Measurement of the conductance of a hydrogen molecule

Recent years have shown steady progress in research towards molecular electronics [1,2], where molecules have been investigated as switches [3-5], diodes [6], and electronic mixers [7]. In much of the previous work a Scanning Tunnelling Microscope was employed to address an individual molecule. As this arrangement does not provide long-term stability, more recently metal-molecule-metal links have been made using break junction devices [8-10]. However, it has been difficult to establish unambiguously that a single molecule forms the contact [11]. Here, we show that a single H2 molecule can form a stable bridge between Pt electrodes. In contrast to results for other organic molecules, the bridge has a nearly perfect conductance of one quantum unit, carried by a single channel. The H2-bridge provides a simple test system and a fundamental step towards understanding transport properties of single-molecule devices.Comment: 6 pages, 4 figure

CYGD: the Comprehensive Yeast Genome Database

The Comprehensive Yeast Genome Database (CYGD) compiles a comprehensive data resource for information on the cellular functions of the yeast Saccharomyces cerevisiae and related species, chosen as the best understood model organism for eukaryotes. The database serves as a common resource generated by a European consortium, going beyond the provision of sequence information and functional annotations on individual genes and proteins. In addition, it provides information on the physical and functional interactions among proteins as well as other genetic elements. These cellular networks include metabolic and regulatory pathways, signal transduction and transport processes as well as co-regulated gene clusters. As more yeast genomes are published, their annotation becomes greatly facilitated using S.cerevisiae as a reference. CYGD provides a way of exploring related genomes with the aid of the S.cerevisiae genome as a backbone and SIMAP, the Similarity Matrix of Proteins. The comprehensive resource is available under http://mips.gsf.de/genre/proj/yeast/

Implementation of a guideline for local health policy making by regional health services: exploring determinants of use by a web survey.

Previous evaluation showed insufficient use of a national guideline for integrated local health policy by Regional Health Services (RHS) in the Netherlands. The guideline focuses on five health topics and includes five checklists to support integrated municipal health policies. This study explores the determinants of guideline use by regional Dutch health professionals

Spectral optical monitoring of 3C390.3 in 1995-2007: I. Light curves and flux variation of the continuum and broad lines

Here we present the results of the long-term (1995-2007) spectral monitoring of the broad line radio galaxy \object{3C~390.3}, a well known AGN with the double peaked broad emission lines, usually assumed to be emitted from an accretion disk. To explore dimensions and structure of the BLR, we analyze the light curves of the broad H$\alpha$ and H$\beta$ line fluxes and the continuum flux. In order to find changes in the BLR, we analyze the H$\alpha$ and H$\beta$ line profiles, as well as the change in the line profiles during the monitoring period. First we try to find a periodicity in the continuum and H$\beta$ light curves, finding that there is a good chance for quasi-periodical oscillations. Using the line shapes and their characteristics (as e.g. peaks separation and their intensity ratio, or FWHM) of broad H$\beta$ and H$\alpha$ lines, we discuss the structure of the BLR. Also, we cross-correlate the continuum flux with H$\beta$ and H$\alpha$ lines to find dimensions of the BLR. We found that during the monitoring period the broad emission component of the H$\alpha$ and H$\beta$ lines, and the continuum flux varied by a factor of $\approx$4-5. Also, we detected different structure in the line profiles of H$\alpha$ and H$\beta$. It seems that an additional central component is present and superposed to the disk emission. In the period of high activity (after 2002), H$\beta$ became broader than H$\alpha$ and red wing of H$\beta$ was higher than the one of H$\alpha$. We found time lags of $\sim$95 days between the continuum and H$\beta$ flux, and about 120 days between the continuum and H$\alpha$ flux. Variation in the line profiles, as well as correlation between the line and continuum flux during the monitoring period is in the favor of the disk origin of the broad lines with the possible contribution of some additional region and/or some kind of perturbation in the disk.Comment: 32 pages, accepted to A&A, typos correcte

