A single amino acid substitution in the novel H7N9 influenza A virus NS1 protein increases CPSF30 binding and virulence

Although an effective interferon antagonist in human and avian cells, the novel H7N9 influenza virus NS1 protein is defective at inhibiting CPSF30. An I106M substitution in H7N9 NS1 can restore CPSF30 binding together with the ability to block host gene expression. Furthermore, a recombinant virus expressing H7N9 NS1-I106M replicates to higher titers in vivo, and is subtly more virulent, than parental. Natural polymorphisms in H7N9 NS1 that enhance CPSF30 binding may be cause for concern

Positive regulatory role of the e3 ubiquitin ligase TRIM65 downstream the IFNβ induction pathway.

Introduction: Viral infection triggers a fast and effective cellular response mediated primarily by the production of interferon β (IFNβ) that induces an anti-viral state through complex signal cascades. Therefore, the regulation of its induction and subsequent IFNβ signaling needs to be tightly controlled. There is growing evidence implicating the members of Tripartite-motif (TRIM) protein family of E3 ligases as critical players in this regulation. However, the exact role, mechanism of action, and the physiological relevance of their activity in vivo still remain poorly investigated. Previous work in our lab revealed that an unprecedented large number of TRIMs play critical roles as enhancers in the regulation of innate immune signaling pathways. Methods: To study the role of TRIM65 in innate immune signaling we have used luciferase assays, overexpression in A549 and 293T cells, transient knock down using siRNAs in 293T cells, TRIM65 CRISPR knock out cell lines, Western blots, RT-qPCR, PR8-GLuc antiviral assays and immunofluorescence. Results: Our recent studies focused on TRIM65 showed that this protein possesses antiviral activity comparable to TRIM25 in a PR8-GLuc antiviral assay. We have also demonstrated that its overexpression strongly increased not only the 2CARD-RIG-I- but also the IRF3-dependent activation of the INFβ and ISRE reporters. Consequently, IFNβ, ISG54 as well as other cytokines and ISGs mRNA levels are decreased in TRIM65 knock down and knock out (KO) cells upon infection compared to infected/treated control cells. Re-constitution assays on TRIM65 KO cells reverted the inhibition of IFNβ and ISG54 confirming the phenotype. Altogether, these data indicates a stimulatory role for TRIM65 downstream the interferon induction pathway. Since the E3 ubiquitin ligase activity of many TRIMs has been linked to their antiviral functions, we have identified IRF3 and IRF7 as TRIM65 interacting factors and putative substrates. Immunofluorescence experiments suggest that IRF3 binds TRIM65 in the nucleus and in vitro ubiquitination assays indicates that TRIM65 is able to ubiquitinate IRF3 in a RING-independent manner. Our current studies are focused on completely delineate the molecular mechanism by which TRIM65-mediated ubiquitination or TRIM65 E3 Ub ligase-independent function could regulate the response to viral infection. Conclusion: A better understanding of positive regulatory networks of the IFN response will provide new knowledge that will help to design more effective therapeutics

Investimentos e gastos com pessoal : a lei de responsabilidade fiscal (lrf) e a efetividade dos serviços de saúde dos municípios brasileiros

