Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial.

Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506765.

Binding of double-strand breaks in DNA by human Rad52 protein.

Double-strand breaks (DSBs) in DNA are caused by ionizing radiation. These chromosomal breaks can kill the cell unless repaired efficiently, and inefficient or inappropriate repair can lead to mutation, gene translocation and cancer. Two proteins that participate in the repair of DSBs are Rad52 and Ku: in lower eukaryotes such as yeast, DSBs are repaired by Rad52-dependent homologous recombination, whereas vertebrates repair DSBs primarily by Ku-dependent non-homologous end-joining. The contribution of homologous recombination to vertebrate DSB repair, however, is important. Biochemical studies indicate that Ku binds to DNA ends and facilitates end-joining. Here we show that human Rad52, like Ku, binds directly to DSBs, protects them from exonuclease attack and facilitates end-to-end interactions. A model for repair is proposed in which either Ku or Rad52 binds the DSB. Ku directs DSBs into the non-homologous end-joining repair pathway, whereas Rad52 initiates repair by homologous recombination. Ku and Rad52, therefore, direct entry into alternative pathways for the repair of DNA breaks.

Double seronegative myasthenia gravis with antiphospholipid syndrome: a case report.

INTRODUCTION: Myasthenia gravis is an autoimmune disease characterized by fluctuating muscle weakness. It is often associated with other autoimmune disorders, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Many aspects of autoimmune diseases are not completely understood, particularly when they occur in association, which suggests a common pathogenetic mechanism. CASE PRESENTATION: We report a case of a 42-year-old Caucasian woman with antiphospholipid syndrome, in whom myasthenia gravis developed years later. She tested negative for both antibodies against the acetylcholine receptor and against muscle-specific receptor tyrosine-kinase, but had typical decremental responses at the repetitive nerve stimulation testing, so that a generalized myasthenia gravis was diagnosed. Her thromboplastin time and activated partial thromboplastin time were high, anticardiolipin and anti-β2 glycoprotein-I antibodies were slightly elevated, as a manifestation of the antiphospholipid syndrome. She had a good clinical response when treated with a combination of pyridostigmine, prednisone and azathioprine. CONCLUSIONS: Many patients with myasthenia gravis test positive for a large variety of auto-antibodies, testifying of an immune dysregulation, and some display mild T-cell lymphopenia associated with hypergammaglobulinemia and B-cell hyper-reactivity. Both of these mechanisms could explain the occurrence of another autoimmune condition, such as antiphospholipid syndrome, but further studies are necessary to shed light on this matter.Clinicians should be aware that patients with an autoimmune diagnosis such as antiphospholipid syndrome who develop signs and neurological symptoms suggestive of myasthenia gravis are at risk and should prompt an emergent evaluation by a specialist.

Long-range-interactions induced ordered structures in deposition processes

We present a new model of sequential adsorption in which the adsorbing particles experience dipolar interactions. We show that in the presence of these long-range interactions, highly ordered structures in the adsorbed layer may be induced at low temperatures. The new phenomenology is manifest through significant variations of the pair correlation function and the jamming limit, with respect to the case of noninteracting particles. Our study could be relevant in understanding the adsorption of magnetic colloidal particles in the presence of a magnetic field.

LAYERED DOUBLE HYDROXIDES: NANOMATERIALS FOR APPLICATIONS IN AGRICULTURE

The current research aims to introduce Layered Double Hydroxides (LDH) as nanomaterials to be used in agriculture, with particular reference to its use as storage and slow release matrix of nutrients and agrochemicals for plant growing. Structural characteristics, main properties, synthesis methods and characterization of LDH were covered in this study. Moreover, some literature data have been reported to demonstrate their potential for storage and slow release of nitrate, phosphate, agrochemicals, besides as being used as adsorbent for the wastewater treatment. This research aims to expand, in near future, the investigation field on these materials, with application in agriculture, increasing the interface between chemistry and agronomy.

A Phase IIB, Randomized, Double-Blind, Multicenter, Immunogenicity Study of Vacc-4x Versus Placebo in HIV-1-infected Patients

Background: Vacc-4x is a peptide-based HIV therapeutic vaccine to conserved domains on p24Gag. Recently conserved 'sectors' on HIV p24, critical for virus viability and thereby immunologically vulnerable have been identified. Elite controllers target immune responses to such regions. The Vacc-4x peptides lie within a number of these conserved sectors of HIV p24. The co-primary endpoints of this study were to compare changes in CD4 counts and return to ART between treatmentand placebo groups during a 24 week treatment interruption. Secondary endpoints included safety, viral load and immunogenicity.Methods: This prospective, randomized, double blind phase IIB clinical study (NCT00659789) was carried out in 13 European and 5 US centers recruiting 135 patients on ART. After 6 immunizations on ART over 28 weeks, treatment was interrupted for up to 24 weeks (to week 52) (Vacc-4x n = 88; placebo n = 38). Immunological analyses (ELISPOT, proliferation, intracellular cytokine staining) were carried out at central laboratories.Results: There were no Vacc-4x-related serious adverse events. Of the 135 patients recruited (male n = 92; female n = 43), 126 patients completed the study. Median prestudy CD4 count was 712 (Vacc-4x) and 619 cells/mm3 (placebo), and median CD4 nadir 300 (Vacc-4x) and 285 cells/mm3 (placebo). There was no statistically significant difference between the two groups regarding change in CD4 counts (p = 0.12) or ART resumption (p = 0.89) during treatment interruption. A statistically significant treatment difference between Vacc-4x and placebo groupsfor viral load (VL) was found for patients who achieved a 6 month ART-free period (p = 0.0022). There was a positive correlation between ELISPOT responses and lower viral load in the Vacc-4x group compared to placebo (p = 0.02). Long-term follow-up of patients up t o week 104 was completed in June 2011.Conclusion: Vacc-4x was found to be safe and well tolerated. TheVacc-4x group experienced a significant reduction in viral load compared to placebo.

