Abstract
Cosmic ray (CR) currents through magnetized plasma drive strong instabilities producing amplification of the magnetic field. This amplification helps explain the CR energy spectrum as well ...as observations of supernova remnants and radio galaxy hotspots. Using magnetohydrodynamic simulations, we study the behaviour of the non-resonant hybrid (NRH) instability (also known as the Bell instability) in the case of CR currents perpendicular and parallel to the initial magnetic field. We demonstrate that extending simulations of the perpendicular case to 3D reveals a different character to the turbulence from that observed in 2D. Despite these differences, in 3D the perpendicular NRH instability still grows exponentially far into the non-linear regime with a similar growth rate to both the 2D perpendicular and 3D parallel situations. We introduce some simple analytical models to elucidate the physical behaviour, using them to demonstrate that the transition to the non-linear regime is governed by the growth of thermal pressure inside dense filaments at the edges of the expanding loops. We discuss our results in the context of supernova remnants and jets in radio galaxies. Our work shows that the NRH instability can amplify magnetic fields to many times their initial value in parallel and perpendicular shocks.
During the development of humoral immunity, activated B lymphocytes undergo vigorous proliferative, transcriptional, metabolic, and DNA remodeling activities; hence, their genomes are constantly ...exposed to an onslaught of genotoxic agents and processes. Branched DNA intermediates generated during replication and recombinational repair pose genomic threats if left unresolved and so, they must be eliminated by structure-selective endonucleases to preserve the integrity of these DNA transactions for the faithful duplication and propagation of genetic information. To investigate the role of two such enzymes, GEN1 and MUS81, in B cell biology, we established B-cell conditional knockout mouse models and found that deletion of GEN1 and MUS81 in early B-cell precursors abrogates the development and maturation of B-lineage cells while the loss of these enzymes in mature B cells inhibit the generation of robust germinal centers. Upon activation, these double-null mature B lymphocytes fail to proliferate and survive while exhibiting transcriptional signatures of p53 signaling, apoptosis, and type I interferon response. Metaphase spreads of these endonuclease-deficient cells showed severe and diverse chromosomal abnormalities, including a preponderance of chromosome breaks, consistent with a defect in resolving recombination intermediates. These observations underscore the pivotal roles of GEN1 and MUS81 in safeguarding the genome to ensure the proper development and proliferation of B lymphocytes.
The development of drugs that can inactivate disease-causing cells (e.g. cancer cells or parasites) without causing collateral damage to healthy or to host cells is complicated by the fact that many ...proteins are very similar between organisms. Nevertheless, due to subtle, quantitative differences between the biochemical reaction networks of target cell and host, a drug can limit the flux of the same essential process in one organism more than in another. We identified precise criteria for this 'network-based' drug selectivity, which can serve as an alternative or additive to structural differences. We combined computational and experimental approaches to compare energy metabolism in the causative agent of sleeping sickness, Trypanosoma brucei, with that of human erythrocytes, and identified glucose transport and glyceraldehyde-3-phosphate dehydrogenase as the most selective antiparasitic targets. Computational predictions were validated experimentally in a novel parasite-erythrocytes co-culture system. Glucose-transport inhibitors killed trypanosomes without killing erythrocytes, neurons or liver cells.
Peripheral neutrophil hyper-responsiveness in chronic periodontitis leads to excessive reactive oxygen species (ROS) production. We aimed to determine whether neutrophil hyper-responsiveness was ...constitutive or reactive, and to discover the effect of non-surgical therapy. Peripheral blood neutrophils from patients (n = 19), before and 3 months after therapy, and matched control individuals were Fcγ-receptor-stimulated with/without priming with P. gingivalis and F. nucleatum. Total and extracellular ROS were determined by luminol/isoluminol chemiluminescence. The high total ROS generation of patients’ neutrophils compared with that of control individuals (P = 0.016) continued at a reduced level post-therapy (P = 0.059). Reduced activity post-therapy was also seen with priming. Unstimulated total ROS levels did not differ between patients and control individuals before or after therapy. However, the high unstimulated, extracellular ROS production by patients’ neutrophils compared with control individuals (P < 0.05) continued post-therapy and was unaffected by priming. Therapy reduced Fcγ-receptor-stimulated total ROS production, but not unstimulated extracellular radical release, suggesting that constitutive and reactive mechanisms underlie neutrophil hyper-responsiveness.
