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.


    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


    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


    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.


    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.


    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


    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


    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.


    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


    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.


    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



    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.


    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.


    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


    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


    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


    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


    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


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

    Andresen, Steinar; Rosendal, Kristin G.


    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)

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

    Katrin Köppert


    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.

  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


    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.


    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


    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


    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


    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;


    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.


    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)


    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


    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


    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.


    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


    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


    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


    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


    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


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

    Rivero Francisco


    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.

  11. TEM-Grundlagenuntersuchungen zur Gefügeentwicklung in aushärtbaren Glimmerglaskeramiken

    Bürke, Harald


    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...

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

    MA Juhui; Yuejian ZHU; Richard WOBUS; Panxing WANG


    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. 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.

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

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


    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.

  15. Hotelzon's B2B content marketing plan

    Nguyen, Trang


    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.


    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


    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


    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


    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


    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. 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...

  2. B2B Pioneer A Millionaire Maker


    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

  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.;


    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.


    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


    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


    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


    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


    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.


    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


    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.


    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


    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


    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. To be or not B2B?

    Symons, L J


    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...

  16. 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.

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

    Kern B


    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


    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


    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.


    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


    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


    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


    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


    Latipova Liliya Nikolaevna; Latipov Zagir Azgarovich


    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


    ... 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, ...




    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.


    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


    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.


    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

    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

    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: [Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160 (United States)


    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


    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,, ...

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

    Donaldson Julie G


    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.

  19. Organizational patterns for knowledge capture in B2B engagements

    Niwe, Moses


    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...

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

    Storbeck, Markus


    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)


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

    Tietel, Erhard


    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 "...

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

    Stubenvoll, Florian Michael


    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...

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

    Dieter, Heribert


    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...

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

    Kegel, Christian


    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...

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

    Lehner, Harald


    "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. Gefügebildung und Langzeitbeständigkeit alternativer mineralischer Oberflächenabdichtungen von Abfalldeponien

    Kiewitt, Sebastian


    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...

  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.


    ... 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. ORM-based semantics of B2B transactions.

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


    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

  11. Frontotemporal dementia caused by CHMP2B mutations

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


    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...

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

    Keenan, Jemma


    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


    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)


    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


    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. Sosiaalisen median strategia B2B-yritykselle

    Johansson, Mia


    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...

  19. B2B virksomheders brug af sociale medier

    Persdatter Gotfredsen, Karoline


    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...

  20. Frontotemporal dementia caused by CHMP2B mutations

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


    . 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....

  1. 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

  2. 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....

  3. Branding of electricity in B2B markets

    Rolanda Simenaite 1986


    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 ...

  4. Scope of Internal Marketing in B2B Companies

    Nigam, Niharika


    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...

  5. B2B emarketplace announcements and shareholder wealth

    Andrew H. Chen; Siems, Thomas F.


    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...

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

    Eiden, Fritz; Wanner, Klaus Th.


    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.


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


    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...

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

    Benno Gammerl


    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.

  10. 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


    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.

  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


    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


    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


    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. Digitaalisen markkinoinnin suunnitelma b2b-yritykselle

    Harhakoski, Oskari


    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...

  17. B2B-asiantuntijayritys ja sosiaalinen media

    Sahlman, Katriina


    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...

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

    Toivonen, Niina; Jesar, Rama


    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...

  19. Customized E-Learning for B2B Companies

    Tim Thomasma


    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.

  20. Supporting B2B Business Documents in XML Web Services

    KIM Hyoungdo


    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.

  1. Marketing-sales interface configurations in B2B firms

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


    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

  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


    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



    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


    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. 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 ...

  7. 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 ...

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

    Bredenkötter, Daniel


    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...


    Monika £obaziewicz


    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...

  10. Content Marketing vs. Traditional Advertising for B2B Companies

    Anthony, Lorena


    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...

  11. Sample preparation for 2b-RAD genotyping



    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 ...

  12. Social media usage: an investigation of B2B salespeople

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


    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...

  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


    ... 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


    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


    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. MED23: a new Mediator of H2B monoubiquitylation.

    Streubel, Gundula; Bracken, Adrian P


    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

  18. B2B-verkkokaupan suunnittelu : Case Laihian Levypala Oy

    Kotilainen, Sanna-Mari


    Tämän opinnäytetyön tarkoituksena oli toteuttaa B2B-verkkokaupan suunnitelma metallialan perheyritys Laihian Levypala Oy:lle. Idea verkkokaupasta lähti 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...

  19. B2B-verkkokaupan markkinointiviestintäsuunnitelma

    Luoma, Hanna


    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...

  20. 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.


    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...

  1. Strategic Insights from Mystery Shopping in B2B Relationships

    Mattsson, Jan


    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...

  2. B2B Integration in Global Supply Chains

    Schubert, Petra; Legner, Christine


    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....

  3. Neoplasia endocrina múltiple tipo-2b

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


    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...


    Iiskola, Jani


    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...


    A. Jakimi


    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


    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


    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


    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. Semantic ETL into i2b2 with Eureka!

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


    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

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

    Goudarzi, Koorosh; Jamali, Mehdi


    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.

  11. Sosiaalisen median strategia pienelle b2b-yritykselle

    Surkko, Antti


    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...

  12. Vortex lattice transitions in YNi2B2C

    S J Levett; C D Dewhurst; D McK Paul


    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.

  13. 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...

  14. Relationship Quality as Predictor of B2B Customer Loyalty

    Shaimaa S. B. Ahmed Doma


    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.

  15. Matchmaking Framework for B2B E-Marketplaces



    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.

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

    Brudzyńska-Němec, Gabriela


    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...

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

    Hansch, Ralf


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

    Barthel, Thomas


    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...

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

    Muñoz Félix, Sofía


    [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


    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


    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


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


    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....

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

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


    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...

  6. B2-B2.5 code benchmarking

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


    ITER-IO currently (and since about 15 years) employs the code for its divertor design, currently version SOLPS4.3. 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


    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:; 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)


    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


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



    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.

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

    Hartono Siswono


    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

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


    ... 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 ...

  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


    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


    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: [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)


    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


    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


    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


    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


    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


    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


    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


    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


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

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


    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....

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

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


    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

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

    Zhang, Kangling


    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


    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. 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...

  14. 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...

  15. 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...

  16. 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...

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

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


    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...

  18. 75 FR 61577 - Wage Methodology for the Temporary Non-Agricultural Employment H-2B Program


    ... 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...

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

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


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

    Chunxia Li; Men Su; Huimin Wang; Yinghe Hu


    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.

  1. 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.

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

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


    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

  4. 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


    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

  5. 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

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

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


    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

  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


    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


    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. 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


    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

  10. 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

  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


    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


    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


    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


    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


    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


    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


    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


    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


    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


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

    Milošević Sanja


    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

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

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


    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

  3. 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...

  4. 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

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

    Taaning, E; Jacobsen, N; Morling, N


    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....

  6. 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


    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

  7. 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

  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


    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. Managing Innovation Through Social Media in B2B SME-Context

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


    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....

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

    Malinen, Mikko


    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 ...