Candidate hypervelocity stars of spectral type G and K revisited

Hypervelocity stars (HVS) move so fast that they are unbound to the Galaxy. When they were first discovered in 2005, dynamical ejection from the supermassive black hole (SMBH) in the Galactic Centre (GC) was suggested as their origin. The two dozen HVSs known today are young massive B stars, mostly of 3-4 solar masses. Recently, 20 HVS candidates of low mass were discovered in the Segue G and K dwarf sample, but none of them originates from the GC. We embarked on a kinematic analysis of the Segue HVS candidate sample using the full 6D phase space information based on new proper motion measurements. Their orbital properties can then be derived by tracing back their trajectories in different mass models of our Galaxy. We present the results for 14 candidate HVSs, for which proper motion measurements were possible. Significantly lower proper motions than found in the previous study were derived. Considering three different Galactic mass models we find that all stars are bound to the Galaxy. We confirm that the stars do not originate from the GC. The distribution of their proper motions and radial velocities is consistent with predictions for runaway stars ejected from the Galactic disk by the binary supernova mechanism. However, their kinematics are also consistent with old disk membership. Moreover, most stars have rather low metallicities and strong $\alpha$-element enrichment as typical for thick disk and halo stars, whereas the metallicity of the three most metal-rich stars could possibly indicate that they are runaway stars from the thin disk. One star shows halo kinematics.Comment: A&A letter accepte

Accreditation in general practice in Denmark:study protocol for a cluster-randomized controlled trial

BACKGROUND: Accreditation is used increasingly in health systems worldwide. However, there is a lack of evidence on the effects of accreditation, particularly in general practice. In 2016 a mandatory accreditation scheme was initiated in Denmark, and during a 3-year period all practices, as default, should undergo accreditation according to the Danish Healthcare Quality Program. The aim of this study is primarily to evaluate the effects of a mandatory accreditation scheme. METHODS/DESIGN: The study is conducted as a cluster-randomized controlled trial among 1252 practices (clusters) with 2211 general practitioners in Denmark. Practices allocated to accreditation in 2016 serve as the intervention group, and practices allocated to accreditation in 2018 serve as controls. The selected outcomes should meet the following criteria: (1) a high degree of clinical relevance; (2) the possibility to assess changes due to accreditation; (3) availability of data from registers with no self-reporting data. The primary outcome is the number of prescribed drugs in patients older than 65 years. Secondary outcomes are changes in outcomes related to other perspectives of safe medication, good clinical practice and mortality. All outcomes relate to quality indicators included in the Danish Healthcare Quality Program, which is based on general principles for accreditation. DISCUSSION: The consequences of accreditation and standard-setting processes are generally under-researched, particularly in general practice. This is the largest study in general practice with a randomized implementation approach to evaluate the clinical effects of a nation-wide mandatory accreditation scheme in general practice. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02762240. Registered on 24 May 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-017-1818-6) contains supplementary material, which is available to authorized users

Chromosomal aberrations in patients with head and neck squamous cell carcinoma do not vary based on severity of tobacco/alcohol exposure

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) have been causally associated with tobacco and alcohol exposure. However, 10–15% of HNSCC develop in absence of significant carcinogen exposure. Several lines of evidence suggest that the genetic composition of HNSCC varies based on the extent of tobacco/alcohol exposure, however, no genome wide measures have been applied to address this issue. We used comparative genomic hybridization (CGH) to screen for the genetic aberrations in 71 patients with head and neck squamous cell carcinoma and stratified the findings by the status of tobacco/alcohol exposure. RESULTS: Although the median number of abnormalities (9), gains (6) and losses (2) per case and the overall pattern of abnormalities did not vary significantly by the extent of tobacco/alcohol exposure, individual abnormalities segregating these patients were identified. Gain of 1p (p = 0.03) and 3q amplification (p = 0.05) was significantly more common in patients with a history of tobacco/alcohol exposure. CONCLUSIONS: This data suggests that the overall accumulated chromosomal aberrations in head and neck squamous cell carcinoma are not significantly influenced by the severity of tobacco/alcohol exposure with limited exceptions

