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Sample records for activator inhibitor-2 pai-2

  1. Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes.

    PubMed

    Swartz, Jonathan M; Byström, Jonas; Dyer, Kimberly D; Nitto, Takeaki; Wynn, Thomas A; Rosenberg, Helene F

    2004-10-01

    Plasminogen activator inhibitor-2 (PAI-2) as a potential eosinophil protein was inferred from our gene microarray study of mouse eosinophilopoiesis. Here, we detect 47 kDa intracellular and approximately 60 kDa secretory forms of PAI-2 in purified human eosinophil extracts. PAI-2 is present at variable concentrations in eosinophil lysates, ranging from 30 to 444 ng/10(6) cells, with a mean of 182 ng/10(6) cells from 10 normal donors, which is the highest per-cell concentration among all leukocyte subtypes evaluated. Enzymatic assay confirmed that eosinophil-derived PAI-2 is biologically active and inhibits activation of its preferred substrate, urokinase. Immunohistochemical and immunogold staining demonstrated PAI-2 localization in eosinophil-specific granules. Immunoreactive PAI-2 was detected in extracellular deposits in and around the eosinophil-enriched granuloma tissue encapsulating the parasitic egg in livers of wild-type mice infected with the helminthic parasite Schistosoma mansoni. Among the possibilities, we consider a role for eosinophil-derived PAI-2 in inflammation and remodeling associated with parasitic infection as well as allergic airways disease, respiratory virus infection, and host responses to tumors and metastasis in vivo.

  2. The role of proteasome beta subunits in gastrin-mediated transcription of plasminogen activator inhibitor-2 and regenerating protein1.

    PubMed

    O'Hara, Adrian; Howarth, Alice; Varro, Andrea; Dimaline, Rod

    2013-01-01

    The hormone gastrin physiologically regulates gastric acid secretion and also contributes to maintaining gastric epithelial architecture by regulating expression of genes such as plasminogen activator inhibitor 2 (PAI-2) and regenerating protein 1 (Reg1). Here we examine the role of proteasome subunit PSMB1 in the transcriptional regulation of PAI-2 and Reg1 by gastrin, and its subcellular distribution during gastrin stimulation. We used the gastric cancer cell line AGS, permanently transfected with the CCK2 receptor (AGS-GR) to study gastrin stimulated expression of PAI-2 and Reg1 reporter constructs when PSMB1 was knocked down by siRNA. Binding of PSMB1 to the PAI-2 and Reg1 promoters was assessed by chromatin immunoprecipitation (ChIP) assay. Subcellular distribution of PSMB1 was determined by immunocytochemistry and Western Blot. Gastrin robustly increased expression of PAI-2 and Reg1 in AGS-GR cells, but when PSMB1 was knocked down the responses were dramatically reduced. In ChIP assays, following immunoprecipitation of chromatin with a PSMB1 antibody there was a substantial enrichment of DNA from the gastrin responsive regions of the PAI-2 and Reg1 promoters compared with chromatin precipitated with control IgG. In AGS-GR cells stimulated with gastrin there was a significant increase in the ratio of nuclear:cytoplasmic PSMB1 over the same timescale as recruitment of PSMB1 to the PAI-2 and Reg1 promoters seen in ChIP assays. We conclude that PSMB1 is part of the transcriptional machinery required for gastrin stimulated expression of PAI-2 and Reg1, and that its change in subcellular distribution in response to gastrin is consistent with this role.

  3. The sGC activator inhibits the proliferation and migration, promotes the apoptosis of human pulmonary arterial smooth muscle cells via the up regulation of plasminogen activator inhibitor-2

    SciTech Connect

    Zhang, Shuai; Zou, Lihui; Yang, Ting; Yang, Yuanhua; Zhai, Zhenguo; Xiao, Fei; Wang, Chen

    2015-03-15

    Background: Different types of pulmonary hypertension (PH) share the same process of pulmonary vascular remodeling, the molecular mechanism of which is not entirely clarified by far. The abnormal biological behaviors of pulmonary arterial smooth muscle cells (PASMCs) play an important role in this process. Objectives: We investigated the regulation of plasminogen activator inhibitor-2 (PAI-2) by the sGC activator, and explored the effect of PAI-2 on PASMCs proliferation, apoptosis and migration. Methods: After the transfection with PAI-2 overexpression vector and specific siRNAs or treatment with BAY 41-2272 (an activator of sGC), the mRNA and protein levels of PAI-2 in cultured human PASMCs were detected, and the proliferation, apoptosis and migration of PASMCs were investigated. Results: BAY 41-2272 up regulated the endogenous PAI-2 in PASMCs, on the mRNA and protein level. In PAI-2 overexpression group, the proliferation and migration of PASMCs were inhibited significantly, and the apoptosis of PASMCs was increased. In contrast, PAI-2 knockdown with siRNA increased PASMCs proliferation and migration, inhibited the apoptosis. Conclusions: PAI-2 overexpression inhibits the proliferation and migration and promotes the apoptosis of human PASMCs. Therefore, sGC activator might alleviate or reverse vascular remodeling in PH through the up-regulation of PAI-2. - Highlights: • sGC activator BAY41-2272 up regulated PAI-2 in PASMCs, on the mRNA and protein level. • PAI-2 overexpression inhibits the proliferation and migration of human PASMCs. • PAI-2 overexpression promotes the apoptosis of human PASMCs. • sGC activator might alleviate the vascular remodeling in pulmonary hypertension.

  4. Ochratoxin A inhibits the production of tissue factor and plasminogen activator inhibitor-2 by human blood mononuclear cells: Another potential mechanism of immune-suppression

    SciTech Connect

    Rossiello, Maria R.; Rotunno, Crescenzia; Coluccia, Addolorata; Carratu, Maria R.; Di Santo, Angelomaria; Evangelista, Virgilio; Semeraro, Nicola; Colucci, Mario

    2008-06-01

    The mycotoxin ochratoxin A (OTA), an ubiquitous contaminant of food products endowed with a wide spectrum of toxicity, affects several functions of mononuclear leukocytes. Monocytes/macrophages play a major role in fibrin accumulation associated with immune-inflammatory processes through the production of tissue factor (TF) and plasminogen activator inhibitor 2 (PAI-2). We studied the effect of OTA on TF and PAI-2 production by human blood mononuclear cells (MNC). The cells were incubated for 3 or 18 h at 37 deg. C with non toxic OTA concentrations in the absence and in the presence of lipopolysaccharide (LPS) or other inflammatory agents. TF activity was measured by a one-stage clotting test. Antigen assays were performed by specific ELISAs in cell extracts or conditioned media and specific mRNAs were assessed by RT-PCR. OTA had no direct effect on TF and PAI-2 production by MNC. However, OTA caused a dose-dependent reduction in LPS-induced TF (activity, antigen and mRNA) and PAI-2 (antigen and mRNA) production with > 85% inhibition at 1 {mu}g/ml. Similar results were obtained when monocyte-enriched preparations were used instead of MNC. TF production was also impaired by OTA (1 {mu}g/ml) when MNC were stimulated with phorbol myristate acetate (98% inhibition), IL-1{beta} (83%) or TNF-{alpha} (62%). The inhibition of TF and PAI-2 induction might represent a hitherto unrecognized mechanism whereby OTA exerts immunosuppressant activity.

  5. Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2.

    PubMed

    Zeng, Ping; Liu, Bin; Wang, Qun; Fan, Qin; Diao, Jian-Xin; Tang, Jing; Fu, Xiu-Qiong; Sun, Xue-Gang

    2015-01-01

    Macrophage survival is believed to be a contributing factor in the development of early atherosclerotic lesions. Dysregulated apoptosis of macrophages is involved in the inflammatory process of atherogenesis. Apigenin is a flavonoid that possesses various clinically relevant properties such as anti-inflammatory, antiplatelet, and antitumor activities. Here we showed that apigenin attenuated atherogenesis in apoE (-/-) mice in an in vivo test. In vitro experiments suggested that apigenin induced apoptosis of oxidized low density lipoprotein- (OxLDL-) loaded murine peritoneal macrophages (MPMs). Proteomic analysis showed that apigenin reduced the expression of plasminogen activator inhibitor 2 (PAI-2). PAI-2 has antiapoptotic effects in OxLDL-loaded MPMs. Enhancing PAI-2 expression significantly reduced the proapoptosis effects of apigenin. Molecular docking assay with AutoDock software predicted that residue Ser473 of Akt1 is a potential binding site for apigenin. Lentiviral-mediated overexpression of Akt1 wild type weakened the proapoptosis effect of apigenin in OxLDL-loaded MPMs. Collectively, apigenin executes its anti-atherogenic effects through inducing OxLDL-loaded MPMs apoptosis. The proapoptotic effects of apigenin were at least partly attributed to downregulation of PAI-2 through suppressing phosphorylation of AKT at Ser473.

  6. Auranofin Suppresses Plasminogen Activator Inhibitor-2 Expression through Annexin A5 Induction in Human Prostate Cancer Cells

    PubMed Central

    Shin, Dong-Won; Kwon, Yeo-Jung; Ye, Dong-Jin; Baek, Hyoung-Seok; Lee, Joo-Eun; Chun, Young-Jin

    2017-01-01

    Auranofin has been developed as antirheumatic drugs, which is currently under clinical development for the treatment of chronic lymphocytic leukemia. Previous report showed that auranofin induced apoptosis by enhancement of annexin A5 expression in PC-3 cells. To understand the role of annexin A5 in auranofin-mediated apoptosis, we performed microarray data analysis to study annexin A5-controlled gene expression in annexin A5 knockdown PC-3 cells. Of differentially expressed genes, plasminogen activator inhibitor (PAI)-2 was increased by annexin A5 siRNA confirmed by qRT-PCR and western blot. Treatment with auranofin decreased PAI-2 and increased annexin A5 expression as well as promoting apoptosis. Furthermore, auranofin-induced apoptosis was recovered by annexin A5 siRNA but it was promoted by PAI-2 siRNA. Interestingly, knockdown of annexin A5 rescued PAI-2 expression suppressed by auranofin. Taken together, our study suggests that induction of annexin A5 by auranofin may enhance apoptosis through suppression of PAI-2 expression in PC-3 cells. PMID:27956714

  7. Data in support of a central role of plasminogen activator inhibitor-2 polymorphism in recurrent cardiovascular disease risk in the setting of high HDL cholesterol and C-reactive protein using Bayesian network modeling.

    PubMed

    Corsetti, James P; Salzman, Peter; Ryan, Dan; Moss, Arthur J; Zareba, Wojciech; Sparks, Charles E

    2016-09-01

    Data is presented that was utilized as the basis for Bayesian network modeling of influence pathways focusing on the central role of a polymorphism of plasminogen activator inhibitor-2 (PAI-2) on recurrent cardiovascular disease risk in patients with high levels of HDL cholesterol and C-reactive protein (CRP) as a marker of inflammation, "Influences on Plasminogen Activator Inhibitor-2 Polymorphism-Associated Recurrent Cardiovascular Disease Risk in Patients with High HDL Cholesterol and Inflammation" (Corsetti et al., 2016; [1]). The data consist of occurrence of recurrent coronary events in 166 post myocardial infarction patients along with 1. clinical data on gender, race, age, and body mass index; 2. blood level data on 17 biomarkers; and 3. genotype data on 53 presumptive CVD-related single nucleotide polymorphisms. Additionally, a flow diagram of the Bayesian modeling procedure is presented along with Bayesian network subgraphs (root nodes to outcome events) utilized as the data from which PAI-2 associated influence pathways were derived (Corsetti et al., 2016; [1]).

  8. Prevotella intermedia stimulates tissue-type plasminogen activator and plasminogen activator inhibitor-2 expression via multiple signaling pathways in human periodontal ligament cells.

    PubMed

    Guan, Su-Min; He, Jian-Jun; Zhang, Ming; Shu, Lei

    2011-06-01

    Prevotella intermedia is an important periodontal pathogen that induces various inflammatory and immune responses. In this study, we investigated the effects of P. intermedia on the plasminogen system in human periodontal ligament (hPDL) cells and explored the signaling pathways involved. Using semi-quantitative reverse transcription (RT)-PCR and quantitative real-time RT-qPCR, we demonstrated that P. intermedia challenge increased tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-2 expression in a concentration- and time-dependent manner, but exerted no influence on urokinase-type plasminogen activator and PAI-1mRNA expression in hPDL cells. Prevotella intermedia stimulation also enhanced tPA protein secretion as confirmed by enzyme-linked immunosorbent assay. Western blot results revealed that P. intermedia treatment increased phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38). ERK, JNK and protein kinase C inhibitors significantly attenuated the P. intermedia-induced tPA and PAI-2 expression. Furthermore, p38 and phosphatidylinositol 3-kinase inhibitors markedly decreased PAI-2 expression, whereas they showed no or little inhibition on tPA expression. In contrast, inhibition of protein kinase A greatly enhanced the upregulatory effect of P. intermedia on tPA and PAI-2 expression. Our results suggest that P. intermedia may contribute to periodontal tissue destruction by upregulating tPA and PAI-2 expression in hPDL cells via multiple signaling pathways.

  9. The isopeptidase inhibitor 2cPE triggers proteotoxic stress and ATM activation in chronic lymphocytic leukemia cells

    PubMed Central

    Tomasella, Andrea; Picco, Raffaella; Ciotti, Sonia; Sgorbissa, Andrea; Bianchi, Elisa; Manfredini, Rossella; Benedetti, Fabio; Trimarco, Valentina; Frezzato, Federica; Trentin, Livio; Semenzato, Gianpietro; Delia, Domenico; Brancolini, Claudio

    2016-01-01

    Relapse after treatment is a common and unresolved problem for patients suffering of the B-cell chronic lymphocytic leukemia (B-CLL). Here we investigated the ability of the isopeptidase inhibitor 2cPE to trigger apoptosis in leukemia cells in comparison with bortezomib, another inhibitor of the ubiquitin-proteasome system (UPS). Both inhibitors trigger apoptosis in CLL B cells and gene expression profiles studies denoted how a substantial part of genes up-regulated by these compounds are elements of adaptive responses, aimed to sustain cell survival. 2cPE treatment elicits the up-regulation of chaperones, proteasomal subunits and elements of the anti-oxidant response. Selective inhibition of these responses augments apoptosis in response to 2cPE treatment. We have also observed that the product of the ataxia telangiectasia mutated gene (ATM) is activated in 2cPE treated cells. Stimulation of ATM signaling is possibly dependent on the alteration of the redox homeostasis. Importantly ATM inhibition, mutations or down-modulation increase cell death in response to 2cPE. Overall this work suggests that 2cPE could offer new opportunities for the treatment of B-CLL. PMID:27259251

  10. Phosphorylation of inhibitor-2 and activation of MgATP-dependent protein phosphatase by rat skeletal muscle glycogen synthase kinase

    SciTech Connect

    Hegazy, M.G.; Reimann, E.M.; Thysseril, T.J.; Schlender, K.K.

    1986-05-01

    Rat skeletal muscle contains a glycogen synthase kinase (GSK-M) which is not stimulated by Ca/sup 2 +/ or cAMP. This kinase has an apparent Mr of 62,000 and uses ATP but not GTP as a phosphoryl donor. GSK-M phosphorylated glycogen synthase at sites 2 and 3. It phosphorylated ATP-citrate lyase and activated MgATP-dependent phosphatase in the presence of ATP but not GTP. As expected, the kinase also phosphorylated phosphatase inhibitor 2 (I-2). Phosphatase incorporation reached approximately 0.3 mol/mol of I-2. Phosphopeptide maps were obtained by digesting /sup 32/P-labeled I-2 with trypsin and separating the peptides by reversed phase HPLC. Two partially separated /sup 32/P-labeled peaks were obtained when I-2 was phosphorylated with either GSK-M or glycogen synthase kinase 3 (GSK-3) and these peptides were different from those obtained when I-2 was phosphorylated with the catalytic subunit of cAMP-dependent protein kinase (CSU) or casein kinase II (CK-II). When I-2 was phosphorylated with GSK-M or GSK-3 and cleaved by CNBr, a single radioactive peak was obtained. Phosphoamino acid analysis showed that I-2 was phosphorylated by GSK-M or GSK-3 predominately in Thr whereas CSU and CK-II phosphorylated I-2 exclusively in Ser. These results indicate that GSK-M is similar to GSK-3 and to ATP-citrate lyase kinase. However, it appears to differ in Mr from ATP-citrate lyase kinase and it differs from GSK-3 in that it phosphorylates glycogen synthase at site 2 and it does not use GTP as a phosphoryl donor.

  11. SerpinB2 (PAI-2) Modulates Proteostasis via Binding Misfolded Proteins and Promotion of Cytoprotective Inclusion Formation

    PubMed Central

    Farrawell, Natalie; Shearer, Robert F.; Constantinescu, Patrick; Hatters, Danny M.; Schroder, Wayne A.; Suhrbier, Andreas; Wilson, Mark R.; Saunders, Darren N.; Ranson, Marie

    2015-01-01

    SerpinB2 (PAI-2), a member of the clade B family of serine protease inhibitors, is one of the most upregulated proteins following cellular stress. Originally described as an inhibitor of urokinase plasminogen activator, its predominant cytoplasmic localisation suggests an intracellular function. SerpinB2 has been reported to display cytoprotective properties in neurons and to interact with intracellular proteins including components of the ubiquitin-proteasome system (UPS). In the current study we explored the potential role of SerpinB2 as a modulator of proteotoxic stress. Initially, we transiently transfected wild-type SerpinB2 and SerpinB2-/- murine embryonic fibroblasts (MEFs) with Huntingtin exon1-polyglutamine (fused C-terminally to mCherry). Inclusion body formation as result of Huntingtin aggregation was evident in the SerpinB2 expressing cells but significantly impaired in the SerpinB2-/- cells, the latter concomitant with loss in cell viability. Importantly, recovery of the wild-type phenotype and cell viability was rescued by retroviral transduction of SerpinB2 expression. SerpinB2 modestly attenuated Huntingtin and amyloid beta fibril formation in vitro and was able to bind preferentially to misfolded proteins. Given the modest chaperone-like activity of SerpinB2 we tested the ability of SerpinB2 to modulate UPS and autophagy activity using a GFP reporter system and autophagy reporter, respectively. Activity of the UPS was reduced and autophagy was dysregulated in SerpinB2-/- compared to wild-type MEFs. Moreover, we observed a non-covalent interaction between ubiquitin and SerpinB2 in cells using GFP-pulldown assays and bimolecular fluorescence complementation. We conclude that SerpinB2 plays an important role in proteostasis as its loss leads to a proteotoxic phenotype associated with an inability to compartmentalize aggregating proteins and a reduced capacity of the UPS. PMID:26083412

  12. The gap junction inhibitor 2-aminoethoxy-diphenyl-borate protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes and c-jun N-terminal kinase activation

    SciTech Connect

    Du, Kuo; Williams, C. David; McGill, Mitchell R.; Xie, Yuchao; Farhood, Anwar; Vinken, Mathieu; Jaeschke, Hartmut

    2013-12-15

    Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the US. Although many aspects of the mechanism are known, recent publications suggest that gap junctions composed of connexin32 function as critical intercellular communication channels which transfer cytotoxic mediators into neighboring hepatocytes and aggravate liver injury. However, these studies did not consider off-target effects of reagents used in these experiments, especially the gap junction inhibitor 2-aminoethoxy-diphenyl-borate (2-APB). In order to assess the mechanisms of protection of 2-APB in vivo, male C56Bl/6 mice were treated with 400 mg/kg APAP to cause extensive liver injury. This injury was prevented when animals were co-treated with 20 mg/kg 2-APB and was attenuated when 2-APB was administered 1.5 h after APAP. However, the protection was completely lost when 2-APB was given 4–6 h after APAP. Measurement of protein adducts and c-jun-N-terminal kinase (JNK) activation indicated that 2-APB reduced both protein binding and JNK activation, which correlated with hepatoprotection. Although some of the protection was due to the solvent dimethyl sulfoxide (DMSO), in vitro experiments clearly demonstrated that 2-APB directly inhibits cytochrome P450 activities. In addition, JNK activation induced by phorone and tert-butylhydroperoxide in vivo was inhibited by 2-APB. The effects against APAP toxicity in vivo were reproduced in primary cultured hepatocytes without use of DMSO and in the absence of functional gap junctions. We conclude that the protective effect of 2-APB was caused by inhibition of metabolic activation of APAP and inhibition of the JNK signaling pathway and not by blocking connexin32-based gap junctions. - Highlights: • 2-APB protected against APAP-induced liver injury in mice in vivo and in vitro • 2-APB protected by inhibiting APAP metabolic activation and JNK signaling pathway • DMSO inhibited APAP metabolic activation as the solvent of 2-APB

  13. Cytotoxicity of PAI2, C595 and Herceptin vectors labeled with the alpha-emitting radioisotope Bismuth-213 for ovarian cancer cell monolayers and clusters.

    PubMed

    Song, Yan J; Qu, Chang F; Rizvi, Syed M A; Li, Yong; Robertson, G; Raja, Chand; Morgenstern, Alfred; Apostolidis, Christos; Perkins, Alan C; Allen, Barry J

    2006-03-28

    The vectors PAI2, C595 and Herceptin target the membrane-bound uPA, MUC1 and HER2 antigens expressed by cancer cells, respectively. The expression of these receptors was tested in the ovarian cancer cell line OVCAR-3; MUC-1 was strongly expressed (3+), uPA moderately expressed (2+), but HER2 was negative (-). The alpha-emitting radionuclide Bismuth-213 was chelated with these targeting vectors to form alpha conjugates (ACs), the cytotoxicity of which were tested with OVCAR-3 cells. The PAI2 and C595 ACs are highly cytotoxic to the ovarian monolayer cancer cells and cell clusters in a concentration-dependent fashion and cause morphological changes of treated cancer cells, inducing apoptosis. These ACs are potential candidates for the control of ovarian cancer at the minimum residual disease (MRD) stage.

  14. Synthesis, chiral high performance liquid chromatographic resolution and enantiospecific activity of a potent new geranylgeranyl transferase inhibitor, 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid.

    PubMed

    McKenna, Charles E; Kashemirov, Boris A; Błazewska, Katarzyna M; Mallard-Favier, Isabelle; Stewart, Charlotte A; Rojas, Javier; Lundy, Mark W; Ebetino, Frank H; Baron, Rudi A; Dunford, James E; Kirsten, Marie L; Seabra, Miguel C; Bala, Joy L; Marma, Mong S; Rogers, Michael J; Coxon, Fraser P

    2010-05-13

    3-(3-Pyridyl)-2-hydroxy-2-phosphonopropanoic acid (3-PEHPC, 1) is a phosphonocarboxylate (PC) analogue of 2-(3-pyridyl)-1-hydroxyethylidenebis(phosphonic acid) (risedronic acid, 2), an osteoporosis drug that decreases bone resorption by inhibiting farnesyl pyrophosphate synthase (FPPS) in osteoclasts, preventing protein prenylation. 1 has lower bone affinity than 2 and weakly inhibits Rab geranylgeranyl transferase (RGGT), selectively preventing prenylation of Rab GTPases. We report here the synthesis and biological studies of 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid (3-IPEHPC, 3), the PC analogue of minodronic acid 4. Like 1, 3 selectively inhibited Rab11 vs. Rap 1A prenylation in J774 cells, and decreased cell viability, but was 33-60x more active in these assays. After resolving 3 by chiral HPLC (>98% ee), we found that (+)-3-E1 was much more potent than (-)-3-E2 in an isolated RGGT inhibition assay, approximately 17x more potent (LED 3 microM) than (-)-3-E2 in inhibiting Rab prenylation in J774 cells and >26x more active in the cell viability assay. The enantiomers of 1 exhibited a 4-fold or smaller potency difference in the RGGT and prenylation inhibition assays.

  15. A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2.

    PubMed

    Wang, Hong; Brautigan, David L

    2002-12-20

    Protein kinases and protein phosphatases exert coordinated control over many essential cellular processes. Here, we describe the cloning and characterization of a novel human transmembrane protein KPI-2 (Kinase/Phosphatase/Inhibitor-2) that was identified by yeast two-hybrid using protein phosphatase inhibitor-2 (Inh2) as bait. KPI-2 mRNA was predominantly expressed in skeletal muscle. KPI-2 is a 1503-residue protein with two predicted transmembrane helices at the N terminus, a kinase domain, followed by a C-terminal domain. The transmembrane helices were sufficient for targeting proteins to the membrane. KPI-2 kinase domain has about 60% identity with its closest relative, a tyrosine kinase. However, it only exhibited serine/threonine kinase activity in autophosphorylation reactions or with added substrates. KPI-2 kinase domain phosphorylated protein phosphatase-1 (PP1C) at Thr(320), which attenuated PP1C activity. KPI-2 C-terminal domain directly associated with PP1C, and this required a VTF motif. Inh2 associated with KPI-2 C-terminal domain with and without PP1C. Thus, KPI-2 is a kinase with sites to associate with PP1C and Inh2 to form a regulatory complex that is localized to membranes.

  16. Phosphorylation of phosphatase inhibitor-2 (i-2) by a bovine thymus tyrosine protein kinase, p40

    SciTech Connect

    DePaoli-Roach, A.A.; Votaw, P.; Zioncheck, T.F.; Harrison, M.L.; Geahlen, R.L.

    1987-05-01

    Phosphatase inhibitor-2, a heat stable protein of Mr 22,800, is a regulatory component of the ATP-Mg-dependent phosphatase. It has been shown that in the cell tyrosine kinase activation can result in altered phosphorylation at serine and/or threonine residues, but the mechanism involved is unknown. The authors have found that i-2 is a substrate for a tyrosine specific protein kinase, p40, purified from bovine thymus. The purified enzyme is a monomer of Mr 40,000 that is autophosphorylated at tyrosine residue(s). The stoichiometry of phosphorylation of i-2 by this tyrosine protein kinase is up to 1 mol of phosphate per mol of i-2. Phosphoaminoacid analysis revealed that all the phosphate introduced was associated with tyrosine residues. Mapping of TSP-tryptic peptides by TLE and isoelectric focusing showed one major labeled fragment. Using the ATP-Mg-dependent phosphatase, a lesser extent of phosphorylation of i-2 by p40 was obtained although partial activation of the phosphatase was observed. The effect on the activity was not due to FA/GSK-3 contamination. These results could provide an important link between tyrosine protein kinase activity and modulation of phosphorylation at serine and/or threonine residues.

  17. The Protein Phosphatase-1/Inhibitor-2 Complex Differentially Regulates GSK-3 Dephosphorylation and Increases Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase 2 Levels

    PubMed Central

    King, Taj D.; Gandy, Johanna C.; Bijur, Gautam N.

    2007-01-01

    The ubiquitously expressed protein glycogen synthase kinase-3 (GSK3) is constitutively active, however its activity is markedly diminished following phosphorylation of Ser21 of GSK3α and Ser9 of GSK3β. Although several kinases are known to phosphorylate Ser21/9 of GSK3, for example Akt, relatively much less is known about the mechanisms that cause the dephosphorylation of GSK3 at Ser21/9. In the present study KCl-induced plasma membrane depolarization of SH-SY5Y cells, which increases intracellular calcium concentrations caused a transient decrease in the phosphorylation of Akt at Thr308 and Ser473, and GSK3 at Ser21/9. Overexpression of the selective protein phosphatase-1 inhibitor protein, inhibitor-2, increased basal GSK3 phosphorylation at Ser21/9 and significantly blocked the KCl-induced dephosphorylation of GSK3β, but not GSK3α. The phosphorylation of Akt was not affected by the overexpression of inhibitor-2. GSK3 activity is known to affect sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) levels. Overexpression of inhibitor-2 or treatment of cells with the GSK3 inhibitors lithium and SB216763 increased the levels of SERCA2. These results indicate that the protein phosphatase-1/inhibitor-2 complex differentially regulates GSK3 dephosphorylation induced by KCl and that GSK3 activity regulates SERCA2 levels. PMID:16987514

  18. Identification and analysis of the tissue factor pathway inhibitor 2 of Sciaenops ocellatus.

    PubMed

    Zhang, Min; Xiao, Zhi-zhong; Sun, Li

    2011-01-01

    Tissue factor pathway inhibitor 2 (TFPI-2) is a structural homologue of TFPI, a potent inhibitor of tissue factor (TF)-mediated coagulation. Although TFPI-2 has been identified at sequence level in several fish species, no study on piscine TFPI-2 has been documented. In this report, we identified and analyzed a TFPI-2 homologue, SoTFPI2, from red drum Sciaenops ocellatus. The open reading frame of SoTFPI2 is 681 bp, which encodes a 226-residue protein that shares 59.2-82.3% overall sequence identities with known fish TFPI-2. SoTFPI2 possesses three tandem Kunitz domains and is negatively charged at the N-terminus and positively charged at the C-terminus. Expression of SoTFPI2 was detected, in increasing order, in spleen, muscle, gill, brain, liver, kidney, blood, and heart. Bacterial challenge and lipopolysaccharide treatment significantly upregulated SoTFPI2 expression in kidney in time-dependent manners. Recombinant SoTFPI2 purified from Escherichia coli inhibits the proteolytic activity of trypsin and exhibits bactericidal effect on a fish pathogen. Take together, these results indicate that SoTFPI2 is a biologically active serine protease inhibitor with antibacterial property and is likely to play a role in anti-bacterial infection.

  19. Ornithine decarboxylase antizyme inhibitor 2 regulates intracellular vesicle trafficking

    SciTech Connect

    Kanerva, Kristiina; Maekitie, Laura T.; Baeck, Nils; Andersson, Leif C.

    2010-07-01

    Antizyme inhibitor 1 (AZIN1) and 2 (AZIN2) are proteins that activate ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis. Both AZINs release ODC from its inactive complex with antizyme (AZ), leading to formation of the catalytically active ODC. The ubiquitously expressed AZIN1 is involved in cell proliferation and transformation whereas the role of the recently found AZIN2 in cellular functions is unknown. Here we report the intracellular localization of AZIN2 and present novel evidence indicating that it acts as a regulator of vesicle trafficking. We used immunostaining to demonstrate that both endogenous and FLAG-tagged AZIN2 localize to post-Golgi vesicles of the secretory pathway. Immuno-electron microscopy revealed that the vesicles associate mainly with the trans-Golgi network (TGN). RNAi-mediated knockdown of AZIN2 or depletion of cellular polyamines caused selective fragmentation of the TGN and retarded the exocytotic release of vesicular stomatitis virus glycoprotein. Exogenous addition of polyamines normalized the morphological changes and reversed the inhibition of protein secretion. Our findings demonstrate that AZIN2 regulates the transport of secretory vesicles by locally activating ODC and polyamine biosynthesis.

  20. Platelets Contain Tissue Factor Pathway Inhibitor-2 Derived from Megakaryocytes and Inhibits Fibrinolysis*

    PubMed Central

    Vadivel, Kanagasabai; Ponnuraj, Sathya-Moorthy; Kumar, Yogesh; Zaiss, Anne K.; Bunce, Matthew W.; Camire, Rodney M.; Wu, Ling; Evseenko, Denis; Herschman, Harvey R.; Bajaj, Madhu S.; Bajaj, S. Paul

    2014-01-01

    Tissue factor pathway inhibitor-2 (TFPI-2) is a homologue of TFPI-1 and contains three Kunitz-type domains and a basic C terminus region. The N-terminal domain of TFPI-2 is the only inhibitory domain, and it inhibits plasma kallikrein, factor XIa, and plasmin. However, plasma TFPI-2 levels are negligible (≤20 pm) in the context of influencing clotting or fibrinolysis. Here, we report that platelets contain significant amounts of TFPI-2 derived from megakaryocytes. We employed RT-PCR, Western blotting, immunohistochemistry, and confocal microscopy to determine that platelets, MEG-01 megakaryoblastic cells, and bone marrow megakaryocytes contain TFPI-2. ELISA data reveal that TFPI-2 binds factor V (FV) and partially B-domain-deleted FV (FV-1033) with Kd ∼9 nm and binds FVa with Kd ∼100 nm. Steady state analysis of surface plasmon resonance data reveal that TFPI-2 and TFPI-1 bind FV-1033 with Kd ∼36–48 nm and bind FVa with Kd ∼252–456 nm. Further, TFPI-1 (but not TFPI-1161) competes with TFPI-2 in binding to FV. These data indicate that the C-terminal basic region of TFPI-2 is similar to that of TFPI-1 and plays a role in binding to the FV B-domain acidic region. Using pull-down assays and Western blots, we show that TFPI-2 is associated with platelet FV/FVa. TFPI-2 (∼7 nm) in plasma of women at the onset of labor is also, in part, associated with FV. Importantly, TFPI-2 in platelets and in plasma of pregnant women inhibits FXIa and tissue-type plasminogen activator-induced clot fibrinolysis. In conclusion, TFPI-2 in platelets from normal or pregnant subjects and in plasma from pregnant women binds FV/Va and regulates intrinsic coagulation and fibrinolysis. PMID:25262870

  1. Glycolysis inhibitor 2-deoxy-D-glucose suppresses carcinogen-induced rat hepatocarcinogenesis by restricting cancer cell metabolism.

    PubMed

    Wang, Zhaofa; Zhang, Liming; Zhang, Dong; Sun, Rongsheng; Wang, Qingyan; Liu, Xinyi

    2015-03-01

    The abnormal metabolism of cancer cells is a crucial feature of tumors and provides promising therapeutic targets for cancer treatments. Aerobic glycolysis in cancer cells, termed the Warburg effect, is a highlighted characteristic of cancer‑specific metabolism. However, the effect of glycolysis inhibition on hepatocarcinogenesis remains to be elucidated. In the present study, the effects of the glycolysis inhibitor 2‑deoxy‑D‑glucose (2‑DG) on the N‑diethylnitrosamine (DEN)‑induced rat hepatocarcinoma model and its underlying mechanisms were investigated. It was observed that 2‑DG significantly delayed hepatocarcinogenesis and effectively prolonged survival time in the DEN‑treated rats. The glycolysis inhibitor, 2‑DG prominently decreased cell proliferation and increased cell apoptosis in the DEN‑induced rat hepatoma and had no evident impact on the pericarcinomatous liver tissues. Further investigation revealed that 2‑DG resulted in a reduction of glycolysis products, the compensatory increase of hexokinase 2 expression and a decrease in 6‑phosphofructo‑2‑kinase, pyruvate kinase M2 and lactate dehydrogenase A expression in the hepatoma tissues. The inhibition of glycolysis further suppressed the tricarboxylic acid cycle, fatty acid and cholesterol biosynthesis and ATP production, while it promoted autophagic activation. In addition, the in vitro study demonstrated that hypoxia, an important factor in the tumor microenvironment, may assist in increasing 2‑DG‑induced inhibition of cell viability, cell cycle retardation and the decrease of colony formation ability in hepatoma cells. Taken together, the present results suggested that 2‑DG may inhibit hepatocarcinogenesis in the DEN‑treated rats via restricting cancer cell metabolism. This finding provides a promising measure in the prevention and treatment of hepatoma.

  2. Expression of tissue type and urokinase type plasminogen activators as well as plasminogen activator inhibitor type-1 and type-2 in human and rhesus monkey placenta

    PubMed Central

    HU, ZHAO-YUAN; LIU, YI-XUN; LIU, KUI; BYRNE, SIMON; NY, TOR; FENG, QIANG; OCKLEFORD, COLIN D.

    1999-01-01

    The distribution of mRNAs and antigens of tissue type (t) and urokinase type (u) plasminogen activators (PA) plus their corresponding inhibitors, type-1 (PAI-1) and type-2 (PAI-2) were studied in human and rhesus monkey placentae by in situ hybridisation and immunocytochemistry. Specific monkey cRNA and antibodies against human tPA, uPA, PAI-1 and PAI-2 were used as probes. The following results were obtained. (1) All the molecules tPA, uPA, PAI-1 and PAI-2 and their mRNAs were identified in the majority of the extravillous cytotrophoblast cells of the decidual layer between Rohr's and Nitabuch's striae and in cytotrophoblast cells of the chorionic plate, basal plate, intercotyledonary septae and cytotrophoblast cells of the chorionic villous tree. (2) Expression of uPA and PAI-2 was noted in villous trophoblast whereas tPA and PAI-1 were mainly concentrated where detachment from maternal tissue occurs. (3) No expression of tPA, uPA, PAI-1 and PAI-2 was observed in the basal plate endometrial stromal cells, chorionic plate connective tissue cells, septal endometrial stromal cells or villous core mesenchyme. (4) The distribution of probes observed following in situ hybridisation is generally consistent with the immunofluorescence pattern of the corresponding antigens and no significant interspecies differences were noted. It is possible that both decidual and extravillous trophoblast cells of placentae of human and rhesus monkey are capable of producing tPA, uPA, PAI-1 and PAI-2 to differing extents. Coordinated expression of these genes in the tissue may play an essential role in the maintenance of normal placentation and parturition. The differences in distribution we observed are consistent with the suggestion that coordinated expression of tPA and its inhibitor PAI-1 may play a key role in fibrinolytic activity in the early stages of placentation and separation of placenta from maternal tissue at term. On the other hand, uPA with its inhibitor PAI-2 appears

  3. Abnormal expression of plasminogen activator inhibitors in patients with gestational trophoblastic disease.

    PubMed Central

    Estellés, A.; Grancha, S.; Gilabert, J.; Thinnes, T.; Chirivella, M.; España, F.; Aznar, J.; Loskutoff, D. J.

    1996-01-01

    We previously reported significantly elevated levels of plasminogen activator inhibitor type 1 (PAI-1) in plasma and placenta from pregnant women with severe pre-eclampsia, and pre-eclampsia is a frequent problem in molar pregnancies. As increases in PAI-1 may contribute to the placental alterations that occur in pre-eclampsia, we have begun to investigate changes in PAI-1 as well as PAI-2 and several other components of the fibrinolytic system in patients with trophoblastic disease. Significant increases in plasma PAI-1 and decreases in plasma PAI-2 levels were observed in molar pregnancies when compared with the levels in normal pregnant women of similar gestational age. PAI-1 antigen levels also were increased, and PAI-2 levels were decreased in placenta from women with molar pregnancies compared with placenta obtained by spontaneous abortion. Immunohistochemical analysis revealed strong positive and specific staining of PAI-1 in trophoblastic epithelium in molar pregnancies and relatively weak staining of PAI-2. No association between the distribution of PAI-1 and vitronectin was found, and no specific signal for tissue type PA, urokinase type PA, tumor necrosis factor-alpha, or interleukin-1 was detected. In situ hybridization revealed an increase in PAI-1 but not PAI-2 mRNAs in placenta from molar pregnancies in comparison with placenta from abortions. These results demonstrate increased PAI-1 protein and mRNA in trophoblastic disease and suggest that localized elevated levels of PAI-1 may contribute to the hemostatic problems associated with this disorder. Images Figure 1 Figure 2 Figure 3 PMID:8863672

  4. Glycolytic inhibitors 2-deoxyglucose and 3-bromopyruvate synergize with photodynamic therapy respectively to inhibit cell migration.

    PubMed

    Feng, Xiaolan; Wang, Pan; Liu, Quanhong; Zhang, Ting; Mai, Bingjie; Wang, Xiaobing

    2015-06-01

    Most cancer cells have the specially increased glycolytic phenotype, which makes this pathway become an attractive therapeutic target. Although glycolytic inhibitor 2-deoxyglucose (2-DG) has been demonstrated to potentiate the cytotoxicity of photodynamic therapy (PDT), the impacts on cell migration after the combined treatment has never been reported yet. The present study aimed to analyze the influence of glycolytic inhibitors 2-DG and 3-bromopyruvate (3-BP) combined with Ce6-PDT on cell motility of Triple Negative Breast Cancer MDA-MB-231 cells. As determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium-bromide-Tetraz-olium (MTT) assay, more decreased cell viability was observed in 2-DG + PDT and 3-BP + PDT groups when compared with either monotherapy. Under optimal conditions, synergistic potentiation on cell membrane destruction and the decline of cell adhesion and cells migratory ability were observed in both 2-DG + PDT and 3-BP + PDT by electron microscope observation (SEM), wound healing and trans-well assays. Besides, serious microfilament network collapses as well as impairment of matrix metalloproteinases-9 (MMP-9) were notably improved after the combined treatments by immunofluorescent staining. These results suggest that 2-DG and 3-BP can both significantly potentiated Ce6-PDT efficacy of cell migration inhibition.

  5. Effects of tiaprofenic acid on plasminogen activators and inhibitors in human OA and RA synovium.

    PubMed

    Pelletier, J P; McCollum, R; Cloutier, J M; Martel-Pelletier, J

    1992-01-01

    The effect of therapeutic and pharmacological concentrations of tiaprofenic acid, a non-steroidal anti-inflammatory drug (NSAID), on the synthesis of the plasminogen activators, urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA), and the plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2), by human synovial membranes isolated from osteoarthritis (OA) and rheumatoid arthritis (RA) sufferers was evaluated. Both forms of plasminogen activator (PA) and PA inhibitor (PAI) were synthesized by the arthritic synovium. PAI-1 and PAI-2 were both synthesized in greater amounts than the plasminogen activators. Tiaprofenic acid induced a dose-dependent decrease in uPA synthesis in both OA and RA, particularly in OA synovium, but had no true effect on tPA. Tiaprofenic acid also exerted a suppressive effect on the synthesis of PAI-1 in both OA and RA synovial membranes, and on the release of PAI-2 in RA synovium. The results of this study indicate that a decrease in uPA synthesis may be one of the mechanisms by which tiaprofenic acid could exert its effects on the arthritic process. The suppressive action of tiaprofenic acid on PAI is not likely to have a significant impact on the balance of plasminogen activators and plasminogen activator inhibitors, as plasminogen activator inhibitors are synthesized in greater amounts than plasminogen activators.

  6. Identification of brain-specific angiogenesis inhibitor 2 as an interaction partner of glutaminase interacting protein

    SciTech Connect

    Zencir, Sevil; Ovee, Mohiuddin; Dobson, Melanie J.; Banerjee, Monimoy; Topcu, Zeki; Mohanty, Smita

    2011-08-12

    Highlights: {yields} Brain-specific angiogenesis inhibitor 2 (BAI2) is a new partner protein for GIP. {yields} BAI2 interaction with GIP was revealed by yeast two-hybrid assay. {yields} Binding of BAI2 to GIP was characterized by NMR, CD and fluorescence. {yields} BAI2 and GIP binding was mediated through the C-terminus of BAI2. -- Abstract: The vast majority of physiological processes in living cells are mediated by protein-protein interactions often specified by particular protein sequence motifs. PDZ domains, composed of 80-100 amino acid residues, are an important class of interaction motif. Among the PDZ-containing proteins, glutaminase interacting protein (GIP), also known as Tax Interacting Protein TIP-1, is unique in being composed almost exclusively of a single PDZ domain. GIP has important roles in cellular signaling, protein scaffolding and modulation of tumor growth and interacts with a number of physiological partner proteins, including Glutaminase L, {beta}-Catenin, FAS, HTLV-1 Tax, HPV16 E6, Rhotekin and Kir 2.3. To identify the network of proteins that interact with GIP, a human fetal brain cDNA library was screened using a yeast two-hybrid assay with GIP as bait. We identified brain-specific angiogenesis inhibitor 2 (BAI2), a member of the adhesion-G protein-coupled receptors (GPCRs), as a new partner of GIP. BAI2 is expressed primarily in neurons, further expanding GIP cellular functions. The interaction between GIP and the carboxy-terminus of BAI2 was characterized using fluorescence, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy assays. These biophysical analyses support the interaction identified in the yeast two-hybrid assay. This is the first study reporting BAI2 as an interaction partner of GIP.

  7. The diamondback moth, Plutella xylostella, specifically inactivates Mustard Trypsin Inhibitor 2 (MTI2) to overcome host plant defence.

    PubMed

    Yang, Limei; Fang, Zhiyuan; Dicke, Marcel; van Loon, Joop J A; Jongsma, Maarten A

    2009-01-01

    The mustard trypsin inhibitor family has so far only been described among cruciferous species which represent the host plants for the specialist diamondback moth (DBM), Plutella xylostella. The performance of a Dutch and Chinese strain of DBM was assessed on transgenic Arabidopsis expressing Mustard Trypsin Inhibitor 2 (MTI2) at a level of 84 microg/g fresh weight equivalent to 12 microM. No significant differences in larval mortality or development were found relative to the control. Trypsin activity in gut extracts from larvae feeding on either control or transgenic plants were titrated with MTI2 and SKTI (Soybean Kunitz Trypsin Inhibitor) to assess the basis of the insensitivity to MTI2. The specific trypsin activity per gut of larvae reared on MTI2 plants was not significantly higher compared to the control, and ca. 80% of trypsin activity could be inhibited by both inhibitors in both treatments, suggesting no specific induction of PI-insensitive activity in response to MTI2 in the diet. On the basis of the apparent equilibrium dissociation constant of Plutella trypsins for MTI2 (80 nM), the gut trypsin concentration (4.8 microM), and the MTI2 concentration in the leaves (12 microM) it was calculated that 99% of the gut trypsin activity sensitive to MTI2 should be inhibited in vivo, unless MTI2 was degraded. Indeed, we found that a pre-incubation of MTI2 and SKTI with gut proteases for 3 h resulted in complete loss of inhibitory activity of MTI2, but not of SKTI, at the concentration ratios found in planta. This process was enzymatic as it was inactivated by heat. Gut extracts of larvae reared on control or MTI2 leaves were equally well capable of this degradation indicating that the inactivating enzymes are constitutively expressed. In conclusion, it appears that the insensitivity of the diamondback moth to MTI2 can be sufficiently explained by the specific degradation of MTI2, thereby protecting itself against this protease inhibitor which is part of the

  8. Glycolytic inhibitor 2-deoxyglucose simultaneously targets cancer and endothelial cells to suppress neuroblastoma growth in mice.

    PubMed

    Huang, Chao-Cheng; Wang, Shuo-Yu; Lin, Li-Ling; Wang, Pei-Wen; Chen, Ting-Ya; Hsu, Wen-Ming; Lin, Tsu-Kung; Liou, Chia-Wei; Chuang, Jiin-Haur

    2015-10-01

    Neuroblastoma is characterized by a wide range of clinical manifestations and associated with poor prognosis when there is amplification of MYCN oncogene or high expression of Myc oncoproteins. In a previous in vitro study, we found that the glycolytic inhibitor 2-deoxyglucose (2DG) could suppress the growth of neuroblastoma cells, particularly in those with MYCN amplification. In this study, we established a mouse model of neuroblastoma xenografts with SK-N-DZ and SK-N-AS cells treated with 2DG by intraperitoneal injection twice a week for 3 weeks at 100 or 500 mg/kg body weight. We found that 2DG was effective in suppressing the growth of both MYCN-amplified SK-N-DZ and MYCN-non-amplified SK-N-AS neuroblastoma xenografts, which was associated with downregulation of HIF-1α, PDK1 and c-Myc, and a reduction in the number of tumor blood vessels. In vitro study showed that 2DG can suppress proliferation, cause apoptosis and reduce migration of murine endothelial cells, with inhibition of the formation of lamellipodia and filopodia and disorganization of F-actin filaments. The results suggest that 2DG might simultaneously target cancer cells and endothelial cells in the neuroblastoma xenografts in mice regardless of the status of MYCN amplification, providing a potential therapeutic opportunity to use 2DG or other glycolytic inhibitors for the treatment of patients with refractory neuroblastoma.

  9. Targeting inhibitor 2 of protein phosphatase 2A as a therapeutic strategy for prostate cancer treatment

    PubMed Central

    Mukhopadhyay, Archana; Tabanor, Kayann; Chaguturu, Rathnam; Aldrich, Jane V

    2013-01-01

    Inhibitor 2 of protein phosphatase 2A (I2PP2A), a biological inhibitor of the cellular serine/threonine protein phosphatase PP2A, is associated with numerous cellular processes that often lead to the formation and progression of cancer. In this study we hypothesized that targeting the inhibition of I2PP2A’s multiple functions in prostate cancer cells might prevent cancer progression. We have investigated the effect of the small chain C6-ceramide, known to be a bioactive tumor suppressor lipid, on I2PP2A function, thereby affecting c-Myc signaling and histone acetylation in cells. Our data indicated that C6-ceramide treatment of prostate cancer cells induces cell death in PC-3, DU145, and LNCaP cells, but not normal prostate epithelial cells. C6-ceramide was able to disrupt the association between PP2A and I2PP2A. C6-ceramide inhibits I2PP2A’s upregulation of c-Myc and downregulation of histone acetylation in prostate cancer cells. Our data indicated that targeting cancer related signaling pathways through I2PP2A using ceramide as an anti-I2PP2A agent could have beneficial effects as a therapeutic approach to prevent prostate cancer. PMID:24025258

  10. Identification and characterization of the unfolding transition state of chymotrypsin inhibitor 2 by molecular dynamics simulations.

    PubMed

    Li, A; Daggett, V

    1996-03-29

    Temperature-induced unfolding of chymotrypsin inhibitor 2 (CI2) in water has been investigated using molecular dynamics simulations. One simulation (2.2 ns) has been analyzed in detail and three additional simulations (each > or = 1 ns) were performed to check the generality of the results. Concurrent loss of secondary and tertiary structure during unfolding was observed in all the simulations. For each simulation, the major transition state of unfolding was identified based on conformational analysis of protein structures along the unfolding trajectory. The transition state has a considerably weakened hydrophobic core and disrupted secondary structure. Nevertheless, the overall structure of the transition state is closer to the native state than to the unfolded state. The disruption of the hydrophobic core appears to be rate limiting. However, other energy barriers have to be overcome before reaching the major transition state. A method is described to quantitatively compare the structure of the simulated transition state with that characterized by protein engineering experiments. Good agreement with the experimental data is obtained for all four transition state models (the correlation coefficient R = 0.80 to 0.93) and the average over all four models gives the best correlation (R = 0.94). These simulations provide the first comprehensive atomic-level view of what the unfolding transition state of C12 may look like.

  11. Molecular Investigations of the Structure and Function of the Protein Phosphatase 1-Spinophilin-Inhibitor 2 Heterotrimeric Complex

    SciTech Connect

    Dancheck, B.; Allaire, M.; Ragusa, M.J.; Nairn, A.C.; Page, R.; Peti, W.

    2011-01-06

    Regulation of the major Ser/Thr phosphatase protein phosphatase 1 (PP1) is controlled by a diverse array of targeting and inhibitor proteins. Though many PP1 regulatory proteins share at least one PP1 binding motif, usually the RVxF motif, it was recently discovered that certain pairs of targeting and inhibitor proteins bind PP1 simultaneously to form PP1 heterotrimeric complexes. To date, structural information for these heterotrimeric complexes and, in turn, how they direct PP1 activity is entirely lacking. Using a combination of NMR spectroscopy, biochemistry, and small-angle X-ray scattering (SAXS), we show that major structural rearrangements in both spinophilin (targeting) and inhibitor 2 (I-2, inhibitor) are essential for the formation of the heterotrimeric PP1-spinophilin-I-2 (PSI) complex. The RVxF motif of I-2 is released from PP1 during the formation of PSI, making the less prevalent SILK motif of I-2 essential for complex stability. The release of the I-2 RVxF motif allows for enhanced flexibility of both I-2 and spinophilin in the heterotrimeric complex. In addition, we used inductively coupled plasma atomic emission spectroscopy to show that PP1 contains two metals in both heterodimeric complexes (PP1-spinophilin and PP1-I-2) and PSI, demonstrating that PSI retains the biochemical characteristics of the PP1-I-2 holoenzyme. Finally, we combined the NMR and biochemical data with SAXS and molecular dynamics simulations to generate a structural model of the full heterotrimeric PSI complex. Collectively, these data reveal the molecular events that enable PP1 heterotrimeric complexes to exploit both the targeting and inhibitory features of the PP1-regulatory proteins to form multifunctional PP1 holoenzymes.

  12. Plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of melanocytic tumor progression.

    PubMed Central

    de Vries, T. J.; Quax, P. H.; Denijn, M.; Verrijp, K. N.; Verheijen, J. H.; Verspaget, H. W.; Weidle, U. H.; Ruiter, D. J.; van Muijen, G. N.

