On L2 Clustering and Resetting the Null Subject Parameter in L2 Spanish: Implications and Observations.

In this article, along with others, we take the position that the Null-Subject Parameter (NSP) (Chomsky 1981; Rizzi 1982) cluster of properties is narrower in scope than some originally contended. We test for the resetting of the NSP by English L2 learners of Spanish at the intermediate level, including poverty-of-the stimulus knowledge of the Overt Pronoun Constraint (Montalbetti 1984). Our participants are tested before and after five months' residency in Spain in an effort to see if increased amounts of native exposure are particularly beneficial for parameter resetting. Although we demonstrate NSP resetting for some of the L2 learners, our data essentially demonstrate that even with the advent of time/exposure to native input, there is no immediate gainful effect for NSP resetting.

Investigating mechanisms underpinning the detrimental impact of a high-fat diet in the developing and adult hypermuscular myostatin null mouse

Background: Obese adults are prone to develop metabolic and cardiovascular diseases. Furthermore, over-weight expectant mothers give birth to large babies who also have increased likelihood of developing metabolic and cardiovascular diseases. Fundamental advancements to better understand the pathophysiology of obesity are critical in the development of anti-obesity therapies not only for this but also future generations. Skeletal muscle plays a major role in fat metabolism and much work has focused in promoting this activity in order to control the development of obesity. Research has evaluated myostatin inhibition as a strategy to prevent the development of obesity and concluded in some cases that it offers a protective mechanism against a high-fat diet. Results: We hypothesised that myostatin inhibition should protect not only the mother but also its developing foetus from the detrimental effects of a high-fat diet. Unexpectedly, we found muscle development was attenuated in the foetus of myostatin null mice raised on a high-fat diet. We therefore re-examined the effect of the high-fat diet on adults and found myostatin null mice were more susceptible to diet-induced obesity through a mechanism involving impairment of inter-organ fat utilization. Conclusions: Loss of myostatin alters fatty acid uptake and oxidation in skeletal muscle and liver. We show that abnormally high metabolic activity of fat in myostatin null mice is decreased by a high-fat diet resulting in excessive adipose deposition and lipotoxicity. Collectively, our genetic loss-of-function studies offer an explanation of the lean phenotype displayed by a host of animals lacking myostatin signalling. Keywords: Muscle, Obesity, High-fat diet, Metabolism, Myostatin

Toward multifactorial null models of range contraction in terrestrial vertebrates

The contraction of a species’ distribution range, which results from the extirpation of local populations, generally precedes its extinction. Therefore, understanding drivers of range contraction is important for conservation and management. Although there are many processes that can potentially lead to local extirpation and range contraction, three main null models have been proposed: demographic, contagion, and refuge. The first two models postulate that the probability of local extirpation for a given area depends on its relative position within the range; but these models generate distinct spatial predictions because they assume either a ubiquitous (demographic) or a clinal (contagion) distribution of threats. The third model (refuge) postulates that extirpations are determined by the intensity of human impacts, leading to heterogeneous spatial predictions potentially compatible with those made by the other two null models. A few previous studies have explored the generality of some of these null models, but we present here the first comprehensive evaluation of all three models. Using descriptive indices and regression analyses we contrast the predictions made by each of the null models using empirical spatial data describing range contraction in 386 terrestrial vertebrates (mammals, birds, amphibians, and reptiles) distributed across the World. Observed contraction patterns do not consistently conform to the predictions of any of the three models, suggesting that these may not be adequate null models to evaluate range contraction dynamics among terrestrial vertebrates. Instead, our results support alternative null models that account for both relative position and intensity of human impacts. These new models provide a better multifactorial baseline to describe range contraction patterns in vertebrates. This general baseline can be used to explore how additional factors influence contraction, and ultimately extinction for particular areas or species as well as to predict future changes in light of current and new threats.

Analysis of peptides in prohormone convertase 1/3 null mouse brain using quantitative peptidomics

P>Neuropeptides are produced from larger precursors by limited proteolysis, first by endopeptidases and then by carboxypeptidases. Major endopeptidases required for these cleavages include prohormone convertase (PC) 1/3 and PC2. In this study, quantitative peptidomics analysis was used to characterize the specific role PC1/3 plays in this process. Peptides isolated from hypothalamus, amygdala, and striatum of PC1/3 null mice were compared with those from heterozygous and wild-type mice. Extracts were labeled with stable isotopic tags and fractionated by HPLC, after which relative peptide levels were determined using tandem mass spectrometry. In total, 92 peptides were found, of which 35 were known neuropeptides or related peptides derived from 15 distinct secretory pathway proteins: 7B2, chromogranin A and B, cocaine- and amphetamine-regulated transcript, procholecystokinin, proenkephalin, promelanin concentrating hormone, proneurotensin, propituitary adenylate cyclase-activating peptide, proSAAS, prosomatosatin, provasoactive intestinal peptide, provasopressin, secretogranin III, and VGF. Among the peptides derived from these proteins, similar to 1/3 were decreased in the PC1/3 null mice relative to wild-type mice, similar to 1/3 showed no change, and similar to 1/3 increased in PC1/3 null. Cleavage sites were analyzed in peptides that showed no change or that decreased in PC1/3 mice, and these results were compared with peptides that showed no change or decreased in previous peptidomic studies with PC2 null mice. Analysis of these sites showed that while PC1/3 and PC2 have overlapping substrate preferences, there are particular cleavage site residues that distinguish peptides preferred by each PC.

