508 research outputs found

    Reduced languages as omega-generators

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    International audienceWe consider the following decision problem: “Is a rational omega-language generated by a code ?” Since 1994, the codes admit a characterization in terms of infinite words. We derive from this result the definition of a new class of languages, the reduced languages. A code is a reduced language but the converse does not hold. The idea is to “reduce" easy-to-obtain minimal omega-generators in order to obtain codes as omega-generators

    A Variant Mimicking Hyperphosphorylated 4E-BP Inhibits Protein Synthesis in a Sea Urchin Cell-Free, Cap-Dependent Translation System

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    BACKGROUND: 4E-BP is a translational inhibitor that binds to eIF4E to repress cap-dependent translation initiation. This critical protein:protein interaction is regulated by the phosphorylation of 4E-BP. Hypophosphorylated 4E-BP binds to eIF4E and inhibits cap-dependent translation, whereas hyperphosphorylated forms do not. While three 4E-BP proteins exist in mammals, only one gene encoding for 4E-BP is present in the sea urchin genome. The protein product has a highly conserved core domain containing the eIF4E-binding domain motif (YxxxxLPhi) and four of the regulatory phosphorylation sites. METHODOLOGY/PRINCIPAL FINDINGS: Using a sea urchin cell-free cap-dependent translation system prepared from fertilized eggs, we provide the first direct evidence that the sea urchin 4E-BP inhibits cap-dependent translation. We show here that a sea urchin 4E-BP variant, mimicking phosphorylation on four core residues required to abrogate binding to eIF4E, surprisingly maintains physical association to eIF4E and inhibits protein synthesis. CONCLUSIONS/SIGNIFICANCE: Here, we examine the involvement of the evolutionarily conserved core domain and phosphorylation sites of sea urchin 4E-BP in the regulation of eIF4E-binding. These studies primarily demonstrate the conserved activity of the 4E-BP translational repressor and the importance of the eIF4E-binding domain in sea urchin. We also show that a variant mimicking hyperphosphorylation of the four regulatory phosphorylation sites common to sea urchin and human 4E-BP is not sufficient for release from eIF4E and translation promotion. Therefore, our results suggest that there are additional mechanisms to that of phosphorylation at the four critical sites of 4E-BP that are required to disrupt binding to eIF4E

    Linkage analysis of high myopia susceptibility locus in 26 families

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    Purpose: We conducted a linkage analysis in high myopia families to replicate suggestive results from chromosome 7q36 using a model of autosomal dominant inheritance and genetic heterogeneity. We also performed a genome-wide scan to identify novel loci. Methods: Twenty-six families, with at least two high-myopic subjects (ie. refractive value in the less affected eye of -5 diopters) in each family, were included. Phenotypic examination included standard autorefractometry, ultrasonographic eye length measurement, and clinical confirmation of the non-syndromic character of the refractive disorder. Nine families were collected de novo including 136 available members of whom 34 were highly myopic subjects. Twenty new subjects were added in 5 of the 17 remaining families. A total of 233 subjects were submitted to a genome scan using ABI linkage mapping set LMSv2-MD-10, additional markers in all regions where preliminary LOD scores were greater than 1.5 were used. Multipoint parametric and non-parametric analyses were conducted with the software packages Genehunter 2.0 and Merlin 1.0.1. Two autosomal recessive, two autosomal dominant, and four autosomal additive models were used in the parametric linkage analyses. Results: No linkage was found using the subset of nine newly collected families. Study of the entire population of 26 families with a parametric model did not yield a significant LOD score (>3), even for the previously suggestive locus on 7q36. A non-parametric model demonstrated significant linkage to chromosome 7p15 in the entire population (Z-NPL=4.07, p=0.00002). The interval is 7.81 centiMorgans (cM) between markers D7S2458 and D7S2515. Conclusions: The significant interval reported here needs confirmation in other cohorts. Among possible susceptibility genes in the interval, certain candidates are likely to be involved in eye growth and development

    The experiences of those who support researchers struggling with their mental health

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    This international survey examines the nature of the relationships between researchers who struggle with their mental health, and those in the community who try to support them. This work examines who these 'supporters' are, who they help, what they do, and it paints a complex picture of how they feel about this supporting role, and what they need to do it

    Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution

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    Abstract Background Obesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease. Methods We investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the LipoprintŸ system. Results PON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p < 0.05), regardless of PON-1 protein levels. Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p <0.05) and HDL-associated PAF-AH expression compared to obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups. Conclusions Our data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk

    Peptidotriazolamers Inhibit A beta(1-42) Oligomerization and Cross a Blood-Brain-Barrier Model

