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Sample records for initiation factor 2b

  1. Crystal structure of the regulatory subunit of archaeal initiation factor 2B (aIF2B) from hyperthermophilic archaeon Pyrococcus horikoshii OT3: a proposed structure of the regulatory subcomplex of eukaryotic IF2B

    International Nuclear Information System (INIS)

    Kakuta, Yoshimitsu; Tahara, Maino; Maetani, Shigehiro; Yao, Min; Tanaka, Isao; Kimura, Makoto

    2004-01-01

    Eukaryotic translation initiation factor 2B (eIF2B) is the guanine-nucleotide exchange factor for eukaryotic initiation factor 2 (eIF2). eIF2B is a heteropentameric protein composed of α-ε subunits. The α, β, and δ subunits form a regulatory subcomplex, while the γ and ε form a catalytic subcomplex. Archaea possess homologues of α, β, and δ subunits of eIF2B. Here, we report the three-dimensional structure of an archaeal regulatory subunit (aIF2Bα) from the hyperthermophilic archaeon Pyrococcus horikoshii OT3 determined by X-ray crystallography at 2.2 A resolution. aIF2Bα consists of two subdomains, an N-domain (residues 1-95) and a C-domain (residues 96-276), connected by a long α-helix (α5: 78-106). The N-domain contains a five helix bundle structure, while the C-domain folds into the α/β structure, thus showing similarity to D-ribose-5-phosphate isomerase structure. The presence of two molecules in the crystallographic asymmetric unit and the gel filtration analysis suggest a dimeric structure of aIF2Bα in solution, interacting with each other by C-domains. Furthermore, the crystallographic 3-fold symmetry generates a homohexameric structure of aIF2Bα; the interaction is primarily mediated by the long α-helix at the N-domains. This structure suggests an architecture of the three subunits, α, β, and δ, in the regulatory subcomplex within eIF2B

  2. Analysis of the Antigenic and Prophylactic Properties of the Leishmania Translation Initiation Factors eIF2 and eIF2B in Natural and Experimental Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Esther Garde

    2018-04-01

    Full Text Available Different members of intracellular protein families are recognized by the immune system of the vertebrate host infected by parasites of the genus Leishmania. Here, we have analyzed the antigenic and immunogenic properties of the Leishmania eIF2 and eIF2B translation initiation factors. An in silico search in Leishmania infantum sequence databases allowed the identification of the genes encoding the α, β, and γ subunits and the α, β, and δ subunits of the putative Leishmania orthologs of the eukaryotic initiation factors F2 (LieIF2 or F2B (LieIF2B, respectively. The antigenicity of these factors was analyzed by ELISA using recombinant versions of the different subunits. Antibodies against the different LieIF2 and LieIF2B subunits were found in the sera from human and canine visceral leishmaniasis patients, and also in the sera from hamsters experimentally infected with L. infantum. In L. infantum (BALB/c and Leishmania major (BALB/c or C57BL/6 challenged mice, a moderate humoral response against these protein factors was detected. Remarkably, these proteins elicited an IL-10 production by splenocytes derived from infected mice independently of the Leishmania species employed for experimental challenge. When DNA vaccines based on the expression of the LieIF2 or LieIF2B subunit encoding genes were administered in mice, an antigen-specific secretion of IFN-γ and IL-10 cytokines was observed. Furthermore, a partial protection against murine CL development due to L. major infection was generated in the vaccinated mice. Also, in this work we show that the LieIF2α subunit and the LieIF2Bβ and δ subunits have the capacity to stimulate IL-10 secretion by spleen cells from naïve mice. B-lymphocytes were identified as the major producers of this anti-inflammatory cytokine. Taking into account the data found in this study, it may be hypothesized that these proteins act as virulence factors implicated in the induction of humoral responses as well

  3. Analysis of the Antigenic and Prophylactic Properties of the Leishmania Translation Initiation Factors eIF2 and eIF2B in Natural and Experimental Leishmaniasis.

    Science.gov (United States)

    Garde, Esther; Ramírez, Laura; Corvo, Laura; Solana, José C; Martín, M Elena; González, Víctor M; Gómez-Nieto, Carlos; Barral, Aldina; Barral-Netto, Manoel; Requena, José M; Iborra, Salvador; Soto, Manuel

    2018-01-01

    Different members of intracellular protein families are recognized by the immune system of the vertebrate host infected by parasites of the genus Leishmania . Here, we have analyzed the antigenic and immunogenic properties of the Leishmania eIF2 and eIF2B translation initiation factors. An in silico search in Leishmania infantum sequence databases allowed the identification of the genes encoding the α, β, and γ subunits and the α, β, and δ subunits of the putative Leishmania orthologs of the eukaryotic initiation factors F2 (LieIF2) or F2B (LieIF2B), respectively. The antigenicity of these factors was analyzed by ELISA using recombinant versions of the different subunits. Antibodies against the different LieIF2 and LieIF2B subunits were found in the sera from human and canine visceral leishmaniasis patients, and also in the sera from hamsters experimentally infected with L. infantum . In L. infantum (BALB/c) and Leishmania major (BALB/c or C57BL/6) challenged mice, a moderate humoral response against these protein factors was detected. Remarkably, these proteins elicited an IL-10 production by splenocytes derived from infected mice independently of the Leishmania species employed for experimental challenge. When DNA vaccines based on the expression of the LieIF2 or LieIF2B subunit encoding genes were administered in mice, an antigen-specific secretion of IFN-γ and IL-10 cytokines was observed. Furthermore, a partial protection against murine CL development due to L. major infection was generated in the vaccinated mice. Also, in this work we show that the LieIF2α subunit and the LieIF2Bβ and δ subunits have the capacity to stimulate IL-10 secretion by spleen cells from naïve mice. B-lymphocytes were identified as the major producers of this anti-inflammatory cytokine. Taking into account the data found in this study, it may be hypothesized that these proteins act as virulence factors implicated in the induction of humoral responses as well as in the

  4. Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1 and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats

    Directory of Open Access Journals (Sweden)

    Philippe A. Melas

    2018-03-01

    Full Text Available Summary: Reduced eukaryotic Initiation Factor 2 (eIF2α phosphorylation (p-eIF2α enhances protein synthesis, memory formation, and addiction-like behaviors. However, p-eIF2α has not been examined with regard to psychoactive cannabinoids and cross-sensitization. Here, we find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN] reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A, the recruiter of protein phosphatase 1 (PP1. The induction of GADD34 was linked to ERK/CREB signaling and to CREB-binding protein (CBP-mediated histone hyperacetylation at the Gadd34 locus. In vitro, WIN also upregulated eIF2B1, an eIF2 activator subunit. We next found that WIN administration in vivo reduced p-eIF2α in the nucleus accumbens of adolescent, but not adult, rats. By contrast, WIN increased dorsal striatal levels of eIF2B1 and ΔFosB among both adolescents and adults. In addition, we found cross-sensitization between WIN and cocaine only among adolescents. These findings show that cannabinoids can modulate eukaryotic initiation factors, and they suggest a possible link between p-eIF2α and the gateway drug properties of psychoactive cannabinoids. : Melas et al. show that psychoactive cannabinoids modulate levels of two eukaryotic initiation factors (eIF2α and eIF2B1 known to be involved in protein synthesis, memory formation, and drug sensitivity. Cannabinoid modulation of eIF2α in vivo is only observed in adolescent animals, and is associated with cross-sensitization to cocaine. Keywords: drug use, addiction, cannabis, marijuana, cocaine, epigenetics, eIF2a, CREB, GADD34, gateway drugs

  5. Eukaryotic translation initiation factor 2B-beta (eIF2Bβ), a new class of plant virus resistance gene.

    Science.gov (United States)

    Shopan, Jannat; Mou, Haipeng; Zhang, Lili; Zhang, Changtong; Ma, Weiwei; Walsh, John A; Hu, Zhongyuan; Yang, Jinghua; Zhang, Mingfang

    2017-06-01

    Recessive resistances to plant viruses in the Potyvirus genus have been found to be based on mutations in the plant eukaryotic translation initiation factors, eIF4E and eIF4G or their isoforms. Here we report that natural, monogenic recessive resistance to the Potyvirus Turnip mosaic virus (TuMV) has been found in a number of mustard (Brassica juncea) accessions. Bulked segregant analysis and sequencing of resistant and susceptible plant lines indicated the resistance is controlled by a single recessive gene, recessive TuMV resistance 03 (retr03), an allele of the eukaryotic translation initiation factor 2B-beta (eIF2Bβ). Silencing of eIF2Bβ in a TuMV-susceptible mustard plant line and expression of eIF2Bβ from a TuMV-susceptible line in a TuMV-resistant mustard plant line confirmed the new resistance mechanism. A functional copy of a specific allele of eIF2Bβ is required for efficient TuMV infection. eIF2Bβ represents a new class of virus resistance gene conferring resistance to any pathogen. eIF2B acts as a guanine nucleotide exchange factor (GEF) for its GTP-binding protein partner eIF2 via interaction with eIF2·GTP at an early step in translation initiation. Further genotyping indicated that a single non-synonymous substitution (A120G) in the N-terminal region of eIF2Bβ was responsible for the TuMV resistance. A reproducible marker has been developed, facilitating marker-assisted selection for TuMV resistance in B. juncea. Our findings provide a new target for seeking natural resistance to potyviruses and new opportunities for the control of potyviruses using genome editing techniques targeted on eIF2Bβ. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  6. A role for eukaryotic translation initiation factor 2B (eIF2B) in taste memory consolidation and in thermal control establishment during the critical period for sensory development.

    Science.gov (United States)

    Tirosh, Sharon; Elkobi, Alina; Rosenblum, Kobi; Meiri, Noam

    2007-05-01

    All species exhibit critical periods for sensory development, yet very little is known about the molecules involved in the changes in the network wiring that underlies this process. Here the role of transcription regulation of the translation machinery was determined by evaluating the expression of eIF2Bepsilon, an essential component of translation initiation, in both taste-preference development and thermal control establishment in chicks. Analysis of the expression pattern of this gene after passive-avoidance training revealed clear induction of eIF2Bepsilon in both the mesopallium intermediomediale (IMM) and in the striatum mediale (StM). In addition, a correlation was found between the concentration of methylanthranilate (MeA), which was the malaise substrate in the passive-avoidance training procedure, the duration of memory, and the expression level of eIF2Bepsilon. Training chicks on a low concentration of MeA induced short-term memory and low expression level of eIF2Bepsilon, whereas a high concentration of MeA induced long-term memory and a high expression level of eIF2Bepsilon in both the IMM and StM. Furthermore, eIF2Bepsilon-antisense "knock-down" not only reduced the amount of eIF2Bepsilon but also attenuated taste memory formation. In order to determine whether induction of eIF2Bepsilon is a general feature of neuronal plasticity, we checked whether it was induced in other forms of neuronal plasticity, with particular attention to its role in temperature control establishment, which represents hypothalamic-related plasticity. It was established that eIF2Bepsilon-mRNA was induced in the preopotic anterior hypothalamus during heat conditioning. Taken together, these results correlate eIF2Bepsilon with sensory development.

  7. A Yeast Purification System for Human Translation Initiation Factors eIF2 and eIF2B epsilon and Their Use in the Diagnosis of CACH/VWM Disease

    NARCIS (Netherlands)

    de Almeida, R.A.; Fogli, A.; Gaillard, M.; Scheper, G.C.; Boesflug-Tanguy, O.; Pavitt, G.D.

    2013-01-01

    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

  8. Initiation factor eIF2B not p70 S6 kinase is involved in the activation of the PI-3K signalling pathway induced by the v=src oncogene

    Czech Academy of Sciences Publication Activity Database

    Vojtěchová, Martina; Šloncová, Eva; Kučerová, Dana; Jiřička, Jaroslav; Sovová, Vlasta; Tuháčková, Zdena

    2003-01-01

    Roč. 543, 1-3 (2003), s. 81-86 ISSN 0014-5793 R&D Projects: GA ČR GV312/96/K205; GA ČR GA301/00/0269; GA MZd NC5428 Institutional research plan: CEZ:AV0Z5052915 Keywords : phosphoinositide 3-kinase signalling pathway * mRNA translation * 70 kDa ribosomal protein S6 kinase Subject RIV: CE - Biochemistry Impact factor: 3.609, year: 2003

  9. 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

    Science.gov (United States)

    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

    2010-01-01

    Recycling of eIF2-GDP to the GTP-bound form constitutes a core essential, regulated step in eukaryotic translation. This reaction is mediated by eIF2B, a heteropentameric factor with important links to human disease. eIF2 in the GTP-bound form binds to methionyl initiator tRNA to form a ternary complex, and the levels of this ternary complex can be a critical determinant of the rate of protein synthesis. Here we show that eIF2B serves as the target for translation inhibition by various fusel alcohols in yeast. Fusel alcohols are endpoint metabolites from amino acid catabolism, which signal nitrogen scarcity. We show that the inhibition of eIF2B leads to reduced ternary complex levels and that different eIF2B subunit mutants alter fusel alcohol sensitivity. A DNA tiling array strategy was developed that overcame difficulties in the identification of these mutants where the phenotypic distinctions were too subtle for classical complementation cloning. Fusel alcohols also lead to eIF2α dephosphorylation in a Sit4p-dependent manner. In yeast, eIF2B occupies a large cytoplasmic body where guanine nucleotide exchange on eIF2 can occur and be regulated. Fusel alcohols impact on both the movement and dynamics of this 2B body. Overall, these results confirm that the guanine nucleotide exchange factor, eIF2B, is targeted by fusel alcohols. Moreover, they highlight a potential connection between the movement or integrity of the 2B body and eIF2B regulation. PMID:20444979

  10. Social media use in B2B. A study on how social media is used in the initial phase of building relationships.

    OpenAIRE

    Kvick-Nastaj, Nicole; Poblete, Daisy

    2013-01-01

    There has been scarce research into the topic of B2B in the context of social media. Due to this, the aim of this study was to explore how social media is used within B2B in the initial phase of building relationships. The research questions regarded; attracting new customers, which channels that were used and potential drawbacks of using social media. An analytical framework was presented with the factors reputation, familiarity, similarity and knowledge of alternatives from literature withi...

  11. Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.

    Science.gov (United States)

    Tsai, Jordan C; Miller-Vedam, Lakshmi E; Anand, Aditya A; Jaishankar, Priyadarshini; Nguyen, Henry C; Renslo, Adam R; Frost, Adam; Walter, Peter

    2018-03-30

    Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo-electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

    Science.gov (United States)

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

    2016-02-01

    Neuroblastoma is an embryonal pediatric tumor that originates from the developing sympathetic nervous system and shows a broad range of clinical behavior, ranging from fatal progression to differentiation into benign ganglioneuroma. In experimental neuroblastoma systems, retinoic acid (RA) effectively induces neuronal differentiation, and RA treatment has been therefore integrated in current therapies. However, the molecular mechanisms underlying differentiation are still poorly understood. We here investigated the role of transcription factor activating protein 2 beta (TFAP2B), a key factor in sympathetic nervous system development, in neuroblastoma pathogenesis and differentiation. Microarray analyses of primary neuroblastomas (n = 649) demonstrated that low TFAP2B expression was significantly associated with unfavorable prognostic markers as well as adverse patient outcome. We also found that low TFAP2B expression was strongly associated with CpG methylation of the TFAP2B locus in primary neuroblastomas (n = 105) and demethylation with 5-aza-2'-deoxycytidine resulted in induction of TFAP2B expression in vitro, suggesting that TFAP2B is silenced by genomic methylation. Tetracycline inducible re-expression of TFAP2B in IMR-32 and SH-EP neuroblastoma cells significantly impaired proliferation and cell cycle progression. In IMR-32 cells, TFAP2B induced neuronal differentiation, which was accompanied by up-regulation of the catecholamine biosynthesizing enzyme genes DBH and TH, and down-regulation of MYCN and REST, a master repressor of neuronal genes. By contrast, knockdown of TFAP2B by lentiviral transduction of shRNAs abrogated RA-induced neuronal differentiation of SH-SY5Y and SK-N-BE(2)c neuroblastoma cells almost completely. Taken together, our results suggest that TFAP2B is playing a vital role in retaining RA responsiveness and mediating noradrenergic neuronal differentiation in neuroblastoma. Copyright © 2015 Federation of European Biochemical Societies

  13. A Cross-Industry Review of B2B Critical Success Factors.

    Science.gov (United States)

    Eid, Riyad; Trueman, Myfanwy; Ahmed, Abdel Moneim

    2002-01-01

    Presents a comprehensive review of B2B (business-to- business) international Internet marketing and identifies 21 critical success factors in five categories: marketing strategy, including management support, strategic goals, and collaboration; Web site factors, including Web site design; global factors, including multilanguage sites and cultural…

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

    Directory of Open Access Journals (Sweden)

    Sareh Ahmad Khan Beige

    2015-01-01

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

  15. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Science.gov (United States)

    2010-07-01

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

  16. Performance in the FRCR (UK) Part 2B examination: Analysis of factors associated with success

    International Nuclear Information System (INIS)

    Hawtin, K.E.; Williams, H.R.T.; McKnight, L.; Booth, T.C.

    2014-01-01

    Aim: To assess factors that influence pass rates and examination scores in the Fellowship of the Royal College of Radiologists (FRCR) 2B examination. Materials and methods: 2238 attempts at the FRCR 2B examination were evaluated between Spring 2006 and Spring 2010. Pass rates and examination scores were analysed by gender and ethnicity, and the influence of factors such as radiology training (UK versus non-UK), sitting (Spring versus Autumn), and the presence of an undergraduate or postgraduate degree were examined. Results: 1571 candidates made 2238 examination attempts, with an overall pass rate of 59.4% (63.1% at first attempt). 66.2% entrants were male; 48.8% attempts were by candidates from a UK radiology training scheme. UK candidates were significantly more likely to pass than non-UK candidates (p < 0.0001). White candidates were more likely to pass at first or second attempt than non-white candidates (p < 0.0001), but when restricted to UK entrants ethnicity did not influence success at first attempt. Overall, females were more successful than males (p < 0.001). Presence of an undergraduate (p = 0.19) or postgraduate (p = 0.80) degree did not affect pass rate at first attempt for UK candidates. However, logistic regression demonstrated that the only significant factor influencing pass rates at first attempt was whether radiology training was undertaken in the UK (p < 0.0001). A trend towards increased pass rates in autumn sittings was seen (p = 0.06), but ethnicity (p = 0.99) and gender (p = 0.41) were not significant factors. Conclusion: The FRCR 2B examination is non-discriminatory for UK candidates with respect to gender and ethnicity. Poorer performance of non-UK trained candidates is a consistent outcome in the literature. - Highlights: • Factors influencing pass rates and scores in FRCR 2B examination were assessed. • UK candidates are more likely to pass than non-UK candidates. • There is no effect of gender or ethnicity on UK

  17. Sulfate as a pivotal factor in regulation of Serratia sp. strain S2B pigment biosynthesis.

    Science.gov (United States)

    Rastegari, Banafsheh; Karbalaei-Heidari, Hamid Reza

    2016-10-01

    In the present work, we investigated the prodiginine family as secondary metabolite members. Bacterial strain S2B, with the ability to produce red pigment, was isolated from the Sarcheshmeh copper mine in Iran. 16S rDNA gene sequencing revealed that the strain was placed in the Serratia genus. Pigment production was optimized using low-cost culture medium and the effects of various physicochemical factors were studied via statistical approaches. Purification of the produced pigment by silica gel column chromatography showed a strong red pigment fraction and a weaker orange band. Mass spectrometry, FT-IR spectroscopy and (1)H NMR analysis revealed that the red pigment was prodigiosin and the orange band was a prodigiosin-like analog, with molecular weights of 323 and 317 Da, respectively. Genotoxicity and cytotoxicity studies confirmed their membership in the prodiginine family. Analysis of the production pattern of the pigments in the presence of different concentrations of ammonium salts revealed the role of sulfate as an important factor in regulation of the pigment biosynthesis pathway. Overall, the data showed that regulation of the pigment biosynthesis pathway in Serratia sp. strain S2B was affected by inorganic micronutrients, particularly the sulfate ions. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  18. Fibroblast growth factor 10-fibroblast growth factor receptor 2b mediated signaling is not required for adult glandular stomach homeostasis.

    Directory of Open Access Journals (Sweden)

    Allison L Speer

    Full Text Available The signaling pathways that are essential for gastric organogenesis have been studied in some detail; however, those that regulate the maintenance of the gastric epithelium during adult homeostasis remain unclear. In this study, we investigated the role of Fibroblast growth factor 10 (FGF10 and its main receptor, Fibroblast growth factor receptor 2b (FGFR2b, in adult glandular stomach homeostasis. We first showed that mouse adult glandular stomach expressed Fgf10, its receptors, Fgfr1b and Fgfr2b, and most of the other FGFR2b ligands (Fgf1, Fgf7, Fgf22 except for Fgf3 and Fgf20. Fgf10 expression was mesenchymal whereas FGFR1 and FGFR2 expression were mostly epithelial. Studying double transgenic mice that allow inducible overexpression of Fgf10 in adult mice, we showed that Fgf10 overexpression in normal adult glandular stomach increased epithelial proliferation, drove mucous neck cell differentiation, and reduced parietal and chief cell differentiation. Although a similar phenotype can be associated with the development of metaplasia, we found that Fgf10 overexpression for a short duration does not cause metaplasia. Finally, investigating double transgenic mice that allow the expression of a soluble form of Fgfr2b, FGF10's main receptor, which acts as a dominant negative, we found no significant changes in gastric epithelial proliferation or differentiation in the mutants. Our work provides evidence, for the first time, that the FGF10-FGFR2b signaling pathway is not required for epithelial proliferation and differentiation during adult glandular stomach homeostasis.

  19. Agile text mining for the 2014 i2b2/UTHealth Cardiac risk factors challenge.

    Science.gov (United States)

    Cormack, James; Nath, Chinmoy; Milward, David; Raja, Kalpana; Jonnalagadda, Siddhartha R

    2015-12-01

    This paper describes the use of an agile text mining platform (Linguamatics' Interactive Information Extraction Platform, I2E) to extract document-level cardiac risk factors in patient records as defined in the i2b2/UTHealth 2014 challenge. The approach uses a data-driven rule-based methodology with the addition of a simple supervised classifier. We demonstrate that agile text mining allows for rapid optimization of extraction strategies, while post-processing can leverage annotation guidelines, corpus statistics and logic inferred from the gold standard data. We also show how data imbalance in a training set affects performance. Evaluation of this approach on the test data gave an F-Score of 91.7%, one percent behind the top performing system. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. New function of the adaptor protein SH2B1 in brain-derived neurotrophic factor-induced neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Chien-Hung Shih

    Full Text Available Neurite outgrowth is an essential process for the establishment of the nervous system. Brain-derived neurotrophic factor (BDNF binds to its receptor TrkB and regulates axonal and dendritic morphology of neurons through signal transduction and gene expression. SH2B1 is a signaling adaptor protein that regulates cellular signaling in various physiological processes. The purpose of this study is to investigate the role of SH2B1 in the development of the central nervous system. In this study, we show that knocking down SH2B1 reduces neurite formation of cortical neurons whereas overexpression of SH2B1β promotes the development of hippocampal neurons. We further demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth and signaling using the established PC12 cells stably expressing TrkB, SH2B1β or SH2B1β mutants. Our data indicate that overexpressing SH2B1β enhances BDNF-induced MEK-ERK1/2, and PI3K-AKT signaling pathways. Inhibition of MEK-ERK1/2 and PI3K-AKT pathways by specific inhibitors suggest that these two pathways are required for SH2B1β-promoted BDNF-induced neurite outgrowth. Moreover, SH2B1β enhances BDNF-stimulated phosphorylation of signal transducer and activator of transcription 3 at serine 727. Finally, our data indicate that the SH2 domain and tyrosine phosphorylation of SH2B1β contribute to BDNF-induced signaling pathways and neurite outgrowth. Taken together, these findings demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth through enhancing pathways involved MEK-ERK1/2 and PI3K-AKT.

  1. Transforming growth factor type β can act as a potent competence factor for AKR-2B cells

    International Nuclear Information System (INIS)

    Goustin, A.S.; Nuttall, G.A.; Leof, E.B.; Ranganathan, G.; Moses, H.L.

    1987-01-01

    Transforming growth factor type β (TGFβ) is a pleiotropic regulator of cell growth with specific high-affinity cell-surface receptors on a large number of cells; its mechanism of action, however, is poorly defined. In this report, the authors utilized the mouse fibroblast line AKR-2B to explore the question of the temporal requirements during the cell cycle in regard to both the growth inhibitory and the growth stimulatory action of TGFβ. The results indicate that AKR-2B cells are most sensitive to the inhibitory action of TGFβ during early to mid-G 1 . In addition, TGFβ need be present only briefly in order to exert its inhibitory effect on EGF-induced DNA synthesis. Likewise, the stimulatory effect of TGFβ in the absence of EGF requires only an equally brief exposure to TGFβ. Use of homogeneous 125 I-labeled TGFβ in a cell-binding assay demonstrates that TGFβ bound to cell-surface receptors can readily exchange into the culture medium, helping to rule out the possibility that persistent receptor-bound TGFβ is the source of a continuous stimulus. The data indicate that TGFβ exposure induces a stable state in the cell similar to but distinct from the state of competence induced by platelet-derived growth factor (PDGF)

  2. The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF

    DEFF Research Database (Denmark)

    Beyer, Sophie; Kristensen, Malene Maag; Jensen, Kim Steen

    2008-01-01

    of these modifications is exerted by histone methyltransferases and the recently discovered histone demethylases. Here we show that the hypoxia-inducible factor HIF-1a binds to specific recognition sites in the genes encoding the jumonji family histone demethylases JMJD1A and JMJD2B and induces their expression....... Accordingly, hypoxic cells express elevated levels of JMJD1A and JMJD2B mRNA and protein. Furthermore, we find increased expression of JMJD1A and JMJD2B in renal cancer cells that have lost the von Hippel Lindau tumor suppressor protein VHL and therefore display a deregulated expression of HIF. Studies...... on ectopically expressed JMJD1A and JMJD2B indicate that both proteins retain their histone lysine demethylase activity in hypoxia and thereby might impact the hypoxic gene expression program....

  3. Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Chiaki Okuse; Hiroshi Yotsuyanagi; Yoshihiko Nagase; Yuhtaro Kobayashi; Kiyomi Yasuda; Kazuhiko Koike; Shiro Iino; Michihiro Suzuki; Fumio Itoh

    2006-01-01

    AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy.METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy.RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%)despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension,or pretreatment arteriosclerotic changes in the optic fundj. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P=0.004,OR=245.918, 95% CI=5.6-10786.2).CONCLUSION: Retinopathy associated with combination therapy of interferon α-2b and ribavirin tends to develop in patients with hypertension.

  4. Adenosine inhibits neutrophil vascular endothelial growth factor release and transendothelial migration via A2B receptor activation.

    LENUS (Irish Health Repository)

    Wakai, A

    2012-02-03

    The effects of adenosine on neutrophil (polymorphonuclear neutrophils; PMN)-directed changes in vascular permeability are poorly characterized. This study investigated whether adenosine modulates activated PMN vascular endothelial growth factor (vascular permeability factor; VEGF) release and transendothelial migration. PMN activated with tumour necrosis factor-alpha (TNF-alpha, 10 ng\\/mL) were incubated with adenosine and its receptor-specific analogues. Culture supernatants were assayed for VEGF. PMN transendothelial migration across human umbilical vein endothelial cell (HUVEC) monolayers was assessed in vitro. Adhesion molecule receptor expression was assessed flow cytometrically. Adenosine and some of its receptor-specific analogues dose-dependently inhibited activated PMN VEGF release. The rank order of potency was consistent with the affinity profile of human A2B receptors. The inhibitory effect of adenosine was reversed by 3,7-dimethyl-1-propargylxanthine, an A2 receptor antagonist. Adenosine (100 microM) or the A2B receptor agonist 5\\'-N-ethylcarboxamidoadenosine (NECA, 100 microM) significantly reduced PMN transendothelial migration. However, expression of activated PMN beta2 integrins and HUVEC ICAM-1 were not significantly altered by adenosine or NECA. Adenosine attenuates human PMN VEGF release and transendothelial migration via the A2B receptor. This provides a novel target for the modulation of PMN-directed vascular hyperpermeability in conditions such as the capillary leak syndrome.

  5. Empirical testing of selected critical success factors in CRM implementation projects - A study of SMEs in the B2B sector

    OpenAIRE

    Röschmann, Kathrin; Ziyadullaeva, Muhayyo

    2011-01-01

    Purpose:The purpose of this thesis is to describe and analyze critical success factors of CRM implementation projects with a special focus on SME’s in the B2B sector.  Method: This study is based on quantitative research using survey method.  Target Audience: SMEs of B2B business, which are planning to implement a CRM system Academic audience, which is interested in CRM implementation with focus on SME.  Conclusion: There are various critical success factors in CRM implementation projects and...

  6. THE RISK FACTORS FOR INITIAL REPRODUCTIVE LOSS

    Directory of Open Access Journals (Sweden)

    Екатерина Игоревна Лебедева

    2017-09-01

    Conclusion. Mixed somatic and gynecological pathology, abnormalities in hemostasis, combination of inherited and acquired thrombogenic risk factors dominates in women with initial reproductive loss, though only 37,3 % such pregnancies have favorable outcome.

  7. Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

    International Nuclear Information System (INIS)

    Fu, Jiamei; Wang, Juan; Wang, Xiangdong; Wang, Ping; Xu, Jinping; Zhou, Cuiping; Bai, Yang; Shao, Chunlin

    2016-01-01

    Highlights: • Radiation damage of Beas-2B cells was enhanced by macrophage-mediated bilateral bystander responses. • Expressions of TNF-α and IL-8 in the α-irradiated Beas-2B cells were dependent on ERK and p38 pathways. • The neighboring U937 cells further increased the generation of TNF-α and IL-8 in the α-irradiated Beas-2B cells. • NF-κB dependent upregulation of TNF-α and IL-8 was induced in the bystander U937 cells. - Abstract: Although radiation induced bystander effects (RIBE) have been investigated for decades for their potential health risk, the underlying gene regulation is still largely unclear, especially the roles of immune system and inflammatory response in RIBE. In the present study, macrophage U937 cells and epithelial Beas-2B cells were co-cultured to disclose the cascades of bystander signaling factors and intercellular communications. After α-particle irradiation, both ERK and p38 pathways were activated in Beas-2B cells and were associated with the autocrine and paracrine signaling of TNF-α and IL-8, resulting in direct damage to the irradiated cells. Similar upregulation of TNF-α and IL-8 was induced in the bystander U937 cells after co-culture with α-irradiated Beas-2B cells. This upregulation was dependent on the activation of NF-κB pathway and was responsible for the enhanced damage of α-irradiated Beas-2B cells. Interestingly, the increased expressions of TNF-α and IL-8 mRNAs in the bystander U937 cells were clearly relayed on the activated ERK and p38 pathways in the irradiated Beas-2B cells, and the upregulation of TNF-α and IL-8 mRNAs in co-cultured Beas-2B cells was also partly due to the activated NF-κB pathway in the bystander U937 cells. With the pretreatment of U0126 (MEK1/2 inhibitor), SB203580 (p38 inhibitor) or BAY 11-7082 (NF-κB inhibitor), the aggravated damage in the α-irradiated Beas-2B cells could be largely alleviated. Our results disclosed novel signaling cascades of macrophage-mediated bilateral

  8. Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Jiamei; Wang, Juan; Wang, Xiangdong; Wang, Ping; Xu, Jinping; Zhou, Cuiping; Bai, Yang; Shao, Chunlin, E-mail: clshao@shmu.edu.cn

    2016-07-15

    Highlights: • Radiation damage of Beas-2B cells was enhanced by macrophage-mediated bilateral bystander responses. • Expressions of TNF-α and IL-8 in the α-irradiated Beas-2B cells were dependent on ERK and p38 pathways. • The neighboring U937 cells further increased the generation of TNF-α and IL-8 in the α-irradiated Beas-2B cells. • NF-κB dependent upregulation of TNF-α and IL-8 was induced in the bystander U937 cells. - Abstract: Although radiation induced bystander effects (RIBE) have been investigated for decades for their potential health risk, the underlying gene regulation is still largely unclear, especially the roles of immune system and inflammatory response in RIBE. In the present study, macrophage U937 cells and epithelial Beas-2B cells were co-cultured to disclose the cascades of bystander signaling factors and intercellular communications. After α-particle irradiation, both ERK and p38 pathways were activated in Beas-2B cells and were associated with the autocrine and paracrine signaling of TNF-α and IL-8, resulting in direct damage to the irradiated cells. Similar upregulation of TNF-α and IL-8 was induced in the bystander U937 cells after co-culture with α-irradiated Beas-2B cells. This upregulation was dependent on the activation of NF-κB pathway and was responsible for the enhanced damage of α-irradiated Beas-2B cells. Interestingly, the increased expressions of TNF-α and IL-8 mRNAs in the bystander U937 cells were clearly relayed on the activated ERK and p38 pathways in the irradiated Beas-2B cells, and the upregulation of TNF-α and IL-8 mRNAs in co-cultured Beas-2B cells was also partly due to the activated NF-κB pathway in the bystander U937 cells. With the pretreatment of U0126 (MEK1/2 inhibitor), SB203580 (p38 inhibitor) or BAY 11-7082 (NF-κB inhibitor), the aggravated damage in the α-irradiated Beas-2B cells could be largely alleviated. Our results disclosed novel signaling cascades of macrophage-mediated bilateral

  9. Photo-initiated crosslinking extends mapping of the protein-protein interface to membrane-embedded portions of cytochromes P450 2B4 and b(5)

    Czech Academy of Sciences Publication Activity Database

    Ječmen, Tomáš; Ptáčková, Renata; Černá, V.; Dračínská, H.; Hodek, P.; Stiborová, M.; Hudeček, J.; Šulc, Miroslav

    2015-01-01

    Roč. 89, NOV 2015 (2015), s. 128-137 ISSN 1046-2023 R&D Projects: GA ČR(CZ) GAP207/12/0627 Grant - others:OPPC(XE) CZ.2.16/3.1.00/24023 Institutional support: RVO:61388971 Keywords : Protein-protein interaction * Trans-membrane segments * Photo-initiated crosslinking Subject RIV: CE - Biochemistry Impact factor: 3.503, year: 2015

  10. Marketing Optimization for B2B Market

    OpenAIRE

    Kaynova Tatyana V.

    2012-01-01

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

  11. The MSX1 homeobox transcription factor is a downstream target of PHOX2B and activates the Delta-Notch pathway in neuroblastoma

    International Nuclear Information System (INIS)

    Revet, Ingrid; Huizenga, Gerda; Chan, Alvin; Koster, Jan; Volckmann, Richard; Sluis, Peter van; Ora, Ingrid; Versteeg, Rogier; Geerts, Dirk

    2008-01-01

    Neuroblastoma is an embryonal tumour of the peripheral sympathetic nervous system (SNS). One of the master regulator genes for peripheral SNS differentiation, the homeobox transcription factor PHOX2B, is mutated in familiar and sporadic neuroblastomas. Here we report that inducible expression of PHOX2B in the neuroblastoma cell line SJNB-8 down-regulates MSX1, a homeobox gene important for embryonic neural crest development. Inducible expression of MSX1 in SJNB-8 caused inhibition of both cell proliferation and colony formation in soft agar. Affymetrix micro-array and Northern blot analysis demonstrated that MSX1 strongly up-regulated the Delta-Notch pathway genes DLK1, NOTCH3, and HEY1. In addition, the proneural gene NEUROD1 was down-regulated. Western blot analysis showed that MSX1 induction caused cleavage of the NOTCH3 protein to its activated form, further confirming activation of the Delta-Notch pathway. These experiments describe for the first time regulation of the Delta-Notch pathway by MSX1, and connect these genes to the PHOX2B oncogene, indicative of a role in neuroblastoma biology. Affymetrix micro-array analysis of a neuroblastic tumour series consisting of neuroblastomas and the more benign ganglioneuromas showed that MSX1, NOTCH3 and HEY1 are more highly expressed in ganglioneuromas. This suggests a block in differentiation of these tumours at distinct developmental stages or lineages

  12. GRIN2B encephalopathy

    DEFF Research Database (Denmark)

    Platzer, Konrad; Yuan, Hongjie; Schuetz, Hannah

    2017-01-01

    BACKGROUND: We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. METHODS: Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research c...

  13. A novel cell division factor from tobacco 2B-13 cells that induced cell division in auxin-starved tobacco BY-2 cells

    Science.gov (United States)

    Shimizu, Takashi; Eguchi, Kentaro; Nishida, Ikuo; Laukens, Kris; Witters, Erwin; van Onckelen, Harry; Nagata, Toshiyuki

    2006-06-01

    Effects of auxin as plant hormones are widespread; in fact in almost all aspects of plant growth and development auxin plays a pivotal role. Although auxin is required for propagating cell division in plant cells, its effect upon cell division is least understood. If auxin is depleted from the culture medium, cultured cells cease to divide. It has been demonstrated in this context that the addition of auxin to auxin-starved nondividing tobacco BY-2 cells induced semisynchronous cell division. On the other hand, there are some cell lines, named habituated cells, that can grow without auxin. The cause and reason for the habituated cells have not been clarified. A habituated cell line named 2B-13 is derived from the tobacco BY-2 cell line, which has been most intensively studied among plant cell lines. When we tried to find the difference between two cell lines of BY-2 and 2B-13 cells, we found that the addition of culture filtrated from the auxin-habituated 2B-13 cells induced semisynchronous cell division in auxin-starved BY-2 cells. The cell division factor (CDF) that is responsible for inducing cell division in auxin-starved BY-2 cells was purified to near-homogeneity by sequential passage through a hydroxyapatite column, a ConA Sepharose column and a Sephadex gel filtration column. The resulting purified fraction appeared as a single band of high molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels by silver staining and was able to induce cell division in auxin-starved BY-2 cells. Identification of the protein by MALD-TOF-MS/MS revealed that it is structurally related to P-glycoprotein from Gossypioides kirkii, which belongs to ATP-binding cassette (ABC)-transporters. The significance of CDF as a possible ABC-transporter is discussed in relationship to auxin-autotrophic growth and auxin-signaling pathway.

  14. Factors influencing initiation of breast-feeding.

    Science.gov (United States)

    Ekwo, E E; Dusdieker, L B; Booth, B M

    1983-04-01

    We used the critical incidence method to study factors motivating 33 primigravidas and 39 multigravidas to initiate breast-feeding of their infants. Women chose breast-feeding because they believed that it would provide protection to the infant against infection, establish maternal-infant bonding, was convenient, provided better nutrition than cow's milk formula, was emotionally satisfying, and was the natural way to feed infants. The decision to breast-feed was made well in advance of pregnancy by primigravidas and shortly before pregnancy by multigravidas. Friends who had successfully nursed infants were as influential as immediate family members in influencing our study subjects in their decision to breast-feed. Prenatal counseling, though important, may not be the optimal period for motivating women to breast-feed.

  15. Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors.

    Science.gov (United States)

    Zhang, Le; Wang, Gongming; Ma, Jinben; Liu, Chengxiao; Liu, Xijiang; Zhan, Yufeng; Zhang, Mengyuan

    2016-10-01

    The rostral anterior cingulate cortex (rACC) plays an important role in pain affect. Previous investigations have reported that the rACC mediates the negative affective component of inflammatory pain and contributed to the aversive state of nerve injury-induced neuropathic pain. Brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator in the adult brain, is believed to play a role in the development and maintenance of inflammatory and neuropathic pain in the spinal cord. However, whether and how BDNF in the rACC regulates pain-related aversion due to peripheral nerve injury is largely unknown. Behaviorally, using conditioned place preference (CPP) training in rats, which is thought to reveal spontaneous pain-related aversion, we found that CPP was acquired following spinal clonidine in rats with partial sciatic nerve transection. Importantly, BDNF was upregulated within the rACC in of rats with nerve injury and enhanced the CPP acquisition, while a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely blocked this process. Finally, we demonstrated that the BDNF/TrkB pathway exerted its function by activating the NR2B receptor, which is widely accepted to be a crucial factor contributing to pain affect. In conclusion, our results demonstrate that the BDNF/TrkB-mediated signaling pathway in the rACC is involved in the development of neuropathic spontaneous pain-related aversion and that this process is dependent upon activation of NR2B receptors. These findings suggest that suppression of the BDNF-related signaling pathway in the rACC may provide a novel strategy to overcome pain-related aversion. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. MASCARA-2 b

    DEFF Research Database (Denmark)

    Talens, G. J. J.; Justesen, A. B.; Albrecht, S.

    2018-01-01

    In this paper we present MASCARA-2 b, a hot Jupiter transiting the m(v) = 7.6 A2 star HD 185603. Since early 2015, MASCARA has taken more than 1.6 million flux measurements of the star, corresponding to a total of almost 3000 h of observations, revealing a periodic dimming in the flux with a depth...

  17. Histone demethylase JMJD2B functions as a co-factor of estrogen receptor in breast cancer proliferation and mammary gland development.

    Directory of Open Access Journals (Sweden)

    Masahito Kawazu

    2011-03-01

    Full Text Available Estrogen is a key regulator of normal function of female reproductive system and plays a pivotal role in the development and progression of breast cancer. Here, we demonstrate that JMJD2B (also known as KDM4B constitutes a key component of the estrogen signaling pathway. JMJD2B is expressed in a high proportion of human breast tumors, and that expression levels significantly correlate with estrogen receptor (ER positivity. In addition, 17-beta-estradiol (E2 induces JMJD2B expression in an ERα dependent manner. JMJD2B interacts with ERα and components of the SWI/SNF-B chromatin remodeling complex. JMJD2B is recruited to ERα target sites, demethylates H3K9me3 and facilitates transcription of ER responsive genes including MYB, MYC and CCND1. As a consequence, knockdown of JMJD2B severely impairs estrogen-induced cell proliferation and the tumor formation capacity of breast cancer cells. Furthermore, Jmjd2b-deletion in mammary epithelial cells exhibits delayed mammary gland development in female mice. Taken together, these findings suggest an essential role for JMJD2B in the estrogen signaling, and identify JMJD2B as a potential therapeutic target in breast cancer.

  18. AN EXPLORATORY STUDY OF FACTORS AFFECTING ADOPTION AND IMPLEMENTATION OF B2B E-COMMERCE IN AUSTRALIAN HEALTH CARE ORGANIZATIONS

    OpenAIRE

    Chad Lin; Yu-An Huang; Geoffrey Jalleh; Ying-Chieh Liu; Mei-Lien Tung

    2010-01-01

    For the health care industry, the adoption and implementation of business-to-business (B2B) electronic commerce (e-commerce) systems can lead to many benefits, such as an increased accessibility to providers, reduction in supply chain and inventory costs, and reduced medical errors. However, despite high expectations for realizing the benefits of B2B e-commerce in health care, its adoption remains poorly understood and is a relatively under-researched area. Although B2B e-commerce provides th...

  19. Multiple Sclerosis and EIF2B5: A Paradox or a Missing Link.

    Science.gov (United States)

    Zahoor, Insha; Haq, Ehtishamul; Asimi, Ravouf

    2017-01-01

    Multiple sclerosis (MS) is an encumbering inflammatory condition of the central nervous system (CNS) caused by axonal demyelination. There is sufficient evidence suggesting role of eukaryotic translation initiation factor 2B (EIF2B) gene family encoding the five subunits of eIF2B complex-α, β, γ, δ and ε respectively, in causing vanishing white matter (VWM) disease of the brain. Incidentally researchers have proposed overlapping between MS and VWM in terms of clinical, biochemical and genetic aspects, which incited us to write this chapter to explore the association between EIF2B5 and MS. eIF2B plays an essential role in translation initiation and its regulation in eukaryotes. Among EIF2B gene family, EIF2B5 gene encodes the catalytic and a crucial epsilon subunit of the eIF2B protein as most of the alterations have been found in this gene. The recent findings on the association between EIF2B5 and MS susceptibility point towards unfathomable and contentious role of EIF2B5 in MS development. This chapter briefly reviews the insights gleaned from recent studies conducted in understanding the association between EIF2B5 and MS risk. The need of hour is to conduct large scale conclusive studies aimed at expounding the mechanisms behind this relationship.

  20. J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

    Science.gov (United States)

    Moore, Erika M; Swerdlow, Steven H; Gibson, Sarah E

    2017-10-01

    Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Heat shock factors HsfB1 and HsfB2b are involved in the regulation of Pdf1.2 expression and pathogen resistance in Arabidopsis.

    Science.gov (United States)

    Kumar, Mukesh; Busch, Wolfgang; Birke, Hannah; Kemmerling, Birgit; Nürnberger, Thorsten; Schöffl, Friedrich

    2009-01-01

    In order to assess the functional roles of heat stress-induced class B-heat shock factors in Arabidopsis, we investigated T-DNA knockout mutants of AtHsfB1 and AtHsfB2b. Micorarray analysis of double knockout hsfB1/hsfB2b plants revealed as strong an up-regulation of the basal mRNA-levels of the defensin genes Pdf1.2a/b in mutant plants. The Pdf expression was further enhanced by jasmonic acid treatment or infection with the necrotrophic fungus Alternaria brassicicola. The single mutant hsfB2b and the double mutant hsfB1/B2b were significantly improved in disease resistance after A. brassicicola infection. There was no indication for a direct interaction of Hsf with the promoter of Pdf1.2, which is devoid of perfect HSE consensus Hsf-binding sequences. However, changes in the formation of late HsfA2-dependent HSE binding were detected in hsfB1/B2b plants. This suggests that HsfB1/B2b may interact with class A-Hsf in regulating the shut-off of the heat shock response. The identification of Pdf genes as targets of Hsf-dependent negative regulation is the first evidence for an interconnection of Hsf in the regulation of biotic and abiotic responses.

  2. Towards a Classification of Architecture Initiatives: Outlining the External Factors

    DEFF Research Database (Denmark)

    Hansen, Christian Lindschou; Mortensen, Niels Henrik; Hvam, Lars

    2012-01-01

    or bad, without including the contextual differences. The purpose of the external factors is to improve scoping and goal setting of architecture initiatives, and improve comparability between- and transferability of knowledge from architecture initiatives. The external factors are a first step towards......This paper introduced a set of external factors capturing the contextual differences that set the stage for architecture initiatives. These are derived from a systems theoretical approach recognizing the fact that architecture initiatives should respond the challenges posed by the external...

  3. Skp2B overexpression alters a prohibitin-p53 axis and the transcription of PAPP-A, the protease of insulin-like growth factor binding protein 4.

    Directory of Open Access Journals (Sweden)

    Harish Chander

    Full Text Available We previously reported that the degradation of prohibitin by the SCF(Skp2B ubiquitin ligase results in a defect in the activity of p53. We also reported that MMTV-Skp2B transgenic mice develop mammary gland tumors that are characterized by an increased proteolytic cleavage of the insulin-like growth factor binding protein 4 (IGFBP-4, an inhibitor of IGF signaling. However, whether a link exists between a defect in p53 activity and proteolysis of IGFBP-4 was not established.We analyzed the levels of pregnancy-associated plasma protein A (PAPP-A, the protease of IGFBP-4, in MMTV-Skp2B transgenic mice and found that PAPP-A levels are elevated. Further, we found a p53 binding site in intron 1 of the PAPP-A gene and that both wild type and mutant p53 bind to this site. However, binding of wild type p53 results in the transcriptional repression of PAPP-A, while binding of mutant p53 results in the transcriptional activation of PAPP-A. Since MMTV-Skp2B mice express wild type p53 and yet show elevated levels of PAPP-A, at first, these observations appeared contradictory. However, further analysis revealed that the defect in p53 activity in Skp2B overexpressing cells does not only abolish the activity of wild type of p53 but actually mimics that of mutant p53. Our results suggest that in absence of prohibitin, the half-life of p53 is increased and like mutant p53, the conformation of p53 is denatured.These observations revealed a novel function of prohibitin as a chaperone of p53. Further, they suggest that binding of denatured p53 in intron 1 causes an enhancer effect and increases the transcription of PAPP-A. Therefore, these findings indicate that the defect in p53 function and the increased proteolysis of IGFBP-4, we had observed, represent two components of the same pathway, which contributes to the oncogenic function of Skp2B.

  4. Synthesis of interleukin 6 (interferon-β2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP

    International Nuclear Information System (INIS)

    Zhange, Y.; Lin, J.X.; Vilcek, J.

    1988-01-01

    Interleukin 6 (IL-6; also referred to as interferon-β 2 , 26-kDa protein, and B cell stimulatory factor 2) is a cytokine whose actions include a stimulation of immunoglobulin synthesis, enhancement of B cell growth, and modulation of acute phase protein synthesis by hepatocytes. Synthesis of IL-6 is stimulated by interleukin 1 (IL-1), tumor necrosis factor (TNF), or platelet-derived growth factor. The authors examined the role of the cyclic AMP (cAMP)-dependent signal transduction pathway in IL-6 gene expression. Several activators of adenylate cyclase, including prostaglandin E1, forskolin, and cholera toxin, as well as the phosphodiesterase inhibitor isobutylmethylxanthine and the cAMP analog dibutyryl cAMP, shared the ability to cause a dramatic and sustained increase in IL-6 mRNA levels in human FS-4 fibroblasts. Actinomycin D treatment abolished this enhancement. Treatments that increased intracellular cAMP also stimulated the secretion of the IL-6 protein in a biologically active form. Increased intracellular cAMP appears to enhance IL-6 gene expression by a protein kinase C-independent mechanism because down-regulation of protein kinase C by a chronic exposure of cells to a high dose of 12-O-tetradecanoylphorbol 13-acetate did not abolish the enhancement of IL-6 expression by treatments that increase cAMP. IL-1 and TNF too increased IL-6 mRNA levels by a protein kinase C-independent mechanism. The results suggest a role for the cAMP-dependent pathway(s) in IL-6 gene activation by TNF and IL-1

  5. Factors That Influence Breastfeeding Initiation Among African American Women.

    Science.gov (United States)

    Hinson, Tyonne D; Skinner, Asheley Cockrell; Lich, Kristen Hassmiller; Spatz, Diane L

    2018-05-01

    To examine cultural and socioenvironmental factors that affect breastfeeding initiation among African American women. Qualitative descriptive design and conventional content analysis. A large, inner-city, primary care center affiliated with a 500-bed children's hospital within a large, Northeastern U.S. city. Participants were 34 U.S.-born African American mothers of healthy term infants 0 to 3 months of age. Six focus groups were conducted using a 16-question, scripted interview guide. A number of complex factors that influenced breastfeeding initiation included certain cultural beliefs about sexuality, the influence of family and peer networks, information sources, intentions, and a variety of other barriers and facilitators. Our findings suggest that the decision to initiate breastfeeding is not solely determined by the woman within the African American community. Because this decision is contingent on multiple factors external to the woman, it is important to recognize the role that partners, grandmothers, communities, information sources, and health care providers/organizations play in women's decisions. Implementation of multilevel strategies is critical to increase breastfeeding initiation among African American mothers. Copyright © 2018 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

  6. Contextualized B2B Registries

    OpenAIRE

    Radetzki, U; Boniface, M.J.; Surridge, M.

    2007-01-01

    Abstract. Service discovery is a fundamental concept underpinning the move towards dynamic service-oriented business partnerships. The business process for integrating service discovery and underlying registry technologies into busi-ness relationships, procurement and project management functions has not been examined and hence existing Web Service registries lack capabilities required by business today. In this paper we present a novel contextualized B2B registry that supports dynamic regist...

  7. Factors influencing initiation and duration of breast feeding in Ireland.

    LENUS (Irish Health Repository)

    Leahy-Warren, Patricia

    2013-03-05

    The aim of this research was to identify factors associated with mothers breast feeding and to identify, for those who breast fed, factors associated with breast feeding for as long as planned. BACKGROUND: breast-feeding rates in Ireland are amongst the lowest in Europe. Research evidence indicates that in order for mothers to be successful at breast feeding, multiplicities of supports are necessary for both initiation and duration. The nature of these supports in tandem with other influencing factors requires analysis from an Irish perspective. DESIGN: cross-sectional study involving public health nurses and mothers in Ireland. This paper presents the results of the mothers\\' evaluation. METHOD: mothers (n=1715) with children less than three years were offered a choice of completing the self-report questionnaires online or by mail. Data were analysed and reported using descriptive and inferential statistics. FINDINGS: four in every five participants breast fed their infant and two thirds of them breast fed as long as planned. The multivariate logistic regression analysis identified that third level education, being a first time mother or previously having breast fed, participating online, having more than two public health nurse visits, and having a positive infant feeding attitude were independently and statistically significantly associated with breast feeding. Among mothers who breast fed, being aged at least 35 years, participating online, having a positive infant feeding attitude and high breast-feeding self-efficacy were independently and statistically significantly associated with breast feeding for as long as planned. CONCLUSIONS: findings from this study reinforce health inequalities therefore there needs to be a renewed commitment to reducing health inequalities in relation to breast feeding. RELEVANCE TO CLINICAL PRACTICE: this study has identified factors associated with initiation and duration of breast feeding that are potentially modifiable through

  8. Top Five Physical Design Factors Contributing to Fall Initiation.

    Science.gov (United States)

    Pati, Debajyoti; Lee, Jaehoon; Mihandoust, Sahar; Kazem-Zadeh, Mahshad; Oh, Youngha

    2018-01-01

    To develop a prioritized list of physical design questions/interventions to reduce patient falls by conducting expanded analysis (Phase II) of data generated from a completed study phase. Patient falls continue to be a critical concern for healthcare providers, patients, and families. While substantial literature exist on intrinsic factors, scientific evidence on the role of the physical environment is scarce. Expanded analysis of data from 180 videos of trials conducted in a physical mock-up of a medical-surgical inpatient room in a previously completed study phase. The odds of subject's exhibited postures (predictors) on fall initiation (outcome) were examined in a series of generalized linear mixed effects models. Physical design elements and attributes associated with postures exhibiting statistical significance were examined. Turning, pulling, pushing, and bending forward exhibited the highest odds of contributing to fall initiation in the bathroom. Grabbing, pushing, and sitting exhibited the highest odds of contributing to fall initiation around the patient bed. Physical design elements/attributes associated with the above postures are the (1) bathroom door; (2) bathroom spatial configuration-relative locations of door, toilet bowl, and the sink; (3) door, toilet, and sink hardware; (4) space availability/tightness inside the clinician zone; and (5) spatial configuration around patient bed-relative locations of bed, patient chair, and overbed table, in relation to bathroom door, and resulting obstructions originating from the configuration. Patient falls during unassisted ambulation may be reduced through appropriate examination of these five physical elements/attributes.

  9. Kinase activation through dimerization by human SH2-B.

    Science.gov (United States)

    Nishi, Masahiro; Werner, Eric D; Oh, Byung-Chul; Frantz, J Daniel; Dhe-Paganon, Sirano; Hansen, Lone; Lee, Jongsoon; Shoelson, Steven E

    2005-04-01

    The isoforms of SH2-B, APS, and Lnk form a family of signaling proteins that have been described as activators, mediators, or inhibitors of cytokine and growth factor signaling. We now show that the three alternatively spliced isoforms of human SH2-B readily homodimerize in yeast two-hybrid and cellular transfections assays, and this is mediated specifically by a unique domain in its amino terminus. Consistent with previous reports, we further show that the SH2 domains of SH2-B and APS bind JAK2 at Tyr813. These findings suggested a model in which two molecules of SH2-B or APS homodimerize with their SH2 domains bound to two JAK2 molecules, creating heterotetrameric JAK2-(SH2-B)2-JAK2 or JAK2-(APS)2-JAK2 complexes. We further show that APS and SH2-B isoforms heterodimerize. At lower levels of SH2-B or APS expression, dimerization approximates two JAK2 molecules to induce transactivation. At higher relative concentrations of SH2-B or APS, kinase activation is blocked. SH2-B or APS homodimerization and SH2-B/APS heterodimerization thus provide direct mechanisms for activating and inhibiting JAK2 and other kinases from the inside of the cell and for potentiating or attenuating cytokine and growth factor receptor signaling when ligands are present.

  10. PTK2b function during fertilization of the mouse oocyte

    International Nuclear Information System (INIS)

    Luo, Jinping; McGinnis, Lynda K.; Carlton, Carol; Beggs, Hilary E.; Kinsey, William H.

    2014-01-01

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

  11. PTK2b function during fertilization of the mouse oocyte

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-08-01

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

  12. Factors associated with hookah use initiation among adolescents.

    Science.gov (United States)

    Reveles, Caroline C; Segri, Neuber J; Botelho, Clovis

    2013-01-01

    to determine the prevalence and to analyze factors associated with hookah use initiation among adolescents. This was a cross-sectional study, in which questionnaires were collected from 495 students attending public and private schools of the urban area of the city of Várzea Grande, in the state of Mato Grosso, Brazil. Data were analyzed through descriptive, bivariate, and multiple Poisson regression analyses. A total of 19.7% students had tried a hookah. The use of hookah was associated with the final period of adolescence [PR=6.54 (2.79, 15.32)]; enrollment in private schools [PR=2.23 (1.73, 2.88)]; and presence of work activities [PR=1.80 (1.17, 2.78)]. The proportion of adolescents that had tried a hookah was high. The influence of age, work activities, and class period on smoking initiation using the hookah was observed. Preventive measures encompassing all forms of tobacco smoking should be targeted at adolescents in the school environment, aiming at tobacco use control. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Kovács G.

    2013-04-01

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

  14. B2B or Not to Be: Does B2B E-Commerce Increase Labour Productivity?

    OpenAIRE

    Bertschek, Irene; Fryges, Helmut; Kaiser, Ulrich

    2004-01-01

    We implement an endogeneous switching-regression model for labour productivity and firms' decision to use business-to-business (B2B) e-commerce. Our approach allows B2B usage to affect any parameter of the labour productivity equation and to properly take account of strategic complementarities between the input factors and B2B usage. Empirical evidence from 1,394 German firms shows that firms using B2B e-commerce have a significantly higher output elasticity with respect to ICT-investment and...

  15. Factors influencing initial cup stability in total hip arthroplasty.

    Science.gov (United States)

    Amirouche, Farid; Solitro, Giovanni; Broviak, Stefanie; Gonzalez, Mark; Goldstein, Wayne; Barmada, Riad

    2014-12-01

    One of the main goals in total hip replacement is to preserve the integrity of the hip kinematics, by well positioning the cup and to make sure its initial stability is congruent and attained. Achieving the latter is not trivial. A finite element model of the cup-bone interface simulating a realistic insertion and analysis of different scenarios of cup penetration, insertion, under-reaming and loading is investigated to determine certain measurable factors sensitivity to stress-strain outcome. The insertion force during hammering and its relation to the cup penetration during implantation is also investigated with the goal of determining the initial stability of the acetabular cup during total hip arthroplasty. The mathematical model was run in various configurations to simulate 1 and 2mm of under-reaming at various imposed insertion distances to mimic hammering and insertion of cup insertion into the pelvis. Surface contact and micromotion at the cup-bone interface were evaluated after simulated cup insertion and post-operative loading conditions. The results suggest a direct correlation between under-reaming and insertion force used to insert the acetabular cup on the micromotion and fixation at the cup-bone interface. While increased under-reaming and insertion force result in an increase amount of stability at the interface, approximately the same percentage of surface contact and micromotion reduction can be achieved with less insertion force. We need to exercise caution to determine the optimal configuration which achieves a good conformity without approaching the yield strength for bone. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Factors controlling the initiation of Snowball Earth events

    Science.gov (United States)

    Voigt, A.

    2012-12-01

    During the Neoproterozoic glaciations tropical continents were covered by active glaciers that extended down to sea level. To explain these glaciers, the Snowball Earth hypothesis assumes that oceans were completely sea-ice covered during these glaciation, but there is an ongoing debate whether or not some regions of the tropical oceans remained open. In this talk, I will describe past and ongoing climate modelling activities with the comprehensive coupled climate model ECHAM5/MPI-OM that identify and compare factors that control the initiation of Snowball Earth events. I first show that shifting the continents from their present-day location to their Marinoan (635 My BP) low-latitude location increases the planetary albedo, cools the climate, and thereby allows Snowball Earth initiation at higher levels of total solar irradiance and atmospheric CO2. I then present simulations with successively lowered bare sea-ice albedo, disabled sea-ice dynamics, and switched-off ocean heat transport. These simulations show that both lowering the bare sea-ice albedo and disabling sea-ice dynamics increase the critical sea-ice cover in ECHAM5/MPI-OM, but sea-ice dynamics due to strong equatorward sea-ice transport have a much larger influence on the critical CO2. Disabling sea-ice transport allows a state with sea-ice margin at 10 deg latitude by virtue of the Jormungand mechanism. The accumulation of snow on land, in combination with tropical land temperatures below or close to freezing, suggests that tropical land glaciers could easily form in such a state. However, in contrast to aquaplanet simulations without ocean heat transport, there is no sign of a Jormungand hysteresis in the coupled simulations. Ocean heat transport is not responsible for the lack of a Jormungand hysteresis in the coupled simulations. By relating the above findings to previous studies, I will outline promising future avenues of research on the initiation of Snowball Earth events. In particular, an

  17. Factors influencing career choice after initial training in surgery.

    LENUS (Irish Health Repository)

    McHugh, Seamus

    2012-02-01

    INTRODUCTION: Irish general surgery faces a recruitment crisis with only 87 of 145 (60%) basic surgical training (BST) places filled in 2009. We assessed basic surgical trainees to identify objective, and potentially modifiable, factors that influence ultimate recruitment into a general surgical career. METHODS: Candidates commencing BST training during a 5-year period between 2004 and 2008 were included in a quantitative study. In addition a total of 2,536 candidates, representing all those who commenced surgical training in Ireland since 1960 were identified through the Royal College of Surgeons in Ireland (RCSI) database and invited to complete an online survey. Statistical analysis was performed using SPSS version 15, with p < 0.05 considered significant. RESULTS: During the 5-year quantitative study period there were 381 BST trainees. Gender was a significant predictor of career choice with women more likely to ultimately choose a nonsurgical career after initial surgical training (p = 0.049). Passing surgical membership examinations (MRCS) also was predictive of remaining in surgery (p = 0.005). Training region was not a significant predictor of ultimate career choice. There were 418 survey respondents. The influence of role models was most commonly cited as influencing candidates in choosing to commence surgical training. Candidates who rated "academic opportunity" (p = 0.023) and "intellectual challenge" (p = 0.047) as factors that influenced their decision to commence surgical training were more likely to ultimately continue their careers in a surgical speciality. CONCLUSIONS: This study describes the career pathway of surgical trainees and confirms the importance of academic achievement in discriminating between candidates applying for surgical training schemes.

