A chemical genomics approach toward understanding the global functions of the target of rapamycin protein (TOR)

The target of rapamycin protein (TOR) is a highly conserved ataxia telangiectasia-related protein kinase essential for cell growth. Emerging evidence indicates that TOR signaling is highly complex and is involved in a variety of cellular processes. To understand its general functions, we took a chemical genomics approach to explore the genetic interaction between TOR and other yeast genes on a genomic scale. In this study, the rapamycin sensitivity of individual deletion mutants generated by the Saccharomyces Genome Deletion Project was systematically measured. Our results provide a global view of the rapamycin-sensitive functions of TOR. In contrast to conventional genetic analysis, this approach offers a simple and thorough analysis of genetic interaction on a genomic scale and measures genetic interaction at different possible levels. It can be used to study the functions of other drug targets and to identify novel protein components of a conserved core biological process such as DNA damage checkpoint/repair that is interfered with by a cell-permeable chemical compound.

Silicatein α: Cathepsin L-like protein in sponge biosilica

Earth’s biota produces vast quantities of polymerized silica at ambient temperatures and pressures by mechanisms that are not understood. Silica spicules constitute 75% of the dry weight of the sponge Tethya aurantia, making this organism uniquely tractable for analyses of the proteins intimately associated with the biosilica. Each spicule contains a central protein filament, shown by x-ray diffraction to exhibit a highly regular, repeating structure. The protein filaments can be dissociated to yield three similar subunits, named silicatein α, β, and γ. The molecular weights and amino acid compositions of the three silicateins are similar, suggesting that they are members of a single protein family. The cDNA sequence of silicatein α, the most abundant of these subunits, reveals that this protein is highly similar to members of the cathepsin L and papain family of proteases. The cysteine at the active site in the proteases is replaced by serine in silicatein α, although the six cysteines that form disulfide bridges in the proteases are conserved. Silicatein α also contains unique tandem arrays of multiple hydroxyls. These structural features may help explain the mechanism of biosilicification and the recently discovered activity of the silicateins in promoting the condensation of silica and organically modified siloxane polymers (silicones) from the corresponding silicon alkoxides. They suggest the possibility of a dynamic role of the silicateins in silicification of the sponge spicule and offer the prospect of a new synthetic route to silica and siloxane polymers at low temperature and pressure and neutral pH.

Caroço de algodão integral e vitamina E em dietas para bovinos Nelore, confinados por 83, 104 e 111 dias

