Synergistic acceleration of thyroid hormone degradation by phenobarbital and the PPAR alpha agonist WY14643 in rat hepatocytes

Energy balance is maintained by controlling both energy intake and energy expenditure. Thyroid hormones play a crucial role in regulating energy expenditure. Their levels are adjusted by a tight feed back-control led regulation of thyroid hormone production/incretion and by their hepatic metabolism. Thyroid hormone degradation has previously been shown to be enhanced by treatment with phenobarbital or other antiepileptic drugs due to a CAR-dependent induction of phase 11 enzymes of xenobiotic metabolism. We have recently shown, that PPAR alpha agonists synergize with phenobarbital to induce another prototypical CAR target gene, CYP2B1. Therefore, it was tested whether a PPAR alpha agonist could enhance the phenobarbital-dependent acceleration of thyroid hormone elimination. In primary cultures of rat hepatocytes the apparent half-life of T3 was reduced after induction with a combination of phenobarbital and the PPARa agonist WY14643 to a larger extent than after induction with either Compound alone. The synergistic reduction of the half-life could be attributed to a synergistic induction of CAR and the CAR target genes that code for enzymes and transporters involved in the hepatic elimination of T3, such as OATP1A1, OATP1A3, UGT1A3 and UCT1A10. The PPAR alpha-dependent CAR induction and the subsequent induction of T3-eliminating enzymes might be of physiological significance for the fasting-incluced reduction in energy expenditure by fatty acids as natural PPARa ligands. The synergism of the PPAR alpha agonist WY14643 and phenobarbital in inducing thyroid hormone breakdown might serve as a paradigm for the synergistic disruption of endocrine control by other combinations of xenobiotics. (C) 2009 Elsevier Inc. All rights reserved.

Asymptotic Skewness in Exponential Family Nonlinear Models

In this article, we give an asymptotic formula of order n(-1/2), where n is the sample size, for the skewness of the distributions of the maximum likelihood estimates of the parameters in exponencial family nonlinear models. We generalize the result by Cordeiro and Cordeiro ( 2001). The formula is given in matrix notation and is very suitable for computer implementation and to obtain closed form expressions for a great variety of models. Some special cases and two applications are discussed.

A matrix formula for the skewness of maximum likelihood estimators

We give a general matrix formula for computing the second-order skewness of maximum likelihood estimators. The formula was firstly presented in a tensorial version by Bowman and Shenton (1998). Our matrix formulation has numerical advantages, since it requires only simple operations on matrices and vectors. We apply the second-order skewness formula to a normal model with a generalized parametrization and to an ARMA model. (c) 2010 Elsevier B.V. All rights reserved.

Asymptotic skewness in Birnbaum-Saunders nonlinear regression models

The family of distributions proposed by Birnbaum and Saunders (1969) can be used to model lifetime data and it is widely applicable to model failure times of fatiguing materials. We give a simple matrix formula of order n(-1/2), where n is the sample size, for the skewness of the distributions of the maximum likelihood estimates of the parameters in Birnbaum-Saunders nonlinear regression models, recently introduced by Lemonte and Cordeiro (2009). The formula is quite suitable for computer implementation, since it involves only simple operations on matrices and vectors, in order to obtain closed-form skewness in a wide range of nonlinear regression models. Empirical and real applications are analyzed and discussed. (C) 2010 Elsevier B.V. All rights reserved.

Single-mode acceleration of matter waves in circular waveguides

Ultracold gases in ring geometries hold promise for significant improvements of gyroscopic sensitivity. Recent experiments have realized atomic and molecular storage rings with radii in the centimeter range, sizes whose practical use in inertial sensors requires velocities significantly in excess of typical recoil velocities. We use a combination of analytical and numerical techniques to study the coherent acceleration of matter waves in circular waveguides, with particular emphasis on its impact on single-mode propagation. In the simplest case we find that single-mode propagation is best maintained by the application of time-dependent acceleration force with the temporal profile of a Blackmann pulse. We also assess the impact of classical noise on the acceleration process.

Finding a maximum skewness portfolio - A general solution to three-moments portfolio choice

Considering the three first moments and allowing short sales, the efficient portfolios set for n risky assets and a riskless one is found, supposing that agents like odd moments and dislike even ones. Analytical formulas for the solution surface are obtained and important geometric properties provide insights on its shape in the three dimensional space defined by the moments. A special duality result is needed and proved. The methodology is general, comprising situations in which, for instance, the investor trades a negative skewness for a higher expected return. Computation of the optimum portfolio weights is feasible in most cases.

