Gravitational energy of a magnetized Schwarzschild black hole - a teleparallel approach

We investigate the distribution of gravitational energy on the spacetime of a Schwarzschild black hole immersed in a cosmic magnetic field. This is done in the context of the {\it Teleparallel Equivalent of General Relativity}, which is an alternative geometrical formulation of General Relativity, where gravity is describe by a spacetime endowed with torsion, rather than curvature, with the fundamental field variables being tetrads. We calculate the energy enclosed by a two-surface of constant radius - in particular, the energy enclosed by the event horizon of the black hole. In this case we find that the magnetic field has the effect of increasing the gravitational energy as compared to the vacuum Schwarzschild case. We also compute the energy (i) in the weak magnetic field limit, (ii) in the limit of vanishing magnetic field, and (iii) in the absence of the black hole. In all cases our results are consistent with what should be expected on physical grounds.Comment: version to match the one to be published on General Relativity and Gravitatio

Effect of stress relieving heat treatment on surface topography and dimensional accuracy of incrementally formed grade 1 titanium sheet parts

The forming of parts with an optimized surface roughness and high dimensional accuracy is important in many applications of incremental sheet forming (ISF). To realize this, the effect of stress relieving heat treatment of grade-1 Ti parts performed before and after forming on the surface finish and dimensional accuracy was studied. It was found that heat treatment at a temperature of 540 °C for 2 h improves the surface finish of formed parts resulting in a surface with little or no visible tool marks. Additionally, it improves the dimensional accuracy of parts after unclamping from the rig used for forming, in particular, that of parts with shallow wall angles (typically <25°). It was also noted that post-forming heat treatment improves the surface finish of parts. The surface topography of formed parts was studied using interferometry to yield areal surface roughness parameters and subsequently using secondary electron imaging. Back-scatter electron microscopy imaging results coupled with energy-dispersive X-ray (EDX) analysis showed that heat treatment prior to forming leads to tool wear as indicated by the presence of Fe in samples. Furthermore, post-forming heat treatment prevents curling up of formed parts due to compressive stresses if the formed part is trimmed

Timeless standards for species delimitation

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Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

Counter-current chromatography for the separation of terpenoids: A comprehensive review with respect to the solvent systems employed

Copyright @ 2014 The Authors.This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Natural products extracts are commonly highly complex mixtures of active compounds and consequently their purification becomes a particularly challenging task. The development of a purification protocol to extract a single active component from the many hundreds that are often present in the mixture is something that can take months or even years to achieve, thus it is important for the natural product chemist to have, at their disposal, a broad range of diverse purification techniques. Counter-current chromatography (CCC) is one such separation technique utilising two immiscible phases, one as the stationary phase (retained in a spinning coil by centrifugal forces) and the second as the mobile phase. The method benefits from a number of advantages when compared with the more traditional liquid-solid separation methods, such as no irreversible adsorption, total recovery of the injected sample, minimal tailing of peaks, low risk of sample denaturation, the ability to accept particulates, and a low solvent consumption. The selection of an appropriate two-phase solvent system is critical to the running of CCC since this is both the mobile and the stationary phase of the system. However, this is also by far the most time consuming aspect of the technique and the one that most inhibits its general take-up. In recent years, numerous natural product purifications have been published using CCC from almost every country across the globe. Many of these papers are devoted to terpenoids-one of the most diverse groups. Naturally occurring terpenoids provide opportunities to discover new drugs but many of them are available at very low levels in nature and a huge number of them still remain unexplored. The collective knowledge on performing successful CCC separations of terpenoids has been gathered and reviewed by the authors, in order to create a comprehensive document that will be of great assistance in performing future purifications. © 2014 The Author(s)

Fatores de risco para fratura por osteoporose e baixa densidade óssea em mulheres na pré e pós-menopausa

