Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis

Myeloid-derived cells play important modulatory and effector roles in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells, composed of monocytic (MO) and polymorphonuclear (PMN) fractions, which can suppress T cell activities in EAE. Their role in MS remains poorly characterized. We found decreased numbers of circulating MDSCs, driven by lower frequencies of the MO-MDSCs, and higher MDSC expression of microRNA miR-223 in MS versus healthy subjects. To gain mechanistic insights, we interrogated the EAE model. MiR-223 knock out (miR-223 12/ 12) mice developed less severe EAE with increased MDSC numbers in the spleen and spinal cord compared to littermate controls. MiR-223 12/ 12 MO-MDSCs suppressed T cell proliferation and cytokine production in vitro and EAE in vivo more than wild-type MO-MDSCs. They also displayed an increased expression of critical mediators of MDSC suppressive function, Arginase-1(Arg1), and the signal transducer and activator of transcription 3 (Stat3), which herein, we demonstrate being an miR-223 target gene. Consistently, MDSCs from MS patients displayed decreased STAT3 and ARG1 expression compared with healthy controls, suggesting that circulating MDSCs in MS are not only reduced in numbers but also less suppressive. These results support a critical role for miR-223 in modulating MDSC biology in EAE and in MS and suggest potential novel therapeutic applications

Electron Spin Relaxation in a Semiconductor Quantum Well

A fully microscopic theory of electron spin relaxation by the D'yakonov-Perel' type spin-orbit coupling is developed for a semiconductor quantum well with a magnetic field applied in the growth direction of the well. We derive the Bloch equations for an electron spin in the well and define microscopic expressions for the spin relaxation times. The dependencies of the electron spin relaxation rate on the lowest quantum well subband energy, magnetic field and temperature are analyzed.Comment: Revised version as will appear in Physical Review

Higgs Scalars in the Minimal Non-minimal Supersymmetric Standard Model

We consider the simplest and most economic version among the proposed non-minimal supersymmetric models, in which the $\mu$-parameter is promoted to a singlet superfield, whose all self-couplings are absent from the renormalizable superpotential. Such a particularly simple form of the renormalizable superpotential may be enforced by discrete $R$-symmetries which are extended to the gravity-induced non-renormalizable operators as well. We show explicitly that within the supergravity-mediated supersymmetry-breaking scenario, the potentially dangerous divergent tadpoles associated with the presence of the gauge singlet first appear at loop levels higher than 5 and therefore do not destabilize the gauge hierarchy. The model provides a natural explanation for the origin of the $\mu$-term, without suffering from the visible axion or the cosmological domain-wall problem. Focusing on the Higgs sector of this minimal non-minimal supersymmetric standard model, we calculate its effective Higgs potential by integrating out the dominant quantum effects due to stop squarks. We then discuss the phenomenological implications of the Higgs scalars predicted by the theory for the present and future high-energy colliders. In particular, we find that our new minimal non-minimal supersymmetric model can naturally accommodate a relatively light charged Higgs boson, with a mass close to the present experimental lower bound.Comment: 63 pages (12 figures), extended versio

Size Matters: Origin of Binomial Scaling in Nuclear Fragmentation Experiments

The relationship between measured transverse energy, total charge recovered in the detector, and size of the emitting system is investigated. Using only very simple assumptions, we are able to reproduce the observed binomial emission probabilities and their dependences on the transverse energy.Comment: 14 pages, including 4 figure

Wedgebox analysis of four-lepton events from neutralino pair production at the LHC

`Wedgebox' plots constructed by plotting the di-electron invariant mass versus the di-muon invariant mass from pp -> e^+e^- mu^+ mu^- + missing energy signature LHC events. Data sets of such events are obtained across the MSSM input parameter space in event-generator simulations, including cuts designed to remove SM backgrounds. Their study reveals several general features: (1)Regions in the MSSM input parameter space where a sufficient number of events are expected so as to be able to construct a clear wedgebox plot are delineated. (2)The presence of box shapes on a wedgebox plot either indicates the presence of heavy Higgs bosons decays or restricts the location to a quite small region of low \mu and M_2 values \lsim 200 GeV, a region denoted as the `lower island'. In this region, wedgebox plots can be quite complicated and change in pattern rather quickly as one moves around in the (\mu, M_2) plane. (3)Direct neutralino pair production from an intermediate Z^{0*} may only produce a wedge-shape since only \widetilde{\chi}_2^0\widetilde{\chi}_3^0 decays can contribute significantly. (4)A double-wedge or wedge-protruding-from-a-box pattern on a wedgebox plot, which results from combining a variety of MSSM production processes, yields three