bluuebunny/crossref_metadata_2025 huggingface dataset:
A confiança interorganizacional nas compras
Authors: Tacconi Marli de Fátima Ferraz da Silva , Lopes Fernando Dias , Mól Anderson Luiz Rezende , Tacconi Neto Ernesto Alexandre
Published: April 2014

O conceito de confiança interorganizacional apresenta lacunas que requerem maior número de pesquisas para que se possa construir uma teoria coerente que apoie as estratégias de cooperação e integração da cadeia de suprimentos. Esta pesquisa tem o intuito de explicar os antecedentes da confiança interorganizacional pela relação entre os construtos desempenho operacional, características organizacionais, compartilhamento de valores e relacionamento interpessoal nas compras realizadas pelas indústrias de transformação. No que se refere aos aspectos metodológicos, o estudo assume a forma de uma pesquisa descritiva, do tipo survey, e causal, de cunho teórico-empírico, com caráter explicativo, desenvolvida por meio da modelagem de equações estruturais. Os questionários foram aplicados entre os informantes-chave, utilizando-se uma amostragem aleatória simples desenvolvida nas indústrias de transformação (CNAE 10 a 33) localizadas na região da Grande Natal, que constituem um importante setor de atividade econômica com capacidade de gerar dinamismo na economia. Os primeiros resultados das análises demonstram o fenômeno da confiança interorganizacional, a qual consiste em empresas compradoras acreditarem na empresa fornecedora, sentirem-se seguras em relação a esta. O modelo inicial proposto não apresentou ajustamento, precisando ser reespecificado. Esse modelo reespecificado demonstra que os resultados suportam a explicação de que a confiança interorganizacional nas compras depende diretamente do relacionamento interpessoal, do compartilhamento de valores e do desempenho operacional. Conclui-se que essa confiança pode ser explicada por um conjunto de interações entre esses três determinantes, sendo o ponto central o relacionamento interpessoal, que apresentou o maior coeficiente de trajetória para o fator.
Percepções de gestores locais sobre a intersetorialidade no Programa Saúde na Escola
Authors: Ferreira Izabel do Rocio Costa , Moysés Samuel Jorge , França Beatriz Helena Sottile , Carvalho Max Luiz de , Moysés Simone Tetu
Published: April 2014

O objetivo deste estudo foi analisar a percepção de gestores locais sobre a intersetorialidade na condução do Programa Saúde na Escola (PSE) em municípios selecionados. Trata-se de um estudo avaliativo, descritivo, com abordagem qualitativa e amostra intencional. O instrumento para coleta de dados foi por meio de questionário eletrônico. Para a avaliação das questões fechadas, realizou-se a análise descritiva dos dados. Para a análise das questões abertas, utilizou-se a técnica da análise de conteúdo proposta por Bardin, associada ao programa computacional ATLAS.ti. Os resultados revelaram que os respondentes demonstram conhecimentos necessários para o trabalho intersetorial, ainda que precisem de ajustes conceituais. Não se observou participação dos estudantes na definição de prioridades, planejamento e programação das ações. Concluiu-se que capacitações são necessárias para aproximação dos profissionais envolvidos no PSE, a fim de qualificar a comunicação e o entendimento das bases conceituais do programa.
A implantação de cotas na universidade: paternalismo e ameaça à posição dos grupos dominantes
Authors: Lima Marcus Eugênio Oliveira , Neves Paulo Sérgio da Costa , Silva Paula Bacellar e
Published: April 2014

A fim de entender como se manifestam e desenvolvem as atitudes perante as cotas, realizamos dois estudos, um antes da implantação desse sistema e outro depois. Participaram 334 estudantes dos cursos mais concorridos da Universidade Federal de Sergipe (UFS). Os resultados indicaram atitudes muito contrárias às cotas, sobretudo às raciais. Depois da implantação, a oposição cresce para as cotas raciais e diminui para as sociais. Antes da implantação, os contrários afirmaram, sobretudo, que as cotas aumentavam o preconceito contra os negros; depois da implantação, a principal justificativa foi a de que elas discriminavam. Esses resultados são discutidos como indicadores das relações entre as ideologias do paternalismo e do senso de posição grupal no preconceito racial do Brasil.
"Se você não mudar, morrerá": a (con)formação de um trabalhador de novo tipo no discurso de autoajuda
Authors: Turmina Adriana Cláudia , Shiroma Eneida Oto
Published: April 2014

Nesta pesquisa foi abordada a face ideológica do discurso de autoajuda na formação de um novo tipo de trabalhador, explicando o seu papel na construção da hegemonia. Estudamos os princípios desse discurso em três períodos: sua gênese, no século XIX, nas primeiras décadas do século XX e início do século XXI. Analisamos como os princípios de autoajuda foram reproduzidos no Relatório Delors e Faure. Com base em Gramsci e Fairclough, explicamos a autoajuda como um discurso ideológico presente nos relatorios da Organização das Nações Unidas para a Educação, a Ciência e a Cultura (UNESCO). Concluímos que a formação de um novo tipo de homem pelo discurso da autoajuda acontece fora, mas também dentro da escola. Ela contribui para a consolidação de novos padrões de sociabilidade burguesa em tempos de neoliberalismo. Capitalistas, ao longo dos séculos, têm usado a autoajuda para realizar a (con)formação de um novo tipo de força de trabalho.
Las políticas de desarrollo profesional del profesor principiante en el programa de acompañamiento de docentes noveles en su primera inserción laboral de Argentina
Authors: Alliaud Andrea
Published: April 2014

