Analysis of LIGO data for gravitational waves from binary neutron stars

We report on a search for gravitational waves from coalescing compact binary systems in the Milky Way and the Magellanic Clouds. The analysis uses data taken by two of the three LIGO interferometers during the first LIGO science run and illustrates a method of setting upper limits on inspiral event rates using interferometer data. The analysis pipeline is described with particular attention to data selection and coincidence between the two interferometers. We establish an observational upper limit of $\mathcal{R}<$1.7 \times 10^{2}$per year per Milky Way Equivalent Galaxy (MWEG), with 90coalescence rate of binary systems in which each component has a mass in the range 1--3$M_\odot$.Comment: 17 pages, 9 figure

Narrative Exposure Therapy for Posttraumatic Stress Disorder associated with repeated interpersonal trauma in patients with Severe Mental Illness: a mixed methods design

Background: In the Netherlands, most patients with severe mental illness (SMI) receive flexible assertive community treatment (FACT) provided by multidisciplinary community mental health teams. SMI patients with comorbid posttraumatic stress disorder (PTSD) are sometimes offered evidence-based trauma-focused treatment like eye movement desensitization reprocessing or prolonged exposure. There is a large amount of evidence for the effectiveness of narrative exposure therapy (NET) within various vulnerable patient groups with repeated interpersonal trauma. Some FACT-teams provide NET for patients with comorbid PTSD, which is promising, but has not been specifically studied in SMI patients. Objectives: The primary aim is to evaluate NET in SMI patients with comorbid PTSD associated with repeated interpersonal trauma to get insight into whether (1) PTSD and dissociative symptoms changes and (2) changes occur in the present SMI symptoms, care needs, quality of life, global functioning, and care consumption. The second aim is to gain insight into patients’ experiences with NET and to identify influencing factors on treatment results. Methods: This study will have a mixed methods convergent design consisting of quantitative repeated measures and qualitative semi-structured in-depth interviews based on Grounded Theory. The study population will include adult SMI outpatients (n=25) with comorbid PTSD and receiving NET. The quantitative study parameters will be existence and severity of PTSD, dissociative, and SMI symptoms; care needs; quality of life; global functioning; and care consumption. In a longitudinal analysis, outcomes will be analyzed using mixed models to estimate the difference in means between baseline and repeated measurements. The qualitative study parameters will be experiences with NET and perceived factors for success or failure. Integration of quantitative and qualitative results will be focused on interpreting how qualitative results enhance the understanding of quantitative outcomes. Discussion: The results of this study will provide more insight into influencing factors for clinical changes in this population

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Production of Slit2 LRR domains in mammalian cells for structural studies and the structure of human Slit2 domain 3

Slit2 and Roundabout 1 (Robo1) provide a key ligand-receptor interaction for the navigation of commissural neurons during the development of the central nervous system. Slit2 is a large multidomain protein containing an unusual domain organization of four tandem leucine-rich repeat (LRR) domains at its N-terminus. These domains are well known to mediate protein-protein interactions; indeed, the Robo1-binding region has been mapped to the concave face of the second LRR domain. It has also been shown that the fourth LRR domain may mediate Slit dimerization and that both the first and second domains can bind heparin. Thus, while roles have been ascribed for three of the LRR domains, there is still no known role for the third domain. Each of the four LRR domains from human Slit2 have now been successfully expressed in milligram quantities using expression in mammalian cells. Here, the crystallization of the second and third LRR domains and the structure of the third LRR domain are presented. This is the first structure of an LRR domain from human Slit2, which has an extra repeat compared with the Drosophila homologue. It is proposed that a highly conserved patch of surface residues on the concave face may mediate any protein-protein interactions involving this LRR domain, a result that will be useful in guiding further studies on Slit2

Cloning, expression, crystallization and preliminary X-ray analysis of the first two Ig domains from human Roundabout 1 (Robo1).

Activation of Roundabout 1 (Robo1) by Slit proteins results in axon repulsion from the midline. Robo1 is a large transmembrane receptor expressed on the axon growth cone and the minimal Robo1-binding region required for Slit activation has been mapped to the N-terminal Ig1-2 domains. The cDNA encoding the first two Ig domains of Robo1 has been cloned and the protein has been expressed in HEK293 EBNA-1 mammalian cells. Here, the purification and crystallization conditions of this Robo1 construct are reported. The crystals are orthorhombic, space group P21212, with unit-cell parameters a = 38.8, b = 69.4, c = 103.3 Å and one molecule in the asymmetric unit. X-ray diffraction data have been collected to 2.8 Å resolution on beamline ID29 at the ESRF

Structural insights into the Slit-Robo complex

Slits are large multidomain leucine-rich repeat (LRR)-containing proteins that provide crucial guidance cues in neuronal and vascular development. More recently, Slits have been implicated in heart morphogenesis, angiogenesis, and tumor metastasis. Slits are ligands for the Robo (Roundabout) receptors, which belong to the Ig superfamily of transmembrane signaling molecules. The Slit-Robo interaction is mediated by the second LRR domain of Slit and the two N-terminal Ig domains of Robo, but the molecular details of this interaction and how it induces signaling remain unclear. Here we describe the crystal structures of the second LRR domain of human Slit2 (Slit2 D2), the first two Ig domains of its receptor Robo1 (Ig1-2), and the minimal complex between these proteins (Slit2 D2-Robo1 Ig1). Slit2 D2 binds with its concave surface to the side of Ig1 with electrostatic and hydrophobic contact regions mediated by residues that are conserved in other family members. Surface plasmon resonance experiments and a mutational analysis of the interface confirm that Ig1 is the primary domain for binding Slit2. These structures provide molecular insight into Slit-Robo complex formation and will be important for the development of novel cancer therapeutics