    1994-01-01

    Degradation of the extracellular matrix and other tissue barriers by proteases like plasminogen activators (PAs) is a prerequisite for neoplastic growth and metastasis. Recently, we reported that highly metastatic behavior of human melanoma cells in nude mice correlates with urokinase-type PA (u-PA) expression and activity and with PA inhibitor type 1 and 2 (PAI-1, PAI-2) expression. Here we report on the occurrence of components of the PA system in the various stages of human melanoma tumor progression in situ. We studied the protein distribution on freshly frozen lesions of common nevocellular nevi (n = 25), dysplastic (= atypical) nevi (n = 16), early primary melanomas (n = 8), advanced primary melanomas (n = 11), and melanoma metastases (n = 17). Tissue-type PA was present in endothelial cells in all lesions, whereas in metastases it could be detected in tumor cells in a minority of the lesions. u-PA, its receptor, PAI-1, and PAI-2 could not be detected in benign and in early stages but appeared frequently in advanced primary melanoma and melanoma metastasis lesions. u-PA was detected in stromal cells and in tumor cells at the invasive front, the u-PA receptor and PAI-2 in tumor cells, and PAI-1 in the extracellular matrix surrounding tumor cells. Localization of the corresponding messenger RNAs and enzyme activities revealed a similar distribution. We conclude that plasminogen activation is a late event in melanoma tumor progression. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8291613

  13. Phosphatase inhibitor 2 promotes acetylation of tubulin in the primary cilium of human retinal epithelial cells

    PubMed Central

    Wang, Weiping; Brautigan, David L

    2008-01-01

    Background Primary cilia are flagella-like projections from the centriole of mammalian cells that have a key role in cell signaling. Human diseases are linked to defects in primary cilia. Microtubules make up the axoneme of cilia and are selectively acetylated and this is thought to contribute to the stability of the structure. However, mechanisms to regulate tubulin acetylation in cilia are poorly understood. Results Endogenous phosphatase inhibitor-2 (I-2) was found concentrated in cilia of human epithelial cells, and was localized to cilia early in the process of formation, prior to the full acetylation of microtubules. Knockdown of I-2 by siRNA significantly reduced the acetylation of microtubules in cilia, without a net decrease in whole cell tubulin acetylation. There was a reduction in the percentage of I-2 knockdown cells with a primary cilium, but no apparent alteration in the cilium length, suggesting no change in microtubule-based transport processes. Inhibition of either histone deacetylases with trichostatin A, or protein phosphatase-1 with calyculin A in I-2 knockdown cells partially rescued the acetylation of microtubules in cilia and the percentage of cells with a primary cilium. Conclusion The regulatory protein I-2 localizes to the primary cilium where it affects both Ser/Thr phosphorylation and is required for full tubulin acetylation. Rescue of tubulin acetylation in I-2 knockdown cells by different chemical inhibitors shows that deacetylases and phosphatases are functionally interconnected to regulate microtubules. As a multifunctional protein, I-2 may link cell cycle progression to structure and stability of the primary cilium. PMID:19036150

  14. Effect of ethanol concentrations on temperature driven structural changes of chymotrypsin inhibitor 2.

    PubMed

    Mohanta, Dayanidhi; Jana, Madhurima

    2016-04-28

    A series of atomistic molecular dynamics (MD) simulations of a small enzymatic protein Chymotrypsin Inhibitor 2 (CI2) in water-ethanol mixed solutions were carried out to explore the underlying mechanism of ethanol driven conformational changes of the protein. Efforts have been made to probe the influence of ethanol concentrations ranging from 0% to 75% (v/v) at ambient condition (300 K (T1)) and at elevated temperatures (375 K (T2) and 450 K (T3)) to investigate the temperature induced conformational changes of the protein further. Our study showed that the effect of varying ethanol concentrations on protein's structure is almost insignificant at T1 and T2 temperatures whereas at T3 temperature, partial unfolding of CI2 in 10% ethanol solution followed by full unfolding of the protein at ethanol concentrations above 25% occurs. However, interestingly, at T3 temperature CI2's native structure was found to be retained in pure water (0% ethanol solution) indicating that the cosolvent ethanol do play an important role in thermal denaturation of CI2. Such observations were quantified in the light of root-mean-square deviations (RMSDs) and radius of gyration. Although higher RMSD values of β-sheet over α-helix indicate complete destruction of the β-structure of CI2 at high ethanol concentrations, the associated time scale showed that the faster melting of α-helix happens over β-sheet. Around 60%-80% of initial native contacts of the protein were found broken with the separation of hydrophobic core consisting eleven residues at ethanol concentrations greater than 25%. This leads protein to expand with the increase in solvent accessible surface area. The interactions between protein and solvent molecules showed that protein's solvation shell preferred to accommodate ethanol molecules as compared to water thereby excluded water molecules from CI2's surface. Further, concentration dependent differential self-aggregation behavior of ethanol is likely to regulate the

  15. Effect of ethanol concentrations on temperature driven structural changes of chymotrypsin inhibitor 2

    NASA Astrophysics Data System (ADS)

    Mohanta, Dayanidhi; Jana, Madhurima

    2016-04-01

    A series of atomistic molecular dynamics (MD) simulations of a small enzymatic protein Chymotrypsin Inhibitor 2 (CI2) in water-ethanol mixed solutions were carried out to explore the underlying mechanism of ethanol driven conformational changes of the protein. Efforts have been made to probe the influence of ethanol concentrations ranging from 0% to 75% (v/v) at ambient condition (300 K (T1)) and at elevated temperatures (375 K (T2) and 450 K (T3)) to investigate the temperature induced conformational changes of the protein further. Our study showed that the effect of varying ethanol concentrations on protein's structure is almost insignificant at T1 and T2 temperatures whereas at T3 temperature, partial unfolding of CI2 in 10% ethanol solution followed by full unfolding of the protein at ethanol concentrations above 25% occurs. However, interestingly, at T3 temperature CI2's native structure was found to be retained in pure water (0% ethanol solution) indicating that the cosolvent ethanol do play an important role in thermal denaturation of CI2. Such observations were quantified in the light of root-mean-square deviations (RMSDs) and radius of gyration. Although higher RMSD values of β-sheet over α-helix indicate complete destruction of the β-structure of CI2 at high ethanol concentrations, the associated time scale showed that the faster melting of α-helix happens over β-sheet. Around 60%-80% of initial native contacts of the protein were found broken with the separation of hydrophobic core consisting eleven residues at ethanol concentrations greater than 25%. This leads protein to expand with the increase in solvent accessible surface area. The interactions between protein and solvent molecules showed that protein's solvation shell preferred to accommodate ethanol molecules as compared to water thereby excluded water molecules from CI2's surface. Further, concentration dependent differential self-aggregation behavior of ethanol is likely to regulate the

  16. Chronic Oral Administration of the Arginase Inhibitor 2(S)-amino-6-boronohexanoic Acid (ABH) Improves Erectile Function in Aged Rats

    PubMed Central

    Segal, Robert; Hannan, Johanna L.; Liu, Xiaopu; Kutlu, Omer; Burnett, Arthur L.; Champion, Hunter C.; Kim, Jae Hyung; Steppan, Jochen; Berkowitz, Dan E.; Bivalacqua, Trinity J.

    2014-01-01

    Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH) has been shown to improve endothelial dysfunction in aged rats. The objective of this study was to assess whether chronic oral ABH administration affects cavernosal erectile function. Rats were divided into 4 groups: young control, young treated with arginase inhibitor, aged control, and aged treated with arginase inhibitor. Arginase activity was measured and presented as a proportion of young untreated rats. In vivo erectile responses to cavernous nerve stimulation were measured in all cohorts. The cavernous nerve was stimulated with a graded electrical stimulus, and the intracavernosal/ mean arterial pressure ratios and total intracavernosal pressure were recorded. Arginase activity was elevated in the aged rats compared with young controls; however, arginase activity was significantly decreased in aged rats treated with ABH. With the addition of ABH, erectile responses improved in the aged rats (P < .05). Oral inhibition of arginase with ABH results in improved erectile function in aged rats, resulting in erectile hemodynamics similar to young rats. This represents the first documentation of systemic arginase inhibition positively affecting corporal cavernosal function. PMID:22492840

  17. Chronic oral administration of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) improves erectile function in aged rats.

    PubMed

    Segal, Robert; Hannan, Johanna L; Liu, Xiaopu; Kutlu, Omer; Burnett, Arthur L; Champion, Hunter C; Kim, Jae Hyung; Steppan, Jochen; Berkowitz, Dan E; Bivalacqua, Trinity J

    2012-01-01

    Arginase expression and activity have been noted to be heightened in conditions associated with erectile dysfunction, including aging. Previously, arginase inhibition by chronic administration of the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH) has been shown to improve endothelial dysfunction in aged rats. The objective of this study was to assess whether chronic oral ABH administration affects cavernosal erectile function. Rats were divided into 4 groups: young control, young treated with arginase inhibitor, aged control, and aged treated with arginase inhibitor. Arginase activity was measured and presented as a proportion of young untreated rats. In vivo erectile responses to cavernous nerve stimulation were measured in all cohorts. The cavernous nerve was stimulated with a graded electrical stimulus, and the intracavernosal/mean arterial pressure ratios and total intracavernosal pressure were recorded. Arginase activity was elevated in the aged rats compared with young controls; however, arginase activity was significantly decreased in aged rats treated with ABH. With the addition of ABH, erectile responses improved in the aged rats (P < .05). Oral inhibition of arginase with ABH results in improved erectile function in aged rats, resulting in erectile hemodynamics similar to young rats. This represents the first documentation of systemic arginase inhibition positively affecting corporal cavernosal function.

  18. Myocyte contractility can be maintained by storing cells with the myosin ATPase inhibitor 2,3 butanedione monoxime

    PubMed Central

    Chung, Charles S; Mechas, Charles; Campbell, Kenneth S

    2015-01-01

    Isolated intact myocytes can be used to investigate contractile mechanisms and to screen new therapeutic compounds. These experiments typically require euthanizing an animal and isolating fresh cells each day or analyzing cultured myocytes, which quickly lose their rod-shaped morphology. Recent data suggest that the viability of canine myocytes can be prolonged using low temperature and N-benzyl-p-toluene sulfonamide (an inhibitor of skeletal myosin ATPase). We performed similar studies in rat myocytes in order to test whether the cardiac myosin ATPase inhibitors 2,3-Butanedione monoxime (BDM) and blebbistatin help to maintain cell-level function over multiple days. Myocytes were isolated from rats and separated into batches that were stored at 4°C in a HEPES-buffered solution that contained 0.5 mmol L−1 Ca2+ and (1) no myosin ATPase inhibitors; (2) 10 mmol L−1 BDM; or (3) 3 μmol L−1 blebbistatin. Functional viability of myocytes was assessed up to 3 days after the isolation by measuring calcium transients and unloaded shortening profiles induced by electrical stimuli in inhibitor-free Tyrode's solution. Cells stored without myosin ATPase inhibitors had altered morphology (fewer rod-shaped cells, shorter diastolic sarcomere lengths, and membrane blebbing) and were not viable for contractile assays after 24 h. Cells stored in BDM maintained morphology and contractile function for 48 h. Storage in blebbistatin maintained cell morphology for 72 h but inhibited contractility. These data show that storing cells with myosin ATPase inhibitors can extend the viability of myocytes that will be used for functional assays. This may help to refine and reduce the use of animals in experiments. PMID:26116551

  19. Selective CNS Uptake of the GCP-II Inhibitor 2-PMPA following Intranasal Administration

    PubMed Central

    Rais, Rana; Wozniak, Krystyna; Wu, Ying; Niwa, Minae; Stathis, Marigo; Alt, Jesse; Giroux, Marc; Sawa, Akira; Rojas, Camilo; Slusher, Barbara S.

    2015-01-01

    Glutamate carboxypeptidase II (GCP-II) is a brain metallopeptidase that hydrolyzes the abundant neuropeptide N-acetyl-aspartyl-glutamate (NAAG) to NAA and glutamate. Small molecule GCP-II inhibitors increase brain NAAG, which activates mGluR3, decreases glutamate, and provide therapeutic utility in a variety of preclinical models of neurodegenerative diseases wherein excess glutamate is presumed pathogenic. Unfortunately no GCP-II inhibitor has advanced clinically, largely due to their highly polar nature resulting in insufficient oral bioavailability and limited brain penetration. Herein we report a non-invasive route for delivery of GCP-II inhibitors to the brain via intranasal (i.n.) administration. Three structurally distinct classes of GCP-II inhibitors were evaluated including DCMC (urea-based), 2-MPPA (thiol-based) and 2-PMPA (phosphonate-based). While all showed some brain penetration following i.n. administration, 2-PMPA exhibited the highest levels and was chosen for further evaluation. Compared to intraperitoneal (i.p.) administration, equivalent doses of i.n. administered 2-PMPA resulted in similar plasma exposures (AUC0-t, i.n./AUC0-t, i.p. = 1.0) but dramatically enhanced brain exposures in the olfactory bulb (AUC0-t, i.n./AUC0-t, i.p. = 67), cortex (AUC0-t, i.n./AUC0-t, i.p. = 46) and cerebellum (AUC0-t, i.n./AUC0-t, i.p. = 6.3). Following i.n. administration, the brain tissue to plasma ratio based on AUC0-t in the olfactory bulb, cortex, and cerebellum were 1.49, 0.71 and 0.10, respectively, compared to an i.p. brain tissue to plasma ratio of less than 0.02 in all areas. Furthermore, i.n. administration of 2-PMPA resulted in complete inhibition of brain GCP-II enzymatic activity ex-vivo confirming target engagement. Lastly, because the rodent nasal system is not similar to humans, we evaluated i.n. 2-PMPA also in a non-human primate. We report that i.n. 2-PMPA provides selective brain delivery with micromolar concentrations. These studies support

  20. Structural investigation of HIV-1 nonnucleoside reverse transcriptase inhibitors: 2-Aryl-substituted benzimidazoles

    NASA Astrophysics Data System (ADS)

    Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.

    2009-11-01

    Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) is one of the most destructive epidemics in history. Inhibitors of HIV enzymes are the main targets to develop drugs against that disease. Nonnucleoside reverse transcriptase inhibitors of HIV-1 (NNRTIs) are potentially effective and nontoxic. Structural studies provide information necessary to design more active compounds. The crystal structures of four NNRTI derivatives of 2-aryl-substituted N-benzyl-benzimidazole are presented here. Analysis of the geometrical parameters shows that the structures of the investigated inhibitors are rigid. The important geometrical parameter is the dihedral angle between the planes of the π-electron systems of the benzymidazole and benzyl moieties. The values of these dihedral angles are in a narrow range for all investigated inhibitors. There is no significant difference between the structure of the free inhibitor and the inhibitor in the complex with RT HIV-1. X-ray structures of the investigated inhibitors are a good basis for modeling enzyme-inhibitor interactions in rational drug design.

  1. Cytoplasmic Retention of Protein Phosphatase 2A Inhibitor 2 (I2PP2A) Induces Alzheimer-like Abnormal Hyperphosphorylation of Tau*

    PubMed Central

    Arif, Mohammad; Wei, Jianshe; Zhang, Qi; Liu, Fei; Basurto-Islas, Gustavo; Grundke-Iqbal, Inge; Iqbal, Khalid

    2014-01-01

    Abnormal hyperphosphorylation of Tau leads to the formation of neurofibrillary tangles, a hallmark of Alzheimer disease (AD), and related tauopathies. The phosphorylation of Tau is regulated by protein phosphatase 2A (PP2A), which in turn is modulated by endogenous inhibitor 2 (I2PP2A). In AD brain, I2PP2A is translocated from neuronal nucleus to cytoplasm, where it inhibits PP2A activity and promotes abnormal phosphorylation of Tau. Here we describe the identification of a potential nuclear localization signal (NLS) in the C-terminal region of I2PP2A containing a conserved basic motif, 179RKR181, which is sufficient for directing its nuclear localization. The current study further presents an inducible cell model (Tet-Off system) of AD-type abnormal hyperphosphorylation of Tau by expressing I2PP2A in which the NLS was inactivated by 179RKR181 → AAA along with 168KR169 → AA mutations. In this model, the mutant NLS (mNLS)-I2PP2A (I2PP2AAA-AAA) was retained in the cell cytoplasm, where it physically interacted with PP2A and inhibited its activity. Inhibition of PP2A was associated with the abnormal hyperphosphorylation of Tau, which resulted in microtubule network instability and neurite outgrowth impairment. Expression of mNLS-I2PP2A activated CAMKII and GSK-3β, which are Tau kinases regulated by PP2A. The immunoprecipitation experiments showed the direct interaction of I2PP2A with PP2A and GSK-3β but not with CAMKII. Thus, the cell model provides insights into the nature of the potential NLS and the mechanistic relationship between I2PP2A-induced inhibition of PP2A and hyperphosphorylation of Tau that can be utilized to develop drugs preventing Tau pathology. PMID:25128526

  2. Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma

    PubMed Central

    Arakawa, Noriaki; Kobayashi, Hiroshi; Yonemoto, Naohiro; Masuishi, Yusuke; Ino, Yoko; Shigetomi, Hiroshi; Furukawa, Naoto; Ohtake, Norihisa; Miyagi, Yohei; Hirahara, Fumiki; Hirano, Hisashi; Miyagi, Etsuko

    2016-01-01

    Background There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC. Methods Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set. Results The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set. Conclusions TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC. PMID:27798689

  3. Expression of plasminogen activator-related genes in the adipose tissue of lactating dairy sheep in the early post-weaning period.

    PubMed

    Theodorou, G; Lampidonis, A D; Laliotis, G P; Bizelis, I; Politis, I

    2012-06-01

    There is growing evidence that plasminogen activator inhibitor type 1 (PAI-1) is expressed in adipose tissue and its expression is implicated in inflammation that accompanies obesity-associated diseases. The physiological role of other genes implicated in the plasminogen-activating cascade such as urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR) and plasminogen activator inhibitor type 2 (PAI-2) in ovine adipose tissue remains unknown. The objective of this study was to examine the changes in the expression of four plasminogen activator (PA)-related genes during the early post-weaning period in dairy ewes. A total of 21 subcutaneous adipose tissue samples were obtained from seven lactating dairy ewes of the Chios breed at weeks 1, 2 and 4 after weaning. Results indicated that expression of all PA-related genes was detected in most of the samples examined. Greatest expression of u-PAR corresponded to highest (week 1), while greatest expression of PAI-2 corresponded to lowest (week 4) rate of lipolysis, as indicated by the expression of hormone-sensitive lipase, in the ovine adipose tissue. There were no significant differences in the expression of the other two PA-related genes (u-PA, PAI-1) throughout the experimental period. Plasminogen activator-related genes are not expressed in a coordinated manner in the adipose tissue of lactating dairy sheep in the early post-weaning period. In conclusion, adipose tissue mobilization is correlated with highest expression of u-PAR and lowest expression of PAI-2.

  4. Hypersensitivity of Aryl Hydrocarbon Receptor-Deficient Mice to Lipopolysaccharide-Induced Septic Shock▿ †

    PubMed Central

    Sekine, Hiroki; Mimura, Junsei; Oshima, Motohiko; Okawa, Hiromi; Kanno, Jun; Igarashi, Katsuhide; Gonzalez, Frank J.; Ikuta, Togo; Kawajiri, Kaname; Fujii-Kuriyama, Yoshiaki

    2009-01-01

    Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is known to mediate a wide variety of pharmacological and toxicological effects caused by polycyclic aromatic hydrocarbons. Recent studies have revealed that AhR is involved in the normal development and homeostasis of many organs. Here, we demonstrate that AhR knockout (AhR KO) mice are hypersensitive to lipopolysaccharide (LPS)-induced septic shock, mainly due to the dysfunction of their macrophages. In response to LPS, bone marrow-derived macrophages (BMDM) of AhR KO mice secreted an enhanced amount of interleukin-1β (IL-1β). Since the enhanced IL-1β secretion was suppressed by supplementing Plasminogen activator inhibitor-2 (Pai-2) expression through transduction with Pai-2-expressing adenoviruses, reduced Pai-2 expression could be a cause of the increased IL-1β secretion by AhR KO mouse BMDM. Analysis of gene expression revealed that AhR directly regulates the expression of Pai-2 through a mechanism involving NF-κB but not AhR nuclear translocator (Arnt), in an LPS-dependent manner. Together with the result that administration of the AhR ligand 3-methylcholanthrene partially protected mice with wild-type AhR from endotoxin-induced death, these results raise the possibility that an appropriate AhR ligand may be useful for treating patients with inflammatory disorders. PMID:19822660

  5. Crystal structure of the cysteine protease inhibitor 2 from Entamoeba histolytica: Functional convergence of a common protein fold

    SciTech Connect

    Casados-Vázquez, Luz E.; Lara-González, Samuel; Brieb, Luis G.

    2012-04-18

    Cysteine proteases (CP) are key pathogenesis and virulence determinants of protozoan parasites. Entamoeba histolytica contains at least 50 cysteine proteases; however, only three (EhCP1, EhCP2 and EhCP5) are responsible for approximately 90% of the cysteine protease activity in this parasite. CPs are expressed as inactive zymogens. Because the processed proteases are potentially cytotoxic, protozoan parasites have developed mechanisms to regulate their activity. Inhibitors of cysteine proteases (ICP) of the chagasin-like inhibitor family (MEROPS family I42) were recently identified in bacteria and protozoan parasites. E. histolytica contains two ICP-encoding genes of the chagasin-like inhibitor family. EhICP1 localizes to the cytosol, whereas EhICP2 is targeted to phagosomes. Herein, we report two crystal structures of EhICP2. The overall structure of EhICP2 consists of eight {beta}-strands and closely resembles the immunoglobulin fold. A comparison between the two crystal forms of EhICP2 indicates that the conserved BC, DE and FG loops form a flexible wedge that may block the active site of CPs. The positively charged surface of the wedge-forming loops in EhICP2 contrasts with the neutral surface of the wedge-forming loops in chagasin. We postulate that the flexibility and positive charge observed in the DE and FG loops of EhICP2 may be important to facilitate the initial binding of this inhibitor to the battery of CPs present in E. histolytica.

  6. Broad-range TRP channel inhibitors (2-APB, flufenamic acid, SKF-96365) affect differently contraction of resistance and conduit femoral arteries of rat.

    PubMed

    Bencze, Michal; Behuliak, Michal; Vavřínová, Anna; Zicha, Josef

    2015-10-15

    Transient receptor potential (TRP) channels are proposed to contribute to membrane depolarization and Ca2+ influx into vascular smooth muscle (VSM) cells. Our aim was to study the effects of widely used broad-range TRP channel inhibitors--2-aminoethoxydiphenyl borate (2-APB), flufenamic acid (FFA) and SKF-96365--on the contraction of freshly isolated small and large arteries. Endothelium-denuded resistance (≈250 µm) and conduit (≈1000 µm) femoral arteries were isolated from adult Wistar rats and mounted in wire myograph. The effects of the above mentioned TRP channel inhibitors and voltage-dependent calcium channel inhibitor nifedipine were studied on arterial contractions induced by phenylephrine, U-46619 or K+. Phenylephrine-induced contractions were also studied in the absence of extracellular Na+. mRNA expression of particular canonical and melastatin TRP channel subunits in femoral vascular bed was determined. TRP channel inhibitors attenuated K+-induced contraction less than nifedipine. Phenylephrine-induced contraction was more influenced by 2-APB in resistance arteries, while FFA completely prevented U-46619-induced contraction in both sizes of arteries. The absence of extracellular Na+ prevented the inhibitory effects of 2-APB, but not those of FFA. The observed effects of broad-range TRP channel inhibitors, which were dependent on the size of the artery, confirmed the involvement of TRP channels in agonist-induced contractions. The inhibitory effects of 2-APB (but not those of FFA or SKF-96365) were dependent on the presence of extracellular Na+.

  7. Structural analysis of a holoenzyme complex of mouse dihydrofolate reductase with NADPH and a ternary complex with the potent and selective inhibitor 2, 4-diamino-6-(2′-hydroxydibenz[b, f]azepin-5-yl)methylpteridine

    SciTech Connect

    Cody, Vivian; Pace, Jim; Rosowsky, Andre

    2008-09-01

    The structures of mouse DHFR holo enzyme and a ternary complex with NADPH and a potent inhibitor are described. It has been shown that 2, 4-diamino-6-arylmethylpteridines and 2, 4-diamino-5-arylmethylpyrimidines containing an O-carboxylalkyloxy group in the aryl moiety are potent and selective inhibitors of the dihydrofolate reductase (DHFR) from opportunistic pathogens such as Pneumocystis carinii, the causative agent of Pneumocystis pneumonia in HIV/AIDS patients. In order to understand the structure–activity profile observed for a series of substituted dibenz[b, f]azepine antifolates, the crystal structures of mouse DHFR (mDHFR; a mammalian homologue) holo and ternary complexes with NADPH and the inhibitor 2, 4-diamino-6-(2′-hydroxydibenz[b, f]azepin-5-yl)methylpteridine were determined to 1.9 and 1.4 Å resolution, respectively. Structural data for the ternary complex with the potent O-(3-carboxypropyl) inhibitor PT684 revealed no electron density for the O-carboxylalkyloxy side chain. The side chain was either cleaved or completely disordered. The electron density fitted the less potent hydroxyl compound PT684a. Additionally, cocrystallization of mDHFR with NADPH and the less potent 2′-(4-carboxybenzyl) inhibitor PT682 showed no electron density for the inhibitor and resulted in the first report of a holoenzyme complex despite several attempts at crystallization of a ternary complex. Modeling data of PT682 in the active site of mDHFR and P. carinii DHFR (pcDHFR) indicate that binding would require ligand-induced conformational changes to the enzyme for the inhibitor to fit into the active site or that the inhibitor side chain would have to adopt an alternative binding mode to that observed for other carboxyalkyloxy inhibitors. These data also show that the mDHFR complexes have a decreased active-site volume as reflected in the relative shift of helix C (residues 59–64) by 0.6 Å compared with pcDHFR ternary complexes. These data are consistent with the

  8. Structural Analysis of a Holoenzyme Complex of Mouse Dihydrofolate Reductase With NADPH And a Ternary Complex With the Potent And Selective Inhibitor 2,4-Diamino-6-(2'-Hydroxydibenz[b,F]azepin-5-YI)

    SciTech Connect

    Cody, V.; Pace, J.; Rosowsky, A.

    2009-05-12

    It has been shown that 2,4-diamino-6-arylmethylpteridines and 2,4-diamino-5-arylmethylpyrimidines containing an O-carboxylalkyloxy group in the aryl moiety are potent and selective inhibitors of the dihydrofolate reductase (DHFR) from opportunistic pathogens such as Pneumocystis carinii, the causative agent of Pneumocystis pneumonia in HIV/AIDS patients. In order to understand the structure-activity profile observed for a series of substituted dibenz[b,f]azepine antifolates, the crystal structures of mouse DHFR (mDHFR; a mammalian homologue) holo and ternary complexes with NADPH and the inhibitor 2,4-diamino-6-(2{prime}-hydroxydibenz[b,f]azepin-5-yl)methylpteridine were determined to 1.9 and 1.4 A resolution, respectively. Structural data for the ternary complex with the potent O-(3-carboxypropyl) inhibitor PT684 revealed no electron density for the O-carboxylalkyloxy side chain. The side chain was either cleaved or completely disordered. The electron density fitted the less potent hydroxyl compound PT684a. Additionally, cocrystallization of mDHFR with NADPH and the less potent 2{prime}-(4-carboxybenzyl) inhibitor PT682 showed no electron density for the inhibitor and resulted in the first report of a holoenzyme complex despite several attempts at crystallization of a ternary complex. Modeling data of PT682 in the active site of mDHFR and P. carinii DHFR (pcDHFR) indicate that binding would require ligand-induced conformational changes to the enzyme for the inhibitor to fit into the active site or that the inhibitor side chain would have to adopt an alternative binding mode to that observed for other carboxyalkyloxy inhibitors. These data also show that the mDHFR complexes have a decreased active-site volume as reflected in the relative shift of helix C (residues 59-64) by 0.6 A compared with pcDHFR ternary complexes. These data are consistent with the greater inhibitory potency against pcDHFR.

  9. Chronic Dietary Administration of the Glycolytic Inhibitor 2-Deoxy-D-Glucose (2-DG) Inhibits the Growth of Implanted Ehrlich’s Ascites Tumor in Mice

    PubMed Central

    Singh, Saurabh; Pandey, Sanjay; Bhatt, Anant Narayan; Chaudhary, Richa; Bhuria, Vikas; Kalra, Namita; Soni, Ravi; Roy, Bal Gangadhar; Saluja, Daman; Dwarakanath, Bilikere S.

    2015-01-01

    Background Dietary energy restriction (DER) has been well established as a potent anticancer strategy. Non-adoption of restricted diet for an extended period has limited its practical implementation in humans with a compelling need to develop agents that mimic effects similar to DER, without reduction in actual dietary intake. Glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has recently been shown to possess potential as an energy restriction mimetic agent (ERMA). In the present study we evaluated the effect of dietary 2-DG administration on a mouse tumor model, with a focus on several potential mechanisms that may account for the inhibition of tumorigenesis. Methodology/Principal Findings Swiss albino strain ‘A’ mice were administered with 0.2% and 0.4% w/v 2-DG in drinking water for 3 months prior to tumor implantation (Ehrlich’s ascites carcinoma; EAC) and continued till the termination of the study with no adverse effects on general physiology and animal growth. Dietary 2-DG significantly reduced the tumor incidence, delayed the onset, and compromised the tumor growth along with enhanced survival. We observed reduced blood glucose and serum insulin levels along with decreased proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine positive (BrdU+) tumor cells in 2-DG fed mice. Also, reduced levels of certain key players of metabolic pathways such as phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt and hypoxia inducible factor-1 alpha (HIF-1α) were also noted in tumors of 2-DG fed mice. Further, decrease in CD4+/CD8+ ratio and T-regulatory cells observed in 2-DG fed mice suggested enhanced antitumor immunity and T cell effector function. Conclusion/Significance These results strongly suggest that dietary 2-DG administration in mice, at doses easily achievable in humans, suitably modulates several pleotrophic factors mimicking DER and inhibits tumorigenesis, emphasizing the use of ERMAs as a promising cancer preventive strategy. PMID

  10. Determination of three-dimensional structures of proteins by simulated annealing with interproton distance restraints. Application to crambin, potato carboxypeptidase inhibitor and barley serine proteinase inhibitor 2.

    PubMed

    Nilges, M; Gronenborn, A M; Brünger, A T; Clore, G M

    1988-04-01

    An automated method, based on the principle of simulated annealing, is presented for determining the three-dimensional structures of proteins on the basis of short (less than 5 A) interproton distance data derived from nuclear Overhauser enhancement (NOE) measurements. The method makes use of Newton's equations of motion to increase temporarily the temperature of the system in order to search for the global minimum region of a target function comprising purely geometric restraints. These consist of interproton distances supplemented by bond lengths, bond angles, planes and soft van der Waals repulsion terms. The latter replace the dihedral, van der Waals, electrostatic and hydrogen-bonding potentials of the empirical energy function used in molecular dynamics simulations. The method presented involves the implementation of a number of innovations over our previous restrained molecular dynamics approach [Clore, G.M., Brünger, A.T., Karplus, M. and Gronenborn, A.M. (1986) J. Mol. Biol., 191, 523-551]. These include the development of a new effective potential for the interproton distance restraints whose functional form is dependent on the magnitude of the difference between calculated and target values, and the design and implementation of robust and fully automatic protocol. The method is tested on three systems: the model system crambin (46 residues) using X-ray structure derived interproton distance restraints, and potato carboxypeptidase inhibitor (CPI; 39 residues) and barley serine proteinase inhibitor 2 (BSPI-2; 64 residues) using experimentally derived interproton distance restraints. Calculations were carried out starting from the extended strands which had atomic r.m.s. differences of 57, 38 and 33 A with respect to the crystal structures of BSPI-2, crambin and CPI respectively. Unbiased sampling of the conformational space consistent with the restraints was achieved by varying the random number seed used to assign the initial velocities. This ensures

  11. Isolation of a high malic and low acetic acid-producing sake yeast Saccharomyces cerevisiae strain screened from respiratory inhibitor 2,4-dinitrophenol (DNP)-resistant strains.

    PubMed

    Kosugi, Shingo; Kiyoshi, Keiji; Oba, Takahiro; Kusumoto, Kenichi; Kadokura, Toshimori; Nakazato, Atsumi; Nakayama, Shunichi

    2014-01-01

    We isolated 2,4-dinitrophenol (DNP)-resistant sake yeast strains by UV mutagenesis. Among the DNP-resistant mutants, we focused on strains exhibiting high malic acid and low acetic acid production. The improved organic acid composition is unlikely to be under the control of enzyme activities related to malic and acetic acid synthesis pathways. Instead, low mitochondrial activity was observed in DNP-resistant mutants, indicating that the excess pyruvic acid generated during glycolysis is not metabolized in the mitochondria but converted to malic acid in the cytosol. In addition, the NADH/NAD(+) ratio of the DNP-resistant strains was higher than that of the parental strain K901. These results suggest that the increased NADH/NAD(+) ratio together with the low mitochondrial activity alter the organic acid composition because malic acid synthesis requires NADH, while acetic acid uses NAD(+).

  12. Activity.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1984

    1984-01-01

    Presents three activities: (1) investigating succession in a schoolground; (2) investigating oak galls; and (3) making sun prints (photographs made without camera or darkroom). Each activity includes a list of materials needed and procedures used. (JN)

  13. Cardiovascular effects of a novel selective Rho kinase inhibitor, 2-(1H-indazole-5-yl)amino-4-methoxy-6-piperazino triazine (DW1865).

    PubMed

    Oh, Kwang-Seok; Oh, Byung Koo; Park, Cheon Ho; Seo, Ho Won; Kang, Nam Sook; Lee, Jeong Hyun; Lee, Jin Soo; Ho Lee, Byung

    2013-02-28

    The arising critical implications of Rho kinase signaling in cardiovascular diseases have been attracting attention in the pharmacological potential of Rho kinase inhibitors. We identified a novel inhibitor of Rho kinase (2-(1H-indazole-5-yl)amino-4-methoxy-6-piperazino triazine; DW 1865) and characterized its effects in biochemical, cellular, tissue and animal based assays. DW 1865 potently inhibited the kinase activity of both Rho kinase 1 and Rho kinase 2 in vitro, and behaved as an ATP-competitive inhibitor. Interestingly, DW1865 was 10 times more potent in inhibiting Rho kinase activities than fasudil as a selective Rho kinase inhibitor. The activity of DW1865 was shown to be highly selective for Rho kinase in the panel assay of 13 other kinases. In the isolated vascular tissue study, DW1865 exerted vasorelaxation in phenylephrine- or 5-hydroxytriptamine-induced contraction in a concentration-dependent manner manner. In spontaneously hypertensive rats, administration of DW1865 caused a significant and dose-related reduction in blood pressure. Furthermore, DW1865 blocked angiotensin II-induced stress fiber formation and cellular hypertrophy in rat heart-derived H9c2 cells. Taken together, these results suggest that DW1865 is a highly selective and potent Rho kinase inhibitor that will alleviate the pathophysiological actions of Rho kinase such as stress fiber formation, cellular hypertrophy, and hypertension.

  14. Vaccination with a genetically modified Brugia malayi cysteine protease inhibitor-2 reduces adult parasite numbers and affects the fertility of female worms following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae.

    PubMed

    Arumugam, Sridhar; Wei, Junfei; Ward, Danielle; Abraham, David; Lustigman, Sara; Zhan, Bin; Klei, Thomas R

    2014-09-01

    Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0% at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.

  15. Targeted alpha therapy for cancer

    NASA Astrophysics Data System (ADS)

    Allen, Barry J.; Raja, Chand; Rizvi, Syed; Li, Yong; Tsui, Wendy; Zhang, David; Song, Emma; Qu, Chang Fa; Kearsley, John; Graham, Peter; Thompson, John

    2004-08-01

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The 213Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 µCi in human

  16. Towards the chemoinformatic-based identification of DNA methyltransferase inhibitors: 2D- and 3D-similarity profile of screening libraries.

    PubMed

    Yoo, Jakyung; Medina-Franco, José Luis

    2012-12-01

    DNA methyltransferases (DNMTs) are emerging targets for the treatment of cancer and other diseases. The quinolone-based compound, SGI-1027, is a promising inhibitor of DNMT1 with a distinct mode of action and it is an attractive starting point for further research. Several experimental and computational approaches can be used to further develop novel DNMT1 inhibitors based on SGI-1027. In this work, we used a chemoinformatic-based approach to explore the potential to identify novel inhibitors in large screening collections of natural products and synthetic commercial libraries. Using the principles of similarity searching, the similarity profile to the active reference compound SGI-1027 was computed for four different screening libraries using a total of 22 two- and three- dimensional representations and two similarity metrics. The compound library with the overall highest similarity profile to the probe molecule was identified as the most promising collection for experimental testing. Individual compounds with high similarity to the reference were also selected as suitable candidates for experimental validation. During the course of this work, the 22 two- and three- dimensional representations were compared to each other and classified based on the similarity values computed with the reference compound. This classification is valuable to select structure representations for similarity searching of any other screening library. This work represents a step forward to further advance epigenetic therapies using computational approaches.

  17. Crystal structure of the catalytic domain of Clostridium perfringens neuraminidase in complex with a non-carbohydrate-based inhibitor, 2-(cyclohexylamino)ethanesulfonic acid.

    PubMed

    Lee, Youngjin; Youn, Hyung-Seop; Lee, Jung-Gyu; An, Jun Yop; Park, Kyoung Ryoung; Kang, Jung Youn; Ryu, Young Bae; Jin, Mi Sun; Park, Ki Hun; Eom, Soo Hyun

    2017-03-16

    Anti-bacterial and anti-viral neuraminidase agents inhibit neuraminidase activity catalyzing the hydrolysis of terminal N-acetylneuraminic acid (Neu5Ac) from glycoconjugates and help to prevent the host pathogenesis that lead to fatal infectious diseases including influenza, bacteremia, sepsis, and cholera. Emerging antibiotic and drug resistances to commonly used anti-neuraminidase agents such as oseltamivir (Tamiflu) and zanamivir (Relenza) have highlighted the need to develop new anti-neuraminidase drugs. We obtained a serendipitous complex crystal of the catalytic domain of Clostridium perfringens neuraminidase (CpNanICD) with 2-(cyclohexylamino)ethanesulfonic acid (CHES) as a buffer. Here, we report the crystal structure of CpNanICD in complex with CHES at 1.24 Å resolution. Amphipathic CHES binds to the catalytic site of CpNanICD similar to the substrate (Neu5Ac) binding site. The 2-aminoethanesulfonic acid moiety and cyclohexyl groups of CHES interact with the cluster of three arginine residues and with the hydrophobic pocket of the CpNanICD catalytic site. In addition, a structural comparison with other bacterial and human neuraminidases suggests that CHES could serve as a scaffold for the development of new anti-neuraminidase agents targeting CpNanI.

  18. Activities.

    ERIC Educational Resources Information Center

    Bippert, Judy

    1993-01-01

    Presents activities designed to give students an opportunity to solve concrete problems involving spatial relationships and logical thinking utilizing hands-on manipulatives. Provides teacher instructions and four reproducible worksheets. (MDH)

  19. Activities.

    ERIC Educational Resources Information Center

    Kincaid, Charlene; And Others

    1993-01-01

    Presents an activity in which students collect and organize data from a real-world simulation of the scientific concept of half life. Students collect data using a marble sifter, analyze the data using a graphing calculator, and determine an appropriate mathematical model. Includes reproducible worksheets. (MDH)

  20. Involvement of urokinase-type plasminogen activator system in cancer: an overview.

    PubMed

    Mekkawy, Ahmed H; Pourgholami, Mohammad H; Morris, David L

    2014-09-01

    Currently, there are several studies supporting the role of urokinase-type plasminogen activator (uPA) system in cancer. The association of uPA to its receptor triggers the conversion of plasminogen into plasmin. This process is regulated by the uPA inhibitors (PAI-1 and PAI-2). Plasmin promotes degradation of basement membrane and extracellular matrix (ECM) components as well as activation of ECM latent matrix metalloproteases. Degradation and remodeling of the surrounding tissues is crucial in the early steps of tumor progression by facilitating expansion of the tumor mass, release of tumor growth factors, activation of cytokines as well as induction of tumor cell proliferation, migration, and invasion. Hence, many tumors showed a correlation between uPA system component levels and tumor aggressiveness and survival. Therefore, this review summarizes the structure of the uPA system, its contribution to cancer progression, and the clinical relevance of uPA family members in cancer diagnosis. In addition, the review evaluates the significance of uPA system in the development of cancer-targeted therapies.

  1. Novel inhibitors of urokinase-type plasminogen activator and matrix metalloproteinase expression in metastatic cancer cell lines.

    PubMed

    Cakarovski, Kristina; Leung, Jenny Y; Restall, Christina; Carin-Carlson, Anna; Yang, Eunice; Perlmutter, Patrick; Anderson, Robin; Medcalf, Robert; Dear, Anthony E

    2004-07-01

    The plasminogen-activating (PA) and matrix metalloproteinase (MMP) enzyme systems are implicated in proteolytic turnover of the extracellular matrix (ECM) associated with biologic processes including wound healing, inflammation and angiogenesis. Aberrant expression of components of the PA and MMP enzyme systems occurs in the pathogenesis of metastatic cancer. Oxamflatin (Ox), a novel hydroxamic acid derivative, inhibits u-PA mRNA expression and proteolytic activity while simultaneously upregulating the expression of the natural inhibitor of u-PA, plasminogen activator inhibitor type 2 (PAI-2) in metastatic cancer cells. We have characterized the effects of Ox and a novel derivative, Metacept-1 (MCT-1), on PA and MMP-mediated proteolysis and invasion in several metastatic tumor lines. Both compounds are able to inhibit u-PA-, MMP-2- and MMP-9-mediated gene expression at low micromolar concentrations as well as u-PA- and MMP-mediated proteolysis as assessed by zymography, with MCT-1 being the more effective of the 2 agents in some assays. Cellular invasion assays correlate with gene expression and zymography experiments identifying both Ox and MCT-1 as able to inhibit invasion of metastatic cancer cell lines through matrigel at nanomolar concentrations, with MCT-1 more effective than Ox in 2 of the 3 cancer cell lines assessed.

  2. Sialidase Activity in Mycoplasma synoviae

    PubMed Central

    May, Meghan; Kleven, Stanley H.; Brown, Daniel R.

    2008-01-01

    SUMMARY Eleven strains of the avian pathogen Mycoplasma synoviae were evaluated for the presence of sialidase activity by using the fluorogenic substrate 2′-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid and the sialidase inhibitor 2-deoxy-2,3-didehydro-N-acetylneuraminic acid. The kinetics of in vitro growth in modified Frey’s medium were also assessed for each strain. Five strains had been isolated from clinically symptomatic chickens, and strains WVU1853T and K3344 have been demonstrated to be capable of reproducing disease in specific pathogen-free chickens. All strains exhibited sialidase activity, although the amount varied 65 fold (P < 0.0001) from 1.3 x 10−7 to 2.0 x 10−9 activity units/colony-forming unit among strains. Strains originally isolated from clinically symptomatic birds had more (P < 0.05) sialidase activity than strains from asymptomatic birds. Strain WVU1853T exhibited the most sialidase activity (P < 0.0001) and grew to the highest culture density (P < 0.0001) among strains, but across strains the rank correlation of growth rate with sialidase activity was not significant. Negligible activity was detected in conditioned culture supernatant fluid. This is the first report of sialidase activity in pathogenic strains of M. synoviae, which suggests a potential enzymatic basis for virulence of the organism. PMID:18251389

  3. Chiral resolution and pharmacological characterization of the enantiomers of the Hsp90 inhibitor 2-amino-7-[4-fluoro-2-(3-pyridyl)phenyl]-4-methyl-7,8-dihydro-6H-quinazolin-5-one oxime.

    PubMed

    Amici, Raffaella; Bigogno, Chiara; Boggio, Roberto; Colombo, Andrea; Courtney, Stephen M; Dal Zuffo, Roberto; Dondio, Giulio; Fusar, Fulvia; Gagliardi, Stefania; Minucci, Saverio; Molteni, Marco; Montalbetti, Christian A G N; Mortoni, Annalisa; Varasi, Mario; Vultaggio, Stefania; Mercurio, Ciro

    2014-07-01

    Heat-shock protein 90 (Hsp90) is a molecular chaperone involved in the stabilization of key oncogenic signaling proteins, and therefore, inhibition of Hsp90 represents a new strategy in cancer therapy. 2-Amino-7-[4-fluoro-2-(3-pyridyl)phenyl]-4-methyl-7,8-dihydro-6H-quinazolin-5-one oxime is a racemic Hsp90 inhibitor that targets the N-terminal adenosine triphosphatase site. We developed a method to resolve the enantiomers and evaluated their inhibitory activity on Hsp90 and the consequent antitumor effects. The (S) stereoisomer emerged as a potent Hsp90 inhibitor in biochemical and cellular assays. In addition, this enantiomer exhibited high oral bioavailability in mice and excellent antitumor activity in two different human cancer xenograft models.

  4. Heat Shock Protein 70 Inhibitors. 2. 2,5′-Thiodipyrimidines, 5-(Phenylthio)pyrimidines, 2-(Pyridin-3-ylthio)pyrimidines, and 3-(Phenylthio)pyridines as Reversible Binders to an Allosteric Site on Heat Shock Protein 70

    PubMed Central

    2015-01-01

    The discovery and development of heat shock protein 70 (Hsp70) inhibitors is currently a hot topic in cancer. In the preceding paper in this issue (10.1021/jm401551n), we have described structure–activity relationship studies in the first Hsp70 inhibitor class rationally designed to bind to a novel allosteric pocket located in the N-terminal domain of the protein. These ligands contained an acrylamide to take advantage of an active cysteine embedded in the allosteric pocket and acted as covalent protein modifiers upon binding. Here, we perform chemical modifications around the irreversible inhibitor scaffold to demonstrate that covalent modification is not a requirement for activity within this class of compounds. The study identifies derivative 27c, which mimics the biological effects of the irreversible inhibitors at comparable concentrations. Collectively, the back-to-back manuscripts describe the first pharmacophores that favorably and selectively interact with a never explored pocket in Hsp70 and provide a novel blueprint for a cancer-oriented development of Hsp70-directed ligands. PMID:24548239

  5. Upregulation of MicroRNA-15a Contributes to Pathogenesis of Abdominal Aortic Aneurysm (AAA) by Modulating the Expression of Cyclin-Dependent Kinase Inhibitor 2B (CDKN2B).

    PubMed

    Gao, Peng; Si, Jiyuan; Yang, Bin; Yu, Jixiang

    2017-02-18

    BACKGROUND The objective of the present study was to identify the association between miR-15a-5p and CDKN2B, and their roles in regulating the development of abdominal aortic aneurysm (AAA). MATERIAL AND METHODS We searched the miRNA database online (www.mirdb.org) and used a luciferase reporter assay system to study the regulatory relationship between miR-15a-5p and CDKN2B. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of CDKN2B among different patient groups (participants with abdominal aortic aneurysm (AAA) and normal controls) or cells treated with scramble control, miR-15a-5p mimics, CDKN2B siRNA, and miR-15a-5p inhibitors. RESULTS We found that CDKN2B was a virtual target of miR-15a-5p with potential binding sites in the 3'UTR of CDKN2B (77-83 bp). We also showed that miR-15a-5p could bind to the CDKN2B 3'UTR, resulting in a significant decrease in luciferase activity compared with the scramble control. Furthermore, we found that the cells isolated from AAA participants showed an over-expression of miR-15a-5p compared to the normal controls, while the CDKN2B mRNA and protein expression level of the AAA group were much lower than the normal control group. Additionally, the expression of CDKN2B mRNA and the protein of the cells transfected with miR-15a-5p mimics and CDKN2B siRNA was downregulated, while the cells showed upregulated expression subsequent to transfection with miR-15a-5p inhibitors compared to the scramble control. CONCLUSIONS The data revealed a negative regulatory role of miR-15a-5p in the apoptosis of smooth muscle cells via targeting CDKN2B, and showed that miR-15a-5p could be a novel therapeutic target of AAA.

  6. Upregulation of MicroRNA-15a Contributes to Pathogenesis of Abdominal Aortic Aneurysm (AAA) by Modulating the Expression of Cyclin-Dependent Kinase Inhibitor 2B (CDKN2B)

    PubMed Central

    Gao, Peng; Si, Jiyuan; Yang, Bin; Yu, Jixiang

    2017-01-01

    Background The objective of the present study was to identify the association between miR-15a-5p and CDKN2B, and their roles in regulating the development of abdominal aortic aneurysm (AAA). Material/Methods We searched the miRNA database online (www.mirdb.org) and used a luciferase reporter assay system to study the regulatory relationship between miR-15a-5p and CDKN2B. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of CDKN2B among different patient groups (participants with abdominal aortic aneurysm (AAA) and normal controls) or cells treated with scramble control, miR-15a-5p mimics, CDKN2B siRNA, and miR-15a-5p inhibitors. Results We found that CDKN2B was a virtual target of miR-15a-5p with potential binding sites in the 3′UTR of CDKN2B (77–83 bp). We also showed that miR-15a-5p could bind to the CDKN2B 3′UTR, resulting in a significant decrease in luciferase activity compared with the scramble control. Furthermore, we found that the cells isolated from AAA participants showed an over-expression of miR-15a-5p compared to the normal controls, while the CDKN2B mRNA and protein expression level of the AAA group were much lower than the normal control group. Additionally, the expression of CDKN2B mRNA and the protein of the cells transfected with miR-15a-5p mimics and CDKN2B siRNA was downregulated, while the cells showed upregulated expression subsequent to transfection with miR-15a-5p inhibitors compared to the scramble control. Conclusions The data revealed a negative regulatory role of miR-15a-5p in the apoptosis of smooth muscle cells via targeting CDKN2B, and showed that miR-15a-5p could be a novel therapeutic target of AAA. PMID:28214350

  7. Active intranuclear movement of herpesvirus capsids.

    PubMed

    Forest, Thomas; Barnard, Sandra; Baines, Joel D

    2005-04-01

    Although small molecules diffuse rapidly through the interphase nucleus, recent reports indicate that nuclear diffusion is limited for particles that are larger than 100 nm in diameter. Given the apparent size limits to nuclear diffusion, there is some debate as to whether the movement of large particles should be attributed to diffusion or to active transport. Here, we show that 125 nm-diameter herpes simplex virus 1 (HSV-1) capsids are actively transported within infected nuclei. Movement is directed, temperature- and energy-dependent, sensitive to the putative myosin inhibitor 2,3-butanedione monoxime (BDM) and to actin depolymerization with latrunculin-A, but insensitive to actin depolymerization with cytochalasin-D.

  8. Cellular Activity of New Small Molecule Protein Arginine Deiminase 3 (PAD3) Inhibitors.

    PubMed

    Jamali, Haya; Khan, Hasan A; Tjin, Caroline C; Ellman, Jonathan A

    2016-09-08

    The protein arginine deiminases (PADs) catalyze the post-translational deimination of arginine side chains. Multiple PAD isozymes have been characterized, and abnormal PAD activity has been associated with several human disease states. PAD3 has been characterized as a modulator of cell growth via apoptosis inducing factor and has been implicated in the neurodegenerative response to spinal cord injury. Here, we describe the design, synthesis, and evaluation of conformationally constrained versions of the potent and selective PAD3 inhibitor 2. The cell activity of representative inhibitors in this series was also demonstrated for the first time by rescue of thapsigargin-induced cell death in PAD3-expressing HEK293T cells.

  9. Synaptic NMDA receptor stimulation activates PP1 by inhibiting its phosphorylation by Cdk5

    PubMed Central

    Hou, Hailong; Sun, Lu; Siddoway, Benjamin A.; Petralia, Ronald S.; Yang, Hongtian; Gu, Hua; Nairn, Angus C.

    2013-01-01

    The serine/threonine protein phosphatase protein phosphatase 1 (PP1) is known to play an important role in learning and memory by mediating local and downstream aspects of synaptic signaling, but how PP1 activity is controlled in different forms of synaptic plasticity remains unknown. We find that synaptic N-methyl-d-aspartate (NMDA) receptor stimulation in neurons leads to activation of PP1 through a mechanism involving inhibitory phosphorylation at Thr320 by Cdk5. Synaptic stimulation led to proteasome-dependent degradation of the Cdk5 regulator p35, inactivation of Cdk5, and increased auto-dephosphorylation of Thr320 of PP1. We also found that neither inhibitor-1 nor calcineurin were involved in the control of PP1 activity in response to synaptic NMDA receptor stimulation. Rather, the PP1 regulatory protein, inhibitor-2, formed a complex with PP1 that was controlled by synaptic stimulation. Finally, we found that inhibitor-2 was critical for the induction of long-term depression in primary neurons. Our work fills a major gap regarding the regulation of PP1 in synaptic plasticity. PMID:24189275

  10. Silica nanocontainers for active corrosion protection.

    PubMed

    Maia, Frederico; Tedim, João; Lisenkov, Aleksey D; Salak, Andrei N; Zheludkevich, Mikhail L; Ferreira, Mário G S

    2012-02-21

    Novel self-healing protective coatings with nanocontainers of corrosion inhibitors open new opportunities for long-term anticorrosion protection of different metallic materials. In this paper a new type of functional nanoreservoir based on silica nanocapsules (SiNC) synthesized and loaded with corrosion inhibitor 2-mercaptobenzothiazole (MBT) in a one-stage process is reported for the first time. Unlike conventional mesoporous silica nanoparticles, SiNC possess an empty core and shell with gradual mesoporosity, arising from the particular conditions of the synthetic route adopted, which confers significant loading capacity and allows prolonged and stimuli-triggered release of the inhibiting species. The kinetics of inhibitor release was studied at different pH values and concentrations of NaCl. The results show a clear dependence of the release profiles on corrosion relevant triggers such as pH and Cl(-) concentration. When SiNC loaded with MBT are dispersed in NaCl solution, there is a significant decrease of the corrosion activity on aluminium alloy 2024. More importantly, when SiNC-MBT is added to a conventional water-based coating formulation, the modified coating hampers corrosion activity at the metal interface, better than in the case of direct addition of corrosion inhibitor. Furthermore, self-healing is observed before and after artificially inflicting defects in the modified coatings. As a result, the developed nanocontainers show high potential to be used in new generation of active protective coatings.

  11. Silica nanocontainers for active corrosion protection

    NASA Astrophysics Data System (ADS)

    Maia, Frederico; Tedim, João; Lisenkov, Aleksey D.; Salak, Andrei N.; Zheludkevich, Mikhail L.; Ferreira, Mário G. S.

    2012-02-01

    Novel self-healing protective coatings with nanocontainers of corrosion inhibitors open new opportunities for long-term anticorrosion protection of different metallic materials. In this paper a new type of functional nanoreservoir based on silica nanocapsules (SiNC) synthesized and loaded with corrosion inhibitor 2-mercaptobenzothiazole (MBT) in a one-stage process is reported for the first time. Unlike conventional mesoporous silica nanoparticles, SiNC possess an empty core and shell with gradual mesoporosity, arising from the particular conditions of the synthetic route adopted, which confers significant loading capacity and allows prolonged and stimuli-triggered release of the inhibiting species. The kinetics of inhibitor release was studied at different pH values and concentrations of NaCl. The results show a clear dependence of the release profiles on corrosion relevant triggers such as pH and Cl- concentration. When SiNC loaded with MBT are dispersed in NaCl solution, there is a significant decrease of the corrosion activity on aluminium alloy 2024. More importantly, when SiNC-MBT is added to a conventional water-based coating formulation, the modified coating hampers corrosion activity at the metal interface, better than in the case of direct addition of corrosion inhibitor. Furthermore, self-healing is observed before and after artificially inflicting defects in the modified coatings. As a result, the developed nanocontainers show high potential to be used in new generation of active protective coatings.

  12. Depressed phosphatidic acid-induced contractile activity of failing cardiomyocytes.

    PubMed

    Tappia, Paramjit S; Maddaford, Thane G; Hurtado, Cecilia; Panagia, Vincenzo; Pierce, Grant N

    2003-01-10

    The effects of phosphatidic acid (PA), a known inotropic agent, on Ca(2+) transients and contractile activity of cardiomyocytes in congestive heart failure (CHF) due to myocardial infarction were examined. In control cells, PA induced a significant increase (25%) in active cell shortening and Ca(2+) transients. The phospholipase C (PLC) inhibitor, 2-nitro-4-carboxyphenyl N,N-diphenylcarbonate, blocked the positive inotropic action induced by PA, indicating that PA induces an increase in contractile activity and Ca(2+) transients through stimulation of PLC. Conversely, in failing cardiomyocytes there was a loss of PA-induced increase in active cell shortening and Ca(2+) transients. PA did not alter resting cell length. Both diastolic and systolic [Ca(2+)] were significantly elevated in the failing cardiomyocytes. In vitro assessment of the cardiac sarcolemmal (SL) PLC activity revealed that the impaired failing cardiomyocyte response to PA was associated with a diminished stimulation of SL PLC activity by PA. Our results identify an important defect in the PA-PLC signaling pathway in failing cardiomyocytes, which may have significant implications for the depressed contractile function during CHF.

  13. Active-R filter

    DOEpatents

    Soderstrand, Michael A.

    1976-01-01

    An operational amplifier-type active filter in which the only capacitor in the circuit is the compensating capacitance of the operational amplifiers, the various feedback and coupling elements being essentially solely resistive.

  14. Novel small molecular inhibitors disrupt the JAK/STAT3 and FAK signaling pathways and exhibit a potent antitumor activity in glioma cells.