Considerando las dificultades que tienen que enfrentar los docentes cuando se inician en su profesión, particularmente en la actualidad, este trabajo presenta ciertas alternativas de intervención política y pedagógica tomando como referencia el Programa de Acompañamiento de Docentes Noveles en su Primera Inserción Laboral de Argentina. En una primera parte, se exponen los rasgos fundamentales de este programa que constituye una de las líneas de desarrollo profesional docente a nivel nacional. La lógica del acompañar y los distintos dispositivos implementados, las experiencias locales como insumos para la definición de políticas públicas, son algunos de ellos. A continuación, se presentan y analizan las opiniones de los docentes noveles que han recibido acompañamiento en su primera inserción laboral sobre las fortalezas y debilidades que ellos perciben a la hora de enseñar, la valoración de la formación recibida y la propuesta de acompañamiento en sí misma. Finalmente, se ponen en consideración una serie de características que se tendrían que contemplar por cualquier propuesta formativa que apunte al fortalecimiento del oficio de enseñar.
Estrutura da comunidade de algas perifíticas em Eleocharis acutangula (Roxb.) Schult (Cyperaceae) em reservatório tropical raso, São Paulo, SP, Brasil
Authors: Camargo Vanessa Moraes , Ferragut Carla
Published: April 2014

O objetivo do presente estudo foi avaliar a influência da variação sazonal das condições ambientais sobre os atributos estruturais da comunidade de algas perifíticas em Eleocharis acutangula (Roxb.) Schult (Cyperaceae) na zona litorânea do Lago das Ninféias, São Paulo, SP, Brasil. A primavera e o verão caracterizaram-se pelos maiores valores de cobertura de macrófitas, clorofila-a do fitoplâncton, disponibilidade de luz e de fósforo na água. A biomassa e a densidade algal do perifíton foram correlacionadas negativamente com a cobertura de macrófitas e com a clorofila-a do fitoplâncton. A composição de espécies, classes algais e descritoras mudou em escala sazonal. Concluiu-se que a estrutura da comunidade de algas perifíticas em Eleocharis acutangula foi fortemente influenciada pela cobertura de macrófitas e biomassa do fitoplâncton. A disponibilidade de nutrientes na água parece ter menor importância sobre a organização da comunidade. As respostas dos atributos estruturais do perifíton evidenciaram a forte interrelação com macrófitas e fitoplâncton, a qual deve ser mais bem compreendida nos reservatórios tropicais rasos.
Sinopse do gênero Manihot Mill. (Euphorbiaceae) no Estado de São Paulo, Brasil
Authors: Orlandini Priscila , Lima Letícia Ribes de
Published: April 2014

Na família Euphorbiaceae o gênero Manihot destaca-se, principalmente, pela complexidade taxonômica. Trata-se de um gênero neotropical, com 98 espécies distribuídas do Texas até a Argentina. No Brasil, a região do Planalto Central, em especial os Estados de Goiás e Minas Gerais, e o da Bahia no Nordeste podem ser considerados os centros de diversidade do táxon. O objetivo do presente trabalho foi elaborar a monografia do gênero Manihot no Estado de São Paulo. Foram encontradas dez espécies do gênero Manihot: Manihot anomala Pohl, M. caerulescens Pohl, M. fruticulosa Pohl, M. gracilis Pohl, M. grahamii Hook., M. inflata Müll. Arg., M. jolyana Cruz, M. pilosa Pohl, M. procumbens Müll. Arg. e M. tripartita (Spreng.) Müll. Arg. Neste trabalho propõe-se que M. jolyana Cruz e M. handroana Cruz sejam tratadas como uma única espécie, sendo, portanto, proposta a sinonimização.
Riqueza dos fungos ingoldianos e aquáticos facultativos no Parque Municipal do Ibirapuera, São Paulo, SP, Brasil
Authors: Schoenlein-Crusius Iracema Helena , Moreira Carolina Gasch , Takahashi Juliana Possato , Gomes Eduardo Pereira Cabral
Published: April 2014

No Parque Municipal do Ibirapuera em São Paulo, SP, Brasil, 10 amostras de folhedo submerso misto foram coletadas mensalmente de março de 2007 a junho de 2009, às margens de cinco locais em três lagos, concomitantemente à medição de algumas variáveis abióticas. No laboratório as folhas foram lavadas, fracionadas em alíquotas (1 cm²), incubadas em água destilada esterilizada a 22 ºC durante 30 dias e analisadas microscopicamente. Vinte e sete táxons de fungos foram obtidos, sendo 15 de fungos ingoldianos e 12 aquáticos facultativos, com predomínio de Lunulospora curvula Ingold, Triscelophorus monosporus Ingold, Tripospermum myrtii (Lind.) S. J. Hughes, Anguillospora longíssima (Sacc. et Syd.) Ingold e Triscelophorus acuminatus Nawawi. A análise ANOSIM revelou que amostras de locais de coleta em diferentes estações divergiram mais do que entre locais de coleta na mesma estação climática. O intenso assoreamento do local de coleta situado imediatamente após a unidade de flotação quase aniquilou a melhoria das condições abióticas, encorajando o monitoramento cuidadoso para manter a qualidade da água em todo parque.
Isolation and characterization of ten new microsatellite markers in Machaerium villosum Vogel (Fabaceae)
Authors: Giudice-Neto João , Ramos Rafael Flora , Moraes Evandro Marsola de , Silva Márcio José da , Solferini Vera Nisaka
Published: April 2014

