports Server (NTRS)
Howe, G.; Saunders, D.
1983-01-01
Users of the CDC 7600 at Ames are assisted in making the transition to the CRAY-1. Similarities and differences in the basic JCL are summarized, and a dozen or so examples of typical batch jobs for the two systems are shown in parallel. Some changes to look for in FORTRAN programs and in the use of UPDATE are also indicated. No attempt is made to cover magnetic tape handling. The material here should not be considered a substitute for reading the more conventional manuals or the User's Guide for the Advanced Computational Facility, available from the Computer Information Center.
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NASA Astrophysics Data System (ADS)
Asano, Hiroki; Hirose, Tetsuya; Kojima, Yuta; Kuroki, Nobutaka; Numa, Masahiro
2018-04-01
In this paper, we present a wide-load-range switched-capacitor DC-DC buck converter with an adaptive bias comparator for ultra-low-power power management integrated circuit. The proposed converter is based on a conventional one and modified to operate in a wide load range by developing a load current monitor used in an adaptive bias comparator. Measurement results demonstrated that our proposed converter generates a 1.0 V output voltage from a 3.0 V input voltage at a load of up to 100 µA, which is 20 times higher than that of the conventional one. The power conversion efficiency was higher than 60% in the load range from 0.8 to 100 µA.
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Analysis of high voltage step-up nonisolated DC-DC boost converters
NASA Astrophysics Data System (ADS)
Alisson Alencar Freitas, Antônio; Lessa Tofoli, Fernando; Junior, Edilson Mineiro Sá; Daher, Sergio; Antunes, Fernando Luiz Marcelo
2016-05-01
A high voltage step-up nonisolated DC-DC converter based on coupled inductors suitable to photovoltaic (PV) systems applications is proposed in this paper. Considering that numerous approaches exist to extend the voltage conversion ratio of DC-DC converters that do not use transformers, a detailed comparison is also presented among the proposed converter and other popular topologies such as the conventional boost converter and the quadratic boost converter. The qualitative analysis of the coupled-inductor-based topology is developed so that a design procedure can be obtained, from which an experimental prototype is implemented to validate the theoretical assumptions.
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Workshop on Transitioning Structural Health Monitoring Technology to Military Platforms
2012-08-28
sensors that can be multiplexed such as extrinsic Fabry -Perot interferometers (EFPI), but they are rarely used for structural monitoring. We have not...bureau, and outbreak monitoring by the US Centers for Disease Control (CDC). One approach to data management is replacing conventional processing
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Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells
Reihl, Alec M.
2016-01-01
Dendritic cells (DC) play an important role in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease with multiple tissue manifestations. In this review, we summarize recent studies on the roles of conventional DC and plasmacytoid DC in the development of both murine lupus and human SLE. In the past decade, studies using selective DC depletions have demonstrated critical roles of DC in lupus progression. Comprehensive in vitro and in vivo studies suggest activation of DC by self-antigens in lupus pathogenesis, followed by breakdown of immune tolerance to self. Potential treatment strategies targeting DC have been developed. However, many questions remain regarding the mechanisms by which DC modulate lupus pathogenesis that require further investigations. PMID:27034965
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Kim, Hyun-Jin; Bagheri, Rafat; Kim, Young Kyung; Son, Jun Sik; Kwon, Tae-Yub
2017-01-01
This study investigated the influence of curing mode (dual- or self-cure) on the surface energy and sorption/solubility of four self-adhesive resin cements (SARCs) and one conventional resin cement. The degree of conversion (DC) and surface energy parameters including degree of hydrophilicity (DH) were determined using Fourier transform infrared spectroscopy and contact angle measurements, respectively (n = 5). Sorption and solubility were assessed by mass gain or loss after storage in distilled water or lactic acid for 60 days (n = 5). A linear regression model was used to correlate between the results (%DC vs. DH and %DC/DH vs. sorption/solubility). For all materials, the dual-curing consistently produced significantly higher %DC values than the self-curing (p < 0.05). Significant negative linear regressions were established between the %DC and DH in both curing modes (p < 0.05). Overall, the SARCs showed higher sorption/solubility values, in particular when immersed in lactic acid, than the conventional resin cement. Linear regression revealed that %DC and DH were negatively and positively correlated with the sorption/solubility values, respectively. Dual-curing of SARCs seems to lower the sorption and/or solubility in comparison with self-curing by increased %DC and occasionally decreased hydrophilicity. PMID:28772489
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Sliding mode controller with modified sliding function for DC-DC Buck Converter.
Naik, B B; Mehta, A J
2017-09-01
This article presents design of Sliding Mode Controller with proportional integral type sliding function for DC-DC Buck Converter for the controlled power supply. The converter with conventional sliding mode controller results in a steady state error in load voltage. The proposed modified sliding function improves the steady state and dynamic performance of the Convertor and facilitates better choices of controller tuning parameters. The conditions for existence of sliding modes for proposed control scheme are derived. The stability of the closed loop system with proposed sliding mode control is proved and improvement in steady state performance is exemplified. The idea of adaptive tuning for the proposed controller to compensate load variations is outlined. The comparative study of conventional and proposed control strategy is presented. The efficacy of the proposed strategy is endowed by the simulation and experimental results. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.
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Electric power processing, distribution and control for advanced aerospace vehicles.
NASA Technical Reports Server (NTRS)
Krausz, A.; Felch, J. L.
1972-01-01
The results of a current study program to develop a rational basis for selection of power processing, distribution, and control configurations for future aerospace vehicles including the Space Station, Space Shuttle, and high-performance aircraft are presented. Within the constraints imposed by the characteristics of power generation subsystems and the load utilization equipment requirements, the power processing, distribution and control subsystem can be optimized by selection of the proper distribution voltage, frequency, and overload/fault protection method. It is shown that, for large space vehicles which rely on static energy conversion to provide electric power, high-voltage dc distribution (above 100 V dc) is preferable to conventional 28 V dc and 115 V ac distribution per MIL-STD-704A. High-voltage dc also has advantages over conventional constant frequency ac systems in many aircraft applications due to the elimination of speed control, wave shaping, and synchronization equipment.
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The Good, the Bad, and the Ugly of Dendritic Cells during Prion Disease
Mabbott, Neil Andrew; Bradford, Barry Matthew
2015-01-01
Prions are a unique group of proteinaceous pathogens which cause neurodegenerative disease and can be transmitted by a variety of exposure routes. After peripheral exposure, the accumulation and replication of prions within secondary lymphoid organs are obligatory for their efficient spread from the periphery to the brain where they ultimately cause neurodegeneration and death. Mononuclear phagocytes (MNP) are a heterogeneous population of dendritic cells (DC) and macrophages. These cells are abundant throughout the body and display a diverse range of roles based on their anatomical locations. For example, some MNP are strategically situated to provide a first line of defence against pathogens by phagocytosing and destroying them. Conventional DC are potent antigen presenting cells and migrate via the lymphatics to the draining lymphoid tissue where they present the antigens to lymphocytes. The diverse roles of MNP are also reflected in various ways in which they interact with prions and in doing so impact on disease pathogenesis. Indeed, some studies suggest that prions exploit conventional DC to infect the host. Here we review our current understanding of the influence of MNP in the pathogenesis of the acquired prion diseases with particular emphasis on the role of conventional DC. PMID:26697507
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Composite Ceramic Superconducting Wires for Electric Motor Applications
1988-12-30
current a-yi t6-ransition. - Emerson Motor Division has begun work on DC heteropolar and homopolar motor designs. The mechanical stresses on conventional...Emerson Motor Division has begun work on DC heteropolar motor designs and, through Professor Novotny at U. Wisconsin, DC homopolar machines. The...123 3.2 Literature Research .............................. .. 124 3 3.3 Application Study .............................. .. 124 3.3.1 Homopolar Motor
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NASA Astrophysics Data System (ADS)
Wang, Bin; Xu, Jun; Cao, Binggang; Zhou, Xuan
2015-05-01
This paper proposes a novel topology of multimode hybrid energy storage system (HESS) and its energy management strategy for electric vehicles (EVs). Compared to the conventional HESS, the proposed multimode HESS has more operating modes and thus it could in further enhance the efficiency of the system. The rule-based control strategy and the power-balancing strategy are developed for the energy management strategy to realize mode selection and power distribution. Generally, the DC-DC converter will operate at peak efficiency to convey the energy from the batteries to the UCs. Otherwise, the pure battery mode or the pure ultracapacitors (UCs) mode will be utilized without the DC-DC converter. To extend the battery life, the UCs have the highest priority to recycle the energy and the batteries are isolated from being recharged directly during regenerative braking. Simulations and experiments are established to validate the proposed multimode HESS and its energy management strategy. The results reveal that the energy losses in the DC-DC converter, the total energy consumption and the overall system efficiency of the proposed multimode HESS are improved compared to the conventional HESS.
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Simultaneous distribution of AC and DC power
Polese, Luigi Gentile
2015-09-15
A system and method for the transport and distribution of both AC (alternating current) power and DC (direct current) power over wiring infrastructure normally used for distributing AC power only, for example, residential and/or commercial buildings' electrical wires is disclosed and taught. The system and method permits the combining of AC and DC power sources and the simultaneous distribution of the resulting power over the same wiring. At the utilization site a complementary device permits the separation of the DC power from the AC power and their reconstruction, for use in conventional AC-only and DC-only devices.
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NASA Technical Reports Server (NTRS)
Rippel, W. E.; Edwards, D. B.
1984-01-01
Commutation by field-effect transistor allows more efficient operation. High voltage field-effect transistor (FET) controls silicon controlled rectifiers (SCR's). Circuit requires only one capacitor and one inductor in commutation circuit: simpler, more efficient, and more economical than conventional inverters. Adaptable to dc-to-dc converters.
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German, Danielle; Brady, Kathleen; Kuo, Irene; Opoku, Jenevieve; Flynn, Colin; Patrick, Rudy; Park, Ju Nyeong; Adams, Joella; Carroll, Makeda; Simmons, Ron; Smith, Carlton R; Davis, Wendy W
2017-07-01
Baltimore, Philadelphia, and Washington, DC are geographically proximate cities with high HIV prevalence, including among black men who have sex with men (BMSM). Using data collected among BMSM in CDC's National HIV Behavioral Surveillance project, we compared socio-demographic characteristics, HIV risk behaviors, and service utilization to explore similarities and differences that could inform local and regional HIV intervention approaches. BMSM were recruited through venue time location sampling, June-December, 2011. Participants completed identical socio-behavioral surveys and voluntary HIV testing. Analyses were conducted among the full sample and those aged 18-24. Participants included 159 (DC), 364 (Baltimore), and 331 (Philadelphia) eligible BMSM. HIV prevalence was 23.1% (DC), 48.0% (Baltimore), 14.6% (Philadelphia) with 30.6%, 69.0%, 33.3% unrecognized HIV infection, respectively. Among BMSM 18-24, HIV prevalence was 11.1% (DC), 38.9% (Baltimore), 9.6% (Philadelphia) with unrecognized HIV infection 0.0%, 73.8%, 60.0% respectively. Compared with the other 2 cities, Baltimore participants were less likely to identify as gay/homosexual; more likely to report unemployment, incarceration, homelessness, sex exchange; and least likely to use the internet for partners. DC participants were more likely to have a college degree and employment. Philadelphia participants were more likely to report gay/homosexual identity, receptive condomless anal sex, having only main partners, and bars/clubs as partner meeting places. Sexually transmitted disease testing was universally low. Analyses showed especially high HIV prevalence among BMSM in Baltimore including among young BMSM. Socio-demographic characteristics and HIV infection correlates differed across cities but unrecognized HIV infection and unknown partner status were universally high.
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Damiran, Daalkhaijav; Yu, Peiqiang
2010-02-24
Recently, a new "super" genotype of oats (CDC SO-I or SO-I) has been developed. The objectives of this study were to determine structural makeup (features) of oat grain in endosperm and pericarp regions and to reveal and identify differences in protein amide I and II and carbohydrate structural makeup (conformation) between SO-I and two conventional oats (CDC Dancer and Derby) grown in western Canada in 2006, using advanced synchrotron radiation based Fourier transform infrared microspectroscopy (SRFTIRM). The SRFTIRM experiments were conducted at National Synchrotron Light Sources, Brookhaven National Laboratory (NSLS, BNL, U.S. Department of Energy). From the results, it was observed that comparison between the new genotype oats and conventional oats showed (1) differences in basic chemical and protein subfraction profiles and energy values with the new SO-I oats containing lower lignin (21 g/kg of DM) and higher soluble crude protein (530 g/kg CP), crude fat (59 g/kg of DM), and energy values (TDN, 820 g/kg of DM; NE(L3x), 7.8 MJ/kg of DM); (2) significant differences in rumen biodegradation kinetics of dry matter, starch, and protein with the new SO-I oats containing lower EDDM (638 g/kg of DM) and higher EDCP (103 g/kg of DM); (3) significant differences in nutrient supply with highest truly absorbed rumen undegraded protein (ARUP, 23 g/kg of DM) and total metabolizable protein supply (MP, 81 g/kg of DM) from the new SO-I oats; and (4) significant differences in structural makeup in terms of protein amide I in the endosperm region (with amide I peak height from 0.13 to 0.22 IR absorbance unit) and cellulosic compounds to carbohydrate ratio in the pericarp region (ratio from 0.02 to 0.06). The results suggest that with the SRFTIRM technique, the structural makeup differences between the new genotype oats (SO-I) and two conventional oats (Dancer and Derby) could be revealed.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Damiran, D.; Yu, P
Recently, a new 'super' genotype of oats (CDC SO-I or SO-I) has been developed. The objectives of this study were to determine structural makeup (features) of oat grain in endosperm and pericarp regions and to reveal and identify differences in protein amide I and II and carbohydrate structural makeup (conformation) between SO-I and two conventional oats (CDC Dancer and Derby) grown in western Canada in 2006, using advanced synchrotron radiation based Fourier transform infrared microspectroscopy (SRFTIRM). The SRFTIRM experiments were conducted at National Synchrotron Light Sources, Brookhaven National Laboratory (NSLS, BNL, U.S. Department of Energy). From the results, it wasmore » observed that comparison between the new genotype oats and conventional oats showed (1) differences in basic chemical and protein subfraction profiles and energy values with the new SO-I oats containing lower lignin (21 g/kg of DM) and higher soluble crude protein (530 g/kg CP), crude fat (59 g/kg of DM), and energy values (TDN, 820 g/kg of DM; NE{sub L3x}, 7.8 MJ/kg of DM); (2) significant differences in rumen biodegradation kinetics of dry matter, starch, and protein with the new SO-I oats containing lower EDDM (638 g/kg of DM) and higher EDCP (103 g/kg of DM); (3) significant differences in nutrient supply with highest truly absorbed rumen undegraded protein (ARUP, 23 g/kg of DM) and total metabolizable protein supply (MP, 81 g/kg of DM) from the new SO-I oats; and (4) significant differences in structural makeup in terms of protein amide I in the endosperm region (with amide I peak height from 0.13 to 0.22 IR absorbance unit) and cellulosic compounds to carbohydrate ratio in the pericarp region (ratio from 0.02 to 0.06). The results suggest that with the SRFTIRM technique, the structural makeup differences between the new genotype oats (SO-I) and two conventional oats (Dancer and Derby) could be revealed.« less
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Sliding-mode control of single input multiple output DC-DC converter
NASA Astrophysics Data System (ADS)
Zhang, Libo; Sun, Yihan; Luo, Tiejian; Wan, Qiyang
2016-10-01
Various voltage levels are required in the vehicle mounted power system. A conventional solution is to utilize an independent multiple output DC-DC converter whose cost is high and control scheme is complicated. In this paper, we design a novel SIMO DC-DC converter with sliding mode controller. The proposed converter can boost the voltage of a low-voltage input power source to a controllable high-voltage DC bus and middle-voltage output terminals, which endow the converter with characteristics of simple structure, low cost, and convenient control. In addition, the sliding mode control (SMC) technique applied in our converter can enhance the performances of a certain SIMO DC-DC converter topology. The high-voltage DC bus can be regarded as the main power source to the high-voltage facility of the vehicle mounted power system, and the middle-voltage output terminals can supply power to the low-voltage equipment on an automobile. In the respect of control algorithm, it is the first time to propose the SMC-PID (Proportion Integration Differentiation) control algorithm, in which the SMC algorithm is utilized and the PID control is attended to the conventional SMC algorithm. The PID control increases the dynamic ability of the SMC algorithm by establishing the corresponding SMC surface and introducing the attached integral of voltage error, which endow the sliding-control system with excellent dynamic performance. At last, we established the MATLAB/SIMULINK simulation model, tested performance of the system, and built the hardware prototype based on Digital Signal Processor (DSP). Results show that the sliding mode control is able to track a required trajectory, which has robustness against the uncertainties and disturbances.
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Sliding-mode control of single input multiple output DC-DC converter.
Zhang, Libo; Sun, Yihan; Luo, Tiejian; Wan, Qiyang
2016-10-01
Various voltage levels are required in the vehicle mounted power system. A conventional solution is to utilize an independent multiple output DC-DC converter whose cost is high and control scheme is complicated. In this paper, we design a novel SIMO DC-DC converter with sliding mode controller. The proposed converter can boost the voltage of a low-voltage input power source to a controllable high-voltage DC bus and middle-voltage output terminals, which endow the converter with characteristics of simple structure, low cost, and convenient control. In addition, the sliding mode control (SMC) technique applied in our converter can enhance the performances of a certain SIMO DC-DC converter topology. The high-voltage DC bus can be regarded as the main power source to the high-voltage facility of the vehicle mounted power system, and the middle-voltage output terminals can supply power to the low-voltage equipment on an automobile. In the respect of control algorithm, it is the first time to propose the SMC-PID (Proportion Integration Differentiation) control algorithm, in which the SMC algorithm is utilized and the PID control is attended to the conventional SMC algorithm. The PID control increases the dynamic ability of the SMC algorithm by establishing the corresponding SMC surface and introducing the attached integral of voltage error, which endow the sliding-control system with excellent dynamic performance. At last, we established the MATLAB/SIMULINK simulation model, tested performance of the system, and built the hardware prototype based on Digital Signal Processor (DSP). Results show that the sliding mode control is able to track a required trajectory, which has robustness against the uncertainties and disturbances.
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An Attempt to Shorten Loading Time of Epirubicin into DC Beads® Using Vibration and a Sieve.
Sonoda, Akinaga; Nitta, Norihisa; Yamamoto, Takefumi; Tomozawa, Yuki; Ohta, Shinichi; Watanabe, Shobu; Murata, Kiyoshi
2017-04-01
We investigated the possibility of shortening the time required for loading epirubicin into calibrated polyvinyl alcohol-based hydrogel beads (DC Beads ® ) to be used for transarterial chemoembolization. After separating the beads suspended in phosphate-buffered saline (PBS) solution by the use of a sieve (clearance 75 µm), epirubicin hydrochloride (EH) was loaded for 20, 30, or 60 s under vibration into DC beads. The EH loading rate into conventionally prepared (control) beads, i.e., beads loaded for 30 min without vibration, and vibration-loaded beads were calculated from the residual EH concentration in the bead-depleted EH solution. The amount of EH eluted from conventionally and vibration-loaded samples into a PBS solution (pH 7.0) was measured at 15 and 30 min and 1, 2, 6, 12, and 24 h. We also recorded the inhibitory effect of the PBS solution on the loading time. Using frozen sections, the EH load in the beads was evaluated visually under a fluorescence microscope. Spectrophotometry (495 nm) showed that the loading rate was 98.98 ± 0.34, 99.02 ± 0.32, and 99.50 ± 0.11 % with 20-, 30-, and 60-s vibration, respectively. The eluted rate was statistically similar between vibration- and statically loaded (control) beads. The PBS solution hampered EH loading into the beads. Visually, the distribution of EH in conventionally and vibration-loaded DC beads was similar. The use of vibration and the removal of PBS solution when epirubicin hydrochloride was loaded into DC beads dramatically shortened the loading time of epirubicin hydrochloride into DC beads.
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2012-01-24
Kersey et. al., 1997). There are other types of fiber optic sensors that can be multiplexed such as extrinsic Fabry -Perot interferometers (EFPI), but...census bureau, and outbreak monitoring by the US Centers for Disease Control (CDC). • One approach to data management is replacing conventional
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Design of an Input-Parallel Output-Parallel LLC Resonant DC-DC Converter System for DC Microgrids
NASA Astrophysics Data System (ADS)
Juan, Y. L.; Chen, T. R.; Chang, H. M.; Wei, S. E.
2017-11-01
Compared with the centralized power system, the distributed modularized power system is composed of several power modules with lower power capacity to provide a totally enough power capacity for the load demand. Therefore, the current stress of the power components in each module can then be reduced, and the flexibility of system setup is also enhanced. However, the parallel-connected power modules in the conventional system are usually controlled to equally share the power flow which would result in lower efficiency in low loading condition. In this study, a modular power conversion system for DC micro grid is developed with 48 V dc low voltage input and 380 V dc high voltage output. However, in the developed system control strategy, the numbers of power modules enabled to share the power flow is decided according to the output power at lower load demand. Finally, three 350 W power modules are constructed and parallel-connected to setup a modular power conversion system. From the experimental results, compared with the conventional system, the efficiency of the developed power system in the light loading condition is greatly improved. The modularized design of the power system can also decrease the power loss ratio to the system capacity.
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Various meteor scenes II: Cygnid-Draconid Complex (κ-Cygnids)
NASA Astrophysics Data System (ADS)
Koseki, Masahiro
2014-10-01
Japanese video observers caught a rich `κ-Cygnid' recurrent event in 2007 after an outburst observed by DMS in 1993. Classic `κ-Cygnids' were observed photographically in 1950 and 1957. The shower might be recurrent with a 7 year period. This led to a call for 2014 observations in WGN (42:3, p. 89). The author showed in Paper I (Koseki, 2014) that the perception and the conception of a meteor shower are so different that there are many confused results. `κ-Cygnids' are a good such example and give different impressions from different observational techniques and from different years. It is suggested modern so-called `κ-Cygnids' now are not a single shower but a part of the Cygnids-Draconids Complex (CDC). CDC consists of several minor showers: the classic (photographic) one KCG1, the modern recurrent one KCG2, the one in average years KCG3, and three other activities. `κ-Cygnids' in average years are different from classic `&kappa-Cygnids' and ;DC looks different based on the different conception and the different perception (observing methods) of a meteor shower.
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West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United States, 2015.
Krow-Lucal, Elisabeth; Lindsey, Nicole P; Lehman, Jennifer; Fischer, Marc; Staples, J Erin
2017-01-20
Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bites of infected mosquitoes and ticks. The leading cause of domestically acquired arboviral disease in the United States is West Nile virus (WNV) (1). Other arboviruses, including La Crosse, St. Louis encephalitis, Jamestown Canyon, Powassan, and eastern equine encephalitis viruses, also cause sporadic cases and outbreaks. This report summarizes surveillance data reported to CDC in 2015 for nationally notifiable arboviruses. It excludes dengue, chikungunya, and Zika viruses, which are primarily nondomestic viruses typically acquired through travel (and are addressed in other CDC reports). In 2015, 45 states and the District of Columbia (DC) reported 2,282 cases of domestic arboviral disease. Among these cases, 2,175 (95%) were WNV disease and 1,455 (67%) of those were classified as neuroinvasive disease (meningitis, encephalitis, or acute flaccid paralysis). The national incidence of WNV neuroinvasive disease was 0.45 cases per 100,000 population. Because arboviral diseases continue to cause serious illness, maintaining surveillance is important to direct prevention activities such as reduction of vector populations and screening of blood donors.
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Microstructural Evolution in Intensively Melt Sheared Direct Chill Cast Al-Alloys
NASA Astrophysics Data System (ADS)
Jones, S.; Rao, A. K. Prasada; Patel, J. B.; Scamans, G. M.; Fan, Z.
The work presented here introduces the novel melt conditioned direct chill casting (MC-DC) technology, where intensive melt shearing is applied to the conventional direct-chill casting process. MC-DC casting can successfully produce high quality Al-alloy billets. The results obtained from 80 mm diameter billets cast at speed of 200 mm/min show that MC-DC casting of Al-alloys, substantially refines the microstructure and reduces macro-segregation. In this paper, we present the preliminary results and discuss microstructural evolution during MC-DC casting of Al-alloys.
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An Optimal Current Observer for Predictive Current Controlled Buck DC-DC Converters
Min, Run; Chen, Chen; Zhang, Xiaodong; Zou, Xuecheng; Tong, Qiaoling; Zhang, Qiao
2014-01-01
In digital current mode controlled DC-DC converters, conventional current sensors might not provide isolation at a minimized price, power loss and size. Therefore, a current observer which can be realized based on the digital circuit itself, is a possible substitute. However, the observed current may diverge due to the parasitic resistors and the forward conduction voltage of the diode. Moreover, the divergence of the observed current will cause steady state errors in the output voltage. In this paper, an optimal current observer is proposed. It achieves the highest observation accuracy by compensating for all the known parasitic parameters. By employing the optimal current observer-based predictive current controller, a buck converter is implemented. The converter has a convergently and accurately observed inductor current, and shows preferable transient response than the conventional voltage mode controlled converter. Besides, costs, power loss and size are minimized since the strategy requires no additional hardware for current sensing. The effectiveness of the proposed optimal current observer is demonstrated experimentally. PMID:24854061
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High static gain single-phase PFC based on a hybrid boost converter
NASA Astrophysics Data System (ADS)
Flores Cortez, Daniel; Maccarini, Marcello C.; Mussa, Samir A.; Barbi, Ivo
2017-05-01
In this paper, a single-phase unity power factor rectifier, based on a hybrid boost converter, resulting from the integration of a conventional dc-dc boost converter and a switched-capacitor voltage doubler is proposed, analysed, designed and tested. The high-power rectifier is controlled by two feedback loops with the same control strategy employed in the conventional boost-based rectifier. The main feature of the proposed rectifier is its ability to output a dc voltage larger than the double of the peak value of the input line voltage, while subjecting the power switches to half of the dc-link voltage, which contributes to reducing the cost and increasing the efficiency. Experimental data were obtained from a laboratory prototype with an input voltage of 220 Vrms, line frequency of 60 Hz, output voltage of 800 Vdc, load power of 1000 W and switching frequency of 50 kHz. The efficiency of the prototype, measured in the laboratory, was 96.5% for full load and 97% for half load.
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NASA Astrophysics Data System (ADS)
Gu, C.; Li, J.; Toksoz, M. N.
2013-12-01
Induced seismicity occurs both in conventional oil/gas fields due to production and water injection and in unconventional oil/gas fields due to hydraulic fracturing. Source mechanisms of these induced earthquakes are of great importance for understanding their causes and the physics of the seismic processes in reservoirs. Previous research on the analysis of induced seismic events in conventional oil/gas fields assumed a double couple (DC) source mechanism. However, recent studies have shown a non-negligible percentage of a non-double-couple (non-DC) component of source moment tensor in hydraulic fracturing events (Šílený et al., 2009; Warpinski and Du, 2010; Song and Toksöz, 2011). In this study, we determine the full moment tensor of the induced seismicity data in a conventional oil/gas field and for hydrofrac events in an unconventional oil/gas field. Song and Toksöz (2011) developed a full waveform based complete moment tensor inversion method to investigate a non-DC source mechanism. We apply this approach to the induced seismicity data from a conventional gas field in Oman. In addition, this approach is also applied to hydrofrac microseismicity data monitored by downhole geophones in four wells in US. We compare the source mechanisms of induced seismicity in the two different types of gas fields and explain the differences in terms of physical processes.
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Rahman, M Jubayer; Rahir, Gwendoline; Dong, Matthew B; Zhao, Yongge; Rodrigues, Kameron B; Hotta-Iwamura, Chie; Chen, Ye; Guerrero, Alan; Tarbell, Kristin V
2016-03-01
Innate immune signals help break self-tolerance to initiate autoimmune diseases such as type 1 diabetes, but innate contributions to subsequent regulation of disease progression are less clear. Most studies have measured in vitro innate responses of GM-CSF dendritic cells (DCs) that are functionally distinct from conventional DCs (cDCs) and do not reflect in vivo DC subsets. To determine whether autoimmune NOD mice have alterations in type 1 IFN innate responsiveness, we compared cDCs from prediabetic NOD and control C57BL/6 (B6) mice stimulated in vivo with the TLR9 ligand CpG, a strong type 1 IFN inducer. In response to CpG, NOD mice produce more type 1 IFN and express higher levels of CD40, and NOD monocyte DCs make more TNF. However, the overall CpG-induced transcriptional response is muted in NOD cDCs. Of relevance the costimulatory proteins CD80/CD86, signals needed for regulatory T cell homeostasis, are upregulated less on NOD cDCs. Interestingly, NOD Rag1(-/-) mice also display a defect in CpG-induced CD86 upregulation compared with B6 Rag1(-/-), indicating this particular innate alteration precedes adaptive autoimmunity. The impaired response in NOD DCs is likely downstream of the IFN-α/β receptor because DCs from NOD and B6 mice show similar CpG-induced CD86 levels when anti-IFN-α/β receptor Ab is added. IFN-α-induced nuclear localization of activated STAT1 is markedly reduced in NOD CD11c(+) cells, consistent with lower type 1 IFN responsiveness. In conclusion, NOD DCs display altered innate responses characterized by enhanced type 1 IFN and activation of monocyte-derived DCs but diminished cDC type 1 IFN response.
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1987 CRC Octane Number Requirement Survey
1988-08-01
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On Application of Model Predictive Control to Power Converter with Switching
NASA Astrophysics Data System (ADS)
Zanma, Tadanao; Fukuta, Junichi; Doki, Shinji; Ishida, Muneaki; Okuma, Shigeru; Matsumoto, Takashi; Nishimori, Eiji
This paper concerns a DC-DC converter control. In DC-DC converters, there exist both continuous components such as inductance, conductance and resistance and discrete ones, IGBT and MOSFET as semiconductor switching elements. Such a system can be regarded as a hybrid dynamical system. Thus, this paper presents a dc-dc control technique based on the model predictive control. Specifically, a case in which the load of the dc-dc converter changes from active to sleep is considered. In the case, a control method which makes the output voltage follow to the reference quickly in transition, and the switching frequency be constant in steady state. In addition, in applying the model predictive control to power electronics circuits, the switching characteristic of the device and the restriction condition for protection are also considered. The effectiveness of the proposed method is illustrated by comparing a conventional method through some simulation results.
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He, Jingzhen; Zu, Yuliang; Wang, Qing; Ma, Xiangxing
2014-12-01
The purpose of this study was to determine the performance of low-dose computed tomography (CT) scanning with integrated circuit (IC) detector in defining fine structures of temporal bone in children by comparing with the conventional detector. The study was performed with the approval of our institutional review board and the patients' anonymity was maintained. A total of 86 children<3 years of age underwent imaging of temporal bone with low-dose CT (80 kV/150 mAs) equipped with either IC detector or conventional discrete circuit (DC) detector. The image noise was measured for quantitative analysis. Thirty-five structures of temporal bone were further assessed and rated by 2 radiologists for qualitative analysis. κ Statistics were performed to determine the agreement reached between the 2 radiologists on each image. Mann-Whitney U test was used to determine the difference in image quality between the 2 detector systems. Objective analysis showed that the image noise was significantly lower (P<0.001) with the IC detector than with the DC detector. The κ values for qualitative assessment of the 35 fine anatomical structures revealed high interobserver agreement. The delineation for 30 of the 35 landmarks (86%) with the IC detector was superior to that with the conventional DC detector (P<0.05) although there were no differences in the delineation of the remaining 5 structures (P>0.05). The low-dose CT images acquired with the IC detector provide better depiction of fine osseous structures of temporal bone than that with the conventional DC detector.
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-27
... (closed to public). 11-2:30 p.m. Planning and Evaluation Committee. 2:30-3 Budget committee. 3-3:30 Ad Hoc... Embassy Suites DC Convention Center Hotel, located at 900 10th Street, NW., Washington, DC 20001. FOR... the draft March 31, 2010 meeting minutes. Budget Committee Report. Planning and Evaluation Committee...
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The relative immunity of high-frequency transposed stimuli to low-frequency binaural interference
NASA Astrophysics Data System (ADS)
Bernstein, Leslie R.; Trahiotis, Constantine
2004-05-01
We have recently demonstrated that high-frequency transposed stimuli, having envelopes designed to provide high-frequency channels with information similar to that normally available in only low-frequency channels, yield threshold-ITDs and extents of laterality comparable to those obtained with conventional low-frequency stimuli. This enhanced potency of ITDs conveyed by high-frequency transposed stimuli, as compared to conventional high-frequency stimuli, suggested to us that ITDs conveyed by transposed stimuli might be relatively immune to the presence of low-frequency binaural interferers. To investigate this issue, threshold-ITDs and extents of laterality were measured with a variety of conventional and transposed targets centered at 4 kHz. The targets were presented either in the presence or absence of a simultaneously gated diotic noise centered at 500 Hz, the interferer. As expected, the presence of the low-frequency interferer resulted in substantially elevated threshold-ITDs and reduced extents of laterality for the conventional high-frequency stimuli. In contrast, these interference effects were either greatly attenuated or absent for ITDs conveyed by the high-frequency transposed targets. The results will be discussed in the context of current models of binaural interference. [Work supported by NIH DC 04147, NIH DC04073, NIH DC 002304.
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AC to DC Bridgeless Boost Converter for Ultra Low Input Energy Harvesting
NASA Astrophysics Data System (ADS)
Dawam, A. H. A.; Muhamad, M.
2018-03-01
This paper presents design of circuit which converts low input AC voltage to a higher output DC voltage. A buck-boost topology and boost topology are combined to condition cycle of an AC input voltage. the unique integration of a combining circuit of buck-boost and boost circuit have been proposed in order to introduce a new direct ac-dc power converter topology without conventional diode bridge rectifier. The converter achieved to convert a milli-volt scale of input AC voltage into a volt scale of output DC voltages which is from 400mV to 3.3V.
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Type I interferon regulates pDC maturation and Ly49Q expression.
Toma-Hirano, Makiko; Namiki, Sahori; Miyatake, Shoichiro; Arai, Ken-Ichi; Kamogawa-Schifter, Yumiko
2007-10-01
Ly49Q is expressed on peripheral mouse plasmacytoid dendritic cells (pDC). Immature Ly49Q-negative pDC precursors acquire Ly49Q in the bone marrow and then migrate into the periphery. While searching for molecules that regulate pDC maturation, we found that type I interferon (IFN) inhibited Ly49Q acquisition in vitro. Infections that induce type I IFN production by cells other than pDC (a condition mimicked by poly(I:C) injection in vivo) increase the prevalence of Ly49Q(-) pDC in the bone marrow and peripheral lymphoid organs in wild-type but not IFN-alpha/beta receptor knockout BALB/c mice. Moreover, in vivo exposure to type I IFN causes some Ly49Q(-), but not Ly49Q(+), pDC to convert to conventional DC, defined as B220(-) CD11c(+) CD11b(+) cells. These data suggest that type I IFN regulates pDC development and affects their distribution in the body.
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DC-DC power converter research for Orbiter/Station power exchange
NASA Technical Reports Server (NTRS)
Ehsani, M.
1993-01-01
This project was to produce innovative DC-DC power converter concepts which are appropriate for the power exchange between the Orbiter and the Space Station Freedom (SSF). The new converters must interface three regulated power buses on SSF, which are at different voltages, with three fuel cell power buses on the Orbiter which can be at different voltages and should be tracked independently. Power exchange is to be bi-directional between the SSF and the Orbiter. The new converters must satisfy the above operational requirements with better weight, volume, efficiency, and reliability than is available from the present conventional technology. Two families of zero current DC-DC converters were developed and successfully adapted to this application. Most of the converters developed are new and are presented.
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Torres-Aguilar, Honorio; Blank, Miri; Kivity, Shaye; Misgav, Mudi; Luboshitz, Jacob; Pierangeli, Silvia S; Shoenfeld, Yehuda
2012-01-01
The importance of β(2)-glycoprotein I (β(2)GPI)-specific CD4(+) T cells in the development of pathogenic processes in patients with antiphospholipid syndrome (APS) and APS mouse models is well established. Therefore, our objective is to manipulate the β2GPI specific CD4(+) T cells using tolerogenic dendritic cells (tDCs) to induce tolerance. We aim to evaluate the capability of tDCs to induce antigen-specific tolerance in effector/memory T cells from patients with APS and to elucidate the involved mechanism. DCs and tDCs were produced from patients with APS peripheral-blood-monocytes, using specific cytokines. β(2)GPI-specific tolerance induction was investigated by coculturing control DC (cDC) or tDC, β(2)GPI-loaded, with autologous effector/memory T cells, evaluating the proliferative response, phenotype, cytokines secretion, viability and regulatory T cells. Human monocyte-derived DCs treated with interleukin (IL)-10 and transforming growth factor β-1 (10/TGF-DC) induced β(2)GPI-specific-unresponsiveness in effector/memory CD4(+) T cells (46.5% ± 26.0 less proliferation) in 16 of 20 analysed patients with APS, without affecting the proliferative response to an unrelated candidin. In five analysed patients, 10/TGF-DC-stimulated T cells acquired an IL-2(low)interferon γ(low)IL-10(high) cytokine profile, with just a propensity to express higher numbers of Foxp3(+)CTLA-4(+) cells, but with an evident suppressive ability. In four of 10 analysed patients, 10/TGF-DC-stimulated T cell hyporesponsiveness could not be reverted and showed higher percentages of late apoptosis, p<0.02. The inherent tolerance induction resistance of activated T cells present during the development of autoimmune diseases has delayed the application of tDC as an alternative therapy. This study highlights the 10/TGF-DC feasibility to induce antigen-specific unresponsiveness in autoreactive T cells generated in patients with APS by inducing apoptosis or T cells with regulatory abilities.
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NASA Astrophysics Data System (ADS)
Mukhopadhyay, Debraj; Das, Subhrajit; Arunkumar, G.; Elangovan, D.; Ragunath, G.
2017-11-01
In this paper a current fed interleaved DC - DC boost converter which has an isolated topology and used for high voltage step up is proposed. A basic DC to DC boost converter converts uncontrolled DC voltage into controlled DC voltage of higher magnitude. Whereas this topology has the advantages of lower input current ripple, lesser output voltage, lesser stress on switches, faster transient response, improved reliability and much lesser electromagnetic emission over the conventional DC to DC boost converter. Most important benefit of this interleaved DC to DC boost converter is much higher efficiency. The input current is divided into two paths, substantially ohmic loss (I2R) and inductor ac loss gets reduced and finally the system achieves much higher efficiency. With recent mandates on energy saving interleaved DC to DC boost converter may be used as a very powerful tool to maintain good power density keeping the input current manageable. Higher efficiency also allows higher switching frequency and as a result the topology becomes more compact and cost friendly. The proposed topology boosts 48v DC to 200 V DC. Switching frequency is 100 kHz and PSIM 9.1 Platform has been used for the simulation.
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1980-09-01
I STANDARDS I 3- A C) = LLU 3 14 LUJ -J Ua-J I -r < V) F- Als~) C,) LA - LDL -4 LUV 4LI >LL) LU C) =- 0 Lur LD LU0J LUJ...U DC> I - U CDC) I - U Cc I - LU CI - LUC - i r 0. "LC 4± CL 4>" ’-LLUCD>- a-JJ"D - aC- ’l: D’- (a L I -OCi C) I V1- I -0C1IJ)IF- C- OIL ,) I -OCI V)C) I V) 4...J C Ix C-) L.) ca i ) 2-1 ’-4 ~ _ " i CDJ ’-4 "- W- - D ’ D- CD I
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High Latitude Ionospheric Radio Studies.
1988-01-01
AL’TOSCI.ED RES.LTS BY A.R.TL!.S.T. LLCAR OCT 83 S11U2, 2393 :1::’L- -1 5 2 42 !) 1 ? 7 2 2 5.1 10* rOF2 70FI bIIF H’F2 103M ~ WIN :OES W’V -- !I 5.6...4C > % V) L C-C) CC) CCC CC) C C CCD C)CD CD C) C)D CD (CDCC) C)D CDC) CD LC DCD (D C ),C C D DA rH H-4H H I I I HCD CD HHH HH IC DC)CDCD C -A - Ir
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USDA-ARS?s Scientific Manuscript database
Eimeria is a protozoan parasite which causes coccidiosis, a major parasitic disease of poultry that is indigenous to most regions of the world and causes intestinal damage with reduced body weight gain. Conventional disease control methods have relied on prophylactic chemotherapy, but alternative m...
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Pulsed helium ionization detection system
Ramsey, R.S.; Todd, R.A.
1985-04-09
A helium ionization detection system is provided which produces stable operation of a conventional helium ionization detector while providing improved sensitivity and linearity. Stability is improved by applying pulsed dc supply voltage across the ionization detector, thereby modifying the sampling of the detectors output current. A unique pulse generator is used to supply pulsed dc to the detector which has variable width and interval adjust features that allows up to 500 V to be applied in pulse widths ranging from about 150 nsec to about dc conditions.
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Pulsed helium ionization detection system
Ramsey, Roswitha S.; Todd, Richard A.
1987-01-01
A helium ionization detection system is provided which produces stable operation of a conventional helium ionization detector while providing improved sensitivity and linearity. Stability is improved by applying pulsed dc supply voltage across the ionization detector, thereby modifying the sampling of the detectors output current. A unique pulse generator is used to supply pulsed dc to the detector which has variable width and interval adjust features that allows up to 500 V to be applied in pulse widths ranging from about 150 nsec to about dc conditions.
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NASA Astrophysics Data System (ADS)
Sakamoto, Yuko; Ozaki, Sachi; Tanaka, Saki; Tanuma, Ryosuke; Yoshida, Tatsuru; Murata, Jiro
2014-09-01
A new type of trigger-scintillation counter array designed for the MTV experiment at TRIUMF-ISAC has been developed, using aluminum-metallized film tape for wrapping. The MTV experiment aims to perform the finest precision test of time reversal symmetry in nuclear beta decay. In that purpose, we search non-zero T-Violating transverse polarization of electrons emitted from polarized Li-8 nuclei. It uses a cylindrical drift chamber (CDC) as the main electron-tracking detector. The trigger-scintillation counter consists of 12-segmented 1 mm thick 300 mm long thin plastic scintillation counters. This counter is placed inside the CDC to generate a trigger signal. The required assembling precision of +-0.5 mm was a tricky point when we tried to use conventional total reflection mode. Indeed, produce an air-layer surrounding the scintillating bar to keep good light transmission was the main issue. For this reason, we tried to use a new wrapping material made of metallized-aluminum tape, which has a good mirror-like reflecting surface on both sides of the tape. Through this report, we will compare detection efficiency and light attenuation between conventional and new wrapping materials.
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Dual and self-curing potential of self-adhesive resin cements as thin films.
Moraes, R R; Boscato, N; Jardim, P S; Schneider, L F J
2011-01-01
In this study, the dual- and self-curing potential of self-adhesive resin cements (SARCs) as thin, clinically-relevant cement films was investigated. The SARCs tested were: BisCem (BSC; Bisco), Maxcem Elite (MXE; Kerr), RelyX Unicem clicker (UNI; 3M ESPE), seT capsule (SET; SDI), and SmartCem 2 (SC2; Dentsply Caulk). The conventional cement RelyX ARC (3M ESPE) was tested as a reference. The degree of conversion (DC) as a function of time was evaluated by real-time Fourier transform infrared spectroscopy with an attenuated total reflectance (ATR) device. The cements were either photoactivated for 40 seconds (dual-cure mode) or not photoactivated (self-cure mode). The cement film thickness was 50 ± 10 μm. The DC (%) was evaluated 1, 5, 10, 15, 20, 25, and 30 minutes after placing the cement on the ATR cell. Data for DC as a function of time were analyzed by two-way repeated measures analysis of variance (ANOVA). DC values at 30 minutes for the self- and dual-cure modes were submitted to one-way ANOVA. Post hoc comparisons were performed using the Student-Newman-Keuls test (p<0.05). The rate and the extent of conversion were lower for the SARCs compared with the conventional cement. Means ± standard deviations (SD) for the dual-cure mode at 30 minutes were: 75 ± 5 (ARC)a, 73 ± 8 (SET)a, 61 ± 4 (MXE)b, 51 ± 9 (BSC)c, 51 ± 4 (UNI)c, and 48 ± 3 (SC2)c, while in the self-cure mode means and SD were 62 ± 6 (ARC)a, 54 ± 3 (MXE)b, 40 ± 6 (SC2)c, 35 ± 2 (UNI)c, 35 ± 3 (SET)c, and 11 ± 3 (BSC)d. The DC for the dual-cure mode was generally higher than the self-cure, irrespective of the time. Discrepancies in DC between the dual- and self-cure modes from 11% to 79% were observed. In conclusion, SARCs may present slower rate of polymerization and lower final DC than conventional resin cements, in either the dual- or self-cure mode.
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Evaluation of constant current alternating current iontophoresis for transdermal drug delivery.
Yan, Guang; Li, S Kevin; Higuchi, William I
2005-12-10
Previous studies in our laboratory have demonstrated that alternating current (AC) iontophoresis can significantly decrease skin electric resistance and enhance the transport of charged permeants across skin. Flux variability of neutral permeants during AC iontophoresis was also found to be less than that of conventional direct current (DC) iontophoresis. The objectives of the present study were to evaluate flux enhancement of constant current AC transdermal iontophoresis and compare the AC flux with that of constant current DC iontophoresis. Iontophoresis studies of AC amplitude of 1, 2, and 5 mA were conducted in side-by-side diffusion cells with donor solution of 0.015, 0.15, and 1.0 M tetraethylammonium (TEA) chloride and receiver solution of phosphate buffered saline (PBS) using human epidermal membrane (HEM). Conventional constant current DC iontophoresis of 0.2 mA was also performed under similar conditions. TEA and mannitol were the model permeants. The following are the major findings in the present study. The flux of TEA increased proportionally with the AC current for all three TEA chloride concentrations and at the AC frequency used in the present study. When the permeant and its counter ion were the only ionic species in the donor chamber, the fluxes during DC iontophoresis were weakly dependent of its donor concentration. The fluxes of TEA during constant current AC iontophoresis were moderately related to the donor concentration with the highest TEA flux observed under the 1.0 M TEA chloride condition although the relationship between flux and donor concentration was not linear. A trend of decreasing electroosmotic transport with increasing donor TEA chloride concentration was observed with significant sample-to-sample variability during DC iontophoresis. Mannitol permeability was also observed to decrease with increasing TEA chloride concentration in the donor under the AC conditions, but data variability under AC was significantly smaller than that under DC. The results in the present study indicate that constant current AC iontophoresis under conditions tolerable to human (2 and 5 mA) can provide predictable fluxes that were lower than but of comparable magnitude as those of conventional constant current DC iontophoresis (0.2 mA).
