The S100P/RAGE signaling pathway regulates expression of microRNA-21 in colon cancer cells.

Science.gov (United States)

Mercado-Pimentel, Melania E; Onyeagucha, Benjamin C; Li, Qing; Pimentel, Angel C; Jandova, Jana; Nelson, Mark A

2015-08-19

S100P signaling through the receptor for advanced glycation end-products (RAGE) contributes to colon cancer invasion and metastasis, but the mechanistic features of this process are obscure. Here, we investigate whether activation of S100P/RAGE signaling regulates oncogenic microRNA-21 (miR-21). We show that exogenous S100P up-regulates miR-21 levels in human colon cancer cells, whereas knockdown of S100P results in a decrease of miR-21. Furthermore, blockage of RAGE with anti-RAGE antibody suppresses S100P induction of miR-21. In addition, we found that S100P induction of miR-21 expression involves ERK and is suppressed by the MEK inhibitor U0126. Also, S100P treatment stimulates the enrichment of c-Fos, and AP-1 family members, at the miR-21 gene promoter. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

CASO AlbAm S.A.

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Ricardo Goulart Serra

2015-12-01

Full Text Available RESUMO Os analistas financeiros da AlbAm, uma empresa do setor de autopeças, devem avaliar duas opções de aquisições (Cardblue e Garciadores. O objetivo do caso é servir de oportunidade para os alunos vivenciarem uma decisão de investimentos por meio do lucro econômico. Uma análise superficial certamente levará a decisão equivocada. Levando-se todos os aspectos do caso em consideração, chegar-se-á a uma solução que pode surpreender alguns alunos, uma vez que a empresa melhor gerida não será a melhor oportunidade de investimento. Também se pode aproveitar o caso para discutir a superficialidade da adoção do EBITDA como métrica de gestão comparativamente a uma métrica de valor agregado (lucro econômico - a melhor solução também não é aquela que gera o maior aumento em EBITDA. O caso pode ser usado em disciplinas de finanças (finanças corporativas ou avaliação de empresas em cursos de graduação, pós-graduação ou especialização. Todas as empresas e pessoas relatadas neste caso são fictícias.

The 5s25p2 - (5s25p5d + 5s5p3 + 5s25p6s + 5s25p7s) transitions in Sb II and 5s25p - (5s5p2 + 5s2nl) transitions in Sb III

International Nuclear Information System (INIS)

Arcimowicz, B.; Joshi, Y.N.; Kaufman, V.

1989-01-01

The spectrum of antimony was photographed in the 575-2300 A region (1A 10 -10 m) using a hollow cathode and a triggered spark source. The analysis of the 5s 2 5p 2 - (5s 2 5p5d + 5s5p 3 + 5s 2 5p6s + 5s 2 5p7s) transitions in Sb II spectrum was revised and interpreted on the basis of multiconfiguration interaction calculations. Accurate wavelength measurements of Sb III lines lead to a revised ground-state 5s 2 5p 2 P interval value of 6574.5 cm -1 . (author). 15 refs., 9 tabs., 1 fig

Cytochrome P450s--Their expression, regulation, and role in insecticide resistance.

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Liu, Nannan; Li, Ming; Gong, Youhui; Liu, Feng; Li, Ting

2015-05-01

P450s are known to be critical for the detoxification and/or activation of xenobiotics such as drugs and pesticides and overexpression of P450 genes can significantly affect the disposition of xenobiotics in the tissues of organisms, altering their pharmacological/toxicological effects. In insects, P450s play an important role in detoxifying exogenous compounds such as insecticides and plant toxins and their overexpression can result in increased levels of P450 proteins and P450 activities. This has been associated with enhanced metabolic detoxification of insecticides and has been implicated in the development of insecticide resistance in insects. Multiple P450 genes have been found to be co-overexpressed in individual insect species via several constitutive overexpression and induction mechanisms, which in turn are co-responsible for high levels of insecticide resistance. Many studies have also demonstrated that the transcriptional overexpression of P450 genes in resistant insects is regulated by trans and/or cis regulatory genes/factors. Taken together, these earlier findings suggest not only that insecticide resistance is conferred via multi-resistance P450 genes, but also that it is mediated through the interaction of regulatory genes/factors and resistance genes. This chapter reviews our current understanding of how the molecular mechanisms of P450 interaction/gene regulation govern the development of insecticide resistance in insects and our progress along the road to a comprehensive characterization of P450 detoxification-mediated insecticide resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

Selective coupling of the S1P3 receptor subtype to S1P-mediated RhoA activation and cardioprotection.

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Yung, Bryan S; Brand, Cameron S; Xiang, Sunny Y; Gray, Charles B B; Means, Christopher K; Rosen, Hugh; Chun, Jerold; Purcell, Nicole H; Brown, Joan Heller; Miyamoto, Shigeki

2017-02-01

Sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, is generated and released at sites of tissue injury in the heart and can act on S1P 1 , S1P 2 , and S1P 3 receptor subtypes to affect cardiovascular responses. We established that S1P causes little phosphoinositide hydrolysis and does not induce hypertrophy indicating that it does not cause receptor coupling to G q . We previously demonstrated that S1P confers cardioprotection against ischemia/reperfusion by activating RhoA and its downstream effector PKD. The S1P receptor subtypes and G proteins that regulate RhoA activation and downstream responses in the heart have not been determined. Using siRNA or pertussis toxin to inhibit different G proteins in NRVMs we established that S1P regulates RhoA activation through Gα 13 but not Gα 12 , Gα q , or Gα i . Knockdown of the three major S1P receptors using siRNA demonstrated a requirement for S1P 3 in RhoA activation and subsequent phosphorylation of PKD, and this was confirmed in studies using isolated hearts from S1P 3 knockout (KO) mice. S1P treatment reduced infarct size induced by ischemia/reperfusion in Langendorff perfused wild-type (WT) hearts and this protection was abolished in the S1P 3 KO mouse heart. CYM-51736, an S1P 3 -specific agonist, also decreased infarct size after ischemia/reperfusion to a degree similar to that achieved by S1P. The finding that S1P 3 receptor- and Gα 13 -mediated RhoA activation is responsible for protection against ischemia/reperfusion suggests that selective targeting of S1P 3 receptors could provide therapeutic benefits in ischemic heart disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical and genetic tools to explore S1P biology.

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Cahalan, Stuart M

2014-01-01

The zwitterionic lysophospholipid Sphingosine 1-Phosphate (S1P) is a pleiotropic mediator of physiology and pathology. The synthesis, transport, and degradation of S1P are tightly regulated to ensure that S1P is present in the proper concentrations in the proper location. The binding of S1P to five G protein-coupled S1P receptors regulates many physiological systems, particularly the immune and vascular systems. Our understanding of the functions of S1P has been aided by the tractability of the system to both chemical and genetic manipulation. Chemical modulators have been generated to affect most of the known components of S1P biology, including agonists of S1P receptors and inhibitors of enzymes regulating S1P production and degradation. Genetic knockouts and manipulations have been similarly engineered to disrupt the functions of individual S1P receptors or enzymes involved in S1P metabolism. This chapter will focus on the development and utilization of these chemical and genetic tools to explore the complex biology surrounding S1P and its receptors, with particular attention paid to the in vivo findings that these tools have allowed for.

77 FR 35888 - Airworthiness Directives; PIAGGIO AERO INDUSTRIES S.p.A Airplanes

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2012-06-15

...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service.... Relevant Service Information PIAGGIO AERO INDUSTRIES S.p.A. has issued Service Bulletin No. 80- 0318, dated... Instructions of Piaggio Aero Industries S.p.A. Mandatory Service Bulletin No. 80-0318, revision 2, dated March...

sRNA-Mediated Regulation of P-Fimbriae Phase Variation in Uropathogenic Escherichia coli

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Khandige, Surabhi; Kronborg, Tina; Uhlin, Bernt Eric

2015-01-01

Uropathogenic Escherichia coli (UPEC) are capable of occupying physiologically distinct intracellular and extracellular niches within the urinary tract. This feat requires the timely regulation of gene expression and small RNAs (sRNAs) are known to mediate such rapid adjustments in response to ch...... to changing environmental cues. This study aimed to uncover sRNA-mediated gene regulation in the UPEC strain UTI89, during infection of bladder epithelial cells. Hfq is an RNA chaperone known to facilitate and stabilize sRNA and target mRNA interactions with bacterial cells. The co...... to the discovery of a novel virulence-associated trans-acting sRNA-PapR. Deletion of papR was found to enhance adhesion of UTI89 to both bladder and kidney cell lines in a manner independent of type-1 fimbriae. We demonstrate PapR mediated posttranscriptional repression of the P-fimbriae phase regulator gene pap...

Sphingosine 1-Phosphate (S1P) Carrier-dependent Regulation of Endothelial Barrier

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Wilkerson, Brent A.; Grass, G. Daniel; Wing, Shane B.; Argraves, W. Scott; Argraves, Kelley M.

2012-01-01

Sphingosine 1-phosphate (S1P) is a blood-borne lysosphingolipid that acts to promote endothelial cell (EC) barrier function. In plasma, S1P is associated with both high density lipoproteins (HDL) and albumin, but it is not known whether the carriers impart different effects on S1P signaling. Here we establish that HDL-S1P sustains EC barrier longer than albumin-S1P. We showed that the sustained barrier effects of HDL-S1P are dependent on signaling by the S1P receptor, S1P1, and involve persistent activation of Akt and endothelial NOS (eNOS), as well as activity of the downstream NO target, soluble guanylate cyclase (sGC). Total S1P1 protein levels were found to be higher in response to HDL-S1P treatment as compared with albumin-S1P, and this effect was not associated with increased S1P1 mRNA or dependent on de novo protein synthesis. Several pieces of evidence indicate that long term EC barrier enhancement activity of HDL-S1P is due to specific effects on S1P1 trafficking. First, the rate of S1P1 degradation, which is proteasome-mediated, was slower in HDL-S1P-treated cells as compared with cells treated with albumin-S1P. Second, the long term barrier-promoting effects of HDL-S1P were abrogated by treatment with the recycling blocker, monensin. Finally, cell surface levels of S1P1 and levels of S1P1 in caveolin-enriched microdomains were higher after treatment with HDL-S1P as compared with albumin-S1P. Together, the findings reveal S1P carrier-specific effects on S1P1 and point to HDL as the physiological mediator of sustained S1P1-PI3K-Akt-eNOS-sGC-dependent EC barrier function. PMID:23135269

Significance of changes of plasma levels of AM, CGRP, sICAM-1 and THcy in patients with pregnancy induced hypertension (PIM)

International Nuclear Information System (INIS)

Xu Fei; Chen Daozhen; Wang Junfeng; Yang Min; Pan Donghui

2009-01-01

Objective: To study the relationship between changes of plasma levels of adrenomedullin(AM), calcitonin-gene-related peptide(CGRP), soluble intercellular adhesion molecule-1(sICAM-1), total homocysteine(THcy) and the progression of disease in patients with PIH. Methods: Plasma AM, CGRP(with RIA), sICAM-1(with ELISA) and THcy(with CLIA) levels were measured in 1)35 non-pregnant women 2) 35 normal pregnant women and 3) 35 women with PIH(both before and after two weeks' treatment). Results: The plasma AM levels in normal pregnant women were insignificantly higher than those in non-pregnant women (P>0.05). The plasma AM levels in patients with PIH before treatment were significantly higher than those in normal pregnant women (P 0.05). Both plasma sICAM-1 and THcy levels in normal pregnant women were insignificantly higher than those in non-pregnant women. The levels were significantly higher in patients with PIH before treatment than those in normal pregnant women and became only insignificantly higher after treatment. Conclusion: Changes of plasma levels of AM, CGRP, sICAM-1 and THcy were closely related to the disease process in patients with PIH. (authors)

Berberine reduces fibronectin expression by suppressing the S1P-S1P2 receptor pathway in experimental diabetic nephropathy models.

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Kaipeng Huang

Full Text Available The accumulation of glomerular extracellular matrix (ECM is one of the critical pathological characteristics of diabetic renal fibrosis. Fibronectin (FN is an important constituent of ECM. Our previous studies indicate that the activation of the sphingosine kinase 1 (SphK1-sphingosine 1- phosphate (S1P signaling pathway plays a key regulatory role in FN production in glomerular mesangial cells (GMCs under diabetic condition. Among the five S1P receptors, the activation of S1P2 receptor is the most abundant. Berberine (BBR treatment also effectively inhibits SphK1 activity and S1P production in the kidneys of diabetic models, thus improving renal injury. Based on these data, we further explored whether BBR could prevent FN production in GMCs under diabetic condition via the S1P2 receptor. Here, we showed that BBR significantly down-regulated the expression of S1P2 receptor in diabetic rat kidneys and GMCs exposed to high glucose (HG and simultaneously inhibited S1P2 receptor-mediated FN overproduction. Further, BBR also obviously suppressed the activation of NF-κB induced by HG, which was accompanied by reduced S1P2 receptor and FN expression. Taken together, our findings suggest that BBR reduces FN expression by acting on the S1P2 receptor in the mesangium under diabetic condition. The role of BBR in S1P2 receptor expression regulation could closely associate with its inhibitory effect on NF-κB activation.

A Serratia marcescens PigP homolog controls prodigiosin biosynthesis, swarming motility and hemolysis and is regulated by cAMP-CRP and HexS.

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Robert M Q Shanks

Full Text Available Swarming motility and hemolysis are virulence-associated determinants for a wide array of pathogenic bacteria. The broad host-range opportunistic pathogen Serratia marcescens produces serratamolide, a small cyclic amino-lipid, that promotes swarming motility and hemolysis. Serratamolide is negatively regulated by the transcription factors HexS and CRP. Positive regulators of serratamolide production are unknown. Similar to serratamolide, the antibiotic pigment, prodigiosin, is regulated by temperature, growth phase, HexS, and CRP. Because of this co-regulation, we tested the hypothesis that a homolog of the PigP transcription factor of the atypical Serratia species ATCC 39006, which positively regulates prodigiosin biosynthesis, is also a positive regulator of serratamolide production in S. marcescens. Mutation of pigP in clinical, environmental, and laboratory strains of S. marcescens conferred pleiotropic phenotypes including the loss of swarming motility, hemolysis, and severely reduced prodigiosin and serratamolide synthesis. Transcriptional analysis and electrophoretic mobility shift assays place PigP in a regulatory pathway with upstream regulators CRP and HexS. The data from this study identifies a positive regulator of serratamolide production, describes novel roles for the PigP transcription factor, shows for the first time that PigP directly regulates the pigment biosynthetic operon, and identifies upstream regulators of pigP. This study suggests that PigP is important for the ability of S. marcescens to compete in the environment.

Inhibition of p70S6K2 down-regulates Hedgehog/GLI pathway in non-small cell lung cancer cell lines

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Kotani Hidehito

2009-07-01

Full Text Available Abstract Background The Hedgehog (HH pathway promotes tumorigenesis in a diversity of cancers. Activation of the HH signaling pathway is caused by overexpression of HH ligands or mutations in the components of the HH/GLI1 cascade, which lead to increased transactivation of GLI transcription factors. Although negative kinase regulators that antagonize the activity of GLI transcription factors have been reported, including GSK3β, PKA and CK1s, little is known regarding positive kinase regulators that are suitable for use on cancer therapeutic targets. The present study attempted to identify kinases whose silencing inhibits HH/GLI signalling in non-small cell lung cancer (NSCLC. Results To find positive kinase regulators in the HH pathway, kinome-wide siRNA screening was performed in a NSCLC cell line, A549, harboring the GLI regulatory reporter gene. This showed that p70S6K2-silencing remarkably reduced GLI reporter gene activity. The decrease in the activity of the HH pathway caused by p70S6K2-inhibition was accompanied by significant reduction in cell viability. We next investigated the mechanism for p70S6K2-mediated inhibition of GLI1 transcription by hypothesizing that GSK3β, a negative regulator of the HH pathway, is activated upon p70S6K2-silencing. We found that phosphorylated-GSK3β (Ser9 was reduced by p70S6K2-silencing, causing a decreased level of GLI1 protein. Finally, to further confirm the involvement of p70S6K2 in GLI1 signaling, down-regulation in GLI-mediated transcription by PI3KCA-inhibition was confirmed, establishing the pivotal role of the PI3K/p70S6K2 pathway in GLI1 cascade regulation. Conclusion We report herein that inhibition of p70S6K2, known as a downstream effector of the PI3K pathway, remarkably decreases GLI-mediated transactivation in NSCLC by reducing phosphorylated-GSK3β followed by GLI1 degradation. These results infer that p70S6K2 is a potential therapeutic target for NSCLC with hyperactivated HH/GLI pathway.

Smad3 deficiency leads to mandibular condyle degradation via the sphingosine 1-phosphate (S1P)/S1P3 signaling axis.

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Mori, Hiroki; Izawa, Takashi; Tanaka, Eiji

2015-10-01

Temporomandibular joint osteoarthritis is a degenerative disease that is characterized by permanent cartilage destruction. Transforming growth factor (TGF)-β is one of the most abundant cytokines in the bone matrix and is shown to regulate the migration of osteoprogenitor cells. It is hypothesized that TGF-β/Smad3 signaling affects cartilage homeostasis by influencing sphingosine 1-phosphate (S1P)/S1P receptor signaling and chondrocyte migration. We therefore investigated the molecular mechanisms by which crosstalk may occur between TGF-β/Smad3 and S1P/S1P receptor signaling to maintain condylar cartilage and to prevent temporomandibular joint osteoarthritis. Abnormalities in the condylar subchondral bone, including dynamic changes in bone mineral density and microstructure, were observed in Smad3(-/-) mice by microcomputed tomography. Cell-free regions and proteoglycan loss characterized the cartilage degradation present, and increased numbers of apoptotic chondrocytes and matrix metalloproteinase 13(+) chondrocytes were also detected. Furthermore, expression of S1P receptor 3 (S1P3), but not S1P1 or S1P2, was significantly down-regulated in the condylar cartilage of Smad3(-/-) mice. By using RNA interference technology and pharmacologic tools, S1P was found to transactivate Smad3 in an S1P3/TGF-β type II receptor-dependent manner, and S1P3 was found to be required for TGF-β-induced migration of chondrocyte cells and downstream signal transduction via Rac1, RhoA, and Cdc42. Taken together, these results indicate that the Smad3/S1P3 signaling pathway plays an important role in the pathogenesis of temporomandibular joint osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

78 FR 54596 - Airworthiness Directives; AgustaWestland S.p.A. (Type Certificate Formerly Held by Agusta S.p.A...

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2013-09-05

... Internet at http://www.regulations.gov or in person at the Docket Operations Office between 9 a.m. and 5 p... relating to the economic, environmental, energy, or federalism impacts that might result from adopting the... exceeded their life limit. The BTs also provide instructions for mixed usage of the affected blades. The...

Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration.

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Koch, Alexander; Jäger, Manuel; Völzke, Anja; Grammatikos, Georgios; Zu Heringdorf, Dagmar Meyer; Huwiler, Andrea; Pfeilschifter, Josef

2015-06-01

Sphingosine 1-phosphate (S1P) is generated by sphingosine kinase (SK)-1 and -2 and acts mainly as an extracellular ligand at five specific receptors, denoted S1P1-5. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration and survival. Previously, we showed that dexamethasone enhances SK-1 activity and S1P formation, which protected mesangial cells from stress-induced apoptosis. Here we demonstrate that dexamethasone treatment lowered S1P1 mRNA and protein expression levels in rat mesangial cells. This effect was abolished in the presence of the glucocorticoid receptor antagonist RU-486. In addition, in vivo studies showed that dexamethasone downregulated S1P1 expression in glomeruli isolated from mice treated with dexamethasone (10 mg/kg body weight). Functionally, we identified S1P1 as a key player mediating S1P-induced mesangial cell migration. We show that dexamethasone treatment significantly lowered S1P-induced migration of mesangial cells, which was again reversed in the presence of RU-486. In summary, we suggest that dexamethasone inhibits S1P-induced mesangial cell migration via downregulation of S1P1. Overall, these results demonstrate that dexamethasone has functional important effects on sphingolipid metabolism and action in renal mesangial cells.

Interplay between Trx-1 and S100P promotes colorectal cancer cell epithelial-mesenchymal transition by up-regulating S100A4 through AKT activation.

Science.gov (United States)

Zuo, Zhigui; Zhang, Peili; Lin, Feiyan; Shang, Wenjing; Bi, Ruichun; Lu, Fengying; Wu, Jianbo; Jiang, Lei

2018-04-01

We previously reported a novel positive feedback loop between thioredoxin-1 (Trx-1) and S100P, which promotes the invasion and metastasis of colorectal cancer (CRC). However, the underlying molecular mechanisms remain poorly understood. In this study, we examined the roles of Trx-1 and S100P in CRC epithelial-to-mesenchymal transition (EMT) and their underlying mechanisms. We observed that knockdown of Trx-1 or S100P in SW620 cells inhibited EMT, whereas overexpression of Trx-1 or S100P in SW480 cells promoted EMT. Importantly, S100A4 and the phosphorylation of AKT were identified as potential downstream targets of Trx-1 and S100P in CRC cells. Silencing S100A4 or inhibition of AKT phosphorylation eliminated S100P- or Trx-1-mediated CRC cell EMT, migration and invasion. Moreover, inhibition of AKT activity reversed S100P- or Trx-1-induced S100A4 expression. The expression of S100A4 was higher in human CRC tissues compared with their normal counterpart tissues and was significantly correlated with lymph node metastasis and poor survival. The overexpression of S100A4 protein was also positively correlated with S100P or Trx-1 protein overexpression in our cohort of CRC tissues. In addition, overexpression of S100P reversed the Trx-1 knockdown-induced inhibition of S100A4 expression, EMT and migration and invasion in SW620 cells. The data suggest that interplay between Trx-1 and S100P promoted CRC EMT as well as migration and invasion by up-regulating S100A4 through AKT activation, thus providing further potential therapeutic targets for suppressing the EMT in metastatic CRC. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The Yin and Yang of SagS: Distinct Residues in the HmsP Domain of SagS Independently Regulate Biofilm Formation and Biofilm Drug Tolerance

Science.gov (United States)

Dingemans, Jozef; Poudyal, Bandita

2018-01-01

ABSTRACT The formation of inherently drug-tolerant biofilms by the opportunistic pathogen Pseudomonas aeruginosa requires the sensor-regulator hybrid SagS, with ΔsagS biofilms being unstructured and exhibiting increased antimicrobial susceptibility. Recent findings indicated SagS to function as a switch to control biofilm formation and drug tolerance independently. Moreover, findings suggested the periplasmic sensory HmsP domain of SagS is likely to be the control point in the regulation of biofilm formation and biofilm cells transitioning to a drug-tolerant state. We thus asked whether specific amino acid residues present in the HmsP domain contribute to the switch function of SagS. HmsP domain residues were therefore subjected to alanine replacement mutagenesis to identify substitutions that block the sensory function(s) of SagS, which is apparent by attached cells being unable to develop mature biofilms and/or prevent transition to an antimicrobial-resistant state. Mutant analyses revealed 32 residues that only contribute to blocking one sensory function. Moreover, amino acid residues affecting attachment and subsequent biofilm formation but not biofilm tolerance also impaired histidine kinase signaling via BfiS. In contrast, residues affecting biofilm drug tolerance but not attachment and subsequent biofilm formation negatively impacted BrlR transcription factor levels. Structure prediction suggested the two sets of residues affecting sensory functions are located in distinct areas that were previously described as being involved in ligand binding interactions. Taken together, these studies identify the molecular basis for the dual regulatory function of SagS. IMPORTANCE The membrane-bound sensory protein SagS plays a pivotal role in P. aeruginosa biofilm formation and biofilm cells gaining their heightened resistance to antimicrobial agents, with SagS being the control point at which both pathways diverge. Here, we demonstrate for the first time that the two

S1P and the birth of platelets

Science.gov (United States)

Galvani, Sylvain; Rafii, Shahin; Nachman, Ralph

2012-01-01

Recent work has highlighted the multitude of biological functions of sphingosine 1-phosphate (S1P), which include roles in hematopoietic cell trafficking, organization of immune organs, vascular development, and neuroinflammation. Indeed, a functional antagonist of S1P1 receptor, FTY720/Gilenya, has entered the clinic as a novel therapeutic for multiple sclerosis. In this issue of the JEM, Zhang et al. highlight yet another function of this lipid mediator: thrombopoiesis. The S1P1 receptor is required for the growth of proplatelet strings in the bloodstream and the shedding of platelets into the circulation. Notably, the sharp gradient of S1P between blood and the interstitial fluids seems to be essential to ensure the production of platelets, and S1P appears to cooperate with the CXCL12–CXCR4 axis. Pharmacologic modulation of the S1P1 receptor altered circulating platelet numbers acutely, suggesting a potential therapeutic strategy for controlling thrombocytopenic states. However, the S1P4 receptor may also regulate thrombopoiesis during stress-induced accelerated platelet production. This work reveals a novel physiological action of the S1P/S1P1 duet that could potentially be harnessed for clinical translation. PMID:23166370

76 FR 60396 - Airworthiness Directives; Piaggio Aero Industries S.p.A. Airplanes

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2011-09-29

...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service... on other P.180 aeroplanes, and Piaggio Aero Industries (PAI) had issued Service Bulletin (SB) No. 80... information by examining the MCAI in the AD docket. Relevant Service Information Piaggio Aero Industries S.p.A...

Interaction of integrin β4 with S1P receptors in S1P- and HGF-induced endothelial barrier enhancement.

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Ni, Xiuqin; Epshtein, Yulia; Chen, Weiguo; Zhou, Tingting; Xie, Lishi; Garcia, Joe G N; Jacobson, Jeffrey R

2014-06-01

We previously reported sphingosine 1-phosphate (S1P) and hepatocyte growth factor (HGF) augment endothelial cell (EC) barrier function and attenuate murine acute lung inury (ALI). While the mechanisms underlying these effects are not fully understood, S1P and HGF both transactivate the S1P receptor, S1PR1 and integrin β4 (ITGB4) at membrane caveolin-enriched microdomains (CEMs). In the current study, we investigated the roles of S1PR2 and S1PR3 in S1P/HGF-mediated EC signaling and their associations with ITGB4. Our studies confirmed ITGB4 and S1PR2/3 are recruited to CEMs in human lung EC in response to either S1P (1 µM, 5 min) or HGF (25 ng/ml, 5 min). Co-immunoprecipitation experiments identified an S1P/HGF-mediated interaction of ITGB4 with both S1PR2 and S1PR3. We then employed an in situ proximity ligation assay (PLA) to confirm a direct ITGB4-S1PR3 association induced by S1P/HGF although a direct association was not detectable between S1PR2 and ITGB4. S1PR1 knockdown (siRNA), however, abrogated S1P/HGF-induced ITGB4-S1PR2 associations while there was no effect on ITGB4-S1PR3 associations. Moreover, PLA confirmed a direct association between S1PR1 and S1PR2 induced by S1P and HGF. Finally, silencing of S1PR2 significantly attenuated S1P/HGF-induced EC barrier enhancement as measured by transendothelial resistance while silencing of S1PR3 significantly augmented S1P/HGF-induced barrier enhancement. These results confirm an important role for S1PR2 and S1PR3 in S1P/HGF-mediated EC barrier responses that are associated with their complex formation with ITGB4. Our findings elucidate novel mechanisms of EC barrier regulation that may ultimately lead to new therapeutic targets for disorders characterized by increased vascular permeability including ALI. © 2013 Wiley Periodicals, Inc.

Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

Science.gov (United States)

Patmanathan, Sathya Narayanan; Johnson, Steven P; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R; Herr, Deron R; Murray, Paul G; Yap, Lee Fah; Paterson, Ian C

2016-05-10

Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.

78 FR 36691 - Airworthiness Directives; Piaggio Aero Industries S.p.A Airplanes

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2013-06-19

...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service... condition, Piaggio Aero Industries (PAI) issued Service Bulletin (SB) 80-0345 to provide instructions for... in the AD docket. Relevant Service Information Piaggio Aero Industries S.p.A. has issued Mandatory...

Dynamic interaction of p220NPAT and CBP/p300 promotes S-phase entry

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Wang, Aiyan; Ikura, Tsuyoshi; Eto, Kazuhiro; Ota, Masato S.

2004-01-01

Cajal bodies contain cyclin E/cdk2 and the substrate p220 NPAT to regulate the transcription of histones, which is essential for cell proliferation, however, recent mouse knockout studies indicate that cyclin E and cdk2 are dispensable for these events. Because the CBP/p300 histone acetyltransferase are also known to be involved in cell proliferation, we examined the molecular and functional interactions of p220 NPAT with the CBP/p300 at the G1/S boundary as cell cycle regulators. The subnuclear localization of p220 NPAT and CBP/p300 proteins showed that their foci partially overlapped in a cell cycle dependent manner. Overexpression of p220 NPAT and CBP/p300 cooperatively enhanced G1/S transition and DNA synthesis even without cdk2 phosphorylation site. Finally, molecular alignment analysis indicated that p220 NPAT contains several potential substrate sites for CBP/p300. Overall, our findings demonstrate that p220 NPAT and CBP/p300 form a transient complex at the G1/S boundary to play cooperative roles to promote the S-phase entry

Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling.

Science.gov (United States)

Gatfield, John; Monnier, Lucile; Studer, Rolf; Bolli, Martin H; Steiner, Beat; Nayler, Oliver

2014-07-01

The sphingosine-1-phosphate (S1P) type 1 receptor (S1P1R) is a novel therapeutic target in lymphocyte-mediated autoimmune diseases. S1P1 receptor desensitization caused by synthetic S1P1 receptor agonists prevents T-lymphocyte egress from secondary lymphoid organs into the circulation. The selective S1P1 receptor agonist ponesimod, which is in development for the treatment of autoimmune diseases, efficiently reduces peripheral lymphocyte counts and displays efficacy in animal models of autoimmune disease. Using ponesimod and the natural ligand S1P, we investigated the molecular mechanisms leading to different signaling, desensitization and trafficking behavior of S1P1 receptors. In recombinant S1P1 receptor-expressing cells, ponesimod and S1P triggered Gαi protein-mediated signaling and β-arrestin recruitment with comparable potency and efficiency, but only ponesimod efficiently induced intracellular receptor accumulation. In human umbilical vein endothelial cells (HUVEC), ponesimod and S1P triggered translocation of the endogenous S1P1 receptor to the Golgi compartment. However, only ponesimod treatment caused efficient surface receptor depletion, receptor accumulation in the Golgi and degradation. Impedance measurements in HUVEC showed that ponesimod induced only short-lived Gαi protein-mediated signaling followed by resistance to further stimulation, whereas S1P induced sustained Gαi protein-mediated signaling without desensitization. Inhibition of S1P lyase activity in HUVEC rendered S1P an efficient S1P1 receptor internalizing compound and abrogated S1P-mediated sustained signaling. This suggests that S1P lyase - by facilitating S1P1 receptor recycling - is essential for S1P-mediated sustained signaling, and that synthetic agonists are functional antagonists because they are not S1P lyase substrates. Copyright © 2014 Elsevier Inc. All rights reserved.

ClpP deletion causes attenuation of Salmonella Typhimurium virulence through mis-regulation of RpoS and indirect control of CsrA and the SPI genes

DEFF Research Database (Denmark)

Knudsen, Gitte Maegaard; Olsen, John E.; Aabo, Søren

2013-01-01

, suggesting the repression of invasion was directed through RpoS. The expression of the csrA virulence regulator was increased in the ΔclpP mutant and decreased in the rpoS : : amp and ΔclpP/rpoS : : amp mutants, indicating that ClpP affects the csrA expression level as well. Thus, this study suggests...... the proteolytic component ClpP, the stationary phase regulator RpoS and the carbon-storage regulator CsrA. However, the mechanism behind the ClpP regulation is not fully understood. To elucidate this we examined differentially expressed genes in a ΔclpP mutant compared with WT using global transcriptomic analysis...... that ClpP affects SPI1 expression and thereby virulence indirectly through its regulation of both RpoS and CsrA....

A Prokaryotic S1P Lyase Degrades Extracellular S1P In Vitro and In Vivo: Implication for Treating Hyperproliferative Disorders

Science.gov (United States)

Huwiler, Andrea; Bourquin, Florence; Kotelevets, Nataliya; Pastukhov, Oleksandr; Capitani, Guido; Grütter, Markus G.; Zangemeister-Wittke, Uwe

2011-01-01

Sphingosine-1-phosphate (S1P) regulates a broad spectrum of fundamental cellular processes like proliferation, death, migration and cytokine production. Therefore, elevated levels of S1P may be causal to various pathologic conditions including cancer, fibrosis, inflammation, autoimmune diseases and aberrant angiogenesis. Here we report that S1P lyase from the prokaryote Symbiobacterium thermophilum (StSPL) degrades extracellular S1P in vitro and in blood. Moreover, we investigated its effect on cellular responses typical of fibrosis, cancer and aberrant angiogenesis using renal mesangial cells, endothelial cells, breast (MCF-7) and colon (HCT 116) carcinoma cells as disease models. In all cell types, wild-type StSPL, but not an inactive mutant, disrupted MAPK phosphorylation stimulated by exogenous S1P. Functionally, disruption of S1P receptor signaling by S1P depletion inhibited proliferation and expression of connective tissue growth factor in mesangial cells, proliferation, migration and VEGF expression in carcinoma cells, and proliferation and migration of endothelial cells. Upon intravenous injection of StSPL in mice, plasma S1P levels rapidly declined by 70% within 1 h and then recovered to normal 6 h after injection. Using the chicken chorioallantoic membrane model we further demonstrate that also under in vivo conditions StSPL, but not the inactive mutant, inhibited tumor cell-induced angiogenesis as an S1P-dependent process. Our data demonstrate that recombinant StSPL is active under extracellular conditions and holds promise as a new enzyme therapeutic for diseases associated with increased levels of S1P and S1P receptor signaling. PMID:21829623

Sphingosine-1-Phosphate (S1P) Signaling in Neural Progenitors.

Science.gov (United States)

Callihan, Phillip; Alqinyah, Mohammed; Hooks, Shelley B

2018-01-01

Sphingosine-1-phosphate (S1P) and its receptors are important in nervous system development. Reliable in vitro human model systems are needed to further define specific roles for S1P signaling in neural development. We have described S1P-regulated signaling, survival, and differentiation in a human embryonic stem cell-derived neuroepithelial progenitor cell line (hNP1) that expresses functional S1P receptors. These cells can be further differentiated to a neuronal cell type and therefore represent a good model system to study the role of S1P signaling in human neural development. The following sections describe in detail the culture and differentiation of hNP1 cells and two assays to measure S1P signaling in these cells.

RAC1 P29S regulates PD-L1 expression in melanoma

Science.gov (United States)

Vu, Ha Linh; Rosenbaum, Sheera; Purwin, Timothy J.; Davies, Michael A.; Aplin, Andrew E.

2015-01-01

Summary Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5–9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho-protein expression, we identified cyclin B1, PD-L1, Ets-1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD-L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD-L1 is upregulated suggests that oncogenic RAC1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC1 P29S mutations with potential clinical implications as PD-L1 is a candidate biomarker for increased benefit from treatment with anti-PD1 or anti-PD-L1 antibodies. PMID:26176707

Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis

International Nuclear Information System (INIS)

Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

2012-01-01

Highlights: ► The effect of a newly developed S1P 1 -selective antagonist on angiogenic responses. ► S1P 1 is a critical component of VEGF-related angiogenic responses. ► S1P 1 -selective antagonist showed in vitro activity to inhibit angiogenesis. ► S1P 1 -selective antagonist showed in vivo activity to inhibit angiogenesis. ► The efficacy of S1P 1 -selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P 1 ) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P 1 and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P 1 -selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P 1 antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P 1 is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma.

Science.gov (United States)

Rodriguez, A M; Graef, A J; LeVine, D N; Cohen, I R; Modiano, J F; Kim, J-H

2015-01-01

Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival, but it has not been studied in tumors from dogs. S1P/S1P1 signaling will contribute to the progression of hemangiosarcoma (HSA). Thirteen spontaneous HSA tissues, 9 HSA cell lines, 8 nonmalignant tissues, including 6 splenic hematomas and 2 livers with vacuolar degeneration, and 1 endothelial cell line derived from a dog with splenic hematoma were used. This was a retrospective case series and in vitro study. Samples were obtained as part of medically necessary diagnostic procedures. Microarray, qRT-PCR, immunohistochemistry, and immunoblotting were performed to examine S1P1 expression. S1P concentrations were measured by high-performance liquid chromatography/mass spectrometry. S1P signaling was evaluated by intracellular Ca(2+) mobilization; proliferation and survival were evaluated using the MTS assay and Annexin V staining. Canine HSA cells expressed higher levels of S1P1 mRNA than nonmalignant endothelial cells. S1P1 protein was present in HSA tissues and cell lines. HSA cells appeared to produce low levels of S1P, but they selectively consumed S1P from the culture media. Exogenous S1P induced an increase in intracellular calcium as well as increased proliferation and viability of HSA cells. Prolonged treatment with FTY720, an inhibitor of S1P1 , decreased S1P1 protein expression and induced apoptosis of HSA cells. S1P/S1P1 signaling pathway functions to maintain HSA cell viability and proliferation. The data suggest that S1P1 or the S1P pathway in general could be targets for therapeutic intervention for dogs with HSA. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Les localités d’Aménagement Concerté

Directory of Open Access Journals (Sweden)

Jean Marie Théodat

2010-01-01

Full Text Available La fonction de l’aménagement d’un territoire, c’est d’offrir aux hommes un séjour plus durable et plus stable qu’eux-mêmes dans la mesure où les efforts consentis, les investissements nécessaires à la satisfaction des attentes d’une pluralité de personnes dépassent toujours en conséquences la durée d’existence de l’individu. L’aménagement suppose la durabilité des affaires humaines opposées à la vulnérabilité fortuite d’une gestion faite au hasard, selon la nature, suivant la routine des chos...

Exit Strategies: S1P Signaling and T Cell Migration.

Science.gov (United States)

Baeyens, Audrey; Fang, Victoria; Chen, Cynthia; Schwab, Susan R

2015-12-01

Whereas the role of sphingosine 1-phosphate receptor 1 (S1PR1) in T cell egress and the regulation of S1P gradients between lymphoid organs and circulatory fluids in homeostasis are increasingly well understood, much remains to be learned about S1P signaling and distribution during an immune response. Recent data suggest that the role of S1PR1 in directing cells from tissues into circulatory fluids is reprised again and again, particularly in guiding activated T cells from non-lymphoid tissues into lymphatics. Conversely, S1P receptor 2 (S1PR2), which antagonizes migration towards chemokines, confines cells within tissues. Here we review the current understanding of the roles of S1P signaling in activated T cell migration. In this context, we outline open questions, particularly regarding the shape of S1P gradients in different tissues in homeostasis and inflammation, and discuss recent strategies to measure S1P. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

Science.gov (United States)

Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

2008-09-14

PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.

Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme-A systematic review.

Science.gov (United States)

Mahajan-Thakur, Shailaja; Bien-Möller, Sandra; Marx, Sascha; Schroeder, Henry; Rauch, Bernhard H

2017-11-17

The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central regulator in the development of several cancer types. In recent years, intriguing information has become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM), the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5) and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq, and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its receptors in GBM. We further highlight the current insights into the signaling pathways considered fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.

Sexually dimorphic regulation and induction of P450s by the constitutive androstane receptor (CAR)

International Nuclear Information System (INIS)

Hernandez, J.P.; Mota, L.C.; Huang, W.; Moore, D.D.; Baldwin, W.S.