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

    OpenAIRE

    Rui, Liangyou

    2014-01-01

    The Src homology 2B (SH2B) family members (SH2B1, SH2B2 and SH2B3) are adaptor signaling proteins containing characteristic SH2 and PH domains. SH2B1 (also called SH2-B and PSM) and SH2B2 (also called APS) are able to form homo- or hetero-dimers via their N-terminal dimerization domains. Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins, including Janus kinase 2 (JAK2), TrkA, insulin receptors, insulin-like growth factor-1 receptors, insulin receptor substrate-1 (IRS1), and...

  19. Magnitude and factors associated with delayed initiation of ...

    African Journals Online (AJOL)

    Results: In this study, 31.4% mothers delayed initiation of breastfeeding. This was associated with .... occupation, lack of prenatal guidance on advantages of breast feeding, failure to .... shown earlier in increasing uptake of exclusive breast-.

  20. Early smoking initiation and associated factors among in-school ...

    African Journals Online (AJOL)

    Objective: This report examines the prevalence and common correlates of early smoking initiation among male and female school children across seven African countries. Method: The total sample included 17,725 school children aged 13 to 15 years from nationally representative samples in seven African countries.

  1. IGF-1-Involved Negative Feedback of NR2B NMDA Subunits Protects Cultured Hippocampal Neurons Against NMDA-Induced Excitotoxicity.

    Science.gov (United States)

    Li, Yun; Sun, Wei; Han, Song; Li, Jianing; Ding, Shu; Wang, Wei; Yin, Yanling

    2017-01-01

    Insulin-like growth factor 1 (IGF-1) is a multifunctional protein involved in neuronal polarity and axonal guidance. In our previous study, it was discovered that IGF-1 alleviated 50-μM NMDA-induced excitotoxicity against neuronal autophagy via depression of NR2B p-Ser1303 activation. However, it was found that NMDA at a higher dose did not cause neuronal autophagy. And, the performance of IGF-1 under severe excitotoxicity still needs to be clarified. In this study, we observed that IGF-1 can salvage the hippocampal neurons in an autophagy-independent manner after 150-μM NMDA exposure using thiazolyl blue tetrazolium bromide (MTT), lactate dehydrogenase (LDH), Western blot assay, and transmission electron microscopy. In addition, over-activation of post-synaptic NMDARs was found with the whole-cell patch clamp recording method. In order to explore whether there is a positive feedback way for post-synaptic NMDARs and the different pathway caused by 150 μM NMDA, the phosphorylation level of Fyn and the phosphorylation site of NR2B were investigated. It was observed that NR2B p-Tyr1472 was increased by the activation of Fyn after 150-μM NMDA exposure. When the neutralizing antibody against NR2B p-Ser1303 was added into the medium, both the activations of Fyn and NR2B p-Tyr1472 were blocked, suggesting NR2B p-Ser1303 may be the initial step of NMDA-induced excitotoxicity. In addition, since IGF-1 can block the initial step of NR2B activation, its effect is concluded to continue with the development of excitotoxicity. Overall, this study strongly indicates that the relationship between different phosphorylation sites of NR2B should be laid more emphasis on, which may be a vital target for the NR2B-involved excitotoxicity.

  2. An Initial Investigation of Factors Affecting Multi-Task Performance

    National Research Council Canada - National Science Library

    Branscome, Tersa A; Swoboda, Jennifer C; Fatkin, Linda T

    2007-01-01

    This report presents the results of the first in a series of investigations designed to increase fundamental knowledge and understanding of the factors affecting multi-task performance in a military environment...

  3. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Li, Qiuping [Zhongshan Hospital of Fudan University, Shanghai 200032 (China); Yang, Zhiyuan; Wu, Guoqiang [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Gu, Jianxin [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences of Fudan University, Shanghai 200032 (China); Wei, Yuanyan, E-mail: yywei@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Jiang, Jianhai, E-mail: jianhaijiang@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China)

    2010-07-09

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  4. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    International Nuclear Information System (INIS)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan; Li, Qiuping; Yang, Zhiyuan; Wu, Guoqiang; Sun, Shuhui; Gu, Jianxin; Wei, Yuanyan; Jiang, Jianhai

    2010-01-01

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  5. Initial-state interactions, factorization, and the Drell-Yan process

    International Nuclear Information System (INIS)

    Bodwin, G.T.; Brodsky, S.J.; Lepage, G.P.

    1981-12-01

    It is shown that initial state interactions violate the factorization conjecture for the Drell-Yan process order by order in perturbation theory. Also, the effects of elastic and inelastic initial state interactions on the observed cross sections are discussed

  6. Deliberate and Crisis Action Planning and Execution Segments Increment 2B (DCAPES Inc 2B)

    Science.gov (United States)

    2016-03-01

    2016 Major Automated Information System Annual Report Deliberate and Crisis Action Planning and Execution Segments Increment 2B (DCAPES Inc 2B...Information Program Name Deliberate and Crisis Action Planning and Execution Segments Increment 2B (DCAPES Inc 2B) DoD Component Air Force Responsible Office...been established. DCAPES Inc 2B 2016 MAR UNCLASSIFIED 4 Program Description Deliberate and Crisis Action Planning and Execution Segments (DCAPES) is

  7. Factors associated with the lack of antiretroviral therapy initiation ...

    African Journals Online (AJOL)

    that provide antenatal care (ANC) services also provide PMTCT services. ... This open-access article is distributed under. Creative ..... Karcher H, Omondi A, Odera J, Kunz A, Harms G. Risk factors for treatment denial and loss to follow-up in an ...

  8. Factors influencing career choice after initial training in surgery.

    LENUS (Irish Health Repository)

    McHugh, Seamus

    2011-03-01

    Irish general surgery faces a recruitment crisis with only 87 of 145 (60%) basic surgical training (BST) places filled in 2009. We assessed basic surgical trainees to identify objective, and potentially modifiable, factors that influence ultimate recruitment into a general surgical career.

  9. Personality Factors and Nuclear Power Plant Operators: Initial License Success

    Science.gov (United States)

    DeVita-Cochrane, Cynthia

    Commercial nuclear power utilities are under pressure to effectively recruit and retain licensed reactor operators in light of poor candidate training completion rates and recent candidate failures on the Nuclear Regulatory Commission (NRC) license exam. One candidate failure can cost a utility over $400,000, making the successful licensing of new operators a critical path to operational excellence. This study was designed to discover if the NEO-PI-3, a 5-factor measure of personality, could improve selection in nuclear utilities by identifying personality factors that predict license candidate success. Two large U.S. commercial nuclear power corporations provided potential participant contact information and candidate results on the 2014 NRC exam from their nuclear power units nation-wide. License candidates who participated (n = 75) completed the NEO-PI-3 personality test and results were compared to 3 outcomes on the NRC exam: written exam, simulated operating exam, and overall exam result. Significant correlations were found between several personality factors and both written and operating exam outcomes on the NRC exam. Further, a regression analysis indicated that personality factors, particularly Conscientiousness, predicted simulated operating exam scores. The results of this study may be used to support the use of the NEO-PI-3 to improve operator selection as an addition to the current selection protocol. Positive social change implications from this study include support for the use of a personality measure by utilities to improve their return-on-investment in candidates and by individual candidates to avoid career failures. The results of this study may also positively impact the public by supporting the safe and reliable operation of commercial nuclear power utilities in the United States.

  10. Parasitic Cuscuta factor(s) and the detection by tomato initiates plant defense.

    Science.gov (United States)

    Fürst, Ursula; Hegenauer, Volker; Kaiser, Bettina; Körner, Max; Welz, Max; Albert, Markus

    2016-01-01

    Dodders ( Cuscuta spp.) are holoparasitic plants that enwind stems of host plants and penetrate those by haustoria to connect to the vascular bundles. Having a broad host plant spectrum, Cuscuta spp infect nearly all dicot plants - only cultivated tomato as one exception is mounting an active defense specifically against C. reflexa . In a recent work we identified a pattern recognition receptor of tomato, "Cuscuta Receptor 1" (CuRe1), which is critical to detect a "Cuscuta factor" (CuF) and initiate defense responses such as the production of ethylene or the generation of reactive oxygen species. CuRe1 also contributes to the tomato resistance against C. reflexa . Here we point to the fact that CuRe1 is not the only relevant component for full tomato resistance but it requires additional defense mechanisms, or receptors, respectively, to totally fend off the parasite.

  11. TFAP2B mutation and dental anomalies.

    Science.gov (United States)

    Tanasubsinn, Natchaya; Sittiwangkul, Rekwan; Pongprot, Yupada; Kawasaki, Katsushige; Ohazama, Atsushi; Sastraruji, Thanapat; Kaewgahya, Massupa; Kantaputra, Piranit Nik

    2017-08-01

    Mutations inTFAP2B has been reported in patients with isolated patent ductus arteriosus (PDA) and Char syndrome. We performed mutation analysis of TFAP2B in 43 patients with isolated PDA, 7 patients with PDA with other congenital heart defects and 286 patients with isolated tooth agenesis with or without other dental anomalies. The heterozygous c.1006G>A mutation was identified in 20 individuals. Those mutation carriers consisted of 1 patient with term PDA (1/43), 16 patients with isolated tooth agenesis with or without other dental anomalies (16/286; 5.6%), 1 patient with PDA and severe valvular aortic stenosis and tooth agenesis (1/4) and 2 normal controls (2/100; 1%). The mutation is predicted to cause an amino-acid substitution p.Val336Ile in the TFAP2B protein. Tfap2b expression during early mouse tooth development supports the association of TFAP2B mutation and dental anomalies. It is hypothesized that this incidence might have been the result of founder effect. Here we report for the first time that TFAP2B mutation is associated with tooth agenesis, microdontia, supernumerary tooth and root maldevelopment. In addition, we also found that TFAP2B mutations, the common causes of PDA in Caucasian, are not the common cause of PDA in Thai population.

  12. Influencing Factors of the Initiation Point in the Parachute-Bomb Dynamic Detonation System

    Science.gov (United States)

    Qizhong, Li; Ye, Wang; Zhongqi, Wang; Chunhua, Bai

    2017-12-01

    The parachute system has been widely applied in modern armament design, especially for the fuel-air explosives. Because detonation of fuel-air explosives occurs during flight, it is necessary to investigate the influences of the initiation point to ensure successful dynamic detonation. In fact, the initiating position exist the falling area in the fuels, due to the error of influencing factors. In this paper, the major influencing factors of initiation point were explored with airdrop and the regularity between initiation point area and factors were obtained. Based on the regularity, the volume equation of initiation point area was established to predict the range of initiation point in the fuel. The analysis results showed that the initiation point appeared area, scattered on account of the error of attitude angle, secondary initiation charge velocity, and delay time. The attitude angle was the major influencing factors on a horizontal axis. On the contrary, secondary initiation charge velocity and delay time were the major influencing factors on a horizontal axis. Overall, the geometries of initiation point area were sector coupled with the errors of the attitude angle, secondary initiation charge velocity, and delay time.

  13. Risk factors associated with injection initiation among drug users in Northern Thailand

    Directory of Open Access Journals (Sweden)

    Suriyanon Vinai

    2006-03-01

    Full Text Available Abstract Background Circumstances surrounding injection initiation have not been well addressed in many developing country contexts. This study aimed to identify demographic factors, sexual behaviors and drug use characteristics related to injection initiation among drug users in northern Thailand. Methods A cross-sectional survey was conducted among 2,231 drug users admitted to the Northern Drug Treatment Center in Mae Rim, Chiang Mai, Thailand, between February 1, 1999 and December 31, 2000. A multiple logistic regression was employed to identify the independent effects from potential risk factors of transition into injection. Results After controlling for other covariates, being 20 years of age or older, single, ever receiving education, urban residence, and having a history of smoking or incarceration were significantly associated with higher likelihood of injection initiation. Multiple sex partners and an experience of sex abuse were associated with an increased risk of injection initiation. Comparing to those whose first drug was opium, individuals using heroin as their initiation drug had greater risk of injection initiation; conversely, those taking amphetamine as their first drug had less risk of injection initiation. Age of drug initiation was negatively associated with the risk of injection initiation: the older the age of drug initiation, the less the risk of injection initiation. Conclusion Injection initiation was related to several demographic factors, sexual behaviors and drug use characteristics. Understanding these factors will benefit the design of approaches to successfully prevent or delay transition into injection.

  14. A Model of B2B Exchanges

    OpenAIRE

    Gabor Fath; Miklos Sarvary

    2001-01-01

    B2B exchanges are revolutionizing the way businesses will buy and sell a variety of intermediary products and services. It is estimated that most of the roughly $7 trillion worth of business transactions are likely to go through these new institutions within the next decade. This paper tries to understand the economics governing the transactions within B2B exchanges and analyze their likely evolution over time. In doing so, we start by providing the rigorous definitions to a number of critica...

  15. Hotelzon's B2B content marketing plan

    OpenAIRE

    Nguyen, Trang

    2015-01-01

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

  16. Electrification Beyond Light Duty: Class 2b-3 Commercial Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Birky, Alicia [Energetics Incorporated; Laughlin, Michael [Energetics Incorporated; Tartaglia, Katie [Energetics Incorporated; Price, Rebecca [Energetics Incorporated; Lim, Brandon [Energetics Incorporated; Lin, Zhenhong [ORNL

    2018-01-01

    The class 2b-3 truck market covers a wide range of commercial truck applications across a half-million vehicle sales annually. This report collected public information and stakeholder input to assess the opportunity for electrification in this market. Although class 2b-3 pickup truck and van bodies are very similar to personal light vehicles, their functional requirements are quite different due to the demands of the commercial market. These demands vary by application and often vary from day to day for a single application. Fleet customers purchase these vehicles to perform a particular job for their business and are concerned about the overall cost of doing that job. Therefore, the vehicles must meet the job requirements cost effectively. Customers also are sensitive to initial cost. Electrification offers the potential to reduce vehicle operating costs and possibly improve vehicle functionality. However, the current market for class 2b-3 electrified trucks is very small, and the trucks are costly. Increased production volumes are key to cost reductions and may be assisted by sharing components with larger or smaller truck classes. Expanding demand is also crucial and stakeholders identified several niche markets with duty cycles that are likely well-suited to electrified class 2b-3 trucks. To expand beyond these niches, class 2b-3 electric solutions must be robust, flexible, and adaptable in order to cover a wide range of vocations, applications, and duty cycles.

  17. Success factors for strategic change initiatives: a qualitative study of healthcare administrators' perspectives.

    Science.gov (United States)

    Kash, Bita Arbab; Spaulding, Aaron; Johnson, Christopher E; Gamm, Larry

    2014-01-01

    Success factors related to the implementation of change initiatives are well documented and discussed in the management literature, but they are seldom studied in healthcare organizations engaged in multiple strategic change initiatives. The purpose of this study was to identify key success factors related to implementation of change initiatives based on rich qualitative data gathered from health leader interviews at two large health systems implementing multiple change initiatives. In-depth personal interviews with 61 healthcare leaders in the two large systems were conducted and inductive qualitative analysis was employed to identify success factors associated with 13 change initiatives. Results from this analysis were compared to success factors identified in the literature, and generalizations were drawn that add significantly to the management literature, especially to that in the healthcare sector. Ten specific success factors were identified for the implementation of change initiatives. The top three success factors were (1) culture and values, (2) business processes, and (3) people and engagement. Two of the identified success factors are unique to the healthcare sector and not found in the literature on change models: service quality and client satisfaction (ranked fourth of 10) and access to information (ranked ninth). Results demonstrate the importance of human resource functions, alignment of culture and values with change, and business processes that facilitate effective communication and access to information to achieve many change initiatives. The responses also suggest opportunities for leaders of healthcare organizations to more formally recognize the degree to which various change initiatives are dependent on one another.

  18. Mixed messages: Re-initiation factors regulate translation of animal mRNAs

    OpenAIRE

    Obermayer, Benedikt; Rajewsky, Nikolaus

    2014-01-01

    When ribosomes encounter upstream open reading frames (uORFs) during scanning of the 5' untranslated region (5' UTR), translation of the downstream ORF requires re-initiation. In a recent paper in Nature, Schleich et al. describe metazoan factors which specifically promote re-initiation.

  19. Factors to Consider in Selecting an Organisational Improvement Initiative: Survey Results

    Directory of Open Access Journals (Sweden)

    Mohammad Musli

    2017-01-01

    Full Text Available Organisations should select the appropriate improvement initiative that will fit with the context of organisation and provide value to the organisation. This paper presents 18 factors to be considered when selecting an organisational improvement initiative. Organisational improvement initiatives are approaches, management systems, tools and/or techniques that can be used for managing and improving organisations, such as Lean, ISO9001, Six Sigma and Improvement Team. A survey was conducted to identify the level of importance of these 18 factors as criteria for selecting an improvement initiative. Purposive sampling was used for this survey involving practitioners, managers, engineers, executives, consultants and/or academicians, who have been involved in the selection and/or implementation of organisational improvement initiatives in Malaysia. Two factors were rated as ‘very high importance’, which involve: (1 The ability to gain top management commitment and support to introduce and implement the initiative successfully, and (2 The initiative is aligned to the vision, mission and/or purpose of the organisation. All these factors can be adopted by the organisations as decision criteria to assist in the selection of the most appropriate improvement initiative based on rational decision making.

  20. Initial 12-h operative fluid volume is an independent risk factor for pleural effusion after hepatectomy.

    Science.gov (United States)

    Cheng, Xiang; Wu, Jia-Wei; Sun, Ping; Song, Zi-Fang; Zheng, Qi-Chang

    2016-12-01

    Pleural effusion after hepatectomy is associated with significant morbidity and prolonged hospital stays. Several studies have addressed the risk factors for postoperative pleural effusion. However, there are no researches concerning the role of the initial 12-h operative fluid volume. The aim of this study was to evaluate whether the initial 12-h operative fluid volume during liver resection is an independent risk factor for pleural effusion after hepatectomy. In this study, we retrospectively analyzed clinical data of 470 patients consecutively undergoing elective hepatectomy between January 2011 and December 2012. We prospectively collected and retrospectively analyzed baseline and clinical data, including preoperative, intraoperative, and postoperative variables. Univariate and multivariate analyses were carried out to identify whether the initial 12-h operative fluid volume was an independent risk factor for pleural effusion after hepatectomy. The multivariate analysis identified 2 independent risk factors for pleural effusion: operative time [odds ratio (OR)=10.2] and initial 12-h operative fluid volume (OR=1.0003). Threshold effect analyses revealed that the initial 12 h operative fluid volume was positively correlated with the incidence of pleural effusion when the initial 12-h operative fluid volume exceeded 4636 mL. We conclude that the initial 12-h operative fluid volume during liver resection and operative time are independent risk factors for pleural effusion after hepatectomy. Perioperative intravenous fluids should be restricted properly.

  1. Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α Phosphorylation

    OpenAIRE

    Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J.; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed; Pelletier, Jerry

    2006-01-01

    Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2α phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity...

  2. No evidence for a role of Ile587Val polymorphism of EIF2B5 gene in multiple sclerosis in Kashmir Valley of India.

    Science.gov (United States)

    Zahoor, Insha; Asimi, Ravouf; Haq, Ehtishamul

    2015-12-15

    Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the nervous system with a profound genetic element. It is already known that alterations in Eukaryotic Translation Initiation Factor 2B (EIF2B) gene encoding the five subunits of eIF2B complex cause Vanishing White Matter (VWM) disease of the brain and emerging evidences have advocated certain resemblances between MS and VWM in terms of clinical and epidemiological characteristics, thus validating the association study between EIF2B and MS. Moreover, a recent study has implicated EIF2B5 Ile587Val (rs843358) polymorphism as a susceptibility factor for MS. In order to investigate the association of EIF2B5 Ile587Val polymorphism with MS susceptibility in Kashmir region in India, we screened EIF2B5 Exon 13 in 30 MS patients and 65 controls (a total of 95 participants). During the present course of study, we could not find statistically significant difference in the frequency of Ile587Val between MS patients and controls, thus indicating that such alteration does not appear to influence MS development in Kashmiri population. Our results provide evidence against a major role for Ile587Val polymorphism in MS susceptibility. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Factors Associated with the Transition from Drug Abuse to Initiation of Injection Drug Use

    Directory of Open Access Journals (Sweden)

    Mosayeb Yarmohamadi Vasel

    2015-06-01

    Full Text Available Objectives: Drug injection carries with it many risks and therefore it is important to understand the initiating factors of injection and its origins. Thus,  the purpose of this study was to identify factors associated with the initiation of injection drug use among substance abusers. Methods:  Study method was a cross-sectional study. The research statistics universe constitutes all people suffering from a substance dependence disorder with a pattern of injection use in Tehran and Hamedan. This study was conducted among 216 individuals with substance dependence disorders who were selected from harm reduction centers in Tehran and Hamedan. The sampling selection method was simply random. The instruments used for data collection included: demographic information, patterns of drug use and initiation of injection scales.  Results: In this study, the average age of initiation to injections was 22.5 years. Factors associated with initiation of drug injection included: acquired more pleasure, easier use, faster effect of injection, ineffective previous use method, curiosity, peer pressure, lack of availability of the drug, poverty, and low quality drugs. Discussion: Results of this study indicate that initiation factors to drug injection are multifaceted (Psychological, Social, Economic and Environmental, therefore, injection interventionists should consider all these factors for prevention, treatment and harm reduction.

  4. Socio-Cultural Factors Associated with the Initiation of Opium Use in Darab, Iran

    Science.gov (United States)

    Jafari, Siavash; Movaghar, Afarin Rahimi; Craib, Kevin; Baharlou, Souzan; Mathias, Richard

    2009-01-01

    This study aimed to identify socio-cultural factors facilitating initiation of opium use among drug users in Darab, Iran. A qualitative study using in-depth interviews was conducted. The study began in June 2006 and included 76 drug users, aged 20-43, of whom 95% (72) were male, and 5% (4) were female. The five most common factors facilitating…

  5. Gender differences in risk factors for cigarette smoking initiation in childhood.

    Science.gov (United States)

    Sylvestre, Marie-Pierre; Wellman, Robert J; O'Loughlin, Erin K; Dugas, Erika N; O'Loughlin, Jennifer

    2017-09-01

    We investigated whether established risk factors for initiating cigarette smoking during adolescence (parents, siblings, friends smoke; home smoking rules, smokers at home, exposure to smoking in cars, academic performance, susceptibility to smoking, depressive symptoms, self-esteem, school connectedness, use of other tobacco products) are associated with initiation in preadolescents, and whether the effects of these factors differ by gender. In spring 2005, baseline data were collected in self-report questionnaires from 1801 5th grade students including 1553 never-smokers (mean age=10.7years), in the longitudinal AdoQuest I Study in Montréal, Canada. Follow-up data were collected in the fall and spring of 6th grade (2005-2006). Poisson regression analyses with robust variance estimated the effects of each risk factor on initiation and additive interactions with gender were computed to assess the excess risk of each risk factor in girls compared to boys. 101 of 1399 participants in the analytic sample (6.7% of boys; 7.7% of girls) initiated smoking during follow-up. After adjustment for age, gender and maternal education, all risk factors except academic performance and school connectedness were statistically significantly associated with initiation. Paternal and sibling smoking were associated with initiation in girls only, and girls with lower self-esteem had a significant excess risk of initiating smoking in 6th grade. Risk factors for smoking initiation in preadolescents mirror those in adolescents; their effects do not differ markedly by gender. Preventive programs targeting children should focus on reducing smoking in the social environment and the dangers of poly-tobacco use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Factors Associated with Initiation of Ecstasy Use among US Adolescents: Findings from a National Survey

    Science.gov (United States)

    Wu, Ping; Liu, Xinhua; Fan, Bin

    2009-01-01

    Aims To investigate adolescent pathways to ecstasy use by (1) examining how early onsets of smoking, drinking, and marijuana use are related to a child’s risk of initiation of ecstasy use and (2) assessing the influence of other individual and parental factors on ecstasy use initiation. Methods Data on 6,426 adolescents (12–17 years old at baseline) from the National Survey of Parents and Youth (NSPY), a longitudinal, nationally-representative household survey of youth and their parents, were used in the analyses. Information on youth substance use, including ecstasy use, as well as familial and parental characteristics, was available. Results Initiation of ecstasy use is predicted by an adolescent’s early initiation of smoking, drinking, or marijuana use. In particular, early initiation either of marijuana use, or of both smoking and drinking, increases a child’s risk for ecstasy use initiation. Among the familial and parental variables, parent drug use emerged as significantly predictive of child initiation of ecstasy use; living with both parents and close parental monitoring, on the other hand, are negatively associated with ecstasy use initiation, and may be protective against it. At the individual level, sensation seeking tendencies and positive attitudes toward substance use, as well as close associations with deviant peers, are predictive of adolescent initiation of ecstasy use. Conclusion Our findings on the risk and protective factors for initiation of ecstasy use, especially with regard to factors that are modifiable, will be useful for prevention programs targeting youth use not only of ecstasy, but also of other drugs. PMID:19781862

  7. Factors Associated with Breastfeeding Initiation: A Comparison between France and French-Speaking Canada.

    Directory of Open Access Journals (Sweden)

    Lisa-Christine Girard

    Full Text Available Breastfeeding is associated with multiple domains of health for both mothers and children. Nevertheless, breastfeeding initiation is low within certain developed countries. Furthermore, comparative studies of initiation rates using harmonised data across multiple regions is scarce.The aim of the present study was to investigate and compare individual-level determinants of breastfeeding initiation using two French-speaking cohorts.Participants included ~ 3,900 mothers enrolled in two cohort studies in Canada and France. Interviews, questionnaires, and medical records were utilised to collect information on maternal, family, and medical factors associated with breastfeeding initiation.Rates of breastfeeding initiation were similar across cohorts, slightly above 70%. Women in both Canada and France who had higher levels of maternal education, were born outside of their respective countries and who did not smoke during pregnancy were more likely to initiate breastfeeding with the cohort infant. Notably, cohort effects of maternal education at the university level were found, whereby having 'some university' was not statistically significant for mothers in France. Further, younger mothers in Canada, who delivered by caesarean section and who had previous children, had reduced odds of breastfeeding initiation. These results were not found for mothers in France.While some similar determinants were observed, programming efforts to increase breastfeeding initiation should be tailored to the characteristics of specific geographical regions which may be heavily impacted by the social, cultural and political climate of the region, in addition to individual and family level factors.

  8. Initiation of sexual intercourse among middle school adolescents: the influence of psychosocial factors.

    Science.gov (United States)

    Santelli, John S; Kaiser, Javaid; Hirsch, Lesley; Radosh, Alice; Simkin, Linda; Middlestadt, Susan

    2004-03-01

    To explore potential psychosocial predictors for initiation of sexual intercourse among middle-school, inner-city youth, using longitudinal data from the Healthy and Alive! project. We conducted hierarchical, logistic regression with adjustment for intraclass correlation over two sequential periods, including seventh and eighth grades (N = 3163), to assess the independent influence of psychosocial and demographic factors. Internally reliable scales to assess psychosocial influences were created, based on major theories of behavior. The sample was 52% female, 51% black, 30% Hispanic, 9% white, and 3% Asian. At baseline, 13% of girls and 39% of boys reported already having initiated sexual intercourse. Personal and perceived peer norms about refraining from sex were a strong and consistent protective factor. Alcohol and other drug use, poor academic performance, male gender, and black race were consistent risk factors. Self-efficacy showed a mixed effect: protective in the seventh grade but increasing risk in the eighth grade. Speaking a language other than English was a protective factor in seventh grade. Both psychosocial and demographic factors provided independent explanatory power. Psychosocial factors, particularly norms about having sex, influence initiation of sexual intercourse. These data suggest that programs to delay initiation of sexual intercourse should reinforce norms about refraining from sex.

  9. Support for food policy initiatives is associated with knowledge of obesity-related cancer risk factors

    Directory of Open Access Journals (Sweden)

    Wendy Watson

    2017-12-01

    Full Text Available Objectives: To investigate community support for government-led policy initiatives to positively influence the food environment, and to identify whether there is a relationship between support for food policy initiatives and awareness of the link between obesity-related lifestyle risk factors and cancer. Methods: An online survey of knowledge of cancer risk factors and attitudes to policy initiatives that influence the food environment was completed by 2474 adults from New South Wales, Australia. The proportion of participants in support of seven food policy initiatives was quantified in relation to awareness of the link between obesity, poor diet, insufficient fruit and vegetable consumption, and physical inactivity with cancer and other health conditions. Results: Overall, policies that involved taxing unhealthy foods received the least support (41.5%. Support was highest for introducing a colour-coded food labelling system (85.9%, restricting claims being made about the health benefits of foods which are, overall, unhealthy (82.6%, displaying health warning labels on unhealthy foods (78.7% and banning unhealthy food advertising that targets children (72.6%. Participants who were aware that obesity-related lifestyle factors are related to cancer were significantly more likely to support food policy initiatives than those who were unaware. Only 17.5% of participants were aware that obesity, poor diet, insufficient fruit and vegetable consumption, and physical inactivity are linked to cancer. Conclusions: There is strong support for all policies related to food labelling and a policy banning unhealthy food advertising to children. Support for food policy initiatives that positively influence the food environment was higher among those who were aware of the link between cancer and obesity-related lifestyle factors than among those who were unaware of this link. Increasing awareness of the link between obesity-related lifestyle factors and cancer

  10. Factors associated with initiation of antihyperglycaemic medication in UK patients with newly diagnosed type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Sinclair Alan J

    2012-03-01

    Full Text Available Abstract Aim To assess the factors associated with antihyperglycaemic medication initiation in UK patients with newly diagnosed type 2 diabetes. Methods In a retrospective cohort study, patients with newly diagnosed type 2 diabetes were identified during the index period of 2003-2005. Eligible patients were ≥ 30 years old at the date of the first observed diabetes diagnosis (referred to as index date and had at least 2 years of follow-up medical history (N = 9,158. Initiation of antihyperglycaemic medication (i.e., treatment was assessed in the 2-year period following the index date. Adjusted Cox regression models were used to examine the association between time to medication initiation and patient age and other factors. Results Mean (SD HbA1c at diagnosis was 8.1% (2.3. Overall, 51% of patients initiated antihyperglycaemic medication within 2 years (65%, 55%, 46% and 40% for patients in the 30- th, 75th percentile time to treatment initiation was 63 (8, 257 days. Of the patients with HbA1c ≥ 7.5% at diagnosis, 87% initiated treatment within 2 years. These patients with a higher HbA1c also had shorter time to treatment initiation (adjusted hazard ratio (HR = 2.44 [95% confidence interval (CI: 1.61, 3.70]; p Conclusions In this UK cohort of patients with newly diagnosed type 2 diabetes, only 51% had antihyperglycaemic medication initiated over a 2-year period following diagnosis. Older patients were significantly less likely to have been prescribed antihyperglycaemic medications. Elevated HbA1c was the strongest factor associated with initiating antihyperglycaemic medication in these patients.

  11. Eukaryotic Initiation Factor 4H Is under Transcriptional Control of p65/NF-κB

    Science.gov (United States)

    Fiume, Giuseppe; Rossi, Annalisa; de Laurentiis, Annamaria; Falcone, Cristina; Pisano, Antonio; Vecchio, Eleonora; Pontoriero, Marilena; Scala, Iris; Scialdone, Annarita; Masci, Francesca Fasanella; Mimmi, Selena; Palmieri, Camillo; Scala, Giuseppe; Quinto, Ileana

    2013-01-01

    Protein synthesis is mainly regulated at the initiation step, allowing the fast, reversible and spatial control of gene expression. Initiation of protein synthesis requires at least 13 translation initiation factors to assemble the 80S ribosomal initiation complex. Loss of translation control may result in cell malignant transformation. Here, we asked whether translational initiation factors could be regulated by NF-κB transcription factor, a major regulator of genes involved in cell proliferation, survival, and inflammatory response. We show that the p65 subunit of NF-κB activates the transcription of eIF4H gene, which is the regulatory subunit of eIF4A, the most relevant RNA helicase in translation initiation. The p65-dependent transcriptional activation of eIF4H increased the eIF4H protein content augmenting the rate of global protein synthesis. In this context, our results provide novel insights into protein synthesis regulation in response to NF-κB activation signalling, suggesting a transcription-translation coupled mechanism of control. PMID:23776612

  12. Report on series 2B reflood experiment

    International Nuclear Information System (INIS)

    Murao, Yoshio; Iguchi, Tadashi; Sudoh, Takashi; Sudo, Yukio; Sugimoto, Jun

    1976-12-01

    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 600 0 C. 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.)

  13. B2B oriented on-line applications generator

    OpenAIRE

    Vintilă Bogdan-Cătălin

    2008-01-01

    B2B applications are presented. Quality characteristics of B2B applications are defined. B2B application structure is defined. The application for contracts is developed. The advantages are identified.

  14. Synthesis of Ni2B nanoparticles by RF thermal plasma for fuel cell catalyst

    International Nuclear Information System (INIS)

    Cheng, Y; Tanaka, M; Watanabe, T; Choi, S Y; Shin, M S; Lee, K H

    2014-01-01

    The catalyst of Ni 2 B nanoparticles was successfully prepared using nickel and boron as precursors with the quenching gas in radio frequency thermal plasmas. The generating of Ni 2 B needs adequate reaction temperature and boron content in precursors. The quenching gas is beneficial for the synthesis of Ni 2 B in RF thermal plasma. The effect of quenching rate, powder feed rate and boron content in feeding powders on the synthesis of nickel boride nanoparticles was studied in this research. The high mass fraction of 28 % of Ni 2 B nanoparticles can be generated at the fixed initial composition of Ni:B = 2:3. Quenching gas is necessary in the synthesis of Ni 2 B nanoaprticles. In addition, the mass fraction of Ni 2 B increases with the increase of quenching gas flow rate and powder feed rate

  15. Social-cognitive and school factors in initiation of smoking among adolescents: a prospective cohort study

    DEFF Research Database (Denmark)

    Bidstrup, Pernille Envold; Frederiksen, Kirsten; Siersma, Volkert

    2009-01-01

    AIMS: The aim of the present study was to examine the association between social-cognitive factors, school factors, and smoking initiation among adolescents who had never smoked. METHODS: The study was based on longitudinal data on Danish adolescents attending randomly selected public schools....... Adolescents enrolled in grade 7 (mean age, 13 years) who had never smoked (n = 912) were followed up for 6 months after baseline. Those who had still never smoked were followed up again 18 months after baseline, in grade 8 (n = 442). Social-cognitive factors were examined with five measures: self......-efficacy, social influence (norms), social influence (behavior), social influence (pressure), and attitude. We used multilevel analyses to estimate the associations between social-cognitive factors at baseline and smoking initiation as well as the random effects of school, school class, and gender group...

  16. To be or not B2B?

    CERN Document Server

    Symons, L J

    2001-01-01

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

  17. What Happened with Spectrometer Magnet 2B

    International Nuclear Information System (INIS)

    Green, Michael A.

    2010-01-01

    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.

  18. Age at sexual initiation and factors associated with it among youths ...

    African Journals Online (AJOL)

    Background: For behavioral as well as physiological reasons, early sexual debut increases young peoples' risk for infection with HIV and other STIs. ... of the study was to determine the median age at first sexual intercourse and the associated factors of sexual initiation among rural and urban youths (age 15- 24 years).

  19. Development and Initial Validation of the Five-Factor Model Adolescent Personality Questionnaire (FFM-APQ).

    Science.gov (United States)

    Rogers, Mary E; Glendon, A Ian

    2018-01-01

    This research reports on the 4-phase development of the 25-item Five-Factor Model Adolescent Personality Questionnaire (FFM-APQ). The purpose was to develop and determine initial evidence for validity of a brief adolescent personality inventory using a vocabulary that could be understood by adolescents up to 18 years old. Phase 1 (N = 48) consisted of item generation and expert (N = 5) review of items; Phase 2 (N = 179) involved item analyses; in Phase 3 (N = 496) exploratory factor analysis assessed the underlying structure; in Phase 4 (N = 405) confirmatory factor analyses resulted in a 25-item inventory with 5 subscales.

  20. ONLINE ACQUISITIONS IN B2B MODEL

    Directory of Open Access Journals (Sweden)

    Constantin SASU

    2016-12-01

    Full Text Available Within the present paper, we propose to review some of the main aspects documented by the academic research so far with regard to the online purchasing behaviour in the B2B online environment (more specifically, in the case of the small and medium-sized companies. Preliminary conclusions reveal that, at least in the case studies, the dominant feature is that the geographic delimitation creates a potential obstacle when it comes to applying a general principle governing the small and medium-sized enterprises. Despite this, we consider that some theoretical elements can be acknowledged, elements from which future research can start to develop theories and hypothesis aimed at better explaining the phenomenon. Furthermore, the fact that the studies are rarely involving the same sector, makes it impossible to generalise the process.

  1. Identification of controlling factors for the initiation of corrosion of fresh concrete sewers.

    Science.gov (United States)

    Jiang, Guangming; Sun, Xiaoyan; Keller, Jurg; Bond, Philip L

    2015-09-01

    The development of concrete corrosion in new sewer pipes undergoes an initiation process before reaching an active corrosion stage. This initiation period is assumed to last several months to years but the key factors affecting the process, and its duration, are not well understood. This study is therefore focused on this initial stage of the corrosion process and the effect of key environmental factors. Such knowledge is important for the effective management of corrosion in new sewers, as every year of life extension of such systems has a very high financial benefit. This long-term (4.5 year) study has been conducted in purpose-built corrosion chambers that closely simulated the sewer environment, but with control of three key environmental factors being hydrogen sulfide (H2S) gas phase concentration, relative humidity and air temperature. Fresh concrete coupons, cut from an industry-standard sewer pipe, were exposed to the corrosive conditions in the chambers, both in the gas phase and partially submerged in wastewater. A total of 36 exposure conditions were investigated to determine the controlling factors by regular retrieval of concrete coupons for detailed analysis of surface pH, sulfur compounds (elemental sulfur and sulfate) and concrete mass loss. Corrosion initiation times were thus determined for different exposure conditions. It was found that the corrosion initiation time of both gas-phase and partially-submerged coupons was positively correlated with the gas phase H2S concentration, but only at levels of 10 ppm or below, indicating that sulfide oxidation rate rather than the H2S concentration was the limiting factor during the initiation stage. Relative humidity also played a role for the corrosion initiation of the gas-phase coupons. However, the partially-submerged coupons were not affected by humidity as these coupons were in direct contact with the sewage and hence did have sufficient moisture to enable the microbial processes to proceed. The

  2. Factors associated with late antiretroviral therapy initiation among adults in Mozambique.

    Directory of Open Access Journals (Sweden)

    Maria Lahuerta

    Full Text Available Despite recent changes to expand the ART eligibility criteria in sub-Saharan Africa, many patients still initiate ART in the advanced stages of HIV infection, which contributes to increased early mortality rates, poor patient outcomes, and onward transmission.To evaluate individual and clinic-level factors associated with late ART initiation in Mozambique, we conducted a retrospective sex-specific analysis of data from 36,411 adult patients who started ART between January 2005 and June 2009 at 25 HIV clinics in Mozambique. Late ART initiation was defined as CD4 count45_vs.26-30 = 0.72, 95%CI [0.67-0.77], entry into care via PMTCT (AOR(entry_through_PMTCT_vs.VCT = 0.42, 95%CI [0.35-0.50], marital status (AOR(married/in union_vs.single = 0.87, 95%CI [0.83-0.92], education (AOR(secondary_or_higher_vs.primary = 0.87, 95%CI [0.83-0.93] and year of ART initiation were associated with a lower likelihood of late ART initiation. Clinic-level factors independently associated with a lower likelihood of late ART initiation included CD4 machine on-site (AOR(CD4_machine_onsite_vs.offsite = 0.83, 95%CI [0.74-0.94] and presence of PMTCT services onsite (AOR = 0.85, 95%CI [0.77-0.93].The risk of starting ART late remained persistently high. Efforts are needed to ensure identification and enrollment of patients at earlier stages of HIV disease. Individual and clinic level factors identified may provide clues for upstream structural interventions.

  3. Genetic loss of SH2B3 in acute lymphoblastic leukemia.

    Science.gov (United States)

    Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Hadler, Michael; Rigo, Isaura; LeDuc, Charles A; Kelly, Kara; Jalas, Chaim; Paietta, Elisabeth; Racevskis, Janis; Rowe, Jacob M; Tallman, Martin S; Paganin, Maddalena; Basso, Giuseppe; Tong, Wei; Chung, Wendy K; Ferrando, Adolfo A

    2013-10-03

    The SH2B adaptor protein 3 (SH2B3) gene encodes a negative regulator of cytokine signaling with a critical role in the homeostasis of hematopoietic stem cells and lymphoid progenitors. Here, we report the identification of germline homozygous SH2B3 mutations in 2 siblings affected with developmental delay and autoimmunity, one in whom B-precursor acute lymphoblastic leukemia (ALL) developed. Mechanistically, loss of SH2B3 increases Janus kinase-signal transducer and activator of transcription signaling, promotes lymphoid cell proliferation, and accelerates leukemia development in a mouse model of NOTCH1-induced ALL. Moreover, extended mutation analysis showed homozygous somatic mutations in SH2B3 in 2 of 167 ALLs analyzed. Overall, these results demonstrate a Knudson tumor suppressor role for SH2B3 in the pathogenesis of ALL and highlight a possible link between genetic predisposition factors in the pathogenesis of autoimmunity and leukemogenesis.

  4. What Factors are Associated with Consumer Initiation of Shared Decision Making in Mental Health Visits?

    Science.gov (United States)

    Matthias, Marianne S; Fukui, Sadaaki; Salyers, Michelle P

    2017-01-01

    Understanding consumer initiation of shared decision making (SDM) is critical to improving SDM in mental health consultations, particularly because providers do not always invite consumer participation in treatment decisions. This study examined the association between consumer initiation of nine elements of SDM as measured by the SDM scale, and measures of consumer illness self-management and the consumer-provider relationship. In 63 mental health visits, three SDM elements were associated with self-management or relationship factors: discussion of consumer goals, treatment alternatives, and pros and cons of a decision. Limitations, implications, and future directions are discussed.

  5. Gender differences in the factors predicting initial engagement at cardiac rehabilitation.

    Science.gov (United States)

    Galdas, Paul Michael; Harrison, Alexander Stephen; Doherty, Patrick

    2018-01-01

    To determine whether there are gender differences in the factors that predict attendance at the initial cardiac rehabilitation baseline assessment (CR engagement) after referral. Using data from the National Audit of Cardiac Rehabilitation, we analysed data on 95 638 patients referred to CR following a cardiovascular diagnosis/treatment between 2013 and 2016. Eighteen factors that have been shown in previous research to be important predictors of CR participation were investigated and grouped into four categories: sociodemographic factors, cardiac risk factors, patient medical status and service-level factors. Logistic binary regression models were built for male patients and female patients, assessing the likelihood for CR engagement. Each included predictors such as age, number of comorbidities and social deprivation score. There were no important differences in the factors that predict the likelihood of CR engagement in men and women. Seven factors associated with a reduced probability of CR engagement, and eight factors associated with increased probability, were identified. Fourteen of the 15 factors identified as predicting the likelihood for engagement/non-engagement were the same for both men and women. Increasing age, being South Asian or non-white ethnicity (other than Black) and being single were all associated with a reduced likelihood of attending an initial CR baseline assessment in both men and women. Male patients with diabetes were 11% less likely to engage with CR; however, there was no significant association in women. Results showed that the overwhelmingly important determinant of CR engagement observed in both men and women was receiving an invitation to attend an assessment session (OR 4.223 men/4.033women; pgender differences in predictors of CR uptake should probably be more nuanced and informed by the stage of the patient care pathway.

  6. Expression and Function of Xmsx-2B in Dorso-Ventral Axis Formation in Gastrula Embryos.

    Science.gov (United States)

    Onitsuka, I; Takeda, M; Maéno, M

    2000-11-01

    Msx is a homeodomain-containing transcriptional factor that plays an essential role in pattern formation in vertebrata and invertebrata embryos. In Xenopus laevis, two msx genes have been identified (Xmsx-1 and Xmsx-2). In the present study, we attempted to elucidate the expression and function of Xmsx-2B (formerly designated as Xhox7.1') in early embryogenesis. Whole mount in situ hybridization analyses showed that the expression pattern of Xmsx-2B at gastrula and neurula stages was very similar to that of Xmsx-1: the transcript of Xmsx-2B was observed in ventral and lateral sides of the embryo. At the tailbud stage, however, the expression pattern of Xmsx-2B in neural tissues was distinct from that of Xmsx-1. An RNA injection experiment revealed that, like BMP-4, Xmsx-2B has a strong ventralizing activity. In the Xmsx-2B -injected embryos, differentiation of axial structures such as the notochord, muscle, and neural tissue was completely suppressed, whereas alpha-globin mRNA, a blood cell marker, was highly expressed. Simultaneous injection of Xmsx-1 and Xmsx-2B RNAs showed that they function in an additive manner. It was also shown that coinjection of Xmsx-2B with a dominant-negative BMP-4 receptor (tBR), which can induce formation of secondary axis when injected alone in ventral blastomeres, suppressed secondary axis formation. Furthermore, Xmsx-2B also suppressed secondary axis formation, which was induced by a dominant-negative form of Xmsx-1 (VP16/msx-1). Therefore, like Xmsx-1, Xmsx-2B is a downstream nuclear factor of the BMP-4-derived ventralizing signal, and these two factors probably share the same target molecules. In conclusion, Xmsx-1 and Xmsx-2B function in dorso-ventral axis formation in early Xenopus laevis development.

  7. Preliminary Investigation Of Emirati Women Entrepreneurship In The UAE Motivating Factors Challenges And Government Initiatives

    Directory of Open Access Journals (Sweden)

    Mohammad Rehan Shahnawaz

    2015-08-01

    Full Text Available Abstract Purpose The purpose of this research is to conduct an in depth preliminary investigation of the Emirati Women Entrepreneurship in the UAE in terms of the factors motivating the Emirati women to engage in the entrepreneurial activities challenges and issues faced by them in that process and initiatives taken by the government of UAE in overcoming those challenges and in encouraging promoting and safeguarding their interests. Methodology This research is an exploratory one due to the fact that the topic of the research strongly requires an in depth analysis or investigation of the underlying motivating factors challenges and issues and the government initiatives taken on behalf of Emirati women entrepreneurs. The research has used qualitative content analysis technique in which the existing literature secondary data on women and Emirati women entrepreneurship was gathered and discussed to serve the purpose of the research such as from other published researches internet searches and books. DiscussionsFindings The research explored an array of factors motivating the Emirati women towards entrepreneurship and the challenges and issues they come across in that process. The motivating factors were divided into positive and negative factors with main emphasis on the positive factors. Among the positive motivating factors were the Emiratization change in the organizational culture and beliefs relaxation of social and cultural structures inde-pendence and self-improvement and development. The negative motivating factors were the necessity unacceptable working conditions inflexible work hours wage gap between males and females and job frustrations. The major challenges and issues they usually come across are traditions cultural religious and social restrictions lack of managerial experience and basic business knowledge low self-confidence and determination male prejudice stereotyping and preconception minimal networking gender based promotional

  8. The ISS 2B PVTCS Ammonia Leak: An Operational History

    Science.gov (United States)

    Vareha, Anthony

    2014-01-01

    In 2006, the Photovoltaic Thermal Control System (PVTCS) for the International Space Station's 2B power channel began leaking ammonia at a rate of approximately 1.5lbm/year (out of a starting approximately 53lbm system ammonia mass). Initially, the operations strategy was "feed the leak," a strategy successfully put into action via Extra Vehicular Activity during the STS-134 mission. During this mission the system was topped off with ammonia piped over from a separate thermal control system. This recharge was to have allowed for continued power channel operation into 2014 or 2015, at which point another EVA would have been required. Without these periodic EVAs to refill the 2B coolant system, the channel would eventually leak enough fluid as to risk pump cavitation and system failure, resulting in the loss of the 2B power channel - the most critical of the Space Station's 8 power channels. In mid-2012, the leak rate increased to approximately 5lbm/year. Once discovered, an EVA was planned and executed within a 5 week timeframe to drastically alter the architecture of the PVTCS via connection to a dormant thermal control system not intended to be utilized as anything other than spare components. The purpose of this rerouting of the TCS was to increase system volume and to isolate the photovoltaic radiator, thought to be the likely leak source. This EVA was successfully executed on November 1st, 2012 and left the 2B PVTCS in a configuration where the system was now being adequately cooled via a totally different radiator than what the system was designed to utilize. Unfortunately, data monitoring over the next several months showed that the isolated radiator was not leaking, and the system itself continued to leak steadily until May 9th, 2013. It was on this day that the ISS crew noticed the visible presence of ammonia crystals escaping from the 2B channel's truss segment, signifying a rapid acceleration of the leak from 5lbm/year to 5lbm/day. Within 48 hours of the

  9. Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α Phosphorylation

    Science.gov (United States)

    Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J.; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed

    2006-01-01

    Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2α phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2α phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2α to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2α phosphorylation-dependent and -independent pathways that target translation initiation. PMID:16870703

  10. Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation.

    Science.gov (United States)

    Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed; Pelletier, Jerry

    2006-10-01

    Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation.

  11. Factors Affecting Age at Initial Autism Spectrum Disorder Diagnosis in a National Survey

    OpenAIRE

    Rosenberg, Rebecca E.; Landa, Rebecca; Law, J. Kiely; Stuart, Elizabeth A.; Law, Paul A.

    2011-01-01

    Entry into early intervention depends on both age of first parent concern (AOC) and age at initial autism spectrum disorder (ASD) diagnosis (AOD). Using data collected from a national online registry from 6214 children diagnosed with an ASD between 1994 and 2010 in the US, we analyzed the effect of individual, family, and geographic covariates on AOC and AOD in a multivariate linear regression model with random effects. Overall, no single modifiable factor associated with AOC or AOD emerged ...

  12. Incidence and associated factors to adverse reactions of the initial antiretroviral treatment in patients with HIV

    OpenAIRE

    Astuvilca, Juan; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Sociedad Científica de San Fernando. Lima, Perú. Estudiantes de medicina.; Arce-Villavicencio, Yanet; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Sociedad Científica de San Fernando. Lima, Perú. Estudiantes de medicina.; Sotelo, Raúl; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Sociedad Científica de San Fernando. Lima, Perú. Estudiantes de medicina.; Quispe, José; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Sociedad Científica de San Fernando. Lima, Perú. Estudiantes de medicina.; Guillén, Regina; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Estudiantes de medicina.; Peralta, Lillian; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Estudiantes de medicina.; Huaringa, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Estudiantes de medicina.; Gutiérrez, César; Departamento Académico de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima-Perú. Médico epidemiólogo.

    2007-01-01

    The high incidence of adverse reactions to the high activity antiretroviral treatment (HAART) in patients with HIV/AIDS, can affect their quality of life and adherence to the treatment. Objectives: To determinate the incidence of adverse reactions to the initial HAART and to identify the factors associated to the occurrence of adverse reactions when receiving this therapy. Material and methods: Historic cohort study. The population was conformed by all the HIV-infected adult patients (≥18...

  13. Initial absolute calibration factors for some neutron sensitive self-powered detectors

    International Nuclear Information System (INIS)

    Kroon, J.

    1975-01-01

    Self-powered flux detectors have found extensive use as monitoring devices in PWR (Pressurized Water Reactor) cores and CANDU (Canada Deuterium Uranium) type power reactors. The detectors measure fuel power distributions and indicate trip parameters for reactor control and safety requirements. Both applications demand accurate absolute initial calibration factors. Experimental results obtained in calibrating some neutron sensitive self-powered detectors is presented. (author)

  14. Insights into CYP2B6-mediated drug–drug interactions

    Directory of Open Access Journals (Sweden)

    William D. Hedrich

    2016-09-01

    Full Text Available Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously believed. The discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the enzyme. The expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor (CAR and pregnane X receptor (PXR in the liver. In addition to CYP2B6, these receptors also mediate the inductive expression of CYP3A4, and a number of important phase II enzymes and drug transporters. CYP2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide, anesthetics propofol and ketamine, synthetic opioids pethidine and methadone, and the antiretrovirals nevirapine and efavirenz, among others. Significant inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate drugs. These variances arise from a number of sources including genetic polymorphism, and xenobiotic intervention. In this review, we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.

  15. Overall impact of speed-related initiatives and factors on crash outcomes.

    Science.gov (United States)

    D'Elia, A; Newstead, S; Cameron, M

    2007-01-01

    From December 2000 until July 2002 a package of speed-related initiatives and factors took place in Victoria, Australia. The broad aim of this study was to evaluate the overall impact of the package on crash outcomes. Monthly crash counts and injury severity proportions were assessed using Poisson and logistic regression models respectively. The model measured the overall effect of the package after adjusting as far as possible for non-speed road safety initiatives and socio-economic factors. The speed-related package was associated with statistically significant estimated reductions in casualty crashes and suggested reductions in injury severity with trends towards increased reductions over time. From December 2000 until July 2002, three new speed enforcement initiatives were implemented in Victoria, Australia. These initiatives were introduced in stages and involved the following key components: More covert operations of mobile speed cameras, including flash-less operations; 50% increase in speed camera operating hours; and lowering of cameras' speed detection threshold. In addition, during the period 2001 to 2002, the 50 km/h General Urban Speed Limit (GUSL) was introduced (January 2001), there was an increase in speed-related advertising including the "Wipe Off 5" campaign, media announcements were made related to the above enforcement initiatives and there was a speeding penalty restructure. The above elements combine to make up a package of speed-related initiatives and factors. The package represents a broad, long term program by Victorian government agencies to reduce speed based on three linked strategies: more intensive Police enforcement of speed limits to deter potential offenders, i.e. the three new speed enforcement initiatives just described - supported by higher penalties; a reduction in the speed limit on local streets throughout Victoria from 60 km/h to 50 km/h; and provision of information using the mass media (television, radio and billboard) to

  16. A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulation

    DEFF Research Database (Denmark)

    Olsen, Ole H; Rand, Kasper D; Østergaard, Henrik

    2007-01-01

    Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD......) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation...... in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural...

  17. Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India.

    Directory of Open Access Journals (Sweden)

    Durba Paul

    Full Text Available BACKGROUND: Excessive time between diagnosis and initiation of tuberculosis (TB treatment contributes to ongoing TB transmission and should be minimized. In India, Revised National TB Control Programme (RNTCP focuses on indicator start of treatment within 7 days of diagnosis for patients with sputum smear-positive PTB for monitoring DOTS implementation. OBJECTIVES: To determine length of time between diagnosis and initiation of treatment and factors associated with delays of more than 7 days in smear-positive pulmonary TB. METHODS: Using existing programme records such as the TB Register, treatment cards, and the laboratory register, we conducted a retrospective cohort study of all patients with smear-positive pulmonary TB registered from July-September 2010 in two districts in India. A random sample of patients with pulmonary TB who experienced treatment delay of more than 7 days was interviewed using structured questionnaire. RESULTS: 2027 of 3411 patients registered with pulmonary TB were smear-positive. 711(35% patients had >7 days between diagnosis and treatment and 262(13% had delays >15 days. Mean duration between TB diagnosis and treatment initiation was 8 days (range = 0-128 days. Odds of treatment delay >7 days was 1.8 times more likely among those who had been previously treated (95% confidence interval [CI] 1.5-2.3 and 1.6 (95% CI 1.3-1.8 times more likely among those diagnosed in health facilities without microscopy centers. The main factors associated with a delay >7 days were: patient reluctance to start a re-treatment regimen, patients seeking second opinions, delay in transportation of drugs to the DOT centers and delay in initial home visits. To conclude, treatment delay >7 days was associated with a number of factors that included history of previous treatment and absence of TB diagnostic services in the local health facility. Decentralized diagnostic facilities and improved referral procedures may reduce such treatment

  18. Factor Analysis on Criteria Affecting Lean Retrofit for Energy Efficient Initiatives in Higher Learning Institution Buildings

    Directory of Open Access Journals (Sweden)

    Abidin Nur IzieAdiana

    2017-01-01

    Full Text Available The expansion of Higher Learning Institution (HLI is a global concerns on energy demand due to campus act like a small city. Intensive mode of operation of a building is correlated to the energy utilization. Improvement in the current energy efficiency is crucial effort to minimize the environmental effect through minimisation of energy in operation by retrofitting and upgrade the existing building system or components to be more efficient. Basically, there are three recommended steps for the improvement known as lean initiatives, green technology and clean energy in response to becoming zero energy solutions for building. The deliberation of this paper is aimed to highlight the criteria affecting in retrofitting of existing building in HLI with lean initiatives in order to achieve energy efficiency and reduction of energy comsumption. Attention is devoted to reviewing the lean energy retrofitting initiatives criteria for daylighting (side lighting, daylighting (skylight and glazing. The questionnaire survey was employed and distributed to the architects who has an expertise in green building design. Factor analysis was adopted as a method of analysis by using Principal Component with Varimax Rotation. The result is presented through summarizing the sub-criteria according to its importance with a factor loading 0.50 and above. The result found that majority of the criteria developed achieved the significant factor loading value and in accordance with the protocal of analysis. In conclusion the results from analysis of this paper assists the stakeholders in assessing the significant criteria based on the desired lean energy retrofitting initiatives and also provides a huge contribution for future planning improvement in existing buildings to become an energy efficient building.

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

    Directory of Open Access Journals (Sweden)

    Milošević Sanja

    2015-01-01

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

  20. Using service design methods for B2b service brand concept development: Case company

    OpenAIRE

    Molina Escalante, Hugo

    2014-01-01

    A short time before this study was initiated, a small B2b service company had just began op-erating its business without a brand of it’s own. The company owners were looking to design an innovative brand for their business. The purpose of this thesis was to develop the brand for this service Company in the B2b context, using practical service design and Strategic design research methods. This thesis report represents a framework for developing a B2b service brand using research methods c...

  1. The incidence of smoking and risk factors for smoking initiation in medical faculty students: cohort study

    Directory of Open Access Journals (Sweden)

    Turkay Mehtap

    2006-05-01

    Full Text Available Abstract Background Medical education requires detailed investigation because it is a period during which the attitudes and behaviors of physicians develop. The purpose of this study was to calculate the yearly smoking prevalence and incidence rates of medical faculty students and to identify the risk factors for adopting smoking behaviour. Methods This is a cohort study in which every student was asked about their smoking habits at the time of first registration to the medical faculty, and was monitored every year. Smoking prevalence, yearly incidence of initiation of smoking and average years of smoking were calculated in analysis. Results At the time of registration, 21.8% of the students smoked. At the end of six years, males had smoked for an average of 2.6 ± 3.0 years and females for 1.0 ± 1.8 years (p Conclusion The first 3 years of medical education are the most risky period for initiation of smoking. We found that factors such as being male, having a smoking friend in the same environment and having a high trait anxiety score were related to the initiation of smoking. Targeted smoking training should be mandatory for students in the Medical Faculty.

  2. Individual- and contextual-level factors associated with client-initiated HIV testing

    Directory of Open Access Journals (Sweden)

    Claudia Renata dos Santos Barros

    Full Text Available ABSTRACT: Background: Knowing the reasons for seeking HIV testing is central for HIV prevention. Despite the availability of free HIV counseling and testing in Brazil, coverage remains lacking. Methods: Survey of 4,760 respondents from urban areas was analyzed. Individual-level variables included sociodemographic characteristics; sexual and reproductive health; HIV/AIDS treatment knowledge and beliefs; being personally acquainted with a person with HIV/AIDS; and holding discriminatory ideas about people living with HIV. Contextual-level variables included the Human Development Index (HDI of the municipality; prevalence of HIV/AIDS; and availability of local HIV counseling and testing (CT services. The dependent variable was client-initiated testing. Multilevel Poisson regression models with random intercepts were used to assess associated factors. Results: Common individual-level variables among men and women included being personally acquainted with a person with HIV/AIDS and age; whereas discordant variables included those related to sexual and reproductive health and experiencing sexual violence. Among contextual-level factors, availability of CT services was variable associated with client-initiated testing among women only. The contextual-level variable “HDI of the municipality” was associated with client-initiated testing among women. Conclusion: Thus, marked gender differences in HIV testing were found, with a lack of HIV testing among married women and heterosexual men, groups that do not spontaneously seek testing.

