Double generalized linear model for tissue culture proportion data: a Bayesian perspective

Joint generalized linear models and double generalized linear models (DGLMs) were designed to model outcomes for which the variability can be explained using factors and/or covariates. When such factors operate, the usual normal regression models, which inherently exhibit constant variance, will under-represent variation in the data and hence may lead to erroneous inferences. For count and proportion data, such noise factors can generate a so-called overdispersion effect, and the use of binomial and Poisson models underestimates the variability and, consequently, incorrectly indicate significant effects. In this manuscript, we propose a DGLM from a Bayesian perspective, focusing on the case of proportion data, where the overdispersion can be modeled using a random effect that depends on some noise factors. The posterior joint density function was sampled using Monte Carlo Markov Chain algorithms, allowing inferences over the model parameters. An application to a data set on apple tissue culture is presented, for which it is shown that the Bayesian approach is quite feasible, even when limited prior information is available, thereby generating valuable insight for the researcher about its experimental results.

Parametric correlation functions to model the structure of permanent environmental (co)variances in milk yield random regression models

The objective of the present study was to estimate milk yield genetic parameters applying random regression models and parametric correlation functions combined with a variance function to model animal permanent environmental effects. A total of 152,145 test-day milk yields from 7,317 first lactations of Holstein cows belonging to herds located in the southeastern region of Brazil were analyzed. Test-day milk yields were divided into 44 weekly classes of days in milk. Contemporary groups were defined by herd-test-day comprising a total of 2,539 classes. The model included direct additive genetic, permanent environmental, and residual random effects. The following fixed effects were considered: contemporary group, age of cow at calving (linear and quadratic regressions), and the population average lactation curve modeled by fourth-order orthogonal Legendre polynomial. Additive genetic effects were modeled by random regression on orthogonal Legendre polynomials of days in milk, whereas permanent environmental effects were estimated using a stationary or nonstationary parametric correlation function combined with a variance function of different orders. The structure of residual variances was modeled using a step function containing 6 variance classes. The genetic parameter estimates obtained with the model using a stationary correlation function associated with a variance function to model permanent environmental effects were similar to those obtained with models employing orthogonal Legendre polynomials for the same effect. A model using a sixth-order polynomial for additive effects and a stationary parametric correlation function associated with a seventh-order variance function to model permanent environmental effects would be sufficient for data fitting.

Effects of chlorogenic acid on neutrophil locomotion functions in response to inflammatory stimulus

Aim of the study: Species of Lychnophora are used in Brazilian folk medicine as analgesic and anti-inflammatory agents. Chlorogenic acid (CGA) and their analogues are important components of polar extracts of these species, as well in several European and Asian medicinal plants. Some of these phenolic compounds display anti-inflammatory effects. In this paper we report the isolation of CGA from Lychnophora salicifolia and its effects on functions involved in neutrophils locomotion. Materials and methods: LC-MS(n) data confirmed the presence of CGA in the plant. Actions of CGA were investigated on neutrophils obtained from peritoneal cavity of Wistar rats (4h after 1% oyster glycogen solution injection; 10 ml), and incubated with vehicle or with 50, 100 or 1000 mu M CGA in presence of lipopolysaccharide from Escherichia coil (LPS, 5 mu g/ml). Nitric oxide (NO; Griess reaction); prostaglandin E(2) (PGE(2)), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha [TNF-alpha; enzyme-linked immunosorbent assay (EIA)]; protein (flow cytometry) and gene (RT-PCR) expression of L-selectin, beta(2)integrin and platelet-endothelial cell adhesion molecule-1 (PECAM-1) were quantified. In vitro neutrophil adhesion to primary culture of microvascular endothelial cell (PMEC) and neutrophil migration in response to formyl-methionil-leucil-phenilalanine (fMLP, 10(-8)M, Boyden chamber) was determined. Results: CGA treatment did not modify the secretion of inflammatory mediators, but inhibited L-selectin cleavage and reduced beta(2) integrin, independently from its mRNA synthesis, and reduced membrane PECAM-1 expression: inhibited neutrophil adhesion and neutrophil migration induced by fMLP. Conclusions: Based on these findings, we highlight the direct inhibitory actions of CGA on adhesive and locomotion properties of neutrophils, which may contribute to its anti-inflammatory effects and help to explain the use of Lychnophora salicifolia as an anti-inflammatory agent. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Effects of methylmercury on male reproductive functions in Wistar rats