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Economia, Administração e Contabilidade, Programa de Pós-Graduação em Administração, 2012.Com a estabilização monetária, em meados dos anos 1990, veio à tona a difícil situação fiscal dos entes federativos, trazendo para dentro do poder público questões como o ajuste fiscal e o controle dos gastos públicos, gerando a necessidade de se criarem normas mais rígidas para as finanças públicas. No ano 2000 foi aprovada a Lei Complementar 101/2000, a chamada Lei de Responsabilidade Fiscal (LRF). Dentro deste contexto, surgiu o problema da presente pesquisa: identificar se a LRF influenciou os gastos e a efetividade dos serviços de saúde nos municípios brasileiros. Com o fim de encontrar respostas à este problema, foram oletados dados financeiros e de efetividade (mortalidade infantil) nas bases de dados do Ministério da Saúde (DATASUS), abrangendo o período de 2000 a 2009, e os dados foram analisados de forma quantitativa, com o auxílio dos testes de correlação de Spearman-rho e de Wilcoxon, além da estatística descritiva. Os dados mostraram que os gastos totais com saúde apresentaram um grande aumento no período analisado, aumento este justificado principalmente pelos gastos com pessoal, que aumentaram em uma grandeza semelhante aos gastos totais, ao contrário dos gastos com investimentos que, apesar de um aumento no período, teve uma evolução no período bem mais baixa. Os resultados também indicaram que a relação entre os gastos e a mortalidade infantil não é tão linear e direta como acredita-se. Outro resultado encontrado diz respeito aos investimentos em anos eleitorais, que apresentam valores estatisticamente maiores do que nos anos em que não haviam eleições. Com isto, o trabalho apresenta como contribuição a ausência de uma relação linear e direta entre os gastos com saúde e o indicador de Mortalidade Infantil, indicando a necessidade de estudos mais profundos para se estudar quais indicadores podem estar presentes nesta relação, visando tornar as políticas públicas mais eficientes nos municípios brasileiros. Há também que se destacar o comportamento de alta nos investimentos nos anos eleitorais e a necessidade de compreender este comportamento. Sugere-se o continuado uso do gasto público por fins eleitorais, questão que também precisa de estudo em maior profundidade. _______________________________________________________________________________________ ABSTRACTWith the achievement of monetary stability in the mid-1990s, the fiscal situation of the entities of the Brazilian federation came to the forefront of concerns, directing attention to the need for fiscal adjustments, control of public expenditure and the need to apply more rigorous standards in the area of public finance. In 2001, Complementary Law 101/2000, the so-called Law of Fiscal Responsibility (LRF) was passed. It is within this context that the research problem for this dissertation arose: to identify whether the LRF has influenced expenditures for and the effectiveness of health services in Brazilian municipalities. To this end, financial data and data with respect to effectiveness (using infant mortality as proxy) were collected from the data bases of the Health Ministry (DATASUS), covering the period from 2000 through 2009. The data were analyzed using descriptive statistical methods and applying the Spearman-rho and Wilcoxon correlation tests. Results show that total expenditures for health increased during the period analyzed, owing principally to expenditures with personnel, which increased in a way similar to that for overall health costs. This pattern differed from that observed for investment expenditure during the period. Although expenditure for investment also increased, the percentage of increase was considerably less than that observed for personnel or for health expenditures overall. It was also observed that the levels of investment during election years were higher than in non-election years to a statistically significant degree. Results also revealed that the relationship between expenditures and infant mortality is not as direct and linear as has been supposed. Contributions of the study are the observation of the absence of a direct, linear relationship between health expenditure and the infant mortality rate, suggesting the need for further study for identifying more appropriate indicators for policy effectiveness. In addition, the identification of significantly greater investment expenditures during election years highlights the need to understand this behavior. This behavior suggests the continued use of public spending for electoral purposes, an issue that also calls for more study

Comunicação de informações entre as equipes de saúde na transferência do cuidado pré-hospitalar : implicações para a segurança dos pacientes

