938 resultados para work function
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The effects of individual teacher expectations have been the subject of intensive research. Results indicate that teachers use their expectations to adapt their interactions with their students to some degree (as summarized in a review by Jussim & Harber, 2005). This can in turn lead to expectancy-confirming student developments. While there are studies on the Pygmalion effect on individual students, there is only little research on teacher judgements of whole classes and schools. Our study aims to extend the perspective of teacher judgements at the collective level to stereotypes within the context of school tracking. The content and structure of teachers’ school track stereotypes are investigated as well as the question of whether these stereotypical judgements are related to teachers’ perception of obstacles to their teaching and their teaching self-efficacy beliefs. Cross-sectional data on 341 teachers at two different school types from the Panel Study at the Research School „Education and Capabilities“ in North Rhine-Westphalia (PARS) (see Bos et al., 2016) were used for two purposes: First, the structure of teachers’ stereotypes was identified via an exploratory factor analysis. Second, in follow-up regression analyses, the stereotype dimensions extracted were used to predict teachers’ perceptions of obstacles to their classroom work and their individual and collective teacher self-efficacy beliefs. Results showed that – after controlling for the average cognitive abilities and the average cultural capital of the students – teacher stereotypes were indeed related to perceived obstacles concerning their classroom work and their self-efficacy beliefs. After a discussion of the strengths and limitations of the present research, the article closes with a short proposal of a future research framework for collective Pygmalion effects. (DIPF/Orig.)
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Ce projet illustre cinq études, mettant l'emphase sur le développement d'une nouvelle approche diagnostique cardiovasculaire afin d'évaluer le niveau d’oxygène contenu dans le myocarde ainsi que sa fonction microvasculaire. En combinant une séquence de résonance magnétique cardiovasculaire (RMC) pouvant détecter le niveau d’oxygène (OS), des manœuvres respiratoires ainsi que des analyses de gaz artériels peuvent être utilisés comme procédure non invasive destinée à induire une réponse vasoactive afin d’évaluer la réserve d'oxygénation, une mesure clé de la fonction vasculaire. Le nombre de tests diagnostiques cardiaques prescrits ainsi que les interventions, sont en pleine expansion. L'imagerie et tests non invasifs sont souvent effectués avant l’utilisation de procédures invasives. L'imagerie cardiaque permet d’évaluer la présence ou absence de sténoses coronaires, un important facteur économique dans notre système de soins de santé. Les techniques d'imagerie non invasives fournissent de l’information précise afin d’identifier la présence et l’emplacement du déficit de perfusion chez les patients présentant des symptômes d'ischémie myocardique. Néanmoins, plusieurs techniques actuelles requièrent la nécessité de radiation, d’agents de contraste ou traceurs, sans oublier des protocoles de stress pharmacologiques ou physiques. L’imagerie RMC peut identifier une sténose coronaire significative sans radiation. De nouvelles tendances d’utilisation de RMC visent à développer des techniques diagnostiques qui ne requièrent aucun facteur de stress pharmacologiques ou d’agents de contraste. L'objectif principal de ce projet était de développer et tester une nouvelle technique diagnostique afin d’évaluer la fonction vasculaire coronarienne en utilisant l' OS-RMC, en combinaison avec des manœuvres respiratoires comme stimulus vasoactif. Ensuite, les objectifs, secondaires étaient d’utilisés l’OS-RMC pour évaluer l'oxygénation du myocarde et la réponse coronaire en présence de gaz artériels altérés. Suite aux manœuvres respiratoires la réponse vasculaire a été validée chez un modèle animal pour ensuite être utilisé chez deux volontaires sains et finalement dans une population de patients atteints de maladies cardiovasculaires. Chez le modèle animal, les manœuvres respiratoires ont pu induire un changement significatif, mesuré intrusivement par débit sanguin coronaire. Il a été démontré qu’en présence d'une sténose coronarienne hémodynamiquement significative, l’OS-RMC pouvait détecter un déficit en oxygène du myocarde. Chez l’homme sain, l'application de cette technique en comparaison avec l'adénosine (l’agent standard) pour induire une vasodilatation coronarienne et les manœuvres respiratoires ont pu induire une réponse plus significative en oxygénation dans un myocarde sain. Finalement, nous avons utilisé les manœuvres respiratoires parmi un groupe de patients atteint de maladies coronariennes. Leurs myocardes étant altérées par une sténose coronaire, en conséquence modifiant ainsi leur réponse en oxygénation. Par la suite nous avons évalué les effets des gaz artériels sanguins sur l'oxygénation du myocarde. Ils démontrent que la réponse coronarienne est atténuée au cours de l’hyperoxie, suite à un stimuli d’apnée. Ce phénomène provoque une réduction globale du débit sanguin coronaire et un déficit d'oxygénation dans le modèle animal ayant une sténose lorsqu’un supplément en oxygène est donné. En conclusion, ce travail a permis d'améliorer notre compréhension des nouvelles techniques diagnostiques en imagerie cardiovasculaire. Par ailleurs, nous avons démontré que la combinaison de manœuvres respiratoires et l’imagerie OS-RMC peut fournir une méthode non-invasive et rentable pour évaluer la fonction vasculaire coronarienne régionale et globale.