In this study we investigated the effects of subacute exposure to methylmercury (MeHg) on male reproductive functions in rats by means of determination of alterations in structural and functional parameters. Adult male Wistar rats received 0, 0.5, 1.0 or 3.0 mg/kg/body weight/day orally, daily MeHg for 14 days. Sperm motility, the relative sperm count and transit time in the caput/corpus epididymis, were all reduced at all doses. The lowest dose increased the number of sperm head abnormalities; daily sperm production was elevated at the intermediate dose; while at the highest dose there was a decrease in serum testosterone levels and a rise in mercury (Hg) content in reproductive organs, liver and kidneys. In conclusion, MeHg exposure produced damages on male reproductive functions which may be attributed, at least in part, to the reduction in serum testosterone levels. These consequences could potentially result in infertility in rats. (C) 2011 Elsevier Inc. All rights reserved.

Modal functions of future tenses in French

The paper disputes two influential claims in the Romance Linguistics literature. The first is that the synthetic future tenses in spoken Western Romance are now rivalled, if not supplanted, as temporal functors by the more recently developed GO futures. The second is that these synthetic futures now have modal rather than temporal meanings in spoken Romance. These claims are seen as reflecting a universal cycle of diachronic change, in which verb forms originally expressing modal (or aspectual) values take on future temporal reference, becoming tenses. The new modal meanings supplant the temporal, which are then taken up by new forms. Challenges to this theory for French are raised on the basis of empirical evidence of two sorts. Positively, future tenses in spoken Romance continue to be used with temporal meaning. Negatively, evidence of modal meaning for these forms is lacking. The evidence comes froma corpora of spoken French, native speaker judgements and verb data from a daily broadsheet. Cumulatively, it points to the reverse of the claims noted above: the synthetic future in spoken French has temporal but little modal meaning.

Sampling phylogenetic tree space with the generalized Gibbs sampler

The generalized Gibbs sampler (GGS) is a recently developed Markov chain Monte Carlo (MCMC) technique that enables Gibbs-like sampling of state spaces that lack a convenient representation in terms of a fixed coordinate system. This paper describes a new sampler, called the tree sampler, which uses the GGS to sample from a state space consisting of phylogenetic trees. The tree sampler is useful for a wide range of phylogenetic applications, including Bayesian, maximum likelihood, and maximum parsimony methods. A fast new algorithm to search for a maximum parsimony phylogeny is presented, using the tree sampler in the context of simulated annealing. The mathematics underlying the algorithm is explained and its time complexity is analyzed. The method is tested on two large data sets consisting of 123 sequences and 500 sequences, respectively. The new algorithm is shown to compare very favorably in terms of speed and accuracy to the program DNAPARS from the PHYLIP package.

Polytomous item response theory models

Polytomous Item Response Theory Models provides a unified, comprehensive introduction to the range of polytomous models available within item response theory (IRT). It begins by outlining the primary structural distinction between the two major types of polytomous IRT models. This focuses on the two types of response probability that are unique to polytomous models and their associated response functions, which are modeled differently by the different types of IRT model. It describes, both conceptually and mathematically, the major specific polytomous models, including the Nominal Response Model, the Partial Credit Model, the Rating Scale model, and the Graded Response Model. Important variations, such as the Generalized Partial Credit Model are also described as are less common variations, such as the Rating Scale version of the Graded Response Model. Relationships among the models are also investigated and the operation of measurement information is described for each major model. Practical examples of major models using real data are provided, as is a chapter on choosing an appropriate model. Figures are used throughout to illustrate important elements as they are described.

Role of generalized and episode specific memories in the word frequency effect in recognition

Frequency, recency, and type of prior exposure to very low-and high-frequency words were manipulated in a 3-phase (i.e., familiarization training, study, and test) design. Increasing the frequency with which a definition for a very low-frequency word was provided during familiarization facilitated the word's recognition in both yes-no (Experiment 1) and forced-choice paradigms (Experiment 2). Recognition of very low-frequency words not accompanied by a definition during familiarization first increased, then decreased as familiarization frequency increased (Experiment I). Reasons for these differences were investigated in Experiment 3 using judgments of recency and frequency. Results suggested that prior familiarization of a very low-frequency word with its definition may allow a more adequate episodic representation of the word to be formed during a subsequent study trial. Theoretical implications of these results for current models of memory are discussed.