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Sonoda, Akinaga, E-mail: akinagasonoda@yahoo.co.jp; Nitta, Norihisa; Yamamoto, Takefumi
PurposeWe investigated the possibility of shortening the time required for loading epirubicin into calibrated polyvinyl alcohol-based hydrogel beads (DC Beads{sup ®}) to be used for transarterial chemoembolization.MethodAfter separating the beads suspended in phosphate-buffered saline (PBS) solution by the use of a sieve (clearance 75 µm), epirubicin hydrochloride (EH) was loaded for 20, 30, or 60 s under vibration into DC beads. The EH loading rate into conventionally prepared (control) beads, i.e., beads loaded for 30 min without vibration, and vibration-loaded beads were calculated from the residual EH concentration in the bead-depleted EH solution. The amount of EH eluted from conventionally and vibration-loadedmore » samples into a PBS solution (pH 7.0) was measured at 15 and 30 min and 1, 2, 6, 12, and 24 h. We also recorded the inhibitory effect of the PBS solution on the loading time. Using frozen sections, the EH load in the beads was evaluated visually under a fluorescence microscope.ResultsSpectrophotometry (495 nm) showed that the loading rate was 98.98 ± 0.34, 99.02 ± 0.32, and 99.50 ± 0.11 % with 20-, 30-, and 60-s vibration, respectively. The eluted rate was statistically similar between vibration- and statically loaded (control) beads. The PBS solution hampered EH loading into the beads. Visually, the distribution of EH in conventionally and vibration-loaded DC beads was similar.DiscussionThe use of vibration and the removal of PBS solution when epirubicin hydrochloride was loaded into DC beads dramatically shortened the loading time of epirubicin hydrochloride into DC beads.« less
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High-Efficiency Photovoltaic System Using Partially-Connected DC-DC Converter
NASA Astrophysics Data System (ADS)
Uno, Masatoshi; Kukita, Akio; Tanaka, Koji
Power conversion electronics for photovoltaic (PV) systems are desired to operate as efficiently as possible to exploit the power generated by PV modules. This paper proposes a novel PV system in which a dc-dc converter is partially connected to series-connected PV modules. The proposed system achieves high power-conversion efficiency by reducing the passing power and input/output voltages of the converter. The theoretical operating principle was experimentally validated. Resultant efficiency performances of the proposed and conventional systems demonstrated that the proposed system was more efficient in terms of power conversion though the identical converter was used for the both systems.
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Description and performance of an updraft trap for sandflies.
Mutero, C M; Mutinga, M J; Birley, M H; Amimo, F A; Munyinyi, D M
1991-12-01
An updraft trap for sampling sandflies in the field was developed and tested in the Marigat area of Baringo District, Kenya. The main components of the trap were a 12 cm long plastic drain pipe, 9 V d.c. electric motor, aluminium fan and a perspex sandfly collection cage. Comparisons of the updraft trap with a CDC and a 1 x 1 m polythene sheet coated with castor oil (sticky trap) showed the former was more consistent than the other traps in sampling sandflies from animal burrows. A total of 1241 sandflies belonging to eleven species were collected. Sergentomyia bedfordi, Phlebotomus martini, S. antennatus and P. duboscqi were the commonest species comprising 32.5%, 27.0%, 21.1% and 11.3% of the total catch respectively. However, the relative proportion of the different species varied according to the type of trap used. The CDC trap apparently attracted the known vectors of leishmaniases in the area, P. martini and P. duboscqi. Significantly more male than female P. martini and S. antennatus were collected by the various traps. A significantly higher proportion of female S. bedfordi was captured by the updraft and sticky traps while equal numbers of male and female P. duboscqi were collected in all traps.
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Isolated and soft-switched power converter
Peng, Fang Zheng; Adams, Donald Joe
2002-01-01
An isolated and soft-switched power converter is used for DC/DC and DC/DC/AC power conversion. The power converter includes two resonant tank circuits coupled back-to-back through an isolation transformer. Each resonant tank circuit includes a pair of resonant capacitors connected in series as a resonant leg, a pair of tank capacitors connected in series as a tank leg, and a pair of switching devices with anti-parallel clamping diodes coupled in series as resonant switches and clamping devices for the resonant leg. The power converter is well suited for DC/DC and DC/DC/AC power conversion applications in which high-voltage isolation, DC to DC voltage boost, bidirectional power flow, and a minimal number of conventional switching components are important design objectives. For example, the power converter is especially well suited to electric vehicle applications and load-side electric generation and storage systems, and other applications in which these objectives are important. The power converter may be used for many different applications, including electric vehicles, hybrid combustion/electric vehicles, fuel-cell powered vehicles with low-voltage starting, remote power sources utilizing low-voltage DC power sources, such as photovoltaics and others, electric power backup systems, and load-side electric storage and generation systems.
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NASA Technical Reports Server (NTRS)
Gwaltney, David A.; Ferguson, Michael I.
2003-01-01
Evolvable hardware provides the capability to evolve analog circuits to produce amplifier and filter functions. Conventional analog controller designs employ these same functions. Analog controllers for the control of the shaft speed of a DC motor are evolved on an evolvable hardware platform utilizing a second generation Field Programmable Transistor Array (FPTA2). The performance of an evolved controller is compared to that of a conventional proportional-integral (PI) controller. It is shown that hardware evolution is able to create a compact design that provides good performance, while using considerably less functional electronic components than the conventional design. Additionally, the use of hardware evolution to provide fault tolerance by reconfiguring the design is explored. Experimental results are presented showing that significant recovery of capability can be made in the face of damaging induced faults.
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Paiatto, Lisiery N; Silva, Fernanda G D; Yamada, Áureo T; Tamashiro, Wirla M S C; Simioni, Patricia U
2018-01-01
In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms. To induce oral tolerance, BALB/c mice were fed 4mg/mL OVA solution for seven consecutive days. Spleen DCs were isolated from tolerant (tDC) and naïve (nDC) mice, and then adoptively transferred to syngeneic mice. Three days later, colitis was induced in DC treated mice by intrarectal instillation of 100μg2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Control subjects received only intrarectal instillation of either TNBS solution or a vehicle. Five days later, mice from all groups were euthanized and examined for physiological and immunological parameters. Regarding the phenotype, we observed that the frequencies of CD11+ MHC II+ and CD11+ MHCII+ CD86+ cells were significantly lower in DCs isolated from tolerant mice than in those from naive mice. However, pretreatment with both types of DCs was able to significantly reduce clinical signs of colitis such as diarrhea, rectal prolapse, bleeding, and cachexia, although only treatment with tDCs was able to prevent weight loss from instillation of TNBS. In vitro proliferation of spleen cells from mice treated with either type of DCs was significantly lower than that observed in splenic cell cultures of naïve mice. Although no significant difference was observed in the frequencies of Treg cells in the experimental groups, the frequency of Th17+CD4+cellsand the secretion of IL-17 were more reduced in the cultures of spleen cells from mice treated with either type of DCs. The levels of IL-9 and IFN-γ were lower in supernatants of cells from mice treated with nDCs. The results allow us to conclude that the adoptive transfer of cells expressing CD11c is able to reduce the clinical and immunological signs of drug-induced colitis. Adoptive transfer of CD11c+DC isolated from both naive and tolerant mice altered the proliferative and T cell responses. To the best of our knowledge, there is no previously published data showing the protective effects of DCs from naïve or tolerant mice in the treatment of colitis.
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Gelderblom, Mathias; Gallizioli, Mattia; Ludewig, Peter; Thom, Vivien; Arunachalam, Priyadharshini; Rissiek, Björn; Bernreuther, Christian; Glatzel, Markus; Korn, Thomas; Arumugam, Thiruma Valavan; Sedlacik, Jan; Gerloff, Christian; Tolosa, Eva; Planas, Anna M; Magnus, Tim
2018-01-01
Inflammatory mechanisms can exacerbate ischemic tissue damage and worsen clinical outcome in patients with stroke. Both αβ and γδ T cells are established mediators of tissue damage in stroke, and the role of dendritic cells (DCs) in inducing the early events of T cell activation and differentiation in stroke is not well understood. In a murine model of experimental stroke, we defined the immune phenotype of infiltrating DC subsets based on flow cytometry of surface markers, the expression of ontogenetic markers, and cytokine levels. We used conditional DC depletion, bone marrow chimeric mice, and IL-23 (interleukin-23) receptor-deficient mice to further explore the functional role of DCs. We show that the ischemic brain was rapidly infiltrated by IRF4 + /CD172a + conventional type 2 DCs and that conventional type 2 DCs were the most abundant subset in comparison with all other DC subsets. Twenty-four hours after ischemia onset, conventional type 2 DCs became the major source of IL-23, promoting neutrophil infiltration by induction of IL-17 (interleukin-17) in γδ T cells. Functionally, the depletion of CD11c + cells or the genetic disruption of the IL-23 signaling abrogated both IL-17 production in γδ T cells and neutrophil infiltration. Interruption of the IL-23/IL-17 cascade decreased infarct size and improved neurological outcome after stroke. Our results suggest a central role for interferon regulatory factor 4-positive IL-23-producing conventional DCs in the IL-17-dependent secondary tissue damage in stroke. © 2017 American Heart Association, Inc.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Silva, E.R.C. da; Filho, B.J.C.
This paper presents a PWM current clamping circuit for improving a series resonant DC link converter. This circuit is capable of reducing current peaks to about 1.2--1.4 times the DC bias current. When desired, resonant transition creates notches in the dc link current, allowing the converter`s switches to synchronize with external PWM strategy. A regulated DC current source may be obtained--by using a conventional rectifier source--to feed a DC load or a current source inverter. Phase plane approach makes ease the understanding the operation, control and design procedure of the circuit. Another topology is derived and its features compared tomore » the first circuit. Simulation results for the simplified circuit and for a three-phase induction motor driven by such inverter will be presented. Moreover, the principle is corroborated by experimental results.« less
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R Dump Converter without DC Link Capacitor for an 8/6 SRM: Experimental Investigation
Kavitha, Pasumalaithevan; Umamaheswari, Bhaskaran
2015-01-01
The objective of this paper is to investigate the performance of 8/6 switched reluctance motor (SRM) when excited with sinusoidal voltage. The conventional R dump converter provides DC excitation with the help of capacitor. In this paper the converter used is the modified R dump converter without DC link capacitor providing AC or sinusoidal excitation. Torque ripple and speed ripple are investigated based on hysteresis current control. Constant and sinusoidal current references are considered for comparison in both DC and AC excitation. Extensive theoretical and experimental investigations are made to bring out the merits and demerits of AC versus DC excitation. It is shown that the constructionally simple SRM can be favorably controlled with simple R dump converter with direct AC excitation without need for DC link capacitor. A 4-phase 8/6 0.5 kW SRM is used for experimentation. PMID:25642452
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R dump converter without DC link capacitor for an 8/6 SRM: experimental investigation.
Kavitha, Pasumalaithevan; Umamaheswari, Bhaskaran
2015-01-01
The objective of this paper is to investigate the performance of 8/6 switched reluctance motor (SRM) when excited with sinusoidal voltage. The conventional R dump converter provides DC excitation with the help of capacitor. In this paper the converter used is the modified R dump converter without DC link capacitor providing AC or sinusoidal excitation. Torque ripple and speed ripple are investigated based on hysteresis current control. Constant and sinusoidal current references are considered for comparison in both DC and AC excitation. Extensive theoretical and experimental investigations are made to bring out the merits and demerits of AC versus DC excitation. It is shown that the constructionally simple SRM can be favorably controlled with simple R dump converter with direct AC excitation without need for DC link capacitor. A 4-phase 8/6 0.5 kW SRM is used for experimentation.
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Novel bidirectional DC-DC converters based on the three-state switching cell
NASA Astrophysics Data System (ADS)
da Silva Júnior, José Carlos; Robles Balestero, Juan Paulo; Lessa Tofoli, Fernando
2016-05-01
It is well known that there is an increasing demand for bidirectional DC-DC converters for applications that range from renewable energy sources to electric vehicles. Within this context, this work proposes novel DC-DC converter topologies that use the three-state switching cell (3SSC), whose well-known advantages over conventional existing structures are ability to operate at high current levels, while current sharing is maintained by a high frequency transformer; reduction of cost and dimensions of magnetics; improved distribution of losses, with consequent increase of global efficiency and reduction of cost associated to the need of semiconductors with lower current ratings. Three distinct topologies can be derived from the 3SSC: one DC-DC converter with reversible current characteristic able to operate in the first and second quadrants; one DC-DC converter with reversible voltage characteristic able to operate in the first and third quadrants and one DC-DC converter with reversible current and voltage characteristics able to operate in four quadrants. Only the topology with bidirectional current characteristic is analysed in detail in terms of the operating stages in both nonoverlapping and overlapping modes, while the design procedure of the power stage elements is obtained. In order to validate the theoretical assumptions, an experimental prototype is also implemented, so that relevant issues can be properly discussed.
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Martin-Gayo, Enrique; Buzon, Maria Jose; Ouyang, Zhengyu; Hickman, Taylor; Cronin, Jacqueline; Pimenova, Dina; Walker, Bruce D; Lichterfeld, Mathias; Yu, Xu G
2015-06-01
The majority of HIV-1 elite controllers (EC) restrict HIV-1 replication through highly functional HIV-1-specific T cell responses, but mechanisms supporting the evolution of effective HIV-1-specific T cell immunity in these patients remain undefined. Cytosolic immune recognition of HIV-1 in conventional dendritic cells (cDC) can facilitate priming and expansion of HIV-1-specific T cells; however, HIV-1 seems to be able to avoid intracellular immune recognition in cDCs in most infected individuals. Here, we show that exposure of cDCs from EC to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. Emergence of these cell-intrinsic immune responses was associated with a reduced induction of SAMHD1 and LEDGF/p75, and an accumulation of viral reverse transcripts, but inhibited by pharmacological blockade of viral reverse transcription or siRNA-mediated silencing of the cytosolic DNA sensor cGAS. Importantly, improved cell-intrinsic immune recognition of HIV-1 in cDCs from elite controllers translated into stronger abilities to stimulate and expand HIV-1-specific CD8 T cell responses. These data suggest an important role of cell-intrinsic type I interferon secretion in dendritic cells for the induction of effective HIV-1-specific CD8 T cells, and may be helpful for eliciting functional T cell immunity against HIV-1 for preventative or therapeutic clinical purposes.
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Islam, Tariqul; Rahman, Ajijur; Islam, Anwar Ul
2012-01-01
To get better control in disease conditions, many people take herbs with conventional medicines, therefore, posing a risk of potential pharmacokinetic interactions between herbs and conventional drugs. The aqueous extract of the fresh leaves of Abroma augusta L. (Family: Sterculiaceae, Bengali name: Ulatkambal, English name: Devil's cotton, DC) is viscous and used traditionally to treat diabetes mellitus. This study was done to investigate the probable mechanism by which the aqueous extract of Abroma augusta L. is beneficial in managing type 2 DM and to observe the effects of this extract on absorption of metformin hydrochloride from the gastrointestinal tract. Studies were conducted in healthy Long Evans rats using Na-carboxymethyl cellulose (CMC) as positive control. Both Na-CMC and WSF of DC significantly (P < 0.05) reduced the absorption of glucose administered orally in fasted rats. On the other hand, WSF of DC significantly (P < 0.05) reduced the absorption of metformin hydrochloride in alloxan-induced diabetic rats. The results of this study suggest that WSF of DC may be beneficial in diabetic patients to improve glycemic control but should not be coadministered with metformin HCl for management of type 2 diabetes mellitus.
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2009-03-01
lCoo.oDphtt. RiYer Ootuloll.hted d~ A Cob CDmppy, a. Pesi.uyl•ada eorpon.ti<’>ll ("TN JIIHIH. - lUv •r Cufh •IlL Oofll 4 Oolul Co.,ur’’) 1 • I ·-. ’ i G...received by foiWarded b !J He /;tJ!J :f) A ,, i ~ ),J cDC efWr:Z--1 oil be recefved by by r 0 by by ~~rl! tie~ I OH received by -b...regards to the EBS topics of environmental restoration program sites, storage tanks, oil /water separators, solid waste, medical or biohazardous waste
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NASA Astrophysics Data System (ADS)
Chou, Ying-Hung; Yan, Jheng-Tai; Lee, Hsin-Ying; Lee, Ching-Ting
2008-02-01
The co-sputtering Al-doped ZnO (AZO) films with Al nano-particles were used to increase the extraction efficiency of GaN-based light-emitting diodes (LEDs). Fixing the ZnO radio frequency (RF) power of 100W and changing the Al DC power from 0 to 13W, the AZO films with various Al contents can be obtained. In the experimental results, the AZO films deposited with Al DC power of 0, 4.5 and 7W do not have Al segregation. However, the segregated Al nano-particles can be found in the AZO films deposited by Al DC power of 10W and 13W. The co-sputtering 170 nm-thick AZO films with and without Al nano-particles were deposited on the transparent area of LEDs and compared the light output intensity of conventional LEDs. The light intensity of LEDs with AZO films with Al DC power 0, 4.5 and 7W increased 10% than that of conventional LEDs. This was due to the AZO film played a role of anti-reflection coating (ARC) layer. The light intensity of LEDs with AZO film deposited using Al DC power of 10W and 13W increased about 35% and 30%, respectively. It can be deduced that the output light is scattered by the Al nano-particles existed in the AZO film.
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Hybridizing matter-wave and classical accelerometers
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lautier, J.; Volodimer, L.; Hardin, T.
2014-10-06
We demonstrate a hybrid accelerometer that benefits from the advantages of both conventional and atomic sensors in terms of bandwidth (DC to 430 Hz) and long term stability. First, the use of a real time correction of the atom interferometer phase by the signal from the classical accelerometer enables to run it at best performance without any isolation platform. Second, a servo-lock of the DC component of the conventional sensor output signal by the atomic one realizes a hybrid sensor. This method paves the way for applications in geophysics and in inertial navigation as it overcomes the main limitation of atomicmore » accelerometers, namely, the dead times between consecutive measurements.« less
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NASA Astrophysics Data System (ADS)
Liou, L. L.; Jenkins, T.; Huang, C. I.
1997-06-01
The d.c. power limitation of a conventional HBT with dot geometry was studied theoretically using combined electro-thermal and transmission line models. In most cases, the thermal runaway occurs at a power level lower than that set by the intrinsic electronic property of the device. The dependence of the d.c. thermal runaway threshold power density, Pmax, on the emitter dot radius and emitter ballast resistance was calculated. Increasing emitter dot radius lowers Pmax. Although ballast resistance increases Pmax, the effect reduces as the emitter dot radius increases. This is caused by the non-uniform potential distribution in the base layer. When thermal runaway is considered, the nonuniform base-emitter potential offsets the improvement of the power handling capability by the physical ballast resistance. Conventional HBTs with a large radius (greater than 4 μm) exhibit a small Pmax caused by thermal effect. This threshold power density can be increased drastically by using the thermal shunt technique.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Fregosi, D.; Ravula, S.; Brhlik, D.
2015-04-22
Bosch has developed and demonstrated a novel DC microgrid system designed to maximize utilization efficiency for locally generated photovoltaic energy while offering high reliability, safety, redundancy, and reduced cost compared to equivalent AC systems. Several demonstration projects validating the system feasibility and expected efficiency gains have been completed and additional ones are in progress. This work gives an overview of the Bosch DC microgrid system and presents key results from a large simulation study done to estimate the energy savings of the Bosch DC microgrid over conventional AC systems. The study examined the system performance in locations across the Unitedmore » States for several commercial building types and operating profiles and found that the Bosch DC microgrid uses generated PV energy 6%–8% more efficiently than traditional AC systems.« less
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The step-wise pathway of septin hetero-octamer assembly in budding yeast.
Weems, Andrew; McMurray, Michael
2017-05-25
Septin proteins bind guanine nucleotides and form rod-shaped hetero-oligomers. Cells choose from a variety of available septins to assemble distinct hetero-oligomers, but the underlying mechanism was unknown. Using a new in vivo assay, we find that a stepwise assembly pathway produces the two species of budding yeast septin hetero-octamers: Cdc11/Shs1-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Rapid GTP hydrolysis by monomeric Cdc10 drives assembly of the core Cdc10 homodimer. The extended Cdc3 N terminus autoinhibits Cdc3 association with Cdc10 homodimers until prior Cdc3-Cdc12 interaction. Slow hydrolysis by monomeric Cdc12 and specific affinity of Cdc11 for transient Cdc12•GTP drive assembly of distinct trimers, Cdc11-Cdc12-Cdc3 or Shs1-Cdc12-Cdc3. Decreasing the cytosolic GTP:GDP ratio increases the incorporation of Shs1 vs Cdc11, which alters the curvature of filamentous septin rings. Our findings explain how GTP hydrolysis controls septin assembly, and uncover mechanisms by which cells construct defined septin complexes.
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Montoya, Maria; Edwards, Matthew J; Reid, Delyth M; Borrow, Persephone
2005-02-15
In this study, we report the dynamic changes in activation and functions that occur in spleen dendritic cell (sDC) subsets following infection of mice with a natural murine pathogen, lymphocytic choriomeningitis virus (LCMV). Within 24 h postinfection (pi), sDCs acquired the ability to stimulate naive LCMV-specific CD8+ T cells ex vivo. Conventional (CD11chigh CD8+ and CD4+) sDC subsets rapidly up-regulated expression of costimulatory molecules and began to produce proinflammatory cytokines. Their tendency to undergo apoptosis ex vivo simultaneously increased, and in vivo the number of conventional DCs in the spleen decreased markedly, dropping approximately 2-fold by day 3 pi. Conversely, the number of plasmacytoid (CD11clowB220+) DCs in the spleen increased, so that they constituted almost 40% of sDCs by day 3 pi. Type 1 IFN production was up-regulated in plasmacytoid DCs by 24 h pi. Analysis of DC activation and maturation in mice unable to respond to type 1 IFNs implicated these cytokines in driving infection-associated phenotypic activation of conventional DCs and their enhanced tendency to undergo apoptosis, but also indicated the existence of type 1 IFN-independent pathways for the functional maturation of DCs during LCMV infection.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Letant, S E; Kane, S R; Murphy, G A
2008-05-30
This note presents a comparison of Most-Probable-Number Rapid Viability (MPN-RV) PCR and traditional culture methods for the quantification of Bacillus anthracis Sterne spores in macrofoam swabs generated by the Centers for Disease Control and Prevention (CDC) for a multi-center validation study aimed at testing environmental swab processing methods for recovery, detection, and quantification of viable B. anthracis spores from surfaces. Results show that spore numbers provided by the MPN RV-PCR method were in statistical agreement with the CDC conventional culture method for all three levels of spores tested (10{sup 4}, 10{sup 2}, and 10 spores) even in the presence ofmore » dirt. In addition to detecting low levels of spores in environmental conditions, the MPN RV-PCR method is specific, and compatible with automated high-throughput sample processing and analysis protocols.« less
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NASA Astrophysics Data System (ADS)
Alharbi, Salah S.; Alharbi, Saleh S.; Al-bayati, Ali M. S.; Matin, Mohammad
2017-08-01
This paper presents a high-performance dc-dc flyback converter design based on wide bandgap (WBG) semiconductor devices for photovoltaic (PV) applications. Two different power devices, a gallium nitride (GaN)-transistor and a silicon (Si)-MOSFET, are implemented individually in the flyback converter to examine their impact on converter performance. The total power loss of the converter with different power devices is analyzed for various switching frequencies. Converter efficiency is evaluated at different switching frequencies, input voltages, and output power levels. The results reveal that the converter with the GaN-transistor has lower total power loss and better efficiency compared to the converter with the conventional Si-MOSFET.
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Transcriptional and functional defects of dendritic cells derived from the MUTZ-3 leukaemia line
Rasaiyaah, Jane; Noursadeghi, Mahdad; Kellam, Paul; Chain, Benjamin
2009-01-01
Dendritic cells (DC) generated from MUTZ-3, an immortalized acute myeloid leukaemia-derived cell line, have potential application as a model for the study of human DC, and as a tool with which to stimulate immunotherapeutic responses to cancer. However, the relationship of MUTZ-3 DC to their non-transformed counterparts remains incompletely understood. Immunoselected CD14+ MUTZ-3 cells were used to generate a homogeneous population of DC (M3DC). These cells had a cell surface phentoype and morphology characteristic of conventional monocyte-derived DC (MDDC). Whole genome transcriptome comparison of M3DC and MDDC however, revealed extensive differences between these two cell types. Functional ontology-based data analysis revealed three enriched clusters of genes downregulated in M3DC, with functions in pathogen recognition, DC maturation and cytokine/chemokine signalling. Downregulation of protein expression was confirmed for several of these genes. The molecular differences were accompanied by a profoundly impaired phenotypic and functional response of M3DC to microbial stimulation. The immortalized phenotype of MUTZ-3 therefore reflects not only deregulated proliferative capacity, but substantial perturbation of normal antigen-presenting cell function. These results have important implications for studies using MUTZ-3 as a model of MDDC or for cancer immunotherapy. PMID:19538250
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World Wildlife Conference, Efforts to Save Endangered Species.
ERIC Educational Resources Information Center
Department of State, Washington, DC.
A Plenipotentiary Conference to Conclude and International Convention on Trade in Certain Species of Wildlife was held in Washington, D.C., February 12 through March 2, 1973. Its purpose was to prepare and adopt a convention on export, import, and transit of certain species of wild fauna and flora. Representatives and observers from 90 countries…
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4He sample probe for combined microwave and dc transport measurements
NASA Astrophysics Data System (ADS)
Dobrovolskiy, Oleksandr V.; Franke, Jörg; Huth, Michael
2015-03-01
Combined microwave and dc electrical transport measurements at low temperatures represent a valuable experimental method in many research areas. In particular, when samples are conventional superconductors, a typical experiment requires a combination of helium temperatures, a wide range of magnetic fields, and the utilization of coaxial lines along with the usual dc wiring. We report on the general design features and the microwave performance of a custom-made low-temperature sample probe, with a measurement bandwidth tested from dc to 20 GHz. Equipped with six coaxial cables, a heater, Hall and temperature sensors, the probe fits into a ⊘32 mm shaft. We present our setup, analyze its microwave performance, and describe two representative experiments enabled by this system. The proposed setup will be essential for a systematic study of the dc and ac response of the vortex dynamics in nanopatterned superconductors subject to combined dc and microwave stimuli. Besides, it will be valuable for the investigation of a broad class of nonlinear stochastic systems where a combination of dc and high-frequency ac driving in a wide temperature range is necessary.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Fregosi, Daniel; Ravula, Sharmila; Brhlik, Dusan
2015-06-07
Bosch has developed and demonstrated a novel direct current (DC) microgrid system that maximizes the efficiency of locally generated photovoltaic energy while offering high reliability, safety, redundancy, and reduced cost compared to equivalent alternating current (AC) systems. Several demonstration projects validating the system feasibility and expected efficiency gains have been completed and additional ones are in progress. This paper gives an overview of the Bosch DC microgrid system and presents key results from a large simulation study done to estimate the energy savings of the Bosch DC microgrid over conventional AC systems. The study examined the system performance in locationsmore » across the United States for several commercial building types and operating profiles. It found that the Bosch DC microgrid uses generated PV energy 6%-8% more efficiently than traditional AC systems.« less
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da Silva, Eduardo Moreira; Poskus, Laiza Tatiana; Guimarães, José Guilherme Antunes; de Araújo Lima Barcellos, Alexandre; Fellows, Carlos Eduardo
2008-03-01
This study analyzed the influence of light polymerization modes on crosslink density (CD) and the degree of conversion (DC) of dental composites. A minifilled hybrid and a nanofilled dental composite were photoactivated with two light polymerization modes: Conventional-850 mW/cm2 for 20 s and Gradual-50 up to 1,000 mW/cm2 for 10 s+1,000 mW/cm2 for 10 s. DC was determined by the use of FT-Raman-spectrometer. A softening test, using Knoop diamond indentation, was carried out at the top and bottom of 2 mm thick dental composite disks, before and after storage in 100% ethanol for 24 h, in order to represent the amount of crosslink density. Data were analyzed by ANOVA and Student-Newman-Keuls' multiple range test (alpha=0.05). The DC was influenced by light polymerization modes, with Gradual mode presenting lower DC. On bottom surfaces, the nanofilled dental composite was more susceptible to softening by ethanol than minifilled hybrid, and gradual light polymerization of nanofilled dental composite resulted in more softening than when conventional light polymerization was used. The results suggest that nanofilled composites are capable undergoing more plasticization if applied in thick increments.
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Islam, Tariqul; Rahman, Ajijur; Islam, Anwar Ul
2012-01-01
To get better control in disease conditions, many people take herbs with conventional medicines, therefore, posing a risk of potential pharmacokinetic interactions between herbs and conventional drugs. The aqueous extract of the fresh leaves of Abroma augusta L. (Family: Sterculiaceae, Bengali name: Ulatkambal, English name: Devil's cotton, DC) is viscous and used traditionally to treat diabetes mellitus. This study was done to investigate the probable mechanism by which the aqueous extract of Abroma augusta L. is beneficial in managing type 2 DM and to observe the effects of this extract on absorption of metformin hydrochloride from the gastrointestinal tract. Studies were conducted in healthy Long Evans rats using Na-carboxymethyl cellulose (CMC) as positive control. Both Na-CMC and WSF of DC significantly (P < 0.05) reduced the absorption of glucose administered orally in fasted rats. On the other hand, WSF of DC significantly (P < 0.05) reduced the absorption of metformin hydrochloride in alloxan-induced diabetic rats. The results of this study suggest that WSF of DC may be beneficial in diabetic patients to improve glycemic control but should not be coadministered with metformin HCl for management of type 2 diabetes mellitus. PMID:22830057
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Vandenberghe, Bart; Corpas, Livia; Bosmans, Hilde; Yang, Jie; Jacobs, Reinhilde
2011-08-01
The aim of this study was the determination of image accuracy and quality for periodontal diagnosis using various X-ray generators with conventional and digital radiographs. Thirty-one in vitro periodontal defects were evaluated on intraoral conventional (E-, F/E-speed) and digital images (three indirect, two direct sensors). Standardised radiographs were made with an alternating current (AC), a high-frequency (HF) and a direct current (DC) X-ray unit at rising exposure times (20-160 ms with 20-ms interval) with a constant kV of 70. Three observers assessed bone levels for comparison to the gold standard. Lamina dura, contrast, trabecularisation, crater and furcation involvements were evaluated. Irrespective X-ray generator-type, measurement deviations increased at higher exposure times for solid-state, but decreased for photostimulable storage phosphor (PSP) systems. Accuracy for HF or DC was significantly higher than AC (p < 0.0001), especially at low exposure times. At 0.5- to 1-mm clinical deviation, 27-53% and 32-55% dose savings were demonstrated when using HF or DC generators compared to AC, but only for PSP. No savings were found for solid-state sensors, indicating their higher sensitivity. The use of digital sensors compared to film allowed 15-90% dose savings using the AC tube, whilst solid-state sensors allowed approximately 50% savings compared to PSP, depending on tube type and threshold level.. Accuracy of periodontal diagnosis increases when using HF or DC generators and/or digital receptors with adequate diagnostic information at lower exposure times.
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Field Trial on a Rack-mounted DC Power Supply System with 80-Ah Lithium-ion Batteries
NASA Astrophysics Data System (ADS)
Matsushima, Toshio
Using an industrial lithium-ion battery that has higher energy density than conventional valve-regulated lead-acid batteries, a rack-mounted DC-power-supply system was assembled and tested at a base transceiver station (BTS) offering actual services. A nominal output voltage and maximum output current of the system is 53.5V and 20A, respectively. An 80-Ah lithium-ion battery composed of 13 cells connected in series was applied in the system and maintained in a floating charge method. The DC-power-supply system was installed in a 19-inch power rack in the telecommunications equipment box at BTS. The characteristics of the 80Ah lithium-ion battery, specifications of the DC-power-supply system and field-test results were shown in this paper.
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Conductivity of molten sodium chloride in an arbitrarily weak dc electric field.
Delhommelle, Jerome; Cummings, Peter T; Petravic, Janka
2005-09-15
We use nonequilibrium molecular-dynamics (NEMD) simulations to characterize the response of a fluid subjected to an electric field. We focus on the response for very weak fields. Fields accessible by conventional NEMD methods are typically of the order of 10(9) V m(-1), i.e., several orders of magnitude larger than those typically used in experiments. Using the transient time-correlation function, we show how NEMD simulations can be extended to study systems subjected to a realistic dc electric field. We then apply this approach to study the response of molten sodium chloride for a wide range of dc electric fields.
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Pathogen-Sensing and Regulatory T Cells: Integrated Regulators of Immune Responses
Grossman, Zvi; Paul, William E.
2014-01-01
We present the concept that pathogen-sensing and Tregs mutually regulate immune responses to conventional and tumor antigens through countervailing effects on dendritic cells. Normally, conventional CD4 T cells recognizing their cognate antigen-presented by a dendritic cell will respond only if the dendritic cell also receives a signal through its pathogen-sensing/ danger / adjuvant recognition systems (the pathogen-sensing triad). However, if Tregs capable of interacting with the same DC are absent, dendritic cells are competent to present antigens, both foreign and self, even without the stimulation provided by the pathogen-sensing triad. Tregs recognizing an antigen presented by the DC that is also presenting antigen to a conventional CD4 T cell will prevent such responses but a signal delivered by a member of the pathogen-sensing traid will overcome the Tregs’inhibitory action and will allow responses to go forward. These considerations take on special meaning for responses to “weak antigens” such as many of the antigens displayed by spontaneous human tumors. PMID:24894087
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Analysis of a PWM Resonant Buck Chopper for Use as a Ship Service Converter Module
1999-01-01
zonal architecture [2] has a number of advantages over the current radial distribution architecture. The radial network includes generators supplying...Several representative topologies are considered in this section. The literature is replete with softswitching dc-dc converter topologies and control...differs from a conventional PWM buck by the addition of a resonant network consisting of inductor Lr, capacitor Q, an auxiliary switch Sr, an auxiliary
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dc-plasma-sprayed electronic-tube device
Meek, T.T.
1982-01-29
An electronic tube and associated circuitry which is produced by dc plasma arc spraying techniques is described. The process is carried out in a single step automated process whereby both active and passive devices are produced at very low cost. The circuitry is extremely reliable and is capable of functioning in both high radiation and high temperature environments. The size of the electronic tubes produced are more than an order of magnitude smaller than conventional electronic tubes.
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Suppressive role of hepatic dendritic cells in concanavalin A-induced hepatitis
Tomiyama, C; Watanabe, H; Izutsu, Y; Watanabe, M; Abo, T
2011-01-01
Concanavalin A (Con A)-induced hepatitis is a mouse model of acute autoimmune hepatitis. The aim of this study was to investigate the role of hepatic dendritic cells (DC) in the immune modulation of tissue damage. Almost all hepatic DC were plasmacytoid DC (CD11c+ I-Alow B220+); however, conventional DC were CD11c+ I-Ahigh B220–. At an early stage (3–6 h) after Con A administration, the number of DC in both the liver and spleen decreased, increasing thereafter (12–24 h) in parallel with hepatic failure. The hepatic CD11c+ DC population contained many CD11b- cells, while the majority of splenic CD11c+ DC were CD11b+. After Con A administration, the proportion of I-A+ and CD11b+ cells within the CD11c+ DC population tended to increase in the liver, but not in the spleen. Similarly, expression of the activation markers CD80, CD86 and CD40 by CD11c+ DC increased in the liver, but not in the spleen. Next, adoptive transfer of DC isolated from the liver and spleen was performed 3 h after Con A administration to examine the immunomodulatory function of DC. Only hepatic DC had the ability to suppress hepatic failure. Analysis of cytokine production and subsequent identification of the effector cells showed that hepatic DC achieved this by suppressing the production of interleukin (IL)-12 and IL-2, rather than modulating effector cell function. PMID:21985372
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Elimination of cdc2 phosphorylation sites in the cdc25 phosphatase blocks initiation of M-phase.
Izumi, T; Maller, J L
1993-01-01
The cdc25 phosphatase is a mitotic inducer that activates p34cdc2 at the G2/M transition by dephosphorylation of Tyr15 in p34cdc2. cdc25 itself is also regulated through periodic changes in its phosphorylation state. To elucidate the mechanism for induction of mitosis, phosphorylation of cdc25 has been investigated using recombinant proteins. cdc25 is phosphorylated by both cyclin A/p34cdc2 and cyclin B/p34cdc2 at similar sets of multiple sites in vitro. This phosphorylation retards its electrophoretical mobility and activates its ability to increase cyclin B/p34cdc2 kinase activity three- to fourfold in vitro, as found for endogenous Xenopus cdc25 in M-phase extracts. The threonine and serine residues followed by proline that are conserved between Xenopus and human cdc25 have been mutated. Both the triple mutation of Thr48, Thr67, and Thr138 and the quintuple mutation of these three threonine residues plus Ser205 and Ser285, almost completely abolish the shift in electrophoretic mobility of cdc25 after incubation with M-phase extracts or phosphorylation by p34cdc2. These mutations inhibit the activation of cdc25 by phosphorylation with p34cdc2 by 70 and 90%, respectively. At physiological concentrations these mutants cannot activate cyclin B/p34cdc2 in cdc25-immunodepleted oocyte extracts, suggesting that a positive feed-back loop between cdc2 and cdc25 is necessary for the full activation of cyclin B/p34cdc2 that induces abrupt entry into mitosis in vivo. Images PMID:7513216
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NASA Technical Reports Server (NTRS)
Birchenough, Arthur G.
2003-01-01
Improvements in the efficiency and size of DC-DC converters have resulted from advances in components, primarily semiconductors, and improved topologies. One topology, which has shown very high potential in limited applications, is the Series Connected Boost Unit (SCBU), wherein a small DC-DC converter output is connected in series with the input bus to provide an output voltage equal to or greater than the input voltage. Since the DC-DC converter switches only a fraction of the power throughput, the overall system efficiency is very high. But this technique is limited to applications where the output is always greater than the input. The Series Connected Buck Boost Regulator (SCBBR) concept extends partial power processing technique used in the SCBU to operation when the desired output voltage is higher or lower than the input voltage, and the implementation described can even operate as a conventional buck converter to operate at very low output to input voltage ratios. This paper describes the operation and performance of an SCBBR configured as a bus voltage regulator providing 50 percent voltage regulation range, bus switching, and overload limiting, operating above 98 percent efficiency. The technique does not provide input-output isolation.
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NASA Astrophysics Data System (ADS)
Yuan, Jiaxin; Zhou, Hang; Gan, Pengcheng; Zhong, Yongheng; Gao, Yanhui; Muramatsu, Kazuhiro; Du, Zhiye; Chen, Baichao
2018-05-01
To develop mechanical circuit breaker in high voltage direct current (HVDC) system, a fault current limiter is required. Traditional method to limit DC fault current is to use superconducting technology or power electronic devices, which is quite difficult to be brought to practical use under high voltage circumstances. In this paper, a novel concept of high voltage DC transmission system fault current limiter (DCSFCL) based on saturable core was proposed. In the DCSFCL, the permanent magnets (PM) are added on both up and down side of the core to generate reverse magnetic flux that offset the magnetic flux generated by DC current and make the DC winding present a variable inductance to the DC system. In normal state, DCSFCL works as a smoothing reactor and its inductance is within the scope of the design requirements. When a fault occurs, the inductance of DCSFCL rises immediately and limits the steepness of the fault current. Magnetic field simulations were carried out, showing that compared with conventional smoothing reactor, DCSFCL can decrease the high steepness of DC fault current by 17% in less than 10ms, which verifies the feasibility and effectiveness of this method.
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dc Arc Fault Effect on Hybrid ac/dc Microgrid
NASA Astrophysics Data System (ADS)
Fatima, Zahra
The advent of distributed energy resources (DER) and reliability and stability problems of the conventional grid system has given rise to the wide spread deployment of microgrids. Microgrids provide many advantages by incorporating renewable energy sources and increasing the reliability of the grid by isolating from the main grid in case of an outage. AC microgrids have been installed all over the world, but dc microgrids have been gaining interest due to the advantages they provide over ac microgrids. However the entire power network backbone is still ac and dc microgrids require expensive converters to connect to the ac power network. As a result hybrid ac/dc microgrids are gaining more attention as it combines the advantages of both ac and dc microgrids such as direct integration of ac and dc systems with minimum number of conversions which increases the efficiency by reducing energy losses. Although dc electric systems offer many advantages such as no synchronization and no reactive power, successful implementation of dc systems requires appropriate protection strategies. One unique protection challenge brought by the dc systems is dc arc faults. A dc arc fault is generated when there is a gap in the conductor due to insulation degradation and current is used to bridge the gap, resulting in an arc with very high temperature. Such a fault if it goes undetected and is not extinguished can cause damage to the entire system and cause fires. The purpose of the research is to study the effect of the dc arc fault at different locations in the hybrid ac/dc microgrid and provide insight on the reliability of the grid components when it is impacted by arc faults at various locations in the grid. The impact of dc arc fault at different locations on the performance of the PV array, wind generation, and constant power loads (CPL) interfaced with dc/dc converters is studied. MATLAB/Simulink is used to model the hybrid ac/dc microgrid and arc fault.
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Plasmacytoid dendritic cells: no longer an enigma and now key to transplant tolerance?
Rogers, NM; Isenberg, JS; Thomson, AW
2014-01-01
Plasmacytoid (p) dendritic cells (DC) are a specialized subset of DC whose primary role was initially defined by the production of type I interferons in response to viral infection. They are now known to also possess a repertoire of functions capable of determining T cell fate and activation. Under homeostatic conditions, non-lymphoid tissue-resident pDC play a critical role in the regulation of mucosal immunity, as well as the development of central and peripheral tolerance. Although these cells display a number of characteristics that differ from conventional DC, particularly altered costimulatory molecule expression and poor allostimulatory capacity when interacting with T cells, this phenotype favors the generation of alloantigen-specific regulatory CD4+ or CD8+ T cells critical to the development of graft tolerance. In this minireview we discuss pDC ontogeny, functional biology and the emerging data that demonstrate the importance of pDC in the induction of tolerance, as well as recent studies that define mechanisms underlying pDC-mediated tolerance to both solid organ and hematopoietic stem cell transplantats. We also highlight their use in clinical settings and the potential of pDC both as targets and cellular therapeutic agents to improve the outcome of organ transplantation. PMID:23617754
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22 CFR 103.12 - Reporting a violation.
Code of Federal Regulations, 2013 CFR
2013-04-01
... person may notify: United States National Authority, Office of Chemical and Biological Weapons Conventions, Bureau of Arms Control, U.S. Department of State, Washington, DC 20520, Telephone: (703) 235-1204...
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22 CFR 103.12 - Reporting a violation.
Code of Federal Regulations, 2012 CFR
2012-04-01
... person may notify: United States National Authority, Office of Chemical and Biological Weapons Conventions, Bureau of Arms Control, U.S. Department of State, Washington, DC 20520, Telephone: (703) 235-1204...
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22 CFR 103.12 - Reporting a violation.
Code of Federal Regulations, 2011 CFR
2011-04-01
... person may notify: United States National Authority, Office of Chemical and Biological Weapons Conventions, Bureau of Arms Control, U.S. Department of State, Washington, DC 20520, Telephone: (703) 235-1204...
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22 CFR 103.12 - Reporting a violation.
Code of Federal Regulations, 2010 CFR
2010-04-01
... person may notify: United States National Authority, Office of Chemical and Biological Weapons Conventions, Bureau of Arms Control, U.S. Department of State, Washington, DC 20520, Telephone: (703) 235-1204...
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CDC25A phosphatase controls meiosis I progression in mouse oocytes.
Solc, Petr; Saskova, Adela; Baran, Vladimir; Kubelka, Michal; Schultz, Richard M; Motlik, Jan
2008-05-01
CDK1 is a pivotal regulator of resumption of meiosis and meiotic maturation of oocytes. CDC25A/B/C are dual-specificity phosphatases and activate cyclin-dependent kinases (CDKs). Although CDC25C is not essential for either mitotic or meiotic cell cycle regulation, CDC25B is essential for CDK1 activation during resumption of meiosis. Cdc25a -/- mice are embryonic lethal and therefore a role for CDC25A in meiosis is unknown. We report that activation of CDK1 results in a maturation-associated decrease in the amount of CDC25A protein, but not Cdc25a mRNA, such that little CDC25A is present by metaphase I. In addition, expression of exogenous CDC25A overcomes cAMP-mediated maintenance of meiotic arrest. Microinjection of Gfp-Cdc25a and Gpf-Cdc25b mRNAs constructs reveals that CDC25A is exclusively localized to the nucleus prior to nuclear envelope breakdown (NEBD). In contrast, CDC25B localizes to cytoplasm in GV-intact oocytes and translocates to the nucleus shortly before NEBD. Over-expressing GFP-CDC25A, which compensates for the normal maturation-associated decrease in CDC25A, blocks meiotic maturation at MI. This MI block is characterized by defects in chromosome congression and spindle formation and a transient reduction in both CDK1 and MAPK activities. Lastly, RNAi-mediated reduction of CDC25A results in fewer oocytes resuming meiosis and reaching MII. These data demonstrate that CDC25A behaves differently during female meiosis than during mitosis, and moreover, that CDC25A has a function in resumption of meiosis, MI spindle formation and the MI-MII transition. Thus, both CDC25A and CDC25B are critical for meiotic maturation of oocytes.
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W-band GaAs camel-cathode Gunn devices produced by MBE
NASA Astrophysics Data System (ADS)
Beall, R. B.; Battersby, S. J.; Grecian, P. J.; Jones, S.; Smith, G.
1989-06-01
The dc and microwave performance of a novel second-harmonic W-band GaAs Gunn device incorporating a camel barrier are reported. Comparison with conventional Gunn devices shows significant improvement in power output and dc to RF conversion efficiency for the new structure. The frequency at which the maximum power is produced is lower for the camel cathode Gunn device, an observation attributed to a reduction in the length of the acceleration zone.