2009-01-01

The constitutive androstane receptor (CAR) is a xenosensing nuclear receptor and regulator of cytochrome P450s (CYPs). However, the role of CAR as a basal regulator of CYP expression nor its role in sexually dimorphic responses have been thoroughly studied. We investigated basal regulation and sexually dimorphic regulation and induction by the potent CAR activator TCPOBOP and the moderate CAR activator Nonylphenol (NP). NP is an environmental estrogen and one of the most commonly found environmental toxicants in Europe and the United States. Previous studies have demonstrated that NP induces several CYPs in a sexually dimorphic manner, however the role of CAR in regulating NP-mediated sexually dimorphic P450 expression and induction has not been elucidated. Therefore, wild-type and CAR-null male and female mice were treated with honey as a carrier, NP, or TCPOBOP and CYP expression monitored by QPCR and Western blotting. CAR basally regulates the expression of Cyp2c29, Cyp2b13, and potentially Cyp2b10 as demonstrated by QPCR. Furthermore, we observed a shift in the testosterone 6α/15α-hydroxylase ratio in untreated CAR-null female mice to the male pattern, which indicates an alteration in androgen status and suggests a role for androgens as CAR inverse agonists. Xenobiotic-treatments with NP and TCPOBOP induced Cyp2b10, Cyp2c29, and Cyp3a11 in a CAR-mediated fashion; however NP only induced these CYPs in females and TCPOBOP induced these CYPs in both males and females. Interestingly, Cyp2a4, was only induced in wild-type male mice by TCPOBOP suggesting Cyp2a4 induction is not sensitive to CAR-mediated induction in females. Overall, TCPOBOP and NP show similar CYP induction profiles in females, but widely different profiles in males potentially related to lower sensitivity of males to either indirect or moderate CAR activators such as NP. In summary, CAR regulates the basal and chemically inducible expression of several sexually dimorphic xenobiotic metabolizing P

Nepieciešamās profesionālās iemaņas darbā ar bērniem bibliotēkās

OpenAIRE

Jefimova, Sabīne

2006-01-01

Darbā ar bērniem bibliotēkās svarīgas ir bērnu bibliotekāra personiskās īpašības un profesionālās iemaņas. Mūsdienās profesionālam bērnu bibliotekāram tās sevī jāizkopj, jāattīsta un jāpilnveido. Bakalaura darbs “Nepieciešamās profesionālās iemaņas darbā ar bērniem bibliotēkās” atspoguļo bērnu bibliotekāru zināšanu, prasmju un iemaņu teorētiskos un praktiskos aspektus augstvērtīgai bērnu bibliotekārās apkalpošanas nodrošināšanai. Bakalaura darbā tiek skartas aktuālākās bērnu bibliotekār...

4s24p3--4s4p4 and 4s24p3--4s2fp25s transitions in Y VII, Zr VIII, Nb IX, and MoX

International Nuclear Information System (INIS)

Reader, J.; Acquista, N.

1981-01-01

Spectra of ionized Y, Zr, Nb, and Mo have been observed in sliding-spark and triggered-spark discharges on 10.7-m normal- and grazing-incidence spectrographs at the National Bureau of Standards in Washington, D. C. From these observations the 4s 2 4p 3 --4s4p 4 transitions in Y VII, Zr VIII, Nb IX, and Mo X have been identified. The 4s 2 4p 3 --4s 2 4p 2 5s transitions in Y VII-Mo X, previously identified by Rahimullah et al. [Phys. Scr. 14, 221--223 (1976); 18, 96--106 (1978)], have been confirmed. In Y VII the 4s 2 4p 3 --4s 2 4p 2 6s and 4s4p 4 --4p 5 transition also have been found. The parameters obtained from least-squares fits to the energy levels are compared with Hartree--Fock calculations. Preliminary values of the ionization energies have been determined as 110.02 +- 0.15 eV for Y VII, 133.7 +- 0.5 eV for Zr VIII, 159.2 +- 0.7 eV for Nb IX, and 186.4 +- 1.2 eV for Mo X

S P Panda

Indian Academy of Sciences (India)

Home; Journals; Sadhana. S P Panda. Articles written in Sadhana. Volume 40 Issue 1 February 2015 pp 89-106 Electrical and Computer Sciences. Experimental validation of waveform relaxation technique for power system controller testing · S P Panda K A Salunkhe A M Kulkarni · More Details Abstract Fulltext PDF.

Ceramide synthase 2 facilitates S1P-dependent egress of thymocytes into the circulation in mice.

Science.gov (United States)

Rieck, Michael; Kremser, Christiane; Jobin, Katarzyna; Mettke, Elisabeth; Kurts, Christian; Gräler, Markus; Willecke, Klaus; Kolanus, Waldemar

2017-04-01

Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine. We, therefore, investigated whether Cers2 is involved in the regulation of S1P gradients and S1P-dependent egress into the circulation. By analyzing Cers2-deficient mice, we demonstrate that Cers2 limits the levels of S1P in thymus and blood to maintain functional S1P gradients that mediate thymocyte emigration into the circulation. This function is specific for Cers2, as we also show that Cers4 is not involved in the regulation of thymic egress. Our study identified Cers2 as an important regulator of S1P-dependent thymic egress, and thus contributes to the understanding of how S1P gradients are maintained in vivo. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3.

Science.gov (United States)

Lee, Hui Min; Lo, Kwok-Wai; Wei, Wenbin; Tsao, Sai Wah; Chung, Grace Tin Yun; Ibrahim, Maha Hafez; Dawson, Christopher W; Murray, Paul G; Paterson, Ian C; Yap, Lee Fah

2017-05-01

Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

P-S & S-P Elastic Wave Conversions from Linear Arrays of Oriented Microcracks

Science.gov (United States)

Jiang, L.; Modiriasari, A.; Bobet, A.; Pyrak-Nolte, L. J.

2017-12-01

Natural and induced processes can produce oriented mechanical discontinuities such as en echelon cracks, fractures and faults. Previous research has shown that compressional to shear (P-S) wave conversions occur at normal incidence to a fracture because of cross-coupling fracture compliances (Nakagawa et al., 2000). Here, experiments and computer simulation are presented to demonstrate the link among cross-coupling stiffness, microcrack orientation and energy partitioning among P, S, and P-S/S-P waves. A FormLabs 2 3D printer was used to fabricate 7 samples (50 mm x 50 mm x 100 mm) with linear arrays of microcracks oriented at 0, 15, 30, 45, 60, 75, and 900 with a print resolution of 0.025 mm. The microcracks were elliptical in cross-sections (2 mm long by 1 mm wide), through the 50 mm thickness of sample, and spaced 3 mm (center-to-center for adjacent cracks). A 25 mm length of each sample contained no microcracks to act as a reference material. Broadband transducers (0.2-1.5 MHz) were used to transmit and receive P and polarized S wave signals that were propagated at normal incidence to the linear array of microcracks. P-wave amplitude increased, while S-wave amplitude remained relatively constant, as the microcrack orientation increased from 0o to 90o. At normal incidence, P-S and S-P wave conversions emerged and increased in amplitude as the crack inclination increased from 00 to 450. From 450 to 900, the amplitude of these converted modes decreased. Between negative and positive crack angles, the P-to-S and S-to-P waves were 1800 phase reversed. The observed energy partitioning matched the computed compliances obtained from numerical simulations with ABAQUS. The cross-coupling compliance for cracks inclined at 450 was found to be the smallest magnitude. 3D printing enabled the study of microstructural effects on macro-scale wave measurements. Information on the orientation of microcracks or even en echelon fractures and faults is contained in P-S conversions

Regulation of P450-mediated permethrin resistance in Culex quinquefasciatus by the GPCR/Gαs/AC/cAMP/PKA signaling cascade.

Science.gov (United States)

Li, Ting; Liu, Nannan

2017-12-01

This study explores the role of G-protein-coupled receptor-intracellular signaling in the development of P450-mediated insecticide resistance in mosquitoes, Culex quinquefasciatus , focusing on the essential function of the GPCRs and their downstream effectors of Gs alpha subunit protein (Gαs) and adenylyl cyclase (ACs) in P450-mediated insecticide resistance of Culex mosquitoes. Our RNAi-mediated functional study showed that knockdown of Gαs caused the decreased expression of the downstream effectors of ACs and PKAs in the GPCR signaling pathway and resistance P450 genes, whereas knockdown of ACs decreased the expression of PKAs and resistance P450 genes. Knockdown of either Gαs or ACs resulted in an increased susceptibility of mosquitoes to permethrin. These results add significantly to our understanding of the molecular basis of resistance P450 gene regulation through GPCR/Gαs/AC/cAMP-PKA signaling pathways in the insecticide resistance of mosquitoes. The temporal and spatial dynamic analyses of GPCRs, Gαs, ACs, PKAs, and P450s in two insecticide resistant mosquito strains revealed that all the GPCR signaling pathway components tested, namely GPCRs, Gαs, ACs and PKAs, were most highly expressed in the brain for both resistant strains, suggesting the role played by these genes in signaling transduction and regulation. The resistance P450 genes were mainly expressed in the brain, midgut and malpighian tubules (MTs), suggesting their critical function in the central nervous system and importance for detoxification. The temporal dynamics analysis for the gene expression showed a diverse expression profile during mosquito development, indicating their initially functional importance in response to exposure to insecticides during their life stages.

S-Nitrosation destabilizes glutathione transferase P1-1.

Science.gov (United States)

Balchin, David; Stoychev, Stoyan H; Dirr, Heini W

2013-12-23

Protein S-nitrosation is a post-translational modification that regulates the function of more than 500 human proteins. Despite its apparent physiological significance, S-nitrosation is poorly understood at a molecular level. Here, we investigated the effect of S-nitrosation on the activity, structure, stability, and dynamics of human glutathione transferase P1-1 (GSTP1-1), an important detoxification enzyme ubiquitous in aerobes. S-Nitrosation at Cys47 and Cys101 reduces the activity of the enzyme by 94%. Circular dichroism spectroscopy, acrylamide quenching, and amide hydrogen-deuterium exchange mass spectrometry experiments indicate that the loss of activity is caused by the introduction of local disorder at the active site of GSTP1-1. Furthermore, the modification destabilizes domain 1 of GSTP1-1 against denaturation, smoothing the unfolding energy landscape of the protein and introducing a refolding defect. In contrast, S-nitrosation at Cys101 alone introduces a refolding defect in domain 1 but compensates by stabilizing the domain kinetically. These data elucidate the physical basis for the regulation of GSTP1-1 by S-nitrosation and provide general insight into the consequences of S-nitrosation on protein stability and dynamics.

Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

Energy Technology Data Exchange (ETDEWEB)

Fujii, Yasuyuki, E-mail: y.fujii@po.rd.taisho.co.jp [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi [Department of Molecular Function and Pharmacology Laboratories, Taisho Pharmaceutical Co. Ltd., 1-403 Saitama, Saitama 331-9530 (Japan); Igarashi, Yasuyuki [Laboratory of Biomembrane and Biofunctional Chemistry, Hokkaido University, Sapporo, Hokkaido 060-0812 (Japan); Goitsuka, Ryo [Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022 (Japan)

2012-03-23

Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress.

Science.gov (United States)

Sloan, Katherine E; Bohnsack, Markus T; Watkins, Nicholas J

2013-10-17

Several proto-oncogenes and tumor suppressors regulate the production of ribosomes. Ribosome biogenesis is a major consumer of cellular energy, and defects result in p53 activation via repression of mouse double minute 2 (MDM2) homolog by the ribosomal proteins RPL5 and RPL11. Here, we report that RPL5 and RPL11 regulate p53 from the context of a ribosomal subcomplex, the 5S ribonucleoprotein particle (RNP). We provide evidence that the third component of this complex, the 5S rRNA, is critical for p53 regulation. In addition, we show that the 5S RNP is essential for the activation of p53 by p14(ARF), a protein that is activated by oncogene overexpression. Our data show that the abundance of the 5S RNP, and therefore p53 levels, is determined by factors regulating 5S complex formation and ribosome integration, including the tumor suppressor PICT1. The 5S RNP therefore emerges as the critical coordinator of signaling pathways that couple cell proliferation with ribosome production. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Electron excitation cross sections for the 2s(2)2p(3)4S(O) -- 2s(2)2p(3)2D(O) (forbidden) and 4S(O) -- 2s2p(4) 4P (resonance) transitions in O II

Science.gov (United States)

Zuo, M.; Smith, Steven J.; Chutjian, A.; Williams, I. D.; Tayal, S. S.; Mclaughlin, Brendan M.

1995-01-01

Experimental and theoretical excitation cross sections are reported for the first forbidden transition 4S(O) -- 2S(2)2p(3) 2D(O) (lambda-lambda 3726, 3729) and the first allowed (resonance) transition 4S(O) -- 2s2p(4) 4P(lambda-833) in O II. Use is made of electron energy loss and merged-beams methods. The electron energy range covered is 3.33 (threshold) to 15 eV for the S -- D transition, and 14.9 (threshold) to 40 eV for the S -- P transition. Care was taken to assess and minimize the metastable fraction of the O II beam. An electron mirror was designed and tested to reflect inelastically backscattered electrons into the forward direction to account for the full range of polar scattering angles. Comparisons are made between present experiments and 11-state R-matrix calculations. Calculations are also presented for the 4S(O) -- 2s(2)2p(3)2P(O) (lambda-2470) transition.

Coronin 1B regulates S1P-induced human lung endothelial cell chemotaxis: role of PLD2, protein kinase C and Rac1 signal transduction.

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Peter V Usatyuk

Full Text Available Coronins are a highly conserved family of actin binding proteins that regulate actin-dependent processes such as cell motility and endocytosis. We found that treatment of human pulmonary artery endothelial cells (HPAECs with the bioactive lipid, sphingosine-1-phosphate (S1P rapidly stimulates coronin 1B translocation to lamellipodia at the cell leading edge, which is required for S1P-induced chemotaxis. Further, S1P-induced chemotaxis of HPAECs was attenuated by pretreatment with small interfering RNA (siRNA targeting coronin 1B (∼36%, PLD2 (∼45% or Rac1 (∼50% compared to scrambled siRNA controls. Down regulation PLD2 expression by siRNA also attenuated S1P-induced coronin 1B translocation to the leading edge of the cell periphery while PLD1 silencing had no effect. Also, S1P-induced coronin 1B redistribution to cell periphery and chemotaxis was attenuated by inhibition of Rac1 and over-expression of dominant negative PKC δ, ε and ζ isoforms in HPAECs. These results demonstrate that S1P activation of PLD2, PKC and Rac1 is part of the signaling cascade that regulates coronin 1B translocation to the cell periphery and the ensuing cell chemotaxis.

High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation

International Nuclear Information System (INIS)

Akao, Yukihiro; Banno, Yoshiko; Nakagawa, Yoshihito; Hasegawa, Nobuko; Kim, Tack-Joong; Murate, Takashi; Igarashi, Yasuyuki; Nozawa, Yoshinori

2006-01-01

Although most of pharmacological therapies for cancer utilize the apoptotic machinery of the cells, the available anti-cancer drugs are limited due to the ability of prostate cancer cells to escape from the anti-cancer drug-induced apoptosis. A human prostate cancer cell line PC3 is resistant to camptothecin (CPT). To elucidate the mechanism of this resistance, we have examined the involvement of sphingosine kinase (SPHK) and sphingosine 1-phosphate (S1P) receptor in CPT-resistant PC3 and -sensitive LNCaP cells. PC3 cells exhibited higher activity accompanied with higher expression levels of protein and mRNA of SPHK1, and also elevated expression of S1P receptors, S1P 1 and S1P 3 , as compared with those of LNCaP cells. The knockdown of SPHK1 by small interfering RNA and inhibition of S1P receptor signaling by pertussis toxin in PC3 cells induced significant inhibition of cell growth, suggesting implication of SPHK1 and S1P receptors in cell proliferation in PC3 cells. Furthermore, the treatment of PC3 cells with CPT was found to induce up-regulation of the SPHK1/S1P signaling by induction of both SPHK1 enzyme and S1P 1 /S1P 3 receptors. These findings strongly suggest that high expression and up-regulation of SPHK1 and S1P receptors protect PC3 cells from the apoptosis induced by CPT

Understanding A.M. Iqbal’s Vision on Perfect Man

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Imam Bahroni

2013-12-01

Full Text Available This article tries to elucidate A.M Iqbal’s vision on the concept of perfectman. Its significance is at the point that Man can transform both his being andhis surroundings according to his own desires and aspirations. He actually makesimprovements upon what is created by God. God created night, he inventedthe lamp; God created clay, and from it he made the cup; God created deserts,mountains, forests, orchards, gardens, and groves. He makes glass out of stoneand turns poison into an antidote. God created the world, but he made it morebeautiful.Iqbal’s reasoning amply justifies belief in the ascendancy of man overthe universe and his predicted perfection. The perfect man is the ultimate endof the revolutionary process, and he is developed out of the present man, justas the full moon is developed from the crescent.

Role of sphingosine 1-phosphate (S1P and effects of fingolimod, an S1P receptor 1 functional antagonist in lymphocyte circulation and autoimmune diseases

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Kenji Chiba

2014-11-01

Full Text Available Sphingosine 1-phosphate (S1P, a multi-functional phospholipid mediator, is generated from sphingosine by sphingosine kinases and binds to five known G protein-coupled S1P receptors (S1P1, S1P2, S1P3, S1P4, and S1P5. It is widely accepted that S1P receptor 1 (S1P1 plays an essential role in lymphocyte egress from the secondary lymphoid organs (SLO and thymus, because lymphocyte egress from these organs to periphery is at extremely low levels in mice lacking lymphocytic S1P1. Fingolimod hydrochloride (FTY720 is a first-in-class, orally active S1P1 functional antagonist which was discovered by chemical modification of a natural product, myriocin. Since FTY720 has a structure closely related to sphingosine, the phosphorylated FTY720 (FTY720-P is converted by sphingosine kinases and binds 4 types of S1P receptors. FTY720-P strongly induces down-regulation of S1P1 by internalization and degradation of this receptor and acts as a functional antagonist at S1P1. Consequently, FTY720 inhibits S1P1-dependent lymphocyte egress from the SLO and thymus to reduce circulating lymphocytes including autoreactive Th17 cells, and is highly effective in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. In relapsing remitting MS patients, oral FTY720 shows a superior efficacy when compared to intramuscular interferon-β-1a. Based on these data, it is presumed that modulation of the S1P-S1P1 axis provides an effective therapy for autoimmune diseases including MS.

Quasimolecular emission near the Xe(5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance lines induced by collisions with He atoms

Science.gov (United States)

Alekseeva, O. S.; Devdariani, A. Z.; Grigorian, G. M.; Lednev, M. G.; Zagrebin, A. L.

2017-02-01

This study is devoted to the theoretical investigation of the quasimolecular emission of Xe*-He and Kr*-He collision pairs near the Xe (5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance atomic lines. The potential curves of the quasimolecules Xe(5p 56s) + He and Kr(4p 55s) + He have been obtained with the use of the effective Hamiltonian and pseudopotential methods. Based on these potential curves the processes of quasimolecular emission of Xe*+He and Kr*+He mixtures have been considered and the spectral distributions I(ħΔω) of photons emitted have been obtained in the framework of quasistatic approximation.

Observation of the strongest 5s2 5p6 5d-(5s2 5p5 5d6s+5s25p6 7p) transitions in Au XI to Bi XV ions

International Nuclear Information System (INIS)

Churilov, S.S.; Joshi, Y.N.

2001-01-01

The spectra of gold till bismuth were studied in the 90-135 A region. Nine most intense lines belonging to the 5s 2 5p 6 5d-5s 2 5p 5 5d6s array were identified in Au XI to Bi XV ions. The 5s 2 5p 6 7p 2 P 3/2,1/2 levels in Au XI and the 5s 2 5p 6 7p 2 P 3/2 level in Hg XII were also identified. The observed wavelengths and intensities agree quite well with the Hartree-Fock calculations. (orig.)

2s 2p 3P10 → 2s21S0 intercombination line in beryllium-like krypton, molybdenum and tungsten

International Nuclear Information System (INIS)

Glass, R.

1979-01-01

Transition probabilities are evaluated for the 2s 2p 3 P 1 0 → 2s 2 1 S 0 transition in beryllium-like ions for krypton, molybdenum and tungsten, using configuration-interaction wavefunctions. The importance of the 2s 3p 1 P 1 0 configuration is considered

Améliorer la sécurité à Guwahati, en Inde, grâce à l'aménagement ...

International Development Research Centre (IDRC) Digital Library (Canada)

6 sept. 2016 ... Ces solutions comprennent l'augmentation de la fréquence du transport en commun, l'offre de services de base aux endroits qui sont illégalement occupés le temps que le régime foncier soit clarifié, l'intégration des résidents des établissements spontanés aux processus d'aménagement, et la création ...

A role of the sphingosine-1-phosphate (S1P)-S1P receptor 2 pathway in epithelial defense against cancer (EDAC).

Science.gov (United States)

Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

2016-02-01

At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)-S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. © 2016 Yamamoto, Yako, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Des variétés de manioc améliorées accroissent la sécurité alimentaire

International Development Research Centre (IDRC) Digital Library (Canada)

un de ses pires inconvénients, surtout lorsqu'il s'agit d'assurer la survie en ... instauré par le gouvernement de l'Ouganda à Namulonge, une équipe de scientifiques a lancé une initiative d'amélioration génétique audacieuse.

Shake-up transitions in S 2p, S 2s and F 1s photoionization of the SF6 molecule

International Nuclear Information System (INIS)

Decleva, P; Fronzoni, G; Kivimaeki, A; Alvarez Ruiz, J; Svensson, S

2009-01-01

Shake-up transitions occurring upon core photoionization in the SF 6 molecule have been studied experimentally and theoretically. The S 2p, S 2s and F 1s shake-up satellite photoelectron spectra were measured using Al Ka radiation at 1487 eV photon energy. They have been interpreted with the aid of ab initio configuration interaction calculations in the sudden-limit approximation. For the S 2p spectrum, conjugate shake-up transitions were also calculated. Clear evidence of conjugate processes is observed in the S 2p shake-up spectrum measured at 230 eV photon energy. The experimental and theoretical S 2p and S 2s shake-up spectra show very similar structures mainly due to orbital relaxation involving S 3s and 3p participation. For the calculation of the F 1s shake-up spectrum, the symmetry lowering of the molecule in the final states was considered, resulting in a good agreement with the experiment.

Calculation of the total electron excitation cross section in the Born approximation using Slater wave functions for the Li (2s yields 2p), Li (2s yields 3p), Na (3s yields 4p), Mg (3p yields 4s), Ca (4s yields 4p) and K (4s yields 4p) excitations. M.S. Thesis

Science.gov (United States)

Simsic, P. L.

1974-01-01

Excitation of neutral atoms by inelastic scattering of incident electrons in gaseous nebulae were investigated using Slater Wave functions to describe the initial and final states of the atom. Total cross sections using the Born Approximation are calculated for: Li(2s yields 2p), Na(3s yields 4p), k(4s yields 4p). The intensity of emitted radiation from gaseous nebulae is also calculated, and Maxwell distribution is employed to average the kinetic energy of electrons.

Tiesas nolēmumu piespiedu izpilde pārrobežu civillietās un komerclietās

OpenAIRE

Staltmane, Anda

2015-01-01

Autores mērķis, rakstot šo darbu, ir apzināt praksē pastāvošās problēmas pārrobežu civillietās un komerclietās, kas saistītas ar tiesu nolēmumu praktisko izpildi ārvalstīs. Vienlaikus autore izdarīs secinājumus par problēmu cēloņiem, to iespējamiem risinājumiem, t.sk. arī par Latvijas normatīvā regulējuma pilnveidošanu, ņemot vērā arī ārvalstu pieredzi, doktrīnu un citus avotus. Autore, lai sasniegtu šo mērķi, darbā aplūkos galvenokārt starptautiskos dokumentus un nacionālo tiesību regulēj...

Improved wavelengths for the 1s2s3S1-1s2p3P0,2 transitions in helium-like Si12+

International Nuclear Information System (INIS)

Armour, I.A.; Myers, E.G.; Silver, J.D.; Traebert, E.; Oxford Univ.

1979-01-01

The wavelengths of the 1s2s 3 S 1 -1s2p 3 P 0 , 2 transitions in He-like Si 12+ have been remaesured to be 87.86 +- 0.01 nm and 81.48 +- 0.01 nm. The use of Rydberg lines for the calibration of fast beam spectra is discussed. (orig.)

S P Sen Gupta

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science. S P Sen Gupta. Articles written in Bulletin of Materials Science. Volume 24 Issue 2 April 2001 pp 173-180. Particle fracture and plastic deformation in vanadium pentoxide powders induced by high energy vibrational ball-mill · Partha Chatterjee S P Sen Gupta Suchitra Sen.

Essential role for SphK1/S1P signaling to regulate hypoxia-inducible factor 2α expression and activity in cancer.

Science.gov (United States)

Bouquerel, P; Gstalder, C; Müller, D; Laurent, J; Brizuela, L; Sabbadini, R A; Malavaud, B; Pyronnet, S; Martineau, Y; Ader, I; Cuvillier, O

2016-03-14

The sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) signaling pathway has been reported to modulate the expression of the canonical transcription factor hypoxia-inducible HIF-1α in multiple cell lineages. HIF-2α is also frequently overexpressed in solid tumors but its role has been mostly studied in clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, where HIF-2α has been established as a driver of a more aggressive disease. In this study, the role of SphK1/S1P signaling with regard to HIF-2α was investigated in various cancer cell models including ccRCC cells. Under hypoxic conditions or in ccRCC lacking a functional von Hippel-Lindau (VHL) gene and expressing high levels of HIF-2α, SphK1 activity controls HIF-2α expression and transcriptional activity through a phospholipase D (PLD)-driven mechanism. SphK1 silencing promotes a VHL-independent HIF-2α loss of expression and activity and reduces cell proliferation in ccRCC. Importantly, downregulation of SphK1 is associated with impaired Akt and mTOR signaling in ccRCC. Taking advantage of a monoclonal antibody neutralizing extracellular S1P, we show that inhibition of S1P extracellular signaling blocks HIF-2α accumulation in ccRCC cell lines, an effect mimicked when the S1P transporter Spns2 or the S1P receptor 1 (S1P1) is silenced. Here, we report the first evidence that the SphK1/S1P signaling pathway regulates the transcription factor hypoxia-inducible HIF-2α in diverse cancer cell lineages notably ccRCC, where HIF-2α has been established as a driver of a more aggressive disease. These findings demonstrate that SphK1/S1P signaling may act as a canonical regulator of HIF-2α expression in ccRCC, giving support to its inhibition as a therapeutic strategy that could contribute to reduce HIF-2 activity in ccRCC.

Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

Science.gov (United States)

Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

2016-08-01

Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice. Copyright © 2016 the American Physiological Society.

Hsp60 and p70S6K form a complex in human cardiomyocytes

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Kroupskaya I. V.

2011-02-01

Full Text Available Molecular chaperon Hsp60 and protein kinase p70S6K play an important functional role in the regulation of cardiomyocytes vital function or apoptosis. Aim. To study a possibility of in vivo complex formation between Hsp60 and p70S6K in cardiomyocytes. Methods. Co-immunoprecipitation, Western-blot analysis. Results. We have identified in vivo interaction between molecular chaperone Hsp60 and two isoforms of proteinkinase p70S6K in human myocardium, normal and affected by cardiomyopathy. Conclusions. The results obtained suggest a possible participation of molecular chaperon Hsp60 in regulation of p70S6K activity in stressinduced apoptotic signaling pathway in cardiomyocytes.

PPARγ agonists upregulate sphingosine 1-phosphate (S1P) receptor 1 expression, which in turn reduces S1P-induced [Ca(2+)]i increases in renal mesangial cells.

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Koch, Alexander; Völzke, Anja; Puff, Bianca; Blankenbach, Kira; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

2013-11-01

We previously identified peroxisome proliferator-activated receptor gamma (PPARγ) agonists (thiazolidinediones, TZDs) as modulators of the sphingolipid metabolism in renal mesangial cells. TZDs upregulated sphingosine kinase 1 (SK-1) and increased the formation of intracellular sphingosine 1-phosphate (S1P), which in turn reduced the expression of pro-fibrotic connective tissue growth factor. Since S1P also acts as extracellular ligand at specific S1P receptors (S1PR, S1P1-5), we investigated here the effect of TZDs on S1PR expression in mesangial cells and evaluated the functional consequences by measuring S1P-induced increases in intracellular free Ca(2+) concentration ([Ca(2+)]i). Treatment with two different TZDs, troglitazone and rosiglitazone, enhanced S1P1 mRNA and protein expression in rat mesangial cells, whereas S1P2-5 expression levels were not altered. Upregulation of S1P1 mRNA upon TZD treatment was also detected in human mesangial cells and mouse glomeruli. PPARγ antagonism and promoter studies revealed that the TZD-dependent S1P1 mRNA induction involved a functional PPAR response element in the S1P1 promoter. Pharmacological approaches disclosed that S1P-induced [Ca(2+)]i increases in rat mesangial cells were predominantly mediated by S1P2 and S1P3. Interestingly, the transcriptional upregulation of S1P1 by TZDs resulted in a reduction of S1P-induced [Ca(2+)]i increases, which was reversed by the S1P1/3 antagonist VPC-23019, the protein kinase C (PKC) inhibitor PKC-412, and by S1P1 siRNA. These data suggest that PPARγ-dependent upregulation of S1P1 leads to an inhibition of S1P-induced Ca(2+) signaling in a PKC-dependent manner. Overall, these results reveal that TZDs not only modulate intracellular S1P levels but also regulate S1PR signaling by increasing S1P1 expression in mesangial cells. © 2013.

Reseña de: Aguiar Andrade, Amélia y Millán da Costa, Adelaide (Eds. La ville Médiévale en Débat. Instituto de Estudos Medievais, Lisboa, 2013, 206 páginas (Estudos, 8, (Idiomas Francés, Español e Inglés. ISBN: 978-989-97066-9-9.

Directory of Open Access Journals (Sweden)

Ana María Rivera Medina

2017-05-01

Full Text Available Aguiar Andrade, Amélia y Millán da Costa, Adelaide (Eds. La ville Médiévale en Débat. Instituto de Estudos Medievais, Lisboa, 2013, 206 páginas (Estudos, 8, (Idiomas Francés, Español e Inglés. isbn: 978-989-97066-9-9.

Spectral analysis of 5s25p2(6p+6d+7s) configurations of Ba VI

International Nuclear Information System (INIS)

Sharma, M.K.; Tauheed, A.; Rahimullah, K.

2014-01-01

The sixth spectrum of barium (Ba VI) has been investigated with the aid of experimental recordings made on a 3-m normal incidence vacuum spectrograph of Antigonish laboratory (Canada) in the wavelength region 300–2080 Å using triggered spark as an excitation source. The spectral analysis has been extended considerably to include new configuration the 5s 2 5p 2 6p in odd parity matrix and the 5s 2 5p 2 6d and 5s 2 5p 2 7s configurations in even parity matrix. Previously reported levels of the ground configuration (5s 2 5p 3 ) and three lowest excited configurations the 5s5p 4 , 5s 2 5p 2 5d and 5s 2 5p 2 6s have been confirmed and the two unknown levels of the 5s 2 5p 2 5d configuration with J=9/2, have now been established through the identification of transitions from the 5s 2 5p 2 6p levels. All twenty one levels of the 5s 2 5p 2 6p configuration and twenty nine levels out of thirty six of the 5s 2 5p 2 6d and 5s 2 5p 2 7s configurations have now been established. Hartree–Fock calculations involving configuration interactions support the analyses. The accuracy of our wavelength measurement is ±0.005 Å for sharp lines. - Highlights: • The spectrum of Ba was recorded on a 3-m spectrograph with triggered spark source. • Atomic transitions for Ba VI were identified to established new energy levels. • CI calculations with relativistic corrections were made for theoretical predictions. • Weighted oscillator strength (gf) and transition probabilities (gA) were calculated

Electron Excitation Cross Sections for the S II Transitions: 3s(exp 2)3p(exp 3) 4S(exp o) approaches 3s(exp 2)3p(exp 3) 2D(exp o), 2P(exp o), and 3s3p(exp 4) 4P

Science.gov (United States)

Liao, C.; Chutjian, A.; Hitz, D.; Tayal, S. S.

1997-01-01

Experimental and theoretical collisional excitation cross sections are reported for the transitions 3s(exp 2)3p(exp 3)4S(exp o) approaches 3s(exp 2)3p(exp 3) 2D(exp o), 2P(exp o), and 3s3P(exp 4) 4P in S II. The transition wavelengths (energies) are 6716 A (1.85 eV), 4069 A (3.05 eV), and 1256 A (9.87 eV), respectively. In the experiments, use is made of the energy-loss merged-beams method. The metastable fraction of the S II beam was assessed and minimized. The contribution of elastically scattered electrons was reduced by the use of a lowered solenoidal magnetic field and a modulated radio-frequency voltage on the analyzing plates and by retarding grids to reject the elastically scattered electrons with larger Larmor radii. For each transition, comparisons are made among experiments, the new 19 state R-matrix calculation, and three other close-coupling calculations.

Targeting S1P in Inflammatory bowel disease: new avenues for modulating intestinal leukocyte migration.

Science.gov (United States)

Danese, Silvio; Furfaro, Federica; Vetrano, Stefania

2017-07-28

Sphingosine 1 phosphate (S1P) is a bioactive lipid mediator involved in the regulation of several cellular processes though the activation of a G protein-coupled receptor family known as the S1P receptors (S1PRs). Advances in the understanding of the biological activities mediated by S1PRs have sparked great interest in the S1P/S1PRs axes as new therapeutic targets for the modulation of several cellular processes. In particular, S1P/ S1PR1 axis has been identified as key regulator for the lymphocyte migration from lymph nodes. The blockade of this axis is emerging as a new therapeutic approach to control the aberrant leukocytes migration into the mucosa in inflammatory bowel disease (IBD). This review briefly summarizes the current evidence coming from clinical studies and discusses the future prospects of S1P inhibitors for treatment of inflammatory bowel disease. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Interaction between S100P and the anti-allergy drug cromolyn

International Nuclear Information System (INIS)

Penumutchu, Srinivasa R.; Chou, Ruey-Hwang; Yu, Chin

2014-01-01

Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by 1 H- 15 N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex

Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway: Therapeutic Targets in Autoimmunity and Inflammation.

Science.gov (United States)

Tsai, Hsing-Chuan; Han, May H

2016-07-01

Sphingosine-1-phosphate (S1P) and S1P receptors (S1PR) are ubiquitously expressed. S1P-S1PR signaling has been well characterized in immune trafficking and activation in innate and adaptive immune systems. However, the full extent of its involvement in the pathogenesis of autoimmune diseases is not well understood. FTY720 (fingolimod), a non-selective S1PR modulator, significantly decreased annualized relapse rates in relapsing-remitting multiple sclerosis (MS). FTY720, which primarily targets S1P receptor 1 as a functional antagonist, arrests lymphocyte egress from secondary lymphoid tissues and reduces neuroinflammation in the central nervous system (CNS). Recent studies suggest that FTY720 also decreases astrogliosis and promotes oligodendrocyte differentiation within the CNS and may have therapeutic benefit to prevent brain atrophy. Since S1P signaling is involved in multiple immune functions, therapies targeting S1P axis may be applicable to treat autoimmune diseases other than MS. Currently, over a dozen selective S1PR and S1P pathway modulators with potentially superior therapeutic efficacy and better side-effect profiles are in the pipeline of drug development. Furthermore, newly characterized molecules such as apolipoprotein M (ApoM) (S1P chaperon) and SPNS2 (S1P transporter) are also potential targets for treatment of autoimmune diseases. Finally, the application of therapies targeting S1P and S1P signaling pathways may be expanded to treat several other immune-mediated disorders (such as post-infectious diseases, post-stroke and post-stroke dementia) and inflammatory conditions beyond their application in primary autoimmune diseases.

Identification of the 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole inner-shell satellite line in the Ar16+ K-shell x-ray spectrum

Science.gov (United States)

Beiersdorfer, P.; Bitter, M.; Hey, D.; Reed, K. J.

2002-09-01

We have identified the dipole-forbidden 1s2s2p 4P5/2-->1s22s 2S1/2 transition in lithiumlike Ar15+ in high-resolution K-shell x-ray emission spectra recorded at the Livermore EBIT-II electron-beam ion trap and the Princeton National Spherical Tokamak Experiment. Unlike other Ar15+ satellite lines, which can be excited by dielectronic recombination, the line is exclusively excited by electron-impact excitation. Its predicted radiative rate is comparable to that of the well-known 1s2p 3P1-->1s2 1S0 magnetic quadrupole transition in heliumlike Ar16+. As a result, it can also only be observed in low-density plasma. We present calculations of the electron-impact excitation cross sections of the innershell excited Ar15+ satellite lines, including the magnetic sublevels needed for calculating the linear line polarization. We compare these calculations to the relative magnitudes of the observed 1s2s2p-->1s22s transitions and find good agreement, confirming the identification of the lithiumlike 1s2s2p 4P5/2-->1s22s 2S1/2 magnetic quadrupole line.

GADD45a Regulates Olaquindox-Induced DNA Damage and S-Phase Arrest in Human Hepatoma G2 Cells via JNK/p38 Pathways

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Daowen Li

2017-01-01

Full Text Available Olaquindox, a quinoxaline 1,4-dioxide derivative, is widely used as a feed additive in many countries. The potential genotoxicity of olaquindox, hence, is of concern. However, the proper mechanism of toxicity was unclear. The aim of the present study was to investigate the effect of growth arrest and DNA damage 45 alpha (GADD45a on olaquindox-induced DNA damage and cell cycle arrest in HepG2 cells. The results showed that olaquindox could induce reactive oxygen species (ROS-mediated DNA damage and S-phase arrest, where increases of GADD45a, cyclin A, Cdk 2, p21 and p53 protein expression, decrease of cyclin D1 and the activation of phosphorylation-c-Jun N-terminal kinases (p-JNK, phosphorylation-p38 (p-p38 and phosphorylation-extracellular signal-regulated kinases (p-ERK were involved. However, GADD45a knockdown cells treated with olaquindox could significantly decrease cell viability, exacerbate DNA damage and increase S-phase arrest, associated with the marked activation of p-JNK, p-p38, but not p-ERK. Furthermore, SP600125 and SB203580 aggravated olaquindox-induced DNA damage and S-phase arrest, suppressed the expression of GADD45a. Taken together, these findings revealed that GADD45a played a protective role in olaquindox treatment and JNK/p38 pathways may partly contribute to GADD45a regulated olaquindox-induced DNA damage and S-phase arrest. Our findings increase the understanding on the molecular mechanisms of olaquindox.

Pos-modernidade ou antimodernidade? Uma reflexão em torno do debate moderno/pós-moderno

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Everton Garcia da Costa

2016-06-01

Full Text Available Este ensaio constitui-se em uma reflexão histórica em torno do debate moderno/pós-moderno. O objetivo do texto, de modo mais preciso, é apresentar e rebater algumas das críticas que pensadores – tais como Habermas, Rouanet, Giddens e Lipovetsky – lançam em direção às chamadas teorias pós-modernas, acusando-as de serem, na verdade, discursos de antimodernidade. Na visão desses autores, não há uma ruptura real entre a modernidade e aquilo que tem sido chamado de “pós-modernidade”. Contrariamente a essa perspectiva, o trabalho ora apresentado parte do pressuposto de que há, de fato, um conjunto de deslocamentos – descontinuidades, desencaixes, pontos de ruptura – que separam uma matriz moderna de uma matriz pós-moderna.

Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of extravillous trophoblast migration.

