Extent and limitations of density functional theory in describing magnetic systems

The performance of density-functional theory to solve the exact, nonrelativistic, many-electron problem for magnetic systems has been explored in a new implementation imposing space and spin symmetry constraints, as in ab initio wave function theory. Calculations on selected systems representative of organic diradicals, molecular magnets and antiferromagnetic solids carried out with and without these constraints lead to contradictory results, which provide numerical illustration on this usually obviated problem. It is concluded that the present exchange-correlation functionals provide reasonable numerical results although for the wrong physical reasons, thus evidencing the need for continued search for more accurate expressions.

El compromis ètic en la investigació etnogràfica

En aquest article explorarem alguns aspectes étics que ens semblen rellevants de considerar quan estem implicats en una recerca etnogrófica. Com se sap, una investigació d'aquest tipus té la finalitat de descriure, comprendre i interpretar la vida d'una persona, d'un col-lectiu, d'una institució, etc.; és a dir, s'interessa pel que les persones fan, diuen, pensen, creuen ... El que s'intenta comprendre és com interactuen, com es comporten, quines creences i quins valors orienten les seves accions i els seus punts de vista. I tracta de fer-ho des de "dins" considerant les perspectives de totes les persones implicades. Tot aixó requereix a qui investiga ser en els escenaris on les persones actuen, observar els seus comportaments i descriure el que passa, el que es diu, com es diu, les expressions, els signes, els gestos, etc. Alhora, també exigeix conéixer els significats i les interpretacions que donen de la seva actuació. Per tant, qui investiga haura de realitzar entrevistes amb les persones implicades per comprendre els seus punts de vista. I també requerira analitzar la documentació que produeixin les persones a qui es vol comprendre en relació amb el que es vol investigar.

Optimization Of Promoter Sequences In Order To Mimic Physiological Pde6b Expression

Purpose: Many retinal degenerations result from defective retina-specific gene expressions. Thus, it is important to understand how the expression of a photoreceptor-specific gene is regulated in vivo in order to achieve successful gene therapy. The present study aims to design an AAV2/8 vector that can regulate the transcript level in a physiological manner to replace missing PDE6b in Rd1 and Rd10 mice. In previous studies (Ogieta, et al., 2000), the short 5' flanking sequence of the human PDE6b gene (350 bp) was shown to be photoreceptor-specific in transgenic mice. However, the efficiency and specificity of the 5' flanking region of the human PDE6b was not investigated in the context of gene therapy during retinal degeneration. In this study, two different sequences of the 5' flanking region of the human PDE6b gene were studied as promoter elements and their expression will be tested in wild type and diseased retinas (Rd 10 mice).Methods: Two 5' flanking fragments of the human PDE6b gene: (-93 to +53 (150 bp) and -297 to +53 (350 bp)) were cloned in different plasmids in order to check their expression in vitro and in vivo by constructing an AAV2/8 vector. These elements drove the activity of either luciferase (pGL3 plasmids) or EGFP. jetPEI transfection in Y 79 cells was used to evaluate gene expression through luciferase activity. Constructs encoding EGFP under the control of the two promoters were performed in AAV2.1-93 (or 297)-EGFP plasmids to produce AAV2/8 vectors.Results: When pGL3-93 (150 bp) or pGL3-297 (350 bp) were transfected in the Y-79 cells, the smaller fragment (150 bp) showed higher gene expression compared to the 350 bp element and to the SV40 control, as previously reported. The 350 bp drove similar levels of expression when compared to the SV40 promoter. In view of these results, the fragments (150 bp or 350 bp) were integrated into the AAV2.1-EGFP plasmid to produce AAV2/8 vector, and we are currently evaluating the efficiency and specificity of the produced constructs in vivo in normal and diseased retinas.Conclusions: Comparisons of these vectors with vectors bearing ubiquitous promoters should reveal which construct is the most suitable to drive efficient and specific gene expression in diseased retinas in order to restore a normal function on the long term.

