On the kinematics of a corotating relativistic plasma stream in the perpendicular rotator model of a pulsar magnetosphere

An investigation of the kinematics of a rotating relativistic plasma stream in the perpendicular rotator model of the pulsar magnetosphere is presented. It is assumed that the plasma (ejected from the pulsar) moves along the pulsar magnetic field lines and also corotates with them. The field lines are considered to be radial straight lines, located in the plane which is perpendicular to the pulsar rotation axis. The necessity of taking particle inertia into account is discussed. It is argued that the "massless" ("force-free") approximation cannot be used for the description of this problem. The frame selection is discussed and it is shown that it is convenient to discuss the problem in the noninertial frame of ZAMOs (Zero Angular Momentum Observers). The equation of motion and the exact set of equations describing the behaviour of a relativistic plasma stream in the pulsar magnetosphere is obtained. The possible relevance of this investigation for the understanding of the formation process of a pulsar magnetosphere is discussed.Comment: Plain LaTe

Upregulation of Haploinsufficient Gene Expression in the Brain by Targeting a Long Non-coding RNA Improves Seizure Phenotype in a Model of Dravet Syndrome

AbstractDravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism controlling the expression of SCN1A that is mediated by an antisense non-coding RNA (SCN1ANAT). Using oligonucleotide-based compounds (AntagoNATs) targeting SCN1ANAT we were able to induce specific upregulation of SCN1A both in vitro and in vivo, in the brain of Dravet knock-in mouse model and a non-human primate. AntagoNAT-mediated upregulation of Scn1a in postnatal Dravet mice led to significant improvements in seizure phenotype and excitability of hippocampal interneurons. These results further elucidate the pathophysiology of Dravet syndrome and outline a possible new approach for the treatment of this and other genetic disorders with similar etiology

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Auditory evoked potentials from deaf individuals using cochlear implants

Auditory evoked potentials (AEPs) provide an objective measure central electrode where the grand average amplitudes were largest period (HIGH: mean 244.78±50.18 months, LOW: mean of auditory cortical function. However AEPs from cochlear i l ( ) i d b h l i l f for both groups (approximately FCz). AEP peak amplitudes and l i d i d i i i d 532.44±34.16 months; t(16)=-4.74, p<.001) implant CI) users are contaminated by the electrical artefact d d b th d i I d d t t l i (ICA) latencies were determined using a semi-automatic procedure as produced by the device. Independent component analysis i l t d i kd t ( bill il/ kd t ht l) h b t d t tt t th CI t f t d th implemented in peakdet.m www.billauer.co.peakdet.html). has been reported to attenuate the artefact and recover the AEPs. Here the effects of CI artefact attenuation on the quality of Results the AEPs were systematically investigated Electroencephalogram investigated. data were recorded from 18 adult CI users presented with ICA sensitivity- there was not a single CI user dataset where AEPs auditory and visual stimuli. The CI artefact attenuation rate was were not buried by large electrical CI artefact. calculated to investigate ICA sensitivity and AEP quality was Figure 1 – Cochlear implant (CI) artefact evoked by determined based on a signal to noise ratio ( SNR) measure. ICA g ) different environmental sounds. Panels in the top row specificity was evaluated with a hybrid simulation approach and show the sound profile of two stimuli used in the p y y pp experiment, on the left side a “sheep” sound, on the by comparing visual evoked potentials (VEPs) from CI users with sheep right side a “hitting baseball bat” sound. The panels in and without CI artefact attenuation. The results showed that the middle row show the root mean square (RMS) of the EEG activity of two CI users when stimulated with AEPs could be recovered from all CI users, indicating high i i i li d hi hl l d y f the two sounds, respectively. Both implantees used a sensitivity. Moreover, AEP amplitudes were highly correlated N l CI t th i ht id ith th ESP it G i h d i h i di id l diff ll Nucleus system on the right side with the ESPrit processor and the ACE speech processing strategy. The Figure 5 – Comparison of clinical profiles from cochlear implant (CI) users with low (light grey) and high (dark grey) with age, demonstrating that individual differences were well d CI ith hi h AEP SNR h t i d b p p p g gy topography at the latency of maximum amplitude is illustrated for the same subject on both panels The SNR AEPs. All panels show mean ± SEM values. A) Self-reported duration of deafness in months. B) Age at preserved. users with a high were characterised by a implantation in months i e age when the CI device was switched on C) Experience with the CI device in months D) significantly shorter duration of deafness compared to low AEP panels. panels in the bottom row show RMS activity for months, i.e. on. months. Speech scores: percentage correct on the Bamford-Kowal-Bench (BKB) speech recognition test in quiet. SNR individuals The results confirm that ICA is a valid tool to another two CI users and the respective topography at individuals. the latency of maximum amplitude for one of them attenuate CI artefacts allowing the objective non-invasive study them. Both implantees used the Advanced Bionics CI system ICA specificity: CI users VEPs evaluation artefacts, objective, d l of auditory cortex rehabilitation in CI users on the left side with the AB Harmony processor and the HiRes-S with Fidelity 120 speech processing strategy CI-corrected VEPs were minimal users

Models versus radiosondes in the free atmosphere: A new detection and attribution analysis of temperature

This analysis revisits detection and attribution of free atmosphere temperatures from radiosondes, almost a decade after previous studies. Since that time, data sets have not only become longer, but understanding of observational uncertainty has vastly improved. In addition, a coordinated set of experiments exploring the effects of human and natural forcings on past climate change has been made with a new generation of climate models. These advances allow a much more thorough analysis of the effects of modeling and observational uncertainty on attribution results than previously possible. Observational uncertainty is explored using multiple radiosonde reconstructions including those with ensembles of realizations exploring the effects of processing choices. Modeling uncertainty is explored by calculating multiple fingerprints of natural influence (from changes in solar irradiance and volcanic aerosols) and of human influence (due to greenhouse gases and due to the effects of combined anthropogenic forcings including stratospheric ozone depletion). With increased confidence over previous studies, human influences (both greenhouse gas and other anthropogenic forcings) have been detected in spatiotemporal changes in free atmosphere temperature from 1961 to 2010, irrespective of whether the full atmospheric column (30–850 hPa) is examined or purely the troposphere, with stratospheric ozone depletion dominating the cooling that has been observed in the lower stratosphere. Thus the advances of the last decade yield increased confidence that anthropogenic influences have made a substantial contribution to the evolution of free atmosphere temperatures