Impact of increasing mean air temperature on the development of rice and red rice

The objective of this study was to assess the development response of cultivated rice and red rice to different increases in minimum and maximum daily air temperatures, in Santa Maria, Rio Grande do Sul State, Brazil. One hundred years climate scenarios of temperatures 0, +1, +2, +3, +4, and +5ºC, with symmetric and asymmetric increases in minimum and maximum daily air temperatures were created, using the LARS-WG Weather Generator, and a 1969-2003 database. Nine cultivated rice genotypes (IRGA 421, IRGA 416, IRGA 417, IRGA 420, BRS 7 TAIM, BR-IRGA 409, EPAGRI 109, EEA 406 and a hybrid), and two red rice biotypes (awned black hull-ABHRR, and awned yellow hull-AYHRR) were used. The dates of panicle differentiation (R1), anthesis (R4), and all grains with brown hulls (R9) were estimated with a nonlinear simulation model. Overall, the duration of the emergence-R1 phase decreased, whereas the duration of the R1-R4 and R4-R9 phases most often increased, as temperature increased in the climate change scenarios. The simulated rice development response to elevated temperature was not the same, when the increase in minimum and maximum temperature was symmetric or asymmetric.

Extraintestinal manifestations in inflammatory bowel disease: frequency and associated risk factors in the nationwide Swiss IBD cohort study (SIBDCS)

Background: Data on the frequency of extraintestinal manifestations (EIM) in Crohnʼs disease (CD) and ulcerative colitis (UC) are scarce. Goal: to evaluate prevalences, forms of EIM and risk factors in a large nationwide IBD cohort. Methods: Data from validated physician enrolment questionnaires of the adult Swiss IBD cohort were analyzed. Logistic regression models were used to identify EIM risk factors. Results: 950 patients were included, 580 (61%) with CD (mean age 43yrs) and 370 (39%) with UC (mean age 49yrs), of these, 249 (43%) of CD and 113 (31%) of UC patients had one to 5 EIM. The following EIM were found: arthritis (CD 33%, UC 21%), aphthous stomatitis (CD 10%, UC 4%), uveitis (CD 6%, UC 4%), erythema nodosum (CD 6%, UC 3%), ankylosing spondylitis (CD 6%, UC 2%), psoriasis (CD 2%, UC 1%), pyoderma gangrenosum (CD and UC each 2%), primary sclerosing cholangitis (CD 1%, UC 4%). Logistic regression in CD identified the following items as risk factors for ongoing EIM: active disease (OR 1.95, 95% CI 1.17-3.23, P=0.01), positive IBD family history (OR 1.77, 95% CI 1.07-2.92, P=0.025). No risk factors were identified in UC patients. Conclusions: EIM are a frequent problem in CD and UC patients. Active disease and positive IBD family history are associated with ongoing EIM in CD patients. Identification of EIM prevalence and associated risk factors may result in increased awareness for this problem and thereby facilitate their diagnosis and management.

A hybrid algorithm combining metaheuristic with Monte Carlo simulation for solving the Stochastic Flow Shop problem

In this paper, a hybrid simulation-based algorithm is proposed for the StochasticFlow Shop Problem. The main idea of the methodology is to transform the stochastic problem into a deterministic problem and then apply simulation to the latter. In order to achieve this goal, we rely on Monte Carlo Simulation and an adapted version of a deterministic heuristic. This approach aims to provide flexibility and simplicity due to the fact that it is not constrained by any previous assumption and relies in well-tested heuristics.

EADock : design of a new molecular docking algorithm and some of its applications