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The accumulation of mannosyl-glycerate (MG), the salinity stress response osmolyte of Thermococcales, was investigated as a function of hydrostatic pressure in Thermococcus barophilus strain MP, a hyperthermophilic, piezophilic archaeon isolated from the Snake Pit site (MAR), which grows optimally at 40 MPa. Strain MP accumulated MG primarily in response to salinity stress, but in contrast to other Thermococcales, MG was also accumulated in response to thermal stress. MG accumulation peaked for combined stresses. The accumulation of MG was drastically increased under sub-optimal hydrostatic pressure conditions, demonstrating that low pressure is perceived as a stress in this piezophile, and that the proteome of T. barophilus is low-pressure sensitive. MG accumulation was strongly reduced under supra-optimal pressure conditions clearly demonstrating the structural adaptation of this proteome to high hydrostatic pressure. The lack of MG synthesis only slightly altered the growth characteristics of two different MG synthesis deletion mutants. No shift to other osmolytes was observed. Altogether our observations suggest that the salinity stress response in T. barophilus is not essential and may be under negative selective pressure, similarly to what has been observed for its thermal stress response. Introduction
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International audience
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Spiking neural networks - networks that encode information in the timing of spikes - are arising as a new approach in the artificial neural networks paradigm, emergent from cognitive science. One of these new models is the pulsed neural network with radial basis function, a network able to store information in the axonal propagation delay of neurons. Learning algorithms have been proposed to this model looking for mapping input pulses into output pulses. Recently, a new method was proposed to encode constant data into a temporal sequence of spikes, stimulating deeper studies in order to establish abilities and frontiers of this new approach. However, a well known problem of this kind of network is the high number of free parameters - more that 15 - to be properly configured or tuned in order to allow network convergence. This work presents for the first time a new learning function for this network training that allow the automatic configuration of one of the key network parameters: the synaptic weight decreasing factor.
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In this work we isolated a novel crotamine like protein from the Crotalus durissus cascavella venom by combination of molecular exclusion and analytical reverse phase HPLC. Its primary structure was:YKRCHKKGGHCFPKEKICLPPSSDLGKMDCRWKRK-CCKKGS GK. This protein showed a molecular mass of 4892.89 da that was determined by Matrix Assisted Laser Desorption Ionization Time-of-flight (MALDI-TOF) mass spectrometry. The approximately pI value of this protein was determined in 9.9 by two-dimensional electrophoresis. This crotamine-like protein isolated here and that named as Cro 2 produced skeletal muscle spasm and spastic paralysis in mice similarly to other crotamines like proteins. Cro 2 did not modify the insulin secretion at low glucose concentration (2.8 and 5.6 mM), but at high glucose concentration (16.7 mM) we observed an insulin secretion increasing of 2.7-3.0-fold than to control. The Na+ channel antagonist tetrodoxin (6 mM) decreased glucose and Cro 2-induced insulin secretion. These results suggested that Na+ channel are involved in the insulin secretion. In this article, we also purified some peptide fragment from the treatment of reduced and carboxymethylated Cro 2 (RC-Cro 2) with cyanogen bromide and protease V8 from Staphylococcus aureus. The isolated pancreatic beta-cells were then treated with peptides only at high glucose concentration (16.7 mM), in this condition only two peptides induced insulin secretion. The amino acid sequence homology analysis of the whole crotamine as well as the biologically-active peptide allowed determining the consensus region of the biologically-active crotamine responsible for insulin secretion was KGGHCFPKE and DCRWKWKCCKKGSG.
