Electrical properties of ferroelectric YMnO3 films deposited on n-type Si (111) substrates

YMnO3 thin films were grown on n - type Si substrate by nebulized spray pyrolysis in Metal - Ferroelectric - Semiconductor (MFS) configuration. The C-V characteristics of the film in MFS structure exhibit hysteretic behavior consistent with the polarization charge switching direction, with the memory window decreasing with increase in temperature. The density of interface states decreases with the increase in the annealing temperature. Mapping of the silicon energy band gap with the interface states has been carried out. The leakage current measured in the accumulation region, is lower in well-crystallized thin films and obeys a space- charge limited conduction mechanism. The calculated activation energy from the dc leakage current characteristics of Arhennius plot reveals that the activation energy correspond to the oxygen vacancy motionComment: 26 pages, 1 table, 8 figures, submitted to submitted to J. Phys. D; applied physics on 5th feb 200

Genetics and beyond - the transcriptome of human monocytes and disease susceptibility

BACKGROUND: Variability of gene expression in human may link gene sequence variability and phenotypes; however, non-genetic variations, alone or in combination with genetics, may also influence expression traits and have a critical role in physiological and disease processes. METHODOLOGY/PRINCIPAL FINDINGS: To get better insight into the overall variability of gene expression, we assessed the transcriptome of circulating monocytes, a key cell involved in immunity-related diseases and atherosclerosis, in 1,490 unrelated individuals and investigated its association with >675,000 SNPs and 10 common cardiovascular risk factors. Out of 12,808 expressed genes, 2,745 expression quantitative trait loci were detected (P<5.78x10(-12)), most of them (90%) being cis-modulated. Extensive analyses showed that associations identified by genome-wide association studies of lipids, body mass index or blood pressure were rarely compatible with a mediation by monocyte expression level at the locus. At a study-wide level (P<3.9x10(-7)), 1,662 expression traits (13.0%) were significantly associated with at least one risk factor. Genome-wide interaction analyses suggested that genetic variability and risk factors mostly acted additively on gene expression. Because of the structure of correlation among expression traits, the variability of risk factors could be characterized by a limited set of independent gene expressions which may have biological and clinical relevance. For example expression traits associated with cigarette smoking were more strongly associated with carotid atherosclerosis than smoking itself. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the monocyte transcriptome is a potent integrator of genetic and non-genetic influences of relevance for disease pathophysiology and risk assessment

Mapping Through Listening

Gesture-to-sound mapping is generally defined as the association between gestural and sound parameters. This article describes an approach that brings forward the perception-action loop as a fundamental design principle for gesture–sound mapping in digital music instrument. Our approach considers the processes of listening as the foundation – and the first step – in the design of action-sound relationships. In this design process, the relationship between action and sound is derived from actions that can be perceived in the sound. Building on previous works on listening modes and gestural descriptions we proposed to distinguish between three mapping strategies: instantaneous, temporal, and metaphoric. Our approach makes use of machine learning techniques for building prototypes, from digital music instruments to interactive installations. Four different examples of scenarios and prototypes are described and discussed