3 Summary 3. 1 English The pharmaceutical industry has been facing several challenges during the last years, and the optimization of their drug discovery pipeline is believed to be the only viable solution. High-throughput techniques do participate actively to this optimization, especially when complemented by computational approaches aiming at rationalizing the enormous amount of information that they can produce. In siiico techniques, such as virtual screening or rational drug design, are now routinely used to guide drug discovery. Both heavily rely on the prediction of the molecular interaction (docking) occurring between drug-like molecules and a therapeutically relevant target. Several softwares are available to this end, but despite the very promising picture drawn in most benchmarks, they still hold several hidden weaknesses. As pointed out in several recent reviews, the docking problem is far from being solved, and there is now a need for methods able to identify binding modes with a high accuracy, which is essential to reliably compute the binding free energy of the ligand. This quantity is directly linked to its affinity and can be related to its biological activity. Accurate docking algorithms are thus critical for both the discovery and the rational optimization of new drugs. In this thesis, a new docking software aiming at this goal is presented, EADock. It uses a hybrid evolutionary algorithm with two fitness functions, in combination with a sophisticated management of the diversity. EADock is interfaced with .the CHARMM package for energy calculations and coordinate handling. A validation was carried out on 37 crystallized protein-ligand complexes featuring 11 different proteins. The search space was defined as a sphere of 15 R around the center of mass of the ligand position in the crystal structure, and conversely to other benchmarks, our algorithms was fed with optimized ligand positions up to 10 A root mean square deviation 2MSD) from the crystal structure. This validation illustrates the efficiency of our sampling heuristic, as correct binding modes, defined by a RMSD to the crystal structure lower than 2 A, were identified and ranked first for 68% of the complexes. The success rate increases to 78% when considering the five best-ranked clusters, and 92% when all clusters present in the last generation are taken into account. Most failures in this benchmark could be explained by the presence of crystal contacts in the experimental structure. EADock has been used to understand molecular interactions involved in the regulation of the Na,K ATPase, and in the activation of the nuclear hormone peroxisome proliferatoractivated receptors a (PPARa). It also helped to understand the action of common pollutants (phthalates) on PPARy, and the impact of biotransformations of the anticancer drug Imatinib (Gleevec®) on its binding mode to the Bcr-Abl tyrosine kinase. Finally, a fragment-based rational drug design approach using EADock was developed, and led to the successful design of new peptidic ligands for the a5ß1 integrin, and for the human PPARa. In both cases, the designed peptides presented activities comparable to that of well-established ligands such as the anticancer drug Cilengitide and Wy14,643, respectively. 3.2 French Les récentes difficultés de l'industrie pharmaceutique ne semblent pouvoir se résoudre que par l'optimisation de leur processus de développement de médicaments. Cette dernière implique de plus en plus. de techniques dites "haut-débit", particulièrement efficaces lorsqu'elles sont couplées aux outils informatiques permettant de gérer la masse de données produite. Désormais, les approches in silico telles que le criblage virtuel ou la conception rationnelle de nouvelles molécules sont utilisées couramment. Toutes deux reposent sur la capacité à prédire les détails de l'interaction moléculaire entre une molécule ressemblant à un principe actif (PA) et une protéine cible ayant un intérêt thérapeutique. Les comparatifs de logiciels s'attaquant à cette prédiction sont flatteurs, mais plusieurs problèmes subsistent. La littérature récente tend à remettre en cause leur fiabilité, affirmant l'émergence .d'un besoin pour des approches plus précises du mode d'interaction. Cette précision est essentielle au calcul de l'énergie libre de liaison, qui est directement liée à l'affinité du PA potentiel pour la protéine cible, et indirectement liée à son activité biologique. Une prédiction précise est d'une importance toute particulière pour la découverte et l'optimisation de nouvelles molécules actives. Cette thèse présente un nouveau logiciel, EADock, mettant en avant une telle précision. Cet algorithme évolutionnaire hybride utilise deux pressions de sélections, combinées à une gestion de la diversité sophistiquée. EADock repose sur CHARMM pour les calculs d'énergie et la gestion des coordonnées atomiques. Sa validation a été effectuée sur 37 complexes protéine-ligand cristallisés, incluant 11 protéines différentes. L'espace de recherche a été étendu à une sphère de 151 de rayon autour du centre de masse du ligand cristallisé, et contrairement aux comparatifs habituels, l'algorithme est parti de solutions optimisées présentant un RMSD jusqu'à 10 R par rapport à la structure cristalline. Cette validation a permis de mettre en évidence l'efficacité de notre heuristique de recherche car des modes d'interactions présentant un RMSD inférieur à 2 R par rapport à la structure cristalline ont été classés premier pour 68% des complexes. Lorsque les cinq meilleures solutions sont prises en compte, le taux de succès grimpe à 78%, et 92% lorsque la totalité de la dernière génération est prise en compte. La plupart des erreurs de prédiction sont imputables à la présence de contacts cristallins. Depuis, EADock a été utilisé pour comprendre les mécanismes moléculaires impliqués dans la régulation de la Na,K ATPase et dans l'activation du peroxisome proliferatoractivated receptor a (PPARa). Il a également permis de décrire l'interaction de polluants couramment rencontrés sur PPARy, ainsi que l'influence de la métabolisation de l'Imatinib (PA anticancéreux) sur la fixation à la kinase Bcr-Abl. Une approche basée sur la prédiction des interactions de fragments moléculaires avec protéine cible est également proposée. Elle a permis la découverte de nouveaux ligands peptidiques de PPARa et de l'intégrine a5ß1. Dans les deux cas, l'activité de ces nouveaux peptides est comparable à celles de ligands bien établis, comme le Wy14,643 pour le premier, et le Cilengitide (PA anticancéreux) pour la seconde.

