Gaining ligand selectivity in thyroid hormone receptors via entropy

Nuclear receptors are important targets for pharmaceuticals, but similarities between family members cause difficulties in obtaining highly selective compounds. Synthetic ligands that are selective for thyroid hormone (TH) receptor beta (TR beta) vs. TR alpha reduce cholesterol and fat without effects on heart rate; thus, it is important to understand TR beta-selective binding. Binding of 3 selective ligands (GC-1, KB141, and GC-24) is characterized at the atomic level; preferential binding depends on a nonconserved residue (Asn-331 beta) in the TR beta ligand-binding cavity (LBC), and GC-24 gains extra selectivity from insertion of a bulky side group into an extension of the LBC that only opens up with this ligand. Here we report that the natural TH 3,5,3`-triodothyroacetic acid (Triac) exhibits a previously unrecognized mechanism of TR beta selectivity. TR x-ray structures reveal better fit of ligand with the TR alpha LBC. The TR beta LBC, however, expands relative to TR alpha in the presence of Triac (549 angstrom(3) vs. 461 angstrom(3)), and molecular dynamics simulations reveal that water occupies the extra space. Increased solvation compensates for weaker interactions of ligand with TR beta and permits greater flexibility of the Triac carboxylate group in TR beta than in TR alpha. We propose that this effect results in lower entropic restraint and decreases free energy of interactions between Triac and TR beta, explaining subtype-selective binding. Similar effects could potentially be exploited in nuclear receptor drug design.

Relative entropy measures applied to healthy and pathological voice characterization

Nowadays, noninvasive methods of diagnosis have increased due to demands of the population that requires fast, simple and painless exams. These methods have become possible because of the growth of technology that provides the necessary means of collecting and processing signals. New methods of analysis have been developed to understand the complexity of voice signals, such as nonlinear dynamics aiming at the exploration of voice signals dynamic nature. The purpose of this paper is to characterize healthy and pathological voice signals with the aid of relative entropy measures. Phase space reconstruction technique is also used as a way to select interesting regions of the signals. Three groups of samples were used, one from healthy individuals and the other two from people with nodule in the vocal fold and Reinke`s edema. All of them are recordings of sustained vowel /a/ from Brazilian Portuguese. The paper shows that nonlinear dynamical methods seem to be a suitable technique for voice signal analysis, due to the chaotic component of the human voice. Relative entropy is well suited due to its sensibility to uncertainties, since the pathologies are characterized by an increase in the signal complexity and unpredictability. The results showed that the pathological groups had higher entropy values in accordance with other vocal acoustic parameters presented. This suggests that these techniques may improve and complement the recent voice analysis methods available for clinicians. (C) 2008 Elsevier Inc. All rights reserved.

Entropy Drives an Attached Water Molecule from the C- to N-Terminus on Protonated Proline

Results from infrared photodissociation (IRPD) spectroscopy and kinetics of singly hydrated, protonated proline indicate that the water molecule hydrogen bonds preferentially to the formally neutral carboxylic acid at low temperatures and at higher temperatures to the protonated N-terminus, which bears the formal charge. Hydration isomer populations obtained from IRPD kinetic data as a function of temperature are used to generate a van`t Hoff plot that reveals that C-terminal binding is enthalpically favored by 4.2-6.4 kJ/mol, whereas N-terminal binding is entropically favored by 31-43 J/(mol K), consistent with a higher calculated barrier for water molecule rotation at the C-terminus.

Average Annual Wind Resource Potential in Maine

http://digitalcommons.colby.edu/atlasofmaine2006/1000/thumbnail.jpg

Educational Opportunities and Average Income in Maine Towns

http://digitalcommons.colby.edu/atlasofmaine2006/1015/thumbnail.jpg

Average Annual Precipitation in Maine

http://digitalcommons.colby.edu/atlasofmaine2005/1011/thumbnail.jpg

A panel data approach to economic forecasting: the bias-corrected average forecast

In this paper, we propose a novel approach to econometric forecasting of stationary and ergodic time series within a panel-data framework. Our key element is to employ the (feasible) bias-corrected average forecast. Using panel-data sequential asymptotics we show that it is potentially superior to other techniques in several contexts. In particular, it is asymptotically equivalent to the conditional expectation, i.e., has an optimal limiting mean-squared error. We also develop a zeromean test for the average bias and discuss the forecast-combination puzzle in small and large samples. Monte-Carlo simulations are conducted to evaluate the performance of the feasible bias-corrected average forecast in finite samples. An empirical exercise based upon data from a well known survey is also presented. Overall, theoretical and empirical results show promise for the feasible bias-corrected average forecast.