Flow structures at an idealized bifurcation : a numerical experiment

River bifurcations are key nodes within braided river systems controlling the flow and sediment partitioning and therefore the dynamics of the river braiding process. Recent research has shown that certain geometrical configurations induce instabilities that lead to downstream mid-channel bar formation and the formation of bifurcations. However, we currently have a poor understanding of the flow division process within bifurcations and the flow dynamics in the downstream bifurcates, both of which are needed to understand bifurcation stability. This paper presents results of a numerical sensitivity experiment undertaken using computational fluid dynamics (CFD) with the purpose of understanding the flow dynamics of a series of idealized bifurcations. A geometric sensitivity analysis is undertaken for a range of channel slopes (0.005 to 0.03), bifurcation angles (22 degrees to 42 degrees) and a restricted set of inflow conditions based upon simulating flow through meander bends with different curvature on the flow field dynamics through the bifurcation. The results demonstrate that the overall slope of the bifurcation affects the velocity of flow through the bifurcation and when slope asymmetry is introduced, the flow structures in the bifurcation are modified. In terms of bifurcation evolution the most important observation appears to be that once slope asymmetry is greater than 0.2 the flow within the steep bifurcate shows potential instability and the potential for alternate channel bar formation. Bifurcation angle also defines the flow structures within the bifurcation with an increase in bifurcation angle increasing the flow velocity down both bifurcates. However, redistributive effects of secondary circulation caused by upstream curvature can very easily counter the effects of local bifurcation characteristics. Copyright (C) 2011 John Wiley & Sons, Ltd.

Is the Gibraltar strait a barrier to gene flow for the bat Myotis myotis (Chiroptera: Vespertilionidae)?

Because of their role in limiting gene flow, geographical barriers like mountains or seas often coincide with intraspecific genetic discontinuities. Although the Strait of Gibraltar represents such a potential barrier for both plants and animals, few studies have been conducted on its impact on gene flow. Here we test this effect on a bat species (Myotis myotis) which is apparently distributed on both sides of the strait. Six colonies of 20 Myotis myotis each were sampled in southern Spain and northern Morocco along a linear transect of 1350 km. Results based on six nuclear microsatellite loci reveal no significant population structure within regions, but a complete isolation between bats sampled on each side of the strait. Variability at 600 bp of a mitochondrial gene (cytochrome b) confirms the existence of two genetically distinct and perfectly segregating clades, which diverged several million years ago. Despite the narrowness of the Gibraltar Strait (14 km), these molecular data suggest that neither males, nor females from either region have ever reproduced on the opposite side of the strait. Comparisons of molecular divergence with bats from a closely related species (M. blythii) suggest that the North African clade is possibly a distinct taxon warranting full species rank. We provisionally refer to it as Myotis cf punicus Felten 1977, but a definitive systematic understanding of the whole Mouse-eared bat species complex awaits further genetic sampling, especially in the Eastern Mediterranean areas.

Apprentissage automatique de la morphologie : le cas des structures racine-schème