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This project examines the current available work on the explicit and implicit parallelization of the R scripting language and reports on experimental findings for the development of a model for predicting effective points for automatic parallelization to be performed, based upon input data sizes and function complexity. After finding or creating a series of custom benchmarks, an interval based on data size and time complexity where replacement becomes a viable option was found; specifically between O(N) and O(N3) exclusive. As data size increases, the benefits of parallel processing become more apparent and a point is reached where those benefits outweigh the costs in memory transfer time. Based on our observations, this point can be predicted with a fair amount of accuracy using regression on a sample of approximately ten data sizes spread evenly between a system determined minimum and maximum size.
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The velocity function (VF) is a fundamental observable statistic of the galaxy population that is similar to the luminosity function in importance, but much more difficult to measure. In this work we present the first directly measured circular VF that is representative between 60 < v_circ < 320 km s^-1 for galaxies of all morphological types at a given rotation velocity. For the low-mass galaxy population (60 < v_circ < 170 km s^-1), we use the HI Parkes All Sky Survey VF. For the massive galaxy population (170 < v_circ < 320 km s^-1), we use stellar circular velocities from the Calar Alto Legacy Integral Field Area Survey (CALIFA). In earlier work we obtained the measurements of circular velocity at the 80% light radius for 226 galaxies and demonstrated that the CALIFA sample can produce volume-corrected galaxy distribution functions. The CALIFA VF includes homogeneous velocity measurements of both late and early-type rotation-supported galaxies and has the crucial advantage of not missing gas-poor massive ellipticals that HI surveys are blind to. We show that both VFs can be combined in a seamless manner, as their ranges of validity overlap. The resulting observed VF is compared to VFs derived from cosmological simulations of the z = 0 galaxy population. We find that dark-matter-only simulations show a strong mismatch with the observed VF. Hydrodynamic simulations fare better, but still do not fully reproduce observations.
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Sepsis is commonly associated with brain dysfunction, but the underlying mechanisms remain unclear, although mitochondrial dysfunction and microvascular abnormalities have been implicated. We therefore assessed whether cerebral mitochondrial dysfunction during systemic endotoxemia in mice increased mitochondrial sensitivity to a further bioenergetic insult (hyoxemia), and whether hypothermia could improve outcome. Mice (C57bl/6) were injected intraperitoneally with lipopolysaccharide (LPS) (5 mg/kg; n = 85) or saline (0.01 ml/g; n = 47). Six, 24 and 48 h later, we used confocal imaging in vivo to assess cerebral mitochondrial redox potential and cortical oxygenation in response to changes in inspired oxygen. The fraction of inspired oxygen (FiO2) at which the cortical redox potential changed was compared between groups. In a subset of animals, spontaneous hypothermia was maintained or controlled hypothermia induced during imaging. Decreasing FiO2 resulted in a more reduced cerebral redox state around veins, but preserved oxidation around arteries. This pattern appeared at a higher FiO2 in LPS-injected animals, suggesting an increased sensitivity of cortical mitochondria to hypoxemia. This increased sensitivity was accompanied by a decrease in cortical oxygenation, but was attenuated by hypothermia. These results suggest that systemic endotoxemia influences cortical oxygenation and mitochondrial function, and that therapeutic hypothermia can be protective.
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This paper outlines the purposes, predications, functions, and contexts of information organization frameworks; including: bibliographic control, information retrieval, resource discovery, resource description, open access scholarly indexing, personal information management protocols, and social tagging in order to compare and contrast those purposes, predications, functions, and contexts. Information organization frameworks, for the purpose of this paper, consist of information organization systems (classification schemes, taxonomies, ontologies, bibliographic descriptions, etc.), methods of conceiving of and creating the systems, and the work processes involved in maintaining these systems. The paper first outlines the theoretical literature of these information organization frameworks. In conclusion, this paper establishes the first part of an evaluation rubric for a function, predication, purpose, and context analysis.