  3. Modifying chemotherapy response by targeted inhibition of eukaryotic initiation factor 4A

    International Nuclear Information System (INIS)

    Cencic, R; Robert, F; Galicia-Vázquez, G; Malina, A; Ravindar, K; Somaiah, R; Pierre, P; Tanaka, J; Deslongchamps, P; Pelletier, J

    2013-01-01

    Translation is regulated predominantly at the initiation phase by several signal transduction pathways that are often usurped in human cancers, including the PI3K/Akt/mTOR axis. mTOR exerts unique administration over translation by regulating assembly of eukaryotic initiation factor (eIF) 4F, a heterotrimeric complex responsible for recruiting 40S ribosomes (and associated factors) to mRNA 5′ cap structures. Hence, there is much interest in targeted therapies that block eIF4F activity to assess the consequences on tumor cell growth and chemotherapy response. We report here that hippuristanol (Hipp), a translation initiation inhibitor that selectively inhibits the eIF4F RNA helicase subunit, eIF4A, resensitizes Eμ-Myc lymphomas to DNA damaging agents, including those that overexpress eIF4E—a modifier of rapamycin responsiveness. As Mcl-1 levels are significantly affected by Hipp, combining its use with the Bcl-2 family inhibitor, ABT-737, leads to a potent synergistic response in triggering cell death in mouse and human lymphoma and leukemia cells. Suppression of eIF4AI using RNA interference also synergized with ABT-737 in murine lymphomas, highlighting eIF4AI as a therapeutic target for modulating tumor cell response to chemotherapy

  4. INFLUENCE OF HEXAVALENT CHROMIUM INITIAL CONCENTRATION ON RETARDATION FACTOR AND CONTAMINANT VELOCITY IN A SOIL MEDIA

    Directory of Open Access Journals (Sweden)

    K. SHIVA PRASHANTH KUMAR

    2016-02-01

    Full Text Available Sources of soil and ground water contamination are many and include many folds of accidental spills and leaks of toxic and hazardous chemicals. Preparation of ground water contamination model needs good understanding of the behavior of contaminant transport through soil media for predicting the level of contamination of ground water in the near future at the intended site conditions. Sorption is a natural process; due to its presence, the contaminant can move slowly as compared to the ground water and hence the effects of sorption must be taken into consideration while predicting the travel time of the contaminant to reach the ground water sources. This paper discusses the results of column test studies carried out in the laboratory under controlled conditions about the spreading of contaminant (Hexavalent chromium, Cr (VI through the clay mixed red soil at two different initial concentrations (800 mg/L and 4200 mg/L. The variations of the contaminant flow velocity and retardation factor for two different initial concentrations of contaminant were brought out and discussed. The contaminant flow velocity drastically coming down for a relative concentration of 0 to 0.2 and beyond this range, the contaminant flow velocity value is decreasing in a slow rate for both the lower and higher initial contaminant concentrations tested. At the lower relative concentration, the higher retardation factor was observed and it may be due to slowly filling the available sorption sites in the soil column.

  5. Lymphogranuloma Venereum-Serovar L2b Presenting With Painful Genital Ulceration: An Emerging Clinical Presentation?

    Science.gov (United States)

    Haber, Roger; Maatouk, Ismaël; de Barbeyrac, Bertille; Bagot, Martine; Janier, Michel; Fouéré, Sébastien

    2017-05-01

    These 5 cases of atypical inflammatory lymphogranula venereum (LGV) serovar L2b presenting initially with edema and persistent painful ulceration illustrate that clinical manifestations of LGV in the current outbreak in men who have sex with men reflect the influence of both the serovars virulence and the host immune system and are not confined to proctitis. L2b serovar could have a particular high virulence profile, and the need for awareness of LGV as a cause of genital ulceration is crucial.

  6. Critical discussion of social-cognitive factors in smoking initiation among adolescents

    DEFF Research Database (Denmark)

    Bidstrup, Pernille Envold; Tjørnhøj-Thomsen, Tine; Mortensen, Erik Lykke

    2011-01-01

    Social-cognitive models have often been used in research on prevention in adolescent populations, even though the models were designed to describe adult behavior. The aim of the study reported here was to examine critically and constructively the five social-cognitive factors in the 'attitude......, social influence, self-efficacy' (ASE) model. Methods. The examination draws on the results of a qualitative follow-up study of smoking initiation based on semi-structured interviews and observations of 12 adolescents in two Danish school classes, grades 7 and 8. The qualitative study was conducted...... and if relevant discussed these aspects using other theoretical frameworks. Results. The results showed that aspects other than those in the ASE model are also important. Smoking initiation was often situational and unplanned and was sometimes used in negotiating social relationships and identity. Furthermore...

  7. Factors Related to Cigarette Smoking Initiation and Use among College Students

    Directory of Open Access Journals (Sweden)

    Ebert Sheryl

    2005-01-01

    Full Text Available Abstract The purpose of this cross-sectional study was to examine the impact of personality factors (neuroticism, extraversion, openness, agreeableness, and conscientiousness, cognitive factors (sense of coherence and self-efficacy, coping resources (family and friend social support and demographic factors (gender and ethnicity on cigarette smoking behaviors (initiation, frequency, and amount of cigarette smoking among college students. A total of 161 U.S. college students, aged 18–26, who enrolled in an introductory psychology course completed self-report questionnaires. The majority of the students had tried smoking (55%; among those who had tried, 42% were current smokers. The majority (77% who had smoked a whole cigarette did so at age 16 years or younger. Students who reported lower levels of conscientiousness and self-efficacy had a greater likelihood to had tried cigarette smoking. Also, students who had lower levels of self-efficacy reported smoking more frequently and greater quantities of cigarettes than students with higher levels of self-efficacy. Self-efficacy was the most significant predictor of smoking behaviors. Health promotion programs focused on self-efficacy may be an effective tool for reducing the initiation, frequency, and amount of cigarette smoking among college students.

  8. Novel characteristics of the biological properties of the yeast Saccharomyces cerevisiae eukaryotic initiation factor 2A.

    Science.gov (United States)

    Komar, Anton A; Gross, Stephane R; Barth-Baus, Diane; Strachan, Ryan; Hensold, Jack O; Goss Kinzy, Terri; Merrick, William C

    2005-04-22

    Eukaryotic initiation factor 2A (eIF2A) has been shown to direct binding of the initiator methionyl-tRNA (Met-tRNA(i)) to 40 S ribosomal subunits in a codon-dependent manner, in contrast to eIF2, which requires GTP but not the AUG codon to bind initiator tRNA to 40 S subunits. We show here that yeast eIF2A genetically interacts with initiation factor eIF4E, suggesting that both proteins function in the same pathway. The double eIF2A/eIF4E-ts mutant strain displays a severe slow growth phenotype, which correlated with the accumulation of 85% of the double mutant cells arrested at the G(2)/M border. These cells also exhibited a disorganized actin cytoskeleton and elevated actin levels, suggesting that eIF2A might be involved in controlling the expression of genes involved in morphogenic processes. Further insights into eIF2A function were gained from the studies of eIF2A distribution in ribosomal fractions obtained from either an eIF5BDelta (fun12Delta) strain or a eIF3b-ts (prt1-1) strain. It was found that the binding of eIF2A to 40 and 80 S ribosomes was not impaired in either strain. We also found that eIF2A functions as a suppressor of Ure2p internal ribosome entry site-mediated translation in yeast cells. The regulation of expression from the URE2 internal ribosome entry site appears to be through the levels of eIF2A protein, which has been found to be inherently unstable with a half-life of approximately 17 min. It was hypothesized that this instability allows for translational control through the level of eIF2A protein in yeast cells.

  9. Factors Associated with Gender-Affirming Surgery and Age of Hormone Therapy Initiation Among Transgender Adults

    Science.gov (United States)

    Beckwith, Noor; Reisner, Sari L.; Zaslow, Shayne; Mayer, Kenneth H.; Keuroghlian, Alex S.

    2017-01-01

    Abstract Purpose: Gender-affirming surgeries and hormone therapy are medically necessary treatments to alleviate gender dysphoria; however, significant gaps exist in the research and clinical literature on surgery utilization and age of hormone therapy initiation among transgender adults. Methods: We conducted a retrospective review of electronic health record data from a random sample of 201 transgender patients of ages 18–64 years who presented for primary care between July 1, 2010 and June 30, 2015 (inclusive) at an urban community health center in Boston, MA. Fifty percent in our analyses were trans masculine (TM), 50% trans feminine, and 24% reported a genderqueer/nonbinary gender identity. Regression models were fit to assess demographic, gender identity-related, sexual history, and mental health correlates of gender-affirming surgery and of age of hormone therapy initiation. Results: Overall, 95% of patients were prescribed hormones by their primary care provider, and the mean age of initiation of masculinizing or feminizing hormone prescriptions was 31.8 years (SD=11.1). Younger age of initiation of hormone prescriptions was associated with being TM, being a student, identifying as straight/heterosexual, having casual sexual partners, and not having past alcohol use disorder. Approximately one-third (32%) had a documented history of gender-affirming surgery. Factors associated with increased odds of surgery were older age, higher income levels, not identifying as bisexual, and not having a current psychotherapist. Conclusion: This study extends our understanding of prevalence and factors associated with gender-affirming treatments among transgender adults seeking primary care. Findings can inform future interventions to expand delivery of clinical care for transgender patients. PMID:29159310

  10. Factors associated with contraceptive use and initiation of coital activity after childbirth

    Directory of Open Access Journals (Sweden)

    John E Ekabua

    2010-08-01

    Full Text Available John E Ekabua1, Kufre J Ekabua2, Patience Odusolu1, Chritopher U Iklaki1, Thomas U Agan1, Aniekan J Etokidem21Department of Obstetrics and Gynecology, University of Calabar Teaching Hospital, Calabar, Cross River State, Nigeria; 2Department of Community Medicine, University of Calabar Teaching Hospital, Calabar, Cross River State, NigeriaAbstract: The aim of the study is to identify the factors influencing contraceptive use and initiation of sexual intercourse after childbirth. This was a cross-sectional descriptive survey involving 256 consecutive women, who delivered between April and October, 2007, presenting at the Immunization Clinic, University of Calabar Teaching Hospital, Nigeria in April, 2008. Data was obtained using an interviewer-administered structured questionnaire. Women who had antenatal and postnatal counseling were significantly more likely to use contraceptives than those who did not have counseling (odds ratio (OR 0.29; 95% confidence interval (CI 0.14–0.59; P = 0.0002 and OR 0.18; 95% CI 0.08–0.38; P = 0.0000002 respectively. Other variables significantly associated with contraceptive use included education (P = 0.0470 and reproductive goal (P = 0.0303. Linear regression analysis showed direct relationship between caesarean section and episiotomy as modes of delivery, and initiation of coitus (r2 = 0.439 and 0.45 respectively. Concerning residence after childbirth, staying at home and with in-laws showed direct relationship with initiation of coitus (r2 = 0.208 and 10.750 respectively. The number of women abstaining from intercourse showed a decreasing trend with increasing months after childbirth. Initiation of coitus was significantly associated with resumption of menstruation (P < 0.0001 and non-contraceptive use (P = 0.0089. In conclusion, this study shows the need for use of postpartum contraception before fecund women become susceptible to pregnancy.Keywords: postpartum contraception, factors affecting use

  11. Risk factors associated with recurrent hemorrhage after the initial improvement of colonic diverticular bleeding.

    Science.gov (United States)

    Nishikawa, Hiroki; Maruo, Takanori; Tsumura, Takehiko; Sekikawa, Akira; Kanesaka, Takashi; Osaki, Yukio

    2013-03-01

    We elucidated risk factors contributing to recurrent hemorrhage after initial improvement of colonic diverticular bleeding. 172 consecutive hospitalized patients diagnosed with colonic diverticular bleeding were analyzed. Recurrent hemorrhage after initial improvement of colonic diverticular bleeding is main outcome measure. We analyzed factors contributing to recurrent hemorrhage risk in univariate and multivariate analyses. The length of the observation period after improvement of colonic diverticular bleeding was 26.4 +/- 14.6 months (range, 1-79 months). The cumulative recurrent hemorrhage rate in all patients at 1 and 2 years was 34.8% and 41.8%, respectively. By univariate analysis, age > 70 years (P = 0.021), BMI > 25 kg/m2 (P = 0.013), the use of anticoagulant drugs (P = 0.034), the use of NSAIDs (P = 0.040), history of hypertension (P = 0.011), history of smoking (P = 0.030) and serum creatinine level > 1.5 mg/dL (P bleeding. By multivariate analysis, age > 70 years (Hazard ratio (HR), 1.905, 95% confidence interval (CI), 1.067-3.403, P = 0.029), history of hypertension (HR, 0.493, 95% CI, 0.245-0.993, P = 0.048) and serum creatinine level > 1.5 mg/dL (HR, 95% CI, 0.288-0.964, P = 0.044) were shown to be significant independent risk factors. Close observation after the initial improvement of colonic diverticular bleeding is needed, especially in elderly patients or patients with history of hypertension or renal deficiency.

  12. Incidence of pregnancy following antiretroviral therapy initiation and associated factors in eight West African countries

    Science.gov (United States)

    Burgos-Soto, Juan; Balestre, Eric; Minga, Albert; Ajayi, Samuel; Sawadogo, Adrien; Zannou, Marcel D.; Leroy, Valériane; Ekouevi, Didier K.; Dabis, François; Becquet, Renaud

    2014-01-01

    Introduction This study aimed at estimating the incidence of pregnancy after antiretroviral therapy (ART) initiation in eight West African countries over a 10-year period. Methods A retrospective analysis was conducted within the international database of the IeDEA West Africa Collaboration. All HIV-infected women aged Pregnancy after ART initiation was the main outcome and was based on clinical reporting. Poisson regression analysis accounting for country heterogeneity was computed to estimate first pregnancy incidence post-ART and to identify its associated factors. Pregnancy incidence rate ratios were adjusted on country, baseline CD4 count and clinical stage, haemoglobin, age, first ART regimen and calendar year. Results Overall 29,425 HIV-infected women aged 33 years in median [Inter Quartile Range: 28–38] contributed for 84,870 women-years of follow-up to this analysis. The crude incidence of first pregnancy (2,304 events) was 2.9 per 100 women-years [95% confidence interval [CI]: 2.7–3.0], the highest rate being reported among women aged 25–29 years: 4.7 per 100 women-years; 95% CI: 4.3–5.1. The overall Kaplan-Meier probability of pregnancy occurrence by the fourth year on ART was 10.9% (95% CI: 10.4–11.4) and as high as 28.4% (95% CI: 26.3–30.6) among women aged 20–29 years at ART initiation. Conclusion The rate of pregnancy occurrence after ART initiation among HIV-infected women living in the West Africa region was high. Family planning services tailored to procreation needs should be provided to all HIV-infected women initiating ART and health consequences carefully monitored in this part of the world. PMID:25216079

  13. 7 CFR 301.85-2b - Exempted articles. 1

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles are...

  14. Component Based System Framework for Dynamic B2B Interaction

    NARCIS (Netherlands)

    Hu jinmin, Jinmin; 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 support

  15. TRUST IN B2B E-MARKETPLACES

    Directory of Open Access Journals (Sweden)

    SEBASTIAN KOT

    2011-01-01

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

  16. Factors Affecting Age at Initial Autism Spectrum Disorder Diagnosis in a National Survey

    Directory of Open Access Journals (Sweden)

    Rebecca E. Rosenberg

    2011-01-01

    Full Text Available Entry into early intervention depends on both age of first parent concern (AOC and age at initial autism spectrum disorder (ASD diagnosis (AOD. Using data collected from a national online registry from 6214 children diagnosed with an ASD between 1994 and 2010 in the US, we analyzed the effect of individual, family, and geographic covariates on AOC and AOD in a multivariate linear regression model with random effects. Overall, no single modifiable factor associated with AOC or AOD emerged but cumulative variation in certain individual- and family-based features, as well as some geographic factors, all contribute to AOC and AOD variation. A multipronged strategy is needed for targeted education and awareness campaigns to maximize outcomes and decrease disparities in ASD care.

  17. Factors influencing timely initiation and completion of gestational diabetes mellitus screening and diagnosis

    DEFF Research Database (Denmark)

    Nielsen, Karoline Kragelund; Rheinländer, Thilde; Kapur, Anil

    2017-01-01

    BACKGROUND: In 2007, universal screening for gestational diabetes mellitus (GDM) was introduced in Tamil Nadu, India. To identify factors hindering or facilitating timely initiation and completion of the GDM screening and diagnosis process, our study investigated how pregnant women in rural...... and urban Tamil Nadu access and navigate different GDM related health services. METHODS: The study was carried out in two settings: an urban private diabetes centre and a rural government primary health centre. Observations of the process of screening and diagnosis at the health centres as well as semi...... norms and cultural practices. CONCLUSIONS: Minimising and aligning complex stepwise processes of prenatal care and GDM screening delivery and attention to the factors influencing it are important for further improving and expanding GDM screening and related services, not only in Tamil Nadu but in other...

  18. Emergence of canine parvovirus subtype 2b (CPV-2b) infections in Australian dogs.

    Science.gov (United States)

    Clark, Nicholas J; Seddon, Jennifer M; Kyaw-Tanner, Myat; Al-Alawneh, John; Harper, Gavin; McDonagh, Phillip; Meers, Joanne

    2018-03-01

    Tracing the temporal dynamics of pathogens is crucial for developing strategies to detect and limit disease emergence. Canine parvovirus (CPV-2) is an enteric virus causing morbidity and mortality in dogs around the globe. Previous work in Australia reported that the majority of cases were associated with the CPV-2a subtype, an unexpected finding since CPV-2a was rapidly replaced by another subtype (CPV-2b) in many countries. Using a nine-year dataset of CPV-2 infections from 396 dogs sampled across Australia, we assessed the population dynamics and molecular epidemiology of circulating CPV-2 subtypes. Bayesian phylogenetic Skygrid models and logistic regressions were used to trace the temporal dynamics of CPV-2 infections in dogs sampled from 2007 to 2016. Phylogenetic models indicated that CPV-2a likely emerged in Australia between 1973 and 1988, while CPV-2b likely emerged between 1985 and 1998. Sequences from both subtypes were found in dogs across continental Australia and Tasmania, with no apparent effect of climate variability on subtype occurrence. Both variant subtypes exhibited a classical disease emergence pattern of relatively high rates of evolution during early emergence followed by subsequent decreases in evolutionary rates over time. However, the CPV-2b subtype maintained higher mutation rates than CPV-2a and continued to expand, resulting in an increase in the probability that dogs will carry this subtype over time. Ongoing monitoring programs that provide molecular epidemiology surveillance will be necessary to detect emergence of new variants and make informed recommendations to develop reliable detection and vaccine methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Regulation of PI-2b Pilus Expression in Hypervirulent Streptococcus agalactiae ST-17 BM110.

    Directory of Open Access Journals (Sweden)

    Bruno Périchon

    Full Text Available The widely spread Streptococcus agalactiae (also known as Group B Streptococcus, GBS "hypervirulent" ST17 clone is strongly associated with neonatal meningitis. The PI-2b locus is mainly found in ST17 strains but is also present in a few non ST17 human isolates such as the ST-7 prototype strain A909. Here, we analysed the expression of the PI-2b pilus in the ST17 strain BM110 as compared to the non ST17 A909. Comparative genome analyses revealed the presence of a 43-base pair (bp hairpin-like structure in the upstream region of PI-2b operon in all 26 ST17 genomes, which was absent in the 8 non-ST17 strains carrying the PI-2b locus. Deletion of this 43-bp sequence in strain BM110 resulted in a 3- to 5-fold increased transcription of PI-2b. Characterization of PI-2b promoter region in A909 and BM110 strains was carried out by RNAseq, primer extension, qRT-PCR and transcriptional fusions with gfp as reporter gene. Our results indicate the presence of a single promoter (Ppi2b with a transcriptional start site (TSS mapped 37 bases upstream of the start codon of the first PI-2b gene. The large operon of 16 genes located upstream of PI-2b codes for the group B carbohydrate (also known as antigen B, a major constituent of the bacterial cell wall. We showed that the hairpin sequence located between antigen B and PI-2b operons is a transcriptional terminator. In A909, increased expression of PI-2b probably results from read-through transcription from antigen B operon. In addition, we showed that an extended 5' promoter region is required for maximal transcription of gfp as a reporter gene in S. agalactiae from Ppi2b promoter. Gene reporter assays performed in Lactococcus lactis strain NZ9000, a related non-pathogenic Gram-positive species, revealed that GBS-specific regulatory factors are required to drive PI-2b transcription. PI-2b expression is up-regulated in the BM110ΔcovR mutant as compared to the parental BM110 strain, but this effect is probably

  20. Adenosine A2b receptor promotes progression of human oral cancer

    International Nuclear Information System (INIS)

    Kasama, Hiroki; Sakamoto, Yosuke; Kasamatsu, Atsushi; Okamoto, Atsushi; Koyama, Tomoyoshi; Minakawa, Yasuyuki; Ogawara, Katsunori; Yokoe, Hidetaka; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2015-01-01

    Adenosine A2b receptor (ADORA2B) encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. Little is known about the relevance of ADORA2B to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of ADORA2B in OSCC. The ADORA2B expression levels in nine OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using an ADORA2B knockdown model, we assessed cellular proliferation and expression of hypoxia-inducible factor1α (HIF-1α). We examined the adenosine receptor expression profile under both normoxic and hypoxic conditions in the OSCC-derived cells. In addition to in vitro data, the clinical correlation between the ADORA2B expression levels in primary OSCCs (n = 100 patients) and the clinicopathological status by immunohistochemistry (IHC) also was evaluated. ADORA2B mRNA and protein were up-regulated significantly (p < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. Suppression of ADORA2B expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells. HIF-1α also was down-regulated in ADORA2B knockdown OSCC cells. During hypoxia, ADORA2B expression was induced significantly (p < 0.05) in the mRNA and protein after 24 hours of incubation in OSCC-derived cells. IHC showed that ADORA2B expression in primary OSCCs was significantly (p < 0.05) greater than in the normal oral counterparts and that ADORA2B-positive OSCCs were correlated closely (p < 0.05) with tumoral size. Our results suggested that ADORA2B controls cellular proliferation via HIF-1α activation, indicating that ADORA2B may be a key regulator of tumoral progression in OSCCs. The online version of this article (doi:10.1186/s12885-015-1577-2) contains

  1. Translation initiation on mRNAs bound by nuclear cap-binding protein complex CBP80/20 requires interaction between CBP80/20-dependent translation initiation factor and eukaryotic translation initiation factor 3g.

    Science.gov (United States)

    Choe, Junho; Oh, Nara; Park, Sungjin; Lee, Ye Kyung; Song, Ok-Kyu; Locker, Nicolas; Chi, Sung-Gil; Kim, Yoon Ki

    2012-05-25

    In the cytoplasm of mammalian cells, either cap-binding proteins 80 and 20 (CBP80/20) or eukaryotic translation initiation factor (eIF) 4E can direct the initiation of translation. Although the recruitment of ribosomes to mRNAs during eIF4E-dependent translation (ET) is well characterized, the molecular mechanism for CBP80/20-dependent translation (CT) remains obscure. Here, we show that CBP80/20-dependent translation initiation factor (CTIF), which has been shown to be preferentially involved in CT but not ET, specifically interacts with eIF3g, a component of the eIF3 complex involved in ribosome recruitment. By interacting with eIF3g, CTIF serves as an adaptor protein to bridge the CBP80/20 and the eIF3 complex, leading to efficient ribosome recruitment during CT. Accordingly, down-regulation of CTIF using a small interfering RNA causes a redistribution of CBP80 from polysome fractions to subpolysome fractions, without significant consequence to eIF4E distribution. In addition, down-regulation of eIF3g inhibits the efficiency of nonsense-mediated mRNA decay, which is tightly coupled to CT but not to ET. Moreover, the artificial tethering of CTIF to an intercistronic region of dicistronic mRNA results in translation of the downstream cistron in an eIF3-dependent manner. These findings support the idea that CT mechanistically differs from ET.

  2. Analysis list: Gtf2b [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Gtf2b Blood,Cardiovascular,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/m...m9/target/Gtf2b.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Gtf2b.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Gtf2b.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2b.Blo...od.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2b.Cardiovascular.t...sv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Gtf2b.Liver.tsv http://dbarchive.biosciencedbc.jp/kyu

  3. Factor C*, the specific initiation component of the mouse RNA polymerase I holoenzyme, is inactivated early in the transcription process.

    OpenAIRE

    Brun, R P; Ryan, K; Sollner-Webb, B

    1994-01-01

    Factor C* is the component of the RNA polymerase I holoenzyme (factor C) that allows specific transcriptional initiation on a factor D (SL1)- and UBF-activated rRNA gene promoter. The in vitro transcriptional capacity of a preincubated rDNA promoter complex becomes exhausted very rapidly upon initiation of transcription. This is due to the rapid depletion of C* activity. In contrast, C* activity is not unstable in the absence of transcription, even in the presence of nucleoside triphosphates ...

  4. A case-control study on reduced HDL2b in patients with polycystic ovarian syndrome.

    Science.gov (United States)

    Hu, Weihong; Chen, Lin; Mao, Sha; Qiao, Jie

    2016-10-01

    High-density lipoprotein (HDL) is an important factor associated with the increasing risk of future ischaemic heart disease. In this study, we analyzed serum HDL2b level in the patients with polycystic ovary syndrome (PCOS). Total of 60 female patients with PCOS was enrolled for assessment and another 60 non-PCOS females with matched age and weight were selected as control. A highly sensitive microfluidic chip was employed to analyze the serum HDL subfractions. Serum HDL2b and HDL2b/HDL ratio were decreased in PCOS group than those in the control group (p PCOS patients by using the microfluidic chip method assessment. Hyperandrogenism was the main factor to affect HDL2b and its ratio to total HDL in PCOS patients, and it might increase the incidence of atherosclerosis as well as the risk of coronary heart disease.

  5. Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

    Science.gov (United States)

    Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

    2017-06-01

    Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

  6. Factors affecting science reform: Bridging the gap between reform initiatives and teaching practices

    Science.gov (United States)

    Pensak, Karl John

    In response to the perceived deficiencies in science education today, and to the expressed need for research into the culture of schools (due primarily to the failure of many science reforms in the past), this study used a broad based approach to study the gap between science education research and science education practice. This study identified 47 factors that may encourage or inhibit science curriculum reform. A survey was conducted to determine which factors were perceived to be important by local and national K-12 classroom teachers, science supervisors/coordinators, and college/university professors. Continual staff development (scheduled as part of teachers' work day/week/month), funding (for long-term staff development, teacher training and support, science laboratory facilities and materials), teacher motivation and "ownership" of the reform, the need for collaborative opportunities for classroom teachers, teachers' college preparation, textbook reform, community support, and reform initiatives that are "in tune" with assessment, are major factors identified as having a substantial affect on the successful adoption, implementation, and institutionalization of science reforms.

  7. Recessive Resistance to Plant Viruses: Potential Resistance Genes Beyond Translation Initiation Factors

    Directory of Open Access Journals (Sweden)

    Masayoshi Hashimoto

    2016-10-01

    Full Text Available The ability of plant viruses to propagate their genomes in host cells depends on many host factors. In the absence of an agrochemical that specifically targets plant viral infection cycles, one of the most effective methods for controlling viral diseases in plants is taking advantage of the host plant’s resistance machinery. Recessive resistance is conferred by a recessive gene mutation that encodes a host factor critical for viral infection. It is a branch of the resistance machinery and, as an inherited characteristic, is very durable. Moreover, recessive resistance may be acquired by a deficiency in a negative regulator of plant defense responses, possibly due to the autoactivation of defense signaling. Eukaryotic translation initiation factor (eIF 4E and eIF4G and their isoforms are the most widely exploited recessive resistance genes in several crop species, and they are effective against a subset of viral species. However, the establishment of efficient, recessive resistance-type antiviral control strategies against a wider range of plant viral diseases requires genetic resources other than eIF4Es. In this review, we focus on recent advances related to antiviral recessive resistance genes evaluated in model plants and several crop species. We also address the roles of next-generation sequencing and genome editing technologies in improving plant genetic resources for recessive resistance-based antiviral breeding in various crop species.

  8. Infantile onset Vanishing White Matter disease associated with a novel EIF2B5 variant, remarkably long life span, severe epilepsy, and hypopituitarism.

    Science.gov (United States)

    Woody, April L; Hsieh, David T; McIver, Harkirtin K; Thomas, Linda P; Rohena, Luis

    2015-04-01

    Vanishing White Matter disease (VWM) is an inherited progressive leukoencephalopathy caused by mutations in the genes EIF2B1-5, which encode for the 5 subunits of the eukaryotic initiation factor 2B (eIF2B), a regulator of protein synthesis. VWM typically presents with acute neurological decline following febrile infections or minor head trauma, and subsequent progressive neurological and cognitive regression. There is a varied clinical spectrum of VWM, with earlier onset associated with more severe phenotypes. Brain magnetic resonance imaging is usually diagnostic with diffusely abnormal white matter, progressing over time to cystic degeneration. We are reporting on a patient with infantile onset VWM associated with three heterozygous missense variants in EIF2B5, including a novel missense variant on exon 6 of EIF2B5 (D262N), as well as an interstitial duplication at 7q21.12. In addition, our case is unusual because of a severe epilepsy course, a novel clinical finding of hypopituitarism manifested by hypothyroidism and adrenal insufficiency, and a prolonged life span with current age of survival of 4 years and 11 months. © 2015 Wiley Periodicals, Inc.

  9. Early Initiation of Antenatal Care and Factors Associated with Early Antenatal Care Initiation at Health Facilities in Southern Ethiopia

    Directory of Open Access Journals (Sweden)

    Mengesha Boko Geta

    2017-01-01

    Full Text Available Antenatal care (ANC is care given to pregnant mothers to timely identify and mitigate pregnancy related problems that can harm mother or fetus. Most of Ethiopian mothers present late for ANC. The aim of this paper was to assess determinants of early antenatal care initiation among pregnant women. Mothers attending Shebedino District Health Centers for ANC between January 12 and February 18, 2015, were invited to the study. Multistage sampling technique and structured questionnaire were used to collect data by trained data collectors. Univariate and bivariate analysis were conducted to study the association between explanatory and outcome variable. Out of 608 women, 132 [21.71%] had their first ANC within the recommended time [before or at 3 months]. Media access [AOR = 2.11 95% CI 1.00, 3.22], knowledge about the correct time of ANC booking [AOR = 4.49 95% CI 2.47, 6.16], and having been advised to book within 12 weeks [AOR = 4.14 95% CI 3.80, 5.21] were determinants of first-trimester booking. Health professionals and care providers should provide full information, advice, and appropriate care about early ANC for every eligible mother.

  10. Use of the i2b2 research query tool to conduct a matched case-control clinical research study: advantages, disadvantages and methodological considerations.

    Science.gov (United States)

    Johnson, Emilie K; Broder-Fingert, Sarabeth; Tanpowpong, Pornthep; Bickel, Jonathan; Lightdale, Jenifer R; Nelson, Caleb P

    2014-01-30

    A major aim of the i2b2 (informatics for integrating biology and the bedside) clinical data informatics framework aims to create an efficient structure within which patients can be identified for clinical and translational research projects.Our objective was to describe the respective roles of the i2b2 research query tool and the electronic medical record (EMR) in conducting a case-controlled clinical study at our institution. We analyzed the process of using i2b2 and the EMR together to generate a complete research database for a case-control study that sought to examine risk factors for kidney stones among gastrostomy tube (G-tube) fed children. Our final case cohort consisted of 41/177 (23%) of potential cases initially identified by i2b2, who were matched with 80/486 (17%) of potential controls. Cases were 10 times more likely to be excluded for inaccurate coding regarding stones vs. inaccurate coding regarding G-tubes. A majority (67%) of cases were excluded due to not meeting clinical inclusion criteria, whereas a majority of control exclusions (72%) occurred due to inadequate clinical data necessary for study completion. Full dataset assembly required complementary information from i2b2 and the EMR. i2b2 was critical as a query analysis tool for patient identification in our case-control study. Patient identification via procedural coding appeared more accurate compared with diagnosis coding. Completion of our investigation required iterative interplay of i2b2 and the EMR to assemble the study cohort.

  11. Origins of robustness in translational control via eukaryotic translation initiation factor (eIF) 2.

    Science.gov (United States)

    Khan, Mohammad Farhan; Spurgeon, Sarah; von der Haar, Tobias

    2018-05-14

    Phosphorylation of eukaryotic translation initiation factor 2 (eIF2) is one of the best studied and most widely used means for regulating protein synthesis activity in eukaryotic cells. This pathway regulates protein synthesis in response to stresses, viral infections, and nutrient depletion, among others. We present analyses of an ordinary differential equation-based model of this pathway, which aim to identify its principal robustness-conferring features. Our analyses indicate that robustness is a distributed property, rather than arising from the properties of any one individual pathway species. However, robustness-conferring properties are unevenly distributed between the different species, and we identify a guanine nucleotide dissociation inhibitor (GDI) complex as a species that likely contributes strongly to the robustness of the pathway. Our analyses make further predictions on the dynamic response to different types of kinases that impinge on eIF2. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

    DEFF Research Database (Denmark)

    Aznar, Susana; Knudsen, Gitte M

    2011-01-01

    . This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals......The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development...... with a genetic linkage to depression, there may be an increased vulnerability towards the initiation of a detrimental neurodegenerative cascade. The following review will deal with the various observations reported within the different neurobiological systems known to be involved and affected in depression, like...

  13. Risk factors for lower limb injuries during initial naval training: a prospective study.

    Science.gov (United States)

    Bonanno, Daniel R; Munteanu, S E; Murley, G S; Landorf, K B; Menz, H B

    2018-04-06

    This study aimed to identify risk factors associated with the development of common lower limb injuries during initial defence training in naval recruits who were enrolled in a randomised trial. Three-hundred and six naval recruits were randomly allocated flat insoles (n=153) or foot orthoses (n=153) while undertaking 11 weeks of initial training. Participant characteristics (including anthropometrics, general health, physical activity, fitness and foot characteristics) were collected at the baseline assessment and injuries were documented prospectively. Injury was defined as the combined incidence of participants with medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy and plantar fasciitis/plantar heel pain throughout the 11 weeks of training. A discriminant function analysis was used to explore the ability of baseline measures to predict injury. Overall, 67 (21.9%) participants developed an injury. Discriminant function analysis revealed that participants who sustained an injury were slightly younger (mean 21.4±SD 4.1 vs 22.5±5.0 years) and were less likely to be allocated to the foot orthosis group (40% vs 53%) compared with those who remained uninjured. The accuracy of these baseline variables to predict injury was moderate (78.1%). Lower limb injury was not accurately predicted from health questionnaires, fitness results and clinical assessments in naval recruits undertaking initial defence training. However, although not reaching statistical significance, the use of foot orthoses may be protective against common lower limb injuries. ACTRN12615000024549; Post-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Implementation of oral health initiatives by Australian rural communities: Factors for success.

    Science.gov (United States)

    Taylor, Judy; Carlisle, Karen; Farmer, Jane; Larkins, Sarah; Dickson-Swift, Virginia; Kenny, Amanda

    2018-01-01

    In this paper, we consider factors significant in the success of community participation in the implementation of new oral health services. Our analysis draws on data from the Rural Engaging Communities in Oral Health (Rural ECOH) study (2014-2016). We aimed to assess the Australian relevance of a Scottish community participation framework for health service development; Remote Service Futures. Internationally, community participation in planning of health initiatives is common, but less common in new service implementation. Health managers query the legitimacy of "lay" community members, whether they will persist, and whether they can act as change agents. Our data provide evidence that helps answer these queries. Six communities, located within regions covered by two large rural primary healthcare organisations (Medicare Locals), were selected in two Australian states. Two university-based facilitators worked with a group of local residents (for each community) to monitor implementation of new oral health initiatives designed through participatory processes. Data about implementation were collected through interviews with 28 key stakeholders at the beginning of implementation and 12 months later. Data were coded, themed and analysed abductively. Five themes emerged; the inter-relationship between community motivation to participate with the fortunes of the oral health initiatives, having the "right" people involved, continuing involvement of sponsors and/or significant people, trusting working relationships between participants and perceiving benefits from participation. Findings provide evidence of a role for community participation in implementing new community services if solid partnerships with relevant providers can be negotiated and services are seen to be relevant and useful to the community. © 2017 John Wiley & Sons Ltd.

  15. Haplotypes frequencies of CYP2B6 in Malaysia

    Directory of Open Access Journals (Sweden)

    N Musa

    2012-01-01

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

  16. Factors affecting the initial literacy development of urban and rural learners in the Iganga district, Uganda

    Directory of Open Access Journals (Sweden)

    Banda, Felix

    2005-12-01

    Full Text Available The initial motivation for the study was data from the Ministry of Education in Uganda that suggests that in terms of academic performance, urban learners continually outperform rural schools at primary and secondary school levels (Ministry of Education 2002. At present all government examinations are written in English. However, the language in education policy in Uganda differentially stipulates the use English as medium of instruction in urban schools and the use of the mother tongue in rural schools (cf. Kyeyune 2004. Other factors which mitigate against rural learners’ successful academic performance are untrained educators, poor infrastructure and school management practices in rural schools, poverty, lack of supportive academic discourse practices, and a general lack of enthusiasm among rural parents (most of whom have very little formal education for their children’s education. Using data from observations of selected urban and rural homes and schools in The Iganga district and field notes in the form of diary entries, the study draws on New Literacy Studies (NLS particularly the notion of literacy as social practice (Street 2001; Gee 2000; Baynham 2000, 2001, to explore the differential effect of urban and rural-based acculturation processes on the initial literacy development of learners. Finally, since 88% of Ugandans live in rural areas (Uganda Bureau of Statistics 2002, the pedagogical implications for primary schools are discussed and suggestions are made on how to establish an inclusive education system.

  17. Sexual milestones and factors associated with coitus initiation among Israeli high school students.

    Science.gov (United States)

    Shtarkshall, Ronny A; Carmel, Sara; Jaffe-Hirschfield, Dena; Woloski-Wruble, Anna

    2009-08-01

    In view of the developmental approach to sexual behavior, this article presents the stages of sexual behavior leading to coitus in four grades of high school students in Israel and the sociodemographic factors associated with initiating coitus. Analyses were based on data from the first national study dealing comprehensively with sexuality in 30 years. A self-administered questionnaire was completed by a random sample of 4,609 students of the General Educational (secular) system that included 68% of the Hebrew-speaking sector or 55% of all students in Israel. Our findings indicated a progressive set of stages of sexual behavior forming a Guttman scale, from kissing and petting over the clothes though petting under the clothes and genital touching to coitus. In comparison to results of a 1970 Israeli survey, we found an increase in practice in all Guttman scale stages of sexual behavior, as well as a diminished gap between genders. The gap fully disappeared in the three lower stages. Predictive variables of coitus initiation included gender, religiosity, immigration status, family structure, perceptions of academic achievements, and the proportion of peers practicing coitus. In addition to gender, perception of the proportion of peers that already practiced intercourse was the best predictor followed by grade, perception of academic achievement, and family structure. Marked differences were noticed between genders regarding associations with religiosity and immigration status. The discussion focused on comparisons to findings in other countries, the contribution of the findings to the understanding of Israeli adolescents' sexual behavior, and practical educational implications.

  18. Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.

    Directory of Open Access Journals (Sweden)

    Gabriela Galicia-Vázquez

    Full Text Available Gene expression during muscle cell differentiation is tightly regulated at multiple levels, including translation initiation. The PI3K/mTOR signalling pathway exerts control over protein synthesis by regulating assembly of eukaryotic initiation factor (eIF 4F, a heterotrimeric complex that stimulates recruitment of ribosomes to mRNA templates. One of the subunits of eIF4F, eIF4A, supplies essential helicase function during this phase of translation. The presence of two cellular eIF4A isoforms, eIF4AI and eIF4AII, has long thought to impart equivalent functions to eIF4F. However, recent experiments have alluded to distinct activities between them. Herein, we characterize distinct regulatory mechanisms between the eIF4A isoforms during muscle cell differentiation. We find that eIF4AI levels decrease during differentiation whereas eIF4AII levels increase during myofiber formation in a MyoD-dependent manner. This study characterizes a previously undefined mechanism for eIF4AII regulation in differentiation and highlights functional differences between eIF4AI and eIF4AII. Finally, RNAi-mediated alterations in eIF4AI and eIF4AII levels indicate that the myogenic process can tolerate short term reductions in eIF4AI or eIF4AII levels, but not both.

  19. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

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

    Lifescience Database Archive (English)

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

  1. Factores cognitivos asociados con el inicio del consumo de tabaco en adolescentes Cognitive factors associated with smoking initiation in adolescents

    Directory of Open Access Journals (Sweden)

    Mònica Cortés

    2005-02-01

    Full Text Available Objetivo: Estudiar la asociación de los factores cognitivos del modelo de cambio conductual Attitude Self-Efficacy (ASE a las diferentes fases de inicio del consumo de tabaco en adolescentes. Método: Se realizó un estudio transversal (durante el año 2000 en el que se encuestó al alumnado de 2.o de Educación Secundaria Obligatoria (13-14 años de edad de los institutos de educación secundaria públicos de Cornellà de Llobregat (Barcelona sobre las actitudes y el consumo de tabaco. Se realizó un análisis de regresión logística para identificar las variables asociadas con cada estado del consumo de tabaco (odds ratio [OR] de experimentadores frente a no fumadores y de fumadores frente a experimentadores. Resultados: La prevalencia del consumo diario de tabaco fue del 22,9% (intervalo de confianza [IC] del 95%, 16,5-29,3 en los chicos y del 36,2% (IC del 95%, 29,7-42,6 en las chicas. Los determinantes de la experimentación (frente a no fumar fueron las actitudes hacia el tabaco -desacuerdo con los espacios sin humo (OR = 3,46; IC del 95%, 1,65-7,24 y acuerdo con la promoción del tabaco (OR = 3,42; IC del 95%, 1,42-8,28- y la norma subjetiva (amigos percibidos como fumadores: OR = 2,50; IC del 95%, 1,17-5,35. Los factores asociados con el consumo regular de tabaco (frente a experimentar fueron de autoeficacia y actitudinales. Conclusiones: Parece indicado trabajar los determinantes de norma subjetiva y las actitudes hacia el tabaco en programas dirigidos a edades más tempranas, ya que están más asociados con el paso de no fumador a experimentador, e insistir más tarde en las habilidades para el rechazo de tabaco ofrecido por amigos que cobró importancia en la fase de experimentador a fumador.Objective: To study the association between cognitive factors of the behavioral change model «Attitude Self Efficacy» (ASE at different phases of smoking initiation among adolescents. Methods: We carried out a cross-sectional survey among

  2. Harnessing marketing automation for B2B content marketing

    OpenAIRE

    Järvinen, Joel; Taiminen, Heini

    2016-01-01

    The growing importance of the Internet to B2B customer purchasing decisions has motivated B2B sellers to create digital content that leads potential buyers to interact with their company. This trend has engendered a new paradigm referred to as ‘content marketing.’ This study investigates the organizational processes for developing valuable and timely content to meet customer needs and for integrating content marketing with B2B selling processes. The results of this single case study demonstra...

  3. Risk factors for reoperation after initial burr hole trephination in chronic subdural hematomas.

    Science.gov (United States)

    Schwarz, Falko; Loos, Franz; Dünisch, Pedro; Sakr, Yasser; Safatli, Diaa Al; Kalff, Rolf; Ewald, Christian

    2015-11-01

    The optimal management of chronic subdural hematomas remains a challenge. Twist drill craniotomy or burr hole trephination are considered optimal initial treatments, but the reoperation rate for hematoma recurrence and other complications is still high. Therefore, evaluation of possible risk factors for initial treatment failure is crucial. In this context, we performed a study to define a possible subpopulation that may benefit from a more invasive initial treatment regime. We retrospectively reviewed the medical charts of 193 patients with 250 chronic subdural hematomas who had undergone burr hole trephination as first-line therapy in our institution between January 2005 and October 2012. To identify risk factors for reoperation, a multivariable logistic regression analysis was performed with reoperation as the dependent variable. Surgical complications, including acute rebleeding, infection and chronic hematoma recurrence, were analyzed separately using a logistic regression model. The mean age of the cohort was 71.4 years. The male/female ratio was 137:56. Reoperation was necessary in 56 cases (29%) for recurrent hematomas and surgical complications. Predictors for reoperation for surgical complications were midline shift (odds ratio [OR] (per mm) 1.16, 95% confidence interval [CI]: 1.05-1.29, p=0.006), arterial hypertension (OR 5.44, 95% CI: 1.45-20.41, p=0.012) and bilateral hematomas (OR 4.22, 95% CI: 1.22-14.58, p=0.023). There was a trend toward a higher risk of surgically-relevant hematoma recurrence in patients with prior treatment with vitamin K antagonists (OR 1.76, 95% CI: 0.75-4.13, p=0.191). Burr hole trephination is the therapy of choice in most chronic subdural hematomas, but the rate of recurrent hematomas is high. Every hematoma should be treated individually especially in relation to midline-shift and pre-existing conditions. Further prospective studies evaluating types of treatment and hematoma density are needed. Copyright © 2015 Elsevier B

  4. Risk factors for adverse events after vaccinations performed during the initial hospitalization of infants born prematurely.

    Science.gov (United States)

    Wilińska, Maria; Warakomska, Małgorzata; Głuszczak-Idziakowska, Ewa; Jackowska, Teresa

    There are significant delays in implementing vaccination among preterm infants. Description of the frequency and kinds of adverse events following immunization in preterms. Establishment of the group of preterms who will distinctively be susceptible to adverse events. Demographical, clinical data and the occurrence of adverse events after DTaP, HIB and pneumococcal vaccination among preterms during their initial hospitalization were prospectively collected with the use of an electronic data form between 1st June 2011 and 31st May 2015. The analysis was conducted on 138 patients. The groups were divided according to maturity (I: ≤ GA 28w n=73 and GA 29-36 w n=65). There were no statistically significant differences between the groups in the occurrence of adverse events. Out of the total group, following vaccination apnoea developed in 6 newborns (4%) and activity dysfunctions were observed in 13 newborns (10%). The occurrence of apnoea after vaccination positively correlated with the time of non-invasive ventilation and the occurrence of late infection. There were no statistically significant demographical or clinical risk factors for the development of activity dysfunctions following vaccination. Term vaccination in clinically stable preterm infants is a safe medical procedure. However, long-term non-invasive respiratory support and late infections are risk factors for apnea following vaccinations. In these patients vaccinations should be considered during hospitalization.

  5. Evaluation of occupational factors on continuation of breastfeeding and formula initiation in employed mothers.

    Science.gov (United States)

    Ahmadi, Mahshid; Moosavi, Seyyed Mohammad

    2013-09-25

    During recent decades, women have been increasingly involved in social activities. Despite the fact that mothers prefer to breastfeed, their return to work is associated with a reduction in breastfeeding frequency and duration. The present study evaluates the impact of occupational factors on continuation of breastfeeding and formula initiation in employed mothers with infants aged 6-12 months in Bandar-Abbas, Iran in 2010. This is a descriptive-analytic study on employed mothers with infants aged 6-12 months referring to healthcare centers of Bandar-Abbas in 2010. Data were collected through a questionnaire dealing with work-related factors in mothers' workplace. Out of 212 mothers who responded, 52.38% used formula to feed their children, and 27.36% had discontinued breastfeeding. The rate of formula use was significantly higher in mothers who had less than 6 months of maternity leave, those who did not have a suitable nursery or place to milk themselves and preserve the milk in their workplace, those working more than 6 hours per day, and those who could not take a breastfeeding break. It is essential to identify and support breastfeeding employed women. The employers should provide facilities such as nurseries, a suitable physical space for milking, as well as the equipment necessary for milk preservation. Also, such mothers should be granted breastfeeding breaks to feed their child or milk their breasts.

  6. Understanding the factors associated with initiation and adherence of osteoporosis medication in Japan: An analysis of patient perceptions

    Directory of Open Access Journals (Sweden)

    Hajime Orimo

    2017-12-01

    Conclusions: Different factors were found to be associated with initiation and adherence of osteoporosis medication. Patient knowledge of their disease and the perception of barriers were found to be the most influential. Empowering patients with the knowledge to better understand their disease and decreasing the perception of barriers through education initiatives may be effective in improving patient outcomes.

  7. PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours.

    Science.gov (United States)

    Hung, Yin P; Lee, John P; Bellizzi, Andrew M; Hornick, Jason L

    2017-11-01

    Neuroblastoma shows considerable histological overlap with other small round blue cell tumours. PHOX2B, a transcription factor that is essential for autonomic nervous system development, has been reported as an immunohistochemical marker for neuroblastoma. The aim of this study was to validate the specificity and diagnostic utility of PHOX2B for peripheral neuroblastic tumours. We evaluated 240 cases (133 in whole-tissue sections; 107 in tissue microarrays), including 76 peripheral neuroblastic tumours (median age 2 years; including four adults) and 164 other tumours: 44 Wilms tumours; 20 Ewing sarcomas; 10 each of CIC-rearranged round cell sarcomas, poorly differentiated synovial sarcomas, lymphoblastic lymphomas, alveolar rhabdomyosarcomas, embryonal rhabdomyosarcomas, mesenchymal chondrosarcomas, Merkel cell carcinomas, olfactory neuroblastomas, and melanomas; and five each of NUT midline carcinomas and desmoplastic small round cell tumours. Immunohistochemistry for PHOX2B was performed with a rabbit monoclonal antibody. PHOX2B positivity was defined as the presence of nuclear immunoreactivity in ≥5% of cells. PHOX2B was positive in 70 (92%) peripheral neuroblastic tumours, including 68 of 72 (94%) paediatric and two of four (50%) adult cases. Furthermore, PHOX2B was consistently negative in all non-peripheral neuroblastic tumours, with staining being absent in 160 cases and limited in four cases. PHOX2B is a highly sensitive and specific immunohistochemical marker for peripheral neuroblastic tumours, including neuroblastoma. PHOX2B reliably distinguishes neuroblastoma from histological mimics such as Wilms tumour, Ewing sarcoma, and CIC-rearranged round cell sarcoma. PHOX2B negativity in two of four adult neuroblastoma cases raises the possibility that some adult neuroblastomas are of a different lineage than paediatric cases. © 2017 John Wiley & Sons Ltd.

  8. Using the Internet for B2B Activities: A Review and Future Directions for Research.

    Science.gov (United States)

    Gattiker, Urs E.; Perlusz, Stefano; Bohmann, Kristoffer

    2000-01-01

    Illustrates some of the challenges that electronic commerce practitioners and researchers face, focusing on business to business (B2B) transactions. Highlights include a conceptual framework of Web user behavior; purchasing context; socio-demographic characteristics; cultural factors; economic factors; attitudes toward information technology;…

  9. Gratitude, hope, mindfulness and personal-growth initiative: buffers or risk factors for problem gambling?

    Directory of Open Access Journals (Sweden)

    Jasmine M Y Loo

    Full Text Available The majority of prevention and intervention research in problem gambling (PG has focused on identifying negative risk factors. However, not all at-risk individuals go on to develop anticipated disorders and many thrive in spite of them. In healthcare settings, PG and other disorders are typically conceptualized from the biomedical perspective that frame disorders as something negative residing within the individual and reduction in negativity is seen as success. Indeed, this problem-focused conceptualization may be adequate in many cases as reducing PG behaviour is undoubtedly an important outcome, but the focus on negativity alone is too narrow to capture the complexity of human behaviour. Hence, this study attempts to bridge the gap in literature by providing an evaluation of the predictive ability of the positive dispositions on problem gambling severity, gambling-related cognitions, and gambling urges. The positive psychological dispositions examined were curiosity, gratitude, hope, personal growth initiative, and mindfulness. Participants consisted of 801 Taiwanese Chinese students and community individuals (Mean age = 25.36 years. Higher levels of gratitude and hope have been found to predict lower PG, gambling-related cognitions, or gambling urges. Meanwhile, higher mindfulness predicted lower PG, but only among Chinese males. However, lower personal growth initiative predicted lower PG, gambling-related cognitions, and gambling urges. These analyses have small to medium effect sizes with significant predictions. Findings of this study have essential implications in understanding and treating Chinese problem gamblers. These positive dispositions should be addressed by mental health professionals in preventative and treatment programs among Chinese individuals. Further implications and suggestions for future research are discussed.

  10. Assurance of Myeloid Growth Factor Administration in an Infusion Center: Pilot Quality Improvement Initiative.

    Science.gov (United States)

    Ramirez, Pamela Maree; Peterson, Barry; Holtshopple, Christine; Borja, Kristina; Torres, Vincent; Valdivia-Peppers, Lucille; Harriague, Julio; Joe, Melanie D

    2017-12-01

    Four incident reports involving missed doses of myeloid growth factors (MGFs) triggered the need for an outcome-driven initiative. From March 1, 2015, to February 29, 2016, at University of California Irvine Health Chao Infusion Center, 116 of 3,300 MGF doses were missed (3.52%), including pegfilgrastim, filgrastim, and sargramostim. We hypothesized that with the application of Lean Six Sigma methodology, we would achieve our primary objective of reducing the number of missed MGF doses to < 0.5%. This quality improvement initiative was conducted at Chao Infusion Center as part of a Lean Six Sigma Green Belt Certification Program. Therefore, Lean Six Sigma principles and tools were used throughout each phase of the project. Retrospective and prospective medical record reviews and data analyses were performed to evaluate the extent of the identified problem and impact of the process changes. Improvements included systems applications, practice changes, process modifications, and safety-net procedures. Preintervention, 24 missed doses (20.7%) required patient supportive care measures, resulting in increased hospital costs and decreased quality of care. Postintervention, from June 8, 2016, to August 7, 2016, zero of 489 MGF doses were missed after 2 months of intervention ( P < .001). Chao Infusion Center reduced missed doses from 3.52% to 0%, reaching the goal of < 0.5%. The establishment of simplified and standardized processes with safety checks for error prevention increased quality of care. Lean Six Sigma methodology can be applied by other institutions to produce positive outcomes and implement similar practice changes.

  11. The relationship between transcription initiation RNAs and CCCTC-binding factor (CTCF localization

    Directory of Open Access Journals (Sweden)

    Taft Ryan J

    2011-08-01

    Full Text Available Abstract Background Transcription initiation RNAs (tiRNAs are nuclear localized 18 nucleotide RNAs derived from sequences immediately downstream of RNA polymerase II (RNAPII transcription start sites. Previous reports have shown that tiRNAs are intimately correlated with gene expression, RNA polymerase II binding and behaviors, and epigenetic marks associated with transcription initiation, but not elongation. Results In the present work, we show that tiRNAs are commonly found at genomic CCCTC-binding factor (CTCF binding sites in human and mouse, and that CTCF sites that colocalize with RNAPII are highly enriched for tiRNAs. To directly investigate the relationship between tiRNAs and CTCF we examined tiRNAs originating near the intronic CTCF binding site in the human tumor suppressor gene, p21 (cyclin-dependent kinase inhibitor 1A gene, also known as CDKN1A. Inhibition of CTCF-proximal tiRNAs resulted in increased CTCF localization and increased p21 expression, while overexpression of CTCF-proximal tiRNA mimics decreased CTCF localization and p21 expression. We also found that tiRNA-regulated CTCF binding influences the levels of trimethylated H3K27 at the alternate upstream p21 promoter, and affects the levels of alternate p21 (p21alt transcripts. Extending these studies to another randomly selected locus with conserved CTCF binding we found that depletion of tiRNA alters nucleosome density proximal to sites of tiRNA biogenesis. Conclusions Taken together, these data suggest that tiRNAs modulate local epigenetic structure, which in turn regulates CTCF localization.

  12. Drivers of relationships affecting B2B firms in an e-commerce environment

    Directory of Open Access Journals (Sweden)

    Irene Samanta

    2014-09-01

    Full Text Available The advent of the internet has created numerous opportunities for B2B marketing professionals to enhance current marketing practices, including electronic relationships. However, the investigation of e-relationships and the factors that influence e-relationships in an internet environment is scant. Further, there appears to be no investigation of this phenomenon within the context of Greek B2B Medium-sized firms (MSF. Τhe research problem investigated in this research is: “Which drivers in B2B e-commerce use affect inter-firm relationships in medium-sized B2B firms?”. A framework for B2B e-commerce relationships in a changing and globalized environment was synthesised and integrated with the literature about relationship marketing to arrive at the following research issues: “How do relationship marketing drivers affect the management of B2B e-relationships?”. An explanatory quantitative research approach was used and quantitative data was collected from B2B firms in Greece, which represents a case of e-commerce progress during the last six years. Regarding social exchange, some important differences emerge where cooperation between B2B e-commerce firms is concerned. Suppliers engaged in electronic commerce are more committed and oriented to a long-term relationship than buyers, based on both previous and current experience with them. Confidence in the relationships, consistency and honesty with their obligations and the exchange of reliable, trustworthy information and advisory services between firms are important factors in the development and establishment of their e-relationships. The main contribution of this research is the development of a theoretical framework for e-relationships in medium-sized Β2Β firms. That framework is the first rigorously researched step towards understanding the importance of these powerful streams of relationship drivers in total, and the business activity of e-marketing and electronic relationships.

  13. PODAAC-RSX12-L2B11

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the RapidScat Level 2B 12.5km Version 1.1 science-quality ocean surface wind vectors. The Level 2B wind vectors are binned on a 12.5 km Wind...

  14. Expression and purification of recombinant Shiga toxin 2B from ...

    African Journals Online (AJOL)

    Expression and purification of recombinant Shiga toxin 2B from Escherichia coli O157:H7. ... (SDS-PAGE) and StxB2 yield was 450 μg ml-1 confirmed by Bradford assay. Recombinant Stx2B protein was produced in highly pure yield using ...

  15. ORM-based semantics of B2B transactions.

    NARCIS (Netherlands)

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

    2009-01-01

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

  16. Association analysis of polymorphism in KIAA1717, HUMMLC2B ...

    African Journals Online (AJOL)

    Single nucleotide polymorphisms (SNPs) in KIAA1717, HUMMLC2B, DECR1, and FTO genes have been found to be associated with some pork meat quality traits. ... with meat color (CIE L), backfat thickness, drip loss, water-holding capacity, and pH24hr; a SNP in HUMMLC2B was associated with chemical composition ...

  17. Slow Epidemic of Lymphogranuloma Venereum L2b Strain

    Science.gov (United States)

    Spaargaren, Joke; Schachter, Julius; Moncada, Jeanne; de Vries, Henry J.C.; Fennema, Han S.A.; Peña, A. Salvador; Coutinho, Roel A.

    2005-01-01

    We traced the Chlamydia trachomatis L2b variant in Amsterdam and San Francisco. All recent lymphogranuloma venereum cases in Amsterdam were caused by the L2b variant. This variant was also present in the 1980s in San Francisco. Thus, the current "outbreak" is most likely a slowly evolving epidemic. PMID:16318741

  18. Frontotemporal dementia caused by CHMP2B mutations

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  19. Leishmania eukaryotic initiation factor (LeIF inhibits parasite growth in murine macrophages.

    Directory of Open Access Journals (Sweden)

    Olga Koutsoni

    Full Text Available The leishmaniases constitute neglected global public health problems that require adequate control measures, prophylactic clinical vaccines and effective and non-toxic drug treatments. In this study, we explored the potential of Leishmania infantum eukaryotic initiation factor (LieIF, an exosomal protein, as a novel anti-infective therapeutic molecule. More specifically, we assessed the efficacy of recombinant LieIF, in combination with recombinant IFN-γ, in eliminating intracellular L. donovani parasites in an in vitro macrophage model. J774A.1 macrophages were initially treated with LieIF/IFN-γ prior to in vitro infection with L. donovani stationary phase promastigotes (pre-infection treatment, and resistance to infection was observed 72 h after infection. J774A.1 macrophages were also treated with LieIF/IFN-γ after L. donovani infection (post-infection treatment, and resistance to infection was also observed at both time points tested (19 h and 72 h after infection. To elucidate the LieIF/IFN-γ-induced mechanism(s that mediate the reduction of intracellular parasite growth, we examined the generation of potent microbicidal molecules, such as nitric oxide (NO and reactive oxygen species (ROS, within infected macrophages. Furthermore, macrophages pre-treated with LieIF/IFN-γ showed a clear up-regulation in macrophage inflammatory protein 1α (MIP-1α as well as tumor necrosis factor alpha (TNF-α expression. However, significant different protein levels were not detected. In addition, macrophages pre-treated with LieIF/IFN-γ combined with anti-TNF-α monoclonal antibody produced significantly lower amounts of ROS. These data suggest that during the pre-treatment state, LieIF induces intramacrophage parasite growth inhibition through the production of TNF-α, which induces microbicidal activity by stimulating NO and ROS production. The mechanisms of NO and ROS production when macrophages are treated with LieIF after infection are probably

  20. B2B myynnin johtaminen ravintola-alalla

    OpenAIRE

    Pajari, Katja

    2014-01-01

    Tämän opinnäytetyön tavoitteena oli selvittää, miten ravintola-alan yrityksissä johdetaan B2B myyntiä. Tarkoituksena oli kartoittaa, miten yrityksissä panostetaan B2B myyntiin ja sen johtamiseen sekä millä tavoin yritysmyyntiä johdetaan. Tutkimus pohjautuu opinnäytetyön tietoperustaan, jossa käsitellään B2B myyntiprosessia ja myynnin johtamista. Työssä käsitellään B2B myyntiä ja selvitetään myyntiprosessin eri vaiheita. Aihe on rajattu koskemaan nimenomaan johtamisen näkökulmaa B2B myynni...