RÉSUMÉ Cette thèse porte sur le développement de méthodes algorithmiques pour découvrir automatiquement la structure morphologique des mots d'un corpus. On considère en particulier le cas des langues s'approchant du type introflexionnel, comme l'arabe ou l'hébreu. La tradition linguistique décrit la morphologie de ces langues en termes d'unités discontinues : les racines consonantiques et les schèmes vocaliques. Ce genre de structure constitue un défi pour les systèmes actuels d'apprentissage automatique, qui opèrent généralement avec des unités continues. La stratégie adoptée ici consiste à traiter le problème comme une séquence de deux sous-problèmes. Le premier est d'ordre phonologique : il s'agit de diviser les symboles (phonèmes, lettres) du corpus en deux groupes correspondant autant que possible aux consonnes et voyelles phonétiques. Le second est de nature morphologique et repose sur les résultats du premier : il s'agit d'établir l'inventaire des racines et schèmes du corpus et de déterminer leurs règles de combinaison. On examine la portée et les limites d'une approche basée sur deux hypothèses : (i) la distinction entre consonnes et voyelles peut être inférée sur la base de leur tendance à alterner dans la chaîne parlée; (ii) les racines et les schèmes peuvent être identifiés respectivement aux séquences de consonnes et voyelles découvertes précédemment. L'algorithme proposé utilise une méthode purement distributionnelle pour partitionner les symboles du corpus. Puis il applique des principes analogiques pour identifier un ensemble de candidats sérieux au titre de racine ou de schème, et pour élargir progressivement cet ensemble. Cette extension est soumise à une procédure d'évaluation basée sur le principe de la longueur de description minimale, dans- l'esprit de LINGUISTICA (Goldsmith, 2001). L'algorithme est implémenté sous la forme d'un programme informatique nommé ARABICA, et évalué sur un corpus de noms arabes, du point de vue de sa capacité à décrire le système du pluriel. Cette étude montre que des structures linguistiques complexes peuvent être découvertes en ne faisant qu'un minimum d'hypothèses a priori sur les phénomènes considérés. Elle illustre la synergie possible entre des mécanismes d'apprentissage portant sur des niveaux de description linguistique distincts, et cherche à déterminer quand et pourquoi cette coopération échoue. Elle conclut que la tension entre l'universalité de la distinction consonnes-voyelles et la spécificité de la structuration racine-schème est cruciale pour expliquer les forces et les faiblesses d'une telle approche. ABSTRACT This dissertation is concerned with the development of algorithmic methods for the unsupervised learning of natural language morphology, using a symbolically transcribed wordlist. It focuses on the case of languages approaching the introflectional type, such as Arabic or Hebrew. The morphology of such languages is traditionally described in terms of discontinuous units: consonantal roots and vocalic patterns. Inferring this kind of structure is a challenging task for current unsupervised learning systems, which generally operate with continuous units. In this study, the problem of learning root-and-pattern morphology is divided into a phonological and a morphological subproblem. The phonological component of the analysis seeks to partition the symbols of a corpus (phonemes, letters) into two subsets that correspond well with the phonetic definition of consonants and vowels; building around this result, the morphological component attempts to establish the list of roots and patterns in the corpus, and to infer the rules that govern their combinations. We assess the extent to which this can be done on the basis of two hypotheses: (i) the distinction between consonants and vowels can be learned by observing their tendency to alternate in speech; (ii) roots and patterns can be identified as sequences of the previously discovered consonants and vowels respectively. The proposed algorithm uses a purely distributional method for partitioning symbols. Then it applies analogical principles to identify a preliminary set of reliable roots and patterns, and gradually enlarge it. This extension process is guided by an evaluation procedure based on the minimum description length principle, in line with the approach to morphological learning embodied in LINGUISTICA (Goldsmith, 2001). The algorithm is implemented as a computer program named ARABICA; it is evaluated with regard to its ability to account for the system of plural formation in a corpus of Arabic nouns. This thesis shows that complex linguistic structures can be discovered without recourse to a rich set of a priori hypotheses about the phenomena under consideration. It illustrates the possible synergy between learning mechanisms operating at distinct levels of linguistic description, and attempts to determine where and why such a cooperation fails. It concludes that the tension between the universality of the consonant-vowel distinction and the specificity of root-and-pattern structure is crucial for understanding the advantages and weaknesses of this approach.

Time of ruin in a risk model with generalized Erlang (n) interclaim times and a constant dividend barrier

In this paper we analyze the time of ruin in a risk process with the interclaim times being Erlang(n) distributed and a constant dividend barrier. We obtain an integro-differential equation for the Laplace Transform of the time of ruin. Explicit solutions for the moments of the time of ruin are presented when the individual claim amounts have a distribution with rational Laplace transform. Finally, some numerical results and a compare son with the classical risk model, with interclaim times following an exponential distribution, are given.

Double blind controlled trial of D-penicillamine in patients with primary biliary cirrhosis.

One hundred and eighty nine patients with primary biliary cirrhosis were entered into a double blind, placebo controlled randomised trial starting in January 1978 to assess the therapeutic value of d-penicillamine 1200 mg daily. Eighteen of the 98 patients receiving d-penicillamine and 22 of the 91 placebo treated patients died during the study. Thirty six per cent of those on d-penicillamine and 8% of those on placebo were withdrawn from the study. No difference in overall survival was noted between the two groups of patients whether the results were analysed for the entire period of observation or only during the period in which the patients were receiving therapy. The mortality rate of those receiving d-penicillamine in histological stage I to II, however, was one third of that of the placebo group although this difference did not reach statistical significance. Using the occurrence rate ratio as the statistical method of analysis, no effect of d-penicillamine was noted on any clinical, biochemical or hist

Les sociologues ont-ils perdu l'esprit ? À la recherche des structures élémentaires de la vie sociale

Ce texte est un « droit de réponse » par les auteurs de l'article « Vers un naturalisme social. À la croisée des sciences sociales et des sciences cognitives », publié par SociologieS en octobre 2011, au débat qu'il a suscité. Après une brève mise au point sur la forme même du débat, ainsi que sur les dissensions ponctuelles qui opposent les différents protagonistes, l'article répond aux inquiétudes parfaitement légitimes et aux questions de fond que soulève le naturalisme social.