Charged Particle Motion in a Highly Ionized Plasma

A recently introduced method utilizing dimensional continuation is employed to compute the energy loss rate for a non-relativistic particle moving through a highly ionized plasma. No restriction is made on the charge, mass, or speed of this particle. It is, however, assumed that the plasma is not strongly coupled in the sense that the dimensionless plasma coupling parameter g=e^2\kappa_D/ 4\pi T is small, where \kappa_D is the Debye wave number of the plasma. To leading and next-to-leading order in this coupling, dE/dx is of the generic form g^2 \ln[C g^2]. The precise numerical coefficient out in front of the logarithm is well known. We compute the constant C under the logarithm exactly for arbitrary particle speeds. Our exact results differ from approximations given in the literature. The differences are in the range of 20% for cases relevant to inertial confinement fusion experiments. The same method is also employed to compute the rate of momentum loss for a projectile moving in a plasma, and the rate at which two plasmas at different temperatures come into thermal equilibrium. Again these calculations are done precisely to the order given above. The loss rates of energy and momentum uniquely define a Fokker-Planck equation that describes particle motion in the plasma. The coefficients determined in this way are thus well-defined, contain no arbitrary parameters or cutoffs, and are accurate to the order described. This Fokker-Planck equation describes the longitudinal straggling and the transverse diffusion of a beam of particles. It should be emphasized that our work does not involve a model, but rather it is a precisely defined evaluation of the leading terms in a well-defined perturbation theory.Comment: Comments: Published in Phys. Rep. 410/4 (2005) 237; RevTeX, 111 Pages, 17 Figures; Transcription error corrected in temperature equilibration rate (3.61) and (12.44) which replaces \gamma-2 by \gamma-

Familial Amyotrophic Lateral Sclerosis-associated Mutations Decrease the Thermal Stability of Distinctly Metallated Species of Human Copper/Zinc Superoxide Dismutase

We report the thermal stability of wild type (WT) and 14 different variants of human copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis (FALS). Multiple endothermic unfolding transitions were observed by differential scanning calorimetry for partially metallated SOD1 enzymes isolated from a baculovirus system. We correlated the metal ion contents of SOD1 variants with the occurrence of distinct melting transitions. Altered thermal stability upon reduction of copper with dithionite identified transitions resulting from the unfolding of copper-containing SOD1 species. We demonstrated that copper or zinc binding to a subset of “WT-like” FALS mutants (A4V, L38V, G41S, G72S, D76Y, D90A, G93A, and E133Δ) conferred a similar degree of incremental stabilization as did metal ion binding to WT SOD1. However, these mutants were all destabilized by ∼1–6 °C compared with the corresponding WT SOD1 species. Most of the “metal binding region” FALS mutants (H46R, G85R, D124V, D125H, and S134N) exhibited transitions that probably resulted from unfolding of metal-free species at ∼4–12 °C below the observed melting of the least stable WT species. We conclude that decreased conformational stability shared by all of these mutant SOD1s may contribute to SOD1 toxicity in FALS

Communications Biophysics

Contains reports on three research projects

Communications Biophysics

Contains reports on four research projects

Communications Biophysics

Contains reports on six research projects

Communications Biophysics

Contains research objectives and reports on three research projects.U.S. Air Force under Contract AF19(604)-411

CPT and Lorentz Tests in Penning Traps

A theoretical analysis is performed of Penning-trap experiments testing CPT and Lorentz symmetry through measurements of anomalous magnetic moments and charge-to-mass ratios. Possible CPT and Lorentz violations arising from spontaneous symmetry breaking at a fundamental level are treated in the context of a general extension of the SU(3) x SU(2) x U(1) standard model and its restriction to quantum electrodynamics. We describe signals that might appear in principle, introduce suitable figures of merit, and estimate CPT and Lorentz bounds attainable in present and future Penning-trap experiments. Experiments measuring anomaly frequencies are found to provide the sharpest tests of CPT symmetry. Bounds are attainable of approximately $10^{-20}$ in the electron-positron case and of $10^{-23}$ for a suggested experiment with protons and antiprotons. Searches for diurnal frequency variations in these experiments could also limit certain types of Lorentz violation to the level of $10^{-18}$ in the electron-positron system and others at the level of $10^{-21}$ in the proton-antiproton system. In contrast, measurements comparing cyclotron frequencies are sensitive within the present theoretical framework to different kinds of Lorentz violation that preserve CPT. Constraints could be obtained on one figure of merit in the electron-positron system at the level of $10^{-16}$, on another in the proton-antiproton system at $10^{-24}$, and on a third at $10^{-25}$ using comparisons of $H^-$ ions with antiprotons.Comment: 31 pages, published in Physical Review

Longitudinal biomarkers in amyotrophic lateral sclerosis

OBJECTIVE: To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, and assess their utility as pharmacodynamic biomarkers for monitoring treatment effects. METHODS: De-identified, longitudinal plasma, and cerebrospinal fluid (CSF) samples from PALS (n = 108; 85 with samples from \u3e /=2 visits) and controls without neurological disease (n = 41) were obtained from the Northeast ALS Consortium (NEALS) Biofluid Repository. Seventeen of 108 PALS had familial ALS, of whom 10 had C9orf72 mutations. Additional healthy control CSF samples (n = 35) were obtained from multiple sources. We stratified PALS into fast- and slow-progression subgroups using the ALS Functional Rating Scale-Revised change rate. We compared cytokines/chemokines and neurofilament (NF) levels between PALS and controls, among progression subgroups, and in those with C9orf72 mutations. RESULTS: We found significant elevations of cytokines, including MCP-1, IL-18, and neurofilaments (NFs), indicators of neurodegeneration, in PALS versus controls. Among PALS, these cytokines and NFs were significantly higher in fast-progression and C9orf72 mutation subgroups versus slow progressors. Analyte levels were generally stable over time, a key feature for monitoring treatment effects. We demonstrated that CSF/plasma neurofilament light chain (NFL) levels may predict disease progression, and stratification by NFL levels can enrich for more homogeneous patient groups. INTERPRETATION: Longitudinal stability of cytokines and NFs in PALS support their use for monitoring responses to immunomodulatory and neuroprotective treatments. NFs also have prognostic value for fast-progression patients and may be used to select similar patient subsets in clinical trials

Effect of maternal Schistosoma mansoni infection and praziquantel treatment during pregnancy on Schistosoma mansoni infection and immune responsiveness among offspring at age five years.

INTRODUCTION: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. METHODS: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. RESULTS: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. CONCLUSION: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease