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Sample records for 2b eif2b gef

  1. eIF2B promotes eIF5 dissociation from eIF2•GDP to facilitate guanine nucleotide exchange for translation initiation

    Jennings, Martin D.; Zhou, Yu; Mohammad-Qureshi, Sarah S.; Bennett, David; Pavitt, Graham D.

    2013-01-01

    Protein synthesis factor eIF2 delivers initiator tRNA to the ribosome. Two proteins regulate its G-protein cycle: eIF5 has both GTPase-activating protein (GAP) and GDP dissociation inhibitor (GDI) functions, and eIF2B is the guanine nucleotide exchange factor (GEF). Jennings et al. now establish a second activity for eIF2B (as a GDI displacement factor [GDF]) and demonstrate that this function is independent of its GEF activity. This study suggests that eIF2B is a bifunctional protein and def...

  2. Architecture of the eIF2B regulatory subcomplex and its implications for the regulation of guanine nucleotide exchange on eIF2.

    Kuhle, Bernhard; Eulig, Nora K; Ficner, Ralf

    2015-11-16

    Eukaryal translation initiation factor 2B (eIF2B) acts as guanine nucleotide exchange factor (GEF) for eIF2 and forms a central target for pathways regulating global protein synthesis. eIF2B consists of five non-identical subunits (α-ϵ), which assemble into a catalytic subcomplex (γ, ϵ) responsible for the GEF activity, and a regulatory subcomplex (α, β, δ) which regulates the GEF activity under stress conditions. Here, we provide new structural and functional insight into the regulatory subcomplex of eIF2B (eIF2B(RSC)). We report the crystal structures of eIF2Bβ and eIF2Bδ from Chaetomium thermophilum as well as the crystal structure of their tetrameric eIF2B(βδ)2 complex. Combined with mutational and biochemical data, we show that eIF2B(RSC) exists as a hexamer in solution, consisting of two eIF2Bβδ heterodimers and one eIF2Bα2 homodimer, which is homologous to homohexameric ribose 1,5-bisphosphate isomerases. This homology is further substantiated by the finding that eIF2Bα specifically binds AMP and GMP as ligands. Based on our data, we propose a model for eIF2B(RSC) and its interactions with eIF2 that is consistent with previous biochemical and genetic data and provides a framework to better understand eIF2B function, the molecular basis for Gcn(-), Gcd(-) and VWM/CACH mutations and the evolutionary history of the eIF2B complex. PMID:26384431

  3. Adult-Onset Vanishing White Matter Disease Due to a Novel EIF2B3 Mutation

    La Piana, Roberta; Vanderver, Adeline; van der Knaap, Marjo; Roux, Louise; Tampieri, Donatella; Brais, Bernard; Bernard, Geneviève

    2014-01-01

    Objective To report a novel mutation in the gene EIF2B3 responsible for a late-onset form of vanishing white matter disease. Design Case report. Setting University teaching hospital. Patient A 29-year-old pregnant woman with a history of premature ovarian failure and hemiplegic migraines presented with a 10-week history of progressive confusion and headaches. Magnetic resonance imaging of the brain revealed a diffuse leukoencephalopathy. Results Sequencing of the exons and intron boundaries of EIF2B3 uncovered 2 missense mutations: c.260C>T (p.Ala87Val) and c.272G>A (p.Arg91His). To our knowledge, the latter missense mutation has never been previously reported. Conclusion This is the second report of adult-onset vanishing white matter disease due to mutations in EIF2B3 and the first report of the c.272G>A (p.Arg91His) missense mutation. PMID:22312164

  4. Developmental splicing deregulation in leukodystrophies related to EIF2B mutations.

    Aurélia Huyghe

    Full Text Available Leukodystrophies (LD are rare inherited disorders that primarily affect the white matter (WM of the central nervous system. The large heterogeneity of LD results from the diversity of the genetically determined defects that interfere with glial cells functions. Astrocytes have been identified as the primary target of LD with cystic myelin breakdown including those related to mutations in the ubiquitous translation initiation factor eIF2B. EIF2B is involved in global protein synthesis and its regulation under normal and stress conditions. Little is known about how eIF2B mutations have a major effect on WM. We performed a transcriptomic analysis using fibroblasts of 10 eIF2B-mutated patients with a severe phenotype and 10 age matched patients with other types of LD in comparison to control fibroblasts. ANOVA was used to identify genes that were statistically significantly differentially expressed at basal state and after ER-stress. The pattern of differentially expressed genes between basal state and ER-stress did not differ significantly among each of the three conditions. However, 70 genes were specifically differentially expressed in eIF2B-mutated fibroblasts whatever the stress conditions tested compared to controls, 96% being under-expressed. Most of these genes were involved in mRNA regulation and mitochondrial metabolism. The 13 most representative genes, including genes belonging to the Heterogeneous Nuclear Ribonucleoprotein (HNRNP family, described as regulators of splicing events and stability of mRNA, were dysregulated during the development of eIF2B-mutated brains. HNRNPH1, F and C mRNA were over-expressed in foetus but under-expressed in children and adult brains. The abnormal regulation of HNRNP expression in the brain of eIF2B-mutated patients was concomitant with splicing dysregulation of the main genes involved in glial maturation such as PLP1 for oligodendrocytes and GFAP in astrocytes. These findings demonstrate a developmental

  5. eIF2B-Related Disorders: Antenatal Onset and Involvement of Multiple Organs

    van der Knaap, Marjo S.; van Berkel, Carola G. M.; Herms, Jochen; van Coster, Rudy; Baethmann, Martina; Naidu, Sakkubai; Boltshauser, Eugen; Willemsen, Michèl A. A. P.; Plecko, Barbara; Hoffmann, Georg F.; Proud, Christopher G.; Scheper, Gert C.; Pronk, Jan C.

    2003-01-01

    Leukoencephalopathy with vanishing white matter, also called “childhood ataxia with central nervous system hypomyelination,” is the first human disease related to mutations in any of the five genes encoding subunits of eukaryotic initiation factor eIF2B or any translation factor at all. eIF2B is essential in all cells of the body for protein synthesis and the regulation of this protein synthesis under different stress conditions. It is surprising that mutations in the eIF2B genes have been reported to lead to abnormalities of the white matter of the brain only, although it has been shown recently that ovarian failure may accompany the leukoencephalopathy. Another surprising observation is that the onset of the disease varies from early childhood to adulthood, with the exception of Cree leukoencephalopathy, a disease related to a particular mutation in one of the eIF2B genes, which invariably has its onset within the first year of life. We analyzed the eIF2B genes of nine patients with an antenatal- or early-infantile–onset encephalopathy and an early demise and found mutations in eight of the patients. In addition to signs of a serious encephalopathy, we found oligohydramnios, intrauterine growth retardation, cataracts, pancreatitis, hepatosplenomegaly, hypoplasia of the kidneys, and ovarian dysgenesis. Until now, no evidence had been found for a genotype-phenotype correlation, but the consistently severe phenotype in affected siblings among our patients and in Cree encephalopathy patients suggests an influence of the genotype on the phenotype. PMID:14566705

  6. Fusel Alcohols Regulate Translation Initiation by Inhibiting eIF2B to Reduce Ternary Complex in a Mechanism That May Involve Altering the Integrity and Dynamics of the eIF2B Body

    Taylor, Eleanor J.; Campbell, Susan G.; Griffiths, Christian D.; Reid, Peter J.; Slaven, John W.; Harrison, Richard J.; Sims, Paul F G; Pavitt, Graham D.; Delneri, Daniela; Ashe, Mark P.

    2010-01-01

    Recycling of eIF2-GDP to the GTP-bound form constitutes a core essential, regulated step in eukaryotic translation. This reaction is mediated by eIF2B, a heteropentameric factor with important links to human disease. eIF2 in the GTP-bound form binds to methionyl initiator tRNA to form a ternary complex, and the levels of this ternary complex can be a critical determinant of the rate of protein synthesis. Here we show that eIF2B serves as the target for translation inhibition by various fusel ...

  7. Dynamic cycling of eIF2 through a large eIF2B-containing cytoplasmic body

    Campbell, Susan G.; Hoyle, Nathaniel P.; Mark P Ashe

    2005-01-01

    The eukaryotic translation initiation factor 2B (eIF2B) provides a fundamental controlled point in the pathway of protein synthesis. eIF2B is the heteropentameric guanine nucleotide exchange factor that converts eIF2, from an inactive guanosine diphosphate–bound complex to eIF2-guanosine triphosphate. This reaction is controlled in response to a variety of cellular stresses to allow the rapid reprogramming of cellular gene expression. Here we demonstrate that in contrast to other translation ...

  8. Poor cerebral inflammatory response in eIF2B knock-in mice: implications for the aetiology of vanishing white matter disease.

    Yuval Cabilly

    Full Text Available BACKGROUND: Mutations in any of the five subunits of eukaryotic translation initiation factor 2B (eIF2B can lead to an inherited chronic-progressive fatal brain disease of unknown aetiology termed leucoencephalopathy with vanishing white matter (VWM. VWM is one of the most prevalent childhood white matter disorders, which markedly deteriorates after inflammation or exposure to other stressors. eIF2B is a major housekeeping complex that governs the rate of global protein synthesis under normal and stress conditions. A previous study demonstrated that Eif2b5(R132H/R132H mice suffer delayed white matter development and fail to recover from cuprizone-induced demyelination, although eIF2B enzymatic activity in the mutant brain is reduced by merely 20%. PRINCIPAL FINDINGS: Poor astrogliosis was observed in Eif2b5(R132H/R132H mice brain in response to systemic stress induced by peripheral injections of lipopolysaccharide (LPS. Even with normal rates of protein synthesis under normal conditions, primary astrocytes and microglia isolated from mutant brains fail to adequately synthesise and secrete cytokines in response to LPS treatment despite proper induction of cytokine mRNAs. CONCLUSIONS: The mild reduction in eIF2B activity prevents the appropriate increase in translation rates upon exposure to the inflammatory stressor LPS. The data underscore the importance of fully-functional translation machinery for efficient cerebral inflammatory response upon insults. It highlights the magnitude of proficient translation rates in restoration of brain homeostasis via microglia-astrocyte crosstalk. This study is the first to suggest the involvement of microglia in the pathology of VWM disease. Importantly, it rationalises the deterioration of clinical symptoms upon exposure of VWM patients to physiological stressors and provides possible explanation for their high phenotypic variability.

  9. Association of eukaryotic translation initiation factor eIF2B with fully solubilized CXCR4.

    Palmesino, Elena; Apuzzo, Tiziana; Thelen, Sylvia; Mueller, Bernd; Langen, Hanno; Thelen, Marcus

    2016-06-01

    Chemokine receptors are key regulators of leukocyte trafficking but also have an important role in development, tumor growth, and metastasis. Among the chemokine receptors, CXCR4 is the only one that leads to perinatal death when genetically ablated in mice, indicating a more-widespread function in development. To identify pathways that are activated downstream of CXCR4, a solubilization protocol was elaborated, which allows for the isolation of the endogenous receptor from human cells in its near-native conformation. Solubilized CXCR4 is recognized by the conformation-sensitive monoclonal antibody 12G5 and retains the ability to bind CXCL12 in solution, which was abolished in the presence of receptor antagonists. Mass spectrometry of CXCR4 immunoprecipitates revealed a specific interaction with the pentameric eukaryotic translation initiation factor 2B. The observation that the addition of CXCL12 leads to the dissociation of eukaryotic translation initiation factor 2B from CXCR4 suggests that stimulation of the receptor may trigger the local protein synthesis required for efficient cell movement. PMID:26609049

  10. Mutations Linked to Leukoencephalopathy with Vanishing White Matter Impair the Function of the Eukaryotic Initiation Factor 2B Complex in Diverse Ways

    Li, Wei; Wang, Xuemin; van der Knaap, Marjo S.; Proud, Christopher G.

    2004-01-01

    Leukoencephalopathy with vanishing white matter (VWM) is a severe inherited human neurodegenerative disorder that is caused by mutations in the genes for the subunits of eukaryotic initiation factor 2B (eIF2B), a heteropentameric guanine nucleotide exchange factor that regulates both global and mRNA-specific translation. Marked variability is evident in the clinical severity and time course of VWM in patients. Here we have studied the effects of VWM mutations on the function of human eIF2B. All the mutations tested cause partial loss of activity. Frameshift mutations in genes for eIF2Bɛ or eIF2Bβ lead to truncated polypeptides that fail to form complexes with the other subunits and are effectively null mutations. Certain point mutations also impair the ability of eIF2Bβ or -ɛ to form eIF2B holocomplexes and also diminish the intrinsic nucleotide exchange activity of eIF2B. A point mutation in the catalytic domain of eIF2Bɛ impairs its ability to bind the substrate, while two mutations in eIF2Bβ actually enhance eIF2 binding. We provide evidence that expression of VWM mutant eIF2B may enhance the translation of specific mRNAs. The variability of the clinical phenotype in VWM may reflect the multiple ways in which VWM mutations affect eIF2B function. PMID:15060152

  11. Childhood Ataxia with Cerebral Hypomyelination Syndrome: a Variant of Patient with Early Childhood Onset Related to EIF2B3 Mutation. A Case Report.

    Perfetto, F; Stoppino, L P; Calì, A; Milillo, P; Grilli, G; Vinci, R; Macarini, L

    2012-03-01

    Childhood ataxia with central nervous system hypomyelination (CACH) syndrome is an autosomal recessive transmitted leukodystrophy characterised by early childhood onset and acute deterioration following febrile illnesses or head trauma. We describe the case of a child with early onset of CACH syndrome. He presented with cerebellar ataxia beginning around two years of age with mild mental retardation. MRI showed diffuse white matter signal changes with thinning of the corpus callosum. PMID:24028880

  12. Mutations Linked to Leukoencephalopathy with Vanishing White Matter Impair the Function of the Eukaryotic Initiation Factor 2B Complex in Diverse Ways

    Li, Wei; Wang, Xuemin; Marjo S. van der Knaap; Proud, Christopher G.

    2004-01-01

    Leukoencephalopathy with vanishing white matter (VWM) is a severe inherited human neurodegenerative disorder that is caused by mutations in the genes for the subunits of eukaryotic initiation factor 2B (eIF2B), a heteropentameric guanine nucleotide exchange factor that regulates both global and mRNA-specific translation. Marked variability is evident in the clinical severity and time course of VWM in patients. Here we have studied the effects of VWM mutations on the function of human eIF2B. A...

  13. A yeast purification system for human translation initiation factors eIF2 and eIF2Bε and their use in the diagnosis of CACH/VWM disease.

    Rogerio A de Almeida

    Full Text Available Recessive inherited mutations in any of five subunits of the general protein synthesis factor eIF2B are responsible for a white mater neurodegenerative disease with a large clinical spectrum. The classical form is called Childhood Ataxia with CNS hypomyelination (CACH or Vanishing White Matter Leukoencephalopathy (VWM. eIF2B-related disorders affect glial cells, despite the fact that eIF2B is a ubiquitous protein that functions as a guanine-nucleotide exchange factor (GEF for its partner protein eIF2 in the translation initiation process in all eukaryotic cells. Decreased eIF2B activity measured by a GEF assay in patients' immortalised lymphocytic cells provides a biochemical diagnostic assay but is limited by the availability of eIF2 protein, which is classically purified from a mammalian cell source by column chromatography. Here we describe the generation of a recombinant expression system to produce purified human eIF2 from yeast cells. We demonstrate that human eIF2 can function in yeast cells in place of the equivalent yeast factor. We purify human eIF2 and the C-terminal domain of human eIF2Bε using affinity chromatography from engineered yeast cells and find that both function in a GEF assay: the first demonstration that this human eIF2Bε domain has GEF function. We show that CACH/VWM mutations within this domain reduce its activity. Finally we demonstrate that the recombinant eIF2 functions similarly to eIF2 purified from rat liver in GEF assays with CACH/VWM eIF2B-mutated patient derived lymphocytic cells.

  14. GEF small grants programme - overview

    NONE

    1997-12-01

    This paper describes the GEF small grants program which seeks to enhance the role of households and communities in conserving global biodiversity, mitigating global climate change, and protecting international waters. Grants up to $50k have been granted for projects in 33 countries, with plans for 12 other countries. The author describes the framework that the program works under, and the methodology followed in developing and planning projects. The approach to climate change concerns is to emphasize the development of non-carbon energy development activities to provide energy sources and economic development.

  15. Global Ensemble Forecast System (GEFS) [1 Deg.

    National Oceanic and Atmospheric Administration, Department of Commerce — The Global Ensemble Forecast System (GEFS) is a weather forecast model made up of 21 separate forecasts, or ensemble members. The National Centers for Environmental...

  16. Quantitative Analysis of Guanine Nucleotide Exchange Factors (GEFs) as Enzymes

    Randazzo, Paul A.; Jian, Xiaoying; Chen, Pei-Wen; Zhai, Peng; Soubias, Olivier; Northup, John K.

    2014-01-01

    The proteins that possess guanine nucleotide exchange factor (GEF) activity, which include about ~800 G protein coupled receptors (GPCRs), 1 15 Arf GEFs, 2 81 Rho GEFs, 3 8 Ras GEFs, 4 and others for other families of GTPases, 5 catalyze the exchange of GTP for GDP on all regulatory guanine nucleotide binding proteins. Despite their importance as catalysts, relatively few exchange factors (we are aware of only eight for ras superfamily members) have been rigorously characterized kinetically. ...

  17. General Description of Fission Observables: GEF Model Code

    Schmidt, Karl-Heinz; Jurado, Beatriz; Amouroux, Charlotte; Schmitt, C.

    2015-01-01

    The GEF (" GEneral description of Fission observables ") model code is documented. It describes the observables for spontaneous fission, neutron-induced fission and, more generally, for fission of a compound nucleus from any other entrance channel, with given excitation energy and angular momentum. The GEF model is applicable for a wide range of isotopes from Z = 80 to Z = 112 and beyond, up to excitation energies of about 100 MeV. The results of the GEF model are compared with fission barrie...

  18. Hydrographic data from the GEF Patagonia cruises

    M. Charo

    2014-02-01

    Full Text Available The hydrographic data reported here were collected within the framework of the Coastal Contamination, Prevention and Marine Management project (GEF Patagonia, which was part of the scientific agenda of the United Nations Development Program (UNDP. The project goal was to strengthen efforts to improve sustainable management of marine biodiversity and reduce pollution of the Patagonia marine environment. The observational component of the project included three multi-disciplinary oceanographic cruises designed to improve the knowledge base of the marine environment and to determine the seasonal variability of physical, biological and chemical properties of highly productive regions in the southwest South Atlantic continental shelf. The cruises were carried out on board R/V Ara Puerto Deseado, in October 2005 and March and September 2006. In each cruise, hydrographic stations were occupied along cross-shelf sections spanning the shelf from near-shore to the western boundary currents between 38° and 55° S. This paper reports the quasi-continuous vertical profiles (CTD and underway surface temperature and salinity data collected during the GEF Patagonia cruises. These data sets are available at the National Oceanographic Data Center, NOAA. US, doi:10.7289/V5RN35S0.

  19. Model Calculation of Fission Product Yields Data using GEF Code

    Fission yields data are classified with spontaneous fission data and neutron induced fission data. The fission product yields data at several energy points for the limited actinides are included in nuclear data libraries such as ENDF/B, JEFF and JENDL because production of those is based mainly on experimental results and it is very difficult to conduct experiments for all actinides and continuous energies. Therefore, in order to obtain fission yields data without experimental data, a theoretical fission model should be introduced to produce the yields data. GEneral Fission model (GEF) is developed to predict the properties for fissioning systems that have not been measured and that are not accessible to experiment. In this study, the fission yields data generated from GEF code are compared with the measured data and the recently available nuclear data libraries. The GEF code is very powerful tool to generate fission yields without measurements. Also, it can produce the distribution of fission product yields for continuous neutron energy while measured data are given only at several energies. The fission yields data of 235U have been tentatively generated with GEF code in this work. Comparing GEF results with measurements and recently released evaluated fission yields data, it is confirmed that GEF code can successfully predict the fission yields data. With its sophisticated model, GEF code is playing a significant role in nuclear industry

  20. B2B marketing

    Pospíšilová, Lucie

    2010-01-01

    The main goal of this bachelor thesis is to apply theoretical knowledge in B2B marketing to the example of marketing processes in a particular company, to evaluate the current situation of its activities with regard to B2B principles and to suggest relevant recommendations. The theoretical part focuses on specific characteristics of B2B marketing, describes its differences from marketing on consumer markets, deals with buying behaviour of organizations and specifies particular features of mar...

  1. Global Ensemble Forecast System (GEFS) [2.5 Deg.

    National Oceanic and Atmospheric Administration, Department of Commerce — The Global Ensemble Forecast System (GEFS) is a weather forecast model made up of 21 separate forecasts, or ensemble members. The National Centers for Environmental...

  2. Superoxide Inhibits Guanine Nucleotide Exchange Factor (GEF) Action on Ras, but not on Rho, through Desensitization of Ras to GEF

    Wey, Michael; Phan, Vinh; Yepez, Gerardo; Heo, Jongyun

    2014-01-01

    Ras and Rho GTPases are molecular switches for various vital cellular signaling pathways. Overactivation of these GTPases often causes development of cancer. Guanine nucleotide exchange factors (GEFs) and oxidants function to upregulate these GTPases through facilitation of guanine nucleotide exchange (GNE) of these GTPases. However, the effect of oxidants on GEF functions, or vice versa, has not been known. We show that, via targeting Ras Cys51, an oxidant inhibits the catalytic action of Cd...

  3. Coevolution of RAC Small GTPases and their Regulators GEF Proteins

    Jiménez-Sánchez, Alejandro

    2016-01-01

    RAC proteins are small GTPases involved in important cellular processes in eukaryotes, and their deregulation may contribute to cancer. Activation of RAC proteins is regulated by DOCK and DBL protein families of guanine nucleotide exchange factors (GEFs). Although DOCK and DBL proteins act as GEFs on RAC proteins, DOCK and DBL family members are evolutionarily unrelated. To understand how DBL and DOCK families perform the same function on RAC proteins despite their unrelated primary structure, phylogenetic analyses of the RAC, DBL, and DOCK families were implemented, and interaction patterns that may suggest a coevolutionary process were searched. Interestingly, while RAC and DOCK proteins are very well conserved in humans and among eukaryotes, DBL proteins are highly divergent. Moreover, correlation analyses of the phylogenetic distances of RAC and GEF proteins and covariation analyses between residues in the interacting domains showed significant coevolution rates for both RAC–DOCK and RAC–DBL interactions. PMID:27226705

  4. Combating Land Degradation in Production Landscapes : Learning from GEF Projects Applying Integrated Approaches

    Global Environment Facility

    2014-01-01

    During the Fifth Replenishment Phase of the Global Environment Facility (GEF-5), portfolio monitoring and learning review were introduced as key components of knowledge management in the GEF Secretariat. These strategies were intended to address the need to generate knowledge on innovative practices, experiences, and lessons from projects financed by the GEF. In that regard, the Land Degra...

  5. Queere Archive des Ephemeren. Raum, Gefühl: Unbestimmtheit

    Katrin Köppert

    2015-08-01

    Full Text Available Der Artikel folgt dem ‚Geschmack‘ dreier Archive in Berlin, San Francisco und New York und stellt einen Beitrag zum archival turn in queer theory zur Verfügung. Ihm zugrunde liegt somit die Frage, wie wir queere Bewegungsgeschichte erinnern wollen – auch um eine Vision queerer Zukunft entwerfen zu können. Er beschäftigt sich mit Raum- und Gefühlspolitiken von queeren Archiven und ‚Archiven von hinten‘. Im Zentrum der Analyse steht das Wechselverhältnis der Bedeutung von Gefühlen für die Konstitution des Raums Archiv und der Relevanz von räumlichen Veränderungen für die Ausprägung von Gefühlen. Dabei interessieren insbesondere negative Gefühle. Diese werden als Störungen inmitten von Professionalisierungsanstrengungen diskutiert. Zudem werden sie unter der Prämisse ihres Potentials für eine queere Kritik an der heteronormativen Historiografie einerseits und der auf binären Trennungen (Alltag-Wissen, Privatheit-Öffentlichkeit basierenden Wissenspolitik anderseits erörtert.

  6. The Global Environment Facility (GEF): Right mechanism for improved implementation?

    Andresen, Steinar; Rosendal, Kristin G.

    2012-11-01

    The purpose is to feed into the international discussions of environmental financial mechanisms such as for forestry and mercury by examining the performance of the GEF. We discuss performance against effectiveness and legitimacy and focus on institutional set-up and key actors as explanatory factors. Methodologically, we use document and literature analysis and interviews with key actors in organizations, state representatives and NGOs. The dominant position of the USA and the World Bank has probably contributed to the bias towards a northern environmental agenda and emphasis on effectiveness and climate change projects. The GEF has somewhat predictably diverted the flow of international money from the poorest countries to more rapidly developing countries. Still, despite turf battles between the organizations involved, the broad organisational and thematic composition of the GEF has comparative advantages. This enhances the score on legitimacy especially for biodiversity projects, although they receive less overall funding. The GEF may be seen as an indication of how, regardless of choosing established or new institutions, basic power structures and interests of dominating parties will be largely decisive for what can be achieved in global environmental governance.(auth)

  7. Interferon Alfa-2b Injection

    Interferon alfa-2b injection is used to treat a number of conditions.Interferon alfa-2b injection is used alone or in ... Hodgkin's lymphoma (NHL; a slow-growing blood cancer). Interferon alfa-2b is in a class of medications ...

  8. Entzündliche Gefäßerkrankungen

    Graninger M

    2005-01-01

    Full Text Available Die Präsenz von Leukozyten in der Gefäßwand ergibt gemeinsam mit einem morphologisch sichtbaren Schaden der Gefäßwand definitionsgemäß die histopathologische Diagnose einer Vaskulitis. Die funktionellen Konsequenzen einer Verletzung der Integrität des Blutgefäßes können Aneurysmen und Blutungen sein; eine Einschränkung des Lumens durch Endothelschaden und Proliferation der Wandschichten führt zu Ischämie und Nekrose. Im Gegensatz zu atherothrombotischen Gefäßschäden oder zur Thrombangitis obliterans kann das entzündliche Infiltrat bei den „idiopathischen“ oder Systemvaskulitiden über die Gefäßwand hinausgehen und zu nachhaltigen Parenchymschäden durch Granulombildung führen. Eine systemische Reaktion mit Fieber und Allgemeinsymptomen kann schließlich mit zu fatalen Verläufen beitragen. Mit einer rechtzeitigen Diagnosestellung und dem frühen Beginn einer immunsuppressiven Therapie können schwere Krankheitsfolgen vermieden werden. In der Pathogenese des entzündlichen Infiltrats spielen das Endothel und die Expression von Adhäsionsmolekülen und Zytokinen eine entscheidende Rolle [1]. Besonders bei den Systemvaskulitiden wird eine aberrante Immunantwort postuliert, die zu Entzündung und Nekrose führt. Eine praktische Konsequenz aus den (noch immer unvollständigen immunologischen Hypothesen entsteht erstmals durch die gezielt mögliche Antagonisierung von Co-Stimulationsmolekülen, Adhäsionsmolekülen und Zytokinen durch therapeutische Antikörper und Rezeptorkonstrukte, die einen über die bisher übliche unspezifische Immunsuppression mit Kortikosteroiden und Antimetaboliten hinausgehenden prognostischen Fortschritt versprechen.

  9. Brief introduction of GEF efficient industrial boiler project in China

    Meijian, T.

    1996-12-31

    The present situation of installed industrial boilers, their efficiency and environmental impact are assessed. And the factors contribute to the low efficiency and serious pollution are summarized. Based on WB-assisted GEF project, {open_quotes}Efficient Industrial Boiler Project{close_quotes} aimed at CO{sub 2} mitigation in China, a series of effective measures to bring the GHG emission under control are addressed, in technology, system performance, and operation management aspects.

  10. General Description of Fission Observables - JEFF Report 24. GEF Model

    The Joint Evaluated Fission and Fusion (JEFF) Project is a collaborative effort among the member countries of the OECD Nuclear Energy Agency (NEA) Data Bank to develop a reference nuclear data library. The JEFF library contains sets of evaluated nuclear data, mainly for fission and fusion applications; it contains a number of different data types, including neutron and proton interaction data, radioactive decay data, fission yield data and thermal scattering law data. The General fission (GEF) model is based on novel theoretical concepts and ideas developed to model low energy nuclear fission. The GEF code calculates fission-fragment yields and associated quantities (e.g. prompt neutron and gamma) for a large range of nuclei and excitation energy. This opens up the possibility of a qualitative step forward to improve further the JEFF fission yields sub-library. This report describes the GEF model which explains the complex appearance of fission observables by universal principles of theoretical models and considerations on the basis of fundamental laws of physics and mathematics. The approach reveals a high degree of regularity and provides a considerable insight into the physics of the fission process. Fission observables can be calculated with a precision that comply with the needs for applications in nuclear technology. The relevance of the approach for examining the consistency of experimental results and for evaluating nuclear data is demonstrated. (authors)

  11. Improving GEFS Weather Forecasts for Indian Monsoon with Statistical Downscaling

    Agrawal, Ankita; Salvi, Kaustubh; Ghosh, Subimal

    2014-05-01

    Weather forecast has always been a challenging research problem, yet of a paramount importance as it serves the role of 'key input' in formulating modus operandi for immediate future. Short range rainfall forecasts influence a wide range of entities, right from agricultural industry to a common man. Accurate forecasts actually help in minimizing the possible damage by implementing pre-decided plan of action and hence it is necessary to gauge the quality of forecasts which might vary with the complexity of weather state and regional parameters. Indian Summer Monsoon Rainfall (ISMR) is one such perfect arena to check the quality of weather forecast not only because of the level of intricacy in spatial and temporal patterns associated with it, but also the amount of damage it can cause (because of poor forecasts) to the Indian economy by affecting agriculture Industry. The present study is undertaken with the rationales of assessing, the ability of Global Ensemble Forecast System (GEFS) in predicting ISMR over central India and the skill of statistical downscaling technique in adding value to the predictions by taking them closer to evidentiary target dataset. GEFS is a global numerical weather prediction system providing the forecast results of different climate variables at a fine resolution (0.5 degree and 1 degree). GEFS shows good skills in predicting different climatic variables but fails miserably over rainfall predictions for Indian summer monsoon rainfall, which is evident from a very low to negative correlation values between predicted and observed rainfall. Towards the fulfilment of second rationale, the statistical relationship is established between the reasonably well predicted climate variables (GEFS) and observed rainfall. The GEFS predictors are treated with multicollinearity and dimensionality reduction techniques, such as principal component analysis (PCA) and least absolute shrinkage and selection operator (LASSO). Statistical relationship is

  12. Bemerkenswerte Vorkommen gefährdeter Pflanzenarten in der Stadt Oldenburg (Oldb)

    Becker, Ralf

    2010-01-01

    Aktuelle Neu- und Wiederfunde von 33 gefährdeten Arten der Gefäßpflanzen sowie zwei gefährdeten Armleuchteralgen-Sippen in der Stadt Oldenburg werden beschrieben. Die Untersuchungen erfolgten seit 2005 schwerpunktmäßig an Stillgewässern, Gräben, in Grünlandgebieten und auf dem ehemaligen Fliegerhorst Alexandersfeld. Die Gefährdungssituation und die Bestandsentwicklung der Arten wird dargestellt. Durchgeführte und zukünftig erforderliche Schutz-, Pflege- und Entwicklungsmaßnahmen ...

  13. Süd-Nord-Gefälle in West- und Ostdeutschland?

    Lammers, Konrad

    2003-01-01

    Die regionale Entwicklung in Westdeutschland war bis zur Wiedervereinigung durch ein ausgeprägtes Süd-Nord-Gefälle gekennzeichnet. Hat sich das Süd-Nord-Gefälle verändert? Sind in Ostdeutschland ebenfalls regionale Süd-Nord- Entwicklungsunterschiede festzustellen?

  14. Genetic screening of Scandinavian families with febrile seizures and epilepsy or GEFS+

    Selmer, K K; Egeland, T; Solaas, M H;

    2008-01-01

    Background - Mutations in the three genes SCN1A, SCN1B and GABRG2, all encoding subunits of ion channels, have been known to cause generalized epilepsy with febrile seizures plus (GEFS+) in families of different origin. Objective - To study the occurrence of mutations in these genes in families...... with GEFS+ or a GEFS+ resembling phenotype of Scandinavian origin. Material and methods - We performed linkage analysis in 19 Scandinavian families with a history of febrile seizures (FS) and epilepsy or GEFS+. Where linkage could not be excluded, the genes of interest were sequenced. Results - We...... identified only one mutation in SCN1A, which seems to be a rare variant with no functional consequence. Conclusion - This suggests that mutations in these three genes are not a prevalent cause of familial cases of FS and epilepsy or GEFS+ in Scandinavia....

  15. General Description of Fission Observables: GEF Model Code

    Schmidt, K.-H.; Jurado, B.; Amouroux, C.; Schmitt, C.

    2016-01-01

    The GEF ("GEneral description of Fission observables") model code is documented. It describes the observables for spontaneous fission, neutron-induced fission and, more generally, for fission of a compound nucleus from any other entrance channel, with given excitation energy and angular momentum. The GEF model is applicable for a wide range of isotopes from Z = 80 to Z = 112 and beyond, up to excitation energies of about 100 MeV. The results of the GEF model are compared with fission barriers, fission probabilities, fission-fragment mass- and nuclide distributions, isomeric ratios, total kinetic energies, and prompt-neutron and prompt-gamma yields and energy spectra from neutron-induced and spontaneous fission. Derived properties of delayed neutrons and decay heat are also considered. The GEF model is based on a general approach to nuclear fission that explains a great part of the complex appearance of fission observables on the basis of fundamental laws of physics and general properties of microscopic systems and mathematical objects. The topographic theorem is used to estimate the fission-barrier heights from theoretical macroscopic saddle-point and ground-state masses and experimental ground-state masses. Motivated by the theoretically predicted early localisation of nucleonic wave functions in a necked-in shape, the properties of the relevant fragment shells are extracted. These are used to determine the depths and the widths of the fission valleys corresponding to the different fission channels and to describe the fission-fragment distributions and deformations at scission by a statistical approach. A modified composite nuclear-level-density formula is proposed. It respects some features in the superfluid regime that are in accordance with new experimental findings and with theoretical expectations. These are a constant-temperature behaviour that is consistent with a considerably increased heat capacity and an increased pairing condensation energy that is

  16. Pancreatic Cancer Stage 2B

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  17. NtGNL1a ARF-GEF acts in endocytosis in tobacco cells

    Jelínková, A. (Adriana); Müller, K.; Pařezová, M. (Markéta); Petrášek, J. (Jan)

    2015-01-01

    Background Processes of anterograde and retrograde membrane trafficking play an important role in cellular homeostasis and dynamic rearrangements of the plasma membrane (PM) in all eukaryotes. These processes depend on the activity of adenosine ribosylation factors (ARFs), a family of GTP-binding proteins and their guanine exchange factors (GEFs). However, knowledge on the function and specificity of individual ARF-GEFs for individual steps of membrane trafficking pathways is still limited in...

  18. Closing the Gap GEF Experiences in Global Energy Efficiency

    Yang, Ming

    2013-01-01

    Energy efficiency plays and will continue to play an important role in the world to save energy and mitigate greenhouse gas (GHG) emissions. However, little is known on how much additional capital should be invested to ensure using energy efficiently as it should be, and very little is known which sub-areas, technologies, and countries shall achieve maximum greenhouse gas emissions mitigation per dollar of investment in energy efficiency worldwide. Analyzing completed and slowly moving energy efficiency projects by the Global Environment Facility during 1991-2010, Closing the Gap: GEF Experiences in Global Energy Efficiency evaluates impacts of multi-billion-dollar investments in the world energy efficiency. It covers the following areas: 1.       Reviewing the world energy efficiency investment and disclosing the global energy efficiency gap and market barriers that cause the gap; 2.       Leveraging private funds with public funds and other resources in energy efficiency investments; using...

  19. Vanishing White Matter Disease in a Spanish Population

    Turón-Viñas, Eulàlia; Pineda, Mercè; Cusí, Victòria; López-Laso, Eduardo; del Pozo, Rebeca Losada; Gutiérrez-Solana, Luis González; Moreno, David Conejo; Sierra-Córcoles, Concha; Olabarrieta-Hoyos, Naiara; Madruga-Garrido, Marcos; Aguirre-Rodríguez, Javier; González-Álvarez, Verónica; O’Callaghan, Mar; Muchart, Jordi; Armstrong-Moron, Judith

    2014-01-01

    Vanishing white matter (VWM) leukoencephalopathy is one of the most prevalent hereditary white matter diseases. It has been associated with mutations in genes encoding eukaryotic translation initiation factor (eIF2B). We have compiled a list of all the patients diagnosed with VWM in Spain; we found 21 children. The first clinical manifestation in all of them was spasticity, with severe ataxia in six patients, hemiparesis in one child, and dystonic movements in another. They suffered from progressive cognitive deterioration and nine of them had epilepsy too. In four children, we observed optic atrophy and three also had progressive macrocephaly, which is not common in VWM disease. The first two cases were diagnosed before the 1980s. Therefore, they were diagnosed by necropsy studies. The last 16 patients were diagnosed according to genetics: we found mutations in the genes eIF2B5 (13 cases), eIF2B3 (2 cases), and eIF2B4 (1 case). In our report, the second mutation in frequency was c.318A>T; patients with this mutation all followed a slow chronic course, both in homozygous and heterozygous states. Previously, there were no other reports to confirm this fact. We also found some mutations not described in previous reports: c.1090C>T in eIF2B4, c.314A>G in eIF2B5, and c.877C>T in eIF2B5. PMID:25089094

  20. Marketing Optimization for B2B Market

    Kaynova Tatyana V.

    2012-01-01

    The article presents market definition B2B, the necessity to optimize marketing B2B market, provides a system for B2B-marketing and developed stages of its formation. On this basis it was identified key factors of customer loyalty and are the stages of development of loyalty programs for customers market B2B.

  1. Stiffness-activated GEF-H1 expression exacerbates LPS-induced lung inflammation.

    Isa Mambetsariev

    Full Text Available Acute lung injury (ALI is accompanied by decreased lung compliance. However, a role of tissue mechanics in modulation of inflammation remains unclear. We hypothesized that bacterial lipopolysacharide (LPS stimulates extracellular matrix (ECM production and vascular stiffening leading to stiffness-dependent exacerbation of endothelial cell (EC inflammatory activation and lung barrier dysfunction. Expression of GEF-H1, ICAM-1, VCAM-1, ECM proteins fibronectin and collagen, lysyl oxidase (LOX activity, interleukin-8 and activation of Rho signaling were analyzed in lung samples and pulmonary EC grown on soft (1.5 or 2.8 kPa and stiff (40 kPa substrates. LPS induced EC inflammatory activation accompanied by expression of ECM proteins, increase in LOX activity, and activation of Rho signaling. These effects were augmented in EC grown on stiff substrate. Stiffness-dependent enhancement of inflammation was associated with increased expression of Rho activator, GEF-H1. Inhibition of ECM crosslinking and stiffening by LOX suppression reduced EC inflammatory activation and GEF-H1 expression in response to LPS. In vivo, LOX inhibition attenuated LPS-induced expression of GEF-H1 and lung dysfunction. These findings present a novel mechanism of stiffness-dependent exacerbation of vascular inflammation and escalation of ALI via stimulation of GEF-H1-Rho pathway. This pathway represents a fundamental mechanism of positive feedback regulation of inflammation.

  2. Regulating Rac in the Nervous System: Molecular Function and Disease Implication of Rac GEFs and GAPs

    Yanyang Bai

    2015-01-01

    Full Text Available Rho family GTPases, including RhoA, Rac1, and Cdc42 as the most studied members, are master regulators of actin cytoskeletal organization. Rho GTPases control various aspects of the nervous system and are associated with a number of neuropsychiatric and neurodegenerative diseases. The activity of Rho GTPases is controlled by two families of regulators, guanine nucleotide exchange factors (GEFs as the activators and GTPase-activating proteins (GAPs as the inhibitors. Through coordinated regulation by GEFs and GAPs, Rho GTPases act as converging signaling molecules that convey different upstream signals in the nervous system. So far, more than 70 members of either GEFs or GAPs of Rho GTPases have been identified in mammals, but only a small subset of them have well-known functions. Thus, characterization of important GEFs and GAPs in the nervous system is crucial for the understanding of spatiotemporal dynamics of Rho GTPase activity in different neuronal functions. In this review, we summarize the current understanding of GEFs and GAPs for Rac1, with emphasis on the molecular function and disease implication of these regulators in the nervous system.

  3. DRhoGEF2 regulates cellular tension and cell pulsations in the Amnioserosa during Drosophila dorsal closure.

    Dulce Azevedo

    Full Text Available Coordination of apical constriction in epithelial sheets is a fundamental process during embryogenesis. Here, we show that DRhoGEF2 is a key regulator of apical pulsation and constriction of amnioserosal cells during Drosophila dorsal closure. Amnioserosal cells mutant for DRhoGEF2 exhibit a consistent decrease in amnioserosa pulsations whereas overexpression of DRhoGEF2 in this tissue leads to an increase in the contraction time of pulsations. We probed the physical properties of the amnioserosa to show that the average tension in DRhoGEF2 mutant cells is lower than wild-type and that overexpression of DRhoGEF2 results in a tissue that is more solid-like than wild-type. We also observe that in the DRhoGEF2 overexpressing cells there is a dramatic increase of apical actomyosin coalescence that can contribute to the generation of more contractile forces, leading to amnioserosal cells with smaller apical surface than wild-type. Conversely, in DRhoGEF2 mutants, the apical actomyosin coalescence is impaired. These results identify DRhoGEF2 as an upstream regulator of the actomyosin contractile machinery that drives amnioserosa cells pulsations and apical constriction.

  4. Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations.

    Scheffer, Ingrid E; Harkin, Louise A; Grinton, Bronwyn E; Dibbens, Leanne M; Turner, Samantha J; Zielinski, Marta A; Xu, Ruwei; Jackson, Graeme; Adams, Judith; Connellan, Mary; Petrou, Steven; Wellard, R Mark; Briellmann, Regula S; Wallace, Robyn H; Mulley, John C; Berkovic, Samuel F

    2007-01-01

    SCN1B, the gene encoding the sodium channel beta 1 subunit, was the first gene identified for generalized epilepsy with febrile seizures plus (GEFS+). Only three families have been published with SCN1B mutations. Here, we present four new families with SCN1B mutations and characterize the associated phenotypes. Analysis of SCN1B was performed on 402 individuals with various epilepsy syndromes. Four probands with missense mutations were identified. Detailed electroclinical phenotyping was performed on all available affected family members including quantitative MR imaging in those with temporal lobe epilepsy (TLE). Two new families with the original C121W SCN1B mutation were identified; novel mutations R85C and R85H were each found in one family. The following phenotypes occurred in the six families with SCN1B missense mutations: 22 febrile seizures, 20 febrile seizures plus, five TLE, three other GEFS+ phenotypes, two unclassified and ten unaffected individuals. All individuals with confirmed TLE had the C121W mutation; two underwent temporal lobectomy (one with hippocampal sclerosis and one without) and both are seizure free. We confirm the role of SCN1B in GEFS+ and show that the GEFS+ spectrum may include TLE alone. TLE with an SCN1B mutation is not a contraindication to epilepsy surgery. PMID:17020904

  5. Rabin8 regulates neurite outgrowth in both GEF activity-dependent and -independent manners.

    Homma, Yuta; Fukuda, Mitsunori

    2016-07-01

    Many aspects of membrane-trafficking events are regulated by Rab-family small GTPases. Neurite outgrowth requires massive addition of proteins and lipids to the tips of growing neurites by membrane trafficking, and although several Rabs, including Rab8, Rab10, and Rab11, have been implicated in this process, their regulatory mechanisms during neurite outgrowth are poorly understood. Here, we show that Rabin8, a Rab8-guanine nucleotide exchange factor (GEF), regulates nerve growth factor (NGF)-induced neurite outgrowth of PC12 cells. Knockdown of Rabin8 results in inhibition of neurite outgrowth, whereas overexpression promotes it. We also find that Rab10 is a novel substrate of Rabin8 and that both Rab8 and Rab10 function during neurite outgrowth downstream of Rabin8. Surprisingly, however, a GEF activity-deficient isoform of Rabin8 also promotes neurite outgrowth, indicating the existence of a GEF activity-independent role of Rabin8. The Arf6/Rab8-positive recycling endosomes (Arf6/Rab8-REs) and Rab10/Rab11-positive REs (Rab10/Rab11-REs) in NGF-stimulated PC12 cells are differently distributed. Rabin8 localizes on both RE populations and appears to activate Rab8 and Rab10 there. These localizations and functions of Rabin8 are Rab11 dependent. Thus Rabin8 regulates neurite outgrowth both by coordinating with Rab8, Rab10, and Rab11 and by a GEF activity-independent mechanism. PMID:27170183

  6. NEDD4-1 regulates migration and invasion of glioma cells through CNrasGEF ubiquitination in vitro.

    Hao Zhang

    Full Text Available Neuronal precursor cell-expressed developmentally down-regulated 4-1 (NEDD4-1 plays a great role in tumor cell growth, but its function and mechanism in cell invasive behavior are totally unknown. Here we report that NEDD4-1 regulates migration and invasion of malignant glioma cells via triggering ubiquitination of cyclic nucleotide Ras guanine nucleotide exchange factor (CNrasGEF using cultured glioma cells. NEDD4-1 overexpression promoted cell migration and invasion, while its downregulation specifically inhibited them. However, NEDD4-1 did not affect the proliferation and apoptosis of glioma cells. NEDD4-1 physically interacted with CNrasGEF and promoted its poly-ubiquitination and degradation. Contrary to the effect of NEDD4-1, CNrasGEF downregulation promoted cell migration and invasion, while its overexpression inhibited them. Importantly, downregulation of CNrasGEF facilitated the effect of NEDD4-1-induced cell migration and invasion. Interestingly, aberrant up-regulated NEDD4-1 showed reverse correlation with CNrasGEF protein level but not with its mRNA level in glioma tissues. Combined with the in vitro results, the result of glioma tissues indicated post-translationally modification effect of NEDD4-1 on CNrasGEF. Our study suggests that NEDD4-1 regulates cell migration and invasion through ubiquitination of CNrasGEF in vitro.

  7. GIPC1 Interacts with MyoGEF and Promotes MDA-MB-231 Breast Cancer Cell Invasion*

    Wu, Di; Haruta, Akiko; Wei, Qize

    2010-01-01

    GIPC1/synectin, a single PDZ domain-containing protein, binds to numerous proteins and is involved in multiple biological processes, including cell migration. We reported previously that MyoGEF, a guanine nucleotide exchange factor, plays a role in regulating breast cancer cell polarization and invasion. Here, we identify GIPC1 as an interacting partner of MyoGEF. Both in vitro and in vivo binding assays show that the GIPC1 PDZ domain binds to the PDZ-binding motif at the C terminus of MyoGEF...

  8. Peginterferon Alfa-2b (PEG-Intron)

    ... damage and who have not been treated with interferon alpha (medication similar to peginterferon alfa-2b) in the ... doctor prescribed. Do not use another brand of interferon or switch between peginterferon alfa-2b in vials and injection pens without talking ...

  9. GxcDD, a putative RacGEF, is involved in Dictyostelium development

    Rivero Francisco; Neelamegan Dhamodharan; Mondal Subhanjan; Noegel Angelika A

    2007-01-01

    Abstract Background Rho subfamily GTPases are implicated in a large number of actin-related processes. They shuttle from an inactive GDP-bound form to an active GTP-bound form. This reaction is catalysed by Guanine nucleotide exchange factor (GEFs). GTPase activating proteins (GAPs) help the GTPase return to the inactive GDP-bound form. The social amoeba Dictyostelium discoideum lacks a Rho or Cdc42 ortholog but has several Rac related GTPases. Compared to our understanding of the downstream ...

  10. TEM-Grundlagenuntersuchungen zur Gefügeentwicklung in aushärtbaren Glimmerglaskeramiken

    Bürke, Harald

    2006-01-01

    Untersuchung der Keimbildung und des Kristallisationsverhaltens einer mit Zirkoniumoxid verstärkten Glimmerglaskeramik mit Na- Fluorphlogopit als kristalliner Hauptphase. Es der Einfluss des Zirkoniumoxides auf die Keimbildung untersucht. Die Möglichkeiten und Mechanismen der mechanischen Verfestigung der vorkristallisierten Glaskeramik in einem zweiten Temperschritt durch gezielte Gefügeeinstellung, Wachstum der Zirkoniumoxidkristalle auf eine umwandlungsfähige Größe, sowie durch Ausscheidun...

  11. GxcDD, a putative RacGEF, is involved in Dictyostelium development

    Rivero Francisco

    2007-06-01

    Full Text Available Abstract Background Rho subfamily GTPases are implicated in a large number of actin-related processes. They shuttle from an inactive GDP-bound form to an active GTP-bound form. This reaction is catalysed by Guanine nucleotide exchange factor (GEFs. GTPase activating proteins (GAPs help the GTPase return to the inactive GDP-bound form. The social amoeba Dictyostelium discoideum lacks a Rho or Cdc42 ortholog but has several Rac related GTPases. Compared to our understanding of the downstream effects of Racs our understanding of upstream mechanisms that activate Rac GTPases is relatively poor. Results We report on GxcDD (Guanine exchange factor for Rac GTPases, a Dictyostelium RacGEF. GxcDD is a 180-kDa multidomain protein containing a type 3 CH domain, two IQ motifs, three PH domains, a RhoGEF domain and an ArfGAP domain. Inactivation of the gene results in defective streaming during development under different conditions and a delay in developmental timing. The characterization of single domains revealed that the CH domain of GxcDD functions as a membrane association domain, the RhoGEF domain can physically interact with a subset of Rac GTPases, and the ArfGAP-PH tandem accumulates in cortical regions of the cell and on phagosomes. Our results also suggest that a conformational change may be required for activation of GxcDD, which would be important for its downstream signaling. Conclusion The data indicate that GxcDD is involved in proper streaming and development. We propose that GxcDD is not only a component of the Rac signaling pathway in Dictyostelium, but is also involved in integrating different signals. We provide evidence for a Calponin Homology domain acting as a membrane association domain. GxcDD can bind to several Rac GTPases, but its function as a nucleotide exchange factor needs to be studied further.

  12. An Effective Configuration of Ensemble Size and Horizontal Resolution for the NCEP GEFS

    MA Juhui; Yuejian ZHU; Richard WOBUS; Panxing WANG

    2012-01-01

    Two important questions are addressed in this paper using the Global Ensemble Forecast System (GEFS)from the National Centers for Environmental Prediction (NCEP):(1) How many ensemble members are needed to better represent forecast uncertainties with limited computational resources? (2) What is the relative impact on forecast skill of increasing model resolution and ensemble size? Two-month experiments at T126L28 resolution were used to test the impact of varying the ensemble size from 5 to 80 menbers at the 500-hPa geopotential height.Results indicate that increasing the ensemble size leads to significant improvements in the performance for all forecast ranges when measured by probabilistic metrics,but these improvements are not significant beyond 20 members for long forecast ranges when measured by deterministic metrics.An ensemble of 20 to 30 members is the most effective configuration of ensemble sizes by quantifying the tradeoff between ensemble performance and the cost of computational resources.Two representative configurations of the GEFS-the T126L28 model with 70 members and the T190L28 model with 20 members,which have equivalent computing costs-were compared.Results confirm that,for the NCEP GEFS,increasing the model resolution is more (less) beneficial than increasing the ensemble size for a short (long) forecast range.

  13. Assessing Tropical Cyclone Forecast Skill in the GEFS Reforecast Version 2

    Wang, Z.; LI, W.; Peng, M.

    2015-12-01

    The prediction skill of tropical cyclone (TC) activity in the Global Ensemble Forecasting System (GEFS) Reforecast Version-2 is evaluated. The GEFS captures the seasonality of TC genesis (TCG) reasonably well over the Atlantic. The performance of the model varies over different basins, and quantitative errors are found in the spatial distribution of TCGs. The biases in TC tracks are largely attributed to the biases in the TCG and the the large-scale steering flows. Analyzing the genesis potential index (GPI) shows that the biases in the monsoon trough and subtropical high induce the TC biases in the western North Pacific, while the southward displacement of the ITCZ leads to errors in TCG over the eastern North Pacific. The over-prediction of TCGs near the West African coast is associated with the hyperactive tropical easterly waves over the African continent. The diabatic heating rate (Q1) field in the GEFS forecasts suggests a much deeper and stronger convection than in the ERA-Interim, which can be attributed to the deficiency of model cumulus scheme. The study suggests that the better prediction of the large-scale circulation and synoptic-scale waves can help improve the TC forecasts.

  14. The regulation of RhoGEF Lfc by dynein light chain Tctex-1

    Balan, Marc

    Lfc is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RhoA, and its GEF activity is tightly regulated through protein-protein interactions, phosphorylation, and cellular localization. Lfc is anchored to microtubules through its interaction with the dynein light chain Tctex-1, which results in inhibition of Lfc's GEF activity. Here we present a crystallographic structure of Tctex-1 in complex with Lfc with residues 143-155 of Lfc bound at the Tctex-1 dimer interface. Structural alignment of our structure with Tctex-1 in complex with the dynein intermediate chain (DIC) shows the binding site of the DIC peptide and Lfc substantially overlap. Biochemical evidence, NMR perturbations assays and intrinsic fluorescence provide structural validation and support an extension of the Lfc binding site to the andalpha;-helices that may accommodate additional contact points with Tctex-1. We postulate a potential mechanism for Lfcandrsquo;s recruitment to the microtubules through a tripartite complex with Tctex-1 and DIC.

  15. Hotelzon's B2B content marketing plan

    Nguyen, Trang

    2015-01-01

    This thesis follows a research-based structure. The objective of this research was to help the case company Hotelzon develop a practical business-to-business (B2B) content marketing plan to engage new customers. The research topic came up when the case company named Hotelzon started expanding its business to many other countries. Therefore, attracting new prospects has become a critical issue to B2B corporates in this online world and constantly changing business environment. The first pa...

  16. SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localizes preferentially at post-synaptic specializations of inhibitory synapses

    Fukaya, M; Kamata, A.; Hara, Y; Tamaki, H.; Katsumata, O.; Ito, N.; Takeda, S.; Hata, Y; Suzuki, T.; Watanabe, M.(Niigata University, 950-2181, Niigata, Japan); Harvey, R J; Sakagami, H.

    2011-01-01

    SynArfGEF, also known as BRAG3 or IQSEC3, is a member of the brefeldin A-resistant Arf-GEF/IQSEC family and was originally identified by screening for mRNA species associated with the post-synaptic density fraction. In this study, we demonstrate that synArfGEF activates Arf6, using Arf pull down and transferrin incorporation assays. Immunohistochemical analysis reveals that synArfGEF is present in somata and dendrites as puncta in close association with inhibitory synapses, whereas immunoelec...

  17. SynArfGEF is a guanine nucleotide exchange factor for Arf6 and localizes preferentially at post-synaptic specializations of inhibitory synapses.

    Fukaya, Masahiro; Kamata, Akifumi; Hara, Yoshinobu; Tamaki, Hideaki; Katsumata, Osamu; Ito, Naoki; Takeda, Shin'ichi; Hata, Yutaka; Suzuki, Tatsuo; Watanabe, Masahiko; Harvey, Robert J; Sakagami, Hiroyuki

    2011-03-01

    SynArfGEF, also known as BRAG3 or IQSEC3, is a member of the brefeldin A-resistant Arf-GEF/IQSEC family and was originally identified by screening for mRNA species associated with the post-synaptic density fraction. In this study, we demonstrate that synArfGEF activates Arf6, using Arf pull down and transferrin incorporation assays. Immunohistochemical analysis reveals that synArfGEF is present in somata and dendrites as puncta in close association with inhibitory synapses, whereas immunoelectron microscopic analysis reveals that synArfGEF localizes preferentially at post-synaptic specializations of symmetric synapses. Using yeast two-hybrid and pull down assays, we show that synArfGEF is able to bind utrophin/dystrophin and S-SCAM/MAGI-2 scaffolding proteins that localize at inhibitory synapses. Double immunostaining reveals that synArfGEF co-localizes with dystrophin and S-SCAM in cultured hippocampal neurons and cerebellar cortex, respectively. Both β-dystroglycan and S-SCAM were immunoprecipitated from brain lysates using anti-synArfGEF IgG. Taken together, these findings suggest that synArfGEF functions as a novel regulator of Arf6 at inhibitory synapses and associates with the dystrophin-associated glycoprotein complex and S-SCAM. PMID:21198641

  18. Activation of G proteins by GIV-GEF is a pivot point for insulin resistance and sensitivity.

    Ma, Gary S; Lopez-Sanchez, Inmaculada; Aznar, Nicolas; Kalogriopoulos, Nicholas; Pedram, Shabnam; Midde, Krishna; Ciaraldi, Theodore P; Henry, Robert R; Ghosh, Pradipta

    2015-11-15

    Insulin resistance (IR) is a metabolic disorder characterized by impaired insulin signaling and cellular glucose uptake. The current paradigm for insulin signaling centers upon the insulin receptor (InsR) and its substrate IRS1; the latter is believed to be the sole conduit for postreceptor signaling. Here we challenge that paradigm and show that GIV/Girdin, a guanidine exchange factor (GEF) for the trimeric G protein Gαi, is another major hierarchical conduit for the metabolic insulin response. By virtue of its ability to directly bind InsR, IRS1, and phosphoinositide 3-kinase, GIV serves as a key hub in the immediate postreceptor level, which coordinately enhances the metabolic insulin response and glucose uptake in myotubes via its GEF function. Site-directed mutagenesis or phosphoinhibition of GIV-GEF by the fatty acid/protein kinase C-theta pathway triggers IR. Insulin sensitizers reverse phosphoinhibition of GIV and reinstate insulin sensitivity. We also provide evidence for such reversible regulation of GIV-GEF in skeletal muscles from patients with IR. Thus GIV is an essential upstream component that couples InsR to G-protein signaling to enhance the metabolic insulin response, and impairment of such coupling triggers IR. We also provide evidence that GIV-GEF serves as therapeutic target for exogenous manipulation of physiological insulin response and reversal of IR in skeletal muscles. PMID:26378251

  19. GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors.

    Atsuko Fukazawa

    2008-11-01

    Full Text Available Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1 mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-kappaB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-kappaB activation by H-Ala-D-gammaGlu-DAP (gammaTriDAP. GEF-H1 is essential for NF-kappaB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens.