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This thesis explores two distinct parts of mitochondrial physiology: the role of mitochondria in generation of reactive oxygen species (ROS) and mitochondrial morphology and dynamics within cells. The first area of research is covered in Chapters 1-8. Mitochondrial biofunctionality and ROS production are discussed in Chapter 1, followed by the strategy of targeting bioactive compounds to mitochondria by linking them to lipophilic triphenylphosphonium cations (TPP) (Chapter 2). ROS sensors relevant to the research are reviewed in Chapter 3. Chapter 4 presents design and synthesis of novel probes for superoxide detection in mitochondria (MitoNeo-D), cytosol (Neo-D) and extracellular environment (ExCellNeo-D). The results of biological validation of MitoNeo-D and Neo-D performed in the MRC MBU in Cambridge are presented in Chapter 5. A dicationic hydrogen peroxide sensor that utilizes in situ click chemistry is discussed in Chapter 6. Preliminary work on the synthesis of mitochondria-targeted superoxide generators, which led to the development of mitochondria-targeted analogue of paraquat, MitoPQ, is presented in Chapter 7. A set of bifunctional probes (BCN-Mal, BCN-E-BCN and Mito-iTag) for assessing the redox states of protein thiols is discussed in Chapter 8 along with their biological validation. The second part of the thesis is aimed at the study of mitochondrial morphology and dynamics and is presented in Chapters 9-11. Chapter 9 provides background on the classes of fluorophores relevant to the research, the phenomenon of fluorescence quenching and the principle of photoactivation with examples of photoactivatable fluorophores. Next, the background on mitochondrial morphology and heterogeneity is presented in Chapter 10, followed by the ways of imaging and tracking mitochondria within cells by conventional fluorophores and by photoactivatable fluorophores exploiting super-resolution microscopy. Chapter 11 presents the design and synthesis of four photoactivatable fluorophores for mitochondrial tracking, MitoPhotoRhod110, MitoPhotoNIR, Photo-E+, MitoPhoto-E+, along with results of biological validation of MitoPhotoNIR. The results and discussion concludes with Chapter 12, which is a summary and suggestions for future work, followed by the chemistry experimental procedures (Chapter 13), materials and methods for biological experiments (Chapter 14) and references.
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During pregnancy, the maternal cardiovascular system undergoes major adaptation. One of these changes is a 40-50 % increase in circulating blood volume which requires a systemic remodelling of the vasculature in order to regulate maternal blood pressure and maximise blood supply to the developing placenta and fetus. These changes are broadly conserved between humans and rats making them an appropriate pre-clinical model in which to study the underlying mechanisms of pregnancy-dependent cardiovascular remodelling. Whilst women are normally protected against cardiovascular disease; pregnancy marks a period of time where women are susceptible to cardiovascular complications. Cardiovascular disease is the leading cause of maternal mortality in the United Kingdom; in particular hypertensive conditions are among the most common complications of pregnancy. One of the main underlying pathologies of these pregnancy complications is thought to be a failure of the maternal cardiovascular system to adapt. The remodelling of the uterine arteries, which directly supply the maternal-fetal interface, is paramount to a healthy pregnancy. Failure of the uterine arteries to remodel sufficiently can result in a number of obstetric complications such as preeclampsia, fetal growth restriction and spontaneous pregnancy loss. At present, it is poorly understood whether this deficient vascular response is due to a predisposition from existing maternal cardiovascular risk factors, the physiological changes that occur during pregnancy or a combination of both. Previous work in our group employed the stroke prone spontaneously hypertensive rat (SHRSP) as a model to investigate pregnancy-dependent remodelling of the uterine arteries. The SHRSP develops hypertension from 6 weeks of age and can be contrasted with the control strain, the Wistar Kyoto (WKY) rat. The phenotype of the SHRSP is therefore reflective of the clinical situation of maternal chronic hypertension during pregnancy. We showed that the SHRSP exhibited a deficient uterine artery remodelling response with respect to both structure and function accompanied by a reduction in litter size relative to the WKY at gestational day (GD) 18. A previous intervention study using nifedipine in the SHRSP achieved successful blood pressure reduction from 6 weeks of age and throughout pregnancy; however uterine artery remodelling and litter size at GD18 was not improved. We concluded that the abnormal uterine artery remodelling present in the SHRSP was independent of chronic hypertension. From these findings, we hypothesised that the SHRSP could be a novel model of spontaneously deficient uterine artery remodelling in response to pregnancy which was underpinned by other as yet unidentified cardiovascular risk factors. In Chapter 1 of this thesis, I have characterised the maternal, placental and fetal phenotype in pregnant (GD18) SHRSP and WKY. The pregnant SHRSP exhibit features of left ventricular hypertrophy in response to pregnancy and altered expression of maternal plasma biomarkers which have been previously associated with hypertension