A haplotype at the UCP1 gene locus contributes to genetic risk for type 2 diabetes in Asian Indians (CURES-72)

BACKGROUND: The gene encoding for uncoupling protein-1 (UCP1) is considered to be a candidate gene for type 2 diabetes because of its role in thermogenesis and energy expenditure. The objective of the study was to examine whether genetic variations in the UCP1 gene are associated with type 2 diabetes and its related traits in Asian Indians. METHODS: The study subjects, 810 type 2 diabetic subjects and 990 normal glucose tolerant (NGT) subjects, were chosen from the Chennai Urban Rural Epidemiological Study (CURES), an ongoing population-based study in southern India. The polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies. RESULTS: The three polymorphisms, namely -3826A-->G, an A-->C transition in the 5'-untranslated region (UTR) and Met229Leu, were not associated with type 2 diabetes. However, the frequency of the A-C-Met (-3826A-->G-5'UTR A-->C-Met229Leu) haplotype was significantly higher among the type 2 diabetic subjects (2.67%) compared with the NGT subjects (1.45%, P < 0.01). The odds ratio for type 2 diabetes for the individuals carrying the haplotype A-C-Met was 1.82 (95% confidence interval, 1.29-2.78, P = 0.009). CONCLUSIONS: The haplotype, A-C-Met, in the UCP1 gene is significantly associated with the increased genetic risk for developing type 2 diabetes in Asian Indians.

Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population

Peroxisome proliferator-activated receptor-gamma2 (PPARG2) is a nuclear hormone receptor of ligand-dependent transcription factor involved in adipogenesis and a molecular target of the insulin sensitizers thiazolidinediones. We addressed the question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the PPARG2 gene are associated with type 2 diabetes mellitus and its related traits in a South Indian population. The study subjects (1000 type 2 diabetes mellitus and 1000 normal-glucose-tolerant subjects) were chosen randomly from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The variants were screened by single-stranded conformational variant, direct sequencing, and restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. The -1279G/A, Pro12Ala, and His478His variants of the PPARG2 gene were not associated with type 2 diabetes mellitus. However, the 2-loci analyses showed that, in the presence of Pro/Pro genotype of the Pro12Ala variant, the -1279G/A promoter variant showed increased susceptibility to type 2 diabetes mellitus (odds ratio, 2.092; 95% confidence interval, 1.22-3.59; P = .008), whereas in the presence of 12Ala allele, the -1279G/A showed a protective effect against type 2 diabetes mellitus (odds ratio, 0.270; 95% confidence interval, 0.15-0.49; P < .0001). The 3-loci haplotype analysis showed that the A-Ala-T (-1279G/A-Pro12Ala-His478His) haplotype was associated with a reduced risk of type 2 diabetes mellitus (P < .0001). Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population.

Effect of polymorphisms in the PPARGC1A gene on body fat in Asian Indians

OBJECTIVE: To evaluate whether polymorphisms in the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A) gene were related to body fat in Asian Indians. METHODS: Three polymorphisms of PPARGC1A gene, the Thr394Thr, Gly482Ser and +A2962G, were genotyped on 82 type 2 diabetic and 82 normal glucose tolerant (NGT) subjects randomly chosen from the Chennai Urban Rural Epidemiology Study using PCR-RFLP, and the nature of the variants were confirmed using direct sequencing. Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies using an expectation-maximization algorithm. Visceral, subcutaneous and total abdominal fat were measured using computed tomography, whereas dual X-ray absorptiometry was used to measure central abdominal and total body fat. RESULTS: None of the three polymorphisms studied were in LD. The genotype (0.59 vs 0.32, P=0.001) and allele (0.30 vs 0.17, P=0.007) frequencies of Thr394Thr polymorphism were significantly higher in type 2 diabetic subjects compared to those in NGT subjects. The odds ratio for diabetes (adjusted for age, sex and body mass index) for the susceptible genotype, XA (GA+AA) of Thr394Thr polymorphism, was 2.53 (95% confidence intervals: 1.30-5.04, P=0.009). Visceral and subcutaneous fat were significantly higher in NGT subjects with XA genotype of the Thr394Thr polymorphism compared to those with GG genotype (visceral fat: XA 148.2+/-46.9 vs GG 106.5+/-51.9 cm(2), P=0.001; subcutaneous fat: XA 271.8+/-167.1 vs GG 181.5+/-78.5 cm(2), P=0.001). Abdominal (XA 4521.9+/-1749.6 vs GG 3445.2+/-1443.4 g, P=0.004), central abdominal (XA 1689.0+/-524.0 vs GG 1228.5+/-438.7 g, P<0.0001) and non-abdominal fat (XA 18763.8+/-8789.4 vs GG 13160.4+/-4255.3 g, P<0.0001) were also significantly higher in the NGT subjects with XA genotype compared to those with GG genotype. The Gly482Ser and +A2962G polymorphisms were not associated with any of the body fat measures. CONCLUSION: Among Asian Indians, the Thr394Thr (G --> A) polymorphism is associated with increased total, visceral and subcutaneous body fat.

