5,886 research outputs found

    Analysis domain model for shared virtual environments

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    The field of shared virtual environments, which also encompasses online games and social 3D environments, has a system landscape consisting of multiple solutions that share great functional overlap. However, there is little system interoperability between the different solutions. A shared virtual environment has an associated problem domain that is highly complex raising difficult challenges to the development process, starting with the architectural design of the underlying system. This paper has two main contributions. The first contribution is a broad domain analysis of shared virtual environments, which enables developers to have a better understanding of the whole rather than the part(s). The second contribution is a reference domain model for discussing and describing solutions - the Analysis Domain Model

    Maturidade fisiológica das sementes e emergência de plântulas de Nó-de-cachorro (Heteropterys tomentosa).

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    A proposal for a generalized canonical osp(1,2) quantization of dynamical systems with constraints

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    The aim of this paper is to consider a possibility of constructing for arbitrary dynamical systems with first-class constraints a generalized canonical quantization method based on the osp(1,2) supersymmetry principle. This proposal can be considered as a counterpart to the osp(1,2)-covariant Lagrangian quantization method introduced recently by Geyer, Lavrov and M\"ulsch. The gauge dependence of Green's functions is studied. It is shown that if the parameter m^2 of the osp(1,2) superalgebra is not equal to zero then the vacuum functional and S-matrix depend on the gauge. In the limit m→0m\to 0 the gauge independence of vacuum functional and S - matrix are restored. The Ward identities related to the osp(1,2) symmetry are derived.Comment: Revised version. To appear in Mod.Phys.Lett.

    Optimal experimental design for estimating the kinetic parameters of processes described by the Weibull probability distribution function

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    The optimum experimental design for determining the kinetic parameters of the model resulting from the Weibull probability density junction was studied, by defining the sampling conditions that lead to a minimum confidence region of the estimates, for a number of observations equal to the number of parameters. It was found that for one single isothermal experiment the optimum sampling times corresponded always to fractional concentrations that are irrational numbers (approximately 0.70 and 0.19) whose product is exactly l/e’. The experimental determination of the equilibtium conversion (for growth kinetics) is vety important, but in some situations this is not possible, e.g. due to product degradation over the length of time required. Sampling times leading to a maximum precision were determined as a function of the maximum conversion (or yield) attainable. For studies of kinetic parameters over a range of temperatures, performed with a minimum of three isothermal experiments, it was proved that the optimum design consists of two experiments at one limit temperature with two sampling times (those corresponding to fractional concentrations of approximate[v 0.70 and 0.19) and another at the other limit temperature for a sampling time such that the fractional concentration is lie. Case studies are included for clarijication of the concepts and procedures

    Embrapa Pantanal e o 17º Batalhão de Fronteira já iniciaram as colheitas.

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    Modulation of Molecular Chaperones in Huntington's Disease and Other Polyglutamine Disorders

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    Polyglutamine expansion mutations in specific proteins underlie the pathogenesis of a group of progressive neurodegenerative disorders, including Huntington's disease, spinal and bulbar muscular atrophy, dentatorubral-pallidoluysian atrophy, and several spinocerebellar ataxias. The different mutant proteins share ubiquitous expression and abnormal proteostasis, with misfolding and aggregation, but nevertheless evoke distinct patterns of neurodegeneration. This highlights the relevance of the full protein context where the polyglutamine expansion occurs and suggests different interactions with the cellular proteostasis machinery. Molecular chaperones are key elements of the proteostasis machinery and therapeutic targets for neurodegeneration. Here, we provide a focused review on Hsp90, Hsp70, and their co-chaperones, and how their genetic or pharmacological modulation affects the proteostasis and disease phenotypes in cellular and animal models of polyglutamine disorders. The emerging picture is that, in principle, Hsp70 modulation may be more amenable for long-term treatment by promoting a more selective clearance of mutant proteins than Hsp90 modulation, which may further decrease the necessary wild-type counterparts. It seems, nevertheless, unlikely that a single Hsp70 modulator will benefit all polyglutamine diseases. Indeed, available data, together with insights from effects on tau and alpha-synuclein in models of Alzheimer's and Parkinson's diseases, indicates that Hsp70 modulators may lead to different effects on the proteostasis of different mutant and wild-type client proteins. Future studies should include the further development of isoform selective inhibitors, namely to avoid off-target effects on Hsp in the mitochondria, and their characterization in distinct polyglutamine disease models to account for client protein-specific differences

    Propriedades físicas de sementes de Baru em função da secagem.

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    O conhecimento das propriedades físicas das sementes são informações que auxiliam o dimensionamento de máquinas de pré-processamento, processamento e classificação das mesmas. O experimento teve o objetivo de efetuar a caracterização das propriedades físicas de sementes de Baru. Foram avaliados 4 tratamentos: T1 = sementes não secadas; T2 = sementes secadas em estufa de circulação forçada de ar por 48 horas à 40 Celsius; T3 = sementes secadas em estufa de circulação forçada de ar por 96 horas a 40 graus Celsius e T4 = sementes secadas em estufa de circulação forçada de ar por 24 horas a 105 graus Celsius, considerada desidratada. Foram avaliadas a massa específica aparente, esfericidade, circularidade, porosidade e massa específica real. Houve diferenças entre os tratamentos para a massa específica aparente e porosidade. A maior massa específica e a menor porosidade foram verificadas no tratamento T1. A massa específica aparente diminuiu com a secagem. Massa de sementes in natura apresentou menor porosidade.CONBEA 2013

    In Situ Mitochondrial Ca2+ Buffering Differences of Intact Neurons and Astrocytes from Cortex and Striatum