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NASA Astrophysics Data System (ADS)
El-Sayed, S. A.; Morsy, M. A.
2018-05-01
Amorphous chalcogenide composition AS4Se3Te3 is prepared by conventional quenching technique. The separate annealing or γ quanta irradiation not effect on the dc conductivity properties of the prepared composition. When the prepared samples are subjected to simultaneous annealing at temperature 413 K and γ quanta irradiation the dc conductivity increases. The dark dc conductivity increases by increasing the time of exposure to γ irradiation. At irradiation dose 1.47 × 104 Gy the dc conductivity starts to have metallic like conductivity character. These samples could be used as high temperature γ quanta dosimeter. By applying scaling theory on the samples irradiated with different dose of γ irradiation the critical exponents are determined and found to be < 2. The dark dc conductivity continuously decreases to 0 as temperature tends to zero. The steric value is low in the insulator side of conductivity, but high and almost saturated in the metallic side of conductivity.
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Dendritic cell based vaccines: progress in immunotherapy studies for prostate cancer.
Ragde, Haakon; Cavanagh, William A; Tjoa, Benjamin A
2004-12-01
No effective treatment is currently available for metastatic prostate cancer. Dendritic cell (DC) based cancer vaccine research has emerged from the laboratories to human clinical trials. We describe progress in the development of DC based prostate cancer vaccine. The literature was reviewed for major contributions to a growing number of studies that demonstrate the potential of DC based immunotherapeutics for prostate cancer. Background topics relating to DC based immunotherapy theory and practice are also addressed. DCs have been recognized as the most efficient antigen presenting cells that have the capacity to initiate naive T cell response in vitro and in vivo. During their differentiation and maturation pathways, dendritic cells can efficiently capture, process and present antigens for T cell activation. These characteristics make DC an attractive choice as the cellular adjuvant for cancer vaccines. Advances in DC generation, loading, and maturation methodologies have made it possible to generate clinical grade vaccines for various human trials. More than 100 DC vaccine trials, including 7 studies of patients with advanced prostate cancer have been reported to date. These vaccines were generally well tolerated with no significant adverse toxicity reported. Clinical responders have been identified in these studies. The new prospects opened by DC based vaccines for prostate cancer are fascinating. When compared to conventional treatments, DC vaccinations have few side effects. Improvements in patient selection, vaccine delivery strategies, immune monitoring and vaccine manufacturing will be crucial in moving DC based prostate cancer vaccines closer to the clinics.
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[Status of measures against angiography room infection as determined by questionnaire].
Tsukamoto, Atsuko; Ito, Makiko; Takahashi, Kanji; Watanabe, Emi; Kikuchi, Tatsuya; Tajima, Osamu; Masuda, Kazuhiro; Wakamatsu, Osamu; Sato, Tsugio; Nakazawa, Yasuo
2006-11-20
Although the cleanliness of the angiography room and that of the operating room have long been equally attended to, the concept of Standard Precautions (including the basic measures and procedures to prevent infection) of the Centers for Disease Control and Prevention (CDC), 1996, as well as the introduction of transmission-based precautions, have been changing to preventive measures that are based on concrete measures. Therefore, a questionnaire was introduced in order to determine the actual status of countermeasures against infection used in the angiography room. The questionnaire was sent to 530 institutions, and 286 responded, a response rate of 54.0%. Its results significantly revealed the following: 1) unexpectedly low recognition of the need and importance for the CDC preventive measures against infection, 2) a considerable number of institutions continuing to perform the conventional preventive measures, 3) problems with education systems on preventive measures, and 4) handwashing, the most important measure against infection, failing to be adequately carried out noticeably among radiological technologists.
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Enhancing Air Interdiction of WMD
2014-04-01
The Convention on International Civil Aviation, 9th ed., 9 and 10 and Jennifer K. Elsa , Weapons of Mass Destruction Counterproliferation: Legal...Issues for Ships and Aircraft, CRS Report RL32097, (Washington D.C: CRS, 1 October 2003), 24. 15 Elsa , Weapons of Mass Destruction Counterproliferation...Legal Issues for Ships and Aircraft, 20. 16 The Convention on International Civil Aviation, 9th ed., 4. 17 Elsa , Weapons of Mass Destruction
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The Control Principles of the Wind Energy Based DC Microgrid
NASA Astrophysics Data System (ADS)
Zaleskis, G.; Rankis, I.
2018-04-01
According to the strategical objectives of the use of the renewable energy sources, it is important to minimise energy consumption of conventional power grid by effective use of the renewable energy sources and provi-ding stable operation of the consumers. The main aim of research is to develop technical solutions that can provide effective operation of the wind generators in the small power DC microgrids, which also means wind energy conversion at as wider generator speed range as possible.
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Soft-commutated direct current motor
Hsu, John S.
1999-01-01
A method and circuit is disclosed for soft-commutation of a direct current (DC) motor. An attenuation circuit is connected through auxiliary brushes A, A', B and B' to the commutator (16) to drain circuit from successive armature coils (15) before the main brushes (27, 28) disconnects from each of the coils (15). This prevents the spark generation that normally occurs in conventional DC motors. The attenuation circuit may also be connected before energization of the coil (15) for a soft turning on operation.
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Goffeau, Jacques R.
1979-01-01
An improved Up-and-Down Chopper Circuit is provided which is useful for voltage regulation in a bi-directional DC power system. In the down mode, power is switched from a DC power source to a lower voltage energy storing load while in the up mode stored energy in the load is transferred to the higher voltage source. The system uses Darlington transistor switches in a conventional connection. The improvement relates to circuit additions to eliminate the effects of inter-electrode capacitance inherent with this Darlington transistor switching arrangement.
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Life Balancing -- A Better Way to Balance Large Batteries
DOE Office of Scientific and Technical Information (OSTI.GOV)
Anderson, R. Dyche; Zane, Regan; Plett, Gregory
2017-03-28
A new cell balancing technology was developed under a Department of Energy contract which merges the DC/DC converter function into cell balancing. Instead of conventional passive cell balancing technology which bypasses current through a resistor, or active cell balancing which moves current from one cell to another, with significant cost and additional inefficiencies, this concept takes variable amount of current from each cell or small group of cells and converts it to current for the low voltage system.
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Soft-commutated direct current motor
Hsu, J.S.
1999-07-27
A method and circuit is disclosed for soft-commutation of a direct current (DC) motor. An attenuation circuit is connected through auxiliary brushes A, A[prime], B and B[prime] to the commutator (16) to drain circuit from successive armature coils (15) before the main brushes (27, 28) disconnects from each of the coils (15). This prevents the spark generation that normally occurs in conventional DC motors. The attenuation circuit may also be connected before energization of the coil (15) for a soft turning on operation. 13 figs.
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The effect of DNA replication on mutation of the Saccharomyces cerevisiae CDC8 gene.
Zaborowska, D; Zuk, J
1990-04-01
Incubation in YPD medium under permissive conditions when DNA replication is going on, strongly stimulates the induction of cdc+ colonies of UV-irradiated cells of yeast strains HB23 (cdc8-1/cdc8-3), HB26 (cdc8-3/cdc8-3) and HB7 (cdc8-1/cdc8-1). Inhibition of DNA replication by hydroxyurea, araCMP, cycloheximide or caffeine or else by incubation in phosphate buffer pH 7.0, abolishes this stimulation. Thus the replication of DNA is strongly correlated with the high induction of cdc+ colonies by UV irradiation. It is postulated that these UV-induced cdc+ colonies arise as the result infidelity in DNA replication.
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Ubiquitination of Cdc20 by the APC occurs through an intramolecular mechanism
Foe, Ian T.; Foster, Scott A.; Cheung, Stephanie K.; DeLuca, Steven Z.; Morgan, David O.; Toczyski, David P.
2012-01-01
SUMMARY Background Cells control progression through late mitosis by regulating Cdc20 and Cdh1, the two mitotic activators of the Anaphase Promoting Complex (APC). The control of Cdc20 protein levels during the cell cycle is not well understood. Results Here, we demonstrate that Cdc20 is degraded in budding yeast by multiple APC-dependent mechanisms. We find that the majority of Cdc20 turnover does not involve a second activator molecule, but instead depends on in cis Cdc20 autoubiquitination while it is bound to its activator-binding site on the APC core. Unlike in trans ubiquitination of Cdc20 substrates, the APC ubiquitinates Cdc20 independent of APC activation by Cdc20’s C-box. Cdc20 turnover by this intramolecular mechanism is cell cycle-regulated, contributing to the decline in Cdc20 levels that occurs after anaphase. Interestingly, high substrate levels in vitro significantly reduce Cdc20 autoubiquitination. Conclusion We show here that Cdc20 fluctuates through the cell cycle via a distinct form of APC-mediated ubiquitination. This in cis autoubiquitination may preferentially occur in early anaphase, following depletion of Cdc20 substrates. This suggests that distinct mechanisms are able to target Cdc20 for ubiquitination at different points during the cell cycle. PMID:22079111
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A Compact, Soft-Switching DC-DC Converter for Electric Propulsion
NASA Technical Reports Server (NTRS)
Button, Robert; Redilla, Jack; Ayyanar, Raja
2003-01-01
A hybrid, soft-switching, DC-DC converter has been developed with superior soft switching characteristics, high efficiency, and low electro-magnetic interference. This hybrid topology is comprised of an uncontrolled bridge operating at full pulse-width, and a controlled section operating as a conventional phase modulated converter. The unique topology is able to maintain zero voltage switching down to no load operating conditions. A breadboard prototype was developed and tested to demonstrate the benefits of the topology. Improvements were then made to reduce the size of passive components and increase efficiency in preparation for packaging. A packaged prototype was then designed and built, and several innovative packaging techniques are presented. Performance test data is presented that reveals deficiencies in the design of the power transformer. A simple redesign of the transformer windings eliminated the deficiency. Future plans to improve the converter and packaging design are presented along with several conclusions.
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Maximum Power Point tracking charge controllers for telecom applications -- Analysis and economics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wills, R.H.
Simple charge controllers connect photovoltaic modules directly to the battery bank resulting in a significant power loss if the battery bank voltage differs greatly from the PV Maximum Power Point (MPP) voltage. Recent modeling work at AES has shown that dc-dc converter type MPP tracking charge controllers can deliver more than 30% more energy from PV modules to the battery when the PV modules are cool and the battery state of charge is low--this is typically both the worst case condition (i.e., winter) and also the design condition that determines the PV array size. Economic modeling, based on typical telecommore » system installed costs shows benefits of more than $3/Wp for MPPT over conventional charge controllers in this application--a value that greatly exceeds the additional cost of the dc-dc converter.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lammer, Johannes, E-mail: johannes.lammer@meduniwien.ac.a; Malagari, Katarina; Vogl, Thomas
2010-02-15
Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomizationmore » was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.« less
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Stephenson, Robert; Hosler, Marcus R; Gavande, Navnath S; Ghosh, Arun K; Weake, Vikki M
2015-01-16
Cdc7 is a serine-threonine kinase that phosphorylates components of the pre-replication complex during DNA replication initiation. Cdc7 is highly conserved, and Cdc7 orthologs have been characterized in organisms ranging from yeast to humans. Cdc7 is activated specifically during late G1/S phase by binding to its regulatory subunit, Dbf4. Drosophila melanogaster contains a Dbf4 ortholog, Chiffon, which is essential for chorion amplification in Drosophila egg chambers. However, no Drosophila ortholog of Cdc7 has yet been characterized. Here, we report the functional and biochemical characterization of a Drosophila ortholog of Cdc7. Co-expression of Drosophila Cdc7 and Chiffon is able to complement a growth defect in yeast containing a temperature-sensitive Cdc7 mutant. Cdc7 and Chiffon physically interact and can be co-purified from insect cells. Cdc7 phosphorylates the known Cdc7 substrates Mcm2 and histone H3 in vitro, and Cdc7 kinase activity is stimulated by Chiffon and inhibited by the Cdc7-specific inhibitor XL413. Drosophila egg chamber follicle cells deficient for Cdc7 have a defect in two types of DNA replication, endoreplication and chorion gene amplification. However, follicle cells deficient for Chiffon have a defect in chorion gene amplification but still undergo endocycling. Our results show that Cdc7 interacts with Chiffon to form a functional Dbf4-dependent kinase complex and that Cdc7 is necessary for DNA replication in Drosophila egg chamber follicle cells. Additionally, we show that Chiffon is a member of an expanding subset of DNA replication initiation factors that are not strictly required for endoreplication in Drosophila. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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Complement-dependent cytotoxicity (CDC) to detect Anti-HLA antibodies: old but gold.
Saito, Patrícia Keiko; Yamakawa, Roger Haruki; Pereira, Lucieni Christina Marques da Silva; da Silva, Waldir Veríssimo; Borelli, Sueli Donizete
2014-07-01
The criterion (gold) standard to detect anti-human leukocyte antigen (HLA) antibodies is the complement-dependent cytotoxicity (CDC) assay. Recently, more sensitive methods have been used for the same purpose. This study analyzed 70 serum samples of patients with end-stage renal disease using CDC, CDC with the addition of anti-human globulin (CDC-AHG), CDC with the addition of dithiothreitol (CDC-DTT), and the recent solid-phase immunoassay (SPI; Labscreen PRA) to detect anti-HLA antibodies. Mean percent panel reactive antibodies (PRA) detected by SPI was 37.5% (±34.2) higher than the values detected by the other methods. Comparative analyses revealed significant difference between CDC and CDC-AHG, and between CDC and SPI (P < 0.0001), but not between CDC-AHG and SPI (P = 0.8026). Although the CDC-AHG method is "old," its performance to detect anti-HLA antibodies in the samples analyzed was comparable to the SPI in the evaluation of percent class I PRA. © 2014 Wiley Periodicals, Inc.
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cdc25 cell cycle-activating phosphatases and c-myc expression in human non-Hodgkin's lymphomas.
Hernández, S; Hernández, L; Beà, S; Cazorla, M; Fernández, P L; Nadal, A; Muntané, J; Mallofré, C; Montserrat, E; Cardesa, A; Campo, E
1998-04-15
cdc25A, cdc25B, and cdc25C are a family of human phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and cdc25B have been shown to have oncogenic potential, and they have been identified as transcriptional targets of c-myc. To determine the role of cdc25 genes in the pathogenesis of human lymphomas and their possible correlation with c-myc deregulation, we have analyzed the expression of cdc25A, cdc25B, and cdc25C and c-myc genes in a series of 63 non-Hodgkin's lymphomas and 8 nonneoplastic lymphoid tissues. The mRNA levels of the three phosphatases in the nonneoplastic tissues were negative or negligible. cdc25B overexpression was detected in 35 tumors (56%). This overexpression was more frequently found in aggressive (81%) than in indolent lymphomas (36%; P < 0.01). cdc25B overexpression was also significantly associated with a higher proliferative activity of the tumors. No cdc25B gene amplification or rearrangements were detected by Southern blot analysis. A biallelic EcoRI polymorphism of cdc25B gene was identified with a similar distribution in patients with lymphoma and in a normal population. cdc25A was overexpressed in three aggressive lymphomas. No detectable cdc25C mRNA levels were seen in any of the tumors. c-myc was overexpressed in 43% of tumors, and it correlated significantly with the presence of cdc25B up-regulation. Twenty-six of 35 (74%) lymphomas with high levels of cdc25B mRNA also showed c-myc overexpression, whereas 27 of 28 (96%) tumors without detectable or with very low cdc25B expression also had undetectable c-myc levels (P < 0.0001). In addition, a significant linear correlation was found between the cdc25B and c-myc mRNA levels (r = 0.575, P < 0.001). These findings suggest that cdc25B overexpression in non-Hodkin's lymphoma may participate in the pathogenesis of aggressive variants, and it may cooperate with c-myc oncogene in the development of these tumors.
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Design of a -1 MV dc UHV power supply for ITER NBI
NASA Astrophysics Data System (ADS)
Watanabe, K.; Yamamoto, M.; Takemoto, J.; Yamashita, Y.; Dairaku, M.; Kashiwagi, M.; Taniguchi, M.; Tobari, H.; Umeda, N.; Sakamoto, K.; Inoue, T.
2009-05-01
Procurement of a dc -1 MV power supply system for the ITER neutral beam injector (NBI) is shared by Japan and the EU. The Japan Atomic Energy Agency as the Japan Domestic Agency (JADA) for ITER contributes to the procurement of dc -1 MV ultra-high voltage (UHV) components such as a dc -1 MV generator, a transmission line and a -1 MV insulating transformer for the ITER NBI power supply. The inverter frequency of 150 Hz in the -1 MV power supply and major circuit parameters have been proposed and adopted in the ITER NBI. The dc UHV insulation has been carefully designed since dc long pulse insulation is quite different from conventional ac insulation or dc short pulse systems. A multi-layer insulation structure of the transformer for a long pulse up to 3600 s has been designed with electric field simulation. Based on the simulation the overall dimensions of the dc UHV components have been finalized. A surge energy suppression system is also essential to protect the accelerator from electric breakdowns. The JADA contributes to provide an effective surge suppression system composed of core snubbers and resistors. Input energy into the accelerator from the power supply can be reduced to about 20 J, which satisfies the design criteria of 50 J in total in the case of breakdown at -1 MV.
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cdc-25.4, a Caenorhabditis elegans Ortholog of cdc25, Is Required for Male Mating Behavior
Oh, Sangmi; Kawasaki, Ichiro; Park, Jae-Hyung; Shim, Yhong-Hee
2016-01-01
Cell division cycle 25 (cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression. Among the four cdc25 orthologs in Caenorhabditis elegans, we found that cdc-25.4 mutant males failed to produce outcrossed progeny. This was not caused by defects in sperm development, but by defects in male mating behavior. The cdc-25.4 mutant males showed various defects during male mating, including contact response, backing, turning, and vulva location. Aberrant turning behavior was the most prominent defect in the cdc-25.4 mutant males. We also found that cdc-25.4 is expressed in many neuronal cells throughout development. The turning defect in cdc-25.4 mutant males was recovered by cdc-25.4 transgenic expression in neuronal cells, suggesting that cdc-25.4 functions in neurons for male mating. However, the neuronal morphology of cdc-25.4 mutant males appeared to be normal, as examined with several neuronal markers. Also, RNAi depletion of wee-1.3, a C. elegans ortholog of Wee1/Myt1 kinase, failed to suppress the mating defects of cdc-25.4 mutant males. These findings suggest that, for successful male mating, cdc-25.4 does not target cell cycles that are required for neuronal differentiation and development. Rather, cdc-25.4 likely regulates noncanonical substrates in neuronal cells. PMID:27770028
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cdc-25.4, a Caenorhabditis elegans Ortholog of cdc25, Is Required for Male Mating Behavior.
Oh, Sangmi; Kawasaki, Ichiro; Park, Jae-Hyung; Shim, Yhong-Hee
2016-12-07
Cell division cycle 25 (cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression. Among the four cdc25 orthologs in Caenorhabditis elegans, we found that cdc-25.4 mutant males failed to produce outcrossed progeny. This was not caused by defects in sperm development, but by defects in male mating behavior. The cdc-25.4 mutant males showed various defects during male mating, including contact response, backing, turning, and vulva location. Aberrant turning behavior was the most prominent defect in the cdc-25.4 mutant males. We also found that cdc-25.4 is expressed in many neuronal cells throughout development. The turning defect in cdc-25.4 mutant males was recovered by cdc-25.4 transgenic expression in neuronal cells, suggesting that cdc-25.4 functions in neurons for male mating. However, the neuronal morphology of cdc-25.4 mutant males appeared to be normal, as examined with several neuronal markers. Also, RNAi depletion of wee-1.3, a C. elegans ortholog of Wee1/Myt1 kinase, failed to suppress the mating defects of cdc-25.4 mutant males. These findings suggest that, for successful male mating, cdc-25.4 does not target cell cycles that are required for neuronal differentiation and development. Rather, cdc-25.4 likely regulates noncanonical substrates in neuronal cells. Copyright © 2016 Oh et al.
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Araujo-Palomares, Cynthia L; Richthammer, Corinna; Seiler, Stephan; Castro-Longoria, Ernestina
2011-01-01
Rho-type GTPases are key regulators that control eukaryotic cell polarity, but their role in fungal morphogenesis is only beginning to emerge. In this study, we investigate the role of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. rac and cdc-42 deletion mutants are viable, but generate highly compact colonies with severe morphological defects. Double mutants carrying conditional and loss of function alleles of rac and cdc-42 are lethal, indicating that both GTPases share at least one common essential function. The defects of the GTPase mutants are phenocopied by deletion and conditional alleles of the guanine exchange factor (GEF) cdc-24, and in vitro GDP-GTP exchange assays identify CDC-24 as specific GEF for both CDC-42 and RAC. In vivo confocal microscopy shows that this module is organized as membrane-associated cap that covers the hyphal apex. However, the specific localization patterns of the three proteins are distinct, indicating different functions of RAC and CDC-42 within the hyphal tip. CDC-42 localized as confined apical membrane-associated crescent, while RAC labeled a membrane-associated ring excluding the region labeled by CDC42. The GEF CDC-24 occupied a strategic position, localizing as broad apical membrane-associated crescent and in the apical cytosol excluding the Spitzenkörper. RAC and CDC-42 also display distinct localization patterns during branch initiation and germ tube formation, with CDC-42 accumulating at the plasma membrane before RAC. Together with the distinct cellular defects of rac and cdc-42 mutants, these localizations suggest that CDC-42 is more important for polarity establishment, while the primary function of RAC may be maintaining polarity. In summary, this study identifies CDC-24 as essential regulator for RAC and CDC-42 that have common and distinct functions during polarity establishment and maintenance of cell polarity in N. crassa.
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XCII. A Low-Cost Voltammetric Signal Generator for the Electroanalytical Chemistry Laboratory
ERIC Educational Resources Information Center
Ewing, Galen W., Ed
1977-01-01
Describes the construction of a versatile signal generator suitable for use in cyclic voltammetric experiments, which can also be adapted to a conventional dc polarograph by replacing its ramp source. (MLH)
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... DC, Wewalka M, et al. Adjustable gastric band surgery or medical management in patients with type 2 diabetes: a randomized ... 25900871 . Kushner RF, Ryan DH. Assessment and lifestyle management of patients with ... surgery versus conventional medical treatment in obese patients with ...
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USA Science and Engineering Festival 2014
2014-04-25
A NASA staff member discusses planets with attendees of the USA Science and Engineering Festival, which took place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)
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13 CFR 120.822 - CDC membership.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...
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13 CFR 120.822 - CDC membership.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...
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13 CFR 120.822 - CDC membership.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...
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13 CFR 120.822 - CDC membership.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...
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13 CFR 120.822 - CDC membership.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC membership. 120.822 Section... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.822 CDC membership. (a) CDC Membership. A CDC must have at least 25 members (or stockholders for for-profit CDCs approved...
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Code of Federal Regulations, 2013 CFR
2013-01-01
... new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business Credit...) Extending A Cdc's Area of Operations § 120.837 SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. The processing District Office must solicit the comments of any...
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Code of Federal Regulations, 2014 CFR
2014-01-01
... new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business Credit...) Extending A Cdc's Area of Operations § 120.837 SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. The processing District Office must solicit the comments of any...
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Code of Federal Regulations, 2011 CFR
2011-01-01
... new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business Credit...) Extending A Cdc's Area of Operations § 120.837 SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. The processing District Office must solicit the comments of any...
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Code of Federal Regulations, 2012 CFR
2012-01-01
... new CDC or for an existing CDC to expand Area of Operations. 120.837 Section 120.837 Business Credit...) Extending A Cdc's Area of Operations § 120.837 SBA decision on application for a new CDC or for an existing CDC to expand Area of Operations. The processing District Office must solicit the comments of any...
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DC-DC Type High-Frequency Link DC for Improved Power Quality of Cascaded Multilevel Inverter
NASA Astrophysics Data System (ADS)
Sadikin, Muhammad; Senjyu, Tomonobu; Yona, Atsushi
2013-06-01
Multilevel inverters are emerging as a new breed of power converter options for power system applications. Recent advances in power switching devices enabled the suitability of multilevel inverters for high voltage and high power applications because they are connecting several devices in series without the need of component matching. Usually, a transformerless battery energy storage system, based on a cascaded multilevel inverter, is used as a measure for voltage and frequency deviations. System can be reduced in size, weight, and cost of energy storage system. High-frequency link circuit topology is advantageous in realizing compact and light-weight power converters for uninterruptible power supply systems, new energy systems using photovoltaic-cells, fuel-cells and so on. This paper presents a DC-DC type high-frequency link DC (HFLDC) cascaded multilevel inverter. Each converter cell is implemented a control strategy for two H-bridge inverters that are controlled with the same multicarrier pulse width modulation (PWM) technique. The proposed cascaded multilevel inverter generates lower voltage total harmonic distortion (THD) in comparison with conventional cascaded multilevel inverter. Digital simulations are carried out using PSCAD/EMTDC to validate the performance of the proposed cascaded multilevel inverter.
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Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong
2010-01-01
Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods. PMID:20808670
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Yoo, Changhee; Do, Hyun-Ah; Jeong, In Gab; Park, Hongzoo; Hwang, Jung-Jin; Hong, Jun Hyuk; Cho, Jin Seon; Choo, Myong-Soo; Ahn, Hanjong; Kim, Choung-Soo
2010-09-01
Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E(2) and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.
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A hybrid electrical power system for aircraft application.
NASA Technical Reports Server (NTRS)
Lee, C. H.; Chin, C. Y.
1971-01-01
Possible improvements to present aircraft electrical power systems for use in future advanced types of aircraft have been investigated. The conventional power system is examined, the characteristics of electric loads are reviewed, and various methods of power generation and distribution are appraised. It is shown that a hybrid system, with variable-frequency generation and high-voltage dc distribution, could overcome some of the limitations of the conventional system.
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Ashmawy, Tarek Mohy; El Talawy, Dina Bahgat; Shaheen, Nasser Hussein
2014-09-01
To objectively evaluate the effect of mini-implant- supported mandibular overdentures on electromyographic activity (EMG) of the masseter muscle during chewing of hard and soft foods. Twelve completely edentulous patients (4 females and 8 males) with maladaptive experience of wearing mandibular dentures received new maxillary and mandibular dentures. After 3 months of adaptation, four mini dental implants (MDIs) were inserted in the interforaminal region of the mandible, and the new mandibular dentures were connected to the implants immediately with O/ring attachments. The activity of masseter muscle (EMG) and the duration of chewing cycle were measured during chewing hard (carrot) and soft (gum) foods. The measurements were made 3 months after wearing each of the following prostheses: the new conventional dentures; and the MDI-retained mandibular overdentures. The EMG of masseter muscle increased and the DC decreased with MDI-retained mandibular overdentures when compared to conventional dentures. Hard food (carrot) was associated with increased EMG and decreased DC when compared to soft food (gum) for both conventional dentures and MDI-retained mandibular overdentures. Mini-implant-supported mandibular overdentures are associated with increased activity of masseter muscle and decreased duration of chewing cycle for both hard and soft foods when compared to conventional dentures.
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NASA Technical Reports Server (NTRS)
Hamilton, H. B.; Strangas, E.
1980-01-01
The conventional series motor model is discussed as well as procedures for obtaining, by test, the parameters necessary for calculating performance and losses. The calculated results for operation from ripple free DC are compared with observed test results, indicating approximately 5% or less error. Experimental data indicating the influence of brush shift and chopper frequency are also presented. Both factors have a significant effect on the speed and torque relationships. The losses and loss mechanisms present in a DC series motor are examined and an attempt is made to evaluate the added losses due to harmonic currents and fluxes. Findings with respect to these losses is summarized.
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Injuries and Mass Casualty Events
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[Expression levels of Cdc2 and Cdc25A mRNA in cattle, yak, and cattle-yak testis].
Dong, Li-Yan; Li, Qi-Fa; Qu, Xu-Guang; Li, Yin-Xia; Li, Xin-Fu; Hu, Hong-Tao; Xie, Zhuang
2009-05-01
The infertility of cattle-yak, which is the hybrid offspring of cattle and yak, is a difficult problem in crossbreeding and improvement of yak. Cdc2 and Cdc25A are the key genes of meiosis. The decline of their expression levels will cause the spermatogenesis failure and lead to infertility. Therefore, this study was conducted to study the relationship between the infertility of cattle-yak and the expression levels of Cdc2/Cdc25A genes. The expression profiles were obtained by RT-PCR. Cdc2 and Cdc25A genes were widely expressed in many tissues, which confirmed their important role in cell division and the progression of cell cycle. Real-time quantitative PCR analysis indicated that the expression levels of Cdc2 and Cdc25A in cattle and yak testis were higher than those in cattle-yak (P<0.05). Therefore, low expression levels of Cdc2 and Cdc25A genes may have a relationship with the infertility of cattle-yak.
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The Cdc48 Protein and Its Cofactor Vms1 Are Involved in Cdc13 Protein Degradation*
Baek, Guem Hee; Cheng, Haili; Kim, Ikjin; Rao, Hai
2012-01-01
Vms1 is a newly identified Cdc48-binding protein. The biological function of Vms1 remains obscure. Here, we show that both Cdc48 and Vms1, but not Cdc48 cofactors Ufd1 and Ufd2, are crucial for the degradation of Cdc13, a telomere regulator. Interestingly, both autophagy and the proteasome are involved in Cdc13 turnover. Toxicity associated with accumulation of large amounts of Cdc13 in vms1Δ or autophagy mutants underscores the significance of the proteolytic regulation of Cdc13. Because few ubiquitylated yeast proteins are known to be degraded by autophagy under non-stress conditions, the identification of Cdc13 as a target of autophagy provides a valuable tool to unravel the mechanism of autophagy-mediated selective protein degradation. PMID:22718752
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Marty, Amber J; Gauthier, Gregory M
2013-01-01
Blastomyces dermatitidis, the etiologic agent of blastomycosis, belongs to a group of thermally dimorphic fungi that change between mold (22°C) and yeast (37°C) in response to temperature. The contribution of structural proteins such as septins to this phase transition in these fungi remains poorly understood. Septins are GTPases that serve as a scaffold for proteins involved with cytokinesis, cell polarity, and cell morphology. In this study, we use a GFP sentinel RNA interference system to investigate the impact of CDC3, CDC10, CDC12, and ASPE on the morphology and phase transition of B. dermatitidis. Targeting CDC3, CDC10, and CDC12 by RNA interference resulted in yeast with aberrant morphology at 37°C with defects in cytokinesis. Downshifting the temperature to 22°C promoted the conversion to the mold phase, but did not abrogate the morphologic defects. CDC3, CDC10, and CDC12 knockdown strains grew as mold with curved, thickened hyphae. Knocking down ASPE transcript did not alter morphology of yeast at 37°C or mold at 22°C. Following an increase in temperature from 22°C to 37°C, all septin knockdown strains were able to revert to yeast. In conclusion, CDC3, CDC10, and CDC12 septin- encoding genes are required for proper morphology of yeast and hyphae, but are dispensable for the phase transition.
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Jiang, Yiqun; Bernard, Denzil; Yu, Yanke; Xie, Yehua; Zhang, Tao; Li, Yanyan; Burnett, Joseph P.; Fu, Xueqi; Wang, Shaomeng; Sun, Duxin
2010-01-01
Hsp90 requires cochaperone Cdc37 to load its clients to the Hsp90 superchaperone complex. The purpose of this study was to utilize split Renilla luciferase protein fragment-assisted complementation (SRL-PFAC) bioluminescence to study the full-length human Hsp90-Cdc37 complex and to identity critical residues and their contributions for Hsp90/Cdc37 interaction in living cells. SRL-PFAC showed that full-length human Hsp90/Cdc37 interaction restored dramatically high luciferase activity through Hsp90-Cdc37-assisted complementation of the N and C termini of luciferase (compared with the set of controls). Immunoprecipitation confirmed that the expressed fusion proteins (NRL-Hsp90 and Cdc37-CRL) preserved their ability to interact with each other and also with native Hsp90 or Cdc37. Molecular dynamic simulation revealed several critical residues in the two interaction patches (hydrophobic and polar) at the interface of Hsp90/Cdc37. Mutagenesis confirmed the critical residues for Hsp90-Cdc37 complex formation. SRL-PFAC bioluminescence evaluated the contributions of these critical residues in Hsp90/Cdc37 interaction. The results showed that mutations in Hsp90 (Q133A, F134A, and A121N) and mutations in Cdc37 (M164A, R167A, L205A, and Q208A) reduced the Hsp90/Cdc37 interaction by 70–95% as measured by the resorted luciferase activity through Hsp90-Cdc37-assisted complementation. In comparison, mutations in Hsp90 (E47A and S113A) and a mutation in Cdc37 (A204E) decreased the Hsp90/Cdc37 interaction by 50%. In contrast, mutations of Hsp90 (R46A, S50A, C481A, and C598A) and mutations in Cdc37 (C54S, C57S, and C64S) did not change Hsp90/Cdc37 interactions. The data suggest that single amino acid mutation in the interface of Hsp90/Cdc37 is sufficient to disrupt its interaction, although Hsp90/Cdc37 interactions are through large regions of hydrophobic and polar interactions. These findings provides a rationale to develop inhibitors for disruption of the Hsp90/Cdc37 interaction. PMID:20413594
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Jiang, Yiqun; Bernard, Denzil; Yu, Yanke; Xie, Yehua; Zhang, Tao; Li, Yanyan; Burnett, Joseph P; Fu, Xueqi; Wang, Shaomeng; Sun, Duxin
2010-07-02
Hsp90 requires cochaperone Cdc37 to load its clients to the Hsp90 superchaperone complex. The purpose of this study was to utilize split Renilla luciferase protein fragment-assisted complementation (SRL-PFAC) bioluminescence to study the full-length human Hsp90-Cdc37 complex and to identity critical residues and their contributions for Hsp90/Cdc37 interaction in living cells. SRL-PFAC showed that full-length human Hsp90/Cdc37 interaction restored dramatically high luciferase activity through Hsp90-Cdc37-assisted complementation of the N and C termini of luciferase (compared with the set of controls). Immunoprecipitation confirmed that the expressed fusion proteins (NRL-Hsp90 and Cdc37-CRL) preserved their ability to interact with each other and also with native Hsp90 or Cdc37. Molecular dynamic simulation revealed several critical residues in the two interaction patches (hydrophobic and polar) at the interface of Hsp90/Cdc37. Mutagenesis confirmed the critical residues for Hsp90-Cdc37 complex formation. SRL-PFAC bioluminescence evaluated the contributions of these critical residues in Hsp90/Cdc37 interaction. The results showed that mutations in Hsp90 (Q133A, F134A, and A121N) and mutations in Cdc37 (M164A, R167A, L205A, and Q208A) reduced the Hsp90/Cdc37 interaction by 70-95% as measured by the resorted luciferase activity through Hsp90-Cdc37-assisted complementation. In comparison, mutations in Hsp90 (E47A and S113A) and a mutation in Cdc37 (A204E) decreased the Hsp90/Cdc37 interaction by 50%. In contrast, mutations of Hsp90 (R46A, S50A, C481A, and C598A) and mutations in Cdc37 (C54S, C57S, and C64S) did not change Hsp90/Cdc37 interactions. The data suggest that single amino acid mutation in the interface of Hsp90/Cdc37 is sufficient to disrupt its interaction, although Hsp90/Cdc37 interactions are through large regions of hydrophobic and polar interactions. These findings provides a rationale to develop inhibitors for disruption of the Hsp90/Cdc37 interaction.
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Burrows, Nilka Rios; Hora, Israel; Geiss, Linda S; Gregg, Edward W; Albright, Ann
2017-11-03
During 2014, 120,000 persons in the United States and Puerto Rico began treatment for end-stage renal disease (ESRD) (i.e., kidney failure requiring dialysis or transplantation) (1). Among these persons, 44% (approximately 53,000 persons) had diabetes listed as the primary cause of ESRD (ESRD-D) (1). Although the number of persons initiating ESRD-D treatment each year has increased since 1980 (1,2), the ESRD-D incidence rate among persons with diagnosed diabetes has declined since the mid-1990s (2,3). To determine whether ESRD-D incidence has continued to decline in the United States overall and in each state, the District of Columbia (DC), and Puerto Rico, CDC analyzed 2000-2014 data from the U.S. Renal Data System and the Behavioral Risk Factor Surveillance System. During that period, the age-standardized ESRD-D incidence among persons with diagnosed diabetes declined from 260.2 to 173.9 per 100,000 diabetic population (33%), and declined significantly in most states, DC, and Puerto Rico. No state experienced an increase in ESRD-D incidence rates. Continued awareness of risk factors for kidney failure and interventions to improve diabetes care might sustain and improve these trends.
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Smolen, Kinga K; Cai, Bing; Fortuno, Edgardo S; Gelinas, Laura; Larsen, Martin; Speert, David P; Chamekh, Mustapha; Kollmann, Tobias R
2014-01-01
Innate immunity instructs adaptive immunity, and suppression of innate immunity is associated with increased risk for infection. We had previously shown that whole blood cellular components from a cohort of South African children secreted significantly lower levels of most cytokines following stimulation of pattern recognition receptors (PRR) as compared to whole blood from cohorts of Ecuadorian, Belgian, or Canadian children. To begin dissecting the responsible molecular mechanisms, we now set out to identify the relevant cellular source of these differences. Across the four cohorts represented in our study, we identified significant variation in the cellular composition of whole blood; however, significant reduction of the intracellular cytokine production on the single cell level was only detected in South African childrens’ monocytes, cDC, and pDC. We also uncovered a marked reduction in polyfunctionality for each of these cellular compartments in South African children as compared to children from other continents. Together our data identify differences in cell composition as well as profoundly lower functional responses of innate cells in our cohort of South African children. A possible link between altered innate immunity and increased risk for infection or lower response to vaccines in South African infants needs to be explored. PMID:25135829
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USA Science and Engineering Festival 2014
2014-04-25
A NASA staff member describes landing technology to an attendee of the USA Science and Engineering Festival, which took place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)
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Multiphase High-Frequency Isolated DC-DC Converter for Industrial Applications
NASA Astrophysics Data System (ADS)
Maurya, Rakesh; Srivastava, S. P.; Agarwal, Pramod
2014-01-01
Industrial applications such as welding, plasma cutting, and surface hardening require a large DC current at low voltage. In such applications, the rating of power supply varies from few kilowatts to hundreds of kilowatts. The power supply employs in such applications particularly in arc welding process is expected to operate from open-circuit (no-load) to short-circuit (when the electrode sticks to the workpiece for a short span of time) quickly. In this paper, high-frequency isolated multiphase DC-DC converter is proposed which is well suited for aforementioned applications. Based on mathematical analysis, a simulation study with 5 kW, 5 V/1,000 A proposed model is carried out using Simulink block set and Sim Power System tool box and its performances are evaluated under symmetrical control methods. To verify the simulation results, scaled prototype model of rating 1.5 V/100 A is developed and tested with aforementioned control method under different operating conditions. In comparison with conventional welding power supply employed in many industries, the performance of proposed converter is improved significantly in terms of size and weight, efficiency and dynamic response.
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An Improved Power Quality BIBRED Converter-Based VSI-Fed BLDC Motor Drive
NASA Astrophysics Data System (ADS)
Singh, Bhim; Bist, Vashist
2014-01-01
This paper presents an IHQRR (integrated high-quality rectifier regulator) BIBRED (boost integrated buck rectifier energy storage DC-DC) converter-based VSI (voltage source inverter)-fed BLDC (brushless DC) motor drive. The speed control of BLDC motor is achieved by controlling the DC link voltage of the VSI using a single voltage sensor. This allows VSI to operate in fundamental frequency switching mode for electronic commutation of BLDC motor which reduces the switching losses due to high-frequency switching used in conventional approach of PWM (pulse width modulation)-based VSI-fed BLDC motor drive. A BIBRED converter is operated in a dual-DCM (discontinuous conduction mode) thus using a voltage follower approach for PFC (power factor correction) and DC link voltage control. The performance of the proposed drive is evaluated for improved power quality over a wide range of speed control and supply voltage variation for demonstrating the behavior of proposed drive. The power quality indices thus obtained are within the recommended limits by international PQ (power quality) standards such as IEC 61000-3-2.
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Five years of full-scale utility demonstration of pulsed energization of electric precipitators
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schultz, S.A.; Jacobus, P.L.; Casey, P.J.
1996-11-01
In a conventional electrostatic precipitator (ESP) the applied dc voltage fulfills three functions: (1) generation of negative ions, (2) charging of particles, and (3) transport of the charged particles to the collecting plates. In the case of high resistivity fly-ash (often associated with the burning of low sulfur coal) the dc voltage is limited by repeated electrical discharges and in extreme cases by back-corona. Lowering the applied dc voltage reduces sparking and back-corona, but also reduces the field on the discharge wires and leads to poorly distributed ion generation as well as reduced charging and particle transport forces. Pulsed energization,more » which consists of superimposing high voltage pulses of short duration onto the existing base dc voltage, offers an attractive way to improve the collection efficiency of ESPs suffering from poor energization. The superimposed pulses become responsible for uniform ion generation while the underlying dc field continues to fulfill the function of particle charging and transport. This paper describes the five-year test of the ESP at Madison Gas and Electric`s Blount Station.« less
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NASA Astrophysics Data System (ADS)
Konishi, Takeshi; Nakamura, Taketsune; Amemiya, Naoyuki
Induction motor instead of dc one has been applied widely for dc electric rolling stock because of the advantage of its utility and efficiency. However, further improvement of motor characteristics will be required to realize environment-friendly dc railway system in the future. It is important to study more efficient machine applying dc electric rolling stock for next generation high performance system. On the other hand, the methods to reuse regenerative energy produced by motors effectively are also important. Therefore, we carried out fundamental study on saving energy for electrified railway system. For the first step, we introduced the energy storage system applying electric double-layer capacitors (EDLC), and its control system. And then, we tried to obtain the specification of high temperature superconductor induction/synchronous motor (HTS-ISM), which performance is similar with that of the conventional induction motors. Furthermore, we tried to evaluate an electrified railway system applying energy storage system and HTS-ISM based on simulation. We succeeded in showing the effectiveness of the introductions of energy storage system and HTS-ISM in DC electrified railway system.
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Tamura, Takahiko; Kimura, Kazumi; Yui, Katsuyuki; Yoshida, Shigeto
2015-12-01
Dendritic cells (DCs) play critical roles in innate and adaptive immunity and in pathogenesis during the blood stage of malaria infection. The mechanisms underlying DC homeostasis during malaria infection are not well understood. In this study, the numbers of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in the spleens after lethal rodent malaria infection were examined, and were found to be significantly reduced. Concomitant with up-regulation of maturation-associated molecules, activation of caspase-3 was significantly increased, suggesting induction of cell death. Studies using neutralizing antibody and gene-deficient mice showed that type I and II interferons were critically involved in activation induced cell death of cDCs during malaria infection. These results demonstrate that DCs rapidly disappeared following IFN-mediated DC activation, and that homeostasis of DCs was significantly impaired during malaria infection. Copyright © 2015 Elsevier Inc. All rights reserved.
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On the mechanism of charge transport in low density polyethylene
NASA Astrophysics Data System (ADS)
Upadhyay, Avnish K.; Reddy, C. C.
2017-08-01
Polyethylene based polymeric insulators, are being increasingly used in the power industry for their inherent advantages over conventional insulation materials. Specifically, modern power cables are almost made with these materials, replacing the mass-impregnated oil-paper cable technology. However, for ultra-high dc voltage applications, the use of these polymeric cables is hindered by ununderstood charge transport and accumulation. The conventional conduction mechanisms (Pool-Frenkel, Schottky, etc.) fail to track high-field charge transport in low density polyethylene, which is semi-crystalline in nature. Until now, attention was devoted mainly to the amorphous region of the material. In this paper, authors propose a novel mechanism for conduction in low density polyethylene, which could successfully track experimental results. As an implication, a novel, substantial relationship is established for electrical conductivity that could be effectively used for understanding conduction and breakdown in polyethylene, which is vital for successful development of ultra-high voltage dc cables.
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Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype.
Yao, Likun; Chen, Jing; Wu, Xiaotong; Jia, Shunji; Meng, Anming
2017-11-01
Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N-ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis. Embryos homozygous for a cdc6 hypomorphic mutation, cdc6tsu21cd, develop normally during embryogenesis. Later on, compared with their wild-type (WT) siblings, cdc6tsu21cd mutant fish show growth retardation, and their body weight and length in adulthood are greatly reduced, which resemble human MGS. Surprisingly, cdc6tsu21cd mutant fish become males with a short life and fail to mate with WT females, suggesting defective reproduction. Overexpression of Cdc6 mutant forms, which mimic human CDC6(T323R) mutation found in a MGS patient, in zebrafish cdc6tsu4305 mutant embryos partially represses cell death phenotype, suggesting that the human CDC6(T323R) mutation is a hypomorph. cdc6tsu21cd mutant fish will be useful to detect more tissue defects and develop medical treatment strategies for MGS patients. © The Author 2017. Published by Oxford University Press.