The biology of inequalities in health: The LIFEPATH project

Socioeconomic differences in health have been consistently observed worldwide. Physical health deteriorates more rapidly with age among men and women with lower socioeconomic status (SES) than among those with higher SES. The biological processes underlying these differences are best understood by adopting a life course approach. In this paper we introduce the pan- European LIFEPATH project which uses multiple cohorts - including biomarker data - to investigate ageing as a phenomenon with two broad stages across life: build-up and decline. The ‘build-up’ stage, from conception and early intra-uterine life to late adolescence or early twenties, is characterised by rapid successions of developmentally and socially sensitive periods. The second stage, starting in early adulthood, is a period of ‘decline’ from maximum attained health to loss of function, overt disease and death. LIFEPATH adopts a study design that integrates social science and public health approaches with biology (including molecular epidemiology), using well-characterised population cohorts and omics measurements (particularly epigenomics). LIFEPATH includes information and biological samples from 17 cohorts, including several with extensive phenotyping and repeat biological samples, and a very large cohort (1 million individuals) without biological samples (WHIP, from Italy). The countries that are covered by the cohorts are France, Italy, Portugal, Ireland, UK, Finland, Switzerland and Australia. These cohorts are only a small proportion of all cohorts available in Europe, but we have chosen them for the combination of good measures of socioeconomic status, risk factors for non-communicable diseases (NCDs) and biomarkers already measured (or availability of blood samples for further testing). The majority of cohorts include ‘hard’ outcomes (diabetes, cancer, Cardiovascular Disease (CVD), total mortality), and the extensively phenotyped cohorts also include several measurements of the functional components of healthy ageing, including frailty, impaired vision, cognitive function, renal and brain function, osteoporosis, sleep disturbances and mental health. All age groups are represented with two birth cohorts, one cohort of adolescents and several cohorts encompassing young adults (age 18 and above). Furthermore, there is a strong representation of elderly subjects in seven cohorts. The specific objectives of the project are: (a) to show that healthy ageing is an achievable goal for society; (b) to improve the understanding of the mechanisms through which healthy ageing pathways diverge by SES, by investigating life course biological pathways using omic technologies; (c) to examine the consequences of the current economic recession on health and the biology of ageing (and the consequent increase in social inequalities); (d) to provide updated, relevant and innovative evidence for healthy ageing policies (particularly ‘health in all policies’) using both observational studies and an experimental approach based on a reanalysis of data from a ‘conditional cash transfer’ randomised experiment in New York and new data collected as part of an earned income tax credit randomised experiment in Atlanta and New York. To achieve these objectives, data are used from three categories of studies: 1. national census-based followup data to obtain mortality by socioeconomic status; 2. cohorts with intense phenotyping and repeat biological samples; 3. large cohorts with biological samples. With these objectives and methodologies, LIFEPATH seeks to provide updated, relevant and innovative evidence to underpin future policies and strategies for the promotion of healthy ageing, targeted disease prevention and clinical interventions that address the issue of social disparities in ageing and the social determinants of health. The present paper describes the design and some initial results of LIFEPATH as an example of the integration of social and biological sciences to provide evidence for public health policies

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

Reduced antioxidant defense in early onset first-episode psychosis: a case-control study

Background:Our objective is to determine the activity of the antioxidant defense system at admission in patients with early onset first psychotic episodes compared with a control group. Methods: Total antioxidant status (TAS) and lipid peroxidation (LOOH) were determined in plasma. Enzyme activities and total glutathione levels were determined in erythrocytes in 102 children and adolescents with a first psychotic episode and 98 healthy controls. Results: A decrease in antioxidant defense was found in patients, measured as decreased TAS and glutathione levels. Lipid damage (LOOH) and glutathione peroxidase activity was higher in patients than controls. Our study shows a decrease in the antioxidant defense system in early onset first episode psychotic patients. Conclusions: Glutathione deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in early-onset schizophrenia. Oxidative damage is present in these patients, and may contribute to its pathophysiology

Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: A multi-cohort analysis

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) has been proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently, and the magnitude of the effects differed depending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception of smoking, which had a significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity

Structure and Functional Analysis of the RNA- and Viral Phosphoprotein-Binding Domain of Respiratory Syncytial Virus M2-1 Protein

Respiratory syncytial virus (RSV) protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp) complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties are related to the core region of M2-1 encompassing residues S58 to K177. Here we report the NMR structure of the RSV M2-158–177 core domain, which is structurally homologous to the C-terminal domain of Ebola virus VP30, a transcription co-factor sharing functional similarity with M2-1. The partial overlap of RNA and P interaction surfaces on M2-158–177, as determined by NMR, rationalizes the previously observed competitive behavior of RNA versus P. Using site-directed mutagenesis, we identified eight residues located on these surfaces that are critical for an efficient transcription activity of the RdRp complex. Single mutations of these residues disrupted specifically either P or RNA binding to M2-1 in vitro. M2-1 recruitment to cytoplasmic inclusion bodies, which are regarded as sites of viral RNA synthesis, was impaired by mutations affecting only binding to P, but not to RNA, suggesting that M2-1 is associated to the holonucleocapsid by interacting with P. These results reveal that RNA and P binding to M2-1 can be uncoupled and that both are critical for the transcriptional antitermination function of M2-1