    PubMed

    Swiatek-Machado, Karolina; Mieczkowski, Jakub; Ellert-Miklaszewska, Aleksandra; Swierk, Piotr; Fokt, Izabela; Szymanski, Slawomir; Skora, Stanislaw; Szeja, Wiesław; Grynkiewicz, Grzegorz; Lesyng, Bogdan; Priebe, Waldemar; Kaminska, Bozena

    2012-06-01

    JAK (Janus kinase)/STAT (signal transducers and activators of transcription) signaling is involved in the regulation of cell growth, differentiation and apoptosis. Constitutive activation of STATs, in particular STAT3, is observed in a large number of human tumors, including gliomas and may contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis, thus it emerges as a promising target for anti-cancer therapy. To investigate the therapeutic potential of blocking STAT3 in glioma cells a set of small synthetic molecules - caffeic acid derivatives, structurally related to AG490 was screened for its ability to inhibit STAT3. Inhibitor 2 (E)-2-cyano-N-[(S)-1-phenylethyl]-3-(pyridin-2-yl)acrylamide was the most effective in inhibition of JAK/STAT3 signaling and at doses ≥ 25 μM significantly reduced the level of phosphorylated JAK1, JAK2 and STAT3 (at Tyr705) and downregulated the expression of known STAT3 targets. In treated cells we observed rapid detachment and rounding of cells associated with reduction of focal adhesion kinase phosphorylation and activity, followed by upregulation of phosphorylated p38, JNK and ERK1/2 levels. Accumulation of cells with fragmented DNA, increases of the cleaved caspase 3 and fragmented PARP levels were detected 24 h after the treatment suggesting ongoing apoptotic cell death. Three human malignant glioblastoma cell lines defective in tumor suppressors TP53 and/or PTEN were susceptible to inhibitor 2 that induced the programmed cell death. Global gene expression profiling revealed modulation of numerous genes in cells treated with inhibitor 2 revealing novel, potential JAK/STAT targets. Our study demonstrates that suitably modified caffeic acid molecules exhibit significant cytotoxic potential toward glioma cells.

  15. Discovery of a Potent HIV Integrase Inhibitor That Leads to a Prodrug with Significant anti-HIV Activity

    PubMed Central

    2011-01-01

    Worldwide research efforts in drug discovery involving HIV integrase have produced only one compound, raltegravir, that has been approved for clinical use in HIV/AIDS. As resistance, toxicity, and drug–drug interactions are recurring issues with all classes of anti-HIV drugs, the discovery of novel integrase inhibitors remains a significant scientific challenge. We have designed a lead HIV-1 strand transfer (ST) inhibitor (IC50 70 nM), strategically assembled on a pyridinone scaffold. A focused structure–activity investigation of this parent compound led to a significantly more potent ST inhibitor, 2 (IC50 6 ± 3 nM). Compound 2 exhibits good stability in pooled human liver microsomes. It also displays a notably favorable profile with respect to key human cytochrome P450 (CYP) isozymes and human UDP glucuronosyl transferases (UGTs). The prodrug of inhibitor 2, i.e., compound 10, was found to possess remarkable anti-HIV-1 activity in cell culture (EC50 9 ± 4 nM, CC50 135 ± 7 μM, therapeutic index = 15 000). PMID:22328963

  16. Get Active

    MedlinePlus

    ... Basics: Health Benefits What are the benefits of physical activity? Physical activity increases your chances of living longer. ... pain Help you feel better about yourself Is physical activity for everyone? Yes! Physical activity is good for ...

  17. Airport Activity Statistics of Certificated Route Air Carriers.

    DTIC Science & Technology

    1982-12-31

    4. 77 I4 3404A 1,1973 1.9. 3.44A t AA 3* 34433 0.61 Is.. 4. 2 4.06 .4.6 7 W.34 87 4ILL 3𔃾IL! 1375.24 .44 C6 .06 344 34 I 0.444 ’.---3 2 .6[0 533.64I...2d 4; /03 SY4- I(. it -5t 3 1 1 3 0 2 " IL 34433 3351 02/-03 135 IS A$-L 1-1115 24l l 1.45" 6 43 3-1-3 2 2 l’-1, -jIs PA-/I 2AL 10/3 58,4 to, 11k,..a

  18. Methods to distinguish various types of protein phosphatase activity

    SciTech Connect

    Brautigan, D.L.; Shriner, C.L.

    1988-01-01

    To distinguish the action of protein Tyr(P) and protein Ser(P)/Thr(P) phosphatases on /sup 32/P-labeled phosphoproteins in subcellular fractions different inhibitors and activators are utilized. Comparison of the effects of added compounds provides a convenient, indirect method to characterize dephosphorylation reactions. Protein Tyr(P) phosphatases are specifically inhibited by micromolar Zn2+ or vanadate, and show maximal activity in the presence of EDTA. The other class of cellular phosphatases, specific for protein Ser(P) and Thr(P) residues, are inhibited by fluoride and EDTA. In this class of enzymes two major functional types can be distinguished: those sensitive to inhibition by the heat-stable protein inhibitor-2 and not stimulated by polycations, and those not sensitive to inhibition and stimulated by polycations. Preparation of /sup 32/P-labeled Tyr(P) and Ser(P) phosphoproteins also is presented for the direct measurement of phosphatase activities in preparations by the release of acid-soluble (/sup 32/P)phosphate.

  19. Self-etching adhesives increase collagenolytic activity in radicular dentin.

    PubMed

    Tay, Franklin R; Pashley, David H; Loushine, Robert J; Weller, R Norman; Monticelli, Francesca; Osorio, Raquel

    2006-09-01

    Endogenous matrix metalloproteinases (MMPs) release from crown dentin and their activation results in degradation of hybrid layers created by dentin adhesives. This study tested the hypothesis that instrumented intraradicular dentin possesses latent collagenolytic activity that is activated by mild self-etching adhesives. Root dentin shavings were produced from 50 cleaned and shaped, saline-irrigated root canals using Gates Glidden drills and rinsed with sodium azide to prevent bacterial growth. Dried dentin powder aliquots were treated with two clinically-relevant MMP inhibitors, 2% chlorhexidine for 10 minutes and 17% EDTA for 1 minute. Additional dentin powder was mixed with Clearfil Liner Bond 2V or Clearfil Tri-S Bond for 1 minute followed by extracting the adhesives with acetone. Dentin powder was also treated with 2% chlorhexidine for 10 minutes before or after adhesive application. Collagenolytic activities of the nine groups were assayed with a fluorometer in 96-well plates, by recording the changes in fluorescence before and after addition of fluorescein-labeled type I collagen. Epoxy resin-embedded powders were examined with TEM for the extent of demineralization. Instrumented, mineralized intraradicular dentin possessed low but detectable collagenolytic activity that was inhibited by chlorhexidine (p < 0.001) and EDTA (p < 0.001). Both adhesives partially demineralized the dentin powder and activated latent MMPs, with 14- to 15-fold increases in collagenolytic activities (p < 0.001) that were significantly (p < 0.001) but incompletely inactivated after 10 min application of chlorhexidine. Mild self-etching adhesives activate latent MMPs without denaturing these enzymes, and may adversely affect the longevity of bonded root canal fillings and posts.

  20. Phosphorylation of TPX2 by Plx1 enhances activation of Aurora A.

    PubMed

    Eckerdt, Frank; Pascreau, Gaetan; Phistry, Meridee; Lewellyn, Andrea L; DePaoli-Roach, Anna A; Maller, James L

    2009-08-01

    Entry into mitosis requires the activation of mitotic kinases, including Aurora A and Polo-like kinase 1 (Plk1). Increased levels of these kinases are frequently found associated with human cancers, and therefore it is imperative to understand the processes leading to their activation. We demonstrate that TPX2, but neither Ajuba nor Inhibitor-2, can activate Aurora A directly. Moreover, Plx1 can induce Aurora A T-loop phosphorylation indirectly in vivo during oocyte maturation. We identify Ser204 in TPX2 as a Plx1 phosphorylation site. Mutating Ser204 to alanine decreases activation of Aurora A, whereas a phosphomimetic Asp mutant exhibits enhanced activating ability. Finally, we show that phosphorylation of TPX2 with Plx1 increases its ability to activate Aurora A. Taken together, our data indicate that Plx1 promotes activation of Aurora A, most likely through TPX2. In light of the current literature, we propose a model in which Plx1 and Aurora A activate each other in a positive feedback loop.

  1. Hydrolase activity in the venom of the pupal endoparasitic wasp, Pimpla hypochondriaca.

    PubMed

    Dani, M P; Edwards, J P; Richards, E H

    2005-07-01

    Venom from the pupal endoparasitoid, Pimpla hypochondriaca has previously been shown to contain a mixture of biologically active molecules. Currently, P. hypochondriaca venom was examined for the presence of hydrolase activity. Six hydrolases were consistently detected using the API ZYM semiquantitative colourimetric kit. The main hydrolases detected were; acid phosphatase, beta-glucosidase, esterase, beta-galactosidase, esterase lipase, and lipase. The most rapid and intense colour reaction was detected for acid phosphatase. The pH optimum and the specific activity of venom acid phosphatase was determined using p-nitrophenol phosphate as a substrate and were 4.8 and 0.47 nmol p-nitrophenol/min/microg of venom protein, respectively. The acid phosphatase activity was inhibited in a dose dependent manner by sodium fluoride (IC(50) 4.2 x 10(-4) M), and by cocktail inhibitor 2 (CI 2). P. hypochondriaca venom has previously been shown to display potent cytotoxic activity towards Lacanobia oleracea haemocytes maintained in vitro. The contribution of acid phosphatase in venom to this cytotoxic activity was investigated by titrating venom against CI 2 prior to the addition of L. oleracea haemocytes. The results suggest that, despite the relatively high levels of acid phosphatase activity in venom, venom acid phosphatase plays no role in the antihaemocytic activity of P. hypochondriaca venom in vitro.

  2. Activation detector

    DOEpatents

    Bell, Zane William [Oak Ridge, TN; Boatner, Lynn Allen [Oak Ridge, TN

    2009-12-08

    A method of detecting an activator, the method including impinging with an activator a receptor material lacking a photoluminescent material and generating a by-product of a radioactive decay due to the activator impinging the reeptor material. The method further including, generating light from the by-product via the Cherenkov effect and identifying a characteristic of the activator based on the light.

  3. Discovery of Pyrrolopyridine−Pyridone Based Inhibitors of Met Kinase: Synthesis, X-ray Crystallographic Analysis, and Biological Activities

    SciTech Connect

    Kim, Kyoung Soon; Zhang, Liping; Schmidt, Robert; Cai, Zhen-Wei; Wei, Donna; Williams, David K.; Lombardo, Louis J.; Trainor, George L.; Xie, Dianlin; Zhang, Yaquan; An, Yongmi; Sack, John S.; Tokarski, John S.; Darienzo, Celia; Kamath, Amrita; Marathe, Punit; Zhang, Yueping; Lippy, Jonathan; Jeyaseelan, Sr., Robert; Wautlet, Barri; Henley, Benjamin; Gullo-Brown, Johnni; Manne, Veeraswamy; Hunt, John T.; Fargnoli, Joseph; Borzilleri, Robert M.

    2008-10-02

    Conformationally constrained 2-pyridone analogue 2 is a potent Met kinase inhibitor with an IC50 value of 1.8 nM. Further SAR of the 2-pyridone based inhibitors of Met kinase led to potent 4-pyridone and pyridine N-oxide inhibitors such as 3 and 4. The X-ray crystallographic data of the inhibitor 2 bound to the ATP binding site of Met kinase protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues showed potent antiproliferative activities against the Met dependent GTL-16 gastric carcinoma cell line. Compound 2 also inhibited Flt-3 and VEGFR-2 kinases with IC{sub 50} values of 4 and 27 nM, respectively. It possesses a favorable pharmacokinetic profile in mice and demonstrates significant in vivo antitumor activity in the GTL-16 human gastric carcinoma xenograft model.

  4. Imaging of sialidase activity in rat brain sections by a highly sensitive fluorescent histochemical method.

    PubMed

    Minami, Akira; Shimizu, Hirotaka; Meguro, Yuko; Shibata, Naoki; Kanazawa, Hiroaki; Ikeda, Kiyoshi; Suzuki, Takashi

    2011-09-01

    Sialidase (EC 3.2.1.18) removes sialic acid from sialoglycoconjugates. Since sialidase extracellularly applied to the rat hippocampus influences many neural functions, including synaptic plasticity and innervations of glutamatergic neurons, endogenous sialidase activities on the extracellular membrane surface could also affect neural functions. However, the distribution of sialidase activity in the brain remains unknown. To visualize extracellular sialidase activity on the membrane surface in the rat brain, acute brain slices were incubated with 5-bromo-4-chloroindol-3-yl-α-d-N-acetylneuraminic acid (X-Neu5Ac) and Fast Red Violet LB (FRV LB) at pH 7.3. After 1h, myelin-abundant regions showed intense fluorescence in the rat brain. Although the hippocampus showed weak fluorescence in the brain, mossy fiber terminals in the hippocampus showed relatively intense fluorescence. These fluorescence intensities were attenuated with a sialidase-specific inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA, 1mM). Additionally, the fluorescence intensities caused by X-Neu5Ac and FRV LB were correlated with the sialidase activity measured with 4-methylumbelliferyl-α-d-N-acetylneuraminic acid (4MU-Neu5Ac), a classical substrate for quantitative measurement of sialidase activity, in each brain region. Therefore, staining with X-Neu5Ac and FRV LB is specific for sialidase and useful for quantitative analysis of sialidase activities. The results suggest that white matter of the rat brain has intense sialidase activity.

  5. Differential regulation of S6 phosphorylation by insulin and epidermal growth factor in Swiss mouse 3T3 cells: insulin activation of type 1 phosphatase.

    PubMed Central

    Olivier, A R; Ballou, L M; Thomas, G

    1988-01-01

    Insulin and epidermal growth factor (EGF) induce distinct kinetics of S6 kinase activation and S6 phosphorylation in Swiss 3T3 cells. Both events are differentially regulated by specific phosphatases. The major S6 phosphatase in cell extracts was identified as a type 1 enzyme by its chromatographic properties, its sensitivity to inhibitor 2, and its substrate specificity. This enzyme is different from the major S6 kinase phosphatase, which is a type 2A enzyme. Insulin at physiological concentrations causes up to a 2-fold activation of a type 1 S6 phosphatase, whereas at higher concentrations this effect is significantly diminished. EGF alone has little effect on this enzyme, and with both agents together the total phosphatase activity remains basal. The results are consistent with the phosphorylation state of S6 observed in vivo and suggest a role of phosphatase type 1 in the regulation of protein synthesis. Images PMID:2838844

  6. Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model

    PubMed Central

    Roel, María; Rubiolo, Juan A.; Guerra-Varela, Jorge; Silva, Siguara B. L.; Thomas, Olivier P.; Cabezas-Sainz, Pablo; Sánchez, Laura; López, Rafael; Botana, Luis M.

    2016-01-01

    The marine environment constitutes an extraordinary resource for the discovery of new therapeutic agents. In the present manuscript we studied the effect of 3 different sponge derived guanidine alkaloids, crambescidine-816, -830, and -800. We show that these compounds strongly inhibit tumor cell proliferation by down-regulating cyclin-dependent kinases 2/6 and cyclins D/A expression while up-regulating the cell cyclin-dependent kinase inhibitors -2A, -2D and -1A. We also show that these guanidine compounds disrupt tumor cell adhesion and cytoskeletal integrity promoting the activation of the intrinsic apoptotic signaling, resulting in loss of mitochondrial membrane potential and concomitant caspase-3 cleavage and activation. The crambescidin 816 anti-tumor effect was fnally assayed in a zebrafish xenotransplantation model confirming its potent antitumor activity against colorectal carcinoma in vivo. Considering these results crambescidins could represent promising natural anticancer agents and therapeutic tools. PMID:27825113

  7. Trichoderma asperellum Induces Maize Seedling Growth by Activating the Plasma Membrane H(+)-ATPase.

    PubMed

    López-Coria, M; J L Hernández-Mendoza; Sánchez-Nieto, S

    2016-10-01

    Although Trichoderma spp. have beneficial effects on numerous plants, there is not enough knowledge about the mechanism by which they improves plant growth. In this study, we evaluated the participation of plasma membrane (PM) H(+)-ATPase, a key enzyme involved in promoting cell growth, in the elongation induced by T. asperellum and compared it with the effect of 10 μM indol acetic acid (IAA) because IAA promotes elongation and PM H(+)-ATPase activation. Two seed treatments were tested: biopriming and noncontact. In neither were the tissues colonized by T. asperellum; however, the seedlings were longer than the control seedlings, which also accumulated IAA and increased root acidification. An auxin transport inhibitor (2,3,5 triiodobenzoic acid) reduced the plant elongation induced by Trichoderma spp. T. asperellum seed treatment increased the PM H(+)-ATPase activity in plant roots and shoots. Additionally, the T. asperellum extracellular extract (TE) activated the PM H(+)-ATPase activity of microsomal fractions of control plants, although it contained 0.3 μM IAA. Furthermore, the mechanism of activation of PM H(+)-ATPase was different for IAA and TE; in the latter, the activation depends on the phosphorylation state of the enzyme, suggesting that, in addition to IAA, T. asperellum excretes other molecules that stimulate PM H(+)-ATPase to induce plant growth.

  8. Sensitive fluorimetric assays for α-glucosidase activity and inhibitor screening based on β-cyclodextrin-coated quantum dots.

    PubMed

    Liu, Si-Yao; Wang, Huan; He, Tian; Qi, Liang; Zhang, Zhi-Qi

    2016-02-01

    A fluorescence method was established for a α-glucosidase activity assay and inhibitor screening based on β-cyclodextrin-coated quantum dots. p-Nitrophenol, the hydrolysis product of the α-glucosidase reaction, could quench the fluorescence of β-cyclodextrin-coated quantum dots via an electron transfer process, leading to fluorescence turn-off, whereas the fluorescence of the system turned on in the presence of α-glucosidase inhibitors. Taking advantage of the excellent properties of quantum dots, this method provided a very simple, rapid and sensitive screening method for α-glucosidase inhibitors. Two α-glucosidase inhibitors, 2,4,6-tribromophenol and acarbose, were used to evaluate the feasibility of this screening model, and IC50 values of 24 μM and 0.55 mM were obtained respectively, which were lower than those previously reported. The method may have potential application in screening α-glucosidase inhibitors.

  9. Catalyst activator

    DOEpatents

    McAdon, Mark H.; Nickias, Peter N.; Marks, Tobin J.; Schwartz, David J.

    2001-01-01

    A catalyst activator particularly adapted for use in the activation of metal complexes of metals of Group 3-10 for polymerization of ethylenically unsaturated polymerizable monomers, especially olefins, comprising two Group 13 metal or metalloid atoms and a ligand structure including at least one bridging group connecting ligands on the two Group 13 metal or metalloid atoms.

  10. Outdoor Activities.

    ERIC Educational Resources Information Center

    Minneapolis Independent School District 275, Minn.

    Twenty-four activities suitable for outdoor use by elementary school children are outlined. Activities designed to make children aware of their environment include soil painting, burr collecting, insect and pond water collecting, studies of insect galls and field mice, succession studies, and a model of natural selection using dyed toothpicks. A…

  11. Physical activity

    MedlinePlus

    ... activity -- which includes an active lifestyle and routine exercise -- plus eating well, is the best way to stay healthy. ... goal. Your goal might be to: Manage a health condition Reduce stress ... other benefits, such as: Better control of your weight and ...

  12. Astronomy Activities.

    ERIC Educational Resources Information Center

    Greenstone, Sid

    This document consists of activities and references for teaching astronomy. The activities (which include objectives, list of materials needed, and procedures) focus on: observing the Big Dipper and locating the North Star; examining the Big Dipper's stars; making and using an astrolabe; examining retograde motion of Mars; measuring the Sun's…

  13. Activation of STING requires palmitoylation at the Golgi

    PubMed Central

    Mukai, Kojiro; Konno, Hiroyasu; Akiba, Tatsuya; Uemura, Takefumi; Waguri, Satoshi; Kobayashi, Toshihide; Barber, Glen N.; Arai, Hiroyuki; Taguchi, Tomohiko

    2016-01-01

    Stimulator of interferon genes (STING) is essential for the type I interferon response against DNA pathogens. In response to the presence of DNA and/or cyclic dinucleotides, STING translocates from the endoplasmic reticulum to perinuclear compartments. However, the role of this subcellular translocation remains poorly defined. Here we show that palmitoylation of STING at the Golgi is essential for activation of STING. Treatment with palmitoylation inhibitor 2-bromopalmitate (2-BP) suppresses palmitoylation of STING and abolishes the type I interferon response. Mutation of two membrane-proximal Cys residues (Cys88/91) suppresses palmitoylation, and this STING mutant cannot induce STING-dependent host defense genes. STING variants that constitutively induce the type I interferon response were found in patients with autoimmune diseases. The response elicited by these STING variants is effectively inhibited by 2-BP or an introduction of Cys88/91Ser mutation. Our results may lead to new treatments for cytosolic DNA-triggered autoinflammatory diseases. PMID:27324217

  14. Rational Design of Fatty Acid Amide Hydrolase Inhibitors that Act by Covalently Bonding to Two Active Site Residues

    PubMed Central

    Otrubova, Katerina; Brown, Monica; McCormick, Michael S.; Han, Gye W.; O’Neal, Scott T.; Cravatt, Benjamin F.; Stevens, Raymond C.; Lichtman, Aron H.; Boger, Dale L.

    2013-01-01

    The design and characterization of α-ketoheterocycle fatty acid amide hydrolase (FAAH) inhibitors are disclosed that additionally and irreversibly target a cysteine (Cys269) found in the enzyme cytosolic port while maintaining the reversible covalent Ser241 attachment responsible for their rapid and initially reversible enzyme inhibition. Two α-ketooxazoles (3 and 4) containing strategically placed electrophiles at the C5 position of the pyridyl substituent of 2 (OL-135) were prepared and examined as inhibitors of FAAH. Consistent with the observed time-dependent non-competitive inhibition, the co-crystal X-ray structure of 3 bound to a humanized variant of rat FAAH revealed that 3 was not only covalently bound to the active site catalytic nucleophile Ser241 as a deprotonated hemiketal, but also to Cys269 through the pyridyl C5-substituent, thus providing an inhibitor with dual covalent attachment in the enzyme active site. In vivo characterization of the prototypical inhibitors in mice demonstrate that they raise endogenous brain levels of FAAH substrates to a greater extent and for a much longer duration (>6 h) than the reversible inhibitor 2, indicating that the inhibitors accumulate and persist in the brain to completely inhibit FAAH for a prolonged period. Consistent with this behavior and the targeted irreversible enzyme inhibition, 3 reversed cold allodynia in the chronic constriction injury model of neuropathic pain in mice for a sustained period (>6 h) beyond that observed with the reversible inhibitor 2, providing effects that were unchanged over the 1–6 h time course monitored. PMID:23581831

  15. Discovery of Potent Carbonic Anhydrase and Acetylcholinesterase Inhibitors: 2-Aminoindan β-Lactam Derivatives

    PubMed Central

    Genç, Hayriye; Kalin, Ramazan; Köksal, Zeynep; Sadeghian, Nastaran; Kocyigit, Umit M.; Zengin, Mustafa; Gülçin, İlhami; Özdemir, Hasan

    2016-01-01

    β-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. β-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that β-lactams are inhibitors of hCA I, II and AChE. The Ki values of β-lactams (2a–k) were 0.44–6.29 nM against hCA I, 0.93–8.34 nM against hCA II, and 0.25–1.13 nM against AChE. Our findings indicate that β-lactams (2a–k) inhibit both carbonic anhydrases (CA) isoenzymes and AChE at low nanomolar concentrations. PMID:27775608

  16. Riluzole attenuates excitatory amino acid transporter type 3 activity in Xenopus oocytes via protein kinase C inhibition.

    PubMed

    Choi, Jung-Seok; Ryu, Jung-Hee; Zuo, Zhiyi; Yang, Seong-Mi; Chang, Hye-Won; Do, Sang-Hwan

    2013-08-05

    This study aimed to evaluate the effect of riluzole on the activity of excitatory amino acid transporter type 3 (EAAT3), a neuronal glutamate transporter, and to investigate the role of protein kinase C (PKC) in this effect. EAAT3 expression was induced in Xenopus oocytes by injecting EAAT3 mRNA. Using the two-electrode voltage clamping method, membrane currents were recorded before, during, and after applying l-glutamate (30 μM) in the absence and presence of prior incubation with riluzole (0.3-100 μM). To study the effect of PKC on the riluzole-induced change in EAAT3 activity, oocytes were preincubated with 100 μM phorbol-12-myristate-13-acetate (PMA), a PKC activator, or PKC inhibitors (2 µM staurosporine and 100 µM chelerythrine) before the recording. Responses were quantified by integrating current traces and are reported in microCoulombs (μC). Riluzole reduced EAAT3 activity in a concentration-dependent manner (0.3-100 μM). Treatment of oocytes with PMA significantly increased the baseline and riluzole-reduced EAAT activity (P<0.05). In addition, treatment of oocytes with PKC inhibitors reduced basal transporter currents, but did not show a further significant decrease in the riluzole-reduced EAAT3 activity. These results suggest that riluzole reduces EAAT3 activity through PKC inhibition.

  17. Activated Charcoal

    MedlinePlus

    ... is used to treat poisonings, reduce intestinal gas (flatulence), lower cholesterol levels, prevent hangover, and treat bile ... lower cholesterol levels in the blood. Decreasing gas (flatulence). Some studies show that activated charcoal is effective ...

  18. Activity Theory.

    ERIC Educational Resources Information Center

    Koschmann, Timothy; Roschelle, Jeremy; Nardi, Bonnie A.

    1998-01-01

    Includes three articles that discuss activity theory, based on "Context and Consciousness." Topics include human-computer interaction; computer interfaces; hierarchical structuring; mediation; contradictions and development; failure analysis; and designing educational technology. (LRW)

  19. Plant metacaspase activation and activity.

    PubMed

    Minina, Elena A; Stael, Simon; Van Breusegem, Frank; Bozhkov, Peter V

    2014-01-01

    Metacaspases are essential for cell death regulation in plants. Further understanding of biochemistry of metacaspases and their molecular function in plant biology requires a set of robust methods for detection of metacaspase activation and quantitative analysis of corresponding proteolytic activity. Here we describe methods for purification of recombinant metacaspases, measurement of enzymatic activity of recombinant and endogenous metacaspases in vitro and in cell lysates, respectively, and finally detection of metacaspase activation in vivo. Additionally, an in vitro metacaspase protein substrate cleavage assay based on the cell-free production of substrate protein followed by proteolysis with recombinant metacaspase is presented. These methods have been originally developed for type II metacaspases from Arabidopsis and Norway spruce (Picea abies), but they can be used as templates for type I metacaspases, as well as for type II metacaspases from other species.

  20. Active colloids

    NASA Astrophysics Data System (ADS)

    Aranson, Igor S.

    2013-01-01

    A colloidal suspension is a heterogeneous fluid containing solid microscopic particles. Colloids play an important role in our everyday life, from food and pharmaceutical industries to medicine and nanotechnology. It is useful to distinguish two major classes of colloidal suspensions: equilibrium and active, i.e., maintained out of thermodynamic equilibrium by external electric or magnetic fields, light, chemical reactions, or hydrodynamic shear flow. While the properties of equilibrium colloidal suspensions are fairly well understood, active colloids pose a formidable challenge, and the research is in its early exploratory stage. One of the most remarkable properties of active colloids is the possibility of dynamic self-assembly, a natural tendency of simple building blocks to organize into complex functional architectures. Examples range from tunable, self-healing colloidal crystals and membranes to self-assembled microswimmers and robots. Active colloidal suspensions may exhibit material properties not present in their equilibrium counterparts, e.g., reduced viscosity and enhanced self-diffusivity, etc. This study surveys the most recent developments in the physics of active colloids, both in synthetic and living systems, with the aim of elucidation of the fundamental physical mechanisms governing self-assembly and collective behavior.

  1. Active microwaves

    NASA Technical Reports Server (NTRS)

    Evans, D.; Vidal-Madjar, D.

    1994-01-01

    Research on the use of active microwaves in remote sensing, presented during plenary and poster sessions, is summarized. The main highlights are: calibration techniques are well understood; innovative modeling approaches have been developed which increase active microwave applications (segmentation prior to model inversion, use of ERS-1 scatterometer, simulations); polarization angle and frequency diversity improves characterization of ice sheets, vegetation, and determination of soil moisture (X band sensor study); SAR (Synthetic Aperture Radar) interferometry potential is emerging; use of multiple sensors/extended spectral signatures is important (increase emphasis).

  2. Activated Sludge.

    ERIC Educational Resources Information Center

    Saunders, F. Michael

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers: (1) activated sludge process; (2) process control; (3) oxygen uptake and transfer; (4) phosphorus removal; (5) nitrification; (6) industrial wastewater; and (7) aerobic digestion. A list of 136 references is also presented. (HM)

  3. Activities: Spirolaterals.

    ERIC Educational Resources Information Center

    Brannan, Richard; McFadden, Scott

    1981-01-01

    A set of activities designed to help students discover properties about order-3 spirolaterals on square grid paper is presented. The materials are prepared on worksheets designed for easy duplication. The lessons can lead to investigations involving spirolaterals of many other orders and shapes. (MP)

  4. Leaf Activities.

    ERIC Educational Resources Information Center

    Mingie, Walter

    Leaf activities can provide a means of using basic concepts of outdoor education to learn in elementary level subject areas. Equipment needed includes leaves, a clipboard with paper, and a pencil. A bag of leaves may be brought into the classroom if weather conditions or time do not permit going outdoors. Each student should pick a leaf, examine…

  5. Learning Activities.

    ERIC Educational Resources Information Center

    Tipton, Tom, Ed.

    1983-01-01

    Presents a flow chart for naming inorganic compounds. Although it is not necessary for students to memorize rules, preliminary skills needed before using the chart are outlined. Also presents an activity in which the mass of an imaginary atom is determined using lead shot, Petri dishes, and a platform balance. (JN)

  6. Activity report

    SciTech Connect

    Yu, S W

    2008-08-11

    This report is aimed to show the author's activities to support the LDRD. The title is 'Investigation of the Double-C Behavior in the Pu-Ga Time-Temperature-Transformation Diagram' The sections are: (1) Sample Holder Test; (2) Calculation of x-ray diffraction patterns; (3) Literature search and preparing publications; (4) Tasks Required for APS Experiments; and (5) Communications.

  7. Antimicrobial Activity.

    PubMed

    2016-01-01

    Natural products of higher plants may possess a new source of antimicrobial agents with possibly novel mechanisms of action. They are effective in the treatment of infectious diseases while simultaneously mitigating many of the side effects that are often associated with conventional antimicrobials. A method using scanning electron microscope (SEM) to study the morphology of the bacterial and fungal microbes and thus determining antimicrobial activity is presented in the chapter.

  8. Subunit interactions of Rubisco activase: polyethylene glycol promotes self-association, stimulates ATPase and activation activities, and enhances interactions with Rubisco.

    PubMed

    Salvucci, M E

    1992-11-01

    The effect of polyethylene glycol (PEG) on the enzymatic and physical properties of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activase was examined. In the presence of PEG, Rubisco activase exhibited higher ATPase and Rubisco activating activities, concomitant with increased apparent affinity for ATP and Rubisco. Specific ATPase activity, which was dependent on Rubisco activase concentration, was also higher in the presence of Ficoll, polyvinylpyrrolidone, and bovine serum albumin. The ability of Rubisco activase to facilitate dissociation of the tight-binding inhibitor 2-carboxyarabinitol 1-phosphate from carbamylated Rubisco was also enhanced in the presence of PEG. Mixing experiments with Rubisco activase from two different sources showed that tobacco Rubisco activase, which exhibited little activation of spinach Rubisco by itself, was inhibitory when included with spinach Rubisco activase. Polyethylene glycol improved the ability of tobacco and a mixture of tobacco plus spinach Rubisco activase to activate spinach Rubisco. Estimates based on rate zonal sedimentation and gel-filtration chromatography indicated that the apparent molecular mass of Rubisco activase was two- to fourfold higher in the presence of PEG. The increase in apparent molecular mass was consistent with the propensity of solvent-excluding reagents like PEG to promote self-association of proteins. Likewise, the change in enzymatic properties of Rubisco activase in the presence of PEG and the dependence of specific activity on protein concentration resembled changes that often accompany self-association. For Rubisco activase, high concentrations of protein in the chloroplast stroma would provide an environment conducive to self-association and cause expression of properties that would enhance its ability to function efficiently in vivo.

  9. Analgesic Activity.

    PubMed

    2016-01-01

    Analgesics are agents which selectively relieve pain by acting in the CNS and peripheral pain mediators without changing consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical, and technical problems. Both peripheral and central pain models are included to make the test more evident for the analgesic property of the plant. This chapter highlights methods such as hot plate and formalin and acetic acid-induced pain models to check the analgesic activity of medicinal plants.

  10. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-02

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time.

  11. Active tectonics

    SciTech Connect

    Not Available

    1986-01-01

    This study is part of a series of Studies in Geophysics that have been undertaken for the Geophysics Research Forum by the Geophysics Study Committee. One purpose of each study is to provide assessments from the scientific community to aid policymakers in decisions on societal problems that involve geophysics. An important part of such assessments is an evaluation of the adequacy of current geophysical knowledge and the appropriateness of current research programs as a source of information required for those decisions. The study addresses our current scientific understanding of active tectonics --- particularly the patterns and rates of ongoing tectonic processes. Many of these processes cannot be described reasonably using the limited instrumental or historical records; however, most can be described adequately for practical purposes using the geologic record of the past 500,000 years. A program of fundamental research focusing especially on Quaternary tectonic geology and geomorphology, paleoseismology, neotectonics, and geodesy is recommended to better understand ongoing, active tectonic processes. This volume contains 16 papers. Individual papers are indexed separately on the Energy Database.

  12. Distance between two active-site lysines of ribulosebis-phosphate carboxylase/oxygenase

    SciTech Connect

    Lee, E.H.; Hartman, F.C.

    1986-05-01

    Previous affinity labeling studies and comparative sequence analyses have identified two different lysines at the active site of the title enzyme (Lys-166 and Lys-329 in the Rhodospirillum rubrum enzyme and Lys-175 and Lys-334 in the spinach enzyme). Because the two lysines are mutually exclusive to various reagents, they appear to be in proximity. To challenge this postulate, the authors have explored the reactions of the R. rubrum enzyme (a homodimer) with chemical cross-linking agents. 4,4'-Diisothiocyano-2,2'-disulfonate stilbene, which spans 12 A, rapidly inactivates the enzyme with protection afforded by the competitive inhibitor 2-carboxyribitol-1,5-bisphosphate. The inactivated enzyme was subjected to gel filtration in the presence of urea to remove material arising from intersubunit or intermolecular cross-linking. The monomeric fraction was digested with trypsin; inspection of the digest by HPLC revealed that over-half of the incorporated reagent was associated with a single peptide. This peptide was purified by successive ion-exchange chromatography and gel filtration. The amino acid composition and sequence of the purified peptide demonstrated that it is comprised of two chains, encompassing position 149-168 and 314-337 of the original protein subunit and connected by a cross-link between Lys-166 and Lys-329. Thus, the two active-site lysines can be juxtaposed only 12 A apart.

  13. Attenuation of ribosomal protein S6 phosphatase activity in chicken embryo fibroblasts transformed by Rous sarcoma virus.

    PubMed Central

    Belandia, B; Brautigan, D; Martín-Pérez, J

    1994-01-01

    In chicken embryo fibroblasts, phosphorylation of the 40S ribosomal protein S6 increases during G1 but returns to basal level by mitosis. In contrast, in Rous sarcoma virus (RSV)-transformed fibroblasts, S6 remains highly phosphorylated throughout mitosis. This study investigated the mechanism by which RSV alters the pattern of S6 phosphorylation. Pulse-chase experiments demonstrate that phosphate turnover in S6 is rapid in normal cells and in cells infected with an RSV transformation-defective virus. In contrast, phosphate turnover in S6 is severely reduced in cells infected with temperature-sensitive RSV at a temperature permissive for transformation, indicating a diminished S6 phosphatase activity. Fractionation of cell lysates by DEAE chromatography showed an almost threefold lower S6 phosphatase activity in RSV-transformed versus normal cells. The S6 phosphatase was sensitive to inhibitor 2 and specifically recognized by an antibody to type 1 phosphatase (PP1). The S6 phosphatase activity recovered by immunoprecipitation of PP1 was threefold lower in transformed cells, but the steady-state level of expression and the rate of synthesis of PP1 were not altered by oncogenic transformation. Together, the results show that transformation by RSV reduced the S6-PP1 activity. Images PMID:8264587

  14. IASS Activity

    NASA Astrophysics Data System (ADS)

    Hojaev, Alisher S.; Ibragimova, Elvira M.

    2015-08-01

    It’s well known, astronomy in Uzbekistan has ancient roots and traditions (e.g., Mirzo Ulugh Beg, Abū al-Rayhān al-Bīrūnī, Abū ‘Abdallāh al-Khwārizmī) and astronomical heritage carefully preserved. Nowadays uzbek astronomers play a key role in scientific research but also in OAD and Decadal Plan activity in the Central Asia region. International Aerospace School (IASS) is an amazing and wonderful event held annually about 30 years. IASS is unique project in the region, and at the beginning we spent the Summer and Winter Schools. At present in the summer camp we gather about 50 teenage and undergraduate students over the country and abroad (France, Malaysia, Turkey, Azerbaijan, Pakistan, Russia, etc.). They are selected on the basis of tests of astronomy and space issues. During two weeks of IASS camp the invited scientists, cosmonauts and astronauts as well as other specialists give lectures and engage in practical exercises with IASS students in astronomy, including daily observations of the Sun and night sky observations with meniscus telescope, space research and exploration, aerospace modelling, preparation and presentation of original projects. This is important that IASS gives not theoretical grounds only but also practically train the students and the hands-on training is the major aims of IASS. Lectures and practice in the field of astronomy carried out with the direct involvement and generous assistance of Uranoscope Association (Paris, France). The current 26-th IASS is planned to held in July 2015.

  15. Physical Activity (Exercise)

    MedlinePlus

    ... Physical activity (exercise) fact sheet ePublications Physical activity (exercise) fact sheet How can physical activity improve my ... recent hip surgery More information on physical activity (exercise) For more information about physical activity (exercise), call ...

  16. Activation Energy

    NASA Technical Reports Server (NTRS)

    Gadeken, Owen

    2002-01-01

    Teaming is so common in today's project management environment that most of us assume it comes naturally. We further assume that when presented with meaningful and challenging work, project teams will naturally engage in productive activity to complete their tasks. This assumption is expressed in the simple (but false) equation: Team + Work = Teamwork. Although this equation appears simple and straightforward, it is far from true for most project organizations whose reality is a complex web of institutional norms based on individual achievement and rewards. This is illustrated by the very first successful team experience from my early Air Force career. As a young lieutenant, I was sent to Squadron Officer School, which was the first in the series of Air Force professional military education courses I was required to complete during my career. We were immediately formed into teams of twelve officers. Much of the course featured competition between these teams. As the most junior member of my team, I quickly observed the tremendous pressure to show individual leadership capability. At one point early in the course, almost everyone in our group was vying to become the team leader. This conflict was so intense that it caused us to fail miserably in our first outdoor team building exercise. We spent so much time fighting over leadership that we were unable to complete any of the events on the outdoor obstacle course. This complete lack of success was so disheartening to me that I gave our team little hope for future success. What followed was a very intense period of bickering, conflict, and even shouting matches as our dysfunctional team tried to cope with our early failures and find some way to succeed. British physician and researcher Wilfred Bion (Experiences in Groups, 1961) discovered that there are powerful psychological forces inherent in all groups that divert from accomplishing their primary tasks. To overcome these restraining forces and use the potential

  17. NEU1 and NEU3 Sialidase Activity Expressed in Human Lung Microvascular Endothelia

    PubMed Central

    Cross, Alan S.; Hyun, Sang Won; Miranda-Ribera, Alba; Feng, Chiguang; Liu, Anguo; Nguyen, Chinh; Zhang, Lei; Luzina, Irina G.; Atamas, Sergei P.; Twaddell, William S.; Guang, Wei; Lillehoj, Erik P.; Puché, Adam C.; Huang, Wei; Wang, Lai-Xi; Passaniti, Antonino; Goldblum, Simeon E.

    2012-01-01

    The microvascular endothelial surface expresses multiple molecules whose sialylation state regulates multiple aspects of endothelial function. To better regulate these sialoproteins, we asked whether endothelial cells (ECs) might express one or more catalytically active sialidases. Human lung microvascular EC lysates contained heat-labile sialidase activity for a fluorogenic substrate, 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (4-MU-NANA), that was dose-dependently inhibited by the competitive sialidase inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid but not its negative control. The EC lysates also contained sialidase activity for a ganglioside mixture. Using real time RT-PCR to detect mRNAs for the four known mammalian sialidases, NEU1, -2, -3, and -4, NEU1 mRNA was expressed at levels 2700-fold higher that those found for NEU2, -3, or -4. Western analyses indicated NEU1 and -3 protein expression. Using confocal microscopy and flow cytometry, NEU1 was immunolocalized to both the plasma membrane and the perinuclear region. NEU3 was detected both in the cytosol and nucleus. Prior siRNA-mediated knockdown of NEU1 and NEU3 each decreased EC sialidase activity for 4-MU-NANA by >65 and >17%, respectively, and for the ganglioside mixture by 0 and 40%, respectively. NEU1 overexpression in ECs reduced their migration into a wound by >40%, whereas NEU3 overexpression did not. Immunohistochemical studies of normal human tissues immunolocalized NEU1 and NEU3 proteins to both pulmonary and extrapulmonary vascular endothelia. These combined data indicate that human lung microvascular ECs as well as other endothelia express catalytically active NEU1 and NEU3. NEU1 restrains EC migration, whereas NEU3 does not. PMID:22403397

  18. Ceramide-Initiated Protein Phosphatase 2A Activation Contributes to Arterial Dysfunction In Vivo

    PubMed Central

    Bharath, Leena P.; Ruan, Ting; Li, Youyou; Ravindran, Anindita; Wan, Xin; Nhan, Jennifer Kim; Walker, Matthew Lewis; Deeter, Lance; Goodrich, Rebekah; Johnson, Elizabeth; Munday, Derek; Mueller, Robert; Kunz, David; Jones, Deborah; Reese, Van; Summers, Scott A.; Babu, Pon Velayutham Anandh; Holland, William L.; Zhang, Quan-Jiang; Abel, E. Dale

    2015-01-01

    Prior studies have implicated accumulation of ceramide in blood vessels as a basis for vascular dysfunction in diet-induced obesity via a mechanism involving type 2 protein phosphatase (PP2A) dephosphorylation of endothelial nitric oxide synthase (eNOS). The current study sought to elucidate the mechanisms linking ceramide accumulation with PP2A activation and determine whether pharmacological inhibition of PP2A in vivo normalizes obesity-associated vascular dysfunction and limits the severity of hypertension. We show in endothelial cells that ceramide associates with the inhibitor 2 of PP2A (I2PP2A) in the cytosol, which disrupts the association of I2PP2A with PP2A leading to its translocation to the plasma membrane. The increased association between PP2A and eNOS at the plasma membrane promotes dissociation of an Akt-Hsp90-eNOS complex that is required for eNOS phosphorylation and activation. A novel small-molecule inhibitor of PP2A attenuated PP2A activation, prevented disruption of the Akt-Hsp90-eNOS complex in the vasculature, preserved arterial function, and maintained normal blood pressure in obese mice. These findings reveal a novel mechanism whereby ceramide initiates PP2A colocalization with eNOS and demonstrate that PP2A activation precipitates vascular dysfunction in diet-induced obesity. Therapeutic strategies targeted to reducing PP2A activation might be beneficial in attenuating vascular complications that exist in the context of type 2 diabetes, obesity, and conditions associated with insulin resistance. PMID:26253611

  19. Staying Active: Physical Activity and Exercise

    MedlinePlus

    ... How much physical activity should I do each week? The Centers for Disease Control and Prevention recommend ... 150 minutes of moderate-intensity aerobic activity a week, along with muscle-strengthening activities on 2 days ...

  20. Imaging Sites of Inhibition of Proteolysis in Pathomimetic Human Breast Cancer Cultures by Light-Activated Ruthenium Compound

    PubMed Central

    Ramalho, Suelem D.; Sharma, Rajgopal; White, Jessica K.; Aggarwal, Neha; Chalasani, Anita; Sameni, Mansoureh; Moin, Kamiar; Vieira, Paulo C.; Turro, Claudia; Kodanko, Jeremy J.; Sloane, Bonnie F.

    2015-01-01

    The cysteine protease cathepsin B has been causally linked to progression and metastasis of breast cancers. We demonstrate inhibition by a dipeptidyl nitrile inhibitor (compound 1) of cathepsin B activity and also of pericellular degradation of dye-quenched collagen IV by living breast cancer cells. To image, localize and quantify collagen IV degradation in real-time we used 3D pathomimetic breast cancer models designed to mimic the in vivo microenvironment of breast cancers. We further report the synthesis and characterization of a caged version of compound 1, [Ru(bpy)2(1)2](BF4)2 (compound 2), which can be photoactivated with visible light. Upon light activation, compound 2, like compound 1, inhibited cathepsin B activity and pericellular collagen IV degradation by the 3D pathomimetic models of living breast cancer cells, without causing toxicity. We suggest that caged inhibitor 2 is a prototype for cathepsin B inhibitors that can control both the site and timing of inhibition in cancer. PMID:26562785

  1. Antiviral Activity of a Novel Compound CW-33 against Japanese Encephalitis Virus through Inhibiting Intracellular Calcium Overload

    PubMed Central

    Huang, Su-Hua; Lien, Jin-Cherng; Chen, Chao-Jung; Liu, Yu-Ching; Wang, Ching-Ying; Ping, Chia-Fong; Lin, Yu-Fong; Huang, An-Cheng; Lin, Cheng-Wen

    2016-01-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has five genotypes (I, II, III, IV, and V). JEV genotype I circulates widely in some Asian countries. However, current JEV vaccines based on genotype III strains show low neutralizing capacities against genotype I variants. In addition, JE has no specific treatment, except a few supportive treatments. Compound CW-33, an intermediate synthesized derivative of furoquinolines, was investigated for its antiviral activities against JEV in this study. CW-33 exhibited the less cytotoxicity to Syrian baby hamster kidney (BHK-21) and human medulloblastoma (TE761) cells. CW-33 dose-dependently reduced the cytopathic effect and apoptosis of JEV-infected cells. Supernatant virus yield assay pinpointed CW-33 as having potential anti-JEV activity with IC50 values ranging from 12.7 to 38.5 μM. Time-of-addition assay with CW-33 indicated that simultaneous and post-treatment had no plaque reduction activity, but continuous and simultaneous treatments proved to have highly effective antiviral activity, with IC50 values of 32.7 and 48.5 μM, respectively. CW-33 significantly moderated JEV-triggered Ca2+ overload, which correlated with the recovery of mitochondria membrane potential as well as the activation of Akt/mTOR and Jak/STAT1 signals in treated infected cells. Phosphopeptide profiling by LC-MS/MS revealed that CW-33 upregulated proteins from the enzyme modulator category, such as protein phosphatase inhibitor 2 (I-2), Rho GTPase-activating protein 35, ARF GTPase-activating protein GIT2, and putative 3-phosphoinositide-dependent protein kinase 2. These enzyme modulators identified were associated with the activation of Akt/mTOR and Jak/STAT1 signals. Meanwhile, I-2 treatment substantially inhibited the apoptosis of JEV-infected cells. The results demonstrated that CW-33 exhibited a significant potential in the development of anti-JEV agents. PMID:27563890

  2. Dopamine and baclofen inhibit the hyperpolarization-activated cation current in rat ventral tegmental neurones.

    PubMed Central

    Jiang, Z G; Pessia, M; North, R A

    1993-01-01

    1. Whole-cell patch-clamp recordings were made from dopamine-containing ventral tegmental area neurones in slices of rat midbrain. An inward current (Ih) was activated by hyperpolarization from -60 mV. 2. Dopamine (30 microM) reduced the amplitude of Ih by 10-30% at potentials from -70 to -120 mV. The effect was concentration dependent, mimicked by the D2 agonist quinpirole, and prevented by the D2 antagonist (-)-sulpiride. Baclofen (0.3-3 microM) also inhibited Ih; this action was antagonized by 2-hydroxysaclofen but not by (-)-sulpiride. The decrease in Ih resulted from a reduction in the maximal current with no change in the voltage dependence. 3. The action of dopamine was unaffected by cadmium (200 microM), forskolin (10 microM), the adenylyl cyclase inhibitor 2',3'-dideoxyadenosine (100 microM), or by intracellular solution containing cyclic AMP (2 mM). 4. Ih was progressively reduced during the first 5-10 min of recording with electrodes containing guanosine 5'-O-(3-thiotriphosphate); after this time, dopamine had no further effect. 5. It is concluded that agonists acting at D2 receptors and GABAB receptors reduce Ih in ventral tegmental neurones. PMID:8392580

  3. Janus and PI3-kinases mediate glucocorticoid resistance in activated chronic leukemia cells

    PubMed Central

    Oppermann, Sina; Lam, Avery J.; Tung, Stephanie; Shi, Yonghong; McCaw, Lindsay; Wang, Guizhei; Ylanko, Jarkko; Leber, Brian; Andrews, David; Spaner, David E.

    2016-01-01

    Glucorticoids (GCs) such as dexamethasone (DEX) remain important treatments for Chronic Lymphocytic Leukemia (CLL) but the mechanisms are poorly understood and resistance is inevitable. Proliferation centers (PC) in lymph nodes and bone marrow offer protection against many cytotoxic drugs and circulating CLL cells were found to acquire resistance to DEX-mediated killing in conditions encountered in PCs including stimulation by toll-like receptor agonists and interactions with stromal cells. The resistant state was associated with impaired glucocorticoid receptor-mediated gene expression, autocrine activation of STAT3 through Janus Kinases (JAKs), and increased glycolysis. The JAK1/2 inhibitor ruxolitinib blocked STAT3-phosphorylation and partially improved DEX-mediated killing of stimulated CLL cells in vitro but not in CLL patients in vivo. An automated microscopy-based screen of a kinase inhibitor library implicated an additional protective role for the PI3K/AKT/FOXO pathway. Blocking this pathway with the glycolysis inhibitor 2-deoxyglucose (2-DG) or the PI3K-inhibitors idelalisib and buparlisib increased DEX-mediated killing but did not block STAT3-phosphorylation. Combining idelalisib or buparlisib with ruxolitinib greatly increased killing by DEX. These observations suggest that glucocorticoid resistance in CLL cells may be overcome by combining JAK and PI3K inhibitors. PMID:27579615

  4. Signalling mechanisms mediating Zn2+-induced TRPM2 channel activation and cell death in microglial cells

    PubMed Central

    Mortadza, Sharifah Syed; Sim, Joan A.; Stacey, Martin; Jiang, Lin-Hua

    2017-01-01

    Excessive Zn2+ causes brain damage via promoting ROS generation. Here we investigated the role of ROS-sensitive TRPM2 channel in H2O2/Zn2+-induced Ca2+ signalling and cell death in microglial cells. H2O2/Zn2+ induced concentration-dependent increases in cytosolic Ca2+ concentration ([Ca2+]c), which was inhibited by PJ34, a PARP inhibitor, and abolished by TRPM2 knockout (TRPM2-KO). Pathological concentrations of H2O2/Zn2+ induced substantial cell death that was inhibited by PJ34 and DPQ, PARP inhibitors, 2-APB, a TRPM2 channel inhibitor, and prevented by TRPM2-KO. Further analysis indicate that Zn2+ induced ROS production, PARP-1 stimulation, increase in the [Ca2+]c and cell death, all of which were suppressed by chelerythrine, a protein kinase C inhibitor, DPI, a NADPH-dependent oxidase (NOX) inhibitor, GKT137831, a NOX1/4 inhibitor, and Phox-I2, a NOX2 inhibitor. Furthermore, Zn2+-induced PARP-1 stimulation, increase in the [Ca2+]c and cell death were inhibited by PF431396, a Ca2+-sensitive PYK2 inhibitor, and U0126, a MEK/ERK inhibitor. Taken together, our study shows PKC/NOX-mediated ROS generation and PARP-1 activation as an important mechanism in Zn2+-induced TRPM2 channel activation and, TRPM2-mediated increase in the [Ca2+]c to trigger the PYK2/MEK/ERK signalling pathway as a positive feedback mechanism that amplifies the TRPM2 channel activation. Activation of these TRPM2-depenent signalling mechanisms ultimately drives Zn2+-induced Ca2+ overloading and cell death. PMID:28322340

  5. Endoplasmic reticulum stress induced by 2-deoxyglucose but not glucose starvation activates AMPK through CaMKKβ leading to autophagy.

    PubMed

    Xi, Haibin; Barredo, Julio C; Merchan, Jaime R; Lampidis, Theodore J

    2013-05-15

    Autophagy, a well-conserved cellular self-eating process, has been shown to play a critical role in the pathophysiology of cancer. Previously, we reported that under normal O₂ conditions (21% O₂), the dual glucose metabolism inhibitor 2-deoxyglucose (2-DG) activates a cytoprotective autophagic response in cancer cells mainly through the induction of endoplasmic reticulum (ER) stress rather than ATP² reduction. However, the pathway(s) by which this occurs was unknown. Here, we find that ER stress induced by 2-DG as well as tunicamycin activates AMPK via Ca²⁺-CaMKKβ leading to stimulation of autophagy. These results suggest a new role for AMPK as a sensor of ER stress. In contrast, we find that although physiologic glucose starvation (GS) leads to ER stress which contributes to autophagy activation, it does so by a different mechanism. In addition to ER stress, GS also stimulates autophagy through lowering ATP and activating the canonical LKB1-AMPK energy sensing pathway as well as through increasing reactive oxygen species resulting in the activation of ERK. Furthermore, under hypoxia we observe that both 2-DG and GS inhibit rather than activate autophagy. This inhibition correlates with dramatically depleted ATP levels, and occurs through reduction of the PI3K III-Beclin1 complex for autophagy initiation, blockage of the conjugation of ATG12 to ATG5 for autophagosome expansion, as well as inhibition of the functional lysosomal compartment for autophagic degradation. Taken together, our data support a model where under normoxia therapeutic (2-DG) and physiologic (GS) glucose restriction differentially activate autophagy, while under hypoxia they similarly inhibit it.

