Structural Evidence for a Copper-Bound Carbonate Intermediate in the Peroxidase and Dismutase Activities of Superoxide Dismutase

Copper-zinc superoxide dismutase (SOD) is of fundamental importance to our understanding of oxidative damage. Its primary function is catalysing the dismutation of superoxide to O2 and H2O2. SOD also reacts with H2O2, leading to the formation of a strong copper-bound oxidant species that can either inactivate the enzyme or oxidise other substrates. In the presence of bicarbonate (or CO2) and H2O2, this peroxidase activity is enhanced and produces the carbonate radical. This freely diffusible reactive oxygen species is proposed as the agent for oxidation of large substrates that are too bulky to enter the active site. Here, we provide direct structural evidence, from a 2.15 Å resolution crystal structure, of (bi)carbonate captured at the active site of reduced SOD, consistent with the view that a bound carbonate intermediate could be formed, producing a diffusible carbonate radical upon reoxidation of copper. The bound carbonate blocks direct access of substrates to Cu(I), suggesting that an adjunct to the accepted mechanism of SOD catalysed dismutation of superoxide operates, with Cu(I) oxidation by superoxide being driven via a proton-coupled electron transfer mechanism involving the bound carbonate rather than the solvent. Carbonate is captured in a different site when SOD is oxidised, being located in the active site channel adjacent to the catalytically important Arg143. This is the probable route of diffusion from the active site following reoxidation of the copper. In this position, the carbonate is poised for re-entry into the active site and binding to the reduced copper. © 2012 Strange et al

Stochastic quantization of a self-interacting nonminimal scalar field in semiclassical gravity

We employ stochastic quantization for a self-interacting nonminimal massive scalar field in curved spacetime. The covariant background field method and local momentum space representation are used to obtain the Euclidean correlation function and evaluate multi-loop quantum corrections through simultaneous expansions in the curvature tensor and its covariant derivatives and in the noise fields. The stochastic correlation function reproduces the well-known result by Bunch and Parker and is used to construct the effective potential in curved spacetime in an arbitrary dimension $D$ up to the first order in curvature. Furthermore, we present a sample of numerical simulations for $D=3$ in the first order in curvature.Comment: Corrected formulations, some two-loop results added. Fits the version accepted in Physics Letters

HPC Cloud for Scientific and Business Applications: Taxonomy, Vision, and Research Challenges

High Performance Computing (HPC) clouds are becoming an alternative to on-premise clusters for executing scientific applications and business analytics services. Most research efforts in HPC cloud aim to understand the cost-benefit of moving resource-intensive applications from on-premise environments to public cloud platforms. Industry trends show hybrid environments are the natural path to get the best of the on-premise and cloud resources---steady (and sensitive) workloads can run on on-premise resources and peak demand can leverage remote resources in a pay-as-you-go manner. Nevertheless, there are plenty of questions to be answered in HPC cloud, which range from how to extract the best performance of an unknown underlying platform to what services are essential to make its usage easier. Moreover, the discussion on the right pricing and contractual models to fit small and large users is relevant for the sustainability of HPC clouds. This paper brings a survey and taxonomy of efforts in HPC cloud and a vision on what we believe is ahead of us, including a set of research challenges that, once tackled, can help advance businesses and scientific discoveries. This becomes particularly relevant due to the fast increasing wave of new HPC applications coming from big data and artificial intelligence.Comment: 29 pages, 5 figures, Published in ACM Computing Surveys (CSUR

Gauge invariance of the background average effective action

Using the background field method for the functional renormalization group approach in the case of a generic gauge theory, we study the background field symmetry and gauge dependence of the background average effective action, when the regulator action depends on external fields. The final result is that the symmetry of the average effective action can be maintained for a wide class of regulator functions, but in all cases the dependence of the gauge fixing remains on-shell. The Yang-Mills theory is considered as the main particular example.Comment: Fits the version accepted in EPJ