Machaerium villosum is an important tree species from Southeastern Brazil. We report hereby 10 new microsatellite markers to investigate the structure and genetic diversity of this species. Ninety-seven alleles were detected in 60 specimens from a natural population in Minas Gerais State. High genetic diversity has been found. The mean observed and expected heterozygosities were 0.771 and 0.802, respectively. One locus showed significant Hardy-Weinberg departure and five loci combinations showed significant linkage disequilibrium. These 10 new microsatellite loci will be used to evaluate the genetic diversity of this species in order to understand the fragmentation effects of the Brazilian Atlantic Rain Forest.
Comasiella, Desmodesmus, Pectinodesmus e Scenedesmus na comunidade perifítica em ecossistema lêntico tropical, Brasil Central
Authors: Souza Danúzia Batista da Silva e , Felisberto Sirlene Aparecida
Published: April 2014

Este trabalho objetivou o estudo taxonômico de Comasiella, Desmodesmus, Pectinodesmus e Scenedesmus no perifíton em ambiente lêntico tropical. As amostras de perifíton foram coletadas em pecíolos de plantas aquáticas (Cyperaceae) na região litorânea da represa, em setembro e novembro de 2010 (período de seca) e janeiro e março de 2011 (período de chuva). Nós identificamos 19 táxons, distribuídos em Comasiella (um), Desmodesmus (14), Pectinodesmus (dois) e Scenedesmus (dois). Considerando os períodos climáticos, oito espécies foram registradas exclusivamente na seca e um no período de chuvas, enquanto 10 espécies foram analisadas para ambos os períodos. Dentre as espécies identificadas Comasiella arcuata (Lemmermann) var. platydisca (Smith) Hegewald & Wolf, Desmodesmus spinulatus (Biswas) Hegewald, Scenedesmus acunae Comas e Pectinodesmus pectinatus (Meyen) Hegewald & Wolf, constituem primeira citação para o Estado de Goiás.
Deep borehole disposal of nuclear waste: engineering challenges
Authors: Beswick A. John , Gibb Fergus G. F. , Travis Karl P.
Published: April 2014

In recent years, geological disposal of radioactive waste has focused on placement of high- and intermediate-level wastes in mined underground caverns at depths of 500–800 m. Notwithstanding the billions of dollars spent to date on this approach, the difficulty of finding suitable sites and demonstrating to the public and regulators that a robust safety case can be developed has frustrated attempts to implement disposal programmes in several countries, and no disposal facility for spent nuclear fuel exists anywhere. The concept of deep borehole disposal was first considered in the 1950s, but was rejected as it was believed to be beyond existing drilling capabilities. Improvements in drilling and associated technologies and advances in sealing methods have prompted a re-examination of this option for the disposal of high-level radioactive wastes, including spent fuel and plutonium. Since the 1950s, studies of deep boreholes have involved minimal investment. However, deep borehole disposal offers a potentially safer, more secure, cost-effective and environmentally sound solution for the long-term management of high-level radioactive waste than mined repositories. Potentially it could accommodate most of the world's spent fuel inventory. This paper discusses the concept, the status of existing supporting equipment and technologies and the challenges that remain.
Consolidation of clayey gouge amid permeating rock masses
Authors: Trivedi Ashutosh , Banik Tanmay , Sukumar Tanay , Kumar Naresh , Jain Akshay , Kumar Amit
Published: April 2014

There are numerous occurrences of soil–rock–water interaction in the natural geo-environment involving saturated clayey gouge consolidating amid permeating rock masses and draining laterally through a network of joints. In this paper, the concept of two-dimensional drainage for consolidation along the vertical direction for saturated clay has been applied to a layer of gouge amid rock joints. Solutions for pore water pressure distribution and average degree of consolidation have been computed. The orthogonal directions along which the drainage has been assumed for the derivation of these expressions are vertical direction (as in Terzaghi’s theory of one-dimensional consolidation) and lateral direction. Initially, such a case corresponds to a Dirichlet problem applied to a rectangular gouge lamina. The deformations appearing in the vertical direction are a result of the effects of drainage in the lateral and vertical directions together. An expression for the relationship of time factor with the average degree of consolidation as a function of dimensionless parameter relating rock mass characteristics has been proposed.
Benefits of using expansive and shrinkage-reducing agents in UHPC for volume stability
Authors: Park Jung-Jun , Yoo Doo-Yeol , Kim Sung-Wook , Yoon Young-Soo
Published: April 2014

This study investigated the effects of expansive agent (EA) and shrinkage-reducing agent (SRA) on the mechanical and shrinkage properties of ultra-high-performance concrete. Along with a reference specimen, the work considered five different specimens with different ratios of SRA (1% and 2%), EA (5% and 7·5%) and a combination of 1% SRA and 7·5% EA. The test results revealed that compressive strength varied with the inclusion of SRA and EA, while tensile strength decreased according to the admixing of SRA and EA. The free shrinkage strain was obviously reduced by including SRA and EA, and the specimen with 7·5% EA showed the lowest shrinkage strain. The inner steel strain was also decreased by incorporating SRA and EA, and the specimen with a combination of 1% SRA and 7·5% EA exhibited the smallest strain even though it showed a larger free shrinkage strain than the specimen with 7·5% EA. Furthermore, the specimens with EA exhibited a decrease in steel strain after nearly 10 d due to the tensile creep effect.
Exiting Poverty: Does Sex Matter?
Authors: Curtis Lori J. , Rybczynski Kate
Published: April 2014