Estudo com objetivo de analisar a comunicação de informações entre as equipes de saúde na transferência do cuidado pré-hospitalar e as suas implicações para a segurança do paciente. Delineamento descritivo-exploratório, com abordagem qualitativa, realizado no Serviço de Atendimento Móvel de Urgência – SAMU 192 de Porto Alegre- RS. Participaram do estudo médicos, enfermeiros e técnicos/auxiliares de enfermagem envolvidos na assistência às vítimas. Os dados foram coletados por meio de observação não-participante e entrevista semiestruturada, realizados nos meses de abril a junho de 2018. Foram entrevistados 28 profissionais e observados 34 períodos com média de 4 horas de duração. Projeto aprovado pelo Comitê de Ética em Pesquisa da instituição proponente e da instituição coparticipante. Os dados foram submetidos à análise de conteúdo e resultaram nas categorias: (1) caracterização das informações; (2) circunstâncias que dificultam a transferência do cuidado; (3) circunstâncias que contribuem para transferência do cuidado; (4) intervenientes na segurança do paciente e da equipe; (5) a dimensão (inter)pessoal/profissional da transferência do cuidado. A primeira categoria incluiu aspectos referentes à qualidade e completude das informações coletadas, registras e transferidas. A segunda categoria contemplou a falta de padronizações durante as transferências do cuidado, a superlotação dos serviços e a forma como o SAMU e os pacientes são recebidos pelas equipes que darão continuidade ao cuidado. Na terceira categoria, foram apontadas as pactuações na rede de atenção às urgências e emergências e a visibilidade dos casos graves nas transferências do cuidado. A quarta categoria aborda as diferentes perspectivas entre os serviços e os diversos riscos para o paciente e equipe durante o transporte e transferência do cuidado. A quinta categoria revelou que uma comunicação verticalizada pelas hierarquias, é influenciada por características pessoais e emocionais e influencia na qualidade das transferências. Concluiu-se que são necessários investimentos, como a elaboração de protocolos e a realização de treinamentos específicos para o processo de comunicação de informações entre as equipes de saúde na transferência do cuidado pré-hospitalar, visando o incremento de ações de segurança do paciente.Study aimed at analyzing the communication of information between health teams in the transfer of the pre-hospital care and its implications for patient safety. Descriptive-exploratory design, with a qualitative approach, carried out at the Mobile Emergency Service - SAMU 192 of Porto Alegre, RS. Doctors, nurses and technicians/nursing assistants involved in victims’ assistance participated in the study. The data were collected through non-participant observation and semi-structured interviews, carried out in the months from April to June, 2018. Twenty-eight professionals were interviewed and thirty-four periods were observed with an average of four hours. Project approved by the Research Ethics Committee of the proposing institution and of the co-participating institution. The data were submitted to content analysis and resulted in the following categories: (1) characterization of the information; (2) circumstances that hinder the transfer of the care provision; (3) circumstances that contribute to the transfer of the care provision; (4) stakeholders for the patient and team safety; (5) the (inter)personal/professional dimension of the care provision transfer. The first category included aspects related to the quality and completeness of the information collected, registered and transferred. The second category addressed the lack of standardization during the care provision transfers, overcrowding of the services, and the way SAMU and patients are received by the teams that will continue to provide care. In the third category, it was pointed out the agreements in the care network to emergencies and the visibility of severe cases in the transfers of care provision. The fourth category addresses the different perspectives among the services and the several risks to the patient and staff during transportation and transfer of care provision. The fifth category revealed that hierarchical communication is influenced by personal and emotional characteristics and influences the quality of transfers. It was concluded that investments are needed, such as the elaboration of protocols and the execution of specific training for the process of communication of information among health teams in the transfer of pre-hospital care, aiming at increasing patient safety actions

Evolução da exploração agrícola no Rio Grande do Sul

The geographical studies of rural space in recent years are above all directed towards agrarian organization. The present work approaches the question of the process of accupation of the territory of Rio Grande do Sul trying to capture the dynamics of space organization through an analysis of the evolution of agriculture in the State. The relationships that results from the natural environment and from the historical process are understood as determinant elements of the structural and conjunctural transformations that were estabilished in recent years, separating the Old Rio Grande from the New Rio Grande.Os estudos geográficos do espaço rural nos últimos anos estão direcionados, sobretudo, à organização agrária. Este trabalho, aborda o processo de ocupação do território sul-rio-grandense tentando captar a dinâmica da organização espacial através da análise da evolução agrícola do Estado. As relações advindas do meio natural e do processo histórico, são apreendidas como elementos determinantes das transformações estruturais e conjunturais que se estabeleceram nos últimos anos, separando o “Velho Rio Grande” do “Rio Grande de hoje”

Growth and Physical Structure of Amorphous Boron Carbide Deposited by Magnetron Sputtering on a Silicon Substrate with a Titanium Interlayer