  6. Phospholipase C-η1 is activated by intracellular Ca(2+) mobilization and enhances GPCRs/PLC/Ca(2+) signaling.

    PubMed

    Kim, Jung Kuk; Choi, Jung Woong; Lim, Seyoung; Kwon, Ohman; Seo, Jeong Kon; Ryu, Sung Ho; Suh, Pann-Ghill

    2011-06-01

    Phospholipase C-η1 (PLC-η1) is the most recently identified PLC isotype and is primarily expressed in nerve tissue. However, its functional role is unclear. In the present study, we report for the first time that PLC-η1 acts as a signal amplifier in G protein-coupled receptor (GPCR)-mediated PLC and Ca(2+) signaling. Short-hairpin RNA (shRNA)-mediated knockdown of endogenous PLC-η1 reduced lysophosphatidic acid (LPA)-, bradykinin (BK)-, and PACAP-induced PLC activity in mouse neuroblastoma Neuro2A (N2A) cells, indicating that PLC-η1 participates in GPCR-mediated PLC activation. Interestingly, ionomycin-induced PLC activity was significantly decreased by PLC-η1, but not PLC-η2, knockdown. In addition, we found that intracellular Ca(2+) source is enough for PLC-η1 activation. Furthermore, the IP(3) receptor inhibitor, 2-APB, inhibited LPA-induced PLC activity in control N2A cells, whereas this effect was not observed in PLC-η1 knockdown N2A cells, suggesting a pivotal role of intracellular Ca(2+) mobilization in PLC-η1 activation. Finally, we found that LPA-induced ERK1/2 phosphorylation and expression of the downstream target gene, krox-24, were significantly decreased by PLC-η1 knockdown, and these knockdown effects were abolished by 2-APB. Taken together, our results strongly suggest that PLC-η1 is activated via intracellular Ca(2+) mobilization from the ER, and therefore amplifies GPCR-mediated signaling.

  7. Activation of asparaginyl endopeptidase leads to Tau hyperphosphorylation in Alzheimer disease.

    PubMed

    Basurto-Islas, Gustavo; Grundke-Iqbal, Inge; Tung, Yunn Chyn; Liu, Fei; Iqbal, Khalid

    2013-06-14

    Neurofibrillary pathology of abnormally hyperphosphorylated Tau is a key lesion of Alzheimer disease and other tauopathies, and its density in the brain directly correlates with dementia. The phosphorylation of Tau is regulated by protein phosphatase 2A, which in turn is regulated by inhibitor 2, I2(PP2A). In acidic conditions such as generated by brain ischemia and hypoxia, especially in association with hyperglycemia as in diabetes, I2(PP2A) is cleaved by asparaginyl endopeptidase at Asn-175 into the N-terminal fragment (I2NTF) and the C-terminal fragment (I2CTF). Both I2NTF and I2CTF are known to bind to the catalytic subunit of protein phosphatase 2A and inhibit its activity. Here we show that the level of activated asparaginyl endopeptidase is significantly increased, and this enzyme and I2(PP2A) translocate, respectively, from neuronal lysosomes and nucleus to the cytoplasm where they interact and are associated with hyperphosphorylated Tau in Alzheimer disease brain. Asparaginyl endopeptidase from Alzheimer disease brain could cleave GST-I2(PP2A), except when I2(PP2A) was mutated at the cleavage site Asn-175 to Gln. Finally, an induction of acidosis by treatment with kainic acid or pH 6.0 medium activated asparaginyl endopeptidase and consequently produced the cleavage of I2(PP2A), inhibition of protein phosphatase 2A, and hyperphosphorylation of Tau, and the knockdown of asparaginyl endopeptidase with siRNA abolished this pathway in SH-SY5Y cells. These findings suggest the involvement of brain acidosis in the etiopathogenesis of Alzheimer disease, and asparaginyl endopeptidase-I2(PP2A)-protein phosphatase 2A-Tau hyperphosphorylation pathway as a therapeutic target.

  8. Hypoxia-Inducible Factor-1α Causes Renal Cyst Expansion through Calcium-Activated Chloride Secretion

    PubMed Central

    Schley, Gunnar; Faria, Diana; Kroening, Sven; Willam, Carsten; Schreiber, Rainer; Klanke, Bernd; Burzlaff, Nicolai; Jantsch, Jonathan; Kunzelmann, Karl; Eckardt, Kai-Uwe

    2014-01-01

    Polycystic kidney diseases are characterized by numerous bilateral renal cysts that continuously enlarge and, through compression of intact nephrons, lead to a decline in kidney function over time. We previously showed that cyst enlargement is accompanied by regional hypoxia, which results in the stabilization of hypoxia-inducible transcription factor-1α (HIF-1α) in the cyst epithelium. Here we demonstrate a correlation between cyst size and the expression of the HIF-1α–target gene, glucose transporter 1, and report that HIF-1α promotes renal cyst growth in two in vitro cyst models—principal-like MDCK cells (plMDCKs) within a collagen matrix and cultured embryonic mouse kidneys stimulated with forskolin. In both models, augmenting HIF-1α levels with the prolyl hydroxylase inhibitor 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate enhanced cyst growth. In addition, inhibition of HIF-1α degradation through tubule-specific knockdown of the von Hippel-Lindau tumor suppressor increased cyst size in the embryonic kidney cyst model. In contrast, inhibition of HIF-1α by chetomin and knockdown of HIF-1α both decreased cyst growth in these models. Consistent with previous reports, plMDCK cyst enlargement was driven largely by transepithelial chloride secretion, which consists, in part, of a calcium-activated chloride conductance. plMDCKs deficient for HIF-1α almost completely lacked calcium-activated chloride secretion. We conclude that regional hypoxia in renal cysts contributes to cyst growth, primarily due to HIF-1α–dependent calcium-activated chloride secretion. These findings identify the HIF system as a novel target for inhibition of cyst growth. PMID:24203996

  9. Adolescent sexual activity.

    PubMed

    Braverman, P K; Strasburger, V C

    1993-11-01

    Adolescents are becoming sexually active at younger ages. One half of the adolescents in the United States are sexually active. This article reviews adolescent sexual activity, including rates of sexual activity, sexual practices, gay and lesbian youth, and factors affecting the initiation of sexual activity. In addition, adolescent pregnancy, with possible outcomes and effects on teen parents and their offspring, is discussed.

  10. Guide to Physical Activity

    MedlinePlus

    ... Families ( We Can! ) Health Professional Resources Guide to Physical Activity Physical activity is an important part of your ... to injury. Examples of moderate-intensity amounts of physical activity Common Chores Washing and waxing a car for ...

  11. Physical Activity Assessment

    Cancer.gov

    Current evidence convincingly indicates that physical activity reduces the risk of colon and breast cancer. Physical activity may also reduce risk of prostate cancer. Scientists are also evaluating potential relationships between physical activity and other cancers.

  12. Discovery of a New Inhibitor of Myeloid Differentiation 2 from Cinnamamide Derivatives with Anti-Inflammatory Activity in Sepsis and Acute Lung Injury.

    PubMed

    Chen, Gaozhi; Zhang, Yali; Liu, Xing; Fang, Qilu; Wang, Zhe; Fu, Lili; Liu, Zhiguo; Wang, Yi; Zhao, Yunjie; Li, Xiaokun; Liang, Guang

    2016-03-24

    Acute inflammatory diseases, including acute lung injury and sepsis, remain the most common life-threatening illness in intensive care units worldwide. Cinnamamide has been incorporated in several synthetic compounds with therapeutic potentials including anti-inflammatory properties. However, the possible mechanism and direct molecular target of cinnamamides for their anti-inflammatory effects were rarely investigated. In this study, we synthesized a series of cinnamamides and evaluated their anti-inflammatory activities. The most active compound, 2i, was found to block LPS-induced MD2/TLR4 pro-inflammatory signaling activation in vitro and to attenuate LPS-caused sepsis and acute lung injury in vivo. Mechanistically, we demonstrated that 2i exerts its anti-inflammatory effects by directly targeting and binding MD2 in Arg90 and Tyr102 residues and inhibiting MD2/TLR4 complex formation. Taken together, this work presents a novel MD2 inhibitor, 2i, which has the potential to be developed as a candidate for the treatment of sepsis, and provides a new lead structure for the development of anti-inflammatory agents targeting MD2.

  13. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-Mercaptobenzothiazole Part I: Fathead minnow

    EPA Science Inventory

    Development of adverse outcome pathways linking specific chemical-induced pathway perturbations to adverse outcomes relevant to regulatory decision-making has potential to support the development of alternatives to traditional whole organism toxicity tests, such as the fish early...

  14. Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole - Part II: zebrafish

    EPA Science Inventory

    Disruption of the thyroid hormone (TH) system is increasingly being recognized as an important mode of action that can lead to ecologically relevant adverse outcomes, especially during embryonic development. The present study was designed to further characterize the effects of di...

  15. Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk

    PubMed Central

    Campa, Daniele; Pastore, Manuela; Gentiluomo, Manuel; Talar-Wojnarowska, Renata; Kupcinskas, Juozas; Malecka-Panas, Ewa; Neoptolemos, John P.; Niesen, Willem; Vodicka, Pavel; Fave, Gianfranco Delle; Bueno-de-Mesquita, H. Bas; Gazouli, Maria; Pacetti, Paola; Di Leo, Milena; Ito, Hidemi; Klüter, Harald; Soucek, Pavel; Corbo, Vincenzo; Yamao, Kenji; Hosono, Satoyo; Kaaks, Rudolf; Vashist, Yogesh; Gioffreda, Domenica; Strobel, Oliver; Shimizu, Yasuhiro; Dijk, Frederike; Andriulli, Angelo; Ivanauskas, Audrius; Bugert, Peter; Tavano, Francesca; Vodickova, Ludmila; Zambon, Carlo Federico; Lovecek, Martin; Landi, Stefano; Key, Timothy J.; Boggi, Ugo; Pezzilli, Raffaele; Jamroziak, Krzysztof; Mohelnikova-Duchonova, Beatrice; Mambrini, Andrea; Bambi, Franco; Busch, Olivier; Pazienza, Valerio; Valente, Roberto; Theodoropoulos, George E.; Hackert, Thilo; Capurso, Gabriele; Cavestro, Giulia Martina; Pasquali, Claudio; Basso, Daniela; Sperti, Cosimo; Matsuo, Keitaro; Büchler, Markus; Khaw, Kay-Tee; Izbicki, Jakob; Costello, Eithne; Katzke, Verena; Michalski, Christoph; Stepien, Anna; Rizzato, Cosmeri; Canzian, Federico

    2016-01-01

    The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk. PMID:27486979

  16. Antizyme inhibitor 2 hypomorphic mice. New patterns of expression in pancreas and adrenal glands suggest a role in secretory processes.

    PubMed

    López-Garcia, Carlos; Ramos-Molina, Bruno; Lambertos, Ana; López-Contreras, Andrés J; Cremades, Asunción; Peñafiel, Rafael

    2013-01-01

    The intracellular levels of polyamines, polycations implicated in proliferation, differentiation and cell survival, are regulated by controlling their biosynthesis, catabolism and transport. Antizymes and antizyme inhibitors are key regulatory proteins of polyamine levels by affecting ornithine decarboxylase, the rate-limiting biosynthetic enzyme, and polyamine uptake. We recently described the molecular function of a novel antizyme inhibitor (AZIN2). However, the physiological function of AZIN2 in mammals is mostly unknown. To gain insight on the tissue expression profile of AZIN2 and to find its possible physiological role, we have generated, transgenic mice with severe Azin2 hypomorphism. This mouse model expresses transgenic bacterial β-D-galactosidase as a reporter gene, under the control of the Azin2 endogenous promoter, what allows a very sensitive and specific detection of the expression of the gene in the different tissues of transgenic mice. The biochemical and histochemical analyses of β-D-galactosidase together with the quantification of Azin2 mRNA levels, corroborated that AZIN2 is mainly expressed in testis and brain, and showed for the first time that AZIN2 is also expressed in the adrenal glands and pancreas. In these tissues, AZIN2 was not expressed in all type of cells, but rather in specific type of cells. Thus, AZIN2 was mainly found in the haploid germinal cells of the testis and in different brain regions such as hippocampus and cerebellum, particularly in specific type of neurons. In the adrenal glands and pancreas, the expression was restricted to the adrenal medulla and to the Langerhans islets, respectively. Interestingly, plasma insulin levels were significantly reduced in the transgenic mice. These results support the idea that AZIN2 may have a role in the modulation of reproductory and secretory functions and that this mouse model might be an interesting tool for the progress of our understanding on the role of AZIN2 and polyamines in specific mammalian cells.

  17. Derivation of rat embryonic stem cells and generation of protease-activated receptor-2 knockout rats.

    PubMed

    Yamamoto, Satoshi; Nakata, Mitsugu; Sasada, Reiko; Ooshima, Yuki; Yano, Takashi; Shinozawa, Tadahiro; Tsukimi, Yasuhiro; Takeyama, Michiyasu; Matsumoto, Yoshio; Hashimoto, Tadatoshi

    2012-08-01

    One of the remarkable achievements in knockout (KO) rat production reported during the period 2008-2010 is the derivation of authentic embryonic stem (ES) cells from rat blastocysts using a novel culture medium containing glycogen synthase kinase 3 and mitogen-activated protein kinase kinase inhibitors (2i medium). Here, we report gene-targeting technology via homologous recombination in rat ES cells, demonstrating its use through production of a protease-activated receptor-2 gene (Par-2) KO rat. We began by generating germline-competent ES cells from Dark Agouti rats using 2i medium. These ES cells, which differentiate into cardiomyocytes in vitro, can produce chimeras with high ES cell contribution when injected into blastocysts. We then introduced a targeting vector with a neomycin-resistant gene driven by the CAG promoter to disrupt Par-2. After a 7-day drug selection, 489 neomycin-resistant colonies were obtained. Following screening by polymerase chain reaction (PCR) genotyping and quantitative PCR analysis, we confirmed three homologous recombinant clones, resulting in chimeras that transmitted the Par-2 targeted allele to offspring. Par-2 KO rats showed a loss of Par-2 messenger RNA expression in their stomach cells and a lack of PAR-2 mediated smooth muscle relaxation in the aorta as indicated by pharmacological testing. Compared with mice, rats offer many advantages in biomedical research, including a larger body size; consequently, they are widely used in scientific investigation. Thus, the establishment of a gene-targeting technology using rat ES cells will be a valuable tool in human disease model production and drug discovery.

  18. Effects of three reputed carboxylesterase inhibitors upon rat serum esterase activity.

    PubMed

    Chambers, J P; Hartgraves, S L; Murphy, M R; Wayner, M J; Kumar, N; Valdes, J J

    1991-01-01

    Rats have very high endogenous levels of serum carboxylesterase (CAE) compared to primates. This difference accounts for the lower sensitivity of rats to toxic organophosphates, which interact with CAE instead of the more critical acetylcholinesterase. Pretreatment of rats with CAE inhibitors potentiates the effects of organophosphates. In this study, the effects of three putative CAE inhibitors, 2-(o-Cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP), bis-p-nitrophenyl-phosphate (BNPP), and tetraisopropyl pyrophosphoramide (Iso-OMPA), on the hydrolysis of several commercially available substrates were determined. Respective kinetic constants Km and Vmax were derived and effects of inhibitors compared using saturating amounts of substrate. Data presented here indicate significant differences in substrate affinity (Km), reactivity (Vmax), as well as effects of inhibitors. CBDP inhibits hydrolysis of specific naphthyl and paranitrophenyl esters at relatively low concentrations (1-10 microM). In contrast, significantly higher concentrations (mM) of BNPP and Iso-OMPA were required for inhibition of serum esterase activity. Of the inhibitors tested, Iso-OMPA in general exhibited the smallest inhibitory effect on ester hydrolysis. Although inhibition of hydrolysis of specific paranitrophenyl and naphthyl esters occurred in the presence of similar amounts of CBDP, the degree of inhibition differed significantly (50-75% vs. greater than 90%, respectively). These data suggest that there exists in rat serum, a pool of naphthyl ester esterase activity that is very sensitive ex vivo (greater than 90% inhibition) to CBDP and may be very useful in validating a rodent model for soman toxicity.

  19. Political activity for physical activity: health advocacy for active transport

    PubMed Central

    2011-01-01

    Effective health advocacy is a priority for efforts to increase population participation in physical activity. Local councils are an important audience for this advocacy. The aim of the current study was to describe features of advocacy for active transport via submissions to city council annual plans in New Zealand, and the impact of an information sheet to encourage the health sector to be involved in this process. Written submissions to city council's annual consultation process were requested for 16 city councils over the period of three years (2007/08, 2008/09, and 2009/10). Submissions were reviewed and categories of responses were created. An advocacy information sheet encouraging health sector participation and summarising some of the evidence-base related to physical activity, active transport and health was released just prior to the 2009/10 submission time. Over the period of the study, city councils received 47,392 submissions, 17% of which were related to active transport. Most submissions came from city residents, with a small proportion (2%) from the health sector. The largest category of submissions was in support of pedestrian and cycling infrastructure, design and maintenance of facilities and additional features to support use of these transport modes. Health arguments featured prominently in justifications for active transport initiatives, including concerns about injury risk, obesity, physical inactivity, personal safety and facilities for people with disabilities. There was evidence that the information sheet was utilised by some health sector submitters (12.5%), providing tentative support for initiatives of this nature. In conclusion, the study provides novel information about the current nature of health advocacy for active transport and informs future advocacy efforts about areas for emphasis, such as health benefits of active transport, and potential alliances with other sectors such as environmental sustainability, transport and urban

  20. Home Activities for Fours.

    ERIC Educational Resources Information Center

    Ferguson-Florissant School District, Ferguson, MO.

    These home learning activity guides have been developed for parents to use with their 4-year-old children. Most of the activities require only household items that are often thrown away and can be recycled for learning activities. Some require no materials at all. The guides frequently begin with a discussion of home activities; progress through…

  1. Active commuting to school

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Declines in physical activity levels have coincided with increasing rates of obesity in children. This is problematic because physical activity has been shown to attenuate weight gain in children. Active commuting to school is one way of increasing children's physical activity. However, given the hi...

  2. Civil Law: 12 Activities.

    ERIC Educational Resources Information Center

    Dresbach, Debra

    These learning activities on civil law are intended to supplement the secondary level Scholastic materials "Living Law." Case studies, simulations, and role-play activities are included. Information provided for each activity includes a brief overview, background information, teacher instructions and a description of each activity.…

  3. Increasing Youth Physical Activity with Activity Calendars

    ERIC Educational Resources Information Center

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  4. Runx2 Trans-Activation Mediated by the Msx2-Interacting Nuclear Target Requires Homeodomain Interacting Protein Kinase-3

    PubMed Central

    Sierra, Oscar L.; Towler, Dwight A.

    2010-01-01

    Runt-related transcription factor 2 (Runx2) and muscle segment homeobox homolog 2-interacting nuclear target (MINT) (Spen homolog) are transcriptional regulators critical for mammalian development. MINT enhances Runx2 activation of osteocalcin (OC) fibroblast growth factor (FGF) response element in an FGF2-dependent fashion in C3H10T1/2 cells. Although the MINT N-terminal RNA recognition motif domain contributes, the muscle segment homeobox homolog 2-interacting domain is sufficient for Runx2 activation. Intriguingly, Runx1 cannot replace Runx2 in this assay. To better understand this Runx2 signaling cascade, we performed structure-function analysis of the Runx2-MINT trans-activation relationship. Systematic truncation and domain swapping in Runx1:Runx2 chimeras identified that the unique Runx2 activation domain 3 (AD3), encompassed by residues 316–421, conveys MINT+FGF2 trans-activation in transfection assays. Ala mutagenesis of Runx2 Ser/Thr residues identified that S301 and T326 in AD3 are necessary for full MINT+FGF2 trans-activation. Conversely, phosphomimetic Asp substitution of these AD3 Ser/Thr residues enhanced activation by MINT. Adjacent Pro residues implicated regulation by a proline-directed protein kinase (PDPK). Systematic screening with PDPK inhibitors identified that the casein kinase-2/homeodomain-interacting protein kinase (HIPK)/dual specificity tyrosine phosphorylation regulated kinase inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT), but not ERK, c-Jun N-terminal kinase, p38MAPK, or other casein kinase-2 inhibitors, abrogated Runx2-, MINT-, and FGF2-activation. Systematic small interfering RNA-mediated silencing of DMAT-inhibited PDPKs revealed that HIPK3 depletion reduced MINT+FGF2-dependent activation of Runx2. HIPK3 and Runx2 coprecipitate after in vitro transcription-translation, and recombinant HIPK3 recognizes Runx2 AD3 as kinase substrate. Furthermore, DMAT treatment and HIPK3 RNAi inhibited MINT+FGF2 activation of

  5. Cultural Activation of Consumers.

    PubMed

    Siegel, Carole E; Reid-Rose, Lenora; Joseph, Adriana M; Hernandez, Jennifer C; Haugland, Gary

    2016-02-01

    This column discusses "cultural activation," defined as a consumer's recognition of the importance of providing cultural information to providers about cultural affiliations, challenges, views about, and attitudes toward behavioral health and general medical health care, as well as the consumer's confidence in his or her ability to provide this information. An aid to activation, "Cultural Activation Prompts," and a scale that measures a consumer's level of activation, the Cultural Activation Measurement Scale, are described. Suggestions are made about ways to introduce cultural activation as a component of usual care.

  6. Adenosine promotes burst activity in guinea-pig geniculocortical neurones through two different ionic mechanisms.

    PubMed Central

    Pape, H C

    1992-01-01

    1. The mechanisms of action of adenosine were examined in relay neurones of the dorsal lateral geniculate nucleus (LGND) using in vitro intracellular recording techniques in guinea-pig thalamic slices. 2. Adenosine hyperpolarized LGND relay neurones due to an increase in membrane potassium conductance. The K+ currents generated by near maximal stimulation of adenosine and GABAB receptors were non-additive. 3. Blockage of membrane K+ conductances by barium unmasked a second response to adenosine; an outward shift of the current versus voltage relationship negative to -65 mV associated with an increase in membrane input resistance. The beta-adrenoceptor agonist isoprenaline elicited an inward current in the same voltage range, which was inhibited and replaced by an outward current during activation of adenosine receptors. The effects of adenosine were due to a decrease in amplitude and rate of rise of the hyperpolarization-activated cation current, Ih. Maximal reduction by 66% of Ih amplitude occurred near the range of half-activation. 4. Both responses to adenosine were mimicked by the selective A1 receptor agonists N6-cyclopentyladenosine or N6-cyclohexyladenosine, and reversibly blocked by the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). 5. The decrease in Ih by adenosine may be mediated by an inhibition of adenylyl cyclase activity and hence a decrease in the intracellular level of cyclic AMP, since local application of the adenylyl cyclase inhibitor 2',3'-dideoxyadenosine imitated the decrease in Ih. Local application of the adenylyl cyclase stimulant forskolin or 8-bromo-cyclic AMP resulted in an enhancement in Ih, and forskolin inhibited the action on Ih evoked by N6-cyclopentyladenosine. 6. The adenosine-induced effects interacted with the intrinsic electrophysiological properties of LGND neurones in that (i) the hyperpolarization due to an increase in K+ conductance inhibited single spike firing and promoted calcium

  7. Smoking, physical activity, and active life expectancy.

    PubMed

    Ferrucci, L; Izmirlian, G; Leveille, S; Phillips, C L; Corti, M C; Brock, D B; Guralnik, J M

    1999-04-01

    The effect of smoking and physical activity on active and disabled life expectancy was estimated using data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE). Population-based samples of persons aged > or = 65 years from the East Boston, Massachusetts, New Haven, Connecticut, and Iowa sites of the EPESE were assessed at baseline between 1981 and 1983 and followed for mortality and disability over six annual follow-ups. A total of 8,604 persons without disability at baseline were classified as "ever" or "never" smokers and doing "low," "moderate," or "high" level physical activity. Active and disabled life expectancies were estimated using a Markov chain model. Compared with smokers, men and women nonsmokers survived 1.6-3.9 and 1.6-3.6 years longer, respectively, depending on level of physical activity. When smokers were disabled and close to death, most nonsmokers were still nondisabled. Physical activity, from low to moderate to high, was significantly associated with more years of life expectancy in both smokers (9.5, 10.5, 12.9 years in men and 11.1, 12.6, 15.3 years in women at age 65) and nonsmokers (11.0, 14.4, 16.2 years in men and 12.7, 16.2, 18.4 years in women at age 65). Higher physical activity was associated with fewer years of disability prior to death. These findings provide strong and explicit evidence that refraining from smoking and doing regular physical activity predict a long and healthy life.

  8. Population Education. Awareness Activities.

    ERIC Educational Resources Information Center

    Brouse, Deborah E.

    1990-01-01

    Described are awareness activities that deal with human population growth, resources, and the environment. Activities include simulations, mathematical exercises, and discussions of the topic. Specific examples of what individuals can do to help are listed. (KR)

  9. Major operations and activities

    SciTech Connect

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development.

  10. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  11. Active magnetic regenerator

    DOEpatents

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  12. ACS Community Activities Contests

    NASA Astrophysics Data System (ADS)

    Burgener, Marisa

    2007-08-01

    The Committee on Community Activities and the Office of Community Activities announce the winners of the Illustrated Haiku Contest, Earth Day 2007 and the Poster Contest, National Chemistry Week 2006.

  13. Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC/IP(3) pathway and the ryanodine receptor.

    PubMed

    Ortiz-Capisano, M Cecilia; Reddy, Mahendranath; Mendez, Mariela; Garvin, Jeffrey L; Beierwaltes, William H

    2013-02-01

    The calcium-sensing receptor (CaSR) is a G-coupled protein expressed in renal juxtaglomerular (JG) cells. Its activation stimulates calcium-mediated decreases in cAMP content and inhibits renin release. The postreceptor pathway for the CaSR in JG cells is unknown. In parathyroids, CaSR acts through G(q) and/or G(i). Activation of G(q) stimulates phospholipase C (PLC), and inositol 1,4,5-trisphosphate (IP(3)), releasing calcium from intracellular stores. G(i) stimulation inhibits cAMP formation. In afferent arterioles, the ryanodine receptor (RyR) enhances release of stored calcium. We hypothesized JG cell CaSR activation inhibits renin via the PLC/IP(3) and also RyR activation, increasing intracellular calcium, suppressing cAMP formation, and inhibiting renin release. Renin release from primary cultures of isolated mouse JG cells (n = 10) was measured. The CaSR agonist cinacalcet decreased renin release 56 ± 7% of control (P < 0.001), while the PLC inhibitor U73122 reversed cinacalcet inhibition of renin (104 ± 11% of control). The IP(3) inhibitor 2-APB also reversed inhibition of renin from 56 ± 6 to 104 ± 11% of control (P < 0.001). JG cells were positively labeled for RyR, and blocking RyR reversed CaSR-mediated inhibition of renin from 61 ± 8 to 118 ± 22% of control (P < 0.01). Combining inhibition of IP(3) and RyR was not additive. G(i) inhibition with pertussis toxin plus cinacalcet did not reverse renin inhibition (65 ± 12 to 41 ± 8% of control, P < 0.001). We conclude stimulating JG cell CaSR activates G(q), initiating the PLC/IP(3) pathway, activating RyR, increasing intracellular calcium, and resulting in calcium-mediated renin inhibition.

  14. Activity Theory and Ontology

    ERIC Educational Resources Information Center

    Peim, Nick

    2009-01-01

    This paper seeks to re-examine Yrio Engestrom's activity theory as a technology of knowledge designed to enable positive transformations of specific practices. The paper focuses on a key paper where Engestrom defines the nature and present state of activity theory. Beginning with a brief account of the relations between activity theory and…

  15. Measurement of Physical Activity.

    ERIC Educational Resources Information Center

    Dishman, Rod K.; Washburn, Richard A.; Schoeller, Dale A.

    2001-01-01

    Valid assessment of physical activity must be unobtrusive, practical to administer, and specific about physical activity type, frequency, duration, and intensity. Assessment methods can be categorized according to whether they provide direct or indirect (e.g., self-report) observation of physical activity, body motion, physiological response…

  16. Horticultural Practices. Activity Guides.

    ERIC Educational Resources Information Center

    Bania, Kent; Cummings, John, Ed.

    The 88 activity guides in this document are intended to supplement the initial or organized instruction of the agricultural teacher at the secondary educational level. Some of the activities require one student to complete, others may need two or more students working in a team. Some activities also require followup checking within a few days to…

  17. Highlights of 1981 activities

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The highlights of NASA's 1981 activities are presented, including the results of the two flights of the space shuttle Columbia and the Voyager 2 encounter with Saturn. Accomplishments in the areas of space transportation operations; space science; aeronautical, energy, and space research and development; as well as space tracking, international activities, and 1981 launch activities are discussed.

  18. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Provides on-task activities to fill in unexpected extra moments in elementary classes. The activities require little preparation and take 5-15 minutes to complete. There are activities for math, language arts, social science, science, critical thinking, and computer. An outer space board game is also included. (SM)

  19. Activity Sheets. Draft Copy.

    ERIC Educational Resources Information Center

    Duke Power Company, Educational Services Dept., Charlotte, NC.

    This document consists of energy vocabulary activities, three games, worksheets, laboratory activities/exercises, and an introductory classroom exercise designed to introduce energy concepts to students. Vocabulary activities focus on coal and energy consumption. The three games (with instructions) focus on various aspects of energy and energy…

  20. Technology Learning Activities I.

    ERIC Educational Resources Information Center

    International Technology Education Association, Reston, VA.

    This guide contains 30 technology learning activities. Activities may contain all or some of the following: an introduction, objectives, materials and equipment, challenges, limitations, notes and investigations, resources and references used, and evaluation ideas. Activity titles are: (1) Occupations in Construction Technology; (2) Designing a…

  1. Technology Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Brame, Ray; And Others

    This guide contains 43 modules of laboratory activities for technology education courses. Each module includes an instructor's resource sheet and the student laboratory activity. Instructor's resource sheets include some or all of the following elements: module number, course title, activity topic, estimated time, essential elements, objectives,…

  2. Computers + Student Activities Handbook.

    ERIC Educational Resources Information Center

    Masie, Elliott; Stein, Michele

    Designed to provide schools with the tools to start utilizing computers for student activity programs without additional expenditures, this handbook provides beginning computer users with suggestions and ideas for using computers in such activities as drama clubs, yearbooks, newspapers, activity calendars, accounting programs, room utilization,…

  3. Climate Change: An Activity.

    ERIC Educational Resources Information Center

    Lewis, Garry

    1995-01-01

    Presents a segment of the Geoscience Education booklet, Climate Change, that contains information and activities that enable students to gain a better appreciation of the possible effects human activity has on the Earth's climate. Describes the Terrace Temperatures activity that leads students through an investigation using foraminifera data to…

  4. Identification and functional characterization of the intermediate-conductance Ca(2+)-activated K(+) channel (IK-1) in biliary epithelium.

    PubMed

    Dutta, Amal K; Khimji, Al-karim; Sathe, Meghana; Kresge, Charles; Parameswara, Vinay; Esser, Victoria; Rockey, Don C; Feranchak, Andrew P

    2009-11-01

    In the liver, adenosine triphosphate (ATP) is an extracellular signaling molecule that is released into bile and stimulates a biliary epithelial cell secretory response via engagement of apical P2 receptors. The molecular identities of the ion channels involved in ATP-mediated secretory responses have not been fully identified. Intermediate-conductance Ca(2+)-activated K(+) channels (IK) have been identified in biliary epithelium, but functional data are lacking. The aim of these studies therefore was to determine the location, function, and regulation of IK channels in biliary epithelial cells and to determine their potential contribution to ATP-stimulated secretion. Expression of IK-1 mRNA was found in both human Mz-Cha-1 biliary cells and polarized normal rat cholangiocyte (NRC) monolayers, and immunostaining revealed membrane localization with a predominant basolateral signal. In single Mz-Cha-1 cells, exposure to ATP activated K(+) currents, increasing current density from 1.6 +/- 0.1 to 7.6 +/- 0.8 pA/pF. Currents were dependent on intracellular Ca(2+) and sensitive to clotrimazole and TRAM-34 (specific IK channel inhibitors). Single-channel recording demonstrated that clotrimazole-sensitive K(+) currents had a unitary conductance of 46.2 +/- 1.5 pS, consistent with IK channels. In separate studies, 1-EBIO (an IK activator) stimulated K(+) currents in single cells that were inhibited by clotrimazole. In polarized NRC monolayers, ATP significantly increased transepithelial secretion which was inhibited by clotrimazole. Lastly, ATP-stimulated K(+) currents were inhibited by the P2Y receptor antagonist suramin and by the inositol 1,4,5-triphosphate (IP3) receptor inhibitor 2-APB. Together these studies demonstrate that IK channels are present in biliary epithelial cells and contribute to ATP-stimulated secretion through a P2Y-IP3 receptor pathway.

  5. Peptidyl arginine deiminase-4 activation exacerbates kidney ischemia-reperfusion injury.

    PubMed

    Ham, Ahrom; Rabadi, May; Kim, Mihwa; Brown, Kevin M; Ma, Zhe; D'Agati, Vivette; Lee, H Thomas

    2014-11-01

    Peptidyl arginine deiminase (PAD)4 is a nuclear enzyme that catalyzes the posttranslational conversion of arginine residues to citrulline. Posttranslational protein citrullination has been implicated in several inflammatory autoimmune diseases, including rheumatoid arthritis, colitis, and multiple sclerosis. Here, we tested the hypothesis that PAD4 contributes to ischemic acute kidney injury (AKI) by exacerbating the inflammatory response after renal ischemia-reperfusion (I/R). Renal I/R injury in mice increased PAD4 activity as well as PAD4 expression in the mouse kidney. After 30 min of renal I/R, vehicle-treated mice developed severe AKI with large increases in plasma creatinine. In contrast, mice pretreated with PAD4 inhibitors (2-chloroamidine or streptonigrin) had significantly reduced renal I/R injury. Further supporting a critical role for PAD4 in generating ischemic AKI, mice pretreated with recombinant human PAD4 (rPAD4) protein and subjected to mild (20 min) renal I/R developed exacerbated ischemic AKI. Consistent with the hypothesis that PAD4 regulates renal tubular inflammation after I/R, mice treated with a PAD4 inhibitor had significantly reduced renal neutrophil chemotactic cytokine (macrophage inflammatory protein-2 and keratinocyte-derived cytokine) expression and had decreased neutrophil infiltration. Furthermore, mice treated with rPAD4 had significantly increased renal tubular macrophage inflammatory protein-2 and keratinocyte-derived cytokine expression as well as increased neutrophil infiltration and necrosis. Finally, cultured mouse kidney proximal tubules treated with rPAD4 had significantly increased proinflammatory chemokine expression compared with vehicle-treated cells. Taken together, our results suggest that PAD4 plays a critical role in renal I/R injury by increasing renal tubular inflammatory responses and neutrophil infiltration after renal I/R.

  6. Peptidyl arginine deiminase-4 activation exacerbates kidney ischemia-reperfusion injury

    PubMed Central

    Ham, Ahrom; Rabadi, May; Kim, Mihwa; Brown, Kevin M.; Ma, Zhe; D'Agati, Vivette

    2014-01-01

    Peptidyl arginine deiminase (PAD)4 is a nuclear enzyme that catalyzes the posttranslational conversion of arginine residues to citrulline. Posttranslational protein citrullination has been implicated in several inflammatory autoimmune diseases, including rheumatoid arthritis, colitis, and multiple sclerosis. Here, we tested the hypothesis that PAD4 contributes to ischemic acute kidney injury (AKI) by exacerbating the inflammatory response after renal ischemia-reperfusion (I/R). Renal I/R injury in mice increased PAD4 activity as well as PAD4 expression in the mouse kidney. After 30 min of renal I/R, vehicle-treated mice developed severe AKI with large increases in plasma creatinine. In contrast, mice pretreated with PAD4 inhibitors (2-chloroamidine or streptonigrin) had significantly reduced renal I/R injury. Further supporting a critical role for PAD4 in generating ischemic AKI, mice pretreated with recombinant human PAD4 (rPAD4) protein and subjected to mild (20 min) renal I/R developed exacerbated ischemic AKI. Consistent with the hypothesis that PAD4 regulates renal tubular inflammation after I/R, mice treated with a PAD4 inhibitor had significantly reduced renal neutrophil chemotactic cytokine (macrophage inflammatory protein-2 and keratinocyte-derived cytokine) expression and had decreased neutrophil infiltration. Furthermore, mice treated with rPAD4 had significantly increased renal tubular macrophage inflammatory protein-2 and keratinocyte-derived cytokine expression as well as increased neutrophil infiltration and necrosis. Finally, cultured mouse kidney proximal tubules treated with rPAD4 had significantly increased proinflammatory chemokine expression compared with vehicle-treated cells. Taken together, our results suggest that PAD4 plays a critical role in renal I/R injury by increasing renal tubular inflammatory responses and neutrophil infiltration after renal I/R. PMID:25164081

  7. Vestibular activation of sympathetic nerve activity

    NASA Technical Reports Server (NTRS)

    Ray, C. A.; Carter, J. R.

    2003-01-01

    AIM: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well-established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure. CONCLUSION: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.

  8. Metabolism Supports Macrophage Activation

    PubMed Central

    Langston, P. Kent; Shibata, Munehiko; Horng, Tiffany

    2017-01-01

    Macrophages are found in most tissues of the body, where they have tissue- and context-dependent roles in maintaining homeostasis as well as coordinating adaptive responses to various stresses. Their capacity for specialized functions is controlled by polarizing signals, which activate macrophages by upregulating transcriptional programs that encode distinct effector functions. An important conceptual advance in the field of macrophage biology, emerging from recent studies, is that macrophage activation is critically supported by metabolic shifts. Metabolic shifts fuel multiple aspects of macrophage activation, and preventing these shifts impairs appropriate activation. These findings raise the exciting possibility that macrophage functions in various contexts could be regulated by manipulating their metabolism. Here, we review the rapidly evolving field of macrophage metabolism, discussing how polarizing signals trigger metabolic shifts and how these shifts enable appropriate activation and sustain effector activities. We also discuss recent studies indicating that the mitochondria are central hubs in inflammatory macrophage activation. PMID:28197151

  9. Activated carbon from biomass

    NASA Astrophysics Data System (ADS)

    Manocha, S.; Manocha, L. M.; Joshi, Parth; Patel, Bhavesh; Dangi, Gaurav; Verma, Narendra

    2013-06-01

    Activated carbon are unique and versatile adsorbents having extended surface area, micro porous structure, universal adsorption effect, high adsorption capacity and high degree of surface reactivity. Activated carbons are synthesized from variety of materials. Most commonly used on a commercial scale are cellulosic based precursors such as peat, coal, lignite wood and coconut shell. Variation occurs in precursors in terms of structure and carbon content. Coir having very low bulk density and porous structure is found to be one of the valuable raw materials for the production of highly porous activated carbon and other important factor is its high carbon content. Exploration of good low cost and non conventional adsorbent may contribute to the sustainability of the environment and offer promising benefits for the commercial purpose in future. Carbonization of biomass was carried out in a horizontal muffle furnace. Both carbonization and activation were performed in inert nitrogen atmosphere in one step to enhance the surface area and to develop interconnecting porosity. The types of biomass as well as the activation conditions determine the properties and the yield of activated carbon. Activated carbon produced from biomass is cost effective as it is easily available as a waste biomass. Activated carbon produced by combination of chemical and physical activation has higher surface area of 2442 m2/gm compared to that produced by physical activation (1365 m2/gm).

  10. Factor XII Contact Activation.

    PubMed

    Naudin, Clément; Burillo, Elena; Blankenberg, Stefan; Butler, Lynn; Renné, Thomas

    2017-03-27

    Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation-associated disease states.

  11. Marine Biology Activities. Ocean Related Curriculum Activities.

    ERIC Educational Resources Information Center

    Pauls, John

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  12. NEU1 and NEU3 sialidase activity expressed in human lung microvascular endothelia: NEU1 restrains endothelial cell migration, whereas NEU3 does not.

    PubMed

    Cross, Alan S; Hyun, Sang Won; Miranda-Ribera, Alba; Feng, Chiguang; Liu, Anguo; Nguyen, Chinh; Zhang, Lei; Luzina, Irina G; Atamas, Sergei P; Twaddell, William S; Guang, Wei; Lillehoj, Erik P; Puché, Adam C; Huang, Wei; Wang, Lai-Xi; Passaniti, Antonino; Goldblum, Simeon E

    2012-05-04

    The microvascular endothelial surface expresses multiple molecules whose sialylation state regulates multiple aspects of endothelial function. To better regulate these sialoproteins, we asked whether endothelial cells (ECs) might express one or more catalytically active sialidases. Human lung microvascular EC lysates contained heat-labile sialidase activity for a fluorogenic substrate, 2'-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (4-MU-NANA), that was dose-dependently inhibited by the competitive sialidase inhibitor, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid but not its negative control. The EC lysates also contained sialidase activity for a ganglioside mixture. Using real time RT-PCR to detect mRNAs for the four known mammalian sialidases, NEU1, -2, -3, and -4, NEU1 mRNA was expressed at levels 2700-fold higher that those found for NEU2, -3, or -4. Western analyses indicated NEU1 and -3 protein expression. Using confocal microscopy and flow cytometry, NEU1 was immunolocalized to both the plasma membrane and the perinuclear region. NEU3 was detected both in the cytosol and nucleus. Prior siRNA-mediated knockdown of NEU1 and NEU3 each decreased EC sialidase activity for 4-MU-NANA by >65 and >17%, respectively, and for the ganglioside mixture by 0 and 40%, respectively. NEU1 overexpression in ECs reduced their migration into a wound by >40%, whereas NEU3 overexpression did not. Immunohistochemical studies of normal human tissues immunolocalized NEU1 and NEU3 proteins to both pulmonary and extrapulmonary vascular endothelia. These combined data indicate that human lung microvascular ECs as well as other endothelia express catalytically active NEU1 and NEU3. NEU1 restrains EC migration, whereas NEU3 does not.

  13. A membrane-associated adenylate cyclase modulates lactate dehydrogenase and creatine kinase activities required for bull sperm capacitation induced by hyaluronic acid.

    PubMed

    Fernández, Silvina; Córdoba, Mariana

    2017-04-01

    Hyaluronic acid, as well as heparin, is a glycosaminoglycan present in the female genital tract of cattle. The aim of this study was to evaluate oxidative metabolism and intracellular signals mediated by a membrane-associated adenylate cyclase (mAC), in sperm capacitation with hyaluronic acid and heparin, in cryopreserved bull sperm. The mAC inhibitor, 2',5'-dideoxyadenosine, was used in the present study. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities and lactate concentration were determined spectrophotometrically in the incubation medium. Capacitation and acrosome reaction were evaluated by chlortetracycline technique, while plasma membrane and acrosome integrity were determined by trypan blue stain/differential interference contrast microscopy. Heparin capacitated samples had a significant decrease in LDH and CK activities, while in hyaluronic acid capacitated samples LDH and CK activities both increased compared to control samples, in heparin and hyaluronic acid capacitation conditions, respectively. A significant increase in lactate concentration in the incubation medium occurred in hyaluronic acid-treated sperm samples compared to heparin treatment, indicating this energetic metabolite is produced during capacitation. The LDH and CK enzyme activities and lactate concentrations in the incubation medium were decreased with 2',5'-dideoxyadenosine treatment in hyaluronic acid samples. The mAC inhibitor significantly inhibited heparin-induced capacitation of sperm cells, but did not completely inhibit hyaluronic acid capacitation. Therefore, hyaluronic acid and heparin are physiological glycosaminoglycans capable of inducing in vitro capacitation in cryopreserved bull sperm, stimulating different enzymatic pathways and intracellular signals modulated by a mAC. Hyaluronic acid induces sperm capacitation involving LDH and CK activities, thereby reducing oxidative metabolism, and this process is mediated by mAC.

  14. Patterns in Active Nematics

    NASA Astrophysics Data System (ADS)

    Yeomans, Julia M.

    Active systems, from bacterial suspensions to cellular monolayers, are continuously driven out of equilibrium by local injection of energy from their constituent elements and exhibit turbulent-like, chaotic patterns. We describe how active systems can be stabilised by tuning a physical feature of the system, friction. We demonstrate how the crossover between wet active systems, whose behaviour is dominated by hydrodynamics, and dry active matter where any flow is screened, can be achieved by using friction as a control parameter and demonstrate vortex ordering at the wet-dry crossover. We show that the self organisation of vortices into lattices is accompanied by the spatial ordering of topological defects leading to active crystal-like structures. The emergence of vortex lattices which leads to the positional ordering of topological defects may be a useful step towards the design and control of active materials.

  15. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, C.W.; Mangel, W.F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  16. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  17. Activity in distant comets

    NASA Technical Reports Server (NTRS)

    Luu, Jane X.

    1992-01-01

    Activity in distant comets remains a mystery in the sense that we still have no complete theory to explain the various types of activity exhibited by different comets at large distances. This paper explores the factors that should play a role in determining activity in a distant comet, especially in the cases of comet P/Tempel 2, comet Schwassmann-Wachmann 1, and 2060 Chiron.

  18. Thermally Activated Driver

    NASA Technical Reports Server (NTRS)

    Kinard, William H.; Murray, Robert C.; Walsh, Robert F.

    1987-01-01

    Space-qualified, precise, large-force, thermally activated driver (TAD) developed for use in space on astro-physics experiment to measure abundance of rare actinide-group elements in cosmic rays. Actinide cosmic rays detected using thermally activated driver as heart of event-thermometer (ET) system. Thermal expansion and contraction of silicone oil activates driver. Potential applications in fluid-control systems where precise valve controls are needed.

  19. [Biomedical activity of biosurfactants].

    PubMed

    Krasowska, Anna

    2010-07-23

    Biosurfactants, amphiphilic compounds, synthesized by microorganisms have surface, antimicrobial and antitumor properties. Biosurfactants prevent adhesion and biofilms formation by bacteria and fungi on various surfaces. For many years microbial surfactants are used as antibiotics with board spectrum of activity against microorganisms. Biosurfactants act as antiviral compounds and their antitumor activities are mediated through induction of apoptosis. This work presents the current state of knowledge related to biomedical activity of biosurfactants.

  20. NASA metrication activities

    NASA Technical Reports Server (NTRS)

    Vlannes, P. N.

    1978-01-01

    NASA's organization and policy for metrification, history from 1964, NASA participation in Federal agency activities, interaction with nongovernmental metrication organizations, and the proposed metrication assessment study are reviewed.

  1. Active Flow Control Activities at NASA Langley

    NASA Technical Reports Server (NTRS)

    Anders, Scott G.; Sellers, William L., III; Washburn, Anthony E.

    2004-01-01

    NASA Langley continues to aggressively investigate the potential advantages of active flow control over more traditional aerodynamic techniques. This paper provides an update to a previous paper and describes both the progress in the various research areas and the significant changes in the NASA research programs. The goals of the topics presented are focused on advancing the state of knowledge and understanding of controllable fundamental mechanisms in fluids as well as to address engineering challenges. An organizational view of current research activities at NASA Langley in active flow control as supported by several projects is presented. On-center research as well as NASA Langley funded contracts and grants are discussed at a relatively high level. The products of this research are to be demonstrated either in bench-top experiments, wind-tunnel investigations, or in flight as part of the fundamental NASA R&D program and then transferred to more applied research programs within NASA, DOD, and U.S. industry.

  2. Active Students in Webinars

    ERIC Educational Resources Information Center

    Kolås, Line; Nordseth, Hugo; Yri, Jørgen Sørlie

    2015-01-01

    To ensure student activity in webinars we have defined 10 learning tasks focusing on production and communication e.g. collaborative writing, discussion and polling, and investigated how the technology supports the learning activities. The three project partners in the VisPed-project use different video-conferencing systems, and we analyzed how it…

  3. [Field Learning Activities].

    ERIC Educational Resources Information Center

    Nolde Forest Environmental Education Center, Reading, PA.

    Seventy field activities, pertinent to outdoor, environmental studies, are described in this compilation. Designed for elementary and junior high school students, the activities cover many discipline areas--science, social studies, language arts, health, history, mathematics, and art--and many are multidisciplinary in use. Topics range from soil…

  4. Warm-Up Activities.

    ERIC Educational Resources Information Center

    Mingguang, Yang

    1999-01-01

    Discusses how warm-up activities can help to make the English-as-a-foreign-language classroom a lively and interesting place. Warm-up activities are games carried out at the beginning of each class to motivate students to make good use of class time. (Author/VWL)

  5. Nutrition Activities Resource Guide.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Div. of Special Education.

    The resource guide suggests activities to help special education students make appropriate choices about their nutritional habits. It is explained that the activities can be infused into other curriculum areas. The guide consists of five themes and includes performance objectives for each: foods eaten at school (planning a school lunch, keeping a…

  6. Science World Activities Book.

    ERIC Educational Resources Information Center

    Wisconsin Academy of Sciences, Arts and Letters, Madison.

    This document consists of three sections. Section I contains 19 activities developed by master teachers for the Science World '84 summer science program. These activities focus on studies involving airplane controls, trash bag kites, computers, meteorology, compass orienteering, soils, aquatic ecosystems, bogs, and others. Objectives, materials…

  7. The Journal Synthesizing Activity.

    ERIC Educational Resources Information Center

    Garber, Zev

    The journal synthesizing activity is intended to combine aspects of the formal essay with that of a diary. Activities associated with lecture topics are written up as short journal entries of approximately five typewritten pages and are turned in during the weekly class session at which the related topic is being discussed. The journal project…

  8. Activation of fly ash

    DOEpatents

    Corbin, D.R.; Velenyi, L.J.; Pepera, M.A.; Dolhyj, S.R.

    1986-08-19

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  9. Activating Event Knowledge

    ERIC Educational Resources Information Center

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-01-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or…

  10. Coordinating Shared Activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley

    2004-01-01

    Shared Activity Coordination (ShAC) is a computer program for planning and scheduling the activities of an autonomous team of interacting spacecraft and exploratory robots. ShAC could also be adapted to such terrestrial uses as helping multiple factory managers work toward competing goals while sharing such common resources as floor space, raw materials, and transports. ShAC iteratively invokes the Continuous Activity Scheduling Planning Execution and Replanning (CASPER) program to replan and propagate changes to other planning programs in an effort to resolve conflicts. A domain-expert specifies which activities and parameters thereof are shared and reports the expected conditions and effects of these activities on the environment. By specifying these conditions and effects differently for each planning program, the domain-expert subprogram defines roles that each spacecraft plays in a coordinated activity. The domain-expert subprogram also specifies which planning program has scheduling control over each shared activity. ShAC enables sharing of information, consensus over the scheduling of collaborative activities, and distributed conflict resolution. As the other planning programs incorporate new goals and alter their schedules in the changing environment, ShAC continually coordinates to respond to unexpected events.

  11. Activities: More Calculator Capers.

    ERIC Educational Resources Information Center

    Schmalz, Rosemary

    1983-01-01

    Provided is an activity designed to give grades 7-12 students opportunities to discover numerical patterns and to derive general conclusions from observing data. The activity focuses attention on patterns in products such as 33x34, 333x334, and 3333x3334. Three worksheets and answers are included. (JN)

  12. Choreography of AMPK activation.

    PubMed

    Langendorf, Christopher G; Kemp, Bruce E

    2015-01-01

    A recent study published in Cell Research by Li and colleagues reports a detailed biophysical and structural study of AMPK's intra-molecular interactions during activation. By employing subunit tagging and proximity analysis with the aid of AlphaScreen instrumentation, Li et al. add to our understanding of the choreography of activation of AMPK by both nucleotides and phosphorylation.

  13. Rainy Day Activities.

    ERIC Educational Resources Information Center

    Texas Child Care, 1997

    1997-01-01

    Experienced caregivers plan ahead for rainy days. This article describes specific rainy day activities for young children, such as books and crafts to learn about rain (rain in a jar, making a rainbow), simple cooking activities (taffy pull, cinnamon candy tea), and games (mummy wrap, hunt the thimble, rain lotto). (EV)

  14. Laboratory Activities in Israel

    ERIC Educational Resources Information Center

    Mamlok-Naaman, Rachel; Barnea, Nitza

    2012-01-01

    Laboratory activities have long had a distinctive and central role in the science curriculum, and science educators have suggested that many benefits accrue from engaging students in science laboratory activities. Many research studies have been conducted to investigate the educational effectiveness of laboratory work in science education in…

  15. Peak Longevity Physical Activity

    Cancer.gov

    People who engage in three to five times the recommended minimum level of leisure-time physical activity derive the greatest benefit in terms of mortality reduction when compared with people who do not engage in leisure-time physical activity.

  16. Curriculum Activities on Aging.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.; Benge, Nancy

    This paper contains learning activities on aging for use with elementary, high school, and university students in health, family relationships, social studies, and art courses. The activities are intended to help youth develop a more realistic understanding of the aging process and to become aware of both the problems and benefits associated with…

  17. Students Active in Leadership.

    ERIC Educational Resources Information Center

    Brutcher, Robert

    2001-01-01

    Describes SAIL (Students Active in Leadership) as a school-based, youth-directed group. States that the program helps teenagers learn leadership skills by developing and implementing community service activities. SAIL finds partners with whom to collaborate among local businesses, government, and health associations, and these partners provide the…

  18. Ten Minute Writing Activities.

    ERIC Educational Resources Information Center

    Markus, Sharyn

    Designed with junior high school students in mind, the activities in this booklet are offered as ways to stimulate interest in writing using as little as ten minutes of class time. The activities are arranged in six sections: (1) developing observation skills and paying attention to details; (2) word play, descriptive words, and word collections…

  19. Nature's engines: active matter

    NASA Astrophysics Data System (ADS)

    Yeomans, Julia M.

    2017-03-01

    Active materials, bacteria, molecular motors, and self-propelled colloids, continuously transform chemical energy from the environment to mechanical work. Dense active matter, from layers of cells to flocks of birds, self-assembles into intricate patterns. Nature's engines are complex and efficient, and we would like to exploit her ideas to fabricate nano-machines.

  20. Activation of fly ash

    DOEpatents

    Corbin, David R.; Velenyi, Louis J.; Pepera, Marc A.; Dolhyj, Serge R.

    1986-01-01

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  1. Activity Book: Ocean Ecology.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Presents a collection of activities to help elementary students study ocean ecology. The activities have students investigate ocean inhabitants, analyze animal adaptations, examine how temperature and saltiness affect ocean creatures, and learn about safeguarding the sea. Student pages offer reproducible learning sheets. (SM)

  2. [Biosignals of dermal activity].

    PubMed

    Rathkolb, O; Gallei, L

    1993-01-01

    Electrodermal activity (EDA) summarizes different electrophysiological dimensions of human skin. EDA is based on the activity of sweat glands and their innervation by the autonomic nervous system. EDA is used as indicator in the additional diagnostic assessment of patients in the fields of neurology and psychosomatic medicine.

  3. Active galactic nuclei

    PubMed Central

    Fabian, Andrew C.