Little is understood about the factors associated with poverty duration in Canada, or which factors, if any, may affect women and men differently. Moreover, research pays scant attention to how far Canadians transition out of poverty. For example, some may exit poverty only marginally, while others exit much further above the poverty line. We investigate the determinants of poverty duration among women and men in Canada. A major contribution of this article is the examination of poverty duration across different exit destinations (competing risks): exits to just above the poverty line versus exits to further above the poverty line. We find that nearly one-quarter of poverty spells end within 110 percent of the poverty line (near poverty). Many of those who exit to near poverty experience multiple spells. As expected, we find that higher education increases the probability of transitioning further out of poverty, but very little is correlated with exits to near poverty relative to remaining in poverty. The longer the poverty spell, the lower the probability of exit, particularly to higher income levels. We find few significant gender differences in the coefficient estimates. Differences are present in the characteristics associated with exits close to or further away from the poverty line.
The Prince and the Pauper: Movement of Children up and down the Canadian Income Distribution
Authors: Burton Peter , Phipps Shelley , Zhang Lihui
Published: April 2014

This paper uses longitudinal microdata from the Statistics Canada National Longitudinal Survey of Children and Youth (NLSCY) to study the family income dynamics of Canadian children from the time they are 4 or 5 until they are 14 or 15. Dynamics of family income have been studied less often than dynamics of child poverty. Yet we argue that from the perspective of equity, it is important to know the extent to which some children are always affluent while other children are always poor. Also, since our social safety net is designed to shelter Canadians, including children, from both economic hardship and economic loss, it is also important, from the perspective of policy, to assess risk factors for persistent low income as well as correlates of major economic loss.
Quality of Supervised Research Report in Relation to Postgraduate Medical Qualifications of Bangladesh
Authors: Khan Md Abdul Wohab , Talukder Humayun Kabir , Miah Md Abdal , Rabbi Golam , Khanam Rawshan Ara , Ali SM Idris , Rahman Tawhidur , Ahmed Wakil , Islam Mohammad Saiful
Published: April 2014

In any academic field the question of quality is central issue. Evaluation of the quality in supervised research in medical education is very important in higher education and teaching. The purpose of the supervised research project is to provide the learner an experience in scientific writing, to familiarize the student with the steps of research, to promote critical and analytical thinking of the learner and to contribute something new to knowledge base. The objectives of this study were to determine the quality in postgraduate supervised research report writing, according to the standard recommended and implied by the post graduate medical institutes of Bangladesh and thus to assess the achievement of the intended purposes. For that an exploratory and descriptive study was performed on 64 theses and dissertations submitted during the period of 2008-2010 in two selected post graduate medical institutes of Dhaka city. The overall quality was found marginal in 93.8% (60) of the reports. There were indications that the prescribed standard was not followed properly. It was observed from the study that there are problems in learning and inadequacy in fulfillment of the purpose of supervised research program. It was perceived that probably the supervision was not enough. Theoretical knowledge gap was also apparent at various levels. To address these issues planning, designing, supervision and assessment systems of supervised research program in relation to the postgraduate medical qualifications of Bangladesh needs critical attention.DOI: http://dx.doi.org/10.3329/bjme.v3i1.18588 Bangladesh Journal of Medical Education Vol.3(1) 2012: 1-7
Views of Medical Educators and Intern Doctors on the Existing MBBS Curriculum
Authors: Mosaddek Abu Syed Md , Nargis Waheeda , Ahamed Borhan Uddin , Islam Md Zakirul , Chaudhury Habib S , Begum Most. Fahmida , Rahman Md Faizur , Alim Rumana
Published: April 2014

This study was carried out to get an idea about the views of medical educators and intern doctors regarding the current undergraduate medical curriculum. A partially descriptive open ended questionnaire was distributed among teachers of all three phases and intern doctors in undergraduate curriculum in different public and private medical colleges in Bangladesh and was returned by 120 teachers and 663 intern doctors. Qualitative analysis of data was done. Among teachers 70% agreed to need for changes, 68.4% were in favor of present internship training system and 85% were against carry on system. But 94% and 51% of intern doctors were in favor of need changes of curriculum and present internship training respectively. 91% were against carry on system. DOI: http://dx.doi.org/10.3329/bjme.v3i1.18589 Bangladesh Journal of Medical Education Vol.3(1) 2012: 8-11
B7h Triggering Inhibits the Migration of Tumor Cell Lines
Authors: Dianzani Chiara , Minelli Rosalba , Gigliotti Casimiro Luca , Occhipinti Sergio , Giovarelli Mirella , Conti Laura , Boggio Elena , Shivakumar Yogesh , Baldanzi Gianluca , Malacarne Valeria , Orilieri Elisabetta , Cappellano Giuseppe , Fantozzi Roberto , Sblattero Daniele , Yagi Junji , Rojo Josè Maria , Chiocchetti Annalisa , Dianzani Umberto
Published: April 2014

Vascular endothelial cells (ECs) and several cancer cells express B7h, which is the ligand of the ICOS T cell costimulatory molecule. We have previously shown that B7h triggering via a soluble form of ICOS (ICOS-Fc) inhibits the adhesion of polymorphonuclear and tumor cell lines to HUVECs; thus, we suggested that ICOS-Fc may act as an anti-inflammatory and antitumor agent. Because cancer cell migration and angiogenesis are crucial for metastasis dissemination, the aim of this work was to evaluate the effect of ICOS-Fc on the migration of cancer cells and ECs. ICOS-Fc specifically inhibited the migration of HUVECs, human dermal lymphatic ECs, and the HT29, HCT116, PC-3, HepG2, JR8, and M14 tumor cell lines expressing high levels of B7h, whereas it was ineffective in the RPMI7932, PCF-2, LM, and BHT-101 cell lines expressing low levels of B7h. Furthermore, ICOS-Fc downmodulated hepatocyte growth factor facilitated the epithelial-to-mesenchymal transition in HepG2 cells. Moreover, ICOS-Fc downmodulated the phosphorylation of focal adhesion kinase and the expression of β-Pix in both HUVECs and tumor cell lines. Finally, treatment with ICOS-Fc inhibited the development of lung metastases upon injection of NOD-SCID-IL2Rγnull mice with CF-PAC1 cells, as well as C57BL/6 mice with B16-F10 cells. Therefore, the B7h−ICOS interaction may modulate the spread of cancer metastases, which suggests the novel use of ICOS-Fc as an immunomodulatory drug. However, in the B16-F10–metastasized lungs, ICOS-Fc also increased IL-17A/RORc and decreased IL-10/Foxp3 expression, which indicates that it also exerts positive effects on the antitumor immune response.
Leukotriene B4 Modulates P2X7 Receptor–MediatedLeishmania amazonensisElimination in Murine Macrophages
Authors: Chaves Mariana M. , Marques-da-Silva Camila , Monteiro Ana Paula T. , Canetti Cláudio , Coutinho-Silva Robson
Published: April 2014

