Thymic selection generates a large T cell pool recognizing a self-peptide in humans.

The low frequency of self-peptide-specific T cells in the human preimmune repertoire has so far precluded their direct evaluation. Here, we report an unexpected high frequency of T cells specific for the self-antigen Melan-A/MART-1 in CD8 single-positive thymocytes from human histocompatibility leukocyte antigen-A2 healthy individuals, which is maintained in the peripheral blood of newborns and adults. Postthymic replicative history of Melan-A/MART-1-specific CD8 T cells was independently assessed by quantifying T cell receptor excision circles and telomere length ex vivo. We provide direct evidence that the large T cell pool specific for the self-antigen Melan-A/MART-1 is mostly generated by thymic output of a high number of precursors. This represents the only known naive self-peptide-specific T cell repertoire directly accessible in humans.

Higher education as formation of the self and citizenship: an ethnography of the University Students from Amman, Jordan

My interest in higher education and citizenship in the Middle East at large and in Jordan in particular is fostered by some of the reflections Eickelman proposed (1992). Being a quite recent phenomenon, intimately linked with the more general topic of state formation it seemed to me more suitable to study it in a little country with a recent history (a field study left almost unexplored until now as far as Jordan is concerned, to the best of my knowledge, since Antoun 1994 focuses on the migration as a quest for higher education). The process of state formation in Jordan is quite studied. I thus intended to study the higher education policies as an attempt both to create a national citizenry and more recently as a way of controlling the more problematic part of the population (youth, which constitutes more than the double of the population. See UNDP and Ministry of Planning 2000). How do the young students enter the university system, and in which way does this system work? How is this system designed, in order to retain social control of the students (since they are usually perceived to be a factor of social and political instability, as in Iran or in Egypt)? Is there any significant difference between different faculties? And if so, why? My conclusions at this stage are that the university system is an integral part of the survival of the regime. The system works quite well, and Jordan has one of the best educational position in the region. Yet there are important distinctions to be made: the access to the better faculties is socially selective while the less valued faculties are left to the poorer and less wealthy youth. This results in a different treatment of the students and of the courses that I analysed. In the better faculties the teaching standards are quite high, and the relationship between professors and students is almost on a same-level base, while in the less privileged faculties the opposite is true. Thus we can observe a concrete politics of divide et impera intended to split the youth in two. For the more privileged there are some freedoms, both within and outside classes, designed I guess at forging them as autonomous individuals. On the opposite the less privileged are kept under tight control, even if also these students are a privileged category among youth at large.

Quantification, self-renewal, and genetic tracing of FL1+ tumor-initiating cells in a large cohort of human gliomas.

Evidence has emerged that the initiation and growth of gliomas is sustained by a subpopulation of cancer-initiating cells (CICs). Because of the difficulty of using markers to tag CICs in gliomas, we have previously exploited more robust phenotypic characteristics, including a specific morphology and intrincic autofluorescence, to identify and isolate a subpopulation of glioma CICs, called FL1(+). The objective of this study was to further validate our method in a large cohort of human glioma and a mouse model of glioma. Seventy-four human gliomas of all grades and the GFAP-V(12)HA-ras B8 mouse model were analyzed for in vitro self-renewal capacity and their content of FL1(+). Nonneoplastic brain tissue and embryonic mouse brain were used as control. Genetic traceability along passages was assessed with microsatellite analysis. We found that FL1(+) cells from low-grade gliomas and from control nonneoplasic brain tissue show a lower level of autofluorescence and undergo a restricted number of cell divisions before dying in culture. In contrast, we found that FL1(+) cells derived from many but not all high-grade gliomas acquire high levels of autofluorescence and can be propagated in long-term cultures. Moreover, FL1(+) cells show a remarkable traceability over time in vitro and in vivo. Our results show that FL1(+) cells can be found in all specimens of a large cohort of human gliomas of different grades and in a model of genetically induced mouse glioma as well as nonneoplastic brain. However, their self-renewal capacity is variable and seems to be dependent on the tumor grade.