Reprodutibilidade de três classificações de fraturas na região proximal do úmero

OBJECTIVE: To propose a new system for classifying proximal humeral neck fractures, and to evaluate intra- and interobserver agreement using the Neer system that is the most commonly used in the area and the Arbeit Gemeinschaft für Osteosynthesefragen system created by an European group, and a new classification system proposed by the authors of this study. METHODS: A total of 56 patients with proximal humeral fractures were selected, and submitted to digitized simple radiography in antero-posterior shoulder and scapular profile. Radiographs were analyzed by three observers at time one, and then three and six weeks later. The kappa coefficient modified by Fleiss was used for the analysis. RESULTS: The mean intra-observer Kappa agreement index (k=0.687) of the new classification, was higher than both the Neer classification (k=0.362) and the Arbeit Gemeinschaft für Osteosynthesefragen (k=0.46). The mean interobserver Kappa agreement index (0.446) of the new classification, also had better results than both the Neer classification (k=0.063) and the Arbeit Gemeinschaft für Osteosynthesefragen (k=0.028). CONCLUSION: the new classification considering bone compression had higher results for intra- and interobserver compared to the Neer system, and the Arbeit Gemeinschaft für Osteosynthesefragen system.OBJETIVO: Propor um novo sistema para classificação das fraturas que envolvem o colo do úmero e avaliar a concordância intra e interobservador do sistema de classificação de Neer (a mais utilizada em nosso meio), do sistema proposto pelo grupo europeu Arbeit Gemeinschaft für Osteosynthesefragen e de um novo sistema de classificação proposto pelos autores. MÉTODOS: Foram selecionados 56 pacientes com fraturas da região proximal do úmero, com radiografias simples digitalizadas nas incidências anteroposterior do ombro e perfil da escápula. Quatro observadores avaliaram as imagens radiográficas em três momentos diferentes, com intervalos de 3 semanas. Os dados foram analisados segundo o coeficiente de concordância kappa, modificado por Fleiss. RESULTADOS: O índice de concordância kappa intraobservador médio da nova classificação (k=0,687) foi superior ao da classificação de Neer (k=0,362) e da Arbeit Gemeinschaft für Osteosynthesefragen (k=0,46). O índice de concordância kappa interobservador da nova classificação (k=0,446) também apresentou um valor médio maior que o da classificação de Neer (k=0,063) e da Arbeit Gemeinschaft für Osteosynthesefragen (k=0,028). CONCLUSÃO: A nova classificação, que considera o conceito de compressão óssea, apresentou melhores resultados inter e intraobservador, em relação às classificações de Neer e Arbeit Gemeinschaft für Osteosynthesefragen.Hospital Israelita Albert EinsteinUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

A comparison of dry and wet season aerosol number fluxes over the Amazon rain forest

Vertical number fluxes of aerosol particles and vertical fluxes of CO(2) were measured with the eddy covariance method at the top of a 53 m high tower in the Amazon rain forest as part of the LBA (The Large Scale Biosphere Atmosphere Experiment in Amazonia) experiment. The observed aerosol number fluxes included particles with sizes down to 10 nm in diameter. The measurements were carried out during the wet and dry season in 2008. In this study focus is on the dry season aerosol fluxes, with significant influence from biomass burning, and these are compared with aerosol fluxes measured during the wet season. Net particle deposition fluxes dominated in daytime in both seasons and the deposition flux was considerably larger in the dry season due to the much higher dry season particle concentration. The particle transfer velocity increased linearly with increasing friction velocity in both seasons. The difference in transfer velocity between the two seasons was small, indicating that the seasonal change in aerosol number size distribution is not enough for causing any significant change in deposition velocity. In general, particle transfer velocities in this study are low compared to studies over boreal forests. The reasons are probably the high percentage of accumulation mode particles and the low percentage of nucleation mode particles in the Amazon boundary layer, both in the dry and wet season, and low wind speeds in the tropics compared to the midlatitudes. In the dry season, nocturnal particle fluxes behaved very similar to the nocturnal CO(2) fluxes. Throughout the night, the measured particle flux at the top of the tower was close to zero, but early in the morning there was an upward particle flux peak that is not likely a result of entrainment or local pollution. It is possible that these morning upward particle fluxes are associated with emission of primary biogenic particles from the rain forest. Emitted particles may be stored within the canopy during stable conditions at nighttime, similarly to CO(2), and being released from the canopy when conditions become more turbulent in the morning.National Institute for Research in the Amazon (INPA)LBACNPq/MCTFAPES