A hybrid algorithm combining metaheuristic with Monte Carlo simulation for solving the Stochastic Flow Shop problem

In this paper, a hybrid simulation-based algorithm is proposed for the StochasticFlow Shop Problem. The main idea of the methodology is to transform the stochastic problem into a deterministic problem and then apply simulation to the latter. In order to achieve this goal, we rely on Monte Carlo Simulation and an adapted version of a deterministic heuristic. This approach aims to provide flexibility and simplicity due to the fact that it is not constrained by any previous assumption and relies in well-tested heuristics.

J2 effect and elliptic inclined periodic orbits in the collision three-body problem

The existence of a new class of inclined periodic orbits of the collision restricted three-body problem is shown. The symmetric periodic solutions found are perturbations of elliptic kepler orbits and they exist only for special values of the inclination and are related to the motion of a satellite around an oblate planet

Alcohol drinking and cardiovascular risk in a population with high mean alcohol consumption

Résumé : Description : Ce travail de thèse évalue l'impact de la consommation importante d'alcool sur les facteurs de risque cardiovasculaire et l'estimation du risque cardiovasculaire à 10 ans (risque de développer une maladie coronarienne}, dans une population avec une consommation moyenne élevée d'alcool. La consommation modérée d'alcool a été liée à un risque plus faible de développer une maladie coronarienne. Cependant, les données concernant la consommation importante d'alcool et le risque de développer une maladie coronarienne sont conflictuelles. Il y a également peu d'études dans lesquelles les consommations importantes d'alcool ont pu être évaluées en raison du petit nombre de sujets présentant une telle consommation. Résultats: Nous avons utilisé les données de l'étude CoLaus, une étude populationnelle qui inclut des adultes, âgés de 35 à 75 ans, de la ville de Lausanne. Nous avons inclus 5'769 participants, sans maladie cardiovasculaire, pour lesquels la consommation d'alcool d'une semaine a été catégorisée en 0, 1 à 6, 7 à 13, 14 à 20, 21 à 27, 28 à 34 et >=35 verres/semaine et en non-consommateur (0 verre/semaine), consommateur modéré (1 à 13 verres/semaine), important (14 à 34 verres/semaine) et très important (>= 35). La tension artérielle et les lipides ont été mesurés et le risque de développer une maladie coronarienne à 10 ans a été calculé en utilisant le score de Framingham. 73% des participants consommaient de l'alcool; 16% étaient des consommateurs importants et 2% des consommateurs très importants. L'analyse rnultivariée a montré une augmentation du cholestérol HDL avec la consommation d'alcool (de 1.570.01 [moyenne +- erreur standard] chez les non consommateurs à 1.880.03 mmol/L chez les consommateurs très importants), des triglycérides (1.17+-1.01 à 1.32+-1.05 mmol/L) et des valeurs de tension artérielle systolique (127.4+-0.4 à 132.2+-.4 mm Hg) et diastolique (78.7+-0.3 à 81.7+-0.9 mm Hg, toutes les valeurs de p pour trend<0.001). Quant au risque de développer une maladie coronarienne à 10 ans, il a augmenté de 4.31%+-0.10 à 4.90%+-0.37 (p=0.03) avec la consommation d'alcool, en décrivant une courbe en J. En examinant le type de consommation, on a vu que la consommation de vin a plus d'effet sur l'augmentation des valeurs de cholestérol HDL, alors que la consommation de bière ou de spiritueux a plus d'effet sur l'augmentation des valeurs de triglycérides. Conclusions et perspectives: Nos résultats montrent qu'en ce qui concerne l'estimation du risque cardiovasculaire à 10 ans, l'effet protecteur de la consommation d'alcool disparaît pour des consommations très importantes, car l'effet bénéfique des valeurs augmentées de cholestérol HDL est contrecarré par l'augmentation des valeurs de tension artérielle. Quant aux différents types d'alcool, d'autres études sont nécessaires pour mieux évaluer leur effet spécifique sur les facteurs de risque cardiovasculaire.