SRAO CO Observation of 11 Supernova Remnants in l = 70 to 190 deg

We present the results of 12CO J = 1-0 line observations of eleven Galactic supernova remnants (SNRs) obtained using the Seoul Radio Astronomy Observatory (SRAO) 6-m radio telescope. The observation was made as a part of the SRAO CO survey of SNRs between l = 70 and 190 deg, which is intended to identify SNRs interacting with molecular clouds. The mapping areas for the individual SNRs are determined to cover their full extent in the radio continuum. We used halfbeam grid spacing (60") for 9 SNRs and full-beam grid spacing (120") for the rest. We detected CO emission towards most of the remnants. In six SNRs, molecular clouds showed a good spatial relation with their radio morphology, although no direct evidence for the interaction was detected. Two SNRs are particularly interesting: G85.4+0.7, where there is a filamentary molecular cloud along the radio shell, and 3C434.1, where a large molecular cloud appears to block the western half of the remnant. We briefly summarize the results obtained for individual SNRs.Comment: Accepted for publication in Astrophysics & Space Science. 12 pages, 12 figures, and 3 table

Conformational Preferences of a 14-Residue Fibrillogenic Peptide from Acetylcholinesterase†

A 14-residue fragment from near the C-terminus of the enzyme acetylcholinesterase (AChE) is believed to have a neurotoxic/neurotrophic effect acting via an unknown pathway. While the peptide is α-helical in the full-length enzyme, the structure and association mechanism of the fragment are unknown. Using multiple molecular dynamics simulations, starting from a tetrameric complex of the association domain of AChE and systematicall disassembled subsets that include the peptide fragment, we show that the fragment is incapable of retaining its helicity in solution. Extensive replica exchange Monte Carlo folding and unfolding simulations in implicit solvent with capped and uncappted termini failed to converge to any consistent cluster of structures, suggesting that the fragment remains largely unstructured in solution under the conditions considered. Furthermore, extended molecular dynamics simulations of two steric zipper models show that the peptide is likely to form a zipper with antiparallel sheets and that peptides with mutations known to prevent fibril formation likely do so by interfering with this packing. The results demonstrate how the local environment of a peptide can stabilize a particular conformation

A case series of familial ARID1B variants illustrating variable expression and suggestions to update the ACMG criteria

ARID1B is one of the most frequently mutated genes in intellectual disability (~1%). Most variants are readily classified, since they are de novo and are predicted to lead to loss of function, and therefore classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines for the interpretation of sequence variants. However, familial loss-of-function variants can also occur and can be challenging to interpret. Such variants may be pathogenic with variable expression, causing only a mild phenotype in a parent. Alternatively, since some regions of the ARID1B gene seem to be lacking pathogenic variants, loss-of-function variants in those regions may not lead to ARID1B haploinsufficiency and may therefore be benign. We describe 12 families with potential loss-of-function variants, which were either familial or with unknown inheritance and were in regions where pathogenic variants have not been described or are otherwise challenging to interpret. We performed detailed clinical and DNA methylation studies, which allowed us to confidently classify most variants. In five families we observed transmission of pathogenic variants, confirming their highly variable expression. Our findings provide further evidence for an alternative translational start site and we suggest updates for the ACMG guidelines for the interpretation of sequence variants to incorporate DNA methylation studies and facial analyses

Identifying Human Disease Genes through Cross-Species Gene Mapping of Evolutionary Conserved Processes

Understanding complex networks that modulate development in humans is hampered by genetic and phenotypic heterogeneity within and between populations. Here we present a method that exploits natural variation in highly diverse mouse genetic reference panels in which genetic and environmental factors can be tightly controlled. The aim of our study is to test a cross-species genetic mapping strategy, which compares data of gene mapping in human patients with functional data obtained by QTL mapping in recombinant inbred mouse strains in order to prioritize human disease candidate genes.We exploit evolutionary conservation of developmental phenotypes to discover gene variants that influence brain development in humans. We studied corpus callosum volume in a recombinant inbred mouse panel (C57BL/6J×DBA/2J, BXD strains) using high-field strength MRI technology. We aligned mouse mapping results for this neuro-anatomical phenotype with genetic data from patients with abnormal corpus callosum (ACC) development.).This approach that exploits highly diverse mouse strains provides an efficient and effective translational bridge to study the etiology of human developmental disorders, such as autism and schizophrenia