    1999-01-01

    Active galactic nuclei are the most powerful, long-lived objects in the Universe. Recent data confirm the theoretical idea that the power source is accretion into a massive black hole. The common occurrence of obscuration and outflows probably means that the contribution of active galactic nuclei to the power density of the Universe has been generally underestimated. PMID:10220363

  4. Reflections on Activity Theory

    ERIC Educational Resources Information Center

    Bakhurst, David

    2009-01-01

    It is sometimes suggested that activity theory represents the most important legacy of Soviet philosophy and psychology. But what exactly "is" activity theory? The canonical account in the West is given by Engestrom, who identifies three stages in the theory's development: from Vygotsky's insights, through Leontiev's articulation of the…

  5. Student Activities. Managing Liability.

    ERIC Educational Resources Information Center

    Bennett, Barbara; And Others

    This monograph suggests ways that college or university administrations can undertake a systematic and careful review of the risks posed by students' activities. Its purpose is to provide guidance in integrating the risk management process into a school's existing approaches to managing student organizations and activities. It is noted that no…

  6. The Activity of Trypsin

    ERIC Educational Resources Information Center

    Russo, Salvatore F.; Holzman, Tom

    1977-01-01

    Describes an experiment that illustrates the following points concerning the experimental determination of trypsin activity: (1) there is a difference in basing enzyme concentration on weight, absorbance, or active sites; and (2) the method of expressing enzyme concentration determines the value of specific, molecular, and catalytic center…

  7. Metastasis and AKT activation.

    PubMed

    Qiao, Meng; Sheng, Shijie; Pardee, Arthur B

    2008-10-01

    Metastasis is responsible for 90% of cancer patient deaths. More information is needed about the molecular basis for its potential detection and treatment. The activated AKT kinase is necessary for many events of the metastatic pathway including escape of cells from the tumor's environment, into and then out of the circulation, activation of proliferation, blockage of apoptosis, and activation of angiogenesis. A series of steps leading to metastatic properties can be initiated upon activation of AKT by phosphorylation on Ser-473. These findings lead to the question of how this activation is connected to metastasis. Activated AKT phosphorylates GSK-3beta causing its proteolytic removal. This increases stability of the negative transcription factor SNAIL, thereby decreasing transcription of the transmembrane protein E-cadherin that forms adhesions between adjacent cells, thereby permitting their detachment. How is AKT hyperactivated in metastatic cells? Increased PI3K or TORC2 kinase activity- or decreased PHLPP phosphatase could be responsible. Furthermore, a positive feedback mechanism is that the decrease of E-cadherin lowers PTEN and thereby increases PIP3, further activating AKT and metastasis.

  8. Aging and Semantic Activation.

    ERIC Educational Resources Information Center

    Howard, Darlene V.

    Three studies tested the theory that long term memory consists of a semantically organized network of concept nodes interconnected by leveled associations or relations, and that when a stimulus is processed, the corresponding concept node is assumed to be temporarily activated and this activation spreads to nearby semantically related nodes. In…

  9. Activities of the ILO.

    ERIC Educational Resources Information Center

    Labour Education, 1984

    1984-01-01

    Seven articles on International Labour Organization (ILO) activities cover study groups at ILO headquarters, a Philippine rural workers seminar, women's participation in Central American union activities, worksite courses in India, and seminars and symposia in Cape Verde, Mauritius, and Sierra Leone. (SK)

  10. Learning Activities for Toddlers.

    ERIC Educational Resources Information Center

    Texas Child Care, 1996

    1996-01-01

    Suggests activities to help toddlers develop skills in the four important areas of self-help, creativity, world mastery, and coordination. Activities include hand washing, button practice, painting, movement and music, bubble making, creation of a nature mural, and a shoe print trail. (TJQ)

  11. Active and Healthy Schools

    ERIC Educational Resources Information Center

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  12. ZOOMsci Activity Guide.

    ERIC Educational Resources Information Center

    Wade, Meredith

    This activity guide is based on the Public Broadcasting System's (PBS) program "ZOOM." It is designed for educators with activities that are categorized into three themes: (1) Things That Go, which includes "Air" which explores air pressure, "Rubber Bands" which discovers the potential energy of rubber bands,…

  13. Emotionally Intense Science Activities

    ERIC Educational Resources Information Center

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-01-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of…

  14. A pre-steady state and steady state kinetic analysis of the N-ribosyl hydrolase activity of hCD157.

    PubMed

    Preugschat, Frank; Carter, Luke H; Boros, Eric E; Porter, David J T; Stewart, Eugene L; Shewchuk, Lisa M

    2014-12-15

    hCD157 catalyzes the hydrolysis of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The release of nicotinamide or nicotinic acid from NR or NAR was confirmed by spectrophotometric, HPLC and NMR analyses. hCD157 is inactivated by a mechanism-based inhibitor, 2'-deoxy-2'-fluoro-nicotinamide arabinoside (fNR). Modification of the enzyme during the catalytic cycle by NR, NAR, or fNR increased the intrinsic protein fluorescence by approximately 50%. Pre-steady state and steady state data were used to derive a minimal kinetic scheme for the hydrolysis of NR. After initial complex formation a reversible step (360 and 30s(-1)) is followed by a slow irreversible step (0.1s(-1)) that defined the rate limiting step, or kcat. The calculated KMapp value for NR in the hydrolytic reaction is 6nM. The values of the kinetic constants suggest that one biological function of cell-surface hCD157 is to bind and slowly hydrolyze NR, possibly converting it to a ligand-activated receptor. Differences in substrate preference between hCD157 and hCD38 were rationalized through a comparison of the crystal structures of the two proteins. This comparison identified several residues in hCD157 (F108 and F173) that can potentially hinder the binding of dinucleotide substrates (NAD+).

  15. Active optical zoom system

    DOEpatents

    Wick, David V.

    2005-12-20

    An active optical zoom system changes the magnification (or effective focal length) of an optical imaging system by utilizing two or more active optics in a conventional optical system. The system can create relatively large changes in system magnification with very small changes in the focal lengths of individual active elements by leveraging the optical power of the conventional optical elements (e.g., passive lenses and mirrors) surrounding the active optics. The active optics serve primarily as variable focal-length lenses or mirrors, although adding other aberrations enables increased utility. The active optics can either be LC SLMs, used in a transmissive optical zoom system, or DMs, used in a reflective optical zoom system. By appropriately designing the optical system, the variable focal-length lenses or mirrors can provide the flexibility necessary to change the overall system focal length (i.e., effective focal length), and therefore magnification, that is normally accomplished with mechanical motion in conventional zoom lenses. The active optics can provide additional flexibility by allowing magnification to occur anywhere within the FOV of the system, not just on-axis as in a conventional system.

  16. Emotionally Intense Science Activities

    NASA Astrophysics Data System (ADS)

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-08-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of each lesson were analysed to identify individual student's emotions. Results from two representative students are presented as case studies. Using a theoretical perspective drawn from theories of emotions founded in sociology, two assertions emerged. First, during the demonstration activity, students experienced the emotions of wonder and surprise; second, during a laboratory activity, students experienced the intense positive emotions of happiness/joy. Characteristics of these activities that contributed to students' positive experiences are highlighted. The study found that choosing activities that evoked strong positive emotional experiences, focused students' attention on the phenomenon they were learning, and the activities were recalled positively. Furthermore, such positive experiences may contribute to students' interest and engagement in science and longer term memorability. Finally, implications for science teachers and pre-service teacher education are suggested.

  17. List 9 - Active CERCLIS Sites:

    EPA Pesticide Factsheets

    The List 9 displays the sequence of activities undertaken at active CERCLIS sites. An active site is one at which site assessment, removal, remedial, enforcement, cost recovery, or oversight activities are being planned or conducted.

  18. THE ACTIVE CENTAURS

    SciTech Connect

    Jewitt, David

    2009-05-15

    The Centaurs are recent escapees from the Kuiper Belt that are destined either to meet fiery oblivion in the hot inner regions of the solar system or to be ejected to the interstellar medium by gravitational scattering from the giant planets. Dynamically evolved Centaurs, when captured by Jupiter and close enough to the Sun for near-surface water ice to sublimate, are conventionally labeled as 'short-period' (specifically, Jupiter-family) comets. Remarkably, some Centaurs show comet-like activity even when far beyond the orbit of Jupiter, suggesting mass loss driven by a process other than the sublimation of water ice. We observed a sample of 23 Centaurs and found nine to be active, with mass-loss rates measured from several kg s{sup -1} to several tonnes s{sup -1}. Considered as a group, we find that the 'active Centaurs' in our sample have perihelia smaller than the inactive Centaurs (median 5.9 AU versus 8.7 AU), and smaller than the median perihelion distance computed for all known Centaurs (12.4 AU). This suggests that their activity is thermally driven. We consider several possibilities for the origin of the mass loss from the active Centaurs. Most are too cold for activity at the observed levels to originate via the sublimation of crystalline water ice. Solid carbon monoxide and carbon dioxide have the opposite problem: they are so volatile that they should drive activity in Centaurs at much larger distances than observed. We consider the possibility that activity in the Centaurs is triggered by the conversion of amorphous ice into the crystalline form accompanied by the release of trapped gases, including carbon monoxide. By imposing the condition that crystallization should occur when the crystallization time is shorter than the orbital period we find a qualitative match to the perihelion distribution of the active Centaurs and conclude that the data are consistent with the hypothesis that the Centaurs contain amorphous ice.

  19. Physics of solar activity

    NASA Technical Reports Server (NTRS)

    Sturrock, Peter A.

    1993-01-01

    The aim of the research activity was to increase our understanding of solar activity through data analysis, theoretical analysis, and computer modeling. Because the research subjects were diverse and many researchers were supported by this grant, a select few key areas of research are described in detail. Areas of research include: (1) energy storage and force-free magnetic field; (2) energy release and particle acceleration; (3) radiation by nonthermal electrons; (4) coronal loops; (5) flare classification; (6) longitude distributions of flares; (7) periodicities detected in the solar activity; (8) coronal heating and related problems; and (9) plasma processes.

  20. Phosphorylation of Nrf2 in the transcription activation domain by casein kinase 2 (CK2) is critical for the nuclear translocation and transcription activation function of Nrf2 in IMR-32 neuroblastoma cells.

    PubMed

    Apopa, Patrick L; He, Xiaoqing; Ma, Qiang

    2008-02-01

    The antioxidant-activated transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the induction of cytoprotective genes against chemical toxicity and oxidative injuries. The role of phosphorylation in Nrf2 activation has been suggested but remains elusive. We report that phenolic antioxidant/pro-oxidant tert-butylhydroquinone (tBHQ) induced two forms of the Nrf2 protein in neuroblastoma cells (IMR-32), which migrated as distinctive bands on SDS-PAGE. In vitro treatment with lambda phosphatase eliminated the slower migrating form and increased the amount of the faster migrating form of Nrf2. In vivo (32)Pi-phosphorylation resulted in (32)Pi-labeling of the Nrf2 protein in the presence of tBHQ that can be dephosphorylated by lambda phosphotase, indicating that the slower migrating form is a phosphorylated Nrf2 protein and the faster form an unphosphorylated Nrf2. Unphosphorylated Nrf2 predominated in the cytoplasm, whereas the phosphorylated form preferentially localized in the nucleus. Nuclear Nrf2 can be dephosphorylated by lambda phosphotase in vitro and be converted to the faster migrating form, implicating phosphorylation of Nrf2 in the cytoplasmic-nuclear translocation of the protein. Deletional analyses from both the carboxyl- and amino-ends revealed the transcription activation (TA) domains Neh4 (Nrf2-ECH homology 4) and Neh5 (Nrf2-ECH homology 5) as a major region necessary for the phosphorylation. The TA domains are characterized by the presence of multiple phosphorylation sites of casein kinase 2 (CK2). Moreover, CK2 phosphorylated the TA domains in vitro. Treatment with CK2 inhibitor 2-dimethylamino-4,5,6,7,-tetrabromo-1H-benzimidazole (DMAT) blocked the induction of endogenous target genes of Nrf2 in cells and inhibited the TA activities of both the full length and the TA domains of Nrf2 to a large extent. Finally, phosphorylation of the TA domains correlated with the nuclear translocation of Nrf2 that was inhibited by DMAT in a

  1. Algorithm-development activities

    NASA Technical Reports Server (NTRS)

    Carder, Kendall L.

    1994-01-01

    The task of algorithm-development activities at USF continues. The algorithm for determining chlorophyll alpha concentration, (Chl alpha) and gelbstoff absorption coefficient for SeaWiFS and MODIS-N radiance data is our current priority.

  2. MARIHUANA ACTIVITY OF CANNABINOL.

    PubMed

    Loewe, S

    1945-12-14

    Cannabinol, generally believed to be an inert component of hemp oil, is shown to have marihuana activity. The significance of this observation with regard to the relationship between structure and mamactivity in the class of cannabinols is discussed.

  3. Balance Food and Activity

    MedlinePlus

    ... eNewsletters Calendar Balance Food and Activity What is Energy Balance? Energy is another word for "calories." Your ... adults, fewer calories are needed at older ages. Energy Balance in Real Life Think of it as ...

  4. Activities in Teaching Weather

    ERIC Educational Resources Information Center

    Tonn, Martin

    1977-01-01

    Presented is a unit composed of activities for teaching weather. Topics include cloud types and formation, simple weather instruments, and the weather station. Illustrations include a weather chart and instruments. A bibliography is given. (MA)

  5. Extravehicular activity technology discipline

    NASA Technical Reports Server (NTRS)

    Webbon, Bruce W.

    1990-01-01

    Viewgraphs on extravehicular activity technology discipline for Space Station Freedom are presented. Topics covered include: extravehicular mobility unit; airlock and EMU support equipment; tools, mobility aids, and workstations; and telerobotic work aids interfaces.

  6. French space activities

    NASA Technical Reports Server (NTRS)

    Blanc, R.

    1982-01-01

    The four main points of research and development of space programs by France are explained. The National Center of Space Studies is discussed, listing the missions of the Center and describing the activities of the staff.

  7. Active Fire Mapping Program

    MedlinePlus

    Active Fire Mapping Program Current Large Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS Data Fire Data in Google Earth ...

  8. ERLN Activities Details

    EPA Pesticide Factsheets

    Environmental Response Laboratory Network activities include the All Hazard Receipt Facility and Screening Protocol, standardizing chemical methods, Chemical Warfare Agent Fixed Laboratory Pilot Project, microbial efforts, and WLA response plan.

  9. The Activity Centre.

    ERIC Educational Resources Information Center

    Australian Mathematics Teacher, 1989

    1989-01-01

    Presents four examples on arithmetic mean and harmonic mean. Provides solution of each of the examples and instructional activities related to the examples. Lists eight references on mathematical problem solving. (YP)

  10. Active at Any Size

    MedlinePlus

    ... a row. Your muscles need time to recover. Mind and body exercise Your local hospital or fitness, ... can be viewed at www.ClinicalTrials.gov . Additional Reading Tips to Help You Get Active Identifies and ...

  11. Exercise and activity - children

    MedlinePlus

    ... and most other organized sports (such as soccer, swimming, and dancing) Younger children cannot stick with the ... your child's preferences and abilities. Individual activities include swimming, running, skiing, or biking. Group sports are another ...

  12. Active terahertz metamaterials

    SciTech Connect

    Chen, Hou-tong

    2009-01-01

    We demonstrate planar terahertz metamaterial devices enabling actively controllable transmission amplitude, phase, or frequency at room temperature via carrier depletion or photoexcitation in the semiconductor substrate or in semiconductor materials incorporated into the metamaterial structure.

  13. Enrichment Activities for Geometry.

    ERIC Educational Resources Information Center

    Usiskin, Zalman

    1983-01-01

    Enrichment activities that teach about geometry as they instruct in geometry are given for some significant topics. The facets of geometry included are tessellations, round robin tournaments, geometric theorems on triangles, and connections between geometry and complex numbers. (MNS)

  14. Interactive Design Activism

    NASA Astrophysics Data System (ADS)

    Goulev, Petar; Farrer, Joan

    The following sections are included: * Introduction * Computers and Human Well-being * To Fuzzy or Yes (No)! * Interactive Design Activism * Sensing the Sun * Personalised Public Health Advice * Modifying Human Behaviour * Transdisciplinarity, Knowledge Transfer and Multi-domain

  15. Island Watershed Activity.

    ERIC Educational Resources Information Center

    Benson, Rod

    2003-01-01

    Describes a 90-minute "Island Watershed" activity to help earth science students understand the concept of the water cycle. Introduces a surface waters unit appropriate for students in grades 7-10. Includes watershed project guidelines. (Author/KHR)

  16. Active Limiters For Photodetectors

    NASA Technical Reports Server (NTRS)

    Katz, Joseph; Cheng, Li-Jen

    1990-01-01

    Active or "smart" electro-optical shutters proposed for protection of photodetectors, imaging devices, and other sensitive optical or optoelectronic elements. Responds rapidly and automatically to increase in illumination above prescribed level.

  17. Math Lab Activities

    ERIC Educational Resources Information Center

    Brumbaugh, Douglas K.; Hynes, Michael C.

    1974-01-01

    The goals, objects, materials and grade levels are specified in this description of a laboratory activity involving analytic geometry concepts. Students mark out bicycle gymkhana courses in which directions to participants are given by Cartesian coordinates. (JP)

  18. Low activation ferritic alloys

    DOEpatents

    Gelles, David S.; Ghoniem, Nasr M.; Powell, Roger W.

    1986-01-01

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  19. Low activation ferritic alloys

    DOEpatents

    Gelles, D.S.; Ghoniem, N.M.; Powell, R.W.

    1985-02-07

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  20. RAVEN Quality Assurance Activities

    SciTech Connect

    Cogliati, Joshua Joseph

    2015-09-01

    This report discusses the quality assurance activities needed to raise the Quality Level of Risk Analysis in a Virtual Environment (RAVEN) from Quality Level 3 to Quality Level 2. This report also describes the general RAVEN quality assurance activities. For improving the quality, reviews of code changes have been instituted, more parts of testing have been automated, and improved packaging has been created. For upgrading the quality level, requirements have been created and the workflow has been improved.

  1. Activated partial thromboplastin time.

    PubMed

    Ignjatovic, Vera

    2013-01-01

    Activated partial thromboplastin time (APTT) is a commonly used coagulation assay that is easy to perform, is affordable, and is therefore performed in most coagulation laboratories, both clinical and research, worldwide. The APTT is based on the principle that in citrated plasma, the addition of a platelet substitute, factor XII activator, and CaCl2 allows for formation of a stable clot. The time required for the formation of a stable clot is recorded in seconds and represents the actual APTT result.

  2. Active aperture phased arrays

    NASA Astrophysics Data System (ADS)

    Shenoy, R. P.

    1989-04-01

    Developments towards the realization of active aperture phased arrays are reviewed. The technology and cost aspects of the power amplifier and phase shifter subsystems are discussed. Consideration is given to research concerning T/R modules, MESFETs, side lobe control, beam steering, optical control techniques, and printed circuit antennas. Methods for configuring the array are examined, focusing on the tile and brick configurations. It is found that there is no technological impediment for introducing active aperture phased arrays.

  3. Intercreativity: Mapping Online Activism

    NASA Astrophysics Data System (ADS)

    Meikle, Graham

    How do activists use the Internet? This article maps a wide range of activist practice and research by applying and developing Tim Berners-Lee's concept of ‘intercreativity' (1999). It identifies four dimensions of Net activism: intercreative texts, tactics, strategies and networks. It develops these through examples of manifestations of Net activism around one cluster of issues: support campaigns for refugees and asylum seekers.

  4. ABB: active bandwidth broker

    NASA Astrophysics Data System (ADS)

    Wong, Kason; Law, Eddie

    2001-07-01

    In this paper, we shall discuss a novel design on the policy-based management for the Internet. This design deploys the concept of active networking. As opposed to the traditional network design, active network empowers network node with the ability to manipulate data and program code in packets, and configure the network properties according to the needs of different applications. The policy-based management can control network routers in order to realize end-to-end Quality of Service (QoS), such as differentiated and integrated services, across the Internet. For the moment, the Internet Engineering Task Force (IETF) has defined the framework of the policy-based management. It employs a simple client/server model that uses Common Open Policy Service (COPS) protocol to facilitate policy management and control. Our design of Active Bandwidth Broker (ABB) belongs to an active application. Our goals are to distribute centralized workload of the policy-based management over multiple active nodes in the active networks, introduce mobility of the bandwidth brokers, and allows load sharing to the policy-based management. This results a network-wide intelligent, highly available, and consistent QoS control that allows performance protection for voice, video and Internet business application while reducing costs for growing networks.

  5. Rheology of Active Gels

    NASA Astrophysics Data System (ADS)

    Chen, Daniel

    2015-03-01

    Active networks drive a diverse range of critical processes ranging from motility to division in living cells, yet a full picture of their rheological capabilities in non-cellular contexts is still emerging, e.g., How does the rheological response of a network capable of remodeling under internally-generated stresses differ from that of a passive biopolymer network? In order to address this and other basic questions, we have engineered an active gel composed of microtubules, bidirectional kinesin motors, and molecular depletant that self-organizes into a highly dynamic network of active bundles. The network continually remodels itself under ATP-tunable cycles of extension, buckling, fracturing, and self-healing. Using confocal rheometry we have simultaneously characterized the network's linear and non-linear rheological responses to shear deformation along with its dynamic morphology. We find several surprising and unique material properties for these active gels; most notably, rheological cloaking, the ability of the active gel to drive large-scale fluid mixing over several orders of flow magnitude while maintaining an invariant, solid-like rheological profile and spontaneous flow under confinement, the ability to exert micro-Newton forces to drive persistent directed motion of the rheometer tool. Taken together, these results and others to be discussed highlight the rich stress-structure-dynamics relationships in this class of biologically-derived active gels.

  6. Antimicrobial activity of flavonoids.

    PubMed

    Cushnie, T P Tim; Lamb, Andrew J

    2005-11-01

    Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (-)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2'-trihydroxy-5'-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.

  7. Phytase activity in lichens.

    PubMed

    Higgins, Niall F; Crittenden, Peter D

    2015-10-01

    Phytase activity was investigated in 13 lichen species using a novel assay method. The work tested the hypothesis that phytase is a component of the suite of surface-bound lichen enzymes that hydrolyse simple organic forms of phosphorus (P) and nitrogen (N) deposited onto the thallus surface. Hydrolysis of inositol hexaphosphate (InsP6 , the substrate for phytase) and appearance of lower-order inositol phosphates (InsP5 -InsP1 ), the hydrolysis products, were measured by ion chromatography. Phytase activity in Evernia prunastri was compared among locations with contrasting rates of N deposition. Phytase activity was readily measurable in epiphytic lichens (e.g. 11.3 μmol InsP6 hydrolysed g(-1)  h(-1) in Bryoria fuscescens) but low in two terricolous species tested (Cladonia portentosa and Peltigera membranacea). Phytase and phosphomonoesterase activities were positively correlated amongst species. In E. prunastri both enzyme activities were promoted by N enrichment and phytase activity was readily released into thallus washings. InsP6 was not detected in tree canopy throughfall but was present in pollen leachate. Capacity to hydrolyse InsP6 appears widespread amongst lichens potentially promoting P capture from atmospheric deposits and plant leachates, and P cycling in forest canopies. The enzyme assay used here might find wider application in studies on plant root-fungal-soil systems.

  8. T cell activation.

    PubMed

    Smith-Garvin, Jennifer E; Koretzky, Gary A; Jordan, Martha S

    2009-01-01

    This year marks the 25th anniversary of the first Annual Review of Immunology article to describe features of the T cell antigen receptor (TCR). In celebration of this anniversary, we begin with a brief introduction outlining the chronology of the earliest studies that established the basic paradigm for how the engaged TCR transduces its signals. This review continues with a description of the current state of our understanding of TCR signaling, as well as a summary of recent findings examining other key aspects of T cell activation, including cross talk between the TCR and integrins, the role of costimulatory molecules, and how signals may negatively regulate T cell function.Acronyms and DefinitionsAdapter protein: cellular protein that functions to bridge molecular interactions via characteristic domains able to mediate protein/protein or protein/lipid interactions Costimulation: signals delivered to T cells by cell surface receptors other than the TCR itself that potentiate T cell activation cSMAC: central supramolecular activation cluster Immunoreceptor tyrosine-based activation motif (ITAM): a short peptide sequence in the cytoplasmic tails of key surface receptors on hematopoietic cells that is characterized by tyrosine residues that are phosphorylated by Src family PTKs, enabling the ITAM to recruit activated Syk family kinases Inside-out signaling: signals initiated by engagement of immunoreceptors that lead to conformational changes and clustering of integrins, thereby increasing the affinity and avidity of the integrins for their ligands NFAT: nuclear factor of activated T cells PI3K: phosphoinositide 3-kinase PKC: protein kinase C PLC: phospholipase C pMHC: peptide major histocompatibility complex (MHC) complex pSMAC: peripheral supramolecular activation cluster PTK: protein tyrosine kinase Signal transduction: biochemical events linking surface receptor engagement to cellular responses TCR: T cell antigen receptor

  9. Sirtuin activators and inhibitors

    PubMed Central

    Villalba, José M.; Alcaín, Francisco J.

    2012-01-01

    Sirtuins 1-7 (SIRT1-7) belong to the third class of deacetylase enzymes, which are dependent on NAD+ for activity. Sirtuins activity is linked to gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy aging. Because sirtuins modulation could have beneficial effects on human diseases there is a growing interest in the discovery of small molecules modifying their activity. We review here those compounds known to activate or inhibit sirtuins, discussing the data that support the use of sirtuin-based therapies. Almost all sirtuin activators have been described only for SIRT1. Resveratrol is a natural compound which activates SIRT1, and may help in the treatment or prevention of obesity, and in preventing tumorigenesis and the aging-related decline in heart function and neuronal loss. Due to its poor bioavailability, reformulated versions of resveratrol with improved bioavailability have been developed (resVida, Longevinex®, SRT501). Molecules that are structurally unrelated to resveratrol (SRT1720, SRT2104, SRT2379, among others) have been also developed to stimulate sirtuin activities more potently than resveratrol. Sirtuin inhibitors with a wide range of core structures have been identified for SIRT1, SIRT2, SIRT3 and SIRT5 (splitomicin, sirtinol, AGK2, cambinol, suramin, tenovin, salermide, among others). SIRT1 inhibition has been proposed in the treatment of cancer, immunodeficiency virus infections, Fragile X mental retardation syndrome and for preventing or treating parasitic diseases, whereas SIRT2 inhibitors might be useful for the treatment of cancer and neurodegenerative diseases. PMID:22730114

  10. Antimutagenic activity of spearmint.

    PubMed

    Yu, Tian-Wei; Xu, Meirong; Dashwood, Roderick H

    2004-01-01

    The antimutagenic activity of spearmint (Mentha spicata), a popular food flavoring agent, was studied in the Salmonella assay. Spearmint leaves were brewed in hot water for 5 min at concentrations up to 5% (w/v), and the water extracts were tested against the direct-acting mutagens 4-nitro-1,2-phenylenediamine (NPD) and 2-hydroxyamino-3-methyl-3H-imidazo[4,5-f]quinoline (N-OH-IQ) using Salmonella typhimurium strain TA98. Nontoxic concentrations of spearmint extract inhibited the mutagenic activity of N-OH-IQ in a concentration-dependent fashion, but had no effect against NPD. These experiments by design focused on the water extract consumed commonly as an herbal tea, but chloroform and methanol extracts of spearmint also possessed antimutagenic activity against N-OH-IQ. Water extract of spearmint inhibited the mutagenic activity of the parent compound, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), in the presence of rat liver S9; however, the concentration for 50% inhibition (IC50) against IQ was approximately 10-fold higher than in assays with N-OH-IQ minus S9. At concentrations similar to those used in the Salmonella assays, spearmint extract inhibited two of the major enzymes that play a role in the metabolic activation of IQ, namely, cytochromes P4501A1 and 1A2, based on ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase assays in vitro. In vivo, rats were given spearmint water extract (2%; w/v) as the sole source of drinking fluid before, during, and after 2-week treatment with IQ; colonic aberrant crypt foci were inhibited significantly at 8 weeks (P < 0.05, compared with rats given IQ alone). Collectively, these findings suggest that spearmint tea protects against IQ and possibly other heterocyclic amines through inhibition of carcinogen activation and via direct effects on the activated metabolite(s).

  11. Zingerone enhances glutamatergic spontaneous excitatory transmission by activating TRPA1 but not TRPV1 channels in the adult rat substantia gelatinosa.

    PubMed

    Yue, Hai-Yuan; Jiang, Chang-Yu; Fujita, Tsugumi; Kumamoto, Eiichi

    2013-08-01

    Transient receptor potential (TRP) channels are thought to play a role in regulating nociceptive transmission to spinal substantia gelatinosa (SG) neurons. It remains to be unveiled whether the TRP channels in the central nervous system are different in property from those involved in receiving nociceptive stimuli in the peripheral nervous system. We examined the effect of the vanilloid compound zingerone, which activates TRPV1 channels in the cell body of a primary afferent neuron, on glutamatergic excitatory transmission in the SG neurons of adult rat spinal cord slices by using the whole cell patch-clamp technique. Bath-applied zingerone reversibly and concentration-dependently increased spontaneous excitatory postsynaptic current (EPSC) frequency. This effect was accompanied by an inward current at -70 mV that was resistant to glutamate receptor antagonists. These zingerone effects were repeated and persisted in Na(+)-channel blocker tetrodotoxin-, La(3+)-, or IP3-induced Ca(2+)-release inhibitor 2-aminoethoxydiphenyl borate-containing or Ca(2+)-free Krebs solution. Zingerone activity was resistant to the selective TRPV1 antagonist capsazepine but sensitive to the nonselective TRP antagonist ruthenium red, the TRPA1 antagonist HC-030031, and the Ca(2+)-induced Ca(2+)-release inhibitor dantrolene. TRPA1 agonist allyl isothiocyanate but not capsaicin inhibited the facilitatory effect of zingerone. On the other hand, zingerone reduced monosynaptically evoked EPSC amplitudes, as did TRPA1 agonists. Like allyl isothiocyanate, zingerone enhanced GABAergic spontaneous inhibitory transmission in a manner sensitive to tetrodotoxin. We conclude that zingerone presynaptically facilitates spontaneous excitatory transmission, probably through Ca(2+)-induced Ca(2+)-release mechanisms, and produces a membrane depolarization in SG neurons by activating TRPA1 but not TRPV1 channels.

  12. [Inflammasome: activation mechanisms].

    PubMed

    Suárez, Raibel; Buelvas, Neudo

    2015-03-01

    Inflammation is a rapid biologic response of the immune system in vascular tissues, directed to eliminate stimuli capable of causing damage and begin the process of repair. The macromolecular complexes known as "inflammasomes" are formed by a receptor, either NOD (NLR) or ALR, the receptor absent in melanoma 2 (AIM2). In addition, the inflammasome is formed by the speck-like protein associated to apoptosis (ASC) and procaspase-1, that may be activated by variations in the ionic and intracellular and extracellular ATP concentrations; and the loss of stabilization of the fagolisosomme by internalization of insoluble crystals and redox mechanisms. As a result, there is activation of the molecular platform and the processing of inflammatory prointerleukins to their active forms. There are two modalities of activation of the inflammasome: canonical and non-canonical, both capable of generating effector responses. Recent data associate NLRP 3, IL-1β and IL-18 in the pathogenesis of a variety of diseases, including atherosclerosis, type II diabetes, hyperhomocysteinemia, gout, malaria and hypertension. The inflammasome cascade is emerging as a new chemotherapeutic target in these diseases. In this review we shall discuss the mechanisms of activation and regulation of the inflammasome that stimulate, modulate and resolve inflammation.

  13. Chromatin as active matter

    NASA Astrophysics Data System (ADS)

    Agrawal, Ankit; Ganai, Nirmalendu; Sengupta, Surajit; Menon, Gautam I.

    2017-01-01

    Active matter models describe a number of biophysical phenomena at the cell and tissue scale. Such models explore the macroscopic consequences of driving specific soft condensed matter systems of biological relevance out of equilibrium through ‘active’ processes. Here, we describe how active matter models can be used to study the large-scale properties of chromosomes contained within the nuclei of human cells in interphase. We show that polymer models for chromosomes that incorporate inhomogeneous activity reproduce many general, yet little understood, features of large-scale nuclear architecture. These include: (i) the spatial separation of gene-rich, low-density euchromatin, predominantly found towards the centre of the nucleus, vis a vis. gene-poor, denser heterochromatin, typically enriched in proximity to the nuclear periphery, (ii) the differential positioning of individual gene-rich and gene-poor chromosomes, (iii) the formation of chromosome territories, as well as (iv), the weak size-dependence of the positions of individual chromosome centres-of-mass relative to the nuclear centre that is seen in some cell types. Such structuring is induced purely by the combination of activity and confinement and is absent in thermal equilibrium. We systematically explore active matter models for chromosomes, discussing how our model can be generalized to study variations in chromosome positioning across different cell types. The approach and model we outline here represent a preliminary attempt towards a quantitative, first-principles description of the large-scale architecture of the cell nucleus.

  14. Active flows on trees

    NASA Astrophysics Data System (ADS)

    Forrow, Aden; Woodhouse, Francis G.; Dunkel, Jörn

    2016-11-01

    Coherent, large scale dynamics in many nonequilibrium physical, biological, or information transport networks are driven by small-scale local energy input. We introduce and explore a generic model for compressible active flows on tree networks. In contrast to thermally-driven systems, active friction selects discrete states with only a small number of oscillation modes activated at distinct fixed amplitudes. This state selection can interact with graph topology to produce different localized dynamical time scales in separate regions of large networks. Using perturbation theory, we systematically predict the stationary states of noisy networks. Our analytical predictions agree well with a Bayesian state estimation based on a hidden Markov model applied to simulated time series data on binary trees. While the number of stable states per tree scales exponentially with the number of edges, the mean number of activated modes in each state averages 1 / 4 the number of edges. More broadly, these results suggest that the macroscopic response of active networks, from actin-myosin networks in cells to flow networks in Physarum polycephalum, can be dominated by a few select modes.

  15. Interpreting EEG alpha activity.

    PubMed

    Bazanova, O M; Vernon, D

    2014-07-01

    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  16. Active thermal cloak

    NASA Astrophysics Data System (ADS)

    Nguyen, Dang Minh; Xu, Hongyi; Zhang, Youming; Zhang, Baile

    2015-09-01

    Thermal cloaking, as an ultimate thermal "illusion" phenomenon, is the result of advanced heat manipulation with thermal metamaterials—heat can be guided around a hidden object smoothly without disturbing the ambient thermal environment. However, all previous thermal metamaterial cloaks were passive devices, lacking the functionality of switching on/off and the flexibility of changing geometries. In this letter, we report an active thermal cloaking device that is controllable. Different from previous thermal cloaking approaches, this thermal cloak adopts active thermoelectric components to "pump" heat from one side to the other side of the hidden object, in a process controlled by input electric voltages. Our work not only incorporates active components in thermal cloaking but also provides controllable functionality in thermal metamaterials that can be used to construct more flexible thermal devices.

  17. Activity Cycles in Stars

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.

    2009-01-01

    Starspots and stellar activity can be detected in other stars using high precision photometric and spectrometric measurements. These observations have provided some surprises (starspots at the poles - sunspots are rarely seen poleward of 40 degrees) but more importantly they reveal behaviors that constrain our models of solar-stellar magnetic dynamos. The observations reveal variations in cycle characteristics that depend upon the stellar structure, convection zone dynamics, and rotation rate. In general, the more rapidly rotating stars are more active. However, for stars like the Sun, some are found to be inactive while nearly identical stars are found to be very active indicating that periods like the Sun's Maunder Minimum (an inactive period from 1645 to 1715) are characteristic of Sun-like stars.

  18. Antimicrobial activity of spices.

    PubMed

    Arora, D S; Kaur, J

    1999-08-01

    Spices have been shown to possess medicinal value, in particular, antimicrobial activity. This study compares the sensitivity of some human pathogenic bacteria and yeasts to various spice extracts and commonly employed chemotherapeutic substances. Of the different spices tested only garlic and clove were found to possess antimicrobial activity. The bactericidal effect of garlic extract was apparent within 1 h of incubation and 93% killing of Staphylococcus epidermidis and Salmonella typhi was achieved within 3 h. Yeasts were totally killed in 1 h by garlic extract but in 5 h with clove. Some bacteria showing resistance to certain antibiotics were sensitive to extracts of both garlic and clove. Greater anti-candidal activity was shown by garlic than by nystatin. Spices might have a great potential to be used as antimicrobial agents.

  19. PRODUCTS OF ACTIVATED LYMPHOCYTES

    PubMed Central

    Sorg, Clemens; Bloom, Barry R.

    1973-01-01

    General methods were developed and applied to the biosynthesis and purification of products of activated lymphocytes available in minute quantities. The activity studied here was the migration inhibitory factor (MIF) produced by purified protein derivative (PPD)- or concanavalin A (Con A)-stimulated lymphocytes obtained from one guinea pig or less. The methods selected yielded results in terms of two chemical parameters characteristic of the molecules involved, namely Kd on Sephadex G-75 and isoionic point, pI, on isoelectric focusing. When supernatants were fractionated on G-75 columns, there were several areas even in control supernatants which produced migration inhibition relative to medium controls. However, in PPD- and Con A-stimulated supernatants, at least one peak of MIF activity was found solely in the stimulated cultures, with a Kd of 0.15. A double-labeling technique was used to characterize the proteins of this peak. Control, unstimulated cultures were labeled with [14C]leucine and stimulated cultures were labeled with [3H]leucine. After mixing the supernatants and G-75 filtration, a major "ratiolabeled" broad peak. i.e. one with increased 3H/14C ratio, was found. When a narrow portion of this peak about Kd 0.15, containing most of the MIF activity, was subjected to analytical isoelectric focusing, all of the label was associated with proteins of lower net charge than albumin. A unique ratiolabeled peak was found in PPD- and Con A-stimulated fractions with a pI of approx. 5.3. A micropreparative isoelectric focusing technique was developed and yielded MIF activity in the same region as the major ratiolabeled peak. Further study will be required to ascertain whether the ratiolabeled protein is MIF. By following the Kd, pI, and 3H/14C labeling ratio, at least 14 products of activated lymphocytes, synthesized either de novo or in increased amounts, could be distinguished. PMID:4688317

  20. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces premature activation of the KLF2 regulon during thymocyte development.

    PubMed

    McMillan, Brian J; McMillan, Susanne N; Glover, Ed; Bradfield, Christopher A

    2007-04-27

    The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) causes numerous and diverse toxic events via activation of the aryl hydrocarbon receptor, including atrophy of the thymus. Exposure to TCDD induces acute thymocyte cell loss, which occurs concomitantly with proliferation arrest and premature emigration of triple negative (TN; CD4(-), CD8(-), CD3(-)) T cell progenitors. In this report, we demonstrate that TCDD exposure results in dysregulation of KLF2 (Kruppel-like factor 2) expression in developing thymocytes. The Klf2 gene encodes an Sp1-like zinc finger transcription factor that functions as a central regulator of T lymphocyte proliferation and trafficking. During normal thymocyte development, KLF2 is expressed exclusively in CD4 and CD8 single positive T cells and promotes a nonproliferative, promigratory phenotype. In mice exposed to TCDD, however, the Klf2 gene is prematurely expressed in TN thymocytes. Administration of a 100 microg/kg dose of TCDD results in a approximately 15-fold induction of KLF2 as early as the TN2 (CD44(+), CD25(+)) stage of development and immediately precedes acute cell loss in the TN3, TN4, and double positive (CD4(+), CD8(+)) cell stages. Induction of KLF2 occurs within 12 h of TCDD exposure and is fully dependent on expression of the aryl hydrocarbon receptor. In addition, TCDD exposure alters the expression of several factors comprising the KLF2 regulon, including Edg1/S1P(1), beta(7) integrin, CD52, Cdkn2d (cyclin-dependent kinase inhibitor 2D), s100a4, and IL10R alpha. These findings indicate that the pollutant TCDD interferes with early thymopoeisis via ectopic expression of the KLF2 regulon.

  1. Inducible nitric oxide synthase activity contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites

    PubMed Central

    Ferguson, J W; Dover, A R; Chia, S; Cruden, N L M; Hayes, P C; Newby, D E

    2006-01-01

    Background Overexpression of inducible nitric oxide synthase (iNOS) and increased nitric oxide generation may be associated with the hyperdynamic circulation of patients with cirrhosis. We have, for the first time, used the highly selective iNOS inhibitor, 1400W, to determine whether iNOS activity contributes to the regulation of vascular tone in patients with cirrhosis and ascites. Methods Bilateral forearm blood flow was measured using strain gauge plethysmography in eight patients with cirrhosis and ascites, and eight matched healthy volunteers during intrabrachial infusion of 1400W (0.1–1 μmol/min), NG‐monomethyl‐L‐arginine (L‐NMMA, a non‐selective NOS inhibitor; 2–8 μmol), and norepinephrine (a control vasoconstrictor; 60–480 pmol/min). Results In patients with cirrhosis, 1400W, L‐NMMA, and norepinephrine caused dose dependent reductions in forearm blood flow: peak reductions of 11 (5)%, 37 (4)%, and 48 (5)%, respectively (p<0.05 for all). In contrast, 1400W had no effect on blood flow (+4 (8)%; NS) in healthy controls despite similar reductions in blood flow with L‐NMMA and norepinephrine (39 (5)% and 49 (5)%, respectively; p<0.05 for both). Conclusions We have, for the first time, demonstrated that 1400W causes peripheral vasoconstriction in patients with cirrhosis but not healthy matched controls. This suggests that iNOS contributes to the regulation of peripheral vascular tone in patients with cirrhosis and ascites, and may contribute towards the hyperdynamic circulation associated with this condition. PMID:16299035

  2. Active cleaning technique device

    NASA Technical Reports Server (NTRS)

    Shannon, R. L.; Gillette, R. B.

    1973-01-01

    The objective of this program was to develop a laboratory demonstration model of an active cleaning technique (ACT) device. The principle of this device is based primarily on the technique for removing contaminants from optical surfaces. This active cleaning technique involves exposing contaminated surfaces to a plasma containing atomic oxygen or combinations of other reactive gases. The ACT device laboratory demonstration model incorporates, in addition to plasma cleaning, the means to operate the device as an ion source for sputtering experiments. The overall ACT device includes a plasma generation tube, an ion accelerator, a gas supply system, a RF power supply and a high voltage dc power supply.

  3. Actively coupled optical waveguides

    NASA Astrophysics Data System (ADS)

    Alexeeva, N. V.; Barashenkov, I. V.; Rayanov, K.; Flach, S.

    2014-01-01

    We consider light propagation through a pair of nonlinear optical waveguides with absorption, placed in a medium with power gain. The active medium boosts the in-phase component of the overlapping evanescent fields of the guides, while the nonlinearity of the guides couples it to the damped out-of-phase component creating a feedback loop. As a result, the structure exhibits stable stationary and oscillatory regimes in a wide range of gain-loss ratios. We show that the pair of actively coupled (AC) waveguides can act as a stationary or integrate-and-fire comparator sensitive to tiny differences in their input powers.

  4. MCO Monitoring activity description

    SciTech Connect

    SEXTON, R.A.

    1998-11-09

    Spent Nuclear Fuel remaining from Hanford's N-Reactor operations in the 1970s has been stored under water in the K-Reactor Basins. This fuel will be repackaged, dried and stored in a new facility in the 200E Area. The safety basis for this process of retrieval, drying, and interim storage of the spent fuel has been established. The monitoring of MCOS in dry storage is a currently identified issue in the SNF Project. This plan outlines the key elements of the proposed monitoring activity. Other fuel stored in the K-Reactor Basins, including SPR fuel, will have other monitoring considerations and is not addressed by this activity description.

  5. Inflammasomes and Their Activation

    PubMed Central

    Khare, Sonal; Luc, Nancy; Dorfleutner, Andrea; Stehlik, Christian

    2011-01-01

    The innate immune system relies on the recognition of pathogens by pattern recognition receptors as a first line of defense and to initiate the adaptive immune response. Substantial progress has been made in defining the role of Nod (nucleotide-binding oligimerization domain)-like receptors and AIM2 (absent in melanoma 2) as pattern recognition receptors that activate inflammasomes in macrophages. Inflammasomes are protein platforms essential for the activation of inflammatory caspases and subsequent maturation of their pro-inflammatory cytokine substrates and induction of pyroptosis. This paper summarizes recent developments regarding the function of Nod-like receptors in immunity and disease. PMID:21083527

  6. Activated carbon material

    DOEpatents

    Evans, A. Gary

    1978-01-01

    Activated carbon particles for use as iodine trapping material are impregnated with a mixture of selected iodine and potassium compounds to improve the iodine retention properties of the carbon. The I/K ratio is maintained at less than about 1 and the pH is maintained at above about 8.0. The iodine retention of activated carbon previously treated with or coimpregnated with triethylenediamine can also be improved by this technique. Suitable flame retardants can be added to raise the ignition temperature of the carbon to acceptable standards.

  7. Antibacterial activity of grepafloxacin.

    PubMed

    Wiedemann, B; Heisig, P

    1997-12-01

    Grepafloxacin has an extremely broad spectrum of activity. Its activity against Gram-positive bacteria exceeds that of currently available quinolones. Grepafloxacin-resistant mutants seem to occur less frequently than ciprofloxacin- or ofloxacin-resistant mutants, and the increase in MIC against the former mutants is less than that of the latter. This applies only to the relative differences (in dilution steps); the absolute values are similar. Grepafloxacin kills Gram-positive bacteria at concentrations little above the MIC. Its pharmacodynamic profile against pneumococci is promising, favouring use of this drug for respiratory tract infections.

  8. Active seismic experiment

    NASA Technical Reports Server (NTRS)

    Kovach, R. L.; Watkins, J. S.; Talwani, P.

    1972-01-01

    The Apollo 16 active seismic experiment (ASE) was designed to generate and monitor seismic waves for the study of the lunar near-surface structure. Several seismic energy sources are used: an astronaut-activated thumper device, a mortar package that contains rocket-launched grenades, and the impulse produced by the lunar module ascent. Analysis of some seismic signals recorded by the ASE has provided data concerning the near-surface structure at the Descartes landing site. Two compressional seismic velocities have so far been recognized in the seismic data. The deployment of the ASE is described, and the significant results obtained are discussed.

  9. Space construction activities

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The Center for Space Construction at the University of Colorado at Boulder was established in 1988 as a University Space Engineering Research Center. The mission of the Center is to conduct interdisciplinary engineering research which is critical to the construction of future space structures and systems and to educate students who will have the vision and technical skills to successfully lead future space construction activities. The research activities are currently organized around two central projects: Orbital Construction and Lunar Construction. Summaries of the research projects are included.

  10. Cosmogenic activation of materials

    NASA Astrophysics Data System (ADS)

    Amaré, J.; Beltrán, B.; Capelli, S.; Capozzi, F.; Carmona, J. M.; Cebrián, S.; Cremonesi, O.; García, E.; Irastorza, I. G.; Gómez, H.; Luzón, G.; Martínez, M.; Morales, J.; Ortiz de Solórzano, A.; Pavan, M.; Pobes, C.; Puimedón, J.; Rodríguez, A.; Ruz, J.; Sarsa, M. L.; Torres, L.; Villar, J. A.

    2005-09-01

    The problem of cosmogenic activation produced at sea level in materials typically used in underground experiments looking for rare events is being studied. Several nuclear data libraries have been screened looking for relevant isotope production cross-sections and different codes which can be applied to activation studies have been reviewed. The excitation functions for some problems of interest like production of 60Co and 68Ge in germanium and production of 60Co in tellurium have been obtained taking into account both measurements and calculations and a preliminary estimate of the corresponding rates of production at sea level has been performed.

  11. [Problem Solving Activities.

    ERIC Educational Resources Information Center

    Wisconsin Univ. - Stout, Menomonie. Center for Vocational, Technical and Adult Education.

    The teacher directed problem solving activities package contains 17 units: Future Community Design, Let's Build an Elevator, Let's Construct a Catapult, Let's Design a Recreational Game, Let's Make a Hand Fishing Reel, Let's Make a Wall Hanging, Let's Make a Yo-Yo, Marooned in the Past, Metrication, Mousetrap Vehicles, The Multi System…

  12. [Biological activity of Spirulina].

    PubMed

    Blinkova, L P; Gorobets, O B; Baturo, A P

    2001-01-01

    In this review information of Spirulina platensis (SP), a blue-green alga (photosynthesizing cyanobacterium) having diverse biological activity is presented. Due to high content of highly valuable proteins, indispensable amino acids, vitamins, beta-carotene and other pigments, mineral substances, indispensable fatty acids and polysaccharides, PS has been found suitable for use as bioactive additive. SP produces an immunostimulating effect by enhancing the resistance of humans, mammals, chickens and fish to infections, the capacity of influencing hemopoiesis, stimulating the production of antibodies and cytokines. Under the influence of SP macrophages, T and B cells are activated. SP sulfolipids have proved to be effective against HIV. Preparations obtained from SP biomass have also been found active against herpesvirus, cytomegalovirus, influenza virus, etc. SP extracts are capable in inhibiting cancerogenesis. SP preparations are regarded as functional products contributing to the preservation of the resident intestinal microflora, especially lactic acid bacilli and bifidobacteria, and to a decrease in the level of Candida albicans. The biological activity of SP with respect to microorganisms holds good promise for using these microalgae as components of culture media.

  13. Active Authentication: Beyond Passwords

    DTIC Science & Technology

    2011-11-18

    semantic analysis (how you construct sentences); Forensic authorship Keystroke pattern; Mouse movement Fingerprint ; Iris pattern; Vein...Solutions Physiological Biometrics Sensors tracking the physical attributes of you • DNA • Ear Geometry • Facial Geometry • Fingerprint • Iris...Preview Fingerprint Forensic authorship2 Mouse tracking1 How you behave Physical aspects of you The context you exist in • The Active Authentication

  14. An Active Attraction.

    ERIC Educational Resources Information Center

    Burns, Joseph C.; Buzzelli, Cary

    1992-01-01

    Describes a unit on magnetism that utilizes hands-on activities in which students make hypotheses for discrepant behavior, discover whether a magnet attracts one object through another, measure the strength of magnets, explore levitating paper clips, and play a game dependent on magnetic attraction. (MDH)

  15. Active control system trends

    NASA Technical Reports Server (NTRS)

    Yore, E. E.; Gunderson, D. C.

    1976-01-01

    The active control concepts which achieve the benefit of improved mission performance and lower cost and generate system trends towards improved dynamic performance, more integration, and digital fly by wire mechanization are described. Analytical issues and implementation requirements and tools and approaches developed to address the analytical and implementation issues are briefly discussed.

  16. Arsenic activation neutron detector

    DOEpatents

    Jacobs, Eddy L.

    1981-01-01

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5 Mev neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  17. Arsenic activation neutron detector

    DOEpatents

    Jacobs, E.L.

    1980-01-28

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5-MeV neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  18. Earthfest. Activity Book.

    ERIC Educational Resources Information Center

    Weilbacher, Mike

    1991-01-01

    An activity book to help elementary teachers and students explore the environment offers information and questions about spaceships; an ecology primer and poster with questions; information on animal adaptation with poster and questions; ecological and dramatic arts projects; a script for performance; and suggestions to make Earth Day celebrations…

  19. Regional Activities Division. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on library network activities in Canada, the Third World, Japan, Malaysia, Brazil, and Sweden which were presented at the 1982 International Federation of Library Associations (IFLA) conference include: (1) "Canada: A Voluntary and Flexible Network," a review by Guy Sylvestre of the political, social, and economic structures…

  20. Learning Activity Package, Algebra.

    ERIC Educational Resources Information Center

    Evans, Diane

    A set of ten teacher-prepared Learning Activity Packages (LAPs) in beginning algebra and nine in intermediate algebra, these units cover sets, properties of operations, number systems, open expressions, solution sets of equations and inequalities in one and two variables, exponents, factoring and polynomials, relations and functions, radicals,…

  1. Educating for Political Activity

    ERIC Educational Resources Information Center

    Chitty, Clyde

    2010-01-01

    The term "political activity" can be interpreted in a myriad of different ways, but in this paper, it is taken to mean involvement in a variety of campaigns around issues affecting the way we live and the sort of society we want to live in. At a time when support for the main political parties has never been weaker, it is essential that…

  2. Active microwave water equivalence

    NASA Technical Reports Server (NTRS)

    Boyne, H. S.; Ellerbruch, D. A.

    1980-01-01

    Measurements of water equivalence using an active FM-CW microwave system were conducted over the past three years at various sites in Colorado, Wyoming, and California. The measurement method is described. Measurements of water equivalence and stratigraphy are compared with ground truth. A comparison of microwave, federal sampler, and snow pillow measurements at three sites in Colorado is described.

  3. Active Learning Methods

    ERIC Educational Resources Information Center

    Zayapragassarazan, Z.; Kumar, Santosh

    2012-01-01

    Present generation students are primarily active learners with varied learning experiences and lecture courses may not suit all their learning needs. Effective learning involves providing students with a sense of progress and control over their own learning. This requires creating a situation where learners have a chance to try out or test their…

  4. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1993

    1993-01-01

    Elementary level activity book presents suggestions for teaching students about endangered and threatened species worldwide. Students learn about what is causing the rapid extinction rate and what needs to be done. They also discover the value of rainforests and why conservationists are fighting to save them. (SM)

  5. Macrophage activation and polarization.

    PubMed

    Martinez, Fernando Oneissi; Sica, Antonio; Mantovani, Alberto; Locati, Massimo

    2008-01-01

    Macrophages are widely distributed immune system cells that play an indispensable role in homeostasis and defense. They can be phenotypically polarized by the microenvironment to mount specific functional programs. Polarized macrophages can be broadly classified in two main groups: classically activated macrophages (or M1), whose prototypical activating stimuli are IFNgamma and LPS, and alternatively activated macrophages (or M2), further subdivided in M2a (after exposure to IL-4 or IL-13), M2b (immune complexes in combination with IL-1beta or LPS) and M2c (IL-10, TGFbeta or glucocorticoids). M1 exhibit potent microbicidal properties and promote strong IL-12-mediated Th1 responses, whilst M2 support Th2-associated effector functions. Beyond infection M2 polarized macrophages play a role in resolution of inflammation through high endocytic clearance capacities and trophic factor synthesis, accompanied by reduced pro-inflammatory cytokine secretion. Similar functions are also exerted by tumor-associated macrophages (TAM), which also display an alternative-like activation phenotype and play a detrimental pro-tumoral role. Here we review the main functions of polarized macrophages and discuss the perspectives of this field.

  6. Active Ingredient - AZ

    EPA Pesticide Factsheets

    EPA Pesticide Chemical Search allows a user to easily find the pesticide chemical or active ingredient that they are interested in by using an array of simple to advanced search options. Chemical Search provides a single point of reference for easy access to information previously published in a variety of locations, including various EPA web pages and Regulations.gov.

  7. Shark Tagging Activities.

    ERIC Educational Resources Information Center

    Current: The Journal of Marine Education, 1998

    1998-01-01

    In this group activity, children learn about the purpose of tagging and how scientists tag a shark. Using a cut-out of a shark, students identify, measure, record data, read coordinates, and tag a shark. Includes introductory information about the purpose of tagging and the procedure, a data sheet showing original tagging data from Tampa Bay, and…

  8. Engineers and Active Responsibility.

    PubMed

    Pesch, Udo

    2015-08-01

    Knowing that technologies are inherently value-laden and systemically interwoven with society, the question is how individual engineers can take up the challenge of accepting the responsibility for their work? This paper will argue that engineers have no institutional structure at the level of society that allows them to recognize, reflect upon, and actively integrate the value-laden character of their designs. Instead, engineers have to tap on the different institutional realms of market, science, and state, making their work a 'hybrid' activity combining elements from the different institutional realms. To deal with this institutional hybridity, engineers develop routines and heuristics in their professional network, which do not allow societal values to be expressed in a satisfactory manner. To allow forms of 'active' responsibility, there have to be so-called 'accountability forums' that guide moral reflections of individual actors. The paper will subsequently look at the methodologies of value-sensitive design (VSD) and constructive technology assessment (CTA) and explore whether and how these methodologies allow engineers to integrate societal values into the design technological artifacts and systems. As VSD and CTA are methodologies that look at the process of technological design, whereas the focus of this paper is on the designer, they can only be used indirectly, namely as frameworks which help to identify the contours of a framework for active responsibility of engineers.