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    In peptidotriazolamers every second peptide bond is replaced by a 1H-1,2,3-triazole. Such foldamers are expected to bridge the gap in molecular weight between small-molecule drugs and protein-based drugs. Amyloid beta (A beta) aggregates play an important role in Alzheimer's disease. We studied the impact of amide bond replacements by 1,4-disubstituted 1H-1,2,3-triazoles on the inhibitory activity of the aggregation "hot spots" (KLVFF20)-L-16 and G(39)VVIA(42) in A beta(1-42). We found that peptidotriazolamers act as modulators of the A beta(1-42) oligomerization. Some peptidotriazolamers are able to interfere with the formation of toxic early A beta oligomers, depending on the position of the triazoles, which is also supported by computational studies. Preliminary in vitro results demonstrate that a highly active peptidotriazolamer is also able to cross the blood-brain-barrier.Peer reviewe

    Étude de trois facteurs clĂ©s pour comprendre la persĂ©vĂ©rance Ă  l’universitĂ©

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    La premiĂšre annĂ©e Ă  l’universitĂ© est marquĂ©e par un taux de rĂ©ussite et de persĂ©vĂ©rance assez faible. Pour expliquer ce phĂ©nomĂšne, on a d’abord pris en compte les caractĂ©ristiques sociodĂ©mographiques et le passĂ© scolaire des Ă©tudiants. Mais, depuis une trentaine d’annĂ©es, d’autres dimensions ont Ă©tĂ© Ă©tudiĂ©es en se basant sur des courants thĂ©oriques distincts. D’une part, les modĂšles Ă©ducationnels (Tinto, 1975, 1997 ; Bean, 1980) soulignent Ă  la fois l’importance des expĂ©riences sociales et acadĂ©miques vĂ©cues lors de la transition Ă  l’universitĂ© et l’importance de l’ajustement entre les caractĂ©ristiques individuelles et institutionnelles ; d’autre part, les modĂšles motivationnels (Wigfield & Eccles, 2000 ; Eccles & Wigfield, 2002 ; Kahn & Nauta, 2001) se focalisent sur les attributs personnels des Ă©tudiants (par exemple le sentiment de compĂ©tence, les reprĂ©sentations des buts, etc.). En validant le modĂšle de Tinto dans le contexte Ă©ducationnel belge et en analysant le rĂŽle complĂ©mentaire du sentiment d’efficacitĂ© personnelle, nous tentons ici de mettre en Ă©vidence l’apport de ces diffĂ©rents courants thĂ©oriques dans la comprĂ©hension des facteurs de persĂ©vĂ©rance. Cette contribution s’intĂ©resse particuliĂšrement Ă  l’intention de persĂ©vĂ©rance, mesurĂ©e dĂšs les premiĂšres semaines passĂ©es Ă  l’universitĂ©, car elle constitue l’un des facteurs majeurs dans la persĂ©vĂ©rance effective et est positivement associĂ©e Ă  la rĂ©ussite finale. Nos rĂ©sultats dĂ©montrent que la persĂ©vĂ©rance et la rĂ©ussite, loin d’ĂȘtre dĂ©terminĂ©es exclusivement par le bagage d’entrĂ©e de l’étudiant, sont significativement influencĂ©es par des variables individuelles et des variables contextuelles, ainsi que par l’interaction entre les deux. Cet article met ainsi en lumiĂšre l’importance du contexte Ă©ducatif et le rĂŽle que peuvent jouer les acteurs du terrain. Ces derniers peuvent soutenir la persĂ©vĂ©rance et la rĂ©ussite des Ă©tudiants, non seulement par la mise en Ɠuvre de dispositifs pĂ©dagogiques adaptĂ©s (misant sur les relations entre pairs, l’apprentissage coopĂ©ratif, l’utilitĂ© et l’intĂ©rĂȘt des activitĂ©s), mais aussi par leurs interventions auprĂšs des Ă©tudiants pour soutenir leur sentiment d’efficacitĂ© personnelle et la construction de leur projet de formation.During the first year at university, a remarkably small number of students stay in school and succeed. To explain that phenomenon, we first take into account the students’ socio-demographic characteristics and school backgrounds. For thirty years, other elements have also been studied based on different theoretical trends. On the one hand educational models (Tinto, 1975, 1997; Bean, 1980) underline both the importance of social and school experiences the students have when entering university right after high school and their adaptation to new individual and institutional features. On the other hand motivation models (Wigfield & Eccles, 2000; Eccles & Wigfield, 2002; Kahn & Nauta, 2001) focus upon the students’ personal features (for instance feeling competent, recognizing goals, etc.). Validating the model of Tinto in the Belgian educational environment and analyzing the complementary role of the feeling of personal efficiency, we try here to clearly show what those different theoretical trends bring to understanding what makes the students continue their studies. This paper focuses in particular on the intention to continue, measured from the very first weeks at university because it is one of the main elements for real perseverance and success and is positively linked to final success. Our results show that perseverance and success, far from being determined solely by the students’ school backgrounds, are significantly influenced by personal and contextual factors as well as the interactions between those factors. This article thus brings