Maps as risk mitigation tools. Adaptation of the Swiss hazard assessment and mapping methodology to a Moroccan site: Beni Mellal

Dans le contexte climatique actuel, les régions méditerranéennes connaissent une intensification des phénomènes hydrométéorologiques extrêmes. Au Maroc, le risque lié aux inondations est devenu problématique, les communautés étant vulnérables aux événements extrêmes. En effet, le développement économique et urbain rapide et mal maîtrisé augmente l'exposition aux phénomènes extrêmes. La Direction du Développement et de la Coopération suisse (DDC) s'implique activement dans la réduction des risques naturels au Maroc. La cartographie des dangers et son intégration dans l'aménagement du territoire représentent une méthode efficace afin de réduire la vulnérabilité spatiale. Ainsi, la DDC a mandaté ce projet d'adaptation de la méthode suisse de cartographie des dangers à un cas d'étude marocain (la ville de Beni Mellal, région de Tadla-Azilal, Maroc). La méthode suisse a été adaptée aux contraintes spécifiques du terrain (environnement semi-aride, morphologie de piémont) et au contexte de transfert de connaissances (caractéristiques socio-économiques et pratiques). Une carte des phénomènes d'inondations a été produite. Elle contient les témoins morphologiques et les éléments anthropiques pertinents pour le développement et l'aggravation des inondations. La modélisation de la relation pluie-débit pour des événements de référence, et le routage des hydrogrammes de crue ainsi obtenus ont permis d'estimer quantitativement l'aléa inondation. Des données obtenues sur le terrain (estimations de débit, extension de crues connues) ont permis de vérifier les résultats des modèles. Des cartes d'intensité et de probabilité ont été obtenues. Enfin, une carte indicative du danger d'inondation a été produite sur la base de la matrice suisse du danger qui croise l'intensité et la probabilité d'occurrence d'un événement pour obtenir des degrés de danger assignables au territoire étudié. En vue de l'implémentation des cartes de danger dans les documents de l'aménagement du territoire, nous nous intéressons au fonctionnement actuel de la gestion institutionnelle du risque à Beni Mellal, en étudiant le degré d'intégration de la gestion et la manière dont les connaissances sur les risques influencent le processus de gestion. L'analyse montre que la gestion est marquée par une logique de gestion hiérarchique et la priorité des mesures de protection par rapport aux mesures passives d'aménagement du territoire. Les connaissances sur le risque restent sectorielles, souvent déconnectées. L'innovation dans le domaine de la gestion du risque résulte de collaborations horizontales entre les acteurs ou avec des sources de connaissances externes (par exemple les universités). Des recommandations méthodologiques et institutionnelles issues de cette étude ont été adressées aux gestionnaires en vue de l'implémentation des cartes de danger. Plus que des outils de réduction du risque, les cartes de danger aident à transmettre des connaissances vers le public et contribuent ainsi à établir une culture du risque. - Severe rainfall events are thought to be occurring more frequently in semi-arid areas. In Morocco, flood hazard has become an important topic, notably as rapid economic development and high urbanization rates have increased the exposure of people and assets in hazard-prone areas. The Swiss Agency for Development and Cooperation (SADC) is active in natural hazard mitigation in Morocco. As hazard mapping for urban planning is thought to be a sound tool for vulnerability reduction, the SADC has financed a project aimed at adapting the Swiss approach for hazard assessment and mapping to the case of Morocco. In a knowledge transfer context, the Swiss method was adapted to the semi-arid environment, the specific piedmont morphology and to socio-economic constraints particular to the study site. Following the Swiss guidelines, a hydro-geomorphological map was established, containing all geomorphic elements related to known past floods. Next, rainfall / runoff modeling for reference events and hydraulic routing of the obtained hydrographs were carried out in order to assess hazard quantitatively. Field-collected discharge estimations and flood extent for known floods were used to verify the model results. Flood hazard intensity and probability maps were obtained. Finally, an indicative danger map as defined within the Swiss hazard assessment terminology was calculated using the Swiss hazard matrix that convolves flood intensity with its recurrence probability in order to assign flood danger degrees to the concerned territory. Danger maps become effective, as risk mitigation tools, when implemented in urban planning. We focus on how local authorities are involved in the risk management process and how knowledge about risk impacts the management. An institutional vulnerability "map" was established based on individual interviews held with the main institutional actors in flood management. Results show that flood hazard management is defined by uneven actions and relationships, it is based on top-down decision-making patterns, and focus is maintained on active mitigation measures. The institutional actors embody sectorial, often disconnected risk knowledge pools, whose relationships are dictated by the institutional hierarchy. Results show that innovation in the risk management process emerges when actors collaborate despite the established hierarchy or when they open to outer knowledge pools (e.g. the academia). Several methodological and institutional recommendations were addressed to risk management stakeholders in view of potential map implementation to planning. Hazard assessment and mapping is essential to an integrated risk management approach: more than a mitigation tool, danger maps represent tools that allow communicating on hazards and establishing a risk culture.

Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen

Human cancer vaccines are often prepared with altered "analog" or "heteroclitic" antigens that have been optimized for HLA class I binding, resulting in enhanced immunogenicity. Here, we take advantage of CpG oligodeoxynucleotides as powerful vaccine adjuvants and demonstrate the induction of high T cell frequencies in melanoma patients, despite the use of natural (unmodified) tumor antigenic peptide. Compared with vaccination with analog peptide, natural peptide induced T cell frequencies that were approximately twofold lower. However, T cells showed superior tumor reactivity because of (i) increased functional avidity for natural antigen and (ii) enhancement of T cell activation and effector function. Thus, novel vaccine formulations comprising potent immune stimulators may allow to circumvent the need for modified antigens and can induce highly functional T cells with precise antigen specificity

Mortality risk of obesity and underweight is overestimated with self-reported body mass index.

Obese persons (those with a body mass index [BMI] ≥30 kg/m2) tend to underestimate their weight, leading to an underestimation of their true (measured) BMI and obesity prevalence.1,2 In contrast, underweight people (BMI <18.5 kg/m2) tend to report themselves heavier, resulting in a higher BMI compared with measured BMI and an underestimation of underweight prevalence.

Cre recombinase-mediated inactivation of H-2Dd transgene expression: evidence for partial missing self-recognition by Ly49A NK cells.

We have established H-2D(d)-transgenic (Tg) mice, in which H-2D(d) expression can be extinguished by Cre recombinase-mediated deletion of an essential portion of the transgene (Tg). NK cells adapted to the expression of the H-2D(d) Tg in H-2(b) mice and acquired reactivity to cells lacking H-2D(d), both in vivo and in vitro. H-2D(d)-Tg mice crossed to mice harboring an Mx-Cre Tg resulted in mosaic H-2D(d) expression. That abrogated NK cell reactivity to cells lacking D(d). In D(d) single Tg mice it is the Ly49A+ NK cell subset that reacts to cells lacking D(d), because the inhibitory Ly49A receptor is no longer engaged by its D(d) ligand. In contrast, Ly49A+ NK cells from D(d) x MxCre double Tg mice were unable to react to D(d)-negative cells. These Ly49A+ NK cells retained reactivity to target cells that were completely devoid of MHC class I molecules, suggesting that they were not anergic. Variegated D(d) expression thus impacts specifically missing D(d) but not globally missing class I reactivity by Ly49A+ NK cells. We propose that the absence of D(d) from some host cells results in the acquisition of only partial missing self-reactivity.

Trends in self-reported prevalence and management of hypertension, dyslipidaemia and diabetes in adults in Switzerland, 1992-2007