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Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype
Yao, Likun; Chen, Jing; Wu, Xiaotong; Jia, Shunji; Meng, Anming
2017-01-01
Abstract Cell Division Cycle 6 (Cdc6) is a component of pre-replicative complex (preRC) forming on DNA replication origins in eukaryotes. Recessive mutations in ORC1, ORC4, ORC6, CDT1 or CDC6 of the preRC in human cause Meier-Gorlin syndrome (MGS) that is characterized by impaired post-natal growth, short stature and microcephaly. However, vertebrate models of MGS have not been reported. Through N-ethyl-N-nitrosourea mutagenesis and Cas9 knockout, we generate several cdc6 mutant lines in zebrafish. Loss-of-function mutations of cdc6, as manifested by cdc6tsu4305 and cdc6tsu7cd mutants, lead to embryonic lethality due to cell cycle arrest at the S phase and extensive apoptosis. Embryos homozygous for a cdc6 hypomorphic mutation, cdc6tsu21cd, develop normally during embryogenesis. Later on, compared with their wild-type (WT) siblings, cdc6tsu21cd mutant fish show growth retardation, and their body weight and length in adulthood are greatly reduced, which resemble human MGS. Surprisingly, cdc6tsu21cd mutant fish become males with a short life and fail to mate with WT females, suggesting defective reproduction. Overexpression of Cdc6 mutant forms, which mimic human CDC6(T323R) mutation found in a MGS patient, in zebrafish cdc6tsu4305 mutant embryos partially represses cell death phenotype, suggesting that the human CDC6(T323R) mutation is a hypomorph. cdc6tsu21cd mutant fish will be useful to detect more tissue defects and develop medical treatment strategies for MGS patients. PMID:28985365
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Savel, Thomas G.; Lee, Brian A.; Ledbetter, Greg; Brown, Sara; LaValley, Dale; Taylor, Julie; Thompson, Pam
2013-01-01
Objectives: This manuscript describes the development of PTT (Partial Thromboplastin Time) Advisor, one of the first of a handful of iOS-based mobile applications to be released by the US Centers for Disease Control and Prevention (CDC). PTT Advisor has been a collaboration between two groups at CDC (Informatics R&D and Laboratory Science), and one partner team (Clinical Laboratory Integration into Healthcare Collaborative - CLIHC). The application offers clinicians a resource to quickly select the appropriate follow-up tests to evaluate patients with a prolonged PTT and a normal Prothrombin Time (PT) laboratory result. Methods: The application was designed leveraging an agile methodology, and best practices in user experience (UX) design and mobile application development. Results: As it is an open-source project, the code to PTT Advisor was made available to the public under the Apache Software License. On July 6, 2012, the free app was approved by Apple, and was published to their App Store. Conclusions: Regardless of the complexity of the mobile application, the level of effort required in the development process should not be underestimated. There are several issues that make designing the UI for a mobile phone challenging (not just small screen size): the touchscreen, users' mobile mindset (tasks need to be quick and focused), and the fact that mobile UI conventions/expectations are still being defined and refined (due to the maturity level of the field of mobile application development). PMID:23923100
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Enterococcus caccae sp. nov., isolated from human stools.
Carvalho, Maria da Glória S; Shewmaker, P Lynn; Steigerwalt, Arnold G; Morey, Roger E; Sampson, A J; Joyce, Kevin; Barrett, Timothy J; Teixeira, Lucia M; Facklam, Richard R
2006-07-01
The National Antimicrobial Resistance Monitoring System Laboratory at the Centers for Disease Control and Prevention (CDC) isolated two enterococcus-like strains that were referred to the CDC Streptococcus Laboratory for further identification. The isolates were recovered from human stool samples collected on different occasions from the same individual in Portland (OR, USA) in July 2000. Conventional physiological tests distinguished these strains from all known species of enterococci. Analyses of whole-cell-protein electrophoretic profiles showed the same unique profile for the two isolates, being most similar those of Enterococcus moraviensis and Enterococcus haemoperoxidus albeit not close enough to allow conclusive inclusion in any enterococcal species. Both isolates gave positive results in tests using the AccuProbe Enterococcus genetic probe, and Lancefield extracts reacted with CDC group D antiserum. Comparative 16S rRNA gene sequencing studies also revealed that these strains were closely related to the species E. moraviensis (99.6 % identity). The results of DNA-DNA relatedness experiments confirmed that these strains represented a single novel taxon. The highest level of DNA-DNA relatedness found between the novel taxon and any of the currently recognized species of Enterococcus was 32 %, for both E. moraviensis and E. haemoperoxidus. On the basis of this evidence, it is proposed that these stool isolates constitute a novel species, for which the name Enterococcus caccae sp. nov. is proposed. The type strain is 2215-02(T) (=SS-1777(T)=ATCC BAA-1240(T)=CCUG 51564(T)).
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Li, Wei-Guo; Wang, He-Qun
2016-01-01
Hepatocellular carcinoma (HCC) is the one of the most common cancers and the third leading cause of cancer related mortality in the world. Unacceptable side effect and development of treatment resistance are the major concerns with the conventional chemotherapeutic agents. Combination therapy using phytotherapeutic agents is attracting the attention of investigators in view of the current needs. In the present study we have evaluated the synergistic effect of silibinin, a nontoxic phytotherapeutic agent in combination with doxorubicin, in advanced HCC using HEPG2 cells and an orthotopic rat model of HCC. The results showed that silibinin strongly synergized with doxorubicin-induced growth inhibition, G2-M arrest, and apoptosis of HEPG2 cells. Silibinin-doxorubicin combination also inhibited cdc2/p34 kinase activity when histone H1 was used as substrate. The combination regimen also moderately increased the expression of cdc25C-cyclin B1-cdc2/p34 associated upstream kinases (Chk1). Simultaneous treatment with silibinin-doxorubicin combination showed a 41% increase in the apoptotic cell death (p=0.01), which was 3-fold higher than what was observed with silibinin or doxorubicin individually. In the orthotopic rat model treatment with silibinin-doxorubicin reduced tumor growth by close to 30% at nearly twice lower dose of individual drugs in the combination group. Our study suggests that combination therapy using silibinin-doxorubicin may show a better therapeutic efficacy in patients with HCC. These findings need to be further validated in human clinical trials.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Gao, Zhiming; Curran, Scott; Daw, C Stuart
2013-01-01
In-cylinder blending of gasoline and diesel fuels to achieve low-temperature reactivity controlled compression ignition (RCCI) can reduce NOx and PM emissions while maintaining or improving brake thermal efficiency compared to conventional diesel combustion (CDC). Moreover, the dual-fueling RCCI is able to achieve these benefits by tailoring combustion reactivity over a wider range of engine operation than is possible with a single fuel. However, the currently demonstrated range of stable RCCI combustion just covers a portion of the engine speed-load range required in several light-duty drive cycles. This means that engines must switch from RCCI to CDC when speed and loadmore » fall outside of the stable RCCI range. In this study we investigated the impact of RCCI as it has recently been demonstrated on practical engine-out exhaust temperature and emissions by simulating a multi-mode RCCI-enabled vehicle operating over two urban and two highway driving cycles. To implement our simulations, we employed experimental engine maps for a multi-mode RCCI/CDC engine combined with a standard mid-size, automatic transmission, passenger vehicle in the Autonomie vehicle simulation platform. Our results include both detailed transient and cycle-averaged engine exhaust temperature and emissions for each case, and we note the potential implications of the modified exhaust properties on catalytic emissions control and utilization of waste heat recovery on future RCCI-enabled vehicles.« less
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Savel, Thomas G; Lee, Brian A; Ledbetter, Greg; Brown, Sara; Lavalley, Dale; Taylor, Julie; Thompson, Pam
2013-01-01
This manuscript describes the development of PTT (Partial Thromboplastin Time) Advisor, one of the first of a handful of iOS-based mobile applications to be released by the US Centers for Disease Control and Prevention (CDC). PTT Advisor has been a collaboration between two groups at CDC (Informatics R&D and Laboratory Science), and one partner team (Clinical Laboratory Integration into Healthcare Collaborative - CLIHC). The application offers clinicians a resource to quickly select the appropriate follow-up tests to evaluate patients with a prolonged PTT and a normal Prothrombin Time (PT) laboratory result. The application was designed leveraging an agile methodology, and best practices in user experience (UX) design and mobile application development. As it is an open-source project, the code to PTT Advisor was made available to the public under the Apache Software License. On July 6, 2012, the free app was approved by Apple, and was published to their App Store. Regardless of the complexity of the mobile application, the level of effort required in the development process should not be underestimated. There are several issues that make designing the UI for a mobile phone challenging (not just small screen size): the touchscreen, users' mobile mindset (tasks need to be quick and focused), and the fact that mobile UI conventions/expectations are still being defined and refined (due to the maturity level of the field of mobile application development).
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Carbide-derived carbon (CDC) linear actuator properties in combination with conducting polymers
NASA Astrophysics Data System (ADS)
Kiefer, Rudolf; Aydemir, Nihan; Torop, Janno; Kilmartin, Paul A.; Tamm, Tarmo; Kaasik, Friedrich; Kesküla, Arko; Travas-Sejdic, Jadranka; Aabloo, Alvo
2014-03-01
Carbide-derived Carbon (CDC) material is applied for super capacitors due to their nanoporous structure and their high charging/discharging capability. In this work we report for the first time CDC linear actuators and CDC combined with polypyrrole (CDC-PPy) in ECMD (Electrochemomechanical deformation) under isotonic (constant force) and isometric (constant length) measurements in aqueous electrolyte. CDC-PPy actuators showing nearly double strain under cyclic voltammetric and square wave potential measurements in comparison to CDC linear actuators. The new material is investigated by SEM (scanning electron microscopy) and EDX (energy dispersive X-ray analysis) to reveal how the conducting polymer layer and the CDC layer interfere together.
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Fission yeast cdc24(+) encodes a novel replication factor required for chromosome integrity.
Gould, K L; Burns, C G; Feoktistova, A; Hu, C P; Pasion, S G; Forsburg, S L
1998-07-01
A mutation within the Schizosaccharomyces pombe cdc24(+) gene was identified previously in a screen for cell division cycle mutants and the cdc24(+) gene was determined to be essential for S phase in this yeast. We have isolated the cdc24(+) gene by complementation of a new temperature-sensitive allele of the gene, cdc24-G1. The DNA sequence predicts the presence of an open reading frame punctuated by six introns which encodes a pioneer protein of 58 kD. A cdc24 null mutant was generated by homologous recombination. Haploid cells lacking cdc24(+) are inviable, indicating that cdc24(+) is an essential gene. The transcript of cdc24(+) is present at constant levels throughout the cell cycle. Cells lacking cdc24(+) function show a checkpoint-dependent arrest with a 2N DNA content, indicating a block late in S phase. Arrest is accompanied by a rapid loss of viability and chromosome breakage. An S. pombe homolog of the replicative DNA helicase DNA2 of S. cerevisiae suppresses cdc24. These results suggest that Cdc24p plays a role in the progression of normal DNA replication and is required to maintain genomic integrity.
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Fission yeast cdc24(+) encodes a novel replication factor required for chromosome integrity.
Gould, K L; Burns, C G; Feoktistova, A; Hu, C P; Pasion, S G; Forsburg, S L
1998-01-01
A mutation within the Schizosaccharomyces pombe cdc24(+) gene was identified previously in a screen for cell division cycle mutants and the cdc24(+) gene was determined to be essential for S phase in this yeast. We have isolated the cdc24(+) gene by complementation of a new temperature-sensitive allele of the gene, cdc24-G1. The DNA sequence predicts the presence of an open reading frame punctuated by six introns which encodes a pioneer protein of 58 kD. A cdc24 null mutant was generated by homologous recombination. Haploid cells lacking cdc24(+) are inviable, indicating that cdc24(+) is an essential gene. The transcript of cdc24(+) is present at constant levels throughout the cell cycle. Cells lacking cdc24(+) function show a checkpoint-dependent arrest with a 2N DNA content, indicating a block late in S phase. Arrest is accompanied by a rapid loss of viability and chromosome breakage. An S. pombe homolog of the replicative DNA helicase DNA2 of S. cerevisiae suppresses cdc24. These results suggest that Cdc24p plays a role in the progression of normal DNA replication and is required to maintain genomic integrity. PMID:9649516
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cdc-25.2, a C. elegans ortholog of cdc25, is required to promote oocyte maturation.
Kim, Jiyoung; Kawasaki, Ichiro; Shim, Yhong-Hee
2010-03-15
Cdc25 is an evolutionarily conserved protein phosphatase that promotes progression through the cell cycle. Some metazoans have multiple isoforms of Cdc25, which have distinct functions and different expression patterns during development. C. elegans has four cdc-25 genes. cdc-25.1 is required for germline mitotic proliferation. To determine if the other members of the cdc-25 family also contribute to regulation of cell division in the germ line, we examined phenotypes of loss-of-function mutants of the other cdc-25 family genes. We found that cdc-25.2 is also essential for germline development. cdc-25.2 homozygous mutant hermaphrodites exhibited sterility as a result of defects in oogenesis: mutant oocytes were arrested as endomitotic oocytes that were not fertilized successfully. Spermatogenesis and male germline development were not affected. Through genetic interaction studies, we found that CDC-25.2 functions upstream of maturation-promoting factor containing CDK-1 and CYB-3 to promote oocyte maturation by counteracting function of WEE-1.3. We propose that cdc-25 family members function as distinct but related cell cycle regulators to control diverse cell cycles in C. elegans germline development.
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Liu, Huiquan; Zhang, Shijie; Ma, Jiwen; Dai, Yafeng; Li, Chaohui; Lyu, Xueliang; Wang, Chenfang; Xu, Jin-Rong
2015-06-01
Eukaryotic cell cycle involves a number of protein kinases important for the onset and progression through mitosis, most of which are well characterized in the budding and fission yeasts and conserved in other fungi. However, unlike the model yeast and filamentous fungi that have a single Cdc2 essential for cell cycle progression, the wheat scab fungus Fusarium graminearum contains two CDC2 orthologs. The cdc2A and cdc2B mutants had no obvious defects in growth rate and conidiation but deletion of both of them is lethal, indicating that these two CDC2 orthologs have redundant functions during vegetative growth and asexual reproduction. However, whereas the cdc2B mutant was normal, the cdc2A mutant was significantly reduced in virulence and rarely produced ascospores. Although deletion of CDC2A had no obvious effect on the formation of penetration branches or hyphopodia, the cdc2A mutant was limited in the differentiation and growth of infectious growth in wheat tissues. Therefore, CDC2A plays stage-specific roles in cell cycle regulation during infectious growth and sexual reproduction. Both CDC2A and CDC2B are constitutively expressed but only CDC2A was up-regulated during plant infection and ascosporogenesis. Localization of Cdc2A- GFP to the nucleus but not Cdc2B-GFP was observed in vegetative hyphae, ascospores, and infectious hyphae. Complementation assays with chimeric fusion constructs showed that both the N- and C-terminal regions of Cdc2A are important for its functions in pathogenesis and ascosporogenesis but only the N-terminal region is important for its subcellular localization. Among the Sordariomycetes, only three Fusarium species closely related to F. graminearum have two CDC2 genes. Furthermore, F. graminearum uniquely has two Aurora kinase genes and one additional putative cyclin gene, and its orthologs of CAK1 and other four essential mitotic kinases in the budding yeast are dispensable for viability. Overall, our data indicate that cell cycle regulation is different between vegetative and infectious hyphae in F. graminearum and Cdc2A, possibly by interacting with a stage-specific cyclin, plays a more important role than Cdc2B during ascosporogenesis and plant infection.
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Alexander, Nick; Rowe, Sylvia; Brackett, Robert E; Burton-Freeman, Britt; Hentges, Eric J; Kretser, Alison; Klurfeld, David M; Meyers, Linda D; Mukherjea, Ratna; Ohlhorst, Sarah
2015-06-01
Officers and other representatives of more than a dozen food-, nutrition-, and health-related scientific societies and organizations, food industry scientists, and staff of the USDA, the CDC, the Food and Drug Administration, and the NIH convened on 8 December 2014 in Washington, DC, to reach a consensus among individuals participating on guiding principles for the development of research-oriented, food- and nutrition-related public-private partnerships. During the daylong working meeting, participants discussed and revised 12 previously published guidelines to ensure integrity in the conduct of food and nutrition research collaborations among public, nonprofit, and private sectors. They agreed to reconvene periodically to reassess the public-private partnership principles. This article presents the guiding principles and potential benefits, outlines key discussion points, and articulates points of agreement and reservation. © 2015 American Society for Nutrition.
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Hu, Kai; Harris, Deshea L.; Yamaguchi, Takefumi; von Andrian, Ulrich H.; Hamrah, Pedram
2015-01-01
The cornea is the shield to the foreign world and thus, a primary site for peripheral infections. However, transparency and vision are incompatible with inflammation and scarring that may result from infections. Thus, the cornea is required to perform a delicate balance between fighting infections and preserving vision. To date, little is known about the specific role of antigen-presenting cells in viral keratitis. In this study, utilizing an established murine model of primary acute herpes simplex virus (HSV)-1 keratitis, we demonstrate that primary HSV keratitis results in increased conventional dendritic cells (cDCs) and macrophages within 24 hours after infection. Local depletion of cDCs in CD11c-DTR mice by subconjuntival diphtheria toxin injections, led to increased viral proliferation, and influx of inflammatory cells, resulting in increased scarring and clinical keratitis. In addition, while HSV infection resulted in significant corneal nerve destruction, local depletion of cDCs resulted in a much more severe loss of corneal nerves. Further, local cDC depletion resulted in decreased corneal nerve infection, and subsequently decreased and delayed systemic viral transmission in the trigeminal ganglion and draining lymph node, resulting in decreased mortality of mice. In contrast, sham depletion or depletion of macrophages through local injection of clodronate liposomes had neither a significant impact on the cornea, nor an effect on systemic viral transmission. In conclusion, we demonstrate that corneal cDCs may play a primary role in local corneal defense during viral keratitis and preserve vision, at the cost of inducing systemic viral dissemination, leading to increased mortality. PMID:26332302
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Cheng, An Ning; Jiang, Shih Sheng; Fan, Chi-Chen; Lo, Yu-Kang; Kuo, Chan-Yen; Chen, Chung-Hsing; Liu, Ying-Lan; Lee, Chun-Chung; Chen, Wei-Shone; Huang, Tze-Sing; Wang, Tao-Yeuan; Lee, Alan Yueh-Luen
2013-09-01
Cdc7-Dbf4 kinase (Dbf4-dependent kinase, DDK) is an essential factor of DNA replication and DNA damage response (DDR), which is associated with tumorigenesis. However, Cdc7 expression has never been associated to the outcome of oral squamous cell carcinoma (OSCC) patients, and the mechanism underlying cancer cell survival mediated by Cdc7 remains unclear. The Cdc7 protein expression of 105 OSCC tumor and 30 benign tissues was examined by immunohistochemistry assay. Overall survival rates of 80 OSCC patients were measured using Kaplan-Meier estimates and the log-rank tests. Cdc7 overexpression by adenovirus system was used to scrutinize the underlying mechanism contributed to cancer cell survival upon DDR. In silico analysis showed that increased Cdc7 is a common feature of cancer. Cdc7 overexpression was found in 96 of 105 (91.4%) studied cases of OSCC patients. Patients with higher Cdc7 expression, either categorized into two groups: Cdc7 high expression (2+ to 3+) versus Cdc7 low expression (0 to 1+) [hazard ratios (HR)=2.6; 95% confidence interval (CI)=1.28-5.43; P=0.0087] or four groups (0 to 3+) [HR=1.71; 95% CI=1.20-2.44; P=0.0032], exhibited a poorer outcome. Multivariate analysis showed that Cdc7 is an independent marker for survival prediction. Overexpressed Cdc7 inhibits genotoxin-induced apoptosis to increase the survival of cancer cells. In summary, Cdc7 expression, which is universally upregulated in cancer, is an independent prognostic marker of OSCC. Cdc7 inhibits genotoxin-induced apoptosis and increases survival in cancer cells upon DDR, suggesting that high expression of Cdc7 enhances the resistance to chemotherapy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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Younis, Rania H.; Cao, Wei; Lin, Ruxian; Xia, Ronghui; Liu, Zhenqiu; Edelman, Martin J.; Mei, Yuping; Mao, Li; Ren, Hening
2012-01-01
Objective Lung cancer remains number one cause of cancer related deaths worldwide. Cell cycle deregulation plays a major role in the pathogenesis of Non-Small Cell Lung Cancer (NSCLC). CDC25A represents a critical cell cycle regulator that enhances cell cycle progression. In this study we aimed to investigate the role of a novel CDC25A transcriptional variant, CDC25AQ110del, on the regulation of the CDC25A protein, and its impact on prognosis of NSCLC patients. Methodology/Principal Findings Here we report a novel CDC25A transcript variant with codon 110 (Glutamine) deletion, that we termed CDC25AQ110del in NSCLC cells. In 9 (75%) of the 12 NSCLC cell lines, CDC25AQ110del expression accounted for more than 20% of the CDC25A transcripts. Biological effects of CDC25AQ110del were investigated in H1299 and HEK-293F cells using UV radiation, flowcytometry, cyclohexamide treatment, and confocal microscopy. Compared to CDC25Awt, CDC25AQ110del protein had longer half-life; cells expressing CDC25AQ110del were more resistant to UV irradiation and showed more mitotic activity. Taqman-PCR was used to quantify CDC25AQ110del expression levels in 88 primary NSCLC tumor/normal tissue pairs. In patients with NSCLC, Kaplan Meier curves showed tumors expressing higher levels of CDC25AQ110del relative to the adjacent lung tissues to have significantly inferior overall survival (P = .0018). Significance Here we identified CDC25AQ110del as a novel transcriptional variant of CDC25A in NSCLC. The sequence-specific nature of the abnormality could be a prognostic indicator in NSCLC patients as well as a candidate target for future therapeutic strategies. PMID:23071577
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SOI MESFETs on high-resistivity, trap-rich substrates
NASA Astrophysics Data System (ADS)
Mehr, Payam; Zhang, Xiong; Lepkowski, William; Li, Chaojiang; Thornton, Trevor J.
2018-04-01
The DC and RF characteristics of metal-semiconductor field-effect-transistors (MESFETs) on conventional CMOS silicon-on-insulator (SOI) substrates are compared to nominally identical devices on high-resistivity, trap-rich SOI substrates. While the DC transfer characteristics are statistically identical on either substrate, the maximum available gain at GHz frequencies is enhanced by ∼2 dB when using the trap-rich substrates, with maximum operating frequencies, fmax, that are approximately 5-10% higher. The increased fmax is explained by the reduced substrate conduction at GHz frequencies using a lumped-element, small-signal model.
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Report of the Annual Scientific Sessions of the American College of Cardiology (ACC), Washington DC.
Hiro, Takafumi
2017-05-25
The 66 th Annual Scientific Sessions and Expo of the American College of Cardiology (ACC) were held at the Walter E. Washington Convention Center, Washington DC, from March 17 th to 19 th , 2017. This meeting offered 23 Late-Breaking Clinical Trial (LBCT) presentations, 17 Featured Clinical Research presentations with and without LBCT, and 2,572 abstracts presented in oral and poster sessions by over 2,000 experts. This report presents the highlights of this meeting, including the opening showcase, several important LBCTs and some international joint symposiums.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lencioni, Riccardo, E-mail: riccardo.lencioni@med.unipi.it; Baere, Thierry de; Burrel, Marta
2012-10-15
Tranarterial chemoembolization (TACE) has been established by a meta-analysis of randomized controlled trials as the standard of care for nonsurgical patients with large or multinodular noninvasive hepatocellular carcinoma (HCC) isolated to the liver and with preserved liver function. Although conventional TACE with administration of an anticancer-in-oil emulsion followed by embolic agents has been the most popular technique, the introduction of embolic drug-eluting beads has provided an alternative to lipiodol-based regimens. Experimental studies have shown that TACE with drug-eluting beads has a safe pharmacokinetic profile and results in effective tumor killing in animal models. Early clinical experiences have confirmed that drug-elutingmore » beads provide a combined ischemic and cytotoxic effect locally with low systemic toxic exposure. Recently, the clinical value of a TACE protocol performed by using the embolic microsphere DC Bead loaded with doxorubicin (DEBDOX; drug-eluting bead doxorubicin) has been shown by randomized controlled trials. An important limitation of conventional TACE has been the inconsistency in the technique and the treatment schedules. This limitation has hampered the acceptance of TACE as a standard oncology treatment. Doxorubicin-loaded DC Bead provides levels of consistency and repeatability not available with conventional TACE and offers the opportunity to implement a standardized approach to HCC treatment. With this in mind, a panel of physicians took part in a consensus meeting held during the European Conference on Interventional Oncology in Florence, Italy, to develop a set of technical recommendations for the use of DEBDOX in HCC treatment. The conclusions of the expert panel are summarized.« less
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ERIC Educational Resources Information Center
Friedman, Dana E., Ed.
Included in this document are 24 preconference workshop papers prepared for the 1982 annual convention of the National Association for the Education of Young Children (NAEYC), entitled "Shaping the Employer Role in Child Care." The purposes of the workshop were (1) to provide NAEYC members with a realistic picture of current employer involvement…
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Cell cycle entry triggers a switch between two modes of Cdc42 activation during yeast polarization
Witte, Kristen; Strickland, Devin; Glotzer, Michael
2017-01-01
Cell polarization underlies many cellular and organismal functions. The GTPase Cdc42 orchestrates polarization in many contexts. In budding yeast, polarization is associated with a focus of Cdc42•GTP which is thought to self sustain by recruiting a complex containing Cla4, a Cdc42-binding effector, Bem1, a scaffold, and Cdc24, a Cdc42 GEF. Using optogenetics, we probe yeast polarization and find that local recruitment of Cdc24 or Bem1 is sufficient to induce polarization by triggering self-sustaining Cdc42 activity. However, the response to these perturbations depends on the recruited molecule, the cell cycle stage, and existing polarization sites. Before cell cycle entry, recruitment of Cdc24, but not Bem1, induces a metastable pool of Cdc42 that is sustained by positive feedback. Upon Cdk1 activation, recruitment of either Cdc24 or Bem1 creates a stable site of polarization that induces budding and inhibits formation of competing sites. Local perturbations have therefore revealed unexpected features of polarity establishment. DOI: http://dx.doi.org/10.7554/eLife.26722.001 PMID:28682236
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Alao, John P; Sjölander, Johanna J; Baar, Juliane; Özbaki-Yagan, Nejla; Kakoschky, Bianca; Sunnerhagen, Per
2014-01-01
Cdc25 is required for Cdc2 dephosphorylation and is thus essential for cell cycle progression. Checkpoint activation requires dual inhibition of Cdc25 and Cdc2 in a Rad3-dependent manner. Caffeine is believed to override activation of the replication and DNA damage checkpoints by inhibiting Rad3-related proteins in both S chizosaccharomyces pombe and mammalian cells. In this study, we have investigated the impact of caffeine on Cdc25 stability, cell cycle progression and checkpoint override. Caffeine induced Cdc25 accumulation in S . pombe independently of Rad3. Caffeine delayed cell cycle progression under normal conditions but advanced mitosis in cells treated with replication inhibitors and DNA-damaging agents. In the absence of Cdc25, caffeine inhibited cell cycle progression even in the presence of hydroxyurea or phleomycin. Caffeine induces Cdc25 accumulation in S . pombe by suppressing its degradation independently of Rad3. The induction of Cdc25 accumulation was not associated with accelerated progression through mitosis, but rather with delayed progression through cytokinesis. Caffeine-induced Cdc25 accumulation appears to underlie its ability to override cell cycle checkpoints. The impact of Cdc25 accumulation on cell cycle progression is attenuated by Srk1 and Mad2. Together our findings suggest that caffeine overrides checkpoint enforcement by inducing the inappropriate nuclear localization of Cdc25. PMID:24666325
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The Climate Data Centre of Deutscher Wetterdienst (DWD)
NASA Astrophysics Data System (ADS)
Kaspar, F.; Schreiber, K.-J.; Behrendt, J.
2010-09-01
In 2009 the German meteorological service (Deutscher Wetterdienst, DWD) has started to set up a Climate Data Centre (CDC) in order to provide unified access to its variety of climate data especially to users from research, educational and public institutions. CDC acts as a central point of contact to various data collections of DWD. These include observations from German weather stations and DWD's observatories, special data as e.g. from hydroclimatology, agro-climatology and medical climatology, but also from international activities of DWD, such as the Global Precipitation Climatology Center (GPCC), EUMETSAT's Satellite Application Facility on Climate Monitoring (CM-SAF) or marine climatological data (ship and buoy observations) of the Global Collecting Centre for Marine Climatological Data. Data are based on conventional surface observations over land and ocean as well as on various remote sensing methods, such as satellite observation. The major part consists of climate data from the past, but CDC will also include results from scenario calculations and projections for the future. In addition to pure observational data, CDC offers derived statistical parameters and spatial analyses as gridded datasets. As first step, a central data catalogue provides standardised descriptions and information on data access. It follows national and international rules for the description of geo-referenced data (GDI-DE; INSPIRE). The individual data providers of DWD can use the catalogue to easily edit and publish their metadata in a unified way. These metadata contain information on data access, data policy, data quality, spatial and temporal coverage, responsible persons, etc. The catalogue is based on an open source software product (geonetwork-opensource) that is also used by a large number of international organizations. Metadata can be exchanged (harvested) between these catalogues. This will allow implementing a structure that provides search capabilities over institutions. The software also allows implementing web-based mapping services and group-specific data access policies.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Curran, Scott; Briggs, Thomas E; Cho, Kukwon
2011-01-01
In-cylinder blending of gasoline and diesel to achieve Reactivity Controlled Compression Ignition (RCCI) has been shown to reduce NOx and PM emissions while maintaining or improving brake thermal efficiency as compared to conventional diesel combustion (CDC). The RCCI concept has an advantage over many advanced combustion strategies in that by varying both the percent of premixed gasoline and EGR rate, stable combustion can be extended over more of the light-duty drive cycle load range. Changing the percent premixed gasoline changes the fuel reactivity stratification in the cylinder providing further control of combustion phasing and pressure rise rate than the usemore » of EGR alone. This paper examines the combustion and emissions performance of light-duty diesel engine using direct injected diesel fuel and port injected gasoline to carry out RCCI for steady-state engine conditions which are consistent with a light-duty drive cycle. A GM 1.9L four-cylinder engine with the stock compression ratio of 17.5:1, common rail diesel injection system, high-pressure EGR system and variable geometry turbocharger was modified to allow for port fuel injection with gasoline. Engine-out emissions, engine performance and combustion behavior for RCCI operation is compared against both CDC and a premixed charge compression ignition (PCCI) strategy which relies on high levels of EGR dilution. The effect of percent of premixed gasoline, EGR rate, boost level, intake mixture temperature, combustion phasing and pressure rise rate is investigated for RCCI combustion for the light-duty modal points. Engine-out emissions of NOx and PM were found to be considerably lower for RCCI operation as compared to CDC and PCCI, while HC and CO emissions were higher. Brake thermal efficiency was similar or higher for many of the modal conditions for RCCI operation. The emissions results are used to estimate hot-start FTP-75 emissions levels with RCCI and are compared against CDC and PCCI modes.« less
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Antigen presenting capacity of murine splenic myeloid cells.
Hey, Ying-Ying; Quah, Benjamin; O'Neill, Helen C
2017-01-11
The spleen is an important site for hematopoiesis. It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised although dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. Recently a novel dendritic-like cell type in spleen named 'L-DC' was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin. That study also redefined splenic eosinophils as well as resident and inflammatory monocytes in spleen. L-DC are shown to be distinct from known splenic macrophages and monocyte subsets. Using a new flow cytometric procedure, it has been possible to identify and isolate L-DC in order to assess their functional competence and ability to activate T cells both in vivo and in vitro. L-DC are readily accessible to antigen given intravenously through receptor-mediated endocytosis. They are also capable of CD8 + T cell activation through antigen cross presentation, with subsequent induction of cytotoxic effector T cells. L-DC are MHCII - cells and unable to activate CD4 + T cells, a property which clearly distinguishes them from conventional DC. The myeloid subsets of resident monocytes, inflammatory monocytes, neutrophils and eosinophils, were found to have varying capacities to take up antigen, but were uniformly unable to activate either CD4 + T cells or CD8 + T cells. The results presented here demonstrate that L-DC in spleen are distinct from other myeloid cells in that they can process antigen for CD8 + T cell activation and induction of cytotoxic effector function, while both L-DC and myeloid subsets remain unable to activate CD4 + T cells. The L-DC subset in spleen is therefore distinct as an antigen presenting cell.
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NASA Astrophysics Data System (ADS)
Lan, Chunbo; Tang, Lihua; Harne, Ryan L.
2018-05-01
Nonlinear piezoelectric energy harvester (PEH) has been widely investigated during the past few years. Among the majority of these researches, a pure resistive load is used to evaluate power output. To power conventional electronics in practical application, the alternating current (AC) generated by nonlinear PEH needs to be transformed into a direct current (DC) and rectifying circuits are required to interface the device and electronic load. This paper aims at exploring the critical influences of AC and DC interface circuits on nonlinear PEH. As a representative nonlinear PEH, we fabricate and evaluate a monostable PEH in terms of generated power and useful operating bandwidth when it is connected to AC and DC interface circuits. Firstly, the harmonic balance analysis and equivalent circuit representation method are utilized to tackle the modeling of nonlinear energy harvesters connected to AC and DC interface circuits. The performances of the monostable PEH connected to these interface circuits are then analyzed and compared, focusing on the influences of the varying load, excitation and electromechanical coupling strength on the nonlinear dynamics, bandwidth and harvested power. Subsequently, the behaviors of the monostable PEH with AC and DC interface circuits are verified by experiment. Results indicate that both AC and DC interface circuits have a peculiar influence on the power peak shifting and operational bandwidth of the monostable PEH, which is quite different from that on the linear PEH.
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Dendritic cell fate is determined by BCL11A
Ippolito, Gregory C.; Dekker, Joseph D.; Wang, Yui-Hsi; Lee, Bum-Kyu; Shaffer, Arthur L.; Lin, Jian; Wall, Jason K.; Lee, Baeck-Seung; Staudt, Louis M.; Liu, Yong-Jun; Iyer, Vishwanath R.; Tucker, Haley O.
2014-01-01
The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of innate and adaptive immunity. pDC development has not been unequivocally traced, nor has its transcriptional regulatory network been fully clarified. Here we confirm an essential requirement for the BCL11A transcription factor in fetal pDC development, and demonstrate this lineage-specific requirement in the adult organism. Furthermore, we identify BCL11A gene targets and provide a molecular mechanism for its action in pDC commitment. Embryonic germ-line deletion of Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted in perturbed yet continued generation of progenitors, loss of downstream pDC and B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell lineages. Challenge with virus resulted in a marked reduction of antiviral response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA binding and expression revealed that BCL11A regulates transcription of E2-2 and other pDC differentiation modulators, including ID2 and MTG16. Our results identify BCL11A as an essential, lineage-specific factor that regulates pDC development, supporting a model wherein differentiation into pDCs represents a primed “default” pathway for common dendritic cell progenitors. PMID:24591644
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Hagedorn, Martin; Bögershausen, Ansgar; Rischer, Matthias; Schubert, Rolf; Massing, Ulrich
2017-09-15
The development of nanosuspensions of poorly soluble APIs takes a lot of time and high amount of active material is needed. In this publication the use of dual centrifugation (DC) for an effective and rapid API-nanomilling is described for the first time. DC differs from normal centrifugation by an additional rotation of the samples during centrifugation, resulting in a very fast and powerful movement of the samples inside the vials, which - in combination with milling beads - result in effective milling. DC-nanomilling was compared to conventional wet ball milling and results in same or even smaller particle sizes. Also drug concentrations up to 40% can be processed. The process is fast (typical 90min) and the temperature can be controlled. DC-nanomilling appears to be very gentle, experiments showed no change of the crystal structure during milling. Since batch sizes are very small (100-1000mg) and since 40 sample vials can be processed in parallel, DC is ideal for the screening of suitable polymer/surfactant combinations. Fenofibrate was used to investigate DC-nanomilling for formulation screening by applying a DoE-approach. The presented data also show that the results of DC-nanomilling experiments are highly comparable to the results obtained by common agitator mills. Copyright © 2017 Elsevier B.V. All rights reserved.
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Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.
Yan, Z; DeGregori, J; Shohet, R; Leone, G; Stillman, B; Nevins, J R; Williams, R S
1998-03-31
Cdc6 has a critical regulatory role in the initiation of DNA replication in yeasts, but its function in mammalian cells has not been characterized. We show here that Cdc6 is expressed selectively in proliferating but not quiescent mammalian cells, both in culture and within tissues of intact animals. During the transition from a growth-arrested to a proliferative state, transcription of mammalian Cdc6 is regulated by E2F proteins, as revealed by a functional analysis of the human Cdc6 promoter and by the ability of exogenously expressed E2F proteins to stimulate the endogenous Cdc6 gene. Immunodepletion of Cdc6 by microinjection of anti-Cdc6 antibody blocks initiation of DNA replication in a human tumor cell line. We conclude that expression of human Cdc6 is regulated in response to mitogenic signals though transcriptional control mechanisms involving E2F proteins, and that Cdc6 is required for initiation of DNA replication in mammalian cells.
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Choi, Ye-Na; Oh, Bong-Kyeong; Kawasaki, Ichiro; Oh, Wan-Suk; Lee, Yi; Paik, Young-Ki; Shim, Yhong-Hee
2010-02-28
The cdc25 gene, which is highly conserved in many eukaryotes, encodes a phosphatase that plays essential roles in cell cycle regulation. We identified a cdc25 ortholog in the pinewood nematode, Bursaphelenchus xylophilus. The B. xylophilus ortholog (Bx-cdc25) was found to be highly similar to Caenorhabditis elegans cdc-25.2 in sequence as well as in gene structure, both having long intron 1. The Bx-cdc25 gene was determined to be composed of seven exons and six introns in a 2,580 bp region, and was shown to encode 360 amino acids of a protein containing a highly-conserved phosphatase domain. Bx-cdc25 mRNA was hardly detectable throughout the juvenile stages but was highly expressed in eggs and in both female and male adults. Functional conservation during germline development between C. elegans cdc25 and Bx-cdc25 was revealed by Bx-cdc25 RNA interference in C. elegans.
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Asakawa, K; Yoshida, S; Otake, F; Toh-e, A
2001-01-01
Exit from mitosis requires the inactivation of cyclin-dependent kinase (CDK) activity. In the budding yeast Saccharomyces cerevisiae, a number of gene products have been identified as components of the signal transduction network regulating inactivation of CDK (called the MEN, for the mitotic exit network). Cdc15, one of such components of the MEN, is an essential protein kinase. By the two-hybrid screening, we identified Cdc15 as a binding protein of Tem1 GTPase, another essential regulator of the MEN. Coprecipitation experiments revealed that Tem1 binds to Cdc15 in vivo. By deletion analysis, we found that the Tem1-binding domain resides near the conserved kinase domain of Cdc15. The cdc15-LF mutation, which was introduced into the Tem1-binding domain, reduced the interaction with Cdc15 and Tem1 and caused temperature-sensitive growth.The kinase activity of Cdc15 was not so much affected by the cdc15-LF mutation. However, Cdc15-LF failed to localize to the SPB at the restrictive temperature. Our data show that the interaction with Tem1 is important for the function of Cdc15 and that Cdc15 and Tem1 function in a complex to direct the exit from mitosis. PMID:11290702
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Wang, Jirong R; Wang, Chaojun J; Xu, Chengyun Y; Wu, Xiaokai K; Hong, Dun; Shi, Wei; Gong, Ying; Chen, Haixiao X; Long, Fanxin; Wu, Ximei M
2016-03-01
Endochondral ossification consists of successive steps of chondrocyte differentiation, including mesenchymal condensation, differentiation of chondrocytes, and hypertrophy followed by mineralization and ossification. Loss-of-function studies have revealed that abnormal growth plate cartilage of the Cdc42 mutant contributes to the defects in endochondral bone formation. Here, we have investigated the roles of Cdc42 in osteogenesis and signaling cascades governing Cdc42-mediated chondrogenic differentiation. Though deletion of Cdc42 in limb mesenchymal progenitors led to severe defects in endochondral ossification, either ablation of Cdc42 in limb preosteoblasts or knockdown of Cdc42 in vitro had no obvious effects on bone formation and osteoblast differentiation. However, in Cdc42 mutant limb buds, loss of Cdc42 in mesenchymal progenitors led to marked inactivation of p38 and Smad1/5, and in micromass cultures, Cdc42 lay on the upstream of p38 to activate Smad1/5 in bone morphogenetic protein-2-induced mesenchymal condensation. Finally, Cdc42 also lay on the upstream of protein kinase B to transactivate Sox9 and subsequently induced the expression of chondrocyte differential marker in transforming growth factor-β1-induced chondrogenesis. Taken together, by using biochemical and genetic approaches, we have demonstrated that Cdc42 is involved not in osteogenesis but in chondrogenesis in which the BMP2/Cdc42/Pak/p38/Smad signaling module promotes mesenchymal condensation and the TGF-β/Cdc42/Pak/Akt/Sox9 signaling module facilitates chondrogenic differentiation. Copyright © 2016 by the Genetics Society of America.
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The AC photovoltaic module is here!
NASA Astrophysics Data System (ADS)
Strong, Steven J.; Wohlgemuth, John H.; Wills, Robert H.
1997-02-01
This paper describes the design, development, and performance results of a large-area photovoltaic module whose electrical output is ac power suitable for direct connection to the utility grid. The large-area ac PV module features a dedicated, integrally mounted, high-efficiency dc-to-ac power inverter with a nominal output of 250 watts (STC) at 120 Vac, 60 H, that is fully compatible with utility power. The module's output is connected directly to the building's conventional ac distribution system without need for any dc wiring, string combiners, dc ground-fault protection or additional power-conditioning equipment. With its advantages, the ac photovoltaic module promises to become a universal building block for use in all utility-interactive PV systems. This paper discusses AC Module design aspects and utility interface issues (including islanding).
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Guo, Wei; Feng, Jinfei; Li, Lanhai; Yang, Haishui; Wang, Xiaohua; Bian, Xinmin
2014-01-01
Drip irrigation is broadly extended in order to save water in the arid cotton production region of China. Biochar is thought to be a useful soil amendment to reduce greenhouse gas (GHG) emissions. Here, a field study was conducted to compare the emissions of nitrous oxide (N2O) and methane (CH4) under different irrigation methods (drip irrigation (D) and furrow irrigation (F)) and fertilization regimes (conventional fertilization (C) and conventional fertilization + biochar (B)) during the cotton growth season. The accumulated N2O emissions were significantly lower with FB, DC, and DB than with FC by 28.8%, 36.1%, and 37.6%, while accumulated CH4 uptake was 264.5%, 226.7%, and 154.2% higher with DC, DB, and FC than that with FB, respectively. Irrigation methods showed a significant effect on total global warming potential (GWP) and yield-scaled GWP (P < 0.01). DC and DB showed higher cotton yield, water use efficiency (WUE), and lower yield-scaled GWP, as compared with FC and FB. This suggests that in northwestern China mulched-drip irrigation should be a better approach to increase cotton yield with depressed GHG. In addition, biochar addition increased CH4 emissions while it decreased N2O emissions. PMID:25133229
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Gu, Changzhan; Li, Ruijiang; Zhang, Hualiang; Fung, Albert Y C; Torres, Carlos; Jiang, Steve B; Li, Changzhi
2012-11-01
Accurate respiration measurement is crucial in motion-adaptive cancer radiotherapy. Conventional methods for respiration measurement are undesirable because they are either invasive to the patient or do not have sufficient accuracy. In addition, measurement of external respiration signal based on conventional approaches requires close patient contact to the physical device which often causes patient discomfort and undesirable motion during radiation dose delivery. In this paper, a dc-coupled continuous-wave radar sensor was presented to provide a noncontact and noninvasive approach for respiration measurement. The radar sensor was designed with dc-coupled adaptive tuning architectures that include RF coarse-tuning and baseband fine-tuning, which allows the radar sensor to precisely measure movement with stationary moment and always work with the maximum dynamic range. The accuracy of respiration measurement with the proposed radar sensor was experimentally evaluated using a physical phantom, human subject, and moving plate in a radiotherapy environment. It was shown that respiration measurement with radar sensor while the radiation beam is on is feasible and the measurement has a submillimeter accuracy when compared with a commercial respiration monitoring system which requires patient contact. The proposed radar sensor provides accurate, noninvasive, and noncontact respiration measurement and therefore has a great potential in motion-adaptive radiotherapy.
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13 CFR 120.857 - Voluntary transfer and surrender of CDC certification.
Code of Federal Regulations, 2014 CFR
2014-01-01
... of CDC certification. 120.857 Section 120.857 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Other Cdc Requirements § 120.857 Voluntary transfer and surrender of CDC certification. A CDC may not transfer its certification or withdraw from the...
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13 CFR 120.810 - Applications for certification as a CDC.
Code of Federal Regulations, 2011 CFR
2011-01-01
... a CDC. 120.810 Section 120.810 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810 Applications for certification as a CDC. (a) An applicant for certification as a CDC must apply to the SBA...
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13 CFR 120.810 - Applications for certification as a CDC.
Code of Federal Regulations, 2012 CFR
2012-01-01
... a CDC. 120.810 Section 120.810 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810 Applications for certification as a CDC. (a) An applicant for certification as a CDC must apply to the SBA...
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13 CFR 120.857 - Voluntary transfer and surrender of CDC certification.
Code of Federal Regulations, 2010 CFR
2010-01-01
... of CDC certification. 120.857 Section 120.857 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Other Cdc Requirements § 120.857 Voluntary transfer and surrender of CDC certification. A CDC may not transfer its certification or withdraw from the...
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13 CFR 120.810 - Applications for certification as a CDC.
Code of Federal Regulations, 2014 CFR
2014-01-01
... a CDC. 120.810 Section 120.810 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810 Applications for certification as a CDC. (a) An applicant for certification as a CDC must apply to the SBA...
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13 CFR 120.810 - Applications for certification as a CDC.
Code of Federal Regulations, 2013 CFR
2013-01-01
... a CDC. 120.810 Section 120.810 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Certification Procedures to Become A Cdc § 120.810 Applications for certification as a CDC. (a) An applicant for certification as a CDC must apply to the SBA...
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13 CFR 120.857 - Voluntary transfer and surrender of CDC certification.
Code of Federal Regulations, 2011 CFR
2011-01-01
... of CDC certification. 120.857 Section 120.857 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Other Cdc Requirements § 120.857 Voluntary transfer and surrender of CDC certification. A CDC may not transfer its certification or withdraw from the...
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13 CFR 120.857 - Voluntary transfer and surrender of CDC certification.
Code of Federal Regulations, 2013 CFR
2013-01-01
... of CDC certification. 120.857 Section 120.857 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Other Cdc Requirements § 120.857 Voluntary transfer and surrender of CDC certification. A CDC may not transfer its certification or withdraw from the...
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13 CFR 120.857 - Voluntary transfer and surrender of CDC certification.
Code of Federal Regulations, 2012 CFR
2012-01-01
... of CDC certification. 120.857 Section 120.857 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Other Cdc Requirements § 120.857 Voluntary transfer and surrender of CDC certification. A CDC may not transfer its certification or withdraw from the...
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Achieving recognition that mental health is part of the mission of CDC.