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.

Hypotheses Testing on a Multivariate Null Intercept Errors-in-Variables Model

Considering the Wald, score, and likelihood ratio asymptotic test statistics, we analyze a multivariate null intercept errors-in-variables regression model, where the explanatory and the response variables are subject to measurement errors, and a possible structure of dependency between the measurements taken within the same individual are incorporated, representing a longitudinal structure. This model was proposed by Aoki et al. (2003b) and analyzed under the bayesian approach. In this article, considering the classical approach, we analyze asymptotic test statistics and present a simulation study to compare the behavior of the three test statistics for different sample sizes, parameter values and nominal levels of the test. Also, closed form expressions for the score function and the Fisher information matrix are presented. We consider two real numerical illustrations, the odontological data set from Hadgu and Koch (1999), and a quality control data set.

Bayesian analysis for a skew extension of the multivariate null intercept measurement error model

Skew-normal distribution is a class of distributions that includes the normal distributions as a special case. In this paper, we explore the use of Markov Chain Monte Carlo (MCMC) methods to develop a Bayesian analysis in a multivariate, null intercept, measurement error model [R. Aoki, H. Bolfarine, J.A. Achcar, and D. Leao Pinto Jr, Bayesian analysis of a multivariate null intercept error-in -variables regression model, J. Biopharm. Stat. 13(4) (2003b), pp. 763-771] where the unobserved value of the covariate (latent variable) follows a skew-normal distribution. The results and methods are applied to a real dental clinical trial presented in [A. Hadgu and G. Koch, Application of generalized estimating equations to a dental randomized clinical trial, J. Biopharm. Stat. 9 (1999), pp. 161-178].

Fractal structures in nonlinear plasma physics

Fractal structures appear in many situations related to the dynamics of conservative as well as dissipative dynamical systems, being a manifestation of chaotic behaviour. In open area-preserving discrete dynamical systems we can find fractal structures in the form of fractal boundaries, associated to escape basins, and even possessing the more general property of Wada. Such systems appear in certain applications in plasma physics, like the magnetic field line behaviour in tokamaks with ergodic limiters. The main purpose of this paper is to show how such fractal structures have observable consequences in terms of the transport properties in the plasma edge of tokamaks, some of which have been experimentally verified. We emphasize the role of the fractal structures in the understanding of mesoscale phenomena in plasmas, such as electromagnetic turbulence.

Results of Joint Experiments and other IAEA activities on research using small tokamaks

This paper presents an overview of the results obtained during the Joint Experiments organized in the framework of the IAEA Coordinated Research Project on `Joint Research Using Small Tokamaks` that have been carried out on the tokamaks CASTOR at IPP Prague, Czech Republic (2005), T-10 at RRC `Kurchatov Institute`, Moscow, Russia (2006), and the most recent one at ISTTOK at IST, Lisbon, Portugal, in 2007. Experimental programmes were aimed at diagnosing and characterizing the core and the edge plasma turbulence in a tokamak in order to investigate correlations between the occurrence of transport barriers, improved confinement, electric fields and electrostatic turbulence using advanced diagnostics with high spatial and temporal resolution. On CASTOR and ISTTOK, electric fields were generated by biasing an electrode inserted into the edge plasma and an improvement of the global particle confinement induced by the electrode positive biasing has been observed. Geodesic acoustic modes were studied using heavy ion beam diagnostics on T-10 and ISTTOK and correlation reflectometry on T-10. ISTTOK is equipped with a gallium jet injector and the technical feasibility of gallium jets interacting with plasmas has been investigated in pulsed and ac operation. The first Joint Experiments have clearly demonstrated that small tokamaks are suitable for broad international cooperation to conduct dedicated joint research programmes. Other activities within the IAEA Coordinated Research Project on Joint Research Using Small Tokamaks are also overviewed.

Transport control in fusion plasmas by changing electric and magnetic field spatial profiles

For magnetically confined plasmas in tokamaks, we have numerically investigated how Lagrangian chaos at the plasma edge affects the plasma confinement. Initially, we have considered the chaotic motion of particles in an equilibrium electric field with a monotonic radial profile perturbed by drift waves. We have showed that an effective transport barrier may be created at the plasma edge by modifying the electric field radial profile. In the second place, we have obtained escape patterns and magnetic footprints of chaotic magnetic field lines in the region near a tokamak wall with resonant modes due to the action of an ergodic magnetic limiter. For monotonic plasma current density profiles we have obtained distributions of field line connections to the wall and line escape channels with the same spatial pattern as the magnetic footprints on the tokamak walls. (c) 2008 Elsevier B.V. All rights reserved.