Science.gov (United States)

Westwood, Melissa; Al-Saghir, Khiria; Finn-Sell, Sarah; Tan, Cherlyn; Cowley, Elizabeth; Berneau, Stéphane; Adlam, Daman; Johnstone, Edward D

2017-12-01

Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH) 2 D 3 . QPCR and immunolocalisation were used to demonstrate EVT S1P receptor expression. EVTs express S1P receptors 1, 2 and 3. S1P inhibited EVT migration. This effect was abolished in the presence of the specific S1PR2 inhibitor, JTE-013 (p S1P alone) whereas treatment with the S1R1/3 inhibitor, FTY720, had no effect. In other cell types S1PR2 is regulated by vitamin D; here we found that treatment with 1,25(OH) 2 D 3 for 48 or 72 h reduces S1PR2 (4-fold; S1P did not inhibit the migration of cells exposed to 1,25(OH) 2 D 3 (p S1P receptor isoforms, S1P predominantly signals through S1PR2/Gα 12/13 to activate Rho and thereby acts as potent inhibitor of EVT migration. Importantly, expression of S1PR2, and therefore S1P function, can be down-regulated by vitamin D. Our data suggest that vitamin D deficiency, which is known to be associated with PE, may contribute to the impaired trophoblast migration that underlies this condition. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interaction between S100P and the anti-allergy drug cromolyn

Energy Technology Data Exchange (ETDEWEB)

Penumutchu, Srinivasa R. [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Chou, Ruey-Hwang [Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China); Yu, Chin, E-mail: cyu.nthu@gmail.com [Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan (China); The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 (China)

2014-11-21

Highlights: • The interaction between S100P–cromolyn was investigated by fluorescence spectroscopy. • The interfacial residues on S100P and cromolyn contact surface were mapped by {sup 1}H-{sup 15}N HSQC experiments. • S100P–cromolyn complex model was generated from NMR restraints using HADDOCK program. • The stability of the S100P–cromolyn complex was studied using molecular dynamics simulations. - Abstract: The S100P protein has been known to mediate cell proliferation by binding the receptor for advanced glycation end products (RAGE) to activate signaling pathways, such as the extracellular regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. S100P/RAGE signaling is involved in a variety of diseases, such as cancer, metastasis, and diabetes. Cromolyn is an anti-allergy drug that binds S100P to block the interaction between S100P and RAGE. In the present study, we characterized the properties of the binding between cromolyn and calcium-bound S100P using various biophysical techniques. The binding affinity for S100P and cromolyn was measured to be in the millimolar range by fluorescence spectroscopy. NMR-HSQC titration experiments and HADDOCK modeling was employed to determine the spatial structure of the proposed heterotetramer model of the S100P–cromolyn complex. Additional MD simulation results revealed the important properties in the complex stability and conformational flexibility of the S100P–cromolyn complex. This proposed model has provided an understanding of the molecular level interactions of S100P–cromolyn complex.

Determination of the 1s2{\\ell }2{{\\ell }}^{\\prime } state production ratios {{}^{4}P}^{o}/{}^{2}P, {}^{2}D/{}^{2}P and {{}^{2}P}_{+}/{{}^{2}P}_{-} from fast (1{s}^{2},1s2s\\,{}^{3}S) mixed-state He-like ion beams in collisions with H2 targets

Science.gov (United States)

Benis, E. P.; Zouros, T. J. M.

2016-12-01

New results are presented on the ratio {R}m={σ }{T2p}( {}4P)/{σ }{T2p}({}2P) concerning the production cross sections of Li-like 1s2s2p quartet and doublet P states formed in energetic ion-atom collisions by single 2p electron transfer to the metastable 1s2s {}3S component of the He-like ion beam. Spin statistics predict a value of R m = 2 independent of the collision system in disagreement with most reported measurements of {R}m≃ 1{--}9. A new experimental approach is presented for the evaluation of R m having some practical advantages over earlier approaches. It also allows for the determination of the separate contributions of ground- and metastable-state beam components to the measured spectra. Applying our technique to zero-degree Auger projectile spectra from 4.5 MeV {{{B}}}3+ (Benis et al 2002 Phys. Rev. A 65 064701) and 25.3 MeV {{{F}}}7+ (Zamkov et al 2002 Phys. Rev. A 65 062706) mixed state (1{s}2 {}1S,1s2s {}3S) He-like ion collisions with H2 targets, we report new values of {R}m=3.5+/- 0.4 for boron and {R}m=1.8+/- 0.3 for fluorine. In addition, the ratios of {}2D/{}2P and {{}2P}+/{{}2P}- populations from either the metastable and/or ground state beam component, also relevant to this analysis, are evaluated and compared to previously reported results for carbon collisions on helium (Strohschein et al 2008 Phys. Rev. A 77 022706) including a critical comparison to theory.

The 4p-5d, 6d and 4p-6s, 7s transitions of Mo IX

International Nuclear Information System (INIS)

Khatoon, S.; Chaghtai, M.S.Z.; Rahimullah, K.

1979-01-01

The transitions 4p-5d, 6d and 4p-6s, 7s have been studied for the first time in Mo IX. The authors have identified 42 4p-5d, 36 4p-6d, 22 4p-6s and 22 4p-7s transitions, establishing 16 4p 3 5d, 14 4p 3 6d and all the ten 4p 3 6s, 7s levels of the spectrum concerned. The ionization energy is estimated to be (1 323 700 +- 700)cm -1 or (164.11 +- 0.09)eV. The spectrum was recorded in sliding and open spark discharges with a 5 m grazing incidence spectrograph of Lund University (Sweden) from about 40 A to 440 A. (Auth.)

La recherche aide à améliorer la sécurité alimentaire et la nutrition

International Development Research Centre (IDRC) Digital Library (Canada)

Corey Piccioni

à grande échelle des solutions qui améliorent la sécurité alimentaire et la nutrition dans le monde en développement. Le CRDI apporte une contribution importante à l'augmentation de la productivité agricole, à l'amélioration de la nutrition et à l'accroissement des revenus des exploitants agricoles, hommes et femmes.

Prognostic significance of cytosolic pS2 content in ovarian tumors

International Nuclear Information System (INIS)

Raigoso, P.; Allende, T.; Zeidan, N.; Llana, B.; Bernardo, L.; Roiz, C.; Tejuca, S.; Vazquez, J.; Lamelas, M.L.

2002-01-01

Aim: pS2 is an estrogen regulated peptide which has been associated with a good prognosis an with a more favorable response to treatment in breast cancer patients. In ovarian tumors, the expression of pS2 was demonstrated at both mRNA and protein levels. In addition, it has been showed significant association of pS2 with mucinous differentiation or well differentiation grade of the tumors. However, it is little know about the prognostic significance of the pS2 content in ovarian carcinomas. The aims of the present work were to analyze the cytosolic pS2 content in benign and malignant ovarian tumors, its relationship with clinico-pathologic parameters, steroid receptor status, and prognostic significance. Material and Methods: We analysed the cytosolic concentrations of pS2 in 91 specimen ovarian tissues by an immunoradiometric assay (ELSA-pS2, CIS, France). The tissues were 8 normal ovaries, 43 benign tumors and 40 malignant ovarian tumors. The same ovarian tissues processed to pS2 were analyzed to Estrogen (ER) and Progesterone (PgR) Receptor status. These steroid receptors were quantified biochemically following commercial ELISA method (ABBOTT Diagnostics, Germany). The relationship between cytosolic content and clinico-pathologic factors was examined by the Mann-Whitney or Kruskall-Wallis test. Correlation between steroid receptors and pS2 content was calculated with the Spearman test. Survival curves were calculated using the Kaplan-Meier method and compared by the log-rank test. Differences were considered significant at 5% probability level. Results: pS2 could be detected in 30 cases (32.9%) with values ranged from 0.04 to 89 ng/mg prt. Only one normal ovary showed detectable levels of pS2 and there were not differences in cytosolic content between benign and malignant ovarian tumors. The pS2 levels were only associated to mucinous differentiation in both benign and malignant ovarian tumors (p=0.029 and p=0.015, respectively). Significantly higher

Downregulated long non-coding RNA MEG3 in breast cancer regulates proliferation, migration and invasion by depending on p53’s transcriptional activity

Energy Technology Data Exchange (ETDEWEB)

Sun, Lin [West Biostatistics and Cost-effectiveness Research Center, Medical Insurance Office, West China Hospital of Sichuan University, 610041, Sichuan (China); Li, Yu [Department of Anesthesiology, West China Hospital, Sichuan University, 610041, Sichuan (China); Yang, Bangxiang, E-mail: b19933009@qq.coom [Department of Pain Management, West China Hospital of Sichuan University, 610041, Sichuan (China)

2016-09-09

Long non-coding RNAs (lncRNAs) was found to play critical roles in tumorigenesis, hence, screen of tumor-related lncRNAs, identification of their biological roles is important for understanding the processes of tumorigenesis. In this study, we identified the expressing difference of several tumor-related lncRNAs in breast cancer samples and found that, MEG3, which is downregulated in non-small cell lung cancer (NSCLC) tumor tissues, is also downregulated in breast cancer samples compared with adjacent tissues. For figuring out the effect of MEG3 in breast cancer cells MCF7 and MB231, we overexpressed MEG3 in these cells, and found that it resulted the inhibition of proliferation, colony formation, migration and invasion capacities by enhancing p53’s transcriptional activity on its target genes, including p21, Maspin and KAI1. MEG3 presented similar effects in MB157, which is a p53-null breast cancer cell line, when functional p53 but not p53R273H mutant, which lacks transcriptional activity, was introduced. Surprisingly, overexpression of MEG3 activates p53’s transcriptional activity by decreasing MDM2’s transcription level, and thus stabilizes and accumulates P53. Taken together, our findings indicate that MEG3 is downregulated in breast cancer tissues and affects breast cancer cells’ malignant behaviors, which indicate MEG3 a potential therapeutic target for breast cancer. - Highlights: • MEG3 RNA is widely downregulated in breast tumor tissue. • MEG3 regulates P53 indirectly through transcriptional regulation of MDM2. • Under unstressed condition, MEG3-related P53 accumulation transcriptionally activates p53’s target genes. • MEG3 expression level tightly regulates proliferation, colony formation, migration and invasion in breast tumor cells.

The effect of nonhuman’s external regulation on detecting the natural development process of young children’s self-regulation during learning tasks

NARCIS (Netherlands)

Agina, Adel Masaud; Agina, Adel M.; Kommers, Petrus A.M.; Steehouder, M.F.

2011-01-01

The present study explored the effect of nonhuman’s external regulation on children’s natural development of self-regulation and the effect of each natural developed class on children’s spontaneous thinking aloud and satisfaction. The Aginian’s methodology (Agina et al., 2011a) that relied on

Telomerase and Tel1p Preferentially Associate with Short Telomeres in S. cerevisiae

Science.gov (United States)

Sabourin, Michelle; Tuzon, Creighton T.; Zakian, Virginia A.

2009-01-01

SUMMARY In diverse organisms, telomerase preferentially elongates short telomeres. We generated a single short telomere in otherwise wild-type (WT) S. cerevisiae cells. The binding of the positive regulators Ku and Cdc13p was similar at short and WT-length telomeres. The negative regulators Rif1p and Rif2p were present at the short telomere, although Rif2p levels were reduced. Two telomerase holoenzyme components, Est1p and Est2p, were preferentially enriched at short telomeres in late S/G2 phase, the time of telomerase action. Tel1p, the yeast ATM-like checkpoint kinase, was highly enriched at short telomeres from early S through G2 phase and even into the next cell cycle. Nonetheless, induction of a single short telomere did not elicit a cell-cycle arrest. Tel1p binding was dependent on Xrs2p and required for preferential binding of telomerase to short telomeres. These data suggest that Tel1p targets telomerase to the DNA ends most in need of extension. PMID:17656141

[Role and related mechanism of S1P/S1P1 signal pathway during post conditioning of hypertrophic cardiomyocytes].

Science.gov (United States)

Bao, X H; Li, H X; Tao, J; Li, X M; Yang, Y N; Ma, Y T; Chen, B D

2016-05-24

To study the role and mechanism of sphingosine-1-phosphate (S1P)/ sphingosine-1-phosphate receptor 1(S1P1) signal pathway during post conditioning of hypertrophic cardiomyocytes. Neonatal rat cardiomyocytes were isolated and cultured, then stimulated by norepinephrine (NE) to induce cardiomyocytes hypertrophy. Using tri-gas incubator to create hypoxia and reoxygenation enviroment to mimic ischemia-reperfusion and postconditioning. Hypertrophic cardiomyoctyes were divided into five groups according to the presence or absence of various drugs and postconditiong and relevant signal pathways changes were detected: (1) IPost group (hypoxia+ postconditioning); (2) IPost+ S1P group (cells were pretreated with S1P (1 μmol/L) for 2 h before IPost); (3) IPost+ W-146+ S1P group (cells in IPost+ W-146+ S1P group were pretreated with S1P1 inhibitor W-146 (0.4 μmol/L) for 20 min); (4) IPost+ PD98059+ S1P group (cells in IPost+ S1P group were pretreated with MAPK antagonist PD98059 (125 μmol/L) for 20 min); (5) IPost+ LY-294002+ S1P group (cells in IPost+ S1P group were pretreated with PI3K antagonist LY294002 (0.1 μmol/L) for 20 min). Apoptosis was detected by flow cytometry and protein expression of relevant signal pathways were detected by Western blot. (1)Apoptosis rate was significantly increased in hypoxia/reoxygenation (27.90±4.49)% group compared with normal control group (7.97±2.18)%, which could be significantly reduced in IPost group (15.90±1.77)% (all PS1P and IPost+ S1P+ LY-294002 groups than in IPost and IPost+ S1P+ W-146 and IPost+ S1P+ PD98059 group (all PS1P and IPost+ S1P+ LY-294002 group than in IPost and IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 group (all PS1P+ W-146 and IPost+ S1P+ PD98059 groups. p-ERK1/2 and p-Akt levels in IPost+ S1P+ W-146 group and IPost+ S1P+ PD98059 were similar as in IPost group. S1P can play protective role on NE induced cardiomyocytes hypertrophy during post conditioning through downregulating caspase-3 expression and

Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor.

Science.gov (United States)

Onuma, Takashi; Tanabe, Kumiko; Kito, Yuko; Tsujimoto, Masanori; Uematsu, Kodai; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Doi, Tomoaki; Nagase, Kiyoshi; Akamatsu, Shigeru; Tokuda, Haruhiko; Ogura, Shinji; Iwama, Toru; Kozawa, Osamu; Iida, Hiroki

2017-08-01

Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation. Co-stimulation with S1P and collagen suppressed collagen-induced platelet activation, but the effect was weaker than that of S1P-pretreatment. The collagen-stimulated secretion of platelet-derived growth factor (PDGF)-AB and the soluble CD40 ligand (sCD40L) release were significantly reduced by S1P. In addition, S1P suppressed the collagen-induced release of HSP27 as well as the phosphorylation of HSP27. S1P significantly suppressed the collagen-induced phosphorylation of p38 mitogen-activated protein kinase. S1P increased the levels of GTP-bound Gαi and GTP-bound Gα13 coupled to S1PPR1 and/or S1PR4. CYM50260, a selective S1PR4 agonist, but not SEW2871, a selective S1PR1 agonist, suppressed the collagen-stimulated platelet aggregation, PDGF-AB secretion and sCD40L release. In addition, CYM50260 reduced the release of phosphorylated-HSP27 by collagen as well as the phosphorylation of HSP27. The selective S1PR4 antagonist CYM50358, which failed to affect collagen-induced HSP27 phosphorylation, reversed the S1P-induced attenuation of HSP27 phosphorylation by collagen. These results strongly suggest that S1P inhibits the collagen-induced human platelet activation through S1PR4 but not S1PR1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling.

Science.gov (United States)

Moon, Eunjung; Han, Jeong Eun; Jeon, Sejin; Ryu, Jong Hoon; Choi, Ji Woong; Chun, Jerold

2015-01-01

Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling

Directory of Open Access Journals (Sweden)

Eunjung Moon

2015-01-01

Full Text Available Initial and recurrent stroke produces central nervous system (CNS damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain.

S1P4 Regulates Passive Systemic Anaphylaxis in Mice but Is Dispensable for Canonical IgE-Mediated Responses in Mast Cells

Directory of Open Access Journals (Sweden)

Joseph M. Kulinski

2018-04-01

Full Text Available Mast cells are key players in the development of inflammatory allergic reactions. Cross-linking of the high-affinity receptor for IgE (FcεRI on mast cells leads to the generation and secretion of the sphingolipid mediator, sphingosine-1-phosphate (S1P which is able, in turn, to transactivate its receptors on mast cells. Previous reports have identified the expression of two of the five receptors for S1P on mast cells, S1P1 and S1P2, with functions in FcεRI-mediated chemotaxis and degranulation, respectively. Here, we show that cultured mouse mast cells also express abundant message for S1P4. Genetic deletion of S1pr4 did not affect the differentiation of bone marrow progenitors into mast cells or the proliferation of mast cells in culture. A comprehensive characterization of IgE-mediated responses in S1P4-deficient bone marrow-derived and peritoneal mouse mast cells indicated that this receptor is dispensable for mast cell degranulation, cytokine/chemokine production and FcεRI-mediated chemotaxis in vitro. However, interleukin-33 (IL-33-mediated enhancement of IgE-induced degranulation was reduced in S1P4-deficient peritoneal mast cells, revealing a potential negative regulatory role for S1P4 in an IL-33-rich environment. Surprisingly, genetic deletion of S1pr4 resulted in exacerbation of passive systemic anaphylaxis to IgE/anti-IgE in mice, a phenotype likely related to mast cell-extrinsic influences, such as the high circulating levels of IgE in these mice which increases FcεRI expression and consequently the extent of the response to FcεRI engagement. Thus, we provide evidence that S1P4 modulates anaphylaxis in an unexpected manner that does not involve regulation of mast cell responsiveness to IgE stimulation.

Sphingosine-1-Phosphate (S1P) Lyase Inhibition Causes Increased Cardiac S1P Levels and Bradycardia in Rats.

Science.gov (United States)

Harris, Christopher M; Mittelstadt, Scott; Banfor, Patricia; Bousquet, Peter; Duignan, David B; Gintant, Gary; Hart, Michelle; Kim, Youngjae; Segreti, Jason

2016-10-01

Inhibition of the sphingosine-1-phosphate (S1P)-catabolizing enzyme S1P lyase (S1PL) elevates the native ligand of S1P receptors and provides an alternative mechanism for immune suppression to synthetic S1P receptor agonists. S1PL inhibition is reported to preferentially elevate S1P in lymphoid organs. Tissue selectivity could potentially differentiate S1PL inhibitors from S1P receptor agonists, the use of which also results in bradycardia, atrioventricular block, and hypertension. But it is unknown if S1PL inhibition would also modulate cardiac S1P levels or cardiovascular function. The S1PL inhibitor 6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile was used to determine the relationship in rats between drug concentration, S1P levels in select tissues, and circulating lymphocytes. Repeated oral doses of the S1PL inhibitor fully depleted circulating lymphocytes after 3 to 4 days of treatment in rats. Full lymphopenia corresponded to increased levels of S1P of 100- to 1000-fold in lymph nodes, 3-fold in blood (but with no change in plasma), and 9-fold in cardiac tissue. Repeated oral dosing of the S1PL inhibitor in telemeterized, conscious rats resulted in significant bradycardia within 48 hours of drug treatment, comparable in magnitude to the bradycardia induced by 3 mg/kg fingolimod. These results suggest that S1PL inhibition modulates cardiac function and does not provide immune suppression with an improved cardiovascular safety profile over fingolimod in rats. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

SIRT1 mediates Sphk1/S1P-induced proliferation and migration of endothelial cells.

Science.gov (United States)

Gao, Zhan; Wang, Hua; Xiao, Feng-Jun; Shi, Xue-Feng; Zhang, Yi-Kun; Xu, Qin Qin; Zhang, Xiao-Yan; Ha, Xiao-Qin; Wang, Li-Sheng

2016-05-01

Angiogenesis is one of the most important components of embryonic organ formation and vessel growth after birth. Sphingosine kinase 1 (Sphk1) and S1P has been confirmed to participate in various cell signaling pathways and physiological processes including neovascularisation. However, the mechanisms that Sphk1/S1P regulates neovascularisation remain unclear. In this study, we elucidated that Sphk1/S1P upregulates sirtuin 1 (SIRT1), a NAD+ dependent deacetylases protease which exerts multiple cellular functions, to regulate the proliferation and migration of endothelial cells. By using CCK8 and Transwell assays, we demonstrated that Sphk1 and SIRT1 knockdown could significantly decrease proliferation and migration of HUVEC cells. Sphk1 inhibition results in SIRT1 downregulation which could be reversed by exogenous S1P in HUVEC cells. Treatment of HUVECs with S1P reverses the impaired proliferation and migration caused by SIRT1 knockdown. Furthermore, Sphk1 knockdown inhibits the phosphorylation of P38 MAPK, ERK and AKT. Treatment of HUVECs with PD98059, SB203580 and Wortmannin, which are the inhibitors of ERK, P38 MAPK and AKT respectively, resulted in decreased SIRT1 expression and reduced migration of HUVEC cells. Thus, we conclude that Sphk1/S1P induces SIRT1 upregulation through multiple pathways including P38 MAPK, ERK and AKT signals. This is the first report to disclose the existence and roles of Sphk1/S1P/SIRT1 axis in regulation of endothelial cell proliferation and migration, which may provide a theoretical basis for angiogenesis. Copyright © 2016. Published by Elsevier Ltd.

Novel extrahepatic cytochrome P450s

International Nuclear Information System (INIS)

Karlgren, Maria; Miura, Shin-ichi; Ingelman-Sundberg, Magnus

2005-01-01

The cytochrome P450 enzymes are highly expressed in the liver and are involved in the metabolism of xenobiotics. Because of the initiatives associated with the Human Genome Project, a great progress has recently been seen in the identification and characterization of novel extrahepatic P450s, including CYP2S1, CYP2R1, CYP2U1 and CYP2W1. Like the hepatic enzymes, these P450s may play a role in the tissue-specific metabolism of foreign compounds, but they may also have important endogenous functions. CYP2S1 has been shown to metabolize all-trans retinoic acid and CYP2R1 is a major vitamin D 25-hydroxylase. Regarding their metabolism of xenobiotics, much remains to be established, but CYP2S1 metabolizes naphthalene and it is likely that these P450s are responsible for metabolic activation of several different kinds of xenobiotic chemicals and contribute to extrahepatic toxicity and carcinogenesis

Regulation of actomyosin ATPase activity by troponin-tropomyosin: effect of the binding of the myosin subfragment 1 (S-1) ATP complex

International Nuclear Information System (INIS)

Greene, L.E.; Williams, D.L. Jr.; Eisenberg, E.

1987-01-01

In the authors' model of regulation, the observed lack of cooperativity in the binding of myosin subfragment 1 (S-1) with bound ATP to the troponin-tropomyosin-actin complex (regulated actin) is explained by S-1 ATP having about the same affinity for the conformation of the regulated actin that activates the myosin ATPase activity (turned-on form) and the conformation that does not activate the myosin ATPase activity (turned-off form). This predicts that, in the absence of Ca 2+ , S-1 ATP should not turn on the regulated actin filament. In the present study, they tested this prediction by using either unmodified S-1 or S-1 chemically modified with N,N'-p-phenylenedimaleimide (pPDM S-1) so that functionally it acts like S-1 ATP, although it does not hydrolyze ATP. [ 14 C]pPDM and [ 32 P]ATP were used as tracers. They found that, in the absence of Ca 2+ , neither S-1 ATP nor pPDM S-1 ATP significantly turns on the ATPase activity of the regulated complex of actin and S-1 (acto S-1). In contrast, in the presence of Ca 2+ , pPDM S-1 ATP binding almost completely turns on the regulated acto S-1 ATPase activity. These results can be explained by their original cooperativity model, with pPDM S-1 ATP binding only ≅ 2 fold more strongly to the turned-on form that to the turned-off form of regulated actin. However, the results are not consistent with our alternative model, which predicts that if pPDM S-1 ATP binds to actin in the absence of Ca 2+ but does not turn on the ATPase activity, then it should also turn on the ATPase activity in the presence of Ca 2+

ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs.

Science.gov (United States)

Ren, Kun; Lu, Yan-Ju; Mo, Zhong-Cheng; -Liu, Xing; Tang, Zhen-Li; Jiang, Yue; Peng, Xiao-Shan; Li, Li; Zhang, Qing-Hai; Yi, Guang-Hui

2017-05-01

Endothelial dysfunction plays a vital role during the initial stage of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) induces vascular endothelial injury and vessel wall inflammation. Sphingosine-1-phosphate (S1P) exerts numerous vasoprotective effects by binding to diverse S1P receptors (S1PRs; S1PR1-5). A number of studies have shown that in endothelial cells (ECs), S1PR2 acts as a pro-atherosclerotic mediator by stimulating vessel wall inflammation through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Scavenger receptor class B member I (SR-BI), a high-affinity receptor for apolipoprotein A-I (apoA-I)/high-density lipoprotein (HDL), inhibits nuclear factor-κB (NF-κB) translocation and decreases the plasma levels of inflammatory mediators via the PI3K/Akt pathway. We hypothesized that the inflammatory effects of S1P/S1PR2 on ECs may be regulated by apoA-I/SR-BI. The results showed that ox-LDL, a pro-inflammatory factor, augmented the S1PR2 level in human umbilical vein endothelial cells (HUVECs) in a dose- and time-dependent manner. In addition, S1P/S1PR2 signaling influenced the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-10, aggravating inflammation in HUVECs. Moreover, the pro-inflammatory effects induced by S1P/S1PR2 were attenuated by SR-BI overexpression and enhanced by an SR-BI inhibitor, BLT-1. Further experiments showed that the PI3K/Akt signaling pathway was involved in this process. Taken together, these results demonstrate that apoA-I/SR-BI negatively regulates S1P/S1PR2-mediated inflammation in HUVECs by activating the PI3K/Akt signaling pathway.

The calculation of oscillator strengths for the 5s21S0→5s5p1,3P1 transitions in Cd-like ions

International Nuclear Information System (INIS)

Li Guangyuan

1998-01-01

The screened hydrogenic model is employed to calculate the oscillator strength of the 5s 2 1 S 0 -5s5p 1 P 1 resonance transition in Cd-like ions (Z = 48 -74). The expression for the oscillator strength of the 5s 2 1 S 0 -5s5p 3 P1 is given, with the introduction of the correctional coefficient K and the mixing angle in jj-coupling. The results are compared with that of other authors, and some discussions are also given

Exploring the ϒ (4 S ,5 S ,6 S )→hb(1 P )η hidden-bottom hadronic transitions

Science.gov (United States)

Zhang, Yawei; Li, Gang

2018-01-01

Recently, the Belle Collaboration has reported the measurement of the spin-flipping transition ϒ (4 S )→hb(1 P )η with an unexpectedly large branching ratio: B (ϒ (4 S )→hb(1 P )η )=(2.18 ±0.11 ±0.18 )×10-3 . Such a large branching fraction contradicts with the anticipated suppression for the spin flip. In this work, we examine the effects induced by intermediate bottomed meson loops and point out that these effects are significantly important. Using the effective Lagrangian approach (ELA), we find the experimental data on ϒ (4 S )→hb(1 P )η can be accommodated with the reasonable inputs. We then explore the decays ϒ (5 S ,6 S )→hb(1 P )η and find that these two channels also have sizable branching fractions. We also calculate these processes in the framework of nonrelativistic effective field theory (NREFT). For the decays ϒ (4 S )→hb(1 P )η , the NREFT results are at the same order of magnitude but smaller than the ELA results by a factor of 2 to 5. For the decays ϒ (5 S ,6 S )→hb(1 P )η , the NREFT results are smaller than the ELA results by approximately 1 order of magnitude. We suggest a future experiment Belle-II to search for the ϒ (5 S ,6 S )→hb(1 P )η decays, which will be helpful for understanding the transition mechanism.

Frontiers of environmental regulation: environmental management systems: a regulator`s perspective

Energy Technology Data Exchange (ETDEWEB)

Stone, M.J. [South Australian Dept. of Mines and Energy, Adelaide, SA (Australia)

1996-12-31

Leading edge companies throughout the world have embraced management systems to achieve optimal sustainable performance in the ever changing business environment of the 1990s. Given that the natural environment and environmental performance have become major issues affecting organizations, the need for integrating environmental management with all the other components of an organization`s overall management approach is now widely recognized. This paper is organized in five parts. The first explores recently released environmental standards, the interim environmental management systems (EMS) general guidelines standard AS/NZS ISO 14004 (Int) and identifies how this has dealt with the regulator/community/company interface. The second identifies company requirements for addressing environmental issues. The third, considers regulatory theory to identify current requirements for an effective regulatory system and how this can interface with a company`s EMS. These form the basis in the fourth section for identifying some opportunities which occur at the company/ regulator interface. The fifth and final section draws a number of conclusions about the current frontiers of environmental regulation. The coincidence of the requirements of a regulatory framework with the areas of interface between what is referred to in the draft International Standard for EMS as `Interested Parties`, the regulators and community, are identified. (author). 1 tab., 2 figs., 20 refs.

Interventions pour améliorer la santé des mères, des nouveau-nés ...

International Development Research Centre (IDRC) Digital Library (Canada)

Améliorer la qualité des soins. - Assurer la bonne continuité de la prise en charge des mères et des enfants. - S'attaquer aux problèmes financiers et géographiques liés au paludisme saisonnier. De la grossesse à l'accouchement. Dans les deux pays visés, les chercheurs évalueront le rôle de quatre interventions sur les ...

pH-Dependent DNA Distortion and Repression of Gene Expression by Pectobacterium atrosepticum PecS.

Science.gov (United States)

Deochand, Dinesh K; Meariman, Jacob K; Grove, Anne

2016-07-15

Transcriptional activity is exquisitely sensitive to changes in promoter DNA topology. Transcription factors may therefore control gene activity by modulating the relative positioning of -10 and -35 promoter elements. The plant pathogen Pectobacterium atrosepticum, which causes soft rot in potatoes, must alter gene expression patterns to ensure growth in planta. In the related soft-rot enterobacterium Dickeya dadantii, PecS functions as a master regulator of virulence gene expression. Here, we report that P. atrosepticum PecS controls gene activity by altering promoter DNA topology in response to pH. While PecS binds the pecS promoter with high affinity regardless of pH, it induces significant DNA distortion only at neutral pH, the pH at which the pecS promoter is repressed in vivo. At pH ∼8, DNA distortions are attenuated, and PecS no longer represses the pecS promoter. A specific histidine (H142) located in a crevice between the dimerization- and DNA-binding regions is required for pH-dependent changes in DNA distortion and repression of gene activity, and mutation of this histidine renders the mutant protein incapable of repressing the pecS promoter. We propose that protonated PecS induces a DNA conformation at neutral pH in which -10 and -35 promoter elements are suboptimally positioned for RNA polymerase binding; on deprotonation of PecS, binding is no longer associated with significant changes in DNA conformation, allowing gene expression. We suggest that this mode of gene regulation leads to differential expression of the PecS regulon in response to alkalinization of the plant apoplast.

Quenching of 4He(21S,21P) and 3He(21S,21P) states by collisions with Ne(1S0) atoms

International Nuclear Information System (INIS)

Blagoev, K.B.; Dimova, E.; Petrov, G.M.

2004-01-01

The cross sections and rate constants for quenching 4 He(2 1 S), 4 He(2 1 P), 3 He(2 1 S) and 3 He(2 1 P) states by collisions with ground state Ne atoms are measured by a time-resolved method in a He-Ne electron beam excited plasma at low pressure. These rate constants at T g =600 K are: k 4 He(2 1 S) =(1.6±0.2)x10 -10 , k 4 He(2 1 P) =(3.4±2.5)x10 -10 , k 3 He(2 1 S) =(1.6±0.2)x10 -10 and k 3 He(2 1 P) =(5.7±1.2)x10 -10 cm 3 s -1 . The cross sections derived from the rate constant are σ 4 He(2 1 S) =(8.4±0.8)x10 -16 , σ 4 He(2 1 P) =(1.8±1.3)x10 -15 , σ 3 He(2 1 S) =(7.1±0.9)x10 -16 and σ 3 He(2 1 P) =(2.6±0.5)x10 -15 cm 2 , respectively. The diffusion coefficient of 3 He(2 1 S) in 3 He is estimated to be D 3 He(2 1 S)- 3 He =1.9D 4 He(2 1 S)- 4 He , based on comparison with 4 He. A time-dependent collisional radiative model for an e-beam sustained He-Ne plasma is developed and the predicted line intensity of NeI λ=6328 A line is compared with the experimental data. The influence of different processes involved in population and depopulation dynamics of He(2 1 S) state are evaluated

Instituições do Estado desenvolvimentista na América Latina no contexto pós-neoliberal: os casos do Brasil e Argentina em perspectiva comparada.

Directory of Open Access Journals (Sweden)

Moisés Villamil Balestro

2013-02-01

Full Text Available O artigo analisa características do Estado desenvolvimentista no período pós-neoliberal no Brasil e na Argentina. A emergência de uma fase pós-neoliberal na América Latina está associada, ainda que sob diferentes matizes ideológicas, à ideia de expansão de políticas sociais e à retomada do papel do Estado na formulação e incentivo a estratégias de desenvolvimento econômico. Um aspecto fundamental para a eficácia das estratégias de desenvolvimento são as instituições e organizações envolvidas politica e economicamente. Como mostra a literatura, o desafio de construir um Estado desenvolvimentista requer a combinação de um Estado facilitador com uma estratégia de upgrading industrial acompanhada de aumento da inclusão social. Uma diferença relevante no caso brasileiro em relação ao caso argentino foi a permanência de instituições que foram construídas durante o período desenvolvimentista, com especial destaque para o BNDES. Ao verificar a relação entre Estado e desenvolvimento nos dois países, foi possível identificar quatro diferenças fundamentais do Brasil em relação à Argentina; uma forte instituição financeira de desenvolvimento e instituições financeiras públicas, uma maior capacidade estatal com uma burocracia estável e meritocrática no caso brasileiro, políticas sociais de longo prazo e uma relação mais cooperativa entre Estado e empresariado.

Characterization of three different clusters of 18S-26S ribosomal DNA genes in the sea urchin P. lividus: Genetic and epigenetic regulation synchronous to 5S rDNA.

Science.gov (United States)

Bellavia, Daniele; Dimarco, Eufrosina; Caradonna, Fabio

2016-04-15

We previously reported the characterization 5S ribosomal DNA (rDNA) clusters in the common sea urchin Paracentrotus lividus and demonstrated the presence of DNA methylation-dependent silencing of embryo specific 5S rDNA cluster in adult tissue. In this work, we show genetic and epigenetic characterization of 18S-26S rDNA clusters in this specie. The results indicate the presence of three different 18S-26S rDNA clusters with different Non-Transcribed Spacer (NTS) regions that have different chromosomal localizations. Moreover, we show that the two largest clusters are hyper-methylated in the promoter-containing NTS regions in adult tissues, as in the 5S rDNA. These findings demonstrate an analogous epigenetic regulation in small and large rDNA clusters and support the logical synchronism in building ribosomes. In fact, all the ribosomal RNA genes must be synchronously and equally transcribed to perform their unique final product. Copyright © 2016 Elsevier B.V. All rights reserved.

Sphingosine-1-Phosphate (S1P) Impacts Presynaptic Functions by Regulating Synapsin I Localization in the Presynaptic Compartment.

Science.gov (United States)

Riganti, Loredana; Antonucci, Flavia; Gabrielli, Martina; Prada, Ilaria; Giussani, Paola; Viani, Paola; Valtorta, Flavia; Menna, Elisabetta; Matteoli, Michela; Verderio, Claudia

2016-04-20

Growing evidence indicates that sphingosine-1-P (S1P) upregulates glutamate secretion in hippocampal neurons. However, the molecular mechanisms through which S1P enhances excitatory activity remain largely undefined. The aim of this study was to identify presynaptic targets of S1P action controlling exocytosis. Confocal analysis of rat hippocampal neurons showed that S1P applied at nanomolar concentration alters the distribution of Synapsin I (SynI), a presynaptic phosphoprotein that controls the availability of synaptic vesicles for exocytosis. S1P induced SynI relocation to extrasynaptic regions of mature neurons, as well as SynI dispersion from synaptic vesicle clusters present at axonal growth cones of developing neurons. S1P-induced SynI relocation occurred in a Ca(2+)-independent but ERK-dependent manner, likely through the activation of S1P3 receptors, as it was prevented by the S1P3 receptor selective antagonist CAY1044 and in neurons in which S1P3 receptor was silenced. Our recent evidence indicates that microvesicles (MVs) released by microglia enhance the metabolism of endogenous sphingolipids in neurons and stimulate excitatory transmission. We therefore investigated whether MVs affect SynI distribution and whether endogenous S1P could be involved in the process. Analysis of SynI immunoreactivity showed that exposure to microglial MVs induces SynI mobilization at presynaptic sites and growth cones, whereas the use of inhibitors of sphingolipid cascade identified S1P as the sphingolipid mediating SynI redistribution. Our data represent the first demonstration that S1P induces SynI mobilization from synapses, thereby indicating the phosphoprotein as a novel target through which S1P controls exocytosis. Growing evidence indicates that the bioactive lipid sphingosine and its metabolite sphingosine-1-P (S1P) stimulate excitatory transmission. While it has been recently clarified that sphingosine influences directly the exocytotic machinery by activating the

Senior Senator from Florida and Chairman, Senate Committee on Space, Aeronautics and Related Sciences W. Nelson, visiting the ATLAS cavern and LHC tunnel with ATLAS Collaboration Spokesperson P. Jenni and AMS Collaboration Spokesperson S.C.C.Ting, 16 March 2008.

CERN Multimedia

Maximilien Brice

2008-01-01

Senior Senator from Florida and Chairman, Senate Committee on Space, Aeronautics and Related Sciences W. Nelson, visiting the ATLAS cavern and LHC tunnel with ATLAS Collaboration Spokesperson P. Jenni and AMS Collaboration Spokesperson S.C.C.Ting, 16 March 2008.

Mean life of the 2p4(1S)3s 2S state in fluorine

International Nuclear Information System (INIS)

Cheng, K.T.; Chen, M.H.

1985-01-01

In this work, we calculate the radiationless as well as the radiative decay rates for the 2p 4 ( 1 S)3s 2 S state. For comparison purposes, we also make similar calculations for the 2p 4 ( 1 D)4s 2 D state. Our calculation is based on the multi-configuration Dirac-Fock (MCDF) method. As spin-orbit interaction is built in, this method is capable of studying LS forbidden Auger transitions. Details of the Auger transition calculations have been given before. 9 refs

Isoelectronic comparison of the Al-like 3s23p 2P-3s3p24P transitions in the ions P III-Mo XXX

International Nuclear Information System (INIS)

Jupen, C.; Curtis, L.J.

1996-01-01

New observations of the 3s 2 3p 2 P-3s3p 2 4 P intercombination transitions in Al-like ions have been made for Cl V from spark spectra recorded at Lund and for Kr XXIV and Mo XXX from spectra obtained at the JET tokamak. The new results have been combined with other identifications of these transitions along the sequence and empirically systematized and compared with theoretical calculations. A set of smoothed and interpolated values for the excitation energies of the 3s3p 2 4 P levels in P III-Mo XXX is presented. (orig.)

Molecular Symmetry Analysis of Low-Energy Torsional and Vibrational States in the S_{0} and S_{1} States of p-XYLENE to Interpret the Rempi Spectrum

Science.gov (United States)

Groner, Peter; Gardner, Adrian M.; Tuttle, William Duncan; Wright, Timothy G.

2017-06-01

The electronic transition S_{1} ← S_{0} of p-xylene (pXyl) has been observed by REMPI spectroscopy. Its analysis required a detailed investigation of the molecular symmetry of pXyl whose methyl groups are almost free internal rotors. The molecular symmetry group of pXyl has 72 operators. This group, called [33]D_{2h}, is isomorphic to G_{36}(EM), the double group for ethane and dimethyl acetylene even though it is NOT a double group for pXyl. Loosely speaking, the group symbol, [33]D_{2h}, indicates that is for a molecule with two threefold rotors on a molecular frame with D_{2h} point group symmetry. The transformation properties of the (i) free internal rotor basis functions for the torsional coordinates, (ii) the asymmetric rotor (Wang) basis functions for the Eulerian angles, (iii) nuclear spin functions, (iv) potential function, and (v) transitions dipole moment functions were determined. The forms of the torsional potential in the S_{0} and S_{1} states and the dependence of the first order torsional splittings on the potential coefficients have been obtained. AM Gardner, WD Tuttle, P. Groner, TG Wright, J. Chem. Phys., submitted Dec 2016 P Groner, JR Durig, J. Chem. Phys., 66 (1977) 1856 PR Bunker, P Jensen, Molecular Symmetry and Spectroscopy (1998, NRC Research Press, Ottawa, 2nd ed.)