ATP is an important signaling molecule in the immune system, and it is able to bind the P2X7 purinergic receptor. Recently, our group showed that ATP-treated macrophages eliminate Leishmania amazonensis. It has been reported that leukotriene B4 (LTB4) reduces the parasitic load of infected macrophages. Additionally, it has been demonstrated that the P2X7 receptor can induce PLA2 activation and arachidonic acid mobilization. Based on these findings, we investigated whether LTB4 is produced upon P2X7 receptor activation and examined whether LTB4 modulates parasite elimination. Using macrophages lacking the P2X7 receptor, we observed that ATP was not able to reduce L. amazonensis load. This result suggests a role of the P2X7 purinergic receptor in parasite elimination. In addition, ATP was sufficient to induce LTB4 release from infected control macrophages but not from macrophages lacking the P2X7 receptor. Moreover, we found that ATP failed to decrease the parasitic load in 5-lipoxygenase (LO)–deficient macrophages. Treatment with the 5-LO inhibitor AA861 also impairs the ATP effect on parasitic loads. Furthermore, macrophages from 5-LO knockout mice eliminated L. amazonensis in the presence of exogenous LTB4, and macrophages obtained from P2X7 receptor knockout mice eliminated L. amazonensis when incubated with ionomycin. Finally, we demonstrated that in the presence of CP105696, an antagonist for LTB4 high-affinity receptor, ATP was not able to reduce parasitic load. These results indicate that P2X7 receptor activation leads to LTB4 formation, which is required for L. amazonensis elimination.
A Silencer-Proximal Intronic Region Is Required for Sustained CD4 Expression in Postselection Thymocytes
Authors: Henson David M. , Chou Chun , Sakurai Nagisa , Egawa Takeshi
Published: April 2014

It has been proposed that differential kinetics of CD4/CD8 coreceptors regulate fate choice of selected thymocytes. Sustained signals by interaction between MHC class II and TCR/CD4 is required for commitment to the CD4 helper lineage. Although prematurely terminated MHC–TCR/CD4 interaction in transgenic mouse models results in lineage redirection, it is unclear whether CD4 expression is actively maintained by endogenous cis-elements to facilitate prolonged signaling under physiological conditions. In this article, we show that sustained CD4 expression in postselection thymocytes requires an intronic sequence containing an uncharacterized DNase I hypersensitivity (DHS) site located 3′ to the silencer. Despite normal CD4 expression before selection, thymocytes lacking a 1.5-kb sequence in intron 1 including the 0.4-kb silencer and the DHS, but not the 0.4-kb silencer alone, failed to maintain CD4 expression upon positive selection and are redirected to the CD8 lineage after MHC class II–restricted selection. Furthermore, CpG dinucleotides adjacent to the DHS are hypermethylated in CD8+ T cells. These results indicate that the 1.5-kb cis-element is required in postselection thymocytes for helper lineage commitment, presumably mediating the maintenance of CD4 expression, and suggest that inactivation of the cis-element by DNA methylation may contribute to epigenetic Cd4 silencing.
Smurf2 Negatively Modulates RIG-I–Dependent Antiviral Response by Targeting VISA/MAVS for Ubiquitination and Degradation
Authors: Pan Yu , Li Rui , Meng Jun-Ling , Mao He-Ting , Zhang Yu , Zhang Jun
Published: April 2014

VISA (also known as MAVS, Cardif, IPS-1) is the essential adaptor protein for virus-induced activation of IFN regulatory factors 3 and 7 and production of type I IFNs. Understanding the regulatory mechanisms for VISA will provide detailed insights into the positive or negative regulation of innate immune responses. In this study, we identified Smad ubiquitin regulatory factor (Smurf) 2, one of the Smad ubiquitin regulator factor proteins, as an important negative regulator of virus-triggered type I IFN signaling, which targets at the VISA level. Overexpression of Smurf2 inhibits virus-induced IFN-β and IFN-stimulated response element activation. The E3 ligase defective mutant Smurf2/C716A loses the ability to suppress virus-induced type I IFN signaling, suggesting that the negative regulation is dependent on the ubiquitin E3 ligase activity of Smurf2. Further studies demonstrated that Smurf2 interacted with VISA and targeted VISA for K48-linked ubiquitination, which promoted the degradation of VISA. Consistently, knockout or knockdown of Smurf2 expression therefore promoted antiviral signaling, which was correlated with the increase in protein stability of VISA. Our findings suggest that Smurf2 is an important nonredundant negative regulator of virus-triggered type I IFN signaling by targeting VISA for K48-linked ubiquitination and degradation.
Phagocytosis of Staphylococcus aureus by Human Neutrophils Prevents Macrophage Efferocytosis and Induces Programmed Necrosis
Authors: Greenlee-Wacker Mallary C. , Rigby Kevin M. , Kobayashi Scott D. , Porter Adeline R. , DeLeo Frank R. , Nauseef William M.
Published: April 2014