  20. KlROM2 encodes an essential GEF homologue in Kluyveromyces lactis.

    Lorberg, Anja; Schmitz, Hans-Peter; Gengenbacher, Ute; Heinisch, Jürgen J

    2003-05-01

    Cellular integrity in yeasts is ensured by a rigid cell wall whose synthesis is controlled by a MAP kinase signal transduction cascade. In Saccharomyces cerevisiae upstream regulatory components of this MAP kinase pathway involve a single protein kinase C, which is regulated in part by interaction with the small GTPase Rho1p. This small G protein is in turn rendered inactive (GDP-bound) or is activated (GTP-bound) by the influence of GTPase activating proteins (GAPs) and the GDP/GTP exchange factors (GEFs), respectively. We report here on the isolation of a gene from Kluyveromyces lactis, KlROM2, which encodes a member of the latter protein family. The nucleotide sequence contains an open reading frame of 1227 amino acids, with an overall identity of 57% to the Rom2 protein of S. cerevisiae. Four conserved sequence motifs could be identified: a RhoGEF domain, a DEP sequence, a CNH domain and a less conserved pleckstrin homology (PH) sequence. Klrom2 null mutants show a lethal phenotype, which indicates that the gene may encode the only functional GEF regulating the cellular integrity pathway in K. lactis. Conditional genomic expression of KlROM2 resulted in sensitivity towards caffeine and Calcofluor white as typical phenotypes of mutants defective in this pathway. Overexpression of KIROM2 from multicopy plasmids under the control of the ScGAL1 promoter severely impaired growth in both S. cerevisiae and in K. lactis. The fact that the lethal phenotype was not prevented in mpk1 deletion mutants indicates that growth inhibition is not simply caused by hyperactivation of the Pkc1p signal transduction pathway. PMID:12734799

  1. B2B Pioneer A Millionaire Maker

    2007-01-01

    China should soon see its largest group of instant millionaires after Jack Ma,Chief Executive Officer and Chairman of Alibaba Group,announced on July 27 that the China’s preeminent e-commerce company has initiated the listing of its B2B unit alibaba.com

  2. 2000 Johnston Site 2B-P

    US Fish and Wildlife Service, Department of the Interior — Underwater Site 2B-P was established at Johnston Atoll by Dr. James Maragos, U.S. Fish & Wildlife Service, on June 30, 2000. With a start point (meter 0) at...

  3. A substrate dependent biological containment systems for Pseudomonas putida based on the Escherichia coli gef gene

    Jensen, Lars Bogø; Ramos, J. L.; Kaneva, Z.;

    1993-01-01

    operon (Pm) and the lacI gene, encoding the Lac repressor, plus xylS2, coding for a positive regulator of Pm. In liquid culture under optimal growth conditions and in sterile and nonsterile soil microcosms, P. putida KT2440 (pWWO) bearing the containment system behaves as designed. In the presence of a......A model substrate-dependent suicide system to biologically contain Pseudomonas putida KT2440 is reported. The system consists of two elements. One element carries a fusion between a synthetic lac promoter (PA1-04/03) and the gef gene, which encodes a killing function. This element is contained...

  4. Dictyostelium Dock180-related RacGEFs Regulate the Actin Cytoskeleton during Cell Motility

    Para, Alessia; Krischke, Miriam; Merlot, Sylvain; Shen, Zhouxin; Oberholzer, Michael; Lee, Susan; Briggs, Steven; Firtel, Richard A.

    2009-01-01

    Cell motility of amoeboid cells is mediated by localized F-actin polymerization that drives the extension of membrane protrusions to promote forward movements. We show that deletion of either of two members of the Dictyostelium Dock180 family of RacGEFs, DockA and DockD, causes decreased speed of chemotaxing cells. The phenotype is enhanced in the double mutant and expression of DockA or DockD complements the reduced speed of randomly moving DockD null cells' phenotype, suggesting that DockA ...

  5. Which Way In? The RalF Arf-GEF Orchestrates Rickettsia Host Cell Invasion.

    Kristen E Rennoll-Bankert

    2015-08-01

    Full Text Available Bacterial Sec7-domain-containing proteins (RalF are known only from species of Legionella and Rickettsia, which have facultative and obligate intracellular lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS effector, is a guanine nucleotide exchange factor (GEF of ADP-ribosylation factors (Arfs, activating and recruiting host Arf1 to the Legionella-containing vacuole. In contrast, previous in vitro studies showed R. prowazekii (Typhus Group RalF is a functional Arf-GEF that localizes to the host plasma membrane and interacts with the actin cytoskeleton via a unique C-terminal domain. As RalF is differentially encoded across Rickettsia species (e.g., pseudogenized in all Spotted Fever Group species, it may function in lineage-specific biology and pathogenicity. Herein, we demonstrate RalF of R. typhi (Typhus Group interacts with the Rickettsia T4SS coupling protein (RvhD4 via its proximal C-terminal sequence. RalF is expressed early during infection, with its inactivation via antibody blocking significantly reducing R. typhi host cell invasion. For R. typhi and R. felis (Transitional Group, RalF ectopic expression revealed subcellular localization with the host plasma membrane and actin cytoskeleton. Remarkably, R. bellii (Ancestral Group RalF showed perinuclear localization reminiscent of ectopically expressed Legionella RalF, for which it shares several structural features. For R. typhi, RalF co-localization with Arf6 and PI(4,5P2 at entry foci on the host plasma membrane was determined to be critical for invasion. Thus, we propose recruitment of PI(4,5P2 at entry foci, mediated by RalF activation of Arf6, initiates actin remodeling and ultimately facilitates bacterial invasion. Collectively, our characterization of RalF as an invasin suggests that, despite carrying a similar Arf-GEF unknown from other bacteria, different intracellular lifestyles across Rickettsia and Legionella species have driven divergent roles

  6. Diasporenbankanalyse zum Nachweis gefährdeter Segetalarten auf ehemaligen Ackerstandorten : Keimlingsauflaufverfahren versus Freilandauflaufverfahren

    Kurtz, Christine; Heinken, Thilo

    2011-01-01

    Im Rahmen des DBU-Projekts „100 Äcker für die Vielfalt“ für den Schutz heimischer Ackerwildkrautvegetation wurden im Osten von Brandenburg sieben potenzielle Schutzackerflächen untersucht. Auf den sandigen bis lehmigen, z. T. basen- und kalkreichen Brachen oder Grünlandstandorten in Hanglage, die seit 2, 20 oder 50 Jahren nicht mehr ackerbaulich genutzt werden, wuchsen zur Zeit der Ackernutzung gefährdete Segetalarten wie Agrostemma githago, Arnoseris minima, Nigella arvensis und Stachys annu...

  7. The World Bank's GEF Program in the Middle East and North Africa Region : Global Environmental Benefits Contributing to National Development Goals

    World Bank; Global Environment Facility

    2014-01-01

    The report focuses on the two decades of the World Bank - Global Environment Facility (GEF) partnership with the Middle East and North Africa (MENA) countries. This partnership has had a global environmental impact by working both at the local and national level and engaging all relevant partners and stakeholders. In addition, many GEF financed operations stand as examples of what a more h...

  8. Specific retention of the protostome-specific PsGEF may parallel with the evolution of mushroom bodies in insect and lophotrochozoan brains

    Kohno Keigo

    2009-05-01

    Full Text Available Abstract Background Gene gain and subsequent retention or loss during evolution may be one of the underlying mechanisms involved in generating the diversity of metazoan nervous systems. However, the causal relationships acting therein have not been studied extensively. Results We identified the gene PsGEF (protostome-specific GEF, which is present in all the sequenced genomes of insects and limpet but absent in those of sea anemones, deuterostomes, and nematodes. In Drosophila melanogaster, PsGEF encodes a short version of a protein with the C2 and PDZ domains, as well as a long version with the C2, PDZ, and RhoGEF domains through alternative splicing. Intriguingly, the exons encoding the RhoGEF domain are specifically deleted in the Daphnia pulex genome, suggesting that Daphnia PsGEF contains only the C2 and PDZ domains. Thus, the distribution of PsGEF containing the C2, PDZ, and RhoGEF domains among metazoans appears to coincide with the presence of mushroom bodies. Mushroom bodies are prominent neuropils involved in the processing of multiple sensory inputs as well as associative learning in the insect, platyhelminth, and annelid brains. In the adult Drosophila brain, PsGEF is expressed in mushroom bodies, antennal lobe, and optic lobe, where it is necessary for the correct axon branch formation of alpha/beta neurons in mushroom bodies. PsGEF genetically interacts with Rac1 but not other Rho family members, and the RhoGEF domain of PsGEF induces actin polymerization in the membrane, thus resulting in the membrane ruffling that is observed in cultured cells with activated forms of Rac. Conclusion The specific acquisition of PsGEF by the last common ancestor of protostomes followed by its retention or loss in specific animal species during evolution demonstrates that there are some structural and/or functional features common between insect and lophotrochozoan nervous systems (for example, mushroom bodies, which are absent in all deuterostomes

  9. WTS-2 b: Too close for comfort?

    Kovács G.

    2013-04-01

    Full Text Available We report the discovery of WTS-2 b, a typical hot Jupiter in an unusually close 1.02-day orbit to a K-dwarf star. This is the second planet to be discovered in the infrared light curves of the WFCAM Transit Survey (WTS and is only one-and-a-half times the separation from its host star at which is would be destroyed by Roche lobe overflow. The predicted remaining lifetime of the planet is just 38 Myrs, assuming a tidal dissipation quality factor of Q'* = 106. The magnitude of Q'* is largely unconstrained by observations, thus WTS-2 b provides a useful calibration point for theories describing how frictional processes within a host star affect the tidal orbital evolution of its companion giant planets. It is expected that stars with large convective envelopes are more efficient at dissipating the orbital energy of the planet, and WTS-2 b provides an observational constraint in the sparsely populated K-dwarf regime. In addition, despite its relatively faint magnitude, the favourable size ratio of the WTS-2 star-planet system and the predicted hot equilibrium temperature of the planet will make it possible to characterise the planet's atmosphere via secondary eclipse measurements using existing ground-based instrumentation.

  10. Cdk5-mediated phosphorylation of RapGEF2 controls neuronal migration in the developing cerebral cortex.

    Ye, Tao; Ip, Jacque P K; Fu, Amy K Y; Ip, Nancy Y

    2014-01-01

    During cerebral cortex development, pyramidal neurons migrate through the intermediate zone and integrate into the cortical plate. These neurons undergo the multipolar-bipolar transition to initiate radial migration. While perturbation of this polarity acquisition leads to cortical malformations, how this process is initiated and regulated is largely unknown. Here we report that the specific upregulation of the Rap1 guanine nucleotide exchange factor, RapGEF2, in migrating neurons corresponds to the timing of this polarity transition. In utero electroporation and live-imaging studies reveal that RapGEF2 acts on the multipolar-bipolar transition during neuronal migration via a Rap1/N-cadherin pathway. Importantly, activation of RapGEF2 is controlled via phosphorylation by a serine/threonine kinase Cdk5, whose activity is largely restricted to the radial migration zone. Thus, the specific expression and Cdk5-dependent phosphorylation of RapGEF2 during multipolar-bipolar transition within the intermediate zone are essential for proper neuronal migration and wiring of the cerebral cortex. PMID:25189171

  11. Report on series 2B reflood experiment

    Series 2B reflood experiment was carried out from April to May 1975, as follows: 1) injection of coolant water from the downcomer at a constant head into the test section having a flow resistance simulator of the primary loop, 2) under an atmospheric pressure, 3) in constant power density, 4) with heater rod temperature up to 6000C. The objectives are to examine quantitatively system effect and to check performance of the reflood test rig. The effect of the coolant injection mode, relation between oscillatory phenomena and core thermo-hydrodynamics, and technological problems of the test rig were observed. (auth.)

  12. WTS-2 b: Too close for comfort?

    Kovács G.; Sipőcz B.; Pinfield D.J.; Hodgkin S.T.; Mustill A.; Ivanyuk O.; Koppenhoefer J.; Cruz P; Cappetta M.; Birkby J.L.; Saglia R.; Pavlenko Y.

    2013-01-01

    We report the discovery of WTS-2 b, a typical hot Jupiter in an unusually close 1.02-day orbit to a K-dwarf star. This is the second planet to be discovered in the infrared light curves of the WFCAM Transit Survey (WTS) and is only one-and-a-half times the separation from its host star at which is would be destroyed by Roche lobe overflow. The predicted remaining lifetime of the planet is just 38 Myrs, assuming a tidal dissipation quality factor of Q'* = 106. The magnitude of Q'* is largely u...

  13. The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits

    2005-04-01

    Full Text Available The heterotrimeric G-protein alpha subunit has long been considered a bimodal, GTP-hydrolyzing switch controlling the duration of signal transduction by seven-transmembrane domain (7TM cell-surface receptors. In 1996, we and others identified a superfamily of “regulator of G-protein signaling” (RGS proteins that accelerate the rate of GTP hydrolysis by Gα subunits (dubbed GTPase-accelerating protein or “GAP” activity. This discovery resolved the paradox between the rapid physiological timing seen for 7TM receptor signal transduction in vivo and the slow rates of GTP hydrolysis exhibited by purified Gα subunits in vitro. Here, we review more recent discoveries that have highlighted newly-appreciated roles for RGS proteins beyond mere negative regulators of 7TM signaling. These new roles include the RGS-box-containing, RhoA-specific guanine nucleotide exchange factors (RGS-RhoGEFs that serve as Gα effectors to couple 7TM and semaphorin receptor signaling to RhoA activation, the potential for RGS12 to serve as a nexus for signaling from tyrosine kinases and G-proteins of both the Gα and Ras-superfamilies, the potential for R7-subfamily RGS proteins to couple Gα subunits to 7TM receptors in the absence of conventional Gβγ dimers, and the potential for the conjoint 7TM/RGS-box Arabidopsis protein AtRGS1 to serve as a ligand-operated GAP for the plant Gα AtGPA1. Moreover, we review the discovery of novel biochemical activities that also impinge on the guanine nucleotide binding and hydrolysis cycle of Gα subunits: namely, the guanine nucleotide dissociation inhibitor (GDI activity of the GoLoco motif-containing proteins and the 7TM receptor-independent guanine nucleotide exchange factor (GEF activity of Ric‑8/synembryn. Discovery of these novel GAP, GDI, and GEF activities have helped to illuminate a new role for Gα subunit GDP/GTP cycling required for microtubule force generation and mitotic spindle function in chromosomal

  14. What Happened with Spectrometer Magnet 2B

    Green, Michael A

    2010-05-27

    The spectrometer solenoid is supposed to be the first magnets installed in MICE [1]-[4]. This report described what happened during the test of the MICE spectrometer solenoid 2B. First, the report describes the temperatures in the magnet, the cooler top plate and the shield during the run where the magnet quenched at 258 A. During this quench, a lead between the bottom of the HTS leads and the diode bank burned out causing the magnet to quench. Second, three methods for measuring the net heat flow into the cold mass are described. Third, there is a discussion of possible resistive heating in the HTS leads between liquid helium temperature and the copper plate, which is at about 50 K. Fourth, there is a discussion of the measured first stage heat loads in the magnet, when there is no current in the magnet. The first stage heat load calculations are based on knowing the first stage temperatures of the three two-stage pulse tube coolers and the single stage GM cooler. Fifth, the estimated heat load to the first stage when the magnet has current in it is discussed. Sixth, there is a comparison of the stage 1 heat loads in magnet 1A [5], magnet 2A [6], and magnet 2B [7]. Finally there is a discussion of recommended changes for improving the spectrometer solenoids so that the coolers can keep them cold.

  15. What Happened with Spectrometer Magnet 2B

    The spectrometer solenoid is supposed to be the first magnets installed in MICE (1)-(4). This report described what happened during the test of the MICE spectrometer solenoid 2B. First, the report describes the temperatures in the magnet, the cooler top plate and the shield during the run where the magnet quenched at 258 A. During this quench, a lead between the bottom of the HTS leads and the diode bank burned out causing the magnet to quench. Second, three methods for measuring the net heat flow into the cold mass are described. Third, there is a discussion of possible resistive heating in the HTS leads between liquid helium temperature and the copper plate, which is at about 50 K. Fourth, there is a discussion of the measured first stage heat loads in the magnet, when there is no current in the magnet. The first stage heat load calculations are based on knowing the first stage temperatures of the three two-stage pulse tube coolers and the single stage GM cooler. Fifth, the estimated heat load to the first stage when the magnet has current in it is discussed. Sixth, there is a comparison of the stage 1 heat loads in magnet 1A (5), magnet 2A (6), and magnet 2B (7). Finally there is a discussion of recommended changes for improving the spectrometer solenoids so that the coolers can keep them cold.

  16. To be or not B2B?

    Symons, L J

    2001-01-01

    La question du commerce électronique interentreprises par le web (Business to Business, B2B) est posée actuellement par les grands groupes industriels impliqués dans le commerce mondial. Les prévisions sont imposantes, le B2B atteindra le C.A. de 3000 milliards de dollars en 2003. Les conditions d'accès, la façon de procéder des deux organisateurs (ARIBA et COMMERCE ONE) des plus grandes places de marchés actuelles, sont décrites. La base de l'énorme pyramide est le catalogue électronique multilingue UNSPSC (United Nations Standard Products and Services Classification) et l'organisation ECCMA (Electronic Commerce Code Management Association) qui gère le développement des UNSPSC codes en 8 langues. Dans ce contexte, l'auteur (re)-déclare qu'un des efforts principaux à fournir par le CERN est la création de son propre catalogue électronique. Dans la Division ST, une aide partielle à ce vaste programme pourrait être apportée par la normalisation des codes et désignations des pièces de maint...

  17. Hypokalzämie nach totaler Thyreoidektomie: Welche Patienten sind gefährdet?

    Kern B

    2010-01-01

    Full Text Available Die Hypokalzämie bedingt durch eine Dysfunktion der Nebenschilddrüsen ist eine mögliche Komplikation nach totaler Thyreoidektomie. Die Inzidenz des passageren Hypoparathyreoidismus liegt bei 8 %, die des permanenten Hypoparathyreoidismus bei 1,5 %. Ursachen sind hauptsächlich die Devaskularisation oder die akzidentielle Entfernung der Nebenschilddrüse intraoperativ. Üblicherweise erfolgen nach totaler Thyreoidektomie repetitive Kalziumkontrollen, um einer symptomatischen Hypokalzämie vorzubeugen. Durch die intraoperative Parathormonmessung können Patienten mit postoperativem Hypoparathyreoidismus frühzeitig erkannt und behandelt werden. Dadurch sind auch immer kürzere Spitalsaufenthalte möglich. Ein postoperatives intaktes Parathormon unterhalb des Normwerts oder ein intraoperativer Abfall 75 % vom Ausgangswert zeigt zuverlässig gefährdete Patienten an, welche prophylaktisch behandelt werden sollten.

  18. A substrate dependent biological containment systems for Pseudomonas putida based on the Escherichia coli gef gene

    Jensen, Lars Bogø; Ramos, J. L.; Kaneva, Z.; Molin, Søren

    1993-01-01

    A model substrate-dependent suicide system to biologically contain Pseudomonas putida KT2440 is reported. The system consists of two elements. One element carries a fusion between a synthetic lac promoter (PA1-04/03) and the gef gene, which encodes a killing function. This element is contained...... within a transposaseless mini-Tn5 transposon so that it can be integrated at random locations on the Pseudomonas chromosome. The second element, harbored by plasmid pCC102, is designed to control the first and bears a fusion between the promoter of the P. putida TOL plasmid-encoded meta-cleavage pathway...... operon (Pm) and the lacI gene, encoding the Lac repressor, plus xylS2, coding for a positive regulator of Pm. In liquid culture under optimal growth conditions and in sterile and nonsterile soil microcosms, P. putida KT2440 (pWWO) bearing the containment system behaves as designed. In the presence of a...

  19. Investigation of ambient temperature on the performance of GE-F5 gas turbine

    The role of ambient temperature in determining the performance of GE-F5 gas turbine is analysed by investigating the Shirvan gas turbine power plant 10MW, 15MW and 20MW power output. These parameters have been brought as a function of ambient temperature. The results show when ambient temperature increases 1 deg C, The compressor pressure decreases about 20kPa, compressor outlet temperature increases about 1.13 deg C and exhaust temperature increases about 2.5 deg C. It is revealed that variations are due to decreasing the efficiency of compressor and less due to mass flow rate of air reduction as ambient temperature increases at constant power output. The results shows cycle efficiency reduces 3% with increasing 50 of ambient temperature, also the m increases as ambient temperature increase for constant turbine work. These are also because of reducing the compressor efficiency as ambient temperature increases

  20. Extracellular superoxide dismutase regulates the expression of small gtpase regulatory proteins GEFs, GAPs, and GDI.

    Mikko O Laukkanen

    Full Text Available Extracellular superoxide dismutase (SOD3, which catalyzes the dismutation of superoxide anions to hydrogen peroxide at the cell membranes, regulates the cellular growth in a dose-dependent manner. This enzyme induces primary cell proliferation and immortalization at low expression levels whereas it activates cancer barrier signaling through the p53-p21 pathway at high expression levels, causing growth arrest, senescence, and apoptosis. Because previous reports suggested that the SOD3-induced reduction in the rates of cellular growth and migration also occurred in the absence of functional p53 signaling, in the current study we investigated the SOD3-induced growth-suppressive mechanisms in anaplastic thyroid cancer cells. Based on our data, the robust over-expression of SOD3 increased the level of phosphorylation of the EGFR, ERBB2, RYK, ALK, FLT3, and EPHA10 receptor tyrosine kinases with the consequent downstream activation of the SRC, FYN, YES, HCK, and LYN kinases. However, pull-down experiments focusing on the small GTPase RAS, RAC, CDC42, and RHO revealed a reduced level of growth and migration signal transduction, such as the lack of stimulation of the mitogen pathway, in the SOD3 over-expressing cells, which was confirmed by MEK1/2 and ERK1/2 Western blotting analysis. Interestingly, the mRNA expression analyses indicated that SOD3 regulated the expression of guanine nucleotide-exchange factors (RHO GEF16, RAL GEF RGL1, GTPase-activating proteins (ARFGAP ADAP2, RAS GAP RASAL1, RGS4, and a Rho guanine nucleotide-disassociation inhibitor (RHO GDI 2 in a dose dependent manner, thus controlling signaling through the small G protein GTPases. Therefore, our current data may suggest the occurrence of dose-dependent SOD3-driven control of the GTP loading of small G proteins indicating a novel growth regulatory mechanism of this enzyme.

  1. Extracellular superoxide dismutase regulates the expression of small gtpase regulatory proteins GEFs, GAPs, and GDI.

    Laukkanen, Mikko O; Cammarota, Francesca; Esposito, Tiziana; Salvatore, Marco; Castellone, Maria D

    2015-01-01

    Extracellular superoxide dismutase (SOD3), which catalyzes the dismutation of superoxide anions to hydrogen peroxide at the cell membranes, regulates the cellular growth in a dose-dependent manner. This enzyme induces primary cell proliferation and immortalization at low expression levels whereas it activates cancer barrier signaling through the p53-p21 pathway at high expression levels, causing growth arrest, senescence, and apoptosis. Because previous reports suggested that the SOD3-induced reduction in the rates of cellular growth and migration also occurred in the absence of functional p53 signaling, in the current study we investigated the SOD3-induced growth-suppressive mechanisms in anaplastic thyroid cancer cells. Based on our data, the robust over-expression of SOD3 increased the level of phosphorylation of the EGFR, ERBB2, RYK, ALK, FLT3, and EPHA10 receptor tyrosine kinases with the consequent downstream activation of the SRC, FYN, YES, HCK, and LYN kinases. However, pull-down experiments focusing on the small GTPase RAS, RAC, CDC42, and RHO revealed a reduced level of growth and migration signal transduction, such as the lack of stimulation of the mitogen pathway, in the SOD3 over-expressing cells, which was confirmed by MEK1/2 and ERK1/2 Western blotting analysis. Interestingly, the mRNA expression analyses indicated that SOD3 regulated the expression of guanine nucleotide-exchange factors (RHO GEF16, RAL GEF RGL1), GTPase-activating proteins (ARFGAP ADAP2, RAS GAP RASAL1, RGS4), and a Rho guanine nucleotide-disassociation inhibitor (RHO GDI 2) in a dose dependent manner, thus controlling signaling through the small G protein GTPases. Therefore, our current data may suggest the occurrence of dose-dependent SOD3-driven control of the GTP loading of small G proteins indicating a novel growth regulatory mechanism of this enzyme. PMID:25751262

  2. Telecom 2-B and 2-C (TC2B and TC2C)

    Dulac, J.; Alvarez, H.

    1991-01-01

    The DSN (Deep Space Network) mission support requirements for Telecom 2-B and 2-C (TC2B and TC2C) are summarized. These Telecom missions will provide high-speed data link applications, telephone, and television service between France and overseas territories as a follow-on to TC2A. Mission objectives are outlined and the DSN support requirements are defined through the presentation of tables and narratives describing the spacecraft flight profile; DSN support coverage; frequency assignments; support parameters for telemetry, command and support systems; and tracking support responsibility.

  3. Raumgefühle – Gefühlsräume. Perspektiven auf die Verschränkung von emotionalen Praktiken und Topografien der Moderne

    Benno Gammerl; Rainer Herrn

    2015-01-01

    Ausgehend von verschiedenen Ansätzen in der Forschung zu Gefühlen und Räumen umreißt der Artikel das theoretische, empirische und politische Potenzial des Spannungsfelds zwischen der affektiven Durchkreuzung geordneter Strukturen und der emotionalen Bearbeitung machtdurchwirkter Raumverhältnisse. Praktiken des urban gardening und Debatten über Gentrifizierung zeigen beispielhaft, wie Analysen der dynamischen Interaktionen zwischen Räumen und Gefühlen für eine kritische Perspektive auf Urbanit...

  4. Die Bestimmung der Schwefelbedürftigkeit von Böden mit Hilfe von Gefäßversuchen und Pflanzenanalysen

    Bosold, Madeleine Joana

    2014-01-01

    Die Ergebnisse des Gefäßversuchs zeigen deutlich, welche bedeutende Rolle Schwefel in der Pflanzenernährung spielt. Besonders die Versuchspflanzen Rotklee und Rotkleegras zeigten den positiven Effekt der Schwefelgabe auf. Der Versuchsansatz orientierte sich an den Vorgaben von Hugo Neubauer und sollte die Anwendbarkeit dieser Methode auf den Nährstoff Schwefel prüfen. Die Versuchspflanzen dieses Gefäßversuchs wurden in 10 verschiedene Düngevarianten aufgeteilt. Eine Variante wurde ausschl...

  5. Sodium Channel Gene Mutations in Children with GEFS+ and Dravet Syndrome: A Cross Sectional Study

    Seyed Hassan TONEKABONI

    2013-06-01

    Full Text Available  How to Cite This Article: Tonekaboni SH, Ebrahimi A, Bakhshandeh Bali MK, Houshmand M, Moghaddasi M, Taghdiri MM, Nasehi MM. Sodium Channel Gene Mutations in Children with GEFS+ and Dravet Syndrome: A Cross Sectional Study. Iran J Child Neurol. 2013 Winter; 7 (1:25-29. Objective Dravet syndrome or severe myoclonic epilepsy of infancy (SMEI is a baleful epileptic encephalopathy that begins in the first year of life. This syndrome specified by febrile seizures followed by intractable epilepsy, disturbed psychomotor development, and ataxia. Clinical similarities between Dravet syndrome and generalized epilepsy with febrile seizure plus (GEFS+ includes occurrence of febrile seizures and joint molecular genetic etiology. Shared features of these two diseases support the idea that these two disorders represent a severity spectrum of the same illness. Nowadays, more than 60 heterozygous pattern SCN1A mutations, which many are de novo mutations, have been detected in Dravet syndrome. Materials & Methods From May 2008 to August 2012, 35 patients who referred to Pediatric Neurology Clinic of Mofid Children Hospital in Tehran were enrolled in this study. Entrance criterion of this study was having equal or more than four criteria for Dravet syndrome. We compared clinical features and genetic findings of the patients diagnosed as Dravet syndrome or GEFS+. Results 35 patients (15 girls and 20 boys underwent genetic testing. Mean age of them was 7.7 years (a range of 13 months to 15 years. Three criteria that were best evident in SCN1A mutation positive patients are as follows: Normal development before the onset of seizures, onset of seizure before age of one year, and psychomotor retardation after onset of seizures. Our genetic testing showed that 1 of 3 (33.3% patients with clinical Dravet syndrome and 3 of 20 (15% patients that diagnosed as GEFS+, had SCN1A mutation. Conclusion In this study, normal development before seizure onset, seizures beginning

  6. INTENSIVE TECHNOLOGY IN THE OBJECTIVE OF TRAINING FUTURE TEACHERS OF TECHNOLOGY AND ENTREPRENEURSHIP IN A TRANSITION TO GEF GENERAL EDUCATION

    Latipova Liliya Nikolaevna; Latipov Zagir Azgarovich

    2013-01-01

    The modern secondary school in the transition to the GEF requires higher education system of mobile teachers. The use of intensive technologies in the training of future teachers' efficiency and effectiveness of educators. The article deals with the organization of the educational process of the subject teacher preparation technology and business to use information technology material. Proven technology in our intensive training of future teachers of technology and entrepreneurship can be tra...

  7. 7 CFR 301.80-2b - Exempted articles. 1

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.80-2b Section 301.80-2b....80-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines. (a) The following articles are exempt from the certification and permit...

  8. Genetics Home Reference: CHMP2B-related frontotemporal dementia

    ... Conditions CHMP2B-related frontotemporal dementia CHMP2B-related frontotemporal dementia Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description CHMP2B -related frontotemporal dementia is a progressive brain disorder that affects personality, ...

  9. TRUST IN B2B E-MARKETPLACES

    SEBASTIAN KOT

    2011-01-01

    Full Text Available The paper presents background of B2B exchanges and review of their forms and functionalities. The benefits and fails reasons are noticed. European enterprises interest in B2B trade is next aspect of consideration. Finally, the trust barriers of B2B exchanges are presented.

  10. Component Based System Framework for Dynamic B2B Interaction

    Hu jinmin, H.J.; Grefen, P.W.P.J.

    2002-01-01

    Business-to-business (B2B) collaboration is becoming a pivotal way to bring today's enterprises to success in the dynamically changing, e-business environment. Though many business-to-business protocols are developed to support B2B interaction, none are generally accepted. A B2B system should suppor

  11. [Dangerous dogs as a problem of regulatory law--the GefHuVO NW].

    Klindt, T

    1996-01-01

    The GefHuVO NW Council Regulation, introduced in September 1994 ("Official Ordinance with regard to the Breeding, Teaching, Special Training and Keeping of Dangerous Dogs") deals with the dangers for humankind and animals caused by dangerous dogs. Although the public is regularly disturbed by reports on injuries by certain thoroughbreds (so-called pit-bull terriers), the Regulation leaves out a conclusive catalogue of dog breeds to be classified as dangerous, and rather attempts to circumscribe the danger in abstract terms. Cooperation with the local veterinary surgeons is to provide the information necessary to prepare for the Council intervention. The Regulation lays down a canon with varying and increasing power of legal possibilities of intervention which extend from decrees regarding muzzles to a certificate of expertise, to a ban on keeping animals. In the author's estimation, this new Regulation proves to be legally superfluous and partly--insofar as it creates hitherto unknown possibilities of intervention--as impracticable, as it confronts the Council such as veterinary surgeons in administrative practice with difficult problems of assessment. PMID:8647011

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

    Waadt, Rainer; Schroeder, Julian I.

    2016-01-01

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

  13. PTK2b function during fertilization of the mouse oocyte

    Luo, Jinping [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); McGinnis, Lynda K. [Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Carlton, Carol [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Beggs, Hilary E. [Department of Ophthalmology, University of California, San Francisco, CA (United States); Kinsey, William H., E-mail: wkinsey@kumc.edu [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2014-08-01

    Highlights: • PTK2b is expressed in oocytes and is activated following fertilization. • PTK2b suppression in oocytes prevents fertilization, but not parthenogenetic activation. • PTK2b suppression prevents the oocyte from fusing with or incorporating bound sperm. • PTK2b suppressed oocytes that fail to fertilize do not exhibit calcium oscillations. - Abstract: Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development.

  14. PTK2b function during fertilization of the mouse oocyte

    Highlights: • PTK2b is expressed in oocytes and is activated following fertilization. • PTK2b suppression in oocytes prevents fertilization, but not parthenogenetic activation. • PTK2b suppression prevents the oocyte from fusing with or incorporating bound sperm. • PTK2b suppressed oocytes that fail to fertilize do not exhibit calcium oscillations. - Abstract: Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development

  15. Haplotypes frequencies of CYP2B6 in Malaysia

    N Musa

    2012-01-01

    Full Text Available Background: Drugs with complex pharmacology are used in the management of drug use disorder (DUD and HIV/AIDS in Malaysia and in parts of South-East Asia. Their multiethnic populations suggest complexity due to the genetic polymorphism, such as CYP2B6 that metabolizes methadone and anti-retroviral. Aims: Our aim was to explore the genetic polymorphism of CYP2B6 among Malays, Chinese, Indians, and opiate-dependent individuals in Malaysia. Settings and Design: The study utilized DNA from our previous studies on CYPs and new recruitments from opiate-dependent individuals. Materials and Methods: For the new recruitment, after obtaining consent and baseline demography, 5 ml blood was obtained from patients attending methadone maintenance therapy (MMT Clinics. Genomic DNA was extracted using standard methods. 10 nucleotide changes associated with CYP2B6FNx0110, CYP2B6FNx012, CYP2B6FNx0117, CYP2B6FNx0111, CYP2B6FNx018, CYP2B6FNx0114, CYP2B6FNx019, CYP2B6FNx014, CYP2B6FNx016, CYP2B6FNx0127, and CYP2B6FNx0120 were determined using multiplex nested allele-specific PCR. Statistical Analysis: Descriptive statistics were used to summarize demographic data. Differences in allele frequencies between populations were tested using Chi-squared test and were corrected using the Bonferroni test. Results: CYP2B6 polymorphism in Malaysia is variable with trends that suggest an ethnic difference. Reduced activity CYP2B6FNx016 occurred in 13% to 26% among Malays, Chinese, Indians and opiate-dependent individuals. Another ′reduced activity′, CYP2B6FNx012 allele, was found at much lower percentages in the groups. Conclusions: The relative commonness of reduced-activity CYP2B6 alleles in our study called for attention in terms of dosage requirements for MMT and ARV in Malaysia. It also implored follow-up association studies to determine its relevance and consequences in personalized medicine for drug use disorder and HIV/AIDS.

  16. Analysis list: GTF2B [Chip-atlas[Archive

    Full Text Available GTF2B Blood,Uterus + hg19 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/GT...F2B.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/GTF2B.5.tsv http://dbarchive.biosciencedbc....jp/kyushu-u/hg19/target/GTF2B.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/GTF2B.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/GTF2B.Uterus.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/hg19/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/Uterus.gml ...

  17. Knockdown of the sodium-dependent phosphate co-transporter 2b (NPT2b suppresses lung tumorigenesis.

    Seong-Ho Hong

    Full Text Available The sodium-dependent phosphate co-transporter 2b (NPT2b plays an important role in maintaining phosphate homeostasis. In previous studies, we have shown that high dietary inorganic phosphate (Pi consumption in mice stimulated lung tumorigenesis and increased NPT2b expression. NPT2b has also been found to be highly expressed in human lung cancer tissues. The association of high expression of NPT2b in the lung with poor prognosis in oncogenic lung diseases prompted us to test whether knockdown of NPT2b may regulate lung cancer growth. To address this issue, aerosols that contained small interfering RNA (siRNA directed against NPT2b (siNPT2b were delivered into the lungs of K-ras (LA1 mice, which constitute a murine model reflecting human lung cancer. Our results clearly showed that repeated aerosol delivery of siNPT2b successfully suppressed lung cancer growth and decreased cancer cell proliferation and angiogenesis, while facilitating apoptosis. These results strongly suggest that NPT2b plays a role lung tumorigenesis and represents a novel target for lung cancer therapy.

  18. Organizational patterns for knowledge capture in B2B engagements

    Niwe, Moses

    2010-01-01

    The purpose of this research is to present a means of knowledge capture in form of patterns that are solutions to reoccurring problems for business-to-business (B2B) organizations. Using empirical data, we examine the processes involved in the B2B engagement and capture valuable solutions as best practices. The collection of patterns forms a pattern language for B2B engagements that addresses operational, communication and collaboration areas of the B2B environment. The thesis is organized in...

  19. Arf6 recruits the Rac GEF Kalirin to the plasma membrane facilitating Rac activation

    Donaldson Julie G

    2007-07-01

    Full Text Available Abstract Background Many studies implicate Arf6 activity in Rac-mediated membrane ruffling and cytoskeletal reorganization. Although Arf6 facilitates the trafficking of Rac1 to the plasma membrane and in many cases Arf6 activation leads to the activation of Rac1, the details of how Arf6 influences Rac function remain to be elucidated. Results We demonstrate in binding assays and by co-immunoprecipitation that GDP-bound Arf6 binds to Kalirin5, a Rho family guanine nucleotide exchange factor, through interaction with the spectrin repeat region. In cells, expression of wild type Arf6 recruits spectrin repeat 5 and Kalirin to the plasma membrane and leads to enhanced Kalirin5-induced ruffling. By contrast, expression of an Arf6 mutant that cannot become activated, Arf6 T27N, still recruits spectrin repeat 5 and Kalirin to membranes but inhibits Kalirin5-induced ruffling in HeLa cells. Kalirin5-induced Rac1 activation is increased by the expression of wild type Arf6 and decreased by Arf6T27N. Furthermore, expression of a catalytically-inactive mutant of Kalirin5 inhibits cytoskeletal changes observed in cells expressing EFA6, an Arf6 guanine nucleotide exchange factor that leads to activation of Rac. Conclusion We show here with over-expressed proteins that the GDP-bound form of Arf6 can bind to the spectrin repeat regions in Kalirin Rho family GEFs thereby recruiting Kalirin to membranes. Although Kalirin is recruited onto membranes by Arf6-GDP, subsequent Rac activation and membrane ruffling requires Arf6 activation. From these results, we suggest that Arf6 can regulate through its GTPase cycle the activation of Rac.

  20. Characterization of Neuronal-Specific Tra2b Knock-Out Mice and Identification of Tra2b Splicing Targets

    Storbeck, Markus

    2013-01-01

    TRA2B is a serine-arginine-rich splicing factor that contributes to the alternative splicing of exons and depletion of Tra2b in the mouse causes early embryonic lethality. It modulates splice site selection in a concentration dependent fashion and associates to target exons either directly via GAA binding motifs or indirectly via interactions with other splice factors. TRA2B is highest expressed in neuronal tissue and testis and its expression and activation are controlled via an autoregulato...

  1. Insights into the Molecular Activation Mechanism of the RhoA-specific Guanine Nucleotide Exchange Factor, PDZRhoGEF

    Bielnicki, Jakub A.; Shkumatov, Alexander V.; Derewenda, Urszula; Somlyo, Avril V.; Svergun, Dmitri I.; Derewenda, Zygmunt S. (EMBL); (UV)

    2012-10-09

    PDZRhoGEF (PRG) belongs to a small family of RhoA-specific nucleotide exchange factors that mediates signaling through select G-protein-coupled receptors via G{alpha}{sub 12/13} and activates RhoA by catalyzing the exchange of GDP to GTP. PRG is a multidomain protein composed of PDZ, regulators of G-protein signaling-like (RGSL), Dbl-homology (DH), and pleckstrin-homology (PH) domains. It is autoinhibited in cytosol and is believed to undergo a conformational rearrangement and translocation to the membrane for full activation, although the molecular details of the regulation mechanism are not clear. It has been shown recently that the main autoregulatory elements of PDZRhoGEF, the autoinhibitory 'activation box' and the 'GEF switch,' which is required for full activation, are located directly upstream of the catalytic DH domain and its RhoA binding surface, emphasizing the functional role of the RGSL-DH linker. Here, using a combination of biophysical and biochemical methods, we show that the mechanism of PRG regulation is yet more complex and may involve an additional autoinhibitory element in the form of a molten globule region within the linker between RGSL and DH domains. We propose a novel, two-tier model of autoinhibition where the activation box and the molten globule region act synergistically to impair the ability of RhoA to bind to the catalytic DH-PH tandem. The molten globule region and the activation box become less ordered in the PRG-RhoA complex and dissociate from the RhoA-binding site, which may constitute a critical step leading to PRG activation.

  2. Hat intrathekal appliziertes Baclofen (Lioresal) einen neuroprotektiven Effekt im 4-Gefäßverschlussmodell der Ratte?

    Stubenvoll, Florian Michael

    2015-01-01

    Einleitung: Im 4-Gefäßverschlussmodell der Ratte wird überprüft, ob intrathekal appliziertes Baclofen einen neuroprotektiven Effekt hat. Material und Methoden: Hierzu werden zunächst 1µg/5µl Baclofen über 5 Minuten beginnend 30 Minuten vor einer 10-minütigen zerebralen Ischämie bei männlichen Wistar-Ratten intrazerebroventrikulär appliziert und gegen eine Kontrollgruppe verglichen, dann werden 2µg/5µl Baclofen über 5 Minu...

  3. Strukturelle Schwächen des transatlantischen Abkommens: TTIP gefährdet weit mehr als den Verbraucherschutz

    Dieter, Heribert

    2014-01-01

    In der Diskussion um das geplante transatlantische Handels- und Investitionsabkommen TTIP dominieren bislang Fragen des Verbraucherschutzes. Dies überrascht, denn mit dem Abkommen steht sehr viel mehr auf dem Spiel. Zum einen gefährden TTIP und ähnliche Großprojekte die Zukunft der multilateralen Handelsordnung. Zum anderen sind vor Abschluss des Vertrages gravierende Hürden zu überwinden, die bislang nicht einmal erörtert wurden; das gilt etwa für die Frage der zwischenstaatlichen Streitschl...

  4. Die Verwendung des Beraters - Über die Umformung unverdaulicher emotionaler Erfahrungen in kommunizierbare Gefühle und Gedanken

    Tietel, Erhard

    2000-01-01

    Ausgehend von dem Gefühl, als Berater häufig missbräuchlich benutzt zu werden, geht der Beitrag unter Rückgriff auf Winnicotts Konzept der "Objektverwendung" der Frage nach, wie es denn um die Fähigkeit der Ratsuchenden steht, vom Berater Gebrauch zu machen. Die Sichtung eigener Supervisions- und Beratungsprotokolle führt den Autor zu einer Auflistung der vielfältigen Arten und Weisen, wie und als was er von seinem Klientel als Berater genutzt wird. Vor dem Hintergrund von Bions Konzept des "...

  5. Gefügebildung und Langzeitbeständigkeit alternativer mineralischer Oberflächenabdichtungen von Abfalldeponien

    Kiewitt, Sebastian

    2009-01-01

    Neue Oberflächenabdichtungssysteme müssen dem Kriterium der Gleichwertigkeit gesetzlich vorgegebener Rahmenbedingungen genügen. In Castrop-Rauxel wies ein in einer Versuchsanlage verwirklichtes alternatives Konzept zur Oberflächenabdichtung die vom Gesetzgeber geforderte Langzeitbeständigkeit sowie geringe Wasserdurchlässigkeit auf. Als Ursachen für die geringen Durchlässigkeitsbeiwerte konnte der Mangel an Porenräumen, die Veränderung der Gefügestrukturen mit der Schaffußwalze un...

  6. Das Empfinden der Anderen: über emotionale Pflichterfüllung und Externalisierung von Gefühlen

    Lehner, Harald

    2014-01-01

    "Eines der bisher in der (Emotions-)Soziologie vernachlässigten Phänomene stellt die Möglichkeit zur Externalisierung von Emotionen durch Individuen dar. Wie sich theoretisch zeigen lässt, erfordern spezifische Situationen das Zeigen von Gefühlen, als eine Art soziokulturelles Gebot oder auch Pflicht zur Aufrechterhaltung der sozialen Normalität bzw. zur Verhinderung von Anomalien im symbolischen Raum. Diese Pflicht kann und wird an Dritte delegiert. Somit sind Emotionen unter bestimmten Gege...

  7. Der Verschluss nach alloplastischer infragenualer Gefäßrekonstruktion - Ursachen und Konsequenzen - Eine retrospektive Analyse 1993 - 2001

    Kegel, Christian

    2007-01-01

    Einleitung: In der Behandlung der peripheren arteriellen Verschlusskrankheit (pAVK) hat die Implantation von Kunststoffprothesen einen festen Stellenwert. Allerdings weisen diese, eine höhere Thrombogenität, Infekt- und damit auch Verschlussrate als die Eigenvene auf. Im Falle eines Bypassverschlusses ist die Extremität häufig gefährdet und es ergibt sich ein unmittelbarer Handlungsbedarf. Ziel der hier dargestellten Untersuchung war es, über einen bestimmten Zeitraum alle Fälle mit Bypassver...

  8. Genetic and bibliographic information: HTR2B [GenLibi

    Full Text Available HTR2B 5-hydroxytryptamine (serotonin) receptor 2B human alcoholism (MeSH) Disorders... of Environmental Origin (C21) > Substance-Related Disorders (C21.739) > Alcohol-Related Disorders (C21.739.100) > Alcoholism (C21.739.100.250) 01A0634580 ...

  9. 27 CFR 21.33 - Formula No. 2-B.

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Formula No. 2-B. 21.33... OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.33 Formula No. 2-B. (a) Formula. To every 100 gallons of alcohol add:...

  10. Frontotemporal dementia caused by CHMP2B mutations

    Isaacs, A M; Johannsen, P; Holm, I;

    2011-01-01

    CHMP2B mutations are a rare cause of autosomal dominant frontotemporal dementia (FTD). The best studied example is frontotemporal dementia linked to chromosome 3 (FTD-3) which occurs in a large Danish family, with a further CHMP2B mutation identified in an unrelated Belgian familial FTD patient...

  11. ORM-based semantics of B2B transactions.

    Balsters, H.; van Blommestein, F.; Meersman, R; Herrero, P; Dillon, T

    2009-01-01

    After widespread implementation of Enterprise Resource Planning and Personal Information Management, the next wave in the application of ICT is headed towards business to business (B2B) communication. B2B has a number of specific aspects, one of them being negotiation. This aspect has been largely n

  12. An investigation into the proteins responsible for the translational inhibition seen in the yeast Saccharomyces cerevisiae following fusel alcohol exposure

    Keenan, Jemma

    2013-01-01

    Fusel alcohols signal nitrogen scarcity to elicit a range of responses in the yeast Saccharomyces cerevisiae. These alcohols activate pseudohyphal growth and cause rapid inhibition of translation initiation. Previous work from our lab has highlighted that the translation initiation factor eIF2B is a target for this regulation. eIF2B is the guanine nucleotide exchange factor required for recycling eIF2•GDP to eIF2•GTP. The GTP bound form of eIF2 can interact with the Methionyl initiator tRNA ...

  13. A BAC transgenic mouse model reveals neuron subtype-specific effects of a Generalized Epilepsy with Febrile Seizures Plus (GEFS+) mutation

    Tang, Bin; Dutt, Karoni; Papale, Ligia; Rusconi, Raffaella; Shankar, Anupama; Hunter, Jessica; Tufik, Sergio; Yu, Frank H.; Catterall, William A; Mantegazza, Massimo; Goldin, Alan L.; Escayg, Andrew

    2009-01-01

    Mutations in the voltage-gated sodium channel SCN1A are responsible for a number of seizure disorders including Generalized Epilepsy with Febrile Seizures Plus (GEFS+) and Severe Myoclonic Epilepsy of Infancy (SMEI). To determine the effects of SCN1A mutations on channel function in vivo, we generated a bacterial artificial chromosome (BAC) transgenic mouse model that expresses the human SCN1A GEFS+ mutation, R1648H. Mice with the R1648H mutation exhibit a more severe response to the proconvu...

  14. Activation of p115-RhoGEF Requires Direct Association of G[alpha subscript 13] and the Dbl Homology Domain

    Chen, Zhe; Guo, Liang; Hadas, Jana; Gutowski, Stephen; Sprang, Stephen R.; Sternweis, Paul C. (IIT); (UTSMC); (Montana)

    2012-09-05

    RGS-containing RhoGEFs (RGS-RhoGEFs) represent a direct link between the G{sub 12} class of heterotrimeric G proteins and the monomeric GTPases. In addition to the canonical Dbl homology (DH) and pleckstrin homology domains that carry out the guanine nucleotide exchange factor (GEF) activity toward RhoA, these RhoGEFs also possess RGS homology (RH) domains that interact with activated {alpha} subunits of G{sub 12} and G{sub 13}. Although the GEF activity of p115-RhoGEF (p115), an RGS-RhoGEF, can be stimulated by G{alpha}{sub 13}, the exact mechanism of the stimulation has remained unclear. Using combined studies with small angle x-ray scattering, biochemistry, and mutagenesis, we identify an additional binding site for activated G{alpha}{sub 13} in the DH domain of p115. Small angle x-ray scattering reveals that the helical domain of G{alpha}{sub 13} docks onto the DH domain, opposite to the surface of DH that binds RhoA. Mutation of a single tryptophan residue in the {alpha}3b helix of DH reduces binding to activated G{alpha}{sub 13} and ablates the stimulation of p115 by G{alpha}{sub 13}. Complementary mutations at the predicted DH-binding site in the {alpha}B-{alpha}C loop of the helical domain of G{alpha}{sub 13} also affect stimulation of p115 by G{alpha}{sub 13}. Although the GAP activity of p115 is not required for stimulation by G{alpha}{sub 13}, two hydrophobic motifs in RH outside of the consensus RGS box are critical for this process. Therefore, the binding of G{alpha}{sub 13} to the RH domain facilitates direct association of G{alpha}{sub 13} to the DH domain to regulate its exchange activity. This study provides new insight into the mechanism of regulation of the RGS-RhoGEF and broadens our understanding of G protein signaling.

  15. Recent developments in A2B adenosine receptor ligands.

    Kalla, Rao V; Zablocki, Jeff; Tabrizi, Mojgan Aghazadeh; Baraldi, Pier Giovanni

    2009-01-01

    A selective, high-affinity A(2B) adenosine receptor (AR) antagonist will be useful as a pharmacological tool to help determine the role of the A(2B)AR in inflammatory diseases and angiogenic diseases. Based on early A(2B)AR-selective ligands with nonoptimal pharmaceutical properties, such as 15 (MRS 1754: K(i)(hA(2B)) = 2 nM; K(i)(hA(1)) = 403 nM; K(i)(hA(2A)) = 503 NM, and K(i)(hA(3)) = 570 nM), several groups have discovered second-generation A(2B)AR ligands that are suitable for development. Scientists at CV Therapeutics have discovered the selective, high-affinity A(2B)AR antagonist 22, a 8-(4-pyrazolyl)-xanthine derivative, (CVT-6883, K(i)(hA(2B)) = 22 nM; K(i)(hA(1)) = 1,940 nM; K(i)(hA(2A)) = 3,280; and K(i)(hA(3)) = 1,070 nM). Compound 22 has demonstrated favorable pharmacokinetic (PK) properties (T(1/2) = 4 h and F > 35% rat), and it is a functional antagonist at the A(2B)AR(K (B) = 6 nM). In a mouse model of asthma, compound 22 demonstrated a dose-dependent efficacy supporting the role of the A(2B)AR in asthma. In two Phase I clinical trails, 22 (CVT-6883) was found to be safe, well tolerated, and suitable for once-daily dosing. Baraldi et al. have independently discovered a selective, high-affinity A(2B)AR antagonist, 30 (MRE2029F20), 8-(5-pyrazolyl)-xanthine (K(i)(hA(2B)) = 5.5 nM; K(i)(hA(1)) = 200 nM; K(i)(hA(2A), A(3)) > 1,000, that has been selected for development in conjunction with King Pharmaceuticals. Compound 30 has been demonstrated to be a functional antagonist of the A(2B)AR, and it has been radiolabeled for use in pharmacological studies. A third compound, 58 (LAS-38096), is a 2-aminopyrimidine derivative (discovered by the Almirall group) that has high A(2B)AR affinity and selectivity (K(i)(hA(2B)) = 17 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 2,500; and K(i)(hA(3)) > 1,000 nM), and 58 has been moved into preclinical safety testing. A fourth selective, high-affinity A(2B)AR antagonist, 54 (OSIP339391 K(i))(hA(2B)) = 0.5 nM; K(i))(hA(1

  16. Gamma and x-ray irradiation effects on different Ge and Ge/F doped optical fibers

    We performed electron paramagnetic resonance (EPR) measurements on γ and X ray irradiated Ge doped and Ge/F co-doped optical fibers. We considered three different drawing conditions (speed and tension), and for each type of drawing, we studied Ge and Ge/F doped samples having Ge doping level above 4% by weight. The EPR data recorded for the γ ray irradiated fibers confirm that all the samples exhibit a very close radiation response regardless of the drawing conditions corresponding to values used for the production of specialty fibers. Furthermore, as for the X irradiated materials, in the γ ray irradiated F co-doped fibers, we observed that the Ge(1) and the Ge(2) defects generation is unchanged, whereas it was enhanced for the E'Ge. In the various fibers, the comparison of the γ and X-ray induced concentrations of these kinds of Ge related defects indicates that the two irradiations induce similar effects regardless of the different employed dose rates and sources. Confocal microscopy luminescence results show that the starting content of the Germanium Lone Pair Center (GLPC) is neither strongly affected by the Ge content nor by the drawing conditions, and we consider the similarity of the GLPC content as key factor in determining many of the above reported similarities

  17. Model-based generation of neutron induced fission yields up to 20 MeV by the GEF code

    Model-based fission product yields from the fission of various important target nuclides have been calculated for incident neutron energies up to 20 MeV, divided into a 77 energy group structure. The calculations have been performed with two versions of the GEF code, which have been externally coupled to TALYS-1.4. In this application, the TALYS-1.4 code calculates any pre-fission nucleon or gamma emission from the compound nucleus as well as the probabilities of excitation states at the time it undergoes fission. The obtained quantities, fully characterizing the fissioning nucleus, are then passed to GEF, which generates the corresponding primary fission product yields in a Monte Carlo calculation. Cumulative fission product yields have been calculated using these primary fission product yields together with evaluated radioactive decay data as input. The interim and final results from the modelling, i.e. cross-sections, independent and cumulative fission yields, have been compared to experimental data. Important results from this, as well as sensitivities and reliabilities of the models, are discussed in this paper. The objective of this work was to generate energy dependent fission product yields data to serve as a basis for further investigations on potential improvements of evaluated data for nuclear reactor applications, which are beyond the scope of this publication. (author)

  18. Frontotemporal dementia caused by CHMP2B mutations

    Isaacs, A M; Johannsen, P; Holm, I;

    2011-01-01

    . These mutations lead to C-terminal truncations of the CHMP2B protein and we will review recent advances in our understanding of the molecular effects of these mutant truncated proteins on vesicular fusion events within the endosome-lysosome and autophagy degradation pathways. We will also review the...... clinical features of FTD caused by CHMP2B truncation mutations as well as new brain imaging and neuropathological findings. Finally, we collate the current data on CHMP2B missense mutations, which have been reported in FTD and motor neuron disease....

  19. Sosiaalisen median strategia B2B-yritykselle

    Johansson, Mia

    2013-01-01

    Opinnäytetyössä perehdyttiin sosiaaliseen mediaan ja sen hyödyntämiseen B2B-näkökulmasta. Opinnäytetyön tarkoitus oli selvittää, miten B2B-yritys voi hyödyntää sosiaalista mediaa osana liiketoimintaansa ja miten sosiaalisen median strategia käytännössä toteutetaan. Työn aikana opinnäytetyön tekijä oli osana sosiaalisen median strategian suunnittelua ja valmistumista case-yrityksessä. Case-yritys on oululainen informaatioteknologian alalla toimiva B2B-yritys. Sosiaalisen median avulla...

  20. B2B virksomheders brug af sociale medier

    Persdatter Gotfredsen, Karoline

    2016-01-01

    Purpose: The aim of this master thesis is to explore how B2B firms perceive their own usage of social media to establish and strengthen successful relational exchanges. Approach: In-depth interviews were carried out with three key informants responsible for social media marketing at large B2B firms. The findings from the three interviews were then analysed case-by-case and finally a cross case analysis was conducted. Findings: In relation to the market B2B firms mainly see social media...

  1. Applying conceptual design to B2B sales negotiations

    Illi, Mikko; Ylirisku, Salu

    This paper addresses the challenge of perceiving B2B sales negotiation in a manner that would open up new possibilities for the improvement of the practice. B2B sales agents work under high pressure in developing relevant and appealing proposals when negotiating for a deal with a customer. The key...... problem that will be addressed is the building of understanding of a customer’s current needs and requirements, and then trying to devise an appropriate proposal to match these. The work of the sales agents in B2B sales negotiations is highly complex, as they need to understand both the modular machinery...... the ways in which design sense making artefacts may drive also B2B sales agents’ work....