Clinical proteomics : a focus on transformed human T and B lymphocytes

Résumé large public La protéomique clinique est une discipline qui vise l'étude des protéines dans un but diagnostique ou thérapeutique. Nous avons utilisé cette approche pour étudier les lymphocytes T «tueurs » ou cytotoxiques qui font partie des globules blancs du système sanguin et agissent dans la lutte contre les infections et les tumeurs. Ces cellules sont impliquées dans l'immunothérapie cellulaire qui se fonde sur la capacité naturelle des ces lymphocytes à repérer les cellules tumorales et à les détruire. L'introduction du gène de la télomérase dans les lymphocytes T résulte en une prolongation de leur longévité, ce qui en ferait des candidats intéressants pour l'immunothérapie cellulaire. Il subsiste cependant des doutes quant aux conséquences de l'utilisation de ces lymphocytes «immortalisés ». Pour répondre à cette question, nous avons comparé le profile protéique de lymphocytes T cytotoxiques «jeunes » et vieux » avec celui des lymphocytes «immortalisés ». Nous avons trouvé que ces derniers présentent une double face et partagent à la fois les caractéristiques de la jeunesse et de la vieillesse. Dans une seconde étude de protéomique clinique, nous nous sommes penchés sur les lymphocytes B «immortalisés » cette fois-ci non pas avec la télomérase, mais avec le virus d'Epstein-Barr. Ces derniers sont utilisés comme modèle dans l'étude de la leucodystrophie, une maladie génétique rare qui affecte le cerveau. Notre but est d'identifier des marqueurs biologiques potentiels qui pourraient aider le diagnostic et le traitement de cette maladie neurodégénérative. Nous avons pour ce faire comparé les profiles protéiques des lymphocytes B «immortalisés » provenant d'individus sains et malades. Malheureusement, notre analyse n'a pas révélé de différences notoires entre ces deux classes de lymphocytes. Ceci nous permet toutefois de conclure que la maladie n'affecte pas la synthèse des protéines de manière prépondérante dans ces cellules sanguines. En résumé, le travail présenté dans cette thèse montre à la fois le potentiel et les limites de l'analyse des protéines lymphocytaires, dans différentes situations biologiques. Résumé La protéomique clinique ouvre la porte vers de multiples horizons relatifs au traitement de diverses maladies. Ce domaine particulier alliant la protéomique à la médecine, implique l'intervention de la biologie moléculaire et cellulaire. Dans notre étude, nous nous sommes d'abord intéressés aux lymphocytes T CD8+ cytotoxiques dans le contexte de l'immunothérapie adoptive. Le fondement de cette thérapie repose sur la capacité naturelle de ces lymphocytes à reconnaître les cellules tumorales et à les détruire chez les patients atteints de cancer. L'introduction du gène de la transcriptase réverse de la télomérase (hTERT) dans les lymphocytes T humains permet de rallonger leur durée de vie, sans toutefois induire d'altérations liées à la transformation. Cependant, des incertitudes subsistent quant à la ressemblance physiologique et biochimique entre ces cellules surexprirnant la télomérase et les cellules normales. Afin de répondre à cette question, nous avons comparé l'expression des protéines de lymphocytes humains T CD8+ «jeunes » et «vieux »avec celle de lymphocytes transduits avec hTERT. Nous avons trouvé que les lymphocytes T surexprimant la télomérase ont un profile protéique intermédiaire, avec certaines expressions protéiques similaires aux jeunes cellules T et d'autres se rapprochant des cellules vieilles. Dans la seconde partie de notre étude, nous nous sommes intéressés aux lymphocytes B transformés avec le virus d'Epstein-Barr provenant de patients atteints d'une maladie génétique rare du cerveau, la leucodystrophie. Dans cette maladie, des mutations dans le facteur de transcription eIF2B, impliqué dans la synthèse protéique, ont été trouvées. Afin d'analyser les conséquences de ces mutations et de trouver des biomarqueurs spécifiques à cette maladie, nous avons effectué une analyse protéomique des lymphoblastes provenant de malades et d'individus sains. Nous avons trouvé que les mutations dans le complexe ubiquitaire eIF2B n'affectent pas de manière significative l'expression des protéines des lymphoblastes mutés. En conclusion, notre travail illustre le potentiel et les limitations des technologies protéomiques utilisées pour disséquer l'implication des protéines dans différentes situations biologiques. Summary Clinical proteomics opens the door to multiple applications related to the treatment of diseases. This particular field is at the crossroad of proteomics and medicine and involves tools from cellular and molecular biology. We focused first our investigations on cytotoxic T cells in the context of adoptive immunotherapy, which is an interesting and evolving field. The basis of this therapy relies on the natural capacity of cytotoxic CD8+ T lymphocytes in recognizing tumor cells and destroying them in cancer patients. As their number is reduced, the idea would be to use transformed T lymphocytes with extended life span. Overexpression of telomerase into human T lymphocytes results in the extension of their replicative life span, but it still remains unclear whether these cells are physiologically indistinguishable from normal ones. To address this question, we compared the proteome of young and aged CD8+ T lymphocytes with that of T cells transduced with hTERT and found that the latter cells displayed an intermediate protein pattern, sharing similar protein expression with young, but also with aged T cells. We were then interested in studying Epstein-Barr virus transformed B lymphocytes in the context of a rare human brain genetic disorder called leukodystrophy. In this disease, mutations in the ubiquitous factor eIF2B involved in protein synthesis and its regulation have been reported. In order to analyze the functional consequences of the mutations and to find out specific biomarkers of eIF2B-related disorders, proteomic and peptidomic studies were carried out on lymphoblasts from eIF2Bmutated patients versus healthy patients. Following two-dimensional gel electrophoresis and mass fingerprints, mutations in the eIF2B complex did not appear to significantly affect the proteome of the mutated lymphoblasts extracts. To conclude, our work emphasizes the potentials and the limitations of the proteomic technologies used to analyze the role of lymphocyte proteins in different biological situations.