Posicionamento da cabeça para microcirurgias de aneurismas da circulação anterior

Objective To study the ideal patient's head positioning for the anterior circulation aneurysms microsurgery. Method We divided the study in two parts. Firstly, 10 fresh cadaveric heads were positioned and dissected in order to ideally expose the anterior circulation aneurysm sites. Afterwards, 110 patients were submitted to anterior circulation aneurysms microsurgery. During the surgery, the patient's head was positioned accordingly to the aneurysm location and the results from the cadaveric study. The effectiveness of the position was noted. Results We could determine mainly two patterns for head positioning for the anterior circulation aneurysms. Conclusion The best surgical exposure is related to specific head positions. The proper angle of microscopic view may minimize neurovascular injury and brain retraction.Objetivo Estudar o posicionamento da cabeça para a cirurgia de aneurismas cerebrais da circulação anterior. Método Dividimos o estudo em duas partes. Inicialmente, dez cabeças de cadáveres frescos foram posicionadas e dissecadas de modo a expor, de maneira ideal, os principais sítios de aneurismas na circulação anterior do cérebro. Posteriormente, 110 pacientes foram submetidos a microcirurgia para clipagem de aneurismas cerebrais da circulação anterior. Durante as cirurgias, as cabeças foram posicionadas de acordo com a localização específica de cada aneurisma e o resultado obtido no estudo dos cadáveres. Cada paciente teve sua posição avaliada quanto a sua eficácia. Resultados Obtivemos basicamente dois padrões de posicionamento da cabeça para cirurgias de aneurismas cerebrais da circulação anterior. Conclusão A melhor exposição cirúrgica está relacionada à posição específica da cabeça para cada localização aneurismática. O ângulo de visão microscópica adequado minimiza lesões neurovasculares e a excessiva retração cerebral.Universidade Federal de São Paulo (UNIFESP) Departamento de Neurocirurgia VascularReal e Benemérita Associação Portuguesa de Beneficência Instituto de Ciências Neurológicas Laboratório de MicrocirurgiaSociedade Brasileira de Neurocirurgia Departamento de Neurocirurgia VascularHospital Brigadeiro Departamento de Neurocirurgia VascularUniversidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversidade de São Paulo Faculdade de Medicina Departamento de Cirurgia – LIM02Hospital Beneficência PortuguesaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de NeurologiaUNIFESP, Depto. de Neurocirurgia VascularSciEL

Conceitos de uma população local a respeito da leishmaniose mucocutânea em uma área endêmica

Uma investigação a respeito do que a população local pensa sobre vários aspectos da leishmaniose mucocutânea foi realizada em Três Braços, Bahia, uma área de alta prevalência de infecção por Leishmania braziliensis braziliensis. Os resultados obtidos indicam que essa população tem um entendimento razoavelmente bom sobre alguns aspectos epidemiológicos e tratamento dessa doença, mas demonstram seu pouco conhecimento concernente à etiologia e prevenção. Esses dados poderão ser valiosos, no futuro, em um planejamento do controle de transmissão da doença nesta comunidade.An enquiry regarding the localpeople's views on the nature of mucocutaneous leishmaniasis is reported from Três Braços, Bahia, an area of high prevalence of L. braziliensis braziliensis infections. The results of this survey indicate a generally good understanding by the population of the treatment of this endemic disease, with little knowledge regarding etiology or prevention. Such base line data provides valuable insight into how the group should proceed with plans to eventually control transmission in this rural community

Impactos na saúde humana de partículas emitidas por queimadas na Amazônia brasileira