Gazpacho consumption is associated with lower blood pressure and reduced hypertension in a high cardiovascular risk cohort. Cross-sectional study of the PREDIMED trial

Hypertension is a major public health problem and a leading cause of death and disability in both developed and developing countries, affecting onequarter of the world"s adult population. Our aim was to evaluate whether the consumption of gazpacho, a Mediterranean vegetable-based cold soup rich in phytochemicals, is associated with lower blood pressure (BP) and/or reduced prevalence of hypertension in individuals at high cardiovascular risk. Methods and results: We selected 3995 individuals (58% women, mean age 67 y) at high cardiovascular risk (81% hypertensive) recruited into the PREDIMED study. BP, weight, and dietary and physical activity data were collected. In multivariate linear regression analyses, after adjustment, moderate and high gazpacho consumption categories were associated with reduced mean systolic BP of 1.9 mm Hg [95% confidence interval (CI): 3.4; 0.6] and 2.6 mm Hg (CI: 4.2; 1.0), respectively, and reduced diastolic BP of 1.5 mm Hg (CI: 2.3; 0.6) and 1.9 mm Hg (CI: 2.8; 1.1). By multiple-adjusted logistic regression analysis, gazpacho consumption was associated with a lower prevalence of hypertension, with OR Z 0.85 (CI: 0.73; 0.99) for each 250 g/week increase and OR Z 0.73 (CI: 0.55; 0.98) for high gazpacho consumption groups compared to the no-consumption group. Conclusions: Gazpacho consumption was inversely associated with systolic and diastolic BP and prevalence of hypertension in a cross-sectional Mediterranean population at high cardiovascular risk. The association between gazpacho intake and reduction of BP is probably due to synergy among several bioactive compounds present in the vegetable ingredients used to make the recipe.

Gazpacho consumption is associated with lower blood pressure and reduced hypertension in a high cardiovascular risk cohort. Cross-sectional study of the PREDIMED trial

Hypertension is a major public health problem and a leading cause of death and disability in both developed and developing countries, affecting onequarter of the world"s adult population. Our aim was to evaluate whether the consumption of gazpacho, a Mediterranean vegetable-based cold soup rich in phytochemicals, is associated with lower blood pressure (BP) and/or reduced prevalence of hypertension in individuals at high cardiovascular risk. Methods and results: We selected 3995 individuals (58% women, mean age 67 y) at high cardiovascular risk (81% hypertensive) recruited into the PREDIMED study. BP, weight, and dietary and physical activity data were collected. In multivariate linear regression analyses, after adjustment, moderate and high gazpacho consumption categories were associated with reduced mean systolic BP of 1.9 mm Hg [95% confidence interval (CI): 3.4; 0.6] and 2.6 mm Hg (CI: 4.2; 1.0), respectively, and reduced diastolic BP of 1.5 mm Hg (CI: 2.3; 0.6) and 1.9 mm Hg (CI: 2.8; 1.1). By multiple-adjusted logistic regression analysis, gazpacho consumption was associated with a lower prevalence of hypertension, with OR Z 0.85 (CI: 0.73; 0.99) for each 250 g/week increase and OR Z 0.73 (CI: 0.55; 0.98) for high gazpacho consumption groups compared to the no-consumption group. Conclusions: Gazpacho consumption was inversely associated with systolic and diastolic BP and prevalence of hypertension in a cross-sectional Mediterranean population at high cardiovascular risk. The association between gazpacho intake and reduction of BP is probably due to synergy among several bioactive compounds present in the vegetable ingredients used to make the recipe.

Bayesian Networks and the Value of the Evidence for the Forensic Two-Trace Transfer Problem

Forensic scientists face increasingly complex inference problems for evaluating likelihood ratios (LRs) for an appropriate pair of propositions. Up to now, scientists and statisticians have derived LR formulae using an algebraic approach. However, this approach reaches its limits when addressing cases with an increasing number of variables and dependence relationships between these variables. In this study, we suggest using a graphical approach, based on the construction of Bayesian networks (BNs). We first construct a BN that captures the problem, and then deduce the expression for calculating the LR from this model to compare it with existing LR formulae. We illustrate this idea by applying it to the evaluation of an activity level LR in the context of the two-trace transfer problem. Our approach allows us to relax assumptions made in previous LR developments, produce a new LR formula for the two-trace transfer problem and generalize this scenario to n traces.

Medical treatment of hypertension in Switzerland. The 2009 Swiss Hypertension Survey (SWISSHYPE).