Moderata Fonte y María Zambrano: por cuenta propia

In this paper, Rosa Rius thinks about feminine identity and its history, based on the expressions of freedom of two authors living four centuries apart: the Venetian humanist Moderata Fonte (1555-1592) and the Malagan philosopher María Zambrano (1904-1991). The fact that these women¿s freedom is taken as one of their main identifying elements, and straining the historical action of this freedom, unforeseen by the establishment, does not at all imply that the undeniable discrimination inflicted upon women throughout centuries is forgotten or goes on without protest.

Maladaptive exploratory behavior and neuropathology of the PS-1 P117L Alzheimer transgenic mice.

Patients with the early-onset Alzheimer's disease P117L mutation in the presenilin-1 gene (PS-1) present pathological hallmarks in the hippocampus, the frontal cortex and the basal ganglia. In the present work we determined by immunohistochemistry which brain regions were injured in the transgenic PS-1 P117L mice, in comparison to their littermates, the B6D2 mice. Furthermore, as these regions are involved in novelty detection, we investigated the behavior of these mice in tests for object and place novelty recognition. Limited numbers of senile plaques and neurofibrillary tangles were detected in aged PS-1 P117L mice in the CA1 only, indicating that the disease is restrained to an initial neuropathological stage. Western blots showed a change in PSD-95 expression (p=0.03), not in NR2A subunit, NR2B subunit and synaptophysin expressions in the frontal cortex, suggesting specific synaptic alterations. The behavioral tests repeatedly revealed, despite a non-significant preference for object or place novelty, maladaptive exploratory behavior of the PS-1 P117L mice in novel environmental conditions, not due to locomotor problems. These mice, unlike the B6D2 mice, were less inhibited to visit the center of the cages (p=0.01) and they continued to move excessively in the presence of a displaced object (p=0.021). Overall, the PS-1 P117L mice appear to be in an initial Alzheimer's disease-like neuropathological stage, and they showed a lack of reaction toward novel environmental conditions.

Keep on moving from English to Catalan : El determinisme lingüístic en la traducció del moviment

El propòsit d'aquest treball és fixar, basant-nos en l'anàlisi tipològica, les diferències lingüístiques en la construcció de les expressions de moviment de l'anglès i el català. Partim de la hipòtesi que en funció de l'origen de la llengua, s'apliquen solucions diferents a determinats problemes lingüístics que apareixen a l'hora de traduir un discurs. Analitzarem, doncs, el grau de fidelitat de la traducció quant a l'expressió del trajecte i de la manera. Per consegüent, estudiarem si hi ha cap pèrdua d'informació, de qualitat o de genuïnitat en relació amb el text original servint-nos de la comparació d'ambdós estils narratius.

