23 research outputs found

    Eigenmodes and growth rates of relativistic current filamentation instability in a collisional plasma

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    I theoretically found eigenmodes and growth rates of relativistic current filamentation instability in collisional regimes, deriving a generalized dispersion relation from self-consistent beam-Maxwell equations. For symmetrically counterstreaming, fully relativistic electron currents, the collisional coupling between electrons and ions creates the unstable modes of growing oscillation and wave, which stand out for long-wavelength perturbations. In the stronger collisional regime, the growing oscillatory mode tends to be dominant for all wavelengths. In the collisionless limit, those modes vanish, while maintaining another purely growing mode that exactly coincides with a standard relativistic Weibel mode. It is also shown that the effects of electron-electron collisions and thermal spread lower the growth rate of the relativistic Weibel instability. The present mechanisms of filamentation dynamics are essential for transport of homogeneous electron beam produced by the interaction of high power laser pulses with plasma.Comment: 44 pages, 12 figures. Accepted for publication in Phys. Rev.

    Characterization of covalent inhibitors that disrupt the interaction between the tandem SH2 domains of SYK and FCER1G phospho-ITAM

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    RNA sequencing and genetic data support spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) as putative targets to be modulated for Alzheimer’s disease (AD) therapy. FCER1G is a component of Fc receptor complexes that contain an immunoreceptor tyrosine-based activation motif (ITAM). SYK interacts with the Fc receptor by binding to doubly phosphorylated ITAM (p-ITAM) via its two tandem SH2 domains (SYK-tSH2). Interaction of the FCER1G p-ITAM with SYK-tSH2 enables SYK activation via phosphorylation. Since SYK activation is reported to exacerbate AD pathology, we hypothesized that disruption of this interaction would be beneficial for AD patients. Herein, we developed biochemical and biophysical assays to enable the discovery of small molecules that perturb the interaction between the FCER1G p-ITAM and SYKtSH2. We identified two distinct chemotypes using a high-throughput screen (HTS) and orthogonally assessed their binding. Both chemotypes covalently modify SYK-tSH2 and inhibit its interaction with FCER1G p-ITAM, however, these compounds lack selectivity and this limits their utility as chemical tools

    Long-term effects of medical management on growth and weight in individuals with urea cycle disorders

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    Low protein diet and sodium or glycerol phenylbutyrate, two pillars of recommended long-term therapy of individuals with urea cycle disorders (UCDs), involve the risk of iatrogenic growth failure. Limited evidence-based studies hamper our knowledge on the long-term effects of the proposed medical management in individuals with UCDs. We studied the impact of medical management on growth and weight development in 307 individuals longitudinally followed by the Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD). Intrauterine growth of all investigated UCDs and postnatal linear growth of asymptomatic individuals remained unaffected. Symptomatic individuals were at risk of progressive growth retardation independent from the underlying disease and the degree of natural protein restriction. Growth impairment was determined by disease severity and associated with reduced or borderline plasma branched-chain amino acid (BCAA) concentrations. Liver transplantation appeared to have a beneficial effect on growth. Weight development remained unaffected both in asymptomatic and symptomatic individuals. Progressive growth impairment depends on disease severity and plasma BCAA concentrations, but cannot be predicted by the amount of natural protein intake alone. Future clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth in UCDs
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