  2. Crystal structure and magnetism of YPt2B

    The new ternary YPt2B compound was synthesized by arc-melting, followed by annealing at 1370 K. The structure was refined down to R = 0.0408, wR 2 = 0.0692 from single crystal X-ray diffraction data (CAD-4 diffractometer, Mo Kα, 269 reflections with I > 2σ(I o)) and to R F = 0.0539, R B = 0.0970 from X-ray powder diffraction for 77 reflections. YPt2B was found to crystallize with a CePt2B structure type, P6222 space group (no. 180) (a = 5.2977(1) A, c = 7.8875(2) A, Z = 3, V = 191.715(8) A3, ρ = 12.752 g cm-3). Magnetization and AC-susceptibility measurements indicate that there is no magnetic or superconducting transition in YPt2B down to 2 K

  3. Scope of Internal Marketing in B2B Companies

    Nigam, Niharika

    2007-01-01

    Abstract Previous studies have focused on "internal marketing" from services marketing perspective. There is, therefore, a great dearth of in-depth research on its application to other business types. This research attempts to find the scope of internal marketing in B2B companies. The purpose of this research is to closely examine the elements, their linkage, tools and applications of Internal marketing when applied to B2B settings. Internal marketing, the application of marketing managem...

  4. Branding of electricity in B2B markets

    Rolanda Simenaite 1986

    2013-01-01

    Branding has gained an important role in the B2B (business-to-business) market. Liberation of the energy markets in recent years has increased competition and branding could create a competitive advantage. This thesis analyzes the branding of electricity in a business-to-business context. In depth, this thesis explores the supplier of electricity brand importance for business customers in both Icelandic and Lithuanian B2B markets. The focus of the thesis is to research how much brands matter ...

  5. POLICY CONCERNS FOR ONLINE B2B EXCHANGES

    Hooker, Neal H.; Rha, Jong-Youn; Ernst, Stanley C.; Widdows, Richard

    2002-01-01

    Policy concerns arise as e-business activities become increasingly common. This paper discusses important elements of such concerns, particularly the pro- and anti-competitive assessment of online business-to-business (B2B) exchanges. The definition of markets, the role of quality management and communication, and join purchasing implications within such environments are related to food distribution systems. Other online business-to-consumer (B2C) and consumer-to-business (C2B) policy concern...

  6. B2B emarketplace announcements and shareholder wealth

    Andrew H. Chen; Siems, Thomas F.

    2001-01-01

    In the business-to-business (B2B) sector, new supply-chain models within electronic marketplaces (eMarketplaces) offer firms significantly lower procurement costs, increased operating efficiencies, and expanded market opportunities. Using event-study methodology to look at the period July 1999-March 2000, Andrew Chen and Thomas Siems find that investors reacted favorably to B2B eMarketplace announcements, with slightly higher abnormal returns associated with vertical than with horizontal eMar...

  7. Pyrano- und Naphthopyrano[3,2-b]indol-Derivate

    Eiden, Fritz; Wanner, Klaus Th.

    1985-01-01

    Die Pyrano[3,2-b]indole 4a-4c lassen sich durch regioselektive Reaktion des Tetrahydro-3-pyranons (3) mit den Phenylhydrazinen 6a-6c gewinnen, das Naphthopyrano[3,2-b]indol 24 entsteht durch Umsetzung des Naphthopyranons 23 mit 6a. 23 läßt sich aus dem Dihydropyranon 16 und dem Isobenzofuran 21 durch Cycloaddition und Dehydratisierung der so gewonnenen endo/exo-Epoxynaphthopyranone 22a/22b herstellen.

  8. The FRCR 2B oral examination: Is it reliable?

    Aim: To investigate the reliability of the oral component of the Fellowship of the Royal College of Radiologists (FRCR) 2B examination. Materials and methods: Anonymized candidate test scores were analysed from nine consecutive sittings of the FRCR 2B oral examination covering the period from spring 2006 to spring 2010. Interobserver reliability was assessed using weighted Kappa coefficient, intraclass correlation coefficient, and a modified Bland–Altman plot. Results: During the study period, 2235 candidates sat the FRCR 2B examination. Eighty-five point one percent of candidates obtained paired oral assessment scores within one mark of each other. This figure rises to 95.7% for paired scores within 1.5 marks of each other. Mean difference in scores was 0.67 (95% CI: 0.65–0.70). Agreement rises at the extremities of mean score. Reliability coefficients for the FRCR 2B oral examination were calculated as 0.27 (weighted Kappa) and 0.44 (intraclass correlation coefficient). Conclusion: The calculated reliability coefficients indicate fair to, at best, moderate interobserver reliability in the FRCR 2B oral examination. These findings are disappointing but are comparable with other oral assessment reliability studies. There is scope for improvement, although further work to measure the combined reliability of all the components of the FRCR 2B examination is desirable. Measures that could potentially increase reliability must be carefully considered against any negative impact on test validity, acceptability, and cost

  9. Transforming on-grid renewable energy markets. A review of UNDP-GEF support for feed-in tariffs and related price and market-access instruments

    Glemarec, Yannick; Rickerson, Wilson; Waissbein, Oliver

    2012-11-15

    As a Global Environment Facility (GEF) founding implementing agency, UNDP has worked on over 230 GEF-supported clean energy projects in close to 100 developing countries since 1992. About 100 of these projects in 80 countries have focused on renewable energy, supported by approximately US $ 293 million in GEF funds and leveraging US $1.48 billion in associated co-financing from national governments, international organizations, the private sector and non-governmental organizations. As part of UNDP efforts to codify and share lessons learnt from these initiatives, this report addresses how scarce public resources can be used to catalyze larger private financial flows for renewable energy. It provides an overview of UNDP-GEF’s extensive work supporting development of national renewable energy policies such as feed-in tariffs. In these activities UNDP-GEF assists developing countries to assess key risks and barriers to technology diffusion and then to identify a mix of policy and financial de-risking measures to remove these barriers and drive investment. This approach is illustrated through three case studies in Uruguay, Mauritius and Kazakhstan. This report is complemented by a companion publication presenting an innovative UNDP financial modeling tool to assist policymakers in appraising different public instruments to promote clean energy.

  10. Raumgefühle – Gefühlsräume. Perspektiven auf die Verschränkung von emotionalen Praktiken und Topografien der Moderne

    Benno Gammerl

    2015-08-01

    Full Text Available Ausgehend von verschiedenen Ansätzen in der Forschung zu Gefühlen und Räumen umreißt der Artikel das theoretische, empirische und politische Potenzial des Spannungsfelds zwischen der affektiven Durchkreuzung geordneter Strukturen und der emotionalen Bearbeitung machtdurchwirkter Raumverhältnisse. Praktiken des urban gardening und Debatten über Gentrifizierung zeigen beispielhaft, wie Analysen der dynamischen Interaktionen zwischen Räumen und Gefühlen für eine kritische Perspektive auf Urbanität fruchtbar werden können. Die Beschäftigung mit der Körperlichkeit von Raumgefühlen und der Materialität von Gefühlsräumen bietet willkommene Gelegenheiten, nach Strategien zu suchen, die weder das beharrliche Wirken des Sozialen noch die widerständige Kraft des Materiellen in deterministischer Manier überbetonen, sondern sich stattdessen auf die ambivalenten Dynamiken und Effekte gefühlsräumlicher Prozesse konzentrieren.

  11. A computational study of a recreated G protein-GEF reaction intermediate competent for nucleotide exchange: fate of the Mg ion.

    Mériam Ben Hamida-Rebaï

    Full Text Available Small G-proteins of the superfamily Ras function as molecular switches, interacting with different cellular partners according to their activation state. G-protein activation involves the dissociation of bound GDP and its replacement by GTP, in an exchange reaction that is accelerated and regulated in the cell by guanine-nucleotide exchange factors (GEFs. Large conformational changes accompany the exchange reaction, and our understanding of the mechanism is correspondingly incomplete. However, much knowledge has been derived from structural studies of blocked or inactive mutant GEFs, which presumably closely represent intermediates in the exchange reaction and yet which are by design incompetent for carrying out the nucleotide exchange reaction. In this study we have used comparative modelling to recreate an exchange-competent form of a late, pre-GDP-ejection intermediate species in Arf1, a well-characterized small G-protein. We extensively characterized three distinct models of this intermediate using molecular dynamics simulations, allowing us to address ambiguities related to the mutant structural studies. We observed in particular the unfavorable nature of Mg2+ associated forms of the complex and the establishment of closer Arf1-GEF contacts in its absence. The results of this study shed light on GEF-mediated activation of this small G protein and on predicting the fate of the Mg ion at a critical point in the exchange reaction. The structural models themselves furnish additional targets for interfacial inhibitor design, a promising direction for exploring potentially druggable targets with high biological specificity.

  12. Rap2B GTPase: structure, functions, and regulation.

    Zhu, Zhesi; Di, Jiehui; Lu, Zheng; Gao, Keyu; Zheng, Junnian

    2016-06-01

    Rap2B GTPase, a member of Ras-related protein superfamily, was first discovered from a platelet cDNA library in the early 1990s. Since then, it has been reported to play an important role in regulating cellular processes including cytoskeletal organization, cell growth, and proliferation. It can be stimulated and suppressed by a wide range of external and internal inducers, circulating between GTP-bound active state and GDP-bound inactive state. Increasing focus on Ras signaling pathway reveals critical effects of Rap2B on tumorigenesis. In particular, Rap2B behaves in a p53-dependent manner in regulation of apoptosis and migration. Apart from being an oncogenic activator, Rap2B has been found to participate in many other physiological events via diverse downstream effectors. In this review, we present recent studies on the structure, regulation, and multiple biological functions of Rap2B, shedding light on its potential status in treatment of cancer as well as other diseases. PMID:27012552

  13. PH Domain-Arf G Protein Interactions Localize the Arf-GEF Steppke for Cleavage Furrow Regulation in Drosophila.

    Donghoon M Lee

    Full Text Available The recruitment of GDP/GTP exchange factors (GEFs to specific subcellular sites dictates where they activate small G proteins for the regulation of various cellular processes. Cytohesins are a conserved family of plasma membrane GEFs for Arf small G proteins that regulate endocytosis. Analyses of mammalian cytohesins have identified a number of recruitment mechanisms for these multi-domain proteins, but the conservation and developmental roles for these mechanisms are unclear. Here, we report how the pleckstrin homology (PH domain of the Drosophila cytohesin Steppke affects its localization and activity at cleavage furrows of the early embryo. We found that the PH domain is necessary for Steppke furrow localization, and for it to regulate furrow structure. However, the PH domain was not sufficient for the localization. Next, we examined the role of conserved PH domain amino acid residues that are required for mammalian cytohesins to bind PIP3 or GTP-bound Arf G proteins. We confirmed that the Steppke PH domain preferentially binds PIP3 in vitro through a conserved mechanism. However, disruption of residues for PIP3 binding had no apparent effect on GFP-Steppke localization and effects. Rather, residues for binding to GTP-bound Arf G proteins made major contributions to this Steppke localization and activity. By analyzing GFP-tagged Arf and Arf-like small G proteins, we found that Arf1-GFP, Arf6-GFP and Arl4-GFP, but not Arf4-GFP, localized to furrows. However, analyses of embryos depleted of Arf1, Arf6 or Arl4 revealed either earlier defects than occur in embryos depleted of Steppke, or no detectable furrow defects, possibly because of redundancies, and thus it was difficult to assess how individual Arf small G proteins affect Steppke. Nonetheless, our data show that the Steppke PH domain and its conserved residues for binding to GTP-bound Arf G proteins have substantial effects on Steppke localization and activity in early Drosophila embryos.

  14. Multiple endocrine neoplasia type 2b associated with lichen nitidus.

    Altaykan, Asli; Ersoy-Evans, Sibel; Emre, Serap; Orhan, Diclehan; Güçer, Safak; Erkin, Gül

    2007-01-01

    Multiple endocrine neoplasia (MEN) type 2B syndrome is an autosomal dominantly inherited endocrine disorder with rare skin manifestations. We report the case of a 19-year-old Turkish girl who presented with skin-colored flat papules scattered all over the trunk and extremities. Additionally, she had marfanoid habitus, thick lips, and multiple flesh-colored papules over the inner eyelids and oral mucosa. Histopathological examination of one of the trunk lesions was consistent with lichen nitidus. Her past medical history was significant for medullary thyroid carcinoma. Genetic testing showed a point mutation in exon 16 at codon 918 (M918T) in the RET proto-oncogene. Based on all these findings, MEN type 2B was diagnosed. To the best of our knowledge we report the first case of MEN type 2B associated with lichen nitidus. PMID:17540634

  15. Expanding Interprofessional EHR Data in i2b2.

    Westra, Bonnie L; Christie, Beverly; Johnson, Steven G; Pruinelli, Lisiane; LaFlamme, Anne; Park, Jung In; Sherman, Suzan G; Byrne, Matthew D; Ranallo, Piper; Speedie, Stuart

    2016-01-01

    Emerging issues of team-based care, precision medicine, and big data science underscore the need for health information technology (HIT) tools for integrating complex data in consistent ways to achieve the triple aims of improving patient outcomes, patient experience, and cost reductions. The purpose of this study was to demonstrate the feasibility of creating a hierarchical flowsheet ontology in i2b2 using data-derived information models and determine the underlying informatics and technical issues. This study is the first of its kind to use information models that aggregate team-based care across time, disciplines, and settings into 14 information models that were integrated into i2b2 in a hierarchical model. In the process of successfully creating a hierarchical ontology for flowsheet data in i2b2, we uncovered a variety of informatics and technical issues described in this paper. PMID:27570680

  16. B2B-verkkokaupan internetmarkkinointi : Case: More On Oy

    Toivonen, Niina; Jesar, Rama

    2012-01-01

    Opinnäytetyön tavoitteena on selvittää, millaiseksi More On Oy B2B-liikelahjayrityksen verkko¬-kaupan internetmarkkinointi pitää suunnitella, jotta uusi verkkokauppa antaa hyvän kuvan yrityksestä. Opinnäytetyö on tehty laadullisin tutkimusmenetelmin ja se on rajattu käsittelemään B2B-verkkokaupan internetmarkkinointia erityisesti toimeksiantajayrityksen näkökulmasta. Opinnäytetyön teoriaosuudessa on kerrottu verkkokaupasta yleisesti sekä verkkokaupan inter-netmarkkinoinnin keinoista. More...

  17. Customized E-Learning for B2B Companies

    Tim Thomasma

    2014-06-01

    Full Text Available Business-to-Business (B2B companies have customers that are primarily other corporations. These companies have unique problems in workplace training. They must train their customers and their customers’ employees. A B2B company may operate with only a few dozen employees, but they may need to help thousands of customers learn how to make best use of their product or service. Discussions with industry executives suggest an ideal training solution might include a number of features that are reviewed in this paper.

  18. Digitaalisen markkinoinnin suunnitelma b2b-yritykselle

    Harhakoski, Oskari

    2011-01-01

    Työ käsittelee digitaalisen markkinoinnin suunnitelman tekemistä b2b-yritykselle. Tavoitteena oli kilpailuedun hankkiminen sosiaalisen median tehokkaalla hyödyntämisellä mark-kinoinnissa. Konkreettisemmin yritys halusi lisää näkyvyyttä ja myyntiä. Suunnitelman laatimisessa hyödynnettiin POST-menetelmää. Erityistä huomiota kiinnitettiin b2b-markkinoinnin eroihin b2c-markkinointiin verrattuna. Myös yrityksen toimiminen Suomen markkinoilla huomioitiin. Lisäksi analysoitiin kilpailijoita asia...

  19. B2B-asiantuntijayritys ja sosiaalinen media

    Sahlman, Katriina

    2012-01-01

    Tämän tutkimuksen tarkoituksena on selvittää, miten B2B-asiantuntijayritykset toimivat sosiaalisessa mediassa, miten ne hyödyntävät sitä palvelujensa ja brändinsä markkinointiin sekä lopulta liiketoimintansa edistämiseen. Tutkimus suoritettiin haastattelumuotoisena, laadullisena tutkimuksena. Tutkimukseen haastateltiin yhdeksää B2B-asiantuntijayrityksissä toimivaa, sosiaalista mediaa työkseen tai sen parissa työskentelevää henkilöä, jotka myös vapaa-ajallaan aktiivisesti käyttävät sosiaal...

  20. Marketing-sales interface configurations in B2B firms

    Biemans, Wim G.; Brencic, Maja Makovec; Malshe, Avinash; Makovec Brenciv, M.

    2010-01-01

    As the body of knowledge on marketing-sales interface expands, there is a greater need to investigate the specific aspects of marketing-sales configurations in B2B firms. Using a qualitative methodology and interview data collected from over 100 sales and marketing professionals from the US, The Net

  1. Supporting B2B Business Documents in XML Web Services

    KIM Hyoungdo

    2004-01-01

    While XML web services become recognized as a solution to business-to-business transactions, there are many problems that should be solved. For example, it is not easy to manipulate business documents of existing standards such as RosettaNet and UN/EDIFACT EDI, traditionally regarded as an important resource for managing B2B relationships. As a starting point for the complete implementation of B2B web services, this paper deals with how to support B2B business documents in XML web services. In the first phase, basic requirements for driving XML web services by business documents are introduced. As a solution, this paper presents how to express B2B business documents in WSDL, a core standard for XML web services. This kind of approach facilitates the reuse of existing business documents and enhances interoperability between implemented web services. Furthermore, it suggests how to link with other conceptual modeling frameworks such as ebXML/UMM, built on a rich heritage of electronic business experience.

  2. VO2(B) nanospheres: Hydrothermal synthesis and electrochemical properties

    Monodisperse VO2(B) nanospheres with an average size of 100 nm were synthesized by hydrothermal method. Experiments showed that the surfactant octadecyl-amine played an important role during the formation of the nanospheres, and possible mechanism was suggested. Moreover, the potential uses of VO2 nanospheres were primarily probed as electrodes for lithium-ion batteries.

  3. Il B2B e il paradigma dei costi di transazione (B2B and the Transaction Costs Paradigm

    Pierluigi Sabbatini

    2001-06-01

    Full Text Available Business to Business (B2B Internet commerce causes a significant contraction of transaction costs. According to the Coase paradigm, we would thus expect a deverticalization of the industry and broader scope for anonymous market mechanisms. In reality, such expectations are not fully borne out by the facts. When the industrial structure is concentrated the B2Bgenerally loses its independence, and is owned by the firms which most contribute to its development, e.g. the ones able to bring the liquidity to it. The B2B governance mechanism established by these firms gives hierarchical mechanisms a role which they do not usually play in extensive, anonymous markets.

  4. Mechanochemical synthesis and characterization of pure Co$_2$B nanocrystals

    MUSTAFA BARIS; TUNCAY SIMSEK; ADNAN AKKURT

    2016-08-01

    Cobalt boride (Co$_2$B) is a significant transition metal boride having a wide range of usage area due to its high oxidation, abrasion and corrosion resistance as well as its superior electrochemical, magnetic and anisotropicproperties. In this study, pure Co2B nanocrystals were synthesized with Co, B$_2$O$_3$ and Mg as starting materials via the mechanochemical synthesis (MCS) method by high-energy planetary ball mill in a hardened steel vial withhardened steel balls. All the experiments were conducted under Ar atmosphere at different rotational speeds and at 20:1–30:1–40:1 ball-to-powder ratios. Leaching of Co$_2$B $+$ MgO powder mixtures occurred after milling andpurified with acetic acid and pure Co$_2$B nanocrystals were obtained in solid form. The Co2Bs were characterized through X-ray diffraction, scanning electronmicroscopy, vibrating samplemagnetometer, Brunauer–Emmett–Tellerand specific density analyses, and effects of synthesis parameters on product properties were revealed. Surface areas of the powders synthesized at 40:1 ball-to-powder ratio at different rotational speeds were measured as 21.14,40.36 and 52.33 m$^2$ g$^{−1}$, respectively. Crystallite sizes of Co$_2$B nanocrystals were between 7.27 and 9.84 nm and their specific density varied between 7.61 and 7.78 g cm$^{−3}$. It was determined that all samples were saturated and exhibited hysteresis and ferromagnetic behaviours, and saturation magnetization was between 35 and 50 emu g$^{−1}$.

  5. GRIN2B predicts attention problems among disadvantaged children.

    Riva, Valentina; Battaglia, Marco; Nobile, Maria; Cattaneo, Francesca; Lazazzera, Claudio; Mascheretti, Sara; Giorda, Roberto; Mérette, Chantal; Émond, Claudia; Maziade, Michel; Marino, Cecilia

    2015-07-01

    It is well established that adversities and GRIN2B (coding an N-methyl-D-aspartate receptor subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to adversities have good, long-term outcomes. We hypothesized that among children exposed to adversities, GRIN2B variants would predict the worst cognitive and behavioral outcomes. 6 single nucleotide polymorphisms of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interacting effect of GRIN2B variants with 4 measures of adversities [low socioeconomic status (SES), preterm delivery, maternal smoking during pregnancy, and absence of breastfeeding] was investigated upon blindly assessed cognitive abilities (vocabulary, block design, digit spans of Wechsler's Intelligence Scale, and Rey complex figure) and parents-rated behavioral problems (Child Behavior Checklist/6-18). Rs2268119 × SES interaction (Hotelling's Trace = 0.07; F(12,1154) = 3.53; p = 0.00004) influenced behavior, with more attention problems among children in the 'either A/T or T/T genotype and low SES' group, compared to all other groups. This interaction effect was not significant in an independent, replication sample of 475 subjects from an Italian community-based sample. GRIN2B variants predict children with the worst outcome in attention functioning among children exposed to low SES. Our findings, if replicated, could help in the identification of children with the highest risk and may prompt cost-effective preventive/treatment strategies. PMID:25316095

  6. Rice8987Corresponding Table(f_g_primer): g_0401 [

    Full Text Available g_0401 3UTR_0401 CB0642 D22267 C96749 >TAU87163_1(U87163|pid:g2306768) Triticum aestivum eIF-2 b ... eta subunit mRNA, complete cds; assignment of open reading ... frame based on alignment with other plant eIF2 sub ...

  7. Yeast Interacting Proteins Database: YKR026C, YBR270C [Yeast Interacting Proteins Database

    Full Text Available YKR026C GCN3 Alpha subunit of the translation initiation factor eIF2B, the guanine-nucleotide ex ... sociated complex that regulates actin cytoskeletal dynamics ... during polarized growth and cell wall integrity; i ... sociated complex that regulates actin cytoskeletal dynamics ... during polarized growth and cell wall integrity; i ...

  8. Rolle der extrazellulär regulierten Kinasen (ERK) 1/2 an der Cannabinoid-induzierten Hemmung EDHF-vermittelter Gefäßrelaxation

    Bredenkötter, Daniel

    2009-01-01

    Das vaskuläre Endothel ist in der Lage vasoaktive Autakoide zu synthetisieren und nach entsprechenden neurohumoralen Stimuli (z.B. Bradykinin oder Acetylcholin) oder aber physikalischen Reizen, (z.B. Schubspannung oder Scherkräften) an die Umgebung abzugeben. Neben gefäßkontrahierenden Substanzen wie dem mitogenen Peptid Endothelin produziert das Endothel vasodilatierende Substanzen, von denen bislang drei identifiziert werden konnten: NO, Prostazyklin und der in seiner chemischen Struktur no...

  9. Sample preparation for 2b-RAD genotyping

    sprotocols

    2015-01-01

    Authors: Shi Wang, Eli Meyer, John McKay & Mikhail Matz ### Abstract High-throughput sequencing of restriction site-associated genomic DNA (RAD) is now a widely used approach for simultaneously discovering and profiling genetic polymorphisms. We describe an alternative approach for RAD genotyping with several useful features, called 2b-RAD for the use of type IIB restriction endonucleases (AlfI, BsaXI). The fragments excised by type IIB enzymes are uniform in length, streamlining ...

  10. Social media usage: an investigation of B2B salespeople

    Roberta J. Schultz; Charles H. Schwepker, Jr; David J. Good

    2012-01-01

    A great deal has been written recently in the practitioner press about the strategic importance and usage of social media. However, as practitioners only release limited information about the internal advantages such a tool provides, research in this emerging field remains extremely limited about its usage in the sales area. In this context, the purpose of this paper is to propose and empirically assess a model of social media usage among business-to-business (B2B) salespeople. A survey of 27...

  11. EFFECTIVENESS OF BUSINESS PROCESS MANAGEMENT IN B2B MODEL

    Monika £obaziewicz

    2013-01-01

    A dynamic progress in development of ICT technologies based on B2B, as well as their application in order to improve business processes carried out between enterprises and their business partners, have gained much importance during recent years. It was influenced by such factors as developing and tightening national and international cooperation, high competitiveness, time pressure and striving for improvement of customer and business partners service quality. While the reference books provid...

  12. Content Marketing vs. Traditional Advertising for B2B Companies

    Anthony, Lorena

    2015-01-01

    This thesis follows a traditional research-based structure. The thesis focuses around content marketing and traditional advertising for B2B companies. The thesis was pro-duced for a company called INS and aims at showing that, in present times, content marketing is more valuable than traditional advertising. The first part of the thesis covers different views and theories on both content market-ing and traditional advertising, from definitions, types, roles and stages to planning and mea...

  13. Measurement of Am-242 fission yields at the Lohengrin spectrometer; improvement and Benchmarking of the semi-empirical code GEF

    The study of fission yields has a major impact on the characterization and understanding of the fission process and is mandatory for reactor applications. While the yields are known for the major actinides (U-235, Pu-239) in the thermal neutron-induced fission, only few measurements were performed on Am-242. Moreover, the two main data libraries do not agree among each other on the light peak. Am-241 and Am-242 are nuclei of interest for the MOX-fuel reactors and for the reduction of nuclear waste radiotoxicity using transmutation reactions. Thus, a campaign of precise measurement of the fission mass yields from the reaction Am-241(2n,f) was performed at the Lohengrin mass spectrometer (ILL, France) for both the light and the heavy peak. Forty-one masses were measured. Moreover, the measurement of the isotopic fission yields on the heavy peak by gamma-ray spectrometry led to the extraction of 20 independent isotopic yields. Our measurement was also meant to determine whether there is a difference in fission yields between the Am-242 isomeric state and its ground state as it exists in fission cross sections. The experimental method used to answer this question is based on the measurement a set of fission mass yields as a function of the ratio of Am-242gs to Am-242m fission rate. Results show that the mass yields are independent of the fission rate ratio. A future experimental campaign is proposed to observe a possible influence on the isomeric yields. The theoretical models are nowadays unable to predict the fission yields with enough accuracy and therefore we have to rely on experimental data and phenomenological models. The accuracy of the predictions of the semi empirical GEF fission model predictions makes it a useful tool for evaluation. This thesis also presents the physical content and part of the development of this model. Validation of the kinetic energy distributions, isomeric yields and fission yields predictions was performed. The extension of the GEF

  14. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    2010-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point * (degrees F) Criteria Reactivityfactor 1 80-205 Alkanes... + Dry Point) / 2 (b) Aromatic Hydrocarbon Solvents...

  15. Agent-based services for B2B electronic commerce

    Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

    2000-12-01

    The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

  16. gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by p53-Mediated Signaling Pathway

    Antonia Aránega

    2011-10-01

    Full Text Available Breast cancer research has developed rapidly in the past few decades, leading to longer survival times for patients and opening up the possibility of developing curative treatments for advanced breast cancer. Our increasing knowledge of the biological pathways associated with the progression and development of breast cancer, alongside the failure of conventional treatments, has prompted us to explore gene therapy as an alternative therapeutic strategy. We previously reported that gef gene from E. coli has shown considerable cytotoxic effects in breast cancer cells. However, its action mechanism has not been elucidated. Indirect immunofluorescence technique using flow cytometry and immunocytochemical analysis were used to detect breast cancer markers: estrogen (ER and progesterone (PR hormonal receptors, human epidermal growth factor receptor-2 proto-oncogene (c-erbB-2, ki-67 antigen and p53 protein. gef gene induces an increase in ER and PR expressions and a decrease in ki-67 and c-erbB-2 gene expressions, indicating a better prognosis and response to treatment and a longer disease‑free interval and survival. It also increased p53 expression, suggesting that gef‑induced apoptosis is regulated by a p53-mediated signaling pathway. These findings support the hypothesis that the gef gene offers a new approach to gene therapy in breast cancer.

  17. B2B Integration in Global Supply Chains

    Schubert, Petra; Legner, Christine

    2011-01-01

    we identify five integration scenarios. In the subsequent confirmatory phase of the research we analyse 112 real-world company cases to validate these five integration scenarios. Our research advances and deepens existing studies by developing a B2B reference model, which reflects the current state...... of practice and is independent of specific implementation technologies. In the next stage of the research the emerging reference model will be extended to create an assessment model for analysing the maturity level of a given company in a specific supply chain....

  18. Neoplasia endocrina múltiple tipo-2b

    Lastra, Guido; de Franco, Roberto; Rueda P., Pedro Nel; Pradilla S., Lina P.; Paz C., Óscar

    2014-01-01

    La neoplasia endocrina multiple tipo 2 comprendetres sindromes : la neoplasia endocrina múltiple2A con predisposición genética para desarrollarcarcinoma medular del tiroides,feocromocitoma e hiperplasia primaria deparatiroides. La neoplasia endocrina múltiple 2B,desorden autosómico dominante con feocromocitomay carcinoma medular del tiroides quegeneralmente se presenta a una edad más tempranay es más agresivo que la de tipo 2A, porlo que su diagnóstico precoz es crítico; estospacientes, que t...

  19. Sensors for the CDF Run2b silicon detector

    Akimoto, T.; Aoki, M.; Azzi, P.; Bacchetta, N.(INFN Sezione di Padova, Padova, Italy); Behari, S.; Benjamin, D.; Bisello, D.; Bolla, G.; Booth, P.; Bortoletto, D.; Burghard, A.; Busetto, G.; de Cabrera, S.; Canepa, A.; Cardoso, G.

    2004-01-01

    We describe the characteristics of silicon microstrip sensors fabricated by Hamamatsu Photonics; for the CDF Run 2b silicon detector. A total of 953 sensors, including 117 prototype sensors, have been produced and tested. Five sensors were irradiated with neutrons up to 1.4 x 10(14) n/cm(2) as a part of the sensor quality assurance program. The electrical and mechanical characteristics are found to be superior in all aspects and fulfill our specifications. We comment on charge-up susceptibili...

  20. INTERNET-MARKKINOINTI B2B-LIIKETOIMINNASSA

    Iiskola, Jani

    2010-01-01

    Opinnäyteyö toimeksiantajana toimi Artepro Oy. Työn tarkoituksena oli tutkita Internet-markkinoinnin osa-alueita erityisesti business-to-business liiketoimintaa ajatellen. Työn tavoittee-na oli laatia toimeksiantajayritykselle markkinointiohjeistus ja esittää hyviä käytänteitä verkossa markkinoimiseen. Työssä tutkittiin myös miten markkinointi B2B-liiketoiminnassa eroaa perinteisestä kuluttajamark-kinoinnista, sekä miten Internetin yhteisöllisyyden lisääntyminen on vaikuttanut perinteisii...

  1. MED23: a new Mediator of H2B monoubiquitylation.

    Streubel, Gundula; Bracken, Adrian P

    2015-12-01

    The Mediator multiprotein complex physically links transcription factors to RNA polymerase II and the basal transcription machinery. While the Mediator complex has been shown to be required for transcriptional initiation and elongation, the understanding of its interplay with histone modifying enzymes and post‐translational modifications remains elusive. In this issue of The EMBO Journal, Yao et al (2015) report that the MED23 subunit of the Mediator complex physically associates with the heterodimeric RNF20/40 E3‐ligase complex to facilitate the monoubiquitylation of histone H2B on gene bodies of actively transcribed genes. PMID:26438725

  2. B2B-verkkokaupan suunnittelu : Case Laihian Levypala Oy

    Kotilainen, Sanna-Mari

    2014-01-01

    Tämän opinnäytetyön tarkoituksena oli toteuttaa B2B-verkkokaupan suunnitelma metallialan perheyritys Laihian Levypala Oy:lle. Idea verkkokaupasta lähti Nettikone.com-ilmoituspalvelun kautta saadusta myynnistä ja totesimme yrittäjän kanssa, että verkkokaupan perustaminen voisi olla sopiva opinnäyteprojekti. Projektin alkuvaiheessa toteutettiin kysely lähialueiden maanrakennus-, maatalous- ja metallialan pk-yrityksille. Kyselyn aiheita olivat halukkuus perustaa oma verkkokauppa, yleinen verk...

  3. B2B-verkkokaupan markkinointiviestintäsuunnitelma

    Luoma, Hanna

    2015-01-01

    Opinnäytetyön aiheena oli luoda markkinointiviestintäsuunnitelma Yritys Oy:n kehitteillä olevalle verkkokaupalle. Työn tavoitteena oli markkinointiviestintäsuunnitelman avulla selvittää miten Yritys Oy:n B2B-verkkokauppa saadaan osaksi myyntitoimia ja miten se mahdollisimman tehokkaasti tuodaan asiakkaiden tietoisuuteen. Yritys Oy on vuonna 2003 perustettu perheyritys, jonka toiminta on kiinnitystekniikan tukkumyynti alan ammattilaisille. Yritys Oy:llä on useampi toimipiste ympäri Suomea...

  4. Strategic Insights from Mystery Shopping in B2B Relationships

    Mattsson, Jan

    2012-01-01

    This paper describes how mystery shopping can be used to gain valuable strategic input in B2B service relationships. We account for a longitudinal case study framed as a natural experiment (duration 18 months) in a Swedish group of consultancy companies offering a wide selection of industrial...... services to large Scandinavian corporations. We account for and analyse the process of building a mystery shopping procedure to get strategic insights from engineers delivering temporary consultancy services to these clients. After a successful trial period with three mystery shoppers the experiment (a...

  5. USING UML SCENARIOS IN B2B SYSTEMS

    A. Jakimi

    2010-05-01

    Full Text Available Scenarios has become a popular technique for requirements elicitation and specification building. Since scenarios capture only partial descriptions of the system behavior, an approach for scenario composition and/or integration is needed to produce more complete specifications. The Unified Modeling Language (UML, which has become a standard notation for object-oriented modeling, provides a suitable framework for scenario acquisition using Use Case diagrams and Sequence or Collaboration diagrams. In this paper, we suggest an algorithmic and tool support for composing and integrating scenarios that are represented in form of sequence diagrams. We suggest four operators (;: sequential operator, ||: concurrent operator, ?: conditional operator and  * :iteration operator to compose a set of scenarios that describe a use case of a given system. In this paper, we suggest also to apply the scenario approach to B2B systems (Business to Business. We propose to develop B2B systems as a three activities process deriving formal specifications and code skeletons from UML scenarios. Activities of this proposed process are generally automatic and are supported by a set of developed algorithms and tools.

  6. Getting started with Oracle SOA B2B Integration a hands-on tutorial

    Bhatia, Krishnaprem; Perlovsky, Alan

    2013-01-01

    This hands on tutorial gives you the best possible start you could hope for with Oracle B2B. Learn using real life scenarios and examples to give you a solid footing of B2B.This book is for B2B architects, consultants and developers who would like to design and develop B2B integrations using Oracle B2B. This book assumes no prior knowledge of Oracle B2B and explains all concepts from scratch using illustrations, real world examples and step-by-step instructions. The book covers enough depth and details to be useful for both beginner and advanced B2B users.

  7. UMLB2B: Model-based development of a B2B : A method for building platform independent models

    2003-01-01

    This thesis is more or less developed in parallel with my participation in the Infrastructure project of Norsk EDIPRO. In Norsk EDIPRO we tried to standardise a way for companies to do business over the Internet using new frameworks and technologies like MDA and XML. The contribution of the thesis is a method called UMLB2B which focus on how to build the models that are describing information and business processes of each company in a standard way so it would be easier to integrate their...

  8. FMDV 2B biroporina aktibitatearen liposoma-saioak eta erabilpena antibiralen garapenean

    del Río Lavín, Ane

    2016-01-01

    FMDV 2B biroporinak duen egitura eta funtzio aztertzeko helburuarekin, peptidoetan oinarritutako analisiak egin dira. Modu honetan, 2B proteina ezestrukturalak bi transmintz domeinu agertu ditu, II motako biroporina dela bermatuz. FMDV 2B biroporinaren aminoazido sekuentziak pikornabirusen 2B aminoazido sekuentziekin homologia erakusten du, 2B4 peptidoari dagokion sekuentzia gehigarria kontuan hartu gabe. Sekuentzia gehigarri hau bigarren domeinu litiko bat da, birus familia honetan deigarria...

  9. Vortex lattice transitions in YNi2B2C

    S J Levett; C D Dewhurst; D McK Paul

    2002-05-01

    We have performed extensive small-angle neutron scattering (SANS) diffraction studies of the vortex lattice in single crystal YNi2B2C for $B||c$. High-resolution SANS, combined with a field-oscillation vortex lattice preparation technique, allows us to separate Bragg scattered intensities from two orthogonal domains and accurately determine the unit cell angle, . The data suggest that upon increasing field there is a finite transition width where both low- and high-field distorted hexagonal vortex lattice phases, mutually rotated by 45°, coexist. The smooth variation of diffracted intensity from each phase through the transition corresponds to a redistribution of populations between the two types of domains.

  10. Relationship Quality as Predictor of B2B Customer Loyalty

    Shaimaa S. B. Ahmed Doma

    2013-02-01

    Full Text Available Relationship marketing has become extremely important recently due to the fierce competition in today's marketplace. Companies are required to build long-term profitable relationship with customers and to achieve customer loyalty. Also, switching behaviors frequently occur among most of targeted customers. Fewer studies, however, discuss the effects of relationship quality efforts on customer loyalty. Therefore, this study is aimed to investigate the impact of relationship quality on customer loyalty in B2B context in the Egyptian shipping services sector. Building on prior research, we propose relationship quality as a higher construct comprising trust, commitment and satisfaction. An analytical model is developed as a guideline to test the relationships between relationship quality dimensions and customer loyalty.

  11. Matchmaking Framework for B2B E-Marketplaces

    Fekete ZOLTAN ALPAR

    2010-01-01

    Full Text Available In the recent years trading on the Internet become more popular. Online businesses gradually replace more and more from the conventional business. Much commercial information is exchanged on the internet, especially using the e-marketplaces. The demand and supply matching process becomes complex and difficult on last twenty years since the e-marketplaces play an important role in business management. Companies can achieve significant cost reduction by using e-marketplaces in their trade activities and by using matchmaking systems on finding the corresponding supply for their demand and vice versa. In the literature were proposed many approaches for matchmaking. In this paper we present a conceptual framework of matchmaking in B2B e-marketplaces environment.

  12. Study of Subsonic Flow Over a TOW 2B Missile

    Goudarzi, Koorosh; Jamali, Mehdi

    2016-01-01

    The objective of this investigation is to study the subsonic flow over a missile. In this paper, a model of TOW 2B missile is studied. Two computational approaches are being explored, namely solutions based on the Reynolds-averaged compressible Navier-Stokes equations and solutions based on the inviscid flow (small disturbance theory). The simulations are performed at the Mach number of 0.6, 0.7, 0.8, 0.9 and 1.0 at four angles of attack of 2, 4, 6 and 8 degree. Results obtained from analytical simulation are compared with numerical data. It is found that lift and drag coefficients would go up by increasing of the angle of attack and the Mach number. Trend of changes of the results that obtained from the small disturbance theory is roughly as same as the numeric solution.

  13. Sosiaalisen median strategia pienelle b2b-yritykselle

    Surkko, Antti

    2012-01-01

    Sosiaalinen media on tänä päivänä tärkeä osa ihmisten elämää ja yritysten kannattaa siksi käyttää sitä hyödykseen markkinointitoimissaan. Aihe opinnäytetyöhön tuli toimeksiantajalta, joka on jo mukana sosiaalisen median palveluissa. Toimeksiantajayritys ei kuitenkaan tiedä, miten hyödyntää sosiaalisen median palveluiden täysi potentiaali markkinointikanavana. Opinnäytetyön tarkoituksena oli selvittää, mitä pienen b2b-yrityksen pitäisi ottaa huomioon sosiaalisen median markkinointitoimia aloi...

  14. Semantic ETL into i2b2 with Eureka!

    Post, Andrew R; Krc, Tahsin; Rathod, Himanshu; Agravat, Sanjay; Mansour, Michel; Torian, William; Saltz, Joel H

    2013-01-01

    Clinical phenotyping is an emerging research information systems capability. Research uses of electronic health record (EHR) data may require the ability to identify clinical co-morbidities and complications. Such phenotypes may not be represented directly as discrete data elements, but rather as frequency, sequential and temporal patterns in billing and clinical data. These patterns' complexity suggests the need for a robust yet flexible extract, transform and load (ETL) process that can compute them. This capability should be accessible to investigators with limited ability to engage an IT department in data management. We have developed such a system, Eureka! Clinical Analytics. It extracts data from an Excel spreadsheet, computes a broad set of phenotypes of common interest, and loads both raw and computed data into an i2b2 project. A web-based user interface allows executing and monitoring ETL processes. Eureka! is deployed at our institution and is available for deployment in the cloud. PMID:24303265

  15. Structured Crowdsourcing: A B2B Innovation Roadmap

    Edgeman, Rick; Engell, Toke; Jensen, Nik Grewy;

    Crowdsourcing is an increasingly popular source of both ideas and funding. Crowdsourcing in a B2B context is less well understood and, as such, much of our discussion will highlight business-to-business crowdsourcing. More generally discussion will address crowdsourcing relative to innovation and...... technology development and customer relationship management. Examples will be used to derive a general roadmap, and to identify specific areas worthy of increased attention. The roadmap is developed as a six-stage approach that begins with task specification and concludes with management of inputs generated...... from crowd-sourcing efforts. The roadmap emphasizes on early stages in the overall innovation management activity that is related to development and specification of the task to be crowdsourced, the identification of the crowd, the creation of the environment to connect the crowdsourcer, the task and...

  16. Gefüge- und Strukturausbildung bei der elektrolytischen Abscheidung funktionaler Legierungsschichten der Systeme Kupfer-Blei, Silber-Blei und Gold-Blei

    Barthel, Thomas

    2009-01-01

    Die Arbeit beschäftigt sich mit der galvanischen Legierungsabscheidung für die Systeme Cu-Pb, Ag-Pb und Au-Pb. Es konnte nachgewiesen werden, dass es zur Bildung stark übersättigter Mischkristalle kommt, deren Struktur- und Gefügeeigenschaften direkte Abhängigkeiten von den Abscheidebedingungen zeigen. Es treten für die Einzelsysteme Unterschiedlichkeiten auf, die in direkten Zusammenhang mit dem Gitteraufbau der Matrixelemente gebracht werden können. Besonderes Interesse verdient die Härte d...

  17. Optimierung des PbO-Haushaltes in undotierten und SKN-substituierten PZT-Fasern: Gefüge und Eigenschaften

    Hansch, Ralf

    2003-01-01

    Ziel der vorliegenden Arbeit war eine Optimierung des Mikrogefüges und der funktionalen Eigenschaften von undotierten und substituierten Bleizirkonat-Bleititanat-Fasern (PZT), die über die Sol-Gel-Route hergestellt worden waren. Die Kontrolle der Gefügeausbildung und der damit zusammenhängenden funktionalen Eigenschaften in den Fasern erfolgte über drei Wege: (1) über eine Optimierung des PbO-Gehaltes im Spinnsol, (2) über eine Anpassung der bei der Sinterung eingesetzten PbO-haltigen Puffers...

  18. Für Geist und Auge : Jan Quirin Jahns "Gefühle bei Besuchung des Schönhofer Garten" (1797)

    Brudzyńska-Němec, Gabriela

    2012-01-01

    This article analyses the essay "Gefühle bei Besuchung des Schönhofer Garten" by Jan Quirin Jahn (1739–1802), published in 1797 in the magazine "Apollo". The description of the English garden in Schönhof (Krásný Dvůr), the oldest of its kind in Bohemia, is seen in the light of aesthetic and theoretical discussions. The impression determines the reception of the new art of garden design. Jahn's literary walk through the garden of Schönhof also testified that new forms of aesthetic perception w...

  19. Caracterización de la función del Rho-GEF Rgf1 en el núcleo de la levadura Schizosaccharomyces pombe

    Muñoz Félix, Sofía

    2014-01-01

    [ES]Las GTPasas de la familia Rho son interruptores moleculares que controlan algunos de los procesos clave en biología celular, incluyendo la morfogénesis, el transporte vesicular, la división celular o la motilidad. Los GEFs (guanine nucleotide exchange factors) son los responsables de la activación de las GTPasas de la familia Rho en respuesta distintos estímulos. Modifican el estado de unión a nucleótido de la GTPasa y contienen dominios de interacción entre proteínas que pueden infl...

  20. Das Vorkommen des Ruten-Hasenohrs (Bupleurum virgatum Cav.) im Selketal : Anmerkungen zu Gefährdungsursachen sowie zu Schutz- und Erhaltungsmöglichkeiten der Art

    Herrmann, Nick; Kison, Hans-Ulrich

    2013-01-01

    Die bedeutendste Gefährdung für das in Deutschland vom Aussterben bedrohte Ruten-Hasenohr (Bupleurum virgatum CAV.) geht derzeit vom Menschen aus. Durch touristische Übernutzung wurden am bislang letzten Standort der Art (Selketal: „Alter Falkenstein“) Ruderalisierungs- und Eutrophierungsprozesse initiiert, durch die sich der für B. virgatum verfügbare Lebensraum ständig verkleinert. Darüber hinaus werden jährlich zahlreiche Individuen der annuellen Art durch menschliche Tritteinwirkung gesch...

  1. Il B2B e il paradigma dei costi di transazione (B2B and the Transaction Costs Paradigm

    Pierluigi Sabbatini

    2012-04-01

    Full Text Available Business to Business (B2B Internet commerce causes a significant contraction of transaction costs. According to the Coase paradigm, we would thus expect a deverticalization of the industry and broader scope for anonymous market mechanisms. In reality, such expectations are not fully borne out by the facts. When the industrial structure is concentrated the B2Bgenerally loses its independence, and is owned by the firms which most contribute to its development, e.g. the ones able to bring the liquidity to it. The B2B governance mechanism established by these firms gives hierarchical mechanisms a role which they do not usually play in extensive, anonymous markets.         JEL Codes: D23, L86Keywords: Cost, Transaction Costs, Transactions

  2. SH2B1 regulation of energy balance, body weight, and glucose metabolism

    Liangyou; Rui

    2014-01-01

    The Src homology 2B(SH2B)family members(SH2B1,SH2B2 and SH2B3)are adaptor signaling proteins containing characteristic SH2 and PH domains.SH2B1(also called SH2-B and PSM)and SH2B2(also called APS)are able to form homo-or hetero-dimers via their N-terminal dimerization domains.Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins,including Janus kinase 2(JAK2),TrkA,insulin receptors,insulin-like growth factor-1 receptors,insulin receptor substrate-1(IRS1),and IRS2.SH2B1 enhances leptin signaling by both stimulating JAK2 activity and assembling a JAK2/IRS1/2 signaling complex.SH2B1 promotes insulin signaling by both enhancing insulin receptor catalytic activity and protecting against dephosphorylation of IRS proteins.Accordingly,genetic deletion of SH2B1 results in severe leptin resistance,insulin resistance,hyperphagia,obesity,and type 2 diabetes in mice.Neuronspecific overexpression of SH2B1βtransgenes protects against diet-induced obesity and insulin resistance.SH2B1 in pancreaticβcells promotesβcell expansion and insulin secretion to counteract insulin resistance in obesity.Moreover,numerous SH2B1 mutations are genetically linked to leptin resistance,insulin resistance,obesity,and type 2 diabetes in humans.Unlike SH2B1,SH2B2 and SH2B3 are not required for the maintenance of normal energy and glucose homeostasis.The metabolic function of the SH2B family is conserved from insects to humans.

  3. RE2B8O15 (RE = La, Pr, Nd). Syntheses of three new rare earth borates isotypic to Ce2B8O15

    The rare earth borates RE2B8O15 (RE = La, Pr, Nd) were synthesized in a Walker-type multianvil apparatus under conditions of 5.5 GPa and 1100 C. Starting from the corresponding rare earth oxides and boron oxide, the syntheses yielded crystalline products of all new compounds that allowed crystal structure analyses based on single-crystal X-ray diffraction data for La2B8O15 and Nd2B8O15. The compound Pr2B8O15 could be characterized via X-ray powder diffractometry. The results show that the new compounds crystallize isotypically to Ce2B8O15 in the monoclinic space group P2/c. The infrared spectra of RE2B8O15 (RE = La, Pr, Nd) have also been studied.

  4. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis

    Ren, Decheng; Zhou, Yingjiang; Morris, David; Li, Minghua; Li, Zhiqin; Rui, Liangyou

    2007-01-01

    SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (α, β, γ, and/or δ) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1β was specifically expressed in neural tissue in SH2B1-tran...

  5. Efficient cell culture system for hepatitis C virus genotype 2B

    2014-01-01

    The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from...... transfection experiments revealed that 2b/2a was genetically stable. Conclusion: The developed 2b/2a viruses provide a robust in vitro tool for research in HCV genotype 2b, including vaccine studies and functional analysis....

  6. B2-B2.5 code benchmarking

    Dekeyser, W.; Baelmans, M; Voskoboynikov, S.; Rozhansky, V.; Reiter, D.; Wiesen, S.; Kotov, V.; Boerner, P.

    2011-01-15

    ITER-IO currently (and since about 15 years) employs the SOLPS4.xxx code for its divertor design, currently version SOLPS4.3. SOLPS.xxx is a special variant of the B2-EIRENE code, which was originally developed by an European consortium (FZ Juelich, AEA Culham, ERM Belgium/KU Leuven) in the late eighties and early nineties of the last century under NET contracts. Until today even the very similar edge plasma codes within the SOLPS family, if run on a seemingly identical choice of physical parameters, still sometimes disagree significantly with each other. It is obvious that in computational engineering applications, as they are carried out for the various ITER divertor aspects with SOLPS4.3 for more than a decade now, any transition from one to another code must be fully backward compatible, or, at least, the origin of differences in the results must be identified and fully understood quantitatively. In this report we document efforts undertaken in 2010 to ultimately eliminate the third issue. For the kinetic EIRENE part within SOLPS this backward compatibility (back until 1996) was basically achieved (V. Kotov, 2004-2006) and SOLPS4.3 is now essentially up to date with the current EIRENE master maintained at FZ Juelich. In order to achieve a similar level of reproducibility for the plasma fluid (B2, B2.5) part, we follow a similar strategy, which is quite distinct from the previous SOLPS benchmark attempts: the codes are ''disintegrated'' and pieces of it are run on smallest (i.e. simplest) problems. Only after full quantitative understanding is achieved, the code model is enlarged, integrated, piece by piece again, until, hopefully, a fully backward compatible B2 / B2.5 ITER edge plasma simulation will be achieved. The status of this code dis-integration effort and its findings until now (Nov. 2010) are documented in the present technical note. This work was initiated in a small workshop by the three partner teams of KU Leuven, St. Petersburg

  7. Phonon linewidths in YNi2B2C

    L Pintschovius; F Weber; W Reichardt; A Kreyssig; R Heid; D Reznik; O Stockert; K Hradil

    2008-10-01

    Phonons in a metal interact with conduction electrons which give rise to a finite linewidth. In the normal state, this leads to a Lorentzian shape of the phonon line. Density functional theory is able to predict the phonon linewidths as a function of wave vector for each branch of the phonon dispersion. An experimental verification of such predictions is feasible only for compounds with very strong electron–phonon coupling. YN2B2C was chosen as a test example because it is a conventional superconductor with a fairly high c (15.2 K). Inelastic neutron scattering experiments did largely confirm the theoretical predictions. Moreover, they revealed a strong temperature dependence of the linewidths of some phonons with particularly strong electron–phonon coupling which can as yet only qualitatively be accounted for by theory. For such phonons, marked changes of the phonon frequencies and linewidths were observed from room temperature down to 15 K. Further changes were observed on entering into the superconducting state. These changes can, however, not be described simply by a change of the phonon linewidth.

  8. Natural releases from contaminated groundwater, Example Reference Biosphere 2B

    Simon, I. [CIEMAT/PIRA, Avda Complutense 22, 28040 Madrid (Spain)]. E-mail: isc@csn.es; Naito, M. [Nuclear Waste Management Organization of Japan (NUMO), 4-1-23 Shiba, Minato-ku, Tokyo, 108-0014 (Japan); Thorne, M.C. [Mike Thorne and Associates Limited, Abbotsleigh, Kebroyd Mount, Ripponden, Halifax, West Yorkshire HX6 3JA (United Kingdom); Walke, R. [Enviros QuantiSci, Building D5, Culham Science Centre, Culham, Oxfordshire OX14 3DB (United Kingdom)

    2005-07-01

    Safety assessment is a tool which, by means of an iterative procedure, allows the evaluation of the performance of a disposal system and its potential impact on human health and the environment. Radionuclides from a deep geological disposal facility may not reach the surface environment until many tens of thousands of years after closure of the facility. The BIOMASS Programme on BIOsphere Modelling and ASSessment developed Examples of 'Reference Biospheres' to illustrate the use of the methodology and to demonstrate how biosphere models can be developed and justified as being fit for purpose. The practical examples are also intended to be useful in their own right. The Example Reference Biosphere 2B presented here involves the consideration of alternative types of geosphere-biosphere interfaces and calculation of doses to members of hypothetical exposure groups arising from a wide range of exposure pathways within agricultural and semi-natural environments, but without allowing for evolution of the corresponding biosphere system. The example presented can be used as a generic analysis in some situations although it was developed around a relatively specific conceptual model. It should be a useful practical example, but the above numerical results are not intended to be understood as prescribed biosphere 'conversion factors'.

  9. [Obtaining and characteristics of domestic preparation interferon alpha-2b with prolonged effect].

    Pokholenko, Ia A; Porubleva, L V; Dubeĭ, I Ia; Rebriev, A V; Sutugina, L P; Gromovoĭ, T Iu; Pokrovskiĭ, V A; Obolenskaia, M Iu; Chernykh, S I

    2008-01-01

    Pegylated interferon alpha-2b (PEG-IFN alpha-2b) is a domestic preparation of a modified recombinant interferon alpha-2b with prolonged effect. The preparation was obtained by N-terminal pegylation of IFN alpha-2b with polyethylene glycol (PEG). This paper presents the method of PEG-IFN alpha-2b synthesis and characteristics of the obtained product. PAAG electrophoresis, Western blot analysis and MALDI-TOF mass-spectrometry confirm that the preparation is an N-terminal pegylated IFN alpha-2b that contains no more than 10% of dipegylated IFN alpha-2b. The comparison of PEG-IFN alpha-2b with its foreign analogue has revealed the similarity of their biological activity and pharmacokinetic parameters. PMID:19351063

  10. Graded Channel MOSFET simulation with S-Pisces 2B

    Hartono Siswono

    2004-04-01

    Full Text Available Graded-Channel Metal-Oxide-Semiconductor Field-effect- Transistor or GCMOSFET is being discussed in this paper. GCMOSFET technology has been developed to meet the growing demand for low power and high performance application. In this paper, it will be shown that, compared to ungraded MOSFET, the GCMOSFET device offers the advantage of significantly higher drive current. The higher drive current is achieved because the effecctive channel length of GCMOSFET is shorter than the ungraded MOSFET’s. From the simulation result with S-PISCES 2B and MATLAB, it can been shown that the ID from GCMOSFET is higher than the ID from ungraded MOSFET. As an example, with VG = 4 V and VD = 4 V, ID from MOSFET is equal with 9.78 e-06 A and ID from GCMOSFET is equal with 16.56 e-06 A. Beside that, as an example, to get ID = 1.13 e-05 A with MOSFET will need VG = 4 V and VD = 4.7 V, and with GCMOSFET VG = 4 V and VD = 1.2 V will be needed. This result has shown that GCMOSFET needs lower supply voltage than the ungraded MOSFET which means that GCMOSFET needs lower power consumption than ungraded MOSFET. From the simulation results, it can be proved that GCMOSFETwith shorter LGC (graded channel region length will give larger ID than ID from GCMOSFET with longer LGC. As we can see that for VGS = 4 V and VDS = 2 V, GCMOSFET with LGC = 4 μm will give ID = 16,56E-06 A, GCMOSFET with LGC = 3,5 μm will give ID = 17,51E-06 A, and GCMOSFET with LGC = 3 μm will give ID =18,49E-06

  11. Hanstholm phase 2B. Offshore wave energy test 1994 - 1996

    NONE

    1996-11-01

    The wave power converter consists of a float 2.5 meter in diameter, connected by a rope to a seabed-mounted piston pump, installed on 25 meter deep water 2,5 km offshore Hanstholm, Denmark. The converter is designed to absorb an average maximum power of 1 kW. Measured data in real sea conditions are compared to results based on computer simulations and previous tank testing. Losses caused by rope elasticity and hysteresis, friction in the pump and back flow through the valves are assessed. The economic perspectives of a large wave power plant are presented, based on a revised prototype incorporating the results and experience gained during the test period. The wave energy conversion test `Hanstholm phase 2B` has showed, that it it technically possible to exploit the offshore wave energy resource. This source of energy could become attractive for commercial enterprise. The wave power converter demonstrated a reliable performance over a period of nine months. It produced energy under all wave conditions and survived storm waves of 9,6 m. A 300 MW wave power plant in the Danish part of the North sea is estimated to produce electricity at a cost between 2,1 - 2,4 DKK/kWh. The electrical transmission to shore contribute to approximately 20% of the cost. New data predict a potential of 23 kW per meter wave front. The energy plan Energy 21 proposed by the Danish Department of Energy, includes a scenario incorporating wave energy in the energy system year 2030. A strategy for the development of wave energy, has been proposed as part of the project OWEC-1 supported by the European Joule R and D programme. A proposal for future Danish initiatives to develop second generation point absorber systems is outlined. (ARW) 29 refs.

  12. 20 CFR 655.22 - Obligations of H-2B employers.

    2010-04-01

    ... EMPLOYMENT OF FOREIGN WORKERS IN THE UNITED STATES Labor Certification Process and Enforcement of... States (H-2B Workers) § 655.22 Obligations of H-2B employers. An employer seeking H-2B labor... provided for in DHS regulations at 8 CFR 214.2(h)(5)(xi)(A). This provision does not prohibit employers...

  13. File list: Pol.ALL.50.Polr2b.AllCell [Chip-atlas[Archive

    Full Text Available Pol.ALL.50.Polr2b.AllCell mm9 RNA polymerase Polr2b All cell types SRX373045,SRX595...04153,SRX119655,SRX318115,SRX373044,SRX119652,SRX318112 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.ALL.50.Polr2b.AllCell.bed ...

  14. Vortex phase diagram studies in the weakly pinned single crystals of YNi2B2C and LuNi2B2C

    D Jaiswal-Nagar; D Pal; M R Eskildsen; P C Canfield; H Takeya; S Ramakrishnan; A K Grover

    2006-01-01

    We present a study of magnetization measurements performed on the single crystals of YNi2B2C and LuNi2B2C. For both the compounds, we find flux jumps in magnetisation values in the respective field regions, where the structural transitions in the flux line lattice symmetry have been reported in these systems via the small angle neutron scattering experiments. The magnetisation hysteresis loops and the AC susceptibility measurements show pronounced peak effect as well as second magnetisation peak anomaly for both YNi2B2C and LuNi2B2C. Based on these results, a vortex phase diagram has been constructed for YNi2B2C for $H \\Arrowvert c$ depicting different glassy phases of the vortex matter.

  15. Summary of Session 2.B. Planning and implementation

    Session 2.B. can be summarized by a statement in one of the papers given in the session: 'Dismantling of nuclear facilities is basically not a technical problem but a challenge to project management and logistics once the legal and economical boundary conditions have been clarified'. The session balanced generic principles and concerns raised by decommissioning projects with practical examples of lessons learned from some specific projects and raised some key issues for all involved in decommissioning - whether regulator, operator or other stakeholder. Ideally, planning for decommissioning should start as early as possible, preferably when the facility is being designed. When a facility or activity is shut down it is very important that a formal decision to decommission is made so that the situation is clear to all stakeholders. The impact on the work force and the local community due to the cessation of operation of a facility must be recognized and addressed early in the transition from operation to decommissioning. Factors such as uncertainty, potential job losses and diminution of career paths as research careers are replaced by construction/deconstruction jobs all lead to poor morale and an exodus of qualified staff. Attention to safety culture during all phases of decommissioning will assist in ensuring that safety and environmental protection objectives are met, as well as promoting desired worker retention. Some issues for future consideration include the following: Consider the role of the State in the clearance process, should the State take responsibility for decommissioned sites that cannot be 'green fielded'?; Consider establishing expert missions focused on decommissioning similar to those of the IAEA's Operational Safety Assessment Review Team and WATRAP. Actions that could be taken include: Clarifying the status of all shutdown facilities that have not declared decommissioning; Ensuring that the focus of the decommissioning programme includes all

  16. Impaired ventilatory and thermoregulatory responses to hypoxic stress in newborn Phox2b heterozygous knockout mice

    Nelina eRamanantsoa

    2011-09-01

    Full Text Available The Phox2b gene is necessary for the development of the autonomic nervous system, and especially, of respiratory neuronal circuits. In the present study, we examined the role of Phox2b in ventilatory and thermoregulatory responses to hypoxic stress, which are closely related in the postnatal period. Hypoxic stress was generated by strong thermal stimulus, combined or not with reduced inspired O2. To this end, we exposed 6-day-old Phox2b+/- pups and their wild-type littermates (Phox2b+/+ to hypoxia (10% O2 or hypercapnia (8% CO2 under thermoneutral (33°C or cold (26°C conditions. We found that Phox2b+/- pups showed less normoxic ventilation (VE in the cold than Phox2b+/+ pups. Phox2b+/- pups also showed lower oxygen consumption (VO2 in the cold, reflecting reduced thermogenesis and a lower body temperature. Furthermore, while the cold depressed ventilatory responses to hypoxia and hypercapnia in both genotype groups, this effect was less pronounced in Phox2b+/- pups. Finally, because serotonin (5-HT neurons are pivotal to respiratory and thermoregulatory circuits and depend on Phox2b for their differentiation, we studied 5-HT metabolism using high-pressure liquid chromatography, and found that it was altered in Phox2b+/- pups. We conclude that Phox2b haploinsufficiency alters the ability of newborns to cope with metabolic challenges, possibly due to 5-HT signaling impairments.

  17. Aberrant methylation of N-methyl-D-aspartate receptor type 2B (NMDAR2B) in non-small cell carcinoma

    N-methyl-D-aspartate receptors (NMDAR) act as tumor suppressors of digestive malignancies. The expression and genetic methylation patterns of NMDAR2B in non-small cell lung cancer (NSCLC) are unknown. The relationship between gene methylation and expression of NMDAR2B was analyzed in NSCLC cell lines (N = 9) and clinical tissues (N = 216). The cell lines were studied using RT-PCR and 5-aza-2'-deoxycytidine treatment, while the clinical tissues were examined by methylation specific real-time quantitative PCR and immunohistochemistry. Retrospective investigation of patient records was used to determine the clinical significance of NMDAR2B methylation. NMDAR2B was silenced in five of the nine cell lines; 5-aza-2'-deoxycytidine treatment restored expression, and was inversely correlated with methylation. Aberrant methylation of NMDAR2B, detected in 61% (131/216) of clinical NSCLC tissues, was inversely correlated with the status of protein expression in 20 randomly examined tumors. Aberrant methylation was not associated with clinical factors such as gender, age, histological type, or TNM stage. However, aberrant methylation was an independent prognostic factor in squamous cell carcinoma cases. Aberrant methylation of the NMDAR2B gene is a common event in NSCLC. The prognosis was significantly better for cases of squamous cell carcinoma in which NMDAR2B was methylated. It may have different roles in different histological types

  18. Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

    Wilderman, P. Ross, E-mail: pwilderman@ucsd.edu [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States); Jang, Hyun-Hee [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States); Malenke, Jael R. [Department of Biology, University of Utah, Salt Lake City, UT (United States); Salib, Mariam; Angermeier, Elisabeth; Lamime, Sonia [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States); Dearing, M. Denise [Department of Biology, University of Utah, Salt Lake City, UT (United States); Halpert, James R. [Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA (United States)

    2014-02-01

    Mammalian detoxification processes have been the focus of intense research, but little is known about how wild herbivores process plant secondary compounds, many of which have medicinal value or are drugs. cDNA sequences that code for three enzymes of the cytochrome P450 (CYP) 2B subfamily, here termed 2B35, 2B36, and 2B37 have been recently identified from a wild rodent, the desert woodrat (Malenke et al., 2012). Two variant clones of each enzyme were engineered to increase protein solubility and to facilitate purification, as reported for CYP2B enzymes from multiple species. When expressed in Escherichia coli each of the woodrat proteins gave the characteristic maximum at 450 nm in a reduced carbon monoxide difference spectrum but generally expressed at lower levels than rat CYP2B1. Two enzymes, 2B36 and 2B37, showed dealkylation activity with the model substrates 7-ethoxy-4-(trifluoromethyl)coumarin and 7-benzyloxyresorufin, whereas 2B35 was inactive. Binding of the monoterpene (+)-α-pinene produced a Type I shift in the absorbance spectrum of each enzyme. Mutation of 2B37 at residues 114, 262, or 480, key residues governing ligand interactions with other CYP2B enzymes, did not significantly change expression levels or produce the expected functional changes. In summary, two catalytic and one ligand-binding assay are sufficient to distinguish among CYP2B35, 2B36, and 2B37. Differences in functional profiles between 2B36 and 2B37 are partially explained by changes in substrate recognition site residue 114, but not 480. The results advance our understanding of the mechanisms of detoxification in wild mammalian herbivores and highlight the complexity of this system. - Highlights: • Three CYP2B enzymes from Neotoma lepida were cloned, engineered, and expressed. • A mix of catalytic and binding assays yields unique results for each enzyme. • Mutational analysis indicates CYP{sub 2}B substrate recognition remains to be clarified. • Reported N. lepida gene

  19. The brain-specific neural zinc finger transcription factor 2b (NZF-2b/7ZFMyt1 suppresses cocaine self-administration in rats

    Vijay Chandrasekar

    2010-04-01

    Full Text Available Brain-specific neural-zinc-finger transcription factor-2b (NZF2b/7ZFMyt1 is induced in the mesolimbic dopaminergic region after chronic cocaine exposure and lentiviral-mediated expression of NZF2b/7ZFMyt1 in the nucleus accumbens results in decreased locomotor activity (Chandrasekar and Dreyer, 2009. In this study the role of NZF2b/7ZFMyt1 in active cocaine seeking and of its interaction with histone deacetylase on the altered behavior has been observed. Localized expression of NZF2b/7ZFMyt1 in the nucleus accumbens resulted in attenuated cocaine self-administration, whereas silencing this transcription factor with lentiviruses expressing siRNAs increased the animal′s motivation to self-infuse cocaine. Low doses of sodium butyrate, a potent inhibitor of histone deacetylase, were sufficient to reverse the NZF2b/7ZFMyt1-mediated decrease in cocaine self-administration. NZF2b/7ZFMyt1 expression resulted in strong induction of transcription factors REST1 and NAC1 and of the dopamine D2 receptor, with concomitant inhibition of BDNF and its receptor TrkB. We show that NZF2b/7ZFMyt1 colocalizes with histone deacetylase-2 (HDAC2, probably overcoming the suppression of transcriptional activity caused by Lingo1. These findings show that molecular adaptations mediated by NZF2b/7ZFMyt1 expression possibly lead to decreased responsiveness to the reinforcing properties of cocaine and play a prominent role in affecting the behavioral changes induced by the drug.

  20. Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction

    Deng Xiaolu

    2011-04-01

    Full Text Available Abstract Background Tumor necrosis factor-α (TNF-α, a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC barrier dysfunction. Methods Bend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL. RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER. p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability. Results We observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER. Conclusions Taken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF

  1. Vincristine enhances amoeboid-like motility via GEF-H1/RhoA/ROCK/Myosin light chain signaling in MKN45 cells

    Eitaki Masato

    2012-10-01

    Full Text Available Abstract Background Anti-cancer drugs are widely used in cancer treatment frequently combined with surgical therapy and/or radiation therapy. Although surgery and radiation have been suggested to facilitate invasion and metastasis of tumor cells in some cases, there is so far little information about the effect of anti-cancer drugs on cellular invasive ability and metastasis. In this study, using four different anti-cancer drugs (vincristine, paclitaxel, cisplatin and etoposide, we examined whether these drugs influence the invasive ability of tumor cells. Methods Human gastric adenocarcinoma MKN45 cells were used to evaluate the effect of anti-cancer drugs. After drug treatment, cellular invasive ability was assessed using the Matrigel invasion chamber. Cytoskeletal changes after treatment were examined microscopically with F-actin staining. In addition, we monitored cellular motility in 3D matrigel environment by time-lapse microscopic analysis. The drug-induced activation of RhoA and ROCK was evaluated by pull-down assay and Western blotting using an antibody against phosphorylated myosin light chain (MLC, respectively. Where necessary, a ROCK inhibitor Y27632 and siRNA for guanine nucleotide exchange factor-H1 (GEF-H1 were applied. Results Among all drugs tested, only vincristine stimulated the invasive ability of MKN45 cells. Microscopic analysis revealed that vincristine induced the formation of non-apoptotic membrane blebs and amoeboid-like motility. Vincristine significantly enhanced RhoA activity and MLC phosphorylation, suggesting the involvement of RhoA/ROCK pathway in the vincristine-induced cytoskeletal reorganization and cellular invasion. Furthermore, we found that Y27632 as well as the siRNA for GEF-H1, a RhoA-specific activator, attenuated MLC phosphorylation, the formation of membrane blebs and the invasive ability after vincristine treatment. Conclusions These results indicate that vincristine activates GEF-H1/Rho

  2. Identification and Functional Analysis of A Novel Candidate Oncogene RAP2B in Lung Cancer

    Guobin FU

    2009-04-01

    Full Text Available Background and objective RAP2B is one of the 50 novel candidate genes cloned from the differential expression cDNA libraries constructed in lung cancer cells. Though RAP2B contains conserved domain and belongs to Ras superfamily, the function of RAP2B in carcinogenesis is still poorly understood. The aim of this study is to explore the roles of RAP2B gene in carcinogenesis. Methods RT-PCR was applied to examine transcriptional status of RAP2B in the tumor and corresponding adjacent tissues collected from 27 patients with lung squamous cell carcinoma. RAP2B expression plasmid was constructed and transfected into Rat1 cells to evaluate the in vitro transformation ability through colony formation assay. Reporter gene assay was performed to reveal the relationship between RAP2B geneand NF-kappaB pathway. Results About 67% (18/27 of tumor tissues show higher mRNA expression than that in the corresponding adjacent normal tissues. Typical transforming focus formation was observed in Rat1 cells which were transfected with RAP2B gene. The reporter gene assay data showed that RAP2B activated NF-kappaB pathway more than3 folds compared with the mock vector. Conclusion RAP2B may be a novel candidate oncogene that plays important roles in carcinogenesis through activation of NF-kappaB pathway.

  3. Impacts of the Glucuronidase Genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 on Tamoxifen Metabolism in Breast Cancer Patients.

    Alicia Romero-Lorca

    Full Text Available Tamoxifen is used to prevent and treat estrogen-dependent breast cancer. It is described as a prodrug since most of its antiestrogen effects are exerted through its hydroxylated metabolites 4-OH-tamoxifen and endoxifen. In prior work, we correlated optimal plasma levels of these metabolites with certain genotypes of CYP2D6 and SULT1A2. This descriptive study examines correlations between concentrations of tamoxifen's glucuronide metabolites and genotypes UGT1A4 Pro24Thr, UGT1A4 Leu48Val, UGT2B7 His268Tyr, UGT2B15 Asp85YTyr UGT2B15 Lys523Thr and UGT2B17del in 132 patients with estrogen receptor-positive breast cancer under treatment with tamoxifen. Patients were genotyped by real-time and conventional PCR-RFLP. The glucuronides 4-OH-tamoxifen-N-glucuronide, 4-OH-tamoxifen-O-glucuronide and endoxifen-O-glucuronide were isolated from blood plasma and quantified using a high-pressure liquid chromatography-tandem mass spectrometry system. Individuals who were homozygous for UGT1A448VAL showed significantly lower mean concentrations of both glucuronide metabolites compared to subjects genotyped as wt/wt plus wt/48Val (p=0.037 and p=0.031, respectively. Women homozygous for UGT2B7268Tyr also showed mean substrate/product ratios of 4-OH-tamoxifen/4-OH-tamoxifen-O-glucuronide and 4-OH-tamoxifen/4-OH-tamoxifen-N-glucuronide indicative of reduced glucuronidase activity compared to wt homozygotes or to heterozygotes for the polymorphism (p=0.005 and p=0.003, respectively. In contrast, UGT2B15 Lys523Thr and UGT2B17del were associated with possibly increased enzyme activity. Patients with at least one variant allele UGT2B15523Thr showed significantly higher 4-OH-tamoxifen-O-glucuronide and endoxifen-glucuronide levels (p=0.023 and p=0.025, respectively indicating a variant gene-dose effect. Higher 4-OH-tamoxifen-N-glucuronide levels observed in UGT2B17del genotypes (p=0.042 could be attributed to a mechanism that compensates for the greater expression of

  4. Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B) Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population

    Yongfeng Yang; Wenqiang Li; Hongxing Zhang; Ge Yang; Xiujuan Wang; Minli Ding; Tianzi Jiang; Luxian Lv

    2015-01-01

    Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In ...

  5. Günter Eich : Nicht geführte Gespräche (1964). Ein Gedicht des Schweigens im Dialog (mit sich selbst)1

    Haberkamm, Klaus

    2012-01-01

    Le poème Nicht geführte Gespräche, qui relève de la littérature hermétique, s’inscrit dans la tension paradoxale entre le chiffre, ce qui se ferme à la réception, et l’élan qui pousse de diverses manières à la communication. Comme le montre l’analyse détaillée du texte, le poème est engagé dans un dialogue, entre autres avec lui-même, au sens où il thématise et figure le silence dans l'acte de parole. Il est en dialogue avec son auteur et les théories qu’il représente, au sens où, considéré s...

  6. Rezension von: Barbara Holland-Cunz: Gefährdete Freiheit. Über Hannah Arendt und Simone de Beauvoir. Opladen u.a.: Verlag Barbara Budrich 2012.

    Mirjam Dierkes

    2012-11-01

    Full Text Available Von Barbara Holland-Cunz, die sich mit Simone de Beauvoir und Hannah Arendt bereits einzeln beschäftigt hat, liegt nun ein Band vor, in dem sie sich diesen herausragenden Denkerinnen des 20. Jahrhunderts gemeinsam widmet. In einer beinahe synoptisch anmutenden Herangehensweise fokussiert sie dabei auf den Begriff der Freiheit, der bei beiden von eminenter Bedeutung für das jeweilige Theoriegebäude ist. Holland-Cunz zufolge verstehen beide, bei einigen Unterschieden, Freiheit so, dass sie sich vor allem durch eine in sich eingeschriebene Gefährdung auszeichnet: Diese resultiert aus einem heroisch-emphatischen Gestus, der in paradoxer Weise gepaart wird mit einem abgeklärten Realismus. Über weite Strecken liest sich der Weg zu dieser Deutung, v. a. auch wegen einer teilweise sympathisch unkonventionellen und originellen Herangehensweise, sehr anregend und überzeugend.

  7. Generalized epilepsy with febrile seizure plus (GEFS+ spectrum: Novel de novo mutation of SCN1A detected in a Malaysian patient

    Emmilia H Tan

    2012-01-01

    Full Text Available In this report, we describe a 15-year-old Malaysian male patient with a de novo SCN1A mutation who experienced prolonged febrile seizures after his first seizure at 6 months of age. This boy had generalized tonic clonic seizure (GTCS which occurred with and without fever. Sequencing analysis of voltage-gated sodium channel a1-subunit gene, SCN1A, confirmed a homozygous A to G change at nucleotide 5197 (c.5197A > G in exon 26 resulting in amino acid substitution of asparagines to aspartate at codon 1733 of sodium channel. The mutation identified in this patient is located in the pore-forming loop of SCN1A and this case report suggests missense mutation in pore-forming loop causes generalized epilepsy with febrile seizure plus (GEFS+ with clinically more severe neurologic phenotype including intellectual disabilities (mental retardation and autism features and neuropsychiatric disease (anxiety disorder.

  8. Rap2b promotes proliferation, migration, and invasion of lung cancer cells.

    Peng, Yi-Gen; Zhang, Zheng-Qun; Chen, Yan-Bin; Huang, Jian-An

    2016-10-01

    Rap2b, a member of the guanosine triphosphate-binding proteins, is widely up-regulated in many types of tumors. However, the functional role of Rap2b in tumorigenesis of lung cancer remains to be fully elucidated. In this study, we investigated the effect of Rap2b on the lung cancer malignant phenotype, such as cell proliferation and metastasis. We found that Rap2b could promote the abilities of lung cancer cell wound healing, migration, and invasion via increasing matrix metalloproteinase-2 enzyme activity. Furthermore, Rap2b overexpression could increase the phosphorylation level of extracellular signal-regulated protein kinases 1/2. In conclusion, our results suggested that Rap2b may be a potential therapeutic target for lung cancer. PMID:26671640

  9. Frontotemporal dementia caused by CHMP2B mutation is characterised by neuronal lysosomal storage pathology

    Clayton, Emma L.; Mizielinska, Sarah; Edgar, James R.;

    2015-01-01

    Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The...... human CHMP2B mutation brain than in neurodegenerative disease or age-matched control brains. These data suggest that lysosomal storage pathology is the major neuronal pathology in FTD caused by CHMP2B mutation. Recent evidence suggests that two other genes associated with FTD, GRN and TMEM106B are...... important for lysosomal function. Our identification of lysosomal storage pathology in FTD caused by CHMP2B mutation now provides evidence that endolysosomal dysfunction is a major degenerative pathway in FTD....

  10. Characterization of acetylation of Saccharomyces cerevisiae H2B by mass spectrometry

    Zhang, Kangling

    2008-11-01

    Following the identification of histone H3 modifications in Saccharomyces cerevisiae [K. Zhang, Int. J. Mass Spectrom. 269 (2008) 101-111], here, we report a detailed characterization of post-translational modifications by LC/MS/MS analysis of tryptic and Glu-C digests of H2B proteins isolated from S. cerevisiae. We show that both H2B.1 and H2B.2 are acetylated at K6, K11, K16, K21 and K22 while H2B.2 has an additional acetylation site at K3. All the acetylation sites of yeast H2B except K3 of H2B.2 are located at the same positions on aligned protein sequences of Arabidopsis H2B variants that were reported previously to be acetylated at K6, K11, K27, K32, K38 and K39. A unique acetylation motif AEK is observed in the H2B variants of these two species, indicating a plant/yeast H2B specific acetyltransferase may exist.

  11. Review of magnetic features observed in (A,A')Ni2B2C solid solutions

    The nickel-borocarbides ANi2B2C [A=Y, Ln (lanthanide), An(actinide)], crystallizing in the body-centred tetragonal LuNi2B2C-type structure, are classified according to the existence or coexistence of superconducting and antiferromagnetic states (AF). The magnetic features observed in polycrystalline (A,A')Ni2B2C solid solutions, adopting the same crystal structure, are reviewed and discussed. Published data on the magnetism in (A,Ln)Ni2B2C systems (ANi2B2C nonmagnetic, A=Y,La,Lu) indicate a gradual rise in the threshold content, x(m), in (Y1-xLnx)Ni2B2C (Ln=Gd,Tb,Dy,Ho,Er) for the establishment of AF states. (A,A')Ni2B2C systems with magnetic end compounds show gradual variation in magnetic features when A and A' are both heavy Ln. The behaviour of (A,A')Ni2B2C systems of light A (Pr or U) and heavy A' (Dy or Tm) depends on the magnetic structures of the end compounds. In intermediate compositions, incomplete moment compensation in (Pr,Dy)Ni2B2C decreases TN, while different moment directions in the end compounds in (U,Dy)Ni2B2C lead to a directional frustration of ordered moments. Such a frustration in (U,Tm)Ni2B2C is related to different magnetic structures of the end compounds

  12. Phosphorylation-dependent changes in nucleotide binding, conformation, and dynamics of the first nucleotide binding domain (NBD1) of the sulfonylurea receptor 2B (SUR2B).

    de Araujo, Elvin D; Alvarez, Claudia P; López-Alonso, Jorge P; Sooklal, Clarissa R; Stagljar, Marijana; Kanelis, Voula

    2015-09-11

    The sulfonylurea receptor 2B (SUR2B) forms the regulatory subunit of ATP-sensitive potassium (KATP) channels in vascular smooth muscle. Phosphorylation of the SUR2B nucleotide binding domains (NBD1 and NBD2) by protein kinase A results in increased channel open probability. Here, we investigate the effects of phosphorylation on the structure and nucleotide binding properties of NBD1. Phosphorylation sites in SUR2B NBD1 are located in an N-terminal tail that is disordered. Nuclear magnetic resonance (NMR) data indicate that phosphorylation of the N-terminal tail affects multiple residues in NBD1, including residues in the NBD2-binding site, and results in altered conformation and dynamics of NBD1. NMR spectra of NBD1 lacking the N-terminal tail, NBD1-ΔN, suggest that phosphorylation disrupts interactions of the N-terminal tail with the core of NBD1, a model supported by dynamic light scattering. Increased nucleotide binding of phosphorylated NBD1 and NBD1-ΔN, compared with non-phosphorylated NBD1, suggests that by disrupting the interaction of the NBD core with the N-terminal tail, phosphorylation also exposes the MgATP-binding site on NBD1. These data provide insights into the molecular basis by which phosphorylation of SUR2B NBD1 activates KATP channels. PMID:26198630

  13. 75 FR 61577 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program

    2010-10-05

    ... FR 9385, Feb. 28, 2002; 72 FR 2763, Jan. 23, 2007. Because employers seeking to participate in the H... Process for Temporary Employment in Occupations other than Agriculture or Registered Nursing in the United States (H-2B Workers),'' govern the H-2B labor certification process, as well as the enforcement...

  14. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2011

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Pool 2B. Water-Data Report 2011 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  15. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2010

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Pool 2B. Water-Data Report 2010 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  16. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2009

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Pool 2B. Water-Data Report 2009 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  17. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2012

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Pool 2B. Water-Data Report 2012 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  18. Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations

    Urwin, Hazel; Authier, Astrid; Nielsen, Jørgen Erik;

    2010-01-01

    Mutations in CHMP2B cause frontotemporal dementia (FTD) in a large Danish pedigree, which is termed FTD linked to chromosome 3 (FTD-3), and also in an unrelated familial FTD patient. CHMP2B is a component of the ESCRT-III complex, which is required for function of the multivesicular body (MVB), a...

  19. First identification of Porcine Circovirus Type 2b mutant in pigs from Uruguay.

    Ramos, Natalia; Mirazo, Santiago; Castro, Gustavo; Arbiza, Juan

    2015-07-01

    Porcine Circovirus Type 2 (PCV2) is a worldwide distributed virus and is considered an important emerging pathogen related to several distinct disease syndromes in pigs. PCV2 strains are classified into three genotypes: PCV2a, with five subtypes (2A-2E), PCV2b with three subtypes (1A-1C) and PCV2c, only found in Denmark. Recently, several reports suggested the circulation of newly emerging PCV2b mutants (mPCV2b) isolated from pigs with PCVAD in cases of suspected vaccine failure. In this work, we report for the first time the identification of mPCV2b in pigs from Uruguay, providing an additional evidence of a global circulation. Complete genome characterization and phylogenetic analysis reveal that Uruguayan strains, as well as mPCV2b previously reported are closely related to other sequences already classified as PCV2b-1C. Furthermore, results showed that mPCV2b presented different genetic markers in the capsid protein compared with classical PCV2a/b strains. Further investigation about antigenic shift of the mPCV2b strains including the Uruguayan isolates is needed. PMID:26004195

  20. Coupling of glucose deprivation with impaired histone H2B monoubiquitination in tumors.

    Yasuyo Urasaki

    Full Text Available Metabolic reprogramming is associated with tumorigenesis. However, glucose metabolism in tumors is poorly understood. Here, we report that glucose levels are significantly lower in bulk tumor specimens than those in normal tissues of the same tissue origins. We show that mono-ubiquitinated histone H2B (uH2B is a semi-quantitative histone marker for glucose. We further show that loss of uH2B occurs specifically in cancer cells from a wide array of tumor specimens of breast, colon, lung and additional 23 anatomic sites. In contrast, uH2B levels remain high in stromal tissues or non-cancerous cells in the tumor specimens. Taken together, our data suggest that glucose deficiency and loss of uH2B are novel properties of cancer cells in vivo, which may represent important regulatory mechanisms of tumorigenesis.

  1. Global view of transcriptome in the brains of aged NR2B transgenic mice*****

    Chunxia Li; Men Su; Huimin Wang; Yinghe Hu

    2013-01-01

    NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of the NR2B subunit gene, Grin2b, in the neocortex of transgenic mice using real-time PCR. Next, we used microarrays to examine differences in neocortical gene expression. Pathway and signal-net analyses identified multiple pathways altered in the transgenic mice, in-cluding the P53, Jak-STAT, Wnt, and Notch pathways, as wel as regulation of the actin cytoskeleton and neuroactive ligand-receptor interactions. Further signal-net analysis highlighted the P53 and insulin-like growth factor pathways as key regulatory pathways. Our results provide new insight into understanding the molecular mechanisms of NR2B regulated age-related memory storage, normal organismal aging and age-related disease.

  2. Hall effect in LuNi2B2C and YNi2B2C borocarbides in normal and superconducting mixed states

    It was shown that the Hall resistivity ρxy for LuNi2B2C and YNi2B2C is negative in the normal and mixed states and has no sign reversal below Tc. In the mixed state the scaling relation ρxy approximately ρxxβ (ρxx is the longitudinal resistivity) was found for both compounds with β ∼ 2.0. In the normal state a distinct nonlinearity in the ρxy(H) dependence, accompanied by a large magnetoresistance, was found below 40 K only for LuNi2B2C. The difference in the behavior of Lu- and Y-based borocarbides seems to be connected with the difference in the Fermi surfaces of these compounds

  3. Interferon-alpha-2b induces autophagy in hepatocellular carcinoma cells through Beclin1 pathway

    To determine whether Interferon-alpha-2b (IFN-α2b) can modulate the autophagic response in hepatocellular carcinoma cells. Hepatocellular carcinoma cells were treated with IFN-α2b. Autophagy was assessed by acridine orange staining, GFP-LC3 dotted assay, transmission electron microscopy and immunoblotting. Acridine orange staining showed that IFN-α2b triggered the accumulation of acidic vesicular and autolysosomes in HepG2 cells. The acridine orange HepG2 cell ratios were (4.3±1.0)%, (6.9±1.4)%, and (13.1±2.3)%, respectively, after treatment with 100, 1,000, and 10,000 IU/mL IFN-α2b for 48 h. A markedly punctate pattern was observed in HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h, but only diffuse and weakly fluorescent GFP-LC3 puncta was observed in control cells. HepG2 cells treated with 10,000 IU/mL IFN-α2b for 48 h developed autophagosome-like characteristics, including single- or double-membrane vacuoles containing intact and degraded cellular debris. The Beclin1 and LC3-II protein expression was up-regulated by IFN-α2b treatment. Autophagy can be induced in a dose-dependent manner by treatment with IFN-α2b in HepG2 cells, and the Beclin1 signaling pathway was stimulated by IFN-α2b

  4. Immunogold localization of tobravirus 2b nematode transmission helper protein associated with virus particles.

    Vellios, Evangelos; Duncan, George; Brown, Derek; MacFarlane, Stuart

    2002-08-15

    Transmission of the tobraviruses Tobacco rattle virus (TRV) and Pea early-browning virus (PEBV) by trichodorid vector nematodes requires the viral coat protein (CP) and the 2b protein, a nonstructural protein encoded by RNA2, the smaller of the two viral genomic RNAs. It is hypothesized that the 2b protein functions by interacting with a small, flexible domain located at the C-terminus of the CP, forming a bridge between the virus particle and the internal surface of the vector nematode feeding apparatus. Antibodies specific for the 2b protein of PEBV or TRV did not bind to virus particles that were adsorbed to electron microscope grids and were not able to trap virus particles from extracts of infected plants. However, electron microscopy of thin sections of plants infected with PEBV probed with 2b-specific antibodies which were further gold-labeled showed that the 2b protein localizes exclusively to virus particles. Similarly, immunogold localization studies showed that the 2b protein of TRV isolate PaY4 is associated only with TRV PaY4 virus particles. When a recombinant TRV encoding the PaY4 2b protein and the CP from TRV isolate PpK20 was examined, the 2b protein could not be detected by Western blotting and in IGL experiments was not associated with virus particles. These results suggest that in the absence of a specific interaction between compatible CP and 2b proteins, the 2b protein does not accumulate. PMID:12202212

  5. Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma.

    Ikram, Fakhera; Ackermann, Sandra; Kahlert, Yvonne; Volland, Ruth; Roels, Frederik; Engesser, Anne; Hertwig, Falk; Kocak, Hayriye; Hero, Barbara; Dreidax, Daniel; Henrich, Kai-Oliver; Berthold, Frank; Nürnberg, Peter; Westermann, Frank; Fischer, Matthias

    2016-02-01

    Neuroblastoma is an embryonal pediatric tumor that originates from the developing sympathetic nervous system and shows a broad range of clinical behavior, ranging from fatal progression to differentiation into benign ganglioneuroma. In experimental neuroblastoma systems, retinoic acid (RA) effectively induces neuronal differentiation, and RA treatment has been therefore integrated in current therapies. However, the molecular mechanisms underlying differentiation are still poorly understood. We here investigated the role of transcription factor activating protein 2 beta (TFAP2B), a key factor in sympathetic nervous system development, in neuroblastoma pathogenesis and differentiation. Microarray analyses of primary neuroblastomas (n = 649) demonstrated that low TFAP2B expression was significantly associated with unfavorable prognostic markers as well as adverse patient outcome. We also found that low TFAP2B expression was strongly associated with CpG methylation of the TFAP2B locus in primary neuroblastomas (n = 105) and demethylation with 5-aza-2'-deoxycytidine resulted in induction of TFAP2B expression in vitro, suggesting that TFAP2B is silenced by genomic methylation. Tetracycline inducible re-expression of TFAP2B in IMR-32 and SH-EP neuroblastoma cells significantly impaired proliferation and cell cycle progression. In IMR-32 cells, TFAP2B induced neuronal differentiation, which was accompanied by up-regulation of the catecholamine biosynthesizing enzyme genes DBH and TH, and down-regulation of MYCN and REST, a master repressor of neuronal genes. By contrast, knockdown of TFAP2B by lentiviral transduction of shRNAs abrogated RA-induced neuronal differentiation of SH-SY5Y and SK-N-BE(2)c neuroblastoma cells almost completely. Taken together, our results suggest that TFAP2B is playing a vital role in retaining RA responsiveness and mediating noradrenergic neuronal differentiation in neuroblastoma. PMID:26598443

  6. The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy.

    Fonfara, Sonja; Hetzel, Udo; Oyama, Mark A; Kipar, Anja

    2014-03-01

    Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A contribution of serotonin to valvular disease has been reported, but myocardial expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA expression in dogs with DCM and to correlate results with expression of markers for inflammation and remodelling. Myocardial samples from eight healthy dogs, four dogs with DCM, five with cardiac diseases other than DCM and six with systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using quantitative PCR (qPCR). The results were compared to mRNA expression of selected cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and immunohistochemistry were employed to identify the cells expressing 5-HTR2B. The myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs with DCM, 5-HTR2B mRNA values were significantly greater than in all other groups, with highest levels of expression in the left ventricle and right atrium. Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs and TIMPs was observed. The findings suggest that serotonin might play a role in normal cardiac structure and function and could contribute to myocardial remodelling and functional impairment in dogs with DCM. PMID:24440442

  7. A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.

    Wen, Jiaming; Wang, Bohan; Du, Chuanjun; Xu, Gang; Zhang, Zhewei; Li, Yi; Zhang, Nan

    2015-01-01

    Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED. PMID:26447087

  8. Signatures of spin-glass behaviour in PrIr2B2 and heavy fermion behaviour in PrIr2B2C.

    Anupam; Anand, V K; Hossain, Z; Adroja, D T; Geibel, C

    2011-09-21

    The magnetic and transport properties of PrIr(2)B(2) and PrIr(2)B(2)C have been investigated by dc and ac magnetic susceptibility, specific heat, electrical resistivity and magnetoresistance measurements. PrIr(2)B(2) forms in CaRh(2)B(2)-type orthorhombic crystal structure (space group Fddd). At low fields the dc magnetic susceptibility of PrIr(2)B(2) exhibits a sharp anomaly near 46 K which is followed by an abrupt increase below 10 K with a peak at 6 K, and split-up in ZFC and FC data below 46 K. In contrast, the specific heat exhibits only a broad Schottky type hump near 9 K which indicates that there is no long range magnetic order in this compound. The thermo-remanent magnetization is found to decay very slowly with a mean relaxation time τ = 3917 s. An ac magnetic susceptibility measurement also observes two sharp anomalies; the peak positions strongly depend on the frequency and shift towards high temperature with an increase in frequency, obeying the Vogel-Fulcher law as expected for a canonical spin-glass system. The two spin-glass transitions occur at freezing temperatures T(f1) = 36 K and T(f2) = 3.5 K with shifts in the freezing temperatures per decade of frequency δT(f1) = 0.044 and δT(f2) = 0.09. An analysis of the frequency dependence of the transition temperature with critical slowing down, τ(max)/τ(0) = [(T(f)-T(SG))/T(SG)](-zν), gives τ(0) = 10(-7) s and exponent zν = 8, and the Vogel-Fulcher law gives an activation energy of 84 K for T(f1) and 27.5 K for T(f2). While zν = 8 is typical for spin-glass system, the characteristic relaxation time τ(0) = 10(-7) s is very large and comparable to that of superspin-glass systems. An addition of C in PrIr(2)B(2) leads to PrIr(2)B(2)C which forms in LuNi(2)B(2)C-type tetragonal structure (space group I4/mmm) and remains paramagnetic down to 2 K. The specific heat data show a broad Schottky type anomaly, which could be fairly reproduced with CEF analysis which suggests that the ground state is a

  9. Recombination luminescence in Li2B4O7 doped with manganese and copper

    Non-irradiated and irradiated ceramics of Li2B4O7:Mn, Li2B4O7:Mn,Be, and Li2B4O7:Mn,Cu were studied using electron paramagnetic resonance and luminescence spectroscopy. The emission of Mn2+ centres is observed in the thermoluminescence spectra of the low-temperature and dosimetric high-temperature glow peaks in irradiated samples. Arguments are given in favour of hole mobility being responsible for the dosimetric thermoluminescence peak at 490 K in Li2B4O7:Mn. The co-doping of Li2B4O7:Mn with Cu+ is shown to increase the sensitivity of the material to ionizing radiation. -- Highlights: ► Doped Li2B4O7 ceramics were studied by EPR and optical spectroscopy. ► In Li2B4O7:Mn ceramics Mn2+ emission is observed for the TSL peaks at 90 and 490 K ► We propose the release of holes to be responsible for the dosimetric peak at 490 K

  10. Proteomics-level analysis of myelin formation and regeneration in a mouse model for Vanishing White Matter disease.

    Gat-Viks, Irit; Geiger, Tamar; Barbi, Mali; Raini, Gali; Elroy-Stein, Orna

    2015-08-01

    Vanishing white matter (VWM) is a recessive neurodegenerative disease caused by mutations in translation initiation factor eIF2B and leading to progressive brain myelin deterioration, secondary axonal damage, and death in early adolescence. Eif2b5(R132H/R132H) mice exhibit delayed developmental myelination, mild early neurodegeneration and a robust remyelination defect in response to cuprizone-induced demyelination. In the current study we used Eif2b5(R132H/R132H) mice for mass-spectrometry analyses, to follow the changes in brain protein abundance in normal- versus cuprizone-diet fed mice during the remyelination recovery phase. Analysis of proteome profiles suggested that dysregulation of mitochondrial functions, altered proteasomal activity and impaired balance between protein synthesis and degradation play a role in VWM pathology. Consistent with these findings, we detected elevated levels of reactive oxygen species in mutant-derived primary fibroblasts and reduced 20S proteasome activity in mutant brain homogenates. These observations highlight the importance of tight translational control to precise coordination of processes involved in myelin formation and regeneration and point at cellular functions that may contribute to VWM pathology. Eif2b5(R132H/R132H) mouse model for vanishing white matter (VWM) disease was used for mass spectrometry of brain proteins at two time points under normal conditions and along recovery from cuprizone-induced demyelination. Comparisons of proteome profiles revealed the importance of mitochondrial function and tight coordination between protein synthesis and degradation to myelination formation and regeneration, pointing at cellular functions that contribute to VWM pathology. PMID:25920008

  11. Voraussetzungen für das syntope Vorkommen des Bläulings Maculinea arion und seiner Wirtsameise Myrmica sabuleti - Fallstudie gefährdeter Biodiversität auf Halbtrockenrasen der Schwäbischen Alb

    Grupp, Regina

    2009-01-01

    Der Schwarzgefleckte Ameisenbläuling Maculinea arion ist aufgrund seiner komplexen Habitatansprüche, die resultierend aus anthropogenen Umweltveränderungen nicht mehr abgedeckt werden können, im gesamten europäischen Verbreitungsgebiet stark gefährdet. Diese Tagfalterart ist neben dem Vorkommen der hauptsächlichen Raupenfutterpflanze Thymus pulegioides, seltener Origanum vulgare, vor allem auf syntopes Vorkommen mit seiner einzigen Wirtsameise Myrmica sabuleti angewiesen. Zur Beurteilung der ...

  12. Psychiatric side effects of pegylated interferon alfa-2b as compared to conventional interferon alfa-2b in patients with chronic hepatitis C

    Michael R Kraus; Arne Sch(a)fer; Herbert Csef; Michael Scheurlen

    2005-01-01

    AIM: To assess systematically the spectrum and extent of depressive symptoms comparing patient groups receiving peginterferon or conventional interferon.METHODS: Ninety-eight patients with chronic hepatitis C and interferon-based therapy (+ribavirin) were consecutively enrolled in a longitudinal study. Patients were treated with conventional interferon alfa-2b (48/98patients; 5 MIU interferon alfa-2b thrice weekly) or peginterferon alfa-2b (50/98 patients; 80-150 μgpeginterferon alfa-2b) in combination with weight-adapted ribavirin (800-1 200 mg/d). Repeated psychometric testing was performed before, three times during and once after antiviral therapy: Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS), anger/hostility by the Symptom Checklist-90 Items Revised (SCL-90-R).RESULTS: Therapy with pegylated interferon alfa-2bproduces comparable scores for depression (ANOVA:P = 0.875) as compared to conventional interferon.Maximums of depression scores were even higher and cases of clinically relevant depression were frequent during therapy with peginterferon. Scores for anger/hostility were comparable for both therapy subgroups.CONCLUSION: Our findings suggest that the extent and frequency of depressive symptoms in total are not reduced by peginterferon. Monitoring and management of neuropsychiatric toxicity especially depression have to be considered as much as in antiviral therapy with unmodified interferon.

  13. Histone demethylase KDM2B inhibits the chondrogenic differentiation potentials of stem cells from apical papilla.

    Wang, Jing-Jing; Dong, Rui; Wang, Li-Ping; Wang, Jin-Song; Du, Juan; Wang, Song-Lin; Shan, Zhao-Chen; Fan, Zhi-Peng

    2015-01-01

    Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. Histone methylation, controlled by histone methyltransferases and demethylases, may play a key role in MSCs differentiation. Previous studies determined that KDM2B can regulate the cell proliferation and osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2B is involved in the other cell lineages differentiation of MSCs. Here we used the stem cells from apical papilla (SCAPs) to study the role of KDM2B on the chondrogenic differentiation potentials in MSCs. In this study, Gain- and loss-of-function assays were applied to investigate the role of KDM2B on the chondrogenic differentiation. Alcian Blue Staining and Quantitative Analysis were used to investigate the synthesis of proteoglycans by chondrocytes. Real-time RT-PCR was used to detect the expressions of chondrogenesis related genes. The Alcian Blue staining and Quantitative Analysis results revealed that overexpression of KDM2B decreased the proteoglycans production, and real-time RT-PCR results showed that the expressions of the chondrogenic differentiation markers, COL1, COL2 and SOX9 were inhibited by overexpression of KDM2B in SCAPs. On the contrary, depletion of KDM2B increased the proteoglycans production, and inhibited the expressions of COL1, COL2 and SOX9. In conclusion, our results indicated that KDM2B is a negative regulator of chondrogenic differentiation in SCAPs and suggest that inhibition of KDM2B might improve MSC mediated cartilage regeneration. PMID:25932147

  14. Cloning, expression, and purification of a recombinant Tat-HA-NR2B9c peptide.

    Zhou, Hai-Hui; Zhang, Ai-Xia; Zhang, Yu; Zhu, Dong-Ya

    2012-10-01

    To design a peptide disrupting the interaction between N-methyl-d-aspartate receptors-2B (NR2B) and postsynaptic density protein-95 (PSD-95), a gene fragment encoding a chimeric peptide was constructed using polymerase chain reaction and ligated into a novel expression vector for recombinant expression in a T7 RNA polymerase-based expression system. The chimeric peptide contained a fragment of the cell membrane transduction domain of the human immunodeficiency virus type1 (HIV-1) Tat, a influenza virus hemagglutinin (HA) epitope-tag, and the C-terminal 9 amino acids of NR2B (NR2B9c). We named the chimeric peptide Tat-HA-NR2B9c. The expression plasmid contained a gene fragment encoding the Tat-HA-NR2B9c was ligated to the C-terminal fragment of l-asparaginase (AnsB-C) via a unique acid labile Asp-Pro linker. The recombinant fusion protein was expressed in inclusion body in Escherichia coli under isopropyl β-d-1-thiogalactopyranoside (IPTG) and purified by washing with 2M urea, solubilizing in 4M urea, and then ethanol precipitation. The target chimeric peptide Tat-HA-NR2B9c was released from the fusion partner following acid hydrolysis and purified by isoelectric point precipitation and ultrafiltration. SDS-PAGE analysis and MALDI-TOF-MS analysis showed that the purified Tat-HA-NR2B9c was highly homogeneous. Furthermore, we investigated the effects of Tat-HA-NR2B9c on ischemia-induced cerebral injury in the rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion, and found that the peptide reduced infarct size and improved neurological functions. PMID:22944204

  15. B2B-yrityksen markkinointi, viestintä ja asiakaspalvelu sosiaalisessa mediassa

    Liespuu, Mikael

    2014-01-01

    Tämän opinnäytetyön tarkoituksena oli tehdä tutkimus sosiaalisen median hyödyntämisestä B2B-yrityksessä. Tarkemmin lähestytään yrityksen markkinointia, viestintää sekä asiakaspalvelua sosiaalisessa mediassa. Sosiaalinen media mielletään usein kuluttajasuuntautuneeksi ja sitä se on aiemmin pääosin ollutkin. Tarkoituksena oli selvittää miten B2B-markkinoilla toimiva yritys saa enemmän irti sosiaalisesta mediasta. Ongelmana B2B-yritykselle sosiaalisen median osalta on se, että sosiaalisest...

  16. A B2B Digital Marketing Plan for a Micro Design Company

    Yin, Zi

    2015-01-01

    This product-based thesis was made for a Finnish micro design company – 2.Elämä Design. The objective of the thesis is to create a strategic B2B digital marketing plan for 2.Elämä Design in order to help its business expansion in Finland and globally. The final product of the thesis is a handbook of B2B digital marketing 2.Elämä Design could put into use in 2015. The author set up five project tasks in order to accomplish the thesis project. Firstly a thorough literature review on B2B di...

  17. Varainhankintatuotteiden B2B-markkinointi sosiaalisessa mediassa Case: MKV Oy

    Varvi, Tony

    2014-01-01

    Opinnäytetyössä käsitellään B2B- eli business-to-business-markkinointia sosiaalisessa mediassa. Toimeksiantajana opinnäytetyössä toimii MKV Oy, joka valmistaa, tuottaa ja myy yksilöityjä varainhankitatuotteita erilaisille organisaatioille. Yrityksen kohdeasiakkaita ovat erilaiset urheiluseurat, minkä takia yrityksen toiminta on B2B-toimintaa. Sosiaalista mediaa tarkastellaan eri näkökulmista sekä yleisesti että B2B-markkinointikeinona ja –kanavana. Työssä on käytetty lähteinä sekä kirjallisia...

  18. Social Media Challenges for B2B Organizations : A case study of a large manufacturer

    Berglund, Greger; Nilsson, Markus

    2011-01-01

    When looking at the engagement of social media in general we see that business-to-business (B2B) companies have a significantly lower day-to-day usage compared to business-to-consumer (B2C) companies even though there are more B2B companies present in the social media space. By studying a B2B company in the midst of implementing social media in their efforts to enhance their marketing capabilities we want to know if there are any specific reasons for these facts. When studying the company we ...

  19. Analysis of the Role of Social Media in B2B Marketing for Startups

    Fomicheva, Yekaterina

    2015-01-01

    Social media is a new, yet very prominent concept in present marketing communication. It has been growing steadily and became popular among marketers both in business-to-customer (B2C) and business-to-business (B2B). However, there has been more research done on how to apply and utilize social media in the B2C scenario and there are fewer explanations about B2B cases. Therefore, it was interesting to do research and analysis on how B2B companies operate, what are the factors influencing socia...

  20. Vaccination of dogs with canine parvovirus type 2b (CPV-2b) induces neutralising antibody responses to CPV-2a and CPV-2c.

    Wilson, Stephen; Illambas, Joanna; Siedek, Elisabeth; Stirling, Catrina; Thomas, Anne; Plevová, Edita; Sture, Gordon; Salt, Jeremy

    2014-09-22

    Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1-2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2. In this study we investigated whether vaccination with a CPV-2b containing vaccine would induce cross-reactive antibody responses to the other CPV-2 variants. Two studies where dogs were vaccinated with a multivalent vaccine, subsequently challenged with CPV-2b and sera samples analysed are presented. Six week old pups with defined serological status were vaccinated twice, three weeks apart and challenged either 5 weeks (MDA override study) or one year after vaccination (duration of immunity study). Sera samples were collected before each vaccination and at periods throughout each study. In each study the antibody profiles were very similar; serological responses against CPV-2a, CPV-2b and CPV-2c were higher than those for CPV-2. Nevertheless, responses against CPV-2 were well above levels considered clinically protective. In each study dogs also showed a rapid increase in antibody titres following vaccination, reached a plateau following second vaccination with a slight decline to challenge after which rapid anamnestic responses were seen. Evaluation of the serological responses suggests vaccination with CPV-2b would cross-protect against CPV-2a and CPV-2c, as well as against CPV-2 which is now extinct in the field. In conclusion we have demonstrated that vaccination of minimum aged dogs with a multivalent vaccine containing the CPV-2b variant strain will induce serological responses which are cross-reactive against all currently circulating field strains, CPV-2a and CPV-2c, and the now extinct field strain CPV-2. PMID:25148778

  1. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subclass...... was demonstrated in the patient's serum. In the serum of the bone-marrow donor a weak IgG1 anti-HPA-2b was demonstrated. IgG allotyping of the patient and donor showed identical results. We could not determine the origin of the anti-HPA-2b, although we hypothesize that the anti-HPA-2b was produced by...... immunocompetent donor lymphocytes infused with the suspension of bone-marrow cells....

  2. Kynurenic acid amides as novel NR2B selective NMDA receptor antagonists.

    Borza, István; Kolok, Sándor; Galgóczy, Kornél; Gere, Anikó; Horváth, Csilla; Farkas, Sándor; Greiner, István; Domány, György

    2007-01-15

    A novel series of kynurenic acid amides, ring-enlarged derivatives of indole-2-carboxamides, was prepared and identified as in vivo active NR2B subtype selective NMDA receptor antagonists. The synthesis and SAR studies are discussed. PMID:17074483

  3. High performance of solvothermally prepared VO2(B as anode for aqueous rechargeable lithium batteries

    Milošević Sanja

    2015-01-01

    Full Text Available The VO2 (B was synthesized via a simple solvothermal route at 160oC in ethanol. The initial discharge capacity of VO2 (B anode, in saturated aqueous solution of LiNO3, was 177 mAh g-1 at a current rate of 50 mA g-1. After 50 cycles capacity fade was 4%, but from 20th-50th cycle no capacity drop was observed. The VO2 (B has shown very good cyclability at current rate of even 1000 mA g-1 with initial discharge capacity of 92 mAh g-1. The excellent electrochemical performance of VO2 (B was attributed to the stability of micro-nano structures to repeated intercalation /deintercalation process, very good electronic conductivity as well as the very low charge transfer resistance in the aqueous electrolyte. [Projekat Ministarstva nauke Republike Srbije, br. III45014

  4. UV damage-induced RNA polymerase II stalling stimulates H2B deubiquitylation.

    Mao, Peng; Meas, Rithy; Dorgan, Kathleen M; Smerdon, Michael J

    2014-09-01

    Histone H2B monoubiquitylation plays an important role in RNA polymerase II (RNAPII) elongation. Whether this modification responds to RNAPII stalling is not yet known. We report that both yeast and human cells undergo a rapid and significant H2B deubiquitylation after exposure to UV irradiation. This deubiquitylation occurs concurrently with UV-induced transcription arrest and is significantly reduced in a DNA damage-bypassing RNAPII yeast mutant. Consistent with these results, yeast deubiquitylases Ubp8 and Ubp10 are associated with the RNAPII complex. Moreover, simultaneous deletion of Ubp8 and Ubp10 leads to a lack of H2B deubiquitylation after UV exposure. Consequently, nucleotide excision repair at an actively transcribed gene locus is decreased, whereas UV-induced RNAPII degradation is increased in ubp8Δubp10Δ mutant cells. These results indicate that eukaryotic cells respond to RNAPII arrest by deubiquitylating H2B to coordinate DNA repair and RNAPII degradation. PMID:25136098

  5. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2014

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Crane Creek are described in this report. Water-Data Report 2013 413721083124001 Pool 2B at Ottawa NWR...

  6. NMR study of vortex dynamics in LuNi2B2C

    11B- and 13C-pulsed nuclear magnetic resonance (NMR) measurements have been performed on two single crystals of LuNi2B2C and LuNi2B213C superconductors to investigate the vortex dynamics. 11B NMR for the unenriched crystal, LuNi2B2C, shows a single peak. All data of 11B NMR exhibit significant features characteristic of vortex lattice and fluctuation. On the other hand, 13C NMR for the enriched crystal, LuNi2B213C, evolves to double peaks below Tc. All NMR data for the broad peak of 13C NMR are consistent with those of 11B NMR indicating that this part comes from a superconducting phase. On the contrary, the narrow peak of 13C NMR is found to originate from an impure phase. This suggests that crystallinity is deteriorated during 13C enrichment into the crystal

  7. Managing Innovation Through Social Media in B2B SME-Context

    Lutz, Salla; Madsen, Svend Ole; Brink, Tove

    2015-01-01

    This paper shed light on how social media application can enhance innovation management in SME B2B context. Our study employs a qualitative case study approach with four B2B SMEs for in-depth research in the period from October 2013 to October 2014. The B2B SME managers aim for open business model...... innovation. However, social media application is hindered due to lack of specific local knowledge, lack of knowledge on social media technicalities and bewilderedness on leadership approaches within the social media application. A contribution is hereby made to the B2B SME field, to the academic...... understanding an insight on social media application and open business model innovation....

  8. Reversal of pathology in CHMP2B-mediated frontotemporal dementia patient cells using RNA interference

    Nielsen, Troels Tolstrup; Mizielinska, Sarah; Hasholt, Lis; Isaacs, Adrian M; Nielsen, Jørgen E

    2012-01-01

    BACKGROUND: Frontotemporal dementia is the second most common form of young-onset dementia after Alzheimer's disease, and several genetic forms of frontotemporal dementia are known. A rare genetic variant is caused by a point mutation in the CHMP2B gene. CHMP2B is a component of the ESCRT...... and that the knockdown causes reversal of the abnormal endosomal phenotype observed in patient fibroblasts. CONCLUSIONS: This is the first description of a treatment that reverses the cellular pathology caused by mutant CHMP2B and suggests that RNA interference might be a feasible therapeutic strategy....... Furthermore, it provides the first proof of a direct link between the disease-causing mutation and the cellular phenotype in cells originating from CHMP2B mutation patients. Copyright © 2012 John Wiley & Sons, Ltd....

  9. Magnetic structures in RNi2B2C (R = Ho, Er) superconductors

    Single crystal neutron diffraction techniques have been employed to study the evolution of magnetic structures in RNi2B2C compounds in an attempt to understand the relationship between magnetic ordering and superconductivity in several members of this series. For HoNi2B2C, below the superconducting transition (Tc = 8 K), an incommensurate magnetic structure characterized by two wave vectors (0.585 a* and 0.915 c*) is found in a narrow temperature range between 4.7 K and 6 K. This is the same temperature range where bulk measurements find a deep minimum in the upper critical field, Hc2. Below 4.7 K, HoNi2B2C is a simple collinear antiferromagnet. ErNi2B2C (Tc = 11 K) orders in an incommensurate modulated antiferromagnetic state characterized by an ordering wave vector 0.553 a* below 7 K, which coexists with superconductivity

  10. 1977 reinspection of Pilgrim 1 reactor vessel nozzle N2B

    Boston Edison Company provided NRC with the 1976 and 1977 ISI ultrasonic data of nozzle N2B. This data was used to plot the through wall thickness profiles of the 20% DAC values and 50% DAC values of the flaw between 2700 to 3100 around the N2B nozzle. Conclusions as to flaw growth between the 1976 and 1977 examinations are made from these plots

  11. Managers' perceptions of using of e-marketing in B2B relationships

    Σαμαντά, Ειρήνη; Κυριαζόπουλος, Π.

    2008-01-01

    Researchers agree that the use of the Internet is increasingly expanding in business-tobusiness (B2B) relationships in order to improve effective communication, distribution, and streamline processes with customers and stakeholders. This study examines a sample of 30 firms operating in Greece and discusses the benefits from B2B collaboration by using e-marketing. The method used for the quantitative analysis is the factor analysis and ordinal symmetric measures; Kendall’s tau-b...

  12. Intestinal Npt2b Plays a Major Role in Phosphate Absorption and Homeostasis

    Sabbagh, Yves; O'Brien, Stephen P.; Song, Wenping; Boulanger, Joseph H; Stockmann, Adam; Arbeeny, Cynthia; Schiavi, Susan C.

    2009-01-01

    Intestinal phosphate absorption occurs through both a paracellular mechanism involving tight junctions and an active transcellular mechanism involving the type II sodium-dependent phosphate cotransporter NPT2b (SLC34a2). To define the contribution of NPT2b to total intestinal phosphate absorption, we generated an inducible conditional knockout mouse, Npt2b−/− (Npt2bfl/fl:Cre+/−). Npt2b−/− animals had increased fecal phosphate excretion and hypophosphaturia, but serum phosphate remained unchan...

  13. YNi2B2C: possible anisotropic pressure dependence of the superconducting transition temperature

    The effect of chemical pressure on the superconductivity of the (Y1-xLax)Ni2B2C system was studied. The results give an indication that the experimentally observed hydrostatic pressure for YNi2B2C is possibly a consequence of the balance between positive in-plane and negative out-of-plane uniaxial pressure derivatives. It is suggested that c-uniaxial pressure is detrimental for superconductivity in this system. (author)

  14. Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein.