Safran, Marc A
2009-11-01
For much of its history the U.S. Centers for Disease Control and Prevention (CDC) considered mental health to be outside of its mission. That assumption persisted even after CDC became a leading public health agency and began to face important mental health issues. This narrative describes how the organizational paradigm indicating that mental health was not mission related was challenged and superseded by a new paradigm recognizing mental health as part of CDC's public health mission. Even after the CDC Mental Health Work Group's establishment in 2000, CDC took eight more years to overcome powerful remnants of the old paradigm that had for so long excluded, minimized, or discouraged attention to mental health. The CDC Mental Health Work Group led the agency's mental health efforts without funding or dedicated staffing but with more than 100 CDC professionals from multiple disciplines and centers serving as voluntary members, in addition to their other CDC responsibilities.
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Rodríguez-Rojas, Jorge J; Arque-Chunga, Wilfredo; Fernández-Salas, Ildefonso; Rebollar-Téllez, Eduardo A
2016-06-01
Phlebotominae are the vectors of Leishmania parasites. It is important to have available surveillance and collection methods for the sand fly vectors. The objectives of the present study were to evaluate and compare traps for the collection of sand fly species and to analyze trap catches along months and transects. Field evaluations over a year were conducted in an endemic area of leishmaniasis in the state of Quintana Roo, Mexico. A randomized-block design was implemented in study area with tropical rainforest vegetation. The study design utilized 4 transects with 11 trap types: 1) Centers for Disease Control and Prevention (CDC) light trap with incandescent bulb (CDC-I), 2) CDC light trap with blue light-emitting diodes (LEDs) (CDC-B), 3) CDC light trap with white LEDs (CDC-W), 4) CDC light trap with red LEDs (CDC-R), 5) CDC light trap with green LEDs (CDC-G), 6) Disney trap, 7) Disney trap with white LEDs, 8) sticky panels, 9) sticky panels with white LEDs, 10) delta-like trap, and 11) delta-like trap with white LEDs. A total of 1,014 specimens of 13 species and 2 genera (Lutzomyia and Brumptomyia) were collected. There were significant differences in the mean number of sand flies caught with the 11 traps; CDC-I was (P = 0.0000) more effective than the other traps. Other traps exhibited the following results: CDC-W (17.46%), CDC-B (15.68%), CDC-G (14.89%), and CDC-R (14.30%). The relative abundance of different species varied according to trap types used, and the CDC-I trap attracted more specimens of the known vectors of Leishmania spp., such as like Lutzomyia cruciata, Lu. shannoni, and Lu. ovallesi. Disney trap captured more specimens of Lu. olmeca olmeca. Based on abundance and number of species, CDC light traps and Disney traps appeared to be good candidates for use in vector surveillance programs in this endemic area of Mexico.
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Low-frequency flicker noise in a MSM device made with single Si nanowire (diameter ≈ 50 nm).
Samanta, Sudeshna; Das, Kaustuv; Raychaudhuri, Arup Kumar
2013-04-10
: Low-frequency flicker noise has been measured in a metal-semiconductor-metal (MSM) device made from a single strand of a single crystalline Si nanowire (diameter approximately 50 nm). Measurement was done with an alternating current (ac) excitation for the noise measurement superimposed with direct current (dc) bias that can be controlled independently. The observed noise has a spectral power density ∝1/fα. Application of the superimposed dc bias (retaining the ac bias unchanged) with a value more than the Schottky barrier height at the junction leads to a large suppression of the noise amplitude along with a change of α from 2 to ≈ 1. The dc bias-dependent part of the noise has been interpreted as arising from the interface region. The residual dc bias-independent flicker noise is suggested to arise from the single strand of Si nanowire, which has the conventional 1/f spectral power density.
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Low-frequency flicker noise in a MSM device made with single Si nanowire (diameter ≈ 50 nm)
2013-01-01
Low-frequency flicker noise has been measured in a metal-semiconductor-metal (MSM) device made from a single strand of a single crystalline Si nanowire (diameter approximately 50 nm). Measurement was done with an alternating current (ac) excitation for the noise measurement superimposed with direct current (dc) bias that can be controlled independently. The observed noise has a spectral power density ∝1/fα. Application of the superimposed dc bias (retaining the ac bias unchanged) with a value more than the Schottky barrier height at the junction leads to a large suppression of the noise amplitude along with a change of α from 2 to ≈ 1. The dc bias-dependent part of the noise has been interpreted as arising from the interface region. The residual dc bias-independent flicker noise is suggested to arise from the single strand of Si nanowire, which has the conventional 1/f spectral power density. PMID:23574820
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Microbial degradation of microcystin in Florida’s freshwaters
Ramani, A.; Rein, K.; Shetty, K. G.
2012-01-01
Presence of microcystin (MC), a predominant freshwater algal toxin and a suspected liver carcinogen, in Florida’s freshwaters poses serious health threat to humans and aquatic species. Being recalcitrant to conventional physical and chemical water treatment methods, biological methods of MC removal is widely researched. Water samples collected from five sites of Lake Okeechobee (LO) frequently exposed to toxic Microcystis blooms were used as inoculum for enrichment with microcystin LR (MC-LR) supplied as sole C and N source. After 20 days incubation, MC levels were analyzed using high performance liquid chromatography (HPLC). A bacterial consortium consisting of two isolates DC7 and DC8 from the Indian Prairie Canal sample showed over 74% toxin degradation at the end of day 20. Optimal temperature requirement for biodegradation was identified and phosphorus levels did not affect the MC biodegradation. Based on 16S rRNA sequence similarity the isolate DC8 was found to have a match with Microbacterium sp. and the DC7 isolate with Rhizobium gallicum (AY972457). PMID:21611743
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Perceived insufficient rest or sleep among adults - United States, 2008.
2009-10-30
The importance of chronic sleep insufficiency is under-recognized as a public health problem, despite being associated with numerous physical and mental health problems, injury, loss of productivity, and mortality. Approximately 29% of U.S. adults report sleeping <7 hours per night and 50-70 million have chronic sleep and wakefulness disorders. A CDC analysis of 2006 data from the Behavioral Risk Factor Surveillance System (BRFSS) in four states showed that an estimated 10.1% of adults reported receiving insufficient rest or sleep on all days during the preceding 30 days. To examine the prevalence of insufficient rest or sleep in all states, CDC analyzed BRFSS data for all 50 states, the District of Columbia (DC), and three U.S. territories (Guam, Puerto Rico, and U.S. Virgin Islands) in 2008. This report summarizes the results, which showed that among 403,981 respondents, 30.7% reported no days of insufficient rest or sleep and 11.1% reported insufficient rest or sleep every day during the preceding 30 days. Females (12.4%) were more likely than males (9.9%) and non-Hispanic blacks (13.3%) were more likely than other racial/ethnic groups to report insufficient rest or sleep. State estimates of 30 days of insufficient rest or sleep ranged from 7.4% in North Dakota to 19.3% in West Virginia. Health-care providers should consider adding an assessment of chronic rest or sleep insufficiency to routine office visits so they can make needed interventions or referrals to sleep specialists.
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Immunization information system progress--United States, 2004.
2005-11-18
One of the national health objectives for 2010 is to increase to at least 95% the proportion of children aged <6 years who participate in fully operational, population-based immunization registries (objective no. 14-26). Immunization registries are confidential, computerized information systems that collect and consolidate vaccination data from multiple health-care providers, generate reminder and recall notifications, and assess vaccination coverage within a defined geographic area. A registry with added capabilities, such as vaccine management, adverse event reporting, lifespan vaccination histories, and linkages with electronic data sources, is called an immunization information system (IIS). This report summarizes data from CDC's 2004 IIS Annual Report, a survey of 56 grantees in 50 states, five cities, and the District of Columbia (DC) that receive funding under section 317b of the Public Health Service Act. The findings indicate that approximately 48% of U.S. children aged <6 years participated in an IIS. Moreover, 76% of public vaccination provider sites and 39% of private vaccination provider sites submitted immunization data to an IIS during the last 6 months of 2004. Overcoming challenges and barriers to increasing the number of provider sites and the percentage of children aged <6 years participating in an IIS is critical to achieving the national health objective. CDC has developed a plan of action to address those challenges. Major components of the plan include, but are not limited to, a multiyear IIS business plan for each grantee and enhanced technical assistance to grantees with unresolved challenges.
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ERIC Educational Resources Information Center
Minnigerode, Fred A.
1977-01-01
Early data suggest that homosexuals are becoming more aware of their civil rights and more willing to fight for them. Men and women no longer have to repent for their homosexual feelings and behavior. Presented at the 1976 American Psychological Association Convention, Washington, D.C. (Author)
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p53 mediates bcl-2 phosphorylation and apoptosis via activation of the Cdc42/JNK1 pathway.
Thomas, A; Giesler, T; White, E
2000-11-02
A member of the small G protein family, cdc42, was isolated from a screen undertaken to identify p53-inducible genes during apoptosis in primary baby rat kidney (BRK) cells transformed with E1A and a temperature-sensitive mutant p53 using a PCR-based subtractive hybridization method. Cdc42 is a GTPase that belongs to the Rho/Rac subfamily of Ras-like GTPases. In response to external stimuli, Cdc42 is known to transduce signals to regulate the organization of the actin cytoskeleton, induce DNA synthesis in quiescent fibroblasts, and promote apoptosis in neuronal and immune cells. In this study, we have demonstrated that cdc42 mRNA and protein were up-regulated in the presence of wild-type p53 in BRK cells, followed by cytoplasmic to plasma membrane translocation of Cdc42. Overexpression of Cdc42 in the presence of a dominant-negative mutant p53 induced apoptosis rapidly, indicating that Cdc42 functions downstream of p53. Furthermore, stable expression of a dominant-negative mutant of Cdc42 partially inhibited p53-mediated apoptosis. The Bcl-2 family members Bcl-xL, and the adenovirus protein E1B 19K, inhibited Cdc42-mediated apoptosis, whereas Bcl-2 did not. We provide evidence that PAK1 and JNK1 may play a role downstream of Cdc42 to transduce its apoptotic signal. Cdc42/PAK1 activates JNK1-induced phosphorylation of Bcl-2, thereby inactivating its function, and that a phosphorylation resistant mutant (Bcl-2S70,87A,T56,74A) gains the ability to inhibit Cdc42- and p53-mediated apoptosis. Thus, one mechanism by which p53 promotes apoptosis is through activation of Cdc42 and inactivation of Bcl-2.
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Assembly, molecular organization, and membrane-binding properties of development-specific septins
Garcia, Galo; Finnigan, Gregory C.; Heasley, Lydia R.; Sterling, Sarah M.; Aggarwal, Adeeti; Pearson, Chad G.
2016-01-01
Septin complexes display remarkable plasticity in subunit composition, yet how a new subunit assembled into higher-order structures confers different functions is not fully understood. Here, this question is addressed in budding yeast, where during meiosis Spr3 and Spr28 replace the mitotic septin subunits Cdc12 and Cdc11 (and Shs1), respectively. In vitro, the sole stable complex that contains both meiosis-specific septins is a linear Spr28–Spr3–Cdc3–Cdc10–Cdc10–Cdc3–Spr3–Spr28 hetero-octamer. Only coexpressed Spr3 and Spr28 colocalize with Cdc3 and Cdc10 in mitotic cells, indicating that incorporation requires a Spr28-Spr3 protomer. Unlike their mitotic counterparts, Spr28-Spr3–capped rods are unable to form higher-order structures in solution but assemble to form long paired filaments on lipid monolayers containing phosphatidylinositol-4,5-bisphosphate, mimicking presence of this phosphoinositide in the prospore membrane. Spr28 and Spr3 fail to rescue the lethality of a cdc11Δ cdc12Δ mutant, and Cdc11 and Cdc12 fail to restore sporulation proficiency to spr3Δ/spr3Δ spr28Δ/spr28Δ diploids. Thus, specific meiotic and mitotic subunits endow septin complexes with functionally distinct properties. PMID:26929450
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Kerr, Gary W; Wong, Jin Huei; Arumugam, Prakash
2016-07-26
PP2A(Cdc55) is a highly conserved serine-threonine protein phosphatase that is involved in diverse cellular processes. In budding yeast, meiotic cells lacking PP2A(Cdc55) activity undergo a premature exit from meiosis I which results in a failure to form bipolar spindles and divide nuclei. This defect is largely due to its role in negatively regulating the Cdc Fourteen Early Anaphase Release (FEAR) pathway. PP2A(Cdc55) prevents nucleolar release of the Cdk (Cyclin-dependent kinase)-antagonising phosphatase Cdc14 by counteracting phosphorylation of the nucleolar protein Net1 by Cdk. CDC55 was identified in a genetic screen for monopolins performed by isolating suppressors of spo11Δ spo12Δ lethality suggesting that Cdc55 might have a role in meiotic chromosome segregation. We investigated this possibility by isolating cdc55 alleles that suppress spo11Δ spo12Δ lethality and show that this suppression is independent of PP2A(Cdc55)'s FEAR function. Although the suppressor mutations in cdc55 affect reductional chromosome segregation in the absence of recombination, they have no effect on chromosome segregation during wild type meiosis. We suggest that Cdc55 is required for reductional chromosome segregation during achiasmate meiosis and this is independent of its FEAR function.
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13 CFR 120.823 - CDC Board of Directors.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members, and...
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13 CFR 120.851 - CDC ethical requirements.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their... § 120.140. In addition, they are subject to the following: (a) Any benefit flowing to a CDC's Associate...
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13 CFR 120.823 - CDC Board of Directors.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members, and...
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13 CFR 120.829 - Job Opportunity average a CDC must maintain.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Job Opportunity average a CDC must... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.829 Job Opportunity average a CDC must maintain. (a) A CDC's portfolio must maintain a minimum average of...
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13 CFR 120.851 - CDC ethical requirements.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their... § 120.140. In addition, they are subject to the following: (a) Any benefit flowing to a CDC's Associate...
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13 CFR 120.851 - CDC ethical requirements.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their... § 120.140. In addition, they are subject to the following: (a) Any benefit flowing to a CDC's Associate...
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13 CFR 120.829 - Job Opportunity average a CDC must maintain.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Job Opportunity average a CDC must... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.829 Job Opportunity average a CDC must maintain. (a) A CDC's portfolio must maintain a minimum average of...
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13 CFR 120.823 - CDC Board of Directors.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members, and...
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13 CFR 120.820 - CDC non-profit status and good standing.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...
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13 CFR 120.821 - CDC Area of Operations.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...
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13 CFR 120.823 - CDC Board of Directors.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members, and...
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13 CFR 120.821 - CDC Area of Operations.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...
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13 CFR 120.823 - CDC Board of Directors.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC Board of Directors. 120.823... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.823 CDC Board of Directors. The CDC must have a Board of Directors chosen from the membership by the members, and...
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13 CFR 120.820 - CDC non-profit status and good standing.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...
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13 CFR 120.820 - CDC non-profit status and good standing.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...
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13 CFR 120.820 - CDC non-profit status and good standing.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...
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13 CFR 120.821 - CDC Area of Operations.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...
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13 CFR 120.820 - CDC non-profit status and good standing.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC non-profit status and good... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.820 CDC non-profit status and good standing. A CDC must be a non-profit corporation, except that for...
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13 CFR 120.821 - CDC Area of Operations.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...
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13 CFR 120.821 - CDC Area of Operations.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false CDC Area of Operations. 120.821... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.821 CDC Area of Operations. A CDC must operate only within its designated Area of Operations approved by SBA except as...
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13 CFR 120.829 - Job Opportunity average a CDC must maintain.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Job Opportunity average a CDC must... LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.829 Job Opportunity average a CDC must maintain. (a) A CDC's portfolio must maintain a minimum average of...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-10-05
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--Health Disparities... provide recommendations for consideration to the ACD on strategic and other broad issues facing CDC... collaboration with the CDC Health Equity Workgroup; CDC Director's Annual Health Disparity Report; and briefing...
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cdc-25.2, a Caenorhabditis elegans ortholog of cdc25, is required for male tail morphogenesis.
Oh, Sangmi; Yoon, Sunghee; Youn, Esther; Kawasaki, Ichiro; Shim, Yhong-Hee
2017-01-22
Cell division cycle 25 (Cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression by activating cyclin-dependent kinases (Cdks) which are inactivated by Wee1/Myt1 kinases. It was previously reported that cdc-25.2 promotes oocyte maturation and intestinal cell divisions in Caenorhabditis elegans hermaphrodites. Here, we report a novel function of cdc-25.2 in male tail development which was significantly deformed by cdc-25.2 RNAi depletion and in cdc-25.2 mutant males. The deformation was also observed after RNAi depletion of other cell cycle regulators, cdk-1, cyb-3, cyd-1, and cyl-1. Furthermore, wee-1.3 counteracted cdc-25.2 in male tail development as observed in oocyte maturation and intestine development. The number of cells in ray precursor cell lineages was significantly reduced in cdc-25.2 depleted males. These results indicate that CDC-25.2 is essential for cell divisions in ray precursor cell lineages for proper male tail development. Copyright © 2016 Elsevier Inc. All rights reserved.
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Cdc13 N-Terminal Dimerization DNA Binding and Telomere Length Regulation
DOE Office of Scientific and Technical Information (OSTI.GOV)
M Mitchell; J Smith; M Mason
The essential yeast protein Cdc13 facilitates chromosome end replication by recruiting telomerase to telomeres, and together with its interacting partners Stn1 and Ten1, it protects chromosome ends from nucleolytic attack, thus contributing to genome integrity. Although Cdc13 has been studied extensively, the precise role of its N-terminal domain (Cdc13N) in telomere length regulation remains unclear. Here we present a structural, biochemical, and functional characterization of Cdc13N. The structure reveals that this domain comprises an oligonucleotide/oligosaccharide binding (OB) fold and is involved in Cdc13 dimerization. Biochemical data show that Cdc13N weakly binds long, single-stranded, telomeric DNA in a fashion that ismore » directly dependent on domain oligomerization. When introduced into full-length Cdc13 in vivo, point mutations that prevented Cdc13N dimerization or DNA binding caused telomere shortening or lengthening, respectively. The multiple DNA binding domains and dimeric nature of Cdc13 offer unique insights into how it coordinates the recruitment and regulation of telomerase access to the telomeres.« less
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... and Prevention (CDC). Fact Sheets: Underage Drinking . Atlanta, GA: CDC, 2016. Available at: http://www.cdc.gov/ ... Public Health: Alcohol-Related Disease Impact (ARDI) . Atlanta, GA: CDC, 2016. Available at: http://go.usa.gov/ ...
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Xu, Ji-Dong; Jiang, Hai-Shan; Wei, Tian-Di; Zhang, Ke-Yi; Wang, Xian-Wei; Zhao, Xiao-Fan
2016-01-01
ABSTRACT Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp (Marsupenaeus japonicus) and named it MjCdc42. MjCdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of MjCdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that MjCdc42 interacted with an arginine kinase (MjAK). By analyzing the binding activity and enzyme activity of MjAK and its mutant, ΔMjAK, we found that MjAK could enhance the replication of WSSV in shrimp. MjAK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of MjAK in WSSV replication. Further study demonstrated that the binding of MjCdc42 and MjAK depends on Cys271 of MjAK and suppresses the WSSV replication-promoting effect of MjAK. By interacting with the active site of MjAK and suppressing its enzyme activity, MjCdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies. IMPORTANCE The interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates. PMID:28031362
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Xu, Ji-Dong; Jiang, Hai-Shan; Wei, Tian-Di; Zhang, Ke-Yi; Wang, Xian-Wei; Zhao, Xiao-Fan; Wang, Jin-Xing
2017-03-01
Many types of small GTPases are widely expressed in eukaryotes and have different functions. As a crucial member of the Rho GTPase family, Cdc42 serves a number of functions, such as regulating cell growth, migration, and cell movement. Several RNA viruses employ Cdc42-hijacking tactics in their target cell entry processes. However, the function of Cdc42 in shrimp antiviral immunity is not clear. In this study, we identified a Cdc42 protein in the kuruma shrimp ( Marsupenaeus japonicus ) and named it Mj Cdc42. Mj Cdc42 was upregulated in shrimp challenged by white spot syndrome virus (WSSV). The knockdown of Mj Cdc42 and injection of Cdc42 inhibitors increased the proliferation of WSSV. Further experiments determined that Mj Cdc42 interacted with an arginine kinase ( Mj AK). By analyzing the binding activity and enzyme activity of Mj AK and its mutant, Δ Mj AK, we found that Mj AK could enhance the replication of WSSV in shrimp. Mj AK interacted with the envelope protein VP26 of WSSV. An inhibitor of AK activity, quercetin, could impair the function of Mj AK in WSSV replication. Further study demonstrated that the binding of Mj Cdc42 and Mj AK depends on Cys 271 of Mj AK and suppresses the WSSV replication-promoting effect of Mj AK. By interacting with the active site of Mj AK and suppressing its enzyme activity, Mj Cdc42 inhibits WSSV replication in shrimp. Our results demonstrate a new function of Cdc42 in the cellular defense against viral infection in addition to the regulation of actin and phagocytosis, which has been reported in previous studies. IMPORTANCE The interaction of Cdc42 with arginine kinase plays a crucial role in the host defense against WSSV infection. This study identifies a new mechanism of Cdc42 in innate immunity and enriches the knowledge of the antiviral innate immunity of invertebrates. Copyright © 2017 American Society for Microbiology.
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Binding and inhibition of Cdc25 phosphatases by vitamin K analogues.
Kar, Siddhartha; Lefterov, Iliya M; Wang, Meifang; Lazo, John S; Scott, Colleen N; Wilcox, Craig S; Carr, Brian I
2003-09-09
A synthetic K vitamin analogue, 2-(2-mercaptothenol)-3-methyl-1,4-naphthoquinone or Cpd 5, was previously found to be a potent inhibitor of cell growth [Nishikawa et al., (1995) J. Biol. Chem. 270, 28304-28310]. The mechanisms of cell growth were hypothesized to include the inactivation of cellular protein tyrosine phosphatases, especially the Cdc25 family [Tamura et al. (2000) Cancer Res. 60, 1317-1325]. In this study, we synthesized PD 49, a new biotin containing Cpd 5 derivative, to search for evidence of direct interaction of these arylating analogues with Cdc25A, Cdc25B, and Cdc25C phosphatases. PD 49 was shown to directly bind to GST-Cdc25A, GST-Cdc25B, their catalytic fragments, and GST-Cdc25C. The binding could be competed with excess glutathione or Cpd 5, and a cysteine-to-serine mutation of the catalytic cysteine abolished binding. This was consistent with an involvement in binding of cysteine in the catalytic domain. This interaction between PD 49 and Cdc25 also occurred in lysates of treated cells. PD 49 also bound to protein phosphatases other than Cdc25. We found that the new analogue also inhibited Hep3B human hepatoma cell growth. This growth inhibition involved ERK1/2 phosphorylation and was inhibited by a MEK antagonist. The results demonstrate a direct interaction and binding between this growth-inhibiting K vitamin derivative with both purified as well as with cellular Cdc25A, Cdc25B, and Cdc25C.
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Activation of Rho GTPase Cdc42 promotes adhesion and invasion in colorectal cancer cells.
Gao, Lei; Bai, Lan; Nan, Qing zhen
2013-07-25
The purpose of this study was to investigate the role of activated Rho GTPase cell division control protein 42 homolog (Cdc42) in colorectal cancer cell adhesion, migration, and invasion. The constitutively active form of Cdc42 (GFP-Cdc42L61) or control vector was overexpressed in the colorectal cancer cell line SW480. The localization of active Cdc42 was monitored by immunofluorescence staining, and the effects of active Cdc42 on cell migration and invasion were examined using an attachment assay, a wound healing assay, and a Matrigel migration assay in vitro. Immunofluorescence staining revealed that constitutively active Cdc42 predominately localized to the plasma membrane. Compared to SW480 cells transfected with the control vector, overexpression of constitutively active Cdc42 in SW480 cells promoted filopodia formation and cell stretch and dramatically enhanced cell adhesion to the coated plates. The wound healing assay revealed a significant increase of migration capability in SW480 cells expressing active Cdc42 compared to the control cells. Additionally, the Matrigel invasion assay demonstrated that active Cdc42 significantly promoted SW480 cell migration through the chamber. Our results suggest that active Rho GTPase Cdc42 can greatly enhance colorectal cancer cell SW480 to spread, migrate, and invade, which may contribute to colorectal cancer metastasis.
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Iskander, John; Bang, Gail; Stupp, Emma; Connick, Kathy; Gomez, Onnalee; Gidudu, Jane
2016-01-01
To describe scientific information usage and publication patterns of the Centers for Disease Control and Prevention (CDC) Public Health Library and Information Center patrons. Administratively collected patron usage data and aggregate data on CDC-authored publications from the CDC Library for 3 consecutive years were analyzed. The CDC Public Health Library and Information Center, which serves CDC employees nationally and internationally. Internal patrons and external users of the CDC Library. Three-year trends in full-text article publication and downloads including most common journals used for each purpose, systematic literature searches requested and completed, and subscriptions to a weekly public health current literature awareness service. From 2011 to 2013, CDC scientists published a total of 7718 articles in the peer-reviewed literature. During the same period, article downloads from the CDC Library increased 25% to more than 1.1 million, completed requests for reviews of the scientific literature increased by 34%, and electronic subscriptions to literature compilation services increased by 23%. CDC's scientific output and information use via the CDC Library are both increasing. Researchers and field staff are making greater use of literature review services and other customized information content delivery. Virtual public health library access is an increasingly important resource for the scientific practice of public health.
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Tseng, Shun-Fu; Shen, Zih-Jie; Tsai, Hung-Ji; Lin, Yi-Hsuan; Teng, Shu-Chun
2009-06-01
Budding yeast telomerase is mainly activated by Tel1/Mec1 (yeast ATM/ATR) on Cdc13 from late S to G2 phase of the cell cycle. Here, we demonstrated that the telomerase-recruitment domain of Cdc13 is also phosphorylated by Cdk1 at the same cell cycle stage as the Tel1/Mec1-dependent regulation. Phosphor-specific gel analysis demonstrated that Cdk1 phosphorylates residues 308 and 336 of Cdc13. The residue T308 of Cdc13 is critical for efficient Mec1-mediated S306 phosphorylation in vitro. Phenotypic analysis in vivo revealed that the mutations in the Cdc13 S/TP motifs phosphorylated by Cdk1 caused cell cycle delay and telomere shortening and these phenotypes could be partially restored by the replacement with a negative charge residue. In the absence of Ku or Tel1, Cdk1-mediated phosphorylation of Cdc13 showed no effect on telomere length maintenance. Moreover, this Cdk1-mediated phosphorylation was required to promote the regular turnover of Cdc13. Together these results demonstrate that Cdk1 phosphorylates the telomerase recruitment domain of Cdc13, thereby preserves optimal function and expression level of Cdc13 for precise telomere replication and cell cycle progression.
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13 CFR 120.827 - Other services a CDC may provide to small businesses.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...
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33 CFR 165.503 - Security Zone; Captain of the Port Hampton Roads Zone.
Code of Federal Regulations, 2012 CFR
2012-07-01
... section— Certain dangerous cargo or CDC means a material defined as CDC in 33 CFR 160.204. Designated... a passenger vessel or vessel carrying a CDC, while the passenger vessel or vessel carrying CDC is... vessel or vessel carrying a CDC within the Captain of the Port Hampton Roads zone, unless traveling at...
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13 CFR 120.935 - Deposit from the Borrower that a CDC may require.
Code of Federal Regulations, 2012 CFR
2012-01-01
... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...
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33 CFR 165.503 - Security Zone; Captain of the Port Hampton Roads Zone.
Code of Federal Regulations, 2014 CFR
2014-07-01
... section— Certain dangerous cargo or CDC means a material defined as CDC in 33 CFR 160.204. Designated... a passenger vessel or vessel carrying a CDC, while the passenger vessel or vessel carrying CDC is... vessel or vessel carrying a CDC within the Captain of the Port Hampton Roads zone, unless traveling at...
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42 CFR 73.7 - Registration and related security risk assessments.
Code of Federal Regulations, 2010 CFR
2010-10-01
... requested in the registration application package (APHIS/CDC Form 1) to CDC. To apply for a certificate of... application package (APHIS/CDC Form 1) to CDC or APHIS, but not both. (e) Prior to the issuance of a... entity must immediately notify CDC or APHIS if it loses the services of its Responsible Official. In the...
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-11
... Committee to the Director (ACD), Centers for Disease Control and Prevention (CDC)--National Biosurveillance.... L. 92-463), the CDC announces the following meeting of aforementioned subcommittee: Time and Date: 8.... Purpose: As a subcommittee to the CDC's ACD, the NBAS will provide counsel to the CDC and the Federal...
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13 CFR 120.827 - Other services a CDC may provide to small businesses.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...
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13 CFR 120.827 - Other services a CDC may provide to small businesses.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...
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13 CFR 120.830 - Reports a CDC must submit.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Reports a CDC must submit. 120.830... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.830 Reports a CDC must submit. A CDC must submit the following reports to SBA: (a) An annual report within one hundred-eighty...
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13 CFR 120.827 - Other services a CDC may provide to small businesses.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...
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42 CFR 73.7 - Registration and related security risk assessments.
Code of Federal Regulations, 2011 CFR
2011-10-01
... requested in the registration application package (APHIS/CDC Form 1) to CDC. To apply for a certificate of... application package (APHIS/CDC Form 1) to CDC or APHIS, but not both. (e) Prior to the issuance of a... entity must immediately notify CDC or APHIS if it loses the services of its Responsible Official. In the...
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Code of Federal Regulations, 2010 CFR
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...
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13 CFR 120.935 - Deposit from the Borrower that a CDC may require.
Code of Federal Regulations, 2014 CFR
2014-01-01
... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...
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13 CFR 120.827 - Other services a CDC may provide to small businesses.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Other services a CDC may provide... ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.827 Other services a CDC may provide to small businesses. A CDC may provide a small business...
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13 CFR 120.935 - Deposit from the Borrower that a CDC may require.
Code of Federal Regulations, 2013 CFR
2013-01-01
... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...
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13 CFR 120.935 - Deposit from the Borrower that a CDC may require.
Code of Federal Regulations, 2010 CFR
2010-01-01
... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...
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13 CFR 120.830 - Reports a CDC must submit.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Reports a CDC must submit. 120.830... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.830 Reports a CDC must submit. A CDC must submit the following reports to SBA: (a) An annual report within one hundred-eighty...
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13 CFR 120.830 - Reports a CDC must submit.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Reports a CDC must submit. 120.830... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.830 Reports a CDC must submit. A CDC must submit the following reports to SBA: (a) An annual report within one hundred-eighty...
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Code of Federal Regulations, 2012 CFR
2012-01-01
... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...
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13 CFR 120.830 - Reports a CDC must submit.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Reports a CDC must submit. 120.830... Company Loan Program (504) Requirements for Cdc Certification and Operation § 120.830 Reports a CDC must submit. A CDC must submit the following reports to SBA: (a) An annual report within one hundred-eighty...
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33 CFR 165.503 - Security Zone; Captain of the Port Hampton Roads Zone.
Code of Federal Regulations, 2013 CFR
2013-07-01
... section— Certain dangerous cargo or CDC means a material defined as CDC in 33 CFR 160.204. Designated... a passenger vessel or vessel carrying a CDC, while the passenger vessel or vessel carrying CDC is... vessel or vessel carrying a CDC within the Captain of the Port Hampton Roads zone, unless traveling at...
-
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...
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Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...
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Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Restrictions regarding CDC... Company Loan Program (504) Other Cdc Requirements § 120.852 Restrictions regarding CDC participation in.... A CDC must not invest in or be an Affiliate of a Lender participating in the 7(a) loan program...
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13 CFR 120.935 - Deposit from the Borrower that a CDC may require.
Code of Federal Regulations, 2011 CFR
2011-01-01
... CDC may require. 120.935 Section 120.935 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... Borrower that a CDC may require. At the time of application for a 504 loan, the CDC may require a deposit... application is denied. If the small business withdraws its application, the CDC may deduct from the deposit...
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42 CFR 73.7 - Registration and related security risk assessments.
Code of Federal Regulations, 2012 CFR
2012-10-01
... requested in the registration application package (APHIS/CDC Form 1) to CDC. To apply for a certificate of... application package (APHIS/CDC Form 1) to CDC or APHIS, but not both. (e) Prior to the issuance of a... entity must immediately notify CDC or APHIS if it loses the services of its Responsible Official. In the...
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Teaching Fiction through Visual and Verbal Art
ERIC Educational Resources Information Center
Murphy, Geraldine
1970-01-01
A suggested list of films, short stories, photographs, plays, and paintings is included for a unit on pariahs, lovers, and heroes; a paper presented at annual convention of National Council of Teachers of English (59th, Washington, D.C., November 28, 1969). (RD)
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2018 USA Science and Engineering Festival
2018-04-06
Attendees visit NASA exhibits during Sneak Peek Friday at the USA Science and Engineering Festival, Friday, April 6, 2018 at the Walter E. Washington Convention Center in Washington, DC. The festival is open to the public April 7-8. Photo Credit: (NASA/Joel Kowsky)
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USA Science and Engineering Festival 2014
2014-04-25
Attendees of the USA Science and Engineering Festival explore all of the exhibits at the NASA Stage. The USA Science and Engineering Festival took place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)
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USA Science and Engineering Festival 2014
2014-04-25
Astronaut Rex Walheim spoke at the USA Science and Engineering Festival on April 25, 2014. The festival was open to the public on April 26 and 27, 2014 and was held at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)
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... Safety Website CDC Vital Signs — Preventing Norovirus Outbreaks, Food Service has a Key Role CDC Vital Signs: Making ... Safety Website CDC Vital Signs — Preventing Norovirus Outbreaks, Food Service has a Key Role CDC Vital Signs: Making ...
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NASA Astrophysics Data System (ADS)
Zhang, Biao; Jiang, Wan; Yang, Yang; Yu, Chengyang; Huang, Kama; Liu, Changjun
2015-11-01
A multi-magnetron microwave source, a metamaterial transmitting antenna, and a large power rectenna array are presented to build a near-field 2.45 GHz microwave power transmission system. The square 1 m2 rectenna array consists of sixteen rectennas with 2048 Schottky diodes for large power microwave rectifying. It receives microwave power and converts them into DC power. The design, structure, and measured performance of a unit rectenna as well as the entail rectenna array are presented in detail. The multi-magnetron microwave power source switches between half and full output power levels, i.e. the half-wave and full-wave modes. The transmission antenna is formed by a double-layer metallic hole array, which is applied to combine the output power of each magnetron. The rectenna array DC output power reaches 67.3 W on a 1.2 Ω DC load at a distance of 5.5 m from the transmission antenna. DC output power is affected by the distance, DC load, and the mode of microwave power source. It shows that conventional low power Schottky diodes can be applied to a microwave power transmission system with simple magnetrons to realise large power microwave rectifying.
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A Case Study of Wind-PV-Thermal-Bundled AC/DC Power Transmission from a Weak AC Network
NASA Astrophysics Data System (ADS)
Xiao, H. W.; Du, W. J.; Wang, H. F.; Song, Y. T.; Wang, Q.; Ding, J.; Chen, D. Z.; Wei, W.
2017-05-01
Wind power generation and photovoltaic (PV) power generation bundled with the support by conventional thermal generation enables the generation controllable and more suitable for being sent over to remote load centre which are beneficial for the stability of weak sending end systems. Meanwhile, HVDC for long-distance power transmission is of many significant technique advantages. Hence the effects of wind-PV-thermal-bundled power transmission by AC/DC on power system have become an actively pursued research subject recently. Firstly, this paper introduces the technical merits and difficulties of wind-photovoltaic-thermal bundled power transmission by AC/DC systems in terms of meeting the requirement of large-scale renewable power transmission. Secondly, a system model which contains a weak wind-PV-thermal-bundled sending end system and a receiving end system in together with a parallel AC/DC interconnection transmission system is established. Finally, the significant impacts of several factors which includes the power transmission ratio between the DC and AC line, the distance between the sending end system and receiving end system, the penetration rate of wind power and the sending end system structure on system stability are studied.
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Tribology of carbide derived carbon films synthesized on tungsten carbide
NASA Astrophysics Data System (ADS)
Tlustochowicz, Marcin
Tribologically advantageous films of carbide derived carbon (CDC) have been successfully synthesized on binderless tungsten carbide manufactured using the plasma pressure compaction (P2CRTM) technology. In order to produce the CDC films, tungsten carbide samples were reacted with chlorine containing gas mixtures at temperatures ranging from 800°C to 1000°C in a sealed tube furnace. Some of the treated samples were later dechlorinated by an 800°C hydrogenation treatment. Detailed mechanical and structural characterizations of the CDC films and sliding contact surfaces were done using a series of analytical techniques and their results were correlated with the friction and wear behavior of the CDC films in various tribosystems, including CDC-steel, CDC-WC, CDC-Si3N4 and CDC-CDC. Optimum synthesis and treatment conditions were determined for use in two specific environments: moderately humid air and dry nitrogen. It was found that CDC films first synthesized at 1000°C and then hydrogen post-treated at 800°C performed best in air with friction coefficient values as low as 0.11. However, for dry nitrogen applications, no dechlorination was necessary and both hydrogenated and as-synthesized CDC films exhibited friction coefficients of approximately 0.03. A model of tribological behavior of CDC has been proposed that takes into consideration the tribo-oxidation of counterface material, the capillary forces from adsorbed water vapor, the carbon-based tribofilm formation, and the lubrication effect of both chlorine and hydrogen.
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Romero-Vargas, Frey Francisco; Ponce-Soto, Luis Alberto; Martins-de-Souza, Daniel; Marangoni, Sergio
2010-01-01
This work reports the purification, biological characterization and amino acid sequence of two new basic PLA(2) isoforms, Cdc-9 and Cdc-10, purified from the Crotalus durissus cumanensis venom by one step analytical chromatography reverse phase HPLC. The molecular masses of the PLA(2) were 14,175+/-2.7 Da for Cdc-9 and 14,228+/-3.5 Da for Cdc-10 both deduced by primary structure and confirmed by MALDI-TOF. The isoforms presented an amino acid sequence of 122 amino acid residues, being Cdc-9: SLVQFNKMIK FETRKSGLPF YAAYGCYCGW GGQRPKDATD RCCFVHDCCY GKVAKCNTKW DIYSYSLKSG YITCGKGTWC KEQICECDRV AAECLRRSLS TYKNEYMFYP DSRCREPPEY TC with pI value of 8.25 and Cdc-10: SLLQFNKMIK FETRKSGVPF YAAYGCYCGW GGRRPKDPTD RCCFVHDCCY GKLTKCNTKW DIYSYSLKSG YITCGKGTWC KEQICECDRV AAECLRRSLN TYKNEYMFYP DSRCRGPPEY TC with a pI value of 8.46, showing highly conserved Ca(2+)-binding and catalytic sites. The PLA(2) activity decreased when the isoforms Cdc-9 and Cdc-10 were incubated with 4-bromophenacyl bromide (p-BPB), anhydrous acetic acid and p-nitrobenzene sulfonyl fluoride (NBSF) when compared with the activity of both native isoforms. In mice, the PLA(2) isoforms Cdc-9 and Cdc-10 induced myonecrosis and edema. Myotoxic and edema activities were reduced after treatment of the isoforms with p-BPB; acetylation of the lysine residues and the treatment of PLA(2) with NBSF have also induced edema reduction. However, p-BPB strongly diminishes the local and systemic myotoxic effects.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Sun, Jia; Yang, Yuting; Wan, Ke
Budding yeast Cdc13-Stn1-Ten1 (CST) complex plays an essential role in telomere protection and maintenance, and has been proposed to be a telomere-specific replication protein A (RPA)-like complex. Previous genetic and structural studies revealed a close resemblance between Stn1-Ten1 and RPA32-RPA14. However, the relationship between Cdc13 and RPA70, the largest subunit of RPA, has remained unclear. Here, we report the crystal structure of the N-terminal OB (oligonucleotide/oligosaccharide binding) fold of Cdc13. Although Cdc13 has an RPA70-like domain organization, the structures of Cdc13 OB folds are significantly different from their counterparts in RPA70, suggesting that they have distinct evolutionary origins. Furthermore, ourmore » structural and biochemical analyses revealed unexpected dimerization by the N-terminal OB fold and showed that homodimerization is probably a conserved feature of all Cdc13 proteins. We also uncovered the structural basis of the interaction between the Cdc13 N-terminal OB fold and the catalytic subunit of DNA polymerase {alpha} (Pol1), and demonstrated a role for Cdc13 dimerization in Pol1 binding. Analysis of the phenotypes of mutants defective in Cdc13 dimerization and Cdc13-Pol1 interaction revealed multiple mechanisms by which dimerization regulates telomere lengths in vivo. Collectively, our findings provide novel insights into the mechanisms and evolution of Cdc13.« less
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A magnetic-piezoelectric smart material-structure sensing three axis DC and AC magnetic-fields
NASA Astrophysics Data System (ADS)
Hung, Chiao-Fang; Chen, Chin-Chung; Yeh, Po-Chen; Chen, Po-Wen; Chung, Tien-Kan
2017-12-01
In this paper, we demonstrate a smart material-structure can sense not only three-axis AC magnetic-fields but also three-axis DC magnetic-fields. Under x-axis and z-axis AC magnetic field ranging from 0.2 to 3.2 gauss, sensing sensitivity of the smart material-structure stimulated at resonant frequency is approximate 8.79 and 2.80 mV/gauss, respectively. In addition, under x-axis and z-axis DC magnetic fields ranging from 2 to 12 gauss, the sensitivity of the smart material-structure is 1.24-1.54 and 1.25-1.41 mV/gauss, respectively. In addition, under x-axis and z-axis DC magnetic fields ranging from 12 to 20 gauss, the sensitivity of the smart material-structure is 5.17-6.2 and 3.97-4.57 mV/gauss, respectively. These experimental results show that the smart material-structure successfully achieves three-axis DC and AC magnetic sensing as we designed. Furthermore, we also compare the results of the AC and DC magnetic-field sensing to investigate discrepancies. Finally, when applying composite magnetic-fields to the smart material-structure, the smart material-structure shows decent outputs as expected (consistent to the sensing principle). In the future, we believe the smart material-structure capable of sensing AC and DC magnetic fields will have more applications than conventional structures capable of sensing only DC or AC magnetic field. Thus, the smart material-structure will be an important design reference for future magnetic-field sensing technologies.
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Method and apparatus for monitoring the rotating frequency of de-energized induction motors
Mikesell, H.E.; Lucy, E.
1998-02-03
The rotational speed of a coasting induction motor is measured by sensing e residual electrical voltages at the power terminals of the motor, thus eliminating the need for conventional tachometer equipment, additional mechanical components or modifications to the induction motor itself. The power terminal voltage signal is detected and transformed into a DC voltage proportional to the frequency of the signal. This DC voltage can be input to the control system of a variable frequency motor controller to regulate the output characteristics thereof relative to the speed of the coasting motor. 6 figs.
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Method and apparatus for monitoring the rotating frequency of de-energized induction motors
Mikesell, Harvey E.; Lucy, Eric
1998-01-01
The rotational speed of a coasting induction motor is measured by sensing e residual electrical voltages at the power terminals of the motor, thus eliminating the need for conventional tachometer equipment, additional mechanical components or modifications to the induction motor itself. The power terminal voltage signal is detected and transformed into a DC voltage proportional to the frequency of the signal. This DC voltage can be input to the control system of a variable frequency motor controller to regulate the output characteristics thereof relative to the speed of the coasting motor.
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Jitian, Simion; White, Samuel R; Yang, H-H Wendy; Weisz, Adrian
2014-01-10
Specifications in the U.S. Code of Federal Regulations for the color additive D&C Green No. 8 (Colour Index No. 59040) limit the levels of the subsidiary colors 1,3,6-pyrenetrisulfonic acid trisodium salt (P3S) and 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt (P4S). The present paper describes a comparative study of two possible methods to replace the currently used multi-step TLC/spectrophotometry method of separating and quantifying the minor components P3S and P4S in G8. One of the new approaches uses conventional high-performance liquid chromatography (HPLC) and the other, derivative spectrophotometry. While the derivative spectrophotometric method was shown to be inadequate for the analysis of minor components overwhelmed by components of much higher concentration, the HPLC method was proven highly effective. The closely related, very polar compounds P3S and P4S were separated by the new HPLC method in less than 4 min using a conventional HPLC instrument. P3S and P4S were quantified by using five-point calibration curves with data points that ranged from 0.45 to 7.63% and from 0.13 to 1.82%, by weight, for P3S and P4S, respectively. The HPLC method was applied to the analysis of test portions from 20 batches of D&C Green No. 8 submitted to the U.S. Food and Drug Administration for certification. Published by Elsevier B.V.
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Franz, André; Orth, Michael; Pirson, Paul A; Sonneville, Remi; Blow, J Julian; Gartner, Anton; Stemmann, Olaf; Hoppe, Thorsten
2011-10-07
Faithful transmission of genomic information requires tight spatiotemporal regulation of DNA replication factors. In the licensing step of DNA replication, CDT-1 is loaded onto chromatin to subsequently promote the recruitment of additional replication factors, including CDC-45 and GINS. During the elongation step, the CDC-45/GINS complex moves with the replication fork; however, it is largely unknown how its chromatin association is regulated. Here, we show that the chaperone-like ATPase CDC-48/p97 coordinates degradation of CDT-1 with release of the CDC-45/GINS complex. C. elegans embryos lacking CDC-48 or its cofactors UFD-1/NPL-4 accumulate CDT-1 on mitotic chromatin, indicating a critical role of CDC-48 in CDT-1 turnover. Strikingly, CDC-48(UFD-1/NPL-4)-deficient embryos show persistent chromatin association of CDC-45/GINS, which is a consequence of CDT-1 stabilization. Moreover, our data confirmed a similar regulation in Xenopus egg extracts, emphasizing a conserved coordination of licensing and elongation events during eukaryotic DNA replication by CDC-48/p97. Copyright © 2011 Elsevier Inc. All rights reserved.
