Dawn for the galaxy: creació d'un joc web d'estratègia en temps real, multijugador i massiu

“Dawn or the Galaxy” és un treball de final de carrera que té com a objectiu principal la creació i desenvolupament d’una versió de demostració per a un joc del tipus MMORTS (massive multiplayer online real-time strategy) tractant d’incloure elements innovadors en aquest gènere de jocs i oferint un ampli ventall estratègic des de l’inici del joc. Per tal d’assolir l’objectiu es realitzarà un petit sondeig de mercat inicial i un estudi de models de jocs d’estratègia. El joc estarà integrat per més de seixanta fitxers de codi, una base de dades amb catorze taules interrelacionades no normalitzades i podrà tenir cabuda per a uns cinc-cents jugadors. Un cop programat l’aplicatiu, el joc es provarà en un entorn real, amb usuaris reals. Per a resoldre els problemes durant el transcurs del joc de forma ràpida, la aplicació serà sotmesa a un seguiment exhaustiu. La col·laboració dels jugadors en aquest punt serà fonamental.

Work, risk and health: differences between immigrants and natives in Spain

We analyze the impact of working and contractual conditions, particularly exposure to job risks, on the probability of acquiring a disability. We postulate a model in which this impact is mediated by the choice of occupation, with a level of risk associated to it. We assume this choice is endogenous, and that it depends on preferences and opportunities in the labour market, both of which may differ between immigrants and natives. To test this hypothesis we use data from the Continuous Sample of Working Lives of the Spanish SS system. It contains individual, job and firm information of over a million workers, including a representative sample of immigrants. We find that risk exposure increases the probability of permanent disability by 5.3%; temporary employment also influences health. Migrant status -with differences among regions of origin- significantly affects both disability and the probability of being employed in a risky occupation. Most groups of immigrants work in riskier jobs, but have lower probability of becoming disabled. Nevertheless, our theoretical hypothesis that disability and risk are jointly determined is not valid for immigrants: i.e. for them working conditions is not a matter of choice in terms of health.

EZH2 is essential for glioblastoma cancer stem cell maintenance.

Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) occurs in diverse malignancies, including prostate cancer, breast cancer, and glioblastoma multiforme (GBM). Based on its ability to modulate transcription of key genes implicated in cell cycle control, DNA repair, and cell differentiation, EZH2 is believed to play a crucial role in tissue-specific stem cell maintenance and tumor development. Here, we show that targeted pharmacologic disruption of EZH2 by the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep), or its specific downregulation by short hairpin RNA (shRNA), strongly impairs GBM cancer stem cell (CSC) self-renewal in vitro and tumor-initiating capacity in vivo. Using genome-wide expression analysis of DZNep-treated GBM CSCs, we found the expression of c-myc, recently reported to be essential for GBM CSCs, to be strongly repressed upon EZH2 depletion. Specific shRNA-mediated downregulation of EZH2 in combination with chromatin immunoprecipitation experiments revealed that c-myc is a direct target of EZH2 in GBM CSCs. Taken together, our observations provide evidence that direct transcriptional regulation of c-myc by EZH2 may constitute a novel mechanism underlying GBM CSC maintenance and suggest that EZH2 may be a valuable new therapeutic target for GBM management.

Immunization with PIII, a fraction of Schistosoma mansoni soluble adult worm antigenic preparation, affects nitric oxide production by murine spleen cells

Nitric oxide (NO) is an important effector molecule involved in immune regulation and defense. NO produced by cytokine-activated macrophages was reported to be cytotoxic against the helminth Schistosoma mansoni. Identification and characterization of S. mansoni antigens that can provide protective immunity is crucial for understanding the complex immunoregulatory events that modulate the immune response in schistosomiasis. It is, then, essential to have available defined, purified parasite antigens. Previous work by our laboratory identified a fraction of S. mansoni soluble adult worm antigenic preparation (SWAP), named PIII, able to elicit significant in vitro cell proliferation and at the same time lower in vitro and in vivo granuloma formation when compared either to SEA (soluble egg antigen) or to SWAP. In the present work we report the effect of different in vivo trials with mice on their spleen cells ability to produce NO. We demonstrate that PIII-immunization is able to significantly increase NO production by spleen cells after in vitro stimulation with LPS. These data suggest a possible role for NO on the protective immunity induced by PIII.

Donner la parole aux médecins traitants [Letting the treating physicians speak].