Purpose: to assess the trends of self-reported prevalence of cardiovascular risk factors (CV RFs: hypertension, dyslipidaemia, diabetes) and their management for period 1992 to 2007 in the Swiss population. Methods: four National health interview surveys conducted between 1992 and 2007 in representative samples of the Swiss population (63,782 subjects overall). Self-reported CV RFs prevalence, treatment and controllevels were computed after weighting. Weights were calculated by raking ratio such that the marginal distribution of the weighted totals conforms to the marginal distribution of the targeted population. Multivariate analysis adjusted on age, sex, education, nationality and SMI was conducted using logistic regression. Results: prevalence of ail CV RFs increased between 1992 and 2007, see table. Although the self-reported prevalence of treatment among subjects with CV RFs increased, and this was confirmed by multivariate analysis: OR for hypocholesterolaemic treatment relative to 1992: 0.64 [0.52-0.78]; 1.39 [1.18-1.65] and 2.00 [1.69-2.36] for 1997, 2002 and 2007, respectively. Still, in 2007, circa 40% of hypertensive, 60% of dyslipidaemic and 50% of diabetic subjects weren't treated. Conversely, an adequate control of CV RFs was reported by treated subjects, with an increase during the study period. This increase was confirmed by multivariate analysis (not shown). Conclusion: the self-reported prevalence of hypertension, dyslipidaemia and diabetes increased between 1992 and 2007 in the Swiss population. Despite a good control of treated subjects, still a significant percentage of subjects with CV RFs are not treated.

Media guidelines for reporting suicide and self-harm

These guidelines are for those in the media who have involvement with the reporting or portrayal of suicide and represent an important source of information to help ensure that the quality of reporting and portrayal on this important and sensitive topic is of a high standard.

Dialogism and dialogicality in the study of the self

This article stems from the statement that dialogical approaches to a study of the self face a double challenge: that of developing a conception of the self that both avoids social reductionism and accounts for the stability of the self. In discussing this double challenge, we identify three much debated issues: (a) To what does the notion of "Alter" exactly refer? (b) How could we conceptualize the fact that Subject-Alter interactions are not only interpersonal but entail larger social entities, in particular institutions? (c)What importance should we attach to the materiality of objects? We discuss these three questions from two standpoints - that of linguistics and that of psychology - and illustrate our theoretical proposals with an analysis of an excerpt taken from a focus-group discussion. In conclusion, we argue that the dialogism of discourse provides us with some clues about the dialogicality of the mind, whereas the latter invites us to develop a theory showing the importance of interactions in the construction of the self, to pay more attention to the transpersonal dimension of the social, and to consider that the material world contributes to the construction of the self.

Variant within the promoter region of the CHRNA3 gene associated with FTN dependence is not related to self-reported willingness to quit smoking.

INTRODUCTION: Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region is robustly associated with smoking quantity. Conversely, the association between one of the most significant single nucleotide polymorphisms (SNPs; rs1051730 within the CHRNA3 gene) with perceived difficulty or willingness to quit smoking among current smokers is unknown. METHODS: Cross-sectional study including current smokers, 502 women, and 552 men. Heaviness of smoking index (HSI), difficulty, attempting, and intention to quit smoking were assessed by questionnaire. RESULTS: The rs1051730 SNP was associated with increased HSI (age, gender, and education-adjusted mean ± SE: 2.6 ± 0.1, 2.2 ± 0.1, and 2.0 ± 0.1 for AA, AG, and GG genotypes, respectively, p < .01). Multivariate logistic regression adjusting for gender, age, education, leisure-time physical activity, and personal history of cardiovascular or lung disease showed rs1051730 to be associated with higher smoking dependence (odds ratio [OR] and 95% CI for each additional A-allele: 1.38 [1.11-1.72] for smoking more than 20 cigarette equivalents/day; 1.31 [1.00-1.71] for an HSI ≥5 and 1.32 [1.05-1.65] for smoking 5 min after waking up) and borderline associated with difficulty to quit (OR = 1.29 [0.98-1.70]), but this relationship was no longer significant after adjusting for nicotine dependence. Also, no relationship was found with willingness (OR = 1.03 [0.85-1.26]), attempt (OR = 1.00 [0.83-1.20]), or preparation (OR = 0.95 [0.38-2.38]) to quit. Similar findings were obtained for other SNPs, but their effect on nicotine dependence was no longer significant after adjusting for rs1051730. Conclusions: These data confirm the effect of rs1051730 on nicotine dependence but failed to find any relationship with difficulty, willingness, and motivation to quit.

Gestión en el territorio de una empresa de seguridad mediante estándares GIS e integración de datos con Google Maps.

Estudi teòric sobre els Sistemes d'Informació Geogràfica (GIS) i sobre les especificacions que està publicant el Open Geospatial Consortium (OGC) com estàndards oberts que permetin les comunicacions entre distints GIS.