Transreal proof of the existence of universal possible worlds

Transreal arithmetic is total, in the sense that the fundamental operations of addition, subtraction, multiplication and division can be applied to any transreal numbers with the result being a transreal number [1]. In particular division by zero is allowed. It is proved, in [3], that transreal arithmetic is consistent and contains real arithmetic. The entire set of transreal numbers is a total semantics that models all of the semantic values, that is truth values, commonly used in logics, such as the classical, dialetheaic, fuzzy and gap values [2]. By virtue of the totality of transreal arithmetic, these logics can be implemented using total, arithmetical functions, specifically operators, whose domain and counterdomain is the entire set of transreal numbers

Evaluation of thermal simulation of households in the metropolitan region of So Paulo, Brazil

This paper aims at assessing the performance of a program of thermal simulation (Arquitrop) in different households in the city of Sao Paulo, Brazil. The households were selected for the Wheezing Project which followed up children under 2 years old to monitor the occurrence of respiratory diseases. The results show that in all three study households there is a good approximation between the observed and the simulated indoor temperatures. It was also observed a fairly consistent and realistic behavior between the simulated indoor and the outdoor temperatures, describing the Arquitrop model as an efficient estimator and good representative of the thermal behavior of households in the city of Sao Paulo. The worst simulation is linked to the poorest type of construction. This may be explained by the bad quality of the construction, which the Architrop could not simulate adequately.

Invasive plants: representativeness of research from tropical countries in the global context

Biological invasions threaten the native biota of several countries and this threat is even greater in the tropical regions that have the greatest biodiversity. In order to evaluate the representativeness of studies on invasive plants in tropical countries compared to the world, as well as the region of origin and habits of the most reported invasive plants in research, we analyzed the publications from eight of the most important international journals that address the theme, from January 1995 to December 2004. The articles on biological invasions were classified as theoretical or as case studies, and according to their approach, main question, where the study was conducted, region of origin and habit of the invasive plant. Case studies predominated, as did questions about the environment`s susceptibility to the invasion, the species` invasive power and the impacts it had. The most reported invasive species were herbaceous plants from Asia and Europe. Few articles address tropical environments and only one referred to Brazil. Most referred to North America and Europe. This small number of publications in the tropics indicates the need for a global projection on this subject and underscores the lack of consistent and organized data to understand the phenomenon and propose effective strategies to combat biological invasion.

Bayesian analysis of skew-t multivariate null intercept measurement error model

The multivariate skew-t distribution (J Multivar Anal 79:93-113, 2001; J R Stat Soc, Ser B 65:367-389, 2003; Statistics 37:359-363, 2003) includes the Student t, skew-Cauchy and Cauchy distributions as special cases and the normal and skew-normal ones as limiting cases. In this paper, we explore the use of Markov Chain Monte Carlo (MCMC) methods to develop a Bayesian analysis of repeated measures, pretest/post-test data, under multivariate null intercept measurement error model (J Biopharm Stat 13(4):763-771, 2003) where the random errors and the unobserved value of the covariate (latent variable) follows a Student t and skew-t distribution, respectively. The results and methods are numerically illustrated with an example in the field of dentistry.