O objetivo deste trabalho foi avaliar os efeitos da inclusão de caroço de algodão e vitamina E em dietas para bovinos confinados por 83, 104 e 111 dias sobre as características da carcaça, qualidade da carne e características sensoriais da carne in natura e de hambúrgueres. Foram utilizados 54 bovinos da raça Nelore, machos, não castrados, com média de 350 kg ± 30 kg de peso vivo inicial e 24 meses de idade, divididos em três grupos de acordo com o peso vivo inicial e distribuídos em três dietas: dieta sem inclusão de caroço de algodão (C), dieta contendo 30% MS de caroço de algodão (CA) e dieta contendo 30% MS de caroço de algodão e 500 UI de vitamina E/kg de matéria seca da ração (CAE). As dietas empregadas foram compostas de diferentes concentrados, incluindo milho grão seco, polpa cítrica, bagaço de cana cru e farelo de soja, com relação volumoso:concentrado de 14:86 e média de 16% PB nas três dietas. Os animais abatidos aos 83 dias de confinamento eram correspondentes ao grupo de maior peso vivo, já os animais mais leves foram abatidos aos 111 dias de confinamento. O experimento foi em arranjo fatorial 3 x 3, considerando três dietas e três períodos de confinamento, totalizando 9 tratamentos. Os animais que permaneceram em confinamento por mais tempo apresentaram maior rendimento de carcaça (56,33%) e carnes mais macias (3,02 kg). As dietas CA e CAE resultaram em menor força de cisalhamento (3,15 e 3,31 kg, respectivamente). A inclusão de vitamina E se mostrou indiferente para a cor e TBARS, em relação à dieta CA. A inclusão do caroço de algodão em dietas para bovinos não influenciou no teor de ácidos graxos saturados, porém aumentou os teores de alguns ácidos graxos poli-insaturados (AGPI) nas carnes. Por outro lado, houve um aumento linear nos níveis de ácidos graxos saturados (AGS) à medida que aumentaram os dias de confinamento. Em relação às características sensoriais, no teste descritivo, as carnes in natura dos animais alimentados com CA e CAE foram mais macias e suculentas (P < 0,05), porém apresentaram um sabor mais intenso e os provadores treinados detectaram um sabor estranho nestas carnes (P < 0,05). No entanto, para o teste afetivo, apenas foi detectado sabor estranho para os hambúrgueres provenientes da dieta CA, os atributos aroma e aroma estranho não foram influenciados pelas dietas (P > 0,05). Por meio do teste discriminativo, foi observado que os hambúrgueres provenientes de animais alimentados com CA e CAE por 104 e 111 dias de confinamento apresentaram diferença em relação ao sabor quando comparados aos hambúrgueres de animais do grupo C destes mesmos períodos, e que os hambúrgueres da dieta CA não apresentaram diferença de sabor quanto aos dias de confinamento. A inclusão de 30% MS de caroço de algodão mostrou ser uma boa alternativa para melhorar as características físico-químicas da carne e seu perfil de ácidos graxos, entretanto atribui um sabor estranho ao produto final, independente do período de confinamento, sendo perceptível ao consumidor e reduzindo aceitabilidade. Ao longo dos dias de confinamento, a carne dos animais se torna menos saudável, do ponto de vista de composição lipídica, ao consumo humano. A adição de 500 UI de vitamina E em dietas contendo caroço de algodão mostrou-se desnecessária

Diversidade e desigualdades em empresas brasileiras: um estudo por meio do relatório de sustentabilidade GRI

A diversidade organizacional está contida na dimensão social da sustentabilidade e diz respeito à heterogeneidade de raças, gêneros, idades e habilidades físicas, dentre outros aspectos, das pessoas que compõem as organizações. A gestão da diversidade organizacional impõe desafios às empresas, podendo gerar desigualdades. Uma das formas de divulgação de indicadores sociais é a publicação de relatórios de sustentabilidade, sendo que o mais reconhecido mundialmente e no Brasil é o Global Reporting Initiative (GRI). Assim sendo, o objetivo desta pesquisa foi identificar a diversidade e possíveis desigualdades de gêneros, raças, gerações e pessoas com deficiências nas empresas brasileiras que reportaram o relatório de sustentabilidade GRI, entre 2009 e 2013. Para alcançar tal objetivo, as variáveis foram definidas com base na literatura e em indicadores de diversidade do GRI e a coleta de dados se deu por meio do acesso aos relatórios GRI publicados no Brasil em um período de cinco anos. Para verificação das hipóteses, foram utilizados testes estatísticos não paramétricos e medidas de tendência central (média e mediana). Os resultados mostraram que as empresas analisadas possuíam, em seus quadros funcionais de forma geral, homens e mulheres, variadas raças e diversas gerações e nem todas mencionaram possuir pessoas com deficiências. Constatou-se que há predominância de homens, de brancos e da geração X tanto nos cargos de liderança quanto em demais cargos; que existem diferenças salariais entre homens e mulheres tanto nos cargos de liderança quanto em demais cargos e os homens perfazem maiores salários; que o sexo masculino e a geração Y apresentam maior taxa de rotatividade e que o percentual médio de pessoas com deficiências presentes nas empresas encontra-se dentro da cota estabelecida pela Lei nº 8.213/91. Logo, em meio à diversidade organizacional, verificou-se que havia desigualdades. Neste sentido, a gestão da diversidade deveria ser melhorada e as desigualdades precisariam ser enfrentadas para não comprometerem a sustentabilidade.

