Las propuestas de Kant y Nussbaum para la educación:un diálogo entre la razón y las emociones

Este trabajo tiene como eje central considerar los aspectos positivos que se derivan de hacer dialogar dos posturas pedagógicas aparentemente opuestas, pero según elanálisis aquí presentado, complementarias. Se presenta cada uno de estos modelos pedagógicos orientados a la formación de ciudadanía: el planteamiento racionalista kantiano y el emotivista de Martha Nussbaum. La noción de progreso moral de la humanidad es la base del armazón de la pedagogía kantiana, mientras que la noción de cultivo de la humanidad lo es de la pedagogía de la filósofa norteamericana. Palabras clave: progreso moral de la humanidad, Kant,  Nussbaum, educación,razón, emociones.AbstractThe central axis of this work is to consider the positive aspects derived from creating dialogue between two pedagogical positions that are apparently conflicting but, according to the present analysis are shown as complementary. Both Kant’srationalist approach and Martha Nussbaum’s emotivist approach are pedagogical models oriented toward citizenship training: The notion of the moral progress of humanity is the basis of the framework of Kant’s pedagogy, while the notion of thecultivation of humanity is the basis of the pedagogy of the North American philosopher.Key words: moral progress of humanity, Kant, Nussbaum, education, Reason, emotion

Sampling of conformational ensemble for virtual screening using molecular dynamics simulations and normal mode analysis

Aim: Molecular dynamics simulations and normal mode analysis are well-established approaches to generate receptor conformational ensembles (RCEs) for ligand docking and virtual screening. Here, we report new fast molecular dynamics-based and normal mode analysis-based protocols combined with conformational pocket classifications to efficiently generate RCEs. Materials \& methods: We assessed our protocols on two well-characterized protein targets showing local active site flexibility, dihydrofolate reductase and large collective movements, CDK2. The performance of the RCEs was validated by distinguishing known ligands of dihydrofolate reductase and CDK2 among a dataset of diverse chemical decoys. Results \& discussion: Our results show that different simulation protocols can be efficient for generation of RCEs depending on different kind of protein flexibility

A rational free energy-based approach to understanding and targeting disease-causing missense mutations.

BACKGROUND AND SIGNIFICANCE: Intellectual disability is a condition characterized by significant limitations in cognitive abilities and social/behavioral adaptive skills and is an important reason for pediatric, neurologic, and genetic referrals. Approximately 10% of protein-encoding genes on the X chromosome are implicated in intellectual disability, and the corresponding intellectual disability is termed X-linked ID (XLID). Although few mutations and a small number of families have been identified and XLID is rare, collectively the impact of XLID is significant because patients usually are unable to fully participate in society. OBJECTIVE: To reveal the molecular mechanisms of various intellectual disabilities and to suggest small molecules which by binding to the malfunctioning protein can reduce unwanted effects. METHODS: Using various in silico methods we reveal the molecular mechanism of XLID in cases involving proteins with known 3D structure. The 3D structures were used to predict the effect of disease-causing missense mutations on the folding free energy, conformational dynamics, hydrogen bond network and, if appropriate, protein-protein binding free energy. RESULTS: It is shown that the vast majority of XLID mutation sites are outside the active pocket and are accessible from the water phase, thus providing the opportunity to alter their effect by binding appropriate small molecules in the vicinity of the mutation site. CONCLUSIONS: This observation is used to demonstrate, computationally and experimentally, that a particular condition, Snyder-Robinson syndrome caused by the G56S spermine synthase mutation, might be ameliorated by small molecule binding

Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells

The proliferation and survival of hematopoietic stem cells (HSCs) has to be strictly coordinated to ensure the timely production of all blood cells. Here we report that the splice factor and RNA binding protein hnRNP L (heterogeneous nuclear ribonucleoprotein L) is required for hematopoiesis, since its genetic ablation in mice reduces almost all blood cell lineages and causes premature death of the animals. In agreement with this, we observed that hnRNP L deficient HSCs lack both the ability to self-renew and foster hematopoietic differentiation in transplanted hosts. They also display mitochondrial dysfunction, elevated levels of γH2AX, are Annexin V positive and incorporate propidium iodide indicating that they undergo cell death. Lin-c-Kit+ fetal liver cells from hnRNP L deficient mice show high p53 protein levels and up-regulation of p53 target genes. In addition, cells lacking hnRNP L up-regulated the expression of the death receptors TrailR2 and CD95/Fas and show Caspase-3, Caspase-8 and Parp cleavage. Treatment with the pan-caspase inhibitor Z-VAD-fmk, but not the deletion of p53, restored cell survival in hnRNP L deficient cells. Our data suggest that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways

Initiatives de Promotion de la santé au travail : Un examen des enjeux et du contexte au Québec et au Canada