  1. MAT2B promotes adipogenesis by modulating SAMe levels and activating AKT/ERK pathway during porcine intramuscular preadipocyte differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Cunzhen; Chen, Xiaochang; Wu, Wenjing; Wang, Wusu; Pang, Weijun; Yang, Gongshe, E-mail: gsyang999@hotmail.com

    2016-05-15

    Intramuscular fat (IMF) has been demonstrated as one of the crucial factors of livestock meat quality. The MAT2B protein with MAT2α catalyzes the formation of methyl donor S- adenosylmethionine (SAMe) to mediate cell metabolism including proliferation and apoptosis. However, the regulatory effect of MAT2B on IMF deposition is still unclear. In this study, the effect of MAT2B on adipogenesis and its potential mechanism during porcine intramuscular preadipocyte differentiation was studied. The results showed that overexpression of MAT2B promoted adipogenesis and significantly up-regulated the mRNA and protein levels of adipogenic marker genes including FASN, PPARγ and aP2, consistently, knockdown of MAT2B inhibited lipid accumulation and down-regulated the mRNA and protein levels of the above genes. Furthermore, flow cytometry and EdU-labeling assay indicated that MAT2B regulate adipogenesis was partly due to influence intracellular SAMe levels and further affect cell clonal expansion. Also, increased expression of MAT2B activated the phosphorylations of AKT and ERK1/2, whereas knockdown of MAT2B blocked AKT signaling and repressed the phosphorylation of ERK1/2. Moreover, the inhibitory effect of LY294002 (a specific PI3K inhibitor) on the activities of AKT and ERK1/2 was partially recovered by overexpression of MAT2B in porcine intramuscular adipocytes. Finally, Co-IP experiments showed that MAT2B can directly interact with AKT. Taken together, our findings suggested that MAT2B acted as a positive regulator through modifying SAMe levels as well as activating AKT/ERK signaling pathway to promote porcine intramuscular adipocyte differentiation. - Highlights: • MAT2B up-regulates the expression of adipogenic marker genes and promotes porcine intramuscular preadipocyte differentiation. • MAT2B influences intracellular SAMe levels and further affects cell clonal expansion. • MAT2B interacts with AKT and activates AKT/ERK signaling pathway.

  2. Unique factors rural Veterans' Affairs hospitals face when implementing health care-associated infection prevention initiatives.

    Science.gov (United States)

    Harrod, Molly; Manojlovich, Milisa; Kowalski, Christine P; Saint, Sanjay; Krein, Sarah L

    2014-01-01

    Health care-associated infection (HAI) is costly to hospitals and potentially life-threatening to patients. Numerous infection prevention programs have been implemented in hospitals across the United States. Yet, little is known about infection prevention practices and implementation in rural hospitals. The purpose of this study was to understand the infection prevention practices used by rural Veterans' Affairs (VA) hospitals and the unique factors they face in implementing these practices. This study used a sequential, mixed methods approach. Survey data to identify the HAI prevention practices used by rural VA hospitals were collected, analyzed, and used to inform the development of a semistructured interview guide. Phone interviews were conducted followed by site visits to rural VA hospitals. We found that most rural VA hospitals were using key recommended infection prevention practices. Nonetheless, a number of challenges with practice implementation were identified. The 3 most prominent themes were: (1) lack of human capital including staff with HAI expertise; (2) having to cultivate needed resources; and (3) operating as a system within a system. Rural VA hospitals are providing key infection prevention services to ensure a safe environment for the veterans they serve. However, certain factors, such as staff expertise, limited resources, and local context impacted how and when these practices were used. The creative use of more accessible alternative resources as well as greater flexibility in implementing HAI-related initiatives may be important strategies to further improve delivery of these important services by rural VA hospitals. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  3. B2-B2.5 code benchmarking

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-15

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

  4. Characterization of the domains of E. coli initiation factor IF2 responsible for recognition of the ribosome

    DEFF Research Database (Denmark)

    Manuel Palacios Moreno, Juan; Andersen, Lars Dyrskjøt; Egebjerg Kristensen, Janni

    1999-01-01

    We have studied the interactions between the ribosome and the domains of Escherichia coli translation initiation factor 2, using an in vitro ribosomal binding assay with wild-type forms, N- and C-terminal truncated forms of IF2 as well as isolated structural domains. A deletion mutant of the factor...

  5. Phosphorylation in vitro of eukaryotic initiation factors IF-E2 and IF-E3 by protein kinases

    DEFF Research Database (Denmark)

    Issinger, O G; Benne, R; Hershey, J W

    1976-01-01

    Purified protein synthesis initiation factors IF-E2 and IF-E3 from rabbit reticulocytes were phosphorylated in vitro with protein kinases isolated from the same source. The highest levels of phosphorylation resulted from incubation of the factors with a cyclic nucleotide-independent protein kinase...

  6. Phosphorylation of protein synthesis initiation factor 2 (elF-2) in the yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Romero, D.P.

    1986-01-01

    Initiation Factor 2 (elF-2) in the yeast Saccharomyces cerevisiae is comprised of 3 subunits. The control of protein synthesis in mammalian cells have been shown to involve the phosphorylation of the small (alpha) subunit by a specific protein kinase. Phosphorylation results in an inhibition of protein synthesis. In order to determine whether or not an analogous system is operative in yeast, the phosphorylation state of the alpha subunit of elF-2 in Saccharomyces was determined during various growth and nongrowth conditions. Cells were radiolabelled with 32 P and 35 S, and the whole cell lysates were analyzed by two dimensional gel electrophoresis. These experiments revealed that the smallest subunit (alpha, M/sub r/ = 31,000) is a phosphoprotein in vivo under a variety of growth and nongrowth conditions. This is in direct contrast to the pattern exhibited in mammalian cells. The fact that the small subunit of elF-2 in yeast is phosphorylated under a variety of physiological conditions indicates that such a covalent modification is important for some aspects of elF-2 function. In order to investigate this problem further, a protein kinase that specifically labels the alpha subunit of elF-2 in vitro was isolated. The kinase is not autophosphorylating, utilizes ATP as a phosphate donor, phosphorylates an exogenous protein, casein, modifies serine residues in elF-2, is cyclic nucleotide-independent, and is strongly inhibited by heparin

  7. Deciphering the Translation Initiation Factor 5A Modification Pathway in Halophilic Archaea

    Directory of Open Access Journals (Sweden)

    Laurence Prunetti

    2016-01-01

    Full Text Available Translation initiation factor 5A (IF5A is essential and highly conserved in Eukarya (eIF5A and Archaea (aIF5A. The activity of IF5A requires hypusine, a posttranslational modification synthesized in Eukarya from the polyamine precursor spermidine. Intracellular polyamine analyses revealed that agmatine and cadaverine were the main polyamines produced in Haloferax volcanii in minimal medium, raising the question of how hypusine is synthesized in this halophilic Archaea. Metabolic reconstruction led to a tentative picture of polyamine metabolism and aIF5A modification in Hfx. volcanii that was experimentally tested. Analysis of aIF5A from Hfx. volcanii by LC-MS/MS revealed it was exclusively deoxyhypusinylated. Genetic studies confirmed the role of the predicted arginine decarboxylase gene (HVO_1958 in agmatine synthesis. The agmatinase-like gene (HVO_2299 was found to be essential, consistent with a role in aIF5A modification predicted by physical clustering evidence. Recombinant deoxyhypusine synthase (DHS from S. cerevisiae was shown to transfer 4-aminobutyl moiety from spermidine to aIF5A from Hfx. volcanii in vitro. However, at least under conditions tested, this transfer was not observed with the Hfx. volcanii DHS. Furthermore, the growth of Hfx. volcanii was not inhibited by the classical DHS inhibitor GC7. We propose a model of deoxyhypusine synthesis in Hfx. volcanii that differs from the canonical eukaryotic pathway, paving the way for further studies.

  8. Expression of the Eukaryotic Translation Initiation Factors 4E and 2α in Non-Hodgkin’s Lymphomas

    Science.gov (United States)

    Wang, Songtao; Rosenwald, Igor B.; Hutzler, Michael J.; Pihan, German A.; Savas, Lou; Chen, Jane-Jane; Woda, Bruce A.

    1999-01-01

    Transition of cells from quiescence to proliferation requires an increase in the rate of protein synthesis, which is regulated in part by two key translation initiation factors, 4E and 2α. The expression and activity of both factors are increased transiently when normal resting cells are stimulated to proliferate. They are constitutively elevated in oncogene transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study we investigate an association between the expression of translation initiation factors and lymphomagenesis. We have analyzed the expression of the protein synthesis initiation factors 4E and 2α by immunohistochemistry in reactive lymph nodes and several types of non-Hodgkin’s lymphoma representing a wide range of clinical behaviors based on the Revised European-American Lymphoma behavioral classification. The study included 7 benign lymph nodes with follicular hyperplasia, 26 indolent lymphomas (6 marginal zone lymphomas, 7 small lymphocytic lymphomas, and 13 follicular lymphomas, grades 1 and 2), 16 moderately aggressive lymphomas (8 mantle cell lymphomas and 8 follicular lymphomas, grade 3), 24 aggressive lymphomas (14 large-B-cell lymphomas and 10 anaplastic large-cell lymphomas), and 15 highly aggressive lymphomas (7 lymphoblastic lymphomas and 8 Burkitt’s lymphomas). Strong expression of initiation factors 4E and 2α was demonstrated in the germinal centers of reactive follicles. Minimal or no expression was seen in the mantle zones and surrounding paracortices, indicating that high expression of initiation factors 4E and 2α is associated with the active proliferation of lymphocytes. Most cases of aggressive and highly aggressive lymphomas showed strong expression of initiation factors 4E and 2α, in contrast to the cases of indolent and moderately aggressive lymphoma, in which their expression was intermediate between the germinal centers and the mantles of reactive

  9. Distinctive features of Phox2b-expressing neurons in the rat reticular formation dorsal to the trigeminal motor nucleus.

    Science.gov (United States)

    Nagoya, Kouta; Nakamura, Shiro; Ikeda, Keiko; Onimaru, Hiroshi; Yoshida, Atsushi; Nakayama, Kiyomi; Mochizuki, Ayako; Kiyomoto, Masaaki; Sato, Fumihiko; Kawakami, Kiyoshi; Takahashi, Koji; Inoue, Tomio

    2017-09-01

    Phox2b encodes a paired-like homeodomain-containing transcription factor essential for development of the autonomic nervous system. Phox2b-expressing (Phox2b + ) neurons are present in the reticular formation dorsal to the trigeminal motor nucleus (RdV) as well as the nucleus of the solitary tract and parafacial respiratory group. However, the nature of Phox2b + RdV neurons is still unclear. We investigated the physiological and morphological properties of Phox2b + RdV neurons using postnatal day 2-7 transgenic rats expressing yellow fluorescent protein under the control of Phox2b. Almost all of Phox2b + RdV neurons were glutamatergic, whereas Phox2b-negative (Phox2b - ) RdV neurons consisted of a few glutamatergic, many GABAergic, and many glycinergic neurons. The majority (48/56) of Phox2b + neurons showed low-frequency firing (LF), while most of Phox2b - neurons (35/42) exhibited high-frequency firing (HF) in response to intracellularly injected currents. All, but one, Phox2b + neurons (55/56) did not fire spontaneously, whereas three-fourths of the Phox2b - neurons (31/42) were spontaneously active. K + channel and persistent Na + current blockers affected the firing of LF and HF neurons. The majority of Phox2b + (35/46) and half of the Phox2b - neurons (19/40) did not respond to stimulations of the mesencephalic trigeminal nucleus, the trigeminal tract, and the principal sensory trigeminal nucleus. Biocytin labeling revealed that about half of the Phox2b + (5/12) and Phox2b - RdV neurons (5/10) send their axons to the trigeminal motor nucleus. These results suggest that Phox2b + RdV neurons have distinct neurotransmitter phenotypes and firing properties from Phox2b - RdV neurons and might play important roles in feeding-related functions including suckling and possibly mastication. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.

    Science.gov (United States)

    Dean, Brian; Arison, Byron; Chang, Steve; Thomas, Paul E; King, Christopher

    2004-06-01

    Two UDP-glucuronosyltransferases (UGT2B9(*)2 and UGT2B33) have been isolated from female rhesus monkey liver. Microsomal preparations of the cell lines expressing the UGTs catalyzed the glucuronidation of the general substrate 7-hydroxy-4-(trifluoromethyl)coumarin in addition to selected estrogens (beta-estradiol and estriol) and opioids (morphine, naloxone, and naltrexone). UGT2B9(*)2 displayed highest efficiency for beta-estradiol-17-glucuronide production and did not catalyze the glucuronidation of naltrexone. UGT2B33 displayed highest efficiency for estriol and did not catalyze the glucuronidation of beta-estradiol. UGT2B9(*)2 was found also to catalyze the glucuronidation of 4-hydroxyestrone, 16-epiestriol, and hyodeoxycholic acid, while UGT2B33 was capable of conjugating 4-hydroxyestrone, androsterone, diclofenac, and hyodeoxycholic acid. Three glucocorticoids (cortisone, cortisol, and corticosterone) were not substrates for glucuronidation by liver or kidney microsomes or any expressed UGTs. Our current data suggest the use of beta-estradiol-3-glucuronidation, beta-estradiol-17-glucuronidation, and estriol-17-glucuronidation to assay UGT1A01, UGT2B9(*)2, and UGT2B33 activity in rhesus liver microsomes, respectively.

  11. Itga2b regulation at the onset of definitive hematopoiesis and commitment to differentiation.

    Directory of Open Access Journals (Sweden)

    Stephanie Dumon

    Full Text Available Product of the Itga2b gene, CD41 contributes to hematopoietic stem cell (HSC and megakaryocyte/platelet functions. CD41 expression marks the onset of definitive hematopoiesis in the embryo where it participates in regulating the numbers of multipotential progenitors. Key to platelet aggregation, CD41 expression also characterises their precursor, the megakaryocyte, and is specifically up regulated during megakaryopoiesis. Though phenotypically unique, megakaryocytes and HSC share numerous features, including key transcription factors, which could indicate common sub-regulatory networks. In these respects, Itga2b can serve as a paradigm to study features of both developmental-stage and HSC- versus megakaryocyte-specific regulations. By comparing different cellular contexts, we highlight a mechanism by which internal promoters participate in Itga2b regulation. A developmental process connects epigenetic regulation and promoter switching leading to CD41 expression in HSC. Interestingly, a similar process can be observed at the Mpl locus, which codes for another receptor that defines both HSC and megakaryocyte identities. Our study shows that Itga2b expression is controlled by lineage-specific networks and associates with H4K8ac in megakaryocyte or H3K27me3 in the multipotential hematopoietic cell line HPC7. Correlating with the decrease in H3K27me3 at the Itga2b Iocus, we find that following commitment to megakaryocyte differentiation, the H3K27 demethylase Jmjd3 up-regulation influences both Itga2b and Mpl expression.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-07-01

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

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

    International Nuclear Information System (INIS)

    Simon, I.; Naito, M.; Thorne, M.C.; Walke, R.

    2005-01-01

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

  14. Factors associated with psychoactive drug initiation in a sample of workers in France: results of the VISAT cohort study.

    Science.gov (United States)

    Boeuf-Cazou, O; Niezborala, M; Marquie, J C; Lapeyre-Mestre, M

    2010-03-01

    To identify which psychosocial factors at work are associated with the initiation of psychoactive drug use in a cohort of healthy French workers. This study used data collected from the VISAT ('Vieillissement, Santé, Travail') cohort which included workers aged 32, 42, 52 and 62 years in 1996 with follow-ups conducted over the following 5 years. Data were collected through interviews and five standardized questionnaires in annual occupational medical examinations in 1996, 1999 and 2001. We defined new consumers of psychoactive drugs according to their answers during the follow-ups and compared their psychosocial and working characteristics to non-consumers. A multivariate logistic regression analysis was performed to investigate factors related to a psychoactive drug initiation. Among 1533 subjects, 5.4% began consuming psychoactive drugs during the follow-up with a twofold rate for women than for men. Factors related to psychoactive drug initiation were different according to gender. In men, initiation was mainly found in participants who were separated, showed high emotional reaction scores and were members of the white-collar working class. We did not find any other occupational factors associated to psychoactive drug initiation in men. By contrast, among women, drug initiation was more frequent in participants who were 52 years old and over, and whose job control-reward level was lower. Psychoactive drug initiation concerned 5.4% of workers within the 5-year interval in this study. The pressure of psychosocial environment was more important in men, whereas age and work-related psychosocial factors were the main factors associated with new consumption among women.

  15. Magnetic anisotropy of YNi2B2C single crystals

    International Nuclear Information System (INIS)

    Baran, M.; Gladczuk, L.; Gorecka, J.; Szymczak, H.; Szymczak, R.; Drzazga, Z.; Winiarska, H.

    1994-01-01

    Reversible and irreversible magnetization processes in YNi 2 B 2 C single crystal have been measured and analysed in terms of existing theories. Performed measurements suggest that anisotropy of the effective mass in YNi 2 B 2 C superconductor is rather small and similar to that observed in conventional superconductors. Effect of hydrostatic pressure on T c is shown to be typical of low-temperature superconductors. It is suggested that the layered structure of YNi 2 B 2 C has some effect on the irreversible magnetization processes observed in this superconductor. ((orig.))

  16. Early life factors initiate a 'vicious circle' of affective and gastrointestinal symptoms: A longitudinal study.

    Science.gov (United States)

    Jones, Michael P; Oudenhove, Lukas Van; Koloski, Natasha; Tack, Jan; Talley, Nicholas J

    2013-10-01

    Functional gastrointestinal disorders (FGID) have been shown to be associated with both comorbid mood disorders and traumatic events such as abuse earlier in life. In a longitudinal study, we tested a model that hypothesized: (i) childhood abuse was associated with subsequent mood disorder and pain or interference in life by bowel symptoms both directly and indirectly via neurotic personality; and (ii) an ongoing cycle of mood disorder impacts on bowel symptoms. Subjects from the general population classified as irritable bowel syndrome and/or functional dyspepsia (IBS/FD, n = 207) or free of FGID (n = 100) were prospectively studied every 6 months over 18 months. In addition to bowel symptom interference and abdominal pain, measures of personality (neuroticism), childhood abuse history, depression, and anxiety were obtained. The hypothesized model was tested via Path Modelling. Childhood abuse was found to be directly associated with neuroticism but only indirectly associated with baseline interference and mood disorders (via neuroticism). The data further supported an ongoing cycle of elevations in mood disorders and pain/interference by bowel symptoms. The data supported direct effects of interference at one time point on interference at the subsequent time point in addition to indirect effects of prior anxiety and depression. Repeating the model with pain frequency as the outcome yielded almost identical findings which suggests the findings are generalized across domains of symptoms and quality-of-life. Our data provide support for a model characterized by a 'vicious circle' between mood disorders and FGID symptoms in adulthood, with initial input from early life factors.

  17. Analysis of risk factors associated with unilateral hearing loss in children who initially passed newborn hearing screening.

    Science.gov (United States)

    Appelbaum, Eric N; Howell, Jessica B; Chapman, Derek; Pandya, Arti; Dodson, Kelley M

    2018-03-01

    To analyze 2007 Joint Committee on Infant Hearing (JCIH) risk factors in children with confirmed unilateral hearing loss (UHL) who initially passed newborn hearing screening. Retrospective record review of 16,108 infants who passed newborn hearing screening but had one or more JCIH risk factors prompting subsequent follow-up through the universal newborn hearing screening (UNHS) program in Virginia from 2010 to 2012. The study was reviewed and qualified as exempt by the Virginia Commonwealth University Institutional Review Board (IRB) and the Virginia Department of Health. Over the 2-year study period, 14896 (4.9% of total births) children passed UNHS but had the presence of one or more JCIH risk factor. Ultimately, we identified 121 babies from this group with confirmed hearing loss (0.7%), with 48 babies (0.2%) showing UHL. The most common risk factors associated with the development of confirmed UHL after passing the initial screen were neonatal indicators, craniofacial anomalies, family history, and stigmata of syndrome associated with hearing loss. Neonatal indicators and craniofacial anomalies were the categories most often found in children with confirmed unilateral hearing loss who initially passed their newborn hearing screen. While neonatal indicators were also the most common associated risk factor in all hearing loss, craniofacial abnormalities are relatively more common in children with UHL who initially passed newborn hearing screening. Further studies assessing the etiology underlying the hearing loss and risk factor associations are warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-11-01

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

  19. Beyond the exchange--the future of B2B.

    Science.gov (United States)

    Wise, R; Morrison, D

    2000-01-01

    Using the Internet to facilitate business-to-business commerce promises many benefits, such as dramatic cost reductions and greater access to buyers and sellers. Yet little is known about how B2B e-commerce will evolve. The authors argue that changes in the financial services industry over the past two decades provide important clues. Exchanges, they say, are not the primary source of value in information-intensive markets; value tends to accumulate among a diverse group of specialists that focus on such tasks as packaging, standard setting, arbitrage, and information management. Because scale and liquidity are vitally important to efficient trading, today's exchanges will consolidate into a relatively small set of mega-exchanges. Originators will handle the origination and aggregation of complex transactions before sending them on to mega-exchanges for execution. E-speculators, seeking to capitalize on an abundance of market information, will tend to concentrate where relatively standardized products can be transferred easily among a large group of buyers. In many markets, a handful of independent solution providers with well-known brand names and solid reputations will thrive alongside mega-exchanges. Sell-side asset exchanges will create the networks and provide the tools to allow suppliers to trade orders among themselves, sometimes after initial transactions with customers are made on the mega-exchanges. For many companies, traditional skills in such areas as product development, manufacturing, and marketing may become relatively less important, while the ability to understand and capitalize on market dynamics may become considerably more important.

  20. Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

    2018-02-22

    Cytochrome P450 2B6 (CYP2B6) is an important drug-metabolizing enzyme and is expressed in liver. Although human CYP2B6 variants account for variable enzyme properties among individuals and populations, CYP2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. CYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing. Twenty-three non-synonymous variants were found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques, respectively. By functional characterization using the 14 variant proteins, 8 variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed different rate (>1.5-fold) of testosterone 16β-hydroxylation to wild type. However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in liver microsomes, and the catalytic rates were not substantially different from wild type. Macaque CYP2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP2B6. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. PODAAC-RSX12-L2B13

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the RapidScat Level 2B 12.5km Version 1.3 science-quality ocean surface wind vectors, which are intended as a replacement and continuation of...

  2. Applying conceptual design to B2B sales negotiations

    DEFF Research Database (Denmark)

    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...... on the ways in which design sense making artefacts may drive also B2B sales agents’ work....

  3. B2B Models for DoD Acquisition

    National Research Council Canada - National Science Library

    Kamel, Magdi N

    2008-01-01

    A central vision of B2B e-commerce is that of an electronic marketplace that would bring suppliers together with major buyers of goods and services for the purpose of conducting "frictionless commerce...

  4. PODAAC-QSX12-L2B40

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the latest reprocessed version 4.0 of the Level 2B science-quality ocean surface wind vector retrievals from the QuikSCAT scatterometer. The...

  5. B2B Models for DoD Acquisition

    Science.gov (United States)

    2007-07-30

    product design, demand forecasting, asset management, and sales and marketing plans 35 Proctor & Gamble’s Private Industrial Network SOURCE: Laudon... B2B Models for DoD Acquisition 30 July 2007 by Magdi N. Kamel, Associate Professor Graduate School of Operational & Information Sciences...number. 1. REPORT DATE 30 JUL 2007 2. REPORT TYPE 3. DATES COVERED 00-00-2007 to 00-00-2007 4. TITLE AND SUBTITLE B2B Models for DoD

  6. Creating Competitive Advantage by Rethinking B2B Software Pricing

    OpenAIRE

    Adelstrand, Carl; Brostedt, Emil

    2016-01-01

    The choice of pricing model for software products is a complex procedure due to the different characteristics compared to physical products. This thesis investigates and compares software pricing models in a B2B setting, and describes how KAM plays a role in executing a pricing model. The research has been conducted as an opportunist case study on Adebro, a technology company in the B2B sector. The thesis have come to the following conclusions, with data from interviews and literature: Perpet...

  7. Scope of Internal Marketing in B2B Companies

    OpenAIRE

    Nigam, Niharika

    2007-01-01

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

  8. Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

    Directory of Open Access Journals (Sweden)

    Harry Liu

    2017-02-01

    Full Text Available Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A “gain of toxicity” model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s causes a “loss of function”, resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons of CMT2B are needed to precisely define the disease mechanisms.

  9. Charcot Marie Tooth 2B Peripheral Sensory Neuropathy: How Rab7 Mutations Impact NGF Signaling?

    Science.gov (United States)

    Liu, Harry; Wu, Chengbiao

    2017-02-04

    Charcot-Marie-Tooth 2B peripheral sensory neuropathy (CMT2B) is a debilitating autosomal dominant hereditary sensory neuropathy. Patients with this disease lose pain sensation and frequently need amputation. Axonal dysfunction and degeneration of peripheral sensory neurons is a major clinical manifestation of CMT2B. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M) in Rab7 GTPase. Strong evidence suggests that the Rab7 mutation(s) enhances the cellular levels of activated Rab7 proteins, thus resulting in increased lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor (NGF) in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A "gain of toxicity" model has, thus, been proposed based on these observations. However, studies of fly photo-sensory neurons indicate that the Rab7 mutation(s) causes a "loss of function", resulting in haploinsufficiency. In the review, we summarize experimental evidence for both hypotheses. We argue that better models (rodent animals and human neurons) of CMT2B are needed to precisely define the disease mechanisms.

  10. PROBABILISTIC PROPERTIES OF THE INITIAL VALUES OF WEIGHTING FACTORS IN SYNCHRONIZED ARTIFICIAL NEURAL

    Directory of Open Access Journals (Sweden)

    V. F. Golikov

    2013-01-01

    Full Text Available One of the most efficient ways for identical binary se quences generation is using methods of neural cryptography. The initial weight vestors values influence on speed of synchronization is analized. Equal probability of initial weight vestors motion directions is great advantage. On this base authors suppose new line of research conserned with improvement of network architecture and correction algorithm.

  11. Pulling the Trigger or Not: Factors Affecting Behavior of Initiating a Position in Derivatives Markets

    NARCIS (Netherlands)

    Pennings, J.M.E.

    2002-01-01

    The behavior of managers in initiating a derivatives market position brings to the surface an interesting phenomenon: sometimes managers initiate a position in derivatives markets (i.e., futures and options markets) and sometimes they do not, even though the price volatility of the underlying asset

  12. The Effect of CYP2B6, CYP2D6, and CYP3A4 Alleles on Methadone Binding: A Molecular Docking Study

    Directory of Open Access Journals (Sweden)

    Nik Nur Syazana Bt Nik Mohamed Kamal

    2013-01-01

    Full Text Available Current methadone maintenance therapy (MMT is yet to ensure 100% successful treatment as the optimum dosage has yet to be determined. Overdose leads to death while lower dose causes the opioid withdrawal effect. Single-nucleotide polymorphisms (SNP in cytochrome P450s (CYPs, the methadone metabolizers, have been showen to be the main factor for the interindividual variability of methadone clinical effects. In this study, we investigated the effect of SNPs in three major methadone metabolizers (CYP2B6, CYP2D6, and CYP3A4 on methadone binding affinity. Results showed that CYP2B6*11, CYP2B6*12, CYP2B6*18, and CYP3A4*12 have significantly higher binding affinity to R-methadone compared to wild type. S-methadone has higher binding affinity in CYP3A4*3, CYP3A4*11, and CYP3A4*12 compared to wild type. R-methadone was shown to be the active form of methadone; thus individuals with CYP alleles that binds better to R-methadone will have higher methadone metabolism rate. Therefore, a higher dosage of methadone is necessary to obtain the opiate effect compared to a normal individual and vice versa. These results provide an initial prediction on methadone metabolism rate for individuals with mutant type CYP which enables prescription of optimum methadone dosage for individuals with CYP alleles.

  13. Pauli paramagnetic effects on vortices in superconducting TmNi2B2C

    DEFF Research Database (Denmark)

    DeBeer-Schmitt, L.; Eskildsen, Morten Ring; Ichioka, M.

    2007-01-01

    The magnetic field distribution around the vortices in TmNi2B2C in the paramagnetic phase was studied experimentally as well as theoretically. The vortex form factor, measured by small-angle neutron scattering, is found to be field independent up to 0.6H(c2) followed by a sharp decrease at higher...

  14. Synthesis of 9H-Indeno [1, 2-b] Pyrazine and 11H-Indeno [1, 2-b ...

    African Journals Online (AJOL)

    NICO

    Synthesis of 9H-Indeno [1, 2-b] Pyrazine and. 11H-Indeno [1, 2-b] Quinoxaline Derivatives in. One-step Reaction from 2-Bromo-4-chloro-1-indanone. S. Jasouri1,2, J. Khalafy1,*, M. Badali2 and R.H. Prager3. 1Department of Chemistry, Urmia University, Urmia 57154, Iran. 2Daana Pharmaceutical Co., P.O. Box 5181, Tabriz ...

  15. Unravelling the influence of smoking initiation and cessation on premature mortality using a common latent factor model

    OpenAIRE

    Silvia Balia; Andrew M. Jones

    2007-01-01

    Duration models for lifespan and smoking, that focus on the socio-economic gradient in smoking durations and length of life, are estimated controlling for individual-specific unobservable heterogeneity by means of a latent factor model. The latent factor influences the risk of starting and quitting smoking as well as the hazard of mortality. Frailty could in°uence smoking behaviour through two mechanisms: the effect of life expectancy on initiation of smok- ing and the impact of adverse healt...

  16. Identification of SH2B2β as an Inhibitor for SH2B1- and SH2B2α-Promoted Janus Kinase-2 Activation and Insulin Signaling

    OpenAIRE

    Li, Minghua; Li, Zhiqin; Morris, David L.; Rui, Liangyou

    2007-01-01

    The SH2B family has three members (SH2B1, SH2B2, and SH2B3) that contain conserved dimerization (DD), pleckstrin homology, and SH2 domains. The DD domain mediates the formation of homo- and heterodimers between members of the SH2B family. The SH2 domain of SH2B1 (previously named SH2-B) or SH2B2 (previously named APS) binds to phosphorylated tyrosines in a variety of tyrosine kinases, including Janus kinase-2 (JAK2) and the insulin receptor, thereby promoting the activation of JAK2 or the ins...

  17. What Factors are Associated with Consumer Initiation of Shared Decision Making in Mental Health Visits?

    OpenAIRE

    Matthias, Marianne S.; Fukui, Sadaaki; Salyers, Michelle P.

    2017-01-01

    Understanding consumer initiation of shared decision making (SDM) is critical to improving SDM in mental health consultations, particularly because providers do not always invite consumer participation in treatment decisions. This study examined the association between consumer initiation of nine elements of SDM as measured by the SDM scale, and measures of consumer illness self-management and the consumer-provider relationship. In 63 mental health visits, three SDM elements were associated w...

  18. Characterization of the domains of E. coli initiation factor IF2 responsible for recognition of the ribosome

    DEFF Research Database (Denmark)

    Manuel Palacios Moreno, Juan; Andersen, Lars Dyrskjøt; Egebjerg Kristensen, Janni

    1999-01-01

    We have studied the interactions between the ribosome and the domains of Escherichia coli translation initiation factor 2, using an in vitro ribosomal binding assay with wild-type forms, N- and C-terminal truncated forms of IF2 as well as isolated structural domains. A deletion mutant of the fact...

  19. Review of benchmark tests on JENDL-2B library

    International Nuclear Information System (INIS)

    Kikuchi, Yasuyuki

    1982-01-01

    JENDL-2B is a mixed library consisting of JENDL-2 for the most important nuclides, i.e., 235 U, 238 U, 239 Pu, 240 Pu, 241 Pu, Cr, Fe and Ni and of JENDL-1 for other nuclides. Complete reevaluation work was made for these eight nuclides. The simultaneous evaluation method was adopted in the evaluation for the five heavy nuclides. The resonance structure was carefully studied for the structural materials in the unresolved resonance region up to several MeV. Benchmark tests have been made on JENDL-2B. Various core center characteristics were tested with one-dimensional model for total of 27 assemblies. Satisfactory results were obtained as a whole. The results of spectrum indices, however, suggested some inconsistent spectrum prediction. Moreover, the reactivity worths were overestimated for most of materials, and apparent C/E discrepancies were observed between the Pu and U cores. Applicability of JENDL-2B was further tested to more sophisticated problems for MOZART and ZPPR-3 assemblies. The reaction rate distributions were better predicted with JENDL-2B than with JENDL-1. The positive sodium void reactivity worth was much overestimated with JENDL-2B due to too large moderation components. The control rod worths were well predicted in MOZART, but were considerably underpredicted in ZPPR-3. (author)

  20. Human GRIN2B variants in neurodevelopmental disorders

    Directory of Open Access Journals (Sweden)

    Chun Hu

    2016-10-01

    Full Text Available The development of whole exome/genome sequencing technologies has given rise to an unprecedented volume of data linking patient genomic variability to brain disorder phenotypes. A surprising number of variants have been found in the N-methyl-d-aspartate receptor (NMDAR gene family, with the GRIN2B gene encoding the GluN2B subunit being implicated in many cases of neurodevelopmental disorders, which are psychiatric conditions originating in childhood and include language, motor, and learning disorders, autism spectrum disorder (ASD, attention deficit hyperactivity disorder (ADHD, developmental delay, epilepsy, and schizophrenia. The GRIN2B gene plays a crucial role in normal neuronal development and is important for learning and memory. Mutations in human GRIN2B were distributed throughout the entire gene in a number of patients with various neuropsychiatric and developmental disorders. Studies that provide functional analysis of variants are still lacking, however current analysis of de novo variants that segregate with disease cases such as intellectual disability, developmental delay, ASD or epileptic encephalopathies reveal altered NMDAR function. Here, we summarize the current reports of disease-associated variants in GRIN2B from patients with multiple neurodevelopmental disorders, and discuss implications, highlighting the importance of functional analysis and precision medicine therapies.

  1. The Importance of Brand on B2B Markets: Expert Interviews with Hilti AG Managers

    Directory of Open Access Journals (Sweden)

    Martin Konečný

    2013-12-01

    Full Text Available This paper investigates the importance of brand building in the business-to-business world. Not only B2C companies must take branding into account and put it among their top priorities in order to survive and succeed on the market. The first part of the article deals with the theoretical background of brand importance and market specifics of B2B markets and results in the setting of two hypotheses. The following research has to find out how the managers of a pure business-to-business company perceive the importance of a brand; moreover, it has to evaluate the importance of eight specific brand building factors. Fourteen expert interviews document the growing of brands in the B2B market and their main aspects. At the end of the article, we will focus on future implications for B2B management.

  2. Preoperative short hookwire placement for small pulmonary lesions: evaluation of technical success and risk factors for initial placement failure.

    Science.gov (United States)

    Iguchi, Toshihiro; Hiraki, Takao; Matsui, Yusuke; Fujiwara, Hiroyasu; Masaoka, Yoshihisa; Tanaka, Takashi; Sato, Takuya; Gobara, Hideo; Toyooka, Shinichi; Kanazawa, Susumu

    2018-05-01

    To retrospectively evaluate the technical success of computed tomography fluoroscopy-guided short hookwire placement before video-assisted thoracoscopic surgery and to identify the risk factors for initial placement failure. In total, 401 short hookwire placements for 401 lesions (mean diameter 9.3 mm) were reviewed. Technical success was defined as correct positioning of the hookwire. Possible risk factors for initial placement failure (i.e., requirement for placement of an additional hookwire or to abort the attempt) were evaluated using logistic regression analysis for all procedures, and for procedures performed via the conventional route separately. Of the 401 initial placements, 383 were successful and 18 failed. Short hookwires were finally placed for 399 of 401 lesions (99.5%). Univariate logistic regression analyses revealed that in all 401 procedures only the transfissural approach was a significant independent predictor of initial placement failure (odds ratio, OR, 15.326; 95% confidence interval, CI, 5.429-43.267; p < 0.001) and for the 374 procedures performed via the conventional route only lesion size was a significant independent predictor of failure (OR 0.793, 95% CI 0.631-0.996; p = 0.046). The technical success of preoperative short hookwire placement was extremely high. The transfissural approach was a predictor initial placement failure for all procedures and small lesion size was a predictor of initial placement failure for procedures performed via the conventional route. • Technical success of preoperative short hookwire placement was extremely high. • The transfissural approach was a significant independent predictor of initial placement failure for all procedures. • Small lesion size was a significant independent predictor of initial placement failure for procedures performed via the conventional route.

  3. Drug Use and Sex Work Among At-risk Women: A Qualitative Study of Initial Factors.

    Science.gov (United States)

    Roshanfekr, Payam; Noori, Roya; Dejman, Masoumeh; Fathi Geshnigani, Zahra; Rafiey, Hassan

    2015-06-01

    In recent years, there has been an increasing interest in performing research on drug use and sex work among at-risk women. Although there is a well-documented literature of the initial reasons associated with drug use and sex work among women, there is, however, a paucity of information in this area in Iran. This study aimed to explore the initial reasons associated with drug use and sex work in a group of female treatment seekers, who presented health-related risk behaviors, in Tehran, Iran. This qualitative study enrolled a total of 65 at-risk women, from five women-specific drug clinics, who participated in the study in 2011. Individual in-depth interviews were conducted. Focus group interviews were conducted with 10 key informants. All interviews were audio-taped and thematically written. The recorded data were analyzed using ATLASti qualitative research software version 10. The median age of the sample was 34 years. In addition, 44.6% of subjects were opiate users, and 55.4% were users of opiates and methamphetamine. Sex work was the main source of income for almost half of the sample. The most frequently reported reasons, associated with initial drug use, were extrinsic motivations, including the drug-using family, friends or social networks. Intrinsic motivations, including curiosity and individual willingness to use drugs, were other initial reasons. The most frequently reported reasons, associated with initial sex work, included the need to purchase drugs and financial problems. The study findings demonstrated a number of reasons associated with initial drug use and sex work. The role of sex work in providing drugs necessitates education and prevention. Special treatment programs should be implemented to prevent sex work among at-risk women in Iran.

  4. Cross-Cultural Validation of the Modified Practice Attitudes Scale: Initial Factor Analysis and a New Factor Model.

    Science.gov (United States)

    Park, Heehoon; Ebesutani, Chad K; Chung, Kyong-Mee; Stanick, Cameo

    2018-01-01

    The objective of this study was to create the Korean version of the Modified Practice Attitudes Scale (K-MPAS) to measure clinicians' attitudes toward evidence-based treatments (EBTs) in the Korean mental health system. Using 189 U.S. therapists and 283 members from the Korean mental health system, we examined the reliability and validity of the MPAS scores. We also conducted the first exploratory and confirmatory factor analysis on the MPAS and compared EBT attitudes across U.S. and Korean therapists. Results revealed that the inclusion of both "reversed-worded" and "non-reversed-worded" items introduced significant method effects that compromised the integrity of the one-factor MPAS model. Problems with the one-factor structure were resolved by eliminating the "non-reversed-worded" items. Reliability and validity were adequate among both Korean and U.S. therapists. Korean therapists also reported significantly more negative attitudes toward EBTs on the MPAS than U.S. therapists. The K-MPAS is the first questionnaire designed to measure Korean service providers' attitudes toward EBTs to help advance the dissemination of EBTs in Korea. The current study also demonstrated the negative impacts that can be introduced by incorporating oppositely worded items into a scale, particularly with respect to factor structure and detecting significant group differences.

  5. B2B-myynnin nykytila ja haasteet Suomessa

    OpenAIRE

    Ylimaula, Jukka

    2014-01-01

    Tämä opinnäytetyö tutki B2B-myynnin nykytilaa valituissa suomalaisissa yrityksissä. Tutkimuksen tavoite oli selvittää myyntijohdon mielestä B2B-myynnissä tärkeitä asioita ja hahmottaa tapaa, jolla organisaatio toimii yhteistyössä myynnissä. Näin teemojen pohjalta opinnäytetyö pyrki muodostamaan ajankuvan suomalaisesta B2B-myynnistä. Opinnäytetyö muodostuu teoriaosasta ja empiirisestä osasta. Teoreettinen osuus tutkii myyntiä sekä myyjän että ostajan näkökulmasta. Myös asiakassuhteita ja m...

  6. ORM-Based Semantics of B2B Transactions

    Science.gov (United States)

    Balsters, H.; van Blommestein, F.

    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 neglected by present implementations of standard EDI- or XML-messaging and by B2B webservice implementations. In this paper a precise model is given of the negotiation process. The requirements of a potential Buyer and the offer of a potential Seller are matched and, if the negotiation is successful, a contract is concluded. The negotiation process model is represented in ORM, extended with dynamic constraints. Our model may be implemented in the databases of the trading partners and in message- or service definitions.

  7. Fashion supply chain optimization: Realisation of make-to-orders purchasing using interlinked B2B e-commerce

    DEFF Research Database (Denmark)

    Tambo, Torben; Mikkelsen, Ole Egebjerg

    2015-01-01

    describes a multi-method approach using both traditional B2B and B2C methods of sales initiatives as an e-business system connecting inbound and outbound supply chains. Initiatives can be reverse auctions, time limited discounts, co-selling, bundling, short campaigns supported with letters, e...

  8. Human insulin-like growth factor II leader 2 mediates internal initiation of translation

    DEFF Research Database (Denmark)

    Pedersen, Susanne; Christiansen, Jan; Hansen, T.O.

    2002-01-01

    Insulin-like growth factor II (IGF-II) is a fetal growth factor, which belongs to the family of insulin-like peptides. During fetal life, the IGF-II gene generates three mRNAs with different 5' untranslated regions (UTRs), but identical coding regions and 3' UTRs. We have shown previously that IG...

  9. Teachers' Initial and Sustained Use of an Instructional Assistive Technology Tool: Exploring the Mitigating Factors

    Science.gov (United States)

    Bouck, Emily C.; Flanagan, Sara; Heutsche, Anne; Okolo, Cynthia M.; Englert, Carol Sue

    2011-01-01

    This qualitative research project explored factors that mitigated teachers implementing an instructional assistive technology and factors that mitigated its sustained use. Specifically, it explored these issues in relation to a social studies based instructional assistive technology (Virtual History Museum [VHM]), which was originally implemented…

  10. Speech Delay and Its Affecting Factors (Case Study in a Child with Initial Aq)

    Science.gov (United States)

    Syamsuardi

    2015-01-01

    Any parent wishes an appropriate development for their children. One of the parents' great concerns is the children's speech development; they are worried if their children are late to speak. The children's speech development is influenced by physical and environmental factors. The causes of physical factors are related to the problem but the role…

  11. Translation initiation factor elF3 promotes programmed stop codon readthrough

    Czech Academy of Sciences Publication Activity Database

    Beznosková, Petra; Wagner, Susan; Jansen, Myrte Esmeralda; von der Haar, T.; Valášek, Leoš

    2015-01-01

    Roč. 43, č. 10 (2015), s. 5099-5111 ISSN 0305-1048 R&D Projects: GA ČR(CZ) GA14-05394S Institutional support: RVO:61388971 Keywords : EUKARYOTIC RELEASE FACTOR-1 * RNA RECOGNITION MOTIF * TICK FEVER VIRUS Subject RIV: CE - Biochemistry Impact factor: 9.202, year: 2015

  12. The Ecosystem Factor in Supporting Wiki Initiative for Knowledge Sharing in Malaysian Public Organisation

    Science.gov (United States)

    Khuzaimah, Khairil Hizar Md; Affandi, Haryanti Mohd; Hassan, Fadzil

    2015-01-01

    The purpose of this paper is to highlight the significance of considering the organizational ecosystem in implementing wikis for knowledge sharing.The findings suggest that a prerequisite of an effective wiki is the appreciation of the factors that make up the organizational ecosystem; technical and organizational factors are variable elements of…

  13. Functional and Biochemical Characterization of Human Eukaryotic Translation Initiation Factor 3 in Living Cells

    Czech Academy of Sciences Publication Activity Database

    Wagner, Susan; Herrmannová, Anna; Malík, Radek; Peclinovská, L.; Valášek, Leoš Shivaya

    2014-01-01

    Roč. 34, č. 16 (2014), s. 3041-3052 ISSN 0270-7306 R&D Projects: GA ČR GAP305/10/0335 Institutional support: RVO:61388971 ; RVO:68378050 Keywords : MESSENGER-RNA RECRUITMENT * FACTOR EIF3 * IN-VIVO Subject RIV: CE - Biochemistry Impact factor: 4.777, year: 2014

  14. Digitaalisen markkinoinnin suunnitelma b2b-yritykselle

    OpenAIRE

    Harhakoski, Oskari

    2011-01-01

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

  15. B2B-myyntiprosessi : case: Yritys X

    OpenAIRE

    Lamppu, Samuli

    2017-01-01

    Opinnäytetyön aiheena on B2B-myyntiprosessi yrityksessä x. Työn tavoitteena on kartoittaa yrityksen B2B-myyntiprosessin nykytila, tunnistaa mahdolliset ongelma-alueet ja tehdä tämän perusteella ehdotukset toimenpiteistä prosessin parantamiseksi. Työ tehdään suomalaisen PK-yrityksen toimeksiannosta. Opinnäytetyön taustalla on oma urani yrityksen yritysmyynnissä, ja työni kautta tunnistamani haasteet sekä mahdollisuudet, joita hyödyntämällä yritys voisi kehittää myyntitoimintaansa. Yritykse...

  16. Cosima B2B - Sales Automation for E-Procurement

    OpenAIRE

    Kießling, Werner (Prof. Dr.); Fischer, Stefan; Döring, Sven

    2006-01-01

    E-procurement is one of the fastest growing application areas for e-commerce. Though B2B transaction costs could be reduced recently by establishing XML based standards for electronic product catalogs and data interchange, B2B sales costs are still high due to the amount of human interaction. For the first time we present a fully automated electronic sales agent for e-procurement portals. The key technologies for this breakthrough are based on preferences modeled as strict partial orders, ena...

  17. How has IT impacted the B2B sales process?

    OpenAIRE

    Bjørnstad, Julia Jemli

    2017-01-01

    B2B sales role plays a major role in driving the economy, and this industry has been experiencing major changes over the year with the advances in technology which allow for more cost savings and driving for more efficient ways of conducting sales operations. The objective of this exploratory qualitative research paper was to raise interest in the role technology plays in the B2B sales process today from the salesperson’s view point. It was further partly built on previous rese...

  18. B2B Integration in Global Supply Chains

    DEFF Research Database (Denmark)

    Schubert, Petra; Legner, Christine

    2011-01-01

    The competitiveness of businesses is increasingly dependent on their electronic networks with customers, suppliers, and partners. While the strategic and operational impact of external integration and IOS adoption has been extensively studied, much less attention has been paid to the organizational...... and technical design of electronic relationships. The objective of our longitudinal research project is the development of a framework for understanding and explaining B2B integration. Drawing on existing literature and empirical cases we present a reference model (a classification scheme for B2B Integration...

  19. Factors That Facilitate Or Hinder Fuel-Saving Initiatives and Technology

    Science.gov (United States)

    2015-12-01

    more battery density. (Securing America’s Future Energy, 2013) Initially, the Fuel Sense program was met with much skepticism and pushback . The...59 example, when implementing electronic maps in earlier years, there was pushback from drivers who were used to paper maps. FedEx was able to

  20. Reading the Terrain: Environmental Factors Influencing Religious Literacy Initiatives in Educator Preparation.

    Science.gov (United States)

    Waggoner, Michael D.

    2003-01-01

    Environmental conditions that influence the development of religious literacy initiatives in preservice teacher education include parochialism and Christian privilege, the challenge of foreign traditions, the legacy of church-state separation, shifting bases of authority, the ethos of individualism, and the complexity of public education.…

  1. Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

    DEFF Research Database (Denmark)

    Saydam, Nurten; Kanagaraj, Radhakrishnan; Dietschy, Tobias

    2007-01-01

    is poorly understood. Here we show that WRN physically interacts with the MSH2/MSH6 (MutSalpha), MSH2/MSH3 (MutSbeta) and MLH1/PMS2 (MutLalpha) heterodimers that are involved in the initiation of mismatch repair (MMR) and the rejection of homeologous recombination. MutSalpha and MutSbeta can strongly...

  2. Volunteering within Initial Teacher Education: Factors That Boost and Block Participation

    Science.gov (United States)

    Forster, Daniella J.; Archer, Jennifer; Tajin, Rukhsana T.

    2015-01-01

    Voluntary professional experience can be a powerful way for initial teacher education (ITE) students to develop an understanding of schools and their communities. Do ITE students make use of these opportunities? There is little Australian research that explores genuine volunteering that does not "require" students to engage with the…

  3. Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms.

    Science.gov (United States)

    Kahvejian, Avak; Svitkin, Yuri V; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

    2005-01-01

    Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5'-end of the mRNA to promote the recruitment of the ribosome. Although the 3' poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (approximately 65% vs. approximately 35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5'-end of mRNA.

  4. Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study

    Directory of Open Access Journals (Sweden)

    B P Muzah

    2012-10-01

    Full Text Available Background. The therapeutic goal of antiretroviral therapy (ART is sustained immune recovery and viral suppression. However, some patients experience poor CD4 cell count responses despite achieving viral suppression. Such discordant immune responses have been associated with poor clinical outcomes. Objective. We aimed to determine the prevalence of discordant immune response and explore associated factors in a retrospective cohort of patients attending 2 large public sector clinics, during the 6 months following ART initiation. Methods. Data were analysed from 810 HIV-infected adults initiated on first-line ART at 2 clinics in Johannesburg, between 1 November 2008 and 31 December 2009. Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs to determine associations between discordant immune response and clinical and demographic factors. Results. At ART initiation, 65% (n=592 of participants were female, with a mean age of 38.5 years. Median baseline CD4 cell count was 155 cells/mm3, 70% (n=645 of patients had a haemoglobin level >11 g/dl and 88% (n=803 were initiated on stavudine-lamivudine-efavirenz/nevirapine (D4T-3TC-EFV/NVP. Six months after ART initiation, 24% (n=220 of patients had a discordant immune response and 7% (n=67 a discordant virological response. On multivariate analysis, baseline CD cell count ≥200 cells/mm3 (AOR 3.02; 95% confidence interval (CI 2.08 - 4.38; p

  5. The adaptor Lnk (SH2B3): an emerging regulator in vascular cells and a link between immune and inflammatory signaling.

    Science.gov (United States)

    Devallière, Julie; Charreau, Béatrice

    2011-11-15

    A better knowledge of the process by which inflammatory extracellular signals are relayed from the plasma membrane to specific intracellular sites is a key step to understand how inflammation develops and how it is regulated. This review focuses on Lnk (SH2B3) a member, with SH2B1 and SH2B2, of the SH2B family of adaptor proteins that influences a variety of signaling pathways mediated by Janus kinase and receptor tyrosine kinases. SH2B adaptor proteins contain conserved dimerization, pleckstrin homology, and SH2 domains. Initially described as a regulator of hematopoiesis and lymphocyte differentiation, Lnk now emerges as a key regulator in hematopoeitic and non hematopoeitic cells such as endothelial cells (EC) moderating growth factor and cytokine receptor-mediated signaling. In EC, Lnk is a negative regulator of TNF signaling that reduce proinflammatory phenotype and prevent EC from apoptosis. Lnk is a modulator in integrin signaling and actin cytoskeleton organization in both platelets and EC with an impact on cell adhesion, migration and thrombosis. In this review, we discuss some recent insights proposing Lnk as a key regulator of bone marrow-endothelial progenitor cell kinetics, including the ability to cell growth, endothelial commitment, mobilization, and recruitment for vascular regeneration. Finally, novel findings also provided evidences that mutations in Lnk gene are strongly linked to myeloproliferative disorders but also autoimmune and inflammatory syndromes where both immune and vascular cells display a role. Overall, these studies emphasize the importance of the Lnk adaptor molecule not only as prognostic marker but also as potential therapeutic target. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Expression and purification of Nod factor receptors - Initial characterization of ligand binding

    DEFF Research Database (Denmark)

    Broghammer, Angelique

    Carbohydrate signals have been shown to regulate defence, growth and development in plants. Decorated chitin molecules, lipochitooligosaccharides, synthesized and secreted by rhizobia are the major signal molecules initiating the plant processes establishing legume-rhizobia symbiosis. Lipochitool......Carbohydrate signals have been shown to regulate defence, growth and development in plants. Decorated chitin molecules, lipochitooligosaccharides, synthesized and secreted by rhizobia are the major signal molecules initiating the plant processes establishing legume-rhizobia symbiosis...... and LjNFR5 ectodomains were glycosylated; 3) LjNFR1 retained its in vitro kinase activity and 4) LjNFR1 and LjNFR5 were localized to the plasma membrane. In depth mass spectroscopy analysis of the N-glycan structure of LjNFR5 resulted in identification of two different glycan structures with identical...

  7. Organizational factors affecting length of stay in the emergency department: initial observational study.

    Science.gov (United States)

    Bashkin, Osnat; Caspi, Sigalit; Haligoa, Rachel; Mizrahi, Sari; Stalnikowicz, Ruth

    2015-01-01

    Length of stay (LOS) is considered a key measure of emergency department throughput, and from the perspective of the patient, it is perceived as a measure of healthcare service quality. Prolonged LOS can be caused by various internal and external factors. This study examined LOS in the emergency department and explored the main factors that influence LOS and cause delay in patient care. Observations of 105 patients were performed over a 3-month period at the emergency room of a community urban hospital. Observers monitored patients from the moment of entrance to the department until discharge or admission to another hospital ward. Analysis revealed a general average total emergency department LOS of 438 min. Significant differences in average LOS were found between admitted patients (Mean = 544 min, SD = 323 min) and discharged patients (Mean = 291 min, SD = 286 min). In addition, nurse and physician change of shifts and admissions to hospital wards were found to be significant factors associated with LOS. Using an Ishikawa causal diagram, we explored various latent organizational factors that may prolong this time. The study identified several factors that are associated with high average emergency department LOS. High LOS may lead to increases in expenditures and may have implications for patient safety, whereas certain organizational changes, communication improvement, and time management may have a positive effect on it. Interdisciplinary methods can be used to explore factors causing prolonged emergency department LOS and contribute to a better understanding of them.

  8. A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo

    DEFF Research Database (Denmark)

    Damgaard, Christian Kroun; Kahns, Søren; Lykke-Andersen, Søren

    2008-01-01

    RNAs, harboring wild-type or various 5′ splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5′ splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced...... a promoter-proximal 5′ splice site via its U1 snRNA interaction can feed back to stimulate transcription initiation by enhancing preinitiation complex assembly....

  9. Prediction of hydrological reduction factor and initial loss in urban surface runoff from small ungauged catchments

    DEFF Research Database (Denmark)

    Arnbjerg-Nielsen, K.; Harremoës, P.

    1996-01-01

    An advanced runoff model is compared to a simple one employing only a runoff coefficient and a regression parameter allowing for initial loss. The present study shows that the more detailed description of the runoff processes cannot be justified due to the uncertainty from using only one gauge...... in the evaluation of the yearly discharges. In the case of extreme events, the uncertainty of the predicted runoff of the single event should also be taken into account....

  10. Intelligent Information Integration in B2B Electronic Commerce

    NARCIS (Netherlands)

    Fensel, Dieter; Omelayenko, Borys; Ding, Ying; Klein, Michel; Flett, Alan; Schulten, Ellen; Botquin, Guy; Brown, Mike; Dabiri, Gloria

    2002-01-01

    Internet and web technology penetrates many aspects of our daily life. Its importance as a medium for business transactions will grow exponentially during the next few years. In terms of the involved market volume, the B2B area will hereby be the most interesting area. Also, it will be the place,

  11. Marketing-sales interface configurations in B2B firms

    NARCIS (Netherlands)

    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

  12. Expression and purification of recombinant Shiga toxin 2B from ...

    African Journals Online (AJOL)

    sunny t

    2016-05-25

    May 25, 2016 ... MATERIALS AND METHODS. Bacterial strains, plasmid and media ... toxin 2B gene after purified by wizard genomic DNA purification kit. (Promega, USA) ..... This result was approximately two times higher compared to Halo .... manual, 3rd Eds. New York: Cold Spring Harbor Laboratory Press,. Cold Spring ...

  13. checkCIF/PLATON report Datablock: exp_2b

    Indian Academy of Sciences (India)

    THIS REPORT IS FOR GUIDANCE ONLY. IF USED AS PART OF A REVIEW PROCEDURE. FOR PUBLICATION, IT SHOULD NOT REPLACE THE EXPERTISE OF AN EXPERIENCED. CRYSTALLOGRAPHIC REFEREE. No syntax errors found. CIF dictionary Interpreting this report. Datablock: exp_2b. Bond precision:.

  14. Development of New B2B Venture Corporate Brand Identity

    DEFF Research Database (Denmark)

    Törmälä, Minna; Gyrd-Jones, Richard I.

    2017-01-01

    of interviews and archival data generated during a three-year period to examine the development of corporate brand over time. This study shows that the development of corporate brand identity and the context of the development of new B2B venture are closely intertwined processes and provides a framework...

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

    Directory of Open Access Journals (Sweden)

    Pierluigi Sabbatini

    2001-06-01

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

  16. E-Business Models in B2B: Process Based Categorization and Analysis of B2B Models

    OpenAIRE

    Mahesh S. Raisinghani; Turan Melemez; Lijie Zou; Chris Paslowski; Irma Kimvidze; Susanne Taha; Klaus Simons

    2005-01-01

    The business models in business-to-business (B2B) e-commerce and their effectiveness have been a major topic of research in recent years. Due to the variety of existing models, it seems difficult to find a widely accepted categorization that can be analyzed and assessed. An in-depth study that provides a process-based approach to B2B e-commerce is presented and illustrated with examples from industry. A comparative examination of both the buy and the sell side based on a process-related appro...

  17. The impact of initialization procedures on unsupervised unmixing of hyperspectral imagery using the constrained positive matrix factorization

    Science.gov (United States)

    Masalmah, Yahya M.; Vélez-Reyes, Miguel

    2007-04-01

    The authors proposed in previous papers the use of the constrained Positive Matrix Factorization (cPMF) to perform unsupervised unmixing of hyperspectral imagery. Two iterative algorithms were proposed to compute the cPMF based on the Gauss-Seidel and penalty approaches to solve optimization problems. Results presented in previous papers have shown the potential of the proposed method to perform unsupervised unmixing in HYPERION and AVIRIS imagery. The performance of iterative methods is highly dependent on the initialization scheme. Good initialization schemes can improve convergence speed, whether or not a global minimum is found, and whether or not spectra with physical relevance are retrieved as endmembers. In this paper, different initializations using random selection, longest norm pixels, and standard endmembers selection routines are studied and compared using simulated and real data.

  18. Motivational factors for initiating, implementing, and maintaining physical activity behavior following a rehabilitation program for patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Walker, Karen Christina; Valentiner, Laura Staun; Langberg, Henning

    2018-01-01

    conducted at three separate occasions; at initiation of the rehabilitation program, at completion of the 12-week program, and 52 weeks after enrolment. Interviews were audio-recorded, transcribed, and analyzed according to Systematic Text Condensation. The framework of Self-Determination Theory was applied......Aim: To explore motivational factors for initiating, implementing, and maintaining physical activity following a rehabilitation program for patients with type 2 diabetes mellitus. Methods: Semi-structured, individual, qualitative interviews with five informants from the InterWalk trial were...... to guide analysis after identification of preliminary themes. Results: Commitment and obligation were emphasized as being motivational in initiating physical activity. Toward the termination of the program, this was challenged by an expressed need for autonomy. Successful behavioral change...

  19. Great Lakes water quality initiative technical support document for the procedure to determine bioaccumulation factors. Draft report

    International Nuclear Information System (INIS)

    1993-03-01

    The purpose of the document is to provide the technical information and rationale in support of the proposed procedures to determine bioaccumulation factors. Bioaccumulation factors, together with the quantity of aquatic organisms eaten, determine the extent to which people and wildlife are exposed to chemicals through the consumption of aquatic organisms. The more bioaccumulative a pollutant is, the more important the consumption of aquatic organisms becomes as a potential source of contaminants to humans and wildlife. Bioaccumulation factors are needed to determine both human health and wildlife tier I water quality criteria and tier II values. Also, they are used to define Bioaccumulative Chemicals of Concern among the Great Lakes Initiative universe of pollutants. Bioaccumulation factors range from less than one to several million

  20. Factors Influencing the Initiation of Smokeless Tobacco Consumption Among Low Socioeconomic Community in Bangladesh: A Qualitative Investigation.

    Science.gov (United States)

    Shahjahan, Md; Harun, Md Golam Dostogir; Chowdhury, A B M Alauddin; Ahmed, Kapil; Khan, Hafiz T A

    2017-07-01

    This study explored factors influencing the initiation of smokeless tobacco (SLT) consumption in a low socioeconomic urban community in Bangladesh. The study conducted four focus group discussions among 33 informants involves school teachers, community leaders, women, and betel-nut shops owners. The results were prepared by thematic analysis of the transcripts where informants mean age was 30 ( SD ± 6.8) years with varying level of education. Tradition of hospitality, curiosity, offer from an elderly person, and avoiding nausea during pregnancy and at time of quitting smoking were key factors for the initiation of SLT consumption. The results also revealed most people were aware about the danger of SLT consumption but, in practice, consumed frequently. The research suggested that doctors might advise people not to use any form of SLT while they seeking health services. Furthermore, community-based awareness program could minimize the wider use of SLT among low-income community in Bangladesh.