Intoxicación por munición de plomo en aves silvestres en España y medidas para reducir el riesgo

La intoxicación por ingestión de munición de plomo en aves silvestres es conocida en España desde finales del siglo pasado. Elevadas densidades de perdigones de plomo en diversos humedales de importancia internacional producen tasas de ingestión de perdigones cercanas al 70% en especies como el ánade rabudo (Anas acuta) y el plumbismo llega a ser una de las principales causas de mortalidad de la amenazada malvasía cabeciblanca (Oxyura leucocephala). El plumbismo también ha sido descrito en diversas especies de aves rapaces y se ha comprobado que la exposición al plomo es elevada en las especies más carroñeras y oportunistas. La contaminación de la carne de caza también ha sido objeto de estudio, debido a que en España se da la particularidad de cocinarla en escabeche, lo que incrementa la transferencia de plomo de la munición a la carne. Por el momento, la única acción llevada a cabo para reducir el riesgo de exposición al plomo de la munición en aves y humanos ha sido la prohibición desde 2001 del uso de perdigones de plomo en humedales protegidos. En esta revisión se hace un repaso a los estudios llevados a cabo en España sobre la contaminación por el plomo de la munición y el efecto que están teniendo las medidas hasta el momento adoptadas para reducir este riesgo.

Un médico rural contra la viruela, la epidemia de 1891-92 en Huércanos (Logroño)

La práctica inconstante de la vacunación contra la viruela durante el siglo xix tuvo como consecuencia la aparición de varias oleadas epidémicas en España. La baja aceptación de la vacuna entre la población, unida a la incapacidad del estado para organizar campañas y suministrar vacuna, contribuyeron a perpetuar la enfermedad. Durante la segunda mitad del siglo se abrió un debate sobre la necesidad de hacer obligatoria la vacunación y revacunación, incorporándose, además, el uso de la vacuna animalizada. Un texto de Emilio Casas Arriola, médico de Huércanos (Logroño), describe el brote epidémico sufrido entre 1891 y 1892 en este municipio. La obra tiene la estructura de una topografía médica y fue redactada con la intención de concurrir a un premio de la Real Academia Médica de Madrid. Se analizan las dificultades, vicisitudes y medidas adoptadas para afrontar la epidemia en un entorno aislado y rural.

A Quantile-Based Probabilistic Mean Value Theorem

For non-negative random variables with finite means we introduce an analogous of the equilibrium residual-lifetime distribution based on the quantile function. This allows us to construct new distributions with support (0, 1), and to obtain a new quantile-based version of the probabilistic generalization of Taylor's theorem. Similarly, for pairs of stochastically ordered random variables we come to a new quantile-based form of the probabilistic mean value theorem. The latter involves a distribution that generalizes the Lorenz curve. We investigate the special case of proportional quantile functions and apply the given results to various models based on classes of distributions and measures of risk theory. Motivated by some stochastic comparisons, we also introduce the “expected reversed proportional shortfall order”, and a new characterization of random lifetimes involving the reversed hazard rate function.

In Search of a Feasible EU-Mercosul Free Trade Agreement. CEPS Working Document No. 378, 25 February 2013

This paper aims at identifying ways to pursue the EU–Mercosul negotiations leading to a free trade agreement (FTA). After reviewing their already long history, it outlines a basic framework, in goods, services and other themes, judged possible. The main point is that, given the prevailing conditions on both sides, an agreement to be signed within a reasonable time must be modest, i.e. along the described lines. It then clearly sets up the decisions confronting the negotiators: either to pursue the modest, feasible option or to terminate negotiations under the FTA heading. The latter, however, does not imply an end to the dialogue. Many actions and measures may be taken – which are easier to discuss and fix – that could pave the way for, in due time, a closer-to-ideal FTA to be considered again. These are the subjects of a last section.

Measuring the Modern Social Market Economy. Future Social Market Economy Policy Brief #2012/04

The “Index of Modern Social Market Economies” (MSME Index) defines and measures the features of a modern social market economy in international comparison. In contrast to other indices that measure economic performance, the MSME Index takes an institutional approach, outlining a system of essential institutions and measurable indicators for the construction and assessment of modern social market economies. Among other insights, the index could guide the European Union toward achieving the “highly competitive social market economy” that it defines in the Lisbon Treaty as its desired economic order.