OBJECTIVES: Despite a broad and efficient pharmacological antihypertensive armamentarium, blood pressure (BP) control is suboptimal and heterogeneous throughout Europe. Recent representative data from Switzerland are limited. The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerland in accordance with current guidelines. The influence of risk factors, target organ damage and medication on BP levels and control was also evaluated.METHODS : A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerland. 281 randomly selected physicians provided data on 5 consecutive hypertensive patients attending their practices for BP follow-up. Data were anonymously collected on demographics, comorbidities and current medication, and BP was recorded. Subsequent modification of pharmacological antihypertensive therapy was assessed.RESULTS : Data from 1376 patients were available. Mean age was 65 +/- 12 years, 53.9% were male subjects. 26.4% had complicated hypertension. Overall, BP control (<140/90 mm Hg for uncomplicated and <130/80 mm Hg for complicated hypertension) was achieved in 48.9%. Compared to patients with complicated hypertension, BP control was better in patients with uncomplicated hypertension (59.4% vs. 19.2%, p < 0.001). As a monotherapy the most prescribed drug class were angiotensin receptor blockers (ARB, 41%), followed by angiotensin converting enzyme (ACE) inhibitors (21.5%), betablockers (20.8%) and calcium channel blockers (CCB, 10.8%). The most prescribed drug combinations were ARB + diuretic (30.1%) and ACE inhibitors + diuretic (15.3%). 46% were receiving a fixed drug combination. In only 32.7% of patients with uncontrolled hypertension was a change in drug therapy made.CONCLUSION : This representative survey on treated adult hypertensive patients shows that, compared to earlier reports, the control rate of hypertension has improved in Switzerland for uncomplicated but not for complicated, particularly diabetes-associated hypertension. ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy, whereas diuretics and ARBs were the most used for combination therapy.

Transjugular liver biopsy: prospective evaluation of the angle formed between the hepatic veins and the vena cava main axis and modification of a semi-automated biopsy device in cases of an unfavorable angle.

In cases of transjugular liver biopsies, the venous angle formed between the chosen hepatic vein and the vena cava main axis in a frontal plane can be large, leading to technical difficulties. In a prospective study including 139 consecutive patients who underwent transjugular liver biopsy using the Quick-Core biopsy set, the mean venous angle was equal to 49.6 degrees. For 21.1% of the patients, two attempts at hepatic venous catheterization failed because the venous angle was too large, with a mean of 69.7 degrees. In all of these patients, manual reshaping of the distal curvature of the stiffening metallic cannula, by forming a new mean angle equal to 48 degrees , allowed successful completion of the procedure in less than 10 min.

The problem of nitrogen disposal in the obese

Amino-N is preserved because of the scarcity and nutritional importance of protein. Excretion requires its conversion to ammonia, later incorporated into urea. Under conditions of excess dietary energy, the body cannot easily dispose of the excess amino-N against the evolutively adapted schemes that prevent its wastage; thus ammonia and glutamine formation (and urea excretion) are decreased. High lipid (and energy) availability limits the utilisation of glucose, and high glucose spares the production of ammonium from amino acids, limiting the synthesis of glutamine and its utilisation by the intestine and kidney. The amino acid composition of the diet affects the production of ammonium depending on its composition and the individual amino acid catabolic pathways. Surplus amino acids enhance protein synthesis and growth, and the synthesis of non-protein-N-containing compounds. But these outlets are not enough; consequently, less-conventional mechanisms are activated, such as increased synthesis of NO∙ followed by higher nitrite (and nitrate) excretion and changes in the microbiota. There is also a significant production of N(2) gas, through unknown mechanisms. Health consequences of amino-N surplus are difficult to fathom because of the sparse data available, but it can be speculated that the effects may be negative, largely because the fundamental N homeostasis is stretched out of normalcy, forcing the N removal through pathways unprepared for that task. The unreliable results of hyperproteic diets, and part of the dysregulation found in the metabolic syndrome may be an unwanted consequence of this N disposal conflict.

Microbial communities in Cerrado soils under native vegetation subjected to prescribed fire and under pasture

The objective of this work was to evaluate the effects of fire regimes and vegetation cover on the structure and dynamics of soil microbial communities, through phospholipid fatty acid (PLFA) analysis. Comparisons were made between native areas with different woody covers ("cerrado stricto sensu" and "campo sujo"), under different fire regimes, and a 20-year-old active palisadegrass pasture in the Central Plateau of Brazil. Microbial biomass was higher in the native plots than in the pasture, and the highest monthly values were observed during the rainy season in the native plots. No significant differences were observed between fire regimes or between communities from the two native vegetation types. However, the principal component (PC) analysis separated the microbial communities by vegetation cover (native x pasture) and season (wet x dry), accounting for 45.8% (PC1 and PC3) and 25.6% (PC2 and PC3), respectively, of the total PLFA variability. Changes in land cover and seasonal rainfall in Cerrado ecosystems have significant effects on the total density of soil microorganisms and on the abundance of microbial groups, especially Gram-negative and Gram-positive bacteria.