A panel data approach to economic forecasting: the bias-corrected average forecast

In this paper, we propose a novel approach to econometric forecasting of stationary and ergodic time series within a panel-data framework. Our key element is to employ the bias-corrected average forecast. Using panel-data sequential asymptotics we show that it is potentially superior to other techniques in several contexts. In particular it delivers a zero-limiting mean-squared error if the number of forecasts and the number of post-sample time periods is sufficiently large. We also develop a zero-mean test for the average bias. Monte-Carlo simulations are conducted to evaluate the performance of this new technique in finite samples. An empirical exercise, based upon data from well known surveys is also presented. Overall, these results show promise for the bias-corrected average forecast.

A panel data approach to economic forecasting: the bias-corrected average forecast

In this paper, we propose a novel approach to econometric forecasting of stationary and ergodic time series within a panel-data framework. Our key element is to employ the (feasible) bias-corrected average forecast. Using panel-data sequential asymptotics we show that it is potentially superior to other techniques in several contexts. In particular, it is asymptotically equivalent to the conditional expectation, i.e., has an optimal limiting mean-squared error. We also develop a zeromean test for the average bias and discuss the forecast-combination puzzle in small and large samples. Monte-Carlo simulations are conducted to evaluate the performance of the feasible bias-corrected average forecast in finite samples. An empirical exercise, based upon data from a well known survey is also presented. Overall, these results show promise for the feasible bias-corrected average forecast.

Nonparametric entropy-based tests of independence between stochastic processes

This paper develops nonparametric tests of independence between two stationary stochastic processes. The testing strategy boils down to gauging the closeness between the joint and the product of the marginal stationary densities. For that purpose, I take advantage of a generalized entropic measure so as to build a class of nonparametric tests of independence. Asymptotic normality and local power are derived using the functional delta method for kernels, whereas finite sample properties are investigated through Monte Carlo simulations.

The distribution of average and marginal effective tax rates in European Union member states

Macro-based summary indicators of effective tax burdens do not capture differences in effective tax rates facing different sub-groups of the population. They also cannot provide information on the level or distribution of the marginal effective tax rates thought to influence household behaviour. I use EUROMOD, an EU-wide tax-benefit microsimulation model, to compute distributions of average and marginal effective tax rates across the household population in fourteen European Union Member States. Using different definitions of ‘net taxes’, the tax base and the unit of analysis I present a range of measures showing the contribution of the tax-benefit system to household incomes, the average effective tax rates applicable to income from labour and marginal effective tax rates faced by working men and women. In a second step, effective tax rates are broken down to separately show the influence of each type of tax-benefit instrument. The results show that measures of effective tax rates vary considerably depending on incomes, labour market situations and family circumstances. Using single averages or macro-based indicators will therefore provide an inappropriate picture of tax burdens faced by large parts of the population.

Evaluation of an average numerator relationship matrix model and a Bayesian hierarchical model for growth traits in Nellore cattle with uncertain paternity

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

Study of relations among age at first calving, average weight gains and weights from weaning to maturity in Nellore cattle

Dados de 23.120 animais da raça Nelore foram utilizados para estimar herdabilidade e correlações genéticas para a idade ao primeiro parto, o ganho em peso da desmama ao ano e do ano ao sobreano, o peso à desmama, o peso ao ano, o peso ao sobreano e os pesos aos 2 e aos 5 anos de idade. Utilizou-se o método da máxima verossimilhança restrita, em análise multicaracterística. As herdabilidades estimadas para idade ao primeiro parto, ganho da desmama ao ano, ganho do ano ao sobreano, peso à desmama, peso ao ano, peso ao sobreano e peso aos 2 aos 5 anos foram de 0,17 ± 0,01; 0,23 ± 0,03; 0,25 ± 0,03; 0,28 ± 0,02; 0,26 ± 0,03; 0,30 ± 0,03; 0,32 ± 0,02 e 0,36 ± 0,04, respectivamente. Correlações genéticas baixas e negativas foram estimadas entre a idade ao primeiro parto e os pesos medidos em diferentes idades, que variaram de -0,26 a -0,14. As correlações genéticas estimadas entre a idade ao primeiro parto e os ganhos de peso também foram negativas, porém levemente superiores (-0,29 e -0,32). Os resultados indicam que a seleção para maior ganho de peso pode reduzir a idade ao primeiro parto e aumentar o peso adulto de fêmeas da raça Nelore. Mudança genética mais rápida para diminuição da idade ao primeiro parto das fêmeas pode ser obtida com a inclusão dessa característica nos índices de seleção.

Modeling of average growth curve in Santa Ines sheep using random regression models

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)