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia : further evidence and meta-analysis

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PostprintPeer reviewe

Scanning-helium-ion-beam lithography with hydrogen silsesquioxane resist

A scanning-helium-ion-beam microscope is now commercially available. This microscope can be used to perform lithography similar to, but of potentially higher resolution than, scanning electron-beam lithography. This article describes the control of this microscope for lithography via beam steering/blanking electronics and evaluates the high-resolution performance of scanning helium-ion-beam lithography. The authors found that sub-10 nm-half-pitch patterning is feasible. They also measured a point-spread function that indicates a reduction in the micrometer-range proximity effect typical in electron-beam lithography.National Science Foundation (U.S.). Graduate Research Fellowship Progra

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie

Towards the integration and development of a cross-European research network and infrastructure:the DEterminants of DIet and Physical ACtivity (DEDIPAC) Knowledge Hub

To address major societal challenges and enhance cooperation in research across Europe, the European Commission has initiated and facilitated ‘joint programming’. Joint programming is a process by which Member States engage in defining, developing and implementing a common strategic research agenda, based on a shared vision of how to address major societal challenges that no Member State is capable of resolving independently. Setting up a Joint Programming Initiative (JPI) should also contribute to avoiding unnecessary overlap and repetition of research, and enable and enhance the development and use of standardised research methods, procedures and data management. The Determinants of Diet and Physical Activity (DEDIPAC) Knowledge Hub (KH) is the first act of the European JPI ‘A Healthy Diet for a Healthy Life’. The objective of DEDIPAC is to contribute to improving understanding of the determinants of dietary, physical activity and sedentary behaviours. DEDIPAC KH is a multi-disciplinary consortium of 46 consortia and organisations supported by joint programming grants from 12 countries across Europe. The work is divided into three thematic areas: (I) assessment and harmonisation of methods for future research, surveillance and monitoring, and for evaluation of interventions and policies; (II) determinants of dietary, physical activity and sedentary behaviours across the life course and in vulnerable groups; and (III) evaluation and benchmarking of public health and policy interventions aimed at improving dietary, physical activity and sedentary behaviours. In the first three years, DEDIPAC KH will organise, develop, share and harmonise expertise, methods, measures, data and other infrastructure. This should further European research and improve the broad multi-disciplinary approach needed to study the interactions between multilevel determinants in influencing dietary, physical activity and sedentary behaviours. Insights will be translated into more effective interventions and policies for the promotion of healthier behaviours and more effective monitoring and evaluation of the impacts of such intervention

Flavin-Induced Oligomerization in Escherichia coli Adaptive Response Protein AidB

The process known as “adaptive response” allows Escherichia coli to respond to small doses of DNA-methylating agents by upregulating the expression of four proteins. While the role of three of these proteins in mitigating DNA damage is well understood, the function of AidB is less clear. Although AidB is a flavoprotein, no catalytic role has been established for the bound cofactor. Here we investigate the possibility that flavin plays a structural role in the assembly of the AidB tetramer. We report the generation and biophysical characterization of deflavinated AidB and of an AidB mutant that has greatly reduced affinity for flavin adenine dinucleotide (FAD). Using fluorescence quenching and analytical ultracentrifugation, we find that apo AidB has a high affinity for FAD, as indicated by an apparent dissociation constant of 402.1 ± 35.1 nM, and that binding of substoichiometric amounts of FAD triggers a transition in the AidB oligomeric state. In particular, deflavinated AidB is dimeric, whereas the addition of FAD yields a tetramer. We further investigate the dimerization and tetramerization interfaces of AidB by determining a 2.8 Å resolution crystal structure in space group P32 that contains three intact tetramers in the asymmetric unit. Taken together, our findings provide strong evidence that FAD plays a structural role in the formation of tetrameric AidB.National Institutes of Health (U.S.) (grant R01-GM0272663)National Institutes of Health (U.S.) (grant P30-ES002109)National Science Foundation (U.S.) (grant MCB-0543833