OBJECTIVE: To estimate the prevalence and analyze risk factors associated to osteoporosis and low-trauma fracture in women. METHODS: Cross-sectional study including a total of 4,332 women older than 40 attending primary care services in the Greater São Paulo, Southeastern Brazil, between 2004 and 2007. Anthropometrical and gynecological data and information about lifestyle habits, previous fracture, medical history, food intake and physical activity were obtained through individual quantitative interviews. Low-trauma fracture was defined as that resulting from a fall from standing height or less in individuals 50 years or older. Multiple logistic regression models were designed having osteoporotic fracture and bone mineral density (BMD) as the dependent variables and all other parameters as the independent ones. The significance level was set at p<0.05. RESULTS: The prevalence of osteoporosis and osteoporotic fractures was 33% and 11.5%, respectively. The main risk factors associated with low bone mass were age (OR=1.07; 95% CI: 1.06;1.08), time since menopause (OR=2.16; 95% CI: 1.49;3.14), previous fracture (OR=2.62; 95% CI: 2.08;3.29) and current smoking (OR=1.45; 95% CI: 1.13;1.85). BMI (OR=0.88; 95% CI: 0.86;0.89), regular physical activity (OR=0.78; 95% CI: 0.65;0.94) and hormone replacement therapy (OR=0.43; 95% CI: 0.33;0.56) had a protective effect on bone mass. Risk factors significantly associated with osteoporotic fractures were age (OR=1.05; 95% CI: 1.04;1.06), time since menopause (OR=4.12; 95% CI: 1.79;9.48), familial history of hip fracture (OR=3.59; 95% CI: 2.88;4.47) and low BMD (OR=2.28; 95% CI: 1.85;2.82). CONCLUSIONS: Advanced age, menopause, low-trauma fracture and current smoking are major risk factors associated with low BMD and osteoporotic fracture. The clinical use of these parameters to identify women at higher risk for fractures might be a reasonable strategy to improve the management of osteoporosis.OBJETIVO: Estimar la prevalencia y analizar los factores de riesgo asociados con osteoporosis y fractura por bajo impacto entre mujeres. MÉTODOS: Estudio transversal realizado con 4.332 mujeres encima de 40 años de edad provenientes de atención primaria de salud en el área metropolitana de la gran São Paulo, SP, entre 2004 2007. Datos antropométricos y ginecológico y relativos a hábitos de vida, fractura previa, antecedentes personales, ingestión alimentaria y actividad física fueron evaluados por medio de entrevista individual y cuantitativa. Fractura por bajo impacto fue definida como decurrente de caída de la propia altura o menos en individuos con más de 50 años de edad. Modelos de regresión multivariada y logística analizaron, respectivamente, la densidad ósea y la fractura por osteoporosis, como variables dependientes y todas las otras como independientes. El nivel de significancia estadística establecido fue p<0,05. RESULTADOS: La prevalencia de osteoporosis y de fracturas por fragilidad ósea fue de 33% y 11,5%, respectivamente. Los principales factores de riesgo asociados con baja densidad ósea fueron edad (OR=1,07; IC 95%: 1,06;1,08), menopausia (OR=2,16; IC 95%: 1,49;3,14), fractura previa (OR=2,62; IC 95%: 2,08;3,29) y tabaquismo actual (OR=1,45; IC 95%: 1,13;1,85). Por otro lado, elevado IMC (OR=0,88; IC 95%: 0,86;0,89), actividad física regular (OR=0,78; IC 95%: 0,65;0,94) y terapia hormonal actual (OR=0,43; IC 95%: 0,33;0,56) desempeñaron papel protector. Los factores de riesgo significantemente relacionados con fractura por osteoporosis fueron edad (OR=1,05; IC 95%: 1,04;1,06), menopausia (OR=4,12; IC 95%: 1,79;9,48), historia familiar de fractura de cuadril (OR=3,59; IC 95%: 2,88;4,47) y baja densidad ósea (OR=2,28; IC 95%: 1,85;2,82). CONCLUSIONES: Edad avanzada, menopausia, fractura previa por bajo impacto y tabaquismo actual son los principales factores de riesgo asociados con baja densidad ósea y esta, con las fracturas por fragilidad ósea. El uso clínico de estos parámetros para identificar mujeres de mayor riesgo para fracturas puede ser una estrategia interesante para mejorar el abordaje de la osteoporosis.OBJETIVO: Estimar a prevalência e analisar os fatores de risco associados com osteoporose e fratura por baixo impacto entre mulheres. MÉTODOS: Estudo transversal realizado com 4.332 mulheres acima de 40 anos de idade provenientes de atendimento primário de saúde na área metropolitana da Grande São Paulo, SP, entre 2004 e 2007. Dados antropométricos e ginecológicos e relativos a hábitos de vida, fratura prévia, antecedentes pessoais, ingestão alimentar e atividade física foram avaliados por meio de entrevista individual e quantitativa. Fratura por baixo impacto foi definida como decorrente de queda da própria altura ou menos em indivíduos com mais de 50 anos de idade. Modelos de regressão multivariada e logística analisaram, respectivamente, a densidade óssea e a fratura por osteoporose como variáveis dependentes e todas as outras como independentes. O nível de significância estatística estabelecido foi p < 0,05. RESULTADOS: A prevalência de osteoporose e de fraturas por fragilidade óssea foi de 33% e 11,5%, respectivamente. Os principais fatores de risco associados com baixa densidade óssea foram idade (OR = 1,07; IC 95%: 1,06;1,08), menopausa (OR = 2,16; IC 95%: 1,49;3,14), fratura prévia (OR = 2,62; IC 95%: 2,08;3,29) e tabagismo atual (OR = 1,45; IC 95%: 1,13;1,85). Por outro lado, elevado IMC (OR = 0,88; IC 95%: 0,86;0,89), atividade física regular (OR = 0,78; IC 95%: 0,65;0,94) e terapia hormonal atual (OR = 0,43; IC 95%: 0,33;0,56) desempenharam papel protetor. Os fatores de risco significativamente relacionados com fratura por osteoporose foram idade (OR = 1,05; IC 95%: 1,04;1,06), menopausa (OR = 4,12; IC 95%: 1,79;9,48), história familiar de fratura de quadril (OR = 3,59; IC 95%: 2,88;4,47) e baixa densidade óssea (OR = 2,28; IC 95%: 1,85;2,82). CONCLUSÕES: Idade avançada, menopausa, fratura prévia por baixo impacto e tabagismo atual são os principais fatores de risco associados com baixa densidade óssea, a qual se associa com as fraturas por fragilidade óssea. O uso clínico desses parâmetros para identificar mulheres de maior risco para fraturas pode ser uma estratégia interessante para melhorar a abordagem da osteoporose.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP-EPM Instituto de Diagnóstico por ImagemUNIFESP-EPM Programa de Pós-Graduação em ReumatologiaUNIFESP-EPM Departamento de RadiologiaUNIFESP, EPM, Instituto de Diagnóstico por ImagemUNIFESP, EPM Programa de Pós-Graduação em ReumatologiaUNIFESP, EPM Depto. de RadiologiaSciEL