We solve the linearised Vlasov-Fokker-Planck (VFP) equation to show that heat flow or an electrical current in a magnetized collisional plasma is unstable to the growth of a circularly polarised ...transverse perturbation to a zeroth order uniform magnetic field. The Braginskii 1965 Rev Plasma Phys 1 205 transport equations exhibit the same instability in the appropriate limit. This is relevant to laser-produced plasmas, inertial fusion energy (IFE) and to dense cold interstellar plasmas.
ABSTRACT We report the discovery and analysis of a very strong magnetic field in the rapidly rotating early B-type star HR5907, based on observations obtained as part of the Magnetism in Massive ...Stars (MiMeS) project. We infer a rotation period of 0.508276+0.000015-0.000012d from photometric and Hα EW measurements, making this the shortest period, non-degenerate, magnetic massive star known to date. From the comparison of IUE UV and optical spectroscopy with LTE bruce/kylie models we find a solid-angle integrated, uniform black-body temperature of 17000 ± 1000K, a projected rotational velocity of 290 ± 10kms-1, an equatorial radius of 3.1 ± 0.2R, a stellar mass of 5.5 ± 0.5M, and an inclination angle of the rotation axis to our line-of-sight of 70 ± 10°. Our measurements of the longitudinal magnetic field, which vary between -500 and -2000G, phase coherently with the rotation period and imply a surface dipole field strength of 15.7kG. On the other hand, from fits to mean Least-Squares Deconvolved Stokes V line profiles we infer a dipole field strength of 10.4kG. This disagreement may result from a magnetic configuration more complex than our model, and/or from the non-uniform helium surface abundance distribution. In either case we obtain a magnetic obliquity nearly aligned with the rotation axis (). Our optical spectroscopy also shows weak variability in carbon, silicon and nitrogen lines. The emission variability in hydrogen Balmer and Paschen lines indicates the presence of a dense, highly structured magnetosphere, interpreted as a centrifugally supported, magnetically confined circumstellar disc. PUBLICATION ABSTRACT
Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few ...side-effects, for intractable depression.
An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically.
The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (> or = 50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%).
VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.
Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies.
We studied 11 patients with abdominal ...pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance. Whole-exome sequencing was performed to identify gene variants. We evaluated the function of CD55 in patients' cells, which we confirmed by means of exogenous induction of expression of CD55.
We identified homozygous loss-of-function mutations in the gene encoding CD55 (decay-accelerating factor), which lead to loss of protein expression. Patients' T lymphocytes showed increased complement activation causing surface deposition of complement and the generation of soluble C5a. Costimulatory function and cytokine modulation by CD55 were defective. Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation.
CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
Global efforts to upgrade water, drainage, and sanitation services are hampered by hydrometeorological data-scarcity plus uncertainty about climate change. Intensity–duration–frequency (IDF) tables ...are used routinely to design water infrastructure so offer an entry point for adapting engineering standards. This paper begins with a novel procedure for guiding downscaling predictor variable selection for heavy rainfall simulation using media reports of pluvial flooding. We then present a three-step workflow to: (1) spatially downscale daily rainfall from grid-to-point resolutions; (2) temporally scale from daily series to sub-daily extreme rainfalls and; (3) test methods of temporal scaling of extreme rainfalls
within
Regional Climate Model (RCM) simulations under changed climate conditions. Critically, we compare the methods of moments and of parameters for temporal scaling annual maximum series of daily rainfall into sub-daily extreme rainfalls, whilst accounting for rainfall intermittency. The methods are applied to Kampala, Uganda and Kisumu, Kenya using the Statistical Downscaling Model (SDSM), two RCM simulations covering East Africa (CP4 and P25), and in hybrid form (RCM-SDSM). We demonstrate that Gumbel parameters (and IDF tables) can be reliably scaled to durations of 3 h within observations and RCMs. Our hybrid RCM-SDSM scaling reduces errors in IDF estimates for the present climate when compared with direct RCM output. Credible parameter scaling relationships are also found within RCM simulations under changed climate conditions. We then discuss the practical aspects of applying such workflows to other city-regions.
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