960 resultados para Ca2 Transient
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Los eventos transitorios nicos analgicos (ASET, Analog Single Event Transient) se producen debido a la interaccin de un in pesado o un protn de alta energa con un dispositivo sensible de un circuito analgico. La interaccin del in con un transistor bipolar o de efecto de campo MOS induce pares electrn-hueco que provocan picos que pueden propagarse a la salida del componente analgico provocando transitorios que pueden inducir fallas en el nivel sistema. Los problemas ms graves debido a este tipo de fenmeno se dan en el medioambiente espacial, muy rico en iones pesados. Casos tpicos los constituyen las computadoras de a bordo de satlites y otros artefactos espaciales. Sin embargo, y debido a la continua contraccin de dimensiones de los transistores (que trae aparejado un aumento de sensibilidad), este fenmeno ha comenzado a observarse a nivel del mar, provocado fundamentalmente por el impacto de neutrones atmosfricos. Estos efectos pueden provocar severos problemas a los sistemas informticos con interfaces analgicas desde las que obtienen datos para el procesamiento y se han convertido en uno de los problemas ms graves a los que tienen que hacer frente los diseadores de sistemas de alta escala de integracin. Casos tpicos son los Sistemas en Chip que incluyen mdulos de procesamiento de altas prestaciones como las interfaces analgicas.El proyecto persigue como objetivo general estudiar la susceptibilidad de sistemas informticos a ASETs en sus secciones analgicas, proponiendo estrategias para la mitigacin de los errores.Como objetivos especficos se pretende: -Proponer nuevos modelos de ASETs basados en simulaciones en el nivel dispositivo y resueltas por el mtodo de elementos finitos.-Utilizar los modelos para identificar las secciones ms propensas a producir errores y consecuentemente para ser candidatos a la aplicacin de tcnicas de endurecimiento a radiaciones.-Utilizar estos modelos para estudiar la naturaleza de los errores producidos en sistemas de procesamiento de datos.-Proponer soluciones novedosas para la mitigacin de estos efectos en los mismos circuitos analgicos evitando su propagacin a las secciones digitales.-Proponer soluciones para la mitigacin de los efectos en el nivel sistema.Para llevar a cabo el proyecto se plantea un procedimiento ascendente para las investigaciones a realizar, comenzando por descripciones en el nivel fsico para posteriormente aumentar el nivel de abstraccin en el que se encuentra modelado el circuito. Se propone el modelado fsico de los dispositivos MOS y su resolucin mediante el Mtodo de Elementos Finitos. La inyeccin de cargas en las zonas sensibles de los modelos permitir determinar los perfiles de los pulsos de corriente que deben inyectarse en el nivel circuito para emular estos efectos. Estos procedimientos se realizarn para los distintos bloques constructivos de las interfaces analgicas, proponiendo estrategias de mitigacin de errores en diferentes niveles.Los resultados esperados del presente proyecto incluyen hardware para deteccin de errores y tolerancia a este tipo de eventos que permitan aumentar la confiabilidad de sistemas de tratamiento de la informacin, as como tambin nuevos datos referentes a efectos de la radiacin en semiconductores, nuevos modelos de fallas transitorias que permitan una simulacin de estos eventos en el nivel circuito y la determinacin de zonas sensibles de interfaces analgicas tpicas que deben ser endurecidas para radiacin.
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La transferencia de protenas solubles a la interfase de la membrana lipdica es un paso clave en varios procesos celulares. Esta traslocacin resulta en un importante cambio en el ambiente de la protena con consecuencias sobre su conformacin, estabilidad y actividad biolgica. En este proyecto estudiamos las condiciones que determinan la unin a la membrana, particularmente el balance entre interacciones electrostticas e hidrofbicas, y los factores que determinan la conformacin, estabilidad y dinmica de la protena en interfaces. Particularmente, estudiaremos la interaccin con membranas de la protena transportadora de cido clico de hgado de ave L-BABP, la protena beta-2 glicoprotena humana y la protena asociada a microtbulos SL21. Hemos encontrado que el estado de fase del lpido determina la conformacin y estabilidad de L-BABP unida perifricamente. En este proyecto estudiaremos la naturaleza de las interacciones que determinan esta dependencia. beta-2 glicoprotena humana se une a membranas aninicas e induce cambios estructurales en el lpido cuando ocurre la transicin al estado desplegado de la protena. El proyecto contempla estudiar comparativamente las interacciones del estado nativo y parcialmente desplegado de beta-2 glicoprotena con membranas. Estudiaremos los cambios conformacionales de protenas y lpidos utilizando espectroscopia infrarroja por transformada de Fourier (FTIR), espectroscopia de emisin de fluorescencia y espectroscopia de dicrosmo circular (CD). Utilizaremos calorimetra diferencial de barrido (DSC) para estudios de estabilidad y espectroscopia de fosforescencia para estudiar dinmica rotacional de protenas en la membrana.