Multilayer amorphous boron carbide coatings were produced by radiofrequency magnetron sputtering on silicon substrates. To improve the adhesion, titanium interlayers with different thickness were interposed between the substrate and the coating. Above three hundreds nanometer, the enhanced roughness of the titanium led to the growth of an amorphous boron carbide with a dense and continuing columnar structure, and no delamination effect was observed. Correspondingly, the adhesion of the coating became three time stronger than in the case of a bare silicon substrate. Physical structure and microstructural proprieties of the coatings were investigated by means of a scan electron microscopy, atomic force microscopy and X-ray diffraction. The adhesion of the films was measured by a scratch tester

Modernização, Ações e Processos no Modelo de Produção Rural Familiar do Município de Ijuí, RS*

The present paper aims at to recognize and characterize the actionsof the modernization processes in the agriculture and their effects in familyagriculture areas. Thus, it attempts to analyze in which manner the globalization of Brazilian economy affected the rural area issues, taking asempirical reference the rural properties in Ijuí-RS, Brazil. Some categorieswere analyzed, such as the use of natural resources - primarily, the use ofland - the social resources, the processes and the determiners of productionthat subdue the areas of the family agriculture. The study of the rural areaof the town of Ijuí was accomplished according to a Systemic investigativemethodology, as well as a specific rural study case. In addition, the variablesthat led the study were regarded to three categories: environmental, socialand agricultural production. Thus, the units which had more aggressivemodernization processes because of the influence of modernization overthe environment resulted in changes which can be measured mainly in unitsof family production. It occurred due to the limited availability of land inorder to develop families’ social-economical reproduction.Este estudo teve como objetivo reconhecer e caracterizar as açõesdos processos modernizantes da agricultura e as alterações provocadas naagricultura familiar. Assim, buscou-se analisar os envolvimentos que aglobalização da economia brasileira trouxe para a área rural, tendo comoreferencial empírico o espaço rural do município de Ijuí, RS, Brasil. Considerandocomo elemento de análise a utilização dos recursos naturais, principalmenteo uso da terra, os recursos sociais, os processos e oscondicionantes da produção que submetem às áreas das unidades de produçãofamiliar rural. O modelo investigativo baseado na metodologiasistêmica conduziu o estudo do rural de Ijuí, bem como de um caso específico.As variáveis referentes ao estudo são de três categorias: ambiental,social e de produção agropecuária. . Entretanto, a influência da modernizaçãosobre o meio ambiente resultou em alterações que podem ser medidas,principalmente, em unidades de produção familiar, pois foi nestas unidadesque os processos modernizantes foram mais intensivos devido a disponibilidadede área ser limitada para a reprodução socioeconômica familiar

Design optimization of RF lines in vacuum environment for the MITICA experiment

This contribution regards the Radio Frequency (RF) transmission line of the Megavolt ITER Injector and Concept Advancement (MITICA) experiment. The original design considered copper coaxial lines of 1″ 5/8, but thermal simulations under operating conditions showed maximum temperatures of the lines at regime not compatible with the prescription of the component manufacturer. Hence, an optimization of the design was necessary. Enhancing thermal radiation and increasing the conductor size were considered for design optimization: thermal analyses were carried out to calculate the temperature of MITICA RF lines during operation, as a function of the emissivity value and of other geometrical parameters. Five coating products to increase the conductor surface emissivity were tested, measuring the outgassing behavior of the selected products and the obtained emissivity values

Growth and Physical Structure of Amorphous Boron Carbide Deposited by Magnetron Sputtering on a Silicon Substrate with a Titanium Interlayer

Multilayer amorphous boron carbide coatings were produced by radiofrequency magnetron sputtering on silicon substrates. To improve the adhesion, titanium interlayers with different thickness were interposed between the substrate and the coating. Above three hundreds nanometer, the enhanced roughness of the titanium led to the growth of an amorphous boron carbide with a dense and continuing columnar structure, and no delamination effect was observed. Correspondingly, the adhesion of the coating became three time stronger than in the case of a bare silicon substrate. Physical structure and microstructural proprieties of the coatings were investigated by means of a scan electron microscopy, atomic force microscopy and X-ray diffraction. The adhesion of the films was measured by a scratch tester