OBJECTIVE: Quality assessment in consultation and liaison psychiatry (CLP) is extremely difficult and must take into account numerous factors. The general practitioner (GP) of the patients seen by CL psychiatrists seems an essential factor to be considered in evaluating CL work. However, as far as we know, no study is doing so. Therefore, we have implied the GP to assess our CL work at the hospital St-Loup-Orbe. METHOD: We put up a qualitative study consisting of semi-structured interviews with 18 GPs caring for 45 patients having been submitted to a psychiatric CL intervention. Furthermore, we invited the GPs to assesses CLP as a specialization as well as CLP practiced at St-Loup-Orbe hospital. RESULTS: Impact is judged by the GPs with regard to the total number as: highly favorable> favorable> indifferent> negative. The GPs' critiques, whether positive or negative, are highly informative. CONCLUSIONS: GPs accept favorably CLP interventions and consider them on the whole as constructive. On the other hand, they are not sufficiently considered as partners during their patients' hospital stay. Furthermore, CLP must evaluate its impact at distance from the consultation and take into account the GPs' assessments to improve CL quality.

Water as an essential nutrient: the physiological basis of hydration.

How much water we really need depends on water functions and the mechanisms of daily water balance regulation. The aim of this review is to describe the physiology of water balance and consequently to highlight the new recommendations with regard to water requirements. Water has numerous roles in the human body. It acts as a building material; as a solvent, reaction medium and reactant; as a carrier for nutrients and waste products; in thermoregulation; and as a lubricant and shock absorber. The regulation of water balance is very precise, as a loss of 1% of body water is usually compensated within 24 h. Both water intake and water losses are controlled to reach water balance. Minute changes in plasma osmolarity are the main factors that trigger these homeostatic mechanisms. Healthy adults regulate water balance with precision, but young infants and elderly people are at greater risk of dehydration. Dehydration can affect consciousness and can induce speech incoherence, extremity weakness, hypotonia of ocular globes, orthostatic hypotension and tachycardia. Human water requirements are not based on a minimal intake because it might lead to a water deficit due to numerous factors that modify water needs (climate, physical activity, diet and so on). Water needs are based on experimentally derived intake levels that are expected to meet the nutritional adequacy of a healthy population. The regulation of water balance is essential for the maintenance of health and life. On an average, a sedentary adult should drink 1.5 l of water per day, as water is the only liquid nutrient that is really essential for body hydration.

Systems biology of plants : from intraspecific genome variation to computational morphodynamics

