2,941 research outputs found

    Le Brésil dans la société de l'information : Gouvernement lula, Copyleft et logiciels libres

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    Le Foss (Free open software source) ou logiciel libre, est un mouvement de fond qui valorise le partage de l'effort collectif dans la production logicielle et lutte ainsi contre l'appropriation intellectuelle de toute création humaine que les grandes industries de l'information cherchent à imposer. Le gouvernement brésilien a choisit de favoriser le Foss dans toute la société brésilienne

    Lensing and shadow of a black hole surrounded by a heavy accretion disk

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    We consider a static, axially symmetric spacetime describing the superposition of a Schwarzschild black hole (BH) with a thin and heavy accretion disk. The BH-disk configuration is a solution of the Einstein field equations within the Weyl class. The disk is sourced by a distributional energy-momentum tensor and it is located at the equatorial plane. It can be interpreted as two streams of counter-rotating particles, yielding a total vanishing angular momentum. The phenomenology of the composed system depends on two parameters: the fraction of the total mass in the disk, mm, and the location of the inner edge of the disk, aa. We start by determining the sub-region of the space of parameters wherein the solution is physical, by requiring the velocity of the disk particles to be sub-luminal and real. Then, we study the null geodesic flow by performing backwards ray-tracing under two scenarios. In the first scenario the composed system is illuminated by the disk and in the second scenario the composed system is illuminated by a far-away celestial sphere. Both cases show that, as mm grows, the shadow becomes more prolate. Additionally, the first scenario makes clear that as mm grows, for fixed aa, the geometrically thin disk appears optically enlarged, i.e., thicker, when observed from the equatorial plane. This is to due to light rays that are bent towards the disk, when backwards ray traced. In the second scenario, these light rays can cross the disk (which is assumed to be transparent) and may oscillate up to a few times before reaching the far away celestial sphere. Consequently, an almost equatorial observer sees different patches of the sky near the equatorial plane, as a chaotic "mirage". As m0m\rightarrow 0 one recovers the standard test, i.e., negligible mass, disk appearance.Comment: 24 pages, 15 figure

    Eficácia da nitazoxanida contra Toxocara canis: recuperação larvária e resposta imune humoral em camundongos experimentalmente infectados

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    Foi investigada a eficácia da nitazoxanida (NTZ) na toxocaríase murina experimental e os resultados comparados com os obtidos usando mebendazol (MBZ). Sessenta camundongos BALB/c machos, com idade entre seis e oito semanas foram divididos em grupos de 10 cada, 50 foram infectados oralmente com 300 ovos larvados de T. canise agrupados a seguir: GI: camundongos infectados não tratados; GII: camundongos infectados tratados com MBZ (15 mg/kg/dia) 10 dias pós-infecção (dpi); GIII: camundongos infectados tratados com NTZ (20 mg/kg/dia) 10 dpi, GIV: camundongos infectados tratados com MBZ 60 dpi; GV: camundongos infectados tratados com NTZ 60 dpi; GVI: controle não infectado. Os camundongos foram sangrados via plexo retro orbitário em quatro ocasiões entre o 30º e 120º dpi. Os soros foram processados pela técnica de ELISA para detecção de anticorpos IgG anti- Toxocara.Aos 120 dpi, os animais foram sacrificados para a recuperação larvária do SNC, fígado, pulmões, rins, olhos e carcaça. Os resultados mostraram níveis similares de anticorpos IgG anti- Toxocaraentre os camundongos infectados mas não submetidos a tratamento e os grupos infectados e tratados com MBZ ou NTZ, aos 10 e 60 dpi. Os valores da recuperação larval foram similares nos grupos tratados com NTZ e MBZ 10 dpi. MBZ mostrou melhor eficácia aos 60 dpi, com redução de 72,6% da carga parasitária comparada com NTZ, que mostrou redução somente de 46,5%. Concluímos que a administração destes anti-helmínticos não modificou a resposta humoral na infecção experimental por T. canis. Não foi observada cura parasitológica com nenhuma das drogas; porém maior redução na carga parasitária foi obtida após o tratamento com MBZ.The efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canisand grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocaraantibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- ToxocaraIgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ

    Adipose Tissue-Derived Stem Cells and the Importance of Animal Model Standardization for Pre-Clinical Trials

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    ABSTRACTStem cells are undifferentiated cells and can self-renew and differentiate into various cell types, besides having immuno-modulating properties and paracrine effects in response to tissue injury, and may therefore treat injuries and diseases or even replace damaged or lost cells. Adipose tissue is an attractive source of adult stem cells, since the human body has a large reserve that is obtained in large amounts by minimally invasive methods. Interest in these cells has been increasing steadily due to their properties and possible applications in regenerative medicine and cell therapy. A large part of these investigations are focused on cardiovascular diseases, which are a leading cause of morbidity and mortality worldwide. Although in recent years treatments have advanced in cardiology, the development of new therapies to recover the damaged tissue still remains one of the main goals of cardiac research. However, to achieve effective results, in vivo and in vitro animal models for preclinical studies and consequently for application in humans must be standardized. The development of preclinical models in large animals requires the use of well-characterized animal cell lines, similar to human cells, and the use of the porcine model represents a great advantage for preclinical translational research

    A computational study of aortic insufficiency in patients supported with continuous flow left ventricular assist devices: Is it time for a paradigm shift in management?

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    Background: De novo aortic insufficiency (AI) following continuous flow left ventricular assist device (CF-LVAD) implantation is a common complication. Traditional early management utilizes speed augmentation to overcome the regurgitant flow in an attempt to augment net forward flow, but this strategy increases the aortic transvalvular gradient which predisposes the patient to progressive aortic valve pathology and may have deleterious effects on aortic shear stress and right ventricular (RV) function. Materials and methods: We employed a closed-loop lumped-parameter mathematical model of the cardiovascular system including the four cardiac chambers with corresponding valves, pulmonary and systemic circulations, and the LVAD. The model is used to generate boundary conditions which are prescribed in blood flow simulations performed in a three-dimensional (3D) model of the ascending aorta, aortic arch, and thoracic descending aorta. Using the models, impact of various patient management strategies, including speed augmentation and pharmacological treatment on systemic and pulmonary (PA) vasculature, were investigated for four typical phenotypes of LVAD patients with varying degrees of RV to PA coupling and AI severity. Results: The introduction of mild/moderate or severe AI to the coupled RV and pulmonary artery at a speed of 5,500 RPM led to a reduction in net flow from 5.4 L/min (no AI) to 4.5 L/min (mild/moderate) to 2.1 L/min (severe). RV coupling ratio (Ees/Ea) decreased from 1.01 (no AI) to 0.96 (mild/moderate) to 0.76 (severe). Increasing LVAD speed to 6,400 RPM in the severe AI and coupled scenario, led to a 42% increase in net flow and a 16% increase in regurgitant flow (RF) with a nominal decrease of 1.6% in RV myocardial oxygen consumption (MVO2). Blood pressure control with the coupled RV with severe AI at 5,500 RPM led to an 81% increase in net flow with a 15% reduction of RF and an 8% reduction in RV MVO2. With an uncoupled RV, the introduction of mild/moderate or severe AI at a speed of 5,500 RPM led to a reduction in net flow from 5.0 L/min (no AI) to 4.0 L/min (mild/moderate) to 1.8 L/min (severe). Increasing the speed to 6,400 RPM with severe AI and an uncoupled RV increased net flow by 45%, RF by 15% and reduced RV MVO2 by 1.1%. For the uncoupled RV with severe AI, blood pressure control alone led to a 22% increase in net flow, 4.2% reduction in RF, and 3.9% reduction in RV MVO2; pulmonary vasodilation alone led to a 18% increase in net flow, 7% reduction in RF, and 26% reduction in RV MVO2; whereas, combined BP control and pulmonary vasodilation led to a 113% increase in net flow, 20% reduction in RF and 31% reduction in RV MVO2. Compared to speed augmentation, blood pressure control consistently resulted in a reduction in WSS throughout the proximal regions of the arterial system. Conclusion: Speed augmentation to overcome AI in patients supported by CF-LVAD appears to augment flow but also increases RF and WSS in the aorta, and reduces RV MVO2. Aggressive blood pressure control and pulmonary vasodilation, particularly in those patients with an uncoupled RV can improve net flow with more advantageous effects on the RV and AI RF

    Mechanical Characterization of the Vessel Wall by Data Assimilation of Intravascular Ultrasound Studies

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    Atherosclerotic plaque rupture and erosion are the most important mechanisms underlying the sudden plaque growth, responsible for acute coronary syndromes and even fatal cardiac events. Advances in the understanding of the culprit plaque structure and composition are already reported in the literature, however, there is still much work to be done toward in-vivo plaque visualization and mechanical characterization to assess plaque stability, patient risk, diagnosis and treatment prognosis. In this work, a methodology for the mechanical characterization of the vessel wall plaque and tissues is proposed based on the combination of intravascular ultrasound (IVUS) imaging processing, data assimilation and continuum mechanics models within a high performance computing (HPC) environment. Initially, the IVUS study is gated to obtain volumes of image sequences corresponding to the vessel of interest at different cardiac phases. These sequences are registered against the sequence of the end-diastolic phase to remove transversal and longitudinal rigid motions prescribed by the moving environment due to the heartbeat. Then, optical flow between the image sequences is computed to obtain the displacement fields of the vessel (each associated to a certain pressure level). The obtained displacement fields are regarded as observations within a data assimilation paradigm, which aims to estimate the material parameters of the tissues within the vessel wall. Specifically, a reduced order unscented Kalman filter is employed, endowed with a forward operator which amounts to address the solution of a hyperelastic solid mechanics model in the finite strain regime taking into account the axially stretched state of the vessel, as well as the effect of internal and external forces acting on the arterial wall. Due to the computational burden, a HPC approach is mandatory. Hence, the data assimilation and computational solid mechanics computations are parallelized at three levels: (i) a Kalman filter level; (ii) a cardiac phase level; and (iii) a mesh partitioning level. To illustrate the capabilities of this novel methodology toward the in-vivo analysis of patient-specific vessel constituents, mechanical material parameters are estimated using in-silico and in-vivo data retrieved from IVUS studies. Limitations and potentials of this approach are exposed and discussed.Fil: Maso Talou, Gonzalo Daniel. Laboratorio Nacional de Computacao Cientifica; BrasilFil: Blanco, Pablo Javier. Laboratorio Nacional de Computacao Cientifica; BrasilFil: Ares, Gonzalo Damián. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Mecanica. Grupo de Ingeniería Asistida Por Computador; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Guedes Bezerra, Cristiano. Heart Institute (Incor); BrasilFil: Lemos, Pedro A.. Heart Institute (Incor); BrasilFil: Feijóo, Raúl Antonino. Laboratorio Nacional de Computacao Cientifica; Brasi

    Heterologous expression of Streptococcus mutans cnm in Lactococcus lactis promotes intracellular invasion, adhesion to human cardiac tissues and virulence

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    FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOIn S. mutans, the expression of the surface glycoprotein Cnm mediates binding to extracellular matrix proteins, endothelial cell invasion and virulence in the Galleria mellonella invertebrate model. To further characterize Cnm as a virulence factor, the cnm gene from S. mutans strain OMZ175 was expressed in the non-pathogenic Lactococcus lactis NZ9800 using a nisin-inducible system. Despite the absence of the machinery necessary for Cnm glycosylation, Western blot and immunofluorescence microscopy analyses demonstrated that Cnm was effectively expressed and translocated to the cell wall of L. lactis. Similar to S. mutans, expression of Cnm in L. lactis enabled robust binding to collagen and laminin, invasion of human coronary artery endothelial cells and increased virulence in G. mellonella. Using an ex vivo human heart tissue colonization model, we showed that Cnm-positive strains of either S. mutans or L. lactis outcompete their Cnm-negative counterparts for tissue colonization. Finally, Cnm expression facilitated L. lactis adhesion and colonization in a rabbit model of infective endocarditis. Collectively, our results provide unequivocal evidence that binding to extracellular matrices mediated by Cnm is an important virulence attribute of S. mutans and confirm the usefulness of the L. lactis heterologous system for further characterization of bacterial virulence factors.In S. mutans, the expression of the surface glycoprotein Cnm mediates binding to extracellular matrix proteins, endothelial cell invasion and virulence in the Galleria mellonella invertebrate model. To further characterize Cnm as a virulence factor, the cnm gene from S. mutans strain OMZ175 was expressed in the non-pathogenic Lactococcus lactis NZ9800 using a nisin-inducible system. Despite the absence of the machinery necessary for Cnm glycosylation, Western blot and immunofluorescence microscopy analyses demonstrated that Cnm was effectively expressed and translocated to the cell wall of L. lactis. Similar to S. mutans, expression of Cnm in L. lactis enabled robust binding to collagen and laminin, invasion of human coronary artery endothelial cells and increased virulence in G. mellonella. Using an ex vivo human heart tissue colonization model, we showed that Cnm-positive strains of either S. mutans or L. lactis outcompete their Cnm-negative counterparts for tissue colonization. Finally, Cnm expression facilitated L. lactis adhesion and colonization in a rabbit model of infective endocarditis. Collectively, our results provide unequivocal evidence that binding to extracellular matrices mediated by Cnm is an important virulence attribute of S. mutans and confirm the usefulness of the L. lactis heterologous system for further characterization of bacterial virulence factors811829FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2014/07231-0; 2013/25080-7308644/2011-

    Left Main Compression by a Giant Aneurysm of the Left Sinus of Valsalva: An Extremely Rare Reason for Myocardial Infarction and Cardiogenic Shock

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    Aneurysms of the sinus of Valsalva are very rare and mostly located in the right coronary sinus. They might course with dyspnea, fatigue, and acute coronary syndromes. We present herein an extremely rare case report of a 61-year-old woman diagnosed with external left main coronary compression by a giant aneurysm of the left sinus of Valsalva, which was successfully managed with percutaneous coronary intervention

    Single Low-Dose Ionizing Radiation Induces Genotoxicity in Adult Zebrafish and its Non-Irradiated Progeny

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    This study investigated to what extent a single exposure to low doses of ionizing radiation can induce genotoxic damage in irradiated adult zebrafish (Danio rerio) and its non-irradiated F1 progeny. Four groups of adult zebrafish were irradiated with a single dose of X-rays at 0 (control), 100, 500 and 1000 mGy, respectively, and couples of each group were allowed to reproduce following irradiation. Blood of parental fish and whole-body offspring were analysed by the comet assay for detection of DNA damage. The level of DNA damage in irradiated parental fish increased in a radiation dose-dependent manner at day 1 post-irradiation, but returned to the control level thereafter. The level of DNA damage in the progeny was directly correlated with the parental irradiation dose. Results highlight the genotoxic risk of a single exposure to low-dose ionizing radiation in irradiated individuals and also in its non-irradiated progeny.info:eu-repo/semantics/publishedVersio

    Transcriptional and phenotypic characterization of novel Spx-regulated genes in Streptococcus mutans

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    CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOIn oral biofilms, two of the major environmental challenges encountered by the dental pathogen Streptococcus mutans are acid and oxidative stresses. Previously, we showed that the S. mutans transcriptional regulators SpxA1 and SpxA2 (formerly SpxA and SpxB, respectively) are involved in stress survival by activating the expression of classic oxidative stress genes such as dpr, nox, sodA and tpx. We reasoned that some of the uncharacterized genes under SpxA1/A2 control are potentially involved in oxidative stress management. Therefore, the goal of this study was to use Spx-regulated genes as a tool to identify novel oxidative stress genes in S. mutans. Quantitative real-time PCR was used to evaluate the responses of ten Spx-regulated genes during H2O2 stress in the parent and Delta spx strains. Transcription activation of the H2O2-induced genes (8 out of 10) was strongly dependent on SpxA1 and, to a lesser extent, SpxA2. In vitro transcription assays revealed that one or both Spx proteins directly regulate three of these genes. The gene encoding the FeoB ferrous permease was slightly repressed by H2O2 but constitutively induced in strains lacking SpxA1. Nine genes were selected for downstream mutational analysis but inactivation of smu127, encoding a subunit of the acetoin dehydrogenase was apparently lethal. In vitro and in vivo characterization of the viable mutants indicated that, in addition to the transcriptional activation of reducing and antioxidant pathways, Spx performs an important role in iron homeostasis by regulating the intracellular availability of free iron. In particular, inactivation of the genes encoding the Fe-S biogenesis SUF system and the previously characterized iron-binding protein Dpr resulted in impaired growth under different oxidative stress conditions, increased sensitivity to iron and lower infectivity in rats. These results serve as an entryway into the characterization of novel genes and pathways that allow S. mutans to cope with oxidative stress.In oral biofilms, two of the major environmental challenges encountered by the dental pathogen Streptococcus mutans are acid and oxidative stresses. Previously, we showed that the S. mutans transcriptional regulators SpxA1 and SpxA2 (formerly SpxA and SpxB, respectively) are involved in stress survival by activating the expression of classic oxidative stress genes such as dpr, nox, sodA and tpx. We reasoned that some of the uncharacterized genes under SpxA1/A2 control are potentially involved in oxidative stress management. Therefore, the goal of this study was to use Spx-regulated genes as a tool to identify novel oxidative stress genes in S. mutans. Quantitative real-time PCR was used to evaluate the responses of ten Spx-regulated genes during H2O2 stress in the parent and Delta spx strains. Transcription activation of the H2O2-induced genes (8 out of 10) was strongly dependent on SpxA1 and, to a lesser extent, SpxA2. In vitro transcription assays revealed that one or both Spx proteins directly regulate three of these genes. The gene encoding the FeoB ferrous permease was slightly repressed by H2O2 but constitutively induced in strains lacking SpxA1. Nine genes were selected for downstream mutational analysis but inactivation of smu127, encoding a subunit of the acetoin dehydrogenase was apparently lethal. In vitro and in vivo characterization of the viable mutants indicated that, in addition to the transcriptional activation of reducing and antioxidant pathways, Spx performs an important role in iron homeostasis by regulating the intracellular availability of free iron. In particular, inactivation of the genes encoding the Fe-S biogenesis SUF system and the previously characterized iron-binding protein Dpr resulted in impaired growth under different oxidative stress conditions, increased sensitivity to iron and lower infectivity in rats. These results serve as an entryway into the characterization of novel genes and pathways that allow S. mutans to cope with oxidative stress104CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL E NÍVEL SUPERIORFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES [6849-12-1]FAPESP [2012/032278-3, 2014/03816-4]6849-12-12012/032278-3; 2014/03816-
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