Solitonic-exchange mechanism of surface~diffusion

We study surface diffusion in the framework of a generalized Frenkel-Kontorova model with a nonconvex transverse degree of freedom. The model describes a lattice of atoms with a given concentration interacting by Morse-type forces, the lattice being subjected to a two-dimensional substrate potential which is periodic in one direction and nonconvex (Morse) in the transverse direction. The results are used to describe the complicated exchange-mediated diffusion mechanism recently observed in MD simulations [J.E. Black and Zeng-Ju Tian, Phys. Rev. Lett. {\bf 71}, 2445-2448(1993)].Comment: 22 Revtex pages, 9 figures to appear in Phys. Rev.

CGG Repeat-Induced FMR1 Silencing Depends on the Expansion Size in Human iPSCs and Neurons Carrying Unmethylated Full Mutations

In fragile X syndrome (FXS), CGG repeat expansion greater than 200 triplets is believed to trigger FMR1 gene silencing and disease etiology. However, FXS siblings have been identified with more than 200 CGGs, termed unmethylated full mutation (UFM) carriers, without gene silencing and disease symptoms. Here, we show that hypomethylation of the FMR1 promoter is maintained in induced pluripotent stem cells (iPSCs) derived from two UFM individuals. However, a subset of iPSC clones with large CGG expansions carries silenced FMR1. Furthermore, we demonstrate de novo silencing upon expansion of the CGG repeat size. FMR1 does not undergo silencing during neuronal differentiation of UFM iPSCs, and expression of large unmethylated CGG repeats has phenotypic consequences resulting in neurodegenerative features. Our data suggest that UFM individuals do not lack the cell-intrinsic ability to silence FMR1 and that inter-individual variability in the CGG repeat size required for silencing exists in the FXS population

The non-cancer mortality experience of male workers at British Nuclear Fuels plc, 1946–2005

Background Recent studies of the Hiroshima and Nagasaki A-bomb survivors, together with some (but not all) cohorts exposed occupationally or medically to ionizing radiation, have found an increasing trend in mortality from non-malignant disease with increasing radiation dose. The aim of this study was to establish whether such a trend could be found in a large cohort of employees in the UK nuclear industry

A Modified RMCE-Compatible Rosa26 Locus for the Expression of Transgenes from Exogenous Promoters

Generation of gain-of-function transgenic mice by targeting the Rosa26 locus has been established as an alternative to classical transgenic mice produced by pronuclear microinjection. However, targeting transgenes to the endogenous Rosa26 promoter results in moderate ubiquitous expression and is not suitable for high expression levels. Therefore, we now generated a modified Rosa26 (modRosa26) locus that combines efficient targeted transgenesis using recombinase-mediated cassette exchange (RMCE) by Flipase (Flp-RMCE) or Cre recombinase (Cre-RMCE) with transgene expression from exogenous promoters. We silenced the endogenous Rosa26 promoter and characterized several ubiquitous (pCAG, EF1α and CMV) and tissue-specific (VeCad, αSMA) promoters in the modRosa26 locus in vivo. We demonstrate that the ubiquitous pCAG promoter in the modRosa26 locus now offers high transgene expression. While tissue-specific promoters were all active in their cognate tissues they additionally led to rare ectopic expression. To achieve high expression levels in a tissue-specific manner, we therefore combined Flp-RMCE for rapid ES cell targeting, the pCAG promoter for high transgene levels and Cre/LoxP conditional transgene activation using well-characterized Cre lines. Using this approach we generated a Cre/LoxP-inducible reporter mouse line with high EGFP expression levels that enables cell tracing in live cells. A second reporter line expressing luciferase permits efficient monitoring of Cre activity in live animals. Thus, targeting the modRosa26 locus by RMCE minimizes the effort required to target ES cells and generates a tool for the use exogenous promoters in combination with single-copy transgenes for predictable expression in mice

Current trends in cannulation and neuroprotection during surgery of the aortic arch in Europe†‡

OBJECTIVES To conduct a survey across European cardiac centres to evaluate the methods used for cerebral protection during aortic surgery involving the aortic arch. METHODS All European centres were contacted and surgeons were requested to fill out a short, comprehensive questionnaire on an internet-based platform. One-third of more than 400 contacted centres completed the survey correctly. RESULTS The most preferred site for arterial cannulation is the subclavian-axillary, both in acute and chronic presentation. The femoral artery is still frequently used in the acute condition, while the ascending aorta is a frequent second choice in the case of chronic presentation. Bilateral antegrade brain perfusion is chosen by the majority of centres (2/3 of cases), while retrograde perfusion or circulatory arrest is very seldom used and almost exclusively in acute clinical presentation. The same pumping system of the cardio pulmonary bypass is most of the time used for selective cerebral perfusion, and the perfusate temperature is usually maintained between 22 and 26°C. One-third of the centres use lower temperatures. Perfusate flow and pressure are fairly consistent among centres in the range of 10-15 ml/kg and 60 mmHg, respectively. In 60% of cases, barbiturates are added for cerebral protection, while visceral perfusion still receives little attention. Regarding cerebral monitoring, there is a general tendency to use near-infrared spectroscopy associated with bilateral radial pressure measurement. CONCLUSIONS These data represent a snapshot of the strategies used for cerebral protection during major aortic surgery in current practice, and may serve as a reference for standardization and refinement of different approache

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis

One of the important ‘hallmarks’ of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential

Long-term stability of the French Wechsler Intelligence Scale - Fifth edition (WISC-V) scores in a Swiss French-speaking sample

