Role of Dicer Enzyme in the Regulation of Store Operated Calcium Entry (SOCE) in CD4+ T Cells

Background/Aims: Activation of T cell receptors (TCRs) in CD4+ T cells leads to a cascade of signalling reactions including increase of intracellular calcium (Ca2+) levels with subsequent Ca2+ dependent stimulation of gene expression, proliferation, cell motility and cytokine release. The increase of cytosolic Ca2+ results from intracellular Ca2+ release with subsequent activation of store-operated Ca2+ entry (SOCE). Previous studies suggested miRNAs are required for the development and functions of CD4+ T cells. An enzyme called Dicer is required during the process of manufacturing mature miRNAs from the precursor miRNAs. In this study, we explored whether loss of Dicer in CD4+ T cells affects SOCE and thus Ca2+ dependent regulation of cellular functions. Methods: We tested the expression of Orai1 by q-RT-PCR and flow cytometry. Further, we measured SOCE by an inverted phase-contrast microscope with the Incident-light fluorescence illumination system using Fura-2. Intracellular Ca2+ was also measured by flow cytometry using Ca2+ sensitive dye Fluo-4. Results: We found that in Dicer deficient (DicerΔ/Δ) mice Orai1 was downregulated at mRNA and protein level in CD4+ T cells. Further, SOCE was significantly smaller in DicerΔ/Δ CD4+ T cells than in CD4+ T cells isolated from wild-type (Dicerfl/fl) mice. Conclusion: Our data suggest that miRNAs are required for adequate Ca2+ entry into CD4+ T cells and thus triggering of Ca2+ sensitive immune functions

Impact of deforestation on solid and dissolved organic matter characteristics of tropical peat forests: implications for carbon release

This study compares the organic chemistry of peat beneath one of last remaining pristine tropical peat forests in Southeast Asia with a neighbouring peat dome that has been deforested, but not intentionally drained, in the Belait district of Brunei Darussalam, Borneo. We characterized the solid and dissolved organic matter collected from the two domes, through a combination of methods including elemental analysis, phenolic content and Fourier transform infrared spectroscopy (FTIR) investigation of solid peat, as well as optical characterisation (absorbance, fluorescence) of dissolved organic matter (DOM). The peat had a high content of lignin, consistent with its origin from the Shorea albida trees on the domes. Dissolved organic carbon (DOC) concentration in the pore water was significantly greater in the deforested site (79.9 ± 5.5 mg l[superscript −1]) than the pristine site (62.2 ± 2.2 mg l[superscript −1]). The dissolved organic matter was richer in nitrogen and phenolics in the deforested site. The optical properties (Fluorescence Index) indicated a modification of DOM cycling in the deforested site (enhanced decomposition of the peat and fresh litter). Comparison of the solid peat composition between the two sites also suggests effects of deforestation: sulphur, nitrogen and phenolic contents were higher in the deforested site. Taken together, these observations are consistent with peat enhanced decomposition in the deforested site, even without engineered drainage.Singapore-MIT Alliance for Research and Technology. Center for Environmental Sensing and Modelin

Inclusion of Experimental Information in First Principles Modeling of Materials

We propose a novel approach to model amorphous materials using a first principles density functional method while simultaneously enforcing agreement with selected experimental data. We illustrate our method with applications to amorphous silicon and glassy GeSe$_2$. The structural, vibrational and electronic properties of the models are found to be in agreement with experimental results. The method is general and can be extended to other complex materials.Comment: 11 pages, 8 PostScript figures, submitted to J. Phys.: Condens. Matter in honor of Mike Thorpe's 60th birthda

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients: A Randomized Clinical Trial

Importance: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. Objective: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. Design, setting, and participants: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. Interventions: A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). Main outcomes and measures: The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Results: Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR Conclusions and relevance: In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. Trial registration: ClinicalTrials.gov Identifier: NCT04364737

Far Ultraviolet Absolute Flux of alpha Virginis

We present the far ultraviolet spectrum of alpha Virginis taken with EURD spectrograph on-board MINISAT-01. The spectral range covered is from ~900 to 1080 A with 5 A spectral resolution. We have fitted Kurucz models to IUE spectra of alpha Vir and compared the extension of the model to our wavelengths with EURD data. This comparison shows that EURD fluxes are consistent with the prediction of the model within 20-30%, depending on the reddening assumed. EURD fluxes are consistent with Voyager observations but are ~60% higher than most previous rocket observations of alpha Vir.Comment: 13 pages, 4 figures. Submitted to The Astrophysical Journa

Formalism for dilepton production via virtual photon bremsstrahlung in hadronic reactions

We derive a set of new formulas for various distributions in dilepton production via virtual photon bremsstrahlung from pseudoscalar mesons and unpolarized spin-one-half fermions. These formulas correspond to the leading and sub-leading terms in the Low-Burnett-Kroll expansion for real photon bremsstrahlung. The relation of our leading-term formulas to previous works is also shown. Existing formulas are examined in the light of Lorentz covariance and gauge invariance. Numerical comparison is made in a simple example, where an "exact" formula and real photon data exist. The results reveal large discrepancies among different bremsstrahlung formulas. Of all the leading-term bremsstrahlung formulas, the one derived in this work agrees best with the exact formula. The issues of M_T-scaling and event generators are also addressed.Comment: 37 pages, RevTeX, epsf.sty, 10 embedded figure

Mapping between dissipative and Hamiltonian systems

Theoretical studies of nonequilibrium systems are complicated by the lack of a general framework. In this work we first show that a transformation introduced by Ao recently (J. Phys. A {\bf 37}, L25 (2004)) is related to previous works of Graham (Z. Physik B {\bf 26}, 397 (1977)) and Eyink {\it et al.} (J. Stat. Phys. {\bf 83}, 385 (1996)), which can also be viewed as the generalized application of the Helmholtz theorem in vector calculus. We then show that systems described by ordinary stochastic differential equations with white noise can be mapped to thermostated Hamiltonian systems. A steady-state of a dissipative system corresponds to the equilibrium state of the corresponding Hamiltonian system. These results provides a solid theoretical ground for corresponding studies on nonequilibrium dynamics, especially on nonequilibrium steady state. The mapping permits the application of established techniques and results for Hamiltonian systems to dissipative non-Hamiltonian systems, those for thermodynamic equilibrium states to nonequilibrium steady states. We discuss several implications of the present work.Comment: 18 pages, no figure. final version for publication on J. Phys. A: Math & Theo

A Cost-Effective Design for a Neutrino Factory

There have been active efforts in the U.S., Europe, and Japan on the design of a Neutrino Factory. This type of facility produces intense beams of neutrinos from the decay of muons in a high energy storage ring. In the U.S., a second detailed Feasibility Study (FS2) for a Neutrino Factory was completed in 2001. Since that report was published, new ideas in bunching, cooling and acceleration of muon beams have been developed. We have incorporated these ideas into a new facility design, which we designate as Study 2B (ST2B), that should lead to significant cost savings over the FS2 design.Comment: 46 pages, 38 figures; to be submitted to Physical Review Special Topics: Accelerators and Beam

Analysis of charmonium production at fixed-target experiments in the NRQCD approach

We present an analysis of the existing data on charmonium hadro-production based on non-relativistic QCD (NRQCD) calculations at the next-to-leading order (NLO). All the data on J/psi and psi' production in fixed-target experiments and on pp collisions at low energy are included. We find that the amount of color octet contribution needed to describe the data is about 1/10 of that found at the Tevatron