    Da Ao

    Full Text Available Viroporins are a family of low-molecular-weight hydrophobic transmembrane proteins that are encoded by various animal viruses. Viroporins form transmembrane pores in host cells via oligomerization, thereby destroying cellular homeostasis and inducing cytopathy for virus replication and virion release. Among the Picornaviridae family of viruses, the 2B protein encoded by enteroviruses is well understood, whereas the viroporin activity of the 2B protein encoded by the foot-and-mouth disease virus (FMDV has not yet been described. An analysis of the FMDV 2B protein domains by computer-aided programs conducted in this study revealed that this protein may contain two transmembrane regions. Further biochemical, biophysical and functional studies revealed that the protein possesses a number of features typical of a viroporin when it is overexpressed in bacterial and mammalian cells as well as in FMDV-infected cells. The protein was found to be mainly localized in the endoplasmic reticulum (ER, with both the N- and C-terminal domains stretched into the cytosol. It exhibited cytotoxicity in Escherichia coli, which attenuated 2B protein expression. The release of virions from cells infected with FMDV was inhibited by amantadine, a viroporin inhibitor. The 2B protein monomers interacted with each other to form both intracellular and extracellular oligomers. The Ca(2+ concentration in the cells increased, and the integrity of the cytoplasmic membrane was disrupted in cells that expressed the 2B protein. Moreover, the 2B protein induced intense autophagy in host cells. All of the results of this study demonstrate that the FMDV 2B protein has properties that are also found in other viroporins and may be involved in the infection mechanism of FMDV.

  15. An ontology-based approach to define and manage B2B interoperability

    Gessa, Nicola

    2007-01-01

    Electronic business surely represents the new development perspective for world-wide trade. Together with the idea of ebusiness, and the exigency to exchange business messages between trading partners, the concept of business-to-business (B2B) integration arouse. B2B integration is becoming necessary to allow partners to communicate and exchange business documents, like catalogues, purchase orders, reports and invoices, overcoming architectural, applicative, and semantic differences, accordin...

  16. CRM in the digital age: implementation of CRM in three contemporary B2B firms

    Lipiäinen, Heini

    2015-01-01

    Purpose – The purpose of this study was to contribute to the current discussion on digitization in companies’ marketing from a customer relationship management (CRM) perspective by examining the role and objectives of CRM and the exploitation of social media to serve the objectives of CRM in contemporary business-to-business (B2B) companies. Design/methodology/approach – The data are collected through semi-structured themed interviews with key marketing/sales managers from three B2B...

  17. A core level spectroscopic study on RNi2B2C (R=Y,Er) borocarbides

    Polycrystalline samples of YNi2B2C and magnetic ErNi2B2C were prepared by arc-melting technique with a Tc ∼ 15 K. Core level spectroscopic studies have been performed in order to see the valence of Y, Er and Ni. The results show that Ni and Er exists in 2+ valence state and Y exists in 3+ valence state. (author)

  18. Strategic Marketing Planning for a B2B High-Tech Manufacturer

    Malinen, Mikko

    2013-01-01

    Manufacturing companies in the B2B high-tech sector are facing challenges in adapting to changes in the international and increasingly competitive market environment of today. Strategic marketing management has an important role in creating and delivering value to customers. B2B companies that adopt strategic marketing practices are winning the race for market share. The aim of this study is to create a marketing strategy for Company X, in order to secure its leading position and to increase ...

  19. Gefühlsgemeinschaft“ – Autobiographische Erinnerungen an den BDM und der Erinnerungsdiskurs Community of Feeling—Autobiographical Memories of the BDM and Memory Discourse

    Leonie Wagner

    2008-11-01

    Full Text Available Gisela Miller-Kipp dokumentiert und analysiert 27 Auszüge aus veröffentlichten Erinnerungen ehemaliger BDM-Mitglieder mit dem Ziel, deren Empfindungen und Gefühle zu rekonstruieren. Dabei sind interessante Einblicke möglich, die jedoch die von der Autorin intendierte Repräsentativität nicht einlösen (können. Zudem handelt es sich um Erinnerungen und damit um retrospektiv vorgenommene Konstruktionen, die meist noch mit dem Ziel einer Veröffentlichung aufgeschrieben wurden. Der Band liefert insofern wichtige Anregungen, ist aber in wissenschaftlicher Hinsicht nicht zufriedenstellend.Gisela Miller-Kipp documents and analyzes 27 excerpts from the published memories of former BDM-members with the goal of reconstructing their feelings and perceptions. This approach makes interesting insights possible but it cannot honor the author’s intended representativeness. In addition, because the book is about memories it presents retrospectively collected constructions that were mostly written down after the fact with the goal of publication. The volume therefore provides important perspectives that are not satisfying in a scientific respect.

  20. 基于GEF框架的AFDX网络建模工具的设计与实现%Design and Implementation of AFDX Network Modeling based on GEF

    盛春玲; 饶俊文; 李为民

    2013-01-01

    This paper presents an AFDX network modeling method based on Eclipse GEF framework. Based on this method, a graphical AFDX network modeling tool is developed as a RCP application with a MVC structure. It provides an efficient environment to display and edit an AFDX network. Since an open platform based on Eclipse RCP technology is built, the user is able to integrate any new plug-in function into this platform without any limits. It can increase the expansibility of the AFDX network modeling tool.%本文提出了基于Eclipse GEF框架的AFDX网络建模方法。该方法应用GEF的MVC结构,以RCP的形式实现了图形化的AFDX网络建模工具,为用户提供了高效的展示和编辑AFDX网络模型的环境。由于建立了基于Eclipse RCP技术的开放性平台,用户可以Eclipse插件的形式将任何新的功能无缝地集成在此平台下,极大地提高了工具的可扩展性。

  1. Yields of O2(b 1 Sigma g +) from reactions of HO2. [in planetary atmospheres

    Keyser, L. F.; Choo, K. Y.; Leu, M. T.

    1985-01-01

    The production of O2(b 1 Sigma g +) has been monitored for several reactions of the HO2 radical at 300 K using a discharge-flow apparatus with resonance fluorescence and chemiluminescence detection. In all cases, the resulting quantum efficiencies were found to be less than 0.03. O2(b) was observed when F atoms were added to H2O2 in the gas phase. The signal strengths of O2(b) were proportional to initial concentrations of HO2 formed by the F + H2O2 reaction. Observed /O2(b)/, /HO2/, and /OH/ vs /F/0 were analyzed using a simple three-step mechanism and a more complete computer simulation with 22 reaction steps. The results indicate that the F + HO2 reaction yields O2(b) with an efficiency of (3.6 + or - 1.4) x 10 to the -3rd. Yields from the O + OH2 reaction were less than 0.02, indicating that this reaction cannot be a major source of the O2(b) emission observed in the earth's nightglow.

  2. Magnetic properties of ball-milled TbFe2 and TbFe2B

    J Arout Chelvane; S Kasiviswanathan; M V Rao; G Markandeyulu

    2004-04-01

    The magnetic properties of ball-milled TbFe2 and TbFe2B were studied by magnetization measurements. X-ray diffraction studies on TbFe2B showed that boron occupied interstitial position in the crystal structure, just as hydrogen did. The value of the saturation magnetization of TbFe2B was found to be smaller than that of TbFe2. This is explained on the basis of a charge transfer between the boron atoms and the 3d band of Fe. The anisotropy of TbFe2B was found to be large compared to that of TbFe2. X-ray diffractograms for the ball milled samples showed that after 80 h of milling, a predominantly amorphous phase was obtained. TbFe2B was found to undergo easy amorphization compared to TbFe2. Magnetization of TbFe2 was found to decrease rapidly with initial milling hours and was found to be constant with further hours of milling. TbFe2B exhibited an anomalous behaviour with an increase in moment with milling hours and this may be due to the segregation of -Fe.

  3. Sh3pxd2b mice are a model for craniofacial dysmorphology and otitis media.

    Yang, Bin; Tian, Cong; Zhang, Zhi-guang; Han, Feng-chan; Azem, Rami; Yu, Heping; Zheng, Ye; Jin, Ge; Arnold, James E; Zheng, Qing Y

    2011-01-01

    Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee) mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee) mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) mirrors craniofacial dysmorphology and otitis media in humans. PMID:21818352

  4. O-glycosylation in hinge region of mouse immunoglobulin G2b.

    Kim, H; Yamaguchi, Y; Masuda, K; Matsunaga, C; Yamamoto, K; Irimura, T; Takahashi, N; Kato, K; Arata, Y

    1994-04-22

    Mouse monoclonal immunoglobulin G2b (IgG2b) antibodies are known to contain two forms of the heavy chain that are different in susceptibility to the protease attack. In the present study, by use of an affinity column containing sialic acid-binding lectins from Maackia amurensis seeds, a mouse monoclonal IgG2b was successfully separated into three phenotypes, which are different in the degree of sialylation in the heavy chain. In the N-linked oligosaccharides from all of the IgG2b phenotypes, virtually no sialylation was detected. Elution profiles of the lysyl endopeptidase digestion products were compared for the three phenotypes. The peptides eluted at different retention times were subjected to fast atom bombardment-mass spectrometry and amino acid sequence analyses. It was revealed that approximately 40% of the heavy chain of the mouse IgG2b are O-glycosylated at Thr-221A in the hinge region, predominantly with a tetrasaccharide composed of GalNAc, Gal, and two N-glycolylneuraminic acid residues. We suggest that the O-glycosylation renders the hinge region resistant against the proteolyses of the heavy chain. A therapeutic significance of the O-glycosylation of IgG2b is briefly discussed. PMID:7512967

  5. DAPK1 Interaction with NMDA Receptor NR2B Subunits Mediates Brain Damage in Stroke

    Tu, Weihong; Xu, Xin; Peng, Lisheng; Zhong, Xiaofen; Zhang, Wenfeng; Soundarapandian, Mangala M.; Balel, Cherine; Wang, Manqi; Jia, Nali; Zhang, Wen; Lew, Frank; Chan, Sic Lung; Chen, Yanfang; Lu, Youming

    2010-01-01

    SUMMARY N-methyl-D-aspartate (NMDA) receptors constitute a major subtype of glutamate receptors at extra-synaptic sites that link multiple intracellular catabolic processes responsible for irreversible neuronal death. Here, we report that cerebral ischemia recruits death-associated protein kinase 1 (DAPK1) into the NMDA receptor NR2B protein complex in the cortex of adult mice. DAPK1 directly binds with the NMDA receptor NR2B C-terminal tail consisting of amino acid 1292–1304 (NR2BCT). A constitutively active DAPK1 phosphorylates NR2B subunit at Ser-1303 and in turn enhances the NR1/NR2B receptor channel conductance. Genetic deletion of DAPK1 or administration of NR2BCT that uncouples an activated DAPK1 from an NMDA receptor NR2B subunit in vivo in mice blocks injurious Ca2+ influx through NMDA receptor channels at extrasynaptic sites and protects neurons against cerebral ischemic insults. Thus, DAPK1 physically and functionally interacts with the NMDA receptor NR2B subunit at extra-synaptic sites and this interaction acts as a central mediator for stroke damage. PMID:20141836

  6. Allosteric inhibition of the NS2B-NS3 protease from dengue virus.

    Yildiz, Muslum; Ghosh, Sumana; Bell, Jeffrey A; Sherman, Woody; Hardy, Jeanne A

    2013-12-20

    Dengue virus is the flavivirus that causes dengue fever, dengue hemorrhagic disease, and dengue shock syndrome, which are currently increasing in incidence worldwide. Dengue virus protease (NS2B-NS3pro) is essential for dengue virus infection and is thus a target of therapeutic interest. To date, attention has focused on developing active-site inhibitors of NS2B-NS3pro. The flat and charged nature of the NS2B-NS3pro active site may contribute to difficulties in developing inhibitors and suggests that a strategy of identifying allosteric sites may be useful. We report an approach that allowed us to scan the NS2B-NS3pro surface by cysteine mutagenesis and use cysteine reactive probes to identify regions of the protein that are susceptible to allosteric inhibition. This method identified a new allosteric site utilizing a circumscribed panel of just eight cysteine variants and only five cysteine reactive probes. The allosterically sensitive site is centered at Ala125, between the 120s loop and the 150s loop. The crystal structures of WT and modified NS2B-NS3pro demonstrate that the 120s loop is flexible. Our work suggests that binding at this site prevents a conformational rearrangement of the NS2B region of the protein, which is required for activation. Preventing this movement locks the protein into the open, inactive conformation, suggesting that this site may be useful in the future development of therapeutic allosteric inhibitors. PMID:24164286

  7. Neutron diffraction studies of magnetic ordering in superconducting ErNi2B2C and TmNi2B2C in an applied magnetic field

    The field-induced magnetic structures of ErNi2B2C and TmNi2B2C in are especially interesting because the field suppresses the superconducting order parameter and therefore the magnetic properties can be studied while varying the strength of superconductivity. ErNi2B2C: For magnetic fields along all three symmetry directions, the observed magnetic structures have a period corresponding to the Fermi surface nesting structure. The phase diagrams present all the observed magnetic structures. Two results remain unresolved: 1. When applying the magnetic field along [010], the minority domain (QNB = (0,Q,0) with moments perpendicular to the field) shows no signs of hysteresis. I expected it to be a meta-stable state, which would be gradually suppressed by a magnetic field, and when decreasing the field it would not reappear until some small field of approximately 0.1 T. 2. When the field is applied along [110], the magnetic structure rotates a small angle of 0.5 degrees away from the symmetry direction. TmNi2B2C: A magnetic field applied in the [100] direction suppresses the zero field magnetic structure QF = (0.094,0.094,0) (TN = 1.6 K), in favor of the Fermi surface nesting structure QN = (0.483,0,0). The appearance of the QN phase was initially believed to be caused by the suppression of superconductivity. This suppression should make it favorable to create a magnetic order with a Q-vector determined by the maximum in the magnetic susceptibility at the Fermi surface nesting vector QN. The phase diagram for the magnetic structures is presented, however several properties of the QN magnetic structure cannot be explained within any known models. Quadrupolar ordering is suggested as a possible candidate for explaining these features of the QN structure. (au)

  8. Overlapping B2B and Family Business Marketing : A Study about Family and B2B Firms Exhibiting at Bilsport Performance and Custom Motor Show

    Kervaire Orellana, Brian André; DeLeon, Eber Andres

    2009-01-01

    Background: Family Businesses’ way of doing marketing has similarities with B2B marketing. Usuallyfamily firms focus on what they have traditionally done well and diversify in related areas using their knowledge of how to perform in certain markets with certain customers and by offering certain productsand services. In order to do this, it is important for family firms, as for firms operating in B2Bmarkets, to create and keep good relationships with their stakeholders, so that at the end thei...

  9. Competency-orientated brand cooperations of power supply companies in the B2B sector; Kompetenzorientierte Markenkooperationen von Energieversorgungsunternehmen im B2B-Kundenbereich

    Peuser, M.M.

    2008-07-01

    On the basis of an extensive empirical study with B2B electricity users, the author of the book under consideration examines brand co-operations of power supply companies with companies not working in the area of energy production. Based on the view of various co-operation alternatives, impact relations and success-determining factors of influence in the area of B2B customers are identified. The term of the authority of an energy brand is discussed. Beside this, profiles of concrete brands of current power supply companies from the view of B2B customers are pointed out, and recommendations for the organization of brand co-operation and the structure of mark authority in practice are shown. This contribution is written for lecturers and students of the management economics with the emphasis of marketing and management as well as high-level personnel in the energy industry, who wants to develop strong mark authority by brand co-operation.

  10. Functional characterization of a type 2 metallothionein isoform (OsMTI-2b) from rice.

    Pirzadeh, Soheil; Shahpiri, Azar

    2016-07-01

    Metallothioneins (MTs) are a family of Cys-rich, low molecular weight, cytoplasmic metal binding proteins. MTs are present in all eukaryotes as well as some prokaryotes. Plant MTs are divided into four types based on Cys distribution pattern in their amino acid sequences. In the present work, the gene encoding OsMTI-2b, a type 2 MT found in rice, was cloned into pET41a vector. The resulting construct was transformed into Escherichia coli strain Rosetta (DE3). Following the induction with Isopropyl β-d-1-thiogalactopyranoside the OsMTI-2b was expressed as carboxyl-terminal extensions of glutathione-S-transferase (GST-tag), a 6His-tag, and an S-tag. The expressed recombinant fusion protein was named GST-OsMTI-2b. As compared with control, transgenic E. coli cells expressing GST-OsMTI-2b accumulated more Pb(2+), Ni(2+), Cd(2+), Zn(2+) and Cu(2+) from culture medium and showed increased tolerance against these metals. Furthermore the E. coli cells expressing OsMTI-2b accumulated significantly higher Pb(2+) than previously made strains which expressing other rice OsMT isoforms. The recombinant GST-OsMTI-2b was purified using affinity chromatography. According to in vitro assays the protein GST-OsMTI-2b was able to form complexes with Pb(2+), Ni(2+), Cd(2+) and Zn(2+). However, the binding ability for the different metals differed in the order: Pb(2+)>Cd(2+)>Zn(2+)>Ni(2+). PMID:27079330

  11. Supporting the Health Quality Measures Format in i2b2.

    Klann, Jeffrey G; Murphy, Shawn N

    2013-01-01

    The Health Quality Measures Format (HQMF) is an HL7 standard for expressing computable queries of clinical data. It is becoming increasingly consequential for both quality measurement and population health research. A variety of national leadership is involved in its development and deployment, including the Meaningful Use incentive program, the Query Health initiative, the Joint Commission, the National Quality Forum (NQF), and the Food and Drug Administration. Here we analyze the structure of HQMF and apply this to computation of HQMF on Informatics for Integrating Biology and the Bedside (i2b2). i2b2 is a widely used, modular, open-source clinical research data repository. We implement a translator to convert between HQMF and i2b2-XML format that covers the subset of HQMF supported in i2b2-XML, which will be expanded in the next release of i2b2. This translator is part of the freely-available reference implementation of the QueryHealth initiative. PMID:24303250

  12. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure

    Wiebke Janssen

    2015-01-01

    Full Text Available Objective. The serotonin (5-HT pathway was shown to play a role in pulmonary hypertension (PH, but its functions in right ventricular failure (RVF remain poorly understood. The aim of the current study was to investigate the effects of Terguride (5-HT2A and 2B receptor antagonist or SB204741 (5-HT2B receptor antagonist on right heart function and structure upon pulmonary artery banding (PAB in mice. Methods. Seven days after PAB, mice were treated for 14 days with Terguride (0.2 mg/kg bid or SB204741 (5 mg/kg day. Right heart function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI, and histomorphometric methods. Total secreted collagen content was determined in mouse cardiac fibroblasts isolated from RV tissues. Results. Chronic treatment with Terguride or SB204741 reduced right ventricular fibrosis and showed improved heart function in mice after PAB. Moreover, 5-HT2B receptor antagonists diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro. Conclusion. 5-HT2B receptor antagonists reduce collagen deposition, thereby inhibiting right ventricular fibrosis. Chronic treatment prevented the development and progression of pressure overload-induced RVF in mice. Thus, 5-HT2B receptor antagonists represent a valuable novel therapeutic approach for RVF.

  13. Involvement of CYP2B6 in the biotransformation of propofol by human liver microsomes

    TANG Bing; WANG Jun-ke; FENG Wan-yu

    2008-01-01

    Objective To determine whether the cytochrome P4502B6 (CYP2B6) is involved in the oxidation of propofol by human liver microsomes. Methods The change of propofol concentration in an incubation mixture with human liver microsomes was monitored by the high performance liquid chromatography (HPLC), in order to calculate the rate constants of metabolism of propofol. The correlation between the rate constants and the rate of metabolism of CYP2B6 selective substrate bupropion, and the effect of two different CYP2B6 specific inhibitors on the propofol metabolism were examined. Results The mean rate constant of propofol metabolism by liver microsomes obtained from twelve individuals was 3.9 (95 % confidence intervals 3.3, 4.5) nmol·min-1·mg-1 protein. The rate constants of propofol metabolism by liver microsomes were significantly correlated with bupropion hydroxylation (r=0.888, P<0.001). Both selective chemical inhibitors of CYP2B6, orphenadrine and N, N′, N″-triethylenethiophosphoramide (thioTEPA), reduced the rate constants of propofol metabolism by 37.596 (P<0.001) and 42.796 (P<0.001)in liver microsomes, respectively. Conclusions CYP2B6 is predominantly involved in the oxidation of propofol by human liver microsomes.

  14. Benzimidazolone bioisosteres of potent GluN2B selective NMDA receptor antagonists.

    Lütnant, Ines; Schepmann, Dirk; Wünsch, Bernhard

    2016-06-30

    Overactivation of the NMDA receptor is associated with excitotoxic events leading to neurodegenerative processes as observed during the development of Alzheimer's disease, ParFnson's disease, Chorea Huntington and epilepsy. Negative allosteric modulators addressing selectively the ifenprodil binding site of GluN2B subunit containing NMDA receptors are of major interest due to their neuroprotective potential accompanied by few side effects. Herein benzimidazolone bioisosteres of potent GluN2B antagonists 1-5 were designed and synthesized. A seven step sequence provided the central intermediate 19 in 28% yield. Elimination of water, methylation, epoxidation, epoxide rearrangement and finally reductive amination afforded the [7]annulenobenzimidazolone 30 with a 3-phenylpropylamino substituent in 6-position. Although 30 fits nicely into the pharmacophore of potent GluN2B antagonists, the gluN2B binding affinity of 30 was only moderate (Ki = 697 nM). Additionally, 30 shows low selectivity over the σ2 receptor (Ki = 549 nM). The moderate GluN2B affinity was explained by the rigid tricyclic structure of the [7]annulenobenzimidazolone 30. PMID:27061977

  15. 26 CFR 301.6103(p)(2)(B)-1 - Disclosure of returns and return information by other agencies.

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Disclosure of returns and return information by other agencies. 301.6103(p)(2)(B)-1 Section 301.6103(p)(2)(B)-1 Internal Revenue INTERNAL REVENUE... Information and Returns Returns and Records § 301.6103(p)(2)(B)-1 Disclosure of returns and return...

  16. 77 FR 28764 - Temporary Non-agricultural Employment of H-2B Aliens in the United States

    2012-05-16

    ... published a Final Rule amending the H-2B regulations at 20 CFR part 655, Subpart A. 77 FR 10038, February 21... Agriculture or Registered Nursing in the United States (H-2B Workers), and Other Technical Changes, 73 FR... H-2B Aliens in the United States AGENCY: Employment and Training Administration, Labor. ]...

  17. Genes for resistance to stripe rust on chromosome 2B and their application in wheat breeding

    Peigao Luo; Xueyun Hu; Huaiyu Zhang; Zhenglong Ren

    2009-01-01

    Stripe rust,caused by Puccinia striiformis f.sp.tritici,is one of the most damaging diseases of wheat worldwide.Growing resistant cultivars is the most economic and environmental friendly way to control the disease.There are many resistance genes to stripe rust located on wheat chromosome 2B.Here,we propose a strategy to construct the recombinant wheat chromosome 2B with multiple resistances to stripe rust by making crosses between wheat lines or cultivars carrying Yr genes and using marker-assisted selection,based on the reported information about resistance spectrum,chromosomal location,and linked markers of the genes.Pyramiding the resistance genes on 2B would afford a valuable strategy to control the disease by cultivating varieties with durable resistance.The possibility,efficiency,and prospect of the suggested strategy are reviewed in the paper.

  18. Design, drilling, and construction of well RRL-2B, and piezometer nest RRL-2C

    This document describes the design, drilling and construction of the well RRL-2B and piezometer nest RRL-2C at the RRL-2 location. Well RRL-2B will act as the discharge well for performing large-scale hydraulic tests in units of the Grande Ronde Basalt. Piezometer nest RRL-2C will act as the primary observation points in the vicinity of the RRL-2 location. Water levels will also be measured in RRL-2C as part of the piezometer baseline monitoring program. Well RRL-2B is completed as a 12.25-in. (31.12-cm) open hole at the interim depth of 2858 ft (871.1 m). On completion of testing the Rocky Coulee flow top, the well will be deepened to the next horizon for testing. 33 refs., 25 figs., 4 tabs

  19. RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation.

    Fuchs, Gilad; Shema, Efrat; Vesterman, Rita; Kotler, Eran; Wolchinsky, Zohar; Wilder, Sylvia; Golomb, Lior; Pribluda, Ariel; Zhang, Feng; Haj-Yahya, Mahmood; Feldmesser, Ester; Brik, Ashraf; Yu, Xiaochun; Hanna, Jacob; Aberdam, Daniel; Domany, Eytan; Oren, Moshe

    2012-06-01

    Embryonic stem cells (ESCs) maintain high genomic plasticity, which is essential for their capacity to enter diverse differentiation pathways. Posttranscriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2Bub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of relatively long genes during ESC differentiation. Furthermore, we identify the deubiquitinase USP44 as a negative regulator of H2B ubiquitylation, whose downregulation during ESC differentiation contributes to the increase in H2Bub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner. PMID:22681888

  20. Uso de una conantokina y anticuerpos policlonales para identificar la subunidad NR2B del receptor

    Leonardo Lareo,†; Edgar Reyes M; Edwin Reyes G

    2010-01-01

    Objetivo. Proponer una metodología de identificación de la subunidad NR2B, mediante el uso de conantokina G, así como una adecuada extracción de la subunidad NR2B. Materiales y métodos. Se ensayaron dos metodologías para la extracción de la subunidad NR2B de cerebro de rata adulta, la primera buscó la extracción de la subunidad a partir de la membrana mediante la utilización del detergente deoxicolato de sodio y la segunda, garantizó primero la solubilización y eliminación de proteínas citopl...

  1. Possible coexistence of superconductivity and magnetic order in NdPt2B2C

    S K Dhar; A D Chinchure; E Alleno; C Godart; L C Gupta; R Nagarajan

    2002-05-01

    Coexistence of superconductivity and magnetic order has been one of the exciting aspects of the quaternary borocarbide superconductors. So far, RNi2B2C (R=Tm, Er, Ho and Dy) are the only known magnetic superconductors in this family. Here, we present our resistivity, magnetization and heat capacity studies on NdPt2B2C (nominal composition, NdPt1.5Au0.6B2C and NdPt2.1B2.4C1.2). We find superconductivity in both samples with c,onset∼ 3 K. Bulk magnetic order is found to occur below 1.7 K. We suggest that NdPt2B2C is a possible magnetic superconductor.

  2. A POPULATION-SPECIFIC HTR2B STOP CODON PREDISPOSES TO SEVERE IMPULSIVITY

    Bevilacqua, Laura; Doly, Stéphane; Kaprio, Jaakko; Yuan, Qiaoping; Tikkanen, Roope; Paunio, Tiina; Zhou, Zhifeng; Wedenoja, Juho; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud; Hodgkinson, Colin A.; Dell’Osso, Liliana; Suvisaari, Jaana; Coccaro, Emil; Rose, Richard J; Peltonen, Leena; Virkkunen, Matti; Goldman, David

    2011-01-01

    SUMMARY Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behavior. The complex origins of impulsivity hinder identification of the genes influencing both it and diseases with which it is associated. We performed exon-centric sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B that is common (MAF >1%) but exclusive to Finns was identified. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon that was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviors in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioral phenotypes using founder populations, and suggests a role for HTR2B in impulsivity. PMID:21179162

  3. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    Larsen, T.S.; Pallisgaard, N.; Andersen, M.T.;

    2008-01-01

    Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia...... chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response Udgivelsesdato: 2008/10...

  4. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    Larsen, Thomas Stauffer; Bjerrum, O W; Pallisgaard, N;

    2008-01-01

    Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia...... chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response....

  5. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    Enudi, W

    2012-02-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  6. Thermoluminescence studies on γ-irradiated Mn:Li2B4O7 single crystals

    Manganese doped Li2B4O7 (LTB) crystals were grown by Czochralski technique and various kinetic parameter of thermoluminescence (TL) were measured. Crystals were irradiated with different γ-dose using Co60 source. Thermoluminescence curves were recorded at various heating rates. Trap depth and frequency factor were calculated. Fading of Mn: Li2B4O7 was found only ∼5%-6% in 6 months. Thermoluminescence intensity of Mn: Li2B4O7 was found highly sensitive to the mass of the material, and it varies abruptly with mass change of +/− 1 mg, irradiated with the same dose. Therefore, the accuracy in mass is important parameter for thermoluminescence dosimeter badge.

  7. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    Enudi, W

    2009-08-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  8. Properties of a New Nonlinear Optical Crystal CdZn2B2O6

    ZHANG Fan; SHEN De-Zhong; SHEN Guang-Qiu; WANG Xiao-Qing

    2008-01-01

    @@ Cadmium dizinc diborate (CdZn2B2O6) single crystals have been grown for the first time. The crystal structure of CdZn2B2O6 is the same as that of the Cd3Zn3B4O12. The x-ray diffraction, infrated and Raman spectra,differential scanning calorimetry analysis and density indicate that the physical and chemical properties of both crystals are very similar. Especially, the nonlinear optical coefficients of CdZn2B2O6 and Cd3ZnaB4O12 crystals are 2.6 and 2.4 times as large as that of KH2PO4 crystal respectively. Chemical etching experiments indicated that these crystals are very stable in neutral solution and not hygroscopic in air at room temperature.

  9. Competition of superconductivity and antiferromagnetism in RNi2B2C (R = Tm, Dy, Ho, Er)

    Highlights: • Hamiltonian model to study SC and AFM in RNi2B2C. • A competition between SC and AFM. - Abstract: The co-existence of superconductivity (SC) and antiferromagnetism (AFM) in RNi2B2C (R = Tm, Dy, Ho, Er) is reported in this paper. A mean field Hamiltonian model is taken for the system. The order parameters corresponding to SC and AFM are determined and their variation with temperature are studied for these borocarbide superconductors. The interplay of SC and AFM shows BCS type of two gaps in the quasi-particle density of states. Our theoretical study is an attempt to reveal how far the s-wave pairing taken in our model could explain the coexistence properties of SC and AFM in RNi2B2C

  10. Contributions of PHOX2B in the pathogenesis of Hirschsprung disease.

    Raquel María Fernández

    Full Text Available Hirschsprung disease (HSCR is a congenital malformation of the hindgut resulting from a disruption of neural crest cell migration during embryonic development. It has a complex genetic aetiology with several genes involved in its pathogenesis. PHOX2B plays a key function in the development of neural crest derivatives, and heterozygous mutations cause a complex dysautonomia associating HSCR, Congenital Central Hypoventilation Syndrome (CCHS and neuroblastoma (NB in various combinations. In order to determine the role of PHOX2B in isolated HSCR, we performed a mutational screening in a cohort of 207 Spanish HSCR patients. Our most relevant finding has been the identification of a de novo and novel deletion (c.393_410del18 in a patient with HSCR. Results of in silico and functional assays support its pathogenic effect related to HSCR. Therefore our results support that PHOX2B loss-of-function is a rare cause of HSCR phenotype.

  11. Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo.

    Patterson, Robert; Eley, Thomas; Browne, Christopher; Martineau, Henny M; Werling, Dirk

    2015-11-17

    Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a "proof of concept" vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage. PMID:26476879

  12. Growth and study of LuNi2B2C single crystals

    Rare earth-nickel-borocarbides have attracted much interest in the last years because the compounds show the interplay of superconductivity and magnetic ordering. LuNi2B2C can be considered as non-magnetic reference system of such magnetic borocarbides as HoNi2B2C in which superconducting and antiferromagnetic ordering temperatures, Tc and TN, are similar. So far, LuNi2B2C crystals were only prepared by a flux method. For growing larger crystals we used an optical floating zone (FZ) technique, which already was successful in crystal growth of other RNi2B2C (R = Y,Tb,Ho,Tm,Er) compounds. In the case of LuNi2B2C, the primary crystallization field is far from the stoichiometric composition, and adjacent to the properitectic LuB2C2 phase field an extended region of LuNiBC occurs. Systematic studies of polycrystalline samples revealed that samples with nominal compositions LuNi5B3.5C and LuNi5B3C0.5 are free of the properitectic LuB2C2 and LuNiBC phases. Thus in the FZ crystal growth experiments we used a molten zone which corresponds to these compositions. From the grown LuNi2B2C rods single crystalline pieces have been prepared to investigate Fermi surface peculiarities by magneto-resistance measurements and to study the electronic band structure

  13. Social Media within a B2B context : A qualitative study about how industrial corporations can use social media to maintain B2B relationships

    Andersén, Sophia; Bengtsson, Annie; Gilén, Sandra

    2014-01-01

    The last thirty years there has been a dramatic change in relationship marketing. The use of computers connected to the Internet at work places has increased over time and social media is widely used in marketing strategies. Social media is a new phenomenon to communicate with each other, it enables market information based on individual consumer’s experiences. Therefore managers are seeking a way to incorporate social media into their strategies, but this is more common within B2C than B2B. ...

  14. Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population.

    Yongfeng Yang

    Full Text Available Schizophrenia (SZ is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case-control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively. Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035, as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10(-8, respectively. After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10(-7. In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849-rs12319804-rs10845851, CC (rs12582848-rs7952915, and AAGAC (rs2041986-rs11055665-rs7314376-rs7297101-rs2098469, had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively. In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively. In conclusion, our study provides novel evidence for an association between GRIN2B

  15. Association Study of N-Methyl-D-Aspartate Receptor Subunit 2B (GRIN2B) Polymorphisms and Schizophrenia Symptoms in the Han Chinese Population

    Zhang, Hongxing; Yang, Ge; Wang, Xiujuan; Ding, Minli; Jiang, Tianzi; Lv, Luxian

    2015-01-01

    Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case–control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10-8, respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10-7). In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849—rs12319804—rs10845851), CC (rs12582848—rs7952915), and AAGAC (rs2041986—rs11055665—rs7314376—rs7297101—rs2098469), had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively). In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between

  16. The impact of electronic markets on B2B-relationships

    Haller, Jochen

    2004-01-01

    Although most of the predicted consequences of the internet-revolution in the 90s did not become reality, the internet has lead to sustainable hanges in the organization of most industries. In particular, this is true for business-to-business (B2B) relations between firm. An obvious `proof' for this is the rising number of so-called electronic markets--- especially for B2B transactions---since several years. This paper should help to give a better understanding of the organizational impacts o...

  17. The Role of Information Technology Knowledge in B2B Development

    Blanca Hernandez Ortega; Julio Jimenez Martinez; Ma Jose Martin De Hoyos

    2008-01-01

    The objective of this work is to analyse the importance of firms’ previous experience with different information technologies (Internet, electronic data interchange (EDI)) in their implementation of e-Customer Relationship Management (e-CRM) and B2B. Moreover, we also study the role of e-CRM in B2B development. The results show that experience with systems such as EDI or Internet has a direct influence on the use of e-CRM. There is also a direct and positive transmission of knowledge from e...

  18. A New Evolution Mechanism Model for B2B E-Commerce Network

    Zhihong Tian; Zhenji Zhang; Xiaolan Guan

    2013-01-01

    To study the structure and evolution mechanism of B2B e-commerce network, the authors propose a network with several layers description of B2B e-commerce market. The empirical analysis from Alibaba.com shows that degree distribution of the network structure follows power-law. Based on modified BA (Barabasi-Albert) model, a new model is proposed, adding layers, fitness parameters, and more reasonable growth mechanism. The model reveals that, the structure of the network is stable, and the aver...

  19. Digitale Medien in B2B-Beschaffungsprozessen - eine explorative Untersuchung

    Backhaus, Klaus; Bröker, Ole; Brüne, Philipp; Gausling, Philipp

    2013-01-01

    Die vorliegende Studie befasst sich mit dem Einsatz von digitalen Medien in B2B-Beschaffungsprozessen im deutschen Markt. Dieser wird in der existierenden Literatur nur unzureichend erfasst. Zum einen wird die Vielfalt digitaler Medien nicht berücksichtigt. Zum anderen werden die Heterogenität des B2B-Marktes und ihr Einfluss auf die Ausgestaltung von Beschaffungsprozessen außer Acht gelassen. Auf Basis des Geschäftstypenansatzes von BACKHAUS (1998) wird daher ein Konzept zur Unterscheidung u...

  20. An Inter-enterprise Workflow Model for Supply Chain and B2B E-commerce

    2002-01-01

    The goals of B2B electronic commerce and supply chain management system are to implement interoperability of independent enterprises, to smooth the information flow between them and to deploy business processes over multiple enterprises. The inherent characteristics of workflow system make it suitable to implement the cross organization management. This paper, firstly, proposes an inter-enterprises workflow model based on the agreement to support the construction of supply chain management system and B2B electronic commerce. This model has extended the standard workflow model. After that, an architecture which supports the model has been introduced, especially it details the structure and implementation of interfaces between enterprises.

  1. Agrobacterium-mediated transformation of Cichorium intybus L. with interferon-a2b gene

    Kvasko O. Yu.; Gerasymenko I. M.; Shachovsky A. M.; Matvieieva N. A.; Kuchuk N. V.

    2009-01-01

    An efficient method for the plant regeneration and Agrobacterium mediated transformation with interferon-a2b gene has been developed for chicory C. intybus L. cv. Pala rossa. The regeneration with efficiency about 100 % was induced on the MS medium supplemented with 0.5–2.5 mg/l kinetin and 0.5 mg/l NAA. The transformed plantlets were recovered at a frequency 26,9 % on basal medium with 25 mg/l kanamycin. According to PCR-analysis the nptII and ifn-a2b genes were integrated into the genome of...

  2. Agrobacterium-mediated transformation of Cichorium intybus L. with interferon-a2b gene

    Kvasko O. Yu.

    2009-04-01

    Full Text Available An efficient method for the plant regeneration and Agrobacterium mediated transformation with interferon-a2b gene has been developed for chicory C. intybus L. cv. Pala rossa. The regeneration with efficiency about 100 % was induced on the MS medium supplemented with 0.5–2.5 mg/l kinetin and 0.5 mg/l NAA. The transformed plantlets were recovered at a frequency 26,9 % on basal medium with 25 mg/l kanamycin. According to PCR-analysis the nptII and ifn-a2b genes were integrated into the genome of transformed plants.

  3. Optimizing the value chain in the automotive industry using B2B portals

    Smit, Danie; Kroeze, Jan H; Kirlidog, Melih

    2010-01-01

    Successfully implementing ICT projects is a significant challenge for ICT managers. This paper addresses this problem by adding insights regarding critical success factors of B2B portals in the automotive industry to the existing knowledge in the field of ICT. It might be argued that if a company can become a leader and be more competent than other companies in using B2B portals in optimising the value chain, it should obtain a competitive advantage. ICT managers can potentially use the criti...

  4. Progressive dysphagia in limb-girdle muscular dystrophy type 2B.

    Walsh, Richard

    2012-02-01

    Dysphagia has not been reported in genetically confirmed limb-girdle muscular dystrophy type 2B (LGMD2B). A 40-year-old woman reported exercise-induced calf pain at age 34, followed by progressive lower and upper limb weakness. At age 38, progressive dysphagia for solids, and subsequently liquids, ensued. Endoscopic and videofluoroscopic-radiological findings indicated a myopathic swallowing disorder. Molecular genetic analysis confirmed two dysferlin gene mutations consistent with a compound heterozygote state. Progressive dysphagia should be considered as part of the expanding dysferlinopathy phenotype.

  5. Der B2B-Vertragsschluss im E-Commerce nach deutschem und syrischem Recht

    Haj Hamoud Mouhsen

    2011-01-01

    Der B2B-Vertragsschluss im E-Commerce nach deutschem und syrischem Recht Unternehmer benutzen das Internet, um Waren und Dienstleistungen zu vertreiben. Somit sind neue Geschäftsfelder entstanden, die unter dem Begriff E Commerce gefasst werden. Das beeinflusst die Art, in der Verträge abgeschlossen und abgewickelt werden. Die vorliegende Arbeit befasst sich mit den rechtlichen Aspekten des B2B Vertragsschlusses im WWW und mittels E Mail nach deutschem und syrischem Recht. Hier sind drei Them...

  6. Microwave-assisted synthesis and electrochemical evaluation of VO2 (B) nanostructures

    Ashton, Thomas E.; Borras, David Hevia; Iadecola, Antonella; Wiaderek, Kamila Magdalena; Chapman, Karena W.; Corr, Serena A.

    2015-12-01

    Abstract Understanding how intercalation materials change during electrochemical operation is paramount to optimising their behaviour and function and in situ characterisation methods allow us to observe these changes without sample destruction. Here, we first report the improved intercalation properties of bronze phase vanadium dioxide VO2 (B) prepared by a microwave assisted route which exhibits a larger electrochemical capacity (232 mAh g-1) compared to VO2 (B) prepared by a solvothermal route (197 mAh g-1). These electrochemical differences have also been followed using in situ X-ray absorption spectroscopy allowing us to follow oxidation state changes as they occur during battery operation.

  7. The Importance of Brand on B2B Markets: Case Study of Hilti

    Konečný, Martin

    2012-01-01

    The brand is mostly associated with business-to-customer markets and environment. People would first think of such a brand, because we see marketing and advertising of those brands every day. But business-to-business brands are for companies also very important. The overall goal of my thesis would be to find out how the managers of a pure B2B company perceive the importance of brand in the B2B environment where the company operates. Theoretical part will, in the first chapter, characterize B2...

  8. Li4Ge2B as a new derivative of the Mo2B5 and Li5Sn2 structure types.

    Pavlyuk, Volodymyr; Ciesielski, Wojciech; Rozdzynska-Kielbik, Beata; Dmytriv, Grygoriy; Ehrenberg, Helmut

    2016-07-01

    Binary and multicomponent intermetallic compounds based on lithium and p-elements of Groups III-V of the Periodic Table are useful as modern electrode materials in lithium-ion batteries. However, the interactions between the components in the Li-Ge-B ternary system have not been reported. The structure of tetralithium digermanium boride, Li4Ge2B, exhibits a new structure type, in the noncentrosymmetric space group R3m, in which all the Li, Ge and B atoms occupy sites with 3m symmetry. The title structure is closely related to the Mo2B5 and Li5Sn2 structure types, which crystallize in the centrosymmetric space group R-3m. All the atoms in the title structure are coordinated by rhombic dodecahedra (coordination number = 14), similar to the atoms in related structures. According to electronic structure calculations using the tight-binding-linear muffin-tin orbital-atomic spheres approximation (TB-LMTO-ASA) method, strong covalent Ge-Ge and Ge-B interactions were established. PMID:27377278

  9. Diagnóstico y desarrollo de herramientas para optimizar Clima Organizacional de las agrupaciones sociales y de pescadores artesanales vinculadas al desarrollo del proyecto GEF-Marino en Atacama. Informe Final.

    Toro Jara, Eduardo

    2006-01-01

    Este documento contiene los resultados de la medición de clima organizacional efectuada en el contexto del Proyecto GEF-Marino en la Región de Atacama durante los meses de Agosto a Noviembre 2006, período en el cual se realizó la aplicación de la encuesta y el estudio de clima en la ciudad de Caldera y sus alrededores. En el cuerpo principal de este informe, a continuación en este capitulo I, aparece: fortalezas y debilidades, contexto y área de influencia de este estudio, o...

  10. Synapse-Specific Metaplasticity: To Be Silenced Is Not to Silence 2B

    Philpot, Benjamin D.; Zukin, R. Suzanne

    2010-01-01

    What happens to a single, presynaptically quiescent synapse among a population of active synapses? In this issue of Neuron, Ehlers and colleagues show that, far from being eliminated, these inactive synapses are primed for potentiation and incorporation into a new neural circuit through an upregulation of NR2B-containing NMDA receptors.

  11. New benzoyl urea derivatives as novel NR2B selective NMDA receptor antagonists.

    Borza, I; Greiner, I; Kolok, S; Galgóczy, K; Ignácz-Szendrei, Gy; Horváth, Cs; Farkas, S; Gáti, T; Háda, V; Domány, Gy

    2006-09-01

    A novel series of benzoyl urea derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of the substitution of the piperidine ring on the biological activity of the compounds was studied. Compound 9 was active in the formalin test in mice. PMID:17020160

  12. Development of radiotracers for imaging NR2B subtype NMDA receptors with positron emission tomography

    The aim of this thesis was to develop new radioactive tracers for imaging NR2B subtype NMDA receptors with positron emission tomography. Several compounds including 4-(4-fluoro-benzyl)piperidine and presenting interesting in vivo biological properties were the object of a labelling with a positrons emitter atom (11C or 18F)

  13. Serotonin Receptor 2B Mediates Mechanical Hyperalgesia by Regulating Transient Receptor Potential Vanilloid 1.

    Su, Yeu-Shiuan; Chiu, Yuan-Yi; Lin, Shih-Yuan; Chen, Chih-Cheng; Sun, Wei-Hsin

    2016-05-01

    Serotonin [5-hydroxytryptamine (5-HT)], an inflammatory mediator, contributes to inflammatory pain. The presence of multiple 5-HT subtype receptors on peripheral and central nociceptors complicates the role of 5-HT in pain. Previously, we found that 5-HT2B/2C antagonist could block 5-HT-induced mechanical hyperalgesia. However, the types of neurons or circuits underlying this effect remained unsolved. Here, we demonstrate that the Gq/11-phospholipase Cβ-protein kinase Cε (PKCε) pathway mediated by 5-HT2B is involved in 5-HT-induced mechanical hyperalgesia in mice. Administration of a transient receptor potential vanilloid 1 (TRPV1) antagonist inhibited the 5-HT-induced mechanical hyperalgesia. 5-HT injection enhanced 5-HT- and capsaicin-evoked calcium signals specifically in isolectin B4 (IB4)-negative neurons; signals were inhibited by a 5-HT2B/2C antagonist and PKCε blocker. Thus, 5-HT2B mediates 5-HT-induced mechanical hyperalgesia by regulating TRPV1 function. PMID:26635025

  14. MOLECULAR CLONING AND HETEROLOGOUS EXPRESSION OF HUMAN INTERFERON ALPHA2b GENE

    I. Made Artika

    2013-01-01

    Full Text Available Human alpha Interferons (hIFNα have been shown to have antiviral, antiproliferative and immunomodulatory activities. The human interferon alpha2b (hIFNα2b, is one of the human interferon alpha2 sub variants, naturally synthesized as a polypeptide of 188 amino acid residues, the first 23 residues of which represents a signal peptide. In the present study, the hIFNα2b gene was expressed after being fused with Glutathione S-Transferase (GST gene. The hIFNα2b gene was amplified from human genomic DNA by using a pair of specific primers, cloned into an Escherichia coli expression vector and expressed in E. coli cells under the direction of the tac promoter. The expressed protein was purified using a one-step affinity chromatography column containing immobilized gluthatione-bound resin. The purified protein was shown to react specifically with anti-human-interferon-alpha antibody, confirming that the protein was the human interferon alpha molecule. This strategy has the potential to be used as an alternative mean for production of pure human interferon α proteins for therapeutic purposes and for further studies on their molecular characterization and mechanism of action.

  15. Do self-service technologies affect interfirm relationships? A B2B perspective

    Raechel Johns

    2014-11-01

    Full Text Available While considerable literature examines business-to business (B2B relationships, the impact of technology on these relationships has lacked attention. IT has impacted the way businesses operate in a B2B context as well as influencing services by altering the way services are delivered. To understand the way in which Internet technology has impacted these B2B services, it is essential to examine its impact not only on business processes but on business relationships too. One technology, enabled by modern Internet technologies, which is changing the nature of business relationships is the increased use of self-service technologies (SSTs or technology-enabled services, however, there is a shortage of research in the area in a B2B context. The discussion in this paper provides an overview of the impact of IT on business relationships, using Relationship Marketing theory to provide a theoretical framework. A qualitative study in the Australian banking industry provides findings relating to the theory. The findings of this study provide evidence that while traditional Relationship Marketing theory is still applicable for some business customers, new theory is required for business customers who do not seek relationships. With both practical and theoretical implications, the research detailed in this paper makes a useful contribution to the literature and indicates the necessity for further research to be developed which explores business customers who prefer to remain transaction-oriented, rather than develop interpersonal relationships.

  16. A process-stakeholder analysis of B2B industry standardisation

    J. Rodon; J. Ramis-Pujol; E. Christiaanse

    2007-01-01

    Purpose - Interoperability standards are a crucial aspect in the development of B2B e-business. The aim of this paper is to understand how standardisation evolves by analysing the interplay between activities and stakeholders within the process. Unlike most of the IS research that focuses on the und

  17. Measurements of the Urbach tail for A2B6 mixed crystals by the photothermal method

    Zakrzewski, J; Strzalkowski, K; Firszt, F; Legowski, S; Meczynska, H [Instytut Fizyki, Uniwersytet Mikolaja Kopernika, ul. Grudziadzka 5/7, 87-100 Torun (Poland); Malinski, M, E-mail: jzakrzew@fizyka.umk.p [Department of Electronics and Computer Science Technical University of Koszalin, 2 Sniadeckich St, 75-453, Koszalin (Poland)

    2010-03-01

    This paper presents the influence of the composition of several mixed A2B6 crystals on the broadening of the optical absorption coefficient spectra. This broadening is observed as the change of the piezoelectric spectra associated with the change of the Urbach tail. This effect is interpreted as a result of the increase of the compositional disorder of the crystal lattice.

  18. Evaluation of the 2b-RAD method for genomic selection in scallop breeding.

    Dou, Jinzhuang; Li, Xue; Fu, Qiang; Jiao, Wenqian; Li, Yangping; Li, Tianqi; Wang, Yangfan; Hu, Xiaoli; Wang, Shi; Bao, Zhenmin

    2016-01-01

    The recently developed 2b-restriction site-associated DNA (2b-RAD) sequencing method provides a cost-effective and flexible genotyping platform for aquaculture species lacking sufficient genomic resources. Here, we evaluated the performance of this method in the genomic selection (GS) of Yesso scallop (Patinopecten yessoensis) through simulation and real data analyses using six statistical models. Our simulation analysis revealed that the prediction accuracies obtained using the 2b-RAD markers were slightly lower than those obtained using all polymorphic loci in the genome. Furthermore, a small subset of markers obtained from a reduced tag representation (RTR) library presented comparable performance to that obtained using all markers, making RTR be an attractive approach for GS purpose. Six GS models exhibited variable performance in prediction accuracy depending on the scenarios (e.g., heritability, sample size, population structure), but Bayes-alphabet and BLUP-based models generally outperformed other models. Finally, we performed the evaluation using an empirical dataset composed of 349 Yesso scallops that were derived from five families. The prediction accuracy for this empirical dataset could reach 0.4 based on optimal GS models. In summary, the genotyping flexibility and cost-effectiveness make 2b-RAD be an ideal genotyping platform for genomic selection in aquaculture breeding programs. PMID:26754638

  19. Water‐Data Report 413721083124001 Pool 2B at Ottawa NWR-2013

    US Fish and Wildlife Service, Department of the Interior — Water levels and water quality parameters recorded on Crane Creek. Water-Data Report 2013 413721083124001 Pool 2B at Ottawa NWR LOCATION: Lat. 41°37'21.08"N, long...

  20. Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation

    Rohrer, Jonathan D; Ahsan, R Laila; Isaacs, Adrian M;

    2009-01-01

    BACKGROUND/AIMS: CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease. There are no ...

  1. Johnston Atoll Site 2B-P 6/30/2000 39-40M

    US Fish and Wildlife Service, Department of the Interior — One-meter-square (1 meter x 1 meter) benthic substrate at Johnston Atoll, site 2B-P (16 45.606N, 169 30.705W), between 39 and 40 meters along a permanent transect.

  2. An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives

    Sagyam, Rajeshwar Reddy; Buchikonda, Ravinder; Pitta, Jaya Prakash; Vurimidi, Himabindu; Padi, Pratap Reddy; Ghanta, Mahesh Reddy

    2009-01-01

    The reaction of 2-[2-(4-fluorophenyl)-2-oxo-1-phenylethyl]-4-methyl-3-oxo-pentanoic acid phenylamide with tertiary butyl carbazate and subsequent condensation of the resulting carbamate derivative with a chalcone provided a facile new approach to pyrrolo[1,2-b]pyridazine derivatives.

  3. Impaired discrimination learning in interneuronal NMDAR-GluN2B mutant mice.

    Brigman, Jonathan L; Daut, Rachel A; Saksida, Lisa; Bussey, Timothy J; Nakazawa, Kazu; Holmes, Andrew

    2015-06-17

    Previous studies have established a role for N-methyl-D-aspartate receptor (NMDAR) containing the GluN2B subunit in efficient learning behavior on a variety of tasks. Recent findings have suggested that NMDAR on GABAergic interneurons may underlie the modulation of striatal function necessary to balance efficient action with cortical excitatory input. Here we investigated how loss of GluN2B-containing NMDAR on GABAergic interneurons altered corticostriatal-mediated associative learning. Mutant mice (floxed-GluN2B×Ppp1r2-Cre) were generated to produce loss of GluN2B on forebrain interneurons and phenotyped on a touchscreen-based pairwise visual learning paradigm. We found that the mutants showed normal performance during Pavlovian and instrumental pretraining, but were significantly impaired on a discrimination learning task. Detailed analysis of the microstructure of discrimination performance revealed reduced win→stay behavior in the mutants. These results further support the role of NMDAR, and GluN2B in particular, on modulation of striatal function necessary for efficient choice behavior and suggest that NMDAR on interneurons may play a critical role in associative learning. PMID:25968910

  4. On the critical success factors for B2B e-marketplace

    Sareh Ahmad Khan Beige

    2015-01-01

    Full Text Available Advancement of network technology, quick growth of Internet and Internet based solutions lead many firms to apply online processes as well as electronic businesses. Internet based B2B E-C requires applying Internet and affiliated technologies for exchanging products, services and information. Implementation of business to business (B2B requires long-term commitment of organizations. Carrying out research in this field is regarded as very important issue for recognizing effective factors on successful implementation and execution of B2B and determining current status of organization. This research deals with studying effective critical factors on successful implementation and execution of B2B. Factors are recognized through studying literature review and IT experts. Then, through case study (studying a vehicle manufacturing firm and by using analytical network process (ANP, the importance of factor and their rank are determined. The factors that are regarded at this research are including: culture, commitment and support of senior management, government support, purposes, organizational strategies, trust, partial advantage and technical infrastructure. Results of research show that support and commitment of senior management are the highest priority factors.

  5. Copy number variations in the amylase gene (AMY2B) in Japanese native dog breeds.

    Tonoike, A; Hori, Y; Inoue-Murayama, M; Konno, A; Fujita, K; Miyado, M; Fukami, M; Nagasawa, M; Mogi, K; Kikusui, T

    2015-10-01

    A recent study suggested that increased copy numbers of the AMY2B gene might be a crucial genetic change that occurred during the domestication of dogs. To investigate AMY2B expansion in ancient breeds, which are highly divergent from modern breeds of presumed European origins, we analysed copy numbers in native Japanese dog breeds. Copy numbers in the Akita and Shiba, two ancient breeds in Japan, were higher than those in wolves. However, compared to a group of various modern breeds, Akitas had fewer copy numbers, whereas Shibas exhibited the same level of expansion as modern breeds. Interestingly, average AMY2B copy numbers in the Jomon-Shiba, a unique line of the Shiba that has been bred to maintain their appearance resembling ancestors of native Japanese dogs and that originated in the same region as the Akita, were lower than those in the Shiba. These differences may have arisen from the earlier introduction of rice farming to the region in which the Shiba originated compared to the region in which the Akita and the Jomon-Shiba originated. Thus, our data provide insights into the relationship between the introduction of agriculture and AMY2B expansion in dogs. PMID:26358734

  6. Measurements of the Urbach tail for A2B6 mixed crystals by the photothermal method

    Zakrzewski, J.; Malinski, M.; Strzałkowski, K.; Firszt, F.; Łęgowski, S.; Męczyńska, H.

    2010-03-01

    This paper presents the influence of the composition of several mixed A2B6 crystals on the broadening of the optical absorption coefficient spectra. This broadening is observed as the change of the piezoelectric spectra associated with the change oft he Urbach tail. This effect is interpreted as a result of the increase of the compositional disorder of the crystal lattice.

  7. An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives

    Rajeshwar Reddy Sagyam

    2009-11-01

    Full Text Available The reaction of 2-[2-(4-fluorophenyl-2-oxo-1-phenylethyl]-4-methyl-3-oxo-pentanoic acid phenylamide with tertiary butyl carbazate and subsequent condensation of the resulting carbamate derivative with a chalcone provided a facile new approach to pyrrolo[1,2-b]pyridazine derivatives.

  8. Specific heat of holmium and YNi2B2C. Criticalbehaviour and superconducting properties

    Object of the thesis is the study of the specific heat of holmium and YNi2B2C in the temperature ranges from 50 to 200 KI respectively from 380 mK to 20 K in magnetic fields up to 9 T. In the present thesis the criticalbehaviour of YNi2B2C and properties of the superconducting state of tne non-magnetic rare-earth nickel borocarbide YNi2B2C are studied by means of a self-developed measurement apparatur of the specific heat using the quasi-adiabatic heating-pulse method as well as of holmium by means of the relaxation method. In this thesis reliable statements about the critical exponents on monocrystalline holmium could be made. The study on holmium proves that the critical behaviour of the specific heats cannot be described in the framework of the predictions of the chiral universality classes. By means of measurements of the specific heat in this thesis could be confirmed that YNi2B2C is a multiband superconductor. The positive curvature of the boundary line below Tc in the phase diagram yields a first hint to the many-band character of YNI2B2C. In the zero-field the electronic specific heat in the superconducting state ces(T) can be not explained in the framework of the pure BCS theory. At low temperatures a residual contribution by normally conducting electrons could be detected, which hints to a not completely opened energy gap. A possible explanation would be that a band (or several bands) with low charge-carrier concentration not contribute to the superconductivity. This result agrees with de Haas-van Alphen measurements on isostructural superconducting LuNi2B2C monocrystals, which suggest the many-band character of the superconductivity as well as a vanishing energy gap in one band. The fluctuation behaviour of the specific heat of YNi2B2C in the neighbourhood of the superconducting-normally conducting transition agrees well with that of the 3D-XY model.