The 4s24p3-4s4p4 transition in AsI-like AgXV

International Nuclear Information System (INIS)

Dong Chenzhong; Zhao Jinbao

1992-01-01

Some terms of the 4s 4p 4 configuration in RuXII, RhXIII and PdXIV ions can be improved and all the energy values of the configuration in AgXV can be predicted theoretically by means of a configuration-interaction ab initio analysis for the level structure of the 4s 4p 4 configuration along the AsI sequence of KrIV-AgXV ions. Calculations of the wavelengths and oscillator strenghts are presented for the 4s 2 4p 3 -4s 4p 4 transition in AgXV. (orig.)

Electron Excitation Rate Coefficients for Transitions from the IS21S Ground State to the 1S2S1,3S and 1S2P1,3P0 Excited States of Helium

Science.gov (United States)

Aggarwal, K. M.; Kingston, A. E.; McDowell, M. R. C.

1984-03-01

The available experimental and theoretical electron impact excitation cross section data for the transitions from the 1s2 1S ground state to the 1s2s 1,3S and 1s2p 1,3P0 excited states of helium are assessed. Based on this assessed data, excitation rate coefficients are calculated over a wide electron temperature range below 3.0×106K. A comparison with other published results suggests that the rates used should be lower by a factor of 2 or more.

Investigation of the 33S(d,p)34S reaction

NARCIS (Netherlands)

Baan, J.G. van der; Sikora, B.R.

1971-01-01

Angular distributions have been measured of proton groups, corresponding to 34S states up to Ex = 6.63 MeV excited in the reaction 33S(d, p)34S at Ed = 12 MeV, with the use of a split-pole magnetic spectrograph. The ground state Q-value has been measured as Qo = 9195±6 keV. A DWBA analysis yields ln

Serum concentrations of soluble (s)L- and (s)P-selectins in women with ovarian cancer.

Science.gov (United States)

Majchrzak-Baczmańska, Dominika B; Głowacka, Ewa; Wilczyński, Miłosz; Malinowski, Andrzej

2018-03-01

The aim of the study was to compare serum concentration of soluble L- and P-selectins in women with ovarian cancer (OC) and healthy controls, and to investigate sL- and sP-selectin levels with regard to clinical and pathological parameters. Correlation analysis was used to measure the following: sL- and sP-selectin concentration and Ca125; sP-selectin and platelet concentrations; and sL-selectin and serum leukocyte levels in women with OC. The study included 29 patients with OC and 23 healthy controls. Serum concentrations of sL- and sP-selectins were measured in all subjects. Routine diagnostic tests: CBC and USG (both groups) and Ca125 (study group) were performed. Significantly higher serum concentrations of sL- and sP-selectins were found in the study group as compared to controls. Lower levels of serum sL-selectin were observed in women with poorly-differentiated OC (G3) and advanced stages of the disease (FIGO III, IV), but the results were statistically insignificant. No statistically significant relationship was detected between sP-selectin serum concentration in women with OC and tumour differentiation, histological type, and stage of the disease. No significant correlation was found between sL- and sP-selectins and Ca125 levels. A weak correlation was found between serum concentration of sP-selectin in women with OC and platelet count. No statistically significant correlation was observed between sL-selectin concentration and serum leukocyte levels in women with OC. The analysis of sL- and sP-selectin concentrations may be a useful tool in the diagnosis of OC. The levels of sL-selectin decrease with disease progression.

Power project finance outside the U.S.: S and P's rating perspective

International Nuclear Information System (INIS)

Chew, William

1994-01-01

The growing prevalence of capital market debt financing for power projects outside the U.S. highlights the importance of understanding the risks this type of project poses, both for sponsors and potential investors. Based on its initial review of non-U.S. projects, S and P believes the stronger among them clearly have the potential to achieve ratings equal to or higher than those of U.S. projects. Nevertheless, sponsors still will need to address some of the risks such projects entail. S and P has established criteria that apply to power projects in all markets; however, it also has identified additional risks for projects outside the U.S. that should be addressed. (author)

Human subtilase SKI-1/S1P is a master regulator of the HCV Lifecycle and a potential host cell target for developing indirect-acting antiviral agents.

Directory of Open Access Journals (Sweden)

Andrea D Olmstead

2012-01-01

Full Text Available HCV infection is a major risk factor for liver cancer and liver transplantation worldwide. Overstimulation of host lipid metabolism in the liver by HCV-encoded proteins during viral infection creates a favorable environment for virus propagation and pathogenesis. In this study, we hypothesize that targeting cellular enzymes acting as master regulators of lipid homeostasis could represent a powerful approach to developing a novel class of broad-spectrum antivirals against infection associated with human Flaviviridae viruses such as hepatitis C virus (HCV, whose assembly and pathogenesis depend on interaction with lipid droplets (LDs. One such master regulator of cholesterol metabolic pathways is the host subtilisin/kexin-isozyme-1 (SKI-1--or site-1 protease (S1P. SKI-1/S1P plays a critical role in the proteolytic activation of sterol regulatory element binding proteins (SREBPs, which control expression of the key enzymes of cholesterol and fatty-acid biosynthesis. Here we report the development of a SKI-1/S1P-specific protein-based inhibitor and its application to blocking the SREBP signaling cascade. We demonstrate that SKI-1/S1P inhibition effectively blocks HCV from establishing infection in hepatoma cells. The inhibitory mechanism is associated with a dramatic reduction in the abundance of neutral lipids, LDs, and the LD marker: adipose differentiation-related protein (ADRP/perilipin 2. Reduction of LD formation inhibits virus assembly from infected cells. Importantly, we confirm that SKI-1/S1P is a key host factor for HCV infection by using a specific active, site-directed, small-molecule inhibitor of SKI-1/S1P: PF-429242. Our studies identify SKI-1/S1P as both a novel regulator of the HCV lifecycle and as a potential host-directed therapeutic target against HCV infection and liver steatosis. With identification of an increasing number of human viruses that use host LDs for infection, our results suggest that SKI-1/S1P inhibitors may allow

How to develop the internal responsibility according to P.Ya. Galperin’s conce

Directory of Open Access Journals (Sweden)

Sergey V. Molchanov

2017-09-01

Full Text Available The paper presents the ideas of P.Ya. Galperin on the nature of moral behaviour and the basic patterns of internal responsibility in childhood and adolescence. Distinctive features of objective and subjective responsibility, internal and external responsibility are highlighted. It is argued that internal responsibility expresses the person’s attitude to society and social groups and might be developed only if involved in certain relations and implemented in socially useful activities, i.e. if it is significant for other people. The psychological roles of cooperation for of responsibility are compared in J. Piaget’s works and P.Ya. Galperin’s scientific theory. The research results of internal responsibility in primary school students and adolescents conducted by P.Ya. Galperin and T.V. Morozkina are discussed. The decisive role of value orientation and motivation in solving «affective type» problems and in moral behaviour is shown. According philosophy issues, responsibility is considered as a perceived necessity, which assumes a free moral choice. Three criteria of moral responsibility are introduced: the causal relationship between the subject’s behaviour and its consequence, subject’s ability to predict the possible consequences of his/her behaviour, the possibility of free choice. The psychological content of responsibility is the subject’s commitment and further response regulated by a certain system of norms and regulations on the basis of moral choice and self-regulation. The distinction between the action device and motive as the accepted moral basis for behaviour has been introduced. Accordingly, responsible behaviour is considered as willful behaviour. The genesis of strong-will behaviour is associated with social relations and moral values and is developed in the course of cooperation. Conditions of orientation in moral choice as a prerequisite for actualizing the individual’s internal responsibility are discussed.

Sphingosine kinase 1/sphingosine-1-phosphate (S1P)/S1P receptor axis is involved in ovarian cancer angiogenesis.

Science.gov (United States)

Dai, Lan; Liu, Yixuan; Xie, Lei; Wu, Xia; Qiu, Lihua; Di, Wen

2017-09-26

Sphingosine kinase (SphK)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) signaling pathway has been implicated in a variety of pathological processes of ovarian cancer. However, the function of this axis in ovarian cancer angiogenesis remains incompletely defined. Here we provided the first evidence that SphK1/S1P/S1PR 1/3 pathway played key roles in ovarian cancer angiogenesis. The expression level of SphK1, but not SphK2, was closely correlated with the microvascular density (MVD) of ovarian cancer tissue. In vitro , the angiogenic potential and angiogenic factor secretion of ovarian cancer cells could be attenuated by SphK1, but not SphK2, blockage and were restored by the addition of S1P. Moreover, in these cells, we found S1P stimulation induced the angiogenic factor secretion via S1PR 1 and S1PR 3 , but not S1PR 2 . Furthermore, inhibition of S1PR 1/3 , but not S1PR 2 , attenuated the angiogenic potential and angiogenic factor secretion of the cells. in vivo , blockage of SphK or S1PR 1/3 could attenuate ovarian cancer angiogenesis and inhibit angiogenic factor expression in mouse models. Collectively, the current study showed a novel role of SphK1/S1P/S1PR 1/3 axis within the ovarian cancer, suggesting a new target to block ovarian cancer angiogenesis.

Sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis is involved in liver fibrosis-associated angiogenesis.

Science.gov (United States)

Yang, Le; Yue, Shi; Yang, Lin; Liu, Xin; Han, Zhen; Zhang, Yuanyuan; Li, Liying

2013-07-01

Sphingosine kinase (SphK)/sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) axis is involved in multiple biological processes, including liver fibrosis. Angiogenesis is an important pathophysiological process closely associated with liver fibrosis; however, the functional role of SphK/S1P/S1PR in this process remains incompletely defined. Bile duct ligation or carbon tetrachloride was used to induce liver fibrosis in mice. Human fibrotic samples were obtained from livers of patients undergoing liver transplantation. S1P levels in the liver were examined by HPLC. Expression of angiogenic markers, including angiopoietin 1, CD31, vascular cell adhesion molecule-1, and von Willebrand factor, was characterized by immunofluorescence, real-time RT-PCR, and Western blot in the fibrotic liver and primary mouse hepatic stellate cells (HSCs). SphK inhibitor (SKI) or S1PR antagonists were administered intraperitoneally in mice. S1P levels in the liver were closely correlated with mRNA expression of angiogenic markers. Ang1 is expressed in activated HSCs of the fibrotic liver and in primary HSCs. In HSCs, by using specific antagonists or siRNAs, we demonstrated S1P stimulation induced Ang1 expression via S1PR1 and S1PR3. In vivo, S1P reduction by SKI inhibited angiogenesis in fibrotic mice. Furthermore, S1PR1/3 antagonist significantly blocked upregulation of angiogenic markers in the injured liver, and attenuated the extent of liver fibrosis, while S1PR2 antagonist had no effect on angiogenesis, supporting the key role of S1PR1 and S1PR3 in angiogenesis underlying liver fibrosis process. SphK1/S1P/S1PR1/3 axis plays a crucial role in the angiogenic process required for fibrosis development, which may represent an effective therapeutic strategy for liver fibrosis. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

5S Ribosomal RNA Is an Essential Component of a Nascent Ribosomal Precursor Complex that Regulates the Hdm2-p53 Checkpoint

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Giulio Donati

2013-07-01

Full Text Available Recently, we demonstrated that RPL5 and RPL11 act in a mutually dependent manner to inhibit Hdm2 and stabilize p53 following impaired ribosome biogenesis. Given that RPL5 and RPL11 form a preribosomal complex with noncoding 5S ribosomal RNA (rRNA and the three have been implicated in the p53 response, we reasoned they may be part of an Hdm2-inhibitory complex. Here, we show that small interfering RNAs directed against 5S rRNA have no effect on total or nascent levels of the noncoding rRNA, though they prevent the reported Hdm4 inhibition of p53. To achieve efficient inhibition of 5S rRNA synthesis, we targeted TFIIIA, a specific RNA polymerase III cofactor, which, like depletion of either RPL5 or RPL11, did not induce p53. Instead, 5S rRNA acts in a dependent manner with RPL5 and RPL11 to inhibit Hdm2 and stabilize p53. Moreover, depletion of any one of the three components abolished the binding of the other two to Hdm2, explaining their common dependence. Finally, we demonstrate that the RPL5/RPL11/5S rRNA preribosomal complex is redirected from assembly into nascent 60S ribosomes to Hdm2 inhibition as a consequence of impaired ribosome biogenesis. Thus, the activation of the Hdm2-inhibitory complex is not a passive but a regulated event, whose potential role in tumor suppression has been recently noted.

5S ribosomal RNA is an essential component of a nascent ribosomal precursor complex that regulates the Hdm2-p53 checkpoint.

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Donati, Giulio; Peddigari, Suresh; Mercer, Carol A; Thomas, George

2013-07-11

Recently, we demonstrated that RPL5 and RPL11 act in a mutually dependent manner to inhibit Hdm2 and stabilize p53 following impaired ribosome biogenesis. Given that RPL5 and RPL11 form a preribosomal complex with noncoding 5S ribosomal RNA (rRNA) and the three have been implicated in the p53 response, we reasoned they may be part of an Hdm2-inhibitory complex. Here, we show that small interfering RNAs directed against 5S rRNA have no effect on total or nascent levels of the noncoding rRNA, though they prevent the reported Hdm4 inhibition of p53. To achieve efficient inhibition of 5S rRNA synthesis, we targeted TFIIIA, a specific RNA polymerase III cofactor, which, like depletion of either RPL5 or RPL11, did not induce p53. Instead, 5S rRNA acts in a dependent manner with RPL5 and RPL11 to inhibit Hdm2 and stabilize p53. Moreover, depletion of any one of the three components abolished the binding of the other two to Hdm2, explaining their common dependence. Finally, we demonstrate that the RPL5/RPL11/5S rRNA preribosomal complex is redirected from assembly into nascent 60S ribosomes to Hdm2 inhibition as a consequence of impaired ribosome biogenesis. Thus, the activation of the Hdm2-inhibitory complex is not a passive but a regulated event, whose potential role in tumor suppression has been recently noted. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme.

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Bien-Möller, Sandra; Lange, Sandra; Holm, Tobias; Böhm, Andreas; Paland, Heiko; Küpper, Johannes; Herzog, Susann; Weitmann, Kerstin; Havemann, Christoph; Vogelgesang, Silke; Marx, Sascha; Hoffmann, Wolfgang; Schroeder, Henry W S; Rauch, Bernhard H

2016-03-15

A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P1-S1P5) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient´s survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P1, S1P2, S1P3 and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P1 and S1P2 with patient´s survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P1 and S1P2. The participation of S1P1 and S1P2 in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells.In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation.

Controle da antracnose na pós-colheita de manga 'Ubá' com o uso de produtos alternativos

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Lorena Moreira Carvalho Lemos

2013-12-01

Full Text Available Foi avaliada a eficácia de produtos alternativos aos agroquímicos no controle da antracnose na pós-colheita de mangas 'Ubá'. Frutos fisiologicamente maduros foram pulverizados até o completo molhamento, com suspensão de conídios de Colletotrichum gloeosporioides, na concentração de 2,5 x 10(5 conídios/mL. Após a secagem ao ar, foram pulverizados com água destilada (testemunha, tween 20 (8 mL/L de solução, Prochloraz (1,10 mL de Sportak 450 EC/L de solução, óleo de alho (10 mL/L + 8 mL/L de tween 20, óleo de amêndoa de Acrocomia aculeata + leite em pó instantâneo (LPI (25 mL/L+ 10 g LPI/L, óleo de amêndoa de A. aculeata + tween (25 mL/L + 8 mL/L de tween 20, biofertilizante agro-mos® (100 µL/L, óleo de neen (10 mL/L + 8 mL/L de tween 20, quitosana (10 mL/L + 8 mL/L de tween 20 e biomassa cítrica (10 mL/L + 8 mL/L tween 20.O solvente utilizado foi água destilada. Avaliaram-se o período de incubação, o período latente, a perda de massa fresca, a produção de CO² e, diariamente, a severidade e incidência da doença. Os períodos mais curtos de incubação da doença foram observados nos frutos tratados com óleo de neen, água + tween e biomassa cítrica, com aproximadamente cinco dias. O óleo de amêndoa de A. aculeata + LPI e agro-mos® foram os produtos que mais retardaram o aparecimento dos sintomas, impondo à doença o período de incubação de nove dias após a inoculação do patógeno. Quanto à severidade, o óleo de amêndoa de macaúba + LPI e o Prochloraz foram os mais eficientes em conter o crescimento do patógeno até o oitavo dia após a inoculação, sendo que, logo depois, os frutos tratados com óleo de amêndoa de A. aculeata + LPI se igualaram àqueles tratados com a maioria dos demais produtos. Os frutos tratados com óleo de amêndoa de A. aculeata + LPI e óleo de amêndoa de A. aculeata + tween manifestaram as estruturas do patógeno apenas após 13 e 14 dias de avalia

Expression and subcellular localization of p70S6 kinase under heart failure

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Usenko V. S.

2010-11-01

Full Text Available The PI3K/PDK/Akt/mTOR/p70S6K signaling pathway is primary associated with the activation of insulin receptors and is important for cardiomyocytes survival. p70S6K is a key regulator of the speed and efficiency of protein biosynthesis within the cell. Recently the pro-apoptotic protein BAD has been identified as a new target for р70S6K1. BAD is inactivated in normal cardiomyocytes by р70S6K1 phosphorylation which prevents the cardiomyocytes apoptosis. Aim. To study possible changes in р70S6K1 expression and/or cellular localization at heart failure progression – in DCM- affected human myocardia and murine hearts with experimental DCM-like pathology. Methods. Western-blot analysis and immunohystochemistry. Results. The substantial decrease in р70S6K1 level was observed at the final stage of pathology progression and in the dynamics of DCM pathogenesis as well. For the first time relocalization of the protein to the connective tissue was shown according to the Western-blot results. Conclusions. The data obtained allow us to understand a possible role of р70S6K1 in the regulation of stress-induced apoptotic signaling in cardiomyocytes.

P-MoS2 / n-CdS thin film heterojunction

International Nuclear Information System (INIS)

El Maliki, H.; Gourmelon, E.; Bernede, J.C.; Pouzet, J.; Mebarki, M.; Khelil, A.; Zoaeter, M.

1999-01-01

Full text.Layered transition metal dichacolgenides such as MoS 2 are semiconductors that can be good candidates for solar energy conversion. Photo-electrochemical cells based on single crystals have achieved and efficiency of 17% (1). However, up to day, no solid rectifying contact has been put in evidence in the case of MoS 2 thin films.. Recently we have shown that such high crystalline quality MoS 2 films can be obtained onto textured tungsten slides. This allowed to try to grow sandwich rectifying structures. The bottom electrode will be W, MoS 2 being p-type, the n type film used was CdS and the upper electrode was indium. W foils textured along the (h00) direction were used as substrate and bottom electrode. The use of a W (textured) substrate induces the texturation of the MoS 2 films along the (001) direction when after evaporation of the constituents the films were annealed at T=1073 K for half an hour under argon atmosphere. Upon the MoS 2 a CdS thin film was deposited by chemical bath deposition (CBD). CdS thin films were prepared classically from a solution of cadmium sulfate, thiourea in hydrazine and ammonia. Ammonia was used adjust the solution pH to a value between 9 and 10. Bath temperature has been held constant at 343 K. Thin deposit films of CdS were yellow colored. They were constituted of an homogenous and adherent layer with a thickness of about 100 nm. It has been shown by x-ray diffraction the they were crystallized in their hexagonal structure. At least an indium film was deposited in order to achieve the structure M/MoS 2 p/CdSn/M. In order to check the equality of the W/MoS 2 contact, W/MoS 2 /W samples were also carried out by sputtering deposition of the tungsten upper electrode (300 nm thick). The thickness of the MoS 2 layers was about 500 nm. The J-V characteristics of a W/MoS 2 /W sample are ohmic. Moreover the resistance deduced from the slope ΔV/ΔI increases when the temperature decreases, which shows that there is not any

The hyperfine structure constants for the 4s24p and 4s25s states of Ga

International Nuclear Information System (INIS)

Wang Qingmin; Dong Chenzhong

2012-01-01

The hyperfine structure (hfs) constants for the states 4s 2 4p 2 P 1/2,3/2 and 4s 2 5s 2 S 1/2 of 71 Ga were calculated using the GRASP2K package based on the multiconfiguration Dirac-Fock (MCDF) method. The results indicated that the core polarization effect was important for the hyperfine structure constants. (authors)

A genome-wide siRNA screen in mammalian cells for regulators of S6 phosphorylation.

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Angela Papageorgiou

Full Text Available mTOR complex1, the major regulator of mRNA translation in all eukaryotic cells, is strongly activated in most cancers. We performed a genome-wide RNAi screen in a human cancer cell line, seeking genes that regulate S6 phosphorylation, readout of mTORC1 activity. Applying a stringent selection, we retrieved nearly 600 genes wherein at least two RNAis gave significant reduction in S6-P. This cohort contains known regulators of mTOR complex 1 and is significantly enriched in genes whose depletion affects the proliferation/viability of the large set of cancer cell lines in the Achilles database in a manner paralleling that caused by mTOR depletion. We next examined the effect of RNAi pools directed at 534 of these gene products on S6-P in TSC1 null mouse embryo fibroblasts. 76 RNAis reduced S6 phosphorylation significantly in 2 or 3 replicates. Surprisingly, among this cohort of genes the only elements previously associated with the maintenance of mTORC1 activity are two subunits of the vacuolar ATPase and the CUL4 subunit DDB1. RNAi against a second set of 84 targets reduced S6-P in only one of three replicates. However, an indication that this group also bears attention is the presence of rpS6KB1 itself, Rac1 and MAP4K3, a protein kinase that supports amino acid signaling to rpS6KB1. The finding that S6 phosphorylation requires a previously unidentified, functionally diverse cohort of genes that participate in fundamental cellular processes such as mRNA translation, RNA processing, DNA repair and metabolism suggests the operation of feedback pathways in the regulation of mTORC1 operating through novel mechanisms.

Study of astrophysically important resonant states in 30 S using the 32S(p,t30 S reaction

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Wrede C.

2010-03-01

Full Text Available A small fraction (< 1% of presolar SiC grains is suggested to have been formed in the ejecta of classical novae. The 29P(p,γ30S reaction plays an important role in understanding the Si isotopic abundances in such grains, which in turn provide us with information on the nature of the probable white dwarf progenitor’s core, as well as the peak temperatures achieved during nova outbursts, and thus the nova nucleosynthetic path. The 29P(p,γ30S reaction rate at nova temperatures is determined by two low-lying 3+ and 2+ resonances above the proton threshold at 4399 keV in 30S. Despite several experimental studies in the past, however, only one of these two states has only been observed very recently. We have studied the 30S nuclear structure via the 32S(p,t 30S reaction at 5 laboratory angles between 9° to 62°. We have observed 14 states, eleven of which are above the proton threshold, including two levels at 4692.7 ± 4.5 keV and 4813.8 ± 3.4 keV that are candidates for the 3+ and the previously “issing” 2+ state, respectively.

Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism.

Science.gov (United States)

Werth, Stephan; Müller-Fielitz, Helge; Raasch, Walter

2017-12-01

Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely. © 2017 Society for Endocrinology.

S1P Signaling and De Novo Biosynthesis in Blood Pressure Homeostasis

Science.gov (United States)

Cantalupo, Anna

2016-01-01

Initially discovered as abundant components of eukaryotic cell membranes, sphingolipids are now recognized as important bioactive signaling molecules that modulate a variety of cellular functions, including those relevant to cancer and immunologic, inflammatory, and cardiovascular disorders. In this review, we discuss recent advances in our understanding of the role of sphingosine-1-phosphate (S1P) receptors in the regulation of vascular function, and focus on how de novo biosynthesized sphingolipids play a role in blood pressure homeostasis. The therapeutic potential of new drugs that target S1P signaling is also discussed. PMID:27317800

Quasirelativistic calculation of 4s24p5, 4s24p44d and 4s4p6 configuration spectroscopic parameters for the W39+ ion

International Nuclear Information System (INIS)

Bogdanovich, P; Karpuškienė, R; Kisielius, R

2015-01-01

The ab initio quasirelativistic Hartree–Fock method developed specifically for the calculation of spectral parameters of heavy atoms and highly charged ions is used to derive spectral data for the 4s 2 4p 5 , 4s 2 4p 4 4d and 4s4p 6 configurations of the multicharged tungsten ion W 39+ . The relativistic effects are taken into account in the Breit–Pauli approximation for the quasirelativistic Hartree–Fock radial orbitals. The configuration interaction method is applied to include the electron correlation effects. Produced data are compared with existing experimental measurements and theoretical calculations. (paper)

Sb2S3:C/CdS p-n junction by laser irradiation

International Nuclear Information System (INIS)

Arato, A.; Cardenas, E.; Shaji, S.; O'Brien, J.J.; Liu, J.; Castillo, G. Alan; Das Roy, T.K.; Krishnan, B.

2009-01-01

In this paper, we report laser irradiated carbon doping of Sb 2 S 3 thin films and formation of a p-n junction photovoltaic structure using these films. A very thin carbon layer was evaporated on to chemical bath deposited Sb 2 S 3 thin films of approximately 0.5 μm in thickness. Sb 2 S 3 thin films were prepared from a solution containing SbCl 3 and Na 2 S 2 O 3 at 27 deg. C for 5 h and the films obtained were highly resistive. These C/Sb 2 S 3 thin films were irradiated by an expanded laser beam of diameter approximately 0.5 cm (5 W power, 532 nm Verdi laser), for 2 min at ambient atmosphere. Morphology and composition of these films were analyzed. These films showed p-type conductivity due to carbon diffusion (Sb 2 S 3 :C) by the thermal energy generated by the absorption of laser radiation. In addition, these thin films were incorporated in a photovoltaic structure Ag/Sb 2 S 3 :C/CdS/ITO/Glass. For this, CdS thin film of 50 nm in thickness was deposited on a commercially available ITO coated glass substrate from a chemical bath containing CdCl 2 , sodium citrate, NH 4 OH and thiourea at 70 deg. C . On the CdS film, Sb 2 S 3 /C layers were deposited. This multilayer structure was subjected to the laser irradiation, C/Sb 2 S 3 side facing the beam. The p-n junction formed by p-Sb 2 S 3 :C and n-type CdS showed V oc = 500 mV and J sc = 0.5 mA/cm 2 under illumination by a tungsten halogen lamp. This work opens up a new method to produce solar cell structures by laser assisted material processing

Améliorer la gouvernance, la représentation et l'accès à la justice ...

International Development Research Centre (IDRC) Digital Library (Canada)

Améliorer la gouvernance, la représentation et l'accès à la justice dans les établissements humains spontanés au Ghana. Beaucoup de Ghanéens vivant en milieu urbain ne profitent pas encore des avantages de la stabilité démocratique et de la récente croissance économique dans leur pays. Environ 40 % de la ...

Medicinal Product Regulation: Portugal׳s Framework.

Science.gov (United States)

Herdeiro, Maria Teresa; Bastos, Paulo D; Teixeira-Rodrigues, António; Roque, Fátima

2016-09-01

The pharmaceutical industry is one of the most tightly regulated sectors, and it is essential to know each country׳s legal framework to understand the regulation, approval, and marketing of medicinal products for human use. This article describes the main statutes and procedures governing medicinal products for human use in Portugal and the role of the country׳s National Medicines and Health Products Authority (Autoridade Nacional do Medicamento e Produtos de Saúde, I.P.; INFARMED). From the most recently available data, an update of requests and approvals concerning marketing authorizations, variations, pricing, and reimbursements is provided. Data were sourced from the INFARMED website, Infomed (database of medicinal products for human use), and periodic reports issued by national authorities. Organic laws, acts, and law decrees published in the government gazette (Diário da República) are cited and reproduced as required. In 2015 Portugal ranked fifth in the European System of Medicines Evaluation in terms of the number of completed procedures as a reference member state. Approximately 80% of all approved drug applications in Portugal in 2015 were for generic drugs, mostly pertaining to the nervous system. In Portugal, INFARMED monitors drug quality, safety profile, and efficacy in all stages of the drug life cycle, ensuring patients' safety. The Portuguese market for medicinal products for human use has been appreciably changed by the advent of generic drugs. There is an increased trend for new request applications for biological and biotechnological substances. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Phase diagram of ZnCr2pA12-2pS(Se)4 and Zn1-pCdpCr2S(Se)4

International Nuclear Information System (INIS)

Afif, K.; Benyoussef, A.; Hamedoun, M.; Hourmatallah, A.

1999-06-01

We compute the phase diagram of the nonmetallic compounds ZnCr2 p A1 2-2p S(Se) 4 (I[S,Se]) and Zn 1-p Cd p Cr 2 S(Se) 4 (II[S,Se]). We consider the bond-diluted Ising model on the spinel B site (S.B.S.) lattice with competitive exchange interactions, i.e. the ferromagnetic exchange interaction J 1 between nearest neighbours (n.n.) and the antiferromagnetic superexchange interaction J 2 between next-nearest neighbours' (n.n.n.) (and/or the more distant superexchange interactions J i (i > 1). Dilution and competition are found to be responsible for the spill glass phase and the percolation behaviour. (author)

Electron correlation in the 4d-16p→5s-26p and 5s-15p-16p resonance Auger transitions of Xe

International Nuclear Information System (INIS)

Osmekhin, S.; Nikkinen, J.; Sankari, R.; Maeaettae, M.; Kukk, E.; Huttula, M.; Heinaesmaeki, S.; Aksela, H.; Aksela, S.

2007-01-01

The Xe 4d -1 6p→5s 0 5p 6 6p and 5s 1 5p 5 6p resonant Auger transitions have been studied both theoretically and experimentally. High resolution resonant Auger spectra have been recoded with different photon bandwidths which have enabled to separate the first step Auger transition from the overlapping second step transitions. Theoretical calculations using multi-configuration Dirac-Fock approach with different configuration expansions were carried out, compared to each other and to the experiment. The calculations with the largest basis set were found to reproduce the distribution of the intensity to the main and satellite lines in both the 5s 0 5p 6 6p and 5s 1 5p 5 6p Auger groups reasonably well, and to predict the structure of the 4d -1 6p→5s 0 5p 6 6p main lines very well

Perspectivas da participação do público através de ONGs para a gestão ambiental na América Latina

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Gabriel Eduardo Schütz

Full Text Available Este artigo analisa algumas perspectivas e limitações das organizações não-governamentais (ONGs como instância de participação popular para a gestão ambiental local e regional na América Latina. Em primeiro lugar, é analisado o fundamento ético do trabalho voluntário independente nas democracias regionais e sua relação com a formulação de políticas públicas - principalmente nas áreas de saúde e meio ambiente - no processo de globalização da economia mundial. Este estudo também apresentada uma análise qualitativa de dados demográficos, socioeconômicos e ambientais que correlacionam a referência espacial das ONGs com as paradoxais realidades sociopolíticas e socioeconômicas do continente americano. Tenta-se mostrar que setores governamentais e do empresariado vêm estimulando a substituição da solidariedade compulsória das políticas sociais compensatórias pela filantropia e o trabalho voluntário, e que essa tendência é coerente com a reestruturação do capitalismo mundial. Os dados demonstram que, em geral, as ONGs não aparecem e prosperam na pobreza, mas nas áreas de concentração de poder político-econômico associado ao desenvolvimento humano. É discutida a diferença conceitual entre sociedade civil e terceiro setor, comumente identificados como sinônimos. Finalmente, são apresentadas conclusões que podem servir de estímulo para que gestores e o público em geral reflitam sobre o projeto político e econômico que está por trás do incentivo ao trabalho voluntário em áreas de responsabilidade do Estado, como são as áreas de saúde pública e gestão ambiental.

Tables of Shore and Fano parameters for the helium resonances 2s21S, 2p21D, and 2s 2p 1P excited in p-He collisions E/sub p/ = 33 to 150 keV

International Nuclear Information System (INIS)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Merchez, H.

1976-01-01

Absolute values of Shore and Fano parameters are tabulated for the helium atom 2s 2 1 S, 2p 2 1 D, and 2s 2p 1 P resonances produced by a proton beam. Observations were made on the spectra of ejected electrons. The important variation of the shape of the resonances with ejection angle is illustrated for E/sub p/ = 100 keV; the variation with proton energy is shown at 30 0

Sphingosine-1-phosphate (S1P) enhances glomerular endothelial cells activation mediated by anti-myeloperoxidase antibody-positive IgG.

Science.gov (United States)

Sun, Xiao-Jing; Chen, Min; Zhao, Ming-Hui

2018-03-01

Cumulating evidences suggested an important role of sphingosine-1-phosphate (S1P) and its receptors in regulating endothelial barrier integrity. Our previous study revealed that the circulating S1P levels and renal expression of S1PRs correlated with disease activity and renal damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study investigated the role of S1P and its receptors in myeloperoxidase (MPO)-ANCA-positive IgG-mediated glomerular endothelial cell (GEnC) activation. The effect of S1P on morphological alteration of GEnCs in the presence of MPO-ANCA-positive IgG was observed. Permeability assay was performed to determine endothelial monolayer activation in quantity. Both membrane-bound and soluble ICAM-1 and VCAM-1 levels were measured. Furthermore, antagonists and/or agonists of various S1PRs were employed to determine the role of different S1PRs. S1P enhanced MPO-ANCA-positive IgG-induced disruption of tight junction and disorganization of cytoskeleton in GEnCs. S1P induced further increase in monolayer permeability of GEnC monolayers in the presence of MPO-ANCA-positive IgG. S1P enhanced MPO-ANCA-positive IgG-induced membrane-bound and soluble ICAM-1/VCAM-1 up-regulation of GEnCs. Soluble ICAM-1 levels in the supernatants of GEnCs stimulated by S1P and MPO-ANCA-positive IgG increased upon pre-incubation of S1PR1 antagonist, while pre-incubation of GEnCs with the S1PR1 agonist down-regulated sICAM-1 level. Blocking S1PR2-4 reduced sICAM-1 levels in the supernatants of GEnCs stimulated by S1P and MPO-ANCA-positive IgG. Pre-incubation with S1PR5 agonist could increase sICAM-1 level in the supernatants of GEnC stimulated by S1P and MPO-ANCA-positive IgG. S1P can enhance MPO-ANCA-positive IgG-mediated GEnC activation through S1PR2-5. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Regulation of human protein S gene (PROS1) transcription

NARCIS (Netherlands)

Wolf, Cornelia de

2006-01-01

This thesis describes the investigation of the transcriptional regulation of the gene for anticoagulant plasma Protein S, PROS1. Protein S is a cofactor for Protein C in the Protein C anticoagulant pathway. The coagulation cascade is negatively regulated by this pathway through inactivation of

InP/ZnS QDs exposure induces developmental toxicity in rare minnow (Gobiocypris rarus) embryos.

Science.gov (United States)

Chen, Yao; Yang, Yang; Ou, Fang; Liu, Li; Liu, Xiao-Hong; Wang, Zhi-Jian; Jin, Li

2018-04-05

We investigated the in vivo toxicity of InP/ZnS quantum dots (QDs) in Chinese rare minnow (Gobiocypris rarus) embryos. The 72 h post-fertilization (hpf) LC 50 (median lethal concentration) was 1678.007 nmol/L. Rare minnows exposed to InP/ZnS QDs exhibited decreased spontaneous movement, decreased survival and hatchability rates, and an increased malformation rate. Pericardial edema, spinal curvature, bent tails and vitelline cysts were observed. Embryonic Wnt8a and Mstn mRNA levels were significantly up-regulated after InP/ZnS QDs treatment at 48 hpf (200 nmol/L) (p InP/ZnS QDs treatments did not significantly change the Olive tail moments (p > 0.05). Thus, InP/ZnS QDs caused teratogenic effects and death during the development of Chinese rare minnow embryos, but InP/ZnS QDs did not cause significant genetic toxicity during Chinese rare minnow development. Copyright © 2018 Elsevier B.V. All rights reserved.

Differential S-phase progression after irradiation of p53 functional versus non-functional tumour cells

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Zölzer Friedo

2014-12-01

Full Text Available Background. Many pathways seem to be involved in the regulation of the intra-S-phase checkpoint after exposure to ionizing radiation, but the role of p53 has proven to be rather elusive. Here we have a closer look at the progression of irradiated cells through S-phase in dependence of their p53 status.

Production durable de légumes sous-utilisés en vue d'améliorer la ...

International Development Research Centre (IDRC) Digital Library (Canada)

Production durable de légumes sous-utilisés en vue d'améliorer la sécurité alimentaire en milieu ruralrity (Les légumes indigènes revêtent une importance capitale pour les femmes pauvres vivant en milieu rural, mais ont reçu, à ce jour, peu d'attention de la part des milieux de la recherche, du développement et des ...

Theoretical studies on sRNA-mediated regulation in bacteria

Science.gov (United States)

Chang, Xiao-Xue; Xu, Liu-Fang; Shi, Hua-Lin

2015-12-01

Small RNA(sRNA)-mediated post-transcriptional regulation differs from protein-mediated regulation. Through base-pairing, sRNA can regulate the target mRNA in a catalytic or stoichiometric manner. Some theoretical models were built for comparison of the protein-mediated and sRNA-mediated modes in the steady-state behaviors and noise properties. Many experiments demonstrated that a single sRNA can regulate several mRNAs, which causes crosstalk between the targets. Here, we focus on some models in which two target mRNAs are silenced by the same sRNA to discuss their crosstalk features. Additionally, the sequence-function relationship of sRNA and its role in the kinetic process of base-pairing have been highlighted in model building. Project supported by the National Basic Research Program of China (Grant No. 2013CB834100), the National Natural Science Foundation of China (Grant Nos. 11121403 and 11274320), the Open Project Program of State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, China (Grant No. Y4KF171CJ1), the National Natural Science Foundation for Young Scholar of China (Grant No. 11304115), and the China Postdoctoral Science Foundation (Grant No. 2013M541282).

Down-regulation of S100C is associated with bladder cancer progression and poor survival

DEFF Research Database (Denmark)

Memon, Ashfaque Ahmed; Sorensen, Boe Sandahl; Meldgaard, Peter

2005-01-01

cancer biopsy samples obtained from 88 patients followed for a median of 23 months (range, 1-97 months). RESULTS: We found a significantly lower mRNA expression of S100C in connective tissue invasive tumors (T1, P = 0.0030) and muscle invasive tumors [(T2-T4), P ...PURPOSE: The goal of this study was to identify proteins down-regulated during bladder cancer progression. EXPERIMENTAL DESIGN: By using comparative proteome analysis and measurement of mRNA, we found a significant down-regulation of S100C, a member of the S100 family of proteins, in T24 (grade 3......) as compared with RT4 (grade 1) bladder cancer cell lines. Moreover, quantification of the mRNA level revealed that decreased expression of the protein reflects a low level of transcription of the S100C gene. Based on this observation, we quantified the S100C mRNA expression level with real-time PCR in bladder...

Feminismo e/no pós-colonialismo

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Deepika Bahri

2013-11-01

Full Text Available http://dx.doi.org/10.1590/S0104-026X2013000200018 Neste artigo, a autora discorre sobre a relação entre feminismo e pós-colonialismoa partir dos conceitos-chave nos estudos pós-coloniais, salientando as premissas, os métodose as tensões dessa aliança, bem como os desafios entre os feminismos “ocidental” e “póscolonial”no contexto da globalização.

Proteomic Analysis of a Global Regulator GacS Sensor Kinase in the Rhizobacterium, Pseudomonas chlororaphis O6

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Chul Hong Kim

2014-06-01

Full Text Available The GacS/GacA system in the root colonizer Pseudomonas chlororaphis O6 is a key regulator of many traits relevant to the biocontrol function of this bacterium. Proteomic analysis revealed 12 proteins were down-regulated in a gacS mutant of P. chlororaphis O6. These GacS-regulated proteins functioned in combating oxidative stress, cell signaling, biosynthesis of secondary metabolism, and secretion. The extent of regulation was shown by real-time RT-PCR to vary between the genes. Mutants of P. chlororaphis O6 were generated in two GacS-regulated genes, trpE, encoding a protein involved in tryptophan synthesis, and prnA, required for conversion of tryptophan to the antimicrobial compound, pyrrolitrin. Failure of the trpE mutant to induce systemic resistance in tobacco against a foliar pathogen causing soft rot, Pectobacterium carotovorum SCCI, correlated with reduced colonization of root surfaces implying an inadequate supply of tryptophan to support growth. Although colonization was not affected by mutation in the prnA gene, induction of systemic resistance was reduced, suggesting that pyrrolnitrin was an activator of plant resistance as well as an antifungal agent. Study of mutants in the other GacS-regulated proteins will indicate further the features required for biocontrol-activity in this rhizobacterium.

Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated Lamellipodia Formation in Lung Endothelium.

Science.gov (United States)

Fu, Panfeng; Ebenezer, David L; Berdyshev, Evgeny V; Bronova, Irina A; Shaaya, Mark; Harijith, Anantha; Natarajan, Viswanathan

2016-12-30

Hepatocyte growth factor (HGF) signaling via c-Met is known to promote endothelial cell motility and angiogenesis. We have previously reported that HGF stimulates lamellipodia formation and motility of human lung microvascular endothelial cells (HLMVECs) via PI3K/Akt signal transduction and reactive oxygen species generation. Here, we report a role for HGF-induced intracellular sphingosine-1-phosphate (S1P) generation catalyzed by sphingosine kinase 1 (SphK1), S1P transporter, spinster homolog 2 (Spns2), and S1P receptor, S1P 1 , in lamellipodia formation and perhaps motility of HLMVECs. HGF stimulated SphK1 phosphorylation and enhanced intracellular S1P levels in HLMVECs, which was blocked by inhibition of SphK1. HGF enhanced co-localization of SphK1/p-SphK1 with actin/cortactin in lamellipodia and down-regulation or inhibition of SphK1 attenuated HGF-induced lamellipodia formation in HLMVECs. In addition, down-regulation of Spns2 also suppressed HGF-induced lamellipodia formation, suggesting a key role for inside-out S1P signaling. The HGF-mediated phosphorylation of SphK1 and its localization in lamellipodia was dependent on c-Met and ERK1/2 signaling, but not the PI3K/Akt pathway; however, blocking PI3K/Akt signaling attenuated HGF-mediated phosphorylation of Spns2. Down-regulation of S1P 1 , but not S1P 2 or S1P 3 , with specific siRNA attenuated HGF-induced lamellipodia formation. Further, HGF enhanced association of Spns2 with S1P 1 that was blocked by inhibiting SphK1 activity with PF-543. Moreover, HGF-induced migration of HLMVECs was attenuated by down-regulation of Spns2 . Taken together, these results suggest that HGF/c-Met-mediated lamellipodia formation, and perhaps motility is dependent on intracellular generation of S1P via activation and localization of SphK1 to cell periphery and Spns2-mediated extracellular transportation of S1P and its inside-out signaling via S1P 1 . © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Amós Oz: de lealdades e traições

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Saul Kirschbaum

2015-11-01

Full Text Available Este artigo analisará Judas, o mais recente romance (2014 do escritor israelense Amós Oz. Nessa obra de ficção, Oz utiliza o contexto da suposta traição do apóstolo Judas, narrada nos Evangelhos, e o delicado relacionamento afetivo entre um jovem universitário e uma viúva de guerra de meia idade para abordar as intensas controvérsias no interior do movimento sionista nos anos que antecederam a criação do Estado de Israel, com veementes acusações de traição contra os militantes que se opuseram à linha hegemônica da Organização Sionista e da Agência Judaica – propunham a criação de um estado binacional – e tentativas de deslegitimá-los.

Generalized oscillator strengths for 5s, 5s', and 5p excitations of krypton

International Nuclear Information System (INIS)

Li Wenbin; Zhu Linfan; Yuan Zhensheng; Sun Jianmin; Cheng Huadong; Xu Kezun; Zhong Zhiping; Liu Xiaojing

2003-01-01

The absolute generalized oscillator strengths (GOSs) for 5s, 5s ' , 5p [5/2] 3,2 , 5p [3/2] 1,2 , and 5p [1/2] 0 transitions of krypton have been determined in a large K 2 region at a high electron-impact energy of 2500 eV. The positions of the minima and maxima of these GOSs have been determined. The present results show that the angular resolution and pressure effect have great influence on the position and the amplitude of the minimum for the GOS of 5s+5s ' transitions. When these effects are considered, the measured minimum position for the GOS of 5s+5s ' transitions is in excellent agreement with the calculation of Chen and Msezane [J. Phys. B 33, 5397 (2000)

Limit on the $B^0_s \\bar{B}^0_s$ meson oscillation frequency from $p\\bar{p}$ collision data at $\\sqrt{s} = 1.8$-TeV

Energy Technology Data Exchange (ETDEWEB)

Niu, Hong-quan [Brandeis Univ., Waltham, MA (United States)

2003-01-01

This thesis presents a limit on the B$0\\atop{s}$$\\bar{B}$$0\\atop{s}$ oscillation frequency from p$\\bar{p}$ collision data at √s = 1.8 TeV at CDF. The data sample used is the inclusive electron and muon trigger data of approximately 90 pb^-1 collected during the 1993-95 run.

Thioredoxin 1 regulation of protein S-desulfhydration

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Youngjun Ju

2016-03-01

Full Text Available The importance of H2S in biology and medicine has been widely recognized in recent years, and protein S-sulfhydration is proposed to mediate the direct actions of H2S bioactivity in the body. Thioredoxin 1 (Trx1 is an important reducing enzyme that cleaves disulfides in proteins and acts as an S-denitrosylase. The regulation of Trx1 on protein S-sulfhydration is unclear. Here we showed that Trx1 facilitates protein S-desulfhydration. Overexpression of Trx1 attenuated the basal level and H2S-induced protein S-sulfhydration by direct interaction with S-sulfhydrated proteins, i.e., glyceraldehyde 3-phosphate dehydrogenase and pyruvate carboxylase. In contrast, knockdown of Trx1 mRNA expression by short interfering RNA or blockage of Trx1 redox activity with PX12 or 2,4-dinitrochlorobenzene enhanced protein S-sulfhydration. Mutation of cysteine-32 but not cysteine-35 in the Trp–Cys32–Gly–Pro–Cys35 motif eliminated the binding of Trx1 with S-sulfhydrated proteins and abolished the S-desulfhydrating effect of Trx1. All these data suggest that Trx1 acts as an S-desulfhydrase.

Electron impact excitation-autoionisation of the (2s2)1S, (2p2)1D and (2s2p)1P autoionising states of helium

International Nuclear Information System (INIS)

Samardzic, O.; Hurn, J.A.; Weigold, E.; Brunger, M.J.

1994-01-01

The electron impact excitation of the (2s 2 ) 1 S, (2p 2 ) 1 D and (2s2p) 1 P autoionising states of helium and their subsequent radiationless decay was studied by observation of the ejected electrons. The present work was carried out at an incident energy of 94.6 eV and for ejected electron scattering angles in the range 25-135 deg C. The lineshapes observed in the present ejected electron spectra are analysed using the Shore-Balashov parametrisation. As part of the analysis procedure, numerically rigorous confidence limits were determined for the derived parameters. No previous experimental or theoretical work has been undertaken at the incident energy of the present investigation but, where possible, the resulting parameters are qualitatively compared against the 80 eV results of other experiments and theory. 37 refs., 4 figs

S100 Proteins As an Important Regulator of Macrophage Inflammation

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Chang Xia

2018-01-01

Full Text Available The S100 proteins, a family of calcium-binding cytosolic proteins, have a broad range of intracellular and extracellular functions through regulating calcium balance, cell apoptosis, migration, proliferation, differentiation, energy metabolism, and inflammation. The intracellular functions of S100 proteins involve interaction with intracellular receptors, membrane protein recruitment/transportation, transcriptional regulation and integrating with enzymes or nucleic acids, and DNA repair. The S100 proteins could also be released from the cytoplasm, induced by tissue/cell damage and cellular stress. The extracellular S100 proteins, serving as a danger signal, are crucial in regulating immune homeostasis, post-traumatic injury, and inflammation. Extracellular S100 proteins are also considered biomarkers for some specific diseases. In this review, we will discuss the multi-functional roles of S100 proteins, especially their potential roles associated with cell migration, differentiation, tissue repair, and inflammation.

S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization[S

Science.gov (United States)

Lee, Mi-Hye; Appleton, Kathryn M.; El-Shewy, Hesham M.; Sorci-Thomas, Mary G.; Thomas, Michael J.; Lopes-Virella, Maria F.; Luttrell, Louis M.; Hammad, Samar M.; Klein, Richard L.

2017-01-01

HDL normally transports about 50–70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration. PMID:27881715

Measurement of the relative yields of ψ (2 S ) to ψ (1 S ) mesons produced at forward and backward rapidity in p +p , p +Al , p +Au , and 3He+Au collisions at √{sNN}=200 GeV

Science.gov (United States)

Adare, A.; Aidala, C.; Ajitanand, N. N.; Akiba, Y.; Alfred, M.; Andrieux, V.; Aoki, K.; Apadula, N.; Asano, H.; Ayuso, C.; Azmoun, B.; Babintsev, V.; Bai, M.; Bandara, N. S.; Bannier, B.; Barish, K. N.; Bathe, S.; Bazilevsky, A.; Beaumier, M.; Beckman, S.; Belmont, R.; Berdnikov, A.; Berdnikov, Y.; Blau, D. S.; Boer, M.; Bok, J. S.; Bownes, E. K.; Boyle, K.; Brooks, M. L.; Bryslawskyj, J.; Bumazhnov, V.; Butler, C.; Campbell, S.; Canoa Roman, V.; Cervantes, R.; Chen, C.-H.; Chi, C. Y.; Chiu, M.; Choi, I. J.; Choi, J. B.; Chujo, T.; Citron, Z.; Connors, M.; Cronin, N.; Csanád, M.; Csörgő, T.; Danley, T. W.; Datta, A.; Daugherity, M. S.; David, G.; Deblasio, K.; Dehmelt, K.; Denisov, A.; Deshpande, A.; Desmond, E. J.; Dion, A.; Diss, P. B.; Dixit, D.; Do, J. H.; Drees, A.; Drees, K. A.; Dumancic, M.; Durham, J. M.; Durum, A.; Dusing, J. P.; Elder, T.; Enokizono, A.; En'yo, H.; Esumi, S.; Fadem, B.; Fan, W.; Feege, N.; Fields, D. E.; Finger, M.; Finger, M.; Fokin, S. L.; Frantz, J. E.; Franz, A.; Frawley, A. D.; Fukuda, Y.; Gal, C.; Gallus, P.; Garg, P.; Ge, H.; Giordano, F.; Glenn, A.; Goto, Y.; Grau, N.; Greene, S. V.; Grosse Perdekamp, M.; Gunji, T.; Guragain, H.; Hachiya, T.; Haggerty, J. S.; Hahn, K. I.; Hamagaki, H.; Hamilton, H. F.; Han, S. Y.; Hanks, J.; Hasegawa, S.; Haseler, T. O. S.; Hashimoto, K.; He, X.; Hemmick, T. K.; Hill, J. C.; Hill, K.; Hollis, R. S.; Homma, K.; Hong, B.; Hoshino, T.; Hotvedt, N.; Huang, J.; Huang, S.; Imai, K.; Imrek, J.; Inaba, M.; Iordanova, A.; Isenhower, D.; Ito, Y.; Ivanishchev, D.; Jacak, B. V.; Jezghani, M.; Ji, Z.; Jia, J.; Jiang, X.; Johnson, B. M.; Jorjadze, V.; Jouan, D.; Jumper, D. S.; Kanda, S.; Kang, J. H.; Kapukchyan, D.; Karthas, S.; Kawall, D.; Kazantsev, A. V.; Key, J. A.; Khachatryan, V.; Khanzadeev, A.; Kim, C.; Kim, D. J.; Kim, E.-J.; Kim, G. W.; Kim, M.; Kimball, M. L.; Kimelman, B.; Kincses, D.; Kistenev, E.; Kitamura, R.; Klatsky, J.; Kleinjan, D.; Kline, P.; Koblesky, T.; Komkov, B.; Kotler, J. R.; Kotov, D.; Kudo, S.; Kurita, K.; Kurosawa, M.; Kwon, Y.; Lacey, R.; Lajoie, J. G.; Lallow, E. O.; Lebedev, A.; Lee, S.; Lee, S. H.; Leitch, M. J.; Leung, Y. H.; Lewis, N. A.; Li, X.; Li, X.; Lim, S. H.; Liu, L. D.; Liu, M. X.; Loggins, V.-R.; Loggins, V.-R.; Lovasz, K.; Lynch, D.; Majoros, T.; Makdisi, Y. I.; Makek, M.; Malaev, M.; Manion, A.; Manko, V. I.; Mannel, E.; Masuda, H.; McCumber, M.; McGaughey, P. L.; McGlinchey, D.; McKinney, C.; Meles, A.; Mendez, A. R.; Mendoza, M.; Mignerey, A. C.; Mihalik, D. E.; Milov, A.; Mishra, D. K.; Mitchell, J. T.; Mitsuka, G.; Miyasaka, S.; Mizuno, S.; Mohanty, A. K.; Montuenga, P.; Moon, T.; Morrison, D. P.; Morrow, S. I. M.; Moukhanova, T. V.; Murakami, T.; Murata, J.; Mwai, A.; Nagai, K.; Nagashima, K.; Nagashima, T.; Nagle, J. L.; Nagy, M. I.; Nakagawa, I.; Nakagomi, H.; Nakano, K.; Nattrass, C.; Netrakanti, P. K.; Niida, T.; Nishimura, S.; Nouicer, R.; Novák, T.; Novitzky, N.; Novotny, R.; Nyanin, A. S.; O'Brien, E.; Ogilvie, C. A.; Orjuela Koop, J. D.; Osborn, J. D.; Oskarsson, A.; Ottino, G. J.; Ozawa, K.; Pak, R.; Pantuev, V.; Papavassiliou, V.; Park, J. S.; Park, S.; Pate, S. F.; Patel, M.; Peng, J.-C.; Peng, W.; Perepelitsa, D. V.; Perera, G. D. N.; Peressounko, D. Yu.; Perezlara, C. E.; Perry, J.; Petti, R.; Phipps, M.; Pinkenburg, C.; Pinson, R.; Pisani, R. P.; Press, C. J.; Pun, A.; Purschke, M. L.; Rak, J.; Ramson, B. J.; Ravinovich, I.; Read, K. F.; Reynolds, D.; Riabov, V.; Riabov, Y.; Richford, D.; Rinn, T.; Rolnick, S. D.; Rosati, M.; Rowan, Z.; Rubin, J. G.; Runchey, J.; Safonov, A. S.; Sahlmueller, B.; Saito, N.; Sakaguchi, T.; Sako, H.; Samsonov, V.; Sarsour, M.; Sato, K.; Sato, S.; Schaefer, B.; Schmoll, B. K.; Sedgwick, K.; Seidl, R.; Sen, A.; Seto, R.; Sett, P.; Sexton, A.; Sharma, D.; Shein, I.; Shibata, T.-A.; Shigaki, K.; Shimomura, M.; Shioya, T.; Shukla, P.; Sickles, A.; Silva, C. L.; Silva, J. A.; Silvermyr, D.; Singh, B. K.; Singh, C. P.; Singh, V.; Slunečka, M.; Smith, K. L.; Snowball, M.; Soltz, R. A.; Sondheim, W. E.; Sorensen, S. P.; Sourikova, I. V.; Stankus, P. W.; Stepanov, M.; Stien, H.; Stoll, S. P.; Sugitate, T.; Sukhanov, A.; Sumita, T.; Sun, J.; Syed, S.; Sziklai, J.; Takeda, A.; Taketani, A.; Tanida, K.; Tannenbaum, M. J.; Tarafdar, S.; Taranenko, A.; Tarnai, G.; Tieulent, R.; Timilsina, A.; Todoroki, T.; Tomášek, M.; Towell, C. L.; Towell, R.; Towell, R. S.; Tserruya, I.; Ueda, Y.; Ujvari, B.; van Hecke, H. W.; Vazquez-Carson, S.; Velkovska, J.; Virius, M.; Vrba, V.; Vukman, N.; Wang, X. R.; Wang, Z.; Watanabe, Y.; Watanabe, Y. S.; Wei, F.; White, A. S.; Wong, C. P.; Woody, C. L.; Wysocki, M.; Xia, B.; Xu, C.; Xu, Q.; Xue, L.; Yalcin, S.; Yamaguchi, Y. L.; Yamamoto, H.; Yanovich, A.; Yin, P.; Yoo, J. H.; Yoon, I.; Yu, H.; Yushmanov, I. E.; Zajc, W. A.; Zelenski, A.; Zharko, S.; Zhou, S.; Zou, L.; Phenix Collaboration

2017-03-01

The PHENIX Collaboration has measured the ratio of the yields of ψ (2 S ) to ψ (1 S ) mesons produced in p +p , p +Al , p +Au , and 3He+Au collisions at √{s NN}=200 GeV over the forward and backward rapidity intervals 1.2 <|y |<2.2 . We find that the ratio in p +p collisions is consistent with measurements at other collision energies. In collisions with nuclei, we find that in the forward (p -going or 3He-going) direction, the relative yield of ψ (2 S ) mesons to ψ (1 S ) mesons is consistent with the value measured in p +p collisions. However, in the backward (nucleus-going) direction, the ψ (2 S ) meson is preferentially suppressed by a factor of ˜2 . This suppression is attributed in some models to the breakup of the weakly bound ψ (2 S ) meson through final-state interactions with comoving particles, which have a higher density in the nucleus-going direction. These breakup effects may compete with color screening in a deconfined quark-gluon plasma to produce sequential suppression of excited quarkonia states.

Hepatic S1P deficiency lowers plasma cholesterol levels in apoB-containing lipoproteins when LDLR function is compromised.

Science.gov (United States)

Basu, Debapriya; Huq, Afroza; Iqbal, Jahangir; Hussain, M Mahmood; Jiang, Xian-Cheng; Jin, Weijun

2015-01-01

Site-1 protease (S1P) is the key enzyme required for activation of the sterol regulatory element binding proteins (SREBPs) that govern lipid synthesis. While S1P has been speculated to influence plasma apoB-containing lipoprotein (Blp) metabolism, there has been little investigative work. LDL receptor (LDLR) is the major receptor for clearing plasma LDL cholesterol (LDL-c). Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR. A hepatic-specific knockdown (KD) of S1P was achieved using floxed S1P mouse models (S1P(f/f) and LDLR(-/-)S1P(f/f)) and hepatic expression of Cre recombinase. Lipids were measured in total plasma and size fractionated plasma using colorimetric assays. Realtime polymerase chain reaction, western blotting and ELISA were used to determine hepatic expression of key genes/protein. Plasmid mediated overexpression and siRNA mediated knockdown of genes were performed in mouse primary hepatocytes to determine the mechanistic basis of PCSK9 gene regulation. A hepatic-specific KD of S1P resulted in a 45 % and 38 % reduction in plasma total cholesterol and triglyceride levels, respectively. Hepatic S1P KD had a minimal effect on plasma Blp cholesterol (Blp-c) in S1P(f/f) mice, despite significantly reducing VLDL secretion. Notably, hepatic S1P KD decreased the LDL receptor (LDLR) mRNA expression by 50 %. However, the reduction in LDLR protein levels was less than that of mRNA expression, especially under fed conditions. Further assessment of hepatic S1P deficiency revealed that it increased LDLR protein stability in vivo. Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. This effect was more prominent in the fed condition and sufficient to account for the discordance in LDLR mRNA and protein levels. Furthermore, hepatic S1P was shown to regulate PCSK9

Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells.

Science.gov (United States)

Völzke, Anja; Koch, Alexander; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

2014-01-01

Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases. © 2013.

C/EBPα regulates CRL4Cdt2-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint

Science.gov (United States)

Hall, Jonathan R; Bereman, Michael S; Nepomuceno, Angelito I; Thompson, Elizabeth A; Muddiman, David C; Smart, Robert C

2014-01-01

The bZIP transcription factor, C/EBPα is highly inducible by UVB and other DNA damaging agents in keratinocytes. C/EBPα-deficient keratinocytes fail to undergo cell cycle arrest in G1 in response to UVB-induced DNA damage and mice lacking epidermal C/EBPα are highly susceptible to UVB-induced skin cancer. The mechanism through which C/EBPα regulates the cell cycle checkpoint in response to DNA damage is unknown. Here we report untreated C/EBPα-deficient keratinocytes have normal levels of the cyclin-dependent kinase inhibitor, p21, however, UVB-treated C/EBPα-deficient keratinocytes fail to up-regulate nuclear p21 protein levels despite normal up-regulation of Cdkn1a mRNA levels. UVB-treated C/EBPα-deficient keratinocytes displayed a 4-fold decrease in nuclear p21 protein half-life due to the increased proteasomal degradation of p21 via the E3 ubiquitin ligase CRL4Cdt2. Cdt2 is the substrate recognition subunit of CRL4Cdt2 and Cdt2 mRNA and protein levels were up-regulated in UVB-treated C/EBPα-deficient keratinocytes. Knockdown of Cdt2 restored p21 protein levels in UVB-treated C/EBPα-deficient keratinocytes. Lastly, the failure to accumulate p21 in response to UVB in C/EBPα-deficient keratinocytes resulted in decreased p21 interactions with critical cell cycle regulatory proteins, increased CDK2 activity, and inappropriate entry into S-phase. These findings reveal C/EBPα regulates G1/S cell cycle arrest in response to DNA damage via the control of CRL4Cdt2 mediated degradation of p21. PMID:25483090

Phosphoinositide-3-kinases p110alpha and p110beta mediate S phase entry in astroglial cells in the marginal zone of rat neocortex

Directory of Open Access Journals (Sweden)

Rabea eMüller

2013-03-01

Full Text Available In cells cultured from neocortex of newborn rats, phosphoinositide-3-kinases of class I regulate the DNA synthesis in a subgroup of astroglial cells. We have studied the location of these cells as well as the kinase isoforms which facilitate the S phase entry. Using dominant negative isoforms as well as selective pharmacological inhibitors we quantified S phase entry by nuclear labeling with bromodeoxyuridine. Only in astroglial cells harvested from the marginal zone of the neocortex inhibition of phosphoinositide-3-kinases reduced the nuclear labeling with bromodeoxyuridine, indicating that neocortical astroglial cells differ in the regulation of proliferation. The two kinase isoforms p110 and p110were essential for S phase entry. p110 diminished the level of the p27Kip1 which inactivates the complex of cyclin E and CDK2 necessary for entry into the S phase. p110phosphorylated and inhibited glycogen synthase kinase-3which can prevent S-phase entry. Taken together, both isoforms mediated S phase in a subgroup of neocortical astroglial cells and acted via distinct pathways.

Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect.

Science.gov (United States)

Adamson, R H; Clark, J F; Radeva, M; Kheirolomoom, A; Ferrara, K W; Curry, F E

2014-04-01

Removal of plasma proteins from perfusates increases vascular permeability. The common interpretation of the action of albumin is that it forms part of the permeability barrier by electrostatic binding to the endothelial glycocalyx. We tested the alternate hypothesis that removal of perfusate albumin in rat venular microvessels decreased the availability of sphingosine-1-phosphate (S1P), which is normally carried in plasma bound to albumin and lipoproteins and is required to maintain stable baseline endothelial barriers (Am J Physiol Heart Circ Physiol 303: H825-H834, 2012). Red blood cells (RBCs) are a primary source of S1P in the normal circulation. We compared apparent albumin permeability coefficients [solute permeability (Ps)] measured using perfusates containing albumin (10 mg/ml, control) and conditioned by 20-min exposure to rat RBCs with Ps when test perfusates were in RBC-conditioned protein-free Ringer solution. The control perfusate S1P concentration (439 ± 46 nM) was near the normal plasma value at 37 °C and established a stable baseline Ps (0.9 ± 0.4 × 10(-6) cm/s). Ringer solution perfusate contained 52 ± 8 nM S1P and increased Ps more than 10-fold (16.1 ± 3.9 × 10(-6) cm/s). Consistent with albumin-dependent transport of S1P from RBCs, S1P concentrations in RBC-conditioned solutions decreased as albumin concentration, hematocrit, and temperature decreased. Protein-free Ringer solution perfusates that used liposomes instead of RBCs as flow markers failed to maintain normal permeability, reproducing the "albumin effect" in these mammalian microvessels. We conclude that the albumin effect depends on the action of albumin to facilitate the release and transport of S1P from RBCs that normally provide a significant amount of S1P to the endothelium.

Development of backward equations T(p,h), T(p,s) and p(h,s) for heavy water liquid and vapor

International Nuclear Information System (INIS)

Nick P Petropoulos; Simos E Simopoulos

2005-01-01

Full text of publication follows: Backward equations for heavy water (a) temperature as a function of pressure and enthalpy T(p,h), (b) temperature as a function of pressure and entropy T(p,s) and (c) pressure as a function of enthalpy and entropy p(h,s) presented in this work, are based on the 'IAPS Formulation 1984 for the Thermodynamic Properties of Heavy Water Substance' [1], and also on the respective equations for the ordinary water substance as presented in 'The IAPWS Industrial Formulation 1997 for the Thermodynamic Properties of Water and Steam' [2]. Heavy water and steam thermodynamic properties can be calculated using the basic equations and saturation equations that are included in [1]. However, [1] does not contain any backward functions T(p,h), T(p,s) and p(h,s), which are needed for heavy water thermodynamic process modeling. The development of the two temperature backward functions efficiently increases computational speed for temperature calculations more than three times as pointed out in the similar case problem for ordinary water, addressed successfully in [2]. Without these temperature backward functions calculations may be performed only iteratively using the heavy water state equations at a much greater computing cost. Moreover, the development of the pressure backward function saves even more computing time in modeling problems since two-dimensional iterations from the h(p,T) and s(p,T) heavy water functions may by effectively avoided. In addition, given the pressure function p(h,s), the heavy water temperature T(h,s) can be calculated by the temperature function T(p,h). The numerical consistencies of calculated T and p to the state equations included in [1] are sufficient for most applications in the heavy water nuclear reactors heat cycles. For applications, where the demands on numerical consistency and accuracy are rather high, iterations with the approved state equations may be necessary. In these cases both temperature and pressure

Sphingosine-1-phosphate promotes extravillous trophoblast cell invasion by activating MEK/ERK/MMP-2 signaling pathways via S1P/S1PR1 axis activation.

Science.gov (United States)

Yang, Weiwei; Li, Qinghua; Pan, Zhifang

2014-01-01

Successful placentation depends on the proper invasion of extravillous trophoblast (EVT) cells into maternal tissues. Previous reports demonstrated that S1P receptors are expressed in the EVT cells and S1P could regulate migration and function of trophoblast cells via S1P receptors. However, little is known about roles of S1P in the invasion of EVT cells. Our study was performed to investigate S1P effect on the invasion of EVT cells. We used the extravillous trophoblast cell line HTR8/SVneo cells to evaluate the effect. In vitro invasion assay was employed to determine the invasion of HTR8/SVneo cells induced by S1P. MMP-2 enzyme activity and relative level in the supernatants of HTR8/SVneo was assessed by gelatin zymography and western blot. Based on the above, siRNA and specific inhibitors were used for the intervention and study of potential signal pathways, and Real-time qPCR and western blot were used to test the mRNA and protein level of potential signal targets. We found that S1P could promote HTR8/SVneo cell invasion and upregulates activity and level of MMP-2. The promotion requires activation of MEK-ERK and is dependent on the axis of S1P/S1PR1. Our investigation of S1P may provide new insights into the molecular mechanisms of EVT invasion.

[Involvement of the global regulators GrrS, RpoS, and SplIR in formation of biofilms in Serratia plymuthica].

Science.gov (United States)

Zaĭtseva, Iu V; Voloshina, P V; Liu, X; Ovadis, M I; Berg, G; Chernin, L S; Khmel', I A

2010-05-01

Most bacteria exist in the natural environment as biofilms, multicellular communities attached to hard surfaces. Biofilms have a characteristic architecture and are enclosed in the exopolymer matrix. Bacterial cells in biofilms are extremely resistant to antibacterial factors. It was shown in this work that the GrrA/GrrS system of global regulators of gene expression and the sigma S subunit of RNA polymerase (RpoS) play a significant role in positive regulation of biofilm formation in the rhizospheric bacterium Serratia plymuthica IC1270. Inactivation of grrS and rpoS genes resulted in an up to six-to-sevenfold and four-to-fivefold reduction in biofilm formation, respectively. Mutations in the grrS gene decreased the capacity of the bacterium for swarming motility. The splIR Quorum Sensing (QS) system was shown to negatively influence the biofilm formation. Transfer of the recombinant plasmid containing cloned genes splI/splR of S. plymuthica HRO-C48 into S. plymuthica IC1270 cells led to a twofold decrease of their ability to form biofilms. Inactivation of the splI gene coding for the synthase of N-acyl-homoserine lactones in S. plymuthica HRO-C48 resulted in a 2-2.5-fold increase in the level of biofilm formation, whereas the inclusion of plasmid carrying the cloned splI/splR genes into these mutant cells restored the biofilm formation to the normal level. The results obtained demonstrate that the formation of biofilms in S. plymuthica is positively regulated by the GrrA/GrrS and RpoS global regulators and is negatively regulated by the SplIR QS system.

Differential Effects of Long Term FTY720 Treatment on Endothelial versus Smooth Muscle Cell Signaling to S1P in Rat Mesenteric Arteries

NARCIS (Netherlands)

Shishavan, Mahdi Hamidi; Bidadkosh, Arash; Yazdani, Saleh; Lambooy, Sebastiaan; van den Born, Jacob; Buikema, Hendrik; Henning, Robert H.; Deelman, Leo E.

2016-01-01

The sphingosine-1-phosphate (S1P) analog FTY720 exerts pleiotropic effects on the cardiovascular system and causes down-regulation of S1P receptors. Myogenic constriction is an important mechanism regulating resistance vessel function and is known to be modulated by S1P. Here we investigated

QoS Enabled Resource Allocation Over an UPnP-QoS - GMPLS Controlled Edge

DEFF Research Database (Denmark)

Brewka, Lukasz Jerzy; Sköldström, Pontus; Gavler, Anders

2011-01-01

This paper focuses on the problem of coherent resource allocation within home and access networks. The interdomain QoS signaling discussed here enables the initiation of the QoS provisioning in the home and access from the end device in users home. The home network considered in this paper is UPn......P-QoS enabled while the access network is GMPLS based. We propose and implement an interface between aforementioned network segments allowing for end-to-end QoS establishment. We present the QoS parameters and mechanisms in both UPnP-QoS and GMPLS and how they can be matched to create a coherent Qo...

A quantitative model of regulator's preference factor (RPF) in electricity-environment coordinated regulation system

Energy Technology Data Exchange (ETDEWEB)

Ren, Yulong; Fu, Shijun [Economy and Business Administration School of Chongqing University, Chongqing 400030 (China)

2010-12-15

This paper explores quantification of regulator's preference factor (RPF) in electricity-environment coordinated regulation system. Based on social welfare economics, we articulately depict RPF's qualitative concept and its economic meaning. Then, applying abstract functions (i.e., abstract social welfare function, abstract utility function, and abstract production function), we deduce the partial-social-welfare elasticity, and build the mathematics model of maximizing social welfare. We nest this elasticity into the model's Kuhn-Tucker conditions, and obtain RPF's definition formula. By solving the Kuhn-Tucker conditions, we get RPF's quantitative formula, which solves the problem of hard to quantify regulator's preference in electricity-environment coordinated regulation system. The result shows that RPF only has relationship to subsystems' production function, and is independent of social welfare function and subsystems' utility function. Finally, we provide an empirical research based on the western region of China from year 1995 to 2004. It reveals that regulator has relative stability preference to mitigating pollutants. And validity test confirms that the empirical result is fit well to the practice. The RPF is truly a more general and valid instrument to measure regulator's preference in its regulated field. (author)

Possibilités et avantages des plantes médicinales en Amérique latine

International Development Research Centre (IDRC) Digital Library (Canada)

1 févr. 2011 ... Le parc national Darién au Panama est le plus grand parc national d'Amérique ... kuna et wounaan — installés dans les limites du parc n'ont pratiquement pas ... Avec l'appui du Centre de recherches pour le développement .... Il importe de se rendre compte que la santé humaine est tributaire de celle ...

p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD

DEFF Research Database (Denmark)

Harada, H; Andersen, Jens S.; Mann, M

2001-01-01

Cytokines often deliver simultaneous, yet distinct, cell growth and cell survival signals. The 70-kDa ribosomal protein S6 kinase (p70S6K) is known to regulate cell growth by inducing protein synthesis components. We purified membrane-based p70S6K as a kinase responsible for site-specific phospho...

Transtorno de estresse pós-traumático: o enfoque psicanalítico

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Meshulam-Werebe Daniela

2003-01-01

Full Text Available Os autores abordam o transtorno de estresse pós-traumático (TEPT e sua importância em termos epidemiológicos e de saúde pública. A seguir, traçam um histórico de como emergiram os conceitos psicanalíticos do trauma psíquico. A importância que Freud atribuiu ao trauma como agente causador da neurose é revisada. É discutida a importância do trauma como uma vivência do mundo interno, não necessariamente calcada em fatos exteriores. A importância do uso de técnicas psicanalíticas para determinados casos de TEPT é salientada.

Conjugal plasmid transfer (pAM beta 1) in Lactobacillus plantarum.

OpenAIRE

Shrago, A W; Chassy, B M; Dobrogosz, W J

1986-01-01

The streptococcal plasmid pAM beta 1 (erythromycin resistance) was transferred via conjugation from Streptococcus faecalis to Lactobacillus plantarum and was transferred among L. plantarum strains. Streptococcus sanguis Challis was transformed with pAM beta 1 isolated from these transconjugants, and transformants harboring intact pAM beta 1 could conjugate the plasmid back to L. plantarum.

Compliance with children’s television food advertising regulations in Australia

Science.gov (United States)

2012-01-01

Background The objective of this study was to assess the effectiveness of the Australian co-regulatory system in limiting children’s exposure to unhealthy television food advertising by measuring compliance with mandatory and voluntary regulations. An audit was conducted on food and beverage television advertisements broadcast in five major Australian cities during children’s programming time from 1st September 2010 to 31st October 2010. The data were assessed against mandatory and voluntary advertising regulations, the information contained in an industry report of breaches, and the Australian Guide to Healthy Eating. Results During the two months of data collection there were a total of 951 breaches of the combined regulations. This included 619 breaches of the mandatory regulations (CTS) and 332 breaches of the voluntary regulations (RCMI and QSRI). Almost 83% of all food and beverages advertised during children’s programming times were for foods classified as ‘Extras’ in the Australian Guide to Healthy Eating. There were also breaches in relation to the amount of advertising repetition and the use of promotional appeals such as premium offers, competitions, and endorsements by popular children’s characters. The self-regulatory systems were found to have flaws in their reporting and there were errors in the Australian Food and Grocery Council’s compliance report. Conclusions This audit suggests that current advertising regulations are inadequate. Regulations need to be closely monitored and more tightly enforced to protect children from advertisements for unhealthy foods. PMID:23039855

Compliance with children’s television food advertising regulations in Australia

Directory of Open Access Journals (Sweden)

Roberts Michele

2012-10-01

Full Text Available Abstract Background The objective of this study was to assess the effectiveness of the Australian co-regulatory system in limiting children’s exposure to unhealthy television food advertising by measuring compliance with mandatory and voluntary regulations. An audit was conducted on food and beverage television advertisements broadcast in five major Australian cities during children’s programming time from 1st September 2010 to 31st October 2010. The data were assessed against mandatory and voluntary advertising regulations, the information contained in an industry report of breaches, and the Australian Guide to Healthy Eating. Results During the two months of data collection there were a total of 951 breaches of the combined regulations. This included 619 breaches of the mandatory regulations (CTS and 332 breaches of the voluntary regulations (RCMI and QSRI. Almost 83% of all food and beverages advertised during children’s programming times were for foods classified as ‘Extras’ in the Australian Guide to Healthy Eating. There were also breaches in relation to the amount of advertising repetition and the use of promotional appeals such as premium offers, competitions, and endorsements by popular children’s characters. The self-regulatory systems were found to have flaws in their reporting and there were errors in the Australian Food and Grocery Council’s compliance report. Conclusions This audit suggests that current advertising regulations are inadequate. Regulations need to be closely monitored and more tightly enforced to protect children from advertisements for unhealthy foods.

M P S Chandrawat

Indian Academy of Sciences (India)

It is shown that aluminium phosphate retards the setting process of the cement and improves water-tightness. Volume 24 Issue 3 June 2001 pp 313-316 Cement and Concrete Materials. Effect of bitumen emulsion on setting, strength, soundness and moisture resistance of oxychloride cement · M P S Chandrawat T N Ojha ...

Cyclin E-induced S phase without activation of the pRb/E2F pathway

DEFF Research Database (Denmark)

Lukas, J; Herzinger, T; Hansen, Klaus

1997-01-01

In cells of higher eukaryotes, cyclin D-dependent kinases Cdk4 and Cdk6 and, possibly, cyclin E-dependent Cdk2 positively regulate the G1- to S-phase transition, by phosphorylating the retinoblastoma protein (pRb), thereby releasing E2F transcription factors that control S-phase genes. Here we...

Urate is a ligand for the transcriptional regulator PecS.

Science.gov (United States)

Perera, Inoka C; Grove, Anne

2010-09-24

PecS is a member of the MarR (multiple antibiotic resistance regulator) family, which has been shown in Erwinia to regulate the expression of virulence genes. MarR homologs typically bind a small molecule ligand, resulting in attenuated DNA binding. For PecS, the natural ligand has not been identified. We have previously shown that urate is a ligand for the Deinococcus radiodurans-encoded MarR homolog HucR (hypothetical uricase regulator) and identified residues responsible for ligand binding. We show here that all four residues involved in urate binding and propagation of conformational changes to DNA recognition helices are conserved in PecS homologs, suggesting that urate is the ligand for PecS. Consistent with this prediction, Agrobacterium tumefaciens PecS specifically binds urate, and urate attenuates DNA binding in vitro. PecS binds two operator sites in the intergenic region between the divergent pecS gene and pecM genes, one of which features two partially overlapping repeats to which PecS binds as a dimer on opposite faces of the duplex. Notably, urate dissociates PecS from cognate DNA, allowing transcription of both genes in vivo. Taken together, our data show that urate is a ligand for PecS and suggest that urate serves a novel function in signaling the colonization of a host plant. Copyright © 2010 Elsevier Ltd. All rights reserved.

Transition probabilities for the 3s2 3p(2P0)-3s3p2(4P) intersystem lines of Si II

Science.gov (United States)

Calamai, Anthony G.; Smith, Peter L.; Bergeson, S. D.

1993-01-01

Intensity ratios of lines of the spin-changing 'intersystem' multiplet of S II (4P yields 2P0) at 234 nm have been used to determine electron densities and temperatures in a variety of astrophysical environments. However, the accuracy of these diagnostic calculations have been limited by uncertainties associated with the available atomic data. We report the first laboratory measurement, using an ion-trapping technique, of the radiative lifetimes of the three metastable levels of the 3s3p2 4P term of Si II. Our results are 104 +/- 16, 406 +/- 33, and 811 +/- 77 micro-s for lifetimes of the J = 1/2, 5/2, and 3/2 levels, respectively. A-values were derived from our lifetimes by use of measured branching fractions. Our A-values, which differ from calculated values by 30 percent or more, should give better agreement between modeled and observed Si II line ratios.

Absolute emission cross sections for electron-impact excitation of Zn+(4p 2P) and (5s 2S) terms

International Nuclear Information System (INIS)

Rogers, W.T.; Dunn, G.H.; Olsen, J.O.; Reading, M.; Stefani, G.