Les études sur les avantages financiers des initiatives de Promotion de la santé au travail (PST) se multiplient. L’intérêt pour ces études provient à la fois des entreprises et des gouvernements. D’une part, les entreprises perçoivent ces programmes comme un moyen potentiel d’augmenter leur productivité face à la concurrence mondiale qui s’intensifie. D’autre part, les gouvernements, cherchant des moyens de diminuer ou de freiner l’augmentation des coûts de la santé, voient ces initiatives comme un levier supplémentaire pour atteindre leurs objectifs budgétaires. Le constat qui ressort de ces études et qu’un dollar investi en PST génère en moyenne trois dollars comme bénéfice. Ces bénéfices prennent principalement la forme d’une diminution de l’absentéisme et de coûts d’assurance santé moindres. Les effets indirects sur la productivité sont moins étudiés. Malgré ces constatations, peu d’entreprises investissent dans la PST et de nombreux employés n’ont pas adhéré aux programmes existants. Au Canada, on constate une diminution récente du nombre d’entreprises participant aux initiatives de PST. Plusieurs raisons sont avancées pour expliquer ce manque d’implication. Une première explication repose sur le fait que les études existantes ne tiennent pas souvent compte de tous les facteurs expliquant la présence d’initiatives de PST en entreprise. En conséquence, bien que les entreprises qui implémentent des initiatives de PST en retirent des bénéfices, il n’est pas dit que celles où ces programmes sont absents retireraient les mêmes bénéfices advenant l’implantation de telles initiatives. Une deuxième explication avance que la faible incidence de ces programmes est causée par un manque général d’intérêt et de connaissances du public à ce propos, de ressources insuffisantes au sein des organisations et de faibles pressions politiques. Misant sur la seconde explication, plusieurs gouvernements tels les États-Unis et l’Allemagne ont adopté des mesures législatives qui encouragent la participation à la PST et récompensent les efforts à cet égard. Deux exemples de telles mesures sont la version modifiée du Healthy Workforce Act (loi concernant la santé de la main-d’œuvre), adoptée par le Sénat américain en 2010, et les modifications du German Tax Act (loi sur l’impôt de l’Allemagne) adoptées en 2009. Ces deux lois offrent des allégements fiscaux aux employeurs qui mettent en place certains programmes de PST. Néanmoins, nous concluons que des études supplémentaires seraient nécessaires pour bien évaluer les bénéfices nets de tels programmes.

JNK Contributes to Hif-1α Regulation in Hypoxic Neurons

Hypoxia is an established factor of neurodegeneration. Nowadays, attention is directed at understanding how alterations in the expression of stress-related signaling proteins contribute to age dependent neuronal vulnerability to injury. The purpose of this study was to investigate how Hif-1alpha, a major neuroprotective factor, and JNK signaling, a key pathway in neurodegeneration, relate to hypoxic injury in young (6DIV) and adult (12DIV) neurons. We could show that in young neurons as compared to mature ones, the protective factor Hif-1alpha is more induced while the stress protein phospho-JNK displays lower basal levels. Indeed, changes in the expression levels of these proteins correlated with increased vulnerability of adult neurons to hypoxic injury. Furthermore, we describe for the first time that treatment with the D-JNKI1, a JNK-inhibiting peptide, rescues adult hypoxic neurons from death and contributes to Hif-1alpha upregulation, probably via a direct interaction with the Hif-1alpha protei

Analysis of Long-Lived Slepton NLSP in GMSB model at Linear Collider

We performed an analysis on the detection of a long-lived slepton at a linear collider with $\sqrt{s}=500$ GeV. In GMSB models a long-lived NLSP is predicted for large value of the supersymmetry breaking scale $\sqrt{F}$. Furthermore in a large portion of the parameter space this particle is a stau. Such heavy charged particles will leave a track in the tracking volume and hit the muonic detector. In order to disentangle this signal from the muon background, we explore kinematics and particle identification tools: time of flight device, dE/dX and Cerenkov devices. We show that a linear collider will be able to detect long-lived staus with masses up to the kinematical limit of the machine. We also present our estimation of the sensitivity to the stau lifetime.Comment: Minor changes, Ref. 10 fixed. 12 pages, RevTex, 4 eps figure

Проектирование системы электроснабжения базы по обслуживанию нефтегазодобывающего месторождения

Выпускная квалификационная работа 136 с., 19 рис., 60 табл., 24 источника, 4 приложения. Объектом исследования является ремонтно-механический цех базы по обслуживанию нефтегазодобывающего месторождения. Цель работы: Проектирование системы электроснабжения базы по облуживанию нефтегазодобывающего месторождения. Экономическое обоснование принятых решений. В процессе исследования произведен расчет нагрузок ремонтно-механического цеха и базы в целом с применением различных методов, выбор метода расчета производился на основе исходных данных, а также осуществлен выборThis graduate qualification work includes 136 p., 19 fig., 60 tables, 24 ones in list of references and 4 transcripts. The subject of research is mechanical repair shop of upstream and gas production field operation base. Work objective is energy supply system designing of upstream and gas production field operation base and its business case. In the course of investigations there was estimated a load analysis of upstream and gas production field operation base and its mechanical repair shop by different methods, based on input data. Also there were steps of the equipment selection and its testing of several operations. As a result of investigation the model of such base was engineered, and there was shown its commercial importance and ecological security. Range of application: petro