out the importance of the educational context and the part that different protagonists can play in practice for each student individually (helping them feel competent, see the importance of the courses or find goals for their studies) as well in the setting-up of devices to help them continue their studies and succeed (promoting relationships with peers, highlighting team work).El primer curso de una carrera universitaria se ve marcado por una tasa de estudiantes que fracasan muy importante asĂ­ como un abandono muy elevado. Para explicar este fenĂłmeno se estudiaron primero las caracterĂ­sticas sociodemogrĂĄficas y el pasado escolar de los estudiantes pero desde hace mĂĄs o menos treinta años, se estudiaron otras dimensiones, que se basan en corrientes teĂłricas distintas. Por una parte, los modelos educacionales (Tinto, 1975, 1997 ; Bean, 1980) subrayan a la vez la importancia de las experiencias sociales y acadĂ©micas vividas durante el periodo de transiciĂłn que supone la entrada en la facultad y la importancia del ajuste entre las caracterĂ­sticas individuales e institucionales ; por otra parte, los modelos motivacionales (Wigfield & Eccles, 2000 ; Eccles & Wigfield, 2002 ; Kahn & Nauta, 2001) se focalizan sobre los atributos personales de los estudiantes (por ejemplo el sentimiento de competencia, las representaciones de las metas, etc.) Validando el modelo de Tinto en el contexto educacional belga y analizando el papel complementario del sentimiento de eficacia personal, intentamos aquĂ­ evidenciar el aporte de aquellas diferentes corrientes teĂłricas en la comprensiĂłn de los factores de perseverancia. Este estudio se enfoca particularmente en el deseo de perseverancia que se analiza a partir de las primeras semanas de presencia en la universidad, porque constituye uno de los factores mayores en la perseverancia efectiva y es positivamente asociada al Ă©xito final. Nuestros resultados demuestran que la perseverancia y el Ă©xito distan mucho de ser exclusivamente determinados por los conocimientos del estudiante al ingresar en la facultad y son muy influenciados por variables individuales y contextuales asĂ­ como por la interacciĂłn entre ambos. Este artĂ­culo pone de relieve y a plena luz la importancia del contexto educativo y el papel que pueden desempeñar los actores sobre el terreno, tanto para cada estudiante (fomentar el sentimiento de competencia, la percepciĂłn de la importancia de las clases o ayudar a los estudiantes para que ideen y elaboren metas de formaciĂłn, etc.), como los medios y dispositivos (favorecer las relaciones entre los pares, hacer hincapiĂ© en el aprendizaje cooperativo) para sostener la perseverancia y el Ă©xito de los estudiantes.Das erste Jahr an der französischen UniversitĂ€t wird von einer ziemlich schwachen Ausdauer- und Erfolgsrate gekennzeichnet. Um dieses PhĂ€nomen zu erklĂ€ren, hat man zunĂ€chst die soziodemographischen Merkmale und die schulische Laufbahn der Studenten berĂŒcksichtigt. Doch seit etwa 30 Jahren wurden neue Dimensionen erforscht, die auf verschiedenen theoretischen Grundlagen beruhen. Auf der einen Seite unterstreichen die erzieherischen Modelle (Tinto, 1975, 1997; Bean, 1980) sowohl die Bedeutung der sozialen und akademischen Erlebnisse bei der Umstellung auf die UniversitĂ€t als auch die Bedeutung der Anpassung an den individuellen und institutionellen Charakteristika. Auf der anderen Seite fokussieren sich die Motivationsmodelle (Wigfield & Eccles, 2000; Eccles & Wigfield, 2002; Kahn & Nauta, 2001) auf die persönlichen Attribute der Studenten (z.B. das GefĂŒhl der Kompetenz, die Vorstellung der Ziele, usw.). Mit der Anerkennung des Tintoschen Modells im belgischen Erziehungskontext und mit der Analyse der zusĂ€tzlichen Rolle des GefĂŒhls der persönlichen Effizienz versuchen wir, den Beitrag dieser verschiedenen theoretischen Strömungen im Verstehen der Ausdauerfaktoren zu unterstreichen. Dieser Beitrag befasst sich besonders mit der Ausdauerabsicht, die gleich in den ersten Wochen an der UniversitĂ€t gemessen wird, denn sie stellt einer der wichtigsten Faktoren bei der tatsĂ€chlichen Ausdauer dar und steht in positivem Zusammenhang mit dem Enderfolg. Unsere Ergebnisse zeigen, dass Ausdauer und Erfolg nicht ausschließlich durch die Anfangskenntnisse der Studenten bestimmt sind, sondern dass sie von individuellen und kontextuellen Variablen und von dem Zusammenwirken zwischen beiden erheblich beeinflusst werden. Dieser Artikel hebt somit die Bedeutung des erzieherischen Kontexts hervor und betont die Rolle, die die Lehrenden spielen können sowohl fĂŒr jeden Studenten (das KompetenzgefĂŒhl fördern, die Bedeutung der Vorlesungen wahrnehmen oder den Studenten dabei helfen, die Ziele ihrer Ausbildung zu formulieren) als auch in der Umsetzung von Vorrichtungen, um Ausdauer und Erfolg bei den Studenten zu unterstĂŒtzen (die Beziehungen zwischen Studenten fördern, den Schwerpunkt auf kooperatives Lernen setzen)
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