1982-01-01

Absolute emission cross sections for electron-impact excitation of the 3d 10 4p 2 P and 3d 10 5s 2 S terms of Zn + have been measured from below threshold to about 790 eV 2 P and 390 eV 2 S using the crossed-charged-beams technique. Both transitions have the abrupt onset at threshold characteristic of positive-ion excitation. The 2 P cross section shows considerable structure in the interval from threshold to near 20 eV, above which it falls off smoothly. Agreement with five-state close-coupling theory is excellent below 100 eV when cascading is included in the theory. Above 100 eV, the data lie above the theory. The peak value of the 2 P cross section is 9.4 x 10 -16 cm 2 essentially at threshold, while the peak value of the 2 S cross section is about 0.47 x 10 -16 cm 2 . The net linear polarization of the 3d 10 4p 2 P emission was measured (unresolved from the 3d 10 4d 2 D→3d 10 4p 2 P cascading transition), and these data were used to correct the cross-section data for anisotropy of the emitted light. The effective lifetime of the 3d 9 4s 2 2 D/sub 3/2/ level was measured by observing exponential decay of the 589.6-nm photons resulting from its decay

Selective UV radiation detection on the basis of low-dimensional ZnCdS/ZnMgS/GaP and ZnCdS/ZnS/GaP heterostructures

Energy Technology Data Exchange (ETDEWEB)

Averin, S. V., E-mail: sva278@ire216.msk.su; Kuznetzov, P. I.; Zhitov, V. A.; Zakharov, L. Yu.; Kotov, V. M.; Alkeev, N. V. [Russian Academy of Sciences, Fryazino Branch, Kotel’nikov Institute of Radio Engineering and Electronics (Russian Federation); Gladisheva, N. B. [Pulsar State Plant (Russian Federation)

2015-11-15

The detecting properties of periodic heterostructures with ZnCdS quantum wells separated by ZnMgS or ZnS barrier layers are studied. Heterostructures are grown on semi-insulating GaP substrates by metal organic vapor-phase epitaxy (MOVPE). On their basis, metal–semiconductor–metal (MSM) diodes with interdigital Schottky contacts 3 μm, distances between them of 3 μm, and a total detector area of 100 × 100 μm are fabricated. The detectors have low dark currents (10{sup –12} A); at low bias voltages, they provide a narrow- band response (full-width at half-maximum of FWHM = 18 nm at a wavelength of 350 nm) which is controlled by the ZnCdS quantum-well composition. As bias is increased to 70 V, the maximum detector sensitivity shifts by a wavelength of 450 nm, which is caused by penetration of the external-bias electric field into the semi-insulating GaP substrate. In this case, the narrow-band response of the detector at a wavelength of 350 nm is retained, i.e., the two-color detection of light is provided.

O pós-abolição como problema histórico: balanços e perspectivas

Directory of Open Access Journals (Sweden)

Ana Maria Rios

Full Text Available O artigo discute as variáveis mais importantes nos processos de pós-abolição nas Américas, dando destaque as expectativas alimentadas pela última geração de escravos e suas atitudes nas primeiras décadas após o fim da escravidão. Procura inserir o caso brasileiro e sua especificidade e se detém na análise das atitudes dos libertos do sudeste no sentido de proteger a família, estabelecer uma "boa reputação", exercer o pátrio poder e valorizar aspectos importantes da cidadania. Utiliza diversas fontes, principalmente o registro civil, jornais e depoimentos de netos de escravos.

A regulator`s perspective on NRC`s participation in the operations & maintenance committees

Energy Technology Data Exchange (ETDEWEB)

Wessman, R.H.

1996-12-01

As a regulator fairly new to the American Society of Mechanical Engineers (ASME) Operations and Maintenance (O&M) Committee process, the author does not have a personal historical perspective as do many of the longer-term, and highly respected, members of the O&M Committee. However, as Branch Chief of the Mechanical Engineering Branch, Division of Engineering, in the Office of Nuclear Reactor Regulation at the NRC for just over two years, he has responsibility for the regulatory agency`s review of licensee actions involving the products that come from the efforts of the O&M Committee, as well as responsibility for portions of the activities of interest to other ASME Code groups such as Section III, Section XI, and Qualification of Mechanical Equipment. As a result, the author has learned a great deal about the code process in a short time. Here he gives his perspectives on the process and provides a few thoughts on the direction for the future.

Early Family Relationships Predict Children’s Emotion Regulation and Defense Mechanisms

Directory of Open Access Journals (Sweden)

Jallu Lindblom

2016-12-01

Full Text Available Early family relationships have been suggested to influence the development of children’s affect regulation, involving both emotion regulation and defense mechanisms. However, we lack research on the specific family predictors for these two forms of affect regulation, which have been conceptualized to differ in their functions and accessibility to consciousness. Accordingly, we examine how the (a quality and (b timing of family relationships during infancy predict child’s later emotion regulation and defense mechanisms. Parents (N = 703 reported autonomy and intimacy in marital and parenting relationships at the child’s ages of 2 and 12 months, and the child’s use of emotion regulation and immature and neurotic defenses at 7 to 8 years. As hypothesized, the results showed that functional early family relationships predicted children’s efficient emotion regulation, whereas dysfunctional relationships predicted reliance on defense mechanisms in middle childhood. Further, results showed a timing effect for neurotic defenses, partially confirming our hypothesis of early infancy being an especially important period for the development of defense mechanisms. The findings are discussed from the viewpoints of attachment and family dynamics, emotional self-awareness, and sense of security.

Regulation of adrenomedullin and nitric oxide production by periodontal bacteria.

Science.gov (United States)

Hussain, Q A; McKay, I J; Gonzales-Marin, C; Allaker, R P

2015-10-01

In periodontitis the host response to bacterial challenge includes activity of the multifunctional molecules adrenomedullin (AM) and nitric oxide (NO). The aim of this study was to investigate the role of periodontal bacteria in regulating the production of these molecules from cultured cells. Regulation of AM and NO production from oral keratinocytes when challenged with culture supernatants from Aggregatibacter actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Veillonella atypica, Streptococcus salivarius and Candida albicans was examined. AM and NO were measured in cell culture supernatants using an enzyme-linked immunosorbent assay and the nitrate/nitrite (NO metabolites) Griess assay respectively. Cellular production of AM and inducible NO synthase was also analysed in target cells by immunofluorescence and Western blot analysis. The inter-relationship of AM and NO production were further investigated with macrophages. A. actinomycetemcomitans and C. rectus induced maximal levels of both AM and NO after 6 and 48 h respectively from oral keratinocytes. AM production in macrophages was upregulated in response to the NO donor S-nitrosoglutathione and partially blocked by the inducible NO synthase inhibitor, N(ω) -Nitro-l-arginine methyl ester hydrochloride. Likewise, NO production was increased upon exposure to AM, while the AM receptor antagonist AM 22-52 reduced the release of NO. Pathogens associated with aggressive periodontitis, A. actinomycetemcomitans and C. rectus, were more effective than those associated with chronic periodontitis, P. gingivalis and Prev. intermedia, and commensals, S. salivarius and V. atypica, as regards the upregulation of AM and NO production from oral keratinocytes. Interaction between these molecules was also demonstrated with macrophages. Understanding the coordinated regulation of AM and NO production in response to periodontal bacteria may identify

High resolution emission Fourier transform infrared spectra of the 4p-5s and 5p-6s bands of ArH.

Science.gov (United States)

Baskakov, O I; Civis, S; Kawaguchi, K

2005-03-15

In the 2500-8500 cm(-1) region several strong emission bands of (40)ArH were observed by Fourier transform spectroscopy through a dc glow discharge in a mixture of argon and hydrogen. Rotational-electronic transitions of the two previously unstudied 4p-5s and 5p-6s,v = 0-0, bands of (40)ArH were measured and assigned in the 6060 and 3770 cm(-1) regions, respectively. A simultaneous fit of the emission transitions of the 4p-5s and 5p-6s bands and an extended set of transitions of the 6s-4p band observed by Dabrowski, Tokaryk, and Watson [J. Mol. Spectrosc. 189, 95 (1998)] and remeasured in the present work yielded consistent values of the spectroscopic parameters of the electronic states under investigation. In the branch of the 4p-5s band with transitions of type (Q)Q(f(3)e) we observed a narrowing in the linewidths with increasing rotational quantum number N. The rotational dependence of the linewidth is caused by predissociation of the 5s state by the repulsive ground 4s state through homogeneous coupling and changes in overlap integrals of the vibrational wave functions with the rotational level. Analysis was based on the Fermi's golden rule approximation model. In the 4p-5s band region a vibrational sequence ofv(')-v(")=1-1, 2-2, and 3-3 were recorded and a number of transitions belonging to the strongest (Q)Q(f(3)e) form branch of the 1-1 band were analyzed.

Non-canonical binding interactions of the RNA recognition motif (RRM) domains of P34 protein modulate binding within the 5S ribonucleoprotein particle (5S RNP).

Science.gov (United States)

Kamina, Anyango D; Williams, Noreen

2017-01-01

RNA binding proteins are involved in many aspects of RNA metabolism. In Trypanosoma brucei, our laboratory has identified two trypanosome-specific RNA binding proteins P34 and P37 that are involved in the maturation of the 60S subunit during ribosome biogenesis. These proteins are part of the T. brucei 5S ribonucleoprotein particle (5S RNP) and P34 binds to 5S ribosomal RNA (rRNA) and ribosomal protein L5 through its N-terminus and its RNA recognition motif (RRM) domains. We generated truncated P34 proteins to determine these domains' interactions with 5S rRNA and L5. Our analyses demonstrate that RRM1 of P34 mediates the majority of binding with 5S rRNA and the N-terminus together with RRM1 contribute the most to binding with L5. We determined that the consensus ribonucleoprotein (RNP) 1 and 2 sequences, characteristic of canonical RRM domains, are not fully conserved in the RRM domains of P34. However, the aromatic amino acids previously described to mediate base stacking interactions with their RNA target are conserved in both of the RRM domains of P34. Surprisingly, mutation of these aromatic residues did not disrupt but instead enhanced 5S rRNA binding. However, we identified four arginine residues located in RRM1 of P34 that strongly impact L5 binding. These mutational analyses of P34 suggest that the binding site for 5S rRNA and L5 are near each other and specific residues within P34 regulate the formation of the 5S RNP. These studies show the unique way that the domains of P34 mediate binding with the T. brucei 5S RNP.

CELULE FOTOVOLTAICE CU HETEROJONCŢIUNEA nCdS-pInP

Directory of Open Access Journals (Sweden)

Vasile BOTNARIUC

2015-12-01

Full Text Available Au fost studiate proprietăţile electrice şi fotoelectrice ale heterojoncţiunilor nCdS-pInP cu şi fără strat epitaxial inter-mediar poInP. S-a stabilit că la polarizări directe în mecanismul de transport al curentului predomină procesele de recom-binare în regiunea de sarcină spaţială. La polarizări inverse predomină procesele de tunelare. Prezenţa stratului epitaxial poInP depus repetat măreşte ISC până la 28,2 mA·cm-2, UCD până la 0,780 V, iar eficienţa conversiei energiei până la 15% la 300 K şi iluminare 100 mW/cm2. Fotosensibilitatea CF nCdS-poInP-pInP corespunde intervalului λ=550...950 nm cu un maximum plat localizat în intervalul λ=700...850 nm.HETEROJONCTION nCdS–pInP FOTOVOLTAIC CELLSElectrical and photoelectrical properties of nCdS-pInP hetero-junctions with and without intermediate poInP epitaxial layer were studied. It was established that the current flow mechanism at direct biases is determined mainly by the recombi-nation processes in the space charge region of the junction. At the reverse biases the tunneling processes are predominant. The presence of poInP layer leads to the photo-electrical parameters enhancing of hetero-junction: short circuit current increases up to 28,2 mA·cm -2, open circuit voltage up to 0,780V and the efficiency of solar energy conversion up to 15 % (at 300 K and illumination of 100mw/cm2. The photo-sensitivity of nCdS- poInP -pInP is in the wavelength region of λ= 550-950nm with a maximum localized to λ=700-850nm.

Genes for carbon metabolism and the ToxA virulence factor in Pseudomonas aeruginosa are regulated through molecular interactions of PtxR and PtxS.

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Abdelali Daddaoua

Full Text Available Homologs of the transcriptional regulator PtxS are omnipresent in Pseudomonas, whereas PtxR homologues are exclusively found in human pathogenic Pseudomonas species. In all Pseudomonas sp., PtxS with 2-ketogluconate is the regulator of the gluconate degradation pathway and controls expression from its own promoter and also from the P(gad and P(kgu for the catabolic operons. There is evidence that PtxS and PtxR play a central role in the regulation of exotoxin A expression, a relevant primary virulence factor of Pseudomonas aeruginosa. We show using DNaseI-footprint analysis that in P. aeruginosa PtxR binds to the -35 region of the P(toxA promoter in front of the exotoxin A gene, whereas PtxS does not bind to this promoter. Bioinformatic and DNaseI-footprint analysis identified a PtxR binding site in the P(kgu and P(gad promoters that overlaps the -35 region, while the PtxS operator site is located 50 bp downstream from the PtxR site. In vitro, PtxS recognises PtxR with nanomolar affinity, but this interaction does not occur in the presence of 2-ketogluconate, the specific effector of PtxS. DNAaseI footprint assays of P(kgu and P(gad promoters with PtxS and PtxR showed a strong region of hyper-reactivity between both regulator binding sites, indicative of DNA distortion when both proteins are bound; however in the presence of 2-ketogluconate no protection was observed. We conclude that PtxS modulates PtxR activity in response to 2-ketogluconate by complex formation in solution in the case of the P(toxA promoter, or via the formation of a DNA loop as in the regulation of gluconate catabolic genes. Data suggest two different mechanisms of control exerted by the same regulator.

InP/ZnSe/ZnS core-multishell quantum dots for improved luminescence efficiency

Science.gov (United States)

Greco, Tonino; Ippen, Christian; Wedel, Armin

2012-04-01

Semiconductor quantum dots (QDs) exhibit unique optical properties like size-tunable emission color, narrow emission peak, and high luminescence efficiency. QDs are therefore investigated towards their application in light-emitting devices (QLEDs), solar cells, and for bio-imaging purposes. In most cases QDs made from cadmium compounds like CdS, CdSe or CdTe are studied because of their facile and reliable synthesis. However, due to the toxicity of Cd compounds and the corresponding regulation (e.g. RoHS directive in Europe) these materials are not feasible for customer applications. Indium phosphide is considered to be the most promising alternative because of the similar band gap (InP 1.35 eV, CdSe 1.73 eV). InP QDs do not yet reach the quality of CdSe QDs, especially in terms of photoluminescence quantum yield and peak width. Typically, QDs are coated with another semiconductor material of wider band gap, often ZnS, to passivate surface defects and thus improve luminescence efficiency. Concerning CdSe QDs, multishell coatings like CdSe/CdS/ZnS or CdSe/ZnSe/ZnS have been shown to be advantageous due to the improved compatibility of lattice constants. Here we present a method to improve the luminescence efficiency of InP QDs by coating a ZnSe/ZnS multishell instead of a ZnS single shell. ZnSe exhibits an intermediate lattice constant of 5.67 Å between those of InP (5.87 Å) and ZnS (5.41 Å) and thus acts as a wetting layer. As a result, InP/ZnSe/ZnS is introduced as a new core-shell quantum dot material which shows improved photoluminescence quantum yield (up to 75 %) compared to the conventional InP/ZnS system.

The signaling lipid sphingosine 1-phosphate regulates mechanical pain

Science.gov (United States)

Hill, Rose Z; Hoffman, Benjamin U; Morita, Takeshi; Campos, Stephanie M; Lumpkin, Ellen A; Brem, Rachel B

2018-01-01

Somatosensory neurons mediate responses to diverse mechanical stimuli, from innocuous touch to noxious pain. While recent studies have identified distinct populations of A mechanonociceptors (AMs) that are required for mechanical pain, the molecular underpinnings of mechanonociception remain unknown. Here, we show that the bioactive lipid sphingosine 1-phosphate (S1P) and S1P Receptor 3 (S1PR3) are critical regulators of acute mechanonociception. Genetic or pharmacological ablation of S1PR3, or blockade of S1P production, significantly impaired the behavioral response to noxious mechanical stimuli, with no effect on responses to innocuous touch or thermal stimuli. These effects are mediated by fast-conducting A mechanonociceptors, which displayed a significant decrease in mechanosensitivity in S1PR3 mutant mice. We show that S1PR3 signaling tunes mechanonociceptor excitability via modulation of KCNQ2/3 channels. Our findings define a new role for S1PR3 in regulating neuronal excitability and establish the importance of S1P/S1PR3 signaling in the setting of mechanical pain thresholds. PMID:29561262

To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling.

Science.gov (United States)

Chew, Wee Siong; Wang, Wei; Herr, Deron R

2016-11-01

Sphingosine 1-phosphate (S1P) is an extracellular lipid signaling molecule that acts as a selective, high-affinity ligand for a family of five G protein-coupled receptors. This signaling system was first identified twenty years ago, and has since been shown to regulate a diverse range of physiological processes and disease states, such as cardiovascular development, immune function, hypoxic responses, and cancer. The therapeutic potential of targeting this system took center stage when it was demonstrated that the immune modulator, fingolimod (FTY720/Gilenya), exerts it lymphopenic effect by acting on S1P receptors, primarily on S1P receptor 1 (S1P 1 ). In 2010, fingolimod became the first oral medication approved for the treatment of multiple sclerosis (MS). Since then, second-generation S1P receptor modulators have been under development in an effort to provide improved safety and efficacy profiles for MS, and to broaden their use to other autoimmune indications. Beyond the development of S1P 1 -modulators, there has been considerable effort in targeting other components of the S1P signaling pathway for the treatment of other diseases, such as cardiovascular disease, sepsis, and cancer. This manuscript provides an overview of the clinical and preclinical development of drugs targeting S1P signaling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fabrication of highly luminescent InP/Cd and InP/CdS quantum dots

International Nuclear Information System (INIS)

Park, Jaehyun; Kim, Sunghoon; Kim, Sungwoo; Yu, Seung Tack; Lee, Bunyeoul; Kim, Sang-Wook

2010-01-01

Highly luminescent InP/Cd and InP/CdS core-shell QDs were fabricated by sequential addition of cadmium acetylacetonate and dodecanethiol to InP core solutions, which showed a red-shift in absorption and emission. ICP measurement revealed the existence of cadmium and TEM images showed the increased size of InP/CdS QDs. PXRD data identified zinc blend structures of InP and InP/CdS QDs, which indexed to the (1 1 1), (2 2 0) and (3 1 1) planes. The slight shift of peaks between InP and InP/CdS QDs can demonstrate the existence of CdS shell structures.

Regulation by S-nitrosylation of the Calvin-Benson cycle fructose-1,6-bisphosphatase in Pisum sativum

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Antonio Jesús Serrato

2018-04-01

Full Text Available Redox regulation is of great importance in chloroplasts. Many chloroplast enzymes, such as those belonging to the Calvin-Benson cycle (CBC, have conserved regulatory cysteines which form inhibitory disulphide bridges when physiological conditions become unfavourable. Amongst these enzymes, cFBP1, the CBC fructose-1,6-bisphosphatase (FBPase isoform, is well known to be redox activated by thioredoxin f through the reduction of a disulphide bridge involving Cys153 and Cys173. Moreover, data obtained during recent years point to S-nitrosylation as another redox post-translational modification putatively regulating an increasing number of plant enzymes, including cFBP1. In this study we have shown that the Pisum sativum cFBP1 can be efficiently S-nitrosylated by GSNO and SNAP, triggering the formation of the regulatory disulphide. Using in vivo experiments with P. sativum we have established that cFBP1 S-nitrosylation only occurs during the light period and we have elucidated by activity assays with Cys-to-Ser mutants that this enzyme may be inactivated through the S-nitrosylation of Cys153. Finally, in the light of the new data, we have proposed an extended redox-regulation model by integrating the S-nitrosylation and the TRX f-mediated regulation of cFBP1. Keywords: S-nitrosylation, GSNO, Redox regulation, Fructose-1,6-bisphosphatase, Pisum sativum, Calvin-Benson cycle

Sb{sub 2}S{sub 3}:C/CdS p-n junction by laser irradiation

Energy Technology Data Exchange (ETDEWEB)

Arato, A. [Facultad de Ingenieria Mecanica y Electrica, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Nuevo Leon (Mexico); Centro de Innovacion, Investigacion y Desarrollo en Ingenieria y Tecnologia-Universidad Autonoma de Nuevo Leon, Apodaca, Nuevo Leon (Mexico); Cardenas, E. [Facultad de Ingenieria Mecanica y Electrica, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Nuevo Leon (Mexico); Shaji, S. [Facultad de Ingenieria Mecanica y Electrica, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Nuevo Leon (Mexico); Centro de Innovacion, Investigacion y Desarrollo en Ingenieria y Tecnologia-Universidad Autonoma de Nuevo Leon, Apodaca, Nuevo Leon (Mexico); O' Brien, J.J.; Liu, J. [Center for Nanoscience, University of Missouri-St. Louis, One University Boulevard, St. Louis, Missouri-63121 (United States); Department of Chemistry and Biochemistry, University of Missouri-St. Louis, One University Boulevard, St. Louis, Missouri-63121 (United States); Castillo, G. Alan; Das Roy, T.K. [Facultad de Ingenieria Mecanica y Electrica, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Nuevo Leon (Mexico); Krishnan, B. [Facultad de Ingenieria Mecanica y Electrica, Universidad Autonoma de Nuevo Leon, San Nicolas de los Garza, Nuevo Leon (Mexico); Centro de Innovacion, Investigacion y Desarrollo en Ingenieria y Tecnologia-Universidad Autonoma de Nuevo Leon, Apodaca, Nuevo Leon (Mexico)], E-mail: bkrishnan@fime.uanl.mx

2009-02-02

In this paper, we report laser irradiated carbon doping of Sb{sub 2}S{sub 3} thin films and formation of a p-n junction photovoltaic structure using these films. A very thin carbon layer was evaporated on to chemical bath deposited Sb{sub 2}S{sub 3} thin films of approximately 0.5 {mu}m in thickness. Sb{sub 2}S{sub 3} thin films were prepared from a solution containing SbCl{sub 3} and Na{sub 2}S{sub 2}O{sub 3} at 27 deg. C for 5 h and the films obtained were highly resistive. These C/Sb{sub 2}S{sub 3} thin films were irradiated by an expanded laser beam of diameter approximately 0.5 cm (5 W power, 532 nm Verdi laser), for 2 min at ambient atmosphere. Morphology and composition of these films were analyzed. These films showed p-type conductivity due to carbon diffusion (Sb{sub 2} S{sub 3}:C) by the thermal energy generated by the absorption of laser radiation. In addition, these thin films were incorporated in a photovoltaic structure Ag/Sb{sub 2}S{sub 3}:C/CdS/ITO/Glass. For this, CdS thin film of 50 nm in thickness was deposited on a commercially available ITO coated glass substrate from a chemical bath containing CdCl{sub 2}, sodium citrate, NH{sub 4}OH and thiourea at 70 deg. C . On the CdS film, Sb{sub 2}S{sub 3}/C layers were deposited. This multilayer structure was subjected to the laser irradiation, C/Sb{sub 2}S{sub 3} side facing the beam. The p-n junction formed by p-Sb{sub 2}S{sub 3}:C and n-type CdS showed V{sub oc} = 500 mV and J{sub sc} = 0.5 mA/cm{sup 2} under illumination by a tungsten halogen lamp. This work opens up a new method to produce solar cell structures by laser assisted material processing.

G.P.S. Occhialini 1907-93

International Nuclear Information System (INIS)

Peyrou, C.

1994-01-01

G.P.S. Occhialini, a legendary figure for all who remember the very beginnings of cosmic ray particle physics, died on 30 December. Born on 5 December 1907 in Rossombrone, near Urbino, he studied in Florence. Here he met Bruno Rossi, whom, although only two years his senior, he always regarded as a master. In 1932 Occhialini went to Cambridge where he worked with P.M.S. Blackett. They invented and perfected the counter-triggered Wilson chamber technique, recording cascade showers which confirmed the existence of the positron, discovered slightly earlier by Anderson, and demonstrating its symmetry with the electron

Caractérisation du séchage convectif de la variété de mangue Amélie

African Journals Online (AJOL)

Dans cette étude, une caractérisation du séchage convectif de la variété de mangue « Amélie » est réalisée à travers l'établissement des cinétiques de séchage de 50°C à 70°C et de l'isotherme de désorption à 40°C. La diffusivité effective est identifiée et varie de 0,75x10-9m².s-1 à 50°C, à 1,07x10-9m².s-1 à 60°C et 1 ...

Glutathione S-transferase P influences redox and migration pathways in bone marrow.

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Jie Zhang

Full Text Available To interrogate why redox homeostasis and glutathione S-transferase P (GSTP are important in regulating bone marrow cell proliferation and migration, we isolated crude bone marrow, lineage negative and bone marrow derived-dendritic cells (BMDDCs from both wild type (WT and knockout (Gstp1/p2(-/- mice. Comparison of the two strains showed distinct thiol expression patterns. WT had higher baseline and reactive oxygen species-induced levels of S-glutathionylated proteins, some of which (sarco-endoplasmic reticulum Ca2(+-ATPase regulate Ca(2+ fluxes and subsequently influence proliferation and migration. Redox status is also a crucial determinant in the regulation of the chemokine system. CXCL12 chemotactic response was stronger in WT cells, with commensurate alterations in plasma membrane polarization/permeability and intracellular calcium fluxes; activities of the downstream kinases, ERK and Akt were also higher in WT. In addition, expression levels of the chemokine receptor CXCR4 and its associated phosphatase, SHP-2, were higher in WT. Inhibition of CXCR4 or SHP2 decreased the extent of CXCL12-induced migration in WT BMDDCs. The differential surface densities of CXCR4, SHP-2 and inositol trisphosphate receptor in WT and Gstp1/p2(-/- cells correlated with the differential CXCR4 functional activities, as measured by the extent of chemokine-induced directional migration and differences in intracellular signaling. These observed differences contribute to our understanding of how genetic ablation of GSTP causes different levels of myeloproliferation and migration [corrected

Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness

International Nuclear Information System (INIS)

Young, Nicholas; Van Brocklyn, James R.

2007-01-01

Sphingosine-1-phosphate (S1P) is a bioactive lipid that signals through a family of five G-protein-coupled receptors, termed S1P 1-5 . S1P stimulates growth and invasiveness of glioma cells, and high expression levels of the enzyme that forms S1P, sphingosine kinase-1, correlate with short survival of glioma patients. In this study we examined the mechanism of S1P stimulation of glioma cell proliferation and invasion by either overexpressing or knocking down, by RNA interference, S1P receptor expression in glioma cell lines. S1P 1 , S1P 2 and S1P 3 all contribute positively to S1P-stimulated glioma cell proliferation, with S1P 1 being the major contributor. Stimulation of glioma cell proliferation by these receptors correlated with activation of ERK MAP kinase. S1P 5 blocks glioma cell proliferation, and inhibits ERK activation. S1P 1 and S1P 3 enhance glioma cell migration and invasion. S1P 2 inhibits migration through Rho activation, Rho kinase signaling and stress fiber formation, but unexpectedly, enhances glioma cell invasiveness by stimulating cell adhesion. S1P 2 also potently enhances expression of the matricellular protein CCN1/Cyr61, which has been implicated in tumor cell adhesion, and invasion as well as tumor angiogenesis. A neutralizing antibody to CCN1 blocked S1P 2 -stimulated glioma invasion. Thus, while S1P 2 decreases glioma cell motility, it may enhance invasion through induction of proteins that modulate glioma cell interaction with the extracellular matrix

Calculations of resonances parameters for the ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) doubly excited states of helium-like ions with Z≤10 using a complex rotation method implemented in Scilab

International Nuclear Information System (INIS)

Gning, Youssou; Sow, Malick; Traoré, Alassane; Dieng, Matabara; Diakhate, Babacar; Biaye, Mamadi; Wagué, Ahmadou

2015-01-01

In the present work a special computational program Scilab (Scientific Laboratory) in the complex rotation method has been used to calculate resonance parameters of ((2s 2 ) 1 S e , (2s2p) 1,3 P 0 ) and ((3s 2 ) 1 S e , (3s3p) 1,3 P 0 ) states of helium-like ions with Z≤10. The purpose of this study required a mathematical development of the Hamiltonian applied to Hylleraas wave function for intrashell states, leading to analytical expressions which are carried out under Scilab computational program. Results are in compliance with recent theoretical calculations. - Highlights: • Resonance energy and widths computed for doubly excited states of helium-like ions. • Well-comparable results to the theoretical literature values up to Z=10. • Satisfactory agreements with theoretical calculations for widths

The Hog1p kinase regulates Aft1p transcription factor to control iron accumulation.

Science.gov (United States)

Martins, Telma S; Pereira, Clara; Canadell, David; Vilaça, Rita; Teixeira, Vítor; Moradas-Ferreira, Pedro; de Nadal, Eulàlia; Posas, Francesc; Costa, Vítor

2018-01-01

Iron acquisition systems have to be tightly regulated to assure a continuous supply of iron, since it is essential for survival, but simultaneously to prevent iron overload that is toxic to the cells. In budding yeast, the low‑iron sensing transcription factor Aft1p is a master regulator of the iron regulon. Our previous work revealed that bioactive sphingolipids modulate iron homeostasis as yeast cells lacking the sphingomyelinase Isc1p exhibit an upregulation of the iron regulon. In this study, we show that Isc1p impacts on iron accumulation and localization. Notably, Aft1p is activated in isc1Δ cells due to a decrease in its phosphorylation and an increase in its nuclear levels. Consistently, the expression of a phosphomimetic version of Aft1p-S210/S224 that favours its nuclear export abolished iron accumulation in isc1Δ cells. Notably, the Hog1p kinase, homologue of mammalian p38, interacts with and directly phosphorylates Aft1p at residues S210 and S224. However, Hog1p-Aft1p interaction decreases in isc1Δ cells, which likely contributes to Aft1p dephosphorylation and consequently to Aft1p activation and iron overload in isc1Δ cells. These results suggest that alterations in sphingolipid composition in isc1Δ cells may impact on iron homeostasis by disturbing the regulation of Aft1p by Hog1p. To our knowledge, Hog1p is the first kinase reported to directly regulate Aft1p, impacting on iron homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

UBE2S associated with OSCC proliferation by promotion of P21 degradation via the ubiquitin-proteasome system

International Nuclear Information System (INIS)

Yoshimura, Shusaku; Kasamatsu, Atsushi; Nakashima, Dai; Iyoda, Manabu; Kasama, Hiroki; Saito, Tomoaki; Takahara, Toshikazu; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

2017-01-01

Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitin-proteasome system, is highly expressed in several types of cancers; however, its roles in oral squamous cell carcinoma (OSCC) have not yet been well elucidated. The purpose of this study was to clarify the functional activities of UBE2S in OSCCs. We analyzed the expression levels of UBE2S in nine OSCC cell lines and primary OSCC tissues by quantitative reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry (IHC). The correlations between UBE2S expression and clinical classifications of OSCCs were analyzed using the IHC scoring system. We also used UBE2S knockdown OSCC cells for functional assays (proliferation assay, flow cytometry, and Western blotting). UBE2S was overexpressed in OSCCs in vitro and in vivo and was correlated significantly (P < 0.05) with the primary tumoral size. The cellular growth was decreased and the cell-cycle was arrested in the G2/M phase in the UBE2S knockdown (shUBE2S) cells. The expression level of P21, a target of the ubiquitin-proteasome system, was increased in the shUBE2S cells because of lower anaphase activity that promotes complex subunit 3 (APC3), an E3 ubiquitin ligase, compared with shMock cells. These findings might promote the understanding of the relationship between UBE2S overexpression and oral cancer proliferation, indicating that UBE2S would be a potential biomarker of and therapeutic target in OSCCs. - Highlights: • UBE2S contributes to tumor progression in OSCCs. • UBE2S regulated the cell-cycle arrest at G2/M phase in OSCC cells. • UBE2S and APC3 co-regulate the expression level of P21 at G2/M check point via the ubiquitin-proteasome system. • P21 is one of the proliferation-regulating factors in OSCC. • UBE2S would be a potential therapeutic target for OSCCs.

Calculations of resonances parameters for the ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) doubly excited states of helium-like ions with Z≤10 using a complex rotation method implemented in Scilab

Science.gov (United States)

Gning, Youssou; Sow, Malick; Traoré, Alassane; Dieng, Matabara; Diakhate, Babacar; Biaye, Mamadi; Wagué, Ahmadou

2015-01-01

In the present work a special computational program Scilab (Scientific Laboratory) in the complex rotation method has been used to calculate resonance parameters of ((2s2) 1Se, (2s2p) 1,3P0) and ((3s2) 1Se, (3s3p) 1,3P0) states of helium-like ions with Z≤10. The purpose of this study required a mathematical development of the Hamiltonian applied to Hylleraas wave function for intrashell states, leading to analytical expressions which are carried out under Scilab computational program. Results are in compliance with recent theoretical calculations.

Memories of early work on muscle contraction and regulation in the 1950's and 1960's

International Nuclear Information System (INIS)

Huxley, Hugh E.

2008-01-01

Professor Ebashi's epic work on the biochemistry of the regulation of muscle contraction began in the early 1950's, during the same period that work on the molecular basis of force production in muscle was also beginning. The latter work started in two MRC Research Units in the UK, and was continued jointly by the two workers from those Units who had, independently, gone to MIT to learn the new techniques of electron microscopy and to apply them to muscle. In a somewhat similar fashion, Professor Ebashi also spent one or two years in the USA, continuing his work on the role of calcium in muscle regulation in Lippman's laboratory, before returning to Japan to achieve the great breakthroughs in this work during the 1960's. Hanson and Huxley, after putting forward the overlapping actin and myosin filament arrays model for the striated muscle sarcomere, and subsequently the sliding filament model of muscle contraction (simultaneously with A.F Huxley and R. Niedergerke), returned to the UK to pursue detailed structural studies in separate Research Units, in a mixture of consultation, collaboration, and competition, during the later 1950's and throughout the 1960's. However, the path to enlightenment described here in some detail was somewhat more tortuous than the standard literature perhaps reveals. Nevertheless, by the time of the Cold Spring Harbor Symposium on Muscle Contraction in 1972, the two lines of enquiry on regulation itself, and on the tilting cross-bridge model of force production, had arrived at a good deal of common ground, and indeed the identification of troponin and its periodic distribution along the actin filaments had helped resolve a long-standing puzzle in the interpretation of the low angle X-ray diagram. Since then, an enormous amount of remarkable new work has been necessary to establish troponin regulation and the tilting cross-bridge mechanism in molecular detail, but the work in the 1950's and 1960's has provided a firm and accurate basis

Long noncoding RNA LISPR1 is required for S1P signaling and endothelial cell function.

Science.gov (United States)

Josipovic, Ivana; Pflüger, Beatrice; Fork, Christian; Vasconez, Andrea E; Oo, James A; Hitzel, Juliane; Seredinski, Sandra; Gamen, Elisabetta; Heringdorf, Dagmar Meyer Zu; Chen, Wei; Looso, Mario; Pullamsetti, Soni Savai; Brandes, Ralf P; Leisegang, Matthias S

2018-03-01

Sphingosine-1-Phosphate (S1P) is a potent signaling lipid. The effects of S1P are mediated by the five S1P receptors (S1PR). In the endothelium S1PR1 is the predominant receptor and thus S1PR1 abundance limits S1P signaling. Recently, lncRNAs were identified as a novel class of molecules regulating gene expression. Interestingly, the lncRNA NONHSAT004848 (LISPR1, Long intergenic noncoding RNA antisense to S1PR1), is closely positioned to the S1P1 receptors gene and in part shares its promoter region. We hypothesize that LISPR1 controls endothelial S1PR1 expression and thus S1P-induced signaling in endothelial cells. In vitro transcription and translation as well as coding potential assessment showed that LISPR1 is indeed noncoding. LISPR1 was localized in both cytoplasm and nucleus and harbored a PolyA tail at the 3'end. In human umbilical vein endothelial cells, as well as human lung tissue, qRT-PCR and RNA-Seq revealed high expression of LISPR1. S1PR1 and LISPR1 were downregulated in human pulmonary diseases such as COPD. LISPR1 but also S1PR1 were induced by inflammation, shear stress and statins. Knockdown of LISPR1 attenuated endothelial S1P-induced migration and spheroid outgrowth of endothelial cells. LISPR1 knockdown decreased S1PR1 expression, which was paralleled by an increase of the binding of the transcriptional repressor ZNF354C to the S1PR1 promoter and a reduction of the recruitment of RNA Polymerase II to the S1PR1 5'end. This resulted in attenuated S1PR1 expression and attenuated S1P downstream signaling. Collectively, the disease relevant lncRNA LISPR1 acts as a novel regulatory unit important for S1PR1 expression and endothelial cell function. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tables of Shore and Fano parameters for the helium resonances 2s/sup 2/ /sup 1/S, 2p/sup 2/ /sup 1/D, and 2s 2p /sup 1/P excited in p-He collisions E/sub p/ = 33 to 150 keV

Energy Technology Data Exchange (ETDEWEB)

Bordenave-Montesquieu, A.; Benoit-Cattin, P.; Gleizes, A.; Merchez, H.

1976-02-01

Absolute values of Shore and Fano parameters are tabulated for the helium atom 2s/sup 2/ /sup 1/S, 2p/sup 2/ /sup 1/D, and 2s 2p /sup 1/P resonances produced by a proton beam. Observations were made on the spectra of ejected electrons. The important variation of the shape of the resonances with ejection angle is illustrated for E/sub p/ = 100 keV; the variation with proton energy is shown at 30/sup 0/.

Curcumin ameliorates diabetic nephropathy by inhibiting the activation of the SphK1-S1P signaling pathway.

Science.gov (United States)

Huang, Juan; Huang, Kaipeng; Lan, Tian; Xie, Xi; Shen, Xiaoyan; Liu, Peiqing; Huang, Heqing

2013-01-30

Curcumin, a major polyphenol from the golden spice Curcuma longa commonly known as turmeric, has been recently discovered to have renoprotective effects on diabetic nephropathy (DN). However, the mechanisms underlying these effects remain unclear. We previously demonstrated that the sphingosine kinase 1-sphingosine 1-phosphate (SphK1-S1P) signaling pathway plays a pivotal role in the pathogenesis of DN. This study aims to investigate whether the renoprotective effects of curcumin on DN are associated with its inhibitory effects on the SphK1-S1P signaling pathway. Our results demonstrated that the expression and activity of SphK1 and the production of S1P were significantly down-regulated by curcumin in diabetic rat kidneys and glomerular mesangial cells (GMCs) exposed to high glucose (HG). Simultaneously, SphK1-S1P-mediated fibronectin (FN) and transforming growth factor-beta 1 (TGF-β1) overproduction were inhibited. In addition, curcumin dose dependently reduced SphK1 expression and activity in GMCs transfected with SphK(WT) and significantly suppressed the increase in SphK1-mediated FN levels. Furthermore, curcumin inhibited the DNA-binding activity of activator protein 1 (AP-1), and c-Jun small interference RNA (c-Jun-siRNA) reversed the HG-induced up-regulation of SphK1. These findings suggested that down-regulation of the SphK1-S1P pathway is probably a novel mechanism by which curcumin improves the progression of DN. Inhibiting AP-1 activation is one of the therapeutic targets of curcumin to modulate the SphK1-S1P signaling pathway, thereby preventing diabetic renal fibrosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Intra- and interspecies regulation of gene expression by Actinobacillus actinomycetemcomitans LuxS.