Generalized log-gamma regression models with cure fraction

In this paper, the generalized log-gamma regression model is modified to allow the possibility that long-term survivors may be present in the data. This modification leads to a generalized log-gamma regression model with a cure rate, encompassing, as special cases, the log-exponential, log-Weibull and log-normal regression models with a cure rate typically used to model such data. The models attempt to simultaneously estimate the effects of explanatory variables on the timing acceleration/deceleration of a given event and the surviving fraction, that is, the proportion of the population for which the event never occurs. The normal curvatures of local influence are derived under some usual perturbation schemes and two martingale-type residuals are proposed to assess departures from the generalized log-gamma error assumption as well as to detect outlying observations. Finally, a data set from the medical area is analyzed.

Fragment-guided approach to incorporating structural information into a CoMFA study: BACE-1 as an example

Alzheimer`s disease is an ultimately fatal neurodegenerative disease, and BACE-1 has become an attractive validated target for its therapy, with more than a hundred crystal structures deposited in the PDB. In the present study, we present a new methodology that integrates ligand-based methods with structural information derived from the receptor. 128 BACE-1 inhibitors recently disclosed by GlaxoSmithKline R&D were selected specifically because the crystal structures of 9 of these compounds complexed to BACE-1, as well as five closely related analogs, have been made available. A new fragment-guided approach was designed to incorporate this wealth of structural information into a CoMFA study, and the methodology was systematically compared to other popular approaches, such as docking, for generating a molecular alignment. The influence of the partial charges calculation method was also analyzed. Several consistent and predictive models are reported, including one with r (2) = 0.88, q (2) = 0.69 and r (pred) (2) = 0.72. The models obtained with the new methodology performed consistently better than those obtained by other methodologies, particularly in terms of external predictive power. The visual analyses of the contour maps in the context of the enzyme drew attention to a number of possible opportunities for the development of analogs with improved potency. These results suggest that 3D-QSAR studies may benefit from the additional structural information added by the presented methodology.

Semiparametric Bayesian measurement error modeling

This work presents a Bayesian semiparametric approach for dealing with regression models where the covariate is measured with error. Given that (1) the error normality assumption is very restrictive, and (2) assuming a specific elliptical distribution for errors (Student-t for example), may be somewhat presumptuous; there is need for more flexible methods, in terms of assuming only symmetry of errors (admitting unknown kurtosis). In this sense, the main advantage of this extended Bayesian approach is the possibility of considering generalizations of the elliptical family of models by using Dirichlet process priors in dependent and independent situations. Conditional posterior distributions are implemented, allowing the use of Markov Chain Monte Carlo (MCMC), to generate the posterior distributions. An interesting result shown is that the Dirichlet process prior is not updated in the case of the dependent elliptical model. Furthermore, an analysis of a real data set is reported to illustrate the usefulness of our approach, in dealing with outliers. Finally, semiparametric proposed models and parametric normal model are compared, graphically with the posterior distribution density of the coefficients. (C) 2009 Elsevier Inc. All rights reserved.

Billiards in a General Domain with Random Reflections

We study stochastic billiards on general tables: a particle moves according to its constant velocity inside some domain D R(d) until it hits the boundary and bounces randomly inside, according to some reflection law. We assume that the boundary of the domain is locally Lipschitz and almost everywhere continuously differentiable. The angle of the outgoing velocity with the inner normal vector has a specified, absolutely continuous density. We construct the discrete time and the continuous time processes recording the sequence of hitting points on the boundary and the pair location/velocity. We mainly focus on the case of bounded domains. Then, we prove exponential ergodicity of these two Markov processes, we study their invariant distribution and their normal (Gaussian) fluctuations. Of particular interest is the case of the cosine reflection law: the stationary distributions for the two processes are uniform in this case, the discrete time chain is reversible though the continuous time process is quasi-reversible. Also in this case, we give a natural construction of a chord ""picked at random"" in D, and we study the angle of intersection of the process with a (d - 1) -dimensional manifold contained in D.