Is socioeconomic position early in life associated with physical activity during adulthood following the accumulation of risk model with additive effects?

L'activité physique améliore la santé, mais seulement 4.8% des Canadiens atteignent le niveau recommandé. La position socio-économique est un des déterminants de l'activité physique les plus importants. Elle est associée à l’activité physique de manière transversale à l’adolescence et à l’âge adulte. Cette thèse a tenté de déterminer s'il y a une association à long terme entre la position socio-économique au début du parcours de vie et l’activité physique à l’âge adulte. S'il y en avait une, un deuxième objectif était de déterminer quel modèle théorique en épidémiologie des parcours de vie décrivait le mieux sa forme. Cette thèse comprend trois articles: une recension systématique et deux recherches originales. Dans la recension systématique, des recherches ont été faites dans Medline et EMBASE pour trouver les études ayant mesuré la position socio-économique avant l'âge de 18 ans et l'activité physique à ≥18 ans. Dans les deux recherches originales, la modélisation par équations structurelles a été utilisée pour comparer trois modèles alternatifs en épidémiologie des parcours de vie: le modèle d’accumulation de risque avec effets additifs, le modèle d’accumulation de risque avec effet déclenché et le modèle de période critique. Ces modèles ont été comparés dans deux cohortes prospectives représentatives à l'échelle nationale: la 1970 British birth cohort (n=16,571; première recherche) et l’Enquête longitudinale nationale sur les enfants et les jeunes (n=16,903; deuxième recherche). Dans la recension systématique, 10 619 articles ont été passés en revue par deux chercheurs indépendants et 42 ont été retenus. Pour le résultat «activité physique» (tous types et mesures confondus), une association significative avec la position socio-économique durant l’enfance fut trouvée dans 26/42 études (61,9%). Quand seulement l’activité physique durant les loisirs a été considérée, une association significative fut trouvée dans 21/31 études (67,7%). Dans un sous-échantillon de 21 études ayant une méthodologie plus forte, les proportions d’études ayant trouvé une association furent plus hautes : 15/21 (71,4%) pour tous les types et toutes les mesures d’activité physique et 12/15 (80%) pour l’activité physique de loisir seulement. Dans notre première recherche originale sur les données de la British birth cohort, pour la classe sociale, nous avons trouvé que le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux chez les hommes et les femmes pour l’activité physique de loisir, au travail et durant les transports. Dans notre deuxième recherche originale sur les données canadiennes sur l'activité physique de loisir, nous avons trouvé que chez les hommes, le modèle de période critique s’est ajusté le mieux aux données pour le niveau d’éducation et le revenu, alors que chez les femmes, le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux pour le revenu, tandis que le niveau d’éducation ne s’est ajusté à aucun des modèles testés. En conclusion, notre recension systématique indique que la position socio-économique au début du parcours de vie est associée à la pratique d'activité physique à l'âge adulte. Les résultats de nos deux recherches originales suggèrent un patron d’associations le mieux représenté par le modèle d’accumulation de risque avec effets additifs.

Risk of Cerebral Venous Thrombosis in Obese Women.