Observation of generalized synchronization of chaos in a driven chaotic system

We report on the experimental observation of the generalized synchronization of chaos in a real physical system. We show that under a nonlinear resonant interaction, the chaotic dynamics of a single mode laser can become functionally related to that of a chaotic driving signal and furthermore as the coupling strength is further increased, the chaotic dynamics of the laser approaches that of the driving signal.

Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta 1 subunit gene SCN1B

Febrile seizures affect approximately 3% of all children under six years of age and are by far the most common seizure disorder(1). A small proportion of children with febrile seizures later develop ongoing epilepsy with afebrile seizures(2). Segregation analysis suggests the majority of cases have complex inheritance(3) but rare families show apparent autosomal dominant: inheritance. Two putative loci have been mapped (FEB1 and FEB2), but specific genes have not yet been identified(4,5). We recently described a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS(+)), in which many family members have seizures with fever that may persist beyond six years of age or be associated with afebrile generalized seizures(6). We now report linkage, in another large GEFS(+) family, to chromosome region 19q13.1 and identification of a mutation in the voltage-gated sodium (Na+)-channel beta 1 subunit gene (SCN1B). The mutation changes a conserved cysteine residue disrupting a putative disulfide bridge which normally maintains an extracellular immunoglobulin-like fold. Go-expression of the mutant pr subunit with a brain Na+-channel alpha subunit in Xenopus laevis oocytes demonstrates that the mutation interferes with the ability of the subunit to modulate channel-gating kinetics consistent with a loss-of-function allele. This observation develops the theme that idiopathic epilepsies are a family of channelopathies and raises the possibility of involvement of other Na+-channel subunit genes in febrile seizures and generalized epilepsies with complex inheritance patterns.

Cost functions and duality for stochastic technologies

Cost functions dual to stochastic production technologies are derived and their properties are discussed. These cost functions are shown to be consistent with expected-utility maximization without placing serious structural restrictions on the underlying technology.

Generalized optimal lattice covering of finite-dimensional Euclidean space

A generalization of the classical problem of optimal lattice covering of R-n is considered. Solutions to this generalized problem are found in two specific classes of lattices. The global optimal solution of the generalization is found for R-2. (C) 1998 Elsevier Science Inc. All rights reserved.

The dimerization and topological specificity functions of MinE reside in a structurally autonomous C-terminal domain

Correct placement of the division septum in Escherichia coli requires the co-ordinated action of three proteins, MinC, MinD and MinE. MinC and MinD interact to form a non-specific division inhibitor that blocks septation at all potential division sites. MinE is able to antagonize MinCD in a topologically sensitive manner, as it restricts MinCD activity to the unwanted division sites at the cell poles, Here, we show that the topological specificity function of MinE residues in a structurally autonomous, trypsin-resistant domain comprising residues 31-88, Nuclear magnetic resonance (NMR) and circular dichroic spectroscopy indicate that this domain includes both alpha and beta secondary structure, while analytical ultracentrifugation reveals that it also contains a region responsible for MinE homodimerization. While trypsin digestion indicates that the anti-MinCD domain of MinE (residues 1-22) does not form a tightly folded structural domain, NMR analysis of a peptide corresponding to MinE(1-22) indicates that this region forms a nascent helix in which the peptide rapidly interconverts between disordered (random coil) and alpha-helical conformations, This suggests that the N-terminal region of MinE may be poised to adopt an alpha-helical conformation when it interacts with the target of its anti-MinCD activity, presumably MinD.

Protein fold recognition score functions: Unusual construction strategies

We describe two ways of optimizing score functions for protein sequence to structure threading. The first method adjusts parameters to improve sequence to structure alignment. The second adjusts parameters so as to improve a score function's ability to rank alignments calculated in the first score function. Unlike those functions known as knowledge-based force fields, the resulting parameter sets do not rely on Boltzmann statistics, have no claim to representing free energies and are purely constructions for recognizing protein folds. The methods give a small improvement, but suggest that functions can be profitably optimized for very specific aspects of protein fold recognition, Proteins 1999;36:454-461. (C) 1999 Wiley-Liss, Inc.