HR-funktionens förändrade roll : En studie om linjechefers uppfattning av HR-funktionen i Falu och Avesta kommun

Traditionellt har HR-arbetet främst varit fokuserat på administrativa uppgifter och inte ansetts vara tillräckligt effektivt och värdeskapande. För att HR-arbetet ska bli mer strategiskt behöver funktionen organiseras så att den tillgodoser dessa behov (Boglind et al, 2013). Vi menar att HR-funktionens relation till ledare och linjechefer är avgörande för hur framgångsrikt deras arbete blir. Syftet med detta arbete är därför att undersöka hur chefer uppfattar HR-funktionens förändrade roll och vilken typ av stöd de förväntar sig av den. Vi vill också undersöka om uppfattningen av HR-funktionen skiljer sig åt beroende på hur den är organiserad. Undersökningen är baserad på en multipel fallstudie utförd på Falu och Avesta kommun. Totalt har tretton djupintervjuer genomförts, där fem personer representerar HR-avdelningarna och åtta personer representerar linjecheferna. Falu kommun började genomföra en HR-transformation vid årsskiftet 2013/2014, Avesta kommun har inte genomfört en HR-transformation utan har funktionen uppdelad i två team. Av empirin framkommer att linjecheferna i båda kommunerna har en ganska vag uppfattning om HR-funktionens organisation och trots de strukturella skillnaderna mellan kommunerna efterfrågar linjecheferna något mer. I Avesta är samtliga respondenter överens om att en samsyn kring HR-funktionens arbetsuppgifter inte finns på grund av att en tydlig strategi för HR-funktionen saknas. Cheferna i Avesta efterfrågar ett arbete med personalfrågor från grunden samt ett mer strategiskt arbete. I Falun visar empirin att linjechefer och HR-personer har olika åsikter kring huruvida det finns en samsyn. Även om flera linjechefer i Falun anser att HR-funktionen fungerar bättre efter transformationen efterfrågar samtliga en kontakt med en specifik HR-person istället för att kontakta ett HR-center. Trots att de organisationer vi studerat har HR-funktioner som skiljer sig åt i storlek och struktur kan vi konstatera många likheter. Vi drar därför slutsatsen att de problem som linjecheferna beskriver inte är relaterade till HR-avdelningens organisering, utan snarare kan kopplas till en obalans i HR-arbetets inneboende dualitet som uppstått i och med ett mer strategiskt fokus. Vi anser att båda kommunernas HR-funktioner bör ha en tydlig och kontinuerlig dialog med linjecheferna för att maximera värdeskapandet dem emellan. Sammanfattningsvis menar vi att kommunerna bör lägga fokus på att identifiera vilka aspekter av personalarbetet som är värdefulla och unika för just deras organisation samt arbeta strategiskt utifrån dessa.

Metabolismo da homocisteína e defeitos do tubo neural : um estudo bioquímico e molecular no sul do Brasil