Plasma confinement in tokamaks with robust torus

We present a non-linear symplectic map that describes the alterations of the magnetic field lines inside the tokamak plasma due to the presence of a robust torus (RT) at the plasma edge. This RT prevents the magnetic field lines from reaching the tokamak wall and reduces, in its vicinity, the islands and invariant curve destruction due to resonant perturbations. The map describes the equilibrium magnetic field lines perturbed by resonances created by ergodic magnetic limiters (EMLs). We present the results obtained for twist and non-twist mappings derived for monotonic and non-monotonic plasma current density radial profiles, respectively. Our results indicate that the RT implementation would decrease the field line transport at the tokamak plasma edge. (C) 2010 Elsevier B.V. All rights reserved.

Inference and local influence assessment in skew-normal null intercept measurement error model

In this article, we discuss inferential aspects of the measurement error regression models with null intercepts when the unknown quantity x (latent variable) follows a skew normal distribution. We examine first the maximum-likelihood approach to estimation via the EM algorithm by exploring statistical properties of the model considered. Then, the marginal likelihood, the score function and the observed information matrix of the observed quantities are presented allowing direct inference implementation. In order to discuss some diagnostics techniques in this type of models, we derive the appropriate matrices to assessing the local influence on the parameter estimates under different perturbation schemes. The results and methods developed in this paper are illustrated considering part of a real data set used by Hadgu and Koch [1999, Application of generalized estimating equations to a dental randomized clinical trial. Journal of Biopharmaceutical Statistics, 9, 161-178].

A robust Bayesian approach to null intercept measurement error model with application to dental data

Measurement error models often arise in epidemiological and clinical research. Usually, in this set up it is assumed that the latent variable has a normal distribution. However, the normality assumption may not be always correct. Skew-normal/independent distribution is a class of asymmetric thick-tailed distributions which includes the Skew-normal distribution as a special case. In this paper, we explore the use of skew-normal/independent distribution as a robust alternative to null intercept measurement error model under a Bayesian paradigm. We assume that the random errors and the unobserved value of the covariate (latent variable) follows jointly a skew-normal/independent distribution, providing an appealing robust alternative to the routine use of symmetric normal distribution in this type of model. Specific distributions examined include univariate and multivariate versions of the skew-normal distribution, the skew-t distributions, the skew-slash distributions and the skew contaminated normal distributions. The methods developed is illustrated using a real data set from a dental clinical trial. (C) 2008 Elsevier B.V. All rights reserved.

Superoxide Dismutase 1-mediated Production of Ethanol- and DNA-derived Radicals in Yeasts Challenged with Hydrogen Peroxide MOLECULAR INSIGHTS INTO THE GENOME INSTABILITY OF PEROXIREDOXIN-NULL STRAINS

Peroxiredoxins are receiving increasing attention as defenders against oxidative damage and sensors of hydrogen peroxide-mediated signaling events. In the yeast Saccharomyces cerevisiae, deletion of one or more isoforms of the peroxiredoxins is not lethal but compromises genome stability by mechanisms that remain under scrutiny. Here, we show that cytosolic peroxiredoxin-null cells (tsa1 Delta tsa2 Delta) are more resistant to hydrogen peroxide than wildtype (WT) cells and consume it faster under fermentative conditions. Also, tsa1 Delta tsa2 Delta cells produced higher yields of the 1-hydroxyethyl radical from oxidation of the glucose metabolite ethanol, as proved by spin-trapping experiments. A major role for Fenton chemistry in radical formation was excluded by comparing WT and tsa1 Delta tsa2 Delta cells with respect to their levels of total and chelatable metal ions and of radical produced in the presence of chelators. The main route for 1-hydroxyethyl radical formation was ascribed to the peroxidase activity of Cu, Zn-superoxide dismutase (Sod1), whose expression and activity increased similar to 5- and 2-fold, respectively, in tsa1 Delta tsa2 Delta compared with WT cells. Accordingly, overexpression of human Sod1 in WT yeasts led to increased 1-hydroxyethyl radical production. Relevantly, tsa1 Delta tsa2 Delta cells challenged with hydrogen peroxide contained higher levels of DNA-derived radicals and adducts as monitored by immuno-spin trapping and incorporation of (14)C from glucose into DNA, respectively. The results indicate that part of hydrogen peroxide consumption by tsa1 Delta tsa2 Delta cells is mediated by induced Sod1, which oxidizes ethanol to the 1-hydroxyethyl radical, which, in turn, leads to increased DNA damage. Overall, our studies provide a pathway to account for the hypermutability of peroxiredoxin-null strains.