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Chen, Hongkai; Shi, Nuo; Gao, Yongxiang; Li, Xu; Teng, Maikun; Niu, Liwen
2012-08-01
The yeast Paf1 complex (Paf1C), which is composed of the proteins Paf1, Cdc73, Ctr9, Leo1 and Rtf1, accompanies RNA polymerase II from the promoter to the 3'-end formation site of mRNA- and snoRNA-encoding genes. As one of the first identified subunits of Paf1C, yeast Cdc73 (yCdc73) takes part in many transcription-related processes, including binding to RNA polymerase II, recruitment and activation of histone-modification factors and communication with other transcriptional activators. The human homologue of yCdc73, parafibromin, has been identified as a tumour suppressor linked to breast, renal and gastric cancers. However, the functional mechanism of yCdc73 has until recently been unclear. Here, a 2.2 Å resolution crystal structure of the highly conserved C-terminal region of yCdc73 is reported. It revealed that yCdc73 appears to have a GTPase-like fold. However, no GTPase activity was observed. The crystal structure of yCdc73 will shed new light on the modes of function of Cdc73 and Paf1C.
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Mielenz, Thelma J; Callahan, Leigh F; Edwards, Michael C
2016-03-12
Examine the feasibility of performing an item response theory (IRT) analysis on two of the Centers for Disease Control and Prevention health-related quality of life (CDC HRQOL) modules - the 4-item Healthy Days Core Module (HDCM) and the 5-item Healthy days Symptoms Module (HDSM). Previous principal components analyses confirm that the two scales both assess a mix of mental (CDC-MH) and physical health (CDC-PH). The purpose is to conduct item response theory (IRT) analysis on the CDC-MH and CDC-PH scales separately. 2182 patients with self-reported or physician-diagnosed arthritis completed a cross-sectional survey including HDCM and HDSM items. Besides global health, the other 8 items ask the number of days that some statement was true; we chose to recode the data into 8 categories based on observed clustering. The IRT assumptions were assessed using confirmatory factor analysis and the data could be modeled using an unidimensional IRT model. The graded response model was used for IRT analyses and CDC-MH and CDC-PH scales were analyzed separately in flexMIRT. The IRT parameter estimates for the five-item CDC-PH all appeared reasonable. The three-item CDC-MH did not have reasonable parameter estimates. The CDC-PH scale is amenable to IRT analysis but the existing The CDC-MH scale is not. We suggest either using the 4-item Healthy Days Core Module (HDCM) and the 5-item Healthy days Symptoms Module (HDSM) as they currently stand or the CDC-PH scale alone if the primary goal is to measure physical health related HRQOL.
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Nakano, Masahiko; Yoshikawa, Takeshi; Hirata, So; Seino, Junji; Nakai, Hiromi
2017-11-05
We have implemented a linear-scaling divide-and-conquer (DC)-based higher-order coupled-cluster (CC) and Møller-Plesset perturbation theories (MPPT) as well as their combinations automatically by means of the tensor contraction engine, which is a computerized symbolic algebra system. The DC-based energy expressions of the standard CC and MPPT methods and the CC methods augmented with a perturbation correction were proposed for up to high excitation orders [e.g., CCSDTQ, MP4, and CCSD(2) TQ ]. The numerical assessment for hydrogen halide chains, polyene chains, and first coordination sphere (C1) model of photoactive yellow protein has revealed that the DC-based correlation methods provide reliable correlation energies with significantly less computational cost than that of the conventional implementations. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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Dielectric and AC conductivity studies on SrBi4Ti4O15
NASA Astrophysics Data System (ADS)
Jose, Roshan; Saravanan, K. Venkata
2018-05-01
The four layered SrBi4Ti4O15 ceramics which belong to the aurivillius family of oxide was prepared by conventional solid state reaction technique. Analysis of the dielectric data as a function of temperature and frequency revealed normal phase transition. The frequency dependent ac conductivity follows Jonscher's universal power law. Frequency exponent (n), pre-exponential factor (A), bulk dc conductivity (σdc), and hopping frequency (ωp) were determined from the fitting curves. The variation of frequency exponent with temperature indicates that large polaron hopping mechanism up to curie-temperature, then its changes to small polaron hopping. The activation energies were calculated from ac conductivity, bulk dc conductivity and hopping frequency. The activation energies revealed that conductivity had contributions from migrations of oxygen vacancies, bismuth ion vacancies and strontium ion vacancies.
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Using Repellent Products to Protect against Mosquito-Borne Illnesses
... Illnesses More Information CDC-Avoid Mosquito Bites CDC-Dengue CDC-Zika Virus CDC-Mosquito bite prevention for ... how to protect against the mosquitoes that transmit dengue, Zika, and other viral diseases ( Aedes albopictus and ...
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CDC Health Disparities and Inequalities Report--U.S. 2013
... Health Literacy Health Equity CDC Health Disparities & Inequalities Report (CHDIR) Recommend on Facebook Tweet Share Compartir On ... More Information CDC Releases Second Health Disparities & Inequalities Report - United States, 2013 CDC and its partners work ...
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Non-double-couple earthquakes. 1. Theory
Julian, B.R.; Miller, A.D.; Foulger, G.R.
1998-01-01
Historically, most quantitative seismological analyses have been based on the assumption that earthquakes are caused by shear faulting, for which the equivalent force system in an isotropic medium is a pair of force couples with no net torque (a 'double couple,' or DC). Observations of increasing quality and coverage, however, now resolve departures from the DC model for many earthquakes and find some earthquakes, especially in volcanic and geothermal areas, that have strongly non-DC mechanisms. Understanding non-DC earthquakes is important both for studying the process of faulting in detail and for identifying nonshear-faulting processes that apparently occur in some earthquakes. This paper summarizes the theory of 'moment tensor' expansions of equivalent-force systems and analyzes many possible physical non-DC earthquake processes. Contrary to long-standing assumption, sources within the Earth can sometimes have net force and torque components, described by first-rank and asymmetric second-rank moment tensors, which must be included in analyses of landslides and some volcanic phenomena. Non-DC processes that lead to conventional (symmetric second-rank) moment tensors include geometrically complex shear faulting, tensile faulting, shear faulting in an anisotropic medium, shear faulting in a heterogeneous region (e.g., near an interface), and polymorphic phase transformations. Undoubtedly, many non-DC earthquake processes remain to be discovered. Progress will be facilitated by experimental studies that use wave amplitudes, amplitude ratios, and complete waveforms in addition to wave polarities and thus avoid arbitrary assumptions such as the absence of volume changes or the temporal similarity of different moment tensor components.
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Imataki, O; Kami, M; Kim, S-W; Gotoh, M; Komaba, S; Kasai, M; Hashino, S; Naito, K; Masuda, M; Anan, K; Teshima, H; Togitani, K; Inoue, T; Nishimura, M; Adachi, Y; Fukuhara, T; Yamashita, T; Uike, N; Kobayashi, Y; Hamaguchi, M; Higuchi, M; Kawakami, K; Takaue, Y
2004-06-01
We conducted a nationwide survey to define incidence of deep fungal infections and fungal prophylaxis practices after HSCT. In all, 63 institutions responded. Total number of in-patient transplantations was 935: 367 autologous, 414 allogeneic myeloablative, and 154 allogeneic reduced-intensity (RIST) (n=154). Number of patients who were cared for in a clean room at transplant was 261 (71%) in autologous, 409 (99%) in conventional and 93 (66%) in RIST, respectively. All patients received prophylactic antifungal agents; 89% fluconazole. Number of patients who received the dosage recommended in the CDC guidelines (400 mg/day) was 135 (42%) in conventional transplant and 34 (30%) in RIST (P=0.037). Number of patients who received fluconazole until engraftment and beyond day 75 in conventional transplant vs RIST was, respectively, 324 (100%) vs 109 (97%), and 39 (12%) vs 18 (16%), with no significant difference between the two groups. A total of 37 patients (4.0%) were diagnosed with deep fungal infections; autologous transplantation (0.03%), conventional transplantation (6.0%) and RIST (7.1%). Wide variations in antifungal prophylaxis practice according to the type of transplant and the institutions, and deep fungal infection remain significant problems in RIST.
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Han, Bin; Zhao, Jun-Ying; Wang, Wu-Tao; Li, Zheng-Wei; He, Ai-Ping; Song, Xiao-Yang
2017-05-01
Schwann cells (SCs) are unique glial cells in the peripheral nerve and may secrete multiple neurotrophic factors, adhesion molecules, extracellular matrix molecules to form the microenvironment of peripheral nerve regeneration, guiding and supporting nerve proliferation and migration. Cdc42 plays an important regulatory role in dynamic changes of the cytoskeleton. However, there is a little study referred to regulation and mechanism of Cdc42 on glial cells after peripheral nerve injury. The present study investigated the role of Cdc42 in the proliferation and migration of SCs after sciatic nerve injury. Cdc42 expression was tested, showing that the mRNA and protein expression levels of Cdc42 were significantly up-regulated after sciatic nerve injury. Then, we isolated and purified SCs from injuried sciatic nerve at day 7. The purified SCs were transfected with Cdc42 siRNA and pcDNA3.1-Cdc42, and the cell proliferation, cell cycle and migration were assessed. The results implied that Cdc42 siRNA remarkably inhibited Schwann cell proliferation and migration, and resulted in S phase arrest. While pcDNA3.1-Cdc42 showed a contrary effect. Besides, we also observed that Cdc42 siRNA down-regulated the protein expression of β-catenin, Cyclin D1, c-myc and p-p38, which were up-regulated by pcDNA3.1-Cdc42. Meanwhile, the inhibitor of Wnt/β-catenin and p38 MAPK signaling pathway IWP-2 and SB203580 significantly inhibited the effect of pcDNA3.1-Cdc42 on cell proliferation and migration. Overall, our data indicate that Cdc42 regulates Schwann cell proliferation and migration through Wnt/β-catenin and p38 MAPK signaling pathway after sciatic nerve injury, which provides further insights into the therapy of the sciatic nerve injury.
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Krajicek, Bryan J.; Kottom, Theodore J.; Villegas, Leah
2010-01-01
Pneumocystis carinii (Pc) causes severe pneumonia in immunocompromised hosts. The binding of Pc trophic forms to alveolar epithelial cells is a central feature of infection, inducing the expression and activation of PcSte20, a gene participating in mating, proliferation, and pseudohyphal growth. In related fungi, Ste20 proteins are generally activated by immediate upstream small G proteins of the Cdc42-like family. PcCdc42 has not been previously described in Pneumocystis. To address the potential role of such a G protein in Pneumocystis, PcCdc42 was cloned from a Pc cDNA library. Using the full-length 576-bp PcCdc42 cDNA sequence, a CHEF blot of genomic DNA yielded a single band, providing evidence that this gene is present as a single copy within the genome. The total length of PcCdc42 cDNA was 576 bp with an estimated molecular mass of ∼38 kDa. BLASTP analysis demonstrated greater than 80% homology with other fungal Cdc42p proteins. Northern analysis indicated equal mRNA expression in both cystic and trophic life forms. Heterologous expression of PcCdc42 in Saccharomyces cerevisiae (Sc) demonstrated that PcCdc42p was able to restore growth in an ScCdc42Δ yeast strain. Additional assays with purified PcCdc42 protein demonstrated GTP binding and intrinsic GTPase activity, which was partially but significantly suppressed by Clostridium difficile toxin B, characteristic of Cdc42 GTPases. Furthermore, PcCdc42 protein was also shown to bind to the downstream PCSte20 kinase partner in the presence (but not the absence) of GTP. These data indicate that Pc possesses a Cdc42 gene expressing an active G protein, which binds the downstream regulatory kinase PcSte20, important in Pc life cycle regulation. PMID:19915161
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Stern, Bodo; Nurse, Paul
1998-01-01
The blocking of G1 progression by fission yeast pheromones requires inhibition of the cyclin-dependent kinase cdc2p associated with the B-cyclins cdc13p and cig2p. We show that cyclosome-mediated degradation of cdc13p and cig2p is necessary for down-regulation of B-cyclin–associated cdc2p kinase activity and for phermone-induced G1 arrest. The cyclin-dependent kinase inhibitor rum1p is also required to maintain this G1 arrest; it binds both cdc13p and cig2p and is specifically required for cdc13p proteolysis. We propose that rum1p acts as an adaptor targeting cdc13p for degradation by the cyclosome. In contrast, the cig2p–cdc2p kinase can be down-regulated, and the cyclin cig2p can be proteolyzed independently of rum1p. We suggest that pheromone signaling inhibits the cig2p–cdc2p kinase, bringing about a transient G1 arrest. As a consequence, rum1p levels increase, thus inhibiting and inducing proteolysis of the cdc13p–cdc2p kinase; this is necessary to maintain G1 arrest. We have also shown that pheromone-induced transcription occurs only in G1 and is independent of rum1p. PMID:9614176
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Cdc6 localizes to S- and G2-phase centrosomes in a cell cycle-dependent manner
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Gwang Su; Kang, Jeeheon; Bang, Sung Woong
2015-01-16
Highlights: • Cdc6 protein is a component of the pre-replicative complex required for chromosomal replication initiation. • Cdc6 localized to centrosomes of S and G2 phases in a cell cycle-dependent manner. • The centrosomal localization was governed by centrosomal localization signal sequences of Cdc6. • Deletions or substitution mutations on the centrosomal localization signal interfered with centrosomal localization of the Cdc6 proteins. - Abstract: The Cdc6 protein has been primarily investigated as a component of the pre-replicative complex for the initiation of chromosome replication, which contributes to maintenance of chromosomal integrity. Here, we show that Cdc6 localized to the centrosomesmore » during S and G2 phases of the cell cycle. The centrosomal localization was mediated by Cdc6 amino acid residues 311–366, which are conserved within other Cdc6 homologues and contains a putative nuclear export signal. Deletions or substitutions of the amino acid residues did not allow the proteins to localize to centrosomes. In contrast, DsRed tag fused to the amino acid residues localized to centrosomes. These results indicated that a centrosome localization signal is contained within amino acid residues 311–366. The cell cycle-dependent centrosomal localization of Cdc6 in S and G2 phases suggest a novel function of Cdc6 in centrosomes.« less
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Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall.
Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei
2014-07-08
Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall.
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77 FR 65570 - Center for Scientific Review; Notice of Closed Meetings
Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-29
... Conference Call). Contact Person: Carol Hamelink, Ph.D., Scientific Review Officer, Center for Scientific...--Convention Center, 900 10th Street NW., Washington, DC 20001. Contact Person: Mark P Rubert, Ph.D... for Scientific Review Special Emphasis Panel; Fellowships: Chemistry, Biochemistry and Biophysics...
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Compact Circuit Preprocesses Accelerometer Output
NASA Technical Reports Server (NTRS)
Bozeman, Richard J., Jr.
1993-01-01
Compact electronic circuit transfers dc power to, and preprocesses ac output of, accelerometer and associated preamplifier. Incorporated into accelerometer case during initial fabrication or retrofit onto commercial accelerometer. Made of commercial integrated circuits and other conventional components; made smaller by use of micrologic and surface-mount technology.
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2018 USA Science and Engineering Festival
2018-04-06
Attendees learn about packing for space travel during Sneak Peek Friday at the USA Science and Engineering Festival, Friday, April 6, 2018 at the Walter E. Washington Convention Center in Washington, DC. The festival is open to the public April 7-8. Photo Credit: (NASA/Joel Kowsky)
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What's Relevant in Classical Literature?
ERIC Educational Resources Information Center
Hickman, Sara
1970-01-01
Argues the relevance of various aspects of the Thebian trilogy, "The Iliad," The Odyssey," Great Expectations," and Hamlet" to the concerns of today's high school students; a paper presented at annual convention of National Council of Teachers of English (59th, Washington, D.C., November 29, 1969). (RD)
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Wu, Fei; Lin, Yun; Cui, Peng; Li, Hongyun; Zhang, Lechao; Sun, Zeqiang; Huang, Shengliang; Li, Shun; Huang, Shiming; Zhao, Qingli; Liu, Qingyong
2018-06-01
At least to date, no effective treatment for advanced castration-resistant prostate cancer (CRPC) has been established. Recent studies indicated that cell division cycle 20 homolog (Cdc20) overexpression is associated with poor prognosis in patients with castration-resistant prostate cancer. However, the mechanism of Cdc20 in the development of docetaxel resistance in CRPC remains elusive. In this study, the transcription of Cdc20 was confirmed in three independent CRPC cell lines derived from different tissues, including LNCaP, PC3, and DU145. Docetaxel resistant (DR) cell lines were generated within the background of DU145 and PC3. The protein levels of Cdc20 and the biological phenotype were detected in both wild-type and DR cell lines. To further explore the mechanism of Cdc20 overexpression, stable cell lines with Cdc20 or Bcl-2 interacting mediator of cell death (Bim) deprivation were generated and examined for biological parameters. In addition, a specific Cdc20 inhibitor was used in DR cell lines to explore the potential solution for docetaxel resistant CRPC. Here, we identified Cdc20 is overexpressed in docetaxel resistant CRPC cell lines, including LNCaP, PC3, and DU145. We also reported that DR cell lines, which mimic the recurrent prostate cancer cells after docetaxel treatment, have higher levels of Cdc20 protein compared with the CRPC cell lines. Interestingly, the protein levels of Bim, an E3 ligase substrate of Cdc20, were decreased in DR cell lines compared with the wild-type, while the mRNA levels were similar. More importantly, in DR cell lines, the biological phenotype induced by Cdc20 deletion could be significantly reversed by the additional knockdown of Bim. As a result, docetaxel resistant prostate cancer cells treated with the pharmacological Cdc20 inhibitor became sensitive to docetaxel treatment. In conclusion, our data collectively demonstrated that Cdc20 overexpression facilitates the docetaxel resistant of the CRPC cell lines in a Bim-dependent manner. Furthermore, additionally targeting Cdc20 might be a promising solution for the treatment of the CRPC with docetaxel resistance.
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Research study on multi-KW-DC distribution system
NASA Technical Reports Server (NTRS)
Berkery, E. A.; Krausz, A.
1975-01-01
A detailed definition of the HVDC test facility and the equipment required to implement the test program are provided. The basic elements of the test facility are illustrated, and consist of: the power source, conventional and digital supervision and control equipment, power distribution harness and simulated loads. The regulated dc power supplies provide steady-state power up to 36 KW at 120 VDC. Power for simulated line faults will be obtained from two banks of 90 ampere-hour lead-acid batteries. The relative merits of conventional and multiplexed power control will be demonstrated by the Supervision and Monitor Unit (SMU) and the Automatically Controlled Electrical Systems (ACES) hardware. The distribution harness is supported by a metal duct which is bonded to all component structures and functions as the system ground plane. The load banks contain passive resistance and reactance loads, solid state power controllers and active pulse width modulated loads. The HVDC test facility is designed to simulate a power distribution system for large aerospace vehicles.
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An isolated bridgeless AC-DC PFC converter using a LC resonant voltage doubler rectifier
NASA Astrophysics Data System (ADS)
Lee, Sin-woo; Do, Hyun-Lark
2016-12-01
This paper proposed an isolated bridgeless AC-DC power factor correction (PFC) converter using a LC resonant voltage doubler rectifier. The proposed converter is based on isolated conventional single-ended primary inductance converter (SEPIC) PFC converter. The conduction loss of rectification is reduced than a conventional one because the proposed converter is designed to eliminate a full-bridge rectifier at an input stage. Moreover, for zero-current switching (ZCS) operation and low voltage stresses of output diodes, the secondary of the proposed converter is designed as voltage doubler with a LC resonant tank. Additionally, an input-output electrical isolation is provided for safety standard. In conclusion, high power factor is achieved and efficiency is improved. The operational principles, steady-state analysis and design equations of the proposed converter are described in detail. Experimental results from a 60 W prototype at a constant switching frequency 100 kHz are presented to verify the performance of the proposed converter.
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A Constant Energy-Per-Cycle Ring Oscillator Over a Wide Frequency Range for Wireless Sensor Nodes.
Lee, Inhee; Sylvester, Dennis; Blaauw, David
2016-03-01
This paper presents an energy-efficient oscillator for wireless sensor nodes (WSNs). It avoids short-circuit current by minimizing the time spent in the input voltage range from V thn to [ V dd - | V thp |]. A current-feeding scheme with gate voltage control enables the oscillator to operate over a wide frequency range. A test chip is fabricated in a 0.18 μm CMOS process. The measurements show that the proposed oscillator achieves a constant energy-per-cycle (EpC) of 0.8 pJ/cycle over the 21-60 MHz frequency range and is more efficient than a conventional current-starved ring oscillator (CSRO) below 300 kHz at 1.8 V supply voltage. As an application example, the proposed oscillator is implemented in a switched-capacitor DC-DC converter. The converter is 11%-56% more efficient for load power values ranging from 583 pW to 2.9 nW than a converter using a conventional CSRO.
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NASA Technical Reports Server (NTRS)
Gibbs, R. S.
1974-01-01
Solid state power controllers (SSPC's) are to be considered for use as replacements of electromechanical relays and circuit breakers in future spacecraft and aircraft. They satisfy the combined function of both the relay and circuit breaker and can be remotely controlled by small signals, typically 10 mA, 5 to 28 v(dc). They have the advantage over conventional relay/circuit breaker systems in that they can be located near the utilization equipment and the primary ac or dc bus. The low level control, trip indication and status signals can be circuited by small gauge wire for control, computer interface, logic, electrical multiplexing, onboard testing, power management, and distribution purposes. This results in increased system versatility at appreciable weight saving and increased reliability. Conventional systems require the heavy gage load wiring and the control wiring to be routed from the bus to the load to other remote relay contacts, switches, sensors, etc. and to the circuit breaker located in the flight engineer's compartment for purposes of manual reset.
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Orthogonal fluxgate mechanism operated with dc biased excitation
NASA Astrophysics Data System (ADS)
Sasada, I.
2002-05-01
A mode of operation is presented for an orthogonal fluxgate built with a thin magnetic wire. By adding a proper dc bias to the wire excitation, the new mode is easily established. In this case, the fundamental component of the induced voltage at the sensing coil (secondary voltage) is made sensitive to the axial magnetic field, compared to the second harmonic in a conventional orthogonal fluxgate. The operating principle is explained using a magnetization rotation model. A method is proposed to cancel the offset that is inevitable when the magnetic anisotropy is present in a magnetic wire at an angle to its circumference. Experimental results are shown for a sensor head consisting of a 2-cm-long Co-based amorphous wire 120 μm in diameter with a 220-turn sensing coil. The sensitivity obtained is higher than that obtained using a conventional type of the orthogonal fluxgate built with the same sensor head. It is also demonstrated that the proposed method for canceling the offset works well.
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Orthogonal ion injection apparatus and process
Kurulugama, Ruwan T; Belov, Mikhail E
2014-04-15
An orthogonal ion injection apparatus and process are described in which ions are directly injected into an ion guide orthogonal to the ion guide axis through an inlet opening located on a side of the ion guide. The end of the heated capillary is placed inside the ion guide such that the ions are directly injected into DC and RF fields inside the ion guide, which efficiently confines ions inside the ion guide. Liquid droplets created by the ionization source that are carried through the capillary into the ion guide are removed from the ion guide by a strong directional gas flow through an inlet opening on the opposite side of the ion guide. Strong DC and RF fields divert ions into the ion guide. In-guide orthogonal injection yields a noise level that is a factor of 1.5 to 2 lower than conventional inline injection known in the art. Signal intensities for low m/z ions are greater compared to convention inline injection under the same processing conditions.
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Rho GTPase protein Cdc42 is critical for postnatal cartilage development
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nagahama, Ryo; Department of Orthodontics, School of Dentistry, Showa University, Tokyo; Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp
2016-02-19
Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 {sup fl/fl}; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 {sup fl/fl}) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system.more » The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.« less
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Ran1 functions to control the Cdc10/Sct1 complex through Puc1.
Caligiuri, M; Connolly, T; Beach, D
1997-01-01
We have undertaken a biochemical analysis of the regulation of the G1/S-phase transition and commitment to the cell cycle in the fission yeast Schizosaccharomyces pombe. The execution of Start requires the activity of the Cdc2 protein kinase and the Sct1/Cdc10 transcription complex. Progression through G1 also requires the Ran1 protein kinase whose inactivation leads to activation of the meiotic pathway under conditions normally inhibitory to this process. We have found that in addition to Cdc2, Sct1/Cdc10 complex formation requires Ran1. We demonstrate that the Puc1 cyclin associates with Ran1 and Cdc10 in vivo and that the Ran1 protein kinase functions to control the association between Puc1 and Cdc10. In addition, we present evidence that the phosphorylation state of Cdc10 is altered upon inactivation of Ran1. These results provide biochemical evidence that demonstrate one mechanism by which the Ran1 protein kinase serves to control cell fate through Cdc10 and Puc1. Images PMID:9201720
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Sherman, D A; Pasion, S G; Forsburg, S L
1998-07-01
The members of the MCM protein family are essential eukaryotic DNA replication factors that form a six-member protein complex. In this study, we use antibodies to four MCM proteins to investigate the structure of and requirements for the formation of fission yeast MCM complexes in vivo, with particular regard to Cdc19p (MCM2). Gel filtration analysis shows that the MCM protein complexes are unstable and can be broken down to subcomplexes. Using coimmunoprecipitation, we find that Mis5p (MCM6) and Cdc21p (MCM4) are tightly associated with one another in a core complex with which Cdc19p loosely associates. Assembly of Cdc19p with the core depends upon Cdc21p. Interestingly, there is no obvious change in Cdc19p-containing MCM complexes through the cell cycle. Using a panel of Cdc19p mutants, we find that multiple domains of Cdc19p are required for MCM binding. These studies indicate that MCM complexes in fission yeast have distinct substructures, which may be relevant for function.
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Sherman, Daniel A.; Pasion, Sally G.; Forsburg, Susan L.
1998-01-01
The members of the MCM protein family are essential eukaryotic DNA replication factors that form a six-member protein complex. In this study, we use antibodies to four MCM proteins to investigate the structure of and requirements for the formation of fission yeast MCM complexes in vivo, with particular regard to Cdc19p (MCM2). Gel filtration analysis shows that the MCM protein complexes are unstable and can be broken down to subcomplexes. Using coimmunoprecipitation, we find that Mis5p (MCM6) and Cdc21p (MCM4) are tightly associated with one another in a core complex with which Cdc19p loosely associates. Assembly of Cdc19p with the core depends upon Cdc21p. Interestingly, there is no obvious change in Cdc19p-containing MCM complexes through the cell cycle. Using a panel of Cdc19p mutants, we find that multiple domains of Cdc19p are required for MCM binding. These studies indicate that MCM complexes in fission yeast have distinct substructures, which may be relevant for function. PMID:9658174
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Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination
Grandin, Nathalie; Damon, Christelle; Charbonneau, Michel
2001-01-01
Cdc13 performs an essential function in telomere end protection in budding yeast. Here, we analyze the consequences on telomere dynamics of cdc13-induced telomeric DNA damage in proliferating cells. Checkpoint-deficient cdc13-1 cells accumulated DNA damage and eventually senesced. However, these telomerase-proficient cells could survive by using homologous recombination but, contrary to telomerase-deficient cells, did so without prior telomere shortening. Strikingly, homologous recombination in cdc13-1 mec3, as well as in telomerase-deficient cdc13-1 cells, which were Rad52- and Rad50-dependent but Rad51-independent, exclusively amplified the TG1–3 repeats. This argues that not only short telomeres are substrates for type II recombination. The Cdc13-1 mutant protein harbored a defect in its association with Stn1 and Ten1 but also an additional, unknown, defect that could not be cured by expressing a Cdc13-1– Ten1–Stn1 fusion. We propose that Cdc13 prevents telomere uncapping and inhibits recombination between telomeric sequences through a pathway distinct from and complementary to that used by telomerase. PMID:11689452
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Increased Energy Delivery for Parallel Battery Packs with No Regulated Bus
NASA Astrophysics Data System (ADS)
Hsu, Chung-Ti
In this dissertation, a new approach to paralleling different battery types is presented. A method for controlling charging/discharging of different battery packs by using low-cost bi-directional switches instead of DC-DC converters is proposed. The proposed system architecture, algorithms, and control techniques allow batteries with different chemistry, voltage, and SOC to be properly charged and discharged in parallel without causing safety problems. The physical design and cost for the energy management system is substantially reduced. Additionally, specific types of failures in the maximum power point tracking (MPPT) in a photovoltaic (PV) system when tracking only the load current of a DC-DC converter are analyzed. The periodic nonlinear load current will lead MPPT realized by the conventional perturb and observe (P&O) algorithm to be problematic. A modified MPPT algorithm is proposed and it still only requires typically measured signals, yet is suitable for both linear and periodic nonlinear loads. Moreover, for a modular DC-DC converter using several converters in parallel, the input power from PV panels is processed and distributed at the module level. Methods for properly implementing distributed MPPT are studied. A new approach to efficient MPPT under partial shading conditions is presented. The power stage architecture achieves fast input current change rate by combining a current-adjustable converter with a few converters operating at a constant current.
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Gangadharan, Denise; Smith, Jacinta; Weyant, Robbin
2013-06-28
The CDC and National Institutes of Health (NIH) Biosafety in Microbiological and Biomedical Laboratories (BMBL) manual describes biosafety recommendations for work involving highly pathogenic avian influenza (HPAI) (US Department of Health and Human Services [HHS], CDC. Biosafety in microbiological and biomedical laboratories, 5th ed. Atlanta, GA: CDC; 2009. HHS publication no. [CDC] 21-1112. Available at http://www.cdc.gov/biosafety/publications/bmbl5). The U.S. Department of Agriculture Guidelines for Avian Influenza Viruses builds on the BMBL manual and provides additional biosafety and biocontainment guidelines for laboratories working with HPAI (US Department of Agriculture, Animal and Plant Health Inspection Service, Agricultural Select Agent Program. Guidelines for avian influenza viruses. Washington, DC: US Department of Agriculture; 2011. Available at http://www.selectagents.gov/Guidelines_for_Avian_Influenza_Viruses.html). The recommendations in this report, which are intended for laboratories in the United States, outline the essential baseline biosafety measures for working with the subset of influenza viruses that contain a hemagglutinin (HA) from the HPAI influenza A/goose/Guangdong/1/96 lineage, including reassortant influenza viruses created in a laboratory setting. All H5N1 influenza virus clades known to infect humans to date have been derived from this lineage (WHO/OIE/FAO H5N1 Evolution Working Group. Continued evolution of highly pathogenic avian influenza A [H5N1]: updated nomenclature. Influenza Other Respir Viruses 2012;6:1-5). In 2009, the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules were amended to include specific biosafety and biocontainment recommendations for laboratories working with Recombinant Risk Group 3 influenza viruses, including HPAI H5N1 influenza viruses within the Goose/Guangdong/1/96-like H5 lineage. In February 2013, the NIH guidelines were further revised to provide additional biosafety containment enhancements and practices for research with HPAI H5N1 viruses that are transmissible among mammals by respiratory droplets (i.e., mammalian-transmissible HPAI H5N1) (National Institutes of Health, Office of Biotechnology Activities. NIH guidelines for research involving recombinant or synthetic nucleic acid molecules. Appendix G-II-C-5: biosafety level 3 enhanced for research involving risk group 3 influenza viruses. Bethesda, MD: National Institutes of Health; 2013. Available at http://oba.od.nih.gov/rdna/nih_guidelines_oba.html). The recent revisions to the NIH guidelines focus on a smaller subset of viruses but are applicable and consistent with the recommendations in this report. The biosafety recommendations in this report were developed by CDC with advice from the Intragovernmental Select Agents and Toxins Technical Advisory Committee, which is a panel composed of federal government subject-matter experts, and from public input received in response to the request for information that was published in the Federal Register on October 17, 2012 (US Department of Health and Human Services, CDC. Influenza viruses containing the hemagglutinin from the Goose/ Guangdong/1/96 lineage; proposed rule; request for information and comment. 42 CFR, Part 73. Federal Register 2012;77:63783-5). Work with HPAI H5N1 virus should be conducted, at a minimum, at biosafety level 3 (BSL-3), with specific enhancements to protect workers, the public, animal health, and animal products. Original clinical specimens suspected of containing viruses of this lineage can only be handled at BSL-2 if the procedures do not involve the propagation of the virus. An appropriate biosafety level should be determined in accordance with a biosafety risk assessment. Additional information on performing biosafety risk assessments and establishing effective biosafety containment is available in the BMBL manual.
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Role of cdc25 Phosphatases in Human Breast Cancer
2008-05-01
Cdc25C in these assays, their cat - alytically inactive mutants Cdc25B (C488S) and Cdc25C (C377S) (referred to as mt25B and mt25C) were generated and...chimeras. B and C, N25B and N25C (B) and their corresponding cat - alytically inactive mutants N25B/C and N25C/B (C). Cdc25B Inhibits Cell...HCT116 cells because similar results were obtained using U2OS (osteosarcoma) andHT1080 ( fibrosarcoma ) cells (data not shown). The level of Cdc25B
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Phosphorylation of Rga2, a Cdc42 GAP, by CDK/Hgc1 is crucial for Candida albicans hyphal growth
Zheng, Xin-De; Lee, Raymond Teck Ho; Wang, Yan-Ming; Lin, Qi-Shan; Wang, Yue
2007-01-01
Cyclin-dependent kinases (CDKs) control yeast morphogenesis, although how they regulate the polarity machinery remains unclear. The dimorphic fungus Candida albicans uses Cdc28/Hgc1, a CDK/cyclin complex, to promote persistent actin polarization for hyphal growth. Here, we report that Rga2, a GTPase-activating protein (GAP) of the central polarity regulator Cdc42, undergoes Hgc1-dependent hyperphosphorylation. Using the analog-sensitive Cdc28as mutant, we confirmed that Cdc28 controls Rga2 phosphorylation in vitro and in vivo. Deleting RGA2 produced elongated yeast cells without apparent effect on hyphal morphogenesis. However, deleting it or inactivating its GAP activity restored hyphal growth in hgc1Δ mutants, suggesting that Rga2 represses hyphal development and Cdc28/Hgc1 inactivates it upon hyphal induction. We provide evidence that Cdc28/Hgc1 may act to prevent Rga2 from localizing to hyphal tips, leading to localized Cdc42 activation for hyphal extension. Rga2 also undergoes transient Cdc28-dependent hyperphosphorylation at bud emergence, suggesting that regulating a GAP(s) of Cdc42 by CDKs may play an important role in governing different forms of polarized morphogenesis in yeast. This study reveals a direct molecular link between CDKs and the polarity machinery. PMID:17673907
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Kurasawa, Osamu; Oguro, Yuya; Miyazaki, Tohru; Homma, Misaki; Mori, Kouji; Iwai, Kenichi; Hara, Hideto; Skene, Robert; Hoffman, Isaac; Ohashi, Akihiro; Yoshida, Sei; Ishikawa, Tomoyasu; Cho, Nobuo
2017-04-01
Cell division cycle 7 (Cdc7) is a serine/threonine kinase that plays important roles in the regulation of DNA replication process. A genetic study indicates that Cdc7 inhibition can induce selective tumor-cell death in a p53-dependent manner, suggesting that Cdc7 is an attractive target for the treatment of cancers. In order to identify a new class of potent Cdc7 inhibitors, we generated a putative pharmacophore model based on in silico docking analysis of a known inhibitor with Cdc7 homology model. The pharmacophore model provided a minimum structural motif of Cdc7 inhibitor, by which preliminary medicinal chemistry efforts identified a dihydrothieno[3,2-d]-pyrimidin-4(1H)-one scaffold having a heteroaromatic hinge-binding moiety. The structure-activity relationship (SAR) studies resulted in the discovery of new, potent, and selective Cdc7 inhibitors 14a, c, e. Furthermore, the high selectivity of 14c, e for Cdc7 over Rho-associated protein kinase 1 (ROCK1) is discussed by utilizing a docking study with Cdc7 and ROCK2 crystal structures. Copyright © 2017 Elsevier Ltd. All rights reserved.
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CDC Kerala 1: Organization of clinical child development services (1987-2013).
Nair, M K C; George, Babu; Nair, G S Harikumaran; Bhaskaran, Deepa; Leena, M L; Russell, Paul Swamidhas Sudhakar
2014-12-01
The main objective of establishing the Child Development Centre (CDC), Kerala for piloting comprehensive child adolescent development program in India, has been to understand the conceptualization, design and scaling up of a pro-active positive child development initiative, easily replicable all over India. The process of establishing the Child Development Centre (CDC) Kerala for research, clinical services, training and community extension services over the last 25 y, has been as follows; Step 1: Conceptualization--The life cycle approach to child development; Step 2: Research basis--CDC model early stimulation is effective; Step 3: Development and validation of seven simple developmental screening tools; Step 4: CDC Diagnostic services--Ultrasonology and genetic, and metabolic laboratory; Step 5: Developing seven intervention packages; Step 6: Training--Post graduate diploma in clinical child development; Step 7: CDC Clinic Services--seven major ones; Step 8: CDC Community Services--Child development referral units; Step 9: Community service delivery models--Childhood disability and for adolescent care counselling projects; Step 10: National capacity building--Four child development related courses. CDC Kerala follow-up and clinic services are offered till 18 y of age and premarital counselling till 24 y of age as shown in "CDC Kerala Clinic Services Flow Chart" and 74,291 children have availed CDC clinic services in the last 10 y. CDC Kerala is the first model for comprehensive child adolescent development services using a lifecycle approach in the Government sector and hence declared as the collaborative centre for Rashtriya Bal Swasthya Karyakram (RBSK), in Kerala.
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25 Ways to Reduce the Cost of College
ERIC Educational Resources Information Center
Vedder, Richard; Gillen, Andrew; Bennett, Daniel; Denhart, Matthew; Robe, Jonathan; Holbrook, Todd; Neiger, Peter; Coleman, James; Templeton, Jordan; Leirer, Jonathan; Myers, Luke; Brady, Ryan; Malesick, Michael
2010-01-01
The Center for College Affordability and Productivity (CCAP) is an independent, nonprofit research center based in Washington, DC that is dedicated to researching public policy and economic issues relating to postsecondary education. CCAP aims to facilitate a broader dialogue that challenges conventional thinking about costs, efficiency and…
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USA Science and Engineering Festival 2014
2014-04-25
An attendee of the USA Science and Engineering Festival uses marbles to build a universe consisting of atoms and dark matter. The USA Science and Engineering Festival took place at the Washington Convention Center in Washington, DC on April 26 and 27, 2014. Photo Credit: (NASA/Aubrey Gemignani)
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USA Science and Engineering Festival 2014
2014-04-25
Astronaut Rex Walheim spoke at the USA Science and Engineering Festival on April 25, 2014 at the NASA Stage. The festival was open to the public on April 26 and 27, 2014 and was held at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)
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DeGregorio, Geneva A.; Bradford, Leslie S.; Manga, Simon; Tih, Pius M.; Wamai, Richard; Ogembo, Rebecca; Sando, Zacharie; Liu, Yuxin; Schwaiger, Constance; Rao, Sowmya R.; Kalmakis, Karen; Kennedy Sheldon, Lisa; Nulah, Kathleen; Welty, Edith; Welty, Thomas; Ogembo, Javier Gordon
2016-01-01
Background In 2007, the Cameroon Baptist Convention Health Services (CBCHS) implemented a screen-and-treat cervical cancer prevention program using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC). Methods We retrospectively analyzed 46,048 medical records of women who received care through the CBCHS Women’s Health Program from 2007 through 2014 to determine the prevalence and predictors of positive VIA-DC, rates of same day treatment, and cohort prevalence of invasive cervical cancer (ICC). Results Of the 44,979 women who were screened for cervical cancer, 9.0% were VIA-DC-positive, 66.8% were VIA-DC-negative, 22.0% were VIA-DC-inadequate (normal ectocervix, but portions of the transformation zone were obscured), and 2.2% were VIA-DC-uncertain (cervical abnormalities confounding VIA-DC interpretation). Risk factors significantly associated with VIA-DC-positive screen were HIV-positivity, young age at sexual debut, higher lifetime number of sexual partners, low education status and higher gravidity. In 2014, 31.1% of women eligible for cryotherapy underwent same day treatment. Among the 32,788 women screened from 2007 through 2013, 201 cases of ICC were identified corresponding to a cohort prevalence of 613 per 100,000. Conclusions High rate of VIA-DC-positive screens suggests a significant burden of potential cervical cancer cases and highlights the need for expansion of cervical cancer screening and prevention throughout the 10 regions of Cameroon. VIA-DC-inadequate rates were also high, especially in older women, and additional screening methods are needed to confirm whether these results are truly negative. In comparison to similar screening programs in sub-Saharan Africa there was low utilization of same day cryotherapy treatment. Further studies are required to characterize possible program specific barriers to treatment, for example cultural demands, health system challenges and cost of procedure. The prevalence of ICC among women who presented for screening was high and requires further investigation. PMID:27280882
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DeGregorio, Geneva A; Bradford, Leslie S; Manga, Simon; Tih, Pius M; Wamai, Richard; Ogembo, Rebecca; Sando, Zacharie; Liu, Yuxin; Schwaiger, Constance; Rao, Sowmya R; Kalmakis, Karen; Kennedy Sheldon, Lisa; Nulah, Kathleen; Welty, Edith; Welty, Thomas; Ogembo, Javier Gordon
2016-01-01
In 2007, the Cameroon Baptist Convention Health Services (CBCHS) implemented a screen-and-treat cervical cancer prevention program using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC). We retrospectively analyzed 46,048 medical records of women who received care through the CBCHS Women's Health Program from 2007 through 2014 to determine the prevalence and predictors of positive VIA-DC, rates of same day treatment, and cohort prevalence of invasive cervical cancer (ICC). Of the 44,979 women who were screened for cervical cancer, 9.0% were VIA-DC-positive, 66.8% were VIA-DC-negative, 22.0% were VIA-DC-inadequate (normal ectocervix, but portions of the transformation zone were obscured), and 2.2% were VIA-DC-uncertain (cervical abnormalities confounding VIA-DC interpretation). Risk factors significantly associated with VIA-DC-positive screen were HIV-positivity, young age at sexual debut, higher lifetime number of sexual partners, low education status and higher gravidity. In 2014, 31.1% of women eligible for cryotherapy underwent same day treatment. Among the 32,788 women screened from 2007 through 2013, 201 cases of ICC were identified corresponding to a cohort prevalence of 613 per 100,000. High rate of VIA-DC-positive screens suggests a significant burden of potential cervical cancer cases and highlights the need for expansion of cervical cancer screening and prevention throughout the 10 regions of Cameroon. VIA-DC-inadequate rates were also high, especially in older women, and additional screening methods are needed to confirm whether these results are truly negative. In comparison to similar screening programs in sub-Saharan Africa there was low utilization of same day cryotherapy treatment. Further studies are required to characterize possible program specific barriers to treatment, for example cultural demands, health system challenges and cost of procedure. The prevalence of ICC among women who presented for screening was high and requires further investigation.
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Fukuda, Koji; Miura, Yasushi; Maeda, Toshihisa; Takahashi, Masayasu; Hayashi, Shinya; Kurosaka, Masahiro
2013-10-01
Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TNF-like ligand 1A (TL1A). We previously reported that TNFα-induced DcR3 overexpression in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) protects cells from Fas-induced apoptosis. Previous studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages into osteoclasts. Furthermore, we reported that DcR3 induces very late antigen-4 (VLA--4) expression in THP-1 macrophages, inhibiting cycloheximide-induced apoptosis and that DcR3 binds to membrane-bound TL1A expressed on RA-FLS, resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. In the current study, we used cDNA microarray to search for genes in RA-FLS whose expression was regulated by the ligation of DcR3. The experiments revealed the expression profiles of genes in RA-FLS regulated by DcR3. The profiles showed that among the 100 genes most significantly regulated by DcR3, 45 were upregulated and 55 were downregulated. The upregulated genes were associated with protein complex assembly, cell motility, regulation of transcription, cellular protein catabolic processes, cell membrane, nucleotide binding and glycosylation. The downregulated genes were associated with transcription regulator activity, RNA biosynthetic processes, cytoskeleton, zinc finger region, protein complex assembly, phosphate metabolic processes, mitochondrion, ion transport, nucleotide binding and cell fractionation. Further study of the genes detected in the current study may provide insight into the pathogenesis and treatment of rheumatoid arthritis by DcR3-TL1A signaling.
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Cdc42 deficiency induces podocyte apoptosis by inhibiting the Nwasp/stress fibers/YAP pathway
Huang, Z; Zhang, L; Chen, Y; Zhang, H; Zhang, Q; Li, R; Ma, J; Li, Z; Yu, C; Lai, Y; Lin, T; Zhao, X; Zhang, B; Ye, Z; Liu, S; Wang, W; Liang, X; Liao, R; Shi, W
2016-01-01
Podocyte apoptosis is a major mechanism that leads to proteinuria in many chronic kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. The Rho family of small GTPases has been shown to be required in maintaining podocyte structure and function. Recent studies have indicated that podocyte-specific deletion of Cdc42 in vivo, but not of RhoA or Rac1, leads to congenital nephrotic syndrome and glomerulosclerosis. However, the underlying cellular events in podocyte controlled by Cdc42 remain unclear. Here, we assessed the cellular mechanisms by which Cdc42 regulates podocyte apoptosis. We found that the expression of Cdc42 and its activity were significantly decreased in high glucose-, lipopolysaccharide- or adriamycin-injured podocytes. Reduced Cdc42 expression in vitro and in vivo by small interfering RNA and selective Cdc42 inhibitor ML-141, respectively, caused podocyte apoptosis and proteinuria. Our results further demonstrated that insufficient Cdc42 or Nwasp, its downstream effector, could decrease the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Moreover, our data indicated that the loss of stress fibers caused by Cdc42/Nwasp deficiency also decreased Yes-associated protein (YAP) mRNA and protein expression, and induced podocyte apoptosis. Podocyte apoptosis induced by Cdc42/Nwasp/stress fiber deficiency was significantly inhibited by overexpressing-active YAP. Thus, the Cdc42/Nwasp/stress fibers/YAP signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary Cdc42 would be one potent way to prevent proteinuria kidney diseases. PMID:26986510
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White, W. H.; Johnson, D. I.