  1. Depression and Alzheimer's disease: is stress the initiating factor in a common neuropathological cascade?

    DEFF Research Database (Denmark)

    Aznar, Susana; Knudsen, Gitte M

    2011-01-01

    The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development....... This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals...... serotonergic and cholinergic system, hypothalamic-pituitary-adrenal axis and brain derived neurotrophic factor, and discussed in relation to AD....

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

    Energy Technology Data Exchange (ETDEWEB)

    Peuser, M.M.

    2008-07-01

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

  3. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    International Nuclear Information System (INIS)

    Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio; Hazemann, Isabelle; Jenner, Lasse; Urzhumtsev, Alexandre; Gualerzi, Claudio O.; Klaholz, Bruno P.

    2013-01-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue

  4. Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

    Energy Technology Data Exchange (ETDEWEB)

    Simonetti, Angelita [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Marzi, Stefano [Architecture et Réactivité de l’ARN, UPR 9002 CNRS, IBMC (Institute of Molecular and Cellular Biology), 15 Rue R. Descartes, 67084 Strasbourg, France, Université de Strasbourg, 67000 Strasbourg (France); Fabbretti, Attilio [University of Camerino, 62032 Camerino (Monaco) (Italy); Hazemann, Isabelle; Jenner, Lasse [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale -INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Urzhumtsev, Alexandre [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Gualerzi, Claudio O. [University of Camerino, 62032 Camerino (Monaco) (Italy); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France)

    2013-06-01

    The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.

  5. Factors influencing timely initiation and completion of gestational diabetes mellitus screening and diagnosis - a qualitative study from Tamil Nadu, India.

    Science.gov (United States)

    Nielsen, Karoline Kragelund; Rheinländer, Thilde; Kapur, Anil; Damm, Peter; Seshiah, Veerasamy; Bygbjerg, Ib C

    2017-08-01

    In 2007, universal screening for gestational diabetes mellitus (GDM) was introduced in Tamil Nadu, India. To identify factors hindering or facilitating timely initiation and completion of the GDM screening and diagnosis process, our study investigated how pregnant women in rural and urban Tamil Nadu access and navigate different GDM related health services. The study was carried out in two settings: an urban private diabetes centre and a rural government primary health centre. Observations of the process of screening and diagnosis at the health centres as well as semi-structured interviews with 30 pregnant women and nine health care providers were conducted. Data was analysed using qualitative content analysis. There were significant differences in the process of GDM screening and diagnosis in the urban and rural settings. Several factors hindering or facilitating timely initiation and completion of the process were identified. Timely attendance required awareness, motivation and opportunity to attend. Women had to attend the health centre at the right time and sometimes at the right gestational age to initiate the test, wait to complete the test and obtain the test report in time to initiate further action. All these steps and requirements were influenced by factors within and outside the health system such as getting right information from health care providers, clinic timings, characteristics of the test, availability of transport, social network and support, and social norms and cultural practices. Minimising and aligning complex stepwise processes of prenatal care and GDM screening delivery and attention to the factors influencing it are important for further improving and expanding GDM screening and related services, not only in Tamil Nadu but in other similar low and middle income settings. This study stresses the importance of guidelines and diagnostic criteria which are simple and feasible on the ground.

  6. Factors influencing timely initiation and completion of gestational diabetes mellitus screening and diagnosis - a qualitative study from Tamil Nadu, India

    OpenAIRE

    Nielsen, Karoline Kragelund; Rheinl?nder, Thilde; Kapur, Anil; Damm, Peter; Seshiah, Veerasamy; Bygbjerg, Ib C.

    2017-01-01

    Background In 2007, universal screening for gestational diabetes mellitus (GDM) was introduced in Tamil Nadu, India. To identify factors hindering or facilitating timely initiation and completion of the GDM screening and diagnosis process, our study investigated how pregnant women in rural and urban Tamil Nadu access and navigate different GDM related health services. Methods The study was carried out in two settings: an urban private diabetes centre and a rural government primary health cent...

  7. Prenatal Care Initiation in Low-Income Hispanic Women: Risk and Protective Factors

    Science.gov (United States)

    Luecken, Linda J.; Purdom, Catherine L.; Howe, Rose

    2009-01-01

    Objectives: To examine the psychosocial risk (distress, stress, unintended pregnancy) and protective factors (social support, mastery, familism) associated with entry into prenatal care among low-income Hispanic women. Methods: Between April and September 2005, 483 postpartum Medicaid-eligible Hispanic women completed a survey at the hospital.…

  8. ABCE1: A special factor that orchestrates translation at the crossroad between recycling and initiation

    Czech Academy of Sciences Publication Activity Database

    Mancera-Martínez, E.; Brito Querido, J.; Valášek, Leoš Shivaya; Simonetti, A.; Hashem, Y.

    2017-01-01

    Roč. 14, č. 10 (2017), s. 1279-1285 ISSN 1547-6286 R&D Projects: GA ČR(CZ) GA14-05394S Institutional support: RVO:61388971 Keywords : ABCE1 * cryo-EM * ribosome Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 3.900, year: 2016

  9. An OMERACT Initiative Toward Consensus to Identify and Characterize Candidate Contextual Factors

    DEFF Research Database (Denmark)

    Finger, Monika E; Boonen, Annelies; Woodworth, Thasia G

    2017-01-01

    OBJECTIVE: The importance of contextual factors (CF) for appropriate patient-specific care is widely acknowledged. However, evidence in clinical trials on how CF influence outcomes remains sparse. The 2014 Outcome Measures in Rheumatology (OMERACT) Handbook introduced the role of CF in outcome as...

  10. Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Fernanda Vaisman

    2011-01-01

    Full Text Available BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14. The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease-free status in follow-up. Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014. The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS: Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.

  11. Natural Course of Initially Non-Operated Cases of Acute Subdural Hematoma : The Risk Factors of Hematoma Progression

    Science.gov (United States)

    Son, Seong; Lee, Sang Gu; Kim, Eun Young; Park, Chan Woo; Kim, Woo Kyung

    2013-01-01

    Objective The objectives of the present study were to characterize the natural course of initially non-operated traumatic acute subdural hematoma (ASDH) and to identify the risk factors of hematoma progression. Methods Retrospective analysis was performed using sequential computed tomography (CT) images maintained in a prospective observational database containing 177 ASDH cases treated from 2005 to 2011. Patients were allocated to four groups as followings; 136 (76.8%) patients to the spontaneous resolution group, 12 (6.8%) who underwent operation between 4 hours and 7 days to the rapid worsening group (RWG), 24 (13.6%) who experienced an increase of hematoma and that underwent operation between 7 and 28 days to the subacute worsening group (SWG), and 5 (2.8%) who developed delayed aggravation requiring surgery from one month after onset to the delayed worsening group (DWG). Groups were compared with respect to various factors. Results No significant intergroup difference was found with respect to age, mechanism of injury, or initial Glasgow Coma Scale. The presence of combined cerebral contusion or subarachnoid hemorrhage was found to be a significant prognostic factor. Regarding CT findings, mixed density was common in the RWG and the SWG. Midline shifting, hematoma thickness, and numbers of CT slices containing hematoma were significant prognostic factors of the RWG and the SWG. Brain atrophy was more severe in the SWG and the DWG. Conclusion A large proportion of initially non-operated ASDHs worsen in the acute or subacute phase. Patients with risk factors should be monitored carefully for progression by repeat CT imaging. PMID:24278650

  12. Factors associated with initial incomplete ablation for benign thyroid nodules after radiofrequency ablation: First results of CEUS evaluation.

    Science.gov (United States)

    Zhao, Chong-Ke; Xu, Hui-Xiong; Lu, Feng; Sun, Li-Ping; He, Ya-Ping; Guo, Le-Hang; Li, Xiao-Long; Bo, Xiao-Wan; Yue, Wen-Wen

    2017-01-01

    To assess the factors associated with initial incomplete ablation (ICA) after radiofrequency ablation for benign thyroid nodules (BTNs). 69 BTNs (mean volume 6.35±5.66 ml, range 1.00-25.04 ml) confirmed by fine-needle aspiration cytology (FNAC) in fifty-four patients were treated with ultrasound-guided percutaneous radiofrequency ablation (RFA) and the local treatment efficacy was immediately assessed by intra-procedural contrast-enhanced ultrasound (CEUS). The RFA was performed with a bipolar electrode (CelonProSurge 150-T20, output power: 20 W). CEUS was performed with a second generation contrast agent under low acoustic power (i.e. coded phase inversion, CPI). Characteristics of clinical factors, findings on conventional gray-scale ultrasound, color-Doppler ultrasound, and CEUS were evaluated preoperatively. Factors associated with initial ICA and initial ICA patterns on CEUS were assessed. Volume reduction ratios (VRRs) of ICA nodules were compared with those with complete ablation (CA). The RFA procedures were accomplished with a mean ablation time and mean total energy deposition of 11.13±3.39 min (range, 5.38-22.13 min) and 12612±4466 J (range, 6310-26130 J) respectively. CEUS detected initial ICA in 21 of 69 (30.8%) BTNs and 16 (76.2%) of the 21 BTNs with initial ICA achieved CA after additional RFA, leading to a final CA rate of 92.8% (64/69). The factors associated with initial ICA were predominantly solid nodule, nodule close to danger triangle area, nodule close to carotid artery, and peripheral blood flow on color-Doppler ultrasound (all P 50% at the 6-month follow-up, among which 7 nodules (10.1%) had VRRs of >90%. There were significant differences in VRRs between ICA nodules and CA nodules at the 3- and 6-month follow-up (all P ultrasound. CEUS assists quick treatment response evaluation and facilitates subsequent additional RFA and final CA of the nodules. Nodules with CA achieve a better outcome in terms of VRR in comparison with

  13. Automated work packages architecture: An initial set of human factors and instrumentation and controls requirements

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Vivek [Idaho National Lab. (INL), Idaho Falls, ID (United States); Oxstrand, Johanna H. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Le Blanc, Katya L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-09-01

    The work management process in current fleets of national nuclear power plants is so highly dependent on large technical staffs and quality of work instruction, i.e., paper-based, that this puts nuclear energy at somewhat of a long-term economic disadvantage and increase the possibility of human errors. Technologies like mobile portable devices and computer-based procedures can play a key role in improving the plant work management process, thereby increasing productivity and decreasing cost. Automated work packages are a fundamentally an enabling technology for improving worker productivity and human performance in nuclear power plants work activities because virtually every plant work activity is accomplished using some form of a work package. As part of this year’s research effort, automated work packages architecture is identified and an initial set of requirements identified, that are essential and necessary for implementation of automated work packages in nuclear power plants.

  14. Posterior reversible encephalopathy syndrome in liver transplant patients: clinical presentation, risk factors and initial management.

    Science.gov (United States)

    Cruz, R J; DiMartini, A; Akhavanheidari, M; Iacovoni, N; Boardman, J F; Donaldson, J; Humar, A; Bartynski, W S

    2012-08-01

    Posterior reversible encephalopathy syndrome (PRES) is an uncommon but well-known complication after transplantation diagnosed by characteristic radiological features. As limited data on this complex syndrome exist we sought to better define the incidence, clinical presentation and risk factors for PRES in liver transplant (LTx) patients. We conducted a retrospective analysis of 1923 adult LTx recipients transplanted between 2000 and 2010. PRES was diagnosed radiologically in 19 patients (1%), with 84% of cases occurring within 3 months post-LTX. We compared this cohort of PRES patients to 316 other LTx recipients also requiring radiographic imaging within 3 months after LTx for neurological symptoms. Seizure was the most common clinical manifestation in the PRES group (88% vs. 16%, pliver disease and infection/sepsis. These factors may be related to a common pathway of vascular dysregulation/damage that appears to characterize this complex syndrome. Intracranial bleeding and seizures may be the end result of these phenomena. The relationship of these associated factors to the hypothesized pathophysiology of PRES is discussed. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Factors contributing to initial weight loss among adolescents with polycystic ovary syndrome.

    Science.gov (United States)

    Geier, L M; Bekx, M T; Connor, E L

    2012-12-01

    To evaluate the impact of a multidisciplinary clinic on weight management among adolescents with PCOS. 140 adolescent females were evaluated in a multidisciplinary PCOS clinic from March 2005 to December 2008. The team included a pediatric endocrinologist, health psychologist, dietitian, and pediatric gynecologist. 110 were diagnosed with PCOS based on the Rotterdam Criteria. Height, weight, BMI, number of subspecialists seen, use of metformin, and compliance with return visits were obtained from medical records. American Family Children's Hospital in Madison, Wisconsin. 110 adolescent females with polycystic ovary syndrome. Consultation with a dietitian and health psychologist. Change in weight. The average age at first visit was 15.9 years. The average BMI was 34.7 kg/m(2) (range 18.1-55.5). Seventy-six percent had an initial BMI above the 95(th) percentile. Interactions with providers at the initial visit included a pediatric endocrinologist (100%), health psychologist (60.9%), dietitian (75.5%) and gynecologist (70.9%). Seventy one percent returned for a follow-up visit, (average time of 4.5 months between visits) with 57% achieving weight loss (average 3.5 kg) and an additional 12.6% demonstrating no significant weight gain (weight loss/stabilization. In this multidisciplinary clinic for adolescents with PCOS, nearly 70% of patients succeeded in short-term weight stabilization, with 57% demonstrating weight loss. Interactions with the health psychologist and dietitian appeared to play a key role in successful weight control, supporting the importance of psychology and nutrition expertise in the management of this disorder. Copyright © 2012 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  16. Population-specific regulation of Chmp2b by Lbx1 during onset of synaptogenesis in lateral association interneurons.

    Directory of Open Access Journals (Sweden)

    Jun Xu

    Full Text Available Chmp2b is closely related to Vps2, a key component of the yeast protein complex that creates the intralumenal vesicles of multivesicular bodies. Dominant negative mutations in Chmp2b cause autophagosome accumulation and neurodegenerative disease. Loss of Chmp2b causes failure of dendritic spine maturation in cultured neurons. The homeobox gene Lbx1 plays an essential role in specifying postmitotic dorsal interneuron populations during late pattern formation in the neural tube. We have discovered that Chmp2b is one of the most highly regulated cell-autonomous targets of Lbx1 in the embryonic mouse neural tube. Chmp2b was expressed and depended on Lbx1 in only two of the five nascent, Lbx1-expressing, postmitotic, dorsal interneuron populations. It was also expressed in neural tube cell populations that lacked Lbx1 protein. The observed population-specific expression of Chmp2b indicated that only certain population-specific combinations of sequence specific transcription factors allow Chmp2b expression. The cell populations that expressed Chmp2b corresponded, in time and location, to neurons that make the first synapses of the spinal cord. Chmp2b protein was transported into neurites within the motor- and association-neuropils, where the first synapses are known to form between E11.5 and E12.5 in mouse neural tubes. Selective, developmentally-specified gene expression of Chmp2b may therefore be used to endow particular neuronal populations with the ability to mature dendritic spines. Such a mechanism could explain how mammalian embryos reproducibly establish the disynaptic cutaneous reflex only between particular cell populations.

  17. COSIMA B2B - sales automation for e-procurement

    OpenAIRE

    Döring, Sven

    2004-01-01

    COSIMA B2B - sales automation for e-procurement / W. Kießling, S. Fischer, S. Döring. - In: International Conference on E-Commerce Technology : Proceedings / IEEE International Conference on E-Commerce Technology, CEC 2004 : 6 - 9 July 2004, San Diego, California / ed. by Martin Bichler ... - Los Alamitos, Calif. [u.a.] : IEEE Computer Society, 2004. - S. 59-68

  18. Customer satisfaction in B2B cloud services

    OpenAIRE

    Turunen, Helinä

    2013-01-01

    Tutkimuksen tavoitteena on kirjallisuuskatsauksen kautta esitellä B2B-pilvipalveluiden asiakastyytyväisyyteen vaikuttavia seikkoja, ja kuinka näitä seikkoja tulisi ottaa huomioon asiakastyytyväisyyden parantamisessa. Tässä tutkimuksessa verkkopohjaiseen liiketoimintaan liittyvää asiakastyytyväisyyden tutkimusta käytettiin pohjana etsiessä asiakastyytyväisyyteen vaikuttavia seikkoja pilvipalveluissa. Tutkimuksessa vertaillaan asiakastyytyväisyyteen vaikuttavia seikkoja vertailemalla tyytyväisy...

  19. Mass Customized Technical Textiles in the B2B Sector

    Science.gov (United States)

    Gebhardt, R.; Barteld, M.; Grafmüller, L.; Mosig, T.; Weiß, M.

    2017-10-01

    Mass Customization is a great opportunity for textile companies for both staying competitive in high-wage countries and offering inexpensive, customized products. Within the area of Technical Textiles, this study focuses on the B2B sector and shows the status quo, potentials and strengths. Both management and technological issues are addressed. For the former, business models and the value co-creation process are dealt with, for the latter, the focus is on modelling.

  20. A Review of the Factors Associated With the Timely Initiation of Breastfeeding and Exclusive Breastfeeding in the Middle East

    Science.gov (United States)

    Alzaheb, Riyadh A

    2017-01-01

    Background: Breastfeeding supplies all the nutrients that infants need for their healthy development. Breastfeeding practice is multifactorial, and numerous variables influence mothers’ decisions and ability to breastfeed. This review identifies the factors potentially affecting the timely initiation of breastfeeding within an hour after birth and exclusive breastfeeding in the first 6 months in Middle Eastern countries. Methods: The Medline, ScienceDirect, and Web of Science databases were keyword-searched for primary studies meeting the following inclusion criteria: (1) publication in the English language between January 2001 and May 2017, (2) original research articles reporting primary data on the factors influencing the timely initiation of breastfeeding and/or exclusive breastfeeding, (3) the use of World Health Organization definitions, and (4) Middle Eastern research contexts. A random effect model was used to establish the average prevalence of the timely initiation of breastfeeding and exclusive breastfeeding in the Middle East. Results: The review identified 19 studies conducted in Saudi Arabia (7), Iran (3), Egypt (2), Turkey (2), Kuwait (1), the United Arab Emirates (1), Qatar (1), Lebanon (1), and Syria (1). The meta-analysis established that 34.3% (confidence interval [CI]: 20.2%-51.9%) of Middle Eastern newborns received breastfeeding initiated within an hour of birth, and only 20.5% (CI: 14.5%-28.2%) were fed only breast milk for the first 6 months. The 8 studies exploring breastfeeding initiation most commonly associated it with the following: delivery mode, maternal employment, rooming-in, and prelacteal feeding. The 17 studies investigating exclusive breastfeeding most frequently linked it to the following: maternal age, maternal education, maternal employment, and delivery mode. Conclusions: Middle Eastern health care organizations should fully understand all the determinants of breastfeeding identified by this review to provide suitable

  1. Factors Associated With Initiation of Biologics in Patients With Axial Spondyloarthritis in an Urban Asian City: A PRESPOND Study.

    Science.gov (United States)

    Png, Wan Yu; Kwan, Yu Heng; Lee, Yi Xuan; Lim, Ka Keat; Chew, Eng Hui; Lui, Nai Lee; Tan, Chuen Seng; Thumboo, Julian; Østbye, Truls; Fong, Warren

    2018-04-05

    The aim of this study was to examine if patients' sociodemographic, clinical characteristics, and patient-reported outcomes were associated with biologics initiation in patients with axial spondyloarthritis in Singapore. Data from a dedicated registry from a tertiary referral center in Singapore from January 2011 to July 2016 were used. Initiation of first biologics was the main outcome of interest. Logistic regression analyses were used to explore the association of various factors on biologics initiation. Of 189 eligible patients (aged 37.7 ± 13.3 years; 76.2% were males), 30 (15.9 %) were started on biologics during follow-up. In the multivariable analysis model, age (odds ratio [OR]; 0.93; 95% confidence interval [CI], 0.89-0.98; P < 0.01), mental component summary score of Short-Form 36 Health Survey (OR, 0.18; 95% CI, 0.03-0.89; P = 0.04), erythrocyte sedimentation rate (OR, 1.02; 95% CI, 1.00-1.04; P = 0.02), presence of peptic ulcer disease (OR, 10.4; 95% CI, 2.21-48.8; P < 0.01), and lack of good response to nonsteroidal anti-inflammatory drugs (OR, 4.44; 95% CI, 1.63-12.1; P < 0.01) were found to be associated with biologics initiation. Age, erythrocyte sedimentation rate, mental component summary score, comorbidities of peptic ulcer disease, and responsiveness to nonsteroidal anti-inflammatory drugs were associated with biologics initiation. It is essential that clinicians recognize these factors in order to optimize therapy.

  2. A Review of the Factors Associated With the Timely Initiation of Breastfeeding and Exclusive Breastfeeding in the Middle East

    Directory of Open Access Journals (Sweden)

    Riyadh A Alzaheb

    2017-12-01

    Full Text Available Background: Breastfeeding supplies all the nutrients that infants need for their healthy development. Breastfeeding practice is multifactorial, and numerous variables influence mothers’ decisions and ability to breastfeed. This review identifies the factors potentially affecting the timely initiation of breastfeeding within an hour after birth and exclusive breastfeeding in the first 6 months in Middle Eastern countries. Methods: The Medline, ScienceDirect, and Web of Science databases were keyword-searched for primary studies meeting the following inclusion criteria: (1 publication in the English language between January 2001 and May 2017, (2 original research articles reporting primary data on the factors influencing the timely initiation of breastfeeding and/or exclusive breastfeeding, (3 the use of World Health Organization definitions, and (4 Middle Eastern research contexts. A random effect model was used to establish the average prevalence of the timely initiation of breastfeeding and exclusive breastfeeding in the Middle East. Results: The review identified 19 studies conducted in Saudi Arabia (7, Iran (3, Egypt (2, Turkey (2, Kuwait (1, the United Arab Emirates (1, Qatar (1, Lebanon (1, and Syria (1. The meta-analysis established that 34.3% (confidence interval [CI]: 20.2%-51.9% of Middle Eastern newborns received breastfeeding initiated within an hour of birth, and only 20.5% (CI: 14.5%-28.2% were fed only breast milk for the first 6 months. The 8 studies exploring breastfeeding initiation most commonly associated it with the following: delivery mode, maternal employment, rooming-in, and prelacteal feeding. The 17 studies investigating exclusive breastfeeding most frequently linked it to the following: maternal age, maternal education, maternal employment, and delivery mode. Conclusions: Middle Eastern health care organizations should fully understand all the determinants of breastfeeding identified by this review to provide

  3. Combustion of Na2B4O7 + Mg + C to synthesis B4C powders

    International Nuclear Information System (INIS)

    Jiang Guojian; Xu Jiayue; Zhuang Hanrui; Li Wenlan

    2009-01-01

    Boron carbide powder was fabricated by combustion synthesis (CS) method directly from mixed powders of borax (Na 2 B 4 O 7 ), magnesium (Mg) and carbon. The adiabatic temperature of the combustion reaction of Na 2 B 4 O 7 + 6 Mg + C was calculated. The control of the reactions was achieved by selecting reactant composition, relative density of powder compact and gas pressure in CS reactor. The effects of these different influential factors on the composition and morphologies of combustion products were investigated. The results show that, it is advantageous for more Mg/Na 2 B 4 O 7 than stoichiometric ratio in Na 2 B 4 O 7 + Mg + C system and high atmosphere pressure in the CS reactor to increase the conversion degree of reactants to end product. The final product with the minimal impurities' content could be fabricated at appropriate relative density of powder compact. At last, boron carbide without impurities could be obtained after the acid enrichment and distilled water washing.

  4. Mission and Sustainability of Informatics for Integrating Biology and the Bedside (i2b2).

    Science.gov (United States)

    Murphy, Shawn; Wilcox, Adam

    2014-01-01

    -source platform has a community of developers that are continuously enhancing the analytic capacities of the platform and inventing new functionality. By understanding how i2b2 has been sustained, we hope that other research infrastructure projects may better navigate options in making those initiatives sustainable over time.

  5. Agent-based services for B2B electronic commerce

    Science.gov (United States)

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

    2000-12-01

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

  6. Novel Synthesis of the TiO2(B) Multilayer Templated Films

    Czech Academy of Sciences Publication Activity Database

    Procházka, Jan; Kavan, Ladislav; Zukalová, Markéta; Frank, Otakar; Kalbáč, Martin; Zukal, Arnošt; Klementová, Mariana; Carbone, D.; Graetzel, M.

    2009-01-01

    Roč. 21, č. 8 (2009), s. 1457-1464 ISSN 0897-4756 R&D Projects: GA MŠk LC510; GA AV ČR IAA400400804; GA AV ČR KAN200100801; GA AV ČR KAN100500652 Institutional research plan: CEZ:AV0Z40400503; CEZ:AV0Z40320502 Keywords : TiO2(B) * synthesis * films Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.368, year: 2009

  7. Factors reducing the expected deflection in initial orientation in clock-shifted homing pigeons.

    Science.gov (United States)

    Gagliardo, Anna; Odetti, Francesca; Ioalè, Paolo

    2005-02-01

    To orient from familiar sites, homing pigeons can rely on both an olfactory map and visual familiar landmarks. The latter can in principle be used in two different ways: either within a topographical map exploited for piloting or in a so-called mosaic map associated with a compass bearing. One way to investigate the matter is to put the compass and the topographical information in conflict by releasing clock-shifted pigeons from familiar locations. Although the compass orientation is in general dominant over a piloting strategy, a stronger or weaker tendency to correct towards the home direction by clock-shifted pigeons released from very familiar sites has often been observed. To investigate which factors are involved in the reduction of the deviation due to clock-shift, we performed a series of releases with intact and anosmic pigeons from familiar sites in unshifted and clock-shifted conditions and a series of releases from the same sites with naive clock-shifted birds. Our data suggest that the following factors have a role in reducing deviation due to the clock-shift: familiarity with the release site, the lack of olfactory information and some unknown site-dependent features.

  8. Tendencies in human factor influence on initiating events occurrence in NPP Kozloduy

    International Nuclear Information System (INIS)

    Hristova, R.

    2001-01-01

    Overview of the methods and documents concerning human factor in nuclear safety and selection of the most appropriate methods and concept for human factor assessment in the reported events in Kozloduy NPP are presented. List of human error types and statistical data (the mean time between similar errors, the human rate λ, the number of occurrences ect.) is given. Some general results from the human error behavior investigation for all units of Kozloduy NPP related to the 4 personnel categories: Management personnel, Designers, Operating personnel, Maintenance personnel are also shown. At the end the following conclusion are made:18 % operating personnel errors (for comparison for the same category personnel in similar NPPs abroad this value is between 10 % and 30%); Human errors in Kozloduy NPP tend to increase after year 1990; only for the operating personnel a maximum near year 1997 was observed, after which the error values was decreased; at the beginning of year 2000 the reliability characteristics for all units have similar values; it is necessary to be taken into account the observed tendencies to take measurements for reducing of the most important error types for Kozloduy NPP personnel

  9. Initial management of pneumonia and sepsis: factors associated with improved outcome.

    Science.gov (United States)

    Menéndez, R; Torres, A; Reyes, S; Zalacain, R; Capelastegui, A; Aspa, J; Borderías, L; Martín-Villasclaras, J J; Bello, S; Alfageme, I; de Castro, F R; Rello, J; Molinos, L; Ruiz-Manzano, J

    2012-01-01

    Processes of care and adherence to guidelines have been associated with improved survival in community-acquired pneumonia (CAP). In sepsis, bundles of processes of care have also increased survival. We aimed to audit compliance with guideline-recommended processes of care and its impact on outcome in hospitalised CAP patients with sepsis. We prospectively studied 4,137 patients hospitalised with CAP in 13 hospitals. The processes of care evaluated were adherence to antibiotic prescription guidelines, first dose within 6 h and oxygen assessment. Outcome measures were mortality and length of stay (LOS). Oxygen assessment was measured in 3,745 (90.5%) patients; 3,024 (73.1%) patients received antibiotics according to guidelines and 3,053 (73.8%) received antibiotics within 6 h. In CAP patients with sepsis, the strongest independent factor for survival was antibiotic adherence (OR 0.4). In severe sepsis, only compliance to antibiotic adherence plus first dose within 6 h was associated with lower mortality (OR 0.60), adjusted for fine prognostic scale and hospital. Antibiotic adherence was related to shorter hospital stay. In sepsis, antibiotic adherence is the strongest protective factor of care associated with survival and LOS. In severe sepsis, combined antibiotic adherence and first dose within 6 h may reduce mortality.

  10. Factors Associated With Interest in Same-Day Contraception Initiation Among Females in the Pediatric Emergency Department.

    Science.gov (United States)

    Miller, Melissa K; Randell, Kimberly A; Barral, Romina; Sherman, Ashley K; Miller, Elizabeth

    2016-02-01

    The purposes were to describe interest in hormonal contraception initiation among female adolescent in the emergency department (ED) and to assess for associations with factors known to increase pregnancy risk such as violence victimization. We used a computerized survey to assess sexual and dating practices, pregnancy history/likelihood, contraception use (including long-acting reversible contraception [LARC]) and concerns, contraception initiation interest, violence victimization, medical utilization, and demographics among sexually experienced females aged 14-19 years in our ED. The primary outcome was interest in contraception initiation. We compared responses between subgroups using the chi-square test. A total of 168 adolescents participated (82% of approached; mean age 16.6 years; 41% white; 48% black; 21% commercial insurance). Interest in contraception initiation was high: 60% overall and 70% among those not using hormonal contraception (n = 96). Among those using non-LARC contraception (n = 59), 29% were interested in LARC initiation. Contraception/LARC interest was positively associated with lack of recent well care (p contraception (p contraception at last intercourse. One third (36%) reported violence victimization. Most (70%) reported ≥1 concern about contraception (most commonly cost). Many reported behaviors and exposures, including violence victimization, that increase their risk for pregnancy and most expressed interest in same-day initiation of hormonal contraception, including LARC. These findings may inform novel strategies for increased adolescent access to contraception and pregnancy prevention through use of nontraditional sites such as EDs. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  11. Effects of environment factors on initiation of sperm motility in sea cucumber Apostichopus japonicus (Selenka)

    Science.gov (United States)

    Yu, Li; Shao, Mingyu; Bao, Zhenmin; Hu, Jingjie; Zhang, Zhifeng

    2011-06-01

    Sperm of sea cucumber Apostichopus japonicus (Selenka) were quiescent in electrolyte NaCl solution and artificial seawater (ASW) and nonelectrolyte glucose and mannitol solutions when the osmolality was less than 200 mOsm kg-1. The sperm started to be motile as a result of increased osmolality, indicating an osmolality-dependent initiation of sperm motility in sea cucumber. After a brief incubation in hypotonic NaCl and glucose solutions with osmolalities of 200 and 400 mOsm kg-1, sperm lost partial motile ability. Sperm became immobilized when pH was 6.0 in NaCl, glucose and mannitol solutions, suggesting that an H+ release is involved in sperm activation. The decreased pH had no effect on the percentage of motile sperm in ASW, whereas it delayed the time period to reach the maximum motility (motilitymax). Extracellular Ca2+ in electrolyte solutions was not essential for motility stimulation but shortened the time of reaching motilitymax. When Ca2+ was mixed in nonelectrolyte solutions the sperm motility was completely suppressed. The K+ channel blocker, quinine, suppressed the sperm motility in electrolyte solution, showing a possible involvement of K+ transport in the process. High K+ concentration did not affect the sperm motility in NaCl solution, but decreased it in ASW and almost entirely suppressed it in nonelectrolyte solutions. The different effects of pH and K+ in ASW and NaCl solution indicate that external ions may also regulate sperm motility.

  12. Influence of family and school-level factors on age of sexual initiation.

    Science.gov (United States)

    White, Candace N; Warner, Lynn A

    2015-02-01

    This study examined the association of individual, family, and school-level characteristics with age of sexual initiation (ASI) and focused specifically on school context as a moderator of known predictors of ASI. Data are from Waves I and IV of the National Longitudinal Study of Adolescent Health (N = 10,596). Predictors include grade point average, physical development, attitudes about sex, likelihood of higher education, alcohol use, delinquency, family structure, parents' education level, childhood abuse, maternal approval of sex, parental monitoring, and parent-child relationship quality. School-level predictors are averages of adolescents' attitudes about sex and likelihood of higher education and parents' education. Hierarchical linear models run separately by sex were used to predict ASI. When school-level attitudes about sex are more favorable, both boys and girls report younger ASI, and school mean parental education attainment moderates the influence of individual adolescents' attitudes about sex on ASI. More of the predictors are significant for girls than boys, whereas perception of maternal and peer approval of sexual activity are the most salient predictors of younger ASI for boys. Results highlight the importance of school context for understanding adolescents' motivations for early ASI. Findings support the need for school-wide prevention interventions that engage adolescents, peers, and parents in addressing attitudes about early sex. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  13. Factors Related to Initiating Interpersonal Contacts on Internet Dating Sites: A View From the Social Exchange Theory

    Directory of Open Access Journals (Sweden)

    Rivka Shtatfeld

    2009-12-01

    Full Text Available The purpose of this study was to identify factors that influence dating-site users to initiate contact with potential romantic partners. The study was carried out by observing online behaviors and analyzing the profiles and authentic messages of these users (N = 106 over seven months. Contacts made by and with the research participants were analyzed in terms of the relationships between initiators‘ and receivers‘ demographic variables (marital status, age, level of education, income, writing skills, and stated physical appearance. In addition, the relationship between contacting partners and site accessibility was examined. The findings revealed that dating-site users initiated contact primarily with those having a similar marital status or slightly better characteristics (income, education, writing skills. In regard to writing skills, it was found that skilled writers attracted more contacts than did less skilled writers. However, the factor that was found to be most significantly related to initiating contact was the length of time that elapsed from last connection to the site, which implies the perceived accessibility of potential romantic partners. The findings were explained in terms of the Social Exchange Theory: people are attracted to those who grant them rewards.

  14. Factors Affecting Initial Intimate Partner Violence-Specific Health Care Seeking in the Tokyo Metropolitan Area, Japan.

    Science.gov (United States)

    Kamimura, Akiko; Bybee, Deborah; Yoshihama, Mieko

    2014-09-01

    This study examined the factors affecting a women's initial intimate partner violence (IPV)-specific health care seeking event which refers to the first health care seeking as a result of IPV in a lifetime. Data were collected using the Life History Calendar method in the Tokyo metropolitan area from 101 women who had experienced IPV. Discrete-time survival analysis was used to assess the time to initial IPV-specific health care seeking. IPV-related injury was the most significant factor associated with increased likelihood of seeking IPV-specific health care seeking for the first time. In the presence of a strong effect of formal help seeking, physical and sexual IPV were no longer significantly related to initial IPV-specific health care seeking. The results suggest some victims of IPV may not seek health care unless they get injured. The timing of receiving health care would be important to ensure the health and safety of victims. © The Author(s) 2014.

  15. [Analysis of obstetric-pediatric care in the perinatal period. Are births before 31 weeks' gestation in level 2B maternity units avoidable?

    Science.gov (United States)

    Martin, I; Roussel, A; Olieric, M-F; Feldmann, M; Wallerich, Y; Trabelsi, N; Miton, A; Zuily-Lamy, C; Valdès, V; Fresson, J

    2017-12-01

    Regionalization of perinatal care has been developed to improve the survival of preterm babies. The mortality rate is higher among very premature infants born outside level-3 maternity units. The objective of this study was to evaluate the preventability of these very premature births occurring outside recommendations within level-2B maternity units. The secondary objective was to describe the care of premature infants between 23 and 24 weeks. This is a single-center retrospective qualitative study of the care delivery pathways. Thirty-one deliveries in which the fetus was alive between 23 and 30 weeks+6 days occurred in a level-2B maternity unit in Thionville, France, between 1 January 2013 and 31 December 2015. After oral presentation of the cases, a level 2-3 multidisciplinary committee of experts in Lorraine evaluated the preventability criteria and reasons, and divided the deliveries into three groups: (i) birth in level-2B institutions avoidable, (ii) inevitable with factors related to the mother or the organization of care, (iii) with no inevitable factors. Out of the 31 deliveries included, the committee classified six deliveries as preventable, 14 as inevitable with factors, and 11 as inevitable with no factors. The criteria for preventability of birth in a level-2B unit were underestimation of maternal and fetal risk, an erroneous initial estimate of term or preterm labor, and two births in the upper limits of the French recommendations for in utero transfer. Nineteen of the 35 premature infants before 31 weeks' gestation died, 16 children were transferred to a level-3 maternity ward, and 16 children were allowed to go home. Analysis of the obstetrical-pediatric care course by an expert committee determined the preventability of the average birth and prematurity in level-2B maternity units in Lorraine for a small but significant number of cases. The local regionalization of neonatal care could be improved by the application of this method of analysis to

  16. Controlled synthesis of TiO2-B nanowires and nanoparticles for dye-sensitized solar cells

    International Nuclear Information System (INIS)

    Qi Lihong; Liu Yongjun; Li Chunyan

    2010-01-01

    Controllable synthesis of the TiO 2 -B nanowires (NWs) and nanoparticles (NPs) had been achieved via a facile hydrothermal route, respectively, only by tuning the solution volume. The dye-sensitized solar cells prototypes had been fabricated using TiO 2 -B NW and NP electrodes, respectively. The TiO 2 -B NP cells had higher photocurrent and photoelectrical conversion efficiency than the TiO 2 -B NW cells though the latter exhibited larger photovoltage compared to the former. The key factors such as the photogenerated electron injection drive force, surface defects and the interfacial charge transfer, which determined the photoelectrical properties, had been systematically researched with the surface photovoltage spectra (SPS) and the electrochemical impedance spectra (EIS). The SPS proved that there was larger photoelectron injection drive force in TiO 2 -B NP photoelectrode than that in NW photoelectrode. And the electrochemical impedance spectra (EIS) revealed that TiO 2 -B NP cells had faster interface charge transfer compared to TiO 2 -B NW cells. Both proved that NP cells had the higher photocurrents.

  17. Predictive risk factors of postoperative urinary incontinence following holmium laser enucleation of the prostate during the initial learning period

    Directory of Open Access Journals (Sweden)

    Shuichiro Kobayashi

    Full Text Available ABSTRACT Purpose: To determine the predictive factors for postoperative urinary incontinence (UI following holmium laser enucleation of the prostate (HoLEP during the initial learning period. Patients and Methods: We evaluated 127 patients with benign prostatic hyperplasia who underwent HoLEP between January 2011 and December 2013. We recorded clinical variables, including blood loss, serum prostate-specific antigen levels, and the presence or absence of UI. Blood loss was estimated as a decline in postoperative hemoglobin levels. The predictive factors for postoperative UI were determined using a multivariable logistic regression analysis. Results: Postoperative UI occurred in 31 patients (24.4%, but it cured in 29 patients (93.5% after a mean duration of 12 weeks. Enucleation time >100 min (p=0.043 and blood loss >2.5g/dL (p=0.032 were identified as significant and independent risk factors for postoperative UI. Conclusions: Longer enucleation time and increased blood loss were independent predictors of postoperative UI in patients who underwent HoLEP during the initial learning period. Surgeons in training should take care to perform speedy enucleation maneuver with hemostasis.

  18. Intervening factors for the initiation of treatment of patients with stomach and colorectal cancer.

    Science.gov (United States)

    Valle, Thaína Dalla; Turrini, Ruth Natalia Teresa; Poveda, Vanessa de Brito

    2017-05-15

    to identify the time between symptoms, the request for care and the beginning of treatment in patients with stomach and colorectal cancer as well as the factors that interfere in these processes. correlational descriptive study, including 101 patients diagnosed with stomach or colorectal cancer, treated in a hospital specialized in oncology. the 101 patients investigated there was predominance of males, mean age of 61.7 years. The search for medical care occurred within 30 days after the onset of symptoms, in most cases. The mean total time between the onset of symptoms and the beginning of treatment ranged from 15 to 16 months, and the mean time between the search for medical care and the diagnosis was 4.78 months. The family history of cancer (p=0.008) and the implementation of preventive follow-up (pel tiempo entre los síntomas, la búsqueda de asistencia y el inicio del tratamiento en pacientes con cáncer gástrico y colorrectal y los factores que interfieren en estos procesos. estudio descriptivo correlacional, incluyendo 101 pacientes con diagnostico de cáncer gástrico o colorrectal, atendidos en un hospital especializado en oncología. de 101 pacientes investigados la mayoria eran hombres, con edad media de 61,7 años. La búsqueda de la atención médica se produjo dentro de los 30 días después de la aparición de los síntomas, en la mayoría de los casos. El promedio de tiempo total entre el inicio de los síntomas y el inicio del tratamiento fue de 15,16 meses y el tiempo medio entre la búsqueda de la atención médica y el diagnóstico fue de 4,78 meses. La historia familiar de cáncer (p=0,008) y la realización de seguimiento preventivo (pel tratamiento temprano. Náuseas, vómitos, hematoquecia, pérdida de peso y dolor se asociaron con la búsqueda más rápida de la asistencia. el intervalo más largo entre la búsqueda de la atención médica y el diagnóstico se produjo posiblemente por asociación negativa entre los síntomas que se

  19. Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells

    Science.gov (United States)

    Mimeault, Murielle; Batra, Surinder K

    2013-01-01

    Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency-associated transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis- and epithelial-mesenchymal transition (EMT) programme-associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self-renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse. PMID:23301832

  20. Intervening factors for the initiation of treatment of patients with stomach and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Thaína Dalla Valle

    Full Text Available ABSTRACT Objective: to identify the time between symptoms, the request for care and the beginning of treatment in patients with stomach and colorectal cancer as well as the factors that interfere in these processes. Method: correlational descriptive study, including 101 patients diagnosed with stomach or colorectal cancer, treated in a hospital specialized in oncology. Results: the 101 patients investigated there was predominance of males, mean age of 61.7 years. The search for medical care occurred within 30 days after the onset of symptoms, in most cases. The mean total time between the onset of symptoms and the beginning of treatment ranged from 15 to 16 months, and the mean time between the search for medical care and the diagnosis was 4.78 months. The family history of cancer (p=0.008 and the implementation of preventive follow-up (p<0.001 were associated with shorter periods between the search for care and the beginning of treatment. Nausea, vomiting, hematochezia, weight loss and pain were associated with faster demand for care. Conclusion: the longer interval between the search for medical care and the diagnosis was possibly due to the non-association between the presented symptoms and the disease.

  1. Initial investigation of organisational factors associated with the implementation of active support.

    Science.gov (United States)

    Fyffe, Chris; McCubbery, Jeffrey; Reid, Katharine J

    2008-09-01

    Active support (AS) has been shown to increase the amount of time that residents in shared residential settings are involved in purposeful activities. The organisational processes required to implement AS have been less well researched. Staff in community houses answered questions about the occurrence of organisational activities and processes thought to assist AS implementation (e.g., training and teamwork), their understanding of engagement, and their experience of changes in staff practice consistent with AS (including implementation problems). Non-house-based managers were also interviewed about their role in AS implementation. Reported occurrence of organisational activities and processes (e.g., training and teamwork) and understanding of engagement were associated with more reports of changes in staff practice and fewer staff reports of implementation problems. Staff reports on the role of non-house-based managers were not associated with reports of changes in staff practice or with reports of fewer AS implementation problems. Non-house-based managers' reports overestimated their role in AS implementation when compared with reports from house-based staff groups. While there are limitations in the research design (including the reliance on staff reports), the findings support the importance of wider organisational factors (beyond training programs for direct support staff) as integral to the implementation of AS. There is a need for further research on AS implementation.

  2. Do Maternal Caregiver Perceptions of Childhood Obesity Risk Factors and Obesity Complications Predict Support for Prevention Initiatives Among African Americans?

    Science.gov (United States)

    Alexander, Dayna S; Alfonso, Moya L; Cao, Chunhua; Wright, Alesha R

    2017-07-01

    Objectives African American maternal caregiver support for prevention of childhood obesity may be a factor in implementing, monitoring, and sustaining children's positive health behaviors. However, little is known about how perceptions of childhood obesity risk factors and health complications influence caregivers' support of childhood obesity prevention strategies. The objective of this study was to determine if childhood obesity risk factors and health complications were associated with maternal caregivers' support for prevention initiatives. Methods A convenience sample of maternal caregivers (N = 129, ages 22-65 years) completed the childhood obesity perceptions (COP) survey. A linear regression was conducted to determine whether perceptions about childhood obesity risk factors and subsequent health complications influenced caregivers' support for prevention strategies. Results Caregivers' perceptions of childhood obesity risk factors were moderate (M = 3.4; SD = 0.64), as were their perceptions of obesity-related health complications (M = 3.3; SD = 0.75); however, they perceived a high level of support for prevention strategies (M = 4.2; SD = 0.74). In the regression model, only health complications were significantly associated with caregiver support (β = 0.348; p obesity prevention efforts should emphasize health complications by providing education and strategies that promote self-efficacy and outcome expectations among maternal caregivers.

  3. Fatores determinantes para modificações da terapia antirretroviral inicial Factors determining changes in initial antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Denise Girão Limaverde Lima

    2012-04-01

    Full Text Available OBJETIVO: Investigar os fatores determinantes das mudanças da terapia antirretroviral (TARV inicial dos pacientes assistidos em hospital de referência em AIDS do Ceará. MÉTODOS: O estudo descritivo e exploratório utilizou a análise dos formulários de solicitação de início ou modificação de tratamento do ano de 2008, acompanhando as mudanças de terapia durante o primeiro ano de tratamento. Os dados foram analisados nos programas Statistical Package for the Social Sciences (SPSS e Epi Info, utilizando ANOVA e teste exato do coeficiente de contingência, com significância de p OBJECTIVE: To investigate factors determining changes in initial antiretroviral therapy (ART in patients attended to in an AIDS tertiary care hospital in Ceará, Brazil. METHODS: This descriptive and exploratory study used the analysis of request to initiate or change treatment forms in the year of 2008, and the changes in therapy were followed through the first year of treatment. Data were analyzed with SPSS and EpiInfo by using ANOVA and the exact test of the coefficient of contingency, with significance at p < 0.05. RESULTS: From 301 patients initiating ART, 22.1% (n = 68 needed a change in the first year. These patients were mostly males, aged 20 to 39 years; with only one ART changed needed in 86.8% of the cases (n = 59. Reports of two or three changes in regimen were observed. Zidovudine was the drug most often changed, followed by lopinavir/ritonavir and efavirenz. A significant association was found between changes in initial regimens and the report of adverse reactions (p < 0.001. Conclusion: The main factor determining changes in the initial ART was an adverse reaction report. Most patients had one change in the initial ART over the first year of treatment. ART monitoring contributed to a better control of the specific drug therapy.

  4. Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms

    OpenAIRE

    Kahvejian, Avak; Svitkin, Yuri V.; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

    2005-01-01

    Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for ...

  5. B2B-verkkokaupan markkinointiviestintäsuunnitelma

    OpenAIRE

    Luoma, Hanna

    2015-01-01

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

  6. Strategic Insights from Mystery Shopping in B2B Relationships

    DEFF Research Database (Denmark)

    Mattsson, Jan

    2012-01-01

    This paper describes how mystery shopping can be used to gain valuable strategic input in B2B service relationships. We account for a longitudinal case study framed as a natural experiment (duration 18 months) in a Swedish group of consultancy companies offering a wide selection of industrial...... guideline covering the themes of map, smoke and mirror as metaphors) has been extended to comprise a larger group of engineers and may be taken up in a company-wide way. The experiment was deemed effective in developing both a procedure for mystery shopping and a new way to train the consultants....

  7. [Analysis of factors related to smoking initiation and continued smoking in young adolescents].

    Science.gov (United States)

    Caballero-Hidalgo, Araceli; González, Beatriz; Pinilla, Jaime; Barber, Patricia

    2005-01-01

    To analyse the determining of the acquisition and later consolidation of the tobacco consumption in young adolescents. Longitudinal study of three years of duration (2000-2002). Subjects were students of secondary education between 13 and 14 years old at the beginning of the study. The research was performed in Gran Canaria Island with a final sample of 745 subjects. Models of conditional binary election were considered for longitudinal data where the dependent variable reflects decisions of the adolescents through time, with regard to the probability of beginning to smoke, "beginning model", and the probability of being occasional or habitual smoker, "experimentation model". In the last year, 57% of the young teenagers surveyed use tobacco, a 25% more than in the first year, some of them, 9% on a daily basis. In the "beginning model" the determining of the tobacco consumption are interest in studies (odds ratio [OR] = 0.27; 95% confidence interval (CI), 0.08-0.87 and OR = 0.14; 95% CI, 0.03-0.58 for the students having enough and much interest in studies, respectively), to have a smoker as the best friend (OR = 7.44; 95% CI, 2.59-21.4), the alcohol consumption (OR = 11.82; 95% CI, 4.96-28.2 and OR=15.42; 95% CI, 4.68-50.7 for youngs who drink alcohol occasionally or frequently) and having more pocket money (euros per week) (OR = 1.13; 95% CI, 1.07-1.19). For the "experimentation model", to have a smoker as the best friend (OR = 7.01; 95% CI, 2.96-16.5), the alcohol consumption (OR = 5.71; 95% CI, 1.98-16.4 and OR = 5.22; 95% CI, the 1.56-17.5 for youngs who drink alcohol occasionally or frequently) and the number of years since the student started smoking (OR = 1.44; 95% IC, 1.11-1.86). Our study emphasizes, peer group effect, drinking alcoholic beverages and lack of interest in studies as factors associated to the tobacco consumption.

  8. Effects of Psychological and Social Work Factors on Self-Reported Sleep Disturbance and Difficulties Initiating Sleep.

    Science.gov (United States)

    Vleeshouwers, Jolien; Knardahl, Stein; Christensen, Jan Olav

    2016-04-01

    This prospective cohort study examined previously underexplored relations between psychological/social work factors and troubled sleep in order to provide practical information about specific, modifiable factors at work. A comprehensive evaluation of a range of psychological/social work factors was obtained by several designs; i.e., cross-sectional analyses at baseline and follow-up, prospective analyses with baseline predictors (T1), prospective analyses with average exposure across waves as predictor ([T1 + T2] / 2), and prospective analyses with change in exposure from baseline to follow-up as predictor. Participants consisted of a sample of Norwegian employees from a broad spectrum of occupations, who completed a questionnaire at two points in time, approximately two years apart. Cross-sectional analyses at T1 comprised 7,459 participants, cross-sectional analyses at T2 included 6,688 participants. Prospective analyses comprised a sample 5,070 of participants who responded at both T1 and T2. Univariable and multivariable ordinal logistic regressions were performed. Thirteen psychological/social work factors and two aspects of troubled sleep, namely difficulties initiating sleep and disturbed sleep, were studied. Ordinal logistic regressions revealed statistically significant associations for all psychological and social work factors in at least one of the analyses. Psychological and social work factors predicted sleep problems in the short term as well as the long term. All work factors investigated showed statistically significant associations with both sleep items, however quantitative job demands, decision control, role conflict, and support from superior were the most robust predictors and may therefore be suitable targets of interventions aimed at improving employee sleep. © 2016 Associated Professional Sleep Societies, LLC.

  9. Gene-specific characterization of human histone H2B by electron capture dissociation.

    Science.gov (United States)

    Siuti, Nertila; Roth, Michael J; Mizzen, Craig A; Kelleher, Neil L; Pesavento, James J

    2006-02-01

    The basis set of protein forms expressed by human cells from the H2B gene family was determined by Top Down Mass Spectrometry. Using Electron Capture Dissociation for MS/MS of H2B isoforms, direct evidence for the expression of unmodified H2B.Q, H2B.A, H2B.K/T, H2B.J, H2B.E, H2B.B, H2B.F, and monoacetylated H2B.A was obtained from asynchronous HeLa cells. H2B.A was the most abundant form, with the overall expression profile not changing significantly in cells arrested in mitosis by colchicine or during mid-S, mid-G2, G2/M, and mid-G1 phases of the cell cycle. Modest hyperacetylation of H2B family members was observed after sodium butyrate treatment.

  10. Characteristics of the brand building on the business (B2B market

    Directory of Open Access Journals (Sweden)

    Gligorijević Mirjana

    2011-01-01

    Full Text Available This paper analyzes the characteristics of the brand building in the business (B2B market. Branding strategy at the business market is complex and difficult to implement because of the many limiting factors. Building a brand in the business market is marked by very specific characteristics of industrial products. The value of B2B brands is built through functional characteristics and performances of the product (functional values and emotional value, which together guarantee the delivery a unique experience of business customers. All marketing mix tools can be considered to be branding instruments. The purpose of this paper is to emphasize the importance of applying a branding strategy on business market.

  11. A 9 years boy with MEN-2B variant of medullary thyroid carcinoma.

    Science.gov (United States)

    Sattar, M A; Hadi, H I; Ekramuddoula, F M; Hasanuzzaman, S M

    2013-04-01

    To highlight a rare disease like multiple endocrine neoplasia (MEN)-2B variant of medullary thyroid carcinoma and to optimize the management option in such cases, we present a nine year old boy with thyroid swelling, cervical lymphadenopathy and thick lips. His calcitonin level was raised. Investigation's results of the boy were as following fine needle aspiration cytology (FNAC) was medullary carcinoma of thyroid, preoperative calcitonin was >2000pg/ml, post operative histopathological report was medullary carcinoma. Total thyroidectomy with aggressive initial neck surgery may reduce the recurrence and increase better prognosis and survival rate. Calcitonin is used as diagnostic and follow-up marker.

  12. USING UML SCENARIOS IN B2B SYSTEMS

    Directory of Open Access Journals (Sweden)

    A. Jakimi

    2010-05-01

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

  13. Vortex lattice structures in YNi2B2C

    International Nuclear Information System (INIS)

    Yethiraj, M.; Paul, D.M.; Tomy, C.V.; Forgan, E.M.

    1997-01-01

    The authors observe a flux lattice with square symmetry in the superconductor YNi 2 B 2 C when the applied field is parallel to the c-axis of the crystal. A square lattice observed previously in the isostructural magnetic analog ErNi 2 B 2 C was attributed to the interaction between magnetic order in that system and the flux lattice. Since the Y-based compound does not order magnetically, it is clear that the structure of the flux lattice is unrelated to magnetic order. In fact, they show that the flux lines have a square cross-section when the applied field is parallel to the c-axis of the crystal, since the measured penetration depth along the 100 crystal direction is larger than the penetration depth along the 110 by approximately 60%. This is the likely reason for the square symmetry of the lattice. Although they find considerable disorder in the arrangement of the flux lines at 2.5T, no melting of the vortex lattice was observed

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

    Directory of Open Access Journals (Sweden)

    Cathy Slack

    2010-03-01

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

  15. Stanford type A aortic dissection with closed false lumen: Analysis of prognostic factors at initial CT or MRI

    Energy Technology Data Exchange (ETDEWEB)

    Matsuoka, Yohjiro; Sakamoto, Ichiro; Ogawa, Yohji; Sueyoshi, Eijun; Hayashi, Kuniaki; Takagi, Masatake [Nagasaki Univ. (Japan). School of Medicine; Narimatsu, Motoharu

    1997-08-01

    Nineteen patients with Stanford type A acute aortic dissection with closed false lumen were reviewed. In the follow-up examinations, ulcerlike projection (ULP) in the ascending aorta (AA) or aortic arch (AR) was identified in 8 of 19 patients. In 5 of these 8 patients, acute cardiac tamponade occurred and 3 of them died. In the other 11 patients, there was no mortality, and only one patient underwent elective surgery. The appearance of ULP in the AA/AR is considered an indication for urgent surgery because it is regarded as a precursor of lethal complications such as cardiac tamponade. The purpose of this study was to investigate predictors of the appearance of ULP in the AA/AR with early imagings (CT or MRI) before the appearance of ULP. The patients were divided into two groups: patients with ULP in the AA/AR (8 patients) and others (11 patients). Initial CT or MRI findings of the thoracic aorta were retrospectively statistically analyzed in each group. Three predictive factors were statistically significant for the appearance of ULP in the AA/AR (diameter of the AA{>=}5 cm, thickness of the false lumen of the AA{>=}1 cm, thickness of the false lumen of the AA{>=} that of the descending aorta). Close attention should be paid, if any of these 3 factors is observed at initial CT or MRI. (author)

  16. Stanford type A aortic dissection with closed false lumen: Analysis of prognostic factors at initial CT or MRI

    International Nuclear Information System (INIS)

    Matsuoka, Yohjiro; Sakamoto, Ichiro; Ogawa, Yohji; Sueyoshi, Eijun; Hayashi, Kuniaki; Takagi, Masatake; Narimatsu, Motoharu.

    1997-01-01

    Nineteen patients with Stanford type A acute aortic dissection with closed false lumen were reviewed. In the follow-up examinations, ulcerlike projection (ULP) in the ascending aorta (AA) or aortic arch (AR) was identified in 8 of 19 patients. In 5 of these 8 patients, acute cardiac tamponade occurred and 3 of them died. In the other 11 patients, there was no mortality, and only one patient underwent elective surgery. The appearance of ULP in the AA/AR is considered an indication for urgent surgery because it is regarded as a precursor of lethal complications such as cardiac tamponade. The purpose of this study was to investigate predictors of the appearance of ULP in the AA/AR with early imagings (CT or MRI) before the appearance of ULP. The patients were divided into two groups: patients with ULP in the AA/AR (8 patients) and others (11 patients). Initial CT or MRI findings of the thoracic aorta were retrospectively statistically analyzed in each group. Three predictive factors were statistically significant for the appearance of ULP in the AA/AR (diameter of the AA≥5 cm, thickness of the false lumen of the AA≥1 cm, thickness of the false lumen of the AA≥ that of the descending aorta). Close attention should be paid, if any of these 3 factors is observed at initial CT or MRI. (author)

  17. Prevalence of Tobacco Smoking and Factors Associated with the Initiation of Smoking among University Students in Dhaka, Bangladesh.

    Science.gov (United States)

    Hossain, Sahadat; Hossain, Shakhaoat; Ahmed, Fahad; Islam, Rabiul; Sikder, Tajuddin; Rahman, Abdur

    2017-01-01

    Tobacco smoking is considered to be the key preventable risk factor for morbidity and mortality at the global level. The aim of this study was to determine the prevalence of tobacco smoking and factors associated with the initiation of smoking among university students in Dhaka, Bangladesh. A cross-sectional survey study was conducted with 264 students of Jahangirnagar University, Dhaka, Bangladesh in 2015. A standard, self-administered questionnaire consisting of questions on socio-demographic variables, tobacco smoking status, family and peer tobacco smoking history, attitudes and beliefs about tobacco smoking, as well as knowledge about the negative health consequences of tobacco smoking was administered to participants. Data were analyzed using logistic regression models, chi square, and Fisher exact tests. The overall prevalence of tobacco smoking was 60.2%, where males smoked at higher rates than females (68.81% and 19.56%, respectively). The influence of friends was the most significant reason for initiating tobacco smoking (OR: 0.862; CI: 0.810-0.917). Perception regarding tobacco smoking was significantly related to continuing tobacco use. Logistic regression models identified that smoking-related attitudes, potential health problems, and family members dying from cardiovascular disease and cancer were significantly associated with tobacco smoking. The current tobacco smoking prevalence among university students in Bangladesh is over 60%. We suggest adopting WHO Framework Convention on Tobacco Control (FCTC) policies, especially for university students.

  18. SH2B Regulation of Growth, Metabolism, and Longevity in Both Insects and Mammals

    OpenAIRE

    Song, Wei; Ren, Decheng; Li, Wenjun; Jiang, Lin; Cho, Kae Won; Huang, Ping; Fan, Chen; Song, Yiyun; Liu, Yong; Rui, Liangyou

    2010-01-01

    SH2B1 is a key regulator of body weight in mammals. Here we identified dSH2B as the Drosophila homolog of SH2B1. dSH2B bound to Chico and directly promoted insulin-like signaling. Disruption of dSH2B decreased insulin-like signaling and somatic growth in flies. dSH2B deficiency also increased hemolymph carbohydrate levels, whole body lipid levels, lifespan, and resistance to starvation and oxidative stress. Systemic overexpression of dSH2B resulted in opposite phenotypes. dSH2B overexpression...

  19. Factors affecting the initial adhesion and retention of the plant pathogen Xylella fastidiosa in the foregut of an insect vector.

    Science.gov (United States)

    Killiny, Nabil; Almeida, Rodrigo P P

    2014-01-01

    Vector transmission of bacterial plant pathogens involves three steps: pathogen acquisition from an infected host, retention within the vector, and inoculation of cells into susceptible tissue of an uninfected plant. In this study, a combination of plant and artificial diet systems were used to determine the importance of several genes on the initial adhesion and retention of the bacterium Xylella fastidiosa to an efficient insect vector. Mutant strains included fimbrial (fimA and pilB) and afimbrial (hxfA and hxfB) adhesins and three loci involved in regulatory systems (rpfF, rpfC, and cgsA). Transmission assays with variable retention time indicated that HxfA and HxfB were primarily important for early adhesion to vectors, while FimA was necessary for both adhesion and retention. The long pilus protein PilB was not deficient in initial adhesion but may be important for retention. Genes upregulated under the control of rpfF are important for both initial adhesion and retention, as transmission rates of this mutant strain were initially low and decreased over time, while disruption of rpfC and cgsA yielded trends similar to that shown by the wild-type control. Because induction of an X. fastidiosa transmissible state requires pectin, a series of experiments were used to test the roles of a polygalacturonase (pglA) and the pectin and galacturonic acid carbohydrates on the transmission of X. fastidiosa. Results show that galacturonic acid, or PglA activity breaking pectin into its major subunit (galacturonic acid), is required for X. fastidiosa vector transmission using an artificial diet system. This study shows that early adhesion and retention of X. fastidiosa are mediated by different factors. It also illustrates that the interpretation of results of vector transmission experiments, in the context of vector-pathogen interaction studies, is highly dependent on experimental design.