The risk of falling into the acceleration trap during a privatization process: a case study of a European telecommunication company

A privatização de uma empresa é uma mudança empresarial disruptiva que geralmente coincide com o fim de uma posição de monopólio e da subsequente entrada num ambiente competitivo. Os desafios que a privatização coloca são tão árduos que eles levam muitas vezes a liderança (leadership) para executar planos ambiciosos de mudança empresarial. No entanto, a literatura mostra que muitos deles falharam. Na verdade, esses planos preveem mudanças bruscas e importantes que tendem a empurrar a empresa privatizada na armadilha de aceleração (acceleration trap). Um tipo de “burnout organizacional” (organizational burnout) onde a exaustão e a resignação da força de trabalho afetam drasticamente o desempenho da empresa. A tese, portanto, focalizou em estudar a ligação entre um processo de privatização e o risco de cair na armadilha de aceleração. Uma investigação preliminar sobre a literatura das mudanças empresariais permitiu a concepção de um quadro preliminar teórico que sugere a existência de dois moderadores (moderators) deste relacionamento entre um processo de privatização e a armadilha de aceleração: um “choque cultural” (cultural clash) e um “fraco clima de liderança transformacional” (weak transformational leadership). Em seguida, um estudo de caso - baseado numa empresa de telecomunicações europeia e conduzido através de uma abordagem metodológico não puramente indutivo (non-purely inductive approach) - confirma, mas também aprofunda a compreensão da ação desses dois moderadores. A respeito do moderador “choque cultural” (cultural clash moderator), a análise de dados do estudo de caso da empresa de telecomunicações europeia mostra a importância exercitado tanto por um “choque de identidade corporativa” (corporate identity conflict) como por um “conflito de identidade gerencial” (management identity conflict). Quanto ao moderador “fraco liderança transformacional”, a análise dos dados destaca o papel da “falta de confiança na nova gerência” (lack of trust in the new management), mas também de “sentido do trabalho” (lack of job sense), principalmente através da perda de “orgulho no trabalho” (loss of proudness). Finalmente, a análise dos dados salienta que a “não aceitação do novo sistema de incentivos” (non-acceptance of the new incentive system) afeta significativamente a relação entre a privatização e a armadilha de aceleração, contribuindo tanto para um “choque cultural” como para um “fraco clima de liderança transformacional”.

Acceleration of the decomposition of Sicilian lemon leaves as an auxiliary measure in the control of citrus black spot

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

g-acceleration of gravity: its measurement from the shape of water by using a computerized rotational system

This paper proposes a different experimental setup compared with the traditional ones, in order to determine the acceleration of gravity, which is carried out by using a fluid at a constant rotation. A computerized rotational system-by using a data acquisition system with specific software, a power amplifier and a rotary motion sensor-is employed in order to evaluate the angular velocity and g. An equation to determine g is inferred from fluid mechanics. For this purpose, the fluid's parabolic shape inside a cylindrical receptacle is considered using a rotational movement.

Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Acceleration of Sperm Transit Time and Reduction of Sperm Reserves in the Epididymis of Rats Exposed to Sibutramine

Sibutramine is a drug globally used for the treatment of obesity. The aim of this study was to investigate male reproductive disorders caused by sibutramine in adult rats. Wistar rats were treated for 28 consecutive days (gavage) with 10 mg/kg of sibutramine. Control animals received only vehicle (dimethylsulfoxide and saline). The rats were sacrificed for evaluation of body and reproductive organ weights, sperm parameters, hormone levels (luteinizing hormone, follicle-stimulating hormone, and testosterone), testicular and epididymal histopathology, sexual behavior, fertility and in vitro contractility of the epididymal duct. Sibutramine decreased (P < .05) weights of the epididymis and ventral prostate, but not of other reproductive organs. The sperm number and transit time in the epididymal cauda were decreased (P < .001), but the daily sperm production was not altered. Moreover, morphology and sperm motility, histopathology of the testes and epididymis, sexual behavior, fertility, and serum hormone levels were not altered by the treatment. Sibutramine increased the potency of norepinephrine and, per se, increased the mechanical activity of the epididymal duct in vitro. Thus, although sibutramine in these experimental conditions did not interfere with the reproductive process of rats, it provoked acceleration of the sperm transit time and a decrease in the sperm reserves in the epididymal cauda. This alteration is probably related to the sympathomimetic effect of this drug, as shown by the in vitro assays. In humans, use of this drug might present a threat for male fertility because sperm reserves in men are naturally lower than those in rats.

Consistent modified gravity: dark energy, acceleration and the absence of cosmic doomsday

We discuss modified gravity which includes negative and positive powers of curvature and provides gravitational dark energy. It is shown that in GR plus a term containing a negative power of curvature, cosmic speed-up may be achieved while the effective phantom phase (with w less than -1) follows when such a term contains a fractional positive power of curvature. Minimal coupling with matter makes the situation more interesting: even 1/R theory coupled with the usual ideal fluid may describe the (effective phantom) dark energy. The account of the R(2) term (consistent modified gravity) may help to escape cosmic doomsday.

Holographic dark energy and the universe expansion acceleration

By incorporating the holographic principle in a time-depending Lambda-term cosmology, new physical bounds on the arbitrary parameters of the model can be obtained. Considering then the dark energy as a purely geometric entity, for which no equation of state has to be introduced, it is shown that the resulting range of allowed values for the parameters may explain both the coincidence problem and the universe accelerated expansion, without resorting to any kind of additional structures. (C) 2006 Elsevier B.V. All rights reserved.