OBJECTIVE: To analyze the impact on human health of exposure to particulate matter emitted from burnings in the Brazilian Amazon region. METHODS: This was an ecological study using an environmental exposure indicator presented as the percentage of annual hours (AH%) of PM2.5 above 80 μg/m3. The outcome variables were the rates of hospitalization due to respiratory disease among children, the elderly and the intermediate age group, and due to childbirth. Data were obtained from the National Space Research Institute and the Ministry of Health for all of the microregions of the Brazilian Amazon region, for the years 2004 and 2005. Multiple regression models for the outcome variables in relation to the predictive variable AH% of PM2.5 above 80 μg/m3 were analyzed. The Human Development Index (HDI) and mean number of complete blood counts per 100 inhabitants in the Brazilian Amazon region were the control variables in the regression analyses. RESULTS: The association of the exposure indicator (AH%) was higher for the elderly than for other age groups (β = 0.10). For each 1% increase in the exposure indicator there was an increase of 8% in child hospitalization, 10% in hospitalization of the elderly, and 5% for the intermediate age group, even after controlling for HDI and mean number of complete blood counts. No association was found between the AH% and hospitalization due to childbirth. CONCLUSIONS: The indicator of atmospheric pollution showed an association with occurrences of respiratory diseases in the Brazilian Amazon region, especially in the more vulnerable age groups. This indicator may be used to assess the effects of forest burning on human health.OBJETIVO: Analisar o impacto à saúde humana pela exposição ao material particulado das emissões de queimadas na Amazônia brasileira. MÉTODOS: Estudo ecológico utilizando o indicador de exposição ambiental apresentado como percentagem anual de horas (AH%) de PM2,5 acima de 80 μg/m³ e como desfecho taxas de hospitalização por doenças respiratórias em crianças, idosos e grupos etários intermediários e taxas de hospitalização por parto. Os dados foram obtidos do Instituto Nacional de Pesquisas Espaciais e do Ministério da Saúde para todas as microrregiões da Amazônia Brasileira, nos anos 2004 e 2005. Foram analisados modelos de regressão múltipla das variáveis de desfecho com a variável preditora AH% acima de 80 μg/m³ para PM2,5. O Índice de Desenvolvimento Humano (IDH) e o número médio de hemogramas por 100 habitantes na região da Amazônia brasileira foram variáveis de controle nas análises de regressão. RESULTADOS: Observou-se maior associação do indicador de exposição (AH%) para os idosos do que para outros grupos etários (β = 0,10). Para cada ponto percentual de aumento no indicador de exposição, houve aumento de 10% na taxa de hospitalização de idosos, 8% em internações de crianças, e 5% para a faixa etária intermediária, mesmo ajustando por IDH e número médio de hemogramas. Não foi encontrada associação entre AH% e a taxa de hospitalização por parto. CONCLUSÕES: O indicador de poluição atmosférica mostrou associação com a ocorrência de doenças respiratórias, em especial nos grupos etários mais vulneráveis da Amazônia brasileira, podendo ser utilizado na abordagem dos efeitos da queima das florestas na saúde humana.OBJETIVO: Analizar el impacto a la salud humana por la exposición al material particulado de las emisiones de incendios en el Amazonas brasilero. MÉTODOS: Estudio ecológico utilizando el indicador de exposición ambiental, presentado como porcentaje anual de horas (AH%) de PM2,5 encima de 80 µg/m³ y como resultado tasas de hospitalización por enfermedades respiratorias en niños, ancianos y grupos etarios intermediarios y tasas de hospitalización por parto. Los datos fueron obtenidos del Instituto Nacional de Pesquisas Espaciales y del Ministerio de la Salud de Brasil para todas las microrregiones del Amazonas Brasilero, en los años 2004 y 2005. Fueron analizados modelos de regresión múltiple de las variables de resultado con la variable predoctora AH% encima de 80 µg/m³ para PM2,5. El Índice de Desarrollo Humano (IDH) y el número promedio de hemogramas por 100 habitantes en la región del Amazonas Brasilero fueron variables de control en los análisis de regresión. RESULTADOS: Se observó mayor asociación del indicador de exposición (AH%) para los ancianos en comparación con otros grupos etarios (? = 0,10). Para cada punto porcentual de aumento en el indicador de exposición, hubo aumento de 10% en la tasa de hospitalización de ancianos, 8% en internaciones de niños, y 5% para el grupo etario intermedio, aún ajustando por IDH y número promedio de hemogramas. No fue encontrada asociación entre AH% y la tasa de hospitalización por parto. CONCLUSIONES: El indicador de polución atmosférica mostró asociación con la ocurrencia de enfermedades respiratorias, en especial en los grupos etarios más vulnerables del Amazona Brasilero, pudiendo ser utilizado en el abordaje de los efectos de incendios de las selvas en la salud humana.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Mato Grosso (FAPEMS)/Departamento de Ciência e Tecnologia do Ministério da Saúde - DECI