  9. Activities: Visualization, Estimation, Computation.

    ERIC Educational Resources Information Center

    Maletsky, Evan M.

    1982-01-01

    The material is designed to help students build a cone model, visualize how its dimensions change as its shape changes, estimate maximum volume position, and develop problem-solving skills. Worksheets designed for duplication for classroom use are included. Part of the activity involves student analysis of a BASIC program. (MP)

  10. Intermittent Activity in AGN

    NASA Astrophysics Data System (ADS)

    Janiuk, A.; Czerny, B.; Siemiginowska, A.

    2004-10-01

    There is a growing evidence that the AGN activity could be intermittent. It remains an open question if this behavior is caused by changes in the fuel sup- ply to the supermassive black hole from the large distances, or rather by a processes intrinsic to the active nucleus. We consider the possibility that ac- cretion onto a supermassive black hole is controlled by an accretion disk which is subject to the hydro- gen ionization instability. This drives the observed on-off activity cycle, since periodically the accretion flow becomes inefficient and the disk goes to quies- cence. We consider effects of the MHD turbulence on the viscosity during the evolution of a standard α - disk. We perform a self-consistency check of the α de- scription of the angular momentum transfer. Hav- ing shown that the viscosity parameter is constant throughout the whole instability cycle, as implied by the strength of the MHD turbulence, we calcu- late the time evolution of the disk under the influ- ence of the ionization instability. We demonstrate that if the accretion onto a supermassive black hole proceeds through an outer standard accretion disk and inner, radiatively inefficient and advection dom- inated flow, the modelled amplitudes of disk lumi- nosity variations are sufficiently high to account for the observations. Key words: accretion disks; galaxies: active.

  11. Highlights of 1976 activities

    NASA Technical Reports Server (NTRS)

    Fitzpatrick, M.

    1976-01-01

    Highlights of NASA's 1976 activities are summarized. Sixteen successful launches were made. Two landings of Viking spacecraft on Mars and rollout of the space shuttle orbiter are reviewed. Applications of aerospace science to education, health care, and community services are also discussed.

  12. Activities from Asia.

    ERIC Educational Resources Information Center

    Texas Child Care, 1995

    1995-01-01

    Notes that the best way to learn about another culture is to know how its habits, traditions, and environments differ from or resemble our own. Provides several activities to help young children understand Asian cultures, including cooking, origami, and games and festivals. (HTH)

  13. Highlights of 1978 activities

    NASA Technical Reports Server (NTRS)

    1978-01-01

    General highlights of NASA's activities for 1978 are presented. The highlights are categorized into topics such as space science, space transportation systems, space and terrestrial applications, environment, technology utilization, aeronautics, space research and technology, energy programs, and international. A list of the 1978 launches including: (1) launch date; (2) payload designation; (3) launch vehicle; (4) launch site and (5) mission remarks is also presented.

  14. Multidisciplinary Wildlife Teaching Activities.

    ERIC Educational Resources Information Center

    Hernbrode, William R., Ed.

    This guide provides information and activities descriptions designed to allow the teacher to use wildlife concepts in the teaching of various subjects. The author suggests that wildlife and animals are tremendous motivators for children and hold their attention. In the process, concepts of wildlife interaction with man and the environment are…

  15. Active-bridge oscillator

    DOEpatents

    Wessendorf, Kurt O.

    2001-01-01

    An active bridge oscillator is formed from a differential amplifier where positive feedback is a function of the impedance of one of the gain elements and a relatively low value common emitter resistance. This use of the nonlinear transistor parameter h stabilizes the output and eliminates the need for ALC circuits common to other bridge oscillators.

  16. Immunizations: Active vs. Passive

    MedlinePlus

    ... a certain type of wild animal bites a child. Passive immunizations for hepatitis A (gamma globulin) may be helpful ... A is common. They are typically given before children or adults leave on their ... active vaccination is preferable. Keep in mind that passive immunizations ...

  17. 85 Engaging Movement Activities.

    ERIC Educational Resources Information Center

    Weikart, Phyllis S.; Carlton, Elizabeth B.

    This book presents activities to keep K-6 students moving in a variety of ways as they learn. The movement experiences are planned around key curriculum concepts in movement and music as well as in academic curriculum areas. The experiences develop students' basic timing, language abilities, vocabulary, concentration, planning skills, and…

  18. Classification of Physical Activity

    PubMed Central

    Turksoy, Kamuran; Paulino, Thiago Marques Luz; Zaharieva, Dessi P.; Yavelberg, Loren; Jamnik, Veronica; Riddell, Michael C.; Cinar, Ali

    2015-01-01

    Physical activity has a wide range of effects on glucose concentrations in type 1 diabetes (T1D) depending on the type (ie, aerobic, anaerobic, mixed) and duration of activity performed. This variability in glucose responses to physical activity makes the development of artificial pancreas (AP) systems challenging. Automatic detection of exercise type and intensity, and its classification as aerobic or anaerobic would provide valuable information to AP control algorithms. This can be achieved by using a multivariable AP approach where biometric variables are measured and reported to the AP at high frequency. We developed a classification system that identifies, in real time, the exercise intensity and its reliance on aerobic or anaerobic metabolism and tested this approach using clinical data collected from 5 persons with T1D and 3 individuals without T1D in a controlled laboratory setting using a variety of common types of physical activity. The classifier had an average sensitivity of 98.7% for physiological data collected over a range of exercise modalities and intensities in these subjects. The classifier will be added as a new module to the integrated multivariable adaptive AP system to enable the detection of aerobic and anaerobic exercise for enhancing the accuracy of insulin infusion strategies during and after exercise. PMID:26443291

  19. Production Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Gallaway, Ann, Ed.

    This production systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, domains and objectives, a course description, and a content outline. The guide contains 30 modules on the following topics: production…

  20. Dissemination Activities Report

    ERIC Educational Resources Information Center

    Barclay, Hanna; Batatia, Hudj; Bauters, Merja; Ben Ami, Zvi; Drachman, Raul; Flouris, Giorgos; Jadin, Tanja; Jalonen, Satu; Karlgren, Klas; Karpati, Andrea; Kotzinos, Dimitris; Lakkala, Minna; Lallimo, Jiri; Moen, Anne; Nygard, Kathrine; Paavola, Sami; Padiglia, Sheila; Scapolla, Marina; Sins, Patrick; Vasileva, Tania

    2008-01-01

    In the first 24 months of the project, KP-Lab members were highly dedicated to dissemination and were engaged in various dissemination activities that contributed to the prime objective of the KP-Lab dissemination efforts which is "to make the project widely known to a variety of prospective users and, at a later stage, to promote the…

  1. Designing Metacognitive Activities.

    ERIC Educational Resources Information Center

    Lin, Xiaodong

    2001-01-01

    Proposes a framework for thinking about how metacognition research might apply to design activities. Examines two basic approaches to supporting metacognition: strategy training, and creation of a supportive social environment for metacognition. Identifies two kinds of content that are taught using these two approaches: knowledge about a specific…

  2. Geology: The Active Earth.

    ERIC Educational Resources Information Center

    Braus, Judy, Ed.

    1987-01-01

    Ranger Rick's NatureScope is a creative education series dedicated to inspiring in children an understanding and appreciation of the natural world while developing the skills they will need to make responsible decisions about the environment. The topic of this issue is "Geology: The Active Earth." Contents are organized into the…

  3. Marketing coprovided activities.

    PubMed

    Dickerson, Pamela S

    2014-05-01

    Coproviding is a wonderful way for two or more organizations to work together to provide continuing nursing education. To be transparent to the learners, marketing materials identify the parties involved and prominently note the name of the organization accountable for developing the activity and awarding the contact hours.

  4. Communication Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Sutherland, Barbara, Ed.

    This communication systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, a list of objectives, a course description, and a content outline. The guide contains 32 modules on the following topics: story…

  5. Chaperone activation by unfolding.

    PubMed

    Foit, Linda; George, Jenny S; Zhang, Bin W; Brooks, Charles L; Bardwell, James C A

    2013-04-02

    Conditionally disordered proteins can alternate between highly ordered and less ordered configurations under physiological conditions. Whereas protein function is often associated with the ordered conformation, for some of these conditionally unstructured proteins, the opposite applies: Their activation is associated with their unfolding. An example is the small periplasmic chaperone HdeA, which is critical for the ability of enteric bacterial pathogens like Escherichia coli to survive passage through extremely acidic environments, such as the human stomach. At neutral pH, HdeA is a chaperone-inactive dimer. On a shift to low pH, however, HdeA monomerizes, partially unfolds, and becomes rapidly active in preventing the aggregation of substrate proteins. By mutating two aspartic acid residues predicted to be responsible for the pH-dependent monomerization of HdeA, we have succeeded in isolating an HdeA mutant that is active at neutral pH. We find this HdeA mutant to be substantially destabilized, partially unfolded, and mainly monomeric at near-neutral pH at a concentration at which it prevents aggregation of a substrate protein. These results provide convincing evidence for direct activation of a protein by partial unfolding.

  6. Ocean Drilling Simulation Activity.

    ERIC Educational Resources Information Center

    Telese, James A.; Jordan, Kathy

    The Ocean Drilling Project brings together scientists and governments from 20 countries to explore the earth's structure and history as it is revealed beneath the oceans' basins. Scientific expeditions examine rock and sediment cores obtained from the ocean floor to learn about the earth's basic processes. The series of activities in this…

  7. Organizing Preservation Activities.

    ERIC Educational Resources Information Center

    Cloonan, Michele

    This resource guide considers issues in the staffing and organization of preservation activities. It provides guidance in implementing a systematic preservation program and evaluates the structures of various types of preservation programs. The following articles complement the discussion of program models and implementation: (1)…

  8. Activities: Some Colorful Mathematics.

    ERIC Educational Resources Information Center

    DeTemple, Duane W.; Walker, Dean A.

    1996-01-01

    Describes three activities in discrete mathematics that involve coloring geometric objects: counting colored regions of overlapping simple closed curves, counting colored triangulations of polygons, and determining the number of colors required to paint the plane so that no two points one inch apart are the same color. (MKR)

  9. Physical Activities for Preschool.

    ERIC Educational Resources Information Center

    Adkins, Dorothy C.; And Others

    The underlying premise of the University of Hawaii Physical Activities for Preschool curriculum is that important contributions to a positive self-concept are made by motor independence and a realistic body image. Program objectives include: (1) the development of strength, endurance, and flexibility in skills that involve the muscles,…

  10. Activating silent argonautes.

    PubMed

    Kidwell, Mary Anne; Doudna, Jennifer A

    2013-07-01

    Multiple Argonaute proteins are implicated in gene silencing by RNA interference (RNAi), but only one is known to be an endonuclease that can cleave target mRNAs. Chimeric Argonaute proteins now reveal an unexpected mechanism by which mutations distal to the catalytic center can unmask intrinsic catalytic activity, results hinting at structurally mediated regulation.

  11. Commission 10: Solar Activity

    NASA Astrophysics Data System (ADS)

    van Driel-Gesztelyi, Lidia; Schrijver, Carolus J.; Klimchuk, James A.; Charbonneau, Paul; Fletcher, Lyndsay; Hasan, S. Sirajul; Hudson, Hugh S.; Kusano, Kanya; Mandrini, Cristina H.; Peter, Hardi; Vršnak, Bojan; Yan, Yihua

    2012-04-01

    Commission 10 of the International Astronomical Union has more than 650 members who study a wide range of activity phenomena produced by our nearest star, the Sun. Solar activity is intrinsically related to solar magnetic fields and encompasses events from the smallest energy releases (nano- or even picoflares) to the largest eruptions in the Solar System, coronal mass ejections (CMEs), which propagate into the Heliosphere reaching the Earth and beyond. Solar activity is manifested in the appearance of sunspot groups or active regions, which are the principal sources of activity phenomena from the emergence of their magnetic flux through their dispersion and decay. The period 2008-2009 saw an unanticipated extended solar cycle minimum and unprecedentedly weak polar-cap and heliospheric field. Associated with that was the 2009 historical maximum in galactic cosmic rays flux since measurements begun in the middle of the 20th Century. Since then Cycle 24 has re-started solar activity producing some spectacular eruptions observed with a fleet of spacecraft and ground-based facilities. In the last triennium major advances in our knowledge and understanding of solar activity were due to continuing success of space missions as SOHO, Hinode, RHESSI and the twin STEREO spacecraft, further enriched by the breathtaking images of the solar atmosphere produced by the Solar Dynamic Observatory (SDO) launched on 11 February 2010 in the framework of NASA's Living with a Star program. In August 2012, at the time of the IAU General Assembly in Beijing when the mandate of this Commission ends, we will be in the unique position to have for the first time a full 3-D view of the Sun and solar activity phenomena provided by the twin STEREO missions about 120 degrees behind and ahead of Earth and other spacecraft around the Earth and ground-based observatories. These new observational insights are continuously posing new questions, inspiring and advancing theoretical analysis and

  12. 45 CFR 1226.8 - Prohibited activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICE PROHIBITIONS ON ELECTORAL AND LOBBYING ACTIVITIES Volunteer Activities § 1226.8 Prohibited activities. (a) Electoral Activity. Volunteers shall not engage in any activity which may, directly...

  13. Interdisciplinary Astronomy Activities

    NASA Astrophysics Data System (ADS)

    Nerantzis, Nikolaos; Mitrouda, Aikaterini; Reizopoulou, Ioanna; Sidiropoulou, Eirini; Hatzidimitriou, Antonios

    2016-04-01

    On November 9th, 2015, three didactical hours were dedicated to Interdisciplinary Astronomy Activities (http://wp.me/p6Hte2-1I). Our students and their teachers formed three groups and in rotation, were engaged with the following activities: (a) viewing unique images of the Cosmos in the mobile planetarium STARLAB (http://www.planitario.gr/tholos-starlab-classic-standard.html), (b) watching the following videos: Journey to the end of the universe (https://youtu.be/Ufl_Nwbl8xs), Rosetta update (https://youtu.be/nQ9ivd7wv30), The Solar System (https://youtu.be/d66dsagrTa0), Ambition the film (https://youtu.be/H08tGjXNHO4) in the school's library. Students and teachers were informed about our solar system, the Rosetta mission, the universe, etc. and (c) tactile activities such as Meet our home and Meet our neighbors (http://astroedu.iau.org, http://nuclio.org/astroneighbours/resources) and the creation of planets' 3D models (Geology-Geography A' Class Student's book, pg.15). With the activities above we had the pleasure to join the Cosmic Light Edu Kit / International Year of Light 2015 program. After our Interdisciplinary Astronomy Activities, we did a "small" research: our students had to fill an evaluation about their educational gains and the results can be found here http://wp.me/p6Hte2-2q. Moreover, we discussed about Big Ideas of Science (http://wp.me/p3oRiZ-dm) and through the "big" impact of the Rosetta mission & the infinity of our universe, we print posters with relevant topics and place them to the classrooms. We thank Rosa Doran (Nuclio - President of the Executive Council) for her continuous assistance and support on innovative science teaching proposals. She is an inspiration.

  14. Activities. Inductive and Deductive Reasoning.

    ERIC Educational Resources Information Center

    O'Daffer, Phares G.; And Others

    1990-01-01

    Provided are the activity sheets for students and the teaching guide for this middle school geometry activity. Materials, prerequisites, objectives, and procedures are listed. Extension activities are suggested. An answer key is included. (CW)

  15. Matrix remodeling stimulates stromal autophagy, “fueling” cancer cell mitochondrial metabolism and metastasis

    PubMed Central

    Bonuccelli, Gloria; Molchansky, Alex; Capozza, Franco; Witkiewicz, Agnieszka K; Birbe, Ruth C; Howell, Anthony; Pestell, Richard G; Whitaker-Menezes, Diana; Sotgia, Federica

    2011-01-01

    We have previously demonstrated that loss of stromal caveolin-1 (Cav-1) in cancer-associated fibroblasts is a strong and independent predictor of poor clinical outcome in human breast cancer patients. However, the signaling mechanism(s) by which Cav-1 downregulation leads to this tumor-promoting microenvironment are not well understood. To address this issue, we performed an unbiased comparative proteomic analysis of wild-type (WT) and Cav-1-/- null mammary stromal fibroblasts (MSFs). Our results show that plasminogen activator inhibitor type 1 and type 2 (PAI-1 and PAI-2) expression is significantly increased in Cav-1-/- MSFs. To establish a direct cause-effect relationship, we next generated immortalized human fibroblast lines stably overexpressing either PAI-1 or PAI-2. Importantly, PAI-1/2(+) fibroblasts promote the growth of MDA-MB-231 tumors (a human breast cancer cell line) in a murine xenograft model, without any increases in angiogenesis. Similarly, PAI-1/2(+) fibroblasts stimulate experimental metastasis of MDA-MB-231 cells using an in vivo lung colonization assay. Further mechanistic studies revealed that fibroblasts overexpressing PAI-1 or PAI-2 display increased autophagy (“self-eating”) and are sufficient to induce mitochondrial biogenesis/activity in adjacent cancer cells, in co-culture experiments. In xenografts, PAI-1/2(+) fibroblasts significantly reduce the apoptosis of MDA-MB-231 tumor cells. The current study provides further support for the “Autophagic Tumor Stroma Model of Cancer” and identifies a novel “extracellular matrix”-based signaling mechanism, by which a loss of stromal Cav-1 generates a metastatic phenotype. Thus, the secretion and remodeling of extracellular matrix components (such as PAI-1/2) can directly regulate both (1) autophagy in stromal fibroblasts and (2) epithelial tumor cell mitochondrial metabolism. PMID:21646868

  16. Arabidopsis phosphoribosylanthranilate isomerase: molecular genetic analysis of triplicate tryptophan pathway genes.

    PubMed Central

    Li, J; Zhao, J; Rose, A B; Schmidt, R; Last, R L

    1995-01-01

    Phosphoribosylanthranilate isomerase (PAI) catalyzes the third step of the tryptophan biosynthetic pathway. Arabidopsis PAI cDNAs were cloned from a cDNA expression library by complementation of an Escherichia coli trpC- PAI deficiency mutation. Genomic DNA blot hybridization analysis detected three nonallelic genes encoding PAI in the Arabidopsis genome. DNA sequence analysis of cDNA and genomic clones indicated that the PAI1 and PAI2. All three PAI polypeptides possess an N-terminal putative plastid target sequence, suggesting that these enzymes all function in plastids. The PAI1 gene is flanked by nearly identical direct repeats of approximately 350 nucleotides. Our results indicate that, in contrast to most microorganisms, the Arabidopsis PAI protein is not fused with indole-3-glycerolphosphate synthase, which catalyzes the next step in the pathway. Yeast artificial chromosome hybridization studies indicated that the PAI2 gene is tightly linked to the anthranilate synthase alpha subunit 1 (ASA1) gene on chromosome 5. PAI1 was mapped to the top of chromosome 1 using recombinant inbred lines, and PAI3 is loosely linked to PAI1. cDNA restriction mapping and sequencing and RNA gel blot hybridization analysis indicated that all three genes are transcribed in wild-type plants. The expression of antisense PAI1 RNA significantly reduced the immunologically observable PAI protein and enzyme activity in transgenic plants. The plants expressing antisense RNA also showed two phenotypes consistent with a block early in the pathway: blue fluorescence under UV light and resistance to the anthranilate analog 6-methylanthranilate. The extreme nucleotide conservation between the unlinked PAI1 and PAI2 loci suggests that this gene family is actively evolving. PMID:7773017

  17. 101 Environmental Education Activities. Booklet 6--Social Studies Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    Based on the environment and directed at elementary and intermediate level students, 5 field trips are a significant part of the 12 social studies activities in the sixth booklet by the Upper Mississippi River ECO-Center outlining environmental and outdoor education activities. Most of the activities include objectives, activity description,…

  18. Integration of Active Video Games in Extracurricular Activity at Schools

    ERIC Educational Resources Information Center

    Lee, Jung Eun; Huang, Charles; Pope, Zachary; Gao, Zan

    2015-01-01

    Active video games require players to be physically active. Dance Dance Revolution (DDR) is an interactive dancing game that requires fast-foot movement coordinated with energetic music and visuals. The Wii and Xbox Kinect games have also become good active video games for the promotion of physical activity participation. These games are much more…

  19. Is Enhanced Physical Activity Possible Using Active Videogames?

    PubMed

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-06-01

    Our research indicated that 10-12-year-old children receiving two active Wii(™) (Nintendo(®); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  20. Active braze process

    SciTech Connect

    Levine, I.L.; Pike, R.A.

    1990-11-02

    Active metal bonding using Cusil (silver-copper) braze alloys is a well established method used at GE Neutron Devices (GEND) for bonding metal to metal, metal to ceramics, and ceramics to ceramics. However, there are many instances in which using a silver alloy for bonding is undesirable (e.g., in vacuum tube envelopes, or where sequential braze steps at different temperatures are required to complete an assembly). The Material and Processes Laboratory at GEND has discovered a new method of active brazing with non-silver alloys which has proved especially successful in ceramic-to-ceramic joints. This method has the added advantage of eliminating several steps which are required in conventional bonding techniques. 2 figs., 10 tabs.

  1. Myofilament length dependent activation.

    PubMed

    de Tombe, Pieter P; Mateja, Ryan D; Tachampa, Kittipong; Ait Mou, Younss; Farman, Gerrie P; Irving, Thomas C

    2010-05-01

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca(2+) ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the "Frank-Starling law of the heart" constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  2. Mount Erebus activity

    NASA Astrophysics Data System (ADS)

    An international team of scientists reports that unusually high seismic activity joggled Mount Erebus last fall. However, the Antarctic volcano showed no external signs of an eruption.When scientists from the United States, Japan, and New Zealand returned to the world's southernmost active volcano last November for their annual field expedition, they found that seismic stations recorded 650 small tremors on October 8; prior to that, the number of quakes had averaged between 20 and 80 per day. The October 8 maximum was followed by 140 on October 9 and 120 on October 10. Philip R. Kyle, assistant professor of geochemistry at the New Mexico Institute of Mining and Technology in Socorro and leader of the team studying Mount Erebus, noted that some of the strongest earthquakes recorded during the team's 3 years of observations occurred on October 8; these registered less than 2 on the Richter scale.

  3. UNESCO's activities in ethics.

    PubMed

    ten Have, Henk A M J

    2010-03-01

    UNESCO is an intergovernmental organization with 193 Member States. It is concerned with a broad range of issues regarding education, science and culture. It is the only UN organisation with a mandate in science. Since 1993 it is addressing ethics of science and technology, with special emphasis on bioethics. One major objective of the ethics programme is the development of international normative standards. This is particularly important since many Member States only have a limited infrastructure in bioethics, lacking expertise, educational programs, bioethics committees and legal frameworks. UNESCO has recently adopted the Universal Declaration on Bioethics and Human Rights. The focus of current activities is now on implementation of this Declaration. Three activities are discussed that aim at improving and reinforcing the ethics infrastructure in relation to science and technology: the Global Ethics Observatory, the Ethics Education Programme and the Assisting Bioethics Committees project.

  4. LANSCE Activity Report

    SciTech Connect

    Amy Robinson; Audrey Archuleta; Barbara Maes; Dan Strottman; Earl Hoffman; Garth Tietjen; Gene Farnum; Geoff Greene; Joyce Roberts; Ken Johnson; Paul Lewis; Roger Pynn; Stan Schriber; Steve Sterbenz; Steve Wender; Sue Harper

    1999-02-01

    The Los Alamos Neutron Science Center Activity Report describes scientific and technological progress and achievements in LANSCE Division during the period of 1995 to 1998. This report includes a message from the Division Director, an overview of LANSCE, sponsor overviews, research highlights, advanced projects and facility upgrades achievements, experimental and user program accomplishments, news and events, and a list of publications. The research highlights cover the areas of condensed-matter science and engineering, accelerator science, nuclear science, and radiography. This report also contains a compact disk that includes an overview, the Activity Report itself, LANSCE operations progress reports for 1996 and 1997, experiment reports from LANSCE users, as well as a search capability.

  5. Myofilament length dependent activation

    SciTech Connect

    de Tombe, Pieter P.; Mateja, Ryan D.; Tachampa, Kittipong; Mou, Younss Ait; Farman, Gerrie P.; Irving, Thomas C.

    2010-05-25

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca{sup 2+} ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the 'Frank-Starling law of the heart' constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  6. Techniques for active passivation

    SciTech Connect

    Roscioli, Joseph R.; Herndon, Scott C.; Nelson, Jr., David D.

    2016-12-20

    In one embodiment, active (continuous or intermittent) passivation may be employed to prevent interaction of sticky molecules with interfaces inside of an instrument (e.g., an infrared absorption spectrometer) and thereby improve response time. A passivation species may be continuously or intermittently applied to an inlet of the instrument while a sample gas stream is being applied. The passivation species may have a highly polar functional group that strongly binds to either water or polar groups of the interfaces, and once bound presents a non-polar group to the gas phase in order to prevent further binding of polar molecules. The instrument may be actively used to detect the sticky molecules while the passivation species is being applied.

  7. Nematicidal activity of terpenoids.

    PubMed

    Abdel-Rahman, Fawzia H; Alaniz, Nina M; Saleh, Mahmoud A

    2013-01-01

    Thirty four phytoterpenoids were evaluated for their nematicidal effect using the model nematode Caenorhabditis elegans. Nematicidal activities of the tested compounds at concentrations of 50 μg/mL showed wide variation in their effects ranging from no effect, weak, moderate and strong effects. Terpenoids exerting 50% or higher mortality at 50 μg/mL were further tested at five different concentrations to calculate the concentration that will kill 50% of the nematode population (LC(50)). Among the most effective terpenoids were carvacrol, thymol, nerolidol, α-terpinene, geraniol, citronellol, farnesol, limonene, pseudoionone and eugenol in a descending order. These compounds exhibited a dose-dependent effect. The results suggest that the selected monoterpenoids and essential oils with a high concentration of these compounds mayprovide potential natural nematicides and merit further study as botanical nematicides for the control of both plant and animal parasitic nematodes. In general, oxygenated terpenoids and phenolic terpenoids exhibited higher nematicidal activity than hydrocarbons terpenoids.

  8. Active region seismology

    NASA Technical Reports Server (NTRS)

    Bogdan, Tom; Braun, D. C.

    1995-01-01

    Active region seismology is concerned with the determination and interpretation of the interaction of the solar acoustic oscillations with near-surface target structures, such as magnetic flux concentration, sunspots, and plage. Recent observations made with a high spatial resolution and a long temporal duration enabled measurements of the scattering matrix for sunspots and solar active regions to be carried out as a function of the mode properties. Based on this information, the amount of p-mode absorption, partial-wave phase shift, and mode mixing introduced by the sunspot, could be determined. In addition, the possibility of detecting the presence of completely submerged magnetic fields was raised, and new procedures for performing acoustic holography of the solar interior are being developed. The accumulating evidence points to the mode conversion of p-modes to various magneto-atmospheric waves within the magnetic flux concentration as being the unifying physical mechanism responsible for these diverse phenomena.

  9. Cisplatin triggers platelet activation.

    PubMed

    Togna, G I; Togna, A R; Franconi, M; Caprino, L

    2000-09-01

    Clinical observations suggest that anticancer drugs could contribute to the thrombotic complications of malignancy in treated patients. Thrombotic microangiopathy, myocardial infarction, and cerebrovascular thrombotic events have been reported for cisplatin, a drug widely used in the treatment of many solid tumours. The aim of this study is to explore in vitro cisplatin effect on human platelet reactivity in order to define the potentially active role of platelets in the pathogenesis of cisplatin-induced thrombotic complications. Our results demonstrate that cisplatin increases human platelet reactivity (onset of platelet aggregation wave and thromboxane production) to non-aggregating concentrations of the agonists involving arachidonic acid metabolism. Direct or indirect activation of platelet phospholipase A(2) appears to be implicated. This finding contributes to a better understanding of the pathogenesis of thrombotic complications occurring during cisplatin-based chemotherapy.

  10. Active optical zoom system.

    PubMed

    Wang, Di; Wang, Qiong-Hua; Shen, Chuan; Zhou, Xin; Liu, Chun-Mei

    2014-11-01

    In this work, we propose an active optical zoom system. The zoom module of the system is formed by a liquid lens and a spatial light modulator (SLM). By controlling the focal lengths of the liquid lens and the encoded digital lens on the SLM panel, we can change the magnification of an image without mechanical moving parts and keep the output plane stationary. The magnification can change from 1/3 to 3/2 as the focal length of the encoded lens on the SLM changes from infinity to 24 cm. The proposed active zoom system is simple and flexible, and has widespread application in optical communications, imaging systems, and displays.

  11. Active microchannel heat exchanger

    DOEpatents

    Tonkovich, Anna Lee Y [Pasco, WA; Roberts, Gary L [West Richland, WA; Call, Charles J [Pasco, WA; Wegeng, Robert S [Richland, WA; Wang, Yong [Richland, WA

    2001-01-01

    The present invention is an active microchannel heat exchanger with an active heat source and with microchannel architecture. The microchannel heat exchanger has (a) an exothermic reaction chamber; (b) an exhaust chamber; and (c) a heat exchanger chamber in thermal contact with the exhaust chamber, wherein (d) heat from the exothermic reaction chamber is convected by an exothermic reaction exhaust through the exhaust chamber and by conduction through a containment wall to the working fluid in the heat exchanger chamber thereby raising a temperature of the working fluid. The invention is particularly useful as a liquid fuel vaporizer and/or a steam generator for fuel cell power systems, and as a heat source for sustaining endothermic chemical reactions and initiating exothermic reactions.

  12. Environmental health program activities

    NASA Technical Reports Server (NTRS)

    Bergtholdt, C. P.

    1969-01-01

    Activities reported include studies on toxic air contaminants, excessive noise, poor lighting, food sanitation, water pollution, and exposure to nonionizing radiation as health hazards. Formulations for a radiological health manual provide guidance to personnel in the procurement and safe handling of radiation producing equipment and Apollo mission planning. A literature search and development of a water analysis laboratory are outlined to obtain information regarding microbiological problems involving potable water, waste management, and personal hygiene.

  13. [Chronotropic activity of semax].

    PubMed

    Arushanian, E B; Popov, A V

    2008-01-01

    The chronic administration of nootropic drug Semax, a peptide analog of ACTH (4-10), normalized the circadian locomotor rhythm in rats (with an increase in its amplitude, a shift in the acrophase, and a change of the spectral characteristics) and reduced the integral chronobiological index. It is suggested that the rhythm-synchronizing chronotropic activity may be a part of the specific effect of this cognitive enhancer.

  14. Imaging nervous system activity.

    PubMed

    Fields, Douglas R; Shneider, Neil; Mentis, George Z; O'Donovan, Michael J

    2009-10-01

    This unit describes methods for loading ion- and voltage-sensitive dyes into neurons, with a particular focus on the spinal cord as a model system. In addition, we describe the use of these dyes to visualize neural activity. Although the protocols described here concern spinal networks in culture or an intact in vitro preparation, they can be, and have been, widely used in other parts of the nervous system.

  15. Assay of FAAH Activity.

    PubMed

    Bari, Monica; Feole, Monica; Maccarrone, Mauro

    2016-01-01

    Fatty acid amide hydrolase (FAAH) is an intracellular enzyme responsible for the hydrolysis of endogenous anandamide (AEA), a reaction that terminates the biological effects of this lipid mediator. The final products of this reaction are arachidonic acid and ethanolamine. In the method described herein, FAAH activity is measured through the use of a radioactive substrate by quantification of reaction products, that is, [(14)C]-ethanolamine from [(14)C-ethanolamine]-AEA.

  16. Active inference and learning.

    PubMed

    Friston, Karl; FitzGerald, Thomas; Rigoli, Francesco; Schwartenbeck, Philipp; O'Doherty, John; Pezzulo, Giovanni

    2016-09-01

    This paper offers an active inference account of choice behaviour and learning. It focuses on the distinction between goal-directed and habitual behaviour and how they contextualise each other. We show that habits emerge naturally (and autodidactically) from sequential policy optimisation when agents are equipped with state-action policies. In active inference, behaviour has explorative (epistemic) and exploitative (pragmatic) aspects that are sensitive to ambiguity and risk respectively, where epistemic (ambiguity-resolving) behaviour enables pragmatic (reward-seeking) behaviour and the subsequent emergence of habits. Although goal-directed and habitual policies are usually associated with model-based and model-free schemes, we find the more important distinction is between belief-free and belief-based schemes. The underlying (variational) belief updating provides a comprehensive (if metaphorical) process theory for several phenomena, including the transfer of dopamine responses, reversal learning, habit formation and devaluation. Finally, we show that active inference reduces to a classical (Bellman) scheme, in the absence of ambiguity.

  17. Active Brownian rods

    NASA Astrophysics Data System (ADS)

    Peruani, Fernando

    2016-11-01

    Bacteria, chemically-driven rods, and motility assays are examples of active (i.e. self-propelled) Brownian rods (ABR). The physics of ABR, despite their ubiquity in experimental systems, remains still poorly understood. Here, we review the large-scale properties of collections of ABR moving in a dissipative medium. We address the problem by presenting three different models, of decreasing complexity, which we refer to as model I, II, and III, respectively. Comparing model I, II, and III, we disentangle the role of activity and interactions. In particular, we learn that in two dimensions by ignoring steric or volume exclusion effects, large-scale nematic order seems to be possible, while steric interactions prevent the formation of orientational order at large scales. The macroscopic behavior of ABR results from the interplay between active stresses and local alignment. ABR exhibit, depending on where we locate ourselves in parameter space, a zoology of macroscopic patterns that ranges from polar and nematic bands to dynamic aggregates.

  18. Active polarization descattering.

    PubMed

    Treibitz, Tali; Schechner, Yoav Y

    2009-03-01

    Vision in scattering media is important but challenging. Images suffer from poor visibility due to backscattering and attenuation. Most prior methods for scene recovery use active illumination scanners (structured and gated), which can be slow and cumbersome, while natural illumination is inapplicable to dark environments. The current paper addresses the need for a non-scanning recovery method, that uses active scene irradiance. We study the formation of images under widefield artificial illumination. Based on the formation model, the paper presents an approach for recovering the object signal. It also yields rough information about the 3D scene structure. The approach can work with compact, simple hardware, having active widefield, polychromatic polarized illumination. The camera is fitted with a polarization analyzer. Two frames of the scene are taken, with different states of the analyzer or polarizer. A recovery algorithm follows the acquisition. It allows both the backscatter and the object reflection to be partially polarized. It thus unifies and generalizes prior polarization-based methods, which had assumed exclusive polarization of either of these components. The approach is limited to an effective range, due to image noise and illumination falloff. Thus, the limits and noise sensitivity are analyzed. We demonstrate the approach in underwater field experiments.

  19. Active quantum plasmonics.

    PubMed

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K; M Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G

    2015-12-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics.

  20. THE ACTIVE ASTEROIDS

    SciTech Connect

    Jewitt, David

    2012-03-15

    Some asteroids eject dust, unexpectedly producing transient, comet-like comae and tails. First ascribed to the sublimation of near-surface water ice, mass-losing asteroids (also called 'main-belt comets') can in fact be driven by a surprising diversity of mechanisms. In this paper, we consider 11 dynamical asteroids losing mass, in nine of which the ejected material is spatially resolved. We address mechanisms for producing mass loss including rotational instability, impact ejection, electrostatic repulsion, radiation pressure sweeping, dehydration stresses, and thermal fracture, in addition to the sublimation of ice. In two objects (133P and 238P) the repetitive nature of the observed activity leaves ice sublimation as the only reasonable explanation, while in a third ((596) Scheila), a recent impact is the cause. Another impact may account for activity in P/2010 A2, but this tiny object can also be explained as having shed mass after reaching rotational instability. Mass loss from (3200) Phaethon is probably due to cracking or dehydration at extreme ({approx}1000 K) perihelion temperatures, perhaps aided by radiation pressure sweeping. For the other bodies, the mass-loss mechanisms remain unidentified, pending the acquisition of more and better data. While the active asteroid sample size remains small, the evidence for an astonishing diversity of mass-loss processes in these bodies is clear.

  1. Active quantum plasmonics

    PubMed Central

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K.; M. Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G.

    2015-01-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics. PMID:26824066

  2. Sesterterpenoids with Anticancer Activity

    PubMed Central

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2016-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  3. Transport to Rhebpress activity.

    PubMed

    Garrido, Amanda; Brandt, Marta; Djouder, Nabil

    2016-01-01

    The small GTPases from the rat sarcoma (Ras) superfamily are a heterogeneous group of proteins of about 21 kDa that act as molecular switches, modulating cell signaling pathways and controlling diverse cellular processes. They are active when bound to guanosine triphosphate (GTP) and inactive when bound to guanosine diphosphate (GDP). Ras homolog enriched in brain (Rheb) is a member of the Ras GTPase superfamily and a key activator of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1). We recently determined that microspherule protein 1 (MCRS1) maintains Rheb at lysosomal surfaces in an amino acid-dependent manner. MCRS1 depletion promotes the formation of the GDP-bound form of Rheb, which is then delocalized from the lysosomal platform and transported to endocytic recycling vesicles, leading to mTORC1 inactivation. During this delocalization process, Rheb-GDP remains farnesylated and associated with cellular endomembranes. These findings provide new insights into the regulation of small GTPases, whose activity depends on both their GTP/GDP switch state and their capacity to move between different cellular membrane-bound compartments. Dynamic spatial transport between compartments makes it possible to alter the proximity of small GTPases to their activatory sites depending on the prevailing physiological and cellular conditions.

  4. Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex.

    PubMed

    Furukawa, Tomonori; Yamada, Junko; Akita, Tenpei; Matsushima, Yoshitaka; Yanagawa, Yuchio; Fukuda, Atsuo

    2014-01-01

    γ-Aminobutyric acid (GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABAA receptor (GABAAR) contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABAAR activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67(GFP/GFP)) to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose-response properties of labeled cells to GABA were equivalent among genotypes. However, continuous blockade of GABAAR with the GABAAR antagonist SR95531 accelerated radial migration. This effect of GABAAR blockade in GAD67(GFP/GFP) mice suggested a role for alternative endogenous GABAAR agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABAAR. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidino)ethanesulfonic acid (GES), and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl) oxobutyric acid, as examined through high-performance liquid chromatography. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABAAR-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABAAR conductance, regulating the radial migration of neurons in the developing neocortex.

  5. Roles of taurine-mediated tonic GABAA receptor activation in the radial migration of neurons in the fetal mouse cerebral cortex

    PubMed Central

    Furukawa, Tomonori; Yamada, Junko; Akita, Tenpei; Matsushima, Yoshitaka; Yanagawa, Yuchio; Fukuda, Atsuo

    2014-01-01

    γ-Aminobutyric acid (GABA) depolarizes embryonic cerebrocortical neurons and continuous activation of the GABAA receptor (GABAAR) contributes to their tonic depolarization. Although multiple reports have demonstrated a role of GABAAR activation in neocortical development, including in migration, most of these studies have used pharmacological blockers. Herein, we performed in utero electroporation in GABA synthesis-lacking homozygous GAD67-GFP knock-in mice (GAD67GFP/GFP) to label neurons born in the ventricular zone. Three days after electroporation, there were no differences in the distribution of labeled cells between the genotypes. The dose–response properties of labeled cells to GABA were equivalent among genotypes. However, continuous blockade of GABAAR with the GABAAR antagonist SR95531 accelerated radial migration. This effect of GABAAR blockade in GAD67GFP/GFP mice suggested a role for alternative endogenous GABAAR agonists. Thus, we tested the role of taurine, which is derived from maternal blood but is abundant in the fetal brain. The taurine-evoked currents in labeled cells were mediated by GABAAR. Taurine uptake was blocked by a taurine transporter inhibitor, 2-(guanidino)ethanesulfonic acid (GES), and taurine release was blocked by a volume-sensitive anion channel blocker, 4-(2-butyl-6,7-dichlor-2-cyclopentylindan-1-on-5-yl) oxobutyric acid, as examined through high-performance liquid chromatography. GES increased the extracellular taurine concentration and induced an inward shift of the holding current, which was reversed by SR95531. In a taurine-deficient mouse model, the GABAAR-mediated tonic currents were greatly reduced, and radial migration was accelerated. As the tonic currents were equivalent among the genotypes of GAD67-GFP knock-in mice, taurine, rather than GABA, might play a major role as an endogenous agonist of embryonic tonic GABAAR conductance, regulating the radial migration of neurons in the developing neocortex. PMID:24734001

  6. Thermal activity on Enceladus

    NASA Astrophysics Data System (ADS)

    Tobie, G.; Besserer, J.; Behounkova, M.; Cadek, O.; Choblet, G.; Sotin, C.

    2009-04-01

    Observations by Cassini have revealed that Enceladus' souh pole is highly active, with jets of icy particles and water vapour emanated from narrow tectonic ridges, called "tiger stripes". This jet activity is associated to a very high thermal emission mainly focused along the tectonic ridges. Heat power required to sustain such an activity is probably related to the dissipation of mechanical energy due to tidal forces exerted by Saturn. However, the dissipation process and its relation to the tectonic features are not clearly established. Both shear heating along the tectonic ridges and viscous dissipation in the convective part of the ice shell could contribute to the energy budget (Nimmo et al. 2007, Tobie et al. 2008). Tobie et al. (2008) pointed out that only interior models with a liquid water layer at depth, covering at least ~2/3 of the southern hemisphere, can explain the observed magnitude of dissipation and its particular location at the south pole. However, the long term stability of such a liquid reservoir remains problematic (Roberts and Nimmo 2007) and the possible link between the liquid reservoir and the surface activities is unknown. Concentration of tidal stresses along the tiger ridges have also been invoked as a mechanism to trigger the eruptive processes (Hurtford et al. 2007, Smith-Konter et al. 2008). However, those models do not take into account a realistic rheological structure for the ice shell when computing the fluctuating stress field. Moreover, the effect of the faults on the background tidal stress is neglected. In particular, low viscosity values are expected to be associated with the shear zone along the tiger stripes and may have a significant impact of the global tidal stress field. In order to self-consistently determine the tidal deformation and its impact on the thermal activity on Enceladus, we are currently developing a 3D model that combines a thermal convection code in spherical geometry (Choblet et al. 2007) and a

  7. Gender Issues: An Activity File.

    ERIC Educational Resources Information Center

    Fountain, Susan

    This activity file grew out of research of an "Images of Women in Development" project of the Centre for Global Education at the University of York, England. The activities are intended for students in the 8- to 13-year-old range to learn more about gender issues. The activities are divided into four sections: (1) awareness-raising activities in…

  8. Metric Activities, Grades K-6.

    ERIC Educational Resources Information Center

    Draper, Bob, Comp.

    This pamphlet presents worksheets for use in fifteen activities or groups of activities designed for teaching the metric system to children in grades K through 6. The approach taken in several of the activities is one of conversion between metric and English units. The majority of the activities concern length, area, volume, and capacity. A…

  9. Changing Conceptions of Activation Energy.

    ERIC Educational Resources Information Center

    Pacey, Philip D.

    1981-01-01

    Provides background material which relates to the concept of activation energy, fundamental in the study of chemical kinetics. Compares the related concepts of the Arrhenius activation energy, the activation energy at absolute zero, the enthalpy of activation, and the threshold energy. (CS)

  10. Science Activities in Energy: Conservation.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Presented is a science activities in energy package which includes 14 activities relating to energy conservation. Activities are simple, concrete experiments for fourth, fifth and sixth grades, which illustrate principles and problems relating to energy. Each activity is outlined on a simple card which is introduced by a question. A teacher's…

  11. Epsiodic Activity in Radio Galaxies

    SciTech Connect

    Saikia, D.J.; Konar, C.; Jamrozy, M.; Machalski, J.; Gupta, Neeraj; Stawarz, L.; Mack, K.-H.; Siemiginowska, A.; /Harvard-Smithsonian Ctr. Astrophys.

    2007-10-15

    One of the interesting issues in our understanding of active galactic nuclei is the duration of their active phase and whether such activity is episodic. In this paper we summarize our recent results on episodic activity in radio galaxies obtained with the GMRT and the VLA.

  12. The active asteroids

    NASA Astrophysics Data System (ADS)

    Jewitt, D.

    2014-07-01

    Active asteroids simultaneously possess the orbits of main-belt asteroids and the physical appearances of comets; they show transient dust comae and solar-radiation pressure-swept tails. Apart from the shear surprise at finding such strange objects in the asteroid belt, the active asteroids are scientifically interesting for several reasons. Although we are limited to scarcely more than a dozen examples, the active asteroids already reveal the distinct action of different physical processes, each previously unobserved and carrying big-picture importance for understanding the solar system. 1. IMPACT. An unambiguous asteroid-asteroid impact was observed in 2010, when a 30-m scale body struck 100-km diameter (596) Scheila. Direct observations of impacts hold scientific importance both by sampling this natural process at full scale (compared with laboratory impacts conducted at tiny scales) and because impact statistics will allow us to assess the erosion rate in the asteroid belt and the contribution of asteroid dust to the interplanetary medium. 2. CRITICAL ROTATION. Several objects have been observed in which the best explanation seems to lie with spin-up to critical periods, presumably (but not certainly) caused by YORP. Examples of both likely mass-shedding (P/2010 A2, P/2013 P5) and full break-up (P/2013 R3, shown below) exist. It has been suggested that, at sub-kilometer sizes, spin-up disruption rates may surpass impact disruption rates. Future observations will show whether or not this is true, and may ultimately lead to an improved understanding of the physics of break-up. 3. THERMAL DISINTEGRATION. Geminid parent (3200) Phaethon shows on-going mass-loss at perihelion, driven by the 1000-K surface temperatures found there. The mechanisms appear to be some combination of thermal fracture and desiccation stress. 4. SUBLIMATION. Two objects have shown repeated activity that appears to be correlated with position in the orbit. The best example is 133P, which has

  13. Asthma and physical activity.

    PubMed

    Oseid, S

    1982-01-01

    Physical activity regularly leads to a decline in lung function in children and adolescents with asthma. This decline is a consequence of what is known as exercise-induced asthma (EIA), and can be determined and graded with the help of lung function tests before and after submaximal workloads on the ergometer cycle or the treadmill. Typical EIA appears in asthmatic individuals with entirely normal lung function before the effort, but EIA may also become clinically manifest with exercise in patients who have a subclinical degree of obstruction. The grade of EIA is essentially dependent on the duration and intensity of effort but also on the type of exercise. For example, free running causes much greater bronchoconstriction than swimming. The temperature and humidity of the inspired air may partially explain this difference. At the Voksentoppen Allergy Institute we find that about 85% of children develop a fall in lung function of 15% or more after a six minute ergometer cycle test. With typical EIA the fall may be totally or partially abolished by prophylactic medication 10 minutes before the start of the test. Disodium cromoglycate (Intal) and/or beta-adrenergic drugs are regularly used before all physical activity. Training programmes must be based on the interval principle. Swimming, ball games, relay races and dancing are examples of useful activities in the training and rehabilitation of children and adolescents with asthma. Through prophylactic medication and physical training, the aerobic work capacity, muscle strength and lung function in asthmatic children is improved. Training also leads to a significant mobilisation of mental resources and an increase in social integration.

  14. Active travel intervention and physical activity behaviour: an evaluation.

    PubMed

    Norwood, Patricia; Eberth, Barbara; Farrar, Shelley; Anable, Jillian; Ludbrook, Anne

    2014-07-01

    A physically active lifestyle is an important contributor to individual health and well-being. The evidence linking higher physical activity levels with better levels of morbidity and mortality is well understood. Despite this, physical inactivity remains a major global risk factor for mortality and, consequently, encouraging individuals to pursue physically active lifestyles has been an integral part of public health policy in many countries. Physical activity promotion and interventions are now firmly on national health policy agendas, including policies that promote active travel such as walking and cycling. This study evaluates one such active travel initiative, the Smarter Choices, Smarter Places programme in Scotland, intended to encourage uptake of walking, cycling and the use of public transport as more active forms of travel. House to house surveys were conducted before and after the programme intervention, in May/June 2009 and 2012 (12,411 surveys in 2009 and 9542 in 2012), for the evaluation of the programme. This paper analyses the physical activity data collected, focussing on what can be inferred from the initiative with regards to adult uptake of physical activity participation and whether, for those who participated in physical activity, the initiative impacted on meeting recommended physical activity guidelines. The results suggest that the initiative impacted positively on the likelihood of physical activity participation and meeting the recommended physical activity guidelines. Individuals in the intervention areas were on average 6% more likely to meet the physical activity guidelines compared to individuals in the non intervention areas. However, the absolute prevalence of physical activity participation declined in both intervention and control areas over time. Our evaluation of this active transport initiative indicates that similar programmes may aid in contributing to achieving physical activity targets and adds to the international

  15. Rationales for regulatory activity

    SciTech Connect

    Perhac, R.M.

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  16. GPS Activities at SLAC

    SciTech Connect

    Behrend, Dirk

    2002-11-19

    The Alignment Engineering Group of the Stanford Linear Accelerator Center (SLAC) started to use RTK (real-time kinematic) GPS equipment in order to perform structure mapping and GIS-related tasks on the SLAC campus. In a first step a continuously observing GPS station (SLAC M40) was set up. This station serves as master control station for all differential GPS activities on site and its coordinates have been determined in the well-defined global geodetic datum ITRF2000 at a given reference epoch. Some trials have been performed to test the RTK method. The tests have proven RTK to be very fast and efficient.

  17. Reuse of activated alumina

    SciTech Connect

    Hobensack, J.E.

    1991-12-31

    Activated alumina is used as a trapping media to remove trace quantities of UF{sub 6} from process vent streams. The current uranium recovery method employs concentrated nitric acid which destroys the alumina pellets and forms a sludge which is a storage and disposal problem. A recently developed technique using a distilled water rinse followed by three dilute acid rinses removes on average 97% of the uranium, and leaves the pellets intact with crush strength and surface area values comparable with new material. Trapping tests confirm the effectiveness of the recycled alumina as UF{sub 6} trapping media.

  18. Crew Activity Analyzer

    NASA Technical Reports Server (NTRS)

    Murray, James; Kirillov, Alexander

    2008-01-01

    The crew activity analyzer (CAA) is a system of electronic hardware and software for automatically identifying patterns of group activity among crew members working together in an office, cockpit, workshop, laboratory, or other enclosed space. The CAA synchronously records multiple streams of data from digital video cameras, wireless microphones, and position sensors, then plays back and processes the data to identify activity patterns specified by human analysts. The processing greatly reduces the amount of time that the analysts must spend in examining large amounts of data, enabling the analysts to concentrate on subsets of data that represent activities of interest. The CAA has potential for use in a variety of governmental and commercial applications, including planning for crews for future long space flights, designing facilities wherein humans must work in proximity for long times, improving crew training and measuring crew performance in military settings, human-factors and safety assessment, development of team procedures, and behavioral and ethnographic research. The data-acquisition hardware of the CAA (see figure) includes two video cameras: an overhead one aimed upward at a paraboloidal mirror on the ceiling and one mounted on a wall aimed in a downward slant toward the crew area. As many as four wireless microphones can be worn by crew members. The audio signals received from the microphones are digitized, then compressed in preparation for storage. Approximate locations of as many as four crew members are measured by use of a Cricket indoor location system. [The Cricket indoor location system includes ultrasonic/radio beacon and listener units. A Cricket beacon (in this case, worn by a crew member) simultaneously transmits a pulse of ultrasound and a radio signal that contains identifying information. Each Cricket listener unit measures the difference between the times of reception of the ultrasound and radio signals from an identified beacon

  19. Minor meteor shower activity

    NASA Astrophysics Data System (ADS)

    Rendtel, J.

    2016-01-01

    Video meteor observations provide us with data to analyze structures in minor meteor showers or weak features in flux profiles. Samples obtained independently by other techniques allow to calibrate the data sets and to improve the confidence of results as demonstrated with a few results. Both, the confirmation of events predicted by model calculation and the input of observational data to improve the modelling results may help to better understand meteoroid stream evolution processes. Furthermore, calibrated data series can be used for studies of the long-term evolution of meteor shower activity.

  20. Enceladus: Starting Hydrothermal Activity

    NASA Technical Reports Server (NTRS)

    Matson, D. L.; Castillo-Rogez, J. C.; Johnson, T. V.; Lunine, J. I.; Davies, A. G.

    2011-01-01

    We describe a process for starting the hydrothermal activity in Enceladus' South Polar Region. The process takes advantage of fissures that reach the water table, about 1 kilometer below the surface. Filling these fissures with fresh ocean water initiates a flow of water up from an ocean that can be self-sustaining. In this hypothesis the heat to sustain the thermal anomalies and the plumes comes from a slightly warm ocean at depth. The heat is brought to the surface by water that circulates up, through the crust and then returns to the ocean.

  1. Active terahertz metamaterials

    SciTech Connect

    Chen, Hou-tong; O' Hara, John F; Taylor, Antoinette J

    2009-01-01

    In this paper we present an overview of research in our group in terahertz (THz) metamaterials and their applications. We have developed a series of planar metamaterials operating at THz frequencies, all of which exhibit a strong resonant response. By incorporating natural materials, e.g. semiconductors, as the substrates or as critical regions of metamaterial elements, we are able to effectively control the metamaterial resonance by the application of external stimuli, e.g., photoexcitation and electrical bias. Such actively controllable metamaterials provide novel functionalities for solid-state device applications with unprecedented performance, such as THz spectroscopy, imaging, and many others.

  2. Athena: Assessment Phase Activities

    NASA Astrophysics Data System (ADS)

    Lumb, David; Ayre, Mark

    2015-09-01

    The Athena mission concept has been proposed by the community in response to science themes of the Hot and Energetic Universe. Unlike other, competitive, mission selection exercises this "Large" class observatory mission has essentially been pre-selected. Nevertheless it has to be demonstrated that Athena meets the programmatic constraints of 1Bn euro cost cap, and a readiness level appropriate for formal mission adoption by the end 2019. This should be confirmed through a Phase A study conducted with two parallel industry activities. We describe the technical and programmatic content of these and latest progress in space and ground segment definition.

  3. Activation of solar flares

    SciTech Connect

    Cargill, P.J.; Migliuolo, S.; Hood, A.W.