  20. A Prospective Study on the Influence of Scholastic Factors on the Prevalence and Initiation of Illicit Drug Misuse in Adolescence.

    Science.gov (United States)

    Zubak, Zoran; Zenic, Natasa; Ostojic, Ljerka; Zubak, Ivana; Pojskic, Haris

    2018-04-27

    This study aimed to prospectively investigate the scholastic factors related to illicit drug misuse (IDM) and the initiation of IDM among older adolescents from Bosnia and Herzegovina. This 2-year prospective study included 436 participants (202 females), who were an average of 16 years old at the beginning of the study (baseline). The participants were tested at baseline and follow-up (20 months later). The predictors included variables of scholastic-achievement (grade point average, school absences, unexcused absences and behavioral grade). The criteria were: (i) IDM at baseline; (ii) IDM at follow-up; and (iii) initiation of IDM over the study course. Results : Logistic regression indicated increased odds of IDM in adolescents who were more frequent absent from school (baseline: Odds Ratio (OR): 3.73, 95% Confidence Interval (CI): 2.12⁻6.57; follow-up: OR: 2.91, 95% CI: 1.90⁻4.65). The lower grade point average and more unexcused absences were evidenced for adolescents who consumed drugs on follow-up (OR: 1.67, 95% CI: 1.11⁻2.51; OR: 1.74, 95% CI: 1.30⁻2.32 for grade point average and unexcused absences, respectively). Initiation of IDM was predicted by frequent absences from school (OR: 2.2, 95% CI: 1.3⁻3.8), and lower behavioral grades (OR: 1.9, 95% CI: 1.2⁻3.3). The findings confirmed strong correlations between scholastic failure and IDM. Absences from school and lower behavioral grades at baseline were predictive of the initiation of IDM in older adolescents.

  1. Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization.

    Science.gov (United States)

    Tsunoda, Satoshi; Nakamura, Toshiyuki; Sakurai, Hiroaki; Saiki, Ikuo

    2007-04-01

    Fibroblast growth factor (FGF)-2 has been considered to play a critical role in neovascularization in several tumors; however, its precise role in tumor progression is not fully understood. In the present study, we have characterized the role of FGF-2 in B16-BL6 mouse melanoma cells, focusing on effects during the initial phase of tumor growth. FGF-2 was injected at the tumor inoculation site of dorsal skin during the initial phase. FGF-2 induced marked tumor growth and lymph node metastasis. This was well correlated with an increase in neovascularization in the host stroma. FGF-2 also recruited inflammatory and mesenchymal cells in host stroma. Marked tumor growth, pulmonary metastasis and intensive neovascularization in tumor parenchyma were also observed after a single injection of FGF-2 into the footpad inoculation site. In contrast, repeated injections of FGF-2 at a site remote from the footpad tumor were ineffective in promoting tumor growth and metastasis. These promoting activities of FGF-2 were blocked by local injections of a glucocorticoid hormone, suggesting that host inflammatory responses induced by FGF-2 are associated with FGF-2-induced tumor progression. In addition, although FGF-2 did not promote cellular proliferation and vascular endothelial growth factor A (VEGFA) mRNA expression in B16-BL6 cells in vitro, FGF-2 induced VEGFA expression in host stroma rather than tumor tissue, and local injections of a neutralizing antibody against VEGFA inhibited these activities of FGF-2 in vivo. These results indicate that abundant FGF-2 during the initial phase of tumor growth induces VEGFA-dependent intensive neovascularization in host stroma, and supports marked tumor growth and metastasis.

  2. Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

    Directory of Open Access Journals (Sweden)

    Mello Maria

    2007-03-01

    Full Text Available Abstract Background Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Methods Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C – pregnant control, W – tumour-bearing, and P – pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L – pregnant leucine, WL – tumour-bearing, and PL – pair-fed, which received the same amount of food as ingested by the WL group. Results The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2α and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. Conclusion The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway.

  3. Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice R; Gomes-Marcondes, Maria Cristina C

    2007-01-01

    Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C – pregnant control, W – tumour-bearing, and P – pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L – pregnant leucine, WL – tumour-bearing, and PL – pair-fed, which received the same amount of food as ingested by the WL group. The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2α and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway

  4. Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats

    Energy Technology Data Exchange (ETDEWEB)

    Ventrucci, Gislaine [Laboratório de Nutrição e Câncer, Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-970, São Paulo (Brazil); Mello, Maria Alice R [Departamento de Fisiologia e Biofísica, Instituto Biociências, Universidade Estadual de São Paulo, UNESP, Rio Claro, 13506-900, São Paulo (Brazil); Gomes-Marcondes, Maria Cristina C [Laboratório de Nutrição e Câncer, Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, 13083-970, São Paulo (Brazil)

    2007-03-06

    Cancer-cachexia induces a variety of metabolic disorders on protein turnorver, decreasing protein synthesis and increasing protein degradation. Controversly, insulin, other hormones, and branched-chain amino acids, especially leucine, stimulate protein synthesis and modulate the activity of translation initiation factors involved in protein synthesis. Since the tumour effects are more pronounced when associated with pregnancy, ehancing muscle-wasting proteolysis, in this study, the influence of a leucine-rich diet on the protein synthesis caused by cancer were investigated. Pregnant rats with or without Walker 256 tumour were distributed into six groups. During 20 days of experiment, three groups were fed with a control diet: C – pregnant control, W – tumour-bearing, and P – pair-fed, which received the same amount of food as ingested by the W group; three other groups of pregnant rats were fed a leucine-rich diet: L – pregnant leucine, WL – tumour-bearing, and PL – pair-fed, which received the same amount of food as ingested by the WL group. The gastrocnemius muscle of WL rats showed increased incorporation of leucine in protein compared to W rats; the leucine-rich diet also prevented the decrease in plasma insulin normally seen in W. The expression of translation initiation factors increased when tumour-bearing rats fed leucine-rich diet, with increase of ~35% for eIF2α and eIF5, ~17% for eIF4E and 20% for eIF4G; the expression of protein kinase S6K1 and protein kinase C was also highly enhanced. The results suggest that a leucine-rich diet increased the protein synthesis in skeletal muscle in tumour-bearing rats possibly through the activation of eIF factors and/or the S6kinase pathway.

  5. Evidence that the primary effect of phosphorylation of eukaryotic initiation factor 2(alpha) in rabbit reticulocyte lysate is inhibition of the release of eukaryotic initiation factor-2.GDP from 60 S ribosomal subunits

    International Nuclear Information System (INIS)

    Gross, M.; Redman, R.; Kaplansky, D.A.

    1985-01-01

    The phosphorylation of eukaryotic initiation factor (eIF) 2 alpha that occurs when rabbit reticulocyte lysate is incubated in the absence of hemin or with poly(I.C) causes inhibition of polypeptide chain initiation by preventing a separate factor (termed RF) from promoting the exchange of GTP for GDP on eIF-2. When lysate was incubated in the presence of hemin and [ 14 C] eIF-2 or [alpha- 32 P]GTP, the authors observed binding of eIF-2 and GDP or GTP to 60 S ribosomal subunits that was slightly greater than that bound to 40 S subunits and little binding to 80 S ribosomes. When incubation was in the absence of hemin or in the presence of hemin plus 0.1 microgram/ml poly(I.C), eIF-2 and GDP binding to 60 S subunits was increased 1.5- to 2-fold, that bound to 80 S ribosomes was almost as great as that bound to 60 S subunits, and that bound to 40 S subunits was unchanged. The data indicate that about 40% of the eIF-2 that becomes bound to 60 S subunits and 80 S ribosomes in the absence of hemin or with poly(I.C) is eIF-2(alpha-P) and suggest that the eIF-2 and GDP bound is probably in the form of a binary complex. The rate of turnover of GDP (presumably eIF-2.GDP) on 60 S subunits and 80 S ribosomes in the absence of hemin is reduced to less than 10% the control rate, because the dissociation of eIF-2.GDP is inhibited. Our findings suggest that eIF-2.GTP binding to and eIF-2.GDP release from 60 S subunits may normally occur and serve to promote subunit joining

  6. Matchmaking Framework for B2B E-Marketplaces

    Directory of Open Access Journals (Sweden)

    Fekete ZOLTAN ALPAR

    2010-01-01

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

  7. Relationship Quality as Predictor of B2B Customer Loyalty

    Directory of Open Access Journals (Sweden)

    Shaimaa S. B. Ahmed Doma

    2013-02-01

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

  8. Observations and modeling of the transiting exoplanets XO-2b, HAT-P-18b, and WASP-80b

    Directory of Open Access Journals (Sweden)

    Kjurkchieva Diana P.

    2017-01-01

    Full Text Available We present photometric observations and transit solutions of the exoplanets XO-2b, HAT-P-18b and WASP 80b. Our solution of the XO-2b transit gave system parameters whose values are close to those of the previous studies. The solutions of the new transits of HAT-P-18b and WASP 80b differ from the previous ones by bigger stellar and planet radii. We obtained new values of the target initial epochs corresponding to slightly different periods. Our investigation reaffirmed that small telescopes can be used successfully for the study of exoplanets orbiting stars brighter than 13 mag.

  9. Information management: The adoption of order processing for B2B e-commerce

    Directory of Open Access Journals (Sweden)

    F. W. Voges

    2007-11-01

    Full Text Available The management of information flow in the order processing activities of small enterprises is not always understood. An inefficient supply chain is often the result of the lack of timely and accessible inter-firm information and data exchange. Small suppliers often do not have the technology infrastructure and capable resources available for proper integration with supply chains. This research investigated suppliers and fast moving consumer goods (FMCG retailers, adopting business-to-business (B2B e-commerce. Small businesses are the focus of this research, as they contribute to a large portion of the South African economy and play an important role in the supply chains of retailers. Case study research using evidence obtained from nine small, medium and micro enterprises (SMMEs and suppliers located in the Western Cape, South Africa, was used. It was found that small suppliers have different processes for conducting business with various retailers. Literature revealed little evidence of using the Internet as an enabling technology in on-line order processing. From the analysis, nine improvement areas were identified to enhance the conduct of efficient B2B order processing and associated information flow. These improvement areas were merged with four factors that were identified in a framework when adopting e-supply chains. This resulted in the proposition of guidelines for small suppliers when adopting B2B e-commerce for order processing.

  10. A Novel Role of Serotonin Receptor 2B Agonist as an Anti-Melanogenesis Agent

    Directory of Open Access Journals (Sweden)

    Eun Ju Oh

    2016-04-01

    Full Text Available BW723C86, a serotonin receptor 2B agonist, has been investigated as a potential therapeutic for various conditions such as anxiety, hyperphagia and hypertension. However, the functional role of BW723C86 against melanogenesis remains unclear. In this study, we investigate the effect of serotonin receptor 2B (5-HTR2B agonist on melanogenesis and elucidate the mechanism involved. BW723C86 reduced melanin synthesis and intracellular tyrosinase activity in melan-A cells and normal human melanocytes. The expression of melanogenesis-related proteins (tyrosinase, TRP-1 and TRP-2 and microphthalmia-associated transcription factor (MITF in melan-A cells decreased after BW723C86 treatment. The promoter activity of MITF was also reduced by BW723C86 treatment. The reduced level of MITF was associated with inhibition of protein kinase A (PKA and cAMP response element-binding protein (CREB activation by BW723C86 treatment. These results suggest that the serotonin agonist BW723C86 could be a potential therapeutic agent for skin hyperpigmentation disorders.

  11. Thermoluminescence characteristics of Li2B4O7 single crystal dosimeters doped with Mn

    International Nuclear Information System (INIS)

    Ekdal, E.; Karalı, T.; Kelemen, A.; Ignatovych, M.; Holovey, V.; Harmansah, C.

    2014-01-01

    In this study, thermoluminescence (TL) characterization of newly developed Li 2 B 4 O 7 :Mn single crystal phosphor is reported. It is a very attractive material in personal dosimetry because of its near tissue equivalency (Z eff =7.25). The crystal was grown by the Czochralski method from high purity compounds. Glow curve, dose response, and fading and reproducibility properties of this material were investigated. Its TL glow curve showed two well separated peaks at about 105 and 220 °C with a heating rate of 2 °C s −1 . The main peak at 220 °C has a linear dose response of up to 60 Gy. The thermal fading ratio of the material is about 8% for the main peak in 10 days. The results showed that there is no significant variation of TL responses for 15 sequential measurements. Apart from the dosimetric properties above, the TL kinetic parameters of the main peak at 220 °C of Li 2 B 4 O 7 :Mn single crystal phosphor were also calculated using the various heating rates method. Activation energy and frequency factor were found as 1.21 eV and 3.75×10 11 s −1 , respectively. - Highlights: • Li 2 B 4 O 7 :Mn single crystal was investigated in terms of TL characteristics. • The material shows highly satisfactory dosimetric properties. • Various heating rates method was used for determining the kinetic parameter

  12. The impact of e-marketing orientation on performance in Asian SMEs: a B2B perspective

    Science.gov (United States)

    Chong, Woon Kian; Man, Ka Lok; Kim, Mucheol

    2018-01-01

    Business-to-business (B2B) organisations are increasingly utilising electronic devices in their business operations in order to succeed in increasingly competitive markets. This trend is prevalent in the growing Asian markets, especially in the small and medium-sized enterprises (SMEs) sector. While prior research has focused on this issue in the context of large business-to-customer (B2C) organisations in Asia, there have hardly been any studies that have shed light on the B2B sector in the SME setting. This study aims to critically explore B2B e-marketing critical success factors (B2B-eM-CSFs) for SMEs operating in the Asian B2B marketplace. A key finding is the development of a theoretical framework for SMEs, emerging from the analysis of 406 companies from various industrial sectors. The study shows that interaction with the B2B-eM-CSFs is an important dimension and has a positive and significant impact on e-business efficiency and marketing improvements for Asian SMEs.

  13. A Phox2b BAC Transgenic Rat Line Useful for Understanding Respiratory Rhythm Generator Neural Circuitry.

    Directory of Open Access Journals (Sweden)

    Keiko Ikeda

    Full Text Available The key role of the respiratory neural center is respiratory rhythm generation to maintain homeostasis through the control of arterial blood pCO2/pH and pO2 levels. The neuronal network responsible for respiratory rhythm generation in neonatal rat resides in the ventral side of the medulla and is composed of two groups; the parafacial respiratory group (pFRG and the pre-Bötzinger complex group (preBötC. The pFRG partially overlaps in the retrotrapezoid nucleus (RTN, which was originally identified in adult cats and rats. Part of the pre-inspiratory (Pre-I neurons in the RTN/pFRG serves as central chemoreceptor neurons and the CO2 sensitive Pre-I neurons express homeobox gene Phox2b. Phox2b encodes a transcription factor and is essential for the development of the sensory-motor visceral circuits. Mutations in human PHOX2B cause congenital hypoventilation syndrome, which is characterized by blunted ventilatory response to hypercapnia. Here we describe the generation of a novel transgenic (Tg rat harboring fluorescently labeled Pre-I neurons in the RTN/pFRG. In addition, the Tg rat showed fluorescent signals in autonomic enteric neurons and carotid bodies. Because the Tg rat expresses inducible Cre recombinase in PHOX2B-positive cells during development, it is a potentially powerful tool for dissecting the entire picture of the respiratory neural network during development and for identifying the CO2/O2 sensor molecules in the adult central and peripheral nervous systems.

  14. Risk factors for benign prostatic enlargement: The role of lifestyle habits at younger age. The #Controllati2017 initiative study group.

    Science.gov (United States)

    Mirone, Vincenzo; Carrieri, Giuseppe; Morgia, Giuseppe; Carmignani, Luca; Vespasiani, Giuseppe; Parazzini, Fabio; Artibani, Walter

    2017-12-31

    The risk factors for benign prostatic enlargement (BPE) are not well understood and particularly few data are available from Italian population. This was an observational cross sectional study aimed to examine the association between several risk factors and BPE. During the "#Controllati2017" initiative, men aged 18 years or more were invited to attend participating urologic centers for a free of charge visit for counseling about urologic or andrologic conditions. Each participating man underwent a physical examination including digital rectal examination (DRE). Further he was asked about his medical history, urologic symptoms, sexual activity and related problems. Diagnosis of BPE was made by the urologist after DRE. Out of the 1902 [mean age 54 years (SD 12, range 18-92)] considered men, a total of 603 subjects (31.7%) had diagnosis of BPE. The diagnosis of BPE increased from 9.3% in men aged 60 years. A history of hypertension, diabetes, heart diseases, hypercholesterolemia and hypertriglyceridemia were all significantly associated with an increased risk of BPE in the total series and, although not always in a statistically significant way, in strata of age. Physical activity (PA) was significantly associated with a decreased risk of BPE. We have further analyzed the risk of BPE in men with one or more of the identified risk factors (i.e. hypertension, diabetes, heart disease, hypercholesterolemia, hypertriglyceridemia and low PA): the risk of BPE increased with number of risk factors reported by the subjects. The estimated risk were higher among younger men. In our study a history of hypertension, diabetes, heart disease, hypercholesterolemia and hypertriglyceridemia increased the risk and physical activity lowered the risk of BPE. This risk profile was observed also in men aged < 50 years.

  15. Factors Predictive of Tumor Recurrence and Survival After Initial Complete Response of Esophageal Squamous Cell Carcinoma to Definitive Chemoradiotherapy

    International Nuclear Information System (INIS)

    Ishihara, Ryu; Yamamoto, Sachiko; Iishi, Hiroyasu; Takeuchi, Yoji; Sugimoto, Naotoshi; Higashino, Koji; Uedo, Noriya; Tatsuta, Masaharu; Yano, Masahiko; Imai, Atsushi; Nishiyama, Kinji

    2010-01-01

    Purpose: To assess factors predictive of recurrent disease and survival after achieving initial complete response (CR) to chemoradiotherapy (CRT) for esophageal cancer. Methods and Materials: Patients who had clinical Stage I-IVA esophageal cancer and received definitive CRT between 2001 and 2007 were retrospectively analyzed. Results: Of 269 patients with esophageal cancer, 110 who achieved CR after definitive CRT were included in the analyses. Chemoradiotherapy mainly consisted of 2 cycles of cisplatin and fluorouracil with concurrent radiotherapy of 60 Gy in 30 fractions. We identified 28 recurrences and 28 deaths during follow-up. The cumulative 1- and 3-year recurrence rates were 18% and 32%, respectively. By univariate and multivariate analyses, tumor category (hazard ratio [HR] 6.6; 95% confidence interval [CI] 1.4-30.2; p = 0.015) was an independent risk factor for local recurrence, whereas age (HR 3.9; 95% CI 1.1-14.0; p = 0.034) and primary tumor location (HR 4.5; 95% CI 1.6-12.4; p = 0.004) were independent risk factors for regional lymph node or distant recurrences. The cumulative overall 1- and 3-year survival rates were 91% and 66%, respectively. As expected, recurrence was associated with poor survival (p = 0.019). By univariate and multivariate analyses, primary tumor location (HR 3.8; 95% CI 1.2-12.0; p = 0.024) and interval to recurrence (HR 4.3; 95% CI 1.3-14.4; p = 0.018) were independent factors predictive of survival after recurrence. Conclusion: Risk of recurrence after definitive CRT for esophageal cancer was associated with tumor category, age, and primary tumor location; this information may help in improved prognostication for these patients.

  16. A Fast Healthcare Interoperability Resources (FHIR) layer implemented over i2b2.

    Science.gov (United States)

    Boussadi, Abdelali; Zapletal, Eric

    2017-08-14

    Standards and technical specifications have been developed to define how the information contained in Electronic Health Records (EHRs) should be structured, semantically described, and communicated. Current trends rely on differentiating the representation of data instances from the definition of clinical information models. The dual model approach, which combines a reference model (RM) and a clinical information model (CIM), sets in practice this software design pattern. The most recent initiative, proposed by HL7, is called Fast Health Interoperability Resources (FHIR). The aim of our study was to investigate the feasibility of applying the FHIR standard to modeling and exposing EHR data of the Georges Pompidou European Hospital (HEGP) integrating biology and the bedside (i2b2) clinical data warehouse (CDW). We implemented a FHIR server over i2b2 to expose EHR data in relation with five FHIR resources: DiagnosisReport, MedicationOrder, Patient, Encounter, and Medication. The architecture of the server combines a Data Access Object design pattern and FHIR resource providers, implemented using the Java HAPI FHIR API. Two types of queries were tested: query type #1 requests the server to display DiagnosticReport resources, for which the diagnosis code is equal to a given ICD-10 code. A total of 80 DiagnosticReport resources, corresponding to 36 patients, were displayed. Query type #2, requests the server to display MedicationOrder, for which the FHIR Medication identification code is equal to a given code expressed in a French coding system. A total of 503 MedicationOrder resources, corresponding to 290 patients, were displayed. Results were validated by manually comparing the results of each request to the results displayed by an ad-hoc SQL query. We showed the feasibility of implementing a Java layer over the i2b2 database model to expose data of the CDW as a set of FHIR resources. An important part of this work was the structural and semantic mapping between the

  17. Basal insulin persistence, associated factors, and outcomes after treatment initiation among people with type 2 diabetes mellitus in the US.

    Science.gov (United States)

    Perez-Nieves, Magaly; Kabul, Samaneh; Desai, Urvi; Ivanova, Jasmina I; Kirson, Noam Y; Cummings, Alice Kate; Birnbaum, Howard G; Duan, Ran; Cao, Dachuang; Hadjiyianni, Irene

    2016-01-01

    To assess basal insulin persistence, associated factors, and economic outcomes for insulin-naïve people with type 2 diabetes mellitus (T2DM) in the US. People aged ≥18 years diagnosed with T2DM initiating basal insulin between April 2006 and March 2012 (index date), no prior insulin use, and continuous insurance coverage for 6 months before (baseline) and 24 months after index date (follow-up period) were selected using de-identified administrative claims data in the US. Based on whether there were ≥30 day gaps in basal insulin use in the first year post-index, patients were classified as continuers (no gap), interrupters (≥1 prescription after gap), and discontinuers (no prescription after gap). Factors associated with persistence - assessed using multinomial logistic regression model; annual healthcare resource use and costs during follow-up period - compared separately between continuers and interrupters, and continuers and discontinuers. Of the 19,110 people included in the sample (mean age: 59 years, ∼60% male), 20% continued to use basal insulin, 62% had ≥1 interruption, and 18% discontinued therapy in the year after initiation. Older age, multiple antihyperglycemic drug use, and injectable antihyperglycemic use during baseline were associated with significantly higher likelihoods of continuing basal insulin. Relative to interrupters and discontinuers, continuers had fewer emergency department visits, shorter hospital stays, and lower medical costs (continuers: $10,890, interrupters: $13,674, discontinuers: $13,021), but higher pharmacy costs (continuers: $7449, interrupters: $5239, discontinuers: $4857) in the first year post-index (p US. In addition, persistence patterns were assessed using administrative claims as opposed to actual medication-taking behavior and did not account for measures of glycemic control. Further research is needed to understand the reasons behind basal insulin persistence and the implications thereof, to help

  18. Eukaryotic translation initiation factor 3 subunit e controls intracellular calcium homeostasis by regulation of cav1.2 surface expression.

    Directory of Open Access Journals (Sweden)

    Pawel Buda

    Full Text Available Inappropriate surface expression of voltage-gated Ca(2+channels (CaV in pancreatic ß-cells may contribute to the development of type 2 diabetes. First, failure to increase intracellular Ca(2+ concentrations at the sites of exocytosis impedes insulin release. Furthermore, excessive Ca(2+ influx may trigger cytotoxic effects. The regulation of surface expression of CaV channels in the pancreatic β-cells remains unknown. Here, we used real-time 3D confocal and TIRFM imaging, immunocytochemistry, cellular fractionation, immunoprecipitation and electrophysiology to study trafficking of L-type CaV1.2 channels upon β-cell stimulation. We found decreased surface expression of CaV1.2 and a corresponding reduction in L-type whole-cell Ca(2+ currents in insulin-secreting INS-1 832/13 cells upon protracted (15-30 min stimulation. This internalization occurs by clathrin-dependent endocytosis and could be prevented by microtubule or dynamin inhibitors. eIF3e (Eukaryotic translation initiation factor 3 subunit E is part of the protein translation initiation complex, but its effect on translation are modest and effects in ion channel trafficking have been suggested. The factor interacted with CaV1.2 and regulated CaV1.2 traffic bidirectionally. eIF3e silencing impaired CaV1.2 internalization, which resulted in an increased intracellular Ca(2+ load upon stimulation. These findings provide a mechanism for regulation of L-type CaV channel surface expression with consequences for β-cell calcium homeostasis, which will affect pancreatic β-cell function and insulin production.

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

    Directory of Open Access Journals (Sweden)

    Pierluigi Sabbatini

    2012-04-01

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

  20. Hydrothermal synthesis and electrochemical characterization of VO2 (B) with controlled crystal structures

    International Nuclear Information System (INIS)

    Jiang Wentao; Ni Juan; Yu Ke; Zhu Ziqiang

    2011-01-01

    Three different VO 2 (B) nanostructures, including urchin-like VO 2 (B), VO 2 (B) honeycombs and VO 2 (B) nanorods have been successfully fabricated through hydrothermal process by adjusting the concentrations of the oxalic acid. The microstructure and morphology of the VO 2 nanostructures were evaluated by using X-ray diffraction and scanning and transmission electron microscopies. Electrochemical properties measurements of urchin-like VO 2 (B) and VO 2 (B) honeycombs showed excellent cycling performance, especially the urchin-like VO 2 (B) exhibited higher discharge capacity and better capacity retention.

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

    CERN Document Server

    Bhatia, Krishnaprem; Perlovsky, Alan

    2013-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2011-01-01

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

  3. An Ancient Transcription Factor Initiates the Burst of piRNA Production During Early Meiosis in Mouse Testes

    Science.gov (United States)

    Li, Xin Zhiguo; Roy, Christian K.; Dong, Xianjun; Bolcun-Filas, Ewelina; Wang, Jie; Han, Bo W.; Xu, Jia; Moore, Melissa J.; Schimenti, John C.; Weng, Zhiping; Zamore, Phillip D.

    2013-01-01

    SUMMARY Animal germ cells produce PIWI-interacting RNAs (piRNAs), small silencing RNAs that suppress transposons and enable gamete maturation. Mammalian transposon-silencing piRNAs accumulate early in spermatogenesis, whereas pachytene piRNAs are produced later during post-natal spermatogenesis and account for >95% of all piRNAs in the adult mouse testis. Mutants defective for pachytene piRNA pathway proteins fail to produce mature sperm, but neither the piRNA precursor transcripts nor the trigger for pachytene piRNA production is known. Here, we show that the transcription factor A-MYB initiates pachytene piRNA production. A-MYB drives transcription of both pachytene piRNA precursor RNAs and the mRNAs for core piRNA biogenesis factors, including MIWI, the protein through which pachytene piRNAs function. A-MYB regulation of piRNA pathway proteins and piRNA genes creates a coherent feed-forward loop that ensures the robust accumulation of pachytene piRNAs. This regulatory circuit, which can be detected in rooster testes, likely predates the divergence of birds and mammals. PMID:23523368

  4. Incidence and risk factors for lower limb lymphedema after gynecologic cancer surgery with initiation of periodic complex decongestive physiotherapy.

    Science.gov (United States)

    Deura, Imari; Shimada, Muneaki; Hirashita, Keiko; Sugimura, Maki; Sato, Seiya; Sato, Shinya; Oishi, Tetsuro; Itamochi, Hiroaki; Harada, Tasuku; Kigawa, Junzo

    2015-06-01

    Lower limb lymphedema (LLL) is one of the most frequent postoperative complications of retroperitoneal lymphadenectomy for gynecologic cancer. LLL often impairs quality of life, activities of daily living, sleep, and sex in patients with gynecologic cancer. We conducted this study to evaluate the incidence and risk factors for LLL after gynecologic cancer surgery in patients who received assessment and periodic complex decongestive physiotherapy (CDP). We retrospectively reviewed 126 cases of gynecologic cancer that underwent surgery involving retroperitoneal lymphadenectomy at Tottori University Hospital between 2009 and 2012. All patients received physical examinations to detect LLL and underwent CDP by nurse specialists within several months after surgery. The International Society of Lymphology staging of lymphedema severity was used as the diagnostic criteria. Of 126 patients, 57 (45.2%) had LLL, comprising 45 and 12 patients with stage 1 and stage 2 LLL, respectively. No patient had stage 3 LLL. LLL was present in 37 (29.4%) patients at the initial physical examination. Multivariate analysis revealed that adjuvant concurrent chemoradiotherapy and age ≥ 55 years were independent risk factors for ≥ stage 2 LLL. To minimize the incidence of ≥ stage 2 LLL, gynecologic oncologists should be vigilant for this condition in patients who are ≥ 55 years and in those who undergo adjuvant chemoradiotherapy. Patients should be advised to have a physical assessment for LLL and to receive education about CDP immediately after surgery involving retroperitoneal lymphadenectomy for gynecologic cancer.

  5. The guanosine nucleotide (p)ppGpp initiates development and A-factor production in myxococcus xanthus.

    Science.gov (United States)

    Harris, B Z; Kaiser, D; Singer, M

    1998-04-01

    Guanosine 3'-di-5'-(tri)di-phosphate nucleotides [(p)ppGpp], synthesized in response to amino acid limitation, induce early gene expression leading to multicellular fruiting body formation in Myxococcus xanthus. A mutant (DK527) that fails to accumulate (p)ppGpp in response to starvation was found to be blocked in development prior to aggregation. By use of a series of developmentally regulated Tn5lac transcriptional fusion reporters, the time of developmental arrest in DK527 was narrowed to within the few hours of development, the period of starvation recognition. The mutant is also defective in the production of A-factor, an early extracellular cell-density signal. The relA gene from Escherichia coli, which encodes a ribosome-dependent (p)ppGpp synthetase, rescues this mutant. We also demonstrate that inactivation of the M. xanthus relA homolog blocks development and the accumulation of (p)ppGpp. Moreover, the wild-type allele of Myxococcus relA rescues DK527. These observations support a model in which accumulation of (p)ppGpp, in response to starvation, initiates the program of fruiting body development, including the production of A-factor.

  6. Current status of BL-2B at photon factory

    Energy Technology Data Exchange (ETDEWEB)

    Nambu, Akira, E-mail: akia.nambu.tw@hitachi.com; Ueda, Kazuhiro [Central Research Laboratory, Hitachi, ltd. 1-280 Higashi-Koigakubo, Kokubunji, Tokyo, 185-8601 (Japan); Horiba, Koji; Tsuchiya, Kimichika; Kumigashira, Hiroshi; Amemiya, Kenta [KEK-PF 1-1 Oho, Tsukuba, Ibaraki, 305-0801 (Japan)

    2016-07-27

    A new soft x-ray beamline BL-2B at Photon Factory of High Energy Accelerator Research Organization (KEK-PF) covers energy range from vacuum ultraviolet (30 eV) to soft x-ray (4000 eV). This wide energy range could be achieved by employing two undulators and two monochromators. Two different energy range undulators were installed tandem to a 9-meter straight section of PF storage ring. The 1{sup st} undulator is for VUV (30 eV) to SX (280 eV), while the other one is for SX (280 eV) to HX (4000 eV). It is also necessary to be equipped with two different monochrometors for energy above and under 2000 eV; grating monochrometor and double crystal monochrometor. One of the main purposes of this bemaline is spectroscopic study of light elements contained in several functional materials. The beamline is designed for photoemission spectroscopy (PES), X-ray absorption fine structure (XAFS) and other types of experiments. The performance of the new beamline is reported and typical examples of its application to material science are demonstrated.

  7. Factors associated with acceptance of provider-initiated HIV testing and counseling among pregnant women in Ethiopia.

    Science.gov (United States)

    Gebremedhin, Ketema Bizuwork; Tian, Bingjie; Tang, Chulei; Zhang, Xiaoxia; Yisma, Engida; Wang, Honghong

    2018-01-01

    The global human immunodeficiency virus (HIV) epidemic disproportionately affects sub-Saharan African countries, including Ethiopia. Provider-initiated HIV testing and counseling (PITC) is a tool to identify HIV-positive pregnant women and an effective treatment and prevention strategy. However, its success depends upon the willingness of pregnant women to accept HIV testing. To describe the level of acceptance of PITC and associated factors among pregnant women attending 8 antenatal care clinics in Adama, Ethiopia. Trained nursing students and employees from an HIV clinic conducted face-to-face structured interviews in private offices at the clinics from August to September, 2016. Among the 441 respondents, 309 (70.1%) accepted PITC. Women with more antenatal care visits (odds ratio [OR] =2.59, 95% CI: 1.01-6.63), reported better quality of the PITC service (OR =1.91, 95% CI: 1.19-3.08), and higher level of knowledge on mother-to-child transmission (OR =1.82, 95% CI: 1.03-3.20), were more likely to accept PITC, while women who were older in age (OR =0.37, 95% CI: 0.19-0.74) and perceived negative attitudes from their partners toward HIV-positive results (OR =0.31, 95% CI: 0.10-0.94) were less likely to accept the PITC service. About one-third of pregnant women are not willing to accept PITC. When designing intervention program to improve the acceptance of PITC, we should take into consideration the personal factors, HIV-related knowledge, and attitude of women as well as institutional factors.

  8. Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children

    NARCIS (Netherlands)

    Bienczak, A.; Cook, A.; Wiesner, L.; Mulenga, V.; Kityo, C.; Kekitiinwa, A.; Walker, A.S.; Owen, A.; Gibb, D.M.; Burger, D.M.; McIlleron, H.; Denti, P.

    2017-01-01

    OBJECTIVES: To characterize the effects of CYP2B6 polymorphisms, diurnal variation and demographic factors on nevirapine pharmacokinetics in African children. METHODS: Non-linear mixed-effects modelling conducted in NONMEM 7.3 described nevirapine plasma concentration-time data from 414 children

  9. [Breastfeeding (part one): Frequency, benefits and drawbacks, optimal duration and factors influencing its initiation and prolongation. Clinical guidelines for practice].

    Science.gov (United States)

    Chantry, A A; Monier, I; Marcellin, L

    2015-12-01

    The objectives were to on assess the frequency and the duration of breastfeeding in France. On the other hand, the objectives were to identify its benefits and drawbacks, and to study the factors influencing its initiation and its extension. Bibliographic research in Medline, Google Scholar and in the Cochrane Library. Breastfeeding concerns in France about 70% of children at birth (EL2). Its median duration is about 15 weeks and 3 weeks ½ for exclusive breastfeeding. At three months, only one third of children breastfed at birth are still being breastfed (EL2). Whether this is due to the composition of breast milk or the behavior of mothers with their children or their socio-cultural level, or even by all these components at once, breastfeeding is associated with better cognitive development children (EL2). This effect is even more reinforced that mothers breastfeed exclusively and prolonged (EL2). As part of the prevention of many diseases (ear infections, gastrointestinal infections, atopic diseases, obesity and cardiovascular diseases…), exclusive and prolonged breastfeeding (grade B) between 4 to 6 months is recommended (professional consensus). Breastfeeding is not a means of preventing postpartum depression (professional consensus). To reduce the incidence of breast cancer, prolonged breastfeeding is recommended (grade B). In order to increase the rate of initiation of breastfeeding as well as its duration, it is recommended that health professionals work closely with mothers in their project (grade A), the breastfeeding promotion messages include message to husbands (grade B), and to promote breastfeeding on demand without fixed interval between feedings (grade B). However, there is not enough data to recommend the use of a specific position during breastfeeding, or the use of one or two breast or to early start breastfeeding or not (professional consensus). Exclusive and extended breastfeeding is recommended (grade B) between 4 to 6 months (professional

  10. Use of a Geriatric Quality Initiative to Educate Internal Medicine Residents about Delirium and Its Risk Factors.

    Science.gov (United States)

    Olveczky, Daniele; Mattison, Melissa L P; Mukamal, Kenneth J

    2013-06-01

    Delirium is a common and debilitating complication of inpatient care for many older adults, yet internal medicine residents often do not recognize delirium or its risk factors. Integrating geriatric education (eg, delirium recognition) with inpatient quality improvement (QI) is not well tested. We developed an educational pilot program within an ongoing hospital-wide geriatric QI initiative (Global Risk Assessment and Careplan for the Elderly-Acute Care [GRACE-AC]). GRACE-AC modifies the inpatient computerized provider order entry system to meet the needs of vulnerable older adults and uses a bedside care checklist to identify patients with possible delirium and promote delirium prevention by checking on the need for "tethers" (intravenous fluids, Foley catheters, and telemetry). Residents were assessed before and after each inpatient rotation by using anonymous electronic surveys. A total of 167 eligible residents (91%) completed prerotation surveys, and 102 (56%) residents completed postrotation surveys. All but the first rotating resident group received a standardized 2-minute educational in-service orientation. In a comparison of postrotation responses before and after implementation of the in-service, the proportion of residents who reported improvement in their ability to recall which patients had tethers increased from 17% to 52% for intravenous fluids (P  =  .004), 28% to 75% for Foley catheters (P < .001), and 21% to 50% for telemetry (P  =  .02). Comparing pre- and postrotation surveys, the proportion of correct responses to questions on haloperidol dosing and the characteristics of delirium increased from 26% to 76% and 31% to 63%, respectively (both P < .001). Our pilot program demonstrated that inpatient geriatric QI initiatives can be successfully merged with a brief educational curriculum.

  11. Systems Li2B4O7 (Na2B4O7, K2B4O7)-N2H3H4OH-H2O at 25 deg C

    International Nuclear Information System (INIS)

    Skvortsov, V.G.; Sadetdinov, Sh.V.; Akimov, V.M.; Mitrasov, Yu.N.; Petrova, O.V.; Klopov, Yu.N.

    1994-01-01

    Phase equilibriums in the Li 2 B 4 O 7 (Na 2 B 4 O 7 , K 2 B 4 O 7 )-N 2 H 3 H 4 OH-H 2 O systems were investigated by methods of isothermal solubility, refractometry and PH-metry at 25 deg C for the first time. Lithium and sodium tetraborates was established to form phases of changed composition mM 2 B 4 O 7 ·nN 2 H 3 C 2 H 4 OH·XH 2 O, where M=Li, Na with hydrazine ethanol. K 2 B 4 O 7 ·4H 2 O precipitates in solid phase in the case of potassium salt. Formation of isomorphous mixtures was supported by X-ray diffraction and IR spectroscopy methods

  12. The translation initiation factor 3 subunit eIF3K interacts with PML and associates with PML nuclear bodies

    Energy Technology Data Exchange (ETDEWEB)

    Salsman, Jayme; Pinder, Jordan; Tse, Brenda [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Corkery, Dale [Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada); Dellaire, Graham, E-mail: dellaire@dal.ca [Department of Pathology, Dalhousie University, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2 (Canada); Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia (Canada)

    2013-10-15

    The promyelocytic leukemia protein (PML) is a tumor suppressor protein that regulates a variety of important cellular processes, including gene expression, DNA repair and cell fate decisions. Integral to its function is the ability of PML to form nuclear bodies (NBs) that serve as hubs for the interaction and modification of over 90 cellular proteins. There are seven canonical isoforms of PML, which encode diverse C-termini generated by alternative pre-mRNA splicing. Recruitment of specific cellular proteins to PML NBs is mediated by protein–protein interactions with individual PML isoforms. Using a yeast two-hybrid screen employing peptide sequences unique to PML isoform I (PML-I), we identified an interaction with the eukaryotic initiation factor 3 subunit K (eIF3K), and in the process identified a novel eIF3K isoform, which we term eIF3K-2. We further demonstrate that eIF3K and PML interact both in vitro via pull-down assays, as well as in vivo within human cells by co-immunoprecipitation and co-immunofluorescence. In addition, eIF3K isoform 2 (eIF3K-2) colocalizes to PML bodies, particularly those enriched in PML-I, while eIF3K isoform 1 associates poorly with PML NBs. Thus, we report eIF3K as the first known subunit of the eIF3 translation pre-initiation complex to interact directly with the PML protein, and provide data implicating alternative splicing of both PML and eIF3K as a possible regulatory mechanism for eIF3K localization at PML NBs. - Highlights: • The PML-I C-terminus, encoded by exon 9, interacts with translation factor eIF3K. • We identify a novel eIF3K isoform that excludes exon 2 (eIF3K-2). • eIF3K-2 preferentially associates with PML bodies enriched in PML-I vs. PML-IV. • Alternative splicing of eIF3K regulates association with PML bodies.

  13. Kalirin Binds the NR2B Subunit of the NMDA Receptor, Altering Its Synaptic Localization and Function

    KAUST Repository

    Kiraly, D. D.

    2011-08-31

    The ability of dendritic spines to change size and shape rapidly is critical in modulating synaptic strength; these morphological changes are dependent upon rearrangements of the actin cytoskeleton. Kalirin-7 (Kal7), a Rho guanine nucleotide exchange factor localized to the postsynaptic density (PSD), modulates dendritic spine morphology in vitro and in vivo. Kal7 activates Rac and interacts with several PSD proteins, including PSD-95, DISC-1, AF-6, and Arf6. Mice genetically lacking Kal7 (Kal7KO) exhibit deficient hippocampal long-term potentiation (LTP) as well as behavioral abnormalities in models of addiction and learning. Purified PSDs from Kal7KO mice contain diminished levels of NR2B, an NMDA receptor subunit that plays a critical role in LTP induction. Here we demonstrate that Kal7KO animals have decreased levels of NR2B-dependent NMDA receptor currents in cortical pyramidal neurons as well as a specific deficit in cell surface expression of NR2B. Additionally, we demonstrate that the genotypic differences in conditioned place preference and passive avoidance learning seen in Kal7KO mice are abrogated when animals are treated with an NR2B-specific antagonist during conditioning. Finally, we identify a stable interaction between the pleckstrin homology domain of Kal7 and the juxtamembrane region of NR2B preceding its cytosolic C-terminal domain. Binding of NR2B to a protein that modulates the actin cytoskeleton is important, as NMDA receptors require actin integrity for synaptic localization and function. These studies demonstrate a novel and functionally important interaction between the NR2B subunit of the NMDA receptor and Kalirin, proteins known to be essential for normal synaptic plasticity.

  14. Kalirin Binds the NR2B Subunit of the NMDA Receptor, Altering Its Synaptic Localization and Function

    KAUST Repository

    Kiraly, D. D.; Lemtiri-Chlieh, Fouad; Levine, E. S.; Mains, R. E.; Eipper, B. A.

    2011-01-01

    The ability of dendritic spines to change size and shape rapidly is critical in modulating synaptic strength; these morphological changes are dependent upon rearrangements of the actin cytoskeleton. Kalirin-7 (Kal7), a Rho guanine nucleotide exchange factor localized to the postsynaptic density (PSD), modulates dendritic spine morphology in vitro and in vivo. Kal7 activates Rac and interacts with several PSD proteins, including PSD-95, DISC-1, AF-6, and Arf6. Mice genetically lacking Kal7 (Kal7KO) exhibit deficient hippocampal long-term potentiation (LTP) as well as behavioral abnormalities in models of addiction and learning. Purified PSDs from Kal7KO mice contain diminished levels of NR2B, an NMDA receptor subunit that plays a critical role in LTP induction. Here we demonstrate that Kal7KO animals have decreased levels of NR2B-dependent NMDA receptor currents in cortical pyramidal neurons as well as a specific deficit in cell surface expression of NR2B. Additionally, we demonstrate that the genotypic differences in conditioned place preference and passive avoidance learning seen in Kal7KO mice are abrogated when animals are treated with an NR2B-specific antagonist during conditioning. Finally, we identify a stable interaction between the pleckstrin homology domain of Kal7 and the juxtamembrane region of NR2B preceding its cytosolic C-terminal domain. Binding of NR2B to a protein that modulates the actin cytoskeleton is important, as NMDA receptors require actin integrity for synaptic localization and function. These studies demonstrate a novel and functionally important interaction between the NR2B subunit of the NMDA receptor and Kalirin, proteins known to be essential for normal synaptic plasticity.

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

    Science.gov (United States)

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

    2007-02-01

    SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (alpha, beta, gamma, and/or delta) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1beta was specifically expressed in neural tissue in SH2B1-transgenic (SH2B1(Tg)) mice. SH2B1(Tg) mice were crossed with SH2B1-knockout (SH2B1(KO)) mice to generate SH2B1(TgKO) mice expressing SH2B1 only in neural tissue but not in other tissues. Systemic deletion of the SH2B1 gene resulted in metabolic disorders in SH2B1(KO) mice, including hyperlipidemia, leptin resistance, hyperphagia, obesity, hyperglycemia, insulin resistance, and glucose intolerance. Neuron-specific restoration of SH2B1beta not only corrected the metabolic disorders in SH2B1(TgKO) mice, but also improved JAK2-mediated leptin signaling and leptin regulation of orexigenic neuropeptide expression in the hypothalamus. Moreover, neuron-specific overexpression of SH2B1 dose-dependently protected against high-fat diet-induced leptin resistance and obesity. These observations suggest that neuronal SH2B1 regulates energy balance, body weight, peripheral insulin sensitivity, and glucose homeostasis at least in part by enhancing hypothalamic leptin sensitivity.

  16. VHL type 2B mutations retain VBC complex form and function.

    Directory of Open Access Journals (Sweden)

    Kathryn E Hacker

    Full Text Available von Hippel-Lindau disease is characterized by a spectrum of hypervascular tumors, including renal cell carcinoma, hemangioblastoma, and pheochromocytoma, which occur with VHL genotype-specific differences in penetrance. VHL loss causes a failure to regulate the hypoxia inducible factors (HIF-1alpha and HIF-2alpha, resulting in accumulation of both factors to high levels. Although HIF dysregulation is critical to VHL disease-associated renal tumorigenesis, increasing evidence points toward gradations of HIF dysregulation contributing to the degree of predisposition to renal cell carcinoma and other manifestations of the disease.This investigation examined the ability of disease-specific VHL missense mutations to support the assembly of the VBC complex and to promote the ubiquitylation of HIF. Our interaction analysis supported previous observations that VHL Type 2B mutations disrupt the interaction between pVHL and Elongin C but maintain partial regulation of HIF. We additionally demonstrated that Type 2B mutant pVHL forms a remnant VBC complex containing the active members ROC1 and Cullin-2 which retains the ability to ubiquitylate HIF-1alpha.Our results suggest that subtypes of VHL mutations support an intermediate level of HIF regulation via a remnant VBC complex. These findings provide a mechanism for the graded HIF dysregulation and genetic predisposition for cancer development in VHL disease.

  17. Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks.

    Science.gov (United States)

    Harris, Daniel R; Baus, Adam D; Harper, Tamela J; Jarrett, Traci D; Pollard, Cecil R; Talbert, Jeffery C

    2016-08-01

    We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites.

  18. Characterization of a eukaryotic translation initiation factor 5A homolog from Tamarix androssowii involved in plant abiotic stress tolerance

    Directory of Open Access Journals (Sweden)

    Wang Liuqiang

    2012-07-01

    Full Text Available Abstract Background The eukaryotic translation initiation factor 5A (eIF5A promotes formation of the first peptide bond at the onset of protein synthesis. However, the function of eIF5A in plants is not well understood. Results In this study, we characterized the function of eIF5A (TaeIF5A1 from Tamarix androssowii. The promoter of TaeIF5A1 with 1,486 bp in length was isolated, and the cis-elements in the promoter were identified. A WRKY (TaWRKY and RAV (TaRAV protein can specifically bind to a W-box motif in the promoter of TaeIF5A1 and activate the expression of TaeIF5A1. Furthermore, TaeIF5A1, TaWRKY and TaRAV share very similar expression pattern and are all stress-responsive gene that functions in the abscisic acid (ABA signaling pathway, indicating that they are components of a single regulatory pathway. Transgenic yeast and poplar expressing TaeIF5A1 showed elevated protein levels combined with improved abiotic stresses tolerance. Furthermore, TaeIF5A1-transformed plants exhibited enhanced superoxide dismutase (SOD and peroxidase (POD activities, lower electrolyte leakage and higher chlorophyll content under salt stress. Conclusions These results suggested that TaeIF5A1 is involved in abiotic stress tolerance, and is likely regulated by transcription factors TaWRKY and TaRAV both of which can bind to the W-box motif. In addition, TaeIF5A1 may mediate stress tolerance by increasing protein synthesis, enhancing ROS scavenging by improving SOD and POD activities, and preventing chlorophyll loss and membrane damage. Therefore, eIF5A may play an important role in plant adaptation to changing environmental conditions.

  19. Risk factors of vitamin D deficiency in children with epilepsy taking anticonvulsants at initial and during follow-up

    Directory of Open Access Journals (Sweden)

    Seung Ho Lee

    2015-12-01

    Full Text Available PurposeVitamin D status was evaluated in children with epilepsy taking anticonvulsants to determine the prevalence and risk factors of vitamin D deficiency.MethodsThis study was designed as both a cross-sectional and a retrospective cohort study. A sum of 198 children who were diagnosed with epilepsy at the Department of Pediatrics in Dankook University Hospital was included. Their serum vitamin D levels were reviewed based on clinical information, and analyzed using IBM SPSS ver. 20.0.ResultsOne hundred twenty-four children (62.6% had vitamin D deficiency. Two risk factors were associated: winter to spring season (odds ratio [OR], 3.71; 95% confidence interval [CI], 1.835-7.492 and age more than 12 years (OR, 3.22; 95% CI, 1.377-7.542. Out of the 57 patients who were not vitamin D deficient at the time of initial assay, 47 patients (82.5% became vitamin D deficient during followup. The change of serum 25-hydroxy vitamin D3 (25(OHD levels during follow up showed a weak negative correlation with the duration of medication (r=-0.283, P=0.033. Medication duration was longer and brain magnetic resonance imaging (MRI abnormality, abnormal underlying conditions, and nonambulatory status were more frequently present in twenty-five patients (44% who showed a decline of more than 15 ng/mL during follow-up (P<0.05.ConclusionVitamin D deficiency is common in children with epilepsy taking anticonvulsants, especially in adolescents more than 12 years of age. This study emphasizes the regular monitoring of vitamin D level, especially in the presence of longer duration of medication, brain MRI abnormality, abnormal underlying conditions, and nonambulatory status.

  20. Characterization of a eukaryotic translation initiation factor 5A homolog from Tamarix androssowii involved in plant abiotic stress tolerance.

    Science.gov (United States)

    Wang, Liuqiang; Xu, Chenxi; Wang, Chao; Wang, Yucheng

    2012-07-26

    The eukaryotic translation initiation factor 5A (eIF5A) promotes formation of the first peptide bond at the onset of protein synthesis. However, the function of eIF5A in plants is not well understood. In this study, we characterized the function of eIF5A (TaeIF5A1) from Tamarix androssowii. The promoter of TaeIF5A1 with 1,486 bp in length was isolated, and the cis-elements in the promoter were identified. A WRKY (TaWRKY) and RAV (TaRAV) protein can specifically bind to a W-box motif in the promoter of TaeIF5A1 and activate the expression of TaeIF5A1. Furthermore, TaeIF5A1, TaWRKY and TaRAV share very similar expression pattern and are all stress-responsive gene that functions in the abscisic acid (ABA) signaling pathway, indicating that they are components of a single regulatory pathway. Transgenic yeast and poplar expressing TaeIF5A1 showed elevated protein levels combined with improved abiotic stresses tolerance. Furthermore, TaeIF5A1-transformed plants exhibited enhanced superoxide dismutase (SOD) and peroxidase (POD) activities, lower electrolyte leakage and higher chlorophyll content under salt stress. These results suggested that TaeIF5A1 is involved in abiotic stress tolerance, and is likely regulated by transcription factors TaWRKY and TaRAV both of which can bind to the W-box motif. In addition, TaeIF5A1 may mediate stress tolerance by increasing protein synthesis, enhancing ROS scavenging by improving SOD and POD activities, and preventing chlorophyll loss and membrane damage. Therefore, eIF5A may play an important role in plant adaptation to changing environmental conditions.

  1. Risk factors for late-stage HIV disease presentation at initial HIV diagnosis in Durban, South Africa.

    Directory of Open Access Journals (Sweden)

    Paul K Drain

    Full Text Available After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults.We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count <100 cells/mm(3. We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing ("competing needs to healthcare" on presentation with late-stage HIV disease.Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6% presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4, were male (AOR 1.7, 95% CI 1.2-2.3, worked outside the home (AOR 1.5, 95% CI 1.1-2.1, perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1, and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9 had higher odds of late-stage HIV disease presentation.Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.

  2. Factors associated with time between using a drug and injection initiation among people who inject drugs in Kermanshah, Iran.

    Science.gov (United States)

    Noroozi, Mehdi; Farhadi, Mohammad Hassan; Armoon, Bahram; Farhoudian, Ali; Shushtari, Zahra Jorjoran; Sharhani, Asaad; Karimi, Salah Eddin; Sayadnasiri, Mohammad; Rezaei, Omid; Ghiasvand, Hesam

    2018-05-17

    Background The transition from non-injection to injection drug use dramatically increases the risk of transmitting HIV and other blood borne infections including hepatitis B virus (HBV) and hepatitis C virus (HCV). The aim of this study was to explore factors associated with the transition from first illicit drug use to first injection among drug users. Methods Using snowball sampling and convenience sampling through needle and syringe programmes (NSPs), we recruited 500 people who inject drugs (PWID) in Kermanshah, between September and December 2014. Trained interviewers collected data on socio-demographic characteristics, HIV testing and drug-related risk behaviors over the last month prior to interview using a structured questionnaire. Our main outcome variable was first illicit drug use to first injection (TIJ). TIJ was calculated by subtracting age at first drug injection from age of first illicit drug use. Results Overall, the average age at first drug use and injection were 21.4 [standard deviation (SD 5.6)] and 22.8 (SD 8.9), respectively. The average duration of injection was 6.0 (SD 4.6) years. Overall, the mean of TIJ for participants was 1.4 (IQR = 2, 4) years. Age of first injecting drug use negatively correlated with TIJ (R2 = 0.219, p = 0.001). Education level and socioeconomic status (SES), and negatively correlated with TIJ. Conclusion Some demographic factors and drug use characteristics including educational level, SES, knowledge of HIV status, age of initiating drug use, being a poly drug user and using methamphetamine were predictors of the time to transition.

  3. In Vitro Whole Genome DNA Binding Analysis of the Bacterial Replication Initiator and Transcription Factor DnaA.

    Directory of Open Access Journals (Sweden)

    Janet L Smith

    2015-05-01

    Full Text Available DnaA, the replication initiation protein in bacteria, is an AAA+ ATPase that binds and hydrolyzes ATP and exists in a heterogeneous population of ATP-DnaA and ADP-DnaA. DnaA binds cooperatively to the origin of replication and several other chromosomal regions, and functions as a transcription factor at some of these regions. We determined the binding properties of Bacillus subtilis DnaA to genomic DNA in vitro at single nucleotide resolution using in vitro DNA affinity purification and deep sequencing (IDAP-Seq. We used these data to identify 269 binding regions, refine the consensus sequence of the DnaA binding site, and compare the relative affinity of binding regions for ATP-DnaA and ADP-DnaA. Most sites had a slightly higher affinity for ATP-DnaA than ADP-DnaA, but a few had a strong preference for binding ATP-DnaA. Of the 269 sites, only the eight strongest binding ones have been observed to bind DnaA in vivo, suggesting that other cellular factors or the amount of available DnaA in vivo restricts DnaA binding to these additional sites. Conversely, we found several chromosomal regions that were bound by DnaA in vivo but not in vitro, and that the nucleoid-associated protein Rok was required for binding in vivo. Our in vitro characterization of the inherent ability of DnaA to bind the genome at single nucleotide resolution provides a backdrop for interpreting data on in vivo binding and regulation of DnaA, and is an approach that should be adaptable to many other DNA binding proteins.

  4. Depletion of elongation initiation factor 4E binding proteins by CRISPR/Cas9 genome editing enhances antiviral response in porcine cells

    Science.gov (United States)

    Type I interferons (IFN) are key mediators of the innate antiviral response in mammalian cells. Elongation initiation factor 4E binding proteins (4E-BPs) are translational controllers of interferon regulatory factor 7 (IRF7), the master regulator of IFN transcription. The role of 4EBPs in the negat...

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

    OpenAIRE

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

    2007-01-01

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

  6. The N-terminal region of eukaryotic translation initiation factor 5A signals to nuclear localization of the protein

    International Nuclear Information System (INIS)

    Parreiras-e-Silva, Lucas T.; Gomes, Marcelo D.; Oliveira, Eduardo B.; Costa-Neto, Claudio M.

    2007-01-01

    The eukaryotic translation initiation factor 5A (eIF5A) is a ubiquitous protein of eukaryotic and archaeal organisms which undergoes hypusination, a unique post-translational modification. We have generated a polyclonal antibody against murine eIF5A, which in immunocytochemical assays in B16-F10 cells revealed that the endogenous protein is preferentially localized to the nuclear region. We therefore analyzed possible structural features present in eIF5A proteins that could be responsible for that characteristic. Multiple sequence alignment analysis of eIF5A proteins from different eukaryotic and archaeal organisms showed that the former sequences have an extended N-terminal segment. We have then performed in silico prediction analyses and constructed different truncated forms of murine eIF5A to verify any possible role that the N-terminal extension might have in determining the subcellular localization of the eIF5A in eukaryotic organisms. Our results indicate that the N-terminal extension of the eukaryotic eIF5A contributes in signaling this protein to nuclear localization, despite of bearing no structural similarity with classical nuclear localization signals

  7. Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells

    International Nuclear Information System (INIS)

    Nakai, Yuji; Shiratsuchi, Akiko; Manaka, Junko; Nakayama, Hiroshi; Takio, Koji; Zhang Jianting; Suganuma, Tatsuo; Nakanishi, Yoshinobu

    2005-01-01

    We previously isolated a monoclonal antibody named PH2 that inhibits phosphatidylserine-mediated phagocytosis of apoptotic cells by macrophages [C. Fujii, A. Shiratsuchi, J. Manaka, S. Yonehara, Y. Nakanishi. Cell Death Differ. 8 (2001) 1113-1122]. We report here the identification of the cognate antigen. A protein bound by PH2 in Western blotting was identified as the 170-kDa subunit of eukaryotic translation initiation factor 3 (eIF3 p170/eIF3a). When eIF3a was expressed in a culture cell line as a protein fused to green fluorescence protein, the fusion protein was detected at the cell surface only after the induction of apoptosis. The same phenomenon was seen when the localization of endogenous eIF3a was determined using anti-eIF3a antibody, and eIF3a seemed to be partially degraded during apoptosis. Furthermore, bacterially expressed N-terminal half of eIF3a fused to glutathione S-transferase bound to the surface of macrophages and inhibited phagocytosis of apoptotic cells by macrophages when it was added to phagocytosis reactions. These results collectively suggest that eIF3a translocates to the cell surface upon apoptosis, probably after partial degradation, and bridges apoptotic cells and macrophages to enhance phagocytosis

  8. Initial boost release of transforming growth factor-β3 and chondrogenesis by freeze-dried bioactive polymer scaffolds.

    Science.gov (United States)

    Krüger, Jan Philipp; Machens, Isabel; Lahner, Matthias; Endres, Michaela; Kaps, Christian

    2014-12-01

    In cartilage regeneration, bio-activated implants are used in stem and progenitor cell-based microfracture cartilage repair procedures. Our aim was to analyze the chondrogenic potential of freeze-dried resorbable polymer-based polyglycolic acid (PGA) scaffolds bio-activated with transforming growth factor-β3 (TGFB3) on human subchondral mesenchymal progenitor cells known from microfracture. Progenitor cells derived from femur heads were cultured in the presence of freeze-dried TGFB3 in high-density pellet culture and in freeze-dried TGFB3-PGA scaffolds for chondrogenic differentiation. Progenitor cell cultures in PGA scaffolds as well as pellet cultures with and without continuous application of TGFB3 served as controls. Release studies showed that freeze-dried TGFB3-PGA scaffolds facilitate a rapid, initial boost-like release of 71.5% of TGFB3 in the first 10 h. Gene expression analysis and histology showed induction of typical chondrogenic markers like type II collagen and formation of cartilaginous tissue in TGFB3-PGA scaffolds seeded with subchondral progenitor cells and in pellet cultures stimulated with freeze-dried TGFB3. Chondrogenic differentiation in freeze-dried TGFB3-PGA scaffolds was comparable to cultures receiving TGFB3 continuously, while non-stimulated controls did not show chondrogenesis during prolonged culture for 14 days. These results suggest that bio-activated, freeze-dried TGFB3-PGA scaffolds have chondrogenic potential and are a promising tool for stem cell-mediated cartilage regeneration.

  9. A review on granules initiation and development inside UASB Reactor and the main factors affecting granules formation process

    Energy Technology Data Exchange (ETDEWEB)

    Habeeb, S.A.; Latiff, Ab Aziz Bin Abdul; Daud, Zawawi Bin; Ahmad, Zulkifli Bin [Civil and Environmental Engineering, University Tun Hussein Onn Malaysia (Malaysia)

    2011-07-01

    Decades of investigations and explorations in the field of anaerobic wastewater treatment have resulted in significant indications about the role importance of sludge granules in biodegradation anaerobic process. It is believed that the development of anaerobic granules is reflecting an important role on the performance of reactor. An overview on the concept of up-flow anaerobic sludge bed (UASB) reactor operation as well as the main parts that reactor consists of is briefly explained in this paper, whereas the major theories of anaerobic granules formation are listed by related researchers. The correlations and compositions of such sludge granule have been specifically explained. It is believed that the extracellular polymer (ECP) is totally responsible of bacterial cell correlations and the formation of bacterial communities in the form of granules. In addition, the dependable factors for the performance of anaerobic granules formation process e.g. temperature, organic loading rate, pH, and alkalinity, nutrients, and cations and heavy metals have been discussed in this paper. Strong evidences proved that the process of gas production in the form of biogas is related to the methanogens activities, which are practically found in the core of granules. The aim of this review is to explore and assess the mechanisms of granules initiation and development inside UASB reactor.