Os defeitos de fechamento de tubo neural constituem uma das malformações mais freqüentes na espécie humana, apresentando alta morbi-mortalidade. Sua etiologia é considerada multifatorial, estando envolvidos fatores genéticos e ambientais. Estes fatores estão relacionados principalmente com o metabolismo da homocisteína. Realizamos um estudo de caso-controle com o objetivo de estudar os fatores bioquímicos e genéticos relacionados ao DTN na nossa população. Em pares de afetados com DTN e suas mães e pares de pacientes normais e suas mães foram avaliados dosagem de folato, vitamina B12, homocisteína e polimorfismos da enzima metileno tetraidrofolato redutase (MTHFR), C677T e A1298C. A dosagem de folato nos casos foi 11,37 ng/mL(±6,72) e nos controles 5,64 ng/mL(±4,16) (p<0,001). O folato sérico das mães foi 7,27 ng/mL (±4,48) e 3,90 ng/mL (±1,77) nas mães controles (p<0,001). A média de dosagem de vitamina B12 foi de 641,88 pg/mL ((±262,21) nos casos e 743,27 pg/mL (±433,52) nos controles (p= 0,205). A média de dosagem de vitamina B12 nas mães dos casos foi 354,75 pg/mL (±142,06) e 465,25 pg/mL (±194,91) nas mães controles (p=0,004). O nível de homocisteína plasmático médio foi 6,89 μmol/L(±4,48) para os casos e 5,41 μmol/L (±2,55) para os controles (p=0,099). Nas mães dos casos a dosagem média de homocisteína foi 7,23 μmol/L (±2,64) e 7,00 μmol/L (±2,24) nas mães controles (p=0,666). Não houve diferença entre a freqüência dos genótipos C677T e A1298C da MTHFR nos casos e controles e suas mães. Para o polimorfismo C677T as freqüências dos alelo C e T foram respectivamente 0,6585 e 0,3414 nos pacientes com DTN; 0,6590 e 0,3410 nos controles; 0,6460 e 0,3540 nas mães dos casos e 0,6136 e 0,3860 nas mães controles. Para o polimorfismo A1298C as freqüências dos alelos A e C foram respectivamente 0,7436 e 0,2564 nos pacientes com DTN; 0,7610 e 0,2390 nos controles; 0,8055 e 0,1945 nas mães dos casos e 0,8065 e 0,1935 nas mães controles. Identificamos que indivíduos homozigotos 677TT apresentam um maior nível de homocisteína e este é inversamente relacionado com os níveis de vitamina B12. Estes achados sugerem que uma alteração metabólica relacionada ao metabolismo da homocisteína e principalmente devido à diminuição da vitamina B12 seja um fator de risco para DTN na nossa população.

Estimação de regressões aditivas via backfitting e integração marginal: performance em pequenas amostras

Nesta dissertação realizou-se um experimento de Monte Carlo para re- velar algumas características das distribuições em amostras finitas dos estimadores Backfitting (B) e de Integração Marginal(MI) para uma regressão aditiva bivariada. Está-se particularmente interessado em fornecer alguma evidência de como os diferentes métodos de seleção da janela hn, tais co- mo os métodos plug-in, impactam as propriedades em pequenas amostras dos estimadores. Está-se interessado, também, em fornecer evidência do comportamento de diferentes estimadores de hn relativamente a seqüência ótima de hn que minimiza uma função perda escolhida. O impacto de ignorar a dependência entre os regressores na estimação da janela é tam- bém investigado. Esta é uma prática comum e deve ter impacto sobre o desempenho dos estimadores. Além disso, não há nenhuma rotina atual- mente disponível nos pacotes estatísticos/econométricos para a estimação de regressões aditivas via os métodos de Backfitting e Integração Marginal. É um dos objetivos a criação de rotinas em Gauss para a implementação prática destes estimadores. Por fim, diferentemente do que ocorre atual- mente, quando a utilização dos estimadores-B e MI é feita de maneira completamente ad-hoc, há o objetivo de fornecer a usuários informação que permita uma escolha mais objetiva de qual estimador usar quando se está trabalhando com uma amostra finita.

Os efeitos da poupança pública sobre o crescimento econômico: análise para um painel de países

Este artigo analisou as relações entre poupança pública e crescimento econômico. Inicialmente, a análise teórico-descritiva dessas relações mostrou que a poupança pública é um indicador de sustentabilidade fiscal mais completo do que o superávit primário e tende a apresentar efeitos mais positivos sobre o produto do que o superávit operacional. As equações estimadas e os testes de robustez dos resultados da posterior análise econométrica, que utilizou modelos de regressão múltipla para um painel de 38 nações, comprovaram, a elevados níveis de confiança, a hipótese de relação positiva entre as taxas de poupança pública e de crescimento econômico per capita indicando a direção de causalidade entre ambos, além de fornecerem resultados interessantes e consistentes sobre a forma de associação do desenvolvimento a outras variáveis. A conclusão central foi de que um aumento de uma unidade na taxa de poupança pública deve levar, em média, a uma elevação de 0,17 unidades na taxa de crescimento econômico per capita