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pose a significant threat to human health. Polymorphonuclear leukocytes (PMN) are the first responders during staphylococcal infection, but 15–50% of the initial ingested inoculum survives within the PMN phagosome and likely contributes directly or indirectly to disease pathogenesis. We hypothesize that surviving intracellular CA-MRSA undermine effective phagocyte-mediated defense by causing a decrease in macrophage uptake of PMN containing viable S. aureus and by promoting PMN lysis. In support of this hypothesis, PMN harboring viable CA-MRSA strain USA300 (PMN-SA) upregulated the “don't eat me” signal CD47, remained bound to the surface, and were inefficiently ingested by macrophages. In addition, coculture with PMN-SA altered the macrophage phenotype. Compared to macrophages fed USA300 alone, macrophages challenged with PMN-SA produced more IL-8 and less IL-1 receptor antagonist, TNF-α, activated caspase-1, and IL-1β. Although they exhibited some features of apoptosis within 3 h following ingestion of S. aureus, including phosphatidylserine exposure and mitochondrial membrane depolarization, PMN-SA had sustained levels of proliferating cell nuclear Ag expression, absence of caspase activation, and underwent lysis within 6 h following phagocytosis. PMN lysis was dependent on receptor-interacting protein 1, suggesting that PMN-SA underwent programmed necrosis or necroptosis. These data are the first demonstration, to our knowledge, that bacteria can promote sustained expression of proliferating cell nuclear Ag and that human PMN undergo necroptosis. Together, these findings demonstrate that S. aureus surviving within PMN undermine the innate immune response and may provide insight into the pathogenesis of S. aureus disease.
A Humanized Antibody That Regulates the Alternative Pathway Convertase: Potential for Therapy of Renal Disease Associated with Nephritic Factors
Authors: Paixão-Cavalcante Danielle , Torreira Eva , Lindorfer Margaret A. , Rodriguez de Cordoba Santiago , Morgan B. Paul , Taylor Ronald P. , Llorca Oscar , Harris Claire L.
Published: April 2014

Dysregulation of the complement alternative pathway can cause disease in various organs that may be life-threatening. Severe alternative pathway dysregulation can be triggered by autoantibodies to the C3 convertase, termed nephritic factors, which cause pathological stabilization of the convertase enzyme and confer resistance to innate control mechanisms; unregulated complement consumption followed by deposition of C3 fragments in tissues ensues. The mAb, 3E7, and its humanized derivative, H17, have been shown previously to specifically bind activated C3 and prevent binding of both the activating protein, factor B, and the inhibitor, factor H, which are opposite effects that complicate its potential for therapy. Using ligand binding assays, functional assays, and electron microscopy, we show that these Abs bind C3b via a site that overlaps the binding site on C3 for the Ba domain within factor B, thereby blocking an interaction essential for convertase formation. Both Abs also bind the preformed convertase, C3bBb, and provide powerful inhibition of complement activation by preventing cleavage of C3. Critically, the Abs also bound and inhibited C3 cleavage by the nephritic factor–stabilized convertase. We suggest that by preventing enzyme formation and/or cleavage of C3 to its active downstream fragments, H17 may be an effective therapy for conditions caused by severe dysregulation of the C3 convertase and, in particular, those that involve nephritic factors, such as dense deposit disease.
Autoantibodies Induced by Chimeric Cytokine-HIV Envelope Glycoprotein Immunogens
Authors: Isik Gözde , van Montfort Thijs , Chung Nancy P. Y. , Moore John P. , Sanders Rogier W.
Published: April 2014

Cytokines are often used as adjuvants to increase the immunogenicity of vaccines because they can improve the immune response and/or direct it into a desired direction. As an alternative to codelivering Ags and cytokines separately, they can be fused into a composite protein, with the advantage that both moieties act on the same immune cells. The HIV-1 envelope glycoprotein (Env) spike, located on the outside of virus particles and the only relevant protein for the induction of neutralizing Abs, is poorly immunogenic. The induction of anti-Env Abs can be improved by coupling Env proteins to costimulatory molecules such as a proliferation inducing ligand (APRIL). In this study, we evaluated the immunogenicity of chimeric molecules containing uncleaved Env gp140 fused to the species-matched cytokines IL-21 or GM-CSF in rabbits and mice. Each cytokine was either fused to the C terminus of Env or embedded within Env at the position of the variable loops 1 and 2. The cytokine components of the chimeric Env-GM-CSF and Env-IL-21 molecules were functional in vitro, but none of the Env-cytokine fusion proteins resulted in improved Ab responses in vivo. Both the Env-GM-CSF and the Env-IL-21 molecules induced strong anticytokine Ab responses in both test species. These autoimmune responses were independent of the location of the cytokine in the chimeric Env molecules in that they were induced by cytokines inserted within the variable loops 1 and 2 of Env or fused to its C terminus. The induction of undesired autoimmune responses should be considered when using cytokines as costimulatory molecules in fusion proteins.
The 2007 eruptions and caldera collapse of the Piton de la Fournaise volcano (La Réunion Island) from tilt analysis at a single very broadband seismic station
Authors: Fontaine Fabrice R. , Roult Geneviève , Michon Laurent , Barruol Guilhem , Muro Andrea Di
Published: April 2014