1997-01-01
Cdc24p is the guanine-nucleotide exchange factor for the Cdc42p GTPase, which controls cell polarity in Saccharomyces cerevisiae. To identify new genes that may affect cell polarity, we characterized six UV-induced csl (CDC24 synthetic-lethal) mutants that exhibited synthetic-lethality with cdc24-4(ts) at 23°. Five mutants were not complemented by plasmid-borne CDC42, RSR1, BUD5, BEM1, BEM2, BEM3 or CLA4 genes, which are known to play a role in cell polarity. The csl3 mutant displayed phenotypes similar to those observed with calcium-sensitive, Pet(-) vma mutants defective in vacuole function. CSL5 was allelic to VMA5, the vacuolar H(+)-ATPase subunit C, and one third of csl5 cdc24-4(ts) cells were elongated or had misshapen buds. A cdc24-4(ts) Δvma5::LEU2 double mutant did not exhibit synthetic lethality, suggesting that the csl5/vma5 cdc24-4(ts) synthetic-lethality was not simply due to altered vacuole function. The cdc24-4(ts) mutant, like Δvma5::LEU2 and csl3 mutants, was sensitive to high levels of Ca(2+) as well as Na(+) in the growth media, which did not appear to be a result of a fragile cell wall because the phenotypes were not remedied by 1 M sorbitol. Our results indicated that Cdc24p was required in one V-ATPase mutant and another mutant affecting vacuole morphology, and also implicated Cdc24p in Na(+) tolerance. PMID:9286667
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CDC14A phosphatase is essential for hearing and male fertility in mouse and human.
Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J; Fenollar-Ferrer, Cristina; Bashir, Rasheeda; Bukhari, Ihtisham; Bouzid, Amal; Shaukat, Uzma; Azaiez, Hela; Booth, Kevin T; Kahrizi, Kimia; Najmabadi, Hossein; Maqsood, Azra; Wilson, Elizabeth A; Fitzgerald, Tracy S; Tlili, Abdelaziz; Olszewski, Rafal; Lund, Merete; Chaudhry, Taimur; Rehman, Atteeq U; Starost, Matthew F; Waryah, Ali M; Hoa, Michael; Dong, Lijin; Morell, Robert J; Smith, Richard J H; Riazuddin, Sheikh; Masmoudi, Saber; Kindt, Katie S; Naz, Sadaf; Friedman, Thomas B
2018-03-01
The Cell Division-Cycle-14 gene encodes a dual-specificity phosphatase necessary in yeast for exit from mitosis. Numerous disparate roles of vertebrate Cell Division-Cycle-14 (CDC14A) have been proposed largely based on studies of cultured cancer cells in vitro. The in vivo functions of vertebrate CDC14A are largely unknown. We generated and analyzed mutations of zebrafish and mouse CDC14A, developed a computational structural model of human CDC14A protein and report four novel truncating and three missense alleles of CDC14A in human families segregating progressive, moderate-to-profound deafness. In five of these families segregating pathogenic variants of CDC14A, deaf males are infertile, while deaf females are fertile. Several recessive mutations of mouse Cdc14a, including a CRISPR/Cas9-edited phosphatase-dead p.C278S substitution, result in substantial perinatal lethality, but survivors recapitulate the human phenotype of deafness and male infertility. CDC14A protein localizes to inner ear hair cell kinocilia, basal bodies and sound-transducing stereocilia. Auditory hair cells of postnatal Cdc14a mutants develop normally, but subsequently degenerate causing deafness. Kinocilia of germ-line mutants of mouse and zebrafish have normal lengths, which does not recapitulate the published cdc14aa knockdown morphant phenotype of short kinocilia. In mutant male mice, degeneration of seminiferous tubules and spermiation defects result in low sperm count, and abnormal sperm motility and morphology. These findings for the first time define a new monogenic syndrome of deafness and male infertility revealing an absolute requirement in vivo of vertebrate CDC14A phosphatase activity for hearing and male fertility.
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miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Yuefeng; Zhu, Xiaolan; Xu, Wenlin
2013-02-15
Highlights: ► miR-330 was inversely correlated with Cdc42 in colorectal cancer cells. ► Elevated miR-330 suppressed cell proliferation in vivo and in vitro. ► Elevated miR-330 mimicked the effect of Cdc42 knockdown. ► Restoration of Cdc42 could partially attenuate the effects of miR-330. -- Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the bestmore » characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression.« less
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Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall
Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei
2014-01-01
Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall. DOI: http://dx.doi.org/10.7554/eLife.02839.001 PMID:25006034
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Human replication protein Cdc6 is selectively cleaved by caspase 3 during apoptosis
Pelizon, Cristina; d’Adda di Fagagna, Fabrizio; Farrace, Lorena; Laskey, Ronald A.
2002-01-01
In eukaryotes, the initiation of DNA replication involves the ordered assembly on chromatin of pre-replicative complexes (pre-RCs), including the origin recognition complex (ORC), Cdc6, Cdt1 and the minichromosome maintenance proteins (MCMs). In light of its indispensable role in the formation of pre-RCs, Cdc6 binding to chromatin represents a key step in the regulation of DNA replication and cell proliferation. Here, we study the human Cdc6 (HuCdc6) protein during programmed cell death (apoptosis). We find that HuCdc6, but not HuOrc2 (a member of the ORC) or HuMcm5 (one of the MCMs), is specifically cleaved in several human cell lines induced to undergo apoptosis by a variety of stimuli. Expression of caspase-uncleavable mutant HuCdc6 attenuates apoptosis, delaying cell death. Therefore, an important function for cleavage of HuCdc6 is to prevent a wounded cell from replicating and to facilitate death. PMID:12151338
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Cdc45-induced loading of human RPA onto single-stranded DNA
Tessmer, Ingrid; Prus, Piotr; Schlott, Bernhard; Pospiech, Helmut
2017-01-01
Abstract Cell division cycle protein 45 (Cdc45) is an essential component of the eukaryotic replicative DNA helicase. We found that human Cdc45 forms a complex with the single-stranded DNA (ssDNA) binding protein RPA. Moreover, it actively loads RPA onto nascent ssDNA. Pull-down assays and surface plasmon resonance studies revealed that Cdc45-bound RPA complexed with ssDNA in the 8–10 nucleotide binding mode, but dissociated when RPA covered a 30-mer. Real-time analysis of RPA-ssDNA binding demonstrated that Cdc45 catalytically loaded RPA onto ssDNA. This placement reaction required physical contacts of Cdc45 with the RPA70A subdomain. Our results imply that Cdc45 controlled stabilization of the 8-nt RPA binding mode, the subsequent RPA transition into 30-mer mode and facilitated an ordered binding to ssDNA. We propose that a Cdc45-mediated loading guarantees a seamless deposition of RPA on newly emerging ssDNA at the nascent replication fork. PMID:28100698
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Swaminathan, Vikhram V; Shannon, Mark A; Bashir, Rashid
2015-04-01
Dielectrophoretic separation of particles finds a variety of applications in the capture of species such as cells, viruses, proteins, DNA from biological systems, as well as other organic and inorganic contaminants from water. The ability to capture particles is constrained by poor volumetric scaling of separation force with respect to particle diameter, as well as the weak penetration of electric fields in the media. In order to improve the separation of sub-micron colloids, we present a scheme based on multiple interdigitated electrode arrays under mixed AC/DC bias. The use of high frequency longitudinal AC bias breaks the shielding effects through electroosmotic micromixing to enhance electric fields through the electrolyte, while a transverse DC bias between the electrode arrays enables penetration of the separation force to capture particles from the bulk of the microchannel. We determine the favorable biasing conditions for field enhancement with the help of analytical models, and experimentally demonstrate the improved capture from sub-micron colloidal suspensions with the mixed AC/DC electrostatic excitation scheme over conventional AC-DEP methods.
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A putative homologue of CDC20/CDH1 in the malaria parasite is essential for male gamete development.
Guttery, David S; Ferguson, David J P; Poulin, Benoit; Xu, Zhengyao; Straschil, Ursula; Klop, Onny; Solyakov, Lev; Sandrini, Sara M; Brady, Declan; Nieduszynski, Conrad A; Janse, Chris J; Holder, Anthony A; Tobin, Andrew B; Tewari, Rita
2012-02-01
Cell-cycle progression is governed by a series of essential regulatory proteins. Two major regulators are cell-division cycle protein 20 (CDC20) and its homologue, CDC20 homologue 1 (CDH1), which activate the anaphase-promoting complex/cyclosome (APC/C) in mitosis, and facilitate degradation of mitotic APC/C substrates. The malaria parasite, Plasmodium, is a haploid organism which, during its life-cycle undergoes two stages of mitosis; one associated with asexual multiplication and the other with male gametogenesis. Cell-cycle regulation and DNA replication in Plasmodium was recently shown to be dependent on the activity of a number of protein kinases. However, the function of cell division cycle proteins that are also involved in this process, such as CDC20 and CDH1 is totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for simplicity) suggesting that Plasmodium APC/C has only one regulator. In our genetic approach to delete the endogenous cdc20 gene of P. berghei, we demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis in parasite lines with deletions of two kinase genes involved in male sexual development (map2 and cdpk4), showed a significant increase in cdc20 transcription in activated gametocytes. DNA replication and ultra structural analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and sexual stages, but the level of modification was higher in activated gametocytes and ookinetes. Changes in global protein phosphorylation patterns in the Δcdc20 mutant parasites were largely different from those observed in the Δmap2 mutant. This suggests that CDC20 and MAP2 are both likely to play independent but vital roles in male gametogenesis.
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A Putative Homologue of CDC20/CDH1 in the Malaria Parasite Is Essential for Male Gamete Development
Guttery, David S.; Ferguson, David J. P.; Poulin, Benoit; Xu, Zhengyao; Straschil, Ursula; Klop, Onny; Solyakov, Lev; Sandrini, Sara M.; Brady, Declan; Nieduszynski, Conrad A.; Janse, Chris J.; Holder, Anthony A.; Tobin, Andrew B.; Tewari, Rita
2012-01-01
Cell-cycle progression is governed by a series of essential regulatory proteins. Two major regulators are cell-division cycle protein 20 (CDC20) and its homologue, CDC20 homologue 1 (CDH1), which activate the anaphase-promoting complex/cyclosome (APC/C) in mitosis, and facilitate degradation of mitotic APC/C substrates. The malaria parasite, Plasmodium, is a haploid organism which, during its life-cycle undergoes two stages of mitosis; one associated with asexual multiplication and the other with male gametogenesis. Cell-cycle regulation and DNA replication in Plasmodium was recently shown to be dependent on the activity of a number of protein kinases. However, the function of cell division cycle proteins that are also involved in this process, such as CDC20 and CDH1 is totally unknown. Here we examine the role of a putative CDC20/CDH1 in the rodent malaria Plasmodium berghei (Pb) using reverse genetics. Phylogenetic analysis identified a single putative Plasmodium CDC20/CDH1 homologue (termed CDC20 for simplicity) suggesting that Plasmodium APC/C has only one regulator. In our genetic approach to delete the endogenous cdc20 gene of P. berghei, we demonstrate that PbCDC20 plays a vital role in male gametogenesis, but is not essential for mitosis in the asexual blood stage. Furthermore, qRT-PCR analysis in parasite lines with deletions of two kinase genes involved in male sexual development (map2 and cdpk4), showed a significant increase in cdc20 transcription in activated gametocytes. DNA replication and ultra structural analyses of cdc20 and map2 mutants showed similar blockage of nuclear division at the nuclear spindle/kinetochore stage. CDC20 was phosphorylated in asexual and sexual stages, but the level of modification was higher in activated gametocytes and ookinetes. Changes in global protein phosphorylation patterns in the Δcdc20 mutant parasites were largely different from those observed in the Δmap2 mutant. This suggests that CDC20 and MAP2 are both likely to play independent but vital roles in male gametogenesis. PMID:22383885
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Performance of wind-powered soil electroremediation process for the removal of 2,4-D from soil.
Souza, F L; Llanos, J; Sáez, C; Lanza, M R V; Rodrigo, M A; Cañizares, P
2016-04-15
In this work, it is studied a wind-powered electrokinetic soil flushing process for the removal of pesticides from soil. This approach aims to develop an eco-friendly electrochemical soil treatment technique and to face the in-situ treatment of polluted soils at remote locations. Herbicide 2,4 dichlorophenoxyacetic acid (2,4-D) is selected as a model pollutant for the soil treatment tests. The performance of the wind-powered process throughout a 15 days experiment is compared to the same remediation process powered by a conventional DC power supply. The wind-powered test covered many different wind conditions (from calm to near gale), being performed 20.7% under calm conditions and 17% under moderate or gentle breeze. According to the results obtained, the wind-powered soil treatment is feasible, obtaining a 53.9% removal of 2,4-D after 15 days treatment. Nevertheless, the remediation is more efficient if it is fed by a constant electric input (conventional DC power supply), reaching a 90.2% removal of 2,4-D with a much lower amount of charge supplied (49.2 A h kg(-1) and 4.33 A h kg(-1) for wind-powered and conventional) within the same operation time. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Garmaroodi, Hamid S; Taga, Masatoki
2015-10-01
PDA1-conditionally dispensable chromosome (CDC) of Nectria haematococca MP VI has long served as a model of supernumerary chromosomes in plant pathogenic fungi because of pathogenicity-related genes located on it. In our previous study, we showed the dosage effects of PDA1-CDC on pathogenicity and homoserine utilization by exploiting tagged PDA1-CDC with a marker gene. CDC content of mating partners and progenies analyzed by PCR, PFGE combined with Southern analysis and chromosome painting via FISH. In this study, we analyzed mode of meiotic inheritance of PDA1-CDC in several mating patterns with regard to CDC content and found a correlation between CDC content of parental strains with fertility of crosses. The results showed non-Mendelian inheritance of this chromosome followed by duplication or loss of the CDC in haploid genome through meiosis that probably were due to premature centromere division, not by nondisjunction as reported for the supernumerary chromosomes in other species. Correlation of CDC with fertility is the first time to be examined in fungi in this study. Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
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Comparative analysis of expression of two p97 homologues in Caenorhabditis elegans
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yamauchi, Seiji; Yamanaka, Kunitoshi; Ogura, Teru
2006-06-30
Caenorhabditis elegans possesses two p97/VCP/Cdc48p homologues, named CDC-48.1 (C06A1.1) and CDC-48.2 (C41C4.8), although their expression regulation and functional diversity have not yet been studied. We therefore investigated spatial and temporal expression patterns of two p97 homologues in this study. RT-PCR and Western blot analysis showed that the amount of cdc-48.1 was about twofold of that of cdc-48.2 in adults and that two p97 homologues were induced by ER stress. The amount of cdc-48.1 mRNA did not increase in the cdc-48.2 deletion mutant and vice versa. In situ hybridization showed that two p97 homologues are mainly expressed in germ cells. Inmore » vivo expression analysis by using GFP translational fusion constructs revealed that CDC-48.1::GFP was expressed from embryos through to adult worms, while CDC-48.2::GFP was expressed mainly in embryos. These results suggest that the expression of two p97 homologues of C. elegans is differently regulated and independent of each other.« less
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78 FR 27396 - Statement of Organization, Functions, and Delegations of Authority
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-10
... scientific basis for communication and marketing practice; (2) guides CIOs on applying measures of... and marketing research to interested professionals at CDC, its partners, and other stakeholders; and... media channels, including CDC.gov top tier, CDC en Espanol, mobile apps, and CDC Connects; (4...
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76 FR 38655 - Office for State, Tribal, Local, and Territorial Support
Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-01
... collaborative approaches to these issues and needs. Within the CDC Consultation Policy, it is stated that CDC... the Director (OD), other CDC Centers, Institutes, and Offices, leadership shall actively participate... and presentations from various CDC senior leaderships on activities and areas identified by TAC...
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Negative Capacitance in BaTiO3/BiFeO3 Bilayer Capacitors.
Hou, Ya-Fei; Li, Wei-Li; Zhang, Tian-Dong; Yu, Yang; Han, Ren-Lu; Fei, Wei-Dong
2016-08-31
Negative capacitances provide an approach to reduce heat generations in field-effect transistors during the switch processes, which contributes to further miniaturization of the conventional integrated circuits. Although there are many studies about negative capacitances using ferroelectric materials, the direct observation of stable ferroelectric negative capacitances has rarely been reported. Here, we put forward a dc bias assistant model in bilayer capacitors, where one ferroelectric layer with large dielectric constant and the other ferroelectric layer with small dielectric constant are needed. Negative capacitances can be obtained when external dc bias electric fields are larger than a critical value. Based on the model, BaTiO3/BiFeO3 bilayer capacitors are chosen as study objects, and negative capacitances are observed directly. Additionally, the upward self-polarization effect in the ferroelectric layer reduces the critical electric field, which may provide a method for realizing zero and/or small dc bias assistant negative capacitances.
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LASL benchmark performance 1978. [CDC STAR-100, 6600, 7600, Cyber 73, and CRAY-1
DOE Office of Scientific and Technical Information (OSTI.GOV)
McKnight, A.L.
1979-08-01
This report presents the results of running several benchmark programs on a CDC STAR-100, a Cray Research CRAY-1, a CDC 6600, a CDC 7600, and a CDC Cyber 73. The benchmark effort included CRAY-1's at several installations running different operating systems and compilers. This benchmark is part of an ongoing program at Los Alamos Scientific Laboratory to collect performance data and monitor the development trend of supercomputers. 3 tables.
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Cell cycle regulation in Schizosaccharomyces pombe.
Moser, B A; Russell, P
2000-12-01
Cdc2, a cyclin-dependent kinase, controls cell cycle progression in fission yeast. New details of Cdc2 regulation and function have been uncovered in recent studies. These studies involve cyclins that associate with Cdc2 in G1-phase and the proteins that regulate inhibitory phosphorylation of Cdc2 during S-phase and G2-phase. Recent investigations have also provided a better understanding of proteins that regulate DNA replication and that are directly or indirectly controlled by Cdc2.
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CDC20 maintains tumor initiating cells
Xie, Qi; Wu, Qiulian; Mack, Stephen C.; Yang, Kailin; Kim, Leo; Hubert, Christopher G.; Flavahan, William A.; Chu, Chengwei; Bao, Shideng; Rich, Jeremy N.
2015-01-01
Glioblastoma is the most prevalent and lethal primary intrinsic brain tumor. Glioblastoma displays hierarchical arrangement with a population of self-renewing and tumorigenic glioma tumor initiating cells (TICs), or cancer stem cells. While non-neoplastic neural stem cells are generally quiescent, glioblastoma TICs are often proliferative with mitotic control offering a potential point of fragility. Here, we interrogate the role of cell-division cycle protein 20 (CDC20), an essential activator of anaphase-promoting complex (APC) E3 ubiquitination ligase, in the maintenance of TICs. By chromatin analysis and immunoblotting, CDC20 was preferentially expressed in TICs relative to matched non-TICs. Targeting CDC20 expression by RNA interference attenuated TIC proliferation, self-renewal and in vivo tumor growth. CDC20 disruption mediated its effects through induction of apoptosis and inhibition of cell cycle progression. CDC20 maintains TICs through degradation of p21CIP1/WAF1, a critical negative regulator of TICs. Inhibiting CDC20 stabilized p21CIP1/WAF1, resulting in repression of several genes critical to tumor growth and survival, including CDC25C, c-Myc and Survivin. Transcriptional control of CDC20 is mediated by FOXM1, a central transcription factor in TICs. These results suggest CDC20 is a critical regulator of TIC proliferation and survival, linking two key TIC nodes – FOXM1 and p21CIP1/WAF1 — elucidating a potential point for therapeutic intervention. PMID:25938542
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Rga6 is a fission yeast Rho GAP involved in Cdc42 regulation of polarized growth
Revilla-Guarinos, M. T.; Martín-García, Rebeca; Villar-Tajadura, M. Antonia; Estravís, Miguel; Coll, Pedro M.; Pérez, Pilar
2016-01-01
Active Cdc42 is essential for the establishment of polarized growth. This GTPase is negatively regulated by the GTPase-activating proteins (GAPs), which are important for the spatial specificity of Cdc42 function. Rga4 is the only GAP described as negative regulator of fission yeast Cdc42. We report here that Rga6, another fission yeast Cdc42 GAP, shares some functions with Rga4. Cells lacking Rga6 are viable but slightly shorter and broader than wild type, and cells lacking Rga6 and Rga4 simultaneously are rounded. In these cells, active Cdc42 is observed all around the membrane. These additive effects indicate that both GAPs collaborate in the spatial regulation of active Cdc42. Rga6 localizes to the plasma membrane, forming clusters different from those formed by Rga4. A polybasic region at the Rga6 C-terminus is responsible for its membrane localization. Rga6-GFP fluorescence decreases considerably at the growing tips, and this decrease is dependent on the actin cables. Of note, in the absence of Rga6, the amplitude of active Cdc42 oscillations at the tips decreases, and less GTP-Cdc42 accumulates at the new end of the cells. We propose that Rga6 collaborates with Rga4 to spatially restrict active Cdc42 at the cell tips and maintain cell dimensions. PMID:26960792
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Esaki, Masatoshi; Islam, Md Tanvir; Tani, Naoki; Ogura, Teru
2017-07-14
Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded. By contrast, the aromatic residue in one of the two AAA rings of Cdc48 has been eliminated through evolution. Here, we show that artificial retrieval of this aromatic residue in Cdc48 is lethal, and essential features to support the threading mechanism are required to exhibit the lethal phenotype. In particular, genetic and biochemical analyses of the Cdc48 lethal mutant strongly suggested that when in complex with the 20S proteasome, essential proteins are abnormally forced to thread through the Cdc48 pore to become degraded, which was not detected in wild-type Cdc48. Thus, the widely applicable threading model is less effective for wild-type Cdc48; rather, Cdc48 might function predominantly through an as-yet-undetermined mechanism.
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Sasagawa, Yohei; Higashitani, Atsushi; Urano, Takeshi; Ogura, Teru; Yamanaka, Kunitoshi
2012-08-01
CDC-48/p97 is a AAA (ATPases associated with diverse cellular activities) chaperone involved in protein conformational changes such as the disassembly of protein complexes. We previously reported that Caenorhabditis elegans CDC-48.1 and CDC-48.2 (CDC-48s) are essential for the progression of meiosis I metaphase. Here, we report that CDC-48s are required for proper chromosome segregation during meiosis in C. elegans. In wild-type worms, at the diakinesis phase, phosphorylation of histone H3, one of the known substrates of aurora B kinase (AIR-2), on meiosis I chromatids correlated with AIR-2 localization at the cohesion sites of homologous chromatids. Conversely, depletion of CDC-48s resulted in a significant expansion of signals for AIR-2 and phosphorylated histone H3 over the entire length of meiotic chromosomes, leading to defective chromosome segregation, while the total amount of AIR-2 in lysates was not changed by the depletion of CDC-48s. The defective segregation of meiotic chromosomes caused by the depletion of CDC-48s was suppressed by the simultaneous depletion of AIR-2 and is similar to that observed following the depletion of protein phosphatase 1 (PP1) phosphatases. However, the amount and localization of PP1 were not changed by the depletion of CDC-48s. These results suggest that CDC-48s control the restricted localization of AIR-2 to the cohesion sites of homologous chromatids in meiosis I. Copyright © 2012 Elsevier Inc. All rights reserved.
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Castellano, F; Montcourrier, P; Guillemot, J C; Gouin, E; Machesky, L; Cossart, P; Chavrier, P
1999-04-08
Cdc42, a GTP-binding protein of the Rho family, controls actin cytoskeletal organization and helps to generate actin-based protruding structures, such as filopodia. In vitro, Cdc42 regulates actin polymerization by facilitating the creation of free barbed ends - the more rapidly growing ends of actin filaments - and subsequent elongation at these ends. The Wiskott- Aldrich syndrome protein, WASP, which has a pleckstrin-homology domain and a Cdc42/Rac-binding motif, has been implicated in cell signaling and cytoskeleton reorganization. We have investigated the consequences of local recruitment of activated Cdc42 or WASP to the plasma membrane. We used an activated Cdc42 protein that could be recruited to an engineered membrane receptor by adding rapamycin as a bridge, and added antibody-coupled beads to aggregate these receptors. Inducible recruitment of Cdc42 to clusters of receptors stimulated actin polymerization, resulting in the formation of membrane protrusions. Cdc42-induced protrusions were enriched in the vasodilator-stimulated phosphoprotein VASP and the focal-adhesion-associated proteins zyxin and ezrin. The Cdc42 effector WASP could also induce the formation of protrusions, albeit of different morphology. This is the first demonstration that the local recruitment of activated Cdc42 or its downstream effector, WASP, to a membrane receptor in whole cells is sufficient to trigger actin polymerization that results in the formation of membrane protrusions. Our data suggest that Cdc42-induced actin-based protrusions result from the local and serial recruitment of cytoskeletal proteins including zyxin, VASP, and ezrin.
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13 CFR 120.851 - CDC ethical requirements.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their Associates must act ethically and exhibit good character. They must meet all of the ethical requirements of...
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13 CFR 120.851 - CDC ethical requirements.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false CDC ethical requirements. 120.851... Company Loan Program (504) Other Cdc Requirements § 120.851 CDC ethical requirements. CDCs and their Associates must act ethically and exhibit good character. They must meet all of the ethical requirements of...
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33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.
Code of Federal Regulations, 2014 CFR
2014-07-01
... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...
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33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.
Code of Federal Regulations, 2011 CFR
2011-07-01
... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...
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33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.
Code of Federal Regulations, 2010 CFR
2010-07-01
... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...
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33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...
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33 CFR 105.295 - Additional requirements-Certain Dangerous Cargo (CDC) facilities.
Code of Federal Regulations, 2012 CFR
2012-07-01
... Dangerous Cargo (CDC) facilities. 105.295 Section 105.295 Navigation and Navigable Waters COAST GUARD... Requirements § 105.295 Additional requirements-Certain Dangerous Cargo (CDC) facilities. (a) At all MARSEC Levels, owners or operators of CDC facilities must ensure the implementation of the following security...
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Maximum power point tracking techniques for wind energy systems using three levels boost converter
NASA Astrophysics Data System (ADS)
Tran, Cuong Hung; Nollet, Frédéric; Essounbouli, Najib; Hamzaoui, Abdelaziz
2018-05-01
This paper presents modeling and simulation of three level Boost DC-DC converter in Wind Energy Conversion System (WECS). Three-level Boost converter has significant advantage compared to conventional Boost. A maximum power point tracking (MPPT) method for a variable speed wind turbine using permanent magnet synchronous generator (PMSG) is also presented. Simulation of three-level Boost converter topology with Perturb and Observe algorithm and Fuzzy Logic Control is implemented in MATLAB/SIMULINK. Results of this simulation show that the system with MPPT using fuzzy logic controller has better performance to the Perturb and Observe algorithm: fast response under changing conditions and small oscillation.
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Post, Richard F.
2005-02-22
A motor/generator having its stationary portion, i.e., the stator, positioned concentrically within its rotatable element, i.e., the rotor, along its axis of rotation. The rotor includes a Halbach array. The stator windings are switched or commutated to provide a DC motor/generator much the same as in a conventional DC motor/generator. The voltage and power are automatically regulated by using centrifugal force to change the diameter of the rotor, and thereby vary the radial gap in between the stator and the rotating Halbach array, as a function of the angular velocity of the rotor.
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Alternating current corona discharge/atmospheric pressure chemical ionization for mass spectrometry.
Habib, Ahsan; Usmanov, Dilshadbek; Ninomiya, Satoshi; Chen, Lee Chuin; Hiraoka, Kenzo
2013-12-30
Although alternating current (ac) corona discharge has been widely used in the fields of material science and technology, no reports have been published on its application to an atmospheric pressure chemical ionization (APCI) ion source. In this work, ac corona discharge for an APCI ion source has been examined for the first time. The ambient atmospheric pressure ac corona discharge (15 kHz, 2.6 kVptp ) was generated by using a stainless steel acupuncture needle. The generated ions were measured using an ion trap mass spectrometer. A comparative study on ac and direct current (dc) corona APCI ion sources was carried out using triacetone triperoxide and trinitrotoluene as test samples. The ac corona discharge gave ion signals as strong as dc corona discharge for both positive and negative ion modes. In addition, softer ionization was obtained with ac corona discharge than with dc corona discharge. The erosion of the needle tip induced by ac corona was less than that obtained with positive mode dc corona. A good 'yardstick' for assessing ac corona is that it can be used for both positive and negative ion modes without changing the polarity of the high-voltage power supply. Thus, ac corona can be an alternative to conventional dc corona for APCI ion sources. Copyright © 2013 John Wiley & Sons, Ltd.
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NASA Astrophysics Data System (ADS)
Castellví, Quim; Mercadal, Borja; Moll, Xavier; Fondevila, Dolors; Andaluz, Anna; Ivorra, Antoni
2018-02-01
Electroporation-based treatments typically consist of the application of high-voltage dc pulses. As an undesired side effect, these dc pulses cause electrical stimulation of excitable tissues such as motor nerves. The present in vivo study explores the use of bursts of sinusoidal voltage in a frequency range from 50 kHz to 2 MHz, to induce irreversible electroporation (IRE) whilst avoiding neuromuscular stimulation. A series of 100 dc pulses or sinusoidal bursts, both with an individual duration of 100 µs, were delivered to rabbit liver through thin needles in a monopolar electrode configuration, and thoracic movements were recorded with an accelerometer. Tissue samples were harvested three hours after treatment and later post-processed to determine the dimensions of the IRE lesions. Thermal damage due to Joule heating was ruled out via computer simulations. Sinusoidal bursts with a frequency equal to or above 100 kHz did not cause thoracic movements and induced lesions equivalent to those obtained with conventional dc pulses when the applied voltage amplitude was sufficiently high. IRE efficacy dropped with increasing frequency. For 100 kHz bursts, it was estimated that the electric field threshold for IRE is about 1.4 kV cm-1 whereas that of dc pulses is about 0.5 kV cm-1.
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Personalized Education in Southside School
ERIC Educational Resources Information Center
Spaulding, Robert L.
1970-01-01
This article is based on remarks presented at the annual convention of the National Society for Programmed Instruction, Sheraton Park Hotel, Wash., D.C., Apr 10, 1969. Urges personalized (not just individualized) instruction, in which relevancy is achieved by having the students themselves participate in decision making and daily programming. (MH)
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2018 USA Science and Engineering Festival
2018-04-06
An attendee uses virtual reality goggles to view the Sun during Sneak Peek Friday at the USA Science and Engineering Festival, Friday, April 6, 2018 at the Walter E. Washington Convention Center in Washington, DC. The festival is open to the public April 7-8. Photo Credit: (NASA/Joel Kowsky)
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2018 USA Science and Engineering Festival
2018-04-06
Attendees walk past an inflatable model of NASA's Space Launch System during Sneak Peek Friday at the USA Science and Engineering Festival, Friday, April 6, 2018 at the Walter E. Washington Convention Center in Washington, DC. The festival is open to the public April 7-8. Photo Credit: (NASA/Joel Kowsky)
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2018 USA Science and Engineering Festival
2018-04-06
Attendees view a Moon rock that was returned by the Apollo 17 mission during Sneak Peek Friday at the USA Science and Engineering Festival, Friday, April 6, 2018 at the Walter E. Washington Convention Center in Washington, DC. The festival is open to the public April 7-8. Photo Credit: (NASA/Joel Kowsky)
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2018 USA Science and Engineering Festival
2018-04-06
An attendee guides NASA's Space Launch System in an interactive exhibit during Sneak Peek Friday at the USA Science and Engineering Festival, Friday, April 6, 2018 at the Walter E. Washington Convention Center in Washington, DC. The festival is open to the public April 7-8. Photo Credit: (NASA/Joel Kowsky)
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2018 USA Science and Engineering Festival
2018-04-06
A model of NASA's James Webb Space Telescope is seen during Sneak Peek Friday at the USA Science and Engineering Festival, Friday, April 6, 2018 at the Walter E. Washington Convention Center in Washington, DC. The festival is open to the public April 7-8. Photo Credit: (NASA/Joel Kowsky)
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Exploration Design Challenge 2014
2014-04-25
NASA Administrator Charles Bolden and Lockheed Martin CEO Marillyn Hewson sign the poster at the Orion exhibit at the USA Science and Engineering Festival on April 25, 2014. The USA Science and Engineering Festival takes place April 26-27, 2014 at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)
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76 FR 41826 - Sunshine Act Meetings
Federal Register 2010, 2011, 2012, 2013, 2014
2011-07-15
... International Disability Rights, regarding the United Nations Convention on the Rights of Persons with Disabilities. A public comment session will be held from 1 until 1:30 p.m., ET. Individuals interested in..., Washington, DC. STATUS: This meeting will be open to the public. MATTERS TO BE CONSIDERED: The agenda for the...
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USA Science and Engineering Festival 2014
2014-04-25
A NASA staff member demonstrates how to build a circuit at the USA Science and Engineering festival on April 25, 2014. The festival was open to the public on April 26 and 27, 2014 and was held at the Washington Convention Center in Washington, DC. Photo Credit: (NASA/Aubrey Gemignani)
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NASA Astrophysics Data System (ADS)
Sreenivasu, T.; Tirupathi, P.; Prabahar, K.; Suryanarayana, B.; Chandra Mouli, K.
The solid solutions of (1-x) LaFeO3-xBaTiO3 (0.0≤x≤0.25) have been synthesized successfully by the conventional solid-state reaction method. Room temperature (RT) X-ray diffraction studies reveal the stabilization of orthorhombic phase with Pbnm space group. Complete solubility in the perovskite series was demonstrated up to x=0.25. The dielectric permittivity shows colossal dielectric constant (CDC) at RT. The doping of BaTiO3 in LaFeO3 exhibit pronounced CDC up to a composition x=0.15, further it starts to decrease. The frequency-dependent dielectric loss exhibits polaronic conduction, which can attribute to presence of multiple valence of iron. The relaxation frequency and polaronic conduction mechanism was shifted towards RT as function of x. Moreover, large magnetic moment with weak ferromagnetic behavior is observed in doped LaFeO3 solid solution, which might be the destruction of spin cycloid structure due to insertion of Ti in Fe-O-Fe network of LaFeO3.
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High capacitance of coarse-grained carbide derived carbon electrodes
NASA Astrophysics Data System (ADS)
Dyatkin, Boris; Gogotsi, Oleksiy; Malinovskiy, Bohdan; Zozulya, Yuliya; Simon, Patrice; Gogotsi, Yury
2016-02-01
We report exceptional electrochemical properties of supercapacitor electrodes composed of large, granular carbide-derived carbon (CDC) particles. Using a titanium carbide (TiC) precursor, we synthesized 70-250 μm sized particles with high surface area and a narrow pore size distribution. Electrochemical cycling of these coarse-grained powders defied conventional wisdom that a small particle size is strictly required for supercapacitor electrodes and allowed high charge storage densities, rapid transport, and good rate handling ability. The material showcased capacitance above 100 F g-1 at sweep rates as high as 250 mV s-1 in organic electrolyte. 250-1000 micron thick dense CDC films with up to 80 mg cm-2 loading showed superior areal capacitances. The material significantly outperformed its activated carbon counterpart in organic electrolytes and ionic liquids. Furthermore, large internal/external surface ratio of coarse-grained carbons allowed the resulting electrodes to maintain high electrochemical stability up to 3.1 V in ionic liquid electrolyte. In addition to presenting novel insights into the electrosorption process, these coarse-grained carbons offer a pathway to low-cost, high-performance implementation of supercapacitors in automotive and grid-storage applications.
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Zou, Jun; Iqbal, Muhammad; Chen, Hua; Asif, Mohammad; N’Diaye, Amidou; Navabi, Alireza; Perez-Lara, Enid; Pozniak, Curtis; Yang, Rong-Cai; Randhawa, Harpinder; Spaner, Dean
2017-01-01
Recently, we investigated the effect of the wheat 90K single nucleotide polymorphic (SNP) array and three gene-specific (Ppd-D1, Vrn-A1 and Rht-B1) markers on quantitative trait loci (QTL) detection in a recombinant inbred lines (RILs) population derived from a cross between two spring wheat (Triticum aestivum L.) cultivars, ‘Attila’ and ‘CDC Go’, and evaluated for eight agronomic traits at three environments under organic management. The objectives of the present study were to investigate the effect of conventional management on QTL detection in the same mapping population using the same set of markers as the organic management and compare the results with organic management. Here, we evaluated 167 RILs for number of tillers (tillering), flowering time, maturity, plant height, test weight (grain volume weight), 1000 kernel weight, grain yield, and grain protein content at seven conventionally managed environments from 2008 to 2014. Using inclusive composite interval mapping (ICIM) on phenotypic data averaged across seven environments and a subset of 1203 informative markers (1200 SNPs and 3 gene specific markers), we identified a total of 14 QTLs associated with flowering time (1), maturity (2), plant height (1), grain yield (1), test weight (2), kernel weight (4), tillering (1) and grain protein content (2). Each QTL individually explained from 6.1 to 18.4% of the phenotypic variance. Overall, the QTLs associated with each trait explained from 9.7 to 35.4% of the phenotypic and from 22.1 to 90.8% of the genetic variance. Three chromosomal regions on chromosomes 2D (61–66 cM), 4B (80–82 cM) and 5A (296–297 cM) harbored clusters of QTLs associated with two to three traits. The coincidental region on chromosome 5A harbored QTL clusters for both flowering and maturity time, and mapped about 2 cM proximal to the Vrn-A1 gene, which was in high linkage disequilibrium (0.70 ≤ r2 ≤ 0.75) with SNP markers that mapped within the QTL confidence interval. Six of the 14 QTLs (one for flowering time and plant height each, and two for maturity and kernel weight each) were common between the conventional and organic management systems, which suggests issues in directly utilizing gene discovery results based on conventional management to make in detail selection (decision) for organic management. PMID:28158253
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Xu, Yuli; Gristwood, Tamzin; Hodgson, Ben; Trinidad, Jonathan C.; Albers, Sonja-Verena; Bell, Stephen D.
2016-01-01
The regulated recruitment of Cdc45 and GINS is key to activating the eukaryotic MCM(2-7) replicative helicase. We demonstrate that the homohexameric archaeal MCM helicase associates with orthologs of GINS and Cdc45 in vivo and in vitro. Association of these factors with MCM robustly stimulates the MCM helicase activity. In contrast to the situation in eukaryotes, archaeal Cdc45 and GINS form an extremely stable complex before binding MCM. Further, the archaeal GINS•Cdc45 complex contains two copies of Cdc45. Our analyses give insight into the function and evolution of the conserved core of the archaeal/eukaryotic replisome. PMID:27821767
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Xu, Yuli; Gristwood, Tamzin; Hodgson, Ben; Trinidad, Jonathan C; Albers, Sonja-Verena; Bell, Stephen D
2016-11-22
The regulated recruitment of Cdc45 and GINS is key to activating the eukaryotic MCM(2-7) replicative helicase. We demonstrate that the homohexameric archaeal MCM helicase associates with orthologs of GINS and Cdc45 in vivo and in vitro. Association of these factors with MCM robustly stimulates the MCM helicase activity. In contrast to the situation in eukaryotes, archaeal Cdc45 and GINS form an extremely stable complex before binding MCM. Further, the archaeal GINS•Cdc45 complex contains two copies of Cdc45. Our analyses give insight into the function and evolution of the conserved core of the archaeal/eukaryotic replisome.
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Cdc48 regulates a deubiquitylase cascade critical for mitochondrial fusion
den Brave, Fabian
2018-01-01
Cdc48/p97, a ubiquitin-selective chaperone, orchestrates the function of E3 ligases and deubiquitylases (DUBs). Here, we identify a new function of Cdc48 in ubiquitin-dependent regulation of mitochondrial dynamics. The DUBs Ubp12 and Ubp2 exert opposing effects on mitochondrial fusion and cleave different ubiquitin chains on the mitofusin Fzo1. We demonstrate that Cdc48 integrates the activities of these two DUBs, which are themselves ubiquitylated. First, Cdc48 promotes proteolysis of Ubp12, stabilizing pro-fusion ubiquitylation on Fzo1. Second, loss of Ubp12 stabilizes Ubp2 and thereby facilitates removal of ubiquitin chains on Fzo1 inhibiting fusion. Thus, Cdc48 synergistically regulates the ubiquitylation status of Fzo1, allowing to control the balance between activation or repression of mitochondrial fusion. In conclusion, we unravel a new cascade of ubiquitylation events, comprising Cdc48 and two DUBs, fine-tuning the fusogenic activity of Fzo1. PMID:29309037
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Cilek, James E; Knapp, Jennifer A; Richardson, Alec G
2017-06-01
We conducted a study to compare the effectiveness of the Biogents Gravid Aedes Trap (BG-GAT) and Centers for Disease Control and Prevention (CDC) Autocidal Gravid Ovitrap (AGO) with that of the CDC Gravid Trap (CDC-GT) (as a standard) for their proficiency to collect mosquitoes in an urban residential neighborhood in northeastern Florida. Aedes aegypti , Ae. albopictus, and Culex quinquefasciatus were collected from each trap, with the latter species being predominant. Significantly more Cx. quinquefasciatus were collected from CDC-GT traps compared with the other 2 traps. Pairwise comparison of the efficiency of the CDC-GT revealed that this trap collected 6.7- to 21.5-fold more mosquitoes than the BG-GAT, depending on species. The BG-GAT collected overall more mosquitoes (3- to 6-fold) than the AGO, with the exception of Ae. aegypti, where both traps were nearly equal in effectiveness.
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77 FR 2550 - Office for State, Tribal, Local and Territorial Support (OSTLTS)
Federal Register 2010, 2011, 2012, 2013, 2014
2012-01-18
... in October of 2005 with the primary purpose of providing guidance across the agency to work.../AN access to CDC resources and programs. In November of 2006, an Agency Advisory Committee (the CDC... government-to-government consultation activities rests within the CDC Office of the Director (OD), other CDC...
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13 CFR 120.926 - Referral fee.
Code of Federal Regulations, 2014 CFR
2014-01-01
... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-02
... Intent To Award Affordable Care Act Funding, Funding Opportunity Announcement CDC-RFA-DP09-905 AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS). ACTION: Notice. SUMMARY: This notice provides notice of CDC's intent to fund continuation cooperative agreement...
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13 CFR 120.926 - Referral fee.
Code of Federal Regulations, 2013 CFR
2013-01-01
... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...
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13 CFR 120.926 - Referral fee.
Code of Federal Regulations, 2011 CFR
2011-01-01
... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...
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13 CFR 120.926 - Referral fee.
Code of Federal Regulations, 2012 CFR
2012-01-01
... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...
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13 CFR 120.926 - Referral fee.
Code of Federal Regulations, 2010 CFR
2010-01-01
... Loan Program (504) Third Party Loans § 120.926 Referral fee. The CDC can receive a reasonable referral fee from the Third Party Lender if the CDC secured the Third Party Lender for the Borrower under a written contract between the CDC and the Third Party Lender. Both the CDC and the Third Party Lender are...
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Krueger, Amy; Dietz, Patricia; Van Handel, Michelle; Belcher, Lisa; Johnson, Anna Satcher
2016-12-01
To determine whether CDC-funded HIV testing programs are reaching persons disproportionately affected by HIV infection. The percentage distribution for HIV testing and diagnoses by demographics and transmission risk group (diagnoses only) were calculated using 2013 data from CDC's National HIV Surveillance System and CDC's national HIV testing program data. In 2013, nearly 3.2 million CDC-funded tests were provided to persons aged 13 years and older. Among persons who received a CDC-funded test, 41.1 % were aged 20-29 years; 49.2 % were male, 46.2 % were black/African American, and 56.2 % of the tests were conducted in the South. Compared with the characteristics of all persons diagnosed with HIV in the United States in 2013, among persons diagnosed as a result of CDC-funded tests, a higher percentage were aged 20-29 years (40.3 vs 33.7 %) and black/African American (55.3 vs 46.0 %). CDC-funded HIV testing programs are reaching young people and blacks/African Americans.
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Cdc20 hypomorphic mice fail to counteract de novo synthesis of cyclin B1 in mitosis
Malureanu, Liviu; Jeganathan, Karthik B.; Jin, Fang; Baker, Darren J.; van Ree, Janine H.; Gullon, Oliver; Chen, Zheyan; Henley, John R.
2010-01-01
Cdc20 is an activator of the anaphase-promoting complex/cyclosome that initiates anaphase onset by ordering the destruction of cyclin B1 and securin in metaphase. To study the physiological significance of Cdc20 in higher eukaryotes, we generated hypomorphic mice that express small amounts of this essential cell cycle regulator. In this study, we show that these mice are healthy and not prone to cancer despite substantial aneuploidy. Cdc20 hypomorphism causes chromatin bridging and chromosome misalignment, revealing a requirement for Cdc20 in efficient sister chromosome separation and chromosome–microtubule attachment. We find that cyclin B1 is newly synthesized during mitosis via cytoplasmic polyadenylation element–binding protein-dependent translation, causing its rapid accumulation between prometaphase and metaphase of Cdc20 hypomorphic cells. Anaphase onset is significantly delayed in Cdc20 hypomorphic cells but not when translation is inhibited during mitosis. These data reveal that Cdc20 is particularly rate limiting for cyclin B1 destruction because of regulated de novo synthesis of this cyclin after prometaphase onset. PMID:20956380
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Cdc7 kinase - a new target for drug development.
Swords, Ronan; Mahalingam, Devalingam; O'Dwyer, Michael; Santocanale, Corrado; Kelly, Kevin; Carew, Jennifer; Giles, Francis
2010-01-01
The cell division cycle 7 (Cdc7) is a serine threonine kinase that is of critical importance in the regulation of normal cell cycle progression. Cdc7 kinase is highly conserved during evolution and much has been learned about its biological roles in humans through the study of lower eukaryotes, particularly yeasts. Two important regulator proteins, Dbf4 and Drf1, bind to and modulate the kinase activity of human Cdc7 which phosphorylates several sites on Mcm2 (minichromosome maintenance protein 2), one of the six subunits of the replicative DNA helicase needed for duplication of the genome. Through regulation of both DNA synthesis and DNA damage response, both key functions in the survival of tumour cells, Cdc7 becomes an attractive target for pharmacological inhibition. There are much data available on the pre-clinical anti-cancer effects of Cdc7 depletion and although there are no available Cdc7 inhibitors in clinical trials as yet, several lead compounds are being optimised for this purpose. In this review, we will address the current status of Cdc7 as an important target for new drug development.