Science.gov (United States)

Fong, K P; Chung, W O; Lamont, R J; Demuth, D R

2001-12-01

The cell density-dependent control of gene expression is employed by many bacteria for regulating a variety of physiological functions, including the generation of bioluminescence, sporulation, formation of biofilms, and the expression of virulence factors. Although periodontal organisms do not appear to secrete acyl-homoserine lactone signals, several species, e.g., Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum, have recently been shown to secrete a signal related to the autoinducer II (AI-2) of the signal system 2 pathway in Vibrio harveyi. Here, we report that the periodontal pathogen Actinobacillus actinomycetemcomitans expresses a homolog of V. harveyi luxS and secretes an AI-2-like signal. Cell-free conditioned medium from A. actinomycetemcomitans or from a recombinant Escherichia coli strain (E. coli AIS) expressing A. actinomycetemcomitans luxS induced luminescence in V. harveyi BB170 >200-fold over controls. AI-2 levels peaked in mid-exponential-phase cultures of A. actinomycetemcomitans and were significantly reduced in late-log- and stationary-phase cultures. Incubation of early-log-phase A. actinomycetemcomitans cells with conditioned medium from A. actinomycetemcomitans or from E. coli AIS resulted in a threefold induction of leukotoxic activity and a concomitant increase in leukotoxin polypeptide. In contrast, no increase in leukotoxin expression occurred when cells were exposed to sterile medium or to conditioned broth from E. coli AIS(-), a recombinant strain in which luxS was insertionally inactivated. A. actinomycetemcomitans AI-2 also induced expression of afuA, encoding a periplasmic iron transport protein, approximately eightfold, suggesting that LuxS-dependent signaling may play a role in the regulation of iron acquisition by A. actinomycetemcomitans. Finally, A. actinomycetemcomitans AI-2 added in trans complemented a luxS knockout mutation in P. gingivalis by modulating the expression of the luxS-regulated

S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization.

Science.gov (United States)

Lee, Mi-Hye; Appleton, Kathryn M; El-Shewy, Hesham M; Sorci-Thomas, Mary G; Thomas, Michael J; Lopes-Virella, Maria F; Luttrell, Louis M; Hammad, Samar M; Klein, Richard L

2017-02-01

HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.

MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells.

Science.gov (United States)

Kalhori, Veronica; Törnquist, Kid

2015-03-15

The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The cholesterol, fatty acid and triglyceride synthesis pathways regulated by site 1 protease (S1P) are required for efficient replication of severe fever with thrombocytopenia syndrome virus.

Science.gov (United States)

Urata, Shuzo; Uno, Yukiko; Kurosaki, Yohei; Yasuda, Jiro

2018-06-12

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high mortality rate. Currently, no licensed vaccines or therapeutic agents have been approved for use against SFTSV infection. Here, we report that the cholesterol, fatty acid, and triglyceride synthesis pathways regulated by S1P is involved in SFTSV replication, using CHO-K1 cell line (SRD-12B) that is deficient in site 1 protease (S1P) enzymatic activity, PF-429242, a small compound targeting S1P enzymatic activity, and Fenofibrate and Lovastatin, which inhibit triglyceride and cholesterol synthesis, respectively. These results enhance our understanding of the SFTSV replication mechanism and may contribute to the development of novel therapies for SFTSV infection. Copyright © 2018. Published by Elsevier Inc.

Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

Science.gov (United States)

Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

2016-08-26

The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

Measurement of the spin-forbidden decay rate (3s3d)1D2¿(3s3p)3 P2,1 in 24Mg

DEFF Research Database (Denmark)

Therkildsen, K. T.; Jensen, Brian Bak; Ryder, C. P.

2009-01-01

We have measured the spin-forbidden decay rate from (3s3d)D12¿(3s3p)P32,1 in M24g atoms trapped in a magneto-optical trap. The total decay rate, summing up both exit channels (3s3p)P31 and (3s3p)P32 , yields 196±10s-1 in excellent agreement with resent relativistic many-body calculations of Porse...

Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways*

Science.gov (United States)

Quint, Patrick; Ruan, Ming; Pederson, Larry; Kassem, Moustapha; Westendorf, Jennifer J.; Khosla, Sundeep; Oursler, Merry Jo

2013-01-01

Normal bone turnover requires tight coupling of bone resorption and bone formation to preserve bone quantity and structure. With aging and during several pathological conditions, this coupling breaks down, leading to either net bone loss or excess bone formation. To preserve or restore normal bone metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed that osteoclasts produce the chemokine sphingosine 1-phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts to sites of bone resorption as an initial step in replacing lost bone. In this study we investigated the mechanisms by which S1P stimulates mesenchymal (skeletal) cell chemotaxis. S1P treatment of mesenchymal (skeletal) cells activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1P receptors, S1PR1 and S1PR2, coordinately promoted migration through activation of the JAK/STAT3 and FAK/PI3K/AKT signaling pathways, respectively. These data demonstrate that the chemokine S1P couples bone formation to bone resorption through activation of kinase signaling pathways. PMID:23300082

Comparisons of TRAC-PF-1 calculations with semiscale Mod-3 small-break tests S-SB-P1 and S-SB-P7

International Nuclear Information System (INIS)

Sahota, M.S.

1982-01-01

Semiscale Tests S-SB-P1 and S-SB-P7 conducted in the Semiscale Mod-3 facility at the Idaho National Engineering Laboratory are analyzed using the latest released version of the Transient Reactor Analysis Code (TRAC-PF1). The results are used to assess TRAC-PF1 predictions of thermal-hydraulic phenomena and the effects of break size and pump operation on system response during slow transients. Tests S-SB-P1 and S-SB-P7 simulated an equivalent pressurized-water-reactor (PWR) 2.5% communicative cold-leg break for early and late pump trips, respectively, with only high-pressure injection (HPI) into the cold legs. The parameters examined include break flow, primary-system pressure response, primary-system mass distribution, and core characteristics

Perturbation of Ribosome Biogenesis Drives Cells into Senescence through 5S RNP-Mediated p53 Activation

Directory of Open Access Journals (Sweden)

Kazuho Nishimura

2015-03-01

Full Text Available The 5S ribonucleoprotein particle (RNP complex, consisting of RPL11, RPL5, and 5S rRNA, is implicated in p53 regulation under ribotoxic stress. Here, we show that the 5S RNP contributes to p53 activation and promotes cellular senescence in response to oncogenic or replicative stress. Oncogenic stress accelerates rRNA transcription and replicative stress delays rRNA processing, resulting in RPL11 and RPL5 accumulation in the ribosome-free fraction, where they bind MDM2. Experimental upregulation of rRNA transcription or downregulation of rRNA processing, mimicking the nucleolus under oncogenic or replicative stress, respectively, also induces RPL11-mediated p53 activation and cellular senescence. We demonstrate that exogenous expression of certain rRNA-processing factors rescues the processing defect, attenuates p53 accumulation, and increases replicative lifespan. To summarize, the nucleolar-5S RNP-p53 pathway functions as a senescence inducer in response to oncogenic and replicative stresses.

Les représentations du dieu Hermès et du couple Hestia-Hermès dans le cinéma américain des années 1930 à nos jours

OpenAIRE

Bloch , Jérôme

2012-01-01

ISBN 978-606-14-0550-3; International audience; S'inscrivant dans une démarche analytique et comparative, à la croisée de disciplines aussi fécondes que diversifiées -- l'histoire du cinéma, l'analyse filmique et littéraire, les gender studies... -- notre communication s'attache à dresser un panorama exhaustif des films américains mettant en scène la figure d'Hermès. Suivant une approche chronologique, notre démonstration s'appuie sur l'étude d'une dizaine de films produits sur le territoire ...

Pharmacologic inhibition of S1P attenuates ATF6 expression, causes ER stress and contributes to apoptotic cell death.

Science.gov (United States)

Lebeau, Paul; Byun, Jae Hyun; Yousof, Tamana; Austin, Richard C

2018-04-22

Mammalian cells express unique transcription factors embedded in the endoplasmic reticulum (ER) membrane, such as the sterol regulatory element-binding proteins (SREBPs), that promote de novo lipogenesis. Upon their release from the ER, the SREBPs require proteolytic activation in the Golgi by site-1-protease (S1P). As such, inhibition of S1P, using compounds such as PF-429242 (PF), reduces cholesterol synthesis and may represent a new strategy for the management of dyslipidemia. In addition to the SREBPs, the unfolded protein response (UPR) transducer, known as the activating transcription factor 6 (ATF6), is another ER membrane-bound transcription factor that requires S1P-mediated activation. ATF6 regulates ER protein folding capacity by promoting the expression of ER chaperones such as the 78-kDa glucose-regulated protein (GRP78). ER-resident chaperones like GRP78 prevent and/or resolve ER polypeptide accumulation and subsequent ER stress-induced UPR activation by folding nascent polypeptides. Here we report that pharmacological inhibition of S1P reduced the expression of ATF6 and GRP78 and induced the activation of UPR transducers inositol-requiring enzyme-1α (IRE1α) and protein kinase RNA-like ER kinase (PERK). As a consequence, S1P inhibition also increased the susceptibility of cells to ER stress-induced cell death. Our findings suggest that S1P plays a crucial role in the regulation of ER folding capacity and also identifies a compensatory cross-talk between UPR transducers in order to maintain adequate ER chaperone expression and activity. Copyright © 2018. Published by Elsevier Inc.

Pós-modernismo e pós-colonialismo: questionamentos e interpretações

Directory of Open Access Journals (Sweden)

Maria Helena Sansão Fontes

2010-12-01

Full Text Available Levando-se em conta as guerras de libertação africanas e as contradições inerentes ao processo de dominação cultural e de descolonização, este trabalho visa a uma reflexão em torno da possibilidade de uma vivência do pós-modernismo na obra do escritor angolano Pepetela. A metaficção historiográfica, viés constante na obra de alguns escritores pós-modernistas, também está presente na maioria dos romances de Pepetela, entre os quais se destacam Mayombe, A geração da utopia, O desejo de Kianda e O planalto e a estepe. Ressalta-se que Pepetela, como ex-guerrilheiro e militante no processo de independência de Angola, revela sua experiência de ativista por meio de uma escrita que ficcionalmente indaga sobre todo o processo histórico, utilizando-se das marcas da metaficção historiográfica que seriam a autorreflexividade, o subjetivismo e a transcendência da história.Palavras-chave: Pepetela; Pós-modernismo; Pós-colonialismo; Metaficção historiográfica; Angola.

Job på særlige vilkår

DEFF Research Database (Denmark)

Holt, Helle; Sonnefeld Jørgensen, Martin; Hohnen, Pernille

Job på særlige vilkår afviger fra ordinære job ved, at der kan medfølge et offentligt løntilskud, at jobbet kan være midlertidigt, og/eller at arbejdstid, præstationskrav og løn er anderledes. Ordningerne er en del af regeringens aktive arbejdsmarkedspolitik for at skabe et rummeligt arbejdsmarked...... og dermed undgå, at personer med nedsat arbejdsevne havner i passiv forsørgelse. Denne rapport gennemgår den viden, der findes om job på særlige vilkår. Det gælder både viden om de personer, der er ansat i et job på særlige vilkår, om de virksomheder, der ansætter personer på særlige vilkår, og om...... det system, der visiterer personer til job på særlige vilkår....

Laser spectroscopy of the 4s4p(3) P-2-4s3d(1) D-2 transition on magnetically trapped calcium atoms

NARCIS (Netherlands)

Dammalapati, U.; Norris, I.; Burrows, C.; Riis, E.

2011-01-01

Laser excitation of the 4s4p(3) P-2-4s3d(1) D-2 transition in atomic calcium has been observed and the wavelength determined to 1530.5298(6) nm. The metastable 4s4p(3) P-2 atoms were magnetically trapped in the quadrupole magnetic field of a magneto-optical trap. This state represents the only

Composition of S^p-weighted pseudo almost automorphic functions and applications

Directory of Open Access Journals (Sweden)

Chuan-Hua Chen

2014-11-01

Full Text Available Since the background space of $S^p$-weighted pseudo almost automorphic functions (abbr. $S^p$-wpaa functions is endowed with a norm coming from $L^p$ norm, it is natural to consider the composition of $S^p$-wpaa functions under conditions of $L^p$ norm. However, the known resutls for composition of $S^p$-wpaa functions were always given under conditions of supremum norm. Motivated by this, we establish some new results for the composition of $S^p$-almost automorphic functions and $S^p$-wpaa functions under a ``uniform continuity condition'' with respect to $L^p$ norm. As an application, we prove the existence of mild weighted pseudo almost automorphic solutions for some semilinear differential equations with an $S^p$-wpaa force term. An example of the heat equation illustrates our results.

Differential Effects of Long Term FTY720 Treatment on Endothelial versus Smooth Muscle Cell Signaling to S1P in Rat Mesenteric Arteries.

Science.gov (United States)

Hamidi Shishavan, Mahdi; Bidadkosh, Arash; Yazdani, Saleh; Lambooy, Sebastiaan; van den Born, Jacob; Buikema, Hendrik; Henning, Robert H; Deelman, Leo E

2016-01-01

The sphingosine-1-phosphate (S1P) analog FTY720 exerts pleiotropic effects on the cardiovascular system and causes down-regulation of S1P receptors. Myogenic constriction is an important mechanism regulating resistance vessel function and is known to be modulated by S1P. Here we investigated myogenic constriction and vascular function of mesenteric arteries of rats chronically treated with FTY720. Wistar rats received FTY720 1mg/kg/daily for six weeks. At termination, blood pressure was recorded and small mesenteric arteries collected for vascular studies in a perfusion set up. Myogenic constriction to increased intraluminal pressure was low, but a sub-threshold dose of S1P profoundly augmented myogenic constriction in arteries of both controls and animals chronically treated with FTY720. Interestingly, endothelial denudation blocked the response to S1P in arteries of FTY720-treated animals, but not in control rats. In acute experiments, presence of FTY720 significantly augmented the contractile response to S1P, an effect that was partially abolished after the inhibition of cyclooxygenase (COX-)-derived prostaglandins. FTY720 down regulated S1P1 but not S1P2 in renal resistance arteries and in cultured human endothelial cells. This study therefore demonstrates the endothelium is able to compensate for the complete loss of responsiveness of the smooth muscle layer to S1P after long term FTY720 treatment through a mechanism that most likely involves enhanced production of contractile prostaglandins by the endothelium.

Platelet and Erythrocyte Sources of S1P Are Redundant for Vascular Development and Homeostasis, but Both Rendered Essential After Plasma S1P Depletion in Anaphylactic Shock.

Science.gov (United States)

Gazit, Salomé L; Mariko, Boubacar; Thérond, Patrice; Decouture, Benoit; Xiong, Yuquan; Couty, Ludovic; Bonnin, Philippe; Baudrie, Véronique; Le Gall, Sylvain M; Dizier, Blandine; Zoghdani, Nesrine; Ransinan, Jessica; Hamilton, Justin R; Gaussem, Pascale; Tharaux, Pierre-Louis; Chun, Jerold; Coughlin, Shaun R; Bachelot-Loza, Christilla; Hla, Timothy; Ho-Tin-Noé, Benoit; Camerer, Eric

2016-09-30

Sphingosine-1-phosphate (S1P) signaling is essential for vascular development and postnatal vascular homeostasis. The relative importance of S1P sources sustaining these processes remains unclear. To address the level of redundancy in bioactive S1P provision to the developing and mature vasculature. S1P production was selectively impaired in mouse platelets, erythrocytes, endothelium, or smooth muscle cells by targeted deletion of genes encoding sphingosine kinases -1 and -2. S1P deficiency impaired aggregation and spreading of washed platelets and profoundly reduced their capacity to promote endothelial barrier function ex vivo. However, and in contrast to recent reports, neither platelets nor any other source of S1P was essential for vascular development, vascular integrity, or hemostasis/thrombosis. Yet rapid and profound depletion of plasma S1P during systemic anaphylaxis rendered both platelet- and erythrocyte-derived S1P essential for survival, with a contribution from blood endothelium observed only in the absence of circulating sources. Recovery was sensitive to aspirin in mice with but not without platelet S1P, suggesting that platelet activation and stimulus-response coupling is needed. S1P deficiency aggravated vasoplegia in this model, arguing a vital role for S1P in maintaining vascular resistance during recovery from circulatory shock. Accordingly, the S1P2 receptor mediated most of the survival benefit of S1P, whereas the endothelial S1P1 receptor was dispensable for survival despite its importance for maintaining vascular integrity. Although source redundancy normally secures essential S1P signaling in developing and mature blood vessels, profound depletion of plasma S1P renders both erythrocyte and platelet S1P pools necessary for recovery and high basal plasma S1P levels protective during anaphylactic shock. © 2016 American Heart Association, Inc.

Thioredoxin-1 promotes colorectal cancer invasion and metastasis through crosstalk with S100P.

Science.gov (United States)

Lin, Feiyan; Zhang, Peili; Zuo, Zhigui; Wang, Fule; Bi, Ruichun; Shang, Wenjing; Wu, Aihua; Ye, Ju; Li, Shaotang; Sun, Xuecheng; Wu, Jianbo; Jiang, Lei

2017-08-10

Thioredoxin-1 (Trx-1) is a small redox-regulating protein, which plays an important role in several cellular functions. Despite recent advances in understanding the biology of Trx-1, the role of Trx-1 and its underlying signaling mechanism in colorectal cancer (CRC) metastasis have not been extensively studied. In this study, we observed that Trx-1 expression is increased in CRC tissues compared to the paired non-cancerous tissues and is significantly correlated with clinical staging, lymph node metastasis and poor survival. Overexpression of Trx-1 enhanced CRC cell invasion and metastasis in vitro and in vivo. Conversely, suppression of Trx-1 expression decreased cell invasion and metastasis in vitro and in vivo. Moreover, Trx-1 activates S100P gene transcription. S100P, in turn, promotes Trx-1 expression and nuclear localization by upregulating p-ERK1/2 and downregulating TXNIP expression. Our finding provides new insight into the mechanism of Trx-1/S100P axis in the promotion of CRC metastasis, and suggests that the Trx-1/S100P axis and their related signaling pathways could be novel targets for the treatment of metastatic CRC. Copyright © 2017 Elsevier B.V. All rights reserved.

Selected immunological changes in patients with Goeckerman's therapy TNF-alpha, sE-selectin, sP-selectin, sICAM-1 and IL-8

Energy Technology Data Exchange (ETDEWEB)

Borska, L.; Fiala, Z.; Krejsek, J.; Andrys, C.; Vokurkova, D.; Hamakova, K.; Kremlacek, J.; Ettler, K. [Charles University, Hradec Kralove (Czech Republic). Faculty of Medicine

2006-07-01

Psoriasis is one of the most frequent inflammatory skin diseases in which abnormal individual immune reactivity plays an important role. The aim of the present study was to describe selected immunological changes, concerning pro-inflammatory cytokines (TNF-alpha, IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1), in 56 patients cured by Goeckerman's therapy (GT). GT includes dermal application of crude coal tar (containing polycyclic aromatic hydrocarbons) and exposure to UV radiation.

Nuclear effects in protonium formation low-energy three-body reaction: p̄ + (pμ1s → (p̄pα + μ−: Strong p̄–p interaction in p̄ + (pμ1s

Directory of Open Access Journals (Sweden)

Sultanov Renat A.

2016-01-01

Full Text Available A three-charge-particle system (p̄, μ−, p+ with an additional matter-antimatter, i.e. p̄–p+, nuclear interaction is the subject of this work. Specifically, we carry out a few-body computation of the following protonium formation reaction: p̄ + (p+μ−1s → (p̄p+1s + μ−, where p+ is a proton, p̄ is an antiproton, μ− is a muon, and a bound state of p+ and its counterpart p̄ is a protonium atom: Pn = (p̄p+. The low-energy cross sections and rates of the Pn formation reaction are computed in the framework of a Faddeev-like equation formalism. The strong p̄–p+ interaction is approximately included in this calculation.

Search for a Narrow Baryonic Resonance Decaying to $K^0_s p$ or $K^0_s \\bar{p}$ in Deep Inelastic Scattering at HERA

CERN Document Server

Aktas, A.; Anthonis, T.; Antunovic, B.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Babaev, A.; Backovic, S.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Baudrand, S.; Baumgartner, S.; Becker, J.; Beckingham, M.; Behnke, O.; Behrendt, O.; Belousov, A.; Berger, N.; Bizot, J.C.; Boenig, M.-O.; Boudry, V.; Bracinik, J.; Brandt, G.; Brisson, V.; Bruncko, D.; Busser, F.W.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Contreras, J.G.; Coughlan, J.A.; Cox, B.E.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Dau, W.D.; Daum, K.; de Boer, Y.; Delcourt, B.; Del Degan, M.; De Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dubak, A.; Eckerlin, Guenter; Efremenko, V.; Egli, S.; Eichler, R.; Eisele, F.; Eliseev, A.; Elsen, E.; Essenov, S.; Falkewicz, A.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Finke, L.; Fleischer, M.; Flucke, G.; Fomenko, A.; Franke, G.; Frisson, T.; Gabathuler, E.; Garutti, E.; Gayler, J.; Gerlich, C.; Ghazaryan, Samvel; Ginzburgskaya, S.; Glazov, A.; Glushkov, I.; Goerlich, L.; Goettlich, M.; Gogitidze, N.; Gorbounov, S.; Grab, C.; Greenshaw, T.; Gregori, M.; Grell, B.R.; Grindhammer, G.; Gwilliam, C.; Haidt, D.; Hajduk, L.; Hansson, M.; Heinzelmann, G.; Henderson, R.C.W.; Henschel, H.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Hreus, T.; Hussain, S.; Ibbotson, M.; Ismail, M.; Jacquet, M.; Janauschek, L.; Janssen, X.; Jemanov, V.; Jonsson, L.; Johnson, D.P.; Jung, Andreas Werner; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I.R.; Kiesling, Christian M.; Klein, M.; Kleinwort, C.; Klimkovich, T.; Kluge, T.; Knies, G.; Knutsson, A.; Korbel, V.; Kostka, P.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Kruger, K.; Landon, M.P.J.; Lange, W.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Lindfeld, L.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Lobodzinska, E.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lucaci-Timoce, A.-I.; Lueders, H.; Luke, D.; Lux, T.; Lytkin, L.; Makankine, A.; Malden, N.; Malinovski, E.; Mangano, S.; Marage, P.; Marshall, R.; Marti, L.; Martisikova, M.; Martyn, H.-U.; Maxfield, S.J.; Mehta, A.; Meier, K.; Meyer, A.B.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Milstead, D.; Mladenov, D.; Mohamed, A.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, Matthias Ulrich; Muller, K.; Murin, P.; Nankov, K.; Naroska, B.; Naumann, Th.; Newman, Paul R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Oganezov, R.; Olivier, B.; Olsson, J.E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Papadopoulou, T.; Pascaud, C.; Patel, G.D.; Peng, H.; Perez, E.; Perez-Astudillo, D.; Perieanu, A.; Petrukhin, A.; Pitzl, D.; Placakyte, R.; Portheault, B.; Povh, B.; Prideaux, P.; Rahmat, A.J.; Raicevic, N.; Reimer, P.; Rimmer, A.; Risler, C.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rurikova, Z.; Rusakov, S.; Salvaire, F.; Sankey, D.P.C.; Sauvan, E.; Schatzel, S.; Schmidt, S.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.-C.; Sefkow, F.; Shaw-West, R.N.; Sheviakov, I.; Shtarkov, L.N.; Sloan, T.; Smirnov, P.; Soloviev, Y.; South, D.; Spaskov, V.; Specka, Arnd E.; Steder, M.; Stella, B.; Stiewe, J.; Stoilov, A.; Straumann, U.; Sunar, D.; Tchoulakov, V.; Thompson, Graham; Thompson, P.D.; Toll, T.; Tomasz, F.; Traynor, D.; Truol, P.; Tsakov, I.; Tsipolitis, G.; Tsurin, I.; Turnau, J.; Tzamariudaki, E.; Urban, K.; Urban, Marcel; Usik, A.; Utkin, D.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vargas Trevino, A.; Vazdik, Y.; Veelken, C.; Vinokurova, S.; Volchinski, V.; Wacker, K.; Weber, G.; Weber, R.; Wegener, D.; Werner, C.; Wessels, M.; Wessling, B.; Wissing, Ch.; Wolf, R.; Wunsch, E.; Xella, S.; Yan, W.; Yeganov, V.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhelezov, A.; Zhokin, A.; Zhu, Y.C.; Zimmermann, J.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

2006-01-01

A search for a narrow baryonic resonance decaying to $K^0_s p$ or $K^0_s \\bar p$ is carried out in deep inelastic ep scattering with the H1 detector at HERA. Such a resonance could be a strange pentaquark \\thplns, evidence for which has been reported by several experiments. The $K^0_s p$ and $K^0_s \\bar p$ invariant mass distributions presented here do not show any significant peak in the mass range from threshold up to 1.7 GeV. Mass dependent upper limits on $\\sigma(ep \\to e \\thplf X)\\times BR(\\thplf \\to K^0 p)$ are obtained at the 95% confidence level.

Network based control point for UPnP QoS architecture

DEFF Research Database (Denmark)

Brewka, Lukasz Jerzy; Wessing, Henrik; Rossello Busquet, Ana

2011-01-01

Enabling coexistence of non-UPnP Devices in an UPnP QoS Architecture is an important issue that might have a major impact on the deployment and usability of UPnP in future home networks. The work presented here shows potential issues of placing non-UPnP Device in the network managed by UPnP QoS. We...... address this issue by extensions to the UPnP QoS Architecture that can prevent non-UPnP Devices from degrading the overall QoS level. The obtained results show that deploying Network Based Control Point service with efficient traffic classifier, improves significantly the end-to-end packet delay...

LHCb: Searches for $\\Lambda^0_b$ and $\\Xi^0_b$ decays to $K^0_{\\mathrm{S}}p\\pi^-$ and $K^0_{\\mathrm{S}}pK^-$ final states with first observation of the $\\Lambda^0_b \\rightarrow K^0_{\\mathrm{S}}p\\pi^-$ decay

CERN Multimedia

Whitehead, M

2014-01-01

A search for previously unobserved decays of beauty baryons to the final states $K^0_{\\mathrm{S}}p\\pi^-$ and $K^0_{\\mathrm{S}}pK^-$ is reported. The analysis is based on a data sample corresponding to an integrated luminosity of $1.0\\,\\mathrm{fb}^{-1}$ of $pp$ collisions. The $\\Lambda^0_b \\rightarrow K^0_{\\mathrm{S}}p\\pi^-$ decay is observed for the first time with a significance of $8.6\\,\\sigma$, and a measurement is made of the $CP$ asymmetry, which is consistent with zero. No significant signals are seen for $\\Lambda^0_b \\rightarrow K^0_{\\mathrm{S}}pK^-$ decays, $\\Xi^0_b$ decays to both $K^0_{\\mathrm{S}}p\\pi^-$ and $K^0_{\\mathrm{S}}pK^-$ final states, and the $\\Lambda^0_b \\rightarrow D^-_s (K^0_{\\mathrm{S}}K^-)p decay, and upper limits on their branching fractions are reported.

Search for a Narrow Baryonic Resonance Decaying to $K^0_s p$ or $K^0_s \\bar{p}$ in Deep Inelastic Scattering at HERA

OpenAIRE

Aktas, A.; Andreev, V.; Anthonis, T.; Antunovic, B.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Babaev, A.; Backovic, S.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Baudrand, S.; Baumgartner, S.

2006-01-01

A search for a narrow baryonic resonance decaying to $K^0_s p$ or $K^0_s \\bar p$ is carried out in deep inelastic ep scattering with the H1 detector at HERA. Such a resonance could be a strange pentaquark \\thplns, evidence for which has been reported by several experiments. The $K^0_s p$ and $K^0_s \\bar p$ invariant mass distributions presented here do not show any significant peak in the mass range from threshold up to 1.7 GeV. Mass dependent upper limits on $\\sigma(ep \\to e \\thplf X)\\times ...

Preparation of ZnS microdisks using chemical bath deposition and ZnS/p-Si heterojunction solar cells

Science.gov (United States)

Hsiao, Y. J.; Meen, T. H.; Ji, L. W.; Tsai, J. K.; Wu, Y. S.; Huang, C. J.

2013-10-01

The synthesis and heterojunction solar cell properties of ZnS microdisks prepared by the chemical bath deposition method were investigated. The ZnS deposited on the p-Si blanket substrate exhibits good coverage. The lower reflectance spectra were found as the thickness of the ZnS film increased. The optical absorption spectra of the 80 °C ZnS microdisk exhibited a band-gap energy of 3.4 eV and the power conversion efficiency (PCE) of the AZO/ZnS/p-Si heterojunction solar cell with a 300 nm thick ZnS film was η=2.72%.

Low copulatory activity in selectively bred Sardinian alcohol-nonpreferring (sNP) relative to alcohol-preferring (sP) rats

Science.gov (United States)

Karlsson, Oskar; Colombo, Giancarlo

2015-01-01

Background There is a growing consensus that similar neural mechanisms are involved in the reinforcing properties of natural rewards, like food and sex, and drugs of abuse. Rat lines selectively bred for high and low oral alcohol intake and preference have been useful for understanding factors contributing to excessive alcohol intake and may constitute proper animal models for investigating the neurobiological basis of natural rewarding stimuli. Methods The present study evaluated copulatory behavior in alcohol and sexually naïve Sardinian alcohol-preferring (sP) and -nonpreferring (sNP) male rats in three consecutive copulatory behavior tests. Results The main finding was that, under the conditions used in this study, sNP rats were sexually inactive relative to sP rats. To gain more information about the sexual behavior in sP rats, Wistar rats were included as an external reference strain. Only minor differences between sP and Wistar rats were revealed. Conclusions The reason behind the low copulatory activity of sNP rats remains to be elucidated, but may in part be mediated by innate differences in brain transmitter systems. The comparison between sP and Wistar rats may also suggest that the inherent proclivity to excessive alcohol drinking in sP rats may mainly be dependent on its anxiolytic properties, as previously proposed, and not changes in the reward system. PMID:25728453

Electrophysical properties of nCdS/pCdTe heterosystem

International Nuclear Information System (INIS)

Muzafarova, S.A.

2006-01-01

Full text: In this work results of research of electrophysical properties n CdS/pCdTe heterostructure are given. It is shown that at density of current 10 -8 -10 -5 A.cm -2 vol tamper characteristics in hetero system CdTe/CdS is described by thermo ionic law, and in the range 10 -4 -10 -2 A .cm -2 the current in heterostructure is limited by recombination in electronic neutral part of high-resistance of solid structure CdTe 1-x S x . Certain life time τ p and length of diffusion L p of non basic current carriers in solid structure CdTe 1-x S x , as well as superficial recombination rate v R on border of section between CdS and solid structures were considered at influence of irradiation and γ-quanta on the mechanism of current in n CdS/pCdTe heterostructure. From the analysis of dependence doze of sites the direct volt-ampere characteristics were obtained. It is shown that monotonous increase of doze of irradiation and γ-quanta leads to nonmonotonous change of micro parameters of nCdS/pCdTe heterostructure, superficial recombination rate - v R , values of both τ p and lengths of diffusion L p of non basic carriers of potential barrier - qφ B . On border of CdTe 1-x S x there is CdS-solid structure. (author)

Cytochrome P450s and molecular epidemiology

Science.gov (United States)

Gonzalez, Frank J.; Gelboin, Harry V.

1993-03-01

Cytochrome P450 (P450) represent a superfamily of heme-containing monooxygenases that are found throughout the animal and plant kingdoms and in many microorganisms. A number of these enzymes are involved in biosynthetic pathways of steroid synthesis but in mammals the vast majority of P450s function to metabolize foreign chemicals or xenobiotics. In the classical phase I reactions on the latter, a membrane-bound P450 will hydroxylate a compound, usually hydrophobic in nature, and the hydroxyl group will serve as a substrate for the various transferases or phase II enzymes that attach hydrophilic substituents such as glutathione, sulfate or glucuronic acid. Some chemicals, however, are metabolically-activated by P450s to electrophiles capable of reacting with cellular macromolecules. The cellular concentrations of the chemical and P450, reactivity of the active metabolite with nucleic acid and the repairability of the resultant adducts, in addition to the nature of the cell type, likely determines whether a chemical will be toxic and kill the cell or will transform the cell. Immunocorrelative and cDNA-directed expression have been used to define the substrate specificities of numerous human P450s. Levels of expression of different human P450 forms have been measured by both in vivo and in vitro methodologies leading to the realization that a large degree of interindividual differences occur in P450 expression. Reliable procedures for measuring P450 expression in healthy and diseased subjects will lead to prospective and case- cohort studies to determine whether interindividual differences in levels of P450 are associated with susceptibility or resistance to environmentally-based disease.

Sol-gel synthesis of Cu-doped p-CdS nanoparticles and their analysis as p-CdS/n-ZnO thin film photodiode

Science.gov (United States)

Arya, Sandeep; Sharma, Asha; Singh, Bikram; Riyas, Mohammad; Bandhoria, Pankaj; Aatif, Mohammad; Gupta, Vinay

2018-05-01

Copper (Cu) doped p-CdS nanoparticles have been synthesized via sol-gel method. The as-synthesized nanoparticles were successfully characterized and implemented for fabrication of Glass/ITO/n-ZnO/p-CdS/Al thin film photodiode. The fabricated device is tested for small (-1 V to +1 V) bias voltage. Results verified that the junction leakage current within the dark is very small. During reverse bias condition, the maximum amount of photocurrent is obtained under illumination of 100 μW/cm2. Electrical characterizations confirmed that the external quantum efficiency (EQE), gain and responsivity of n-ZnO/p-CdS photodiode show improved photo response than conventional p-type materials for such a small bias voltage. It is therefore revealed that the Cu-doped CdS nanoparticles is an efficient p-type material for fabrication of thin film photo-devices.

Investigation of the reactions 31P(n, γ)32P and 32S(n, γ)33S

NARCIS (Netherlands)

Middelkoop, G. van; Spilling, P.

1965-01-01

The γ radiation following capture of thermal neutrons in 31P and 32S was investigated with scintillation-spectrometer techniques. Measurements of single and coincidence spectra and of γ-γ angular correlations yield the following spins in 32P: J(0.52) = 0, J(1.32) = (2), J(4.04) = 1, J(4.88) = 1,

Perturbation of ribosome biogenesis drives cells into senescence through 5S RNP-mediated p53 activation.

Science.gov (United States)

Nishimura, Kazuho; Kumazawa, Takuya; Kuroda, Takao; Katagiri, Naohiro; Tsuchiya, Mai; Goto, Natsuka; Furumai, Ryohei; Murayama, Akiko; Yanagisawa, Junn; Kimura, Keiji

2015-03-03

The 5S ribonucleoprotein particle (RNP) complex, consisting of RPL11, RPL5, and 5S rRNA, is implicated in p53 regulation under ribotoxic stress. Here, we show that the 5S RNP contributes to p53 activation and promotes cellular senescence in response to oncogenic or replicative stress. Oncogenic stress accelerates rRNA transcription and replicative stress delays rRNA processing, resulting in RPL11 and RPL5 accumulation in the ribosome-free fraction, where they bind MDM2. Experimental upregulation of rRNA transcription or downregulation of rRNA processing, mimicking the nucleolus under oncogenic or replicative stress, respectively, also induces RPL11-mediated p53 activation and cellular senescence. We demonstrate that exogenous expression of certain rRNA-processing factors rescues the processing defect, attenuates p53 accumulation, and increases replicative lifespan. To summarize, the nucleolar-5S RNP-p53 pathway functions as a senescence inducer in response to oncogenic and replicative stresses. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

RpoS induces expression of the Vibrio anguillarum quorum-sensing regulator VanT.

Science.gov (United States)

Weber, Barbara; Croxatto, Antony; Chen, Chang; Milton, Debra L

2008-03-01

In vibrios, regulation of the Vibrio harveyi-like LuxR transcriptional activators occurs post-transcriptionally via small regulatory RNAs (sRNAs) that destabilize the luxR mRNA at a low cell population, eliminating expression of LuxR. Expression of the sRNAs is modulated by the vibrio quorum-sensing phosphorelay systems. However, vanT mRNA, which encodes a LuxR homologue in Vibrio anguillarum, is abundant at low and high cell density, indicating that VanT expression may be regulated via additional mechanisms. In this study, Western analyses showed that VanT was expressed throughout growth with a peak of expression during late exponential growth. VanO induced partial destabilization of vanT mRNA via activation of at least one Qrr sRNA. Interestingly, the sigma factor RpoS significantly stabilized vanT mRNA and induced VanT expression during late exponential growth. This induction was in part due to RpoS repressing expression of Hfq, an RNA chaperone. RpoS is not part of the quorum-sensing regulatory cascade since RpoS did not regulate expression or activity of VanO, and RpoS was not regulated by VanO or VanT. VanT and RpoS were needed for survival following UV irradiation and for pigment and metalloprotease production, suggesting that RpoS works with the quorum-sensing systems to modulate expression of VanT, which regulates survival and stress responses.

Observation of $S=+1$ Narrow Resonances in the System $pK^0_s$ from $p+\\rm {C_3H_8}$ Collision at 10 GeV/$c$

CERN Document Server

Aslanyan, P Zh; Rikhvitskaya, G G

2004-01-01

Experimental data from a 2 m propane bubble chamber have been analyzed to search for an exotic baryon state, the $\\Theta^+$ baryon, in the $pK^0_s$ decay mode for the reaction $p+{\\rm C_3H_8}$ at 10 GeV/$c$. The $pK^0_s$ invariant mass spectrum shows resonant structures with $M_{p K_s^0}=1540\\pm 8$, $1613\\pm10$, $1821\\pm11$ MeV/$c^2$ and $\\Gamma_{p K_s^0}= 9.2\\pm1.8$, $16.1\\pm4.1$, $28.0\\pm9.4$ MeV/$c^2$. The statistical significance of these peaks has been estimated as $5.5$, $4.8$ and $5.0$ s.d., respectively. There are also small peaks in mass regions of 1487 (3.0 s.d.), 1690 (3.6 s.d.) and 1980 (3.0 s.d.) MeV/$c^2$.

Identification and characterization of small molecule inhibitors of the calcium-dependent S100B-p53 tumor suppressor interaction.

Science.gov (United States)

Markowitz, Joseph; Chen, Ijen; Gitti, Rossi; Baldisseri, Donna M; Pan, Yongping; Udan, Ryan; Carrier, France; MacKerell, Alexander D; Weber, David J

2004-10-07

The binding of S100B to p53 down-regulates wild-type p53 tumor suppressor activity in cancer cells such as malignant melanoma, so a search for small molecules that bind S100B and prevent S100B-p53 complex formation was undertaken. Chemical databases were computationally searched for potential inhibitors of S100B, and 60 compounds were selected for testing on the basis of energy scoring, commercial availability, and chemical similarity clustering. Seven of these compounds bound to S100B as determined by steady state fluorescence spectroscopy (1.0 microM model of one such inhibitor, pentamidine, bound to Ca(2+)-loaded S100B was calculated using intermolecular NOE data between S100B and the drug, and indicates that pentamidine binds into the p53 binding site on S100B defined by helices 3 and 4 and loop 2 (termed the hinge region).

Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer.

Science.gov (United States)

Zhang, Liang; Wang, Xiaoen; Bullock, Andrea J; Callea, Marcella; Shah, Harleen; Song, Jiaxi; Moreno, Kelli; Visentin, Barbara; Deutschman, Douglas; Alsop, David C; Atkins, Michael B; Mier, James W; Signoretti, Sabina; Bhasin, Manoj; Sabbadini, Roger A; Bhatt, Rupal S

2015-04-15

VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach for patients with metastatic renal cell carcinoma (RCC). However, resistance to treatment is inevitable. Identification of novel targets could lead to better treatment for patients with TKI-naïve or -resistant RCC. In this study, we performed transcriptome analysis of VEGFR TKI-resistant tumors in a murine model and discovered that the SPHK-S1P pathway is upregulated at the time of resistance. We tested sphingosine-1-phosphate (S1P) pathway inhibition using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and assessed tumor SPHK expression and S1P plasma levels in patients with metastatic RCC. Resistant tumors expressed several hypoxia-regulated genes. The SPHK1 pathway was among the most highly upregulated pathways that accompanied resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC, suggesting that human RCC behavior could, in part, be due to overproduction of S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both mouse models. Mice bearing tumors that had developed resistance to sunitinib treatment also exhibited tumor growth suppression with sphingomab. Sphingomab treatment led to a reduction in tumor blood flow as measured by MRI. Our findings suggest that S1P inhibition may be a novel therapeutic strategy in patients with treatment-naïve RCC and also in the setting of resistance to VEGFR TKI therapy. ©2015 American Association for Cancer Research.

