Lack of autoantibody production associated with cytomegalovirus infection

To confirm an association between cytomegalovirus (CMV) infection and the presence of antibodies to Smith (Sm), to ribonucleoprotein (RNP), and to a component of the U1 ribonucleoproteins (U1-70 kD), we measured antibodies to these protein antigens using an enzyme immunoassay and an immunoblot. The antibodies were measured in the sera of 80 healthy subjects, one-half of whom were naturally CMV seropositive and one-half were CMV seronegative, and in eight subjects immunized with a live attenuated strain of CMV. None of the vaccinees developed antibodies to Sm, to RNP, or to U1-70 kD at either 4 or 12 months after immunization. Additionally, there was no statistically significant association between levels of antibodies to Sm or to RNP and between sera obtained from vaccinees, natural CMV seropositive individuals, and CMV seronegative individuals. One CMV seropositive serum and one CMV seronegative serum tested positive for antibodies to U1-70 kD. These data indicate that neither wild-type infection nor the live-attenuated Towne vaccine frequently induce autoantibody production

Evidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and progressive weakness. There is considerable inter-patient variability in disease onset and progression, which can confound the results of clinical trials. Here we show that a common null polymorphism (R577X) in ACTN3 results in significantly reduced muscle strength and a longer 10\u2009m walk test time in young, ambulant patients with DMD; both of which are primary outcome measures in clinical trials. We have developed a double knockout mouse model, which also shows reduced muscle strength, but is protected from stretch-induced eccentric damage with age. This suggests that \u3b1-actinin-3 deficiency reduces muscle performance at baseline, but ameliorates the progression of dystrophic pathology. Mechanistically, we show that \u3b1-actinin-3 deficiency triggers an increase in oxidative muscle metabolism through activation of calcineurin, which likely confers the protective effect. Our studies suggest that ACTN3 R577X genotype is a modifier of clinical phenotype in DMD patients

Translational Symmetry Breaking in the Superconducting State of the Cuprates: Analysis of the Quasiparticle Density of States

Motivated by the recent STM experiments of J.E. Hoffman et.al. and C. Howald et.al., we study the effects of weak translational symmetry breaking on the quasiparticle spectrum of a d-wave superconductor. We develop a general formalism to discuss periodic charge order, as well as quasiparticle scattering off localized defects. We argue that the STM experiments in $Bi_2Sr_2CaCu_2O_{8+\delta}$ cannot be explained using a simple charge density wave order parameter, but are consistent with the presence of a periodic modulation in the electron hopping or pairing amplitude. We review the effects of randomness and pinning of the charge order and compare it to the impurity scattering of quasiparticles. We also discuss implications of weak translational symmetry breaking for ARPES experiments.Comment: 12 pages, 9 figs; (v2) minor corrections to formalism, discussions of dispersion, structure factors and sum rules added; (v3) discussion of space-dependent normalization added. To be published in PR

Factors that inhibit snowball Earth simulation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94616/1/palo1176.pd

O/IR Polarimetry for the 2010 Decade (GAN): Science at the Edge, Sharp Tools for All

Science opportunities and recommendations concerning optical/infrared polarimetry for the upcoming decade in the field of Galactic science. Community-based White Paper to Astro2010 in response to the call for such papers.Comment: White Paper to the Galactic Neighborhood (GAN) Science Frontiers Panel of the Astro2010 Decadal Surve

High glucose up-regulates ENaC and SGK1 expression in HCD-cells

Background/Aim: Diabetic nephropathy is associated with progressive renal damage, leading to impaired function and end-stage renal failure. Secondary hypertension stems from a deranged ability of cells within the kidney to resolve and appropriately regulate sodium resorption in response to hyperglycaemia. However, the mechanisms by which glucose alters sodium re-uptake have not been fully characterised. Methods: Here we present RT-PCR, western blot and immunocytochemistry data confirming mRNA and protein expression of the serum and glucocorticoid inducible kinase (SGK1) and the a conducting subunit of the epithelial sodium channel (ENaC) in a model in vitro system of the human cortical collecting duct (HCD). We examined changes in expression of these elements in response to glucose challenge, designed to mimic hyperglycaemia associated with type 2 diabetes mellitus. Changes in Na+ concentration were assessed using single-cell microfluorimetry. Results: Incubation with glucose, the Ca2+-ionophore ionomycin and the cytokine TGF-beta 1 were all found to evoke significant and time-dependent increases in both SGK1 and alpha ENaC protein expression. These molecular changes were correlated to an increase in Na+-uptake at the single-cell level. Conclusion: Together these data offer a potential explanation for glucose-evoked Na+-resorption and a potential contributory role of SGK1 and ENaCs in development of secondary hypertension, commonly linked to diabetic nephropathy