Recently, the introduction of second generation sequencing and further advance-ments in confocal microscopy have enabled system-level studies for the functional characterization of genes. The degree of complexity intrinsic to these approaches needs the development of bioinformatics methodologies and computational models for extracting meaningful biological knowledge from the enormous amount of experi¬mental data which is continuously generated. This PhD thesis presents several novel bioinformatics methods and computational models to address specific biological questions in Plant Biology by using the plant Arabidopsis thaliana as a model system. First, a spatio-temporal qualitative analysis of quantitative transcript and protein profiles is applied to show the role of the BREVIS RADIX (BRX) protein in the auxin- cytokinin crosstalk for root meristem growth. Core of this PhD work is the functional characterization of the interplay between the BRX protein and the plant hormone auxin in the root meristem by using a computational model based on experimental evidence. Hyphotesis generated by the modelled to the discovery of a differential endocytosis pattern in the root meristem that splits the auxin transcriptional response via the plasma membrane to nucleus partitioning of BRX. This positional information system creates an auxin transcriptional pattern that deviates from the canonical auxin response and is necessary to sustain the expression of a subset of BRX-dependent auxin-responsive genes to drive root meristem growth. In the second part of this PhD thesis, we characterized the genome-wide impact of large scale deletions on four divergent Arabidopsis natural strains, through the integration of Ultra-High Throughput Sequencing data with data from genomic hybridizations on tiling arrays. Analysis of the identified deletions revealed a considerable portion of protein coding genes affected and supported a history of genomic rearrangements shaped by evolution. In the last part of the thesis, we showed that VIP3 gene in Arabidopsis has an evo-lutionary conserved role in the 3' to 5' mRNA degradation machinery, by applying a novel approach for the analysis of mRNA-Seq data from random-primed mRNA. Altogether, this PhD research contains major advancements in the study of natural genomic variation in plants and in the application of computational morphodynamics models for the functional characterization of biological pathways essential for the plant. - Récemment, l'introduction du séquençage de seconde génération et les avancées dans la microscopie confocale ont permis des études à l'échelle des différents systèmes cellulaires pour la caractérisation fonctionnelle de gènes. Le degrés de complexité intrinsèque à ces approches ont requis le développement de méthodologies bioinformatiques et de modèles mathématiques afin d'extraire de la masse de données expérimentale générée, des information biologiques significatives. Ce doctorat présente à la fois des méthodes bioinformatiques originales et des modèles mathématiques pour répondre à certaines questions spécifiques de Biologie Végétale en utilisant la plante Arabidopsis thaliana comme modèle. Premièrement, une analyse qualitative spatio-temporelle de profiles quantitatifs de transcripts et de protéines est utilisée pour montrer le rôle de la protéine BREVIS RADIX (BRX) dans le dialogue entre l'auxine et les cytokinines, des phytohormones, dans la croissance du méristème racinaire. Le noyau de ce travail de thèse est la caractérisation fonctionnelle de l'interaction entre la protéine BRX et la phytohormone auxine dans le méristème de la racine en utilisant des modèles informatiques basés sur des preuves expérimentales. Les hypothèses produites par le modèle ont mené à la découverte d'un schéma différentiel d'endocytose dans le méristème racinaire qui divise la réponse transcriptionnelle à l'auxine par le partitionnement de BRX de la membrane plasmique au noyau de la cellule. Cette information positionnelle crée une réponse transcriptionnelle à l'auxine qui dévie de la réponse canonique à l'auxine et est nécessaire pour soutenir l'expression d'un sous ensemble de gènes répondant à l'auxine et dépendant de BRX pour conduire la croissance du méristème. Dans la seconde partie de cette thèse de doctorat, nous avons caractérisé l'impact sur l'ensemble du génome des délétions à grande échelle sur quatre souches divergentes naturelles d'Arabidopsis, à travers l'intégration du séquençage à ultra-haut-débit avec l'hybridation génomique sur puces ADN. L'analyse des délétions identifiées a révélé qu'une proportion considérable de gènes codant était affectée, supportant l'idée d'un historique de réarrangement génomique modelé durant l'évolution. Dans la dernière partie de cette thèse, nous avons montré que le gène VÏP3 dans Arabidopsis a conservé un rôle évolutif dans la machinerie de dégradation des ARNm dans le sens 3' à 5', en appliquant une nouvelle approche pour l'analyse des données de séquençage d'ARNm issue de transcripts amplifiés aléatoirement. Dans son ensemble, cette recherche de doctorat contient des avancées majeures dans l'étude des variations génomiques naturelles des plantes et dans l'application de modèles morphodynamiques informatiques pour la caractérisation de réseaux biologiques essentiels à la plante. - Le développement des plantes est écrit dans leurs codes génétiques. Pour comprendre comment les plantes sont capables de s'adapter aux changements environnementaux, il est essentiel d'étudier comment leurs gènes gouvernent leur formation. Plus nous essayons de comprendre le fonctionnement d'une plante, plus nous réalisons la complexité des mécanismes biologiques, à tel point que l'utilisation d'outils et de modèles mathématiques devient indispensable. Dans ce travail, avec l'utilisation de la plante modèle Arabidopsis thalicinci nous avons résolu des problèmes biologiques spécifiques à travers le développement et l'application de méthodes informatiques concrètes. Dans un premier temps, nous avons investigué comment le gène BREVIS RADIX (BRX) régule le développement de la racine en contrôlant la réponse à deux hormones : l'auxine et la cytokinine. Nous avons employé une analyse statistique sur des mesures quantitatives de transcripts et de produits de gènes afin de démontrer que BRX joue un rôle antagonisant dans le dialogue entre ces deux hormones. Lorsque ce-dialogue moléculaire est perturbé, la racine primaire voit sa longueur dramatiquement réduite. Pour comprendre comment BRX répond à l'auxine, nous avons développé un modèle informatique basé sur des résultats expérimentaux. Les simulations successives ont mené à la découverte d'un signal positionnel qui contrôle la réponse de la racine à l'auxine par la régulation du mouvement intracellulaire de BRX. Dans la seconde partie de cette thèse, nous avons analysé le génome entier de quatre souches naturelles d'Arabidopsis et nous avons trouvé qu'une grande partie de leurs gènes étaient manquant par rapport à la souche de référence. Ce résultat indique que l'historique des modifications génomiques conduites par l'évolution détermine une disponibilité différentielle des gènes fonctionnels dans ces plantes. Dans la dernière partie de ce travail, nous avons analysé les données du transcriptome de la plante où le gène VIP3 était non fonctionnel. Ceci nous a permis de découvrir le rôle double de VIP3 dans la régulation de l'initiation de la transcription et dans la dégradation des transcripts. Ce rôle double n'avait jusqu'alors été démontrée que chez l'homme. Ce travail de doctorat supporte le développement et l'application de méthodologies informatiques comme outils inestimables pour résoudre la complexité des problèmes biologiques dans la recherche végétale. L'intégration de la biologie végétale et l'informatique est devenue de plus en plus importante pour l'avancée de nos connaissances sur le fonctionnement et le développement des plantes.