CTLA-4 Activation of Phosphatidylinositol 3-Kinase (PI 3-K) and Protein Kinase B (PKB/AKT) Sustains T-Cell Anergy without Cell Death

The balance of T-cell proliferation, anergy and apoptosis is central to immune function. In this regard, co-receptor CTLA-4 is needed for the induction of anergy and tolerance. One central question concerns the mechanism by which CTLA-4 can induce T-cell non-responsiveness without a concurrent induction of antigen induced cell death (AICD). In this study, we show that CTLA-4 activation of the phosphatidylinositol 3-kinase (PI 3-K) and protein kinase B (PKB/AKT) sustains T-cell anergy without cell death. CTLA-4 ligation induced PI 3K activation as evidenced by the phosphorylation of PKB/AKT that in turn inactivated GSK-3. The level of activation was similar to that observed with CD28. CTLA-4 induced PI 3K and AKT activation also led to phosphorylation of the pro-apoptotic factor BAD as well as the up-regulation of BcL-XL. In keeping with this, CD3/CTLA-4 co-ligation prevented apoptosis under the same conditions where T-cell non-responsiveness was induced. This effect was PI 3K and PKB/AKT dependent since inhibition of these enzymes under conditions of anti-CD3/CTLA-4 co-ligation resulted in cell death. Our findings therefore define a mechanism by which CTLA-4 can induce anergy (and possibly peripheral tolerance) by preventing the induction of cell death

Hippocampal Desynchronization of Functional Connectivity Prior to the Onset of Status Epilepticus in Pilocarpine-Treated Rats

Status epilepticus (SE), a pro-epileptogenic brain insult in rodent models of temporal lobe epilepsy, is successfully induced by pilocarpine in some, but not all, rats. This study aimed to identify characteristic alterations within the hippocampal neural network prior to the onset of SE. Sixteen microwire electrodes were implanted into the left hippocampus of male Sprague-Dawley rats. After a 7-day recovery period, animal behavior, hippocampal neuronal ensemble activities, and local field potentials (LFP) were recorded before and after an intra-peritoneal injection of pilocarpine (350 mg/kg). The single-neuron firing, population neuronal correlation, and coincident firing between neurons were compared between SE (n = 9) and nonSE rats (n = 12). A significant decrease in the strength of functional connectivity prior to the onset of SE, as measured by changes in coincident spike timing between pairs of hippocampal neurons, was exclusively found in SE rats. However, single-neuron firing and LFP profiles did not show a significant difference between SE and nonSE rats. These results suggest that desynchronization in the functional circuitry of the hippocampus, likely associated with a change in synaptic strength, may serve as an electrophysiological marker prior to SE in pilocarpine-treated rats