Assessment of ion kinetic effects in shock-driven inertial confinement fusion implosions using fusion burn imaging

The significance and nature of ion kinetic effects in D3He-filled, shock-driven inertial confinement fusion implosions are assessed through measurements of fusion burn profiles. Over this series of experiments, the ratio of ion-ion mean free path to minimum shell radius (the Knudsen number, NK) was varied from 0.3 to 9 in order to probe hydrodynamic-like to strongly kinetic plasma conditions; as the Knudsen number increased, hydrodynamic models increasingly failed to match measured yields, while an empirically-tuned, first-step model of ion kinetic effects better captured the observed yield trends [Rosenberg et al., Phys. Rev. Lett. 112, 185001 (2014)]. Here, spatially resolved measurements of the fusion burn are used to examine kinetic ion transport effects in greater detail, adding an additional dimension of understanding that goes beyond zero-dimensional integrated quantities to one-dimensional profiles. In agreement with the previous findings, a comparison of measured and simulated burn profiles shows that models including ion transport effects are able to better match the experimental results. In implosions characterized by large Knudsen numbers (NK3), the fusion burn profiles predicted by hydrodynamics simulations that exclude ion mean free path effects are peaked far from the origin, in stark disagreement with the experimentally observed profiles, which are centrally peaked. In contrast, a hydrodynamics simulation that includes a model of ion diffusion is able to qualitatively match the measured profile shapes. Therefore, ion diffusion or diffusion-like processes are identified as a plausible explanation of the observed trends, though further refinement of the models is needed for a more complete and quantitative understanding of ion kinetic effects

The TAOS Project Stellar Variability II. Detection of 15 Variable Stars

The Taiwanese-American Occultation Survey (TAOS) project has collected more than a billion photometric measurements since 2005 January. These sky survey data-covering timescales from a fraction of a second to a few hundred days-are a useful source to study stellar variability. A total of 167 star fields, mostly along the ecliptic plane, have been selected for photometric monitoring with the TAOS telescopes. This paper presents our initial analysis of a search for periodic variable stars from the time-series TAOS data on one particular TAOS field, No. 151 (RA = 17^{\rm h}30^{\rm m}6\fs67, Dec = 27\degr17\arcmin 30\arcsec, J2000), which had been observed over 47 epochs in 2005. A total of 81 candidate variables are identified in the 3 square degree field, with magnitudes in the range 8 < R < 16. On the basis of the periodicity and shape of the lightcurves, 29 variables, 15 of which were previously unknown, are classified as RR Lyrae, Cepheid, delta Scuti, SX Phonencis, semi-regular and eclipsing binaries.Comment: 20 pages, 6 figures, accepted in The Astronomical Journa

Development of a Floating Dosage Form of Ranitidine Hydrochloride by Statistical Optimization Technique

The objective of this study was to evaluate the effect of formulation variables on the release properties, floating lag time, and hardness, when developing floating tablets of Ranitidine hydrochloride, by the statistical optimization technique. The formulations were prepared based on 32 factorial design, with polymer ratio (HPMC 100 KM: Xanthan gum) and the amount of aerosil, as two independent formulation variables. The four dependent (response) variables considered were: percentage of drug release at the first hour, T50% (time taken to release 50% of the drug), floating lag time, and hardness of the tablet. The release profile data was subjected to a curve fitting analysis, to describe the release mechanism of the drug from the floating tablet. An increase in drug release was observed with an increase in the polymer ratio, and as the amount of aerosil increased, the hardness of the tablet also increased, without causing any change in the floating lag time. The desirability function was used to optimize the response variables, each having a different target, and the observed responses were in accordance with the experimental values. The results demonstrate the feasibility of the model in the development of floating tablets containing Ranitidine hydrochloride