The WISC-V is one of the most used instruments in clinical assessment. The Full Scale IQ (FSIQ) and the five primary index scores are used for individual decisions and predictions. Thus, the stability of these scores across time is crucial. The five index scores are the Verbal Comprehension Index (VCI), the Visual Spatial Index (VSI), the Fluid Reasoning Index (FRI), the Working Memory Index (WMI) and the Processing Speed Index (PSI). The aim of this study was to investigate the long-term stability (interval &gt;1 year) of the French WISC-V scores. 63 Swiss children were assessed twice, using a 1.44 year interval. The mean difference results (t-tests, Cohen’s d) indicated small (FSIQ, VCI, VSI, FRI) to trivial (WMI, PSI) effect sizes, suggesting none or small increase of performance after more than one year. For the stability coefficients (test-retest correlations), only the VSI (.86) and PSI (.85) were stable enough for clinical individual decisions; the other scores were too low for confident individual decisions (&lt;.80). Regarding the intra-individual stability, less than half of the children demonstrated stable intra-individual performance (performance was stable if it was within a confidence interval of ±2 standard errors of measurement). Our results suggest that the VSI and PSI scores are sufficiently stable for clinical decision. Surprisingly, the FSIQ is less stable than these two index scores. These long-term stability results suggest an interpretation of the scores in the “here and now”. Nevertheless, the interpretation of our results should be taken with caution, given the small sample size.</p

Investigating the structure of the French WISC-V for five age groups usingpsychometric network modeling

The most replicated finding in intelligence research is the positive manifold, which refers to the finding that intelligence tests tend to be positively correlated. According to Spearman, this positive manifold can be accounted for by a general factor of intelligence (g factor). The most common interpretation of g is that it represents a general mechanism that influences performance on all intelligence tests. g is considered as a reflective latent variable, a causal psychological attribute. However, recent models suggested that g is a formative latent variable; g is not the cause of the correlations between tests, but the consequence. It does not represent a causal psychological attribute. The psychometric network modeling can be used to test this formative hypothesis, because psychometric network analysis does not assume latent common causes. The aim of this study was to estimate the underlying structure of the Wechsler Intelligence Scale for Children-Fifth Edition (WISC–V) with five standardization sample age groups (6-7, 8-9, 10-11, 12-13, 14-16). Psychometric network analyses were conducted based on the correlation matrices provided for the five age groups in the WISC–V interpretive manual. Psychometric network models revealed 3 clusters (6-7, 10-11, 12-13, 14-16) or 4 clusters of nodes (8-9). The two stable clusters were processing speed and verbal comprehension. The distinction between fluid reasoning and visuospatial ability was never found. Data were not consistent with the five-factors recommended by the publisher of the WISC–V. Psychometric network analysis is an alternative to investigate the underlying structure of intelligence data.</p

Echelonnement Multidimensionnel du WISC-V (Echelle d'intelligence de Wechsler pour enfants et adolescents - 5èd)

Échelonnement Multidimensionnel du WISC-V (Echelle d’intelligence de Wechsler pour enfants et adolescents - 5èd) Selon les développeurs américains et français de la 5ème édition de l’échelle d’intelligence de Wechsler pour enfants et adolescents (WISC-V, Wechsler, 2014, 2016), l’interprétation des scores des sous-tests s’organise autour de 5 indices : Compréhension Verbale (ICV), Visuospatial (IVS), Raisonnement Fluide (IRF), Mémoire de Travail (IMT), et Vitesse de Traitement (IVT). Cette organisation découle d’analyses factorielles confirmatoires réalisées par les développeurs du WISC-V. On peut toutefois noter que cette structure factorielle fait déjà l’objet de débat, puisque certains auteurs ne l’ont pas retrouvée, aussi bien sur la version américaine que française (Beaujean, 2016; Canivez, Watkins, & Dombrowski, 2016, 2017; Dombrowski, Canivez, & Watkins, 2017; Lecerf & Canivez, 2017). Bien que l’étude de la validité interne des tests psychologiques repose le plus souvent sur des analyses factorielles exploratoires et/ou confirmatoires, il est possible de l’étudier avec d’autres méthodes statistiques, comme par exemple les échelonnements multidimensionnels (EMD). Ces méthodes permettent d’obtenir des représentations visuelles des scores, de leurs positions dans un espace euclidien (Jaworska & Chupetlovska-Anastasova, 2009). Dans le domaine de l’intelligence, on peut rappeler que la théorie en facettes développée par Guttman (modèle Radex) repose sur ces méthodes statistiques d’EMD. Selon Guttman, les épreuves se différencient selon 3 dimensions : le processus mental (inférence de règles, application de règles et pratique de règles), la modalité de présentation (verbale, numérique, géométrique), et la modalité de réponse (orale, « papier-crayon », et manipulation manuelle). Récemment, Meyer et Reynolds (2017) ont étudié la structure factorielle de la version américaine du WISC-V à l’aide de l’EMD, et ont observé qu’une solution non métrique à 2 dimensions est acceptable. Meyer et Reynolds observent que les sous-tests Cubes, Puzzles Visuels, Matrices, Balances, Similitudes, Vocabulaire et Information sont des épreuves complexes, qui impliquent l’inférence de règles et l’application de règles. Les épreuves de vitesse de traitement (Code, Symboles et Barrage) sont plus simples et impliquent la pratique de règles..

Etude de la structure factorielle du KABC-II sur un échantillon d'enfants à Haut Potentiel Intellectuel (HPI)

Cette recherche investigue l'influence cognitive sur l'organisation de l'intelligence sur un échantillon d'enfants présentant un Haut Potentiel Intellectuel (HPI)