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de Sá, Ivy Luizi Rodrigues; Sallum, Maria Anice Mureb
2013-01-01
In several countries, surveillance of insect vectors is accomplished with automatic traps. This study addressed the performance of Mosquito Magnet® Independence (MMI) in comparison with those of CDC with CO2 and lactic acid (CDC-A) and CDC light trap (CDC-LT). The collection sites were in a rural region located in a fragment of secondary tropical Atlantic rainforest, southeastern Brazil. Limatus durhami and Limatus flavisetosus were the dominant species in the MMI, whereas Ochlerotatus scapularis was most abundant in CDC-A. Culex ribeirensis and Culex sacchettae were dominant species in the CDC-LT. Comparisons among traps were based on diversity indices. Results from the diversity analyses showed that the MMI captured a higher abundance of mosquitoes and that the species richness estimated with it was higher than with CDC-LT. Contrasting, difference between MMI and CDC-A was not statistically significant. Consequently, the latter trap seems to be both an alternative for the MMI and complementary to it for ecological studies and entomological surveillance. PMID:24402154
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Cdc45-induced loading of human RPA onto single-stranded DNA.
Szambowska, Anna; Tessmer, Ingrid; Prus, Piotr; Schlott, Bernhard; Pospiech, Helmut; Grosse, Frank
2017-04-07
Cell division cycle protein 45 (Cdc45) is an essential component of the eukaryotic replicative DNA helicase. We found that human Cdc45 forms a complex with the single-stranded DNA (ssDNA) binding protein RPA. Moreover, it actively loads RPA onto nascent ssDNA. Pull-down assays and surface plasmon resonance studies revealed that Cdc45-bound RPA complexed with ssDNA in the 8-10 nucleotide binding mode, but dissociated when RPA covered a 30-mer. Real-time analysis of RPA-ssDNA binding demonstrated that Cdc45 catalytically loaded RPA onto ssDNA. This placement reaction required physical contacts of Cdc45 with the RPA70A subdomain. Our results imply that Cdc45 controlled stabilization of the 8-nt RPA binding mode, the subsequent RPA transition into 30-mer mode and facilitated an ordered binding to ssDNA. We propose that a Cdc45-mediated loading guarantees a seamless deposition of RPA on newly emerging ssDNA at the nascent replication fork. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
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Wicky, Sidonie; Tjandra, Hendri; Schieltz, David; Yates, John; Kellogg, Douglas R
2011-01-01
The Wee1 kinase restrains entry into mitosis by phosphorylating and inhibiting cyclin-dependent kinase 1 (Cdk1). The Cdc25 phosphatase promotes entry into mitosis by removing Cdk1 inhibitory phosphorylation. Experiments in diverse systems have established that Wee1 and Cdc25 are regulated by protein phosphatase 2A (PP2A), but a full understanding of the function and regulation of PP2A in entry into mitosis has remained elusive. In budding yeast, entry into mitosis is controlled by a specific form of PP2A that is associated with the Cdc55 regulatory subunit (PP2A(Cdc55)). We show here that related proteins called Zds1 and Zds2 form a tight stoichiometric complex with PP2A(Cdc55) and target its activity to Cdc25 but not to Wee1. Conditional inactivation of the Zds proteins revealed that their function is required primarily at entry into mitosis. In addition, Zds1 undergoes cell cycle-dependent changes in phosphorylation. Together, these observations define a role for the Zds proteins in controlling specific functions of PP2A(Cdc55) and suggest that upstream signals that regulate PP2A(Cdc55) may play an important role in controlling entry into mitosis.
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Dendritic spine geometry can localize GTPase signaling in neurons
Ramirez, Samuel A.; Raghavachari, Sridhar; Lew, Daniel J.
2015-01-01
Dendritic spines are the postsynaptic terminals of most excitatory synapses in the mammalian brain. Learning and memory are associated with long-lasting structural remodeling of dendritic spines through an actin-mediated process regulated by the Rho-family GTPases RhoA, Rac, and Cdc42. These GTPases undergo sustained activation after synaptic stimulation, but whereas Rho activity can spread from the stimulated spine, Cdc42 activity remains localized to the stimulated spine. Because Cdc42 itself diffuses rapidly in and out of the spine, the basis for the retention of Cdc42 activity in the stimulated spine long after synaptic stimulation has ceased is unclear. Here we model the spread of Cdc42 activation at dendritic spines by means of reaction-diffusion equations solved on spine-like geometries. Excitable behavior arising from positive feedback in Cdc42 activation leads to spreading waves of Cdc42 activity. However, because of the very narrow neck of the dendritic spine, wave propagation is halted through a phenomenon we term geometrical wave-pinning. We show that this can account for the localization of Cdc42 activity in the stimulated spine, and, of interest, retention is enhanced by high diffusivity of Cdc42. Our findings are broadly applicable to other instances of signaling in extreme geometries, including filopodia and primary cilia. PMID:26337387
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Phosphorylation of Bem2p and Bem3p may contribute to local activation of Cdc42p at bud emergence
Knaus, Michèle; Pelli-Gulli, Marie-Pierre; van Drogen, Frank; Springer, Sander; Jaquenoud, Malika; Peter, Matthias
2007-01-01
Site-specific activation of the Rho-type GTPase Cdc42p is critical for the establishment of cell polarity. Here we investigated the role and regulation of the GTPase-activating enzymes (GAPs) Bem2p and Bem3p for Cdc42p activation and actin polarization at bud emergence in Saccharomyces cerevisiae. Bem2p and Bem3p are localized throughout the cytoplasm and the cell cortex in unbudded G1 cells, but accumulate at sites of polarization after bud emergence. Inactivation of Bem2p results in hyperactivation of Cdc42p and polarization toward multiple sites. Bem2p and Bem3p are hyperphosphorylated at bud emergence most likely by the Cdc28p-Cln2p kinase. This phosphorylation appears to inhibit their GAP activity in vivo, as non-phosphorylatable Bem3p mutants are hyperactive and interfere with Cdc42p activation. Taken together, our results indicate that Bem2p and Bem3p may function as global inhibitors of Cdc42p activation during G1, and their inactivation by the Cdc28p/Cln kinase contributes to site-specific activation of Cdc42p at bud emergence. PMID:17914457
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Baldwin, Melissa L; Julius, Jeffrey A; Tang, Xianying; Wang, Yanchang; Bachant, Jeff
2009-10-15
Post-translation modification through the SUMO pathway is cell cycle regulated, with specific SUMO conjugates accumulating in mitotic cells. The basis for this regulation, however, and its functional significance remain poorly understood. We present evidence that in budding yeast sumoylation during mitosis may be controlled through the SUMO deconjugating enzyme Smt4/Ulp2. We isolated the polo kinase Cdc5 as an Ulp2-interacting protein, and find a C-terminal region of Ulp2 is phosphorylated during mitosis in a Cdc5-dependent manner. cdc5 mutants display reduced levels of mitotic SUMO conjugates, suggesting Cdc5 may negatively regulate Ulp2 to promote sumoylation. Previously, we found one phenotype associated with ulp2 mutants is an inability to maintain chromatid cohesion at centromere-proximal chromosomal regions. We now show this defect is rescued by inactivating Cdc5, indicating Ulp2 maintains cohesion by counter-acting Cdc5 activity. The cohesinregulator Pds5 is a likely target of this pathway, as Cdc5 overproduction forces Pds5 dissociation from chromosomes and Pds5 overproduction restores cohesion in ulp2 mutants. Overall, these observations reveal Cdc5 is a novel regulator of the SUMO pathway and suggest the outlines of a broader circuitry in which Ulp2 and Cdc5 act in a mutually antagonistic fashion to modulate maintenance and dissolution of cohesion at centromeres.
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Muscarella, Lucia Anna; Turchetti, Daniela; Fontana, Andrea; Baorda, Filomena; Palumbo, Orazio; la Torre, Annamaria; de Martino, Danilo; Franco, Renato; Losito, Nunzia Simona; Repaci, Andrea; Pagotto, Uberto; Cinque, Luigia; Copetti, Massimiliano; Chiofalo, Maria Grazia; Pezzullo, Luciano; Graziano, Paolo; Scillitani, Alfredo; Guarnieri, Vito
2018-04-17
The Hyperparathyroidism with Jaw-Tumours syndrome is caused by mutations of the CDC73 gene: it has been suggested that early onset of the disease and high Ca 2+ levels may predict the presence of a CDC73 mutation. We searched for large deletions at the CDC73 locus in patients with: HPT-JT (nr 2), atypical adenoma (nr 7) or sporadic parathyroid carcinoma (nr 11) with a specific MLPA and qRT-PCR assays applied on DNA extracted from whole blood. A Medline search in database for all the papers reporting a CDC73 gene mutation, clinical/histological diagnosis, age at onset, Ca 2+ , PTH levels for familial/sporadic cases was conducted with the aim to possibly identify biochemical/clinical markers predictive, in first diagnosis, of the presence of a CDC73 gene mutation. A novel genomic deletion of the first 10 exons of the CDC73 gene was found in a 3-generation HPT-JT family, confirmed by SNP array analysis. A classification tree built on the published data, showed the highest probability of having a CDC73 mutation in subjects with age at the onset < 41.5 years (44/47 subjects, 93.6%, had the mutation). Whereas the lowest probability was found in subjects with age at the onset ≥ 41.5 years and Ca 2+ levels <13.96 mg/dL (7/20 subjects, 35.0%, had the mutation, odds ratio = 27.1, p < 0.001). We report a novel large genomic CDC73 gene deletion identified in an Italian HPT-JT family. Age at onset < 41.5 ys and Ca 2+ > 13.96 mg/dL are predictive for the presence of a CDC73 genetic lesion.
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Barile, John P; Horner-Johnson, Willi; Krahn, Gloria; Zack, Matthew; Miranda, David; DeMichele, Kimberly; Ford, Derek; Thompson, William W
2016-10-01
The Short Form Health Survey (SF-36) and the Centers for Disease Control and Prevention (CDC) Healthy Days items are well known measures of health-related quality of life. The validity of the SF-36 for older adults and those with disabilities has been questioned. Assess the extent to which the SF-36 and the Centers for Disease Control and Prevention (CDC) Healthy Days items measure the same aspects of health; whether the SF-36 and the CDC unhealthy days items are invariant across gender, functional status, or the presence of chronic health conditions of older adults; and whether each of the SF-36's eight subscales is independently associated with the CDC Healthy Days items. We analyzed data from 66,269 adult Medicare advantage members age 65 and older. We used confirmatory factor analyses and regression modeling to test associations between the CDC Healthy Days items and subscales of the SF-36. The CDC Healthy Days items were associated with the SF-36 global measures of physical and mental health. The CDC physically unhealthy days item was associated with the SF-36 subscales for bodily pain, physical role limitations, and general health, while the CDC mentally unhealthy days item was associated with the SF-36 subscales for mental health, emotional role limitations, vitality and social functioning. The SF-36 physical functioning subscale was not independently associated with either of the CDC Healthy Days items. The CDC Healthy Days items measure similar domains as the SF-36 but appear to assess HRQOL without regard to limitations in functioning. Copyright © 2016 Elsevier Inc. All rights reserved.
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Barile, John P.; Horner-Johnson, Willi; Krahn, Gloria; Zack, Matthew; Miranda, David; DeMichele, Kimberly; Ford, Derek; Thompson, William W.
2017-01-01
Background The Short Form Health Survey (SF-36) and the Centers for Disease Control and Prevention (CDC) Healthy Days items are well known measures of health-related quality of life. The validity of the SF-36 for older adults and those with disabilities has been questioned. Objective Assess the extent to which the SF-36 and the Centers for Disease Control and Prevention (CDC) Healthy Days items measure the same aspects of health; whether the SF-36 and the CDC unhealthy days items are invariant across gender, functional status, or the presence of chronic health conditions of older adults; and whether each of the SF-36’s eight subscales is independently associated with the CDC Healthy Days items. Methods We analyzed data from 66,269 adult Medicare advantage members age 65 and older. We used confirmatory factor analyses and regression modeling to test associations between the CDC Healthy Days items and subscales of the SF-36. Results The CDC Healthy Days items were associated with the SF-36 global measures of physical and mental health. The CDC physically unhealthy days item was associated with the SF-36 subscales for bodily pain, physical role limitations, and general health, while the CDC mentally unhealthy days item was associated with the SF-36 subscales for mental health, emotional role limitations, vitality and social functioning. The SF-36 physical functioning subscale was not independently associated with either of the CDC Healthy Days items. Conclusions The CDC Healthy Days items measure similar domains as the SF-36 but appear to assess HRQOL without regard to limitations in functioning. PMID:27259343
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Su, Jingjing; Zhou, Houguang; Tao, Yinghong; Guo, Zhuangli; Zhang, Shuo; Zhang, Yu; Huang, Yanyan; Tang, Yuping; Hu, Renming; Dong, Qiang
2015-01-01
Cell cycle processes play a vital role in vascular endothelial proliferation and dysfunction. Cell division cycle protein 14 (Cdc14) is an important cell cycle regulatory phosphatase. Previous studies in budding yeast demonstrated that Cdc14 could trigger the inactivation of mitotic cyclin-dependent kinases (Cdks), which are required for mitotic exit and cytokinesis. However, the exact function of human Cdc14 (hCdc14) in cell cycle regulation during vascular diseases is yet to be elucidated. There are two HCdc14 homologs: hCdc14A and hCdc14B. In the current study, we investigated the potential role of hCdc14A in high glucose-, free fatty acids (FFAs)-, and hypoxia-induced injury in cultured human brain vascular endothelial cells (HBVECs). Data revealed that high glucose, FFA, and hypoxia down-regulated hCdc14A expression remarkably, and also affected the expression of other cell cycle-related proteins such as cyclin B, cyclin D, cyclin E, and p53. Furthermore, the combined addition of the three stimuli largely blocked cell cycle progression, decreased cell proliferation, and increased apoptosis. We also determined that hCdc14A was localized mainly to centrosomes during interphase and spindles during mitosis using confocal microscopy, and that it could affect the expression of other cycle-related proteins. More importantly, the overexpression of hCdc14A accelerated cell cycle progression, enhanced cell proliferation, and promoted neoplastic transformation, whereas the knockdown of hCdc14A using small interfering RNA produced the opposite effects. Therefore, these findings provide novel evidence that hCdc14A might be involved in cell cycle regulation in cultured HBVECs during high glucose-, FFA-, and hypoxia-induced injury. Copyright © 2014 Elsevier Inc. All rights reserved.
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Xiao, Jian-Ying; Liu, Chao; Sun, Xiao-Han; Yu, Bing-Zhi
2012-02-25
To further test whether protein kinase A (PKA) can affect the mitotic cell cycle, one-cell stage mouse embryos at S phase (22 h after hCG injection) were incubated in M16 medium containing various concentrations of H-89, a PKA inhibitor. With increasing concentrations of H-89 (0-50 μmol/L), the G(2) phase of eggs was decreased and the cleavage rate was accelerated. A concentration of 40 μmol/L H-89 led to all of the mouse eggs entering the M phase of mitosis. Furthermore, to study the role of PKA in regulating the phosphorylation status of S149 and S321 sites of cell division cycle 25B (CDC25B) on one-cell stage fertilized mouse eggs, pBSK-CDC25B-WT, pBSK-CDC25B-S149A, pBSK-CDC25B-S321A and pBSK-CDC25B-S149A/S321A were transcribed into mRNAs in vitro, then mRNAs were microinjected into S phase of mouse fertilized eggs and cultured in M16 medium pretreated with H-89. Then, the cleavage of fertilized eggs, maturation promoting factor (MPF) activity and phosphorylation status of CDC2-Tyr15 were observed. In the presence of 40 μmol/L H-89, the cleavage rate of fertilized eggs in CDC25B-S/A-mRNAs and CDC25B-WT-mRNA injected groups was significantly higher than that in the control groups, and the peak of MPF activity appeared in the CDC25B-S/A-mRNAs and CDC25B-WT-mRNA injected groups earlier than that in the control groups. CDC2-Tyr15 phosphorylation state was consistent with MPF activity. In conclusion, the present study suggests that PKA regulates the early development of mouse embryos by phosphorylation of S149 and S321 of CDC25B, which plays an important role in the regulation of G(2)/M transition in the mitotic cell cycle of fertilized mouse eggs.
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Butz, Henriett; Németh, Kinga; Czenke, Dóra; Likó, István; Czirják, Sándor; Zivkovic, Vladimir; Baghy, Kornélia; Korbonits, Márta; Kovalszky, Ilona; Igaz, Péter; Rácz, Károly; Patócs, Attila
2017-07-01
Dysregulation of G1/S checkpoint of cell cycle has been reported in pituitary adenomas. In addition, our previous finding showing that deregulation of Wee1 kinase by microRNAs together with other studies demonstrating alteration of G2/M transition in nonfunctioning pituitary adenomas (NFPAs) suggest that G2/M transition may also be important in pituitary tumorigenesis. To systematically study the expression of members of the G2/M transition in NFPAs and to investigate potential microRNA (miRNA) involvement. Totally, 80 NFPA and 14 normal pituitary (NP) tissues were examined. Expression of 46 genes encoding members of the G2/M transition was profiled on 34 NFPA and 10 NP samples on TaqMan Low Density Array. Expression of CDC25A and two miRNAs targeting CDC25A were validated by individual quantitative real time PCR using TaqMan assays. Protein expression of CDC25A, CDC25C, CDK1 and phospho-CDK1 (Tyr-15) was investigated on tissue microarray and immunohistochemistry. Several genes' expression alteration were observed in NFPA compared to normal tissues by transcription profiling. On protein level CDC25A and both the total and the phospho-CDK1 were overexpressed in adenoma tissues. CDC25A correlated with nuclear localized CDK1 (nCDK1) and with tumor size and nCDK1 with Ki-67 index. Comparing primary vs. recurrent adenomas we found that Ki-67 proliferation index was higher and phospho-CDK1 (inactive form) was downregulated in recurrent tumors compared to primary adenomas. Investigating the potential causes behind CDC25A overexpression we could not find copy number variation at the coding region nor expression alteration of CDC25A regulating transcription factors however CDC25A targeting miRNAs were downregulated in NFPA and negatively correlated with CDC25A expression. Our results suggest that among alterations of G2/M transition of the cell cycle, overexpression of the CDK1 and CDC25A may have a role in the pathogenesis of the NFPA and that CDC25A is potentially regulated by miRNAs.
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Hashiguchi, Kazue; Velez N., Lenin; Kato, Hirotomo; Criollo F., Hipatia; Romero A., Daniel; Gomez L., Eduardo; Martini R., Luiggi; Zambrano C., Flavio; Calvopina H., Manuel; Caceres G., Abraham; Hashiguchi, Yoshihisa
2014-01-01
To study the sand fly fauna, surveys were performed at four different leishmaniasis-endemic sites in Ecuador from February 2013 to April 2014. A modified and simplified version of the conventional Shannon trap was named “mini-Shannon trap” and put to multiple uses at the different study sites in limited, forested and narrow spaces. The mini-Shannon, CDC light trap and protected human landing method were employed for sand fly collection. The species identification of sand flies was performed mainly based on the morphology of spermathecae and cibarium, after dissection of fresh samples. In this study, therefore, only female samples were used for analysis. A total of 1,480 female sand flies belonging to 25 Lutzomyia species were collected. The number of female sand flies collected was 417 (28.2%) using the mini-Shannon trap, 259 (17.5%) using the CDC light trap and 804 (54.3%) by human landing. The total number of sand flies per trap collected by the different methods was markedly affected by the study site, probably because of the various composition of species at each locality. Furthermore, as an additional study, the attraction of sand flies to mini-Shannon traps powered with LED white-light and LED black-light was investigated preliminarily, together with the CDC light trap and human landing. As a result, a total of 426 sand flies of nine Lutzomyia species, including seven man-biting and two non-biting species, were collected during three capture trials in May and June 2014 in an area endemic for leishmaniasis (La Ventura). The black-light proved relatively superior to the white-light with regard to capture numbers, but no significant statistical difference was observed between the two traps. PMID:25589880
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Hashiguchi, Kazue; Velez N, Lenin; Kato, Hirotomo; Criollo F, Hipatia; Romero A, Daniel; Gomez L, Eduardo; Martini R, Luiggi; Zambrano C, Flavio; Calvopina H, Manuel; Caceres G, Abraham; Hashiguchi, Yoshihisa
2014-12-01
To study the sand fly fauna, surveys were performed at four different leishmaniasis-endemic sites in Ecuador from February 2013 to April 2014. A modified and simplified version of the conventional Shannon trap was named "mini-Shannon trap" and put to multiple uses at the different study sites in limited, forested and narrow spaces. The mini-Shannon, CDC light trap and protected human landing method were employed for sand fly collection. The species identification of sand flies was performed mainly based on the morphology of spermathecae and cibarium, after dissection of fresh samples. In this study, therefore, only female samples were used for analysis. A total of 1,480 female sand flies belonging to 25 Lutzomyia species were collected. The number of female sand flies collected was 417 (28.2%) using the mini-Shannon trap, 259 (17.5%) using the CDC light trap and 804 (54.3%) by human landing. The total number of sand flies per trap collected by the different methods was markedly affected by the study site, probably because of the various composition of species at each locality. Furthermore, as an additional study, the attraction of sand flies to mini-Shannon traps powered with LED white-light and LED black-light was investigated preliminarily, together with the CDC light trap and human landing. As a result, a total of 426 sand flies of nine Lutzomyia species, including seven man-biting and two non-biting species, were collected during three capture trials in May and June 2014 in an area endemic for leishmaniasis (La Ventura). The black-light proved relatively superior to the white-light with regard to capture numbers, but no significant statistical difference was observed between the two traps.
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Carbide derived carbon from MAX-phases and their separation applications
NASA Astrophysics Data System (ADS)
Hoffman, Elizabeth N.
Improved sorbents with increased selectivity and permeability are needed to meet growing energy and environmental needs. New forms of carbon based sorbents have been discovered recently, including carbons produced by etching metals from metal carbides, known as carbide derived carbons (CDCs). A common method for the synthesis of CDC is by chlorination at elevated temperatures. The goal of this work is to synthesize CDC from ternary carbides and to explore the links between the initial carbide chemistry and structure with the resulting CDCs properties, including porosity. CDC was produced from MAX-phase carbides, in particular Ti3SiC 2, Ti3AlC2, Ti2AlC, and Ta2AlC. Additionally, CDC was produced from Ta-based binary carbides, TaC and Ta 2C, and one carbo-nitride Ti2AlC0.5N0.5. The CDC structure was characterized using XRD, Raman microspectroscopy, and HRTEM. Porosity characterization was performed using sorption analysis with both Ar and N2 as adsorbates. It was determined the microporosity of CDC is related to the density of the initial carbide. The layered structure of the MAX-phase carbides lent toward the formation of larger mesopores within the resulting CDCs, while the amount of mesopores was dependent on the chemistry of the carbide. Furthermore, CDC produced from carbides with extremely high theoretical porosity resulted in small specific surface areas due to a collapse of the carbon structure. To expand the potential applications for CDC beyond powder and bulk forms, CDC membranes were produced from a thin film of TiC deposited by magnetron sputtering onto porous ceramic substrates. The TiC thin film was subsequently chlorinated to produce a bilayer membrane with CDC as the active layer. Both gases and liquids are capable of passing the membrane. The membrane separates based on selective adsorption, rather than a size separation molecular sieving effect. Two applications for CDC produced from MAX-phases were investigated: protein adsorption and gas separation. Sorbents capable of adsorbing large protein molecules efficiently are desirable for many medical applications, including the treatment of sepsis. Primarily mesoporous Ti2AlC-CDC and Ti3AlC2-CDC were proven to adsorb a significant amount of proteins compared to two current carbon adsorbents. When tested for gas separation, CDC was capable of selectively adsorbing gases including SF6, CO2, CH4, and H2. However, the gases were not separated based on their size, but rather on their interaction with the CDC surface.
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Huard, Sylvain; Elder, Robert T; Liang, Dong; Li, Ge; Zhao, Richard Y
2008-03-01
Human immunodeficiency virus type 1 (HIV-1) Vpr induces cell cycle G(2) arrest in fission yeast (Schizosaccharomyces pombe) and mammalian cells, suggesting the cellular pathway(s) targeted by Vpr is conserved among eukaryotes. Our previous studies in fission yeast demonstrated that Vpr induces G(2) arrest in part through inhibition of Cdc25, a Cdc2-specific phosphatase that promotes G(2)/M transition. The goal of this study was to further elucidate molecular mechanism underlying the inhibitory effect of Vpr on Cdc25. We show here that, similar to the DNA checkpoint controls, expression of vpr promotes subcellular relocalization of Cdc25 from nuclear to cytoplasm and thereby prevents activation of Cdc2 by Cdc25. Vpr-induced nuclear exclusion of Cdc25 appears to depend on the serine/threonine phosphorylation of Cdc25 and the presence of Rad24/14-3-3 protein, since amino acid substitutions of the nine possible phosphorylation sites of Cdc25 with Ala (9A) or deletion of the rad24 gene abolished nuclear exclusion induced by Vpr. Interestingly, Vpr is still able to promote Cdc25 nuclear export in mutants defective in the checkpoints (rad3 and chk1/cds1), the kinases that are normally required for Cdc25 phosphorylation and nuclear exclusion of Cdc25, suggesting that others kinase(s) might modulate phosphorylation of Cdc25 for the Vpr-induced G(2) arrest. We report here that this kinase is Srk1. Deletion of the srk1 gene blocks the nuclear exclusion of Cdc25 caused by Vpr. Overexpression of srk1 induces cell elongation, an indication of cell cycle G(2) delay, in a similar fashion to Vpr; however, no additive effect of cell elongation was observed when srk1 and vpr were coexpressed, indicating Srk1 and Vpr are likely affecting the cell cycle G(2)/M transition through the same cellular pathway. Immunoprecipitation further shows that Vpr and Srk1 are part of the same protein complex. Consistent with our findings in fission yeast, depletion of the MK2 gene, a human homologue of Srk1, either by small interfering RNA or an MK2 inhibitor suppresses Vpr-induced cell cycle G(2) arrest in mammalian cells. Collectively, our data suggest that Vpr induces cell cycle G(2) arrest at least in part through a Srk1/MK2-mediated mechanism.
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Foster, Caleb A.; Tierno, Marni Brisson; Shun, Tong Ying; Shinde, Sunita N.; Paquette, William D.; Brummond, Kay M.; Wipf, Peter; Lazo, John S.
2009-01-01
Abstract The University of Pittsburgh Molecular Library Screening Center (Pittsburgh, PA) conducted a screen with the National Institutes of Health compound library for inhibitors of in vitro cell division cycle 25 protein (Cdc25) B activity during the pilot phase of the Molecular Library Screening Center Network. Seventy-nine (0.12%) of the 65,239 compounds screened at 10 μM met the active criterion of ≥50% inhibition of Cdc25B activity, and 25 (31.6%) of these were confirmed as Cdc25B inhibitors with 50% inhibitory concentration (IC50) values <50 μM. Thirteen of the Cdc25B inhibitors were represented by singleton chemical structures, and 12 were divided among four clusters of related structures. Thirteen (52%) of the Cdc25B inhibitor hits were quinone-based structures. The Cdc25B inhibitors were further characterized in a series of in vitro secondary assays to confirm their activity, to determine their phosphatase selectivity against two other dual-specificity phosphatases, mitogen-activated protein kinase phosphatase (MKP)-1 and MKP-3, and to examine if the mechanism of Cdc25B inhibition involved oxidation and inactivation. Nine Cdc25B inhibitors did not appear to affect Cdc25B through a mechanism involving oxidation because they did not generate detectable amounts of H2O2 in the presence of dithiothreitol, and their Cdc25B IC50 values were not significantly affected by exchanging the dithiothreitol for β-mercaptoethanol or reduced glutathione or by adding catalase to the assay. Six of the nonoxidative hits were selective for Cdc25B inhibition versus MKP-1 and MKP-3, but only the two bisfuran-containing hits, PubChem substance identifiers 4258795 and 4260465, significantly inhibited the growth of human MBA-MD-435 breast and PC-3 prostate cancer cell lines. To confirm the structure and biological activity of 4260465, the compound was resynthesized along with two analogs. Neither of the substitutions to the two analogs was tolerated, and only the resynthesized hit 26683752 inhibited Cdc25B activity in vitro (IC50 = 13.83 ± 1.0 μM) and significantly inhibited the growth of the MBA-MD-435 breast and PC-3 prostate cancer cell lines (IC50 = 20.16 ± 2.0 μM and 24.87 ± 2.25 μM, respectively). The two bis-furan-containing hits identified in the screen represent novel nonoxidative Cdc25B inhibitor chemotypes that block tumor cell proliferation. The availability of non-redox active Cdc25B inhibitors should provide valuable tools to explore the inhibition of the Cdc25 phosphatases as potential mono- or combination therapies for cancer. PMID:19530895
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Makki-Rmida, Faten; Kammoun, Arwa; Mahfoudh, Nadia; Ayadi, Adnene; Gibriel, Abdullah Ahmed; Mallek, Bakhta; Maalej, Leila; Hammami, Zouheir; Maatoug, Samir; Makni, Hafedh; Masmoudi, Saber
2015-12-01
Y chromosome STRs (Y-STRs) are being used frequently in forensic laboratories. Previous studies of Y-STR polymorphisms in different groups of the Tunisian population identified low levels of diversity and discrimination capacity (DC) using various commercial marker sets. This definitely limits the use of such systems for Y-STRs genotyping in Tunisia. In our investigation on South Tunisia, 200 unrelated males were typed for the 12 conventional Y-STRs included in the PowerPlex® Y System. Additional set of nine noncore Y-STRs including DYS446, DYS456, DYS458, DYS388, DYS444, DYS445, DYS449, DYS710, and DYS464 markers were genotyped and evaluated for their potential in improving DC. Allele frequency, gene diversity, haplotype diversity (HD), and DC calculation revealed that DYS464 was the most diverse marker followed by DYS710 and DYS449 markers. The standard panel of 12 Y-STRs (DC = 80.5%) and the nine markers were combined to obtain DC of 99%. Among the 198 different haplotypes observed, 196 haplotypes were unique (HD = 99.999). Out of the nine noncore set, six Y-STRs (DYS458, DYS456, DYS449, DYS710, DYS444, and DYS464) had the greatest impact on enhancing DC. Our data provided putative Y-STRs combination to be used for genetic and forensic applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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NASA Astrophysics Data System (ADS)
Shimojo, Fuyuki; Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya
2008-02-01
A linear-scaling algorithm based on a divide-and-conquer (DC) scheme has been designed to perform large-scale molecular-dynamics (MD) simulations, in which interatomic forces are computed quantum mechanically in the framework of the density functional theory (DFT). Electronic wave functions are represented on a real-space grid, which is augmented with a coarse multigrid to accelerate the convergence of iterative solutions and with adaptive fine grids around atoms to accurately calculate ionic pseudopotentials. Spatial decomposition is employed to implement the hierarchical-grid DC-DFT algorithm on massively parallel computers. The largest benchmark tests include 11.8×106 -atom ( 1.04×1012 electronic degrees of freedom) calculation on 131 072 IBM BlueGene/L processors. The DC-DFT algorithm has well-defined parameters to control the data locality, with which the solutions converge rapidly. Also, the total energy is well conserved during the MD simulation. We perform first-principles MD simulations based on the DC-DFT algorithm, in which large system sizes bring in excellent agreement with x-ray scattering measurements for the pair-distribution function of liquid Rb and allow the description of low-frequency vibrational modes of graphene. The band gap of a CdSe nanorod calculated by the DC-DFT algorithm agrees well with the available conventional DFT results. With the DC-DFT algorithm, the band gap is calculated for larger system sizes until the result reaches the asymptotic value.
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2016-01-01
Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281). PMID:26839476
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-02
... Intent To Award Affordable Care Act Funding, Funding Opportunity Announcement CDC-RFA-DP10-1014 AGENCY... Funding Opportunity CDC-RFA- DP10-1014. It is the intent of CDC to provide continuation funding to one (1... published in the above referenced REACH CORE Funding Opportunity Announcement (FOA). Award Information...
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13 CFR 120.950 - SBA and CDC must appoint agents.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...
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13 CFR 120.950 - SBA and CDC must appoint agents.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...
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13 CFR 120.972 - Third Party Lender participation fee and CDC fee.
Code of Federal Regulations, 2012 CFR
2012-01-01
... fee and CDC fee. 120.972 Section 120.972 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... and CDC fee. (a) Participation fee. For loans approved by SBA after September 30, 1996, SBA must... when the Third Party Lender occupies a senior credit position to SBA in the Project. (b) CDC fee. For...
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13 CFR 120.950 - SBA and CDC must appoint agents.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...
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13 CFR 120.950 - SBA and CDC must appoint agents.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...
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13 CFR 120.846 - Requirements for maintaining and renewing PCLP status.
Code of Federal Regulations, 2013 CFR
2013-01-01
... Requirements for maintaining and renewing PCLP status. (a) To maintain its status as a PCLP CDC, a CDC must... with all Loan Program Requirements. (4) Remain an active CDC. (5) In accordance with statutory... 50 percent of its 504 loans using PCLP procedures. (b) SBA will notify the PCLP CDC in writing of a...
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13 CFR 120.972 - Third Party Lender participation fee and CDC fee.
Code of Federal Regulations, 2011 CFR
2011-01-01
... fee and CDC fee. 120.972 Section 120.972 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... and CDC fee. (a) Participation fee. For loans approved by SBA after September 30, 1996, SBA must... when the Third Party Lender occupies a senior credit position to SBA in the Project. (b) CDC fee. For...
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42 CFR 73.4 - Overlap select agents and toxins.
Code of Federal Regulations, 2012 CFR
2012-10-01
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2013-10-29
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13 CFR 120.846 - Requirements for maintaining and renewing PCLP status.
Code of Federal Regulations, 2010 CFR
2010-01-01
... Requirements for maintaining and renewing PCLP status. (a) To maintain its status as a PCLP CDC, a CDC must... with all Loan Program Requirements. (4) Remain an active CDC. (5) In accordance with statutory... 50 percent of its 504 loans using PCLP procedures. (b) SBA will notify the PCLP CDC in writing of a...
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13 CFR 120.972 - Third Party Lender participation fee and CDC fee.
Code of Federal Regulations, 2014 CFR
2014-01-01
... fee and CDC fee. 120.972 Section 120.972 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... and CDC fee. (a) Participation fee. For loans approved by SBA after September 30, 1996, SBA must... when the Third Party Lender occupies a senior credit position to SBA in the Project. (b) CDC fee. For...
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13 CFR 120.846 - Requirements for maintaining and renewing PCLP status.
Code of Federal Regulations, 2011 CFR
2011-01-01
... Requirements for maintaining and renewing PCLP status. (a) To maintain its status as a PCLP CDC, a CDC must... with all Loan Program Requirements. (4) Remain an active CDC. (5) In accordance with statutory... 50 percent of its 504 loans using PCLP procedures. (b) SBA will notify the PCLP CDC in writing of a...
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13 CFR 120.972 - Third Party Lender participation fee and CDC fee.
Code of Federal Regulations, 2013 CFR
2013-01-01
... fee and CDC fee. 120.972 Section 120.972 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION... and CDC fee. (a) Participation fee. For loans approved by SBA after September 30, 1996, SBA must... when the Third Party Lender occupies a senior credit position to SBA in the Project. (b) CDC fee. For...
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13 CFR 120.846 - Requirements for maintaining and renewing PCLP status.
Code of Federal Regulations, 2014 CFR
2014-01-01
... Requirements for maintaining and renewing PCLP status. (a) To maintain its status as a PCLP CDC, a CDC must... with all Loan Program Requirements. (4) Remain an active CDC. (5) In accordance with statutory... 50 percent of its 504 loans using PCLP procedures. (b) SBA will notify the PCLP CDC in writing of a...
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13 CFR 120.846 - Requirements for maintaining and renewing PCLP status.
Code of Federal Regulations, 2012 CFR
2012-01-01
... Requirements for maintaining and renewing PCLP status. (a) To maintain its status as a PCLP CDC, a CDC must... with all Loan Program Requirements. (4) Remain an active CDC. (5) In accordance with statutory... 50 percent of its 504 loans using PCLP procedures. (b) SBA will notify the PCLP CDC in writing of a...
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13 CFR 120.950 - SBA and CDC must appoint agents.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false SBA and CDC must appoint agents... Development Company Loan Program (504) Debenture Sales and Service Agents § 120.950 SBA and CDC must appoint agents. SBA and the CDC must appoint the following agents to facilitate the sale and service of the...
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Minogue, T D; Daligault, H E; Davenport, K W; Bishop-Lilly, K A; Bruce, D C; Chain, P S; Coyne, S R; Chertkov, O; Freitas, T; Frey, K G; Jaissle, J; Koroleva, G I; Ladner, J T; Palacios, G F; Redden, C L; Xu, Y; Johnson, S L
2014-10-23
The Enterobacteriaceae are environmental and enteric microbes. We sequenced the genomes of two Enterobacter reference strains, E. aerogenes CDC 6003-71 and E. cloacae CDC 442-68, as well as one near neighbor used as an exclusionary reference for diagnostics, Pantoea agglomerans CDC UA0804-01. The genome sizes range from 4.72 to 5.55 Mbp and have G+C contents from 54.6 to 55.1%. Copyright © 2014 Minogue et al.
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NASA Astrophysics Data System (ADS)
Warsito, W.; Noorhamdani, A. S.; Suratmo; Dwi Sapri, R.; Alkaroma, D.; Azhar, A. Z.
2018-04-01
Simple method has been used for the synthesis of benzimidazole derivative from citronellal in kaffir lime oil under microwave irradiation. These compounds were synthesized also by conventional heating for comparison. In addtion, microwave-assited synthesis was also compared between using to dichloromethane and methanol solvents with variation of reaction time for 30 to 70 minutes and 4 to 12 h for conventional heating. The 2-citronellyl benzimidazole compound synthesized were characterised by FT-IR, GC-MS, 1H and 13C NMR spectroscopy. Comparison between conventional and microwave-assisted synthesis was done by comparing between correlation of reaction time and percentage yield. The time optimum of microwave-assisted and conventional synthesis using dichloromethane solvent respectively at 60 minutes (yield 19.23%) and 8 hours (yield 11.54%). In addition, microwave-assited synthesis increasing 157.81 times compared by conventional heating. While using methanol solvent tends to increase linearly however the percentage of yield only 0.77 times of synthesis using dichloromethane solvent.
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de Val, Natalia; McMurray, Michael A.; Lam, Lisa H.; Hsiung, Chris C.-S.; Bertin, Aurélie; Nogales, Eva; Thorner, Jeremy
2013-01-01
Budding yeast septins assemble into hetero-octamers and filaments required for cytokinesis. Solvent-exposed cysteine (Cys) residues provide sites for attaching substituents useful in assessing assembly kinetics and protein interactions. To introduce Cys at defined locations, site-directed mutagenesis was used, first, to replace the native Cys residues in Cdc3 (C124 C253 C279), Cdc10 (C266), Cdc11 (C43 C137 C138), Cdc12 (C40 C278), and Shs1 (C29 C148) with Ala, Ser, Val, or Phe. When plasmid-expressed, each Cys-less septin mutant rescued the cytokinesis defects caused by absence of the corresponding chromosomal gene. When integrated and expressed from its endogenous promoter, the same mutants were fully functional, except Cys-less Cdc12 mutants (which were viable, but exhibited slow growth and aberrant morphology) and Cdc3(C124V C253V C279V) (which was inviable). No adverse phenotypes were observed when certain pairs of Cys-less septins were co-expressed as the sole source of these proteins. Cells grew less well when three Cys-less septins were co-expressed, suggesting some reduction in fitness. Nonetheless, cells chromosomally expressing Cys-less Cdc10, Cdc11, and Cdc12, and expressing Cys-less Cdc3 from a plasmid, grew well at 30ºC. Moreover, recombinant Cys-less septins—or where one of the Cys-less septins contained a single Cys introduced at a new site—displayed assembly properties in vitro indistinguishable from wild-type. PMID:23775754
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Engineering and public health at CDC.
Earnest, G Scott; Reed, Laurence D; Conover, D; Estill, C; Gjessing, C; Gressel, M; Hall, R; Hudock, S; Hudson, H; Kardous, C; Sheehy, J; Topmiller, J; Trout, D; Woebkenberg, M; Amendola, A; Hsiao, H; Keane, P; Weissman, D; Finfinger, G; Tadolini, S; Thimons, E; Cullen, E; Jenkins, M; McKibbin, R; Conway, G; Husberg, B; Lincoln, J; Rodenbeck, S; Lantagne, D; Cardarelli, J
2006-12-22
Engineering is the application of scientific and technical knowledge to solve human problems. Using imagination, judgment, and reasoning to apply science, technology, mathematics, and practical experience, engineers develop the design, production, and operation of useful objects or processes. During the 1940s, engineers dominated the ranks of CDC scientists. In fact, the first CDC director, Assistant Surgeon General Mark Hollis, was an engineer. CDC engineers were involved in malaria control through the elimination of standing water. Eventually the CDC mission expanded to include prevention and control of dengue, typhus, and other communicable diseases. The development of chlorination, water filtration, and sewage treatment were crucial to preventing waterborne illness. Beginning in the 1950s, CDC engineers began their work to improve public health while developing the fields of environmental health, industrial hygiene, and control of air pollution. Engineering disciplines represented at CDC today include biomedical, civil, chemical, electrical, industrial, mechanical, mining, and safety engineering. Most CDC engineers are located in the National Institute for Occupational Safety and Health (NIOSH) and the Agency for Toxic Substances and Disease Registry (ATSDR). Engineering research at CDC has a broad stakeholder base. With the cooperation of industry, labor, trade associations, and other stakeholders and partners, current work includes studies of air contaminants, mining, safety, physical agents, ergonomics, and environmental hazards. Engineering solutions remain a cornerstone of the traditional "hierarchy of controls" approach to reducing public health hazards.
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Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species
Wythe, Joshua D.; Liu, Jiandong; Cartry, Jerome; Vogler, Georg; Mohapatra, Bhagyalaxmi; Otway, Robyn T.; Huang, Yu; King, Isabelle N.; Maillet, Marjorie; Zheng, Yi; Crawley, Timothy; Taghli-Lamallem, Ouarda; Semsarian, Christopher; Dunwoodie, Sally; Winlaw, David; Harvey, Richard P.; Fatkin, Diane; Towbin, Jeffrey A.; Molkentin, Jeffery D.; Srivastava, Deepak; Ocorr, Karen; Bruneau, Benoit G.
2011-01-01
Unraveling the gene regulatory networks that govern development and function of the mammalian heart is critical for the rational design of therapeutic interventions in human heart disease. Using the Drosophila heart as a platform for identifying novel gene interactions leading to heart disease, we found that the Rho-GTPase Cdc42 cooperates with the cardiac transcription factor Tinman/Nkx2-5. Compound Cdc42, tinman heterozygous mutant flies exhibited impaired cardiac output and altered myofibrillar architecture, and adult heart–specific interference with Cdc42 function is sufficient to cause these same defects. We also identified K+ channels, encoded by dSUR and slowpoke, as potential effectors of the Cdc42–Tinman interaction. To determine whether a Cdc42–Nkx2-5 interaction is conserved in the mammalian heart, we examined compound heterozygous mutant mice and found conduction system and cardiac output defects. In exploring the mechanism of Nkx2-5 interaction with Cdc42, we demonstrated that mouse Cdc42 was a target of, and negatively regulated by miR-1, which itself was negatively regulated by Nkx2-5 in the mouse heart and by Tinman in the fly heart. We conclude that Cdc42 plays a conserved role in regulating heart function and is an indirect target of Tinman/Nkx2-5 via miR-1. PMID:21690310
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The Tea4-PP1 landmark promotes local growth by dual Cdc42 GEF recruitment and GAP exclusion.
Kokkoris, Kyriakos; Gallo Castro, Daniela; Martin, Sophie G
2014-05-01
Cell polarization relies on small GTPases, such as Cdc42, which can break symmetry through self-organizing principles, and landmarks that define the axis of polarity. In fission yeast, microtubules deliver the Tea1-Tea4 complex to mark cell poles for growth, but how this complex activates Cdc42 is unknown. Here, we show that ectopic targeting of Tea4 to cell sides promotes the local activation of Cdc42 and cell growth. This activity requires that Tea4 binds the type I phosphatase (PP1) catalytic subunit Dis2 or Sds21, and ectopic targeting of either catalytic subunit is similarly instructive for growth. The Cdc42 guanine-nucleotide-exchange factor Gef1 and the GTPase-activating protein Rga4 are required for Tea4-PP1-dependent ectopic growth. Gef1 is recruited to ectopic Tea4 and Dis2 locations to promote Cdc42 activation. By contrast, Rga4 is locally excluded by Tea4, and its forced colocalization with Tea4 blocks ectopic growth, indicating that Rga4 must be present, but at sites distinct from Tea4. Thus, a Tea4-PP1 landmark promotes local Cdc42 activation and growth both through Cdc42 GEF recruitment and by creating a local trough in a Cdc42 GAP.
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Site-specific regulation of the GEF Cdc24p by the scaffold protein Far1p during yeast mating
Wiget, Philippe; Shimada, Yukiko; Butty, Anne-Christine; Bi, Efrei; Peter, Matthias
2004-01-01
Receptor-mediated cell polarization via heterotrimeric G-proteins induces cytoskeletal rearrangements in a variety of organisms. In yeast, Far1p is required for orienting cell growth towards the mating partner by linking activated Gβγ to the guanine-nucleotide exchange factor (GEF) Cdc24p, which activates the Rho-type GTPase Cdc42p. Here we investigated the role of Far1p in the regulation of Cdc24p in vivo. Using time-lapse microscopy of mating cells and artificial membrane targeting of Far1p, we show that Far1p is necessary and sufficient to recruit Cdc24p to the plasma membrane. Wild-type Far1p contains a PH-like domain, which is required for its membrane localization in vivo. Interestingly, expression of membrane-targeted Far1p causes toxicity, most likely by activating Cdc42p uniformly at the cell cortex. The ability of full-length Far1p to function as an activator of Cdc24p in vivo requires its interaction with Cdc24p and Gβγ. Our results imply that Gβγ not only targets Far1p to the correct site but may also trigger a conformational change in Far1p that is required for its ability to activate Cdc24p in vivo. PMID:14988725
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USDA-ARS?s Scientific Manuscript database
Septins were first discovered in Saccharomyces cerevisiae where they form a scaffold that organizes the bud site and are a component of the morphogenesis checkpoint that coordinates budding with mitosis. Five of the seven S. cerevisiae septins (Cdc3, Cdc10, Cdc11, Cdc12 and Shs1) colocalize as a rin...