The Р60-S6K1 isoform of ribosomal protein S6 kinase 1 is a product of alternative mRNA translation

Directory of Open Access Journals (Sweden)

I. V. Zaiets

2018-07-01

Full Text Available Ribosomal protein S6 kinase 1 (S6K1 is a well-known downstream effector of mTORC1 (mechanistic target of rapamycin complex 1 participating primarily in the regulation of cell growth and metabolism. Deregulation of mTOR/S6K1 signaling can promote numerous human pathologies, including cancer, neurodegeneration, cardiovascular disease, and metabolic disorders. As existing data suggest, the S6K1 gene encodes several protein isoforms, including p85-S6K1, p70-S6K1, and p60-S6K1. The two of these isoforms, p85-S6K1 and p70-S6K1, were extensively studied to date. The origin and functional significance of the p60-S6K1 isoform remains a mystery, however, it was suggested that the isoform could be a product of alternative S6K1 mRNA translation. Herein we report the generation of HEK-293 cells exclusively expressing p60-S6K1 as a result of CRISPR/Cas9-mediated inactivation of p85/p70-S6K1 translation. Moreover, the generated modified cells displayed the elevated level of p60-S6K1 expression compared to that in wild-type HEK-293 cells. Our data confirm an assumption that p60-S6K1 is alternatively translated, most probably, from the common for both p70- and p85-S6K1 mRNA transcript and reveal a link between p60-S6K1 expression and such cellular processes as cell proliferation and motility. In addition, our findings indicate that the p60-S6K1 isoform of S6K1 may undergo a mode of regulation distinct from p70- and p85-S6K1 due to the absence of mTOR-regulated p60-S6K1 phosphorylation at T389 that is important for S6K1 activation.

Observation of $\\eta_{c}(2S) \\to p \\bar p$ and search for $X(3872) \\to p \\bar p$ decays

CERN Document Server

Aaij, Roel

2017-06-10

The first observation of the decay $\\eta_{c}(2S) \\to p \\bar p$ is reported using proton-proton collision data corresponding to an integrated luminosity of $3.0\\rm \\, fb^{-1}$ recorded by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The $\\eta_{c}(2S)$ resonance is produced in the decay $B^{+} \\to [c\\bar c] K^{+}$. The product of branching fractions normalised to that for the $J/\\psi$ intermediate state, ${\\cal R}_{\\eta_{c}(2S)}$, is measured to be \\begin{align*} {\\cal R}_{\\eta_{c}(2S)}\\equiv\\frac{{\\mathcal B}(B^{+} \\to \\eta_{c}(2S) K^{+}) \\times {\\mathcal B}(\\eta_{c}(2S) \\to p \\bar p)}{{\\mathcal B}(B^{+} \\to J/\\psi K^{+}) \\times {\\mathcal B}(J/\\psi\\to p \\bar p)} =~& (1.58 \\pm 0.33 \\pm 0.09)\\times 10^{-2}, \\end{align*} where the first uncertainty is statistical and the second systematic. No signals for the decays $B^{+} \\to X(3872) (\\to p \\bar p) K^{+}$ and $B^{+} \\to \\psi(3770) (\\to p \\bar p) K^{+}$ are seen, and the 95\\% confidence level upper limits on their relative branching ratios ar...

78 FR 14442 - Airworthiness Directives; Turbomeca S.A. Turboshaft Engines

Science.gov (United States)

2013-03-06

...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service... holidays. The AD docket contains this AD, the regulatory evaluation, any comments received, and other... 301 52 001 0, installed, with: (1) A serial number (S/N) 242 through 339, inclusive, or (2) A S/N 691...

HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.

Science.gov (United States)

Levkau, Bodo

2015-01-01

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction.

Dihadron Azimuthal Correlations in p-p Collisions at sNN=7 TeV and p-Pb Collisions at sNN=5.02 TeV

Directory of Open Access Journals (Sweden)

Ting Bai

2015-01-01

Full Text Available The dihadron azimuthal correlations in p-p collisions at sNN=7 TeV and p-Pb collisions at sNN=5.02 TeV are investigated in the framework of a multisource thermal model. The model can approximately describe the experimental results measured in the Large Hadron Collider. We find the px amplitude of the source is magnified and the source translates along the direction.

The DNA Replication Checkpoint Directly Regulates MBF-Dependent G1/S Transcription▿

OpenAIRE

Dutta, Chaitali; Patel, Prasanta K.; Rosebrock, Adam; Oliva, Anna; Leatherwood, Janet; Rhind, Nicholas

2008-01-01

The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF, the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program du...

L_p- and S_{p,q}^rB-discrepancy of (order 2) digital nets

OpenAIRE

Markhasin, Lev

2014-01-01

Dick proved that all order $2$ digital nets satisfy optimal upper bounds of the $L_2$-discrepancy. We give an alternative proof for this fact using Haar bases. Furthermore, we prove that all digital nets satisfy optimal upper bounds of the $S_{p,q}^r B$-discrepancy for a certain parameter range and enlarge that range for order $2$ digitals nets. $L_p$-, $S_{p,q}^r F$- and $S_p^r H$-discrepancy is considered as well.

Lace plant ethylene receptors, AmERS1a and AmERS1c, regulate ethylene-induced programmed cell death during leaf morphogenesis.

Science.gov (United States)

Rantong, Gaolathe; Evans, Rodger; Gunawardena, Arunika H L A N

2015-10-01

The lace plant, Aponogeton madagascariensis, is an aquatic monocot that forms perforations in its leaves as part of normal leaf development. Perforation formation occurs through developmentally regulated programmed cell death (PCD). The molecular basis of PCD regulation in the lace plant is unknown, however ethylene has been shown to play a significant role. In this study, we examined the role of ethylene receptors during perforation formation. We isolated three lace plant ethylene receptors AmERS1a, AmERS1b and AmERS1c. Using quantitative PCR, we examined their transcript levels at seven stages of leaf development. Through laser-capture microscopy, transcript levels were also determined in cells undergoing PCD and cells not undergoing PCD (NPCD cells). AmERS1a transcript levels were significantly lower in window stage leaves (in which perforation formation and PCD are occurring) as compared to all other leaf developmental stages. AmERS1a and AmERS1c (the most abundant among the three receptors) had the highest transcript levels in mature stage leaves, where PCD is not occurring. Their transcript levels decreased significantly during senescence-associated PCD. AmERS1c had significantly higher transcript levels in NPCD compared to PCD cells. Despite being significantly low in window stage leaves, AmERS1a transcripts were not differentially expressed between PCD and NPCD cells. The results suggested that ethylene receptors negatively regulate ethylene-controlled PCD in the lace plant. A combination of ethylene and receptor levels determines cell fate during perforation formation and leaf senescence. A new model for ethylene emission and receptor expression during lace plant perforation formation and senescence is proposed.

Reflexos da pós-modernidade no direito

OpenAIRE

Oliveira, Andressa Caroline de

2013-01-01

A pós-modernidade representa uma forte crítica ao imperialismo da razão instrumental e a incredulidade em relação às utopias da modernidade e seu respectivo projeto. Nesse contexto de crise e mudança representado pela era pós-moderna , seus reflexos no direito não podem ser negados. A idéia de verdade sempre esteve intimamente associada à noção de justiça, o motivo pelo qual o processo, como forma do exercício do poder jurisdicional, adotou a concretização da justiça baseada...

Various forms of organic and inorganic P fertilizers did not negatively affect soil- and root-inhabiting AM fungi in a maize-soybean rotation system.

Science.gov (United States)

Beauregard, M S; Gauthier, M-P; Hamel, C; Zhang, T; Welacky, T; Tan, C S; St-Arnaud, M

2013-02-01

Arbuscular mycorrhizal (AM) fungi are key components of most agricultural ecosystems. Therefore, understanding the impact of agricultural practices on their community structure is essential to improve nutrient mobilization and reduce plant stress in the field. The effects of five different organic or mineral sources of phosphorus (P) for a maize-soybean rotation system on AM fungal diversity in roots and soil were assessed over a 3-year period. Total DNA was extracted from root and soil samples collected at three different plant growth stages. An 18S rRNA gene fragment was amplified and taxa were detected and identified using denaturing gradient gel electrophoresis followed by sequencing. AM fungal biomass was estimated by fatty acid methyl ester analysis. Soil P fertility parameters were also monitored and analyzed for possible changes related with fertilization or growth stages. Seven AM fungal ribotypes were detected. Fertilization significantly modified soil P flux, but had barely any effect on AM fungi community structure or biomass. There was no difference in the AM fungal community between plant growth stages. Specific ribotypes could not be significantly associated to P treatment. Ribotypes were associated with root or soil samples with variable detection frequencies between seasons. AM fungal biomass remained stable throughout the growing seasons. This study demonstrated that roots and soil host distinct AM fungal communities and that these are very temporally stable. The influence of contrasting forms of P fertilizers was not significant over 3 years of crop rotation.

As Estimativas de Pobreza na América Latina são Confiáveis?

OpenAIRE

Sanjay G. Reddy

2008-01-01

Qual é o nível de pobreza monetária na América Latina e tem tal nível diminuído recentemente? As estimativas atuais são confiáveis? A abordagem dominante de aferição da pobreza monetária, regional e globalmente, utiliza as linhas internacionais de pobreza do Banco Mundial de ?um dólar diário? e ?dois dólares diários? por pessoa. O Banco utiliza os indicadores de ?paridade do poder de compra? (PPC) para converter essas linhas internacionais em moedas locais. (...)

Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

Science.gov (United States)

Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

2016-01-15

Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Suppression of $\\psi$(2S) production in p-Pb collisions at $\\sqrt{s_{NN}}$ = 5.02 TeV

CERN Document Server

Abelev, Betty Bezverkhny; Adamova, Dagmar; Aggarwal, Madan Mohan; Aglieri Rinella, Gianluca; Agnello, Michelangelo; Agostinelli, Andrea; Agrawal, Neelima; Ahammed, Zubayer; Ahmad, Nazeer; Ahmed, Ijaz; Ahn, Sang Un; Ahn, Sul-Ah; Aimo, Ilaria; Aiola, Salvatore; Ajaz, Muhammad; Akindinov, Alexander; Alam, Sk Noor; Aleksandrov, Dmitry; Alessandro, Bruno; Alexandre, Didier; Alici, Andrea; Alkin, Anton; Alme, Johan; Alt, Torsten; Altinpinar, Sedat; Altsybeev, Igor; Alves Garcia Prado, Caio; Andrei, Cristian; Andronic, Anton; Anguelov, Venelin; Anielski, Jonas; Anticic, Tome; Antinori, Federico; Antonioli, Pietro; Aphecetche, Laurent Bernard; Appelshaeuser, Harald; Arcelli, Silvia; Armesto Perez, Nestor; Arnaldi, Roberta; Aronsson, Tomas; Arsene, Ionut Cristian; Arslandok, Mesut; Augustinus, Andre; Averbeck, Ralf Peter; Awes, Terry; Azmi, Mohd Danish; Bach, Matthias Jakob; Badala, Angela; Baek, Yong Wook; Bagnasco, Stefano; Bailhache, Raphaelle Marie; Bala, Renu; Baldisseri, Alberto; Baltasar Dos Santos Pedrosa, Fernando; Baral, Rama Chandra; Barbera, Roberto; Barile, Francesco; Barnafoldi, Gergely Gabor; Barnby, Lee Stuart; Ramillien Barret, Valerie; Bartke, Jerzy Gustaw; Basile, Maurizio; Bastid, Nicole; Basu, Sumit; Bathen, Bastian; Batigne, Guillaume; Batista Camejo, Arianna; Batyunya, Boris; Batzing, Paul Christoph; Baumann, Christoph Heinrich; Bearden, Ian Gardner; Beck, Hans; Bedda, Cristina; Behera, Nirbhay Kumar; Belikov, Iouri; Bellini, Francesca; Bellwied, Rene; Belmont Moreno, Ernesto; Belmont Iii, Ronald John; Belyaev, Vladimir; Bencedi, Gyula; Beole, Stefania; Berceanu, Ionela; Bercuci, Alexandru; Berdnikov, Yaroslav; Berenyi, Daniel; Berger, Martin Emanuel; Bertens, Redmer Alexander; Berzano, Dario; Betev, Latchezar; Bhasin, Anju; Bhat, Inayat Rasool; Bhati, Ashok Kumar; Bhattacharjee, Buddhadeb; Bhom, Jihyun; Bianchi, Livio; Bianchi, Nicola; Bianchin, Chiara; Bielcik, Jaroslav; Bielcikova, Jana; Bilandzic, Ante; Bjelogrlic, Sandro; Blanco, Fernando; Blau, Dmitry; Blume, Christoph; Bock, Friederike; Bogdanov, Alexey; Boggild, Hans; Bogolyubskiy, Mikhail; Boehmer, Felix Valentin; Boldizsar, Laszlo; Bombara, Marek; Book, Julian Heinz; Borel, Herve; Borissov, Alexander; Bossu, Francesco; Botje, Michiel; Botta, Elena; Boettger, Stefan; Braun-Munzinger, Peter; Bregant, Marco; Breitner, Timo Gunther; Broker, Theo Alexander; Browning, Tyler Allen; Broz, Michal; Bruna, Elena; Bruno, Giuseppe Eugenio; Budnikov, Dmitry; Buesching, Henner; Bufalino, Stefania; Buncic, Predrag; Busch, Oliver; Buthelezi, Edith Zinhle; Caffarri, Davide; Cai, Xu; Caines, Helen Louise; Calero Diaz, Liliet; Caliva, Alberto; Calvo Villar, Ernesto; Camerini, Paolo; Carena, Francesco; Carena, Wisla; Castillo Castellanos, Javier Ernesto; Casula, Ester Anna Rita; Catanescu, Vasile Ioan; Cavicchioli, Costanza; Ceballos Sanchez, Cesar; Cepila, Jan; Cerello, Piergiorgio; Chang, Beomsu; Chapeland, Sylvain; Charvet, Jean-Luc Fernand; Chattopadhyay, Subhasis; Chattopadhyay, Sukalyan; Chelnokov, Volodymyr; Cherney, Michael Gerard; Cheshkov, Cvetan Valeriev; Cheynis, Brigitte; Chibante Barroso, Vasco Miguel; Dobrigkeit Chinellato, David; Chochula, Peter; Chojnacki, Marek; Choudhury, Subikash; Christakoglou, Panagiotis; Christensen, Christian Holm; Christiansen, Peter; Chujo, Tatsuya; Chung, Suh-Urk; Cicalo, Corrado; Cifarelli, Luisa; Cindolo, Federico; Cleymans, Jean Willy Andre; Colamaria, Fabio Filippo; Colella, Domenico; Collu, Alberto; Colocci, Manuel; Conesa Balbastre, Gustavo; Conesa Del Valle, Zaida; Connors, Megan Elizabeth; Contreras Nuno, Jesus Guillermo; Cormier, Thomas Michael; Corrales Morales, Yasser; Cortese, Pietro; Cortes Maldonado, Ismael; Cosentino, Mauro Rogerio; Costa, Filippo; Crochet, Philippe; Cruz Albino, Rigoberto; Cuautle Flores, Eleazar; Cunqueiro Mendez, Leticia; Dainese, Andrea; Dang, Ruina; Danu, Andrea; Das, Debasish; Das, Indranil; Das, Kushal; Das, Supriya; Dash, Ajay Kumar; Dash, Sadhana; De, Sudipan; Delagrange, Hugues; Deloff, Andrzej; Denes, Ervin Sandor; D'Erasmo, Ginevra; De Caro, Annalisa; De Cataldo, Giacinto; De Cuveland, Jan; De Falco, Alessandro; De Gruttola, Daniele; De Marco, Nora; De Pasquale, Salvatore; De Rooij, Raoul Stefan; Diaz Corchero, Miguel Angel; Dietel, Thomas; Dillenseger, Pascal; Divia, Roberto; Di Bari, Domenico; Di Liberto, Sergio; Di Mauro, Antonio; Di Nezza, Pasquale; Djuvsland, Oeystein; Dobrin, Alexandru Florin; Dobrowolski, Tadeusz Antoni; Domenicis Gimenez, Diogenes; Donigus, Benjamin; Dordic, Olja; Dorheim, Sverre; Dubey, Anand Kumar; Dubla, Andrea; Ducroux, Laurent; Dupieux, Pascal; Dutt Mazumder, Abhee Kanti; Hilden, Timo Eero; Ehlers Iii, Raymond James; Elia, Domenico; Engel, Heiko; Erazmus, Barbara Ewa; Erdal, Hege Austrheim; Eschweiler, Dominic; Espagnon, Bruno; Esposito, Marco; Estienne, Magali Danielle; Esumi, Shinichi; Evans, David; Evdokimov, Sergey; Fabris, Daniela; Faivre, Julien; Falchieri, Davide; Fantoni, Alessandra; Fasel, Markus; Fehlker, Dominik; Feldkamp, Linus; Felea, Daniel; Feliciello, Alessandro; Feofilov, Grigory; Ferencei, Jozef; Fernandez Tellez, Arturo; Gonzalez Ferreiro, Elena; Ferretti, Alessandro; Festanti, Andrea; Figiel, Jan; Araujo Silva Figueredo, Marcel; Filchagin, Sergey; Finogeev, Dmitry; Fionda, Fiorella; Fiore, Enrichetta Maria; Floratos, Emmanouil; Floris, Michele; Foertsch, Siegfried Valentin; Foka, Panagiota; Fokin, Sergey; Fragiacomo, Enrico; Francescon, Andrea; Frankenfeld, Ulrich Michael; Fuchs, Ulrich; Furget, Christophe; Fusco Girard, Mario; Gaardhoeje, Jens Joergen; Gagliardi, Martino; Gago Medina, Alberto Martin; Gallio, Mauro; Gangadharan, Dhevan Raja; Ganoti, Paraskevi; Gao, Chaosong; Garabatos Cuadrado, Jose; Garcia-Solis, Edmundo Javier; Gargiulo, Corrado; Garishvili, Irakli; Gerhard, Jochen; Germain, Marie; Gheata, Andrei George; Gheata, Mihaela; Ghidini, Bruno; Ghosh, Premomoy; Ghosh, Sanjay Kumar; Gianotti, Paola; Giubellino, Paolo; Gladysz-Dziadus, Ewa; Glassel, Peter; Gomez Ramirez, Andres; Gonzalez Zamora, Pedro; Gorbunov, Sergey; Gorlich, Lidia Maria; Gotovac, Sven; Graczykowski, Lukasz Kamil; Grelli, Alessandro; Grigoras, Alina Gabriela; Grigoras, Costin; Grigoryev, Vladislav; Grigoryan, Ara; Grigoryan, Smbat; Grynyov, Borys; Grion, Nevio; Grosse-Oetringhaus, Jan Fiete; Grossiord, Jean-Yves; Grosso, Raffaele; Guber, Fedor; Guernane, Rachid; Guerzoni, Barbara; Guilbaud, Maxime Rene Joseph; Gulbrandsen, Kristjan Herlache; Gulkanyan, Hrant; Gumbo, Mervyn; Gunji, Taku; Gupta, Anik; Gupta, Ramni; Khan, Kamal; Haake, Rudiger; Haaland, Oystein Senneset; Hadjidakis, Cynthia Marie; Haiduc, Maria; Hamagaki, Hideki; Hamar, Gergoe; Hanratty, Luke David; Hansen, Alexander; Harris, John William; Hartmann, Helvi; Harton, Austin Vincent; Hatzifotiadou, Despina; Hayashi, Shinichi; Heckel, Stefan Thomas; Heide, Markus Ansgar; Helstrup, Haavard; Herghelegiu, Andrei Ionut; Herrera Corral, Gerardo Antonio; Hess, Benjamin Andreas; Hetland, Kristin Fanebust; Hippolyte, Boris; Hladky, Jan; Hristov, Peter Zahariev; Huang, Meidana; Humanic, Thomas; Hussain, Nur; Hutter, Dirk; Hwang, Dae Sung; Ilkaev, Radiy; Ilkiv, Iryna; Inaba, Motoi; Innocenti, Gian Michele; Ionita, Costin; Ippolitov, Mikhail; Irfan, Muhammad; Ivanov, Marian; Ivanov, Vladimir; Jacholkowski, Adam Wlodzimierz; Jacobs, Peter Martin; Jahnke, Cristiane; Jang, Haeng Jin; Janik, Malgorzata Anna; Pahula Hewage, Sandun; Jena, Chitrasen; Jena, Satyajit; Jimenez Bustamante, Raul Tonatiuh; Jones, Peter Graham; Jung, Hyungtaik; Jusko, Anton; Kadyshevskiy, Vladimir; Kalcher, Sebastian; Kalinak, Peter; Kalweit, Alexander Philipp; Kamin, Jason Adrian; Kang, Ju Hwan; Kaplin, Vladimir; Kar, Somnath; Karasu Uysal, Ayben; Karavichev, Oleg; Karavicheva, Tatiana; Karpechev, Evgeny; Kebschull, Udo Wolfgang; Keidel, Ralf; Keijdener, Darius Laurens; Keil, Markus; Khan, Mohammed Mohisin; Khan, Palash; Khan, Shuaib Ahmad; Khanzadeev, Alexei; Kharlov, Yury; Kileng, Bjarte; Kim, Beomkyu; Kim, Do Won; Kim, Dong Jo; Kim, Jinsook; Kim, Mimae; Kim, Minwoo; Kim, Se Yong; Kim, Taesoo; Kirsch, Stefan; Kisel, Ivan; Kiselev, Sergey; Kisiel, Adam Ryszard; Kiss, Gabor; 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Marin, Ana Maria; Markert, Christina; Marquard, Marco; Martashvili, Irakli; Martin, Nicole Alice; Martinengo, Paolo; Martinez Hernandez, Mario Ivan; Martinez-Garcia, Gines; Martin Blanco, Javier; Martynov, Yevgen; Mas, Alexis Jean-Michel; Masciocchi, Silvia; Masera, Massimo; Masoni, Alberto; Massacrier, Laure Marie; Mastroserio, Annalisa; Matyja, Adam Tomasz; Mayer, Christoph; Mazer, Joel Anthony; Mazzoni, Alessandra Maria; Meddi, Franco; Menchaca-Rocha, Arturo Alejandro; Mercado-Perez, Jorge; Meres, Michal; Miake, Yasuo; Mikhaylov, Konstantin; Milano, Leonardo; Milosevic, Jovan; Mischke, Andre; Mishra, Aditya Nath; Miskowiec, Dariusz Czeslaw; Mitra, Jubin; Mitu, Ciprian Mihai; Mlynarz, Jocelyn; Mohammadi, Naghmeh; Mohanty, Bedangadas; Molnar, Levente; Montano Zetina, Luis Manuel; Montes Prado, Esther; Morando, Maurizio; Moreira De Godoy, Denise Aparecida; Moretto, Sandra; Morreale, Astrid; Morsch, Andreas; Muccifora, Valeria; Mudnic, Eugen; Muhlheim, Daniel Michael; Muhuri, Sanjib; Mukherjee, Maitreyee; Muller, Hans; Gameiro Munhoz, Marcelo; Murray, Sean; Musa, Luciano; Musinsky, Jan; Nandi, Basanta Kumar; Nania, Rosario; Nappi, Eugenio; Nattrass, Christine; Nayak, Kishora; Nayak, Tapan Kumar; Nazarenko, Sergey; Nedosekin, Alexander; Nicassio, Maria; Niculescu, Mihai; Nielsen, Borge Svane; Nikolaev, Sergey; Nikulin, Sergey; Nikulin, Vladimir; Nilsen, Bjorn Steven; Noferini, Francesco; Nomokonov, Petr; Nooren, Gerardus; Norman, Jaime; Nyanin, Alexander; Nystrand, Joakim Ingemar; Oeschler, Helmut Oskar; Oh, Saehanseul; Oh, Sun Kun; Okatan, Ali; Olah, Laszlo; Oleniacz, Janusz; Oliveira Da Silva, Antonio Carlos; Onderwaater, Jacobus; Oppedisano, Chiara; Ortiz Velasquez, Antonio; Oskarsson, Anders Nils Erik; Otwinowski, Jacek Tomasz; Oyama, Ken; Ozdemir, Mahmut; Sahoo, Pragati; Pachmayer, Yvonne Chiara; Pachr, Milos; Pagano, Paola; Paic, Guy; Painke, Florian; Pajares Vales, Carlos; Pal, Susanta Kumar; Palmeri, Armando; Pant, Divyash; Papikyan, Vardanush; Pappalardo, Giuseppe; Pareek, Pooja; 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Rachevski, Alexandre; Raha, Sibaji; Rak, Jan; Rakotozafindrabe, Andry Malala; Ramello, Luciano; Raniwala, Rashmi; Raniwala, Sudhir; Rasanen, Sami Sakari; Rascanu, Bogdan Theodor; Rathee, Deepika; Rauf, Aamer Wali; Razazi, Vahedeh; Read, Kenneth Francis; Real, Jean-Sebastien; Redlich, Krzysztof; Reed, Rosi Jan; Rehman, Attiq Ur; Reichelt, Patrick Simon; Reicher, Martijn; Reidt, Felix; Renfordt, Rainer Arno Ernst; Reolon, Anna Rita; Reshetin, Andrey; Rettig, Felix Vincenz; Revol, Jean-Pierre; Reygers, Klaus Johannes; Riabov, Viktor; Ricci, Renato Angelo; Richert, Tuva Ora Herenui; Richter, Matthias Rudolph; Riedler, Petra; Riegler, Werner; Riggi, Francesco; Rivetti, Angelo; Rocco, Elena; Rodriguez Cahuantzi, Mario; Rodriguez Manso, Alis; Roeed, Ketil; Rogochaya, Elena; Sharma, Rohni; Rohr, David Michael; Roehrich, Dieter; Romita, Rosa; Ronchetti, Federico; Ronflette, Lucile; Rosnet, Philippe; Rossi, Andrea; Roukoutakis, Filimon; Roy, Ankhi; Roy, Christelle Sophie; Roy, Pradip Kumar; Rubio Montero, Antonio Juan; Rui, Rinaldo; Russo, Riccardo; Ryabinkin, Evgeny; Ryabov, Yury; Rybicki, Andrzej; Sadovskiy, Sergey; Safarik, Karel; Sahlmuller, Baldo; Sahoo, Raghunath; Sahu, Pradip Kumar; Saini, Jogender; Sakai, Shingo; Salgado Lopez, Carlos Alberto; Salzwedel, Jai Samuel Nielsen; Sambyal, Sanjeev Singh; Samsonov, Vladimir; Sanchez Castro, Xitzel; Sanchez Rodriguez, Fernando Javier; Sandor, Ladislav; Sandoval, Andres; Sano, Masato; Santagati, Gianluca; Sarkar, Debojit; Scapparone, Eugenio; Scarlassara, Fernando; Scharenberg, Rolf Paul; Schiaua, Claudiu Cornel; Schicker, Rainer Martin; Schmidt, Christian Joachim; Schmidt, Hans Rudolf; Schuchmann, Simone; Schukraft, Jurgen; Schulc, Martin; Schuster, Tim Robin; Schutz, Yves Roland; Schwarz, Kilian Eberhard; Schweda, Kai Oliver; Scioli, Gilda; Scomparin, Enrico; Scott, Rebecca Michelle; Segato, Gianfranco; Seger, Janet Elizabeth; Sekiguchi, Yuko; Selyuzhenkov, Ilya; Seo, Jeewon; Serradilla Rodriguez, Eulogio; Sevcenco, Adrian; Shabetai, Alexandre; Shabratova, Galina; Shahoyan, Ruben; Shangaraev, Artem; Sharma, Natasha; Sharma, Satish; Shigaki, Kenta; Shtejer Diaz, Katherin; Sibiryak, Yury; Siddhanta, Sabyasachi; Siemiarczuk, Teodor; Silvermyr, David Olle Rickard; Silvestre, Catherine Micaela; Simatovic, Goran; Singaraju, Rama Narayana; Singh, Ranbir; Singha, Subhash; Singhal, Vikas; Sinha, Bikash; Sarkar - Sinha, Tinku; Sitar, Branislav; Sitta, Mario; Skaali, Bernhard; Skjerdal, Kyrre; Slupecki, Maciej; Smirnov, Nikolai; Snellings, Raimond; Soegaard, Carsten; Soltz, Ron Ariel; Song, Jihye; Song, Myunggeun; Soramel, Francesca; Sorensen, Soren Pontoppidan; Spacek, Michal; Spiriti, Eleuterio; Sputowska, Iwona Anna; Spyropoulou-Stassinaki, Martha; Srivastava, Brijesh Kumar; Stachel, Johanna; Stan, Ionel; Stefanek, Grzegorz; Steinpreis, Matthew Donald; Stenlund, Evert Anders; Steyn, Gideon Francois; Stiller, Johannes Hendrik; Stocco, Diego; Stolpovskiy, Mikhail; Strmen, Peter; Alarcon Do Passo Suaide, Alexandre; Sugitate, Toru; Suire, Christophe Pierre; Suleymanov, Mais Kazim Oglu; Sultanov, Rishat; Sumbera, Michal; Susa, Tatjana; Symons, Timothy; Szabo, Alexander; Szanto De Toledo, Alejandro; Szarka, Imrich; Szczepankiewicz, Adam; Szymanski, Maciej Pawel; Takahashi, Jun; Tangaro, Marco-Antonio; Tapia Takaki, Daniel Jesus; Tarantola Peloni, Attilio; Tarazona Martinez, Alfonso; Tarzila, Madalina-Gabriela; Tauro, Arturo; Tejeda Munoz, Guillermo; Telesca, Adriana; Terrevoli, Cristina; Thaeder, Jochen Mathias; Thomas, Deepa; Tieulent, Raphael Noel; Timmins, Anthony Robert; Toia, Alberica; Trubnikov, Victor; Trzaska, Wladyslaw Henryk; Tsuji, Tomoya; Tumkin, Alexandr; Turrisi, Rosario; Tveter, Trine Spedstad; Ullaland, Kjetil; Uras, Antonio; Usai, Gianluca; Vajzer, Michal; Vala, Martin; Valencia Palomo, Lizardo; Vallero, Sara; Vande Vyvre, Pierre; Van Der Maarel, Jasper; Van Hoorne, Jacobus Willem; Van Leeuwen, Marco; Diozcora Vargas Trevino, Aurora; Vargyas, Marton; Varma, Raghava; Vasileiou, Maria; Vasiliev, Andrey; Vechernin, Vladimir; Veldhoen, Misha; Velure, Arild; Venaruzzo, Massimo; Vercellin, Ermanno; Vergara Limon, Sergio; Vernet, Renaud; Verweij, Marta; Vickovic, Linda; Viesti, Giuseppe; Viinikainen, Jussi Samuli; Vilakazi, Zabulon; Villalobos Baillie, Orlando; Vinogradov, Alexander; Vinogradov, Leonid; Vinogradov, Yury; Virgili, Tiziano; Viyogi, Yogendra; Vodopyanov, Alexander; Volkl, Martin Andreas; Voloshin, Kirill; Voloshin, Sergey; Volpe, Giacomo; Von Haller, Barthelemy; Vorobyev, Ivan; Vranic, Danilo; Vrlakova, Janka; Vulpescu, Bogdan; Vyushin, Alexey; Wagner, Boris; Wagner, Jan; Wagner, Vladimir; Wang, Mengliang; Wang, Yifei; Watanabe, Daisuke; Weber, Michael; Wessels, Johannes Peter; Westerhoff, Uwe; Wiechula, Jens; Wikne, Jon; Wilde, Martin Rudolf; Wilk, Grzegorz Andrzej; Wilkinson, Jeremy John; Williams, Crispin; Windelband, Bernd Stefan; Winn, Michael Andreas; Yaldo, Chris G; Yamaguchi, Yorito; Yang, Hongyan; Yang, Ping; Yang, Shiming; Yano, Satoshi; Yasnopolskiy, Stanislav; Yi, Jungyu; Yin, Zhongbao; Yoo, In-Kwon; Yushmanov, Igor; Zaccolo, Valentina; Zach, Cenek; Zaman, Ali; Zampolli, Chiara; Zaporozhets, Sergey; Zarochentsev, Andrey; Zavada, Petr; Zavyalov, Nikolay; Zbroszczyk, Hanna Paulina; Zgura, Sorin Ion; Zhalov, Mikhail; Zhang, Haitao; Zhang, Xiaoming; Zhang, Yonghong; Zhao, Chengxin; Zhigareva, Natalia; Zhou, Daicui; Zhou, Fengchu; Zhou, You; Zhou, Zhuo; Zhu, Hongsheng; Zhu, Jianhui; Zhu, Xiangrong; Zichichi, Antonino; Zimmermann, Alice; Zimmermann, Markus Bernhard; Zinovjev, Gennady; Zoccarato, Yannick Denis; Zyzak, Maksym

2014-12-10

The ALICE Collaboration has studied the inclusive production of the charmonium state $\\psi(2S)$ in proton-lead (p-Pb) collisions at the nucleon-nucleon centre of mass energy $\\sqrt{s_{NN}}$ = 5.02 TeV at the CERN LHC. The measurement was performed at forward ($2.03 < y_{cms} < 3.53$) and backward ($-4.46 < y_{cms} < -2.96$) centre of mass rapidities, studying the decays into muon pairs. In this paper, we present the inclusive production cross sections $\\sigma_{\\psi(2S)}$, both integrated and as a function of the transverse momentum $p_{T}$, for the two $y_{cms}$ domains. The results are compared to those obtained for the 1S vector state (J/$\\psi$), by showing the ratios between the production cross sections, as well as the double ratios $[\\sigma_{\\psi(2S)}/\\sigma_{J/\\psi}]_{pPb}/[\\sigma_{\\psi(2S)}/\\sigma_{J/\\psi}]_{pp}$ between p-Pb and proton-proton collisions. Finally, the nuclear modification factor for inclusive $\\psi(2S)$ is evaluated and compared to the measurement of the same quantity for J...

Energy, fine structure, and hyperfine structure of the core-excited states 1s2s2pnp 5P (n = 2-5) and 1s2p2mp 5S (m = 2-5) for Li- ion

International Nuclear Information System (INIS)

Wang, Z.B.; Gou, B.C.; Chen, F.

2006-01-01

The relativistic energies, the oscillator strength, and the lifetimes of high-lying core-excited states 1s2s2pnp 5 P (n=2-5) and 1s2p 2 mp 5 S 0 (m=2-5) of Li - ion are calculated with the saddle-point variational method and restricted variation method. The fine structure and the hyperfine structure of the core-excited states for this system are also explored. The results are compared with other theoretical and experimental data in the literature. The energy obtained in this work are much lower than the others previously published whereas the wavelengths and radiative life-times are in agreement

A Learner’s Self-Regulated Learning in Writing

Directory of Open Access Journals (Sweden)

Hapsari Hapsari

2016-05-01

Full Text Available The purpose of this study was to analyze  Self-Regulated Learning (SLR upon the process of  writing task.  The Motivated and Learning Strategies Questionnaire (MLSQ developed by Pintrich was used to generate the participant's cognitive and metacognitive activity.  Data were collected from the participant’s journal written during her task performance and from her scores from three essay assignments in Psychology and Instruction subject. The result indicated an improvement in the participant’s writing performance, such as recalling previous knowledge and reviewing her writing. It showed that the participant’s marks among the three assignments significantly increased. The result also indicated participant’s difficulties and strength in her writing. However, The study further suggested time expansion to obtain a more comprehensive SLR performance, such as motivational and emotional aspects. Permalink/DOI:http://dx.doi.org/10.15408/ijee.v2i2.3085

The two-dimensional thiophosphate CsCrP2S7

Directory of Open Access Journals (Sweden)

Kyounghee Kim

2010-09-01

Full Text Available The quaternary title compound, caesium chromium(III heptathiodiphosphate(V, CsCrP2S7, has been synthesized using the reactive halide flux method. It is isotypic with other AMP2S7 (A = alkali metal; M = Cr, V or In structures and consists of two-dimensional ∞2[CrP2S7]− layers extending parallel to (001 which are separated from each other by Cs+ ions (symmetry 2. The layer is built up from slightly distorted octahedral [CrS6] units (symmetry 2 and bent [P2S7] units consisting of two corner-sharing [PS4] tetrahedra. The [CrS6] octahedra share two edges and two corners with the [PS4] tetrahedra. There are only van der Waals interactions present between the layers. The Cs+ ions are located in this van der Waals gap and stabilize the structure through weak ionic interactions. The classical charge balance of the title compound can be expressed as [Cs+][Cr3+][P5+]2[S2−]7.

Talousveden pH-säädön optimointi

OpenAIRE

Elo, Hanne

2009-01-01

Tämän opinnäytetyön aiheena oli Talousveden pH-säädön optimointi. Työn tarkoituksena oli tutkia Forssan Vesihuoltolaitoksella raakaveden pH:n säätöä ja tutustua STEL-80A vedenkäsittelylaitteen toimintaan. Raakaveden pH:n säätökokeita tehtiin eri vahvuisilla lipeä- ja soodaliuoksilla. STEL-80A vedenkäsittelylaite tuottaa ruokasuolasta klooria ja lipeää, joita voidaan käyttää veden desinfiointiin ja pH-säätöön. STEL-80A vedenkäsittelylaitteella tehtiin kokeita eri virran voimakkuuksilla, joiden...

The activation of RhoC in vascular endothelial cells is required for the S1P receptor type 2-induced inhibition of angiogenesis.

Science.gov (United States)

Del Galdo, Sabrina; Vettel, Christiane; Heringdorf, Dagmar Meyer Zu; Wieland, Thomas

2013-12-01

Sphingosine-1-phosphate (S1P) is a multifunctional phospholipid inducing a variety of cellular responses in endothelial cells (EC). S1P responses are mediated by five G protein coupled receptors of which three types (S1P1R-S1P3R) have been described to be of importance in vascular endothelial cells (EC). Whereas the S1P1R regulates endothelial barrier function by coupling to Gαi and the monomeric GTPase Rac1, the signaling pathways involved in the S1P-induced regulation of angiogenesis are ill defined. We therefore studied the sprouting of human umbilical vein EC (HUVEC) in vitro and analyzed the activation of the RhoGTPases RhoA and RhoC. Physiological relevant concentrations of S1P (100-300nM) induce a moderate activation of RhoA and RhoC. Inhibition or siRNA-mediated depletion of the S1P2R preferentially decreased the activation of RhoC. Both manipulations caused an increase of sprouting in a spheroid based in vitro sprouting assay. Interestingly, a similar increase in sprouting was detected after effective siRNA-mediated knockdown of RhoC. In contrast, the depletion of RhoA had no influence on sprouting. Furthermore, suppression of the activity of G proteins of the Gα12/13 subfamily by adenoviral overexpression of the regulator of G protein signaling domain of LSC as well as siRNA-mediated knockdown of the Rho specific guanine nucleotide exchange factor leukemia associated RhoGEF (LARG) inhibited the S1P-induced activation of RhoC and concomitantly increased sprouting of HUVEC with similar efficacy. We conclude that the angiogenic sprouting of EC is suppressed via the S1P2R subtype. Thus, the increase in basal sprouting can be attributed to blocking of the inhibitory action of autocrine S1P stimulating the S1P2R. This inhibitory pathway involves the activation of RhoC via Gα12/13 and LARG, while the simultaneously occurring activation of RhoA is apparently dispensable here. © 2013.

Isotope shift of 40,42,44,48Ca in the 4s 2S1/2 → 4p 2P3/2 transition

Science.gov (United States)

Gorges, C.; Blaum, K.; Frömmgen, N.; Geppert, Ch; Hammen, M.; Kaufmann, S.; Krämer, J.; Krieger, A.; Neugart, R.; Sánchez, R.; Nörtershäuser, W.

2015-12-01

We report on improved isotope shift measurements of the isotopes {}{40,42,{44,48}}Ca in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}3/2 (D2) transition using collinear laser spectroscopy. Accurately known isotope shifts in the 4{{s}}{ }2{{{S}}}1/2\\to 4{{p}}{ }2{{{P}}}1/2(D1) transition were used to calibrate the ion beam energy with an uncertainty of {{Δ }}U≈ +/- 0.25 {{V}}. The accuracy in the D2 transition was improved by a factor of 5-10. A King-plot analysis of the two transitions revealed that the field shift factor in the D2 line is about 1.8(13)% larger than in the D1 transition which is ascribed to relativistic contributions of the 4{{{p}}}1/2 wave function.