IMPORTANCE Obesity is a risk factor for deep vein thrombosis of the leg and pulmonary embolism. To date, however, whether obesity is associated with adult cerebral venous thrombosis (CVT) has not been assessed. OBJECTIVE To assess whether obesity is a risk factor for CVT. DESIGN, SETTING, AND PARTICIPANTS A case-control study was performed in consecutive adult patients with CVT admitted from July 1, 2006 (Amsterdam), and October 1, 2009 (Berne), through December 31, 2014, to the Academic Medical Center in Amsterdam, the Netherlands, or Inselspital University Hospital in Berne, Switzerland. The control group was composed of individuals from the control population of the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study, which was a large Dutch case-control study performed from March 1, 1999, to September 31, 2004, and in which risk factors for deep vein thrombosis and pulmonary embolism were assessed. Data analysis was performed from January 2 to July 12, 2015. MAIN OUTCOMES AND MEASURES Obesity was determined by body mass index (BMI). A BMI of 30 or greater was considered to indicate obesity, and a BMI of 25 to 29.99 was considered to indicate overweight. A multiple imputation procedure was used for missing data. We adjusted for sex, age, history of cancer, ethnicity, smoking status, and oral contraceptive use. Individuals with normal weight (BMI <25) were the reference category. RESULTS The study included 186 cases and 6134 controls. Cases were younger (median age, 40 vs 48 years), more often female (133 [71.5%] vs 3220 [52.5%]), more often used oral contraceptives (97 [72.9%] vs 758 [23.5%] of women), and more frequently had a history of cancer (17 [9.1%] vs 235 [3.8%]) compared with controls. Obesity (BMI ≥30) was associated with an increased risk of CVT (adjusted odds ratio [OR], 2.63; 95% CI, 1.53-4.54). Stratification by sex revealed a strong association between CVT and obesity in women (adjusted OR, 3.50; 95% CI, 2.00-6.14) but not in men (adjusted OR, 1.16; 95% CI, 0.25-5.30). Further stratification revealed that, in women who used oral contraceptives, overweight and obesity were associated with an increased risk of CVT in a dose-dependent manner (BMI 25.0-29.9: adjusted OR, 11.87; 95% CI, 5.94-23.74; BMI ≥30: adjusted OR, 29.26; 95% CI, 13.47-63.60). No association was found in women who did not use oral contraceptives. CONCLUSIONS AND RELEVANCE Obesity is a strong risk factor for CVT in women who use oral contraceptives.

Final report of the highway cost allocation study /

Includes bibliographies.

Joint committee report: signaling, interlocking.

"Statement of the actions of the Signal committee of the Presidents' conference committee, and the Division of valuation of the interstate commerce commission, in respect to the organisation of the Joint committee for the consideration and determination of prices, weights, and cost of signaling and interlocking apparatus": p. i-iii., v. 1.

WHOQOL-BREF as a measure of quality of life in older patients with depression

Objective: To assess the reliability and validity of a brief measure of quality of life recently developed by the World Health Organization, the WHOQOL-BREF, and to examine its association with a variety of clinical and sociodemographic factors in older depressed patients. Design: Cross-sectional study. Methods: Older depressed patients (N=41) underwent diagnostic assessment using the Composite International Diagnostic Interview (CIDI) and were independently assessed on a variety of measures including the WHOQOL-BREF (a 26-item self-report questionnaire generating four domain scores), Hamilton Depression Rating Scale (HAM-D); Geriatric Depression Scale (GDS); Mini-mental State Examination (MMSE); Modified Barthel Index (MBI); Instrumental activities of daily living (IADL), and measures of physical health status and social relationships. Estimates of inter-rater and test-retest reliability, and concurrent validity were made. Results: 39 subjects completed the study. The majority of subjects (94.9%) received a diagnosis of DSM-IV Major Depressive Disorder. Levels of comorbidity were high. Three of the four domains of the WHOQOL-BREF (Physical, Psychological and Environment domains) demonstrated satisfactory reliability and validity. However, the Social Relationships domain exhibited poor validity. Quality of life scores were strongly correlated with severity of depression, number of self-reported physical symptoms and self-assessed general health status. There was no relationship between diagnostic comorbidity and quality of life scores. Conclusions: The WHOQOL-BREF was successfully administered to older depressed patients although the concurrent validity of one of its four domains was poor. Quality of life scores were strongly correlated with severity of depression, raising the issue of measurement redundancy.

Community-based programmes to prevent pedestrian injuries in children 0-14 years: A systematic review

Community-based models for injury prevention have become an accepted part of the overall injury control strategy. This systematic review of the scientific literature examines the evidence for their effectiveness in reducing pedestrian injury in children 0-14 years of age. A comprehensive search of the literature was performed using the following study selection criteria: community-based intervention study; target population was children under 14 years; outcome measure is either pedestrian injury rates or observed child pedestrian or vehicle driver behaviour; and use of a community control or an historical control in the study design. Quality assessment and data abstraction was guided by a standardized procedure and performed independently by two authors. Data synthesis was in tabular and text form with meta-analysis not being possible due to the discrepancy in methods and measures between the studies.