    1984-11-01

    The physics of the activation of two-ribbon solar flares via the MHD instability of coronal arcades is presented. The destabilization of a preflare magnetic field is necessary for a rapid energy release, characteristic of the impulsive phase of the flare, to occur. The stability of a number of configurations are examined, and the physical consequences and relative importance of varying pressure profiles and different sets of boundary conditions (involving field-line tying) are discussed. Instability modes, driven unstable by pressure gradients, are candidates for instability. Shearless vs. sheared equilibria are also discussed. (ESA)

  4. ECLSS medical support activities

    NASA Technical Reports Server (NTRS)

    Crump, William J.; Kilgore, Melvin V., Jr.

    1991-01-01

    During the period from April 10, 1990 to April 9, 1991, the Consortium for the Space Life Sciences provided technical assistance to the NASA/MSFC water recovery efforts. This assistance was in the form of literature reviews, technical recommendations, and presentations. This final report summarizes the activities completed during this period and identifies those areas requiring additional efforts. The tasks which the University of Alabama in Huntsville (UAH) water recovery team addressed were either identified by MSFC technical representatives or chosen from those outlined in the subject statement of work.

  5. Bioethics activities in India.

    PubMed

    Kumar, Nandini K

    2006-01-01

    The Indian Council of Medical Research formulates, coordinates and promotes biomedical research in India. In 1980, they formulated the first national ethical guidelines. They offer a number of different training programmes, from 1 day to 6 months. The council is developing a core curriculum for teaching bioethics, which would be applied uniformly in medical schools throughout the country. Drug development and ethics is also important in India, particularly now that the local pharmaceutical industry is expanding and so many drugs trials are outsourced to the country. The council is also very active in encouraging the development of ethics review committees.

  6. AMS Prototyping Activities

    NASA Technical Reports Server (NTRS)

    Burleigh, Scott

    2008-01-01

    This slide presentation reviews the activity around the Asynchronous Message Service (AMS) prototype. An AMS reference implementation has been available since late 2005. It is aimed at supporting message exchange both in on-board environments and over space links. The implementation incoroporates all mandatory elements of the draft recommendation from July 2007: (1) MAMS, AMS, and RAMS protocols. (2) Failover, heartbeats, resync. (3) "Hooks" for security, but no cipher suites included in the distribution. The performance is reviewed, and a Benchmark latency test over VxWorks Message Queues is shown as histograms of a count vs microseconds per 1000-byte message

  7. Imaging nervous system activity.

    PubMed

    Fields, R D; O'Donovan, M J

    2001-05-01

    Optical imaging methods rely upon visualization of three types of signals: (1) intrinsic optical signals, including light scattering and reflectance, birefringence, and spectroscopic changes of intrinsic molecules, such as NADH or oxyhemoglobin; (2) changes in fluorescence or absorbance of voltage-sensitive membrane dyes; and (3) changes in fluorescence or absorbance of calcium-sensitive indicator dyes. Of these, the most widely used approach is fluorescent microscopy of calcium-sensitive dyes. This unit describes protocols for the use of calcium-sensitive dyes and voltage-dependent dyes for studies of neuronal activity in culture, tissue slices, and en-bloc preparations of the central nervous system.

  8. ASTP RBCC Activities

    NASA Technical Reports Server (NTRS)

    Nelson, Karl W.; McArthur, Craig; Leopard, Larry (Technical Monitor)

    2000-01-01

    This presentation reviews the activities of the Advanced Space Transportation Program (ASTP) in the development of Rocket-Based Combined Cycle (RBCC)technology. The document consist of the presentation slides for a talk scheduled to be given to the World Aviation Congress and Exhibit of SAE. Included in the review is discussion of recent accomplishments in the area of Advanced Reusable technologies (ART), which includes work in flowpath testing, and system studies of the various vehicle/engine combinations including RBCC, Turbine Based Combined Cycle (TBCC) and Pulsed Detonation Engine (PDE). Pictures of the proposed RBCC Flowpaths are included. The next steps in the development process are reviewed.

  9. Hypnotic activity of brotizolam

    PubMed Central

    Uzzan, B.; Warot, D.; Chermat, P.; Dantlo, B.; Bornstein, S.; Simon, P.

    1983-01-01

    1 A double-blind, crossover study was carried out in general practice on the hypnotic activity of 0.25 mg brotizolam in patients aged between 18 and 70 years complaining of insomnia (11 men, 28 women). 2 Patients reported that they slept better, that they awoke less frequently and that they slept longer with brotizolam than with placebo. Overall the patients preferred brotizolam to placebo, and subjective assessments of well-being after brotizolam did not differ from those after placebo. Brotizolam was well tolerated and there were no incidents of note. PMID:6362701

  10. Monitoring international nuclear activity

    SciTech Connect

    Firestone, R.B.

    2006-05-19

    The LBNL Table of Isotopes website provides primary nuclearinformation to>150,000 different users annually. We have developedthe covert technology to identify users by IP address and country todetermine the kinds of nuclear information they are retrieving. Wepropose to develop pattern recognition software to provide an earlywarning system to identify Unusual nuclear activity by country or regionSpecific nuclear/radioactive material interests We have monitored nuclearinformation for over two years and provide this information to the FBIand LLNL. Intelligence is gleaned from the website log files. Thisproposal would expand our reporting capabilities.

  11. Neutron activation analysis system

    DOEpatents

    Taylor, M.C.; Rhodes, J.R.

    1973-12-25

    A neutron activation analysis system for monitoring a generally fluid media, such as slurries, solutions, and fluidized powders, including two separate conduit loops for circulating fluid samples within the range of radiation sources and detectors is described. Associated with the first loop is a neutron source that emits s high flux of slow and thermal neutrons. The second loop employs a fast neutron source, the flux from which is substantially free of thermal neutrons. Adjacent to both loops are gamma counters for spectrographic determination of the fluid constituents. Other gsmma sources and detectors are arranged across a portion of each loop for deterMining the fluid density. (Official Gazette)

  12. Physical Activity in Elderly

    PubMed Central

    Tirpakova, Veronika; Sedliak, Milan; Kern, Helmut; Mayr, Winfried; Hamar, Dušan

    2015-01-01

    Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared. PMID:26913164

  13. Activities for the classroom

    NASA Astrophysics Data System (ADS)

    Stark, Joyce

    From my research experiences on board the R/V Atlantis, I have developed experiments that can be used in an integrated science program or for biology. These activities reflect life in extreme environments on Earth such as the hydrothermal vents and on other planets and moons in our solar system. Students can learn to map the oceans of Europa and discover how plants grow on Mars. Students have designed research projects from the experimentation that I was involved with through the REVEL program.

  14. The Active Solid Earth

    NASA Astrophysics Data System (ADS)

    Ebinger, Cynthia

    2016-04-01

    Dynamic processes in Earth's crust, mantle and core shape Earth's surface and magnetic field over time scales of seconds to millennia, and even longer time scales as recorded in the ca. 4 Ga rock record. Our focus is the earthquake-volcano deformation cycles that occur over human time scales, and their comparison with time-averaged deformation studies, with emphasis on mantle plume provinces where magma and volatile release and vertical tectonics are readily detectable. Active deformation processes at continental and oceanic rift and back arc zones provide critical constraints on mantle dynamics, the role of fluids (volatiles, magma, water), and plate rheology. For example, recent studies of the East African rift zone, which formed above one of Earth's largest mantle upwellings reveal that magma production and volatile release rates are comparable to those of magmatic arcs, the archetypal zones of continental crustal creation. Finite-length faults achieve some plate deformation, but magma intrusion in the form of dikes accommodates extension in continental, back-arc, and oceanic rifts, and intrusion as sills causes permanent uplift that modulates the local time-space scales of earthquakes and volcanoes. Volatile release from magma intrusion may reduce fault friction and permeability, facilitating aseismic slip and creating magma pathways. We explore the implications of active deformation studies to models of the time-averaged structure of plume and extensional provinces in continental and oceanic plate settings.

  15. Raman activated cell sorting.

    PubMed

    Song, Yizhi; Yin, Huabing; Huang, Wei E

    2016-08-01

    Single cell Raman spectra (SCRS) are intrinsic biochemical profiles and 'chemical images' of single cells which can be used to characterise phenotypic changes, physiological states and functions of cells. On the base of SCRS, Raman activated cell sorting (RACS) provides a label-free cell sorting approach, which can link single cells to their chemical or phenotypic profiles. Overcoming naturally weak Raman signals, establishing Raman biomarker as sorting criteria to RACS and improving specific sorting technology are three challenges of developing RACS. Advances on Raman spectroscopy such as stimulated Raman scattering (SRS) and pre-screening helped to increase RACS sorting speed. Entire SCRS can be characterised using pattern recognition methods, and specific Raman bands can be extracted as biomarkers for RACS. Recent advances on cell sorting technologies based on microfluidic device and surface-ejection enable accurate and reliable single cell sorting from complex samples. A high throughput RACS will be achievable in near future by integrating fast Raman detection system such as SRS with microfluidic RACS and Raman activated cell ejection (RACE).

  16. Microbiologically active nanocomposite media

    NASA Astrophysics Data System (ADS)

    Petranovskii, Vitalii; Panina, Lyudmila; Bogomolova, Eugenia; Belostotskaya, Galina

    2003-07-01

    The most recent approach to the development of novel antimicrobial and antifungal agents is based on the application of synthetic and natural zeolites, because zeolites are known to be the carrier and slow releaser of the heavy metals with olygodynamic properties. The microbiological activity of the ion-exchanged zeolites is attributed to the ionic state of the metal sreleased from the zeolites by ion re-exchange. In the present work we used low cost natural clinoptilolite (Cli) as a substrate for copper and silver in different states. The state of oxidation of the exchanged metal in zeolite with supported Cu and Ag species (in the form of cations, small clusters, sub-coloidal particles, large particles) in order to fit them to fulfill the following criteria: to demonstrate their high protective abilities against fungi and long-term stability. The study of structure of samples with XRD, UV-visible spectroscopy, FTIR, their stability with temperature and during storage was carried out for obtaining the correct correlation with microbiological activity.

  17. Activating event knowledge.

    PubMed

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-05-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or typically play a role in. We used short stimulus onset asynchrony priming to demonstrate that (1) event nouns prime people (sale-shopper) and objects (trip-luggage) commonly found at those events; (2) location nouns prime people/animals (hospital-doctor) and objects (barn-hay) commonly found at those locations; and (3) instrument nouns prime things on which those instruments are commonly used (key-door), but not the types of people who tend to use them (hose-gardener). The priming effects are not due to normative word association. On our account, facilitation results from event knowledge relating primes and targets. This has much in common with computational models like LSA or BEAGLE in which one word primes another if they frequently occur in similar contexts. LSA predicts priming for all six experiments, whereas BEAGLE correctly predicted that priming should not occur for the instrument-people relation but should occur for the other five. We conclude that event-based relations are encoded in semantic memory and computed as part of word meaning, and have a strong influence on language comprehension.

  18. Active Near Earth Asteroids

    NASA Astrophysics Data System (ADS)

    Jenniskens, Peter

    2015-08-01

    Past activity from Near Earth Asteroids is recorded in the meteoroid streams that cause our meteor showers. Automated meteoroid orbit surveys by photographic, low-light video, specular radar, and head-echo radar reflections are providing the first maps of meteor shower activity at different particle sizes. There are distinct differences in particle size distributions among streams. The underlaying mechanisms that created these streams are illuminated: fragmentation from spin-up or thermal stresses, meteoroid ejection by water vapor drag, and ejection of icy particles by CO and CO2 sublimation. The distribution of the meteoroid orbital elements probe the subsequent evolution by planetary perturbations and sample the range of dynamical processes to which Near Earth Asteroids are exposed. The non-stream "sporadic" meteors probe early stages in the evolution from meteoroid streams into the zodiacal dust cloud. We see that the lifetime of large meteoroids is generally not limited by collisions. Results obtained by the CAMS video survey of meteoroid orbits are compared to those from other orbit surveys. Since October 2010, over 200,000 meteoroid orbits have been measured. First results from an expansion into the southern hemisphere are also presented, as are first results from the measurement of main element compositions. Among the many streams detected so far, the Geminid and Sextantid showers stand out by having a relatively high particle density and derive from parent bodies that appear to have originated in the main belt.

  19. Visualizing cellulase activity.

    PubMed

    Bubner, Patricia; Plank, Harald; Nidetzky, Bernd

    2013-06-01

    Commercial exploitation of lignocellulose for biotechnological production of fuels and commodity chemicals requires efficient-usually enzymatic-saccharification of the highly recalcitrant insoluble substrate. A key characteristic of cellulose conversion is that the actual hydrolysis of the polysaccharide chains is intrinsically entangled with physical disruption of substrate morphology and structure. This "substrate deconstruction" by cellulase activity is a slow, yet markedly dynamic process that occurs at different length scales from and above the nanometer range. Little is currently known about the role of progressive substrate deconstruction on hydrolysis efficiency. Application of advanced visualization techniques to the characterization of enzymatic degradation of different celluloses has provided important new insights, at the requisite nano-scale resolution and down to the level of single enzyme molecules, into cellulase activity on the cellulose surface. Using true in situ imaging, dynamic features of enzyme action and substrate deconstruction were portrayed at different morphological levels of the cellulose, thus providing new suggestions and interpretations of rate-determining factors. Here, we review the milestones achieved through visualization, the methods which significantly promoted the field, compare suitable (model) substrates, and identify limiting factors, challenges and future tasks.

  20. [Sport and physical activity].

    PubMed

    Bria, S; Zeppilli, P

    2010-01-01

    A regular sport activity involves physical and psychological benefits helping to improve the quality of life at any age. This aspect is even more important in the developing age, when the sport takes on a role of training and education. In this context, instances directed to allow adolescent and young adults with heart disease to practice sports seem justified, and they're becoming more pressing since when the diagnostic and therapeutic advances, especially in cardiac surgery and in interventional hemodynamics, allow an increasing number of patients, previously allocated to physical inactivity, to lead an active lifestyle. However, we have to keep in mind that congenital heart disease population is varied, not only by the nature of the malformation, but also because in the same cardiopathy you can find subjects in "natural history" or after surgery and, between them, subjects treated with several techniques and different outcomes. This justifies the need for a close collaboration between sports doctors, cardiologists and heart surgeons, particularly in the management of the most difficult and delicate problems.

  1. Active Astronomy Roadshow Haiti

    NASA Astrophysics Data System (ADS)

    Laycock, Silas; Oram, Kathleen; Alabre, Dayana; Douyon, Ralph; UMass Lowell Haiti Development Studies Center

    2016-01-01

    College-age Haitian students working with advisors and volunteers from UMass Lowell in 2015 developed and tested an activity-based K-8 curriculum in astronomy, space, and earth science. Our partner school is located in Les Cayes, Haiti a city where only 65% of children attend school, and only half of those will complete 6th grade. Astronomy provides an accessible and non-intimidating entry into science, and activity-based learning contrasts with the predominant traditional teaching techniques in use in Haiti, to reach and inspire a different cohort of learners. Teachers are predominantly women in Haiti, so part of the effort involves connecting them with scientists, engineers and teacher peers in the US. As a developing nation, it is vital for Haitian (as for all) children to grow up viewing women as leaders in science. Meanwhile in the US, few are aware of the reality of getting an education in a 3rd world nation (i.e. most of the world), so we also joined with teachers in Massachusetts to give US school children a peek at what daily life is like for their peers living in our vibrant but impoverished neighbor. Our Haitian partners are committed to helping their sister-schools with curriculum and educator workshops, so that the overall quality of education can rise, and not be limited to the very few schools with access to resources. We will describe the activites, motivation, and and the lessons learned from our first year of the project.

  2. Neutron activation for ITER

    SciTech Connect

    Barnes, C.W.; Loughlin, M.J.; Nishitani, Takeo

    1996-04-29

    There are three primary goals for the Neutron Activation system for ITER: maintain a robust relative measure of fusion power with stability and high dynamic range (7 orders of magnitude); allow an absolute calibration of fusion power (energy); and provide a flexible and reliable system for materials testing. The nature of the activation technique is such that stability and high dynamic range can be intrinsic properties of the system. It has also been the technique that demonstrated (on JET and TFTR) the highest accuracy neutron measurements in DT operation. Since the gamma-ray detectors are not located on the tokamak and are therefore amenable to accurate characterization, and if material foils are placed very close to the ITER plasma with minimum scattering or attenuation, high overall accuracy in the fusion energy production (7--10%) should be achievable on ITER. In the paper, a conceptual design is presented. A system is shown to be capable of meeting these three goals, also detailed design issues remain to be solved.

  3. Tracking dynamic team activity

    SciTech Connect

    Tambe, M.

    1996-12-31

    AI researchers are striving to build complex multi-agent worlds with intended applications ranging from the RoboCup robotic soccer tournaments, to interactive virtual theatre, to large-scale real-world battlefield simulations. Agent tracking - monitoring other agent`s actions and inferring their higher-level goals and intentions - is a central requirement in such worlds. While previous work has mostly focused on tracking individual agents, this paper goes beyond by focusing on agent teams. Team tracking poses the challenge of tracking a team`s joint goals and plans. Dynamic, real-time environments add to the challenge, as ambiguities have to be resolved in real-time. The central hypothesis underlying the present work is that an explicit team-oriented perspective enables effective team tracking. This hypothesis is instantiated using the model tracing technology employed in tracking individual agents. Thus, to track team activities, team models are put to service. Team models are a concrete application of the joint intentions framework and enable an agent to track team activities, regardless of the agent`s being a collaborative participant or a non-participant in the team. To facilitate real-time ambiguity resolution with team models: (i) aspects of tracking are cast as constraint satisfaction problems to exploit constraint propagation techniques; and (ii) a cost minimality criterion is applied to constrain tracking search. Empirical results from two separate tasks in real-world, dynamic environments one collaborative and one competitive - are provided.

  4. Regulation of inflammasome activation.

    PubMed

    Man, Si Ming; Kanneganti, Thirumala-Devi

    2015-05-01

    Inflammasome biology is one of the most exciting and rapidly growing areas in immunology. Over the past 10 years, inflammasomes have been recognized for their roles in the host defense against invading pathogens and in the development of cancer, auto-inflammatory, metabolic, and neurodegenerative diseases. Assembly of an inflammasome complex requires cytosolic sensing of pathogen-associated molecular patterns or danger-associated molecular patterns by a nucleotide-binding domain and leucine-rich repeat receptor (NLR) or absent in melanoma 2 (AIM2)-like receptors (ALR). NLRs and ALRs engage caspase-1, in most cases requiring the adapter protein apoptosis-associated speck-like protein containing a CARD (ASC), to catalyze proteolytic cleavage of pro-interleukin-1β (pro-IL-1β) and pro-IL-18 and drive pyroptosis. Recent studies indicate that caspase-8, caspase-11, IL-1R-associated kinases (IRAK), and receptor-interacting protein (RIP) kinases contribute to inflammasome functions. In addition, post-translational modifications, including ubiquitination, deubiquitination, phosphorylation, and degradation control almost every aspect of inflammasome activities. Genetic studies indicate that mutations in NLRP1, NLRP3, NLRC4, and AIM2 are linked with the development of auto-inflammatory diseases, enterocolitis, and cancer. Overall, these findings transform our understanding of the basic biology and clinical relevance of inflammasomes. In this review, we provide an overview of the latest development of inflammasome research and discuss how inflammasome activities govern health and disease.

  5. Activities in dementia care: A comparative assessment of activity types.

    PubMed

    Lokon, Elizabeth; Sauer, Philip E; Li, Yue

    2016-12-05

    This exploratory study compares the impact of five activity types on the well-being of institutionalized people with dementia: the intergenerational art program Opening Minds through Art, art and music therapies, creative activities, non-creative activities, and no activities at all. We validated the Scripps Modified Greater Cincinnati Chapter Well-Being Observational Tool, and used that instrument to systematically observe N = 67 people with dementia as they participated in different activity types. People with dementia showed the highest well-being scores during Opening Minds through Art compared to all other activities. No significant well-being differences were found between creative activities led by licensed art/music therapist versus regular activity staff. Furthermore, no significant well-being differences were found between creative and non-creative activities that were both led by regular activity staff. Overall, people with dementia benefit from participating in activities, regardless of the type (creative or non-creative), or who conducts them (licensed therapists or activity staff). However, in order for people with dementia to reach significantly high levels of overall well-being, we recommend that activities are specifically designed for people with dementia and incorporate a 1:1 ratio between people with dementia and well-trained volunteers/staff members.

  6. The active video games' narrative impact on children's physical activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Active video games (AVGs) capable of inducing physical activity offer an innovative approach to combating childhood obesity. Unfortunately, children's AVG game play decreases quickly, underscoring the need to identify novel methods for player engagement. Narratives have been demonstrated to influenc...

  7. Active Magnetic Regenerative Liquefier

    SciTech Connect

    Barclay, John A.; Oseen-Send, Kathryn; Ferguson, Luke; Pouresfandiary, Jamshid; Cousins, Anand; Ralph, Heather; Hampto, Tom

    2016-01-12

    This final report for the DOE Project entitled Active Magnetic Regenerative Liquefier (AMRL) funded under Grant DE-FG36-08GO18064 to Heracles Energy Corporation d.b.a. Prometheus Energy (Heracles/Prometheus) describes an active magnetic regenerative refrigerator (AMRR) prototype designed and built during the period from July 2008 through May 2011. The primary goal of this project was to make significant technical advances toward highly efficient liquefaction of hydrogen. Conventional hydrogen liquefiers at any scale have a maximum FOM of ~0.35 due primarily to the intrinsic difficulty of rapid, efficient compression of either hydrogen or helium working gases. Numerical simulation modeling of high performance AMRL designs indicates certain designs have promise to increase thermodynamic efficiency from a FOM of ~0.35 toward ~0.5 to ~0.6. The technical approach was the use of solid magnetic working refrigerants cycled in and out of high magnetic fields to build an efficient active regenerative magnetic refrigeration module providing cooling power for AMRL. A single-stage reciprocating AMRR with a design temperature span from ~290 K to ~120 K was built and tested with dual magnetic regenerators moving in and out of the conductively-cooled superconducting magnet subsystem. The heat transfer fluid (helium) was coupled to the process stream (refrigeration/liquefaction load) via high performance heat exchangers. In order to maximize AMRR efficiency a helium bypass loop with adjustable flow was incorporated in the design because the thermal mass of magnetic refrigerants is higher in low magnetic field than in high magnetic field. Heracles/Prometheus designed experiments to measure AMRR performance under a variety of different operational parameters such as cycle frequency, magnetic field strength, heat transfer fluid flow rate, amount of bypass flow of the heat transfer fluid while measuring work input, temperature span, cooling capability as a function of cold temperature

  8. Overview of Langley activities in active controls research

    NASA Technical Reports Server (NTRS)

    Abel, I.; Newsom, J. R.

    1981-01-01

    The application of active controls technology to reduce aeroelastic response of aircraft structures offers a potential for significant payoffs in terms of aerodynamic efficiency and weight savings. The activities of the Langley Research Center (laRC) in advancing active controls technology. Activities are categorized into the development of appropriate analysis tools, control law synthesis methodology, and experimental investigations aimed at verifying both analysis and synthesis methodology.

  9. Youth Physical Activity Resource Use and Activity Measured by Accelerometry

    ERIC Educational Resources Information Center

    Maslow, Andra L.; Colabianchi, Natalie

    2011-01-01

    Objectives: To examine whether use of physical activity resources (e.g., parks) was associated with daily physical activity measured by accelerometry. Methods: One hundred eleven adolescents completed a travel diary with concurrent accelerometry. The main exposure was self-reported use of a physical activity resource (none /1 resources). The main…

  10. Examining Activism in Practice: A Qualitative Study of Archival Activism

    ERIC Educational Resources Information Center

    Novak, Joy Rainbow

    2013-01-01

    While archival literature has increasingly discussed activism in the context of archives, there has been little examination of the extent to which archivists in the field have accepted or incorporated archival activism into practice. Scholarship that has explored the practical application of archival activism has predominately focused on case…

  11. Activity Based Curriculum for Elementary Education. Additional Activities, K-6.

    ERIC Educational Resources Information Center

    Wichita Public Schools, KS.

    This elementary curriculum is a vehicle to provide manipulative activities that reinforce academic skills through meaningful, relevant, activity-based awareness of modern society. The twenty-six activity plans included in the curriculum place a major emphasis upon realistic or concrete experiences that deal with the manipulation and exploration of…

  12. Active Play: Exploring the Influences on Children's School Playground Activities

    ERIC Educational Resources Information Center

    Hyndman, Brendon; Benson, Amanda; Telford, Amanda

    2016-01-01

    Because children spend so much of their time in schools, their playgrounds offer a good setting for promoting active play in young lives. Teachers, instead of considering active play a taxing demand on their busy day, have begun to develop an informal curriculum for it. The authors review the research on children's active play and explores its…

  13. 101 Environmental Education Activities. Booklet 2--Language Art Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    This booklet containing 20 language arts activities is the second in the series "101 Environmental Education Activities" produced by the Upper Mississippi River ECO-Center. The description of each activity contains learning objectives, directions, and suggested student evaluation standards. Elementary and intermediate level students…

  14. 101 Environmental Education Activities. Booklet 4--Science Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    Fourth in the series "101 Environmental Education Activities" by the Upper Mississippi River ECO-Center, the booklet contains 39 environment-based science activities directed to students in primary, intermediate, and junior high classes. Organization of the activities usually includes grade level, objectives, procedures, and materials,…

  15. 101 Environmental Education Activities. Booklet 1--Art and Music Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    First of a series of 6 publications containing environmental education activities, this booklet by the Upper Mississippi River ECO-Center describes 12 environmentally-based art and music activities for elementary and intermediate grades. Each activity description contains objectives, preparation, materials, directions, student evaluation, and…

  16. Is enhanced physical activity possible using active videogames?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our research indicated that 10– to 12-year-old children receiving two active Wii (TM)(Nintendo (R); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase phys...

  17. Summary of JPL Activities

    NASA Technical Reports Server (NTRS)

    Timmerman, Paul J.; Surampudi, Subbarao

    2000-01-01

    A viewgraph presentation outlines the Jet Propulsion Laboratory (JPL) flight programs, including past, present and future missions targeting Solar System exploration. Details, including launch dates and batteries used, are given for Deep Space 1 (Asteroid Rendezvous), Deep Space 2 (Mars Penetrator), Mars Global Surveyor, Mars Surveyor '98, Stardust, Europa Orbiter, Mars Surveyor 2001, Mars 2003 Lander and Rover, and Genesis (Solar Dust Return). Earth science projects are also outlined: Active Cavity Radiometer Irradiance Monitor (ARIMSAT), Ocean Topography Experiment (TOPEX/Poseidon), Jason-1 (TOPEX follow-on), and QuikScat/Seawinds (Ocean Winds Tracking). The status, background, and plans are given for several batteries: (1) 2.5 inch common pressure vessel (CPV), (2) 3.5 inch CPV, (3) Ni-H2, and (4) Li-Ion.

  18. P21 activated kinases

    PubMed Central

    Rane, Chetan K; Minden, Audrey

    2014-01-01

    The p21 activated kinases (Paks) are well known effector proteins for the Rho GTPases Cdc42 and Rac. The Paks contain 6 members, which fall into 2 families of proteins. The first family consists of Paks 1, 2, and 3, and the second consists of Paks 4, 5, and 6. While some of the Paks are ubiquitously expressed, others have more restrictive tissue specificity. All of them are found in the nervous system. Studies using cell culture, transgenic mice, and knockout mice, have revealed important roles for the Paks in cytoskeletal organization and in many aspects of cell growth and development. This review discusses the basic structures of the Paks, and their roles in cell growth, development, and in cancer. PMID:24658305

  19. Extravehicular activity welding experiment

    NASA Technical Reports Server (NTRS)

    Watson, J. Kevin

    1989-01-01

    The In-Space Technology Experiments Program (INSTEP) provides an opportunity to explore the many critical questions which can only be answered by experimentation in space. The objective of the Extravehicular Activity Welding Experiment definition project was to define the requirements for a spaceflight experiment to evaluate the feasibility of performing manual welding tasks during EVA. Consideration was given to experiment design, work station design, welding hardware design, payload integration requirements, and human factors (including safety). The results of this effort are presented. Included are the specific objectives of the flight test, details of the tasks which will generate the required data, and a description of the equipment which will be needed to support the tasks. Work station requirements are addressed as are human factors, STS integration procedures and, most importantly, safety considerations. A preliminary estimate of the cost and the schedule for completion of the experiment through flight and postflight analysis are given.

  20. Active Piezoelectric Diaphragms

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G.; Effinger, Robert T., IV; Aranda, Isaiah, Jr.; Copeland, Ben M.; Covington, Ed W., III

    2002-01-01

    Several active piezoelectric diaphragms were fabricated by placing unelectroded piezoelectric disks between copper clad films patterned with Inter-Circulating Electrodes "ICE". When a voltage potential is applied to the electrodes, the result is radially distributed electric field that mechanically strains the piezo-ceramic along the Z-axis (perpendicular to the applied electric field), rather than the expected in-plane (XY-axis) direction. Unlike other out of plane piezoelectric actuators, which are benders, these Radial Field Diaphragms (RFDs) strain concentrically yet afford high displacements while maintaining a constant circumference. This paper covers the fabrication and characterization of these diaphragms as a function of poling field strength, ceramic diameter and line spacing, as well as the surface topography, the resulting strain field and displacement as a function of applied voltage ranging from DC to 10 Hz.

  1. Mechanically Activated Ion Channels

    PubMed Central

    Ranade, Sanjeev S.; Syeda, Ruhma; Patapoutian, Ardem

    2015-01-01

    Mechanotransduction, the conversion of physical forces into biochemical signals, is an essential component of numerous physiological processes including not only conscious senses of touch and hearing, but also unconscious senses such as blood pressure regulation. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels. PMID:26402601

  2. DPAL activities in Japan

    NASA Astrophysics Data System (ADS)

    Endo, Masamori; Wani, Fumio

    2015-02-01

    Activities on diode pumped alkali laser (DPAL) in Japan is reviewed. We have started alkali laser works in 2011, and currently, we are the only players in Japan. Our interests are application oriented, and it is not only defense but also industrial. DPAL is a good candidate as a source of remote laser machining, thanks to its scalability and extremely good beam quality. We are studying on scientific and engineering problems of Cs DPAL with a small-scale apparatus. A commercial diode laser with volume Bragg grating outcoupler is used to pump the gain cell longitudinally. A 6.5 W continuous-wave output with optical to optical efficiency of 56% (based on the absorbed power) has been achieved. Numerical simulation codes are developed to understand the physics of DPAL and to help future developments.

  3. Active submarine volcano sampled

    USGS Publications Warehouse

    Taylor, B.

    1983-01-01

    On June 4, 1982, two full dredge hauls of fresh lava were recovered from the upper flanks of Kavachi submarine volcano, Solomon Islands, in the western Pacific Ocean, from the water depths of 1,200 and 2,700 feet. the shallower dredge site was within 0.5 mile of the active submarine vent shown at the surface by an area of slick water, probably caused by gas emissions. Kavachi is a composite stratovolcano that has been observed to erupt every year or two for at least the last 30 years (see photographs). An island formed in 1952, 1961, 1965, and 1978; but, in each case, it rapidly eroded below sea level. The latest eruption was observed by Solair pilots during the several weeks up to and including May 18, 1982. 

  4. Mechanically Activated Ion Channels.

    PubMed

    Ranade, Sanjeev S; Syeda, Ruhma; Patapoutian, Ardem

    2015-09-23

    Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels.

  5. Monitoring active volcanoes

    USGS Publications Warehouse

    Tilling, Robert I.

    1987-01-01

    One of the most spectacular, awesomely beautiful, and at times destructive displays of natural energy is an erupting volcano, belching fume and ash thousands of meters into the atmosphere and pouring out red-hot molten lava in fountains and streams. Countless eruptions in the geologic past have produced volcanic rocks that form much of the Earth's present surface. The gradual disintegration and weathering of these rocks have yielded some of the richest farmlands in the world, and these fertile soils play a significant role in sustaining our large and growing population. Were it not for volcanic activity, the Hawaiian Islands with their sugar cane and pineapple fields and magnificent landscapes and seascapes would not exist to support their residents and to charm their visitors. Yet, the actual eruptive processes are catastrophic and can claim life and property.

  6. CNES gondola development activities

    NASA Astrophysics Data System (ADS)

    Vargas, André; Verdier, Nicolas; Escarnot, Jean-Pierre; Vargas, André

    Recent safety rules and gondola obsolescence oblige CNES to initiate new developments to improve performances according scientific needs. A large project called NOSYCA will able to offer versatile housekeeping and science telemetry system for Zero Pressure Balloons. This concept is modular, use IP protocol for scientific high data rate and mix telemetry systems to perform long duration flight. To respect safety duties, the long duration flight ISBA gondola is modified. New functions are implemented to increase reliability for stratospheric super and zero Pressure balloons flights. "Pointed gondola activity" is also concerned by improvements. After the First Fireball flight, new equipment designs are in progress for future missions. At least, boundary layer balloons performances of science payload and housekeeping system increase with new instrumentation and network telemetry concepts.

  7. Factors regulating microglia activation

    PubMed Central

    Kierdorf, Katrin; Prinz, Marco

    2013-01-01

    Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the “resting” but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence. PMID:23630462

  8. Implementation team activities

    NASA Astrophysics Data System (ADS)

    Linder, F.

    2002-12-01

    The implementation Team (IT) is a body reporting to the SCSB,. It has been assigned the task of preparing and harmonising policy, standards and specification proposals for evaluation, qualification and quality control, thus enabling a coherent and cost-effective ESCC Specification System for the procurement of EEE space components. Among the 10 recommendations issued by the SCAHC, 7 have been studied under the auspices of the Implementation Team. Its main activities have been the updating and modernising of the ESA/SCC system in order to meet user needs and to be compatible with market trends. In particular it updated the technical aspects of generic specifications for the different component families and introduced the QML concept into the SCC system. It has also studied and discussed other topics such as procurement standards, a reliability system, mutual recognition, databases and the preferred parts list. A summary of the progress made in all these fields will be presented below.

  9. Actively stressed marginal networks.

    PubMed

    Sheinman, M; Broedersz, C P; MacKintosh, F C

    2012-12-07

    We study the effects of motor-generated stresses in disordered three-dimensional fiber networks using a combination of a mean-field theory, scaling analysis, and a computational model. We find that motor activity controls the elasticity in an anomalous fashion close to the point of marginal stability by coupling to critical network fluctuations. We also show that motor stresses can stabilize initially floppy networks, extending the range of critical behavior to a broad regime of network connectivities below the marginal point. Away from this regime, or at high stress, motors give rise to a linear increase in stiffness with stress. Finally, we demonstrate that our results are captured by a simple, constitutive scaling relation highlighting the important role of nonaffine strain fluctuations as a susceptibility to motor stress.

  10. Lightning activity on Jupiter

    NASA Technical Reports Server (NTRS)

    Borucki, W. J.; Bar-Nun, A.; Scarf, F. L.; Look, A. F.; Hunt, G. E.

    1982-01-01

    Photographic observations of the nightside of Jupiter by the Voyager 1 spacecraft show the presence of extensive lightning activity. Detection of whistlers by the plasma wave analyzer confirms the optical observations and implies that many flashes were not recorded by the Voyager camera because the intensity of the flashes was below the threshold sensitivity of the camera. Measurements of the optical energy radiated per flash indicate that the observed flashes had energies similar to that for terrestrial superbolts. The best estimate of the lightning energy dissipation rate of 0.0004 W/sq m was derived from a consideration of the optical and radiofrequency measurements. The ratio of the energy dissipated by lightning compared to the convective energy flux is estimated to be between 0.000027 and 0.00005. The terrestrial value is 0.0001.

  11. Small Active Radiation Monitor

    NASA Technical Reports Server (NTRS)

    Badhwar, Gautam D.

    2004-01-01

    A device, named small active radiation monitor, allows on-orbit evaluations during periods of increased radiation, after extravehicular activities, or at predesignated times for crews on such long-duration space missions as on the International Space Station. It also permits direct evaluation of biological doses, a task now performed using a combination of measurements and potentially inaccurate simulations. Indeed the new monitor can measure a full array of radiation levels, from soft x-rays to hard galactic cosmic-ray particles. With refinement, it will benefit commercial (nuclear power-plant workers, airline pilots, medical technicians, physicians/dentists, and others) and military personnel as well as the astronauts for whom thermoluminescent dosimeters are inadequate. Civilian and military personnel have long since graduated from film badges to thermoluminescent dosimeters. Once used, most dosimeters must be returned to a central facility for processing, a step that can take days or even weeks. While this suffices for radiation workers for whom exposure levels are typically very low and of brief duration, it does not work for astronauts. Even in emergencies and using express mail, the results can often be delayed by as much as 24 hours. Electronic dosimeters, which are the size of electronic oral thermometers, and tattlers, small electronic dosimeters that sound an alarm when the dose/dose rate exceeds preset values, are also used but suffer disadvantages similar to those of thermoluminescent dosimeters. None of these devices fully answers the need of rapid monitoring during the space missions. Instead, radiation is monitored by passive detectors, which are read out after the missions. Unfortunately, these detectors measure only the absorbed dose and not the biologically relevant dose equivalent. The new monitor provides a real-time readout, a time history of radiation exposures (both absorbed dose and biologically relevant dose equivalent), and a count of the

  12. Earthquake activity in Oklahoma

    SciTech Connect

    Luza, K.V.; Lawson, J.E. Jr. )

    1989-08-01

    Oklahoma is one of the most seismically active areas in the southern Mid-Continent. From 1897 to 1988, over 700 earthquakes are known to have occurred in Oklahoma. The earliest documented Oklahoma earthquake took place on December 2, 1897, near Jefferson, in Grant County. The largest known Oklahoma earthquake happened near El Reno on April 9, 1952. This magnitude 5.5 (mb) earthquake was felt from Austin, Texas, to Des Moines, Iowa, and covered a felt area of approximately 362,000 km{sup 2}. Prior to 1962, all earthquakes in Oklahoma (59) were either known from historical accounts or from seismograph stations outside the state. Over half of these events were located in Canadian County. In late 1961, the first seismographs were installed in Oklahoma. From 1962 through 1976, 70 additional earthquakes were added to the earthquake database. In 1977, a statewide network of seven semipermanent and three radio-telemetry seismograph stations were installed. The additional stations have improved earthquake detection and location in the state of Oklahoma. From 1977 to 1988, over 570 additional earthquakes were located in Oklahoma, mostly of magnitudes less than 2.5. Most of these events occurred on the eastern margin of the Anadarko basin along a zone 135 km long by 40 km wide that extends from Canadian County to the southern edge of Garvin County. Another general area of earthquake activity lies along and north of the Ouachita Mountains in the Arkoma basin. A few earthquakes have occurred in the shelves that border the Arkoma and Anadarko basins.

  13. Science Activities for School Trips.

    ERIC Educational Resources Information Center

    Quint, Walter C.

    1980-01-01

    Describes ways in which physics-learning activity packets can be used by high school students participating in trips organized by other departments. Provides an example of physics activities incorporated into an airplane trip to Disney World. (CS)

  14. Antinociceptive activity of Helicteres isora.

    PubMed

    Venkatesh, Sama; Laxmi, K Sai; Reddy, B Madhava; Ramesh, M

    2007-02-01

    Helicteres isora root extracts were studied for antinociceptive activity on acetic acid-induced writhing test in mice, at a dose of 250 mg/kg. Petroleum ether, chloroform and aqueous ethanol extracts have shown significant activity.

  15. Physical Activity and Your Heart

    MedlinePlus

    ... more energy than resting. Walking, running, dancing, swimming, yoga, and gardening are a few examples of physical activity. According to the Department of Health and Human Services' 2008 Physical Activity Guidelines for ...

  16. Environmental Education Tips: Weather Activities.

    ERIC Educational Resources Information Center

    Brainard, Audrey H.

    1989-01-01

    Provides weather activities including questions, on weather, heating the earth's surface, air, tools of the meteorologist, clouds, humidity, wind, and evaporation. Shows an example of a weather chart activity. (RT)

  17. Physical activity extends life expectancy

    Cancer.gov

    Leisure-time physical activity is associated with longer life expectancy, even at relatively low levels of activity and regardless of body weight, according to a study by a team of researchers led by the NCI.

  18. Antiviral activities of photoactive perylenequinones.

    PubMed

    Hudson, J B; Imperial, V; Haugland, R P; Diwu, Z

    1997-02-01

    Nine perylenequinones (PQ), including some familiar naturally occurring pigments, were compared for their light-mediated antiviral efficacies. Calphostin C was the most active compound against the two target viruses, herpes simplex virus type 1 and Sindbis virus. Hypocrellins A and B were also very active. However, three cercosporin-like PQ were substantially less active in spite of their high quantum yields of singlet oxygen, whereas phleichrome, another efficient singlet oxygen producer, showed no detectable antiviral activity. One other PQ, which was a very weak singlet oxygen producer, also showed no antiviral activity. None of the active compounds showed significant antiviral activity in the dark. Thus, for some groups of PQ there was correlation between quantum yield of singlet oxygen (1O2) and antiviral efficacy, but there are evidently other structural features of PQ that influence activity.

  19. Papermaking as a Science Activity.

    ERIC Educational Resources Information Center

    Fetters, Marcia K.

    2000-01-01

    Describes a simple procedure for making paper and provides some suggestions for extending and modifying the activity. The activity is correlated to the National Science Standards and Benchmarks for Science Literacy. (SAH)

  20. Diabetes Diet, Eating, & Physical Activity

    MedlinePlus

    ... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Diabetes Diet, Eating, & Physical Activity Nutrition and physical activity ... What foods can I eat if I have diabetes? You may worry that having diabetes means going ...

  1. The Study of Animal Activity

    ERIC Educational Resources Information Center

    Westling, Bruce

    1971-01-01

    Describes how to measure the daily rhythm of activity (photoperiodism) of small mammals. Three methods for recording information are reviewed including instructions for making a recorder. Includes suggestions for activities and experiments. (PR)

  2. Organic active materials for batteries

    SciTech Connect

    Abouimrane, Ali; Weng, Wei; Amine, Khalil

    2016-08-16

    A rechargeable battery includes a compound having at least two active sites, R.sup.1 and R.sup.2; wherein the at least two active sites are interconnected by one or more conjugated moieties; each active site is coordinated to one or more metal ions M.sup.a+ or each active site is configured to coordinate to one or more metal ions; and "a" is 1, 2, or 3.

  3. Insight into hydroxides-activated coals: chemical or physical activation?

    SciTech Connect

    Alcaniz-Monge, J.; Illan-Gomez, M.J.

    2008-02-15

    The objective of this paper is to get an insight into the chemical activation mechanism using KOH and NaOH as activated agents. Three coals have been selected as carbon precursors. It was found that KOH and NaOH develop a similar narrow microporosity, independently of the coal rank, whereas only KOH generates supermicroporosity. Temperature-programmed desorption experiments, carried out with impregnated anthracite, show differences on the gas evolved during the activated carbon preparation using the two activating agents. Thus, whereas hydrogen profiles are quite similar for both activated agents, the CO and H{sub 2}O profiles are different. It is remarkable the high amount of H{sub 2}O evolved at the maximum treatment temperature for both activating agents. The results obtained to allow conclusion that the chemical activation is due to a combination of different process driving the development of material porosity.

  4. Assessing and Increasing Physical Activity

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  5. Encapsulation of new active ingredients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The organic construct consumed as food comes packaged in units that carry the active components, protects the entrapped active materials until delivered to targeted human organ. The packaging and delivery role is mimicked in the microencapsulation tools used to deliver active ingredients in process...

  6. Art Activities for the Handicapped.

    ERIC Educational Resources Information Center

    Laurie, Frank, Comp.

    Intended for professionals interested in incorporating arts activities into the educational programs for disabled students, Part One of the document contains arts activities contributed by clinician-presenters in the 1978 Illinois series of Very Special Arts Festivals; while Part Two contains activities contributed by clinician-presenters and…

  7. Hospitality Services. Student Activity Book.

    ERIC Educational Resources Information Center

    Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

    This student activity book contains pencil-and-paper activities for use in a hospitality services course focusing on the food and lodging segments of the hospitality and tourism industry. The activities are organized into 29 chapters on the following topics: hospitality services industry; professional ethics; organization/management structures in…

  8. Activation Cascading in Sign Production

    ERIC Educational Resources Information Center

    Navarrete, Eduardo; Peressotti, Francesca; Lerose, Luigi; Miozzo, Michele

    2017-01-01

    In this study, we investigated how activation unfolds in sign production by examining whether signs that are not produced have their representations activated by semantics (cascading of activation). Deaf signers were tested with a picture-picture interference task. Participants were presented with pairs of overlapping pictures and named the green…

  9. RELAXIN ACTIVATES PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA

    PubMed Central

    Singh, Sudhir; Bennett, Robert G

    2009-01-01

    SUMMARY Relaxin is a polypeptide hormone that triggers multiple signaling pathways through its receptor RXFP1. Many of relaxin’s functions, including vascular and antifibrotic effects, are similar to those induced by activation of PPARγ. In this study, we tested the hypothesis that relaxin signaling through RXFP1 would activate PPARγ activity. In cells overexpressing RXFP1 (HEK-RXFP1), relaxin increased transcriptional activity through a PPAR response element (PPRE) in a concentration-dependent manner. In cells lacking RXFP1, relaxin had no effect. Relaxin increased both the baseline activity and the response to the PPARγ agonists rosiglitazone and 15d-PGJ2, but not to agonists of PPARα or PPARδ. In HEK-RXFP1 cells infected with adenovirus expressing PPARγ, relaxin increased transcriptional activity through PPRE, and this effect was blocked with an adenovirus expressing a dominant-negative PPARγ. Knockdown of PPARγ using siRNA resulted in a decrease in the response to both relaxin and rosiglitazone. Both relaxin and rosiglitazone increased expression of the PPARγ target genes CD36 and LXRα in HEK-RXFP1 and in THP-1 cells naturally expressing RXFP1. Relaxin did not increase PPARγ mRNA or protein levels. Treatment of cells with GW9662, an inhibitor of PPARγ ligand binding, effectively blocked rosiglitazone-induced PPARγ activation, but had no effect on relaxin activation of PPARγ. These results suggest that relaxin activates PPARγ activity, and increases the overall response in the presence PPARγ agonists. This activation is dependent on the presence of RXFP1. Furthermore, relaxin activates PPARγ via a ligand-independent mechanism. These studies represent the first report that relaxin can activate the transcriptional activity of PPARγ. PMID:19712722

  10. Oriented active shape models.

    PubMed

    Liu, Jiamin; Udupa, Jayaram K

    2009-04-01

    Active shape models (ASM) are widely employed for recognizing anatomic structures and for delineating them in medical images. In this paper, a novel strategy called oriented active shape models (OASM) is presented in an attempt to overcome the following five limitations of ASM: 1) lower delineation accuracy, 2) the requirement of a large number of landmarks, 3) sensitivity to search range, 4) sensitivity to initialization, and 5) inability to fully exploit the specific information present in the given image to be segmented. OASM effectively combines the rich statistical shape information embodied in ASM with the boundary orientedness property and the globally optimal delineation capability of the live wire methodology of boundary segmentation. The latter characteristics allow live wire to effectively separate an object boundary from other nonobject boundaries with similar properties especially when they come very close in the image domain. The approach leads to a two-level dynamic programming method, wherein the first level corresponds to boundary recognition and the second level corresponds to boundary delineation, and to an effective automatic initialization method. The method outputs a globally optimal boundary that agrees with the shape model if the recognition step is successful in bringing the model close to the boundary in the image. Extensive evaluation experiments have been conducted by utilizing 40 image (magnetic resonance and computed tomography) data sets in each of five different application areas for segmenting breast, liver, bones of the foot, and cervical vertebrae of the spine. Comparisons are made between OASM and ASM based on precision, accuracy, and efficiency of segmentation. Accuracy is assessed using both region-based false positive and false negative measures and boundary-based distance measures. The results indicate the following: 1) The accuracy of segmentation via OASM is considerably better than that of ASM; 2) The number of landmarks

  11. High-dose acetaminophen inhibits the lethal effect of doxorubicin in HepG2 cells: the role of P-glycoprotein and mitogen-activated protein kinase p44/42 pathway.

    PubMed

    Manov, Irena; Bashenko, Yulia; Eliaz-Wolkowicz, Anat; Mizrahi, Meital; Liran, Oded; Iancu, Theodore C

    2007-09-01

    Doxorubicin (DOX) is a widely used chemotherapeutic drug for human hepatocellular carcinoma (HCC). A major limitation to its effectiveness is the development of multidrug resistance of cancer cells. In clinical trials, patients with advanced HCC were treated with high-dose acetaminophen (HAAP) in an effort to improve the antitumor activity of chemotherapeutics. In this study, we investigated the effect of concomitant treatment of DOX and HAAP on hepatoma-derived HepG2 cells. Viability, cell cycle distribution, and ultrastructure were examined. Unexpectedly, HAAP, when added to DOX-exposed cells, increased cell viability, released cell cycle arrest, and decreased apoptosis. To elucidate the mechanisms by which HAAP reduces the DOX lethal effect to HepG2 cells, we investigated the multidrug resistance P-glycoprotein (P-gp) and p44/42-mitogen-activated protein kinase (MAPK) pathways. The P-gp function was enhanced by DOX and HAAP, and it was further stimulated during combined treatment, leading to decreased DOX retention. Verapamil (VRP), when added to DOX + HAAP exposure, increased DOX accumulation and restored DOX-induced toxicity. The increased phospho-p44/42-MAPK level in DOX-exposed cells was inhibited by HAAP. In addition, suppression of p44/42 activation by the p44/42-MAPK inhibitor 2'-amino-3'-methoxyflavone (PD98059) blocked DOX-induced apoptosis. These findings suggest that the antagonistic effect of concomitant DOX + HAAP treatment occurs as a result of interactive stimulation of P-gp, generating decreased intracellular drug concentrations. Furthermore, inhibition of the p44/42-MAPK phosphorylation by HAAP could abolish the DOX-induced cell death pathway. Thus, combined treatment by DOX + HAAP, intended to improve chemotherapeutic efficacy, could have an opposite effect facilitating cancer cell survival.

  12. Distributed Active Archive Center

    NASA Technical Reports Server (NTRS)

    Bodden, Lee; Pease, Phil; Bedet, Jean-Jacques; Rosen, Wayne

    1993-01-01

    The Goddard Space Flight Center Version 0 Distributed Active Archive Center (GSFC V0 DAAC) is being developed to enhance and improve scientific research and productivity by consolidating access to remote sensor earth science data in the pre-EOS time frame. In cooperation with scientists from the science labs at GSFC, other NASA facilities, universities, and other government agencies, the DAAC will support data acquisition, validation, archive and distribution. The DAAC is being developed in response to EOSDIS Project Functional Requirements as well as from requirements originating from individual science projects such as SeaWiFS, Meteor3/TOMS2, AVHRR Pathfinder, TOVS Pathfinder, and UARS. The GSFC V0 DAAC has begun operational support for the AVHRR Pathfinder (as of April, 1993), TOVS Pathfinder (as of July, 1993) and the UARS (September, 1993) Projects, and is preparing to provide operational support for SeaWiFS (August, 1994) data. The GSFC V0 DAAC has also incorporated the existing data, services, and functionality of the DAAC/Climate, DAAC/Land, and the Coastal Zone Color Scanner (CZCS) Systems.

  13. Photoperiodism and Enzyme Activity

    PubMed Central

    Queiroz, Orlando; Morel, Claudine

    1974-01-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system. PMID:16658749

  14. Optically active quantum dots

    NASA Astrophysics Data System (ADS)

    Gerard, Valerie; Govan, Joseph; Loudon, Alexander; Baranov, Alexander V.; Fedorov, Anatoly V.; Gun'ko, Yurii K.

    2015-10-01

    The main goal of our research is to develop new types of technologically important optically active quantum dot (QD) based materials, study their properties and explore their biological applications. For the first time chiral II-VI QDs have been prepared by us using microwave induced heating with the racemic (Rac), D- and L-enantiomeric forms of penicillamine as stabilisers. Circular dichroism (CD) studies of these QDs have shown that D- and L-penicillamine stabilised particles produced mirror image CD spectra, while the particles prepared with a Rac mixture showed only a weak signal. It was also demonstrated that these QDs show very broad emission bands between 400 and 700 nm due to defects or trap states on the surfaces of the nanocrystals. These QDs have demonstrated highly specific chiral recognition of various biological species including aminoacids. The utilisation of chiral stabilisers also allowed the preparation of new water soluble white emitting CdS nano-tetrapods, which demonstrated circular dichroism in the band-edge region of the spectrum. Biological testing of chiral CdS nanotetrapods displayed a chiral bias for an uptake of the D- penicillamine stabilised nano-tetrapods by cancer cells. It is expected that this research will open new horizons in the chemistry of chiral nanomaterials and their application in nanobiotechnology, medicine and optical chemo- and bio-sensing.

  15. VERA Geodetic Activities

    NASA Technical Reports Server (NTRS)

    Jike, Takaaki; Tamura, Yoshiaki; Shizugami, Makoto

    2013-01-01

    This report briefly describes the geodetic activities of VERA in the year 2012. The regular geodetic observations are carried out both in K- and S/X-bands. The frequency of regular observations is three times a month-twice for the VERA internal observations in K-band. The networks of the S/X sessions are JADE of GSI and IVS-T2. The raw data of the T2 and JADE sessions are electronically transferred to the Bonn, Haystack, and GSI correlators via Internet. Gravimetric observations are carried out at the VERA stations. An SG was installed at Mizusawa and placed in the vicinity of the VERA antenna in order to monitor vertical displacement at the end of 2008, and the observations continued throughout the year. Also at the VERA-Ishigakijima station, continuous operation of the SG started in 2012. The crustal movements generated by the 2011 earthquake off the Pacific coast of Tohoku continued during 2012, and displacement of the VERA-Mizusawa position by post-seismic creeping continued.

  16. Active control of convection

    NASA Astrophysics Data System (ADS)

    Singer, Jonathan; Bau, Haim H.

    1991-12-01

    It is demonstrated theoretically that active (feedback) control can be used to alter the characteristics of thermal convection in a toroidal, vertical loop heated from below and cooled from above. As the temperature difference between the heated and cooled sections of the loop increases, the flow in the uncontrolled loop changes from no motion to steady, time-independent motion to temporally oscillatory, chaotic motion. With the use of a feedback controller effecting small perturbations in the boundary conditions, one can maintain the no-motion state at significantly higher temperature differences than the critical one corresponding to the onset of convection in the uncontrolled system. Alternatively, one can maintain steady, time-independent flow under conditions in which the flow would otherwise be chaotic. That is, the controller can be used to suppress chaos. Likewise, it is possible to stabilize periodic nonstable orbits that exist in the chaotic regime of the uncontrolled system. Finally, the controller also can be used to induce chaos in otherwise laminar (fully predictable), nonchaotic flow.