  9. Equine cytochrome P450 2B6--genomic identification, expression and functional characterization with ketamine.

    Peters, L M; Demmel, S; Pusch, G; Buters, J T M; Thormann, W; Zielinski, J; Leeb, T; Mevissen, M; Schmitz, A

    2013-01-01

    Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug-drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYPs is essential for a better understanding of drug metabolism in horses. We report annotation, cloning and heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts. After computational annotation of all CYP2B genes, the coding sequence (CDS) of equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an amino acid sequence identity of 77% and a similarity of 93.7% to its human ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two further variants in exon 3 were detected in one and two horses of this group, respectively. Transfected V79 cells were incubated with racemic ketamine and norketamine as probe substrates to determine metabolic activity. The recombinant equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. V(max) for S-/and R-norketamine formation was 0.49 and 0.45nmol/h/mg cellular protein and K(m) was 3.41 and 2.66μM, respectively. The N-demethylation of S-/R-ketamine was inhibited concentration-dependently with clopidogrel showing an IC(50) of 5.63 and 6.26μM, respectively. The functional importance of the recorded genetic variants remains to be explored. Equine CYP2B6 was determined to be a CYP enzyme involved in

  10. Equine cytochrome P450 2B6 — Genomic identification, expression and functional characterization with ketamine

    Peters, L.M.; Demmel, S. [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland); Pusch, G.; Buters, J.T.M. [ZAUM — Center of Allergy and Environment, Helmholtz Zentrum München/Technische Universität München, Biedersteiner Str. 29, 80802 München (Germany); Thormann, W. [Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Murtenstrasse 35, 3010 Bern (Switzerland); Zielinski, J. [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland); Leeb, T. [Institute of Genetics, Vetsuisse Faculty, University Bern, Bremgartenstr. 109, 3012 Bern (Switzerland); Mevissen, M. [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland); Schmitz, A., E-mail: andrea.schmitz@vetsuisse.unibe.ch [Division Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University Bern, Laenggassstr. 124, 3012 Bern (Switzerland)

    2013-01-01

    Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug–drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYPs is essential for a better understanding of drug metabolism in horses. We report annotation, cloning and heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts. After computational annotation of all CYP2B genes, the coding sequence (CDS) of equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an amino acid sequence identity of 77% and a similarity of 93.7% to its human ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two further variants in exon 3 were detected in one and two horses of this group, respectively. Transfected V79 cells were incubated with racemic ketamine and norketamine as probe substrates to determine metabolic activity. The recombinant equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. V{sub max} for S-/and R-norketamine formation was 0.49 and 0.45 nmol/h/mg cellular protein and K{sub m} was 3.41 and 2.66 μM, respectively. The N-demethylation of S-/R-ketamine was inhibited concentration-dependently with clopidogrel showing an IC{sub 50} of 5.63 and 6.26 μM, respectively. The functional importance of the recorded genetic variants remains to be explored. Equine CYP2B6 was determined to be a CYP

  11. Equine cytochrome P450 2B6 — Genomic identification, expression and functional characterization with ketamine

    Ketamine is an anesthetic and analgesic regularly used in veterinary patients. As ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. Since cytochrome P450 enzymes (CYPs) play a pivotal role in the phase I metabolism of the majority of all marketed drugs, drug–drug interactions often occur at the active site of these enzymes. CYPs have been thoroughly examined in humans and laboratory animals, but little is known about equine CYPs. The characterization of equine CYPs is essential for a better understanding of drug metabolism in horses. We report annotation, cloning and heterologous expression of the equine CYP2B6 in V79 Chinese hamster fibroblasts. After computational annotation of all CYP2B genes, the coding sequence (CDS) of equine CYP2B6 was amplified by RT-PCR from horse liver total RNA and revealed an amino acid sequence identity of 77% and a similarity of 93.7% to its human ortholog. A non-synonymous variant c.226G>A in exon 2 of the equine CYP2B6 was detected in 97 horses. The mutant A-allele showed an allele frequency of 82%. Two further variants in exon 3 were detected in one and two horses of this group, respectively. Transfected V79 cells were incubated with racemic ketamine and norketamine as probe substrates to determine metabolic activity. The recombinant equine CYP2B6 N-demethylated ketamine to norketamine and produced metabolites of norketamine, such as hydroxylated norketamines and 5,6-dehydronorketamine. Vmax for S-/and R-norketamine formation was 0.49 and 0.45 nmol/h/mg cellular protein and Km was 3.41 and 2.66 μM, respectively. The N-demethylation of S-/R-ketamine was inhibited concentration-dependently with clopidogrel showing an IC50 of 5.63 and 6.26 μM, respectively. The functional importance of the recorded genetic variants remains to be explored. Equine CYP2B6 was determined to be a CYP enzyme involved in

  12. Atmospheric circulation of eccentric hot Jupiter HAT-P-2B

    Lewis, Nikole K. [Department of Earth, Atmospheric and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Showman, Adam P. [Department of Planetary Sciences and Lunar and Planetary Laboratory, The University of Arizona, Tucson, AZ 85721 (United States); Fortney, Jonathan J. [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States); Knutson, Heather A. [Division of Geological and Planetary Sciences, California Institute of Technology, Pasadena, CA 91125 (United States); Marley, Mark S., E-mail: nklewis@mit.edu [NASA Ames Research Center 245-3, Moffett Field, CA 94035 (United States)

    2014-11-10

    The hot Jupiter HAT-P-2b has become a prime target for Spitzer Space Telescope observations aimed at understanding the atmospheric response of exoplanets on highly eccentric orbits. Here we present a suite of three-dimensional atmospheric circulation models for HAT-P-2b that investigate the effects of assumed atmospheric composition and rotation rate on global scale winds and thermal patterns. We compare and contrast atmospheric models for HAT-P-2b, which assume one and five times solar metallicity, both with and without TiO/VO as atmospheric constituents. Additionally we compare models that assume a rotation period of half, one, and two times the nominal pseudo-synchronous rotation period. We find that changes in assumed atmospheric metallicity and rotation rate do not significantly affect model predictions of the planetary flux as a function of orbital phase. However, models in which TiO/VO are present in the atmosphere develop a transient temperature inversion between the transit and secondary eclipse events that results in significant variations in the timing and magnitude of the peak of the planetary flux compared with models in which TiO/VO are omitted from the opacity tables. We find that no one single atmospheric model can reproduce the recently observed full orbit phase curves at 3.6, 4.5 and 8.0 μm, which is likely due to a chemical process not captured by our current atmospheric models for HAT-P-2b. Further modeling and observational efforts focused on understanding the chemistry of HAT-P-2b's atmosphere are needed and could provide key insights into the interplay between radiative, dynamical, and chemical processes in a wide range of exoplanet atmospheres.

  13. Induction of the CYP2B genes by triphenyldioxane treatment in the rat liver.

    Grigorieva, E; Soshilov, A; Surovtseva, Y; Schwartz, E L; Duzhak, T G; Gulyaeva, L F; Lyakhovich, V V

    2002-08-01

    Triphenyldioxane (TPD) is a potent phenobarbital-type (PB) inducer of the CYP2B cytochrome isoforms, the inducing effect of which is one order of magnitude higher than PB. The fact that TPD is unable to induce CYP2B genes having the proximal promoter disrupted (mouse Cyp2b10) suggests an existence of the proximal promoter-dependent mechanism of the CYP2B induction. So a TPD-dependent activation of the nuclear proteins to the binding with Barbie-box sequence (the most conservative part of the proximal promoter) was studied. In the nuclear extracts from the intact rat liver there were detected five proteins that could be activated to the Barbie-box binding by the TPD treatment in vitro (II, III, NI, NII and NIII). The first three were effected also by another PB-like inducers tested (PB and TCPOBOP), when NII and NIII complexes were formed under the influence of TPD only. It is possible that a direct activation of the NII and NIII proteins by TPD exists as (3)H-labeled TPD was detected in the composition of NII and NIII complexes. However, both of them disappeared from the nuclear extracts after the long exposure time with TPD (6 h or more). A short induction by the direct intra-liver delivery of TPD (15-30 min) led to the stabile activation of one TPD-specific protein. Apart from the activation of the Barbie-box-binding protein, the short TPD treatment caused the activation of three nuclear proteins being able to interact with the NR1 sequence of the distal promoter PBREM element. These findings suggest that TPD is really the first member of the PB-like inducers family for which a special mechanism of CYP2B induction may exist. PMID:12110287

  14. Comparison of three commercial one-dose porcine circovirus type 2 (PCV2) vaccines in a herd with concurrent circulation of PCV2b and mutant PCV2b.

    Jeong, Jiwoon; Park, Changhoon; Choi, Kyuhyung; Chae, Chanhee

    2015-05-15

    Porcine circovirus associated disease (PCVAD) occurred in a farm where pigs had been routinely vaccinated with a commercial PCV2a vaccine. A mutant PCV2b (mPCV2b) was isolated from pigs with PCVAD, perhaps implying a perceived vaccine failure. The objective of this study was to determine and compare the efficacy of 3 one-dose PCV2a vaccines of varying antigen type and dose in the same pig farm with concurrent PCV2b and mPCV2b infection based on clinical (average daily weight gain; ADWG), virological (evidence of viremia), immunological (presence of PCV2-specific neutralizing antibody; NA and interferon-γ secreting cells; IFN-γ-SC), and pathological (lymphoid lesion and PCV2 antigen score within lesion) evaluation. Regardless of which commercial PCV2a vaccine was used, vaccinated animals improved ADWG, and reduced the amount of PCV2b and mPCV2b load in the blood compared to unvaccinated animals. The vaccination of piglets at 3 weeks of age effectively induced higher levels of PCV2b- and mPCV2b-specific NA and IFN-γ-SC compared to unvaccinated animals. A reduction in mPCV2b load in the blood coincided with the appearance of both mPCV2b-specific NA and IFN-γ-SC in the vaccinated animals. The microscopic lymphoid lesions and PCV2-antigen scores within the lymph nodes were significantly lower in vaccinated animals. The perceived vaccine failure could not be explained by incomplete protection of the commercial PCV2a vaccine against mPCV2b. The results of the present study demonstrated that currently available commercial PCV2a vaccines are protective against concurrent PCV2b and mPCV2b infection based on clinical, virological, immunological, and pathological evaluations under field conditions. PMID:25790733

  15. Photoelectron Spectroscopy Study of [Ta2B6]-: a Hexagonal Bipyramdial Cluster

    Jian, Tian; Li, Weili; Romanescu, Constantin; Wang, Lai-Sheng

    2014-06-01

    It has been a long-sought goal in cluster science to discover stable atomic clusters as building blocks for cluster-assembled nanomaterials, as exemplified by the fullerenes and their subsequent bulk syntheses.[1,2] Clusters have also been considered as models to understand bulk properties, providing a bridge between molecular and solid-state chemistry.[3] Herein we report a joint photoelectron spectroscopy and theoretical study on the [Ta2B6]- and [Ta2B6] clusters.[4] The photoelectron spectrum of [Ta2B6]- displays a simple spectral pattern and a large HOMO-LUMO gap, suggesting its high symmetry. Theoretical calculations show that both the neutral and anion are D6h pyramidal. The chemical bonding analyses for [Ta2B6] revealed the nature of the B6 and Ta interactions and uncovered strong covalent bonding between B6 and Ta. The D6h-[TaB6Ta] gaseous cluster is reminiscent of the structural pattern in the ReB6X6Re core in the [(Cp*Re)2B6H4Cl2] and the TiB6Ti motif in the newly synthesized Ti7Rh4Ir2B8 solid-state compound.[5,6] The current work provides an intrinsic link between a gaseous cluster and motifs for solid materials. Continued investigations of the transition-metal boron clusters may lead to the discovery of new structural motifs involving pure boron clusters for the design of novel boride materials. Reference [1] H.W. Kroto, J. R. Heath, S. C. OBrien, R. F. Curl, R. E. Smalley, Nature 1985, 318, 162 - 163. [2] W. Krtschmer, L. D. Lamb, K. Fostiropoulos, D. R. Huffman, Nature 1990, 347, 354 - 358. [3] T. P. Fehlner, J.-F. Halet, J.-Y. Saillard, Molecular Clusters: A Bridge to Solid-State Chemitry, Cambridge University Press, UK, 2007. [4] W. L. Li, L. Xie, T. Jian, C. Romanescu, X. Huang, L.-S. Wang, Angew. Chem. Int. Ed. 2014, 126, 1312 - 1316. [5] B. Le Guennic, H. Jiao, S. Kahlal, J.-Y. Saillard, J.-F. Halet, S. Ghosh, M. Shang, A. M. Beatty, A. L. Rheingold, T. P. Fehlner, J. Am. Chem. Soc. 2004, 126, 3203 - 3217. [6] B. P. T. Fokwa, M. Hermus, Angew

  16. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure

    Swartzwelder, H. Scott; Risher, Mary-Louise; Miller, Kelsey M.; Colbran, Roger J.; Winder, Danny G.; Wills, Tiffany A.

    2016-01-01

    Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70) from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further, the robust change in

  17. Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure.

    H Scott Swartzwelder

    Full Text Available Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70 from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further

  18. Reaction and reorientation of electronically excited H{sub 2}(B)

    Pibel, C.D.

    1992-09-01

    The room temperature rate (TR) constants for fluorescence quenching fluorescence of H{sub 2}, HD, and D{sub 2} B {sup 1}{Sigma}{sub u}{sup +} by {sup 4}He were measured as a function of the initially excited rotational and vibrational level of the hydrogen molecule, and the RT rate constants for molecular angular momentum reorientation of H{sub 2}, HD and D{sub 2} (B {sup 1}{Sigma}{sub u}{sup +}. v{prime}=0, J{prime}=1, M{sub J}=0) in collisions with He, Ne, Ar and H{sub 2}(X {sup 1}{Sigma}{sub g}{sup +}) were also measured. Vibrational state dependence of the quenching cross sections fits a vibrationally adiabatic model of the quenching process. From the vibrational state dependence of the quenching cross section, the barrier height for the quenching reaction is found to be 250{plus_minus}40 cm{sup {minus}1}, and the difference in the H-H stretching frequencies between H{sub 2}(B) and the H{sub 2}-He complex at the barrier to reaction is 140{plus_minus}80 cm{sup {minus}1}. The effective cross sections for angular momentum reorientation in collisions of H{sub 2}, HD, D{sub 2} with He and Ne were found to be about 30 {Angstrom}{sup 2} and were nearly the same for each isotope and with He and Ne as collision partners. Cross sections forreorientation of HD and D{sub 2} in collisions with Ar were 10.6{plus_minus}2.0 and 13.9{plus_minus}3.0 {Angstrom}{sup 2}, respectively. Reorientation of D{sub 2}(B) in collisions with room temperature H{sub 2}(X) occurs with a 7.6{plus_minus}3.4 {Angstrom}{sup 2} cross section. Calculated cross sections using semiclassical and quantum close coupled methods give cross sections for reorientation of H{sub 2}(B) and D{sub 2}(B) in collisions with He that agree quantitatively with experiment. Discrepancy between the calculated and experimental cross sections for HD(B)-HE are likely due to rotational relaxation in HD a Turbo PASCAL version of the data-taking program is included.

  19. Reaction and reorientation of electronically excited H[sub 2](B)

    Pibel, C.D.

    1992-09-01

    The room temperature rate (TR) constants for fluorescence quenching fluorescence of H[sub 2], HD, and D[sub 2] B [sup 1][Sigma][sub u][sup +] by [sup 4]He were measured as a function of the initially excited rotational and vibrational level of the hydrogen molecule, and the RT rate constants for molecular angular momentum reorientation of H[sub 2], HD and D[sub 2] (B [sup 1][Sigma][sub u][sup +]. v[prime]=0, J[prime]=1, M[sub J]=0) in collisions with He, Ne, Ar and H[sub 2](X [sup 1][Sigma][sub g][sup +]) were also measured. Vibrational state dependence of the quenching cross sections fits a vibrationally adiabatic model of the quenching process. From the vibrational state dependence of the quenching cross section, the barrier height for the quenching reaction is found to be 250[plus minus]40 cm[sup [minus]1], and the difference in the H-H stretching frequencies between H[sub 2](B) and the H[sub 2]-He complex at the barrier to reaction is 140[plus minus]80 cm[sup [minus]1]. The effective cross sections for angular momentum reorientation in collisions of H[sub 2], HD, D[sub 2] with He and Ne were found to be about 30 [Angstrom][sup 2] and were nearly the same for each isotope and with He and Ne as collision partners. Cross sections forreorientation of HD and D[sub 2] in collisions with Ar were 10.6[plus minus]2.0 and 13.9[plus minus]3.0 [Angstrom][sup 2], respectively. Reorientation of D[sub 2](B) in collisions with room temperature H[sub 2](X) occurs with a 7.6[plus minus]3.4 [Angstrom][sup 2] cross section. Calculated cross sections using semiclassical and quantum close coupled methods give cross sections for reorientation of H[sub 2](B) and D[sub 2](B) in collisions with He that agree quantitatively with experiment. Discrepancy between the calculated and experimental cross sections for HD(B)-HE are likely due to rotational relaxation in HD a Turbo PASCAL version of the data-taking program is included.

  20. DETECTION OF THERMAL EMISSION OF XO-2b: EVIDENCE FOR A WEAK TEMPERATURE INVERSION

    We estimate flux ratios of the extrasolar planet XO-2b to its host star XO-2 at 3.6, 4.5, 5.8, and 8.0 μm with Infrared Array Camera on the Spitzer Space Telescope to be 0.00081 ± 0.00017, 0.00098 ± 0.00020, 0.00167 ± 0.00036, and 0.00133 ± 0.00049, respectively. The fluxes provide tentative evidence for a weak temperature inversion in the upper atmosphere, the precise nature of which would need to be confirmed by longer wavelength observations. XO-2b substellar flux of 0.76 x 109 erg cm-2 s-1 lies in the predicted transition region between atmospheres with and without upper atmospheric temperature inversion.

  1. Unique features of monoclonal IgG2b in the cleavage reaction with pepsin.

    Sumii,Hiroshi

    1989-06-01

    Full Text Available Preparations of IgG2b purified from several mouse hybridoma clones were highly susceptible, compared to other subclasses, to peptic digestion under conditions usually used to prepare F (ab'2 fragments. Analyses of the digestion products revealed that no F (ab'2 was produced and that the main product was a Fab-like fragment. Demonstration of the hinge disulfides in the Fc portion clearly indicated that in IgG2b the primary peptic cleavage occurs on the NH2-terminal side of the inter-heavy chain disulfide bridge. The resulting Fab failed to bind with antigen, suggesting the importance of the CH1-hinge region in maintaining the native conformation of the antigen-binding site.

  2. A systematic analysis of the Braitenberg vehicle 2b for point-like stimulus sources

    Braitenberg vehicles have been used experimentally for decades in robotics with limited empirical understanding. This paper presents the first mathematical model of the vehicle 2b, displaying so-called aggression behaviour, and analyses the possible trajectories for point-like smooth stimulus sources. This sensory-motor steering control mechanism is used to implement biologically grounded target approach, target-seeking or obstacle-avoidance behaviour. However, the analysis of the resulting model reveals that complex and unexpected trajectories can result even for point-like stimuli. We also prove how the implementation of the controller and the vehicle morphology interact to affect the behaviour of the vehicle. This work provides a better understanding of Braitenberg vehicle 2b, explains experimental results and paves the way for a formally grounded application on robotics as well as for a new way of understanding target seeking in biology. (paper)

  3. Electronic structure study of TiB2 and Ti2B

    In this paper, the electronic properties of TiB2 and Ti2B are computed within the framework of Density Functional Theory (DFT) based on Linear Combination of Atomic Orbitals (LCAO) method. In the present calculations, the generalized gradient approximation (GGA) proposed by Perdew-Burke-Erenzerhof (PBE) and Becke’s scheme are considered to treat the correlation and exchange effects respectively. TiB2 crystallizes in the hexagonal AlB2 type structure which is designated as C32 with the space group P6/mmm. While the crystal structure of Ti2B described in this paper is isomorphous to the body centered tetragonal (Al2Cu - type) structure with space group I4/mcm

  4. Electronic structure study of TiB{sub 2} and Ti{sub 2}B

    Vashistha, M., E-mail: vashistmanju690@gmail.com; Vyas, V. [Department of Physics, Banasthali University, Banasthali-304022 (India); Kabra, K.; Sharma, G. [Department of Pure and Appied Physics, University of Kota, Rajasthan-324010 (India)

    2015-06-24

    In this paper, the electronic properties of TiB{sub 2} and Ti{sub 2}B are computed within the framework of Density Functional Theory (DFT) based on Linear Combination of Atomic Orbitals (LCAO) method. In the present calculations, the generalized gradient approximation (GGA) proposed by Perdew-Burke-Erenzerhof (PBE) and Becke’s scheme are considered to treat the correlation and exchange effects respectively. TiB{sub 2} crystallizes in the hexagonal AlB{sub 2} type structure which is designated as C32 with the space group P6/mmm. While the crystal structure of Ti{sub 2}B described in this paper is isomorphous to the body centered tetragonal (Al{sub 2}Cu - type) structure with space group I4/mcm.

  5. Electronic structure study of TiB2 and Ti2B

    Vashistha, M.; Kabra, K.; Vyas, V.; Sharma, G.

    2015-06-01

    In this paper, the electronic properties of TiB2 and Ti2B are computed within the framework of Density Functional Theory (DFT) based on Linear Combination of Atomic Orbitals (LCAO) method. In the present calculations, the generalized gradient approximation (GGA) proposed by Perdew-Burke-Erenzerhof (PBE) and Becke's scheme are considered to treat the correlation and exchange effects respectively. TiB2 crystallizes in the hexagonal AlB2 type structure which is designated as C32 with the space group P6/mmm. While the crystal structure of Ti2B described in this paper is isomorphous to the body centered tetragonal (Al2Cu - type) structure with space group I4/mcm.

  6. The Histone H2B Monoubiquitination Regulatory Pathway Is Required for Differentiation of Multipotent Stem Cells

    Karpiuk, Oleksandra; Najafova, Zeynab; Kramer, Frank;

    2012-01-01

    Extensive changes in posttranslational histone modifications accompany the rewiring of the transcriptional program during stem cell differentiation. However, the mechanisms controlling the changes in specific chromatin modifications and their function during differentiation remain only poorly...... understood. We show that histone H2B monoubiquitination (H2Bub1) significantly increases during differentiation of human mesenchymal stem cells (hMSCs) and various lineage-committed precursor cells and in diverse organisms. Furthermore, the H2B ubiquitin ligase RNF40 is required for the induction of...... during the transition from an inactive to an active chromatin conformation. Thus, these data indicate that H2Bub1 is required for maintaining multipotency of hMSCs and plays a central role in controlling stem cell differentiation....

  7. Fabrication of VO2 (B Nanobelts and Their Application in Lithium Ion Batteries

    Shibing Ni

    2011-01-01

    Full Text Available VO2 (B nanobelts have been successfully synthesized via a simple hydrothermal route. The products were characterized by X-ray diffraction (XRD, field emission scanning electron microscopy (FE-SEM, and Raman spectrum. These nanobelts are of rectangular cross-section with mean length about 1 μm, mean width about 80 nm, and mean thickness about 50 nm. The as-synthesized VO2 nanobelts were assembled as the cathode electrodes of lithium ion batteries. Their electrochemical properties were studied by conventional charge/discharge tests, which show an initial discharge capacity of 321 mAh g−1 with voltage plateau near 2.5 V. These results indicated that such hydrothermally synthesized VO2 (B nanobelts could be an ideal candidate of cathode material for lithium ion battery.

  8. Modeling the High Speed Research Cycle 2B Longitudinal Aerodynamic Database Using Multivariate Orthogonal Functions

    Morelli, E. A.; Proffitt, M. S.

    1999-01-01

    The data for longitudinal non-dimensional, aerodynamic coefficients in the High Speed Research Cycle 2B aerodynamic database were modeled using polynomial expressions identified with an orthogonal function modeling technique. The discrepancy between the tabular aerodynamic data and the polynomial models was tested and shown to be less than 15 percent for drag, lift, and pitching moment coefficients over the entire flight envelope. Most of this discrepancy was traced to smoothing local measurement noise and to the omission of mass case 5 data in the modeling process. A simulation check case showed that the polynomial models provided a compact and accurate representation of the nonlinear aerodynamic dependencies contained in the HSR Cycle 2B tabular aerodynamic database.

  9. Benzimidazole-2-carboxamides as novel NR2B selective NMDA receptor antagonists.

    Borza, István; Kolok, Sándor; Gere, Anikó; Nagy, József; Fodor, László; Galgóczy, Kornél; Fetter, József; Bertha, Ferenc; Agai, Béla; Horváth, Csilla; Farkas, Sándor; Domány, György

    2006-09-01

    A novel series of benzimidazole-2-carboxamide derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of some structural elements, like H-bond donor groups placed on the benzimidazole skeleton and the substitution pattern of the piperidine ring, on the biological activity was studied. Compound 6a showed excellent analgetic activity in the mouse formalin test following po administration. PMID:16782335

  10. Crystal structure of catalytic domain of the initiation factor 2B epsilon subunit

    Boesen, Thomas; Mohammad, Sarah S.; Pavitt, Graham D.; Andersen, Gregers Rom

    CRYSTAL STRUCTURE OF CATALYTIC DOMAIN OF THE INITIATION FACTOR 2B EPSILON SUBUNIT Thomas Boesen1,Sarah S. Mohammad2, Graham Pavitt2, and Gregers R. Andersen1* 1Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK-8000 Århus C, Denmark 2Department of Biomolecular Science...... of residues important for catalytic function and the location of residues for which mutations in humans give rise the the fatal brain disorder leukoencephalopathy with vanishing white matter....

  11. How to Develop Social Media Marketing Guidelines for a Small B2B Enterprise

    Varis, Ville

    2013-01-01

    The aim of this thesis is to research business-to-business social media marketing and help formulate guidelines for starting Real Clean Finland’s social media marketing efforts. This research seeks to find the easiest and most resource-effective methods and social media channels suitable for B2B marketing. At the time of the thesis process, the company had no established social media presence. Ideas for these guidelines were established through a combination of theoretical study and quali...

  12. The FRCR 2B examination: a survey of candidate perceptions and experiences

    Aim: To survey the views of recent candidates of the Fellowship of the Royal College of Radiologists (FRCR) 2B examination with reference to assessment validity, reliability, and acceptability. Materials and methods: One thousand, two hundred and four UK radiology trainees and consultants were invited to complete an automated internet questionnaire regarding their experiences and perceptions of the FRCR 2B examination. The questionnaire was informed by a review of the literature. Eligible participants were candidates who had taken the examination within the previous 3 years. Results: Four hundred and ninety-seven out of 1204 (41%) responses were received; of which 258/497 (52% of respondents) were eligible for inclusion into the study. The rapid reporting component is perceived to be significantly fairer than the oral section (82 versus 70% agree; p < 0.001). The oral component fared poorly in perceived performance-reducing anxiety levels but well in questions relating to validity and reliability. Female candidates are more likely to find the FRCR 2B unfair (p = 0.01) and experience performance-reducing anxiety (p < 0.001) than males. No gender differences were observed in first-time pass rates (p = 0.6). Candidate first language did not affect anxiety levels (p = 0.9) or first-time pass rates (p = 0.06). Only 12% of candidates agreed that the oral examination should move to an objective structured clinical format. Conclusion: Candidates score the FRCR 2B examination well in test validity with little desire for change to the oral examination format. Efforts to help reduce anxiety levels in the oral component would improve perceived fairness.

  13. Optimizing social media channels for B2B startups : Case of Odd Expert Oy

    Nguyen, Thi Ngoc Anh

    2016-01-01

    In recent years, the dramatic development of social media and its huge advances on global businesses cannot be deniable. With a large user base and useful analytics support, it helps many companies, especially startups, to reach their target audiences. Additionally, it requires low budget on advertising which stimulates all kinds of businesses to utilize social media channels. This thesis analyzes the effectiveness of social media marketing from perspectives of business-to-business (B2B) ...

  14. Social Media Technology Deployment in B2B: A Case Study

    Lashgari, Maryam

    2014-01-01

    The advent of social media as a modern communication tool has been extensively studied in the B2C domain; however its use as a communication platform in the B2B sector has thus far been under researched. This paper will examine two cases of global corporations headquartered in Stockholm including Ericsson and Scania that will demonstrate different approaches to the social media communication paradigm. The inclusion of these techniques in the classical communication theory will be necessary as...

  15. A population-specific HTR2B stop codon predisposes to severe impulsivity.

    Bevilacqua, Laura; Doly, Stéphane; Kaprio, Jaakko; Yuan, Qiaoping; Tikkanen, Roope; Paunio, Tiina; Zhou, Zhifeng; Wedenoja, Juho; Maroteaux, Luc; Diaz, Silvina,; Belmer, Arnaud; Hodgkinson, Colin; Dell'Osso, Liliana; Suvisaari, Jaana; Coccaro, Emil

    2010-01-01

    International audience Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identifie...

  16. Tumor promotion by an anticonvulsant agent, phenytoin, in mouse liver: correlation with CYP2B induction.

    Diwan, B A; Henneman, J R; Nims, R W; Rice, J M

    1993-11-01

    To investigate the liver tumor promoting effects of phenytoin (5,5-diphenylhydantoin; DPH), 5 week old male D2B6F1 mice were given a single i.p. dose of 90 mg N-nitrosodiethylamine (NDEA)/kg body wt in tricaprylin. Control groups received tricaprylin alone. After 2 weeks, the mice were given a diet containing 500, 250 or 125 p.p.m. DPH. Ten mice from each treatment group were killed at 30 weeks of age, at which time 10/10 mice given 500 p.p.m. DPH after NDEA initiation had developed multiple hepatocellular foci and adenomas. Such lesions were found only in 2/10 mice given NDEA alone. By 60 weeks, when the experiment was concluded, the incidences (and multiplicities, in units of tumors per tumor-bearing mouse) of hepatocellular adenomas were 60% (1.8 +/- 0.8), 100% (11.6 +/- 5.5), 77% (4.4 +/- 3.3) or 71% (2.6 +/- 1.3) in mice exposed to NDEA alone, or NDEA followed by 500, 250 or 125 p.p.m. DPH respectively. Hepatocellular carcinomas (87% incidence) and hepatoblastomas (33% incidence) were found only in mice given 500 p.p.m. DPH following NDEA initiation. Dose-dependent and profound increases in hepatic CYP2B-mediated benzyloxyresorufin O-dealkylase activity were detected in livers of B6C3F1 mice exposed for 14 days to dietary DPH (125, 250, 500 or 1000 p.p.m.). Similar increases in this activity were observed in D2B6F1 mice exposed to 500 and 250 p.p.m. for 30 or 60 weeks. Thus, increased hepatic CYP2B activity in mice exposed to DPH correlates with the tumor promoting effect of this compound. PMID:8242847

  17. Mutant genetic background affects the functional rearrangement and kinetic properties of JMJD2b histone demethylase

    Bártová, Eva; Stixová, Lenka; Galiová-Šustáčková, Gabriela; Harničarová, Andrea; Legartová, Soňa; Kozubek, Stanislav

    2011-01-01

    Roč. 405, č. 3 (2011), s. 679-695. ISSN 0022-2836 R&D Projects: GA ČR(CZ) GAP302/10/1022 Grant ostatní: GA MŠk(CZ) LC06027; GA MŠk(CZ) LC535 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : histone code * SUV39h * JMJ2b Subject RIV: BO - Biophysics Impact factor: 4.001, year: 2011

  18. Granulin exacerbates lupus nephritis via enhancing macrophage M2b polarization.

    Xi Chen

    Full Text Available BACKGROUND AND AIMS: Lupus nephritis (LN, with considerable morbidity and mortality, is one of the most severe manifestations of systemic lupus erythematosus (SLE. Yet, the pathogenic mechanisms of LN have not been clearly elucidated, and efficient therapies are still in great need. Granulin (GRN, a multifunctional protein linked to inflammatory diseases, has recently been reported to correlate with the disease activity of autoimmune diseases. However, the role of GRN in the pathogenic process of LN still remains obscure. In this study, we explored its potential role and underlying mechanism in the pathogenesis of LN. METHODOLOGY/PRINCIPAL FINDINGS: We found that serum GRN levels were significantly up-regulated and were positively correlated with the severity of LN. Overexpression of GRN in vivo by transgenic injection remarkably exacerbated LN, whereas down-regulation of GRN with shRNA ameliorated LN, firmly demonstrating the critical role of GRN in the pathogenesis of LN. Notably, macrophage phenotype analysis revealed that overexpression of GRN could enhance macrophage polarization to M2b, a key mediator of the initiation and progression of LN. On the contrary, down-regulation of GRN resulted in impaired M2b differentiation, thus ameliorating LN. Moreover, we found that MAPK signals were necessary for the effect of GRN on macrophage M2b polarization. CONCLUSION/SIGNIFICANCE: We first demonstrated that GRN could aggravate lupus nephritis (LN via promoting macrophage M2b polarization, which might provide insights into the pathogenesis of LN as well as potential therapeutic strategies against LN.

  19. Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk.

    Cathy Slack

    2010-03-01

    Full Text Available Drosophila Lnk is the single ancestral orthologue of a highly conserved family of structurally-related intracellular adaptor proteins, the SH2B proteins. As adaptors, they lack catalytic activity but contain several protein-protein interaction domains, thus playing a critical role in signal transduction from receptor tyrosine kinases to form protein networks. Physiological studies of SH2B function in mammals have produced conflicting data. However, a recent study in Drosophila has shown that Lnk is an important regulator of the insulin/insulin-like growth factor (IGF-1 signaling (IIS pathway during growth, functioning in parallel to the insulin receptor substrate, Chico. As this pathway also has an evolutionary conserved role in the determination of organism lifespan, we investigated whether Lnk is required for normal lifespan in Drosophila. Phenotypic analysis of mutants for Lnk revealed that loss of Lnk function results in increased lifespan and improved survival under conditions of oxidative stress and starvation. Starvation resistance was found to be associated with increased metabolic stores of carbohydrates and lipids indicative of impaired metabolism. Biochemical and genetic data suggest that Lnk functions in both the IIS and Ras/Mitogen activated protein Kinase (MapK signaling pathways. Microarray studies support this model, showing transcriptional feedback onto genes in both pathways as well as indicating global changes in both lipid and carbohydrate metabolism. Finally, our data also suggest that Lnk itself may be a direct target of the IIS responsive transcription factor, dFoxo, and that dFoxo may repress Lnk expression. We therefore describe novel functions for a member of the SH2B protein family and provide the first evidence for potential mechanisms of SH2B regulation. Our findings suggest that IIS signaling in Drosophila may require the activity of a second intracellular adaptor, thereby yielding fundamental new insights into the

  20. B2B relationship calculus: quantifying resource effects in service-dominant logic

    deLeon, Anthony J.; Chatterjee, Sharmila C.; deLeon, Anthony; hatterjee, Sharmila C.

    2013-01-01

    Increasingly, knowledgeable business-to-business (B2B) customers and evolving customer needs are leading to seismic shifts in vendor–client interactions. Across industries, sellers are changing their business models from a simple goods orientation to a hybrid goods–services model, placing greater emphasis on delivering complete customer solutions. In such an environment, companies must find ways to prioritize investments in resource development. The service-dominant (S-D) logic framework offe...

  1. Pressure Studies of Reentrance Behavior in Hc2 of HoNi2B2C

    We have investigated pressure dependence of the superconductivity of HoNi2B2C using high quality single crystals. Upon applying pressures, Tc was slightly suppressed unlike TN taken from M(T) data that increases gradually with pressures. At the same time, reentrance behavior found in Hc2 gets subdued and disappears altogether above 8.3 kbar. Our experimental findings can be understood in terms of the Ginzburg--Landau type analysis. (author)

  2. Modern day roles of B2B customer acquisition applications on the internet

    Orttenvuori, Lauri

    2011-01-01

    My thesis examines the implementation of customer acquisition via the internet. I chose the subject because it is becoming increasingly relevant in business life. The ways the internet is applied on consumers also offers opportunities to B2B customer acquisition and its support. In order for companies to keep up with technological development they must be able to exploit the advantages the internet is offering in comparison to other marketing or communicating instruments. The purpose of...

  3. ERP-toiminnanohjaus ja CRM-asiakkuudenhallintajärjestelmien B2B-markkinointi

    Mostafa Soltani, Nakaroz

    2011-01-01

    Opinnäytetyö on toteutettu toimeksiantona Digilever Business Solutions Oy:lle. B2B- markkinointi on yritykseltä yritykselle markkinoinnin ympäristö, jossa yritykset tarjoavat toisilleen palveluita ja pyrkivät win-win- tilanteeseen eli kaikki osapuolet hyötyvät toimitusratkaisuista ja palvelusopimuksista. Yritykset ovat nykyään vuonna 2011 verkostoituneimpia ja riippuvaisempia toisistaan. ERP-toiminnanohjaus- CRM-asiakkuudenhallintajärjestelmien ja muiden oheistuotteiden kuten taloushalli...

  4. Investigation into thermal dissociation of A2B5 group semiconductors

    Thermal dissociation of the A2B5 group compounds is investigated. It is shown that evaporation mechanism is determined by diffusion processes. These compounds are evaporated congruently under dynamic conditions. Diffusion coefficients of phosphorus in CdP4(1.4x10-18 cm2/s at 592 K) and arsenic in CdAs2(7x10-17 cm2/s at 640 K) are evaluated

  5. Influence of Surface Preparation for Different Groups of A2B6 Mixed Crystals

    Zakrzewski, J.; Maliński, M.; Strzałkowski, K.; Firszt, F.; Łęgowski, S.; Męczyńska, H.

    2010-01-01

    Piezoelectric photothermal spectroscopy has been used for measurements of the optical and thermal parameters of semiconductors. The investigated crystals were grown by the high-pressure Bridgman method under argon overpressure. The obtained photoacoustic (PA) spectra show the complexity of the effects observed for the different groups of selected A2B6 crystals. These effects comprise ideal samples and samples with damaged surfaces. The spectra show the influence of the surface treatment on the PA amplitude and phase spectra.

  6. Pyrrolo[3,2-b]pyrrole-Based Copolymers as Donor Materials for Organic Photovoltaics

    A new accepter unit, pyrrolo[3,2-b]pyrrole-2,5-dione, was prepared and utilized for the synthesis of the conjugated polymers containing electron donor-acceptor pair for OPVs. Pyrrolo[3,2-b]pyrrole-2,5-dione unit, regioisomer of the known pyrrolo[3,4-c]pyrrole-1,4-dione, is originated from the structure of stable synthetic pigment. The new conjugated polymers with 1,4-diphenylpyrrolo[3,2-b]pyrrole-2,5-dione, thiophene and carbazole were synthesized using Suzuki polymerization to generate P1 and P2. The solid films of P1 and P2 show absorption bands with maximum peaks at about 377, 554 and 374, 542 nm and the absorption onsets at 670 and 674 nm, corresponding to band gaps of 1.85 and 1.84 eV, respectively. To improve the hole mobility of the polymer with 1,4-bis(4-butylphenyl)-pyrrolo[3,2-b]-pyrrole-2,5-dione unit, which was previously reported by us, the butyl group at the 4-positions of the N-substituted phenyl group was substituted with hydrogen and methyl group. The field-effect hole mobility of P2 is 9.6 Χ 10-5 cm2/Vs. The device with P2:PC71BM (1:2) showed VOC value of 0.84 V, JSC value of 5.10 mA/cm2, and FF of 0.33, giving PCE of 1.42%

  7. Histone demethylase JMJD2B is required for tumor cell proliferation and survival and is overexpressed in gastric cancer

    Highlights: ► JMJD2B is required for cell proliferation and in vivo tumorigenesis. ► JMJD2B depletion induces apoptosis and/or cell cycle arrest. ► JMJD2B depletion activates DNA damage response and enhances p53 stabilization. ► JMJD2B is overexpressed in human primary gastric cancer. -- Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Jumonji domain containing 2B (JMJD2B) is a newly identified histone demethylase that regulates chromatin structure or gene expression by removing methyl residues from trimethylated lysine 9 on histone H3. Recent observations have shown oncogenic activity of JMJD2B. We explored the functional role of JMJD2B in cancer cell proliferation, survival and tumorigenesis, and determined its expression profile in gastric cancer. Knocking down JMJD2B expression by small interfering RNA (siRNA) in gastric and other cancer cells inhibited cell proliferation and/or induced apoptosis and elevated the expression of p53 and p21CIP1 proteins. The enhanced p53 expression resulted from activation of the DNA damage response pathway. JMJD2B knockdown markedly suppressed xenograft tumor growth in vivo in mice. Moreover, JMJD2B expression was increased in primary gastric-cancer tissues of humans. Thus, JMJD2B is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of gastric cancer.

  8. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

    Svensson, Per-Arne; Wahlstrand, Björn; Olsson, Maja [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Froguel, Philippe; Falchi, Mario [Department of Genomics of Common Disease, School of Public Health, Imperial College London (United Kingdom); Bergman, Richard N. [Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA (United States); McTernan, Philip G. [Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry (United Kingdom); Hedner, Thomas; Carlsson, Lena M.S. [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden); Jacobson, Peter, E-mail: peter.jacobson@medfak.gu.se [Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg (Sweden)

    2014-04-18

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis.

  9. CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus

    Highlights: • The tumor suppressor gene CDKN2B is highly expressed in human adipose tissue. • Risk alleles at the 9p21 locus modify CDKN2B expression in a BMI-dependent fashion. • There is an inverse relationship between expression of CDKN2B and adipogenic genes. • CDKN2B expression influences to postprandial triacylglycerol clearance. • CDKN2B expression in adipose tissue is linked to markers of hepatic steatosis. - Abstract: Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis

  10. Parallel Functional Activity Profiling Reveals Valvulopathogens Are Potent 5-Hydroxytryptamine2B Receptor Agonists: Implications for Drug Safety Assessment

    Huang, Xi-Ping; Setola, Vincent; Yadav, Prem N.; Allen, John A.; Rogan, Sarah C.; Hanson, Bonnie J; Revankar, Chetana; Robers, Matt; Doucette, Chris; Roth, Bryan L.

    2009-01-01

    Drug-induced valvular heart disease (VHD) is a serious side effect of a few medications, including some that are on the market. Pharmacological studies of VHD-associated medications (e.g., fenfluramine, pergolide, methysergide, and cabergoline) have revealed that they and/or their metabolites are potent 5-hydroxytryptamine2B (5-HT2B) receptor agonists. We have shown that activation of 5-HT2B receptors on human heart valve interstitial cells in vitro induces a proliferative response reminiscen...

  11. Oxidative damage of BEAS-2B cells induced by depleted uranium and protection by DMSO

    Objective: To observe the oxidative damage in human bronchial epithelial cells (BEAS-2B) induced by depleted uranium (DU) and protection of DMSO. Methods: The measurement of extracellular superoxide anions (O2-·) was based on the reduction of ferricytochrome C. Quantitative analysis of extracellular hydrogen peroxides (H2O2) was used by the horseradish peroxidase-dependent oxidation of phenol red. The determination of extracellular hydroxyl radicals (· OH) was based on discoloration of safranine T. Ethidium bromide and 2, 7'-dichlorofluorescein, fluorescent products of the membrane-permeable dyes-hydroethineand 2,7'-dichloroflurescin diacetate were used to monitor the intracellular production of O2- · and H2O2 by fluorometric method. The enzyme activity of SOD and GSH were measured by chemiluminescence and spectrophotometric method, respectively. Results: The ROS production, including H2O2, O2- · and · OH, increased remarkably which induced by DU in BEAs-2B cells. The enzyme activity of SOD and GSH was descended remarkedly. These changes could be effectively inhibited by 0.5% of DMSO. Conclusions: DU causes oxidative damage to BEAS-2B cells. Through removing active oxygen, DMSO can inhibit oxidative damage of DU. (authors)

  12. HATS-2b: A transiting extrasolar planet orbiting a K-type star showing starspot activity

    Mohler-Fischer, M; Hartman, J D; Bakos, G B; Penev, K; Bayliss, D; Jordan, A; Csubry, Z; Zhou, G; Rabus, M; Nikolov, N; Brahm, R; Espinoza, N; Buchhave, L A; Beky, B; Suc, V; Csak, B; Henning, T; Wright, D J; Tinney, C G; Addison, B C; Schmidt, B; Noyes, R W; Papp, I; Lazar, J; Sari, P; Conroy, P

    2013-01-01

    We report the discovery of HATS-2b, the second transiting extrasolar planet detected by the HATSouth survey. HATS-2b is moving on a circular orbit around a V=13.6 mag, K-type dwarf star (GSC 6665-00236), at a separation of 0.0230 \\pm 0.0003 AU and with a period of 1.3541 days. The planetary parameters have been robustly determined using a simultaneous fit of the HATSouth, MPG/ESO~2.2\\,m/GROND, Faulkes Telescope South/Spectral transit photometry and MPG/ESO~2.2\\,m/FEROS, Euler~1.2\\,m/CORALIE, AAT~3.9\\,m/CYCLOPS radial-velocity measurements. HATS-2b has a mass of 1.37 \\pm 0.16 M_J, a radius of 1.14 \\pm 0.03 R_J and an equilibrium temperature of 1567 \\pm 30 K. The host star has a mass of 0.88 \\pm 0.04 M_Sun, radius of 0.89 \\pm 0.02 R_Sun and shows starspot activity. We characterized the stellar activity by analysing two photometric follow-up transit light curves taken with the GROND instrument, both obtained simultaneously in four optical bands (covering the wavelength range of 3860-9520 \\AA). The two light curv...

  13. What Caused the Lead burn-out in Spectrometer Magnet 2B

    The spectrometer solenoids are supposed to be the first magnets installed in the MICE Cooling Channel. The results of the test of Spectrometer Magnet 2B are reported in a previous MICE Note. Magnet 2B was tested with all five coils connected in series. The magnet failed because a lead to coil M2 failed before it could be trained to its full design current of 275 A. First, this report describes the condition of the magnet when the lead failure occurred. The lead that failed was between the cold mass feed-through and the heavy lead that connected to coil M2 and the quench protection diodes. It is believed that the lead failed because the minimum propagation zone (MPZ) length was too short. The quench was probably triggered by lead motion in the field external to the magnet center coil. The effect of heat transfer on quench propagation and MPZ length is discussed. The MPZ length is compared for a number of cases that apply to the spectrometer solenoid 2B as built and as it has been repaired. The required heat transfer coefficient for cryogenic stability and the quench propagation velocity along the leads are compared for various parts of the Magnet leads inside the cold mass cryostat. The effect of the insulation on leads on heat transfer is and stability is discussed.

  14. APOSTLE: LONGTERM TRANSIT MONITORING AND STABILITY ANALYSIS OF XO-2b

    The Apache Point Survey of Transit Lightcurves of Exoplanets (APOSTLE) observed 10 transits of XO-2b over a period of 3 yr. We present measurements that confirm previous estimates of system parameters like the normalized semi-major axis (a/R*), stellar density (ρ*), impact parameter (b), and orbital inclination (iorb). Our errors on system parameters like a/R* and ρ* have improved by ∼40% compared to previous best ground-based measurements. Our study of the transit times show no evidence for transit timing variations (TTVs) and we are able to rule out co-planar companions with masses ≥0.20 M⊕ in low order mean motion resonance with XO-2b. We also explored the stability of the XO-2 system given various orbital configurations of a hypothetical planet near the 2:1 mean motion resonance. We find that a wide range of orbits (including Earth-mass perturbers) are both dynamically stable and produce observable TTVs. We find that up to 51% of our stable simulations show TTVs that are smaller than the typical transit timing errors (∼20 s) measured for XO-2b, and hence remain undetectable.

  15. What Caused the Lead burn-out in Spectrometer Magnet 2B

    Green, Michael A

    2010-11-29

    The spectrometer solenoids are supposed to be the first magnets installed in the MICE Cooling Channel. The results of the test of Spectrometer Magnet 2B are reported in a previous MICE Note. Magnet 2B was tested with all five coils connected in series. The magnet failed because a lead to coil M2 failed before it could be trained to its full design current of 275 A. First, this report describes the condition of the magnet when the lead failure occurred. The lead that failed was between the cold mass feed-through and the heavy lead that connected to coil M2 and the quench protection diodes. It is believed that the lead failed because the minimum propagation zone (MPZ) length was too short. The quench was probably triggered by lead motion in the field external to the magnet center coil. The effect of heat transfer on quench propagation and MPZ length is discussed. The MPZ length is compared for a number of cases that apply to the spectrometer solenoid 2B as built and as it has been repaired. The required heat transfer coefficient for cryogenic stability and the quench propagation velocity along the leads are compared for various parts of the Magnet leads inside the cold mass cryostat. The effect of the insulation on leads on heat transfer is and stability is discussed.

  16. Imported Genotype 2B Rubella Virus Caused the 2012 Outbreak in Anqing City, China.

    Zhen Zhu

    Full Text Available A rubella outbreak occurred in Anqing city of Anhui province, China, from February to July of 2012, and a total of 241 clinically diagnosed or lab-confirmed patients were reported. The highest number of rubella cases during this outbreak was recorded in teenagers between 10 and 19 years of age who had not previously received the rubella vaccine. Genotyping results indicated that the genotype 2B rubella virus (RV was responsible for the outbreak. However, a phylogenetic analysis showed that the genotype 2B RVs isolated in Anqing City were not related to 2B RVs found in other cities of Anhui province and in other provinces of China, thus providing evidence for importation. After importation, the transmission of Anqing RVs was interrupted owing to an effective immunization campaign against rubella, suggesting the timeliness and effectiveness of contingency vaccination. Strengthening rubella surveillance, including the integration of epidemiologic information and laboratory data, is a vital strategy for rubella control and elimination. In addition, except for routine immunization, targeted supplementary immunization activities aimed at susceptible groups according to sero-epidemiological surveillance data also play a key role in stopping the continuous transmission of rubella viruses and in preventing further congenital rubella syndrome cases.

  17. Atmospheric Circulation of Eccentric Hot Jupiter HAT-P-2b

    Lewis, Nikole K; Fortney, Jonathan J; Knutson, Heather A; Marley, Mark S

    2014-01-01

    The hot-Jupiter HAT-P-2b has become a prime target for Spitzer Space Telescope observations aimed at understanding the atmospheric response of exoplanets on highly eccentric orbits. Here we present a suite of three-dimensional atmospheric circulation models for HAT-P-2b that investigate the effects of assumed atmospheric composition and rotation rate on global scale winds and thermal patterns. We compare and contrast atmospheric models for HAT-P-2b, which assume one and five times solar metallicity, both with and without TiO/VO as atmospheric constituents. Additionally we compare models that assume a rotation period of half, one, and two times the nominal pseudo-synchronous rotation period. We find that changes in assumed atmospheric metallicity and rotation rate do not significantly affect model predictions of the planetary flux as a function of orbital phase. However, models in which TiO/VO are present in the atmosphere develop a transient temperature inversion between the transit and secondary eclipse even...

  18. A population-specific HTR2B stop codon predisposes to severe impulsivity.

    Bevilacqua, Laura; Doly, Stéphane; Kaprio, Jaakko; Yuan, Qiaoping; Tikkanen, Roope; Paunio, Tiina; Zhou, Zhifeng; Wedenoja, Juho; Maroteaux, Luc; Diaz, Silvina; Belmer, Arnaud; Hodgkinson, Colin A; Dell'osso, Liliana; Suvisaari, Jaana; Coccaro, Emil; Rose, Richard J; Peltonen, Leena; Virkkunen, Matti; Goldman, David

    2010-12-23

    Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity. PMID:21179162

  19. Information management: The adoption of order processing for B2B e-commerce

    F. W. Voges

    2007-11-01

    Full Text Available The management of information flow in the order processing activities of small enterprises is not always understood. An inefficient supply chain is often the result of the lack of timely and accessible inter-firm information and data exchange. Small suppliers often do not have the technology infrastructure and capable resources available for proper integration with supply chains. This research investigated suppliers and fast moving consumer goods (FMCG retailers, adopting business-to-business (B2B e-commerce. Small businesses are the focus of this research, as they contribute to a large portion of the South African economy and play an important role in the supply chains of retailers. Case study research using evidence obtained from nine small, medium and micro enterprises (SMMEs and suppliers located in the Western Cape, South Africa, was used. It was found that small suppliers have different processes for conducting business with various retailers. Literature revealed little evidence of using the Internet as an enabling technology in on-line order processing. From the analysis, nine improvement areas were identified to enhance the conduct of efficient B2B order processing and associated information flow. These improvement areas were merged with four factors that were identified in a framework when adopting e-supply chains. This resulted in the proposition of guidelines for small suppliers when adopting B2B e-commerce for order processing.

  20. A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent

    Eun Ju Oh

    2016-04-01

    Full Text Available BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2 and microphthalmia-associated transcription factor (MITF in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA and cAMP response element-binding protein (CREB activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders.

  1. A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent.

    Oh, Eun Ju; Park, Jong Il; Lee, Ji Eun; Myung, Cheol Hwan; Kim, Su Yeon; Chang, Sung Eun; Hwang, Jae Sung

    2016-01-01

    BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B) agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2) and microphthalmia-associated transcription factor (MITF) in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA) and cAMP response element-binding protein (CREB) activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders. PMID:27077852

  2. A study of single nucleotide polymorphisms of GRIN2B in schizophrenia from Chinese Han population.

    Guo, Zhenming; Niu, Weibo; Bi, Yan; Zhang, Rui; Ren, Decheng; Hu, Jiaxin; Huang, Xiaoye; Wu, Xi; Cao, Yanfei; Yang, Fengping; Wang, Lu; Li, Weidong; Li, Xingwang; Xu, Yifeng; He, Lin; Yu, Tao; He, Guang

    2016-09-01

    Schizophrenia is a severe and complex mental disorder with high heritability. There is evidence that mutations in the gene of Nmethyl-d-aspartate-type glutamate receptors (NMDAR) are associated with schizophrenia. GRIN2B encodes a subunit of NMDARs, and has been identified as a candidate gene for many psychiatric disorders, especially schizophrenia. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in GRIN2B were associated with schizophrenia. Four SNPs (rs890, rs1806191, rs219872, rs172677) were genotyped in 752 schizophrenic patients and 846 healthy controls of the Chinese Han population. Our results indicate differences in allele and genotype frequencies of rs890 between case and control. These results were assessed by adapting different genetic models (codominant, dominant, recessive, overdominant, log-additive models). After controlling for confounding factors including sex and age, rs890 remained associated with schizophrenia. In addition, rs890 and rs1806191 were found to form a haplotype associated with schizophrenia. In summary, our results indicate that the GRIN2B SNP rs890 might be associated with schizophrenia in the Chinese Han population. PMID:27453061

  3. Intensive Farmaco- Surveillance of Interferon Alpha 2b Recombinant in Multiple Sclerosis.

    Leslie Pérez Ruiz

    2007-12-01

    Full Text Available Background: The interferon alpha 2b recombinant, produced in Cuba, is used in the treatment of different illnesses, such as the multiple sclerosis. For its commercialization it is needed to know its safety scope. Objective: To assess the adverse reactions of interferon alpha 2b recombinant in the treatment of multiple sclerosis. Method: During the period between 1996 and 2006, 70 clinical histories and data collection notebooks of patients included in the randomized double blind national clinical trial phase IV were revised. This trial was developed in the Clinic of Multiple Sclerosis of the Hospital "Dr. Gustavo Aldereguía Lima" in Cienfuegos. With regard to the total of manifested adverse reactions we analyzed type, length, and use of a given treatment to counteract them, intensity level (light, moderate, serious or lethal and causality level (definitive, probable, possible, conditional or not related. Results: 53 patients out of the total presented 207 adverse reactions to interferon. The most frequent were: fever, migraine, chills, arthralgia, asthenia and myalgia, being most of them moderate collateral effects of definitive character. In 197 patients the outcome was favorable. Conclusion: The use of the interferon alpha 2b recombinant was safe in the treatment of the multiple sclerosis in these patients. 

  4. The GEF-6 Biodiversity Strategy

    Global Environment Facility

    2014-01-01

    The Convention on Biological Diversity (CBD) defines biodiversity as the variability among living organisms from all sources including, inter alia, terrestrial, marine and other aquatic ecosystems and the ecological complexes of which they are part; this includes diversity within species, between species, and of ecosystems. The Millennium Ecosystem Assessment and TEEB (The Economics of E...

  5. Novel associations of UDP-glucuronosyltransferase 2B gene variants with prostate cancer risk in a multiethnic study

    We have previously shown that a functional polymorphism of the UGT2B15 gene (rs1902023) was associated with increased risk of prostate cancer (PC). Novel functional polymorphisms of the UGT2B17 and UGT2B15 genes have been recently characterized by in vitro assays but have not been evaluated in epidemiologic studies. Fifteen functional SNPs of the UGT2B17 and UGT2B15 genes, including cis-acting UGT2B gene SNPs, were genotyped in African American and Caucasian men (233 PC cases and 342 controls). Regression models were used to analyze the association between SNPs and PC risk. After adjusting for race, age and BMI, we found that six UGT2B15 SNPs (rs4148269, rs3100, rs9994887, rs13112099, rs7686914 and rs7696472) were associated with an increased risk of PC in log-additive models (p < 0.05). A SNP cis-acting on UGT2B17 and UGT2B15 expression (rs17147338) was also associated with increased risk of prostate cancer (OR = 1.65, 95% CI = 1.00-2.70); while a stronger association among men with high Gleason sum was observed for SNPs rs4148269 and rs3100. Although small sample size limits inference, we report novel associations between UGT2B15 and UGT2B17 variants and PC risk. These associations with PC risk in men with high Gleason sum, more frequently found in African American men, support the relevance of genetic differences in the androgen metabolism pathway, which could explain, in part, the high incidence of PC among African American men. Larger studies are required

  6. Mutation of SH2B3 (LNK), a GWAS candidate for hypertension, attenuates Dahl SS hypertension via inflammatory modulation

    Rudemiller, Nathan P.; Lund, Hayley; Priestley, Jessica R. C.; Endres, Bradley T.; Prokop, Jeremy W.; Jacob, Howard J.; Geurts, Aron M.; Cohen, Eric P.; Mattson, David L.