BMP-2 and TGF-beta1 differentially control expression of type II procollagen and alpha 10 and alpha 11 integrins in mouse chondrocytes.

Bone morphogenetic protein (BMP)-2 and transforming growth factor (TGF)-beta1 are multifunctional cytokines both proposed as stimulants for cartilage repair. Thus it is crucial to closely examine and compare their effects on the expression of key markers of the chondrocyte phenotype, at the gene and protein level. In this study, the expression of alpha 10 and alpha 11 integrin subunits and the IIA/IIB spliced forms of type II procollagen have been monitored for the first time in parallel in the same in vitro model of mouse chondrocyte dedifferentiation/redifferentiation. We demonstrated that TGF-beta1 stimulates the expression of the non-chondrogenic form of type II procollagen, IIA isoform, and of a marker of mesenchymal tissues, i.e. the alpha 11 integrin subunit. On the contrary, BMP-2 stimulates the cartilage-specific form of type II procollagen, IIB isoform, and a specific marker of chondrocytes, i.e. the alpha 10 integrin subunit. Collectively, our results demonstrate that BMP-2 has a better capability than TGF-beta1 to stimulate chondrocyte redifferentiation and reveal that the relative expressions of type IIB to type IIA procollagens and alpha 10 to alpha 11 integrin subunits are good markers to define the differentiation state of chondrocytes. In addition, adenoviral expression of Smad6, an inhibitor of BMP canonical Smad signaling, did not affect expression of total type II procollagen or the ratio of type IIA and type IIB isoforms in mouse chondrocytes exposed to BMP-2. This result strongly suggests that signaling pathways other than Smad proteins are involved in the effect of BMP-2 on type II procollagen expression.

Short-time dynamics of colloidal suspensions in confined geometries

We analyze the short-time dynamical behavior of a colloidal suspension in a confined geometry. We analyze the relevant dynamical response of the solvent, and derive the temporal behavior of the velocity autocorrelation function, which exhibits an asymptotic negative algebraic decay. We are able to compare quantitatively with theoretical expressions, and analyze the effects of confinement on the diffusive behavior of the suspension.

La traducción del manga al español: Cuestiones lingüísticas, metodológicas y técnicas.

El trabajo trata la traducción del manga al castellano (cuestiones lingüísticas, metodológicas y técnicas): las características principales del japonés, el proceso de traducción, los métodos y las opciones de adaptación empleados por las editoriales españolas, y la compatibilidad de escritura en equipos españoles. Finalmente, incluye un ejemplo real de traducción.

El doblatge d’una comèdia britànica: The Vicar of Dibley

Aquest treball analitza els problemes de doblatge de l’anglès al català que presenta una sèrie còmica, The Vicar of Dibley. L’objectiu es estudiar tant problemes generals com específics per tal de demostrar la viabilitat del doblatge d’aquesta comèdia. Es proposen possibles solucions per a tots els problemes analitzats.

Interpretaciones de la atenuación en artículos de revisión de Odontología

Este trabajo analiza cómo interpretan la atenuación 25 estudiantes universitarios venezolanos de Odontología, de nuevo ingreso, al responder a dos cuestionarios luego de leer un artículo de revisión. En el primero, con preguntas abiertas, debían interpretar algunas expresiones atenuadas preseleccionadas; en el segundo, debían elegir entre varias interpretaciones cerradas de los mismos fragmentos. Clasificamos sus respuestas en las siguientes categorías: reconocimiento, supresión y aumento de la atenuación, en el primer cuestionario; identificación de aproximadores, escudos, deícticos y construcciones impersonales, en el segundo. En los resultados predomina la identificación de atenuadores asociados a la dimensión semántica: el 30% reconoció la atenuación tal como fue usada en el original, el 30% aumentó su valor y el 40% no la logró identificar. Los estudiantes identificaron con mayor frecuencia los aproximadores, a diferencia de los escudos, las construcciones impersonales y los deícticos temporales. Estos resultados sugieren que es necesario formar a losestudiantes en el uso especializado de las dimensiones pragmática y sociocognitiva de la atenuación, en cursos de lectura y escritura académica. Solo este conocimiento específico permitirá que los estudiantes dominen el discurso científico prototípico de la Odontología.

Essays in equilibrium asset pricing

Introduction This dissertation consists of three essays in equilibrium asset pricing. The first chapter studies the asset pricing implications of a general equilibrium model in which real investment is reversible at a cost. Firms face higher costs in contracting than in expanding their capital stock and decide to invest when their productive capital is scarce relative to the overall capital of the economy. Positive shocks to the capital of the firm increase the size of the firm and reduce the value of growth options. As a result, the firm is burdened with more unproductive capital and its value lowers with respect to the accumulated capital. The optimal consumption policy alters the optimal allocation of resources and affects firm's value, generating mean-reverting dynamics for the M/B ratios. The model (1) captures convergence of price-to-book ratios -negative for growth stocks and positive for value stocks - (firm migration), (2) generates deviations from the classic CAPM in line with the cross-sectional variation in expected stock returns and (3) generates a non-monotone relationship between Tobin's q and conditional volatility consistent with the empirical evidence. The second chapter proposes a standard portfolio-choice problem with transaction costs and mean reversion in expected returns. In the presence of transactions costs, no matter how small, arbitrage activity does not necessarily render equal all riskless rates of return. When two such rates follow stochastic processes, it is not optimal immediately to arbitrage out any discrepancy that arises between them. The reason is that immediate arbitrage would induce a definite expenditure of transactions costs whereas, without arbitrage intervention, there exists some, perhaps sufficient, probability that these two interest rates will come back together without any costs having been incurred. Hence, one can surmise that at equilibrium the financial market will permit the coexistence of two riskless rates that are not equal to each other. For analogous reasons, randomly fluctuating expected rates of return on risky assets will be allowed to differ even after correction for risk, leading to important violations of the Capital Asset Pricing Model. The combination of randomness in expected rates of return and proportional transactions costs is a serious blow to existing frictionless pricing models. Finally, in the last chapter I propose a two-countries two-goods general equilibrium economy with uncertainty about the fundamentals' growth rates to study the joint behavior of equity volatilities and correlation at the business cycle frequency. I assume that dividend growth rates jump from one state to other, while countries' switches are possibly correlated. The model is solved in closed-form and the analytical expressions for stock prices are reported. When calibrated to the empirical data of United States and United Kingdom, the results show that, given the existing degree of synchronization across these business cycles, the model captures quite well the historical patterns of stock return volatilities. Moreover, I can explain the time behavior of the correlation, but exclusively under the assumption of a global business cycle.

The adjective petit 'small, little' in French acquisition data: an example of the relationship between pragmatics and morphosyntactic development

In French the adjective petit 'small, little' has a special status: it fulfills various pragmatic functions in addition to semantic meanings and it is thus highly frequent in discourse. Résumé: This study, based on the data of two children, aged 1;6 to 2;11, argues that petit and its pragmatic meanings play a specific role in the acquisition of French adjectives. In contrast to what is expected in child language, petit favours the early development of a pattern of noun phrase with prenominal attributive adjective. The emergence and distribution of petit in the children's production is examined and related to its distribution in the input, and the detailed pragmatic meanings and functions of petit are analysed. Prenominal petit emerges early as the preferred and most productive adjective. Pragmatic meanings of petit appear to be predominant in this early age and are of two main types: expressions of endearment (in noun phrases) and mitigating devices whose scope is the entire utterance. These results, as well as instances of children's pragmatic overgeneralizations, provide new evidence that at least some pragmatic meanings are prior to semantic meanings in early acquisition.

Diversity and genetic structure of the wood ant Formica lugubris in unmanaged forests

Wood ant species show differences in their social structure, especially in the level of polygyny (number of laying queens per nest) and polydomy (number of nest per colony), both within and between species. We demonstrate here for the first time that Formica lugubris displays two different social forms in close proximity in alpine unmanaged forests of the Swiss National Park. The genetic data (7 microsatellite loci) and field data indicate that one population is mostly monogynous to weakly polygynous (r = 0.438) and monodomous, the second one being polygynous (r = 0.113) and polydomous. Within this latter population new nests are founded by budding, leading to the observed high density of nests. These two different social structures, possibly being two expressions of a same continuum, could be explained by several ecological or environmental factors (e.g. habitat saturation, resource competition) and also historical effects.