  17. ADASY (Active Daylighting System)

    NASA Astrophysics Data System (ADS)

    Vázquez-Moliní, Daniel; González-Montes, Mario; Fernández-Balbuena, Antonio Á.; Bernabéu, Eusebio; García-Botella, Ángel; García-Rodríguez, Lucas; Pohl, Wilfried

    2009-08-01

    The main objective of ADASY (Active Daylighting System) work is to design a façade static daylighting system oriented to office applications, mainly. The goal of the project is to save energy by guiding daylight into a building for lighting purpose. With this approach we can reduce the electrical load for artificial lighting, completing it with sustainable energy. The collector of the system is integrated on a vertical façade and its distribution guide is always horizontal inside of the false ceiling. ADASY is designed with a specific patent pending caption system, a modular light-guide and light extractor luminaire system. Special care has been put on the final cost of the system and its building integration purpose. The current ADASY configuration is able to illuminate 40 m2 area with a 300lx-400lx level in the mid time work hours; furthermore it has a good enough spatial uniformity distribution and a controlled glare. The data presented in this study are the result of simulation models and have been confirmed by a physical scaled prototype. ADASY's main advantages over regular illumination systems are: -Low maintenance; it has not mobile pieces and therefore it lasts for a long time and require little attention once installed. - No energy consumption; solar light continue working even if there has been a power outage. - High quality of light: the colour rendering of light is very high - Psychological benefits: People working with daylight get less stress and more comfort, increasing productivity. - Health benefits

  18. Battery equalization active methods

    NASA Astrophysics Data System (ADS)

    Gallardo-Lozano, Javier; Romero-Cadaval, Enrique; Milanes-Montero, M. Isabel; Guerrero-Martinez, Miguel A.

    2014-01-01

    Many different battery technologies are available for the applications which need energy storage. New researches are being focused on Lithium-based batteries, since they are becoming the most viable option for portable energy storage applications. As most of the applications need series battery strings to meet voltage requirements, battery imbalance is an important matter to be taken into account, since it leads the individual battery voltages to drift apart over time, and premature cells degradation, safety hazards, and capacity reduction will occur. A large number of battery equalization methods can be found, which present different advantages/disadvantages and are suitable for different applications. The present paper presents a summary, comparison and evaluation of the different active battery equalization methods, providing a table that compares them, which is helpful to select the suitable equalization method depending on the application. By applying the same weight to the different parameters of comparison, switch capacitor and double-tiered switching capacitor have the highest ratio. Cell bypass methods are cheap and cell to cell ones are efficient. Cell to pack, pack to cell and cell to pack to cell methods present a higher cost, size, and control complexity, but relatively low voltage and current stress in high-power applications.

  19. Perspectives in active liquid crystals.

    PubMed

    Majumdar, Apala; Cristina, Marchetti M; Virga, Epifanio G

    2014-11-28

    Active soft matter is a young, growing field, with potential applications to a wide variety of systems. This Theme Issue explores this emerging new field by highlighting active liquid crystals. The collected contributions bridge theory to experiment, mathematical theories of passive and active nematics, spontaneous flows to defect dynamics, microscopic to continuum levels of description, spontaneous activity to biological activation. While the perspectives offered here only span a small part of this rapidly evolving field, we trust that they might provide the interested reader with a taste for this new class of non-equilibrium systems and their rich behaviour.

  20. Recurrent Activity in Radio Galaxies

    SciTech Connect

    Jamrozy, Marek; Konar, Chiranjib; Machalski, Jerzy; Mack, Karl-Heinz; Saikia, Dhruba; Siemiginowska, Aneta; Stawarz, Lukasz; /KIPAC, Menlo Park /Jagiellonian U.

    2007-10-15

    One of the outstanding issues concerning extragalactic radio sources is the total duration of their active phase and the possible existence of duty cycles of their nuclear activity. A duty cycle can be recognized if there is a mechanism which preserves the information of past activity for a sufficiently long time after a new activity has started up. If a new cycle starts before the radio lobes created during a former activity period have faded, we can recognize this by the observations of a young radio source embedded in an old relic structure.

  1. Activated sintering of zirconium dioxide

    NASA Astrophysics Data System (ADS)

    Panin, V. E.; Slosman, A. I.; Matrenin, S. V.

    1996-02-01

    A new phenomenon has been observed — the activated sintering of a zirconium ceramic in the hydrogen-nitrogen plasma of a glow discharge. It is shown that the activation energy is considerably lower than the activation energy for sintering in a vacuum furnace. This makes it possible to reduce sintering temperature, refine the grains, and improve the mechanical properties of the ceramic. It is proposed that the mechanism by which sintering is activated is connected with the activating effect of hydrogen during a structural transformation involving the formation of oxynitride phases.

  2. Global optogenetic activation of inhibitory interneurons during epileptiform activity.

    PubMed

    Ledri, Marco; Madsen, Marita Grønning; Nikitidou, Litsa; Kirik, Deniz; Kokaia, Merab

    2014-02-26

    Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. In particular, the possibility to specifically activate by light-determined interneuron populations expressing channelrhodopsin-2 provides an unprecedented opportunity of exploring their contribution to physiological and pathological network activity. There are several subclasses of interneurons in cortical areas with different functional connectivity to the principal neurons (e.g., targeting their perisomatic or dendritic compartments). Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices. Here we demonstrate that such approach results in a brief initial action potential discharge in CA3 pyramidal neurons, followed by prolonged suppression of ongoing epileptiform activity during light exposure. Such sequence of events was caused by massive light-induced release of GABA from ChR2-expressing interneurons. The inhibition of epileptiform activity was less pronounced if only parvalbumin- or somatostatin-expressing interneurons were activated by light. Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration.

  3. Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation.

    PubMed

    Halangk, Walter; Krüger, Burkhard; Ruthenbürger, Manuel; Stürzebecher, Jörg; Albrecht, Elke; Lippert, Hans; Lerch, Markus M

    2002-02-01

    A premature and intracellular activation of digestive zymogens is thought to be responsible for the onset of pancreatitis. Because trypsin has a critical role in initiating the activation cascade of digestive enzymes in the gut, it has been assumed that trypsin also initiates intracellular zymogen activation in the pancreas. We have tested this hypothesis in isolated acini and lobules from rat pancreas. Intracellular trypsinogen activation was induced by supramaximal secretagogue stimulation and measured using either specific trypsin substrates or immunoreactivity of the trypsinogen activation peptide (TAP). To prevent a trypsin-induced trypsinogen activation, we used the cell-permeant, highly specific, and reversible inhibitor Nalpha-(2-naphthylsulfonyl)-3-amidinophenylalanine-carboxymethylpiperazide (S124), and to prevent cathepsin-induced trypsinogen activation, we used the cysteine protease inhibitor E-64d. Incubation of acini or lobules in the presence of S124 completely prevented the generation of trypsin activity in response to supramaximal caerulein but had no effect whatsoever on the generation of TAP. Conversely, when trypsin activity was recovered at the end of the experiment by either washout of S124 from acini or extensive dilution of lobule homogenates, it was up to 400% higher than after caerulein alone and corresponded, in molar terms, to the generation of TAP. Both trypsin activity and TAP release were inhibited in parallel by E-64d. We conclude that caerulein-induced trypsinogen activation in the pancreas is caused by an E-64d-inhibitable mechanism such as cathepsin-induced trypsinogen activation, and neither involves nor requires intracellular trypsin activity. Specific trypsin inhibition, on the other hand, prevents 80% of trypsin inactivation or autodegradation in the pancreas.

  4. Dynamic Patterns in Active Fluids

    NASA Astrophysics Data System (ADS)

    Jülicher, Frank

    2012-02-01

    Biological matter is inherently dynamic and exhibits active properties. A key example is the force generation by molecular motors in the cell cytoskeleton. Such active processes give rise to the generation of active mechanical stresses and spontaneous flows in gel-like cytoskeletal networks. Active material behaviors play a key role for the dynamics of cellular processes such as cell locomotion and cell division. We will discuss intracellular flow patterns that are created by active processes in the cell cortex. By combining theory with quantitative experiments we show that observed flow patterns result from profiles of active stress generation in the system. We will also consider the situation where active stress is regulated by a diffusing molecular species. In this case, spatial concentration patterns are generated by the interplay of stress regulation and self-generated flow fields.

  5. Active Kids Active Minds: A Physical Activity Intervention to Promote Learning?

    ERIC Educational Resources Information Center

    lisahunter; Abbott, Rebecca; Macdonald, Doune; Ziviani, Jennifer; Cuskelly, Monica

    2014-01-01

    This study assessed the feasibility and impact of introducing a programme of an additional 30 minutes per day of moderate physical activity within curriculum time on learning and readiness to learn in a large elementary school in south-east Queensland, Australia. The programme, Active Kids Active Minds (AKAM), involved Year 5 students (n = 107),…

  6. Strategy as active waiting.

    PubMed

    Sull, Donald N

    2005-09-01

    Successful executives who cut their teeth in stable industries or in developed countries often stumble when they face more volatile markets. They falter, in part, because they assume they can gaze deep into the future and develop a long-term strategy that will confer a sustainable competitive advantage. But visibility into the future of volatile markets is sharply limited because so many different variables are in play. Factors such as technological innovation, customers' evolving needs, government policy, and changes in the capital markets interact with one another to create unexpected outcomes. Over the past six years, Donald Sull, an associate professor at London Business School, has led a research project examining some of the world's most volatile markets, from national markets like China and Brazil to industries like enterprise software, telecommunications, and airlines. One of the most striking findings from this research is the importance of taking action during comparative lulls in the storm. Huge business opportunities are relatively rare; they come along only once or twice in a decade. And, for the most part, companies can't manufacture those opportunities; changes in the external environment converge to make them happen. What managers can do is prepare for these golden opportunities by managing smart during the comparative calm of business as usual. During these periods of active waiting, leaders must probe the future and remain alert to anomalies that signal potential threats or opportunities; exercise restraint to preserve their war chests; and maintain discipline to keep the troops battle ready. When a golden opportunity or"sudden death"threat emerges, managers must have the courage to declare the main effort and concentrate resources to seize the moment.

  7. Mechanically Active Electrospun Materials

    NASA Astrophysics Data System (ADS)

    Robertson, Jaimee M.

    Electrospinning, a technique used to fabricate small diameter polymer fibers, has been employed to develop unique, active materials falling under two categories: (1) shape memory elastomeric composites (SMECs) and (2) water responsive fiber mats. (1) Previous work has characterized in detail the properties and behavior of traditional SMECs with isotropic fibers embedded in an elastomer matrix. The current work has two goals: (i) characterize laminated anisotropic SMECs and (ii) develop a fabrication process that is scalable for commercial SMEC manufacturing. The former ((i)) requires electrospinning aligned polymer fibers. The aligned fibers are similarly embedded in an elastomer matrix and stacked at various fiber orientations. The resulting laminated composite has a unique response to tensile deformation: after stretching and releasing, the composite curls. This curling response was characterized based on fiber orientation. The latter goal ((ii)) required use of a dual-electrospinning process to simultaneously electrospin two polymers. This fabrication approach incorporated only industrially relevant processing techniques, enabling the possibility of commercial application of a shape memory rubber. Furthermore, the approach had the added benefit of increased control over composition and material properties. (2) The strong elongational forces experienced by polymer chains during the electrospinning process induce molecular alignment along the length of electrospun fibers. Such orientation is maintained in the fibers as the polymer vitrifies. Consequently, residual stress is stored in electrospun fiber mats and can be recovered by heating through the polymer's glass transition temperature. Alternatively, the glass transition temperature can be depressed by introducing a plasticizing agent. Poly(vinyl acetate) (PVAc) is plasticized by water, and its glass transition temperature is lowered below room temperature. Therefore, the residual stress can be relaxed at room

  8. AMPK activators: mechanisms of action and physiological activities

    PubMed Central

    Kim, Joungmok; Yang, Goowon; Kim, Yeji; Kim, Jin; Ha, Joohun

    2016-01-01

    AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, which coordinates metabolic pathways and thus balances nutrient supply with energy demand. Because of the favorable physiological outcomes of AMPK activation on metabolism, AMPK has been considered to be an important therapeutic target for controlling human diseases including metabolic syndrome and cancer. Thus, activators of AMPK may have potential as novel therapeutics for these diseases. In this review, we provide a comprehensive summary of both indirect and direct AMPK activators and their modes of action in relation to the structure of AMPK. We discuss the functional differences among isoform-specific AMPK complexes and their significance regarding the development of novel AMPK activators and the potential for combining different AMPK activators in the treatment of human disease. PMID:27034026

  9. Fluidization and Active Thinning by Molecular Kinetics in Active Gels.

    PubMed

    Oriola, David; Alert, Ricard; Casademunt, Jaume

    2017-02-24

    We derive the constitutive equations of an active polar gel from a model for the dynamics of elastic molecules that link polar elements. Molecular binding kinetics induces the fluidization of the material, giving rise to Maxwell viscoelasticity and, provided that detailed balance is broken, to the generation of active stresses. We give explicit expressions for the transport coefficients of active gels in terms of molecular properties, including nonlinear contributions on the departure from equilibrium. In particular, when activity favors linker unbinding, we predict a decrease of viscosity with activity-active thinning-of kinetic origin, which could explain some experimental results on the cell cortex. By bridging the molecular and hydrodynamic scales, our results could help understand the interplay between molecular perturbations and the mechanics of cells and tissues.

  10. Being active when you have heart disease

    MedlinePlus

    Heart disease - activity; CAD - activity; Coronary artery disease - activity; Angina - activity ... Getting regular exercise when you have heart disease is important. Exercise can make your heart muscle stronger. It may also help you be more active without chest pain or ...

  11. Prognostic impact of polymorphism of matrix metalloproteinase-2 and metalloproteinase tissue inhibitor-2 promoters in breast cancer in Tunisia: case-control study.

    PubMed

    Ben Néjima, Dalel; Ben Zarkouna, Yosr; Gammoudi, Amor; Manai, Mohamed; Boussen, Hamouda

    2015-05-01

    Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) polymorphism in Tunisian breast cancer patients. MMP-2 genotypes were determined by real-time polymerase chain reaction (RT-PCR), and TIMP-2 genotypes were identified using a PCR-restriction fragment length polymorphism (RFLP) method in 210 breast cancer patients and 250 frequency-matched control women. Association of the clinicopathological parameters and the genetic markers with risk of breast cancer was assessed using univariate analyses. We found that the variant MMP-2 genotype (-1306CT or TT) was associated with substantially reduced risk of breast cancer [odds ratio (OR), 0.49; 95 % confidence interval (95 % CI), 0.033-0.73], compared with the CC genotype. For TIMP-2, a moderately reduced risk of the cancer (OR, 0.57; 95 % CI, 0.37-0.87) was also associated with the variant allele (-418GC or CC), compared with the GG common allele. Furthermore, polymorphisms in both genes seem to have additive effects and the highest risk for breast cancer has been observed in those with MMP-2 CC genotype and TIMP-2 GC or CC genotype (p = 0.006). A significant association was also found between the CC genotype and the aggressive forms of breast cancer as defined by advanced stages at the time of diagnosis and metastasis. This is the first report on the association of MMP-2 and TIMP-2 gene polymorphisms in breast cancer in Tunisian population. Our results suggest that the presence of the variant allele in the promoter of MMP-2 or TIMP-2 may be a protective factor for the development of breast cancer.

  12. GTP cyclohydrolase I inhibition by the prototypic inhibitor 2, 4-diamino-6-hydroxypyrimidine. Mechanisms and unanticipated role of GTP cyclohydrolase I feedback regulatory protein.

    PubMed

    Xie, L; Smith, J A; Gross, S S

    1998-08-14

    2,4-Diamino-6-hydroxypyrimidine (DAHP) is considered to be a selective and direct-acting inhibitor of GTP cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in the pathway for synthesis of tetrahydrobiopterin (BH4). Accordingly, DAHP has been widely employed to distinguish whether de novo BH4 synthesis is required in a given biological system. Although it has been assumed that DAHP inhibits GTPCH by direct competition with substrate GTP, this has never been formally demonstrated. In view of apparent structural homology between DAHP and BH4, we questioned whether DAHP may mimic BH4 in its inhibition of GTPCH by an indirect mechanism, involving interaction with a recently cloned 9.5-kDa protein termed GTPCH Feedback Regulatory Protein (GFRP). We show by reverse transcription-polymerase chain reaction that GFRP mRNA is constitutively expressed in rat aortic smooth muscle cells and further induced by treatment with immunostimulants. Moreover, functional GFRP is expressed and immunostimulant-induced BH4 accumulates in sufficient quantity to trigger feedback inhibition of GTPCH. Studies with DAHP reveal that GFRP is also essential to achieve potent inhibition of GTPCH. Indeed, DAHP inhibits GTPCH by dual mechanisms. At a relatively low concentration, DAHP emulates BH4 and engages the GFRP-dependent feedback inhibitory system; at higher concentrations, DAHP competes directly for binding with GTP substrate. This knowledge predicts that DAHP would preferably target GTPCH in tissues with abundant GFRP.

  13. Blockade of the inward rectifier potassium current by the Ca(2+)-ATPase inhibitor 2',5'-di(tert-butyl)-1,4-benzohydroquinone (BHQ).

    PubMed Central

    Hasséssian, H.; Vaca, L.; Kunze, D. L.

    1994-01-01

    1. We have investigated the effect of 2',5'-di (tert-butyl)-1,4-benzohydroquinone (BHQ) and thapsigargin, inhibitors of the intracellular Ca(2+)-ATPase, on ionic currents in rat basophilic leukaemia (RBL-2H3) cells under whole cell voltage clamp. 2. The whole cell current was inwardly rectifying and reversed at -35 +/- 6 mV (n = 16). The conductance of the inward current increased as the concentration of extracellular K+ was raised from 2.7 to 5.4, 10.8 and 21.6 mM. BaCl2 (100 microM) reduced the current to a small linear component and shifted the reversal potential to -4 +/- 3 mV (n = 6). A concentration of 50 microM BaCl2 produced 45 +/- 10% (n = 4) blockade of the inward current. 3. BHQ and thapsigargin were examined for their effects on the inwardly rectifying current. A maximal blockade of inward current was obtained within 6 min after perfusion with 10 microM BHQ. The small current remaining after blockade with BHQ had a linear voltage-dependence and reversed direction at -6 +/- 9 mV (n = 6). Thapsigargin (up to 3 microM) was without effect on the inward rectifier. 4. In contrast to the blockade of the inward rectifier produced by BaCl2 which was predominantly on the steady state current, particularly at the very hyperpolarized holding potentials (-120 mV), blockade by BHQ was equally strong on the instantaneous as well as the steady state current. 5. Blockade of the inward rectifier by BHQ may cause depolarization of the cell which will affect Ca2+ influx during investigations with BHQ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7952872

  14. Rest Rust ! Physical active for active and healthy ageing

    PubMed Central

    Vollenbroek-Hutten, M; Pais, S; Ponce, S; Dekker-van Weering, M; Jansen-Kosterink, S; Schena, F; Tabarini, N; Carotenuto, F; Iadicicco, V; Illario, M

    2015-01-01

    The aim of this paper is to give an insight on how physical activity can be defined, parameterized and measured in older adults and on different options to deal with citizen physical activity promotion at European level. Three relevant aspects are highlighted: When talking about physical activity, two different aspects are often unfairly mixed up: “physical activity” and “physical capacity”. Physical activity, is referred to as the level of physical activity someone is actually performing in daily life.Physical capacity is referred to as the maximum physical activity a person can perform.Both physical activity and physical capacity can be expressed in different dimensions such as time, frequency, or type of activity with the consequence that there are many tools and techniques available. In order to support people to choose an appropriate instrument in their everyday practice a list of 9 criteria that are considered important is defined.Older adults score differently across the various physical dimensions, so strategies to promote physical activity should consider individual differences, in order to adapt for these variations. PMID:27042429

  15. Activated coconut shell charcoal carbon using chemical-physical activation

    NASA Astrophysics Data System (ADS)

    Budi, Esmar; Umiatin, Nasbey, Hadi; Bintoro, Ridho Akbar; Wulandari, Futri; Erlina

    2016-02-01

    The use of activated carbon from natural material such as coconut shell charcoal as metal absorbance of the wastewater is a new trend. The activation of coconut shell charcoal carbon by using chemical-physical activation has been investigated. Coconut shell was pyrolized in kiln at temperature about 75 - 150 °C for about 6 hours in producing charcoal. The charcoal as the sample was shieved into milimeter sized granule particle and chemically activated by immersing in various concentration of HCl, H3PO4, KOH and NaOH solutions. The samples then was physically activated using horizontal furnace at 400°C for 1 hours in argon gas environment with flow rate of 200 kg/m3. The surface morphology and carbon content of activated carbon were characterized by using SEM/EDS. The result shows that the pores of activated carbon are openned wider as the chemical activator concentration is increased due to an excessive chemical attack. However, the pores tend to be closed as further increasing in chemical activator concentration due to carbon collapsing.

  16. Silicon active photonic devices

    NASA Astrophysics Data System (ADS)

    Dimitropoulos, Dimitrios

    Active photonic devices utilizing the optical nonlinearities of silicon have emerged in the last 5 years and the effort for commercial photonic devices in the material that has been the workhorse of electronics has been building up since. This dissertation presents the theory for some of these devices. We are concerned herein with CW lasers, amplifiers and wavelength converters that are based on the Raman effect. There have already been cursory experimental demonstrations of these devices and some of their limitations are already apparent. Most of the limitations observed are because of the appearance of effects that are competing with stimulated Raman scattering. Under the high optical powers that are necessary for the Raman effect (tens to hundrends of mW's) the process of optical two-photon (TPA) absorption occurs. The absorption of optical power that it causes itself is weak but in the process electrons and holes are generated which can further absorb light through the free-carrier absorption effect (FCA). The effective "lifetime" that these carriers have determines the magnitude of the FCA loss. We present a model for the carrier lifetime in Silicon-On-Insulator (SOI) waveguides and numerical simulations to understand how this critical parameter varies and how it can be controlled. A p-i-n junction built along SOI waveguides can help achieve lifetime of the order of 20--100 ps but the price one has to pay is on-chip electrical power consumption on the order of 100's of mWs. We model CW Raman lasers and we find that the carrier lifetime reduces the output power. If the carrier lifetime exceeds a certain "critical" value optical losses become overwhelming and lasing is impossible. As we show, in amplifiers, the nonlinear loss does not only result in diminished gain, but also in a higher noise figure. Finally the effect of Coherent anti-Stokes Raman scattering (CARS) is examined. The effect is important because with a pump frequency at 1434nm coherent power

  17. Rapid Active Sampling Package

    NASA Technical Reports Server (NTRS)

    Peters, Gregory

    2010-01-01

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

  18. Enhanced NIF neutron activation diagnostics.

    PubMed

    Yeamans, C B; Bleuel, D L; Bernstein, L A

    2012-10-01

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the (89)Zr/(89 m)Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  19. CDPK Activation in PRR Signaling.

    PubMed

    Seybold, Heike; Boudsocq, Marie; Romeis, Tina

    2017-01-01

    Calcium-dependent protein kinases undergo a rapid biochemical activation in response to an intracellular Ca increase induced by the PRR-dependent perception of a pathogen-related stimulus. Based on SDS gel resolution, the in-gel kinase assay allows the analysis of multiple in vivo protein samples in parallel, combining the advantage of protein separation according to molecular mass with the activity read-out of a protein kinase assay. It thus enables to follow the transient CDPK activation and inactivation in response to in vivo elicitation with a time-wise resolution. In addition, changes of CDPK phosphorylation activity often correlate with slight shifts in the enzyme's apparent molecular mass, indicating posttranslational modifications and a conformational change of the active enzyme compared to its inactive resting form. These band shifts can be detected by a simple immunoblotting to monitor CDPK activation.

  20. Swim pressure of active matter

    NASA Astrophysics Data System (ADS)

    Takatori, Sho; Yan, Wen; Brady, John; Caltech Team

    2014-11-01

    Through their self-motion, all active matter systems generate a unique ``swim pressure'' that is entirely athermal in origin. This new source for the active stress exists at all scales in both living and nonliving active systems, and also applies to larger organisms where inertia is important (i.e., the Stokes number is not small). Here we explain the origin of the swim stress and develop a simple thermodynamic model to study the self-assembly and phase separation in active soft matter. Our new swim stress perspective can help analyze and exploit a wide class of active soft matter, from swimming bacteria and catalytic nanobots, schools of fish and birds, and molecular motors that activate the cellular cytoskeleton.

  1. Enhanced NIF neutron activation diagnostics

    SciTech Connect

    Yeamans, C. B.; Bleuel, D. L.; Bernstein, L. A.

    2012-10-15

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the {sup 89}Zr/{sup 89m}Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  2. Active Cells for Multifunctional Structures

    DTIC Science & Technology

    2014-09-24

    techniques to explore a variety of cell designs.  Designed a simplified active cell using Nitinol as the actuation method and relying on Joule heating...for contraction of the cell.  Developed manufacturing techniques for reliably creating Nitinol spring coils in a variety of diameters and gauges...design of the active cells to maximum the stroked length of the active cells by tuning the stiffness of a passive spring in parallel with the Nitinol

  3. Antiangiogenic Activity of Glycyrrhiza Extract

    NASA Astrophysics Data System (ADS)

    Li, Ying-Qiu

    The bioactivity of extract of glycyrrhiza was detected by zebrafish antiangiogenic model after 70% ethanol extract of glycyrrhiza was extracted with petroleum ether, ethyl acetate, n-butanol. The inhibition of the extracts in antiangiogenic activity showed that the highest active components existed in ethyl acetate extract of glycyrrhiza. The ethyl acetate extract of glycyrrhiza was separated by polyamide column chromatography to obtain 7 fractions (Fr1-Fr7), which Fr5 and Fr6 showed antiangiogenic activity.

  4. In Situ Activation of Microcapsules

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R. (Inventor); Mosier, Benjamin (Inventor)

    2000-01-01

    Disclosed are microcapsules comprising a polymer shell enclosing two or more immiscible liquid phases in which a drug, or a prodrug and a drug activator are partitioned into separate phases. or prevented from diffusing out of the microcapsule by a liquid phase in which the drug is poorly soluble. Also disclosed are methods of using the microcapsules for in situ activation of drugs where upon exposure to an appropriate energy source the internal phases mix and the drug is activated in situ.

  5. Macrophage Biochemistry, Activation and Function

    DTIC Science & Technology

    1981-01-01

    glucoeidase +8 . . Sulfatase c +8 Modified from Morahan, 1980. b(+)Exhibit@ activity; (-) lacks activity; (+) weak or marginal activity. ’References: (1...endoplasmic reticulum enzymes, sulfatase c and alkaline a-glucosidase. Dissociation of the lysosomal enzyme patterns from sulfatase c and alkaline r...1974; Beaufay et al., 1974). Peritoneal macrophages are deficient or contain inauf- • -𔃼 :’- 41 ficient quantities of the classical constituents to be

  6. L3 Study Team Activities

    NASA Astrophysics Data System (ADS)

    Shoemaker, David; L3ST Team

    2017-01-01

    The NASA-Chartered L3 Study Team is working to develop the US community participation and to support NASA's contribution to the ESA-led LISA mission to observe gravitational waves via space-based detectors. The present activities of the L3ST will be described, and the next steps for the Study Team will also be given. NASA supports travel activities and support for the Study Team activities.

  7. Active auditory mechanics in mosquitoes.

    PubMed Central

    Göpfert, M. C.; Robert, D.

    2001-01-01

    In humans and other vertebrates, hearing is improved by active contractile properties of hair cells. Comparable active auditory mechanics is now demonstrated in insects. In mosquitoes, Johnston's organ transduces sound-induced vibrations of the antennal flagellum. A non-muscular 'motor' activity enhances the sensitivity and tuning of the flagellar mechanical response in physiologically intact animals. This motor is capable of driving the flagellum autonomously, amplifying sound-induced vibrations at specific frequencies and intensities. Motor-related electrical activity of Johnston's organ strongly suggests that mosquito hearing is improved by mechanoreceptor motility. PMID:11270428

  8. Geomagnetic response to solar activity.

    NASA Technical Reports Server (NTRS)

    Mead, G. D.

    1972-01-01

    The relationship between solar activity and geomagnetic variations is discussed in the light of spacecraft data obtained during the last decade. The effects of centers of solar activity responsible for producing geomagnetic activity on earth are believed to be transmitted through the solar wind, and there is usually a delay of two or three days before the onset of magnetic activity. Attempts to make a one-to-one correspondence between specific solar events and specific magnetic storms, however, are usually unsuccessful, because of the complex and indirect processes linking the two phenomena. Normally, only statistical tendencies can be shown.

  9. Activated T lymphocytes in uveitis.

    PubMed Central

    Deschênes, J.; Char, D. H.; Kaleta, S.

    1988-01-01

    Two colour flow cytometry techniques were used to assess the activation stages of peripheral and intraocular T lymphocytes in uveitis. Increased numbers of T lymphocytes bearing the interleukin-2 (IL-2) receptors were found in intraocular fluids or peripheral blood or both of 35/51 patients with uveitis. This increased expression of IL-2 receptors on lymphocytes correlated with increased expression of other early T lymphocyte activation markers, HLA-DR and L-35. Both T helper cells (Leu-3A+) and suppressor cells (Leu 2A+) were activated in vivo. A positive correlation was seen between lymphocyte activation and clinical uveitis activity. In idiopathic uveitis activation of Leu-3A lymphocytes (helper/inducer) was significantly increased, and intraocular activation of the Leu-2A lymphocytes (cytotoxic/suppressor) was significantly decreased. These data show that some patients with idiopathic uveitis have a perturbation of T helper cells. Twenty-two of 31 patients with idiopathic uveitis, not associated with systemic disease, had increased peripheral T lymphocyte activation. This finding indicates that in some inflammations believed to be restricted to the eye an abnormal systemic immune activation exists. PMID:2964862

  10. Active surveillance for prostate cancer.

    PubMed

    Romero-Otero, Javier; García-Gómez, Borja; Duarte-Ojeda, José M; Rodríguez-Antolín, Alfredo; Vilaseca, Antoni; Carlsson, Sigrid V; Touijer, Karim A

    2016-03-01

    It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized.

  11. International Activities Related to Pesticides

    EPA Pesticide Factsheets

    Regulating pesticides involves many international issues and working with our regulatory partners in other countries. Learn about EPA's activities, upcoming meetings and workshops, and various regulatory issues.

  12. Physical Activity and Cancer Survivorship

    PubMed Central

    Garcia, David O.; Thomson, Cynthia A.

    2015-01-01

    There has been an increase in the cancer survivor population in the United States over the past several decades primarily due to improvements in early detection of first malignancies and effective treatment modalities. A wealth of evidence has demonstrated that regular physical activity is associated with a lower risk of death, all-cause mortality, cancer recurrence, and several chronic diseases, including type 2 diabetes and cardiovascular disease, common comorbid conditions in people who have survived cancer. Physical activity also is a central component of weight management. Methods This review summarizes the current physical activity recommendations and the evidence linking physical activity to improvements in weight management, physiological effects, and psychological health outcomes for cancer survivors. Results The available literature suggests physical activity is safe and is positively associated with weight management, cardiorespiratory fitness, muscular strength and endurance, quality of life, fatigue, and other psychosocial factors in cancer survivors. Yet relationships related to specific cancer diagnoses, treatments, and underlying cardiometabolic mechanisms associated with survival have not been thoroughly examined in randomized controlled trials. Furthermore, factors that influence adherence to physical activity behaviors must be identified to develop effective exercise programs. The use of objective measures of physical activity and the standardization of reporting outcome measures within intervention trials are needed to complement this effort. Conclusions Healthcare providers should consider individual differences among cancer survivors and tailor physical activity programs to meet the individual needs of the patient to assist in the adoption and maintenance of a physically active lifestyle. PMID:25335787

  13. Studies in geophysics: Active tectonics

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Active tectonics is defined within the study as tectonic movements that are expected to occur within a future time span of concern to society. Such movements and their associated hazards include earthquakes, volcanic eruptions, and land subsidence and emergence. The entire range of geology, geophysics, and geodesy is, to some extent, pertinent to this topic. The needs for useful forecasts of tectonic activity, so that actions may be taken to mitigate hazards, call for special attention to ongoing tectonic activity. Further progress in understanding active tectonics depends on continued research. Particularly important is improvement in the accuracy of dating techniques for recent geologic materials.

  14. Demand Activated Manufacturing Architecture

    SciTech Connect

    Bender, T.R.; Zimmerman, J.J.

    2001-02-07

    Honeywell Federal Manufacturing & Technologies (FM&T) engineers John Zimmerman and Tom Bender directed separate projects within this CRADA. This Project Accomplishments Summary contains their reports independently. Zimmerman: In 1998 Honeywell FM&T partnered with the Demand Activated Manufacturing Architecture (DAMA) Cooperative Business Management Program to pilot the Supply Chain Integration Planning Prototype (SCIP). At the time, FM&T was developing an enterprise-wide supply chain management prototype called the Integrated Programmatic Scheduling System (IPSS) to improve the DOE's Nuclear Weapons Complex (NWC) supply chain. In the CRADA partnership, FM&T provided the IPSS technical and business infrastructure as a test bed for SCIP technology, and this would provide FM&T the opportunity to evaluate SCIP as the central schedule engine and decision support tool for IPSS. FM&T agreed to do the bulk of the work for piloting SCIP. In support of that aim, DAMA needed specific DOE Defense Programs opportunities to prove the value of its supply chain architecture and tools. In this partnership, FM&T teamed with Sandia National Labs (SNL), Division 6534, the other DAMA partner and developer of SCIP. FM&T tested SCIP in 1998 and 1999. Testing ended in 1999 when DAMA CRADA funding for FM&T ceased. Before entering the partnership, FM&T discovered that the DAMA SCIP technology had an array of applications in strategic, tactical, and operational planning and scheduling. At the time, FM&T planned to improve its supply chain performance by modernizing the NWC-wide planning and scheduling business processes and tools. The modernization took the form of a distributed client-server planning and scheduling system (IPSS) for planners and schedulers to use throughout the NWC on desktops through an off-the-shelf WEB browser. The planning and scheduling process within the NWC then, and today, is a labor-intensive paper-based method that plans and schedules more than 8,000 shipped parts

  15. Platelet activating factor activity in the phospholipids of bovine spermatozoa

    SciTech Connect

    Parks, J.E.; Hough, S.; Elrod, C. )

    1990-11-01

    Platelet activating factor (PAF) has been detected in sperm from several mammalian species and can affect sperm motility and fertilization. Because bovine sperm contain a high percentage of ether-linked phospholipid precursors required for PAF synthesis, a study was undertaken to determine the PAF activity of bovine sperm phospholipids. Total lipids of washed, ejaculated bull sperm were extracted, and phospholipids were fractionated by thin-layer chromatography. Individual phospholipid fractions were assayed for PAF activity on the basis of (3H)serotonin release from equine platelets. PAF activity was detected in the PAF fraction (1.84 pmol/mumol total phospholipid) and in serine/inositol (PS/PI), choline (CP), and ethanolamine phosphoglyceride (EP) and cardiolipin (CA) fractions. Activity was highest in the CP fraction (8.05 pmol/mumol total phospholipid). Incomplete resolution of PAF and neutral lipids may have contributed to the activity in the PS/PI and CA fractions, respectively. Phospholipids from nonsperm sources did not stimulate serotonin release. Platelet activation by purified PAF and by sperm phospholipid fractions was inhibited by the receptor antagonist SRI 63-675. These results indicate that bovine sperm contain PAF and that other sperm phospholipids, especially CP and EP, which are high in glycerylether components, are capable of receptor-mediated platelet activation.

  16. Brain activation associated with active and passive lower limb stepping

    PubMed Central

    Jaeger, Lukas; Marchal-Crespo, Laura; Wolf, Peter; Riener, Robert; Michels, Lars; Kollias, Spyros

    2014-01-01

    Reports about standardized and repeatable experimental procedures investigating supraspinal activation in patients with gait disorders are scarce in current neuro-imaging literature. Well-designed and executed tasks are important to gain insight into the effects of gait-rehabilitation on sensorimotor centers of the brain. The present study aims to demonstrate the feasibility of a novel imaging paradigm, combining the magnetic resonance (MR)-compatible stepping robot (MARCOS) with sparse sampling functional magnetic resonance imaging (fMRI) to measure task-related BOLD signal changes and to delineate the supraspinal contribution specific to active and passive stepping. Twenty-four healthy participants underwent fMRI during active and passive, periodic, bilateral, multi-joint, lower limb flexion and extension akin to human gait. Active and passive stepping engaged several cortical and subcortical areas of the sensorimotor network, with higher relative activation of those areas during active movement. Our results indicate that the combination of MARCOS and sparse sampling fMRI is feasible for the detection of lower limb motor related supraspinal activation. Activation of the anterior cingulate and medial frontal areas suggests motor response inhibition during passive movement in healthy participants. Our results are of relevance for understanding the neural mechanisms underlying gait in the healthy. PMID:25389396

  17. Active Brownian particles with velocity-alignment and active fluctuations

    NASA Astrophysics Data System (ADS)

    Großmann, R.; Schimansky-Geier, L.; Romanczuk, P.

    2012-07-01

    We consider a model of active Brownian particles (ABPs) with velocity alignment in two spatial dimensions with passive and active fluctuations. Here, active fluctuations refers to purely non-equilibrium stochastic forces correlated with the heading of an individual active particle. In the simplest case studied here, they are assumed to be independent stochastic forces parallel (speed noise) and perpendicular (angular noise) to the velocity of the particle. On the other hand, passive fluctuations are defined by a noise vector independent of the direction of motion of a particle, and may account, for example, for thermal fluctuations. We derive a macroscopic description of the ABP gas with velocity-alignment interaction. Here, we start from the individual-based description in terms of stochastic differential equations (Langevin equations) and derive equations of motion for the coarse-grained kinetic variables (density, velocity and temperature) via a moment expansion of the corresponding probability density function. We focus here on the different impact of active and passive fluctuations on onset of collective motion and show how active fluctuations in the active Brownian dynamics can change the phase-transition behaviour of the system. In particular, we show that active angular fluctuations lead to an earlier breakdown of collective motion and to the emergence of a new bistable regime in the mean-field case.

  18. From Physical Activity Guidelines to a National Activity Plan

    ERIC Educational Resources Information Center

    Bornstein, Daniel B.; Pate, Russell R.

    2014-01-01

    The U.S. National Physical Activity Plan (NPAP) is a comprehensive strategic plan aimed at increasing physical activity levels in all segments of the American population. The purpose of this paper is to summarize the development of the NPAP, provide an update on the status of the NPAP, and comment on the future of the NPAP. The NPAP was released…

  19. How Active Are Your Students? Increasing Physical Activity in Schools

    ERIC Educational Resources Information Center

    Avery, Marybell; Brandt, Janet

    2010-01-01

    The U. S. Department of Health and Human Services recommends that youth engage in at least 60 minutes of physical activity each day, most of which should be either moderate- or vigorous-intensity aerobic physical activity. Half of this amount (30 minutes) should be achieved during the school day. NASPE provides guidance in the form of a…

  20. Reading Aloud Activity in L2 and Cerebral Activation

    ERIC Educational Resources Information Center

    Takeuchi, Osamu; Ikeda, Maiko; Mizumoto, Atsushi

    2012-01-01

    This article explores the cerebral mechanism of reading aloud activities in L2 learners. These activities have been widely used in L2 learning and teaching, and its effect has been reported in various Asian L2 learning contexts. However, the reasons for its effectiveness have not been examined. In order to fill in this gap, two studies using a…

  1. 101 Environmental Education Activities. Booklet 3--Mathematics Activities.

    ERIC Educational Resources Information Center

    Schaljo, Roger, Comp.

    Each of the 14 environment-related mathematics activities included in this publication by the Upper Mississippi River ECO-Center includes objectives, materials needed, preparation, and activity description. Occasionally, variations and helpful hints are added. Because the student can gain experience to help him with the practical application of…

  2. Active microrheology in active matter systems: Mobility, intermittency, and avalanches.

    PubMed

    Reichhardt, C; Reichhardt, C J Olson

    2015-03-01

    We examine the mobility and velocity fluctuations of a driven particle moving through an active matter bath of self-mobile disks for varied density or area coverage and varied activity. We show that the driven particle mobility can exhibit nonmonotonic behavior that is correlated with distinct changes in the spatiotemporal structures that arise in the active media. We demonstrate that the probe particle velocity distributions exhibit specific features in the different dynamic regimes and identify an activity-induced uniform crystallization that occurs for moderate activity levels and is distinct from the previously observed higher activity cluster phase. The velocity distribution in the cluster phase has telegraph noise characteristics produced when the probe particle moves alternately through high-mobility areas that are in the gas state and low-mobility areas that are in the dense phase. For higher densities and large activities, the system enters what we characterize as an active jamming regime. Here the probe particle moves in intermittent jumps or avalanches that have power-law-distributed sizes that are similar to the avalanche distributions observed for nonactive disk systems near the jamming transition.

  3. Basic Business and Economics: Varied Activities Encourage Active Student Involvement.

    ERIC Educational Resources Information Center

    Baker, Robert Lee, Jr.

    1978-01-01

    Describes a variety of activities for the basic business classroom, such as having guest speakers, question-and-answer sessions, simulations, role playing, debates, small group work, field trips, games, and individualized instruction. Includes a report of business teachers' knowledge of and attitudes toward these activities. (MF)

  4. Incorporation of Socio-scientific Content into Active Learning Activities

    NASA Astrophysics Data System (ADS)

    King, D. B.; Lewis, J. E.; Anderson, K.; Latch, D.; Sutheimer, S.; Webster, G.; Moog, R.

    2014-12-01

    Active learning has gained increasing support as an effective pedagogical technique to improve student learning. One way to promote active learning in the classroom is the use of in-class activities in place of lecturing. As part of an NSF-funded project, a set of in-class activities have been created that use climate change topics to teach chemistry content. These activities use the Process Oriented Guided Inquiry Learning (POGIL) methodology. In this pedagogical approach a set of models and a series of critical thinking questions are used to guide students through the introduction to or application of course content. Students complete the activities in their groups, with the faculty member as a facilitator of learning. Through assigned group roles and intentionally designed activity structure, process skills, such as teamwork, communication, and information processing, are developed during completion of the activity. Each of these climate change activities contains a socio-scientific component, e.g., social, ethical and economic data. In one activity, greenhouse gases are used to explain the concept of dipole moment. Data about natural and anthropogenic production rates, global warming potential and atmospheric lifetimes for a list of greenhouse gases are presented. The students are asked to identify which greenhouse gas they would regulate, with a corresponding explanation for their choice. They are also asked to identify the disadvantages of regulating the gas they chose in the previous question. In another activity, where carbon sequestration is used to demonstrate the utility of a phase diagram, students use economic and environmental data to choose the best location for sequestration. Too often discussions about climate change (both in and outside the classroom) consist of purely emotional responses. These activities force students to use data to support their arguments and hypothesize about what other data could be used in the corresponding discussion to

  5. Fluidization and Active Thinning by Molecular Kinetics in Active Gels

    NASA Astrophysics Data System (ADS)

    Oriola, David; Alert, Ricard; Casademunt, Jaume

    2017-02-01

    We derive the constitutive equations of an active polar gel from a model for the dynamics of elastic molecules that link polar elements. Molecular binding kinetics induces the fluidization of the material, giving rise to Maxwell viscoelasticity and, provided that detailed balance is broken, to the generation of active stresses. We give explicit expressions for the transport coefficients of active gels in terms of molecular properties, including nonlinear contributions on the departure from equilibrium. In particular, when activity favors linker unbinding, we predict a decrease of viscosity with activity—active thinning—of kinetic origin, which could explain some experimental results on the cell cortex. By bridging the molecular and hydrodynamic scales, our results could help understand the interplay between molecular perturbations and the mechanics of cells and tissues.

  6. Active Volcanism on Io: Global Distribution and Variations in Activity

    USGS Publications Warehouse

    Lopes-Gautier, R.; McEwen, A.S.; Smythe, W.B.; Geissler, P.E.; Kamp, L.; Davies, A.G.; Spencer, J.R.; Keszthelyi, L.; Carlson, R.; Leader, F.E.; Mehlman, R.; Soderblom, L.

    1999-01-01

    Io's volcanic activity has been monitored by instruments aboard the Galileo spacecraft since June 28, 1996. We present results from observations by the near-infrared mapping spectrometer (NIMS) for the first 10 orbits of Galileo, correlate them with results from the Solid State Imaging System (SSI) and from groundbased observations, and compare them to what was known about Io's volcanic activity from observations made during the two Voyager flybys in 1979. A total of 61 active volcanic centers have been identified from Voyager, groundbased, and Galileo observations. Of these, 41 are hot spots detected by NIMS and/or SSI. Another 25 locations were identified as possible active volcanic centers, mostly on the basis of observed surface changes. Hot spots are correlated with surface colors, particularly dark and red deposits, and generally anti-correlated with white, SO2-rich areas. Surface features corresponding to the hot spots, mostly calderas or flows, were identified from Galileo and Voyager images. Hot spot temperatures obtained from both NIMS and SSI are consistent with silicate volcanism, which appears to be widespread on Io. Two types of hot spot activity are present: persistent-type activity, lasting from months to years, and sporadic events, which may represent either short-lived activity or low-level activity that occasionally flares up. Sporadic events are not often detected, but may make an important contribution to Io's heat flow and resurfacing. The distribution of active volcanic centers on the surface does not show any clear correlation with latitude, longitude, Voyager-derived global topography, or heat flow patterns predicted by the asthenosphere and deep mantle tidal dissipation models. However, persistent hot spots and active plumes are concentrated toward lower latitudes, and this distribution favors the asthenosphere rather than the deep mantle tidal dissipation model. ?? 1999 Academic Press.

  7. Protease activities of rumen protozoa.

    PubMed Central

    Forsberg, C W; Lovelock, L K; Krumholz, L; Buchanan-Smith, J G

    1984-01-01

    Intact, metabolically active rumen protozoa prepared by gravity sedimentation and washing in a mineral solution at 10 to 15 degrees C had comparatively low proteolytic activity on azocasein and low endogenous proteolytic activity. Protozoa washed in 0.1 M potassium phosphate buffer (pH 6.8) at 4 degrees C and stored on ice autolysed when they were warmed to 39 degrees C. They also exhibited low proteolytic activity on azocasein, but they had a high endogenous proteolytic activity with a pH optimum of 5.8. The endogenous proteolytic activity was inhibited by cysteine proteinase inhibitors, for example, iodoacetate (63.1%) and the aspartic proteinase inhibitor, pepstatin (43.9%). Inhibitors specific for serine proteinases and metalloproteinases were without effect. The serine and cysteine proteinase inhibitors of microbial origin, including antipain, chymostatin, and leupeptin, caused up to 67% inhibition of endogenous proteolysis. Hydrolysis of casein by protozoa autolysates was also inhibited by cysteine proteinase inhibitors. Some of the inhibitors decreased endogenous deamination, in particular, phosphoramidon, which had little inhibitory effect on proteolysis. Protozoal and bacterial preparations exhibited low hydrolytic activities on synthetic proteinase and carboxypeptidase substrates, although the protozoa had 10 to 78 times greater hydrolytic activity (per milligram of protein) than bacteria on the synthetic aminopeptidase substrates L-leucine-p-nitroanilide, L-leucine-beta-naphthylamide, and L-leucinamide. The aminopeptidase activity was partially inhibited by bestatin. It was concluded that cysteine proteinases and, to a lesser extent, aspartic proteinases are primarily responsible for proteolysis in autolysates of rumen protozoa. The protozoal autolysates had high aminopeptidase activity; low deaminase activity was observed on endogenous amino acids. PMID:6364968

  8. NSLS 2009 Activity Report

    SciTech Connect

    Nasta K.; Mona R.

    2009-05-01

    2009 was an incredibly exciting year for light sources at Brookhaven. The National Synchrotron Light Source (NSLS) hosted more than 2,200 visiting researchers, who, along with the about 50 members of our scientific staff, produced a total of 957 publications - about 20 percent of which appeared in premier journals. Covering topics ranging from Alzheimer's disease detection to ethanol-powered fuel cells, a sampling of these findings can be found in this Activity Report. We've also seen the resurfacing of some of our long-time users hard work. I was very proud to hear that two of the three recipients of the 2009 Nobel Prize in Chemistry have ties to the NSLS. Venki Ramakrishnan, a former employee in Brookhaven's biology department and long-time user of the NSLS, now at Cambridge University, and Thomas A. Steitz of Yale University, also a long-time NSLS user, shared the prize with Ada E. Yonath of the Weizmann Institute of Science for their work on the structure and function of the ribosome. In the late 1990s, Ramakrishnan and Steitz used protein crystallography at the NSLS to gather atomic-level images of two ribosome subunits: 30S (Ramakrishnan) and 50S (Steitz). Both laureates solved the high-resolution structures for these subunits based on this data. After struggling with a rough budget for several years, we received excellent funding, and then some, this year. In addition to NSLS operations funding, we received $3 million in funds from the American Recovery and Reinvestment Act (ARRA). We used that additional money for two exciting projects: construction of a full-field x-ray microscope and acquisition of several advanced x-ray detectors. The x-ray microscope will be able to image objects with a targeted spatial resolution of 30 nanometers. This capability will be particularly important for new initiatives in energy research and will prepare our users for the projected 1-nanometer resolution benchmark at the National Synchrotron Light Source II (NSLS-II). The

  9. World Cultures through Art Activities.

    ERIC Educational Resources Information Center

    Robinson, Dindy

    The guide is intended to be a supplement to multicultural units in primary grades. The activities are freehand and students should be encouraged to use their imaginations and ideas to improve on a design. The approach is based on a whole language philosophy of learning with simple art activities that encourage creativity and critical thinking in…

  10. Interdisciplinarity in Adapted Physical Activity

    ERIC Educational Resources Information Center

    Bouffard, Marcel; Spencer-Cavaliere, Nancy

    2016-01-01

    It is commonly accepted that inquiry in adapted physical activity involves the use of different disciplines to address questions. It is often advanced today that complex problems of the kind frequently encountered in adapted physical activity require a combination of disciplines for their solution. At the present time, individual research…

  11. Outdoor Recreation Activities at Cispus.

    ERIC Educational Resources Information Center

    Cispus Environmental Center, Randle, WA.

    Most of the activities in this booklet have been developed around skills related to the outdoors and, in particular, to the logging industry and forest fire fighting. The activities attempt to develop muscles, coordination skills, and teamwork. They also give the students (junior high school or high school) and staff the opportunity to do…

  12. Antimicrobial activity of Securidaca longipedunculata.

    PubMed

    Ajali, U; Chukwurah, B K C

    2004-11-01

    The folk herbal uses of Securidaca longipedunculata in the treatment of diarrhea, boils, gonorrhea, and cough prompted phytochemical analyses and antimicrobial activity screening of extracts of the root. Some flavonoids isolated showed activity against many micro-organisms. These flavonoids were isolated using chromatographic methods.

  13. Getting Active in the Classroom

    ERIC Educational Resources Information Center

    Yerigan, Tanya

    2008-01-01

    This paper presents active learning theory and how implementation of dynamic instruction strategies can transform the K-12 classroom. A multi-part study was conducted to determine both the level of active learning knowledge among participants and applicability of newly acquired approaches within the participants' classrooms. First, teachers were…

  14. Cancer, physical activity, and exercise.

    PubMed

    Brown, Justin C; Winters-Stone, Kerri; Lee, Augustine; Schmitz, Kathryn H

    2012-10-01

    This review examines the relationship between physical activity and cancer along the cancer continuum, and serves as a synthesis of systematic and meta-analytic reviews conducted to date. There exists a large body of epidemiologic evidence that conclude those who participate in higher levels of physical activity have a reduced likelihood of developing a variety of cancers compared to those who engage in lower levels of physical activity. Despite this observational evidence, the causal pathway underlying the association between participation in physical activity and cancer risk reduction remains unclear. Physical activity is also a useful adjunct to improve the deleterious sequelae experienced during cancer treatment. These deleterious sequelae may include fatigue, muscular weakness, deteriorated functional capacity, and many others. The benefits of physical activity during cancer treatment are similar to those experienced after treatment. Despite the growing volume of literature examining physical activity and cancer across the cancer continuum, a number of research gaps exist. There is little evidence on the safety of physical activity among all cancer survivors, as most trials have selectively recruited participants. The specific dose of exercise needed to optimize primary cancer prevention or symptom control during and after cancer treatment remains to be elucidated.

  15. Student Perceptions of Active Learning

    ERIC Educational Resources Information Center

    Lumpkin, Angela; Achen, Rebecca M.; Dodd, Regan K.

    2015-01-01

    A paradigm shift from lecture-based courses to interactive classes punctuated with engaging, student-centered learning activities has begun to characterize the work of some teachers in higher education. Convinced through the literature of the values of using active learning strategies, we assessed through an action research project in five college…

  16. Isomorphism: Many Paths, One Activity.

    ERIC Educational Resources Information Center

    Foster, John

    The creation of isomorphic activities can be accomplished when an instructor with a broad repertoire of activities applies a clear definition of purpose to a strong understanding of the clients involved. Experiential education is based on the use of experience to increase human potential. In order to capitalize on specific behaviors for focused…

  17. Manitoba oil activity review, 1997

    SciTech Connect

    1998-12-01

    Annual review is presented of Manitoba Crown oil and gas dispositions, mineral owner leasing and revenue, geophysical and drilling activity, areas of activity, oil production and markets, oil prices, value of production, provincial revenue from oil production, surface owners, spills and reclamation, municipal taxes, the Manitoba Drilling Incentive Program, oil reserves, oil industry expenditures, and industry employment. Highlights of the current year are included.

  18. Activity Book. Celebrate Apollo 11.

    ERIC Educational Resources Information Center

    Barchert, Linda; And Others

    1994-01-01

    An activity book helps students learn about the 1969 Apollo 11 mission to the moon as they get a sense of the mission's impact on their lives. The activities enhance understanding of science, math, social studies, and language arts. A teacher's page offers information on books, magazines, computer materials, and special resources. (SM)

  19. Energy Model of Neuron Activation.

    PubMed

    Romanyshyn, Yuriy; Smerdov, Andriy; Petrytska, Svitlana

    2017-02-01

    On the basis of the neurophysiological strength-duration (amplitude-duration) curve of neuron activation (which relates the threshold amplitude of a rectangular current pulse of neuron activation to the pulse duration), as well as with the use of activation energy constraint (the threshold curve corresponds to the energy threshold of neuron activation by a rectangular current pulse), an energy model of neuron activation by a single current pulse has been constructed. The constructed model of activation, which determines its spectral properties, is a bandpass filter. Under the condition of minimum-phase feature of the neuron activation model, on the basis of Hilbert transform, the possibilities of phase-frequency response calculation from its amplitude-frequency response have been considered. Approximation to the amplitude-frequency response by the response of the Butterworth filter of the first order, as well as obtaining the pulse response corresponding to this approximation, give us the possibility of analyzing the efficiency of activating current pulses of various shapes, including analysis in accordance with the energy constraint.

  20. In Defense of Active Learning

    ERIC Educational Resources Information Center

    Pica, Rae

    2008-01-01

    Effective early childhood teachers use what they know about and have observed in young children to design programs to meet children's developmental needs. Play and active learning are key tools to address those needs and facilitate children's early education. In this article, the author discusses the benefits of active learning in the education of…