    2015-01-01

    Human genome wide association studies (GWAS) have linked SH2B3 (LNK) to hypertension and renal disease, though little experimental investigation has been done to verify a role for SH2B3 in these pathologies. SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor protein that functions as a negative regulator in many signaling pathways, including inflammatory signaling processes. To explore a mechanistic link between SH2B3 and hypertension, we targeted the SH2B3 gene for mutation on the Dahl salt-sensitive (SS) rat genetic background with zinc-finger nucleases (ZFN). The resulting mutation was a 6 base-pair, in-frame deletion within a highly-conserved region of the Src Homology 2 (SH2) domain of SH2B3. This mutation significantly attenuated Dahl salt-sensitive (SS) hypertension and renal disease. Also, infiltration of leukocytes into the kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the Sh2b3em1Mcwi mutant rats. To determine if this was due to differences in immune signaling, bone marrow transplant studies were performed in which Dahl SS and Sh2b3em1Mcwi mutants underwent total body irradiation and were then transplanted with Dahl SS or Sh2b3em1Mcwi mutant bone marrow. Rats that received Sh2b3em1Mcwi mutant bone marrow had a significant reduction in mean arterial pressure and kidney injury when placed on a high salt diet (4% NaCl). These data further support a role for the immune system as a modulator of disease severity in the pathogenesis of hypertension and provide insight into inflammatory mechanisms at play in human hypertension and renal disease. PMID:25776069

  7. 76 FR 29997 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440...

    2011-05-24

    ... . SUPPLEMENTARY INFORMATION: Airworthiness Directive 2011-07-06, amendment 39-16643 (76 FR 18024, April 1, 2011.... Model CL-600-2B19 (Regional Jet Series 100 & 440) Airplanes AGENCY: Federal Aviation Administration (FAA.... Model CL-600-2B19 (Regional Jet Series 100 & 440) airplanes. In the AD as published, the reference...

  8. 75 FR 69609 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440...

    2010-11-15

    ... 12866; 2. Is not a ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034.... Model CL-600-2B19 (Regional Jet Series 100 & 440) Airplanes AGENCY: Federal Aviation Administration (FAA... Part 2, ``Airworthiness Limitations,'' of the Bombardier CL-600-2B19 Maintenance Requirements...

  9. 75 FR 10667 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440...

    2010-03-09

    ... Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic impact, positive or..., Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440) Airplanes AGENCY: Federal Aviation.... Applicability (c) This AD applies to Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 &...

  10. 75 FR 25788 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440...

    2010-05-10

    ... 12866; 2. Is not a ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034.... Model CL-600-2B19 (Regional Jet Series 100 & 440) Airplanes AGENCY: Federal Aviation Administration (FAA...) sufficient heat switches/sensors on CL-600-2B19 aircraft are located at the inboard end of each wing...

  11. 76 FR 53046 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440...

    2011-08-25

    ... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant.... Model CL-600-2B19 (Regional Jet Series 100 & 440) Airplanes AGENCY: Federal Aviation Administration (FAA.... Affected ADs (b) None. Applicability (c) This AD applies to Bombardier, Inc. Model CL-600-2B19...

  12. 75 FR 30740 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B16 (CL-604 Variants (Including CL-605...

    2010-06-02

    ... Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant economic impact, positive or... Directives; Bombardier, Inc. Model CL-600-2B16 (CL- 604 Variants (Including CL-605 Marketing Variant... addition to Bombardier Inc. Models CL-600-2B19, CL-600-2C10 and CL-600-2D24. The latter three models...

  13. 77 FR 10037 - Temporary Non-Agricultural Employment of H-2B Aliens in the United States

    2012-02-21

    ... (the 2008 Final Rule), an employer seeking to fill job opportunities through the H-2B program must... to Employers..... 2.83 1.31 14.64 Total Costs to Government.... 0.14 0.05 0.56 Present Value--7% Real... under the H-2B program that may require experience and/or training. Employer applicants demonstrating...

  14. 76 FR 59896 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program; Postponement of...

    2011-09-28

    ... Employment H-2B Program; Final Rule, 76 FR 3452, Jan. 19, 2011, (the Wage Rule). The Wage Rule revised the... Employment H-2B Program; Amendment of Effective Date; Final Rule, 76 FR 45667, August 1, 2011 revised the.... DATES: The effective date of the rule amending 20 CFR part 655 published at 76 FR 45667, August 1,...

  15. Sandwich iridium complexes with the monoanionic carborane ligand [9-SMe2-7,8-C2B9H10]-

    The reaction of the [(η-9-SMe2-7,8-C2B9H10)IrBr2]2 complex with Tl[Tl(η-7,8-C2B9H11)] afforded the iridacarborane compound (η-9-SMe2-7,8-C2B9H10)Ir(η-7,8-C2B9H11). The cationic complex [Cp*Ir(η-9-SMe2-7,8-C2B9H10)]+PF6- (Cp* is pentamethylcyclopentadienyl) was synthesized by the reaction of [Cp*IrCl2]2 with Na[9-SMe2-7,8-C2B9H10]. The structures of (η-9-SMe2-7,8-C2B9H10)Ir(η-cod) (cod is 1,5-cyclooctadiene) and [Cp*Ir(η-9-SMe2-7,8-C2B9H10]PF6 were established by X-ray diffraction

  16. 77 FR 24225 - Information Collection Approval; Temporary Non-Agricultural Employment of H-2B Aliens in the...

    2012-04-23

    ... Employment of H-2B Aliens in the United States; Final Rule. See 77 FR 10038, Feb. 21, 2012. DATES: On April 8....gov/fdsys/browse/collection.action?collectionCode=FR Web site. Copies of this notice may be obtained..., 2012. See 77 FR 10038. The purpose of the Final Rule was to amend the H-2B regulations at 20 CFR...

  17. Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior and memory deficits in mouse

    Fujiwara, K; Fujita, Y; Kasai, A; Onaka, Y; Hashimoto, H; Okada, H; Yamashita, T

    2016-01-01

    JMJD2B is a histone demethylase enzyme that regulates gene expression through demethylation of H3K9me3. Although mutations of JMJD2B have been suggested to be responsible for neurodevelopmental disorders, the function of JMJD2B in the central nervous system (CNS) remains to be elucidated. Here we show that JMJD2B has a critical role in the development of the CNS. We observed JMJD2B expression, which was especially strong in the hippocampus, throughout the CNS from embryonic periods through adulthood. We generated neuron-specific JMJD2B-deficient mice using the cre-loxP system. We found an increase in total spine number, but a decrease in mature spines, in the CA1 region of the hippocampus. JMJD2B-deficient mice exhibited hyperactive behavior, sustained hyperactivity in a novel environment, deficits in working memory and spontaneous epileptic-like seizures. Together these observations indicate that JMJD2B mutant mice display symptoms reminiscent of neurodevelopmental disorders. Our findings provide evidence for the involvement of histone demethylation in the formation of functional neural networks during development. PMID:27023172

  18. Functional characterization of cadmium-responsive garlic gene AsMT2b: A new member of metallothionein family

    2006-01-01

    A new gene of metallothionein (MT) family was cloned from garlic (Allium sativum) seedlings using RACE method and designated AsMT2b. The full length of AsMT2b cDNA was 520 bp encoding 80 amino acids. The deduced amino acids of AsMT2b showed that AsMT2b contained the characteristic structure of type 2 MT proteins, but the number and arrangement of the cysteine residues in the N- and C-terminal domains was different from other type 2 MT proteins. Semi-quantitative reverse transcriptase-PCR showed that transcript levels of AsMT2b were enhanced only in response to higher concentrations or longer incubation time of Cd. Such an expression pattern of AsMT2b greatly differed from that of other type 2 MT genes. Yeast cells transformed with this gene had improved resistance to Cd. AsMT2b overexpressing Arabidopsis showed stronger Cd tolerance and higher Cd accumulation compared with wild-type plants. These results suggest that AsMT2b should be useful in phytoremediation of Cd-polluted soil in the future.

  19. First-principles calculations of structural, elastic and electronic properties of Li2B12H12

    Highlights: • The fundamental structural parameters and density of states of Li2B12H12 are calculated. • Elastic constants are obtained by the strain energy–strain curves method. • Polycrystalline elastic moduli, Debye temperature and the average elastic wave velocity are determined. • The mechanical stability and elastic anisotropy are analyzed. - Abstract: We investigate the structural, elastic and electronic properties of Li2B12H12 using the first-principles method. Our calculations show that the lowest energy structure of Li2B12H12 is monoclinic C2/m type. We take the monoclinic C2/m Li2B12H12 as a representative to carry out the corresponding theoretical studies. The independent elastic constants are successfully obtained from the strain energy–strain curve calculations. The Shear and Young‘s moduli, as well as Poisson‘s ratio for ideal polycrystalline Li2B12H12 are calculated. The shear anisotropic factors and elastic anisotropy of Li2B12H12 are analyzed. The Debye temperature and the average elastic wave velocity are derived from theoretical elastic constants. According to the obtained results, the monoclinic C2/m Li2B12H12 is found to be mechanically stable and brittle at zero temperature and zero pressure. Furthermore, the density of states and electron charge density distributions are studied. The insulator Li2B12H12 is a technologically interesting indirect hydrogen storage material for further studies

  20. E-hubs: the new B2B (business-to-business) marketplaces.

    Kaplan, S; Sawhney, M

    2000-01-01

    Electronic hubs--Internet-based intermediaries that host electronic marketplaces and mediate transactions among businesses--are generating a lot of interest. Companies like Ariba, Chemdex, and Commerce One have already attained breathtaking stock market capitalizations. Venture capitalists are pouring money into more business-to-business start-ups. Even industrial stalwarts like GM and Ford are making plans to set up their own Web markets. As new entrants with new business models pour into the business-to-business space, it's increasingly difficult to make sense of the landscape. This article provides a blueprint of the e-hub arena. The authors start by looking at the two dimensions of purchasing: what businesses buy--manufacturing inputs or operating inputs--and how they buy--through systematic sourcing or spot sourcing. They classify B2B e-hubs into four categories: MRO hubs, yield managers, exchanges, and catalog hubs, and they discuss each type in detail. Drilling deeper into this B2B matrix, the authors look at how e-hubs create value--through aggregation and matching--and explain when each mechanism works best. They also examine the biases of e-hubs. Although many e-hubs are neutral--they're operated by independent third parties--some favor the buyers or sellers. The authors explain the differences and discuss the pros and cons of each position. The B2B marketplace is changing rapidly. This framework helps buyers, sellers, and market makers navigate the landscape by explaining what the different hubs do and how they add the most value. PMID:11183982

  1. Comparison of gene expression profiles in chromate transformed BEAS-2B cells.

    Hong Sun

    Full Text Available BACKGROUND: Hexavalent chromium [Cr(VI] is a potent human carcinogen. Occupational exposure has been associated with increased risk of respiratory cancer. Multiple mechanisms have been shown to contribute to Cr(VI induced carcinogenesis, including DNA damage, genomic instability, and epigenetic modulation, however, the molecular mechanism and downstream genes mediating chromium's carcinogenicity remain to be elucidated. METHODS/RESULTS: We established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of Cr(VI followed by anchorage-independent growth. These transformed cell lines not only exhibited consistent morphological changes but also acquired altered and distinct gene expression patterns compared with normal BEAS-2B cells and control cell lines (untreated that arose spontaneously in soft agar. Interestingly, the gene expression profiles of six Cr(VI transformed cell lines were remarkably similar to each other yet differed significantly from that of either control cell lines or normal BEAS-2B cells. A total of 409 differentially expressed genes were identified in Cr(VI transformed cells compared to control cells. Genes related to cell-to-cell junction were upregulated in all Cr(VI transformed cells, while genes associated with the interaction between cells and their extracellular matrices were down-regulated. Additionally, expression of genes involved in cell proliferation and apoptosis were also changed. CONCLUSION: This study is the first to report gene expression profiling of Cr(VI transformed cells. The gene expression changes across individual chromate exposed clones were remarkably similar to each other but differed significantly from the gene expression found in anchorage-independent clones that arose spontaneously. Our analysis identified many novel gene expression changes that may contribute to chromate induced cell transformation, and collectively this type of

  2. Preclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma

    Ye H

    2014-09-01

    Full Text Available Hui Ye,1,2 Jiansong Tong,2 Jianzhang Wu,3 Xia Xu,4 Shenjie Wu,5 Botao Tan,6 Mengjing Shi,5 Jianguang Wang,1 Weibo Zhao,5 Heng Jiang,5 Sha Jin5 1School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Cellular and Molecular Biology, Scripps Research Institute, La Jolla, CA, USA; 3Pharmaceutical College, Wenzhou Medical University, Wenzhou, 4School of Medicine, Zhejiang University, Hangzhou, 5School of the 1st Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, 6School of Medicine, Lishui University, Lishui, People’s Republic of China Abstract: Magnetoliposomes are phospholipid vesicles encapsulating magnetic nanoparticles that can be used to encapsulate therapeutic drugs for delivery into specific organs. Herein, we developed magnetoliposomes containing recombinant human IFNα2b, designated as MIL, and evaluated this combination’s biological safety and therapeutic effect on both cellular and animal hepatocellular carcinoma models. Our data showed that MIL neither hemolyzed erythrocytes nor affected platelet-aggregation rates in blood. Nitroblue tetrazolium-reducing testing showed that MIL did not change the absolute numbers or phagocytic activities of leukocytes. Acute-toxicity testing also showed that MIL had no devastating effect on mice behaviors. All the results indicated that the nanoparticles could be a safe biomaterial. Pharmacokinetic analysis and tissue-distribution studies showed that MIL maintained stable and sustained drug concentrations in target organs under a magnetic field, helped to increase bioavailability, and reduced administration time. MIL also dramatically inhibited the growth of hepatoma cells. Targeting of MIL in the livers of nude mice bearing human hepatocellular carcinoma showed that MIL significantly reduced the tumor size to 38% of that of the control group. Further studies proved that growth inhibition of cells or tumors was due to apoptosis

  3. Calcium sensitivity and myofilament lattice structure in titin N2B KO mice

    Lee, Eun-Jeong; Nedrud, Joshua; Schemmel, Peter; Gotthardt, Michael; Irving, Thomas C.; Granzier, Henk L

    2012-01-01

    The cellular basis of the Frank-Starling “Law of the Heart” is the length-dependence of activation, but the mechanisms by which the sarcomere detects length changes and converts this information to altered calcium sensitivity has remained elusive. Here the effect of titin-based passive tension on the length-dependence of activation (LDA) was studied by measuring the tension-pCa relation in skinned mouse LV muscle at two sarcomere lengths (SLs). N2B KO myocardium, where the N2B spring element in titin is deleted and passive tension is elevated, was compared to WT myocardium. Myofilament lattice structure was studied with low-angle X-ray diffraction; the myofilament lattice spacing (d10) was measured as well as the ratio of the intensities of the 1,1 and 1,0 diffraction peaks (I11/I10) as an estimate of the degree of association of myosin heads with the thin filaments. Experiments were carried out in skinned muscle in which the lattice spacing was reduced with Dextran-T500. Experiments with and without lattice compression were also carried out following PKA phosphorylation of the skinned muscle. Under all conditions that were tested, LDA was significantly larger in N2B KO myocardium compared to WT myocardium, with the largest differences following PKA phosphorylation. A positive correlation between passive tension and LDA was found that persisted when the myofilament lattice was compressed with Dextran and that was enhanced following PKA phosphorylation. Low-angle X-ray diffraction revealed a shift in mass from thin filaments to thick filaments as sarcomere length was increased. Furthermore, a positive correlation was obtained between myofilament lattice spacing and passive tension and the change in I11/I10 and passive tension and these provide possible explanations for how titin-based passive tension might regulate calcium sensitivity. PMID:23246787

  4. The Preparation and Characterization of INTEC Phase 2b Composition Variation Study Glasses

    B. A. Staples; B. A. Scholes; L. L. Torres; C. A. Musick; B. R. Boyle (INEEL); D. K. Peeler (SRTC); J. D. Vienna (PNNL)

    2000-02-01

    The second phase of the composition variation study (CVS) for the development of glass compositions to immobilize Idaho Nuclear Technology and Engineering Center (INTEC) high level wastes (HLW) is complete. This phase of the CVS addressed waste composition of high activity waste fractions (HAW) from the initial separations flowsheet. Updated estimates if INTEC calcined HLW compositions and of high activity waste fractions proposed to be separated from dissolved calcine were used as the waste component for this CVS phase. These wastes are of particular interest because high aluminum, calcium, zirconium, fluorine, potassium, and low iron and sodium content places them outside the vitrification experience in the Department of Energy complex. Because of the presence of calcium and fluorine, two major zirconia calcine components not addressed in Phase I, a series of scooping tests, designated Phase 2a, were performed. The results of these tests provided information on the effects of calcium and fluoride solubility and their impacts on product properties and composition boundary information for Phase 2b. Details and results of Phase 2a are reported separately. Through application of statistical techniques and the results of Phase 2a, a test matrix was defined for Phase 2b of the CVS. From this matrix, formulations were systematically selected for preparation and characterization with respect to visual and optical homogeneity, viscosity as a function of melt temperature, liquidus temperature (TL), and leaching properties based on response to the product consistency test. The results of preparing and characterizing the Phase 2b glasses are presented in this document. Based on the results, several formulations investigated have suitable properties for further development. A full analysis of the composition-product characteristic relationship of glasses being developed for immobilizing INTEC wastes will be performed at the completion of composition-property relationship

  5. Spectral analysis of Cu(2+): B(2)O(3)--ZnO--PbO glasses.

    Lakshminarayana, G; Buddhudu, S

    2005-11-01

    A new series of heavy metal oxide (PbO) based zinc borate glasses in the chemical composition of (95-x)B(2)O(3)-5ZnO-xPbO (x=10, 15, 20, 25, 30, 35, 40, 45 and 50 mol%) have been prepared to verify their UV filtering performance. Both direct and indirect optical band gaps (E(opt)) have been evaluated for these glasses. For a reference glass of 45B(2)O(3)-5ZnO-50PbO, refractive indices at different wavelengths are measured and found the results satisfactorily correlated with the theoretical data upon the computation of Cauchy's constants of A=1.766029949, B=159531.024 nm(2) and C=-1.078 x 10(10) nm(4). Measurements concerning X-ray diffraction (XRD), FT-IR, differential scanning colorimeter (DSC) profiles have been carried out for this glass. The FT-IR profile has revealed that the glass has both BO(3) and BO(4) units. From DSC thermogram, glass transition temperature (T(g)), crystallization temperature (T(c)) and melting temperature (T(m)) have been located and from them, other related parameters of the glass have also been calculated. Visible absorption spectra of 45B(2)O(3)-5ZnO-(50-x)PbO-xCuO (x=0. 1, 0.2, 0.5 and 1.0 mol%) have revealed two absorption bands at around 400 nm ((2)B(1g)-->(2)E(g)) and 780 nm ((2)B(1g)-->(2)B(2g)) of Cu(2+) ions, respectively. Emission bands at 422 and 512 nm are found for the 1 mol % CuO doped glass with excitations at 306 and 332 nm. PMID:16257737

  6. Parvimarkkinointiteorian sujuva interaktiivinen toteutus: Verkkosivusto DDB Helsingin B2B-markkinointiin

    Virkki, Sanna

    2009-01-01

    Työn aihe on verkkosivuston suunnittelu ja toteutus mainostoimisto DDB Helsingin B2B-markkinointiin. Verkkosivuston aihe on parvimarkkinointi, joka on myös DDB:n toimitusjohtajan kirjoittaman kirjan teema. Parvimarkkinointi kuvaa markkinoinnin luonnetta digitaalisen median aikana. Työhön kuului verkkosivuston sisällön suunnittelu ja sivuston toteutus. Sisältö vaati parvimarkkinoinnin teorian suomentamista ja tiivistämistä lähdemateriaalista, animaatioiden suunnittelua ja sivuston graafist...

  7. Intralesional interferon alpha - 2b in genital warts : A preliminary study

    Pandhi R; Mittal Asit; Gupta Lalit

    1993-01-01

    Currently available therapy for condyloma acuminata (genital warts) is not consistently effective. Interferon (IFN) has both antiproliferatve and antiviral properties and has been used to treat genital warts with varying degree of success. We conducted an open study on 6 male patients with genital warts. A single wart of comparable area from each patient was injected with 2 x 106 IU of IFN alpha-2b, 3 times weekly for 3 weeks. The response to treatment was assessed during the therapy and at 1...

  8. Common Variants in the ATP2B1 Gene Are Associated With Susceptibility to Hypertension

    Tabara, Yasuharu; Kohara, Katsuhiko; Kita, Yoshikuni; Hirawa, Nobuhito; Katsuya, Tomohiro; Ohkubo, Takayoshi; Hiura, Yumiko; Tajima, Atsushi; Morisaki, Takayuki; Miyata, Toshiyuki; Nakayama, Tomohiro; Takashima, Naoyuki; Nakura, Jun; Kawamoto, Ryuichi; Takahashi, Norio; Hata, Akira; Soma, Masayoshi; Imai, Yutaka; Kokubo, Yoshihiro; Okamura, Tomonori; Tomoike, Hitonobu; Iwai, Naoharu; Ogihara, Toshio; Inoue, Itsuro; Tokunaga, Katsushi; Johnson, Toby; Caulfield, Mark; Munroe, Patricia; Umemura, Satoshi; Ueshima, Hirotsugu; Miki, Tetsuro

    2016-01-01

    Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the ATP2B1 rs2070759 polymorphism with hypertension (P=5.3×10−5; allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in ATP2B1 were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42]; P=4.1×10−11). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21]; P=5.9×10−4). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (P=1.4×10−18). ATP2B1 mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes, FGF5 rs1458038, CYP17A1, rs1004467, and CSK rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12; P=4.6×10−7) compared with the lower risk group. In summary, this study confirmed common genetic variation in ATP2B1, as well as FGF5, CYP17A1, and CSK, to be associated with blood pressure levels and risk of hypertension. PMID:20921432

  9. Towards a standardised line list for G191-B2B, and other DA type objects

    Preval, Simon P; Holberg, Jay B; Dickinson, N J

    2012-01-01

    We present a comprehensive analysis of the far UV spectrum of G191-B2B over the range of 900-1700{\\AA} using co-added data from the FUSE and STIS archives. While previous identifications made by Holberg et al. (2003) are reaffirmed in this work, it is found that many previously unidentified lines can now be attributed to Fe, Ni, and a few lighter metals. Future work includes extending this detailed analysis to a wider range of DA objects, in the expectation that a more complete analysis of their atmospheres can be realised.

  10. Performance in the FRCR (UK) Part 2B examination: Analysis of factors associated with success

    Aim: To assess factors that influence pass rates and examination scores in the Fellowship of the Royal College of Radiologists (FRCR) 2B examination. Materials and methods: 2238 attempts at the FRCR 2B examination were evaluated between Spring 2006 and Spring 2010. Pass rates and examination scores were analysed by gender and ethnicity, and the influence of factors such as radiology training (UK versus non-UK), sitting (Spring versus Autumn), and the presence of an undergraduate or postgraduate degree were examined. Results: 1571 candidates made 2238 examination attempts, with an overall pass rate of 59.4% (63.1% at first attempt). 66.2% entrants were male; 48.8% attempts were by candidates from a UK radiology training scheme. UK candidates were significantly more likely to pass than non-UK candidates (p < 0.0001). White candidates were more likely to pass at first or second attempt than non-white candidates (p < 0.0001), but when restricted to UK entrants ethnicity did not influence success at first attempt. Overall, females were more successful than males (p < 0.001). Presence of an undergraduate (p = 0.19) or postgraduate (p = 0.80) degree did not affect pass rate at first attempt for UK candidates. However, logistic regression demonstrated that the only significant factor influencing pass rates at first attempt was whether radiology training was undertaken in the UK (p < 0.0001). A trend towards increased pass rates in autumn sittings was seen (p = 0.06), but ethnicity (p = 0.99) and gender (p = 0.41) were not significant factors. Conclusion: The FRCR 2B examination is non-discriminatory for UK candidates with respect to gender and ethnicity. Poorer performance of non-UK trained candidates is a consistent outcome in the literature. - Highlights: • Factors influencing pass rates and scores in FRCR 2B examination were assessed. • UK candidates are more likely to pass than non-UK candidates. • There is no effect of gender or ethnicity on UK

  11. Digitaalisen B2B-markkinoinnin kehittäminen Case: Mainoste Print Oy

    Kokkonen, Antti

    2015-01-01

    Digitaalinen markkinointi on tullut jäädäkseen. Se muodostuu suuresta valikoimasta erilaisia markkinointikanavia. Nämä kanavat antavat mahdollisuuden markkinoida aivan uusilla tavoilla, vaikka perinteet muuten olisivat toiminnassa mukana. Toisaalta nämä uudet kanavat pakottavat organisaatiot opettelemaan uutta, jos ne haluavat pysyä kehityksen mukana. Tässä opinnäytetyössä käsiteltiin digitaalisen markkinoinnin kehittämistä Keravalaisessa B2B-yrityksessä Mainoste Print Oy. Työn tarkoituks...

  12. Magnetoelastic tetragonal-to-orthorhombic distortion in ErNi2B2C

    We have performed synchrotron x-ray scattering experiments on single crystals of ErNi2B2C. Below 6.3 K, the (2,0,0) Bragg peak splits, indicating a tetragonal-to-orthorhombic distortion. The mismatch between the a and b lattice parameters appears coincident with the onset of long-range antiferromagnetic order and increases continuously with decreasing temperature, reaching a value of a/b-1∼0.2% at 3.7 K. copyright 1997 The American Physical Society

  13. Exfoliation Corrosion Behavior of 2B06 Aluminum Alloy in a Tropical Marine Atmosphere

    Cui, Z. Y.; Li, X. G.; Xiao, K.; Dong, C. F.; Wang, L. W.; Zhang, D. W.; Liu, Z. Y.

    2015-01-01

    In this study, corrosion behavior of 2B06 aluminum alloy was investigated after exposure to a tropical marine atmosphere for up to 4 years. After 6 months, the specimen showed exfoliation corrosion as well as rapid increase in thickness loss and corrosion rate. Exfoliation corrosion was found to initiate from hydrogen-assisted intergranular cracks and propagate extensively due to the wedge effect of the corrosion products. During the exposure test, corrosion on the groundward surface was considerably more severe than that on the skyward surface, which could be attributed to the different exposure conditions on the two surfaces.

  14. Impact of UGT2B17 gene deletion on the steroid profile of an athlete

    Martín‐Escudero, Pilar; Muñoz‐Guerra, Jesús; Del Prado, Nayade; Galindo Canales, Mercedes; Fuentes Ferrer, Manuel; Vargas, Soledad; Soldevilla, Ana B.; Serrano‐Garde, Ester; Miguel‐Tobal, Francisco; Maestro de las Casas, Marisa; Fernandez‐Pérez, Cristina

    2015-01-01

    Abstract The measurement of the testosterone to epitestosterone ratio (T/E ratio) in urine is often used as a marker for testosterone administration in the doping control field. This study examines the frequencies of the different expression forms of the UGT2B17 gene, and assesses their effects on this marker in volunteer subjects. The sample for this descriptive study was composed of male and female athletes aged between 16 and 55 years old who practiced different sports disciplines. All par...

  15. Myynnin ja markkinoinnin ammattilaisten kokemuksia ja odotuksia B2B-verkkokaupasta

    Manner, Minna

    2015-01-01

    Tämän opinnäytetyön tavoitteena oli selvittää, millaisia kokemuksia ja odotuksia B2B -markkinoinnissa työskentelevillä myynnin ja markkinoinnin ammattilaisilla on verkkokaupasta ja miten he arvioivat ostajien löytävän heidän edustamansa tuotteet ja yrityksen verkkopalveluista. Opinnäytetyö on toimeksiantotutkimus Myynnin ja markkinoinnin ammattilaiset ry:lle. Tutkimus suoritettiin laadullista tutkimusmenetelmää käyttäen. Tutkimuksen tulokset saavutettiin puolistrukturoidun ja avoimia kysymyks...

  16. Direct Observation of Spontaneous Weak Ferromagnetism in the Superconductor ErNi2B2C

    Neutron measurements show that superconducting ErNi2B 2C (TC=11 K) develops antiferromagnetic spin density wave magnetic order (TN=6 K), which squares up with decreasing temperature yielding a series of higher-order magnetic Bragg peaks with odd harmonics. Below TWFM=2.3 K where magnetization indicates a net moment develops, even-order Bragg peaks develop which low field (∼3 Oe) polarized beam measurements show are magnetic in origin. The data directly demonstrate the existence of a net magnetization with a periodicity of 20a , confirming the microscopic coexistence of spontaneous weak ferromagnetism with superconductivity

  17. Superconducting RNi2B2C(R=Y,Lu) nanoparticles: size effects and weak links

    The potential of the arc discharge technique for the growth of complex nanocrystalline systems is demonstrated here with the formation of quaternary superconducting nanoparticles belonging to the recently discovered intermetallic boron carbide family RNi2B2C (R = Y, Lu). The nanoparticles, which were embedded in a glassy carbon matrix and had Tc - 15 K, are reported to exhibit magnetic behavior characterized by finite size effects and weak Josephson links between the particles. The formation and characterization of the nanoparticles are detailed. (orig.)

  18. Sociala Medier som kommunikationskanal för B2B-företag

    Kaddura, Layla; Olsson, Karin

    2010-01-01

    The purpose of this thesis is to show what advantages and opportunities social media offer for B2B-companies (business-to-business), and how they can be used for marketing communications. We have studied how companies can use social media, for example evolving the organization, developing products/services, staying up-to-date, building relations, creating customer loyalty and engagement, building the company’s identity and image, and affecting the buying decisions. We have also studied how B2...

  19. Anisotropic magnetic and superconducting properties of ErNi2B2C single crystals

    We report on studies of the magnetic and superconducting properties of ErNi2B2C single crystals in a wide range of magnetic fields (up to 5 T) and temperatures (2-200 K). It is shown that the magnetic behavior of this compound can be described in terms of the Ising-like model. The temperature dependence of the lower critical field and the irreversibility line clearly indicate an interplay between the superconductivity and the magnetism of the Er sublattice. (orig.)

  20. Small-angle neutron scattering and magnetization study of HoNi2B2C

    The superconducting and magnetic properties of HoNi2B2C single crystals are investigated through transport, magnetometry and small-angle neutron scattering (SANS) measurements. In the magnetic phases that enter below the superconducting critical temperature, the small-angle neutron scattering data uncover networks of magnetic surfaces. These likely originate from uncompensated moments, e.g., at domain walls pinned to crystallographic grain boundaries. The field and temperature dependent behavior of SANS appears consistent with the metamagnetic transitions reported in earlier works.

  1. B2B inter-organisational digitalisation strategies - towards an interaction based approach

    Ivang, Reimer; Rask, Morten; Hinson, Robert

    2009-01-01

    companies with an annual turnover of 3 billion EUR and over 30.000 employees. We specifically seek to understand to what extent the widely used strategic continuum (planning - incremental) is sufficient to understand the process of creating inter-organisational digitalisation strategies in the case......Purpose: Digital technology is increasingly important for businesses as it has the capability to enable, support and sometimes influence the overall strategic direction of the corporation. This paper investigates b2b inter-organisational digitalisation strategies in one of Denmark's biggest...

  2. A INFLUÊNCIA DA MARCA NO AMBIENTE ORGANIZACIONAL (B2B

    Paulo Afonso Barbosa da Silveira

    2009-09-01

    Full Text Available Este artigo versa sobre a importância de uma marca forte no, cada dia mais competitivo, mercado organizacional (B2B e a sua influência no processo de venda corporativa. Serão apresentados alguns conceitos sobre marcas e delineado um breve histórico das mesmas, passando a uma análise sobre a evolução e valorização que as marcas vêm sofrendo ao longo do tempo, dando destaque à sua influência na tomada de decisão de compra no âmbito corporativo.

  3. B2B:登峰造极VS暮气沉沉

    张洁; 顾卓

    2007-01-01

    @@ 说到中国的制造业就不得不说到中国的B2B,说到B2B就不得不说阿里巴巴.这个在马云带领下的B2B网站现在已成为公认的B2B老大,"打着灯笼也找不到竞争对手"的话也并非一时脑热的脱口而出.

  4. Studying freshly-formed surfaces of compounds of A2B6 type

    Investigations of the active surface naturte of A2B6 type compound are continued. Behaviour of freshly formed surfaces of ZnSe, CdSe, ZnTe, obtained by means of dispersion in the active (water) and more inert (acetone) media, is considered. Mechanism of water interaction with zinc and cadmium chalogenide surface is verified. Presence of metalloid vacancies on their freshly formed surface and its enrichment with Zn or Cd coordination-nusaturated atoms are determined. The latters preferably act as active centres in relation to H2O type molecules

  5. B2B-sisältömarkkinoinnin mahdollisuudet asiantuntijapalveluissa - Case: Yritys X

    Yli-Kyyny, Elina

    2014-01-01

    Tämän opinnäytetyön tarkoituksena oli selvittää kuinka B2B-yritykset saadaan kiinnostumaan asiantuntijapalveluista sisältömarkkinoinnin avulla. Tutkimuksessa haluttiin selvittää, kuinka sisältömarkkinoinnilla saavutetaan uusia asiakkuuksia ja mitä mahdollisuuksia sisältömarkkinointi tarjoaa asiantuntijaorganisaatiolle. Opinnäytetyö tehtiin asiantuntijaorganisaatiolle, jonka toimialaan kuuluvat valmennus, -konsultointi –ja markkinointipalvelut. Työn aiheen valintaan vaikutti työskentely yrityk...

  6. hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn.

    McKay, S.J.; Cooke, H

    1992-01-01

    We have previously isolated a protein from mouse liver nuclei that specifically binds to single stranded (TTAGGG)n repeats. TTAGGG is the telomeric repeats of mammals and we therefore named the new protein single stranded telomere binding protein (sTBP). Further studies now identify sTBP as heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 on the basis of amino acid sequence determination and antibody reactivity. A2 and B1 form a major part of the protein component of hnRNP particles and ...

  7. Photothermal Investigation of Surface Defects of Pure Semiconducting A2B6 Materials

    Zakrzewski, J.; Maliński, M.; Strzałkowski, K.; Madaj, D.; Firszt, F.; Łęgowski, S.; Męczyńska, H.

    2012-04-01

    Photoacoustic spectroscopy is a sensitive and useful method to investigate the quality of semiconducting A2B6 crystals. An imperfection of surface quality can strongly influence photoacoustic spectra but it shows the different character for the different kinds of semiconducting materials. To properly interpret the amplitude and phase spectra, the temperature distribution and its modifications, due to the surface defects, are needed. The Blonskij model of the temperature distribution was used to investigate the influence of the defect on the amplitude and phase spectra.

  8. Sales Organization & Tactics : Solutions for improving the sales function in medium sized B-2-B companies

    Aller, Rick Johan

    2010-01-01

    The thesis is a work summarizing the most important obstacles in the sales function in a mid-sized B-2-B company. It suggests solutions to the problems on both an organizational and a tactical level. Practical knowledge and case studies are intertwined in the theory for the reader to quickly grasp the vital points of both organizational and tactical issues. It then provides a guide for applying the suggested solutions in practice. The thesis is helpful to any company or start-up aiming to imp...

  9. The Analysis of B2B Business Model from the Viewpoint of Value Chain

    2002-01-01

    Electronic business impacts differently the busines s process in or between the corporations in variant degree. In view of the new fea tures of the internet, critical questions to be answered inclued: what are t he emerging business models and related to this, which strategic marketing appro aches are applied,or emerging. In the paper, the business models in B2B are clas sified into four types as e-procurement, e-marketplace, e-trade exchange, and collaborative trading community from the value viewpoint...

  10. Some Considerations on B2B in China%对我国B2B的一些思考

    王进; 和金生

    2001-01-01

    从B2B的现状入手,指出中国非常需要B2B;从B2B企业的内部环境对B2B出现的问题加以分析,并提出了相关对策,最后对B2B给予了展望。%Based on the analysis of the present situation of B2B,it indicates the requirement of B2B in China. Then,it analyses the questions in the implementation of B2B in enterprises and puts forward some countermeasures. Finally,the prospect of B2B development is given.

  11. Directional frustration of magnetic moments in (U0.50Dy0.50)Ni2B2C

    Polycrystalline (U0.50Dy0.50)Ni2B2C solid solution was prepared and found by X-ray diffraction to crystallize in BCT LuNi2B2C-type structure (space group I4/mmm) of the end compounds UNi2B2C and DyNi2B2C. AC susceptibility and magnetization show paramagnetic behavior down to 6.5 K, with the values θ=-5(5) K and μeff=7.7(1) μB, compatible with those of the end compounds, and indicate possible cooperative phenomena at lower temperatures. The observed paramagnetism, at variance with antiferromagnetic ordering in (Pr0.50Dy0.50)Ni2B2C, is attributed to a directional frustration of the magnetic moments on the (U,Dy) site

  12. Magnetic flux structures in RNi{sub 2}B{sub 2}C single crystals in normal and superconducting states

    Vinnikov, L Ya; Veshchunov, I S [Institute of Solid State Physics, RAS, Chernogolovka, Moscow region 142432 (Russian Federation); Bud' ko, S L; Canfield, P C; Kogan, V G, E-mail: vinnik@issp.ac.r [Ames Laboratory U.S. DOE, Iowa State University, Ames, Iowa 50011 (United States)

    2009-03-01

    RNi{sub 2}B{sub 2}C single crystals, where R = Lu, Y, Er, Ho and Tb have been studied by high-resolution Bitter decoration technique, over the wide range temperatures and magnetic fields up to 2 T. Diverse vortex lattice structures were investigated: transition from triangular to square lattice for LuNi{sub 2}B{sub 2}C single crystals; peculiar vortex structures associated with antiferromagnetic (AFM) and weak-ferromagnetic (WFM) states below T{sub c} for ErNi{sub 2}B{sub 2}C single crystals . In addition, Bitter decoration revealed structures associated with a long range magnetic order in the non-superconducting TbNi{sub 2}B{sub 2}C as well as ErNi{sub 2}B{sub 2}C in the normal but magnetically ordered state.

  13. PtdIns(3,4,5)P3-dependent Rac Exchanger 1 (PREX1) Rac-Guanine Nucleotide Exchange Factor (GEF) Activity Promotes Breast Cancer Cell Proliferation and Tumor Growth via Activation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Signaling.

    Liu, Heng-Jia; Ooms, Lisa M; Srijakotre, Nuthasuda; Man, Joey; Vieusseux, Jessica; Waters, JoAnne E; Feng, Yue; Bailey, Charles G; Rasko, John E J; Price, John T; Mitchell, Christina A

    2016-08-12

    PtdIns(3,4,5)P3-dependent Rac exchanger 1 (PREX1) is a Rac-guanine nucleotide exchange factor (GEF) overexpressed in a significant proportion of human breast cancers that integrates signals from upstream ErbB2/3 and CXCR4 membrane surface receptors. However, the PREX1 domains that facilitate its oncogenic activity and downstream signaling are not completely understood. We identify that ERK1/2 MAPK acts downstream of PREX1 and contributes to PREX1-mediated anchorage-independent cell growth. PREX1 overexpression increased but its shRNA knockdown decreased ERK1/2 phosphorylation in response to EGF/IGF-1 stimulation, resulting in induction of the cell cycle regulators cyclin D1 and p21(WAF1/CIP1) PREX1-mediated ERK1/2 phosphorylation, anchorage-independent cell growth, and cell migration were suppressed by inhibition of MEK1/2/ERK1/2 signaling. PREX1 overexpression reduced staurosporine-induced apoptosis whereas its shRNA knockdown promoted apoptosis in response to staurosporine or the anti-estrogen drug tamoxifen. Expression of wild-type but not GEF-inactive PREX1 increased anchorage-independent cell growth. In addition, mouse xenograft studies revealed that expression of wild-type but not GEF-dead PREX1 resulted in the formation of larger tumors that displayed increased phosphorylation of ERK1/2 but not AKT. The impaired anchorage-independent cell growth, apoptosis, and ERK1/2 signaling observed in stable PREX1 knockdown cells was restored by expression of wild-type but not GEF-dead-PREX1. Therefore, PREX1-Rac-GEF activity is critical for PREX1-dependent anchorage-independent cell growth and xenograft tumor growth and may represent a possible therapeutic target for breast cancers that exhibit PREX1 overexpression. PMID:27358402

  14. Genetic variability of CYP2B6 polymorphisms in four southern Chinese populations

    Bing-Ying Xu; Ming-Liang He; Li-Ping Guo; Shui-Shan Lee; Qing-Ming Dong; Yi Tan; Hong Yao; Li-Hua Li; Che-Kit Lin; Hsiang-Fu Kung

    2007-01-01

    AIM: To investigate the genotype and allelic frequencies of Cytochrome P450 2B6 polymorphisms in four southern Chinese populations.METHODS: DNA was obtained from blood samples from Han Chinese from Hong Kong and three minority groups,the Wa, Bulang and Lahu from Yunnan in southern China. Genotyping was performed using real-time PCR and confirmed by direct sequencing.RESULTS: A total of 507 subjects from southern China were studied. Results showed there is a high prevalence of 516G > T (34.5%) in ethnic Chinese compared to literature reports on other Asian populations and Caucasians. The frequency of the 516TT genotype is higher in the Hah majority (23.1%) than in three other ethnic minority groups (i.e., 7.4%, 9.1% and 15.8%) in southern China.CONCLUSION: This was the first study to document the spectrum of CYP2B6 allelic variants and genotypes in a southern Chinese population. The 516G > T allele is associated with a defective metabolism of efavirenz (EFV), which therefore may predispose to drug toxicity.Treatment regimens for human immunodeficiency virus (HIV) and heroin addiction may need to be optimized in different populations because of the marked variability of the key metabolizing enzyme.

  15. Genome-wide function of H2B ubiquitylation in promoter and genic regions.

    Batta, Kiran; Zhang, Zhenhai; Yen, Kuangyu; Goffman, David B; Pugh, B Franklin

    2011-11-01

    Nucleosomal organization in and around genes may contribute substantially to transcriptional regulation. The contribution of histone modifications to genome-wide nucleosomal organization has not been systematically evaluated. In the present study, we examine the role of H2BK123 ubiquitylation, a key regulator of several histone modifications, on nucleosomal organization at promoter, genic, and transcription termination regions in Saccharomyces cerevisiae. Using high-resolution MNase chromatin immunoprecipitation and sequencing (ChIP-seq), we map nucleosome positioning and occupancy in mutants of the H2BK123 ubiquitylation pathway. We found that H2B ubiquitylation-mediated nucleosome formation and/or stability inhibits the assembly of the transcription machinery at normally quiescent promoters, whereas ubiquitylation within highly active gene bodies promotes transcription elongation. This regulation does not proceed through ubiquitylation-regulated histone marks at H3K4, K36, and K79. Our findings suggest that mechanistically similar functions of H2B ubiquitylation (nucleosome assembly) elicit different functional outcomes on genes depending on its positional context in promoters (repressive) versus transcribed regions (activating). PMID:22056671

  16. APOSTLE: Longterm Transit Monitoring and Stability Analysis of XO-2b

    Kundurthy, Praveen; Becker, Andrew C; Agol, Eric; Williams, Benjamin F; Gorelick, Noel; Rose, Amy

    2013-01-01

    The Apache Point Survey of Transit Lightcurves of Exoplanets (APOSTLE) observed 10 transits of XO-2b over a period of three years. We present measurements which confirm previous estimates of system parameters like the normalized semi-major axis (a/R_{*}), stellar density (\\rho_{*}), impact parameter (b) and orbital inclination (i_{orb}). Our errors on system parameters like a/R_{*} and \\rho_{*} have improved by ~40% compared to previous best ground-based measurements. Our study of the transit times show no evidence for transit timing variations and we are able to rule out co-planar companions with masses \\ge 0.20 \\mearth\\ in low order mean motion resonance with XO-2b. We also explored the stability of the XO-2 system given various orbital configurations of a hypothetical planet near the 2:1 mean motion resonance. We find that a wide range of orbits (including Earth-mass perturbers) are both dynamically stable and produce observable TTVs. We find that up to 51% of our stable simulations show TTVs that are smal...

  17. The D/H Ratio in Interstellar Gas Towards G191-B2B

    Sahu, M S; Bruhweiler, F C; Gull, T R; Bowers, C A; Lindler, D; Feggans, K; Barstow, M A; Hubeny, I; Holberg, J B

    1999-01-01

    We reinvestigate the question of spatial variation of the local D/H abundance, using both archival GHRS spectra, and new echelle spectra of G191-B2B obtained with the Space Telescope Imaging Spectrograph (STIS) aboard HST. Our analysis uses stratified line-blanketed non-LTE model atmosphere calculations to determine the shape of the intrinsic WD Lyman-alpha profile and estimate the WD photospheric contamination of the interstellar lines. Although three velocity components were reported previously towards G191-B2B, we detect only two velocity components. The first component is at V(hel) ~ 8.6 km/s and the second at V(hel) ~ 19.3 km/s, which we identify with the Local Interstellar Cloud (LIC). From the STIS data we derive D/H = 1.60(+0.39,-0.27)X10^-5 for the LIC component, and D/H > 1.26X10^-5 for the 8.6 km/s component (uncertainties denote 2-sigma or 95% confidence limits). The STIS data provide no evidence for local or component-to-component variation in the D/H ratio. Despite using two velocity components ...

  18. GTC OSIRIS Transiting Exoplanet Atmospheric Survey: Detection of potassium in XO-2b from spectrophotometry

    Sing, D K; Fortney, J J; Etangs, A Lecavelier des; Ballester, G E; Cepa, J; Ehrenreich, D; Lopez-Morales, M; Pont, F; Shabram, M; Vidal-Madjar, A

    2010-01-01

    We present Gran Telescopio Canarias (GTC) optical transit narrow-band photometry of the hot-Jupiter exoplanet XO-2b using the OSIRIS instrument. This unique instrument has the capabilities to deliver high cadence narrow-band photometric lightcurves, allowing us to probe the atmospheric composition of hot Jupiters from the ground. The observations were taken during three transit events which cover four wavelengths at spectral resolutions near 500, necessary for observing atmospheric features, and have near-photon limited sub-mmag precisions. Precision narrow-band photometry on a large aperture telescope allows for atmospheric transmission spectral features to be observed for exoplanets around much fainter stars than those of the well studied targets HD209458b and HD189733b, providing access to the majority of known transiting planets. For XO-2b, we measure planet-to-star radius contrasts of R_pl/R_star=0.10508+/-0.00052 at 6792 Ang, 0.10640+/-0.00058 at 7582 Ang, and 0.10686+/-0.00060 at 7664.9 Ang, and 0.1036...

  19. VHL type 2B mutations retain VBC complex form and function.

    Kathryn E Hacker

    Full Text Available BACKGROUND: von Hippel-Lindau disease is characterized by a spectrum of hypervascular tumors, including renal cell carcinoma, hemangioblastoma, and pheochromocytoma, which occur with VHL genotype-specific differences in penetrance. VHL loss causes a failure to regulate the hypoxia inducible factors (HIF-1alpha and HIF-2alpha, resulting in accumulation of both factors to high levels. Although HIF dysregulation is critical to VHL disease-associated renal tumorigenesis, increasing evidence points toward gradations of HIF dysregulation contributing to the degree of predisposition to renal cell carcinoma and other manifestations of the disease. METHODOLOGY/PRINCIPAL FINDINGS: This investigation examined the ability of disease-specific VHL missense mutations to support the assembly of the VBC complex and to promote the ubiquitylation of HIF. Our interaction analysis supported previous observations that VHL Type 2B mutations disrupt the interaction between pVHL and Elongin C but maintain partial regulation of HIF. We additionally demonstrated that Type 2B mutant pVHL forms a remnant VBC complex containing the active members ROC1 and Cullin-2 which retains the ability to ubiquitylate HIF-1alpha. CONCLUSIONS: Our results suggest that subtypes of VHL mutations support an intermediate level of HIF regulation via a remnant VBC complex. These findings provide a mechanism for the graded HIF dysregulation and genetic predisposition for cancer development in VHL disease.

  20. Orbital Phase Variations of the Eccentric Giant Planet HAT-P-2b

    Lewis, Nikole K; Showman, Adam P; Cowan, Nicolas B; Laughlin, Gregory; Burrows, Adam; Deming, Drake; Crepp, Justin R; Mighell, Kenneth J; Agol, Eric; Bakos, Gáspár Á; Charbonneau, David; Désert, Jean-Michel; Fischer, Debra A; Fortney, Jonathan J; Hartman, Joel D; Hinkley, Sasha; Howard, Andrew W; Johnson, John Asher; Kao, Melodie; Langton, Jonathan; Marcy, Geoffrey W; Winn, Joshua N

    2013-01-01

    We present the first secondary eclipse and phase curve observations for the highly eccentric hot Jupiter HAT-P-2b in the 3.6, 4.5, 5.8, and 8.0 \\mu m bands of the Spitzer Space Telescope. The 3.6 and 4.5 \\mu m data sets span an entire orbital period of HAT-P-2b, making them the longest continuous phase curve observations obtained to date and the first full-orbit observations of a planet with an eccentricity exceeding 0.2. We present an improved non-parametric method for removing the intrapixel sensitivity variations in Spitzer data at 3.6 and 4.5 \\mu m that robustly maps position-dependent flux variations. We find that the peak in planetary flux occurs at 4.39+/-0.28, 5.84+/-0.39, and 4.68+/-0.37 hours after periapse passage with corresponding maxima in the planet/star flux ratio of 0.1138%+/-0.0089%, 0.1162%+/-0.0080%, and 0.1888%+/-0.0072% in the 3.6, 4.5, and 8.0 \\mu m bands respectively. We compare our measured secondary eclipse depths to the predictions from a one-dimensional radiative transfer model, wh...

  1. Anisotropy of the Vortex Magnetic Field Distribution in LuNi2B2

    Eskildsen, M. R.; Debeer-Schmitt, L.; Rovira, K.; Jenkins, N.; Dewhurst, C. D.; Bud'Ko, S. L.; Canfield, P. C.

    2008-03-01

    It is well known that the vortex lattice (VL) symmetry and orientation in type-II superconductors is very sensitive to any anisotropy within the screening current plane. A classic example is the sequence of transitions from hexagonal to rhombic to square symmetry, which was first observed in the borocarbide superconductors and explained by a Fermi surface anisotropy coupled with the non-local electrodynamics responsible for vortex-vortex interactions. Recently, however, this is mounting experimental evidence for a strong gap anisotropy and possible point nodes in the basal plane of these materials. Here we report on small-angle neutron scattering studies of the VL in a carefully annealed, high quality LuNi2B2C single crystal, which permitted us to measure the VL form factor for a large number of reflections. These measurements allow a reconstruction of the real space profile of the magnetic field around the vortices, reflecting the basal plane anisotropy of the screening currents in LuNi2B2C. The results will be compared to predictions for both Fermi surface and gap anisotropies, and will serve as a valuable reference for more complicated compounds as e.g. Sr2RuO4, heavy fermions and high-Tc's.

  2. Efficacy of interferon alpha-2b and lamivudine therapy for chronic hepatitis B in children

    2003-01-01

    Objective To evaluate the efficacy of interferon (IFN) alpha-2b and lamivudine therapy in children with chronic hepatitis B virus (HBV) infection.Method Ten children who developed chronic hepatitis B infection received IFN alpha-2b 10 million international units (IU)/m2 body surface area, subcutaneously three times a week for six months. IFN+lamivudine therapy began to be used in the cases who were unresponsive to IFN treatment. Results Among 27 HBsAg (+) subjects in this study, interferon treatment was given to 11 subjects who developed chronic hepatitis. One case was excluded from the study due to detection of Herpes type 1 encephalitis. At the end of six months of follow-up, complete response was obtained in three (30%) patients and partial response in four (40%) patients, whereas no response was detected in three (30%) patients. Fifty percent of the cases experienced serological response, 70% biochemical response, and all (100%) had histological response. In three cases started concomitant IFN+lamivudine therapy, HBV-DNA became negative at the second month of treatment. Conclusions IFN-alpha and lamivudine can be used for the treatment of chronic hepatitis B infection in children.

  3. Macroscale production of crystalline interferon alfa-2b in microgravity on STS-52

    Nagabhushan, Tattanahalli L.; Reichert, Paul; Long, Marianna M.; DeLucas, Lawrence J.; Bugg, Charles E.

    1995-01-01

    Macroscale crystallization of zinc interferon alfa-2b was achieved on STS-52 in October 1992 in the Protein Crystallization Facility. Conditions for crystallization were established by adapting a microscale vapor diffusion method to a macroscale temperature induction method. A series of earth based pilot experiments established conditions to reproducibly crystallize zinc interferon alfa-2b in high yield and under cleanroom conditions. As a control for the STS-52 mission, a ground experiment was run simultaneously and in the same configuration as the flight experiment. Greater than 95% of the available protein crystallized in both the ground and flight experiments. Using a battery of physical, biochemical and biological characterization assays, demonstrated that sample processing, polysulfone bottle confinement and the conditions used for crystallization did not have a negative effect on protein integrity. Redissolved crystals from the flight and ground experiments showed full biological activity in a cytopathic effect inhibition assay as compared to an interferon control standard. Morphometric analysis comparing the overall length and width of the derived crystals showed a 2.4 fold increase in the length and width of the space grown crystals as compared to earth grown crystals. Space grown crystals have remained a stable free flowing suspension for over 2 years. Based on these results, further experiments are envisioned to investigate macroscale crystallization of biologically active macromolecules in microgravity.

  4. The thermal emission of the exoplanets WASP-1b and WASP-2b

    Wheatley, Peter J; Harrington, Joseph; Fortney, Jonathan J; Simpson, James M; Anderson, David R; Smith, Alexis M S; Aigrain, Suzanne; Clarkson, William I; Gillon, Michael; Haswell, Carole A; Hebb, Leslie; Hébrard, Guillaume; Hellier, Coel; Hodgkin, Simon T; Horne, Keith D; Kane, Stephen R; Maxted, Pierre F L; Norton, Andrew J; Pollacco, Don L; Pont, Frederic; Skillen, Ian; Smalley, Barry; Street, Rachel A; Udry, Stephane; West, Richard G; Wilson, David M

    2010-01-01

    We present a comparative study of the thermal emission of the transiting exoplanets WASP-1b and WASP-2b using the Spitzer Space Telescope. The two planets have very similar masses but suffer different levels of irradiation and are predicted to fall either side of a sharp transition between planets with and without hot stratospheres. WASP-1b is one of the most highly irradiated planets studied to date. We measure planet/star contrast ratios in all four of the IRAC bands for both planets (3.6-8.0um), and our results indicate the presence of a strong temperature inversion in the atmosphere of WASP-1b, particularly apparent at 8um, and no inversion in WASP-2b. In both cases the measured eclipse depths favor models in which incident energy is not redistributed efficiently from the day side to the night side of the planet. We fit the Spitzer light curves simultaneously with the best available radial velocity curves and transit photometry in order to provide updated measurements of system parameters. We do not find ...

  5. Up-regulation and subcellular localization of hnRNP A2/B1 in the development of hepatocellular carcinoma

    Hepatocellular carcinoma (HCC) is one of the world's leading causes of death among cancer patients. It is important to find a new biomarker that diagnoses HCC and monitors its treatment. In our previous work, we screened a single-chain antibody (scFv) N14, which could specifically recognize human HepG2 HCC cells but not human non-cancerous liver LO2 cells. However, the antigen it recognized in the cells remained unknown. Recombinant scFv N14 antibody was expressed as an active antibody. Using this antibody with a combination of immunological and proteomic approaches, we identified the antigen of scFv N14 antibody as the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1). The expression of hnRNP A2/B1 in HCC cells was then investigated by semi-quantitative RT-PCR and immunohistochemistry. We found that the up-regulation of hnRNP A2/B1 was measured at both transcriptional and translational levels in rat HCC cells but not in rat hepatic cells. We also found that in various human hepatic tissues, hnRNP A2/B1 was highly expressed in both human hepatitis virus positive liver tissues and human HCC tissues but not in normal liver tissues. Interestingly, we observed that the localization of hnRNP A2/B1 in HCC cells was altered during the development of HCC. In human hepatitis virus infected tissues hnRNP A2/B1 resides exclusively in the nuclei of hepatocytes. However, when the HCC progressed from a well differentiated to a poorly differentiated stage, hnRNP A2/B1 was increasingly localized in the cytoplasm. In contrast, the HCC tissues with hnRNP A2/B1 highly expressed in the nucleus decreased. This work is the first to show that hnRNP A2/B1 is the antigen specifically recognized by the scFv N14 antibody in HCC cells. The over-expression of hnRNP A2/B1 was confirmed in cultured human and rat HCC cell lines, human virus related hepatitis liver tissues and human HCC tissues. The increased localization of hnRNP A2/B1 in the cytoplasm of HCC cells was revealed

  6. Domain structure in ErNi2 B2 C and HoNi2 B2 C single crystals observed by a high-resolution Bitter decoration technique

    Vinnikov, L. Ya.; Anderegg, J.; Bud'Ko, S. L.; Canfield, P. C.; Kogan, V. G.