  10. Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site

    International Nuclear Information System (INIS)

    Collins, C.J.; Underdahl, J.P.; Levene, R.B.; Ravera, C.P.; Morin, M.J.; Dombalagian, M.J.; Ricca, G.; Livingston, D.M.; Lynch, D.C.

    1987-01-01

    A series of overlapping cosmid genomic clones have been isolated that contain the entire coding unit of the human gene for van Willebrand factor (vWf), a major component of the hemostatic system. The cloned segments span ≅ 175 kilobases of human DNA sequence, and hybridization analysis suggest that the vWf coding unit is ≅150 kilobases in length. Within one of these clones, the vWF transcription initiation site has been mapped and a portion of the vWf promoter region has been sequenced, revealing a typical TATA box, a downstream CCAAT box, and a perfect downstream repeat of the 8 base pairs containing the transcription start site. Sequencing of a segment of another genomic clone has revealed the vWF translation termination codon. Where tested, comparative restriction analysis of cloned and chromosomal DNA segments strongly suggests that no major alterations occurred during cloning and that there is only one complete copy of the vWf gene in the human haploid genome. Similar analyses of DNA from vWf-producing endothelial cells and nonexpressing leukocytes suggest that vWf gene expression is not accompanied by gross genomic rearrangements. In addition, there is significant homology of C-terminal coding sequences among the vWf genes of several vertebrate species

  11. The Arabidopsis eukaryotic initiation factor (iso)4E is dispensable for plant growth but required for susceptibility to potyviruses.

    Science.gov (United States)

    Duprat, Anne; Caranta, Carole; Revers, Frédéric; Menand, Benoît; Browning, Karen S; Robaglia, Christophe

    2002-12-01

    An Arabidopsis thaliana line bearing a transposon insertion in the gene coding for the isozyme form of the plant-specific cap-binding protein, eukaryotic initiation factor (iso) 4E (eIF (iso) 4E), has been isolated. This mutant line completely lacks both eIF(iso)4E mRNA and protein, but was found to have a phenotype and fertility indistinguishable from wild-type plants under standard laboratory conditions. In contrast, the amount of the related eIF4E protein was found to increase in seedling extracts. Furthermore, polysome analysis shows that the mRNA encoding eIF4E was being translated at increased levels. Given the known interaction between cap-binding proteins and potyviral genome-linked proteins (VPg), this plant line was challenged with two potyviruses, Turnip mosaic virus (TuMV) and Lettuce mosaic virus (LMV) and was found resistant to both, but not to the Nepovirus, Tomato black ring virus (TBRV) and the Cucumovirus, Cucumber mosaic virus (CMV). Together with previous data showing that the VPg-eIF4E interaction is necessary for virus infectivity and upregulates genome amplification, this shows that the eIF4E proteins are specifically recruited for the replication cycle of potyviruses.

  12. Official ERS technical standards: Global Lung Function Initiative reference values for the carbon monoxide transfer factor for Caucasians.

    Science.gov (United States)

    Stanojevic, Sanja; Graham, Brian L; Cooper, Brendan G; Thompson, Bruce R; Carter, Kim W; Francis, Richard W; Hall, Graham L

    2017-09-01

    There are numerous reference equations available for the single-breath transfer factor of the lung for carbon monoxide ( T  LCO ); however, it is not always clear which reference set should be used in clinical practice. The aim of the study was to develop the Global Lung Function Initiative (GLI) all-age reference values for T  LCO Data from 19 centres in 14 countries were collected to define T  LCO reference values. Similar to the GLI spirometry project, reference values were derived using the LMS (lambda, mu, sigma) method and the GAMLSS (generalised additive models for location, scale and shape) programme in R.12 660 T  LCO measurements from asymptomatic, lifetime nonsmokers were submitted; 85% of the submitted data were from Caucasians. All data were uncorrected for haemoglobin concentration. Following adjustments for elevation above sea level, gas concentration and assumptions used for calculating the anatomic dead space volume, there was a high degree of overlap between the datasets. Reference values for Caucasians aged 5-85 years were derived for T  LCO , transfer coefficient of the lung for carbon monoxide and alveolar volume.This is the largest collection of normative T  LCO data, and the first global reference values available for T  LCO . Copyright ©ERS 2017.

  13. The time frame of Epstein-Barr virus latent membrane protein-1 gene to disappear in nasopharyngeal swabs after initiation of primary radiotherapy is an independently significant prognostic factor predicting local control for patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Lin, S.-Y.; Chang, K.-P.; Hsieh, M.-S.; Ueng, S.-H.; Hao, S.-P.; Tseng, C.-K.; Pai, P.-C.; Chang, F.-T.; Tsai, M.-H.; Tsang, N.-M.

    2005-01-01

    Purpose: The presence of Epstein-Barr virus latent membrane protein-1 (LMP-1) gene in nasopharyngeal swabs indicates the presence of nasopharyngeal carcinoma (NPC) mucosal tumor cells. This study was undertaken to investigate whether the time taken for LMP-1 to disappear after initiation of primary radiotherapy (RT) was inversely associated with NPC local control. Methods and Materials: During July 1999 and October 2002, there were 127 nondisseminated NPC patients receiving serial examinations of nasopharyngeal swabbing with detection of LMP-1 during the RT course. The time for LMP-1 regression was defined as the number of days after initiation of RT for LMP-1 results to turn negative. The primary outcome was local control, which was represented by freedom from local recurrence. Results: The time for LMP-1 regression showed a statistically significant influence on NPC local control both univariately (p < 0.0001) and multivariately (p = 0.004). In multivariate analysis, the administration of chemotherapy conferred a significantly more favorable local control (p = 0.03). Advanced T status (≥ T2b), overall treatment time of external photon radiotherapy longer than 55 days, and older age showed trends toward being poor prognosticators. The time for LMP-1 regression was very heterogeneous. According to the quartiles of the time for LMP-1 regression, we defined the pattern of LMP-1 regression as late regression if it required 40 days or more. Kaplan-Meier plots indicated that the patients with late regression had a significantly worse local control than those with intermediate or early regression (p 0.0129). Conclusion: Among the potential prognostic factors examined in this study, the time for LMP-1 regression was the most independently significant factor that was inversely associated with NPC local control

  14. Eukaryotic translation initiation factor 5A induces apoptosis in colon cancer cells and associates with the nucleus in response to tumour necrosis factor α signalling

    International Nuclear Information System (INIS)

    Taylor, Catherine A.; Sun Zhong; Cliche, Dominic O.; Ming, Hong; Eshaque, Bithi; Jin Songmu; Hopkins, Marianne T.; Thai, Boun; Thompson, John E.

    2007-01-01

    Eukaryotic translation initiation factor 5A (eIF5A) is thought to function as a nucleocytoplasmic shuttle protein. There are reports of its involvement in cell proliferation, and more recently it has also been implicated in the regulation of apoptosis. In the present study, we examined the effects of eIF5A over-expression on apoptosis and of siRNA-mediated suppression of eIF5A on expression of the tumour suppressor protein, p53. Over-expression of either eIF5A or a mutant of eIF5A incapable of being hypusinated was found to induce apoptosis in colon carcinoma cells. Our results also indicate that eIF5A is required for expression of p53 following the induction of apoptosis by treatment with Actinomycin D. Depiction of eIF5A localization by indirect immunofluorescence has indicated, for the first time, that the protein is rapidly translocated from the cytoplasm to the nucleus by death receptor activation or following treatment with Actinomycin D. These findings collectively indicate that unhypusinated eIF5A may have pro-apoptotic functions and that eIF5A is rapidly translocated to the nucleus following the induction of apoptotic cell death

  15. A heart-hand syndrome gene: Tfap2b plays a critical role in the development and remodeling of mouse ductus arteriosus and limb patterning.

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    Full Text Available BACKGROUND: Patent ductus arteriosus (PDA is one of the most common forms of congenital heart disease. Mutations in transcription factor TFAP2B cause Char syndrome, a human disorder characterized by PDA, facial dysmorphysm and hand anomalies. Animal research data are needed to understand the mechanisms. The aim of our study was to elucidate the pathogenesis of Char syndrome at the molecular level. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression of Tfap2b during mouse development was studied, and newborns of Tfap2b-deficient mice were examined to identify phenotypes. Gel shift assays had been carried out to search for Tfap2 downstream genes. Promoters of candidate genes were cloned into a reporter construct and used to demonstrate their regulation by Tfap2b in cell transfection. In situ hybridizations showed that the murine transcription factor Tfap2b was expressed during the entire development of mouse ductus arteriosus. Histological examination of ductus arteriosus from Tfap2b knockout mice 6 hours after birth revealed that they were not closed. Consequently, the lungs of Tfap2b(-/- mice demonstrated progressive congestion of the pulmonary capillaries, which was postulated to result secondarily from PDA. In addition, Tfap2b was expressed in the limb buds, particularly in the posterior limb field during development. Lack of Tfap2b resulted in bilateral postaxial accessory digits. Further study indicated that expressions of bone morphogenetic protein (Bmp genes, which are reported to be involved in the limb patterning and ductal development, were altered in limb buds of Tfap2b-deficient embryos, due to direct control of Bmp2 and Bmp4 promoter activity by Tfap2b. CONCLUSIONS/SIGNIFICANCE: Tfap2b plays important roles in the development of mouse ductus arteriosus and limb patterning. Loss of Tfap2b results in altered Bmp expression that may cause the heart-limb defects observed in Tfap2b mouse mutants and Char syndrome patients. The Tfap2b knockout

  16. [Association between homozygous c.318A>GT mutation in exon 2 of the EIF2B5 gene and the infantile form of vanishing white matter leukoencephalopathy].

    Science.gov (United States)

    Esmer, Carmen; Blanco Hernández, Gabriela; Saavedra Alanís, Víctor; Reyes Vaca, Jorge Guillermo; Bravo Oro, Antonio

    Vanishing white matter disease is one of the most frequent leukodystrophies in childhood with an autosomal recessive inheritance. A mutation in one of the genes encoding the five subunits of the eukaryotic initiation factor 2 (EIF2B5) is present in 90% of the cases. The diagnosis can be accomplished by the clinical and neuroradiological findings and molecular tests. We describe a thirteen-month-old male with previous normal neurodevelopment, who was hospitalized for vomiting, hyperthermia and irritability. On examination, cephalic perimeter and cranial pairs were normal. Hypotonia, increased muscle stretching reflexes, generalized white matter hypodensity on cranial tomography were found. Fifteen days after discharge, he suffered minor head trauma presenting drowsiness and focal seizures. Magnetic resonance showed generalized hypointensity of white matter. Vanishing white matter disease was suspected, and confirmed by sequencing of the EIF2B5 gene, revealing a homozygous c.318A> T mutation in exon 2. Subsequently, visual acuity was lost and cognitive and motor deterioration was evident. The patient died at six years of age due to severe pneumonia. This case contributes to the knowledge of the mutational spectrum present in Mexican patients and allows to extend the phenotype associated to this mutation. Copyright © 2017. Publicado por Masson Doyma México S.A.

  17. Li2b2-Façade: Simulation of i2b2 Data Warehouse Server and Client for Interaction with Other Systems.

    Science.gov (United States)

    Majeed, Raphael W; Xu, Tingyan; Stöhr, Mark R; Röhrig, Rainer

    2017-01-01

    Since its release in 2004, the i2b2 data warehouse software has become a valuable tool for clinical researchers. Physicians can use its browser-based query frontend intuitively without additional training or reading through documentation. While the i2b2 software describes it's API as "REST", it is neither stateless nor does it follow the common guidelines for RESTful APIs. Thus, interfacing other software with i2b2's custom RPC-style XML-API is a very cumbersome process. To overcome these issues, we developed a lightweight software abstraction layer "lightweight i2b2 façade" (li2b2-façade).

  18. Delayed initiation of antenatal care and associated factors in Ethiopia: a systematic review and meta-analysis.

    Science.gov (United States)

    Tesfaye, Gezahegn; Loxton, Deborah; Chojenta, Catherine; Semahegn, Agumasie; Smith, Roger

    2017-11-15

    Antenatal care uptake is among the key indicators for monitoring the progress of maternal outcomes. Early initiation of antenatal care facilitates the timely management and treatment of pregnancy complications to reduce maternal deaths. In Ethiopia, antenatal care utilization is generally low, and delayed initiation of care is very common. We aimed to systematically identify and synthesize available evidence on delayed initiation of antenatal care and the associated factors in Ethiopia. Studies published in English from 1 January 2002 to 30 April 2017 were systematically searched from PubMed, Medline, EMBASE, CINAHL and other relevant sources. Two authors independently reviewed the identified studies against the eligibility criteria. The included studies were critically appraised using the Joanna Briggs-MAStARI instrument for observational studies. Meta-analysis was conducted in RevMan v5.3 for Windows using a Mantel-Haenszel random effects model. The presence of statistical heterogeneity was checked using the Cochran Q test, and its level was quantified using the I 2 statistics. Pooled estimate of the proportion of the outcome variable was calculated. Pooled Odd Ratios with 95% CI were calculated to measure the effect sizes. The pooled magnitude of delayed antenatal care in Ethiopia was 64% (95% CI: 57%, 70%). Maternal age (OR = 0.70; 95% CI: 0.53, 0.93), place of residence (OR = 0.29, 95% CI: 0.16, 0.50), maternal education (OR = 0.49; 95% CI: 0.38, 0.63), husband's education (OR = 0.44; 95% CI: 0.23, 0.85), maternal occupation (OR = 0.75; 95% CI: 0.61, 0.93), monthly income (OR = 2.06; 95% CI: 1.23, 3.45), pregnancy intention (OR = 0.49; 95% CI: 0.40, 0.60), parity (OR = 0.46; 95% CI: 0.36, 0.58), knowledge of antenatal care (OR = 0.40; 95% CI: 0.32, 0.51), women's autonomy (OR = 0.38; 95% CI: 0.15, 0.94), partner involvement (OR = 0.24; 95% CI: 0.07, 0.75), pregnancy complications (OR = 0.23; 95% CI: 0.06, 0

  19. Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor gamma messenger ribonucleic acid levels.

    Science.gov (United States)

    Yoshiga, Daigo; Sato, Naoichi; Torisu, Takehiro; Mori, Hiroyuki; Yoshida, Ryoko; Nakamura, Seiji; Takaesu, Giichi; Kobayashi, Takashi; Yoshimura, Akihiko

    2007-05-01

    Adipocyte differentiation is regulated by insulin and IGF-I, which transmit signals by activating their receptor tyrosine kinase. SH2-B is an adaptor protein containing pleckstrin homology and Src homology 2 (SH2) domains that have been implicated in insulin and IGF-I receptor signaling. In this study, we found a strong link between SH2-B levels and adipogenesis. The fat mass and expression of adipogenic genes including peroxisome proliferator-activated receptor gamma (PPARgamma) were reduced in white adipose tissue of SH2-B-/- mice. Reduced adipocyte differentiation of SH2-B-deficient mouse embryonic fibroblasts (MEFs) was observed in response to insulin and dexamethasone, whereas retroviral SH2-B overexpression enhanced differentiation of 3T3-L1 preadipocytes to adipocytes. SH2-B overexpression enhanced mRNA level of PPARgamma in 3T3-L1 cells, whereas PPARgamma levels were reduced in SH2-B-deficient MEFs in response to insulin. SH2-B-mediated up-regulation of PPARgamma mRNA was blocked by a phosphatidylinositol 3-kinase inhibitor, but not by a MAPK kinase inhibitor. Insulin-induced Akt activation and the phosphorylation of forkhead transcription factor (FKHR/Foxo1), a negative regulator of PPARgamma transcription, were up-regulated by SH2-B overexpression, but reduced in SH2-B-deficient MEFs. These data indicate that SH2-B is a key regulator of adipogenesis both in vivo and in vitro by regulating the insulin/IGF-I receptor-Akt-Foxo1-PPARgamma pathway.

  20. Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, Mohammad [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Ito, Akihiro, E-mail: akihiro-i@riken.jp [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan); Ishfaq, Muhammad; Bradshaw, Elliot [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Yoshida, Minoru [Chemical Genetics Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Graduate School of Science and Engineering, Saitama University, 645 Shimo-Okubo, Sakura-ku, Saitama 338-8570 (Japan); Japan Agency for Medical Research and Development, AMED-CREST, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004 (Japan)

    2016-02-05

    The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

  1. An isoform of eukaryotic initiation factor 4E from Chrysanthemum morifolium interacts with Chrysanthemum virus B coat protein.

    Directory of Open Access Journals (Sweden)

    Aiping Song

    Full Text Available BACKGROUND: Eukaryotic translation initiation factor 4E (eIF4E plays an important role in plant virus infection as well as the regulation of gene translation. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe the isolation of a cDNA encoding CmeIF(iso4E (GenBank accession no. JQ904592, an isoform of eIF4E from chrysanthemum, using RACE PCR. We used the CmeIF(iso4E cDNA for expression profiling and to analyze the interaction between CmeIF(iso4E and the Chrysanthemum virus B coat protein (CVBCP. Multiple sequence alignment and phylogenetic tree analysis showed that the sequence similarity of CmeIF(iso4E with other reported plant eIF(iso4E sequences varied between 69.12% and 89.18%, indicating that CmeIF(iso4E belongs to the eIF(iso4E subfamily of the eIF4E family. CmeIF(iso4E was present in all chrysanthemum organs, but was particularly abundant in the roots and flowers. Confocal microscopy showed that a transiently transfected CmeIF(iso4E-GFP fusion protein distributed throughout the whole cell in onion epidermis cells. A yeast two hybrid assay showed CVBCP interacted with CmeIF(iso4E but not with CmeIF4E. BiFC assay further demonstrated the interaction between CmeIF(iso4E and CVBCP. Luminescence assay showed that CVBCP increased the RLU of Luc-CVB, suggesting CVBCP might participate in the translation of viral proteins. CONCLUSIONS/SIGNIFICANCE: These results inferred that CmeIF(iso4E as the cap-binding subunit eIF(iso4F may be involved in Chrysanthemum Virus B infection in chrysanthemum through its interaction with CVBCP in spatial.

  2. Dissociation of 5' proximal helical regions in messenger RNAs by eukaryotic initiation factors 4F, 4A, and 4B

    International Nuclear Information System (INIS)

    Thach, R.E.; Lawson, T.G.; Lee, K.A.; Abramson, R.D.; Merrick, W.C.

    1987-01-01

    Ray, et al. demonstrated that the susceptibility of mRNAs to cleavage by ribonucleases is greatly increased by eIF-4A and eIF-4F in an ATP-dependent reaction, and that this reaction is enhanced by the presence of eIF-4B. They now report direct evidence for the dissociation of helical regions at the 5' ends of mRNAs by these factors. Helices were generated at the 5' ends of reovirus and rabbit globin mRNAs by hybridizing to them 32 P-labeled cDNA pentadecamers. The dissociation of the cDNAs from the mRNAs was monitored by Sephadex gel filtration. Addition of eIF-4F to hybrids caused the dissociation of small amounts of cDNAs, and this dissociation required ATP. Addition of eIF-4B stimulated this activity. Neither eIF-4B nor eIF-4A alone caused significant ATP-dependent dissociation, but they did so in combination. Interestingly, cDNAs that were hybridized to 5' distal regions were dissociated with efficiencies and rates similar to those of 5' proximal cDNAs. The presence of unlabelled cDNAs hybridized 5' proximally did not affect distal cDNA dissociation. These results confirm the earlier suggestion that eIF-4A, eIF-4B and eIF-4F play important roles in the disruption of mRNA secondary structure during initiation

  3. Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

    International Nuclear Information System (INIS)

    Tariq, Mohammad; Ito, Akihiro; Ishfaq, Muhammad; Bradshaw, Elliot; Yoshida, Minoru

    2016-01-01

    The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy. - Highlights: • Hypoxia induces acetylation of eIF5A. • Active eIF5A is necessary for HIF-1α activation in hypoxia. • Active eIF5A is important for tumor spheroid growth.

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

    DEFF Research Database (Denmark)

    2014-01-01

    The present inventors developed hepatitis C virus 2b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 2b reference strain J8. Sequence analysis of recovered 2b/2a recombinants from 2...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    This paper shed light on how social media application can enhance innovation management in SME B2B context. Our study employs a qualitative case study approach with four B2B SMEs for in-depth research in the period from October 2013 to October 2014. The B2B SME managers aim for open business mode...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response Udgivelsesdato: 2008/10...

  7. Accessibility of tyrosyl residues altered by formation of the histone 2A/2B complex

    International Nuclear Information System (INIS)

    Callaway, J.E.; Ho, Y.S.; DeLange, R.J.

    1985-01-01

    The availability of tyrosyl residues to surface iodination was analyzed for histone 2A (H2A), histone 2B (H2B), and the H2A/H2B complex. When H2A is free in solution (200 mM NaCl, pH 7.4) tyrosine-39 and one or both tyrosines-50 and -57 were readily iodinated. Tyrosines-83 and -121 of H2B were iodinated, both when the histone was free in solution and when it was associated with H2A, while tyrosines-37, -40, and -42 of H2B were not iodinated under either condition. When H2A and H2B were associated or covalently cross-linked, all tyrosyl residues of H2A were unavailable for iodination. The authors also found that the iodination of nondenatured H2A and H2B did not inhibit formation of the H2A/H2B complex. These results indicate that the amino-terminal regions of the hydrophobic portions of H2A and H2B undergo significant conformational changes upon formation of the H2A/H2B complex. These conformational shifts occur in the same region of the H2A/H2B complex that contains a contact site between H2A and H2B in the nucleosome, thus indicating an involvement of this region in chromatin assembly

  8. Schizophrenia: Evidence Implicating Hippocampal GluN2B protein and REST Epigenetics in Psychosis Pathophysiology

    Science.gov (United States)

    Tamminga, Carol A.; Zukin, R. Suzanne

    2017-01-01

    The hippocampus is strongly implicated in the psychotic symptoms of schizophrenia. Functionally, basal hippocampal activity (perfusion) is elevated in schizophrenic psychosis, as measured with positron emission tomography (PET) and with magnetic resonance (MR) perfusion techniques, while hippocampal activation to memory tasks is reduced. Subfield-specific hippocampal molecular pathology exists in human psychosis tissue which could underlie this neuronal hyperactivity, including increased GluN2B-containing NMDA receptors in hippocampal CA3, along with increased postsynaptic density protein-95 (PSD-95) along with augmented dendritic spines on the pyramidal neuron apical dendrites. We interpret these observations to implicate a reduction in the influence of a ubiquitous gene repressor, repressor element-1 silencing transcription factor (REST) in psychosis; REST is involved in the age-related maturation of the NMDA receptor from GluN2B- to GluN2A-containing NMDA receptors through epigenetic remodeling. These CA3 changes in psychosis leave the hippocampus liable to pathological increases in neuronal activity, feedforward excitation and false memory formation, sometimes with psychotic content. PMID:26211447

  9. Interaction of the RNP1 motif in PRT1 with HCR1 promotes 40S binding of eukaryotic initiation factor 3 in yeast

    DEFF Research Database (Denmark)

    Nielsen, Klaus H; Valásek, Leos; Sykes, Caroah

    2006-01-01

    We found that mutating the RNP1 motif in the predicted RRM domain in yeast eukaryotic initiation factor 3 (eIF3) subunit b/PRT1 (prt1-rnp1) impairs its direct interactions in vitro with both eIF3a/TIF32 and eIF3j/HCR1. The rnp1 mutation in PRT1 confers temperature-sensitive translation initiation...

  10. Enrichment of W2B5 from WO3 and B2O3 by Double SHS Method

    Directory of Open Access Journals (Sweden)

    Bora DERIN

    2018-02-01

    Full Text Available A second self-propagating high-temperature synthesis (SHS was carried out to enrich the W2B5 content in the SHS product containing a mixture of various tungsten boride compounds. In the experiment, the process called Double-SHS (D-SHS was conducted in two steps. In the first SHS reaction, an initial molar composition ratio of WO3:B2O3:Mg mixture was selected as 1:3:8. The product was then hot-leached with hydrochloric acid to eliminate MgO and Mg3B2O6 phases. The leached product, consisting of 72.6 wt.% W2B5, 16.1 wt.% WB, 8.4 wt.% W2B, and 2.9 wt.% W, was again reacted with the Mg and B2O3 mixture by second SHS. After another acid leaching step, W2B5 content in the D-SHS product was found to be 98.2 wt.%. The study showed that D-SHS is an effective method for boron enrichment in the tungsten compounds.DOI: http://dx.doi.org/10.5755/j01.ms.24.1.17834

  11. Genome-wide ChIP-seq analysis of human TOP2B occupancy in MCF7 breast cancer epithelial cells

    Directory of Open Access Journals (Sweden)

    Catriona M. Manville

    2015-11-01

    Full Text Available We report the whole genome ChIP seq for human TOP2B from MCF7 cells. Using three different peak calling methods, regions of binding were identified in the presence or absence of the nuclear hormone estradiol, as TOP2B has been reported to play a role in ligand-induced transcription. TOP2B peaks were found across the whole genome, 50% of the peaks fell either within a gene or within 5 kb of a transcription start site. TOP2B peaks coincident with gene promoters were less frequently associated with epigenetic features marking active promoters in estradiol treated than in untreated cells. Significantly enriched transcription factor motifs within the DNA sequences underlying the peaks were identified. These included SP1, KLF4, TFAP2A, MYF, REST, CTCF, ESR1 and ESR2. Gene ontology analysis of genes associated with TOP2B peaks found neuronal development terms including axonogenesis and axon guidance were significantly enriched. In the absence of functional TOP2B there are errors in axon guidance in the zebrafish eye. Specific heparin sulphate structures are involved in retinal axon targeting. The glycosaminoglycan biosynthesis–heparin sulphate/heparin pathway is significantly enriched in the TOP2B gene ontology analysis, suggesting changes in this pathway in the absence of TOP2B may cause the axon guidance faults.

  12. Changes in the strength of peer influence and cultural factors on substance use initiation between late adolescence and emerging adulthood in a Hispanic sample.

    Science.gov (United States)

    Grigsby, Timothy J; Forster, Myriam; Soto, Daniel W; Unger, Jennifer B

    2017-01-01

    We examine whether peer substance use and cultural factors differentially influence the initiation of tobacco, alcohol, and marijuana use in adolescence and emerging adulthood (EA) among a community-based sample of Hispanics. Participants provided data in 11th grade (M = 16.8 years old, SD = 0.54) and emerging adulthood (M = 20.3 years old, SD = 0.6). Peer tobacco use had a stronger association with initiation of tobacco use in emerging adulthood (OR = 1.46, 95% CI = 1.13, 1.89) than in adolescence (OR = 1.20, 95% CI = 1.03, 1.40), but this pattern was not observed with initiation of alcohol or marijuana use. Cultural orientation is associated with initiation of tobacco use during EA but not with initiation of alcohol or marijuana use.

  13. NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity.

    Science.gov (United States)

    Norcini, Monica; Sideris, Alexandra; Adler, Samantha M; Hernandez, Lourdes A M; Zhang, Jin; Blanck, Thomas J J; Recio-Pinto, Esperanza

    2016-01-01

    Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma's plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23

  14. Characterization of the UV-crosslinked heterodimer of histones H2B and H4

    International Nuclear Information System (INIS)

    Johnson, E.R.; Brown, D.M.; DeLange, R.J.

    1986-01-01

    At relatively high salt concentrations (1.2 M), histone 2B (H2B) and histone 4 (H4) can be covalently crosslinked by irradiation with ultraviolet light to yield a mixture of the three possible dimers: H2B-H2B, H4-H4, and H2B-H4. The formation of the H2B-H4 heterodimer was found to be favored at lower histone concentrations (> 90% H2B-H4 at 0.1 mg/ml total histone protein). CNBr cleavage of the H2B-H4 dimer produced three fragments which were separated by reverse phase HPLC. These fragments were identified by amino acid compositional analysis to be H4(85-102), H2B(62-125), and the crosslinked N-terminal regions H2B(1-59)-H4(1-84). Amino acid sequence analysis of the crosslinked fragment indicated that tyrosine-40 of H2B is likely involved in the covalent crosslinkage which joins the histone monomers to form the heterodimer

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

    Directory of Open Access Journals (Sweden)

    Nelina eRamanantsoa

    2011-09-01

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

  16. Risk Factor Burden, Heart Failure, and Survival in Women of Different Ethnic Groups: Insights From the Women's Health Initiative.

    Science.gov (United States)

    Breathett, Khadijah; Leng, Iris; Foraker, Randi E; Abraham, William T; Coker, Laura; Whitfield, Keith E; Shumaker, Sally; Manson, JoAnn E; Eaton, Charles B; Howard, Barbara V; Ijioma, Nkechinyere; Cené, Crystal W; Martin, Lisa W; Johnson, Karen C; Klein, Liviu

    2018-05-01

    The higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups. In the WHI (Women's Health Initiative; 1993-2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased ( P ethnicity and RF number P =0.18)-African-Americans 1 RF: 1.80 (1.01-3.20), 2 RFs: 3.19 (1.84-5.54), 3+ RFs: 7.31 (4.26-12.56); Whites 1 RF: 1.27 (1.04-1.54), 2 RFs: 1.95 (1.60-2.36), 3+ RFs: 4.07 (3.36-4.93); Hispanics 1 RF: 1.72 (0.68-4.34), 2 RFs: 3.87 (1.60-9.37), 3+ RFs: 8.80 (3.62-21.42). Risk of death before developing HF increased with subsequent RFs ( P ethnic group (interaction P =0.001). The number of RFs was not associated with the risk of death after developing HF in any group ( P =0.25; interaction P =0.48). Among diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups. © 2018 American Heart Association, Inc.

  17. The rice eukaryotic translation initiation factor 3 subunit f (OseIF3f is involved in microgametogenesis

    Directory of Open Access Journals (Sweden)

    Qi eLi

    2016-04-01

    Full Text Available Microgametogenesis is the postmeiotic pollen developmental phase when unicellular microspores develop into mature tricellular pollen. In rice, microgametogenesis can influence grain yields to a great degree because pollen abortion occurs more easily during microgametogenesis than during other stages of pollen development. However, our knowledge of the genes involved in microgametogenesis in rice remains limited. Due to the dependence of pollen development on the regulatory mechanisms of protein expression, we identified the encoding gene of the eukaryotic translation initiation factor 3, subunit f in Oryza sativa (OseIF3f. Immunoprecipitation combined with mass spectrometry confirmed that OseIF3f was a subunit of rice eIF3, which consisted of at least 12 subunits including eIF3a, eIF3b, eIF3c, eIF3d, eIF3e, eIF3f, eIF3g, eIF3h, eIF3i, eIF3k, eIF3l and eIF3m. OseIF3f showed high mRNA levels in immature florets and is highly abundant in developing anthers. Subcellular localization analysis showed that OseIF3f was localized to the cytosol and the endoplasmic reticulum in rice root cells. We further analyzed the biological function of OseIF3f using the double-stranded RNA-mediated interference (RNAi approach. The OseIF3f-RNAi lines grew normally at the vegetative stage but displayed a large reduction in seed production and pollen viability, which is associated with the down-regulation of OseIF3f. Further cytological observations of pollen development revealed that the OseIF3f-RNAi lines showed no obvious abnormalities at the male meiotic stage and the unicellular microspore stage. However, compared to the wild type, OseIF3f-RNAi lines contained a higher percentage of arrested unicellular pollen at the bicellular stage and a higher percentage of arrested unicellular and bicellular pollen, and aborted pollen at the tricellular stage. These results indicate that OseIF3f plays a role in microgametogenesis.

  18. Meteorological Factors and Tree Characteristics Influencing the Initiation and Rate of Stemflow from Deciduous Trees in an Urban Park

    Science.gov (United States)

    Schooling, J. T.; Carlyle-Moses, D. E.

    2013-12-01

    Stemflow, SF, represents that portion of precipitation that is intercepted by a tree's canopy and diverted to the ground at the tree base by flowing along branches and down the bole. The focused input of water and nutrients associated with SF have been shown to be of hydrological and biogeochemical importance in a number of plant communities and forest environments. Although the concentrated water volume and the nutrient / pollutant fluxes associated with SF in urban areas may be highly relevant for stormwater quantity and quality management, they have received only minor study in built environments. In an urban park in Kamloops, British Columbia, Canada, SF volumes generated from 40 deciduous trees representing 22 species were sampled on a precipitation event basis over a period of 16 months. Using this data, we derived the threshold rainfall depth required for SF initiation from each tree by taking the absolute value of the y-intercept of the linear regression of SF volume versus rainfall depth divided by the slope of that regression. The SF discharge rate once the threshold rainfall depth had been reached was taken as the slope of the linear regression equation. Thus, a simplified SF equation was developed: SFv = QSF x (Pg = Pg''), where SFv is stemflow volume (litres), QSF is the discharge rate (litres / mm), and Pg and Pg' represent the precipitation depth and the threshold precipitation depth, respectively. We then examined the influence of meteorological factors (precipitation type [rain / snow / rain + snow], precipitation depth, rainfall intensity, wind speed and direction, and vapour pressure deficit), and tree characteristics (tree diameter at breast height, tree height, leaf size and orientation, bark roughness, crown projection area, leaf area index, canopy cover fraction, branching angle, the proportion of the crown that was comprised of branches, and overlap with other tree canopies) on QSF and Pg' in order to expand on the simplified model and

  19. Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1.

    Science.gov (United States)

    Meyer Zu Schwabedissen, Henriette E; Ferreira, Celio; Schaefer, Anima M; Oufir, Mouhssin; Seibert, Isabell; Hamburger, Matthias; Tirona, Rommel G

    2018-07-01

    Levothyroxine replacement therapy forms the cornerstone of hypothyroidism management. Variability in levothyroxine oral absorption may contribute to the well-recognized large interpatient differences in required dose. Moreover, levothyroxine-drug pharmacokinetic interactions are thought to be caused by altered oral bioavailability. Interestingly, little is known regarding the mechanisms contributing to levothyroxine absorption in the gastrointestinal tract. Here, we aimed to determine whether the intestinal drug uptake transporter organic anion transporting polypeptide 2B1 (OATP2B1) may be involved in facilitating intestinal absorption of thyroid hormones. We also explored whether thyroid hormones regulate OATP2B1 gene expression. In cultured Madin-Darby Canine Kidney II/OATP2B1 cells and in OATP2B1-transfected Caco-2 cells, thyroid hormones were found to inhibit OATP2B1-mediated uptake of estrone-3-sulfate. Competitive counter-flow experiments evaluating the influence on the cellular accumulation of estrone-3-sulfate in the steady state indicated that thyroid hormones were substrates of OATP2B1. Additional evidence that thyroid hormones were OATP2B1 substrates was provided by OATP2B1-dependent stimulation of thyroid hormone receptor activation in cell-based reporter assays. Bidirectional transport studies in intestinal Caco-2 cells showed net absorptive flux of thyroid hormones, which was attenuated by the presence of the OATP2B1 inhibitor, atorvastatin. In intestinal Caco-2 and LS180 cells, but not in liver Huh-7 or HepG2 cells, OATP2B1 expression was induced by treatment with thyroid hormones. Reporter gene assays revealed thyroid hormone receptor α -mediated transactivation of the SLCO2B1 1b and the SLCO2B1 1e promoters. We conclude that thyroid hormones are substrates and transcriptional regulators of OATP2B1. These insights provide a potential mechanistic basis for oral levothyroxine dose variability and drug interactions. Copyright © 2018 by The American

  20. Biological insights into the expression of translation initiation factors from recombinant CHOK1SV cell lines and their relationship to enhanced productivity.

    Science.gov (United States)

    Mead, Emma J; Masterton, Rosalyn J; Feary, Marc; Obrezanova, Olga; Zhang, Lin; Young, Robert; Smales, C Mark

    2015-12-15

    Translation initiation is on the critical pathway for the production of monoclonal antibodies (mAbs) by mammalian cells. Formation of a closed loop structure comprised of mRNA, a number of eukaryotic initiation factors (eIFs) and ribosomal proteins has been proposed to aid re-initiation of translation and therefore increase global translational efficiency. We have determined mRNA and protein levels of the key components of the closed loop, eIFs (eIF3a, eIF3b, eIF3c, eIF3h, eIF3i and eIF4G1), poly(A)-binding protein (PABP) 1 and PABP-interacting protein 1 (PAIP1), across a panel of 30 recombinant mAb-producing GS-CHOK1SV cell lines with a broad range of growth characteristics and production levels of a model recombinant mAb. We have used a multi-level statistical approach to investigate the relationship between key performance indicators (cell growth and recombinant antibody productivity) and the intracellular amounts of target translation initiation factor proteins and the mRNAs encoding them. We show that high-producing cell lines maintain amounts of the translation initiation factors involved in the formation of the closed loop mRNA, maintaining these proteins at appropriate levels to deliver enhanced recombinant protein production. We then utilize knowledge of the amounts of these factors to build predictive models for and use cluster analysis to identify, high-producing cell lines. The present study therefore defines the translation initiation factor amounts that are associated with highly productive recombinant GS-CHOK1SV cell lines that may be targets for screening highly productive cell lines or to engineer new host cell lines with the potential for enhanced recombinant antibody productivity. © 2015 Authors; published by Portland Press Limited.

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

    International Nuclear Information System (INIS)

    Wilderman, P. Ross; Jang, Hyun-Hee; Malenke, Jael R.; Salib, Mariam; Angermeier, Elisabeth; Lamime, Sonia; Dearing, M. Denise; Halpert, James R.

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-02-01

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

  3. Comparative therapeutic response to pegylated interferon plus ribavirin versus interferon alpha-2b in chronic hepatitis C patients

    International Nuclear Information System (INIS)

    Ali, S.; Nazir, G.; Khan, S.A.; Fatima, F.; Iram, S.

    2010-01-01

    Background: Hepatitis C is an epidemic worldwide since discovery in 1989. Conventional interferon alpha-2b plus Ribavirin therapy was started in 1998 but over all sustained viral response (SVR) rates are much below the desired rates to eradicate the diseases and stopping its epidemic. This study was conducted to access the therapeutic and cost-effectiveness of long acting pegylated interferon alpha-2b plus Ribavirin therapy verses conventional interferon alpha-2b plus Ribavirin. Methods: This comparative study was done at PAF Hospital Shorkot Cantt from July 2005 to July 2008. One hundred anti-HCV positive patients were selected randomly for the study according to willingness due to cost afford ability of the patients for conventional interferon. Group-A was labelled as pegylated interferon alpha-2b plus Ribavirin group, and Group-B interferon alpha-2b plus Ribavirin group. Both groups were given treatment for 24 weeks. Early virological response (EVR) was accessed at 12 weeks of the treatment. Sustained virological response (SVR) in both the groups was done at 24 week during the treatment and 6 monthly after treatment for 2 years. Initially non-responders and relapsed patients within 2 years of treatment were re-treated for 24 weeks with the same treatment. In both groups non-responders and relapsed patients were labelled as resistant patients. Both groups were followed with same protocol for 2 years. Results: Out of 100 patients included in the study, 34% were females and 66% were males. Group-A patients over all showed 94% SVR as compare to 80% in Group-B in 2 year follow-up. Group-A showed 6% resistant patients as compare to Group-B (20%). Conventional interferons were better tolerated. Higher incidence of side-effects was seen in Group-A. Conclusion: Pegylated interferon plus Ribavirin showed 94% SVR in 2 years. Pegylated interferon plus Ribavirin is the treatment of choice.

  4. Thermoluminescence properties of Li2B4O7:Cu, B phosphor synthesized using solution combustion technique

    International Nuclear Information System (INIS)

    Ozdemir, A.; Altunal, V.; Kurt, K.; Depci, T.; Yu, Y.; Lawrence, Y.; Nur, N.; Guckan, V.; Yegingil, Z.

    2017-01-01

    To determine the effects of various concentrations of the activators copper (Cu) and boron (B) on the thermoluminescence (TL) properties of lithium tetraborate, the phosphor was first synthesized and doped with five different concentrations of copper (0.1–0.005 wt%) using solution combustion method. 0.01 wt% Cu was the concentration which showed the most significant increase in the sensitivity of the phosphor. The second sort of Li 2 B 4 O 7 :Cu material was prepared by adding B (0.001–0.03 wt%) to it. The newly developed copper-boron activated lithium tetraborate (Li 2 B 4 O 7 :Cu, B) material with 0.01 wt% Cu and 0.001 wt% B impurity concentrations was shown to have promise as a TL phosphor. The material formation was examined using powder x-Ray Diffraction (XRD) analysis and Scanning Electron Microscope (SEM) imaging. Fourier Transform Infrared (FT-IR) spectrum of the synthesized polycrystalline powder sample was also recorded. The TL glow curves were analyzed to determine various dosimetric characteristics of the synthesized luminophosphors. The dose response increased in a “linear” way with the beta-ray exposure between 0.1–20 Gy, a dose range being interested in medical dosimetry. The response with changing photon and electron energy was studied. The rate of decay of the TL signal was investigated both for dark storage and under direct sunlight. Li 2 B 4 O 7 :Cu, B showed no individual variation of response in 9 recycling measurements. The fluorescence spectrum was determined. The kinetic parameters were estimated by different methods and the results discussed. The studied properties of synthesized Li 2 B 4 O 7 :Cu, B were found all favorable for dosimetric purposes. - Highlights: • Li 2 B 4 O 7 :Cu, B synthesis using solution combustion method with various concentrations. • Structure analysis of Li 2 B 4 O 7 :Cu, B using XRD, SEM and FTIR methods. • Investigation of thermoluminescent properties of Li 2 B 4 O 7 :Cu, B. • Relatively good

  5. Translation initiation factors eIF3 and HCR1 control translation termination and stop codon read-through in yeast cells

    Czech Academy of Sciences Publication Activity Database

    Beznosková, P.; Cuchalová, Lucie; Wagner, S.; Shoemaker, Ch. J.; Gunišová, S.; von der Haar, T.; Valášek, L. S.

    2013-01-01

    Roč. 9, č. 11 (2013), e1003962_1-e1003962_17 ISSN 1553-7404 Institutional support: RVO:61389013 Keywords : translation initiation * translation termination * eIF3 Subject RIV: CD - Macromolecular Chemistry Impact factor: 8.167, year: 2013

  6. Effect of baculovirus infection on the mRNA and protein levels of the Spodoptera frugiperda eukaryotic initiation factor 4E

    NARCIS (Netherlands)

    Oers, van M.M.; Veken, van der L.T.J.N.; Vlak, J.M.; Thomas, A.A.M.

    2001-01-01

    The cDNA sequence of eukaryotic translation initiation factor eIF4E was derived from a Spodoptera frugiperda cDNA library. Eight tryptophan residues, typical for eIF4E, are strictly conserved in the encoded 210 amino acid protein. A polyclonal antiserum detected a 26 kDa protein in lepidopteran cell

  7. The relative contribution of genes and environment to alcohol use in early adolescents: are similar factors related to initiation of alcohol use and frequency of drinking?

    NARCIS (Netherlands)

    Poelen, Evelien A. P.; Derks, Eske M.; Engels, Rutger C. M. E.; van Leeuwe, Jan F. J.; Scholte, Ron H. J.; Willemsen, Gonneke; Boomsma, Dorret I.

    2008-01-01

    The present study assessed the relative contribution of genes and environment to individual differences in initiation of alcohol use and frequency of drinking among early adolescents and examined the extent to which the same genetic and environmental factors influence both individual differences in

  8. The Relative Contribution of Genes and Environment to Alcohol Use in Early Adolescents : Are Similar Factors Related to Initiation of Alcohol Use and Frequency of Drinking?

    NARCIS (Netherlands)

    Poelen, E.A.P.; Derks, E.M.; Engels, R.C.M.E.; Scholte, R.H.J.; Willemsen, A.H.M.; Boomsma, D.I.

    2008-01-01

    Background: The present study assessed the relative contribution of genes and environment to individual differences in initiation of alcohol use and frequency of drinking among early adolescents and examined the extent to which the same genetic and environmental factors influence both individual

  9. The relative contribution of genes and environment to alcohol use in early adolescents: Are similar factors related to initiation of alcohol use and frequency of drinking?

    NARCIS (Netherlands)

    Poelen, E.A.P.; Derks, E.M.; Engels, R.C.M.E.; Leeuwe, J.F.J.; Scholte, R.H.J.; Willemsen, G.; Boomsma, D.I.

    2008-01-01

    Background: The present study assessed the relative contribution of genes and environment to individual differences in initiation of alcohol use and frequency of drinking among early adolescents and examined the extent to which the same genetic and environmental factors influence both individual

  10. Trends in baseline CD4 cell counts and risk factors for late antiretroviral therapy initiation among HIV-positive patients in Shanghai, a retrospective cross-sectional study.

    Science.gov (United States)

    Sun, Jianjun; Liu, Li; Shen, Jiayin; Chen, Panpan; Lu, Hongzhou

    2017-04-19

    There are few studies focus on the factors underlying the late initiation of ART in China. We analyzed the trends in the median CD4 cell counts among different patient groups over time and the risk factors for the late initiation of ART in Shanghai, China. A retrospective cross-sectional survey was made in the Department of Infectious Disease of Shanghai Public Health Clinical Center which is a designated diagnosis and treatment center for HIV-positive patients in Shanghai during the period of January 1st, 2008--June 30th, 2014. Late ART initiation was defined as a CD4 cell count 30 years) (p HIV exposure who are male, older even heterosexual orientation should be given more opportunities to receive frequently screening, earlier diagnoses and timely treatment.

  11. Cloning and expression of a rat brain α2B-adrenergic receptor

    International Nuclear Information System (INIS)

    Flordellis, C.S.; Handy, D.E.; Bresnahan, M.R.; Zannis, V.I.; Gavras, H.

    1991-01-01

    The authors isolated a cDNA clone (RBα 2B ) and its homologous gene (GRα 2B ) encoding an α 2B -adrenergic receptor subtype by screening a rat brain cDNA and a rat genomic library. Nucleotide sequence analysis showed that both clones code for a protein of 458 amino acids, which is 87% homologous to the human kidney glycosylated adrenergic receptor (α 2 -C4) and divergent from the rat kidney nonglycosylated α 2B subtype (RNGα 2 ). Transient expression of RBα 2B in COS-7 cells resulted in high-affinity saturable binding for [ 3 H]rauwolscine and a high receptor number in the membranes of transfected COS-7 cells. Pharmacological analysis demonstrated that the expressed receptor bound adrenergic ligands with the following order of potency: rauwolscine > yohimbine > prazosin > oxymetazoline, with a prazosin-to-oxymetazoline K i ratio of 0.34. This profile is characteristic of the α 2B -adrenergic receptor subtype. Blotting analysis of rat brain mRNA gave one major and two minor mRNA species, and hybridization with strand-specific probes showed that both DNA strands of GRα 2B may be transcriptionally active. These findings show that rat brain expresses an α 2B -adrenergic receptor subtype that is structurally different from the rat kidney nonglycosylated α 2B subtype. Thus the rat expresses at least two divergent α 2B -adrenergic receptors

  12. Regulation of UGT2B Expression and Activity by miR-216b-5p in Liver Cancer Cell Lines

    OpenAIRE

    Dluzen, Douglas F.; Sutliff, Aimee K.; Chen, Gang; Watson, Christy J. W.; Ishmael, Faoud T.; Lazarus, Philip

    2016-01-01

    The UDP-glucuronosyltransferase (UGT) 2B enzymes are important in the detoxification of a variety of endogenous and exogenous compounds, including many hormones, drugs, and carcinogens. Identifying novel mechanisms governing their expression is important in understanding patient-specific response to drugs and cancer risk factors. In silico prediction algorithm programs were used to screen for microRNAs (miRNAs) as potential regulators of UGT2B enzymes, with miR-216b-5p identified as a potenti...

  13. Synthesis of nanostructured TiO2 (anatase) and TiO2(B) in ionic liquids

    Czech Academy of Sciences Publication Activity Database

    Mansfeldová, Věra; Lásková, Barbora; Krýsová, Hana; Zukalová, Markéta; Kavan, Ladislav

    2014-01-01

    Roč. 230, JUL 2014 (2014), s. 85-90 ISSN 0920-5861 R&D Projects: GA ČR GA13-07724S; GA MŠk 7E09117 Grant - others:European Commission(XE) NMP-229036 Institutional support: RVO:61388955 Keywords : TiO2(B) * ionic liquid * electrochemistry Subject RIV: CG - Electrochemistry Impact factor: 3.893, year: 2014

  14. SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin.

    Science.gov (United States)

    Duan, Chaojun; Li, Minghua; Rui, Liangyou

    2004-10-15

    Leptin regulates energy homeostasis primarily by binding and activating its long form receptor (LRb). Deficiency of either leptin or LRb causes morbid obesity. Leptin stimulates LRb-associated JAK2, thus initiating multiple pathways including the Stat3 and phosphatidylinositol (PI) 3-kinase pathways that mediate leptin biological actions. Here we report that SH2-B, a JAK2-interacting protein, promotes activation of the PI 3-kinase pathway by recruiting insulin receptor substrate 1 (IRS1) and IRS2 in response to leptin. SH2-B directly bound, via its PH and SH2 domain, to both IRS1 and IRS2 both in vitro and in intact cells and mediated formation of a JAK2/SH2-B/IRS1 or IRS2 tertiary complex. Consequently, SH2-B dramatically enhanced leptin-stimulated tyrosine phosphorylation of IRS1 and IRS2 in HEK293 cells stably expressing LRb, thus promoting association of IRS1 and IRS2 with the p85 regulatory subunit of PI 3-kinase and phosphorylation and activation of Akt. SH2-B mutants with lower affinity for IRS1 and IRS2 exhibited reduced ability to promote association of JAK2 with IRS1, tyrosine phosphorylation of IRS1, and association of IRS1 with p85 in response to leptin. Moreover, deletion of the SH2-B gene impaired leptin-stimulated tyrosine phosphorylation of endogenous IRS1 in mouse embryonic fibroblasts (MEF), which was reversed by reintroduction of SH2-B. Similarly, SH2-B promoted growth hormone-stimulated tyrosine phosphorylation of IRS1 in both HEK293 and MEF cells. Our data suggest that SH2-B is a novel mediator of the PI 3-kinase pathway in response to leptin or other hormones and cytokines that activate JAK2.

  15. Identification of EhTIF-IA: The putative E. histolytica orthologue of the human ribosomal RNA transcription initiation factor-IA.

    Science.gov (United States)

    Srivastava, Ankita; Bhattacharya, Alok; Bhattacharya, Sudha; Jhingan, Gagan Deep

    2016-03-01

    Initiation of rDNA transcription requires the assembly of a specific multi-protein complex at the rDNA promoter containing the RNA Pol I with auxiliary factors. One of these factors is known as Rrn3P in yeast and Transcription Initiation Factor IA (TIF-IA) in mammals. Rrn3p/TIF-IA serves as a bridge between RNA Pol I and the pre-initiation complex at the promoter. It is phosphorylated at multiple sites and is involved in regulation of rDNA transcription in a growth-dependent manner. In the early branching parasitic protist Entamoeba histolytica, the rRNA genes are present exclusively on circular extra chromosomal plasmids. The protein factors involved in regulation of rDNA transcription in E. histolytica are not known. We have identified the E. histolytica equivalent of TIF-1A (EhTIF-IA) by homology search within the database and was further cloned and expressed. Immuno-localization studies showed that EhTIF-IA co-localized partially with fibrillarin in the peripherally localized nucleolus. EhTIF-IA was shown to interact with the RNA Pol I-specific subunit RPA12 both in vivo and in vitro. Mass spectroscopy data identified RNA Pol I-specific subunits and other nucleolar proteins to be the interacting partners of EhTIF-IA. Our study demonstrates for the first time a conserved putative RNA Pol I transcription factor TIF-IA in E. histolytica.

  16. Function of brain α2B-adrenergic receptor characterized with subtype-selective α2B antagonist and KO mice.

    Science.gov (United States)

    Luhrs, Lauren; Manlapaz, Cynthia; Kedzie, Karen; Rao, Sandhya; Cabrera-Ghayouri, Sara; Donello, John; Gil, Daniel

    2016-12-17

    Noradrenergic signaling, through the α 2A and α 2C adrenergic receptors modulates the cognitive and behavioral symptoms of disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. However, it is unknown whether the α 2B receptor has any significant role in CNS function. The present study elucidates the potential role of the α 2B receptor in CNS function via the discovery and use of the first subtype-selective α 2B antagonist (AGN-209419), and behavioral analyses of α-receptor knockout (KO) mice. Using AGN-209419 as radioligand, α 2B receptor binding sites were identified within the olfactory bulb, cortex, thalamus, cerebellum, and striatum. Based on the observed expression patterns of α 2 subtypes in the brain, we compared α 2B KO, α 2A KO and α 2C KO mice behavioral phenotypes with their respective wild-type lines in anxiety (plus maze), compulsive (marble burying), and sensorimotor (prepulse inhibition) tasks. α 2B KO mice exhibited increased marble burying and α 2C KO mice exhibited an increased startle response to a pulse stimulus, but otherwise intact prepulse inhibition. To further explore compulsive behavior, we evaluated novelty-induced locomotor hyperactivity and found that α 2B KO and α 2C KO mice exhibited increased locomotion in the open field. Interestingly, when challenged with amphetamine, α 2C KO mice increased activity at lower doses relative to either α 2A KO or WT mice. However, α 2B KO mice exhibited stereotypy at doses of amphetamine that were only locomotor stimulatory to all other genotypes. Following co-administration of AGN-209419 with low-dose amphetamine in WT mice, stereotypy was observed, mimicking the α 2B KO phenotype. These findings suggest that the α 2B receptor is involved in CNS behaviors associated with sensorimotor gating and compulsivity, and may be therapeutically relevant for disorders such as schizophrenia, ADHD, post-traumatic stress disorder, addiction, and

  17. Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release

    DEFF Research Database (Denmark)

    da Silva Pinheiro, Paulo César; de Wit, Heidi; Walter, Alexander M

    2013-01-01

    Synaptotagmin-1 and -7 constitute the main calcium sensors mediating SNARE-dependent exocytosis in mouse chromaffin cells, but the role of a closely related calcium-binding protein, Doc2b, remains enigmatic. We investigated its role in chromaffin cells using Doc2b knock-out mice and high temporal...... resolution measurements of exocytosis. We found that the calcium dependence of vesicle priming and release triggering remained unchanged, ruling out an obligatory role for Doc2b in those processes. However, in the absence of Doc2b, release was shifted from the readily releasable pool to the subsequent...... sustained component. Conversely, upon overexpression of Doc2b, the sustained component was largely inhibited whereas the readily releasable pool was augmented. Electron microscopy revealed an increase in the total number of vesicles upon Doc2b overexpression, ruling out vesicle depletion as the cause...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates...... in 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....

  19. Factor Analysis with EM Algorithm Never Gives Improper Solutions when Sample Covariance and Initial Parameter Matrices Are Proper

    Science.gov (United States)

    Adachi, Kohei

    2013-01-01

    Rubin and Thayer ("Psychometrika," 47:69-76, 1982) proposed the EM algorithm for exploratory and confirmatory maximum likelihood factor analysis. In this paper, we prove the following fact: the EM algorithm always gives a proper solution with positive unique variances and factor correlations with absolute values that do not exceed one,…

  20. Evolution, development, and communication of branding in B2B markets

    OpenAIRE

    Seyedghorban, Zahra

    2017-01-01

    While, branding was traditionally viewed as having limited significance in business-to-business (B2B) markets, existing research not only acknowledges its existence, but emphasises its strategic importance in enhancing organisations’ competitive positions and financial performance. Given the fragmented research on B2B branding, there is a need to first provide a comprehensive review of B2B branding literature as a field of study by conducting a bibliometric investigation (Essay 1). The result...

  1. Some physico-chemical characteristics of a modified histone H2b on acute radiation affection

    International Nuclear Information System (INIS)

    Khrapunov, S.N.; Mel'nik, G.G.; Blyum, Ya.B.; Tsudzevich, B.A.; Kucherenko, N.E.

    1980-01-01

    A study was made of optical characteristics of histone H2b isolated from liver nuclei 12 h following irradiation in a dose of 0.21 C/kg. It was demonstrated that under similar conditions, the control and exposed histones H2b have different steric organization which correlates with radiation-induced modifications of lateral radicals in H2b histone molecules

  2. Effect of UGT2B7*2 and CYP2C8*4 polymorphisms on diclofenac metabolism.

    Science.gov (United States)

    Lazarska, Katarzyna E; Dekker, Stefan J; Vermeulen, Nico P E; Commandeur, Jan N M

    2018-03-01

    The use of diclofenac is associated with rare but severe drug-induced liver injury (DILI) in a very small number of patients. The factors which predispose susceptible patients to hepatotoxicity of diclofenac are still incompletely understood. Formation of protein-reactive metabolites by UDP-glucuronosyl transferases and cytochromes P450 is commonly considered to play an important role, as indicated by the detection of covalent protein adducts and antibodies in the serum of patients suffering from diclofenac-induced liver injury. Since no associations have been found with HLA-alleles, polymorphisms of genes encoding for proteins involved in the disposition of diclofenac may be important. Previous association studies showed that possession of the UGT2B7*2 and CYP2C8*4 alleles is more common in cases of diclofenac-induced DILI. In the present study, the metabolism of diclofenac by UGT2B7*2 and CYP2C8*4 was compared with their corresponding wild-type enzymes. Enzyme kinetic analysis revealed that recombinant UGT2B7*2 showed an almost 6-fold lower intrinsic clearance of diclofenac glucuronidation compared to UGT2B7*1. The mutant CYP2C8*4 showed approximately 35% reduced activity in the 4'-hydroxylation of diclofenac acyl glucuronide. Therefore, a decreased hepatic exposure to diclofenac acyl glucuronide is expected in patients with the UGT2B7*2 genotype. The increased risk for hepatotoxicity, therefore, might be the result from a shift to oxidative bioactivation to cytotoxic quinoneimines. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  3. Challenges and factors influencing initial trust and behavioral intention to use mobile banking services in the Philippines

    Directory of Open Access Journals (Sweden)

    Jason Lim Chiu

    2017-08-01

    Full Text Available Purpose - This paper aims to assess the direct effects of antecedents of initial trust, the mediating effect of trust and the moderating effect of demographic variables on non-adopters’ behavioral intention to use mobile banking. Design/methodology/approach - The study tested the models of theory of reasoned action and theory of planned behavior to evaluate potential antecedents of trust (diffusion of trust, infrastructure quality, perceived costs, privacy and security moderators (demographic variables and mediators (initial trust that will influence behavioral intention to use mobile banking. The Hayes’ Process Macro developed by Andrew F. Hayes (2013 was used as a statistical analysis in SPSS to estimates the path coefficients using multiple regression. The tool provides insights on the direct and indirect effect of the independent variable on the dependent variable through the existence of moderating variables and mediation variables. Findings - The results show that the non-adopters of mobile banking asserted that the antecedents of initial trust played a significant influence on behavioral intention to use online banking services. Originality/value - There is a dearth of literature addressing mobile banking in the Philippines. The first initial trust formation in internet banking using computer workstations and laptops in the Philippines was conducted by Chiu et al. (2016. This research fills in the gap by expanding and formulating a deeper understanding of the antecedents of initial trust that influence consumer behavioral intention that might be responsible for the slow diffusion of mobile banking services in the country. The results from this study will help financial institutions create a beneficial connection with consumers while alleviating the fears of non-adopters and enhancing their understanding of the benefits of mobile banking.

  4. Crystallization and preliminary crystallographic studies of the W2 domain of Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein

    International Nuclear Information System (INIS)

    Zhao, Hui; Wang, Hong; Liu, Huihui; Teng, Maikun; Li, Xu

    2012-01-01

    The crystallization and preliminary crystallographic studies of the carboxy-terminal domain of D. melanogaster eukaryotic translation initiation factor 5C domain-containing protein are reported. The Drosophila melanogaster eukaryotic translation initiation factor 5C domain-containing protein (ECP) is composed of two independently folded domains which belong to the basic leucine-zipper and W2 domain-containing protein (BZW) family. Based on the sequence similarity between the C-terminal W2 domain of ECP and some eukaryotic translation initiation factors (such as eIF2B∊, eIF4γ, eIF5 etc.), ECP has been speculated to participate in the translation initiation process. Structural information on the C-terminal W2 domain of ECP would be helpful in understanding the specific cellular function of this protein. Here, the W2 domain of ECP was expressed and crystallized. Crystals grown by the hanging-drop vapour-diffusion method diffracted to 2.70 Å resolution and belonged to space group I4, with unit-cell parameters a = b = 81.05, c = 57.44 Å. The Matthews coefficient suggested that there was one molecule per asymmetric unit in the crystal

  5. An assessment of the expected quality of Aeolus Level-2B wind products

    Directory of Open Access Journals (Sweden)

    Rennie Michael P.

    2018-01-01

    Full Text Available The ADM-Aeolus L2B horizontal line-of-sight wind products are discussed, including a brief introduction to the L2B processing methods. Realistic simulation of Aeolus followed by the Ground Segment processing chain is used to assess the expected error statistics of the L2B winds. Examples of the L2B winds simulated from realistic atmospheric cases are discussed. The aim of the paper is to give potential users an impression of the expected characteristics of Aeolus mission’s main product.