in human pregnancy. I developed a protocol for accurate dissection of the rat uteroplacental unit using qPCR probes specific for each layer. This allowed me to make an accurate and specific statement about gene expression in the SHRSP GD18 placenta; where oxidative stress related gene markers were increased in the vascular compartments. The majority of SHRSP placenta presented at GD18 with a blackened ring which encircled the tissue. Further investigation of the placenta using western blot for caspase 3 cleavage determined that this was likely due to increased cell death in the SHRSP placenta. The SHRSP also presented with a loss of one particular placental cell type at GD18: the glycogen cells. These cells could have been the target of cell death in the SHRSP placenta or were utilised early in pregnancy as a source of energy due to the deficient uterine artery blood supply. Blastocyst implantation was not altered but resorption rate was increased between SHRSP and WKY; indicating that the reduction in litter size in the SHRSP was primarily due to late (>GD14) pregnancy loss. Fetal growth was not restricted in SHRSP which led to the conclusion that SHRSP sacrifice part of their litter to deliver a smaller number of healthier pups. Activation of the immune system is a common pathway that has been implicated in the development of both hypertension and adverse pregnancy outcome. In Chapter 2, I proposed that this may be a mechanism of interest in SHRSP pregnancy and measured the pro-inflammatory cytokine, TNFα, as a marker of inflammation in pregnant SHRSP and WKY and in the placentas from these animals. TNFα was up-regulated in maternal plasma and urine from the GD18 SHRSP. In addition, TNFα release was increased from the GD18 SHRSP placenta as was the expression of the pro-inflammatory TNFα receptor 1 (Tnfr1). In order to investigate whether this excess TNFα was detrimental to SHRSP pregnancy, a vehicle-controlled intervention study using etanercept (a monoclonal antibody which works as a TNFα antagonist) was carried out. Etanercept treatment at GD0, 6, 12 and 18 resulted in an improvement in pregnancy outcome in the SHRSP with an increased litter size and reduced resorption rate. Furthermore, there was an improved uterine artery function in GD18 SHRSP treated with etanercept which was associated with an improved uterine artery blood flow over the course of gestation. In Chapter 3, I sought to identify the source of this detrimental excess of TNFα by designing a panel for maternal leukocytes in the blood and placenta at GD18. A population of CD3- CD161+ cells, which are defined as rat natural killer (NK) cells, were increased in number in the SHRSP. Intracellular flow cytometry also identified this cell type as a source of excess TNFα in blood and placenta from pregnant SHRSP. I then went on to evaluate the effects of etanercept treatment on these CD3- CD161+ cells and showed that etanercept reduced the expression of CD161 and the cytotoxic molecule, granzyme B, in the NK cells. Thus, etanercept limits the cytotoxicity and potential damaging effect of these NK cells in the SHRSP placenta. Analysing the urinary peptidome has clinical potential to identify novel pathways involved with disease and/or to develop biomarker panels to aid and stratify diagnosis. In Chapter 4, I utilised the SHRSP as a pre-clinical model to identify novel urinary peptides associated with hypertensive pregnancy. Firstly, a characterisation study was carried out in the kidney of the WKY and SHRSP. Urine samples from WKY and SHRSP taken at pre-pregnancy, mid-pregnancy (GD12) and late pregnancy (GD18) were used in the peptidomic screen. In order to capture peptides which were markers of hypertensive pregnancy from the urinary peptidomic data, I focussed on those that were only changed in a strain dependent manner at GD12 and 18 and not pre-pregnancy. Peptide fragments from the uromodulin protein were identified from this analysis to be increased in pregnant SHRSP relative to pregnant WKY. This increase in uromodulin was validated at the SHRSP kidney level using qPCR. Uromodulin has previously been identified to be a candidate molecule involved in systemic arterial hypertension but not in hypertensive pregnancy thus is a promising target for further study. In summary, we have characterised the SHRSP as the first model of maternal chronic hypertension during pregnancy and identified that inflammation mediated by TNFα and NK cells plays a key role in the pathology. The evidence presented in this thesis establishes the SHRSP as a pre-clinical model for pregnancy research and can be continued into clinical studies in pregnant women with chronic hypertension which remains an area of unmet research need.
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Fleck and Johnson (Int. J. Mech. Sci. 29 (1987) 507) and Fleck et al. (Proc. Inst. Mech. Eng. 206 (1992) 119) have developed foil rolling models which allow for large deformations in the roll profile, including the possibility that the rolls flatten completely. However, these models require computationally expensive iterative solution techniques. A new approach to the approximate solution of the Fleck et al. (1992) Influence Function Model has been developed using both analytic and approximation techniques. The numerical difficulties arising from solving an integral equation in the flattened region have been reduced by applying an Inverse Hilbert Transform to get an analytic expression for the pressure. The method described in this paper is applicable to cases where there is or there is not a flat region.