    2005-06-01

    Peculiarities of the superconducting vortex lattice structures in ErNi2B2C and HoNi2B2C single crystals were studied by the high resolution Bitter decoration technique. Instead of forming uniform vortex lattices, rows of vortices, associated with pinning by magnetic twin boundaries, were observed in the superconducting state, below the antiferromagnetic transition temperatures, in both compounds. Crystallographic aspects of the vortex pinning by the magnetic twin boundaries in the RNi2B2C(R=rareearth) are discussed.

  7. Structural Basis for Phosphotyrosine Recognition by the Src Homology-2 Domains of the Adapter Proteins SH2-B and APS

    Hu,J.; Hubbard, S.

    2006-01-01

    SH2-B, APS, and Lnk constitute a family of adapter proteins that modulate signaling by protein tyrosine kinases. These adapters contain an N-terminal dimerization region, a pleckstrin homology domain, and a C-terminal Src homology-2 (SH2) domain. SH2-B is recruited via its SH2 domain to various protein tyrosine kinases, including Janus kinase-2 (Jak2) and the insulin receptor. Here, we present the crystal structure at 2.35 Angstroms resolution of the SH2 domain of SH2-B in complex with a phosphopeptide representing the SH2-B recruitment site in Jak2 (pTyr813). The structure reveals a canonical SH2 domain-phosphopeptide binding mode, but with specific recognition of a glutamate at the +1 position relative to phosphotyrosine, in addition to recognition of a hydrophobic residue at the +3 position. Biochemical studies of SH2-B and APS demonstrate that, although the SH2 domains of these two adapter proteins share 79% sequence identity, the SH2-B SH2 domain binds preferentially to Jak2, whereas the APS SH2 domain has higher affinity for the insulin receptor. This differential specificity is attributable to the difference in the oligomeric states of the two SH2 domains: monomeric for SH2-B and dimeric for APS.

  8. Thermoluminescence and radioluminescence properties of tissue equivalent Cu-doped Li2B4O7 for radiation dosimetry

    Thermoluminescence (Tl) and radioluminescence (Rl) properties of lithium tetraborate (Li2B4O7) doped with different concentration of copper (0.25, 0.5, 1 wt %) under gamma and beta irradiation has been investigated. The feasibility of using this borate in radiation dosimetry at low doses has been evaluated. Tissue equivalent Li2B4O7 was prepared by solid state reaction using mixing stoichiometric compositions of lithium carbonate (Li2CO3) and boric acid (H3BO3) and a solution of CuCl2 as dopant. The glow curve, of the most efficient copper doped borate (Li2B4O7:Cu 0.5 wt %), shows a main stable peak centered at 225 degrees C and a second low temperature peak centered at 80 degrees C. The low temperature peak disappears completely after 24 hours of storage in darkness and at room temperature or after an annealing at 120 degrees C for 10 seconds. The main peak of the Li2B4O7:Cu remains constant. The Tl response of Li2B4O7:Cu shows good linearity in the analyzed dose range. The stability and repeatability of Rl signals of the borate have been studied and the Li2B4O7:Cu (0.5 wt %) shown the higher Rl emission and a stable and repetitive response. Results show that Li2B4O7:Cu has prospects to be used in gamma and beta radiation dosimetry. (Author)

  9. Amylase activity is associated with AMY2B copy numbers in dog: implications for dog domestication, diet and diabetes.

    Arendt, Maja; Fall, Tove; Lindblad-Toh, Kerstin; Axelsson, Erik

    2014-10-01

    High amylase activity in dogs is associated with a drastic increase in copy numbers of the gene coding for pancreatic amylase, AMY2B, that likely allowed dogs to thrive on a relatively starch-rich diet during early dog domestication. Although most dogs thus probably digest starch more efficiently than do wolves, AMY2B copy numbers vary widely within the dog population, and it is not clear how this variation affects the individual ability to handle starch nor how it affects dog health. In humans, copy numbers of the gene coding for salivary amylase, AMY1, correlate with both salivary amylase levels and enzyme activity, and high amylase activity is related to improved glycemic homeostasis and lower frequencies of metabolic syndrome. Here, we investigate the relationship between AMY2B copy numbers and serum amylase activity in dogs and show that amylase activity correlates with AMY2B copy numbers. We then describe how AMY2B copy numbers vary in individuals from 20 dog breeds and find strong breed-dependent patterns, indicating that the ability to digest starch varies both at the breed and individual level. Finally, to test whether AMY2B copy number is strongly associated with the risk of developing diabetes mellitus, we compare copy numbers in cases and controls as well as in breeds with varying diabetes susceptibility. Although we see no such association here, future studies using larger cohorts are needed before excluding a possible link between AMY2B and diabetes mellitus. PMID:24975239

  10. NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway

    Highlights: → The NR2B component of the NMDARs is important for the NSPC proliferation. → pCaMKIV and pCREB exist in NSPCs. → The CaMKIV/CREB pathway mediates NSPC proliferation. -- Abstract: Accumulating evidence indicates the involvement of N-methyl-D-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Ro 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.

  11. Impulsive alcohol-related risk-behavior and emotional dysregulation among individuals with a serotonin 2B receptor stop codon.

    Tikkanen, R; Tiihonen, J; Rautiainen, M R; Paunio, T; Bevilacqua, L; Panarsky, R; Goldman, D; Virkkunen, M

    2015-01-01

    A relatively common stop codon (Q20*) was identified in the serotonin 2B receptor gene (HTR2B) in a Finnish founder population in 2010 and it was associated with impulsivity. Here we examine the phenotype of HTR2B Q20* carriers in a setting comprising 14 heterozygous HTR2B Q20* carriers and 156 healthy controls without the HTR2B Q20*. The tridimensional personality questionnaire, Brown-Goodwin lifetime aggression scale, the Michigan alcoholism screening test and lifetime drinking history were used to measure personality traits, impulsive and aggressive behavior, both while sober and under the influence of alcohol, and alcohol consumption. Regression analyses showed that among the HTR2B Q20* carriers, temperamental traits resembled a passive-dependent personality profile, and the presence of the HTR2B Q20* predicted impulsive and aggressive behaviors particularly under the influence of alcohol. Results present examples of how one gene may contribute to personality structure and behaviors in a founder population and how personality may translate into behavior. PMID:26575222

  12. High-Throughput Fragment Docking into the BAZ2B Bromodomain: Efficient in Silico Screening for X-Ray Crystallography.

    Lolli, Graziano; Caflisch, Amedeo

    2016-03-18

    Bromodomains are protein modules that bind to acetylated lysine side chains in histones and other proteins. The bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) has been reported to be poorly druggable. Here, we screened an in-house library of 350 fragments by automatic docking to the BAZ2B bromodomain. The top 12 fragments according to the predicted binding energy were selected for experiments of soaking into apo crystals of BAZ2B which yielded the structure of the complex for four of them, which is a hit rate of 33%. Additional crystal structures were solved for BAZ2B and two scaffolds identified by analogy. For three topologically similar fragments, the crystal structures reveal binding modes with different penetration, i.e., with zero, one, and two water molecules, respectively, located between the fragment and the side chain of a conserved tyrosine (Tyr1901) in the bottom of the acetyl lysine pocket of BAZ2B. Furthermore, a remarkable stereoselectivity of the acetyl lysine pocket emerges from the crystal structures of the bromodomains of BAZ2B and SMARCA4 in complex with the chiral diol MPD (2-methyl-2,4-pentanediol). PMID:26942307

  13. Thioredoxin-like protein 2b facilitates colon cancer cell proliferation and inhibits apoptosis via NF-κB pathway.

    Lu, Yuanyuan; Zhao, Xiaodi; Luo, Guanhong; Shen, Gaofei; Li, Kai; Ren, Gui; Pan, Yan; Wang, Xin; Fan, Daiming

    2015-07-28

    Our previous work identified thioredoxin-like protein 2 (Txl-2), a novel thioredoxin family member, as the target of the monoclonal antibody MC3 which can detect colon cancer with high sensitivity and specificity. In the present study, the function of the most abundant isoform Txl-2b in cell proliferation and apoptosis was investigated. Txl-2 overexpression correlated with increased clinical stages. Inhibition of Txl-2b suppressed cell proliferation, induced cell cycle arrest at the G1/S phase, and led to responsiveness to the vincristine-induced apoptosis in SW620 cells. Txl-2b overexpression in LoVo cells had the opposite effect, which was dependent on Trx domain function. In vivo studies validated that Txl-2b expression promoted colon cancer tumorigenesis in nude mice. Further studies revealed that nuclear factor-κB (NF-κB) signaling was activated by Txl-2b. Inhibition of NF-κB activation partly abrogated the pro-proliferation and anti-apoptotic phenotypes mediated by Txl-2b via reduced Cyclin D1, Bcl-2, Bcl-xL and Survivin expression and increased Caspase-3 activation. Overall, our results indicate that Txl-2b expression stimulates cancer cell proliferation, accelerates the cell cycle and contributes to apoptosis resistance in colon cancer and provides a potential therapeutic target for colon cancer treatment. PMID:25555669

  14. Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly.

    Kweon, Hae-Jin; Kim, Dong-Il; Bae, Yeonju; Park, Jae-Yong; Suh, Byung-Chang

    2016-01-01

    Acid-sensing ion channels (ASICs) are proton-activated cation channels that play important roles as typical proton sensors during pathophysiological conditions and normal synaptic activities. Among the ASIC subunits, ASIC2a and ASIC2b are alternative splicing products from the same gene, ACCN1. It has been shown that ASIC2 isoforms have differential subcellular distribution: ASIC2a targets the cell surface by itself, while ASIC2b resides in the ER. However, the underlying mechanism for this differential subcellular localization remained to be further elucidated. By constructing ASIC2 chimeras, we found that the first transmembrane (TM1) domain and the proximal post-TM1 domain (17 amino acids) of ASIC2a are critical for membrane targeting of the proteins. We also observed that replacement of corresponding residues in ASIC2b by those of ASIC2a conferred proton-sensitivity as well as surface expression to ASIC2b. We finally confirmed that ASIC2b is delivered to the cell surface from the ER by forming heteromers with ASIC2a, and that the N-terminal region of ASIC2a is additionally required for the ASIC2a-dependent membrane targeting of ASIC2b. Together, our study supports an important role of ASIC2a in membrane targeting of ASIC2b. PMID:27477936

  15. Primary Purification of Co-expressed Soluble and Insoluble Alpha-interferon 2b from Recombinant E.coli

    徐志南; 岑沛霖

    2002-01-01

    Alpha-interferon 2b(IFN 2b)was produced both in soluble and insoluble forms from recombinant E.coli.The dissolution of the expressed IFN 2b in inclusion body was carried out and it was found that the optimal condition to dissolve the expressed protein was 7 mol·L-1 guanidinium salt solution at pH3.0.The resultant solution was diluted 20 times using pH 6.0 buffer to refold the protein correctly.The cation exchange column was employed to purify both refolded and soluble IFN 2b.For soluble IFN sample,high IFN 2b recovery yield(92.1%)with 91.7% purity was obtained in the eluate.However,for refolded IFN sample.only 72.7% of IFN 2b was recovered with relatively low purity(56.8%)by cation exchange chromatography.Although the expression level of insoluble IFN was higher than that of co-expressed soluble IFN in this recombinant E.coli cells,the productivity of bioactive IFN 2b was higher with soluble expressed IFN after primary purification process.Soluble expression of foreign proteins in recombinant bacteria might be an alternative strategy for efficient production of heterogeneous proteins due to high bioactivity and simple downstream protein purification process.

  16. Controlled synthesis of TiO2-B nanowires and nanoparticles for dye-sensitized solar cells

    Controllable synthesis of the TiO2-B nanowires (NWs) and nanoparticles (NPs) had been achieved via a facile hydrothermal route, respectively, only by tuning the solution volume. The dye-sensitized solar cells prototypes had been fabricated using TiO2-B NW and NP electrodes, respectively. The TiO2-B NP cells had higher photocurrent and photoelectrical conversion efficiency than the TiO2-B NW cells though the latter exhibited larger photovoltage compared to the former. The key factors such as the photogenerated electron injection drive force, surface defects and the interfacial charge transfer, which determined the photoelectrical properties, had been systematically researched with the surface photovoltage spectra (SPS) and the electrochemical impedance spectra (EIS). The SPS proved that there was larger photoelectron injection drive force in TiO2-B NP photoelectrode than that in NW photoelectrode. And the electrochemical impedance spectra (EIS) revealed that TiO2-B NP cells had faster interface charge transfer compared to TiO2-B NW cells. Both proved that NP cells had the higher photocurrents.

  17. Serotonin 2B receptor slows disease progression and prevents degeneration of spinal cord mononuclear phagocytes in amyotrophic lateral sclerosis.

    El Oussini, Hajer; Bayer, Hanna; Scekic-Zahirovic, Jelena; Vercruysse, Pauline; Sinniger, Jérôme; Dirrig-Grosch, Sylvie; Dieterlé, Stéphane; Echaniz-Laguna, Andoni; Larmet, Yves; Müller, Kathrin; Weishaupt, Jochen H; Thal, Dietmar R; van Rheenen, Wouter; van Eijk, Kristel; Lawson, Roland; Monassier, Laurent; Maroteaux, Luc; Roumier, Anne; Wong, Philip C; van den Berg, Leonard H; Ludolph, Albert C; Veldink, Jan H; Witting, Anke; Dupuis, Luc

    2016-03-01

    Microglia are the resident mononuclear phagocytes of the central nervous system and have been implicated in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). During neurodegeneration, microglial activation is accompanied by infiltration of circulating monocytes, leading to production of multiple inflammatory mediators in the spinal cord. Degenerative alterations in mononuclear phagocytes are commonly observed during neurodegenerative diseases, yet little is known concerning the mechanisms leading to their degeneration, or the consequences on disease progression. Here we observed that the serotonin 2B receptor (5-HT2B), a serotonin receptor expressed in microglia, is upregulated in the spinal cord of three different transgenic mouse models of ALS. In mutant SOD1 mice, this upregulation was restricted to cells positive for CD11b, a marker of mononuclear phagocytes. Ablation of 5-HT2B receptor in transgenic ALS mice expressing mutant SOD1 resulted in increased degeneration of mononuclear phagocytes, as evidenced by fragmentation of Iba1-positive cellular processes. This was accompanied by decreased expression of key neuroinflammatory genes but also loss of expression of homeostatic microglial genes. Importantly, the dramatic effect of 5-HT2B receptor ablation on mononuclear phagocytes was associated with acceleration of disease progression. To determine the translational relevance of these results, we studied polymorphisms in the human HTR2B gene, which encodes the 5-HT2B receptor, in a large cohort of ALS patients. In this cohort, the C allele of SNP rs10199752 in HTR2B was associated with longer survival. Moreover, patients carrying one copy of the C allele of SNP rs10199752 showed increased 5-HT2B mRNA in spinal cord and displayed less pronounced degeneration of Iba1 positive cells than patients carrying two copies of the more common A allele. Thus, the 5-HT2B receptor limits degeneration of spinal cord mononuclear

  18. MAD2B, a Novel TCF4-binding Protein, Modulates TCF4-mediated Epithelial-Mesenchymal Transdifferentiation*

    Hong, Chun-Fu; Chou, Yu-Ting; Lin, Young-Sun; Wu, Cheng-Wen

    2009-01-01

    T cell factor 4 (TCF4) interacts with β-catenin in the WNT signaling pathway and transactivates downstream target genes involved in cancer progression. To identify proteins that regulate TCF4-mediated biological responses, we performed a yeast two-hybrid screen to search for a TCF4-binding protein(s) and found that MAD2B interacts with TCF4. We confirmed that MAD2B is a TCF4-binding protein by co-immunoprecipitation. Using the TOPFLASH reporter assay, we found that MAD2B blocks TCF4-mediated ...

  19. Types of B2B E-Business Model Commonly Used: An Empirical Study On Australian Agribusines Firms

    Ng, Eric

    2005-01-01

    This paper explores the various B2B e-business models commonly used using in-depth interviews and case studies conducted with Australian agribusiness firms. There is an apparent need to rethink the types of e-business models to be adopted as businesses make their transition toward the electronic environment. This is particularly evident in the B2B market where e-business has seen a significant growth. From the analysis, 10 B2B e-business models were identified with seven of them regarded as c...

  20. CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction

    Levran, Orna; Peles, Einat; Hamon, Sara; Randesi, Matthew; Adelson, Miriam; Kreek, Mary Jeanne

    2011-01-01

    Adequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success. One of the challenges in dose determination is the inter-individual variability in dose response. Methadone metabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6, and CYP2D6. The CYP2B6*6 allele [SNPs 785A>G (rs2279343) and 516G>T (rs3745274)] was associated with slow methadone metabolism. To explore the effects of CYP2B6*6 allele on methadone dos...

  1. Model of deformation and fracture of TiB2+B4C based cermet under dynamic loading

    One introduces a mathematical model describing deformation and fracture of titanium diboride and boron carbide base (TiB2+B4C) cermet with a metal binder under impact loading. TiB2+B4C base cermet with a metal binder was prepared by means of self-propagating high-temperature synthesis. In terms of the mentioned model one solved the problem dealing with penetration of TiB2+B4C base cermet into aluminium semi-infinite barrier

  2. Modulation of NR2B-regulated contextual fear in the hippocampus by the tissue plasminogen activator system

    Norris, Erin H.; Strickland, Sidney

    2007-01-01

    Contextual fear conditioning is regulated by the hippocampus, and NR2B, a subunit of the NMDA receptor (NR), is involved in this process. We show that acute stress modulates tissue plasminogen activator (tPA) activity in the hippocampus by inducing expression of its inhibitor, plasminogen activator inhibitor-1. Acute stress increases NR2B expression and ERK1/2 phosphorylation, a classical marker of postsynaptic plasticity, in the hippocampus. tPA forms a complex with NR2B and is necessary for...

  3. Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C

    PN; Rao; Abraham; Koshy; Jacob; Philip; Narayanan; Premaletha; Joy; Varghese; Krishnasamy; Narayanasamy; Samir; Mohindra; Nitin; Vikas; Pai; Manoj; Kumar; Agarwal; Ashokna; Konar; Hasmukh; B; Vora

    2014-01-01

    AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for > 65-85 kg; 1200 mg/d for > 85-105 kg; 1400 mg/d for > 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.

  4. TFAP2B influences the effect of dietary fat on weight loss under energy restriction.

    Tanja Stocks

    Full Text Available BACKGROUND: Numerous gene loci are related to single measures of body weight and shape. We investigated if 55 SNPs previously associated with BMI or waist measures, modify the effects of fat intake on weight loss and waist reduction under energy restriction. METHODS AND FINDINGS: Randomized controlled trial of 771 obese adults. ( REGISTRATION: ISRCTN25867281. One SNP was selected for replication in another weight loss intervention study of 934 obese adults. The original trial was a 10-week 600 kcal/d energy-deficient diet with energy percentage from fat (fat% in range of 20-25 or 40-45. The replication study used an 8-weeks diet of 880 kcal/d and 20 fat%; change in fat% intake was used for estimation of interaction effects. The main outcomes were intervention weight loss and waist reduction. In the trial, mean change in fat% intake was -12/+4 in the low/high-fat groups. In the replication study, it was -23/-12 among those reducing fat% more/less than the median. TFAP2B-rs987237 genotype AA was associated with 1.0 kg (95% CI, 0.4; 1.6 greater weight loss on the low-fat, and GG genotype with 2.6 kg (1.1; 4.1 greater weight loss on the high-fat (interaction p-value; p = 0.00007. The replication study showed a similar (non-significant interaction pattern. Waist reduction results generally were similar. Study-strengths include (i the discovery study randomised trial design combined with the replication opportunity (ii the strict dietary intake control in both studies (iii the large sample sizes of both studies. Limitations are (i the low minor allele frequency of the TFAP2B polymorphism, making it hard to investigate non-additive genetic effects (ii the different interventions preventing identical replication-discovery study designs (iii some missing data for non-completers and dietary intake. No adverse effects/outcomes or side-effects were observed. CONCLUSIONS: Under energy restriction, TFAP2B may modify the effect of dietary fat intake on

  5. Polarization-dependent X-ray-absorption spectroscopy of $RNi_{2} B_{2}$ C (R=Er $\\to$ Lu) Reduced Ni-3d occupancy in $YbNi_{2} B_{2} C$

    Mazumdar, C; Von Lips, H; Golden, M S; Fink, J; Canfield, P C; Kaindl, G

    2001-01-01

    We present here the results of polarization-dependent X-ray- absorption near-edge structure (XANES) studies at the B-K, C-K, and Ni-L/sub 3/ thresholds of single-crystalline borocarbide compounds RNi/sub 2/B/sub 2/C (with R=Er to Lu) using bulk-sensitive fluorescence yield technique. The Ni-L/sub 3/ XANES spectrum for YbNi /sub 2/B/sub 2/C with photon polarization parallel to the ab plane is significantly more intense than in analogous spectra of other members of this series. This indicates a reduced Ni-3d occupancy in the Ni /sub 2/B/sub 2/ layer in YbNi/sub 2/B/sub 2/C, a fact that might be responsible for the absence of superconductivity in this material. (26 refs).

  6. Expression of the CLEC2B mRNA and Protein in Vitiligo%白癜风患者皮损CLEC2B mRNA及其蛋白表达

    于旺; 张峻岭; 马秀亮; 索丹凤; 闫翠彦

    2013-01-01

    Objective To investigate the CLEC2B mRNA expression level and the protein location in the lesion of vitiligo,and to define the cellular localization of CLEC2B.Methods Use real-time fluorescence quantitative reverse transcription-polymerase chain reaction method (RT-PCR) to detect the CLEC2B mRNA expression levels of vitiligo patients and normal control group lesion,take the higher transcriptional expression level of CLEC2B as the object,to make sure the positioning of the protein of CLEC2B in vitiligo lesion using immunohistochemical methods.Results The expression of CLEC2B mRNA in vitiligo lesions was significantly higher than that of normal control (t=4.432,P<0.05).The CLEC2B protein was expressed in the dermal layer of lymphocyte nucleus of vitiligo lesions.Conclusion The CLEC2B is highly expressed in the lesion of vitiligo,in the exact,and also in the dermal layer of lymphocyte nucleus.%目的 探讨白癜风患者皮损区CLEC2B(C-type lectin domain family 2,member B)mRNA表达水平及其蛋白的表达,明确CLEC2B基因表达的细胞定位.方法 应用实时荧光定量逆转录-聚合酶链反应(RT-PCR)方法检测白癜风患者与正常对照组皮损区中CLEC2B mRNA表达量,取CLEC2B转录表达明显增高的白癜风患者皮损组织,用免疫组织化学方法进行皮损区CLEC2B蛋白的定位表达.结果 患者组皮损中CLEC2B mRNA表达量高于正常对照组(t=4.432,P<0.05),在白癜风皮肤组织真皮层的淋巴细胞中有CLEC2B蛋白阳性表达.结论 CLEC2B基因在白癜风皮损中高表达,且在真皮层淋巴细胞的细胞核中也有表达.

  7. Ultrasonic reinspection of Pilgrim-I reactor vessel nozzle N2B

    Boston Edison Company provided NRC with ultrasonic test data from the periodic inspections of Pilgrim I carried out in 1974 and again in 1976. The ultrasonic test data specifically concerned the recirculation inlet nozzle N2B which contained a flaw in the seven-inch thick weldment joining the nozzle to the pressure vessel. This ultrasonic test data was used to plot the dimensions of the flaw within the wall, to draw conclusions on any flaw growth, to determine 50 percent DAC dimensions, and to deduce the most conservative or largest possible flaw size. This work was done on a consulting basis for the Division of Operating Reactors/Office of Nuclear Reactor Regulation of NRC at their request

  8. Agile text mining for the 2014 i2b2/UTHealth Cardiac risk factors challenge.

    Cormack, James; Nath, Chinmoy; Milward, David; Raja, Kalpana; Jonnalagadda, Siddhartha R

    2015-12-01

    This paper describes the use of an agile text mining platform (Linguamatics' Interactive Information Extraction Platform, I2E) to extract document-level cardiac risk factors in patient records as defined in the i2b2/UTHealth 2014 challenge. The approach uses a data-driven rule-based methodology with the addition of a simple supervised classifier. We demonstrate that agile text mining allows for rapid optimization of extraction strategies, while post-processing can leverage annotation guidelines, corpus statistics and logic inferred from the gold standard data. We also show how data imbalance in a training set affects performance. Evaluation of this approach on the test data gave an F-Score of 91.7%, one percent behind the top performing system. PMID:26209007

  9. The spectral-kinetics characteristics A2B6 semiconductors at various levels of excitons

    Full text: Semiconductors of A2B6 group are now wide used in several fields of nano electronics and optoelectronics. The application of these semiconductors depends on sample quality with reproduced spectral-kinetic characteristics. However, small information on the formation mechanism and luminescence center structure in these materials is a significant obstacle for development of manufacturing techniques. Objects of research were clean semi-conductors and semi-conductors with impurities: ZnSe, ZnSe(Te), ZnS and CdS. These crystals of A2B6 groups have been grown up according to the technologies: Davidov Markova's method, Btidgmen - Stokbarger's method and CVD - method. The purpose of research was dependence definition of spectral - kinetic characteristics of pulsed cathode luminescence (CL) and pulsed roentgen luminescence (RL) in crystals of A2B6 group on the excitation level. It is known that spectra of semiconductors A2B6 luminescence consist of two bands: regional (up to X=480 nm) and long-wave (λ = 500-750 nm). The basic (working) luminescence band is 640 nm emission. Usually it connects with various complexes of the following type: (CuZn-Zni), (VZn Zni Te), (VZn Zni OSe). More detailed information about semiconductors structure can be found in Morozova N.K. reports. It was supposed that emissions of λ - 640 nm in ZnSe (Te), ZnS, CdS appear due to the complex. This complex includes oxygen in the lattice point, vacancy of zinc and zinc interstice (VZn Zni OSe). Oxygen stabilizes own defects (VZn Zni), located nearby. Tellurium, on the one hand leads to the increase of own defects concentration, and on the other hand promotes the increase of oxygen solubility in ZnSe lattice. We used the pulsed spectrometry method with nanosecond resolution at the temperatures of 25 K, 70 K and 300 K. The beam parameters were the following: electrons energy was ∼ 400 keV; current pulse duration on half height was ∼ 20 ns. Crystals were irradiated in helium cryostat

  10. Thermo-magnetic history effects in the vortex state of YNi2B2C superconductor

    The nature of five-quadrant magnetic isotherms for H || a is different from that for H || c in a single crystal of YNi2B2C, pointing towards an anisotropic behaviour of the flux line lattice (FLL). For H || a, a well defined peak effect (PE) and second magnetization peak (SMP) can be observed and the loop is open prior to the PE. However, for H || c, the loop is closed and one can observe only the PE. We have investigated the history dependence of magnetization hysteresis data for H || a by recording minor hysteresis loops. The observed history dependence in JC{H) across different anomalous regions are rationalized on the basis of superheating/supercooling of the vortex matter across the first-order-like phase transition and possible additional effects due to annealing of the disordered vortex bundles to the underlying equilibrium state.

  11. Magnetism and superconductivity in ErNi2B2C

    N J Bancroft; D McK Paul; G McIntyre; C D Dewhurst; R Cubitt

    2002-05-01

    We have performed a series of neutron diffraction experiments from the magnetic order and the vortex lattice in single crystal ErNi2B2C. The incommensurate magnetic structure develops additional even harmonics below the `ferromagnetic' ordering temperature, F of 2.3 K. This feature and the existence of rods of diffuse scattering suggest the development of ferromagnetic microdomain walls. The magnetic structure is very sensitive to the application of a magnetic field with changes in modulation vector and harmonic content. Studies of the vortex lattice show the presence of a 45° reorientation transition and a distorted hexagonal to square transition as a function of applied field. Further distortions of the vortex lattice occur at N, but no changes are seen at F.

  12. Practical synthesis and cytotoxic evaluation of the pyrazino[1,2-b]-isoquinoline ring system.

    Hernández-Vázquez, Eduardo; Miranda, Luis D

    2016-06-01

    A practical three-step protocol for the synthesis of pyrazino[1,2-b]isoquinolines is reported. This approach includes a one-pot parallel cyclization/cyclization parallel process followed by a non-common 6-endo Heck cyclization that transformed previously constructed Ugi adducts into diversely decorated tricyclic systems. Compounds bearing a t-butyl or 2,6-dimethylphenyl substituent showed significant cytotoxic activity. The most active analogue (6p) showed significant activity against HCT-15 and K562 (IC50 = 41.8 ± 3.3 and 57.7 ± 2.1 μM, respectively) with no cytotoxicity against human gingival fibroblasts. PMID:27161451

  13. Properties and peculiar features of application of isoelectronically doped A2B6 compound based scintillators

    Among 26 compounds, zinc selenide and zinc sulfide crystals are, due to their physico-chemical properties, the best optimized matrices for creation of luminescent materials with output parameters characterizing them as efficient scintillators (highlight output, fast response, high radiation stability, etc.). The first successful experience in this direction was the development of scintillator ZnSe (Te), which has been already shown to be one of the most suitable materials for low-energy X-ray introscopy. With the aim of expanding the application fields of ZnSe and ZnS-based scintillators, we have studied the detect formation processes and luminescent properties if zinc selenide and zinc sulfide crystals doped with anionic (Zn, Cd, Hg) and cationic (O, S, Te) isoelectron dopants (IED). Data are presented on the effect of oxygen, cadmium, tellurium and sulphur upon spectral-kinetic luminescence characteristics of A2B6 compound based scintillator crystals

  14. Can self-ordering scalar fields explain the BICEP2 B-mode signal?

    We show that self-ordering scalar fields (SOSF), i.e. non-topological cosmic defects arising after a global phase transition, cannot explain the B-mode signal recently announced by BICEP2. We compute the full CℓB angular power spectrum of B-modes due to vector and tensor perturbations of SOSF, modeled in the large N limit of a spontaneously broken global O(N) symmetry. We conclude that the low ℓ multipoles detected by BICEP2 cannot be due mainly to SOSF, since they have the wrong spectrum at low multipoles. As a byproduct we derive the first cosmological constraints on this model, showing that the BICEP2 B-mode polarization data admits at most a 2-3% contribution from SOSF in the temperature anisotropies, similar to (but somewhat tighter than) the recently studied case of cosmic strings

  15. Discovery of pyrrolo[1,2-b]pyridazine-3-carboxamides as Janus kinase (JAK) inhibitors.

    Duan, James J-W; Lu, Zhonghui; Jiang, Bin; Yang, Bingwei V; Doweyko, Lidia M; Nirschl, David S; Haque, Lauren E; Lin, Shuqun; Brown, Gregory; Hynes, John; Tokarski, John S; Sack, John S; Khan, Javed; Lippy, Jonathan S; Zhang, Rosemary F; Pitt, Sidney; Shen, Guoxiang; Pitts, William J; Carter, Percy H; Barrish, Joel C; Nadler, Steven G; Salter-Cid, Luisa M; McKinnon, Murray; Fura, Aberra; Schieven, Gary L; Wrobleski, Stephen T

    2014-12-15

    A new class of Janus kinase (JAK) inhibitors was discovered using a rationally designed pyrrolo[1,2-b]pyridazine-3-carboxamide scaffold. Preliminary studies identified (R)-(2,2-dimethylcyclopentyl)amine as a preferred C4 substituent on the pyrrolopyridazine core (3b). Incorporation of amino group to 3-position of the cyclopentane ring resulted in a series of JAK3 inhibitors (4g-4j) that potently inhibited IFNγ production in an IL2-induced whole blood assay and displayed high functional selectivity for JAK3-JAK1 pathway relative to JAK2. Further modifications led to the discovery of an orally bioavailable (2-fluoro-2-methylcyclopentyl)amino analogue 5g which is a nanomolar inhibitor of both JAK3 and TYK2, functionally selective for the JAK3-JAK1 pathway versus JAK2, and active in a human whole blood assay. PMID:25453808

  16. Vortex dynamics in YNi2B2C single crystals by 11B NMR

    11B pulsed nuclear magnetic resonance (NMR) measurements have been performed on a single crystal of YNi2B2C superconductor to investigate the vortex structure and dynamics. As temperature decreases, 11B NMR spectrum, shift, linewidth, and T2-1, exhibit distinct features, from which the authors are able to identify three vortex phases, namely, vortex liquid, vortex glass, and vortex lattice at 1.8T parallel to the c-axis. Also they have observed thermal hysteresis of saddle-point field, motional narrowing of linewidth and the double peak structures of T2-1, all of which indicate unexpectedly significant thermal motion of vortices in this low Tc and nearly isotropic D superconductor

  17. Flux line lattice symmetries in the borocarbide superconductor LuNi2B2C

    M R Eskildsen; A B Abrahamsen; P L Gammel; D J Bishop; N H Andersen; K Mortensen; P C Canfield

    2002-05-01

    We compare the results of small angle neutron scattering on the flux line lattice (FLL) obtained in the borocarbide superconductor LuNi2B2C with the applied field along the - and -axes. For $\\mathbf{H}||\\mathbf{c}$ the temperature dependence of the FLL structural phase transition from square to hexagonal symmetry was investigated. Above 10 K the transition onset field, 2(), rises sharply, bending away from c2() in contradiction to theoretical predictions of the two merging. For $\\mathbf{H}||\\mathbf{a}$ a first order FLL reorientation transition is observed at tr =3-3.5 kOe. Below tr the FLL nearest neighbor direction is parallel to the -axis, and above tr to the -axis. This transition cannot be explained using nonlocal corrections to the London model.

  18. Magnetotransport measurements of single crystalline heavy fermion YbNi2B2C

    We have measured transverse (B perpendicular to I) and longitudinal (B parallel I) magnetoresistance on a single crystalline sample of YbNi2B2C. A remarkably large anisotropic transverse magnetoresistance was found when applying magnetic field parallel or perpendicular to the c-axis of the tetragonal crystallographic structure. A pronounced maximum at 10 T develops below 4 K in the transverse magnetoresistance when the magnetic field is applied along the c-axis, whereas a minimum is found at 7 T below 4 K when the applied field is perpendicular to the c-axis. Above 5 K both configurations (B parallel c and B perpendicular to c) show a negative magnetoresistance. Finally, the possibility of a metamagnetic-like transition in this compound will be discussed in conjunction with high field magnetization experiments. (orig.)

  19. A resonant-photoemission study of YNi2B2C

    Valence level photoemission measurements of the normal-state electronic structure of the new boro-carbide intermetallic superconductor YNi2B2C are presented. The behaviour of the Ni-dominated valence band peak at 1.4 eV binding energy and the states at EF across the Ni3p absorption threshold clearly indicate significant Ni3d contributions at these energies. In addition, the transfer of spectral weight from the main Ni3d valence band to a two-hole bound-state satellite at ∼ 8 eV signals the role played by electron correlation in these materials. The peak in the DOS predicted to lie at EF in band structure calculations is not observed in the experiment, possibly also due to the effects of electron correlation. (orig.)

  20. Conical intersections between X2A1 and A2B2 electronic states of NO

    Sardar, Subhankar; Mukherjee, Saikat; Paul, Amit Kumar; Adhikari, Satrajit

    2013-04-01

    We explore both the general symmetry-allowed accidental (SAA) conical intersections (CIs) and Renner-Teller (RT) interactions prevailed between the ground (X2A1) and first excited (A2B2) electronic states of NO in the configuration space of normal mode coordinates. Global ab initio potential-energy surfaces and Non Adiabatic Coupling Term (NACT) between those states are reported. For each of the three pairs of normal mode (Q1,Q2,Q3), calculated NACT show singularity at different positions, which are used to calculate Adiabatic-to-Diabatic Transformation (ADT) angles and thereby, the diagonal elements of ADT matrix display (i) sign change for odd number of SAA CI (s) and (ii) no sign change for even number of SAA CIs as well as Renner-Teller interactions. Similar to Jahn-Teller CI, the existence of SAA CIs are, further, confirmed by Longuet-Higgins' phase change.

  1. B2B-alan aatoksia sosiaalisen median hyödyntämisestä

    Kuitunen, Maiju

    2015-01-01

    Opinnäytetyön tarkoituksena oli selvittää B2B-yritysten nykyistä sosiaalisen median kanavien käytön tilannetta ja suhtautumista Twitteriin ja samalla muihin sosiaalisen median kanaviin. Tavoitteena oli myös laatia Twitterin käyttöönotto-opas, jota Ovena Oy pääsee hyödyntämään liiketoiminnassaan. Tutkimuksen kohteena oli Ovena Oy:n asiakkaat. Tarkoituksena oli tutkia heidän näkökulmasta ajatuksia ja hyödyllisyyttä sosiaalisesta mediasta. Sähköpostitse lähetetyyn kyselyyn osallistui 32 hen...

  2. Superconducting and magnetic properties of DyNi2B2C single crystals

    We have investigated the superconducting and magnetic properties of DyNi2B2C single crystals for applied fields parallel and perpendicular to the c-axis. Magnetisation measurements show that this compound has highly anisotropic properties in both the normal and the superconducting state. The normal state susceptibility follows a Curie-Weiss temperature dependence for applied field perpendicular to the c-axis and a much weaker temperature dependence if the field is along the c-axis. For magnetic fields applied perpendicular to the c-axis, the magnetisation versus field curves show anomalies below TN with clear discontinuities and eventual saturation for H>30 kOe, while showing a normal paramagnetic behaviour when the field is applied along the c-axis. (orig.)

  3. Synthesis and bioactivity of MSH4 oligomers prepared by an A2 + B2 strategy

    Dehigaspitiya, Dilani Chathurika; Navath, Suryakiran; Weber, Craig S.; Lynch, Ronald M.; Mash, Eugene A.

    2014-01-01

    Oligomers incorporating the tetrapeptide MSH4, the minimum active sequence of melanocyte stimulating hormone, were synthesized by an A2 + B2 strategy involving microwave-assisted copper-catalyzed azide-alkyne cycloaddition. A2 contained an MSH4 core while B2 contained a (Pro-Gly)3 spacer. Soluble mixtures containing compounds with up to eight MSH4 units were obtained from oligomerizations at high monomer concentrations. The avidities of several oligomeric mixtures were evaluated by means of a competitive binding assay using HEK293 cells engineered to overexpress the melanocortin 4 receptor. When based on total MSH4 concentrations, avidities were only minimally enhanced compared with a monovalent control. The lack of variation in the effect of ligands on probe binding is consistent with high off rates for MSH4 in both monovalent and oligomeric constructs relative to that of the competing probe. PMID:26120211

  4. Clinical and research data integration: the i2b2-FSM experience.

    Segagni, Daniele; Tibollo, Valentina; Dagliati, Arianna; Malovini, Alberto; Zambelli, Alberto; Napolitano, Carlo; Priori, Silvia G; Bellazzi, Riccardo

    2013-01-01

    In order to support and improve the efficiency of clinical research in specific health area, the University of Pavia and the IRCCS Fondazione Salvatore Maugeri of Pavia (FSM) are developing and implementing an i2b2 based platform, designed to collect data coming from hospital clinical practice and scientific research. The work made in FSM is committed to support an affordable, less intrusive and more personalized care, increasing the quality of clinical practice as well as improving the scientific results. Such a aim depends on the application of information and communication technologies and the use of data. An integrated data warehouse has been implemented to support clinicians and researchers in two medical fields with a great impact on the population: oncology and cardiology. Furthermore the data warehouse approach has been tested with administrative information, allowing a financial view of clinical data. PMID:24303274

  5. Cognitive impairment in the preclinical stage of dementia in FTD-3 CHMP2B mutation carriers

    Stokholm, Jette; Teasdale, Thomas W; Johannsen, Peter;

    2013-01-01

    -3). Subjects were assessed with neuropsychological tests in 2002, 2005 and 2010. RESULTS: Cross-sectional analyses showed that the mutation carriers scored lower on tests of psychomotor speed, working memory, executive functions and verbal memory than a control group consisting of not-at-risk family...... members and spouses. Longitudinal analyses showed a gradual decline in psychomotor speed, working memory capacity and global executive measures in the group of non-demented mutation carriers that was not found in the control group. In contrast, there were no significant group differences in domain scores...... on memory or visuospatial functions. On an individual level the cognitive changes over time varied considerably. CONCLUSION: Subjects with CHMP2B mutation show cognitive changes dominated by executive dysfunctions, years before they fulfil diagnostic criteria of FTD. However, there is great...

  6. High-temperature Raman spectroscopic study of vanadoborate Na3VO2B6O11

    Ji, Zhang; De-Ming, Zhang; Qing-Li, Zhang; Shao-Tang, Yin

    2016-03-01

    Raman spectra of a vanadoborate (Na3VO2B6O11) crystal from room temperature up to the melting point have been recorded. The main internal vibrational modes of the crystal have been assigned. It was found that all the Raman bands exhibit decreases in frequency and the widths of the Raman bands increase with the increase of temperature. However, no phase transition was observed under 525 °C. The micro-structure of its melt was studied by quantum chemistry ab initio calculation. The continuous three-dimensional network of the crystal collapsed and transformed into VO4 and VBO6 clusters during the melting process with an isomerization reaction from four-coordinated boron to a three-coordinated species. Project supported by the National Natural Science Foundation of China (Grant Nos. 51302268 and 51102239) and the Natural Science Foundation of Anhui Province, China (Grant No. KJ2015A339).

  7. RE{sub 2}B{sub 8}O{sub 15} (RE = La, Pr, Nd). Syntheses of three new rare earth borates isotypic to Ce{sub 2}B{sub 8}O{sub 15}

    Glaetzle, Matthias; Hoerder, Gregor J.; Huppertz, Hubert [Innsbruck Univ. (Austria). Inst. fuer Allgemeine, Anorganische und Theoretische Chemie

    2016-08-01

    The rare earth borates RE{sub 2}B{sub 8}O{sub 15} (RE = La, Pr, Nd) were synthesized in a Walker-type multianvil apparatus under conditions of 5.5 GPa and 1100 C. Starting from the corresponding rare earth oxides and boron oxide, the syntheses yielded crystalline products of all new compounds that allowed crystal structure analyses based on single-crystal X-ray diffraction data for La{sub 2}B{sub 8}O{sub 15} and Nd{sub 2}B{sub 8}O{sub 15}. The compound Pr{sub 2}B{sub 8}O{sub 15} could be characterized via X-ray powder diffractometry. The results show that the new compounds crystallize isotypically to Ce{sub 2}B{sub 8}O{sub 15} in the monoclinic space group P2/c. The infrared spectra of RE{sub 2}B{sub 8}O{sub 15} (RE = La, Pr, Nd) have also been studied.

  8. Impaired hippocampal synaptic plasticity and NR2A/2B expression ratio in remifentanil withdrawal rats.

    Wang, Yi-Yi; Liu, Shichang; Zhang, Nan; Yang, Jing; Zhang, Yinguo

    2016-03-01

    Remifentanil is a kind of synthetic opioid which has gained wide clinical acceptance by anesthesiologists. In this study, we attempted to test whether withdrawal effects on learning mechanisms can be triggered by repeated low-dose remifentanil treatment. Male Sprague-Dawley (SD) rats were subjected to remifentanil (50μg/kgs.c.) twice per day at 12h intervals for 15 days. When the animals of remifentanil group were withdrawn from remifentanil at 10h after the last injection, changes in open field test, Morris water maze test (MWM) and synaptic efficacy were examined in each group. We demonstrated that repeated exposure to 50μg/kg remifentanil produced enhanced locomotor activity indicating that a remifentanil addiction animal model in rats was established. MWM results showed that exposure to remifentanil had no influence on the spatial cognition. After withdrawal of remifentanil rats showed impaired spatial cognition. In electrophysiology test, remifentanil group rats showed a trend for a rightward shift of input/output relationship and significant deficits in maintenance of STP and LTP. Immunohistochemistry results demonstrated increased NR2A/NR2B ratio that should be included depression of LTP. In the whole-cell patch-clamp recording, after elimination from remifentanil incubation, mEPSC frequency was down regulated in hippocampal CA1 neurons, indicating that basal synaptic transmission were affected by remifentanil withdrawal. Taken together, the current findings demonstrate that the remifentanil withdrawn rats exhibit obvious impairment of hippocampus-dependent memory and synaptic plasticity. Increased hippocampal NR2A/NR2B expression ratio and the changes of basal synaptic transmission may participate in the impairment of LTP. PMID:26777139

  9. 19 CFR 351.214 - New shipper reviews under section 751(a)(2)(B) of the Act.

    2010-04-01

    ... shipper reviews under section 751(a)(2)(B) of the Act. (a) Introduction. The URAA established a new...) In an antidumping proceeding involving imports from a nonmarket economy country, a certification...

  10. Identification of novel thiadiazoloacrylamide analogues as inhibitors of dengue-2 virus NS2B/NS3 protease.

    Liu, Hailong; Wu, Ruoming; Sun, Yanyan; Ye, Yan; Chen, Jing; Luo, Xiaomin; Shen, Xu; Liu, Hong

    2014-11-15

    Dengue virus is endemic throughout tropical and subtropical regions, and cause severe epidemic diseases. The NS2B/NS3 protease is a promising drug target for dengue virus. Herein, we report the discovery and modification of a novel class of thiadiazoloacrylamide derivatives with potent inhibitory activity against the NS2B/NS3 protease. Thiadiazolopyrimidinone 1 was firstly determined as a new chemical structure against NS2B/NS3 from a commercial compound library. Then, we sought to identify similar compounds with the thiadiazoloacrylamide core that would exhibit better activity. A series of analogues were synthesized and fourteen of them were identified with strong inhibitory activities, in which the nitrile group in the linker part was discovered as an essential group for the inhibitory activity. The best of these (8b) demonstrated an IC50 at 2.24μM based on in vitro DENV2 NS2B-NS3pro assays. PMID:25438757

  11. The modulating role of ADRA2B in emotional working memory: Attending the negative but remembering the positive.

    Mammarella, Nicola; Fairfield, Beth; Di Domenico, Alberto; D'Onofrio, Laura; Stuppia, Liborio; Gatta, Valentina

    2016-04-01

    Previous studies found that the ADRA2B gene modulates early perception and attention. Here, we aimed to examine whether ADRA2B polymorphisms also influence emotional working memory and the willingness to implement behaviors (switching affective intonation) in order to avoid negative information, both considered indexes of cognitive-affective flexibility. We examined genotype data collected from 212 healthy females, 91 ADRA2B carriers and 121 non-carriers, and found that carriers showed a positivity bias in working memory. That is, carriers remembered a higher number of positive words compared to negative and neutral words. In addition, although carriers were more unwilling to switch intonation in order to avoid negative information, they showed better recognition memory for words read with a positive intonation. These findings suggest that deletion variants of ADRA2B may show greater levels of cognitive-affective flexibility compared to non-carriers. PMID:26899992

  12. Progress in the discovery of selective, high affinity A2B adenosine receptor antagonists as clinical candidates

    Kalla, Rao V.; Zablocki, Jeff

    2008-01-01

    The selective, high affinity A2B adenosine receptor (AdoR) antagonists that were synthesized by several research groups should aid in determining the role of the A2B AdoR in inflammatory diseases like asthma or rheumatoid arthritis (RA) and angiogenic diseases like diabetic retinopathy or cancer. CV Therapeutics scientists discovered the selective, high affinity A2B AdoR antagonist 10, a 8-(4-pyrazolyl)-xanthine derivative [CVT-6883, Ki(hA2B) = 22 nM; Ki(hA1) = 1,940 nM; Ki(hA2A) = 3,280; and...

  13. Superconductivity and magnetism in holmium-nickel-boron carbide of the structure type LuNi2B2C

    The following topics are covered: variation in the chemical composition of HoNi2B2C, equilibrium phases, superconductivity, magnetic behaviour, crystal structure determination, phase diagrams, behaviour under high hydrostatic pressure, influence of thermal treatment (WL)

  14. Progress in the discovery of selective, high affinity A(2B) adenosine receptor antagonists as clinical candidates.

    Kalla, Rao V; Zablocki, Jeff

    2009-03-01

    The selective, high affinity A(2B) adenosine receptor (AdoR) antagonists that were synthesized by several research groups should aid in determining the role of the A(2B) AdoR in inflammatory diseases like asthma or rheumatoid arthritis (RA) and angiogenic diseases like diabetic retinopathy or cancer. CV Therapeutics scientists discovered the selective, high affinity A(2B) AdoR antagonist 10, a 8-(4-pyrazolyl)-xanthine derivative [CVT-6883, K(i)(hA(2B)) = 22 nM; K(i)(hA(1)) = 1,940 nM; K(i)(hA(2A)) = 3,280; and K(i)(hA(3)) = 1,070 nM] that has favorable pharmacokinetic (PK) properties (t (1/2) = 4 h and F > 35% rat). Compound 10 demonstrated functional antagonism at the A(2B) AdoR (K(B) = 6 nM) and efficacy in a mouse model of asthma. In two phase 1 clinical trials, CVT-6883 was found to be safe, well tolerated, and suitable for once daily dosing. A second compound 20, 8-(5-pyrazolyl)-xanthine, has been nominated for development from Baraldi's group in conjunction with King Pharmaceuticals that has favorable A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 5.5 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 1,000; and K(i)(hA(3)) > 1,000 nM], and it has been demonstrated to be a functional antagonist. A third compound 32, a 2-aminopyrimidine, from the Almirall group has high A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 17 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 2,500; and K(i)(hA(3)) > 1,000 nM], and 32 has been moved into preclinical safety testing. Since three highly selective, high affinity A(2B) AdoR antagonists have been nominated for development with 10 (CVT-6883) being the furthest along in the development process, the role of the A(2B) AdoR in various disease states will soon be established. PMID:18568423

  15. Production of 4He, 3He, and tritium from Be irradiated in FFTF-MOTA-2B

    The production of 4He, 3He, and tritium has been calculated for beryllium irradiated in the Materials Open Test Assembly (MOTA)-2B experiment in the Fast Flux Test Facility (FFTF). Reaction rates were based on adjusted neutron spectra determined from reactor dosimetry measurements at seven different elevations in the irradiation assembly. Equations are given so that gas production, dpa, and neutron fluences can be calculated for any specific elevation in the MOTA-2B assembly

  16. Conformational flexibility of DENV NS2B/NS3pro: from the inhibitor effect to the serotype influence.

    Piccirillo, Erika; Merget, Benjamin; Sotriffer, Christoph A; do Amaral, Antonia T

    2016-03-01

    The dengue virus (DENV) has four well-known serotypes, namely DENV1 to DENV4, which together cause 50-100 million infections worldwide each year. DENV NS2B/NS3pro is a protease recognized as a valid target for DENV antiviral drug discovery. However, NS2B/NS3pro conformational flexibility, involving in particular the NS2B region, is not yet completely understood and, hence, a big challenge for any virtual screening (VS) campaign. Molecular dynamics (MD) simulations were performed in this study to explore the DENV3 NS2B/NS3pro binding-site flexibility and obtain guidelines for further VS studies. MD simulations were done with and without the Bz-nKRR-H inhibitor, showing that the NS2B region stays close to the NS3pro core even in the ligand-free structure. Binding-site conformational states obtained from the simulations were clustered and further analysed using GRID/PCA, identifying four conformations of potential importance for VS studies. A virtual screening applied to a set of 31 peptide-based DENV NS2B/NS3pro inhibitors, taken from literature, illustrated that selective alternative pharmacophore models can be constructed based on conformations derived from MD simulations. For the first time, the NS2B/NS3pro binding-site flexibility was evaluated for all DENV serotypes using homology models followed by MD simulations. Interestingly, the number of NS2B/NS3pro conformational states differed depending on the serotype. Binding-site differences could be identified that may be crucial to subsequent VS studies. PMID:26923377

  17. Resveratrol induces cellular senescence with attenuated mono-ubiquitination of histone H2B in glioma cells

    Research highlights: → Resveratrol induces cellular senescence in glioma cell. → Resveratrol inhibits mono-ubiquitination of histone H2B at K120. → Depletion of RNF20, phenocopies the inhibitory effects of resveratrol. → Mono-ubiquitination of histone H2B at K120 is a novel target of resveratrol. → RNF20 inhibits cellular senescence in proliferating glioma cells. -- Abstract: Resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenol naturally occurring in grapes and other plants, has cancer chemo-preventive effects and therapeutic potential. Although resveratrol modulates multiple pathways in tumor cells, how resveratrol or its affected pathways converge on chromatin to mediate its effects is not known. Using glioma cells as a model, we showed here that resveratrol inhibited cell proliferation and induced cellular hypertrophy by transforming spindle-shaped cells to enlarged, irregular and flatten-shaped ones. We further showed that resveratrol-induced hypertrophic cells expressed senescence-associated-β-galactosidase, suggesting that resveratrol-induced cellular senescence in glioma cells. Consistent with these observations, we demonstrated that resveratrol inhibited clonogenic efficiencies in vitro and tumor growth in a xenograft model. Furthermore, we found that acute treatment of resveratrol inhibited mono-ubiquitination of histone H2B at K120 (uH2B) in breast, prostate, pancreatic, lung, brain tumor cells as well as primary human cells. Chronic treatment with low doses of resveratrol also inhibited uH2B in the resveratrol-induced senescent glioma cells. Moreover, we showed that depletion of RNF20, a ubiquitin ligase of histone H2B, inhibited uH2B and induced cellular senescence in glioma cells in vitro, thereby recapitulated the effects of resveratrol. Taken together, our results suggest that uH2B is a novel direct or indirect chromatin target of resveratrol and RNF20 plays an important role in inhibiting cellular senescence programs that are

  18. Functional analysis of histone demethylase Jmjd2b on lipopolysaccharide-treated murine neural stem cells (NSCs).

    Das, Nando Dulal; Choi, Mi Ran; Jung, Kyoung Hwa; Park, Ji Hyun; Lee, Hyung Tae; Das, Amitabh; Kim, Seung Hyun; Chai, Young Gyu

    2013-02-01

    Neural stem cell (NSC) neurogenesis is the formation of new neurons by which the brain maintains its lifelong plasticity in response to extrinsic and intrinsic changes. Here, we show the effect of lipopolysaccharides (LPS) as an in vitro model of inflammation on NSCs to determine whether the inflammatory mediators can epigenetically affect NSCs and alter their proliferation and differentiation abilities. To study the effect of LPS on NSCs, we used an immortalized mouse neuroectodermal stem cell line, NE-4C. We found that Jmjd2b, histone-3 lysine-9 di-/tri-methyl (H3K9me2/3) demethylase, is functional following LPS treatment and is crucial in multiple signaling pathways and biological processes. The global gene expression levels were detected in Jmjd2b-knockdown (kd) NE-4C cells and in LPS-stimulated Jmjd2b-kd NE-4C cells using an Affymetrix GeneChip(®) Mouse Gene 1.0 ST Array. In addition, the datasets were analyzed using MetaCore Pathway Analysis (GeneGo). The attenuation of Jmjd2b in NE-4C cells significantly affected the p65, iNOS, Bcl2, and TGF-β expression levels and had downstream effects on related signaling pathways. In addition, chromatin immunoprecipitation revealed that Jmjd2b-kd could inhibit the Notch1, IL-1β, and IL-2 genes by recruiting repressive H3K9me3 to their promoters. Moreover, this study highlights Jmjd2b role in LPS-mediated inflammation, which suggests an epigenetic regulation in NE-4C cells. Finally, this study establishes novel Jmjd2b targets that potentiate a biological rationale involving Jmjd2b in NSC inflammation. PMID:22890720

  19. Parallel functional activity profiling reveals valvulopathogens are potent 5-hydroxytryptamine(2B) receptor agonists: implications for drug safety assessment.

    Huang, Xi-Ping; Setola, Vincent; Yadav, Prem N; Allen, John A; Rogan, Sarah C; Hanson, Bonnie J; Revankar, Chetana; Robers, Matt; Doucette, Chris; Roth, Bryan L

    2009-10-01

    Drug-induced valvular heart disease (VHD) is a serious side effect of a few medications, including some that are on the market. Pharmacological studies of VHD-associated medications (e.g., fenfluramine, pergolide, methysergide, and cabergoline) have revealed that they and/or their metabolites are potent 5-hydroxytryptamine(2B) (5-HT(2B)) receptor agonists. We have shown that activation of 5-HT(2B) receptors on human heart valve interstitial cells in vitro induces a proliferative response reminiscent of the fibrosis that typifies VHD. To identify current or future drugs that might induce VHD, we screened approximately 2200 U.S. Food and Drug Administration (FDA)-approved or investigational medications to identify 5-HT(2B) receptor agonists, using calcium-based high-throughput screening. Of these 2200 compounds, 27 were 5-HT(2B) receptor agonists (hits); 14 of these had previously been identified as 5-HT(2B) receptor agonists, including seven bona fide valvulopathogens. Six of the hits (guanfacine, quinidine, xylometazoline, oxymetazoline, fenoldopam, and ropinirole) are approved medications. Twenty-three of the hits were then "functionally profiled" (i.e., assayed in parallel for 5-HT(2B) receptor agonism using multiple readouts to test for functional selectivity). In these assays, the known valvulopathogens were efficacious at concentrations as low as 30 nM, whereas the other compounds were less so. Hierarchical clustering analysis of the pEC(50) data revealed that ropinirole (which is not associated with valvulopathy) was clearly segregated from known valvulopathogens. Taken together, our data demonstrate that patterns of 5-HT(2B) receptor functional selectivity might be useful for identifying compounds likely to induce valvular heart disease. PMID:19570945

  20. Examining how B2B SMEs navigate the challenges and opportunities of digital marketing through the lens of Everyman Legal

    Buckley, Thomas

    2015-01-01

    Summary Purpose - The present research aims to explore the digital marketing strategy of Everyman Legal, a business-to-business (B2B) small and medium-sized enterprise (SME) law firm. Specifically, areas of exploration include perceptions of digital marketing from a B2B SME, opportunities and difficulties surrounding digital marketing both present and future, particularly with respect to specific digital technologies and potential for networking and relationship building. Methodol...