Antibacterial activity of Ocimum gratissimum L. essential oil

The essential oil (EO) of Ocimum gratissimum inhibited Staphylococcus aureus at a concentration of 0.75 mg/ml. The minimal inhibitory concentrations (MICs) for Shigella flexineri, Salmonella enteritidis, Escherichia coli, Klebsiella sp., and Proteus mirabilis were at concentrations ranging from 3 to 12 mg/ml. The endpoint was not reached for Pseudomonas aeruginosa (>=24 mg/ml). The MICs of the reference drugs used in this study were similar to those presented in other reports. The minimum bactericidal concentration of EO was within a twofold dilution of the MIC for this organism. The compound that showed antibacterial activity in the EO of O. gratissimum was identified as eugenol and structural findings were further supported by gas chromatography/mass spectra retention time data. The structure was supported by spectroscopic methods.

Tackling Food Poverty: Only a more comprehensive approach will work

Lessons from the Decent Food for All(DFfA) Intervention

Expression of the gene encoding the high-Km glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy.

AIMS/HYPOTHESIS: Excess glucose transport to embryos during diabetic pregnancy causes congenital malformations. The early postimplantation embryo expresses the gene encoding the high-Km GLUT2 (also known as SLC2A2) glucose transporter. The hypothesis tested here is that high-Km glucose transport by GLUT2 causes malformations resulting from maternal hyperglycaemia during diabetic pregnancy. MATERIALS AND METHODS: Glut2 mRNA was assayed by RT-PCR. The Km of embryo glucose transport was determined by measuring 0.5-20 mmol/l 2-deoxy[3H]glucose transport. To test whether the GLUT2 transporter is required for neural tube defects resulting from maternal hyperglycaemia, Glut2+/- mice were crossed and transient hyperglycaemia was induced by glucose injection on day 7.5 of pregnancy. Embryos were recovered on day 10.5, and the incidence of neural tube defects in wild-type, Glut2+/- and Glut2-/- embryos was scored. RESULTS: Early postimplantation embryos expressed Glut2, and expression was unaffected by maternal diabetes. Moreover, glucose transport by these embryos showed Michaelis-Menten kinetics of 16.19 mmol/l, consistent with transport mediated by GLUT2. In pregnancies made hyperglycaemic on day 7.5, neural tube defects were significantly increased in wild-type embryos, but Glut2+/- embryos were partially protected from neural tube defects, and Glut2-/- embryos were completely protected from these defects. The frequency of occurrence of wild-type, Glut2+/- and Glut2-/- embryos suggests that the presence of Glut2 alleles confers a survival advantage in embryos before day 10.5. CONCLUSIONS/INTERPRETATIONS: High-Km glucose transport by the GLUT2 glucose transporter during organogenesis is responsible for the embryopathic effects of maternal diabetes.

Quality Standards for Approved Social Work March 2005 (PDF 1.10MB)

Standards and criteria drawn from the recommendations of A Study of Approved Social Work.

Ultraschalldiagnostik des nichttraumatischen akuten Abdomens: die Ursachen ausserhalb des Gastro-Intestinaltraktes [Ultrasound of non traumatic acute abdomen: extra-digestive causes]

In recent years, management of abdominal pain in emergency care units (ECU) has undergone a radical change. Chronic work overload of ECU and increase in severity and complexity of cases required an optimal medical imaging method, such as ultrasound, to establish an accurate diagnosis as quickly as possible. A great variety of causes may cause acute abdominal pain and the role of sonography is to accurately distinguish between these aetiologies. For the application of sonography, perhaps more so than with other imaging methods, a perfect knowledge of sonographical characteristics and technical possibilities is essential to achieve an optimal answer. The purpose of this review is to present and discuss the sonographic characteristics of extra-digestive causes of acute abdominal pain such as splenic infarction, thoracic pathologies, urinary and gynaecologic diseases or retroperitoneal pathologies.