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    The striatum is particularly vulnerable to neurological disorders, such as Huntington disease. Previous studies, with nonsynaptic mitochondria isolated from cortical and striatal homogenates, suggest that striatal mitochondria are highly vulnerable to Ca2+ loads, possibly influencing striatal vulnerability. However, whether and how neuronal and glial mitochondria from cortex and striatum differ in Ca2+ vulnerability remains unknown. We test this hypothesis using a novel strategy allowing comparisons of mitochondrial Ca2+ buffering capacity in cortical and striatal neuron-astrocyte co-cultures. We provide original evidence that mitochondria not only in neurons but also in astrocytes from striatal origin exhibit a decreased Ca2+ buffering capacity when compared with cortical counterparts. The decreased mitochondrial Ca2+ buffering capacity in striatal versus cortical astrocytes does not stem from variation in mitochondrial concentration or in the rate of intracellular Ca2+ elevation, being mechanistically linked to an increased propensity to undergo cyclosporin A (CsA)-sensitive permeability transition. Indeed, 1 mu M CsA selectively increased the mitochondrial Ca2+ buffering capacity of striatal astrocytes, without modifying that of neurons or cortical astrocytes. Neither thapsigargin nor FK506 modified mitochondrial Ca2+ buffering differences between cell types, excluding a predominant contribution of endoplasmic reticulum or calcineurin. These results provide additional insight into the mechanisms of striatal vulnerability, showing that the increased Ca2+ vulnerability of striatal versus cortical mitochondria resides in both intact neurons and astrocytes, thus positioning the striatum at greater risk for disturbed neuron-astrocyte interactions. Also, the selective effect of CsA over striatal astrocytes suggests that in vivo neuronal sheltering with this compound may indirectly result from astrocytic protection

    Techniques to Investigate Neuronal Mitochondrial Function and its Pharmacological Modulation

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    Mitochondria are central regulators of neuronal homeostasis and survival, and increasingly viewed as a drug target in several acute and chronic neurological disorders, e. g. stroke, Alzheimer's, Parkinson's, and Huntington's diseases. Frequent working hypotheses aim to establish whether and how chemical or genetic lesions affect mitochondrial function in neurons, and whether this can be rescued by pharmacological treatments. However, the generic designation 'mitochondrial function' actually encompasses a wide spectrum of individual activities, too numerous to be fully quantified by any single available technique. This review aims to provide a broad perspective on the roles played by neuronal mitochondria, and addresses multiple techniques that can be used to derive instructive functional indicators. These include measurements of mitochondrial respiration, ATP production, membrane potential, calcium handling, biogenesis, dynamic movement as well as fusion and fission. Technique descriptions are preceded by a summary of mitochondrial physiology and pharmacological tools required for functional modulation and parameter determination. Hopefully, these will assist researchers interested in testing mitochondria as a drug target in neurological disease models

    Human vs Machine learning: rethinking student assessment to foster metacognition of pharmacological skills

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    Introduction: Pharmacology students can recognize propranolol in a multiple choice of beta-adrenergic receptor antagonists (BRA). But can they integrate human physiology to predict the effects of BRA on the cardiovascular system? Can they perform or interpret pharmacological assays that quantify BRA effects? Are they aware of their true level of knowledge, or under the delusion that recognizing drug names (e.g., associative memory of the suffix -olol) is a skill that solves real-world pharmacology problems? The ability to self-assess, monitor, and improve via self-regulation are metacognitive skills that enhance academic learning and emotional intelligence. With the now widespread access to information, metacognitive skills are more valuable than simple associative memory, and should thus be fostered in students [1,2]. Objectives: Implement a learning environment that fosters the development of metacognitive skills, including an assessment strategy that values the demonstration of such skills. Methods: 2nd year Pharmaceutical Sciences students (2021/2022, n = 175) were surveyed for their motivation, initiative, and study strategies (Survey-1); and exposed to 10 weekly formative tests (ForTes) where they predicted their score (metacognitive monitoring and self-assessment). Students received weekly feedback on their ForTes and counselling on active study techniques. In the summative assessment (mid-term Exam), the accuracy of student score prediction was valued as bonus. Students were then surveyed (Survey-2) on their perception of ForTes, and their study adaptations according to counselling (metacognitive regulation). Anonymised data were analysed with R language to compute statistics and perform supervised machine learning. Results: Survey-1 showed that student self-perception of motivation, initiative and study were highly inter-related (internal consistency: IC = 86%; n = 144). The metacognitive ability of students to predict their grade started low (R2 = 0.13 and 0.10 for prediction vs. reality in ForTes 1 and 2), and then increased gradually (R2 = 0.22, 0.41, and 0.46 in ForTes 3, 4, and 5), with the observed maximum in ForTes 9 (R2 = 0.54). Also, the first three ForTes had low IC (44-52%), and then increased gradually to the observed maximum by ForTes 9 (IC = 81%). The Exam had high IC (88%), low standard error (5%), and a grade prediction vs. reality R2 of 0.40. Survey-2 showed that the majority of students consider that the ForTes were very useful (97%) and promoted: their motivation (90%); their regular study (74%); their use of active study techniques (80%); and improved their metacognitive skills (84%). A supervised machine learning (ML) model trained with a random sample of 70% of Exam scores (using as predictors the number of ForTes taken by the students and their average ForTes score) yielded an adjusted R2 of 0.67. Using the remaining 30% Exam scores as a test sample, the ML model predicted Exam scores (scale: 0-20 points) with an error under 2 points (root mean square error = 1.9). Conclusions: This strategy of regular formative tests with student score predictions, feedback, and counselling, increased student motivation and active learning. Moreover, increases in self-assessment accuracy indicate that students self-monitored, and self-regulated to increase their learning - as supported by increased internal consistency of the tests. Together with survey data, these results show that this strategy fostered student metacognitive skills. Further improvements in the ML models of human (student) learning, can potentially
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