Seismic records from La Réunion Island very broadband Geoscope station are investigated to constrain the link between the 2007 eruptive sequence and the related caldera collapse of the Piton de la Fournaise volcano. Tilt estimated from seismic records reveals that the three 2007 eruptions belong to a single inflation‐deflation cycle. Tilt trend indicates that the small‐volume summit eruption of 18 February occurred during a phase of continuous inflation that started in January 2007. Inflation decelerated 24 days before a second short‐lived, small‐volume eruption on 30 March, almost simultaneous with a sudden, large‐scale deflation of the volcano. Deflation rate, which had stabilized at relatively low level, increased anew on 1 April while no magma was erupted, followed on 2 April by a major distal eruption and on 5 April by a summit caldera collapse. Long‐term tilt variation suggests that the 2007 eruptive succession was triggered by a deep magma input.
Effect of granular activated carbon concentration on the content of organic matter and salt, influencing E. coli activity and survival in fluidized bed disinfection reactor
Authors: Racyte Justina , Langenhoff Alette A.M. , Ribeiro Ana F.M.M.R. , Paulitsch‐Fuchs Astrid H. , Bruning Harry , Rijnaarts Huub H.M.
Published: April 2014

Granular activated carbon (GAC) is used in water treatment systems, typically to remove pollutants such as natural organic matter, volatile organic compounds, chlorine, taste, and odor. GAC is also used as a key component of a new technology that combines a fluidized bed reactor with radio frequency electric fields for disinfection. So far, the effects of GAC on bacteria in these fluidized bed reactors are unclear. This paper describes a systematic study of the physico‐chemical changes in five microbial media compositions caused by different concentrations (23–350 g/L) of GAC, and the effects of these physico‐chemical changes on the metabolic activity and survival of a model microorganism (Escherichia coli YMc10) in a fluidized bed reactor. The chemical adsorption taking place in suspensions with specific GAC changed nutritional, osmotic, and pH conditions in the investigated microbial media (LB, diluted LB, PBS, diluted PBS, and tap water), leading to a decay of the metabolic activity and survival of E. coli. Especially media that are poor in organic and mineral compounds (e.g., PBS) with suspended GAC showed a concentration decay of 3.5 Log CFU/mL E. coli after 6 h. Organic compounds depletion and severe pH variation were enhanced in the presence of higher GAC concentrations. Biotechnol. Bioeng. 2014;111: 2009–2018. © 2014 Wiley Periodicals, Inc.
Segmented flow is controlling growth of catalytic biofilms in continuous multiphase microreactors
Authors: Karande Rohan , Halan Babu , Schmid Andreas , Buehler Katja
Published: April 2014

Biofilm reactors are often mass transfer limited due to excessive biofilm growth, impeding reactor performance. Fluidic conditions play a key role for biofilm structural development and subsequently for overall reactor performance. Continuous interfacial forces generated by aqueous‐air segmented flow are controlling biofilm structure and diminish mass transfer limitations in biofilm microreactors. A simple three step method allows the formation of robust biofilms under aqueous‐air segmented flow conditions: a first‐generation biofilm is developing during single phase flow, followed by the introduction of air segments discarding most of the established biofilm. Finally, a second‐generation, mature biofilm is formed in the presence of aqueous‐air segments. Confocal laser scanning microscopy experiments revealed that the segmented flow supports the development of a robust biofilm. This mature biofilm is characterized by a three to fourfold increase in growth rate, calculated from an increase in thickness, a faster spatial distribution (95% surface coverage in 24 h), and a significantly more compact structure (roughness coefficient <1), as compared to biofilms grown under single phase flow conditions. The applicability of the concept in a segmented flow biofilm microreactor was demonstrated using the epoxidation of styrene to (S)‐styrene oxide (ee > 99.8%) catalyzed by Pseudomonas sp. strain VLB120ΔC cells in the mono‐species biofilm. The limiting factor affecting reactor performance was oxygen transfer as the volumetric productivity rose from 11 to 46 g Ltube−1 day−1 after increasing the air flow rate. In summary, different interfacial forces can be applied for separating cell attachment and adaptation resulting in the development of a robust catalytic biofilm in continuous microreactors. Biotechnol. Bioeng. 2014;111: 1831–1840. © 2014 Wiley Periodicals, Inc.
A pilot study linking reduced fronto–Striatal recruitment during reward processing to persistent bingeing following treatment for binge‐eating disorder
Authors: Balodis Iris M. , Grilo Carlos M. , Kober Hedy , Worhunsky Patrick D. , White Marney A. , Stevens Michael C. , Pearlson Godfrey D. , Potenza Marc N.
Published: April 2014

Objective

The primary purpose of this study was to examine neurobiological underpinnings of reward processing that may relate to treatment outcome for binge‐eating disorder (BED).

Method

Prior to starting treatment, 19 obese persons seeking treatment for BED performed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Analyses examined how the neural correlates of reward processing related to binge‐eating status after 4‐months of treatment.

Results

Ten individuals continued to report binge‐eating (BEpost‐tx) following treatment and 9 individuals did not (NBEpost‐tx). The groups did not differ in body mass index. The BEpost‐tx group relative to the NBEpost‐tx group showed diminished recruitment of the ventral striatum and the inferior frontal gyrus during the anticipatory phase of reward processing and reduced activity in the medial prefrontal cortex during the outcome phase of reward processing.