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El Estrs de Retculo Endoplsmico (RE) es inducido por la acumulacin de protenas sin plegar en el lumen de la organela. Esto se puede observar en diversas situaciones fisio-patolgicas como durante una infeccin viral o en proceso isqumico. Adems, contribuye a la base molecular de numerosas enfermedades ya sea ndole metablico (Fibrosis qustica o Diabetes Miellitus) o neurodegenerativas como mal de Alzheimer o Parkinson (Mutat Res, 2005, 569). Para restablecer la homeostasis en la organela se activa una seal de transduccin (UPR), cuya respuesta inmediata es la atenuacin de la sntesis de protena debido a la fosforilacin de subunidad alpha del factor eucaritico de iniciacin de translacin (eIF2) va PERK. Esta es una protena de membrana de RE que detecta estrs. Bajo condiciones normales, PERK est inactiva debido a la asociacin de su dominio luminar con la chaperona BIP (Nat Cell Biol, 2000, 2: 326). Frente a una situacin de estrs, la chaperona se disocia causando desinhibicin. Recientemente, (Plos One 5: e11925) se observ, bajo condiciones de estrs, un aumento de Ca2+ citoslico y un rpido incremento de la expresin de calcineurina (CN), una fosfatasa citoslica dependiente de calcio, heterodimrica formada por una subunidad cataltica (CN-A) y una regulatoria (CN-B). Adems, CN interacciona, sin intermediarios, con el dominio citoslico de PERK favoreciendo su trans-autofosforilacin. Resultados preliminares indican que, astrocitos CNA-/- exhibieron, en condiciones basales, un mayor nmero de clulas muertas y de niveles de eIF2 fosforilado que los astrocitos CNA-/-. Hiptesis: CNA/B interacciona con PERK cuando el Ca2+ citoslico esta incrementado luego de haberse inducido Estrs de RE, lo cual promueve dimerizacin y auto-fosforilacin de la quinasa, acentundose as la fosforilacin de eIF2 e inhibicin de la sntesis de protenas. Esta activacin citoslica de PERK colaborara con la ya descrita, desinhibicin luminal llevada cabo por BIP. Cuando el Ca2+ citoslico retorna a los niveles basales, PERK fosforila a CN, reduciendo su afinidad de unin y disocindose el complejo CN/PERK. Objetivo general: Definir las condiciones por las cuales CN interacciona con PERK y regula la fosforilacin de eIF2 e inhibicin de la sntesis de protena. Objetivos especficos: I-Estudiar la diferencia de afinidades y dependencia de Ca2+, de las dos isoformas de CN ( y ) en su asociacin con PERK. Adems verificar la posible participacin de la subunidad B de CN en esta interaccin. II-Determinar si la auto-fosforilacin de PERK es diferencialmente regulada por las dos isoformas de CN. III-Discernir la relacin del estado de fosforilacin de CN con su unin a PERK. IV-Determinar efectos fisiolgicos de la interaccin de CN-PERK durante la respuesta de Estrs de RE. Para llevar a cabo este proyecto se realizarn experimentos de biologa molecular, interaccin protena-protena, ensayos de fosforilacin in vitro y un perfil de polisoma con astrocitos CNA-/- , CNA-/- y astrocitos controles. Se espera encontrar una mayor afinidad de unin a PERK de la isoforma de CN y en condiciones donde la concentracin de Ca2+ sea del orden micromolar e imite niveles del in durante un estrs. Con respecto al estado de fosforilacin de CN, debido a los resultados preliminares, donde solo se la encontr fosforilada en condiciones basales, se piensa que CN podra interactuar con mayor afinidad con PERK cuando CN se encuentre desfosforilada. Por ltimo, se espera encontrar un aumento de eIF2 fosforilado y una acentuacin de la atenuacin de la sntesis de protena como consecuencia de la mayor activacin de PERK por su asociacin con la isoforma de CN en astrocitos donde el Estrs de RE se indujo por privacin de oxigeno y glucosa. Estos experimentos permitirn avanzar en el estudio de una nueva funcin citoprotectora de CN recientemente descrita por nuestro grupo de trabajo y sus implicancias en un modelo de isquemia. The accumulation of unfolded proteins into the Endoplasmic Reticulum (ER) activates a signal transduction cascade called Unfolding Protein Response (UPR), which attempts to restore homeostasis in the organelle. (PKR)-like-ER kinase (PERK) is an early stress response transmembrane protein that is generally inactive due to its association with the chaperone BIP. During ER stress, BIP is tritrated by the unfolded protein, leading PERK activation and phosphorylation of eukaryotic initiation factor-2 alpha (eIF2alpha), which attenuates protein sntesis. If ER damage is too great and homeostasis is not restored within a certain period of time, an apoptotic response is elicited. We recently demonstrated a cytosolic Ca2+ increase in Xenopus oocytes after induce ER stress. Moreover, calcineurin A/B, a an heterotrimeric Ca2+ dependent phosphatases (CN-A/B), associates with PERK increasing its auto-phosphorylation and significantly enhancing cell viability. Preliminary results suggest that, CN-A-/- knockout astrocytes exhibit a significant higher eIF2 phosphorylated level compared to CN-A-/- astrocytes. Our working hypothesis establishes that: CN binds to PERK when cytosolic Ca2+ is initially increased by ER stress, promoting dimerization and autophosphorylation, which leads to phosphorylation of elF2 and subsequently attenuation of protein translation. When cytosolic Ca2+ returns to resting levels, PERK phosphorylates CN, reducing its binding affinity so that the CN/PERK complex dissociates. The goal of this project is to determine the conditions by which CN binding to PERK attenuates protein translation during the ER stress response and subsequently, to determine how the interaction of CN with PERK is terminated when stress is removed. To perform this project is planed to do molecular biology experiments, pull down assays, in vitro phosphorylations and assess overall mRNA translation efficiency doing a polisome profile.
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FUNDAMENTO: Treinamento fsico (TF) aumenta a sensibilidade dos hormnios tireoidianos (HT) e a expresso gnica de estruturas moleculares envolvidas no movimento intracelular de clcio do miocrdio, enquanto a restrio alimentar (RIA) promove efeitos contrrios ao TF. OBJETIVO: Avaliar os efeitos da associao TF e RIA sobre os nveis plasmticos dos HT e a produo de mRNA dos receptores HT e estruturas moleculares do movimento de clcio do miocrdio de ratos. MTODOS: Utilizaram-se ratos Wistar Kyoto divididos em: controle (C, n = 7), RIA (R50, n = 7), exerccio fsico (EX, n = 7) e exerccio fsico + RIA (EX50, n = 7). A RIA foi de 50% e o TF foi natao (1 hora/dia, cinco sesses/semana, 12 semanas consecutivas). Avaliaram-se as concentraes sricas de triiodotironina (T3), tiroxina (T4) e hormnio tireotrfico (TSH). O mRNA da bomba de clcio do retculo sarcoplasmtico (SERCA2a), fosfolamban (PLB), trocador Na+/Ca+2 (NCX), canal lento de clcio (canal-L), rianodina (RYR), calsequestrina (CQS) e receptor de HT (TRα1 e TRβ1) do miocrdio foram avaliados por reao em cadeia da polimerase (PCR) em tempo real. RESULTADOS: RIA reduziu o T4, TSH e mRNA do TRα1 e aumentou a expresso da PLB, NCX e canal-L. TF aumentou a expresso do TRβ1, canal-L e NCX. A associao TF e RIA reduziu T4 e TSH e aumentou o mRNA do TRβ1, SERCA2a, NCX, PLB e correlao do TRβ1 com a CQS e NCX. CONCLUSO: Associao TF e RIA aumentou o mRNA das estruturas moleculares clcio transiente, porm o eixo HT-receptor no parece participar da transcrio gnica dessas estruturas.
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Magdeburg, Univ., Fak. fr Mathematik, Diss., 2011
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Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)
Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca2+ Handling
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Abstract Background: Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that. Objective: To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling. Methods: Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers. Results: The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats. Conclusion: Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling.
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Abstract Background: Most international studies on epidemiology of transient loss of consciousness (TLC) were performed many years ago. There are no data about the lifetime prevalence of TLC in Russia. Objective: To identify the lifetime prevalence and presumed mechanisms of TLC in an urban Russian population. Methods: 1796 individuals (540 males [30.1%] and 1256 females [69.9%]) aged 20 to 69 years (mean age 45.8 11.9 years) were randomly selected and interviewed within the framework of multicentre randomised observational trial. Results: The overall prevalence of TLC in the studied population was 23.3% (418/1796), with the highest proportion (28%) seen in 40-49 year age group. TLC was significantly more common in women than in men (27.5% vs 13.5%). The mean age of patients at the time of the first event was 16 (11; 23) years, with 333 (85%) individuals experiencing the first episode of TLC under 30 years. The average time after the first episode of TLC was 27 (12; 47) years. The following mechanisms of TLC were determined using the questionnaire: neurally-mediated syncope (56.5%), arrhythmogenic onset of syncope (6.0%), nonsyncopal origin of TLC (1.4%), single episode during lifetime (2.1%). Reasons for TLC remained unidentified in 34% cases. 27 persons (6.5%) reported a family history of sudden death, mainly patients with presumably arrhythmogenic origin (24%). Conclusion: Our findings suggest that the overall prevalence of TLC in individuals aged 20-69 years is high. The most common cause of TLC is neurally-mediated syncope. These data about the epidemiology can help to develop cost-effective management approaches to TLC.
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BACKGROUND/OBJECTIVES: This study aims to assess whether patent foramen ovale (PFO) closure is superior to medical therapy in preventing recurrence of cryptogenic ischemic stroke or transient ischemic attack (TIA). METHODS: We searched PubMed for randomized trials which compared PFO closure with medical therapy in cryptogenic stroke/TIA using the items: "stroke or cerebrovascular accident or TIA" and "patent foramen ovale or paradoxical embolism" and "trial or study". RESULTS: Among 650 potentially eligible articles, 3 were included including 2303 patients. There was no statistically significant difference between PFO-closure and medical therapy in ischemic stroke recurrence (1.91% vs. 2.94% respectively, OR: 0.64, 95%CI: 0.37-1.10), TIA (2.08% vs. 2.42% respectively, OR: 0.87, 95%CI: 0.50-1.51) and death (0.60% vs. 0.86% respectively, OR: 0.71, 95%CI: 0.28-1.82). In subgroup analysis, there was significant reduction of ischemic strokes in the AMPLATZER PFO Occluder arm vs. medical therapy (1.4% vs. 3.04% respectively, OR: 0.46, 95%CI: 0.21-0.98, relative-risk-reduction: 53.2%, absolute-risk-reduction: 1.6%, number-needed-to-treat: 61.8) but not in the STARFlex device (2.7% vs. 2.8% with medical therapy, OR: 0.93, 95%CI: 0.45-2.11). Compared to medical therapy, the number of patients with new-onset atrial fibrillation (AF) was similar in the AMPLATZER PFO Occluder arm (0.72% vs. 1.28% respectively, OR: 1.81, 95%CI: 0.60-5.42) but higher in the STARFlex device (0.64% vs. 5.14% respectively, OR: 8.30, 95%CI: 2.47-27.84). CONCLUSIONS: This meta-analysis does not support PFO closure for secondary prevention with unselected devices in cryptogenic stroke/TIA. In subgroup analysis, selected closure devices may be superior to medical therapy without increasing the risk of new-onset AF, however. This observation should be confirmed in further trials using inclusion criteria for patients with high likelihood of PFO-related stroke recurrence.
T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites.
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T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K+ channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2-/- (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non-rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.
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Effects of insulin upon glucose metabolism were investigated in chick embryos explanted in vitro during the first 30 h of incubation. Insulin stimulated the glucose consumption of the chick gastrula (18 h) and neurula (24 h), but had no effect on the late blastula (0 h:laying) and on the stage of six to eight somites (30 h). The increase in glucose consumption concerned both the embryonic area pellucida (AP) and extraembryonic area opaca (AO). AP responded to a greater extent (50%) and at a lower range of concentrations (0.1-1.0 ng/ml) than AO (30%; 1-100 ng/ml). Insulin had no effect on the oxygen consumption of blastoderms, whereas it stimulated the aerobic lactate production (approximately 70% of the additional glucose consumption was converted to lactate). The nanomolar range of stimulating concentrations suggests that insulin has a specific effect in the chick embryo, and that it could modulate glucose metabolism in ovo as well. The transient sensitivity of the embryo to insulin is discussed in relation to behavior of mesodermal cells.
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Report for the scientific sojourn at the James Cook University, Australia, between June to December 2007. Free convection in enclosed spaces is found widely in natural and industrial systems. It is a topic of primary interest because in many systems it provides the largest resistance to the heat transfer in comparison with other heat transfer modes. In such systems the convection is driven by a density gradient within the fluid, which, usually, is produced by a temperature difference between the fluid and surrounding walls. In the oil industry, the oil, which has High Prandtl, usually is stored and transported in large tanks at temperatures high enough to keep its viscosity and, thus the pumping requirements, to a reasonable level. A temperature difference between the fluid and the walls of the container may give rise to the unsteady buoyancy force and hence the unsteady natural convection. In the initial period of cooling the natural convection regime dominates over the conduction contribution. As the oil cools down it typically becomes more viscous and this increase of viscosity inhibits the convection. At this point the oil viscosity becomes very large and unloading of the tank becomes very difficult. For this reason it is of primary interest to be able to predict the cooling rate of the oil. The general objective of this work is to develop and validate a simulation tool able to predict the cooling rates of high Prandtl fluid considering the variable viscosity effects.
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As computer chips implementation technologies evolve to obtain more performance, those computer chips are using smaller components, with bigger density of transistors and working with lower power voltages. All these factors turn the computer chips less robust and increase the probability of a transient fault. Transient faults may occur once and never more happen the same way in a computer system lifetime. There are distinct consequences when a transient fault occurs: the operating system might abort the execution if the change produced by the fault is detected by bad behavior of the application, but the biggest risk is that the fault produces an undetected data corruption that modifies the application final result without warnings (for example a bit flip in some crucial data). With the objective of researching transient faults in computer systems processor registers and memory we have developed an extension of HPs and AMD joint full system simulation environment, named COTSon. This extension allows the injection of faults that change a single bit in processor registers and memory of the simulated computer. The developed fault injection system makes it possible to: evaluate the effects of single bit flip transient faults in an application, analyze an application robustness against single bit flip transient faults and validate fault detection mechanism and strategies.
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PURPOSE: To highlight meningoencephalitis as a transient ischaemic attack (TIA) mimic and suggest clinical clues for differential diagnosis. METHODS: This was an observational study of consecutively admitted patients over a 9.75-year period presenting as TIAs at a stroke unit. RESULTS: A total of 790 patients with TIAs and seven with TIA-like symptoms but a final diagnosis of viral meningoencephalitis were recognised. The most frequent presentations of meningoencephalitis patients were acute sensory hemisyndrome (6) and cognitive deficits (5). Signs of meningeal irritation were minor or absent on presentation. Predominantly lymphocytic pleocytosis, hyperproteinorachia and a normal cerebrospinal fluid (CSF)/serum glucose index (in 5 out of 6 documented patients) were present. Meningeal thickening on a brain magnetic resonance imaging (MRI) scan was the only abnormal imaging finding. Six patients received initial vascular treatment; one thrombolysed. Finally, six patients were treated with antivirals and/or antibiotics. Although neither bacterial nor viral agents were identified on extensive testing, viral meningoencephalitis was the best explanation for all clinical and laboratory findings. CONCLUSIONS: Aseptic meningoencephalitis should be part of the differential diagnosis in patients presenting as TIA. The threshold for a lumbar puncture in such patients should be set individually and take into account the presence of mild meningeal symptoms, age and other risk factors for vascular disease, the results of brain imaging and the basic diagnostic work-up for a stroke source.