  6. TMEM106B and ApoE polymorphisms in CHMP2B-mediated frontotemporal dementia (FTD-3)

    DEFF Research Database (Denmark)

    Rostgaard, Nina; Roos, Peter; Budtz-Jørgensen, Esben

    2017-01-01

    (ApoE) in FTD is uncertain, though an established risk factor in Alzheimer's disease. In a unique Danish family, inherited FTD is caused by a mutation in the CHMP2B gene located on chromosome 3 (FTD-3). In this family, both risk factors TMEM106B and ApoE were analyzed and correlated to age at onset......Single-nucleotide polymorphisms in the TMEM106B gene have been identified as a risk factor in frontotemporal dementia (FTD). The major allele of SNP rs3173615 is a risk factor in sporadic FTD, whereas the minor allele seems protective in GRN- and C9orf72-mediated FTD. The role of apolipoprotein E...... factor with later AAO and AAI, whereas ε2 seemed to aggravate the disease with earlier AAO and AAD. These results indicate ApoE ε2 as a risk factor in FTD-3 and suggest a protective role of ε4....

  7. The role of social networks and media receptivity in predicting age of smoking initiation: a proportional hazards model of risk and protective factors.

    Science.gov (United States)

    Unger, J B; Chen, X

    1999-01-01

    The increasing prevalence of adolescent smoking demonstrates the need to identify factors associated with early smoking initiation. Previous studies have shown that smoking by social network members and receptivity to pro-tobacco marketing are associated with smoking among adolescents. It is not clear, however, whether these variables also are associated with the age of smoking initiation. Using data from 10,030 California adolescents, this study identified significant correlates of age of smoking initiation using bivariate methods and a multivariate proportional hazards model. Age of smoking initiation was earlier among those adolescents whose friends, siblings, or parents were smokers, and among those adolescents who had a favorite tobacco advertisement, had received tobacco promotional items, or would be willing to use tobacco promotional items. Results suggest that the smoking behavior of social network members and pro-tobacco media influences are important determinants of age of smoking initiation. Because early smoking initiation is associated with higher levels of addiction in adulthood, tobacco control programs should attempt to counter these influences.

  8. DNA dynamics play a role as a basal transcription factor in the positioning and regulation of gene transcription initiation

    OpenAIRE

    Alexandrov, Boian S.; Gelev, Vladimir; Yoo, Sang Wook; Alexandrov, Ludmil B.; Fukuyo, Yayoi; Bishop, Alan R.; Rasmussen, Kim ?.; Usheva, Anny

    2009-01-01

    We assess the role of DNA breathing dynamics as a determinant of promoter strength and transcription start site (TSS) location. We compare DNA Langevin dynamic profiles of representative gene promoters, calculated with the extended non-linear PBD model of DNA with experimental data on transcription factor binding and transcriptional activity. Our results demonstrate that DNA dynamic activity at the TSS can be suppressed by mutations that do not affect basal transcription factor binding–DNA co...

  9. The macrophage A2B adenosine receptor regulates tissue insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Hillary Johnston-Cox

    Full Text Available High fat diet (HFD-induced type 2 diabetes continues to be an epidemic with significant risk for various pathologies. Previously, we identified the A2b adenosine receptor (A2bAR, an established regulator of inflammation, as a regulator of HFD-induced insulin resistance. In particular, HFD was associated with vast upregulation of liver A2bAR in control mice, and while mice lacking this receptor showed augmented liver inflammation and tissue insulin resistance. As the A2bAR is expressed in different tissues, here, we provide the first lead to cellular mechanism by demonstrating that the receptor's influence on tissue insulin sensitivity is mediated via its expression in macrophages. This was shown using a newly generated transgenic mouse model expressing the A2bAR gene in the macrophage lineage on an otherwise A2bAR null background. Reinstatement of macrophage A2bAR expression in A2bAR null mice fed HFD restored insulin tolerance and tissue insulin signaling to the level of control mice. The molecular mechanism for this effect involves A2bAR-mediated changes in cyclic adenosine monophosphate in macrophages, reducing the expression and release of inflammatory cytokines, which downregulate insulin receptor-2. Thus, our results illustrate that macrophage A2bAR signaling is needed and sufficient for relaying the protective effect of the A2bAR against HFD-induced tissue inflammation and insulin resistance in mice.

  10. Field production and functional evaluation of chloroplast-derived interferon-alpha2b.

    Science.gov (United States)

    Arlen, Philip A; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M; Oishi, Karen K; Daniell, Henry

    2007-07-01

    Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-alpha2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-alpha2b for the treatment of hepatitis C infection is $26,000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-alpha2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-alpha2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-alpha2b had similar in vitro biological activity to commercially produced PEG-Introntrade mark when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-alpha2b were also seen in vivo. Chloroplast-derived IFN-alpha2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-alpha2b purified from chloroplast transgenic lines (cpIFN-alpha2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-alpha2b, transgene containment and biological activity akin to that of commercial preparations of IFN-alpha2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization.

  11. Field production and functional evaluation of chloroplast-derived interferon-α2b

    Science.gov (United States)

    Arlen, Philip A.; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M.; Oishi, Karen K.; Daniell, Henry

    2008-01-01

    Summary Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-α2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-α2b for the treatment of hepatitis C infection is $26 000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-α2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-α2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-α2b had similar in vitro biological activity to commercially produced PEG-Intron™ when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-α2b were also seen in vivo . Chloroplast-derived IFN-α2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-α2b purified from chloroplast transgenic lines (cpIFN-α2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-α2b, transgene containment and biological activity akin to that of commercial preparations of IFN-α2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization. PMID:17490449

  12. Biodistribution analysis of 125I-albumin-IFN-alpha2b fusion protein in rats

    International Nuclear Information System (INIS)

    Zhou Yaoyuan; Zhang Rongjun; Cai Gangming; Gu Xiaobo; Jiang Mengjun; Zhang Bo; Yang Min; Cao Guoxian; Yang Jianliang

    2009-01-01

    125 I-albumin-IFN-alpha2b was prepared with the methods of Ch-T and purified with PD-10 column. The radiochemical purity was measured with TCA (trichloroacetic acid) precipitation. The antiviral activities of 125 I-albumin-IFN-alpha2b and albumin-IFN-alpha2b were compared with WISH/VSV system in vitro. SD rats were injected with 125 I-albumin-IFN-alpha2b subcutaneously and sacrificed at 0.5, 2, 6, 24, 48, 90, 180 and 300 h post-injection. Selected organs were dissected, weighed and their radioactivity was measured using γ-counter. The accumulated radioactivity in the tissues was calculated in terms of percentage of injected dose per gram organ (%ID·g -1 ). The labeling yield was 82.72%. The radiochemical purity of 125 I-albumin-IFN-alpha2b was 95.53%, and its radioactivity was 0.26 MBq/μg. The antiviral bioactivities of albumin-IFN-alpha2b and 125 I-albumin- IFN-alpha2b did not change. Biodistribution analysis of 125 I-albumin-IFN-alpha2b in rats showed that concentrated 125 I-albumin-IFN-alpha2b in blood reached maximum at 6 h post injection, and eliminated slowly. No specific accumulation was seen in other tissues. 125 I-albumin-IFN-alpha2b could maintain in peripheral blood for a long time and it meant albumin-IFN-alpha2b would be an effective long-term interferon. (authors)

  13. The ADRA2B gene in the production of false memories for affective information in healthy female volunteers.

    Science.gov (United States)

    Fairfield, Beth; Mammarella, Nicola; Di Domenico, Alberto; D'Aurora, Marco; Stuppia, Liborio; Gatta, Valentina

    2017-08-30

    False memories are common memory distortions in everyday life and seem to increase with affectively connoted complex information. In line with recent studies showing a significant interaction between the noradrenergic system and emotional memory, we investigated whether healthy volunteer carriers of the deletion variant of the ADRA2B gene that codes for the α2b-adrenergic receptor are more prone to false memories than non-carriers. In this study, we collected genotype data from 212 healthy female volunteers; 91 ADRA2B carriers and 121 non-carriers. To assess gene effects on false memories for affective information, factorial mixed model analysis of variances (ANOVAs) were conducted with genotype as the between-subjects factor and type of memory error as the within-subjects factor. We found that although carriers and non-carriers made comparable numbers of false memory errors, they showed differences in the direction of valence biases, especially for inferential causal errors. Specifically, carriers produced fewer causal false memory errors for scripts with a negative outcome, whereas non-carriers showed a more general emotional effect and made fewer causal errors with both positive and negative outcomes. These findings suggest that putatively higher levels of noradrenaline in deletion carriers may enhance short-term consolidation of negative information and lead to fewer memory distortions when facing negative events. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. [Association polymorphic variants of GRIN2B gene with paranoid schizophrenia and response to common neuroleptics in Russians and Tatars from Bashkortostan Republic].

    Science.gov (United States)

    Gareeva, A E; Zakirov, D F; Khusnutdinova, E K

    2013-09-01

    An analysis of the association of paranoid schizophrenia seeking with polymorphic variants of GRIN2B gene was performed in order to identify genetic risk factors of disease development and genetic markers of the response to therapy by neuroleptics in Russian and Tatar patients from Bashkortostan Republic (BB). In the course of the analysis, we revealed the following: 1) genetic markers of increased risk of developing paranoid schizophrenia in various ethnic groups, including, in Tatars, the GRIN2B* T/*Tgenotype (p = 0.003; OR = 2.33) and GRIN2B*T allele (p = 0.001; OR = 2.36), rs1805247; in Russians, the GRIN2B*T/*T genotype (p = 0.038; OR = 2.12) and GRIN2B* T allele (p = 0.028; OR = 2.03), rs1805247, genotype GRIN2B*A/*A (p = 0.042; OR = 2.12), rs1805476; 2) genetic markers of the reduced risk of developing paranoid schizophrenia; 3) genetic markers of therapy response and the risk of side effects development during neuroleptics (haloperidol) treatment in Bashkortostan. The significant interethnic diversity of genetic factors related to the risk of this disease development was noted.

  15. Identification of novel small molecule inhibitors against NS2B/NS3 serine protease from Zika virus

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun; Ren, Jinhong; Nocadello, Salvatore; Rice, Amy J.; Ojeda, Isabel; Light, Samuel; Minasov, George; Vargas, Jason; Nagarathnam, Dhanapalan; Anderson, Wayne F.; Johnson, Michael E. (UIC); (NWU); (Novalex); (DNSK)

    2016-12-26

    Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain–Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. Our studies have identified several compounds with inhibitory activity (IC50) and binding affinity (KD) of ~5–10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a Ki value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a “pre-open conformation”, a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.

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

    DEFF Research Database (Denmark)

    Toft, Katrine Nørgaard

    The field-induced magnetic structures of ErNi2B2C and TmNi2B2C in are especially interesting because the field suppresses the superconducting order parameter and therefore the magnetic properties can be studied while varying the strength ofsuperconductivity. ErNi2B2C: For magnetic fields along all.......483,0,0). The appearance of the QN phase wasinitially believed to be caused by the suppression of superconductivity. This suppression should make it favorable to create a magnetic order with a Q-vector determined by the maximum in the magnetic susceptibility at the Fermi surface nesting vector QN.The phase diagram...... three symmetry directions, the observed magnetic structures have a period corresponding to the Fermi surface nesting structure. The phase diagrams present all the observed magnetic structures.Two results remain unresolved: 1. When applying the magnetic field along [010], the minority domain (QNB = (0,Q...

  17. Whole blood assay for NK activity in splenectomized and non-splenectomized hairy cell leukemia patients during IFN-alpha-2b treatment

    DEFF Research Database (Denmark)

    Nielsen, B; Hokland, P; Ellegaard, J

    1989-01-01

    Natural killer cell (NK) activity in peripheral blood (PB) was followed longitudinally for up to 2 yr after initiation of low-dose IFN-alpha-2b therapy in nine hairy cell leukemia (HCL) patients. A whole blood NK (WB-NK) assay was employed in order to measure the NK activity per unit blood. The p...

  18. AMP and adenosine are both ligands for adenosine 2B receptor signaling.

    Science.gov (United States)

    Holien, Jessica K; Seibt, Benjamin; Roberts, Veena; Salvaris, Evelyn; Parker, Michael W; Cowan, Peter J; Dwyer, Karen M

    2018-01-15

    Adenosine is considered the canonical ligand for the adenosine 2B receptor (A 2B R). A 2B R is upregulated following kidney ischemia augmenting post ischemic blood flow and limiting tubular injury. In this context the beneficial effect of A 2B R signaling has been attributed to an increase in the pericellular concentration of adenosine. However, following renal ischemia both kidney adenosine monophosphate (AMP) and adenosine levels are substantially increased. Using computational modeling and calcium mobilization assays, we investigated whether AMP could also be a ligand for A 2B R. The computational modeling suggested that AMP interacts with more favorable energy to A 2B R compared with adenosine. Furthermore, AMPαS, a non-hydrolyzable form of AMP, increased calcium uptake by Chinese hamster ovary (CHO) cells expressing the human A 2B R, indicating preferential signaling via the G q pathway. Therefore, a putative AMP-A 2B R interaction is supported by the computational modeling data and the biological results suggest this interaction involves preferential G q activation. These data provide further insights into the role of purinergic signaling in the pathophysiology of renal IRI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. 14 CFR 250.2b - Carriers to request volunteers for denied boarding.

    Science.gov (United States)

    2010-01-01

    ... boarding. 250.2b Section 250.2b Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION... boarding. (a) In the event of an oversold flight, every carrier shall request volunteers for denied boarding before using any other boarding priority. A “volunteer” is a person who responds to the carrier's...

  20. RSCAT_LEVEL_2B_OWV_COMP_12_V1.1:1

    Data.gov (United States)

    National Aeronautics and Space Administration — This dataset contains the RapidScat Level 2B 12.5km Version 1.1 science-quality ocean surface wind vectors. The Level 2B wind vectors are binned on a 12.5 km Wind...

  1. Evidence for multiple polytypes of semiconducting boron carbide (C2B10) from electronic structure

    International Nuclear Information System (INIS)

    Lunca-Popa, Petru; Brand, J I; Balaz, Snjezana; Rosa, Luis G; Boag, N M; Bai Mengjun; Robertson, B W; Dowben, P A

    2005-01-01

    Boron carbides fabricated via plasma enhanced chemical vapour deposition from different isomeric source compounds with the same C 2 B 10 H 12 closo-icosahedral structure result in materials with very different direct (optical) band gaps. This provides compelling evidence for the existence of multiple polytypes of C 2 B 10 boron carbide and is consistent with electron diffraction results

  2. Neutron diffraction studies of Ho1-xYxNi2B2C compounds

    DEFF Research Database (Denmark)

    Chang, L.J.; Tomy, C.V.; Paul, D.M.K.

    1996-01-01

    Neutron diffraction measurements have been carried out to investigate the nature of magnetic ordering in Ho(1-x)Y(x)Ni(2)B(2)C (x = 0, 0.1 and 0.2) compounds. HoNi(2)B(2)C shows a complex type of magnetic ordering below the superconducting transition, with a commensurate antiferromagnetic ordering...

  3. GRIN2B encephalopathy : Novel findings on phenotype, variant clustering, functional consequences and treatment aspects

    NARCIS (Netherlands)

    Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah; Winschel, Alexander; Chen, Wenjuan; Hu, Chun; Kusumoto, Hirofumi; Heyne, Henrike O; Helbig, Katherine L; Tang, Sha; Willing, Marcia C; Tinkle, Brad T; Adams, Darius J; Depienne, Christel; Keren, Boris; Mignot, Cyril; Frengen, Eirik; Strømme, Petter; Biskup, Saskia; Döcker, Dennis; Strom, Tim M.; Mefford, Heather C.; Myers, Candace T.; Muir, Alison M; LaCroix, Amy; Sadleir, Lynette G.; Scheffer, Ingrid E.; Brilstra, Eva; van Haelst, Mieke M.; van der Smagt, Jasper J.; Bok, Levinus A; Møller, Rikke S.; Jensen, Uffe Birk; Millichap, John J; Berg, Anne T; Goldberg, Ethan M; De Bie, Isabelle; Fox, Stephanie; Major, Philippe; Jones, Julie R; Zackai, Elaine H.; Abou Jamra, Rami; Rolfs, Arndt; Leventer, Richard J; Lawson, John A; Roscioli, Tony; Jansen, Floor E.; Ranza, Emmanuelle; Korff, Christian M; Lehesjoki, Anna-Elina; Courage, Carolina; Linnankivi, Tarja; Smith, Douglas R; Stanley, Christine; Mintz, Mark; McKnight, Dianalee; Decker, Amy; Tan, Wen-Hann; Tarnopolsky, Mark A; Brady, Lauren I; Wolff, Markus; Dondit, Lutz; Pedro, Helio F; Parisotto, Sarah E; Jones, Kelly L; Patel, Anup D; Franz, David N; Vanzo, Rena; Marco, Elysa; Ranells, Judith D; Di Donato, Nataliya; Dobyns, William B.; Laube, Bodo; Traynelis, Stephen F; Lemke, Johannes R.

    2017-01-01

    Background: We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Methods: Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  5. SRC Inhibition Reduces NR2B Surface Expression and Synaptic Plasticity in the Amygdala

    Science.gov (United States)

    Sinai, Laleh; Duffy, Steven; Roder, John C.

    2010-01-01

    The Src protein tyrosine kinase plays a central role in the regulation of N-methyl-d-aspartate receptor (NMDAR) activity by regulating NMDAR subunit 2B (NR2B) surface expression. In the amygdala, NMDA-dependent synaptic plasticity resulting from convergent somatosensory and auditory inputs contributes to emotional memory; however, the role of Src…

  6. Automated Report Generation for Research Data Repositories: From i2b2 to PDF.

    Science.gov (United States)

    Thiemann, Volker S; Xu, Tingyan; Röhrig, Rainer; Majeed, Raphael W

    2017-01-01

    We developed an automated toolchain to generate reports of i2b2 data. It is based on free open source software and runs on a Java Application Server. It is sucessfully used in an ED registry project. The solution is highly configurable and portable to other projects based on i2b2 or compatible factual data sources.

  7. The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, Vengadesan [Center for Biophysical Sciences and Engineering, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Xu, Yuanyuan [Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Macon, Kevin [Center for Biophysical Sciences and Engineering, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Volanakis, John E. [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Narayana, Sthanam V. L., E-mail: narayana@uab.edu [Center for Biophysical Sciences and Engineering, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

    2009-03-01

    The crystal structure of C2b has been determined at 1.8 Å resolution, which reveals the arrangement of its three complement control protein (CCP) modules. A model for complement component C2 is presented and its conformational changes during the C3-convertase formation are also discussed. The second component of complement (C2) is a multi-domain serine protease that provides catalytic activity for the C3 and C5 convertases of the classical and lectin pathways of human complement. The formation of these convertases requires the Mg{sup 2+}-dependent binding of C2 to C4b and the subsequent cleavage of C2 by C1s or MASP2, respectively. The crystal structure of full-length C2 is not yet available, although the structure of its C-terminal catalytic segment C2a has been determined. The crystal structure of the N-terminal segment C2b of C2 determined to 1.8 Å resolution presented here reveals the arrangement of its three CCP domains. The domains are arranged differently compared with most other CCP-domain assemblies, but their arrangement is similar to that found in the Ba part of the full-length factor B structure. The crystal structures of C2a, C2b and full-length factor B are used to generate a model for C2 and a discussion of the domain association and possible interactions with C4b during formation of the C4b–C2 complex is presented. The results of this study also suggest that upon cleavage by C1s, C2a domains undergo conformational rotation while bound to C4b and the released C2b domains may remain folded together similar to as observed in the intact protein.

  8. The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation

    International Nuclear Information System (INIS)

    Krishnan, Vengadesan; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V. L.

    2009-01-01

    The crystal structure of C2b has been determined at 1.8 Å resolution, which reveals the arrangement of its three complement control protein (CCP) modules. A model for complement component C2 is presented and its conformational changes during the C3-convertase formation are also discussed. The second component of complement (C2) is a multi-domain serine protease that provides catalytic activity for the C3 and C5 convertases of the classical and lectin pathways of human complement. The formation of these convertases requires the Mg 2+ -dependent binding of C2 to C4b and the subsequent cleavage of C2 by C1s or MASP2, respectively. The crystal structure of full-length C2 is not yet available, although the structure of its C-terminal catalytic segment C2a has been determined. The crystal structure of the N-terminal segment C2b of C2 determined to 1.8 Å resolution presented here reveals the arrangement of its three CCP domains. The domains are arranged differently compared with most other CCP-domain assemblies, but their arrangement is similar to that found in the Ba part of the full-length factor B structure. The crystal structures of C2a, C2b and full-length factor B are used to generate a model for C2 and a discussion of the domain association and possible interactions with C4b during formation of the C4b–C2 complex is presented. The results of this study also suggest that upon cleavage by C1s, C2a domains undergo conformational rotation while bound to C4b and the released C2b domains may remain folded together similar to as observed in the intact protein

  9. ADRA2B deletion variant selectively predicts stress-induced enhancement of long-term memory in females.

    Science.gov (United States)

    Zoladz, Phillip R; Kalchik, Andrea E; Hoffman, Mackenzie M; Aufdenkampe, Rachael L; Lyle, Sarah M; Peters, David M; Brown, Callie M; Cadle, Chelsea E; Scharf, Amanda R; Dailey, Alison M; Wolters, Nicholas E; Talbot, Jeffery N; Rorabaugh, Boyd R

    2014-10-01

    Clarifying the mechanisms that underlie stress-induced alterations of learning and memory may lend important insight into susceptibility factors governing the development of stress-related psychological disorders, such as post-traumatic stress disorder (PTSD). Previous work has shown that carriers of the ADRA2B Glu(301)-Glu(303) deletion variant exhibit enhanced emotional memory, greater amygdala responses to emotional stimuli and greater intrusiveness of traumatic memories. We speculated that carriers of this deletion variant might also be more vulnerable to stress-induced enhancements of long-term memory, which would implicate the variant as a possible susceptibility factor for traumatic memory formation. One hundred and twenty participants (72 males, 48 females) submerged their hand in ice cold (stress) or warm (no stress) water for 3min. Immediately afterwards, they studied a list of 42 words varying in emotional valence and arousal and then completed an immediate free recall test. Twenty-four hours later, participants' memory for the word list was examined via free recall and recognition assessments. Stressed participants exhibiting greater heart rate responses to the stressor had enhanced recall on the 24-h assessment. Importantly, this enhancement was independent of the emotional nature of the learned information. In contrast to previous work, we did not observe a general enhancement of memory for emotional information in ADRA2B deletion carriers. However, stressed female ADRA2B deletion carriers, particularly those exhibiting greater heart rate responses to the stressor, did demonstrate greater recognition memory than all other groups. Collectively, these findings implicate autonomic mechanisms in the pre-learning stress-induced enhancement of long-term memory and suggest that the ADRA2B deletion variant may selectively predict stress effects on memory in females. Such findings lend important insight into the physiological mechanisms underlying stress

  10. Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

    DEFF Research Database (Denmark)

    Corsino, P.; Davis, B.; Law, M.

    2007-01-01

    ) promoter results in mammary gland hyperplasia and fibrosis, and mammary tumors. Cell lines isolated from MMTV-cyclin D1-Cdk2 (MMTV-D1K2) tumors exhibit Rb and p130 hyperphosphorylation and up-regulation of the protein products of E2F-dependent genes. These results suggest that cyclin D1/Cdk2 complexes may...... sites. Together, these results suggest that deregulation of the Cdk/Rb/E2F axis reprograms mammary epithelial cells to initiate a paracrine loop with tumor-associated fibroblasts involving TGF beta and HGF, resulting in desmoplasia. The MMTV-DIK2 mice should provide a useful model system...

  11. Investigating potential exogenous tumor initiating and promoting factors for Cutaneous T-Cell Lymphomas (CTCL), a rare skin malignancy

    DEFF Research Database (Denmark)

    Litvinov, Ivan V.; Shtreis, Anna; Kobayashi, Kenneth

    2016-01-01

    -Cell lymphotropic virus type 1 (HTLV1), Epstein-Barr virus (EBV), and herpes simplex virus (HSV). In this report, we review recent evidence evaluating the involvement of these agents in cancer initiation/progression. Most importantly, recent molecular experimental evidence documented for the first time that S....... aureus can activate oncogenic STAT3 signaling in malignant T cells. Specifically, S. aureus Enterotoxin type A (SEA) was recently shown to trigger non-malignant infiltrating T cells to release IL-2 and other cytokines. These signals upon binging to their cognate receptors on malignant T cells...

  12. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth

    DEFF Research Database (Denmark)

    Zhao, Jian; Yuan, Xuejun; Frödin, Morten

    2003-01-01

    -specific transcription initiation factor TIF-IA. Activation of TIF-IA and ribosomal gene transcription is sensitive to PD98059, indicating that TIF-IA is targeted by MAPK in vivo. Phosphopeptide mapping and mutational analysis reveals two serine residues (S633 and S649) that are phosphorylated by ERK and RSK kinases....... Replacement of S649 by alanine inactivates TIF-IA, inhibits pre-rRNA synthesis, and retards cell growth. The results provide a link between growth factor signaling, ribosome production, and cell growth, and may have a major impact on the mechanism of cell transformation....

  13. Impact of weight-based ribavirin with peginterferon alfa-2b in African Americans with hepatitis C virus genotype 1.

    Science.gov (United States)

    Jacobson, Ira M; Brown, Robert S; McCone, Jonathan; Black, Martin; Albert, Clive; Dragutsky, Michael S; Siddiqui, Firdous A; Hargrave, Thomas; Kwo, Paul Y; Lambiase, Louis; Galler, Greg W; Araya, Victor; Freilich, Bradley; Harvey, Joann; Griffel, Louis H; Brass, Clifford A

    2007-10-01

    WIN-R (Weight-based dosing of pegINterferon alfa-2b and Ribavirin) was a multicenter, randomized, open-label, investigator-initiated trial involving 236 community and academic sites in the United States, comparing response to pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in treatment-naive patients with chronic hepatitis C and compensated liver disease. Patients were randomized to receive PEG-IFN alfa-2b at 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based-dose RBV (800 mg/day for weight 85-105 kg, or 1400 mg/day for >105- or =65 kg was the primary end point. Low SVR rates have been reported among African American individuals, in whom there is a preponderance of HCV genotype 1. This subanalysis of WIN-R was conducted to evaluate the efficacy of weight-based dosing among African American individuals with genotype 1 infection enrolled in the trial. Of 362 African American patients in the primary efficacy analysis, 188 received RBV flat dosing and 174 received weight-based dosing. SVR rates were higher (21% versus 10%; P = 0.0006) and relapse rates were lower (22% versus 30%) in the weight-based-dose group than in the flat-dose group. Safety and rates of drug discontinuation were similar between the 2 groups. Weight-based dosing of RBV is more effective than flat dosing in combination with PEG-IFN alfa-2b in African American individuals with HCV genotype 1. Even with weight-based dosing, response rates in African American individuals are lower than reported in other ethnic groups.

  14. Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.

    Science.gov (United States)

    Chung, Liliane; Bailey, Dalan; Leen, Eoin N; Emmott, Edward P; Chaudhry, Yasmin; Roberts, Lisa O; Curry, Stephen; Locker, Nicolas; Goodfellow, Ian G

    2014-08-01

    Viruses have evolved a variety of mechanisms to usurp the host cell translation machinery to enable translation of the viral genome in the presence of high levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man, have evolved a mechanism that relies on the interaction of translation initiation factors with the virus-encoded VPg protein covalently linked to the 5' end of the viral RNA. To further characterize this novel mechanism of translation initiation, we have used proteomics to identify the components of the norovirus translation initiation factor complex. This approach revealed that VPg binds directly to the eIF4F complex, with a high affinity interaction occurring between VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is important for the VPg-eIF4G interaction; viruses with mutations that alter or disrupt this interaction are debilitated or non-viable. Our results shed new light on the unusual mechanisms of protein-directed translation initiation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Timely initiation of breastfeeding and associated factors among mothers in Motta town, East Gojjam zone, Amhara regional state, Ethiopia, 2015: a cross-sectional study.

    Science.gov (United States)

    Tewabe, Tilahun

    2016-10-19

    Timely initiation of breastfeeding within one hour after birth and exclusive breastfeeding is recommended for the first six months of infant life along with continuation of breastfeeding up to two years. Timely initiation of breastfeeding has the potential to prevent 22 % of neonatal deaths. The objective of this study was to assess timely initiation of breastfeeding and associated factors among mothers who have infants less than six months of age in Motta town, East Gojjam, Amhara Regional State, Ethiopia. Community based quantitative cross-sectional study was conducted from April 7, 2015 to May 7, 2015. Simple random sampling technique was applied after taking all registered mothers who have infants less than 6 months old from local health extension workers of each kebele. A total of 423 mothers with infant less than six month old were included in this study. The data was collected from all four Kebeles using interviewer administered questionnaire. Descriptive and inferential statistics were used to present the data. Both bivariate and multivariate logistic regression analyses were used to identify factors associated with timely initiation breastfeeding. Prevalence of timely initiation of breastfeeding was78.8 % [95 % CL: 74.88 %, 82.72 %]. Mothers who gave birth to their infant in a health institution [AOR = 3.486(1.253, 9.700)], birthed vaginally [AOR = 5.722(3.134, 11.246)] and didn't give prelacteal food [AOR = 4.627(2.095, 10.220)] were more likely to initiate breastfeeding early than their counterparts. Prevalence of timely initiation of breastfeeding in the study area was 78.8 %. Place of delivery, mode of delivery and prelactal feeding were the independent predictors of timely initiation of breastfeeding. Recommendations to increase timely initiation of breastfeeding were: encouraging mothers to deliver their child in a health institution, minimizing caesarean delivery as much as possible and educating mothers and community as a whole

  16. ERK 1/2 kinase metabolic pathway is responsible for phosphorylation of translation initiation factor eIF4E during in vitro maturation of pig oocytes

    Czech Academy of Sciences Publication Activity Database

    Ellederová, Zdeňka; Cais, Ondřej; Šušor, Andrej; Uhlířová, Kateřina; Kovářová, Hana; Jelínková, Lucie; Tomek, W.; Kubelka, Michal

    2008-01-01

    Roč. 75, č. 2 (2008), s. 309-317 ISSN 1040-452X R&D Projects: GA ČR GA524/04/0104 Grant - others:Deutsche Forschungsgemeinschaft(DE) 463 TSE 113/28 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50110509 Keywords : meiosis * translation initiation * eIF4E Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.287, year: 2008

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

    DEFF Research Database (Denmark)

    Nielsen, Troels Tolstrup; Mizielinska, Sarah; Hasholt, Lis

    2012-01-01

    role in the pathogenesis of the disease. METHODS: In the present study, we used lentiviral vectors to efficiently knockdown CHMP2B by delivering microRNA embedded small hairpin RNAs. RESULTS: We show that CHMP2B can be efficiently knocked down in patient fibroblasts using an RNA interference approach......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......-III complex, which is involved in endosomal trafficking of proteins targeted for degradation in lysosomes. Mutations in CHMP2B result in abnormal endosomal structures in patient fibroblasts and patient brains, probably through a gain-of-function mechanism, suggesting that the endosomal pathway plays a central...

  18. Nonlinear Elasticity of Borocarbide Superconductor YNi2B2C: A First-Principles Study

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    Lili Liu

    2017-01-01

    Full Text Available First-principles calculations combined with homogeneous deformation methods are used to investigate the second- and third-order elastic constants of YNi2B2C with tetragonal structure. The predicted lattice constants and second-order elastic constants of YNi2B2C agree well with the available data. The effective second-order elastic constants are obtained from the second- and third-order elastic constants for YNi2B2C. Based on the effective second-order elastic constants, Pugh’s modulus ratio, Poisson’s ratio, and Vickers hardness of YNi2B2C under high pressure are further investigated. It is shown that the ductility of YNi2B2C increases with increasing pressure.

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

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    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.

  20. Stoichiometry and Change of the mRNA Closed-Loop Factors as Translating Ribosomes Transit from Initiation to Elongation

    Czech Academy of Sciences Publication Activity Database

    Wang, X.; Xi, W.; Toomey, S.; Chiang, Y.-CH.; Hašek, Jiří; Laue, T.M.; Denis, C.L.

    2016-01-01

    Roč. 11, č. 3 (2016), e0150616 E-ISSN 1932-6203 Institutional support: RVO:61388971 Keywords : DEADENYLATION IN-VIVO * SACCHAROMYCES-CEREVISIAE * POLY(A)-BINDING PROTEIN Subject RIV: EE - Microbiology, Virology Impact factor: 2.806, year: 2016

  1. Analyzing EFL Teachers’ Initial Job Motivation and Factors Effecting Their Motivation in Fezalar Educational Institutions in Iraq

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    Selcuk Koran

    2015-02-01

    Full Text Available Teacher motivation is one of the primary variables of students’ high performance. It is experienced that students whose teachers are highly motivated are more engaged in the learning process. Therefore, it’s mostly the teacher who determines the level of success or failure in achieving institution’s goal in the educational process. Thus, teachers are expected to demonstrate a high job motivation performance by administrations. However, some teachers seem naturally enthusiastic about teaching while others need to be stimulated, inspired and challenged. There are several factors that provide teachers with necessary motivation driven by which they can work effectively. These factors can be emotional, financial, physical or academic. This study is an attempt to find out what motivates teachers to enter this profession, since the reasons of entering this job has significant influence on their commitment to the job, investigate factors which are responsible for high or low motivation of language teachers in Fezalar Educational Institutions (FEI, which is a Turkish private institution that operates in Iraq, and ascertain the degree to which intrinsic and extrinsic motivational factors impact teachers in their work situation. Based on the review of the recent researches of motivation, in general, and of language teacher motivation, in particular, and relying on the qualitative and quantitative study of the issue, a detailed analysis of some aspects of foreign language teacher motivation is presented in the article. Keywords: teacher motivation, job satisfaction, foreign language teaching, L2 teacher motivation

  2. Leading-edge flow criticality as a governing factor in leading-edge vortex initiation in unsteady airfoil flows

    Science.gov (United States)

    Ramesh, Kiran; Granlund, Kenneth; Ol, Michael V.; Gopalarathnam, Ashok; Edwards, Jack R.

    2018-04-01

    A leading-edge suction parameter (LESP) that is derived from potential flow theory as a measure of suction at the airfoil leading edge is used to study initiation of leading-edge vortex (LEV) formation in this article. The LESP hypothesis is presented, which states that LEV formation in unsteady flows for specified airfoil shape and Reynolds number occurs at a critical constant value of LESP, regardless of motion kinematics. This hypothesis is tested and validated against a large set of data from CFD and experimental studies of flows with LEV formation. The hypothesis is seen to hold except in cases with slow-rate kinematics which evince significant trailing-edge separation (which refers here to separation leading to reversed flow on the aft portion of the upper surface), thereby establishing the envelope of validity. The implication is that the critical LESP value for an airfoil-Reynolds number combination may be calibrated using CFD or experiment for just one motion and then employed to predict LEV initiation for any other (fast-rate) motion. It is also shown that the LESP concept may be used in an inverse mode to generate motion kinematics that would either prevent LEV formation or trigger the same as per aerodynamic requirements.

  3. Microstructure and properties of multiphase sintered cermets Fe-Fe{sub 2}B; Mikrostruktura i wlasnosci spiekanych reakcyjnie cermetali Fe-Fe{sub 2}B

    Energy Technology Data Exchange (ETDEWEB)

    Nowacki, J. [Wydzial Inzynierii Materialowej, Politechnika Szczecinska, Szczecin (Poland); Klimek, L. [Instytut Inzynierii Materialowej i Technik Bezwiorowych, Politechnika Lodzka, Lodz (Poland)

    1998-12-31

    The process of multiphase sintering of iron in the vacuum has been analysed. As a result of the process iron-iron boride cermets have been produced. Fe-Fe{sub 2}B cermets were obtained as a result of sintering of the Fe and B pure elements in the vacuum. Attemps at sintering in the solid phase and with the participation of the liquid phase, the Fe-Fe{sub 2}B eutectic, have been made. Metallographic qualitative and quantitative studies, X-ray structural qualitative and qauantitative analysis allowed to determine the structure of Fe{sub 2}B cermets, as well as a description of the kinetics of quantitative changes in phase proportions in the course of sintering. It has been found that their structure varies widely depending on sintering parameters and the composition of the sinters. Measurements of the Fe-Fe{sub 2}B cermets hardness and measurements on wear during dry friction by the pin-on-disc method have shown distinct advantages of the cermets as a modern constructional materials. The hardness of Fe-Fe{sub 2}B cermets, depending on their chemical composition and sintering parameters, ranges widely from 150 to 1500 HV, and their resistance to wear is comparable to that of diffusively boronized steels. FeFe{sub 2}B cermets are a composite material in which iron boride, Fe{sub 2}B, with a hardness of about 1800 HV plays the role of the reinforcement,while iron-iron boride, Fe-Fe{sub 2}B, with a hardness of about 500 HV plays the role of matrix. The eutectic in the spaces between iron boride grains is composed of boron solid solution plates in iron with a hardness of arround 250 HV, and iron boride, Fe{sub 2}B, plates with a hardness of approximaly 1800 HV. The combination of such different materials, a hard reinforcement and a relatively plastic matrix produces favourable properties of the cermet thus produced high hardness (1500 HV) constant over whole cross section of the material, resistance of abrasive wear and acceptable ductility. The properties mentioned above

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

    Science.gov (United States)

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

    2014-03-01

    Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A contribution of serotonin to valvular disease has been reported, but myocardial expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA expression in dogs with DCM and to correlate results with expression of markers for inflammation and remodelling. Myocardial samples from eight healthy dogs, four dogs with DCM, five with cardiac diseases other than DCM and six with systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using quantitative PCR (qPCR). The results were compared to mRNA expression of selected cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and immunohistochemistry were employed to identify the cells expressing 5-HTR2B. The myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs with DCM, 5-HTR2B mRNA values were significantly greater than in all other groups, with highest levels of expression in the left ventricle and right atrium. Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs and TIMPs was observed. The findings suggest that serotonin might play a role in normal cardiac structure and function and could contribute to myocardial remodelling and functional impairment in dogs with DCM. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. KDM2B overexpression correlates with poor prognosis and regulates glioma cell growth

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    Wang Y

    2018-01-01

    Full Text Available Yiwei Wang,1 Jin Zang,1 Dongyong Zhang,2 Zhenxiang Sun,1 Bo Qiu,2 Xiaojie Wang1 1Department of Human Anatomy, Shenyang Medical College, Huanggu District, Shenyang City, 2Department of Neurosurgery, First Affiliated Hospital of China Medical University, Heping District, Shenyang City, Liaoning Province, ChinaBackground: Gliomas are one of the most lethal cancers in the human central nervous system. Despite clinical treatment advancements, the prognosis of patients with glioma remains poor. KDM2B is a histone lysine demethylase, which has been observed in multiple tumors. But the concrete role of KDM2B in gliomas remains to be further illustrated.Methods: The KDM2B expression in gliomas was detected with immunohistochemistry and Western blot assay. Furthermore, knockdown of KDM2B in U87 and U251 glioma cell lines, the proliferation capacity was evaluated by cell viability assay, colon formation assay and flow cytometry in vitro. Western blot assay was used to analyze the p21, EZH2 and cyclinD1 changes followed by knockdown of KDM2B.Results: KDM2B was upregulated in tissues of glioma patients, and the expression was correlated to cancer progression. Downregulation of KDM2B in U87 and U251 glioma cell lines inhibited cell proliferation and arrested cell cycle in G0/G1 phase. In addition, silencing KDM2B promoted the upregulation of p21 while reduced the expression of EZH2 and cyclinD1.Conclusion: Taken together, our results revealed that KDM2B might influence gliomas growth and act as a novel therapeutic target for glioma patients.Keywords: EZH2, glioma, KDM2B, P21

  6. Factors associated with late ANC initiation among pregnant women in select public health centers of Addis Ababa, Ethiopia: unmatched case–control study design

    Science.gov (United States)

    Gebrekidan, Kahasse; Worku, Alemayehu

    2017-01-01

    Background Although Ethiopia has shown remarkable achievements in reducing maternal mortality in the last 10 years, the prevalence of late antenatal care (ANC) initiation is still high in the country. Objective The primary purpose of this study was to identify the factors related to late ANC initiation among pregnant women in selected public health centers in Addis Ababa, Ethiopia. Subjects and methods A total of 402 pregnant women (cases=134, controls=268) were recruited using multistage sampling. The design selected for the study was unmatched case–control. EpiData version 3.02 and SPSS version 20.0 were used for data entry and statistical analysis, respectively. Binary logistic regression model was used to model the odds of late ANC initiation. Results The odds of attending ANC late were significantly higher for mothers with a monthly household income of $8.50 to start the ANC service (AOR=3.04; 95% CI: 1.98, 4.67). Conclusion Low educational level, low income of the household, unplanned pregnancy, stay for ANC service were the main predictors of late ANC initiation. Therefore, any intervention which would need to improve early ANC initiation should focus on economic empowerment of women, and tailored health education for migrant women should be strengthened. PMID:29138615

  7. Factors associated with late ANC initiation among pregnant women in select public health centers of Addis Ababa, Ethiopia: unmatched case-control study design.

    Science.gov (United States)

    Gebrekidan, Kahasse; Worku, Alemayehu

    2017-01-01

    Although Ethiopia has shown remarkable achievements in reducing maternal mortality in the last 10 years, the prevalence of late antenatal care (ANC) initiation is still high in the country. The primary purpose of this study was to identify the factors related to late ANC initiation among pregnant women in selected public health centers in Addis Ababa, Ethiopia. A total of 402 pregnant women (cases=134, controls=268) were recruited using multistage sampling. The design selected for the study was unmatched case-control. EpiData version 3.02 and SPSS version 20.0 were used for data entry and statistical analysis, respectively. Binary logistic regression model was used to model the odds of late ANC initiation. The odds of attending ANC late were significantly higher for mothers with a monthly household income of $8.50 to start the ANC service (AOR=3.04; 95% CI: 1.98, 4.67). Low educational level, low income of the household, unplanned pregnancy, stay for ANC service were the main predictors of late ANC initiation. Therefore, any intervention which would need to improve early ANC initiation should focus on economic empowerment of women, and tailored health education for migrant women should be strengthened.

  8. Psychosocial factors associated with early initiation and frequency of antenatal care (ANC) visits in a rural and urban setting in South Africa: a cross-sectional survey.

    Science.gov (United States)

    Muhwava, Lorrein Shamiso; Morojele, Neo; London, Leslie

    2016-01-25

    Late booking and infrequent antenatal care (ANC) are common but avoidable patient-related risk factors for maternal deaths in South Africa. The aim of the study was to examine the association of psychosocial factors with early initiation of ANC and adequate frequency of attendance of ANC clinics among women in an urban and rural location in South Africa. Data from a 2006 cross-sectional household survey of 363 women from the rural Western Cape and 466 women from urban Gauteng provinces of South Africa for risk of alcohol-exposed pregnancy were analysed. We examined associations between psychosocial variables (self-esteem, cultural influences, religiosity, social capital, social support, pregnancy desire (wanted versus unwanted pregnancy), partner characteristics and mental health) and both early ANC first visit (before 16 weeks) and adequate frequency of ANC visits (4 or more visits) for respondents' last pregnancy. Overall prevalence among urban women of early ANC initiation was 46% and 84% for adequate ANC frequency. Overall prevalence among rural women of early ANC initiation was 45% and 78% for adequate ANC frequency. After adjusting for clustering, psychosocial factors associated with early ANC initiation in the urban site were being employed (OR 1.6; 95% CI 1.0-2.5) and wanted pregnancy (OR 1.8; 95% CI 1.1-3.0). For the rural site, early ANC initiation was significantly associated with being married (OR 1.93; 95% CI 1.0-3.6) but inversely associated with high religiosity (OR 0.5; 95% CI 0.3-0.8). Adequate frequency of ANC attendance in the rural site was associated with wanted pregnancy (OR 4.2; 95% CI 1.9-9.3) and the father of the child being present in the respondent's life (OR 3.0; 95% CI 1.0-9.0) but inversely associated with having a previous miscarriage (OR 0.4; 95% CI 0.2-0.8). There were no significant associations between adequate ANC attendance and the psychosocial factors in the urban site. The majority of women from both sites attended ANC

  9. The RNA-binding protein Celf1 post-transcriptionally regulates p27Kip1 and Dnase2b to control fiber cell nuclear degradation in lens development.

    Directory of Open Access Journals (Sweden)

    Archana D Siddam

    2018-03-01

    Full Text Available Opacification of the ocular lens, termed cataract, is a common cause of blindness. To become transparent, lens fiber cells undergo degradation of their organelles, including their nuclei, presenting a fundamental question: does signaling/transcription sufficiently explain differentiation of cells progressing toward compromised transcriptional potential? We report that a conserved RNA-binding protein Celf1 post-transcriptionally controls key genes to regulate lens fiber cell differentiation. Celf1-targeted knockout mice and celf1-knockdown zebrafish and Xenopus morphants have severe eye defects/cataract. Celf1 spatiotemporally down-regulates the cyclin-dependent kinase (Cdk inhibitor p27Kip1 by interacting with its 5' UTR and mediating translation inhibition. Celf1 deficiency causes ectopic up-regulation of p21Cip1. Further, Celf1 directly binds to the mRNA of the nuclease Dnase2b to maintain its high levels. Together these events are necessary for Cdk1-mediated lamin A/C phosphorylation to initiate nuclear envelope breakdown and DNA degradation in fiber cells. Moreover, Celf1 controls alternative splicing of the membrane-organization factor beta-spectrin and regulates F-actin-crosslinking factor Actn2 mRNA levels, thereby controlling fiber cell morphology. Thus, we illustrate new Celf1-regulated molecular mechanisms in lens development, suggesting that post-transcriptional regulatory RNA-binding proteins have evolved conserved functions to control vertebrate oculogenesis.

  10. Changes in Theory-Based Psychological Factors Predict Weight Loss in Women with Class III Obesity Initiating Supported Exercise

    Directory of Open Access Journals (Sweden)

    James J. Annesi

    2010-01-01

    Full Text Available Background. Psychological factors' effect on weight loss is poorly understood, in general, and specifically in the severely obese. Objective. To examine whether a behavioral model based on tenets of social cognitive and self-efficacy theory will increase understanding of the relationship between exercise and weight loss. Methods. Fifty-one women with severe obesity participated in a 24-week exercise and nutrition information treatment and were measured on changes in psychological factors and exercise attendance. Results. A significant portion of the variance in BMI change (adjusted for number of predictors was accounted for by the behavioral model (2adj=0.23. Entry of exercise session attendance only marginally improved the prediction to 0.27. Only 19% of the weight lost was directly attributable to caloric expenditure from exercise. Conclusions. Findings suggest that participation in an exercise program affects weight loss through psychological pathways and, thus, may be important in the behavioral treatment of severe obesity.

  11. Analysis of psychosocial factors influencing the distribution and projection of Spanish scientific activity: report of the initial qualitative study

    Directory of Open Access Journals (Sweden)

    GESCIT (Grup d'Estudis Socials de la Ciència i la Tecnologia

    2007-11-01

    Full Text Available In this first phase of a longer study, we identify a number of psycho-social factors which are affecting science in Spain: attitudes, stereotypes, prejudices, values, beliefs, and attribution processes. We also examine how these factors might help or hinder Spanish science's greater impact in the international scientific community. This study falls within the framework of the Social Psychology of Science, the main principle of which is to explain scientific work by appeal to psycho-social variables and processes. We use qualitative methods to analyse a wide sample of material gleaned from the Spanish scientific community, and report on those elements that construct and perpetuate the perceptions, images and representations of current Spanish science research.

  12. Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries.

    Science.gov (United States)

    Stubbs, Sharron A; Webber, Lisa J; Stark, Jaroslav; Rice, Suman; Margara, Raul; Lavery, Stuart; Trew, Geoffrey H; Hardy, Kate; Franks, Stephen

    2013-08-01

    Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development. Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries. We used archived ovarian tissue for protein expression studies and small cortical biopsies for follicle isolation and for tissue culture. This was a laboratory-based study, using clinical tissue samples. A total of 54 women, 33 with normal ovaries and 21 with polycystic ovaries, were classified by reference to menstrual cycle history and ultrasonography. We evaluated expression of IGFR-1 mRNA in isolated preantral follicles and of IGFR-1 protein in archived ovarian tissue samples from normal and polycystic ovaries and effects of exogenous IGF-1 on preantral follicle development and survival in cultured fragments of normal and polycystic ovaries. IGFR-1 mRNA and protein was expressed in preantral follicles at all stages of development and enhanced expression was noted in PCOS follicles during early preantral development. IGF-1 stimulated initiation of follicle growth in normal tissue but had little effect on preantral follicle growth in polycystic ovaries in which, characteristically, there was a higher proportion of follicles that had entered the growing phase even before culture. IGFs are plausible candidates in regulation of initiation of human follicle growth, and accelerated preantral follicle growth in PCOS may be due to increased activity of endogenous IGFs.

  13. Positive regulation of raphe serotonin neurons by serotonin 2B receptors.

    Science.gov (United States)

    Belmer, Arnauld; Quentin, Emily; Diaz, Silvina L; Guiard, Bruno P; Fernandez, Sebastian P; Doly, Stéphane; Banas, Sophie M; Pitychoutis, Pothitos M; Moutkine, Imane; Muzerelle, Aude; Tchenio, Anna; Roumier, Anne; Mameli, Manuel; Maroteaux, Luc

    2018-06-01

    Serotonin is a neurotransmitter involved in many psychiatric diseases. In humans, a lack of 5-HT 2B receptors is associated with serotonin-dependent phenotypes, including impulsivity and suicidality. A lack of 5-HT 2B receptors in mice eliminates the effects of molecules that directly target serotonergic neurons including amphetamine derivative serotonin releasers, and selective serotonin reuptake inhibitor antidepressants. In this work, we tested the hypothesis that 5-HT 2B receptors directly and positively regulate raphe serotonin neuron activity. By ex vivo electrophysiological recordings, we report that stimulation by the 5-HT 2B receptor agonist, BW723C86, increased the firing frequency of serotonin Pet1-positive neurons. Viral overexpression of 5-HT 2B receptors in these neurons increased their excitability. Furthermore, in vivo 5-HT 2B -receptor stimulation by BW723C86 counteracted 5-HT 1A autoreceptor-dependent reduction in firing rate and hypothermic response in wild-type mice. By a conditional genetic ablation that eliminates 5-HT 2B receptor expression specifically and exclusively from Pet1-positive serotonin neurons (Htr2b 5-HTKO mice), we demonstrated that behavioral and sensitizing effects of MDMA (3,4-methylenedioxy-methamphetamine), as well as acute behavioral and chronic neurogenic effects of the antidepressant fluoxetine, require 5-HT 2B receptor expression in serotonergic neurons. In Htr2b 5-HTKO mice, dorsal raphe serotonin neurons displayed a lower firing frequency compared to control Htr2b lox/lox mice as assessed by in vivo extracellular recordings and a stronger hypothermic effect of 5-HT 1A -autoreceptor stimulation was observed. The increase in head-twitch response to DOI (2,5-dimethoxy-4-iodoamphetamine) further confirmed the lower serotonergic tone resulting from the absence of 5-HT 2B receptors in serotonin neurons. Together, these observations indicate that the 5-HT 2B receptor acts as a direct positive modulator of serotonin Pet1

  14. Multiple antibacterial histone H2B proteins are expressed in tissues of American oyster.

    Science.gov (United States)

    Seo, Jung-Kil; Stephenson, Jeana; Noga, Edward J

    2011-03-01

    We have previously identified a histone H2B isomer (cvH2B-1) from tissue extracts of the bivalve mollusk, the American oyster (Crassostrea virginica). In this paper, we isolate an additional three antibacterial proteins from acidified gill extract by preparative acid-urea-polyacrylamide gel electrophoresis and reversed-phase high performance liquid chromatography. Extraction of these proteins from tissue was best accomplished by briefly boiling the tissues in a weak acetic acid solution. Addition of protease inhibitors while boiling resulted in somewhat lower yields, with one protein being totally absent with this method. Via mass spectrometry, the masses of one of these purified proteins was 13607.0Da (peak 2), which is consistent with the molecular weight of histone H2B. In addition, via western-blotting using anti-calf histone H2B antibody, all three proteins were positive and were thus named cvH2B-2, cvH2B-3 and cvH2B-4. The antibacterial activity of cvH2B-2 was similar to that of cvH2B-1, with activity against a Gram-positive bacterium (Lactococcus lactis subsp. lactis; minimum effective concentration [MEC] 52-57μg/mL) but inactive against Staphylococcus aureus (MEC>250μg/mL). However, both proteins had relatively potent activity against the Gram-negative oyster pathogen Vibrio parahemolyticus (MEC 11.5-14μg/mL) as well as the human pathogen Vibrio vulnificus (MEC 21.3-25.3μg/mL). cvH2B-3 and cvH2B-4 also had similarly strong activity against Vibrio vulnificus. These data provide further evidence for the antimicrobial function of histone H2B isomers in modulating bacterial populations in oyster tissues. The combined estimated concentrations of these histone H2B isomers were far above the inhibitory concentrations for the tested vibrios, including human pathogens. Our results indicate that the highly conserved histone proteins might be important components not only of immune defenses in oysters but have the potential to influence the abundance of a

  15. Biodegradation of BOD and ammonia-free using bacterial consortium in aerated fixed film bioreactor (AF2B)

    Science.gov (United States)

    Prayitno, Rulianah, Sri; Saroso, Hadi; Meilany, Diah

    2017-06-01

    BOD and Ammonia-free (NH3-N) are pollutants of hospital wastewater which often exceed the quality standards. It is because biological processes in wastewater treatment plant (WWTP) have not been effective in degrading BOD and NH3-N. Therefore, a study on factors that influence the biodegradation of BOD and NH3-N by choosing the type of bacteria to improve the mechanisms of biodegradation processes is required. Bacterial consortium is a collection of several types of bacteria obtained from isolation process, which is known to be more effective than a single bacterial in degrading pollutants. On the other hand, AF2B is a type of reactor in wastewater treatment system. The AF2B contains a filter media that has a large surface area so that the biodegradation process of pollutants by microorganism can be improved. The objective of this research is to determine the effect of volume of starter and air supplies on decreasing BOD and NH3-N in hospital wastewater using bacterial consortium in the AF2B on batch process. The research was conducted in three stages: the making of the growth curve of the bacterial consortium, bacterial consortium acclimatization, and hospital wastewater treatment in the AF2B with batch process. The variables used are the volume of starter (65%, 75%, and 85% in volume) and air supplies (2.5, 5, and 7.5 L/min). Meanwhile, the materials used are hospital wastewater, bacterial consortium (Pseudomonas diminuta, Pseudomonas capica, Bacillius sp, and Nitrobacter sp), blower, and AF2B. AF2B is a plastic basin containing a filter media with a wasp-nest shape used as a medium for growing the bacterial consortium. In the process of making the growth curve, a solid form of bacterial consortium was dissolved in sterilized water, then grown in a nutrient broth (NB). Then, shaking and sampling were done at any time to determine the path growth of bacterial consortium. In the acclimatization process, bacterial isolates were grown using hospital wastewater as a

  16. The Burden of Provider-Initiated Preterm Birth and Associated Factors: Evidence from the Brazilian Multicenter Study on Preterm Birth (EMIP.

    Directory of Open Access Journals (Sweden)

    Renato T Souza

    Full Text Available About 15 million children are born under 37 weeks of gestation worldwide. Prematurity is the leading cause of neonatal deaths and short/long term morbidities, entailing consequences not only for the individual, but also their family, health agencies, facilities and all community. The provider-initiated preterm birth is currently one of the most important obstetric conditions related to preterm births, particularly in middle and high income countries, thus decreasing the need for therapeutic preterm birth is essential to reduce global prematurity. Therefore detailed knowledge on the factors associated with provider-initiated preterm birth is essential for the efforts to reduce preterm birth rates and its consequences. In this current analysis we aimed to assess the proportion of provider-initiated (pi-PTB among preterm births in Brazil and identify associated factors.This is an analysis of a multicenter cross-sectional study with a nested case-control component called Brazilian Multicenter Study on Preterm Birth (EMIP. EMIP was conducted in 20 referral obstetric hospitals located in the three most populated of the five Brazilian regions. We analysed data of women with pi-PTB, defined as childbirth occurring at less than 37 weeks, medically indicated for maternal/fetal compromise or both; and women with term birth, childbirth at or after 37 weeks. Maternal, sociodemographic, obstetric, prenatal care, delivery, and postnatal characteristics were assessed as possible factors associated with pi-PTB, compared to term births. The overall prevalence of preterm births was 12.3%. Of these, approximately one-third of cases were initiated by the provider. Hypertensive disorders, placental abruption, and diabetes were the main maternal conditions leading to pi-PTB. Caesarean section was the most common mode of delivery. Chronic hypertension (OR 7.47; 95%CI 4.02-13.88, preeclampsia/eclampsia/HELLP syndrome (OR 15.35; 6.57-35.88, multiple pregnancy (OR 12

  17. Site-different structures from dilithium hexaboride (Li2b6) to dimagnesium hexaboride (Mg2B6) by first-principles

    International Nuclear Information System (INIS)

    Aydın, Sezgin

    2013-01-01

    Highlights: •All structures are thermodynamically stable. All structures are metallic. •Boron sub-lattice have negative-charged atoms and more covalent bonds. •The inter-octahedral binding is more covalent than inner-octahedral binding. •All structures are also mechanically stable. -- Abstract: The structural, mechanical, electronic and bonding properties of dilithium hexaboride (Li 2 B 6 ) and isostructural hypothetic compounds obtained by replacing Li atoms in different sites to magnesium atoms have been investigated by first-principles density functional pseudopotential plane–wave calculations. It is shown that calculated lattice parameters of Li 2 B 6 agree with the experimental results. All of designed hypothetical structures have negative formation enthalpies, thus all of them are thermodynamically stable and the most stable structure is Mg 2 B 6 . At the same time, from calculated single crystal elastic constants, it is shown that all structures are mechanically stable and related mechanical properties such as bulk, shear and Young moduli are calculated. It is shown that adding magnesium to the structure of Li 2 B 6 is decreasing values of the moduli. Further, hardnesses of the structures are determined theoretically and it is obtained that hardness exhibits same trend with the moduli. From electronic structure calculations including band structure and site-dependent density of states, all structures are metallic, and fully magnesium substituted structure (Mg 2 B 6 ) has the highest metallicity among the structures. Additionally, bonding nature of the structures are analyzed by using electron density maps, Mulliken atomic charges and bond overlap populations

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

    Science.gov (United States)

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

    2014-09-22

    Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1-2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2. In this study we investigated whether vaccination with a CPV-2b containing vaccine would induce cross-reactive antibody responses to the other CPV-2 variants. Two studies where dogs were vaccinated with a multivalent vaccine, subsequently challenged with CPV-2b and sera samples analysed are presented. Six week old pups with defined serological status were vaccinated twice, three weeks apart and challenged either 5 weeks (MDA override study) or one year after vaccination (duration of immunity study). Sera samples were collected before each vaccination and at periods throughout each study. In each study the antibody profiles were very similar; serological responses against CPV-2a, CPV-2b and CPV-2c were higher than those for CPV-2. Nevertheless, responses against CPV-2 were well above levels considered clinically protective. In each study dogs also showed a rapid increase in antibody titres following vaccination, reached a plateau following second vaccination with a slight decline to challenge after which rapid anamnestic responses were seen. Evaluation of the serological responses suggests vaccination with CPV-2b would cross-protect against CPV-2a and CPV-2c, as well as against CPV-2 which is now extinct in the field. In conclusion we have demonstrated that vaccination of minimum aged dogs with a multivalent vaccine containing the CPV-2b variant strain will induce serological responses which are cross-reactive against all currently circulating field strains, CPV-2a and CPV-2c, and the now extinct field strain CPV-2. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses.

    Science.gov (United States)

    Takahama, Michihiro; Fukuda, Mitsunori; Ohbayashi, Norihiko; Kozaki, Tatsuya; Misawa, Takuma; Okamoto, Toru; Matsuura, Yoshiharu; Akira, Shizuo; Saitoh, Tatsuya

    2017-09-19

    Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5), in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING), the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses

    Directory of Open Access Journals (Sweden)

    Michihiro Takahama

    2017-09-01

    Full Text Available Cyclic GMP-AMP synthase (cGAS is a cytosolic DNA sensor that induces the IFN antiviral response. However, the regulatory mechanisms that mediate cGAS-triggered signaling have not been fully explored. Here, we show the involvement of a small GTPase, RAB2B, and its effector protein, Golgi-associated RAB2B interactor-like 5 (GARIL5, in the cGAS-mediated IFN response. RAB2B-deficiency affects the IFN response induced by cytosolic DNA. Consistent with this, RAB2B deficiency enhances replication of vaccinia virus, a DNA virus. After DNA stimulation, RAB2B colocalizes with stimulator of interferon genes (STING, the downstream signal mediator of cGAS, on the Golgi apparatus. The GTP-binding activity of RAB2B is required for its localization on the Golgi apparatus and for recruitment of GARIL5. GARIL5 deficiency also affects the IFN response induced by cytosolic DNA and enhances replication of vaccinia virus. These findings indicate that the RAB2B-GARIL5 complex promotes IFN responses against DNA viruses by regulating the cGAS-STING signaling axis.