Discussion

These results link brain reward circuitry to treatment outcome in BED and suggest that specific brain regions underlying reward processing may represent important therapeutic targets in BED. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:376–384)
Identification of the proteomic variations of invasive relative to non‐invasive non‐functional pituitary adenomas
Authors: Zhan Xianquan , Desiderio Dominic M. , Wang Xiaowei , Zhan Xiaohan , Guo Tianyao , Li Maoyu , Peng Fang , Chen Xiaoyu , Yang Haiyan , Zhang Pengfei , Li Xuejun , Chen Zhuchu
Published: April 2014

The incomplete surgery section of invasive non‐functional pituitary adenomas (NFPAs) carries the increased risks of complications and requires adjuvant radiotherapy and medications. It is necessary to clarify the molecular mechanisms and markers of invasiveness to guide the management of NFPA patients. The study aimed to proteomic variations of invasive and non‐invasive NFPAs and sought the protein markers for invasive NFPAs. Invasive (n = 4) and non‐invasive (n = 4) NFPA tissues were analyzed (n = 3–5/each tissue) with 2DE and PDQuest software. Twenty‐four high‐resolution 2DE gels were quantitatively compared to determine differentially expressed proteins (DEPs) between invasive and non‐invasive NFPAs. Approximately 1200 protein spots were detected in each 2DE map, and 103 differential spots (64 upregulated and 39 downregulated) were identified. Among those 103 differential spots, 57 DEPs (30 upregulated and 27 downregulated) were characterized with peptide mass fingerprint and MS/MS. Gene‐ontology (GO) and ingenuity pathway analyses of those DEPs revealed pathway networks including mitochondrial dysfunction, oxidative stress, mitogen‐activated protein kinase signaling abnormality, TR/RXR activation, proteolysis abnormality, ketogenesis and ketolysis, cyclin‐dependent kinase C signaling abnormality, and amyloid processing that were significantly associated with invasive characteristics of invasive NFPA. Those data demonstrate that proteomic variations exist between invasive and non‐invasive NFPAs. 2DE‐based comparative proteomics is an effective approach to identify proteomic variations and pathway network variations. Those findings will serve as a basis to understand the molecular mechanisms of invasive NFPAs and to discover protein markers to effectively manage patients with invasive NFPAs.
Stationary phases for the enrichment of glycoproteins and glycopeptides
Authors: Huang Bao‐Yu , Yang Chun‐Kai , Liu Ching‐Piao , Liu Chuen‐Ying
Published: April 2014

The analysis of protein glycosylation is important for biomedical and biopharmaceutical research. Recent advances in LC‐MS analysis have enabled the identification of glycosylation sites, the characterisation of glycan structures and the identification and quantification of glycoproteins and glycopeptides. However, this type of analysis remains challenging due to the low abundance of glycopeptides in complex protein digests, the microheterogeneity at glycosylation sites, ion suppression effects and the competition for ionisation by co‐eluting peptides. Specific sample preparation is necessary for comprehensive and site‐specific glycosylation analyses using MS. Therefore, researchers continue to pursue new columns to broaden their applications. The current manuscript covers recent literature published from 2008 to 2013. The stationary phases containing various chemical bonding methods or ligands immobilisation strategies on solid supports that selectively enrich N‐linked or sialylated N‐glycopeptides are categorised with either physical or chemical modes of binding. These categories include lectin affinity, hydrophilic interactions, boronate affinity, titanium dioxide affinity, hydrazide chemistry and other separation techniques. This review should aid in better understanding the syntheses and physicochemical properties of each type of stationary phases for enriching glycoproteins and glycopeptides.
Association of DNA base excision repair genes (OGG1, APE1 and XRCC1) polymorphisms with outcome to platinum‐based chemotherapy in advanced nonsmall‐cell lung cancer patients
Authors: Peng Yu , Li Zheng , Zhang Shiheng , Xiong Yanli , Cun Yanping , Qian Chengyuan , Li Mengxia , Ren Tao , Xia Lei , Cheng Yi , Wang Dong
Published: April 2014

Polymorphism of DNA base excision repair (BER) genes affects DNA repair capacity and may alter sensitivity to platinum‐based chemotherapy regimens. This study investigated polymorphisms of OGG1 Ser326Cys, APE1 Asp148Glu APE1‐141T/G and XRCC1 Arg399Gln for association with clinical outcome in 235 advanced inoperable nonsmall‐cell lung cancer (NSCLC) patients after treatment with platinum‐based chemotherapy. The multivariate analysis showed that OGG1 326 GC was associated with poor PFS [hazard ratio (HR) 1.730, p = 0.005], while XRCC1 399 GA, or GA+AA, was associated with poor OS in short‐term period (HR 1.718, p = 0.003; HR 1.691, p = 0.003, respectively). Patients with OGG1 326/XRCC1 399 variant alleles had a higher risk to die early in short‐term period (HR 1.929, p < 0.001). Furthermore, patients with XRCC1 399 variant allele (GA+AA) had higher risk of hematologic toxicity (p = 0.009), whereas patients carrying the OGG1 326 variant (GG), or the APE1‐141 GG variant, had reduced risk of gastrointestinal toxicity (p = 0.015 and p = 0.023, respectively). The data from the current study provide evidence that OGG1 Ser326Cys, XRCC1 Arg399Gln, APE1 Asp148Glu, and APE1‐141T/G polymorphisms may be useful in predicting clinical outcomes in patients with advanced inoperable NSCLC that will undergo platinum‐based chemotherapy.
Kaposi's Sarcoma in HIV‐infected patients in South Africa: Multicohort study in the antiretroviral therapy era
Authors: Bohlius Julia , Valeri Fabio , Maskew Mhairi , Prozesky Hans , Garone Daniela , Sengayi Mazvita , Fox Matthew P. , Davies Mary‐Ann , Egger Matthias
Published: April 2014

The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV‐infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time‐updated CD4 cell counts and HIV‐1 RNA. A total of 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/μL) were included. During 37,488 person‐years follow‐up 162 patients developed KS. The incidence was 1,682/100,000 person‐years (95% confidence interval [CI] 1,406–2,011) among patients not receiving ART and 138/100,000 person‐years (95% CI 102–187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13–0.28). Low CD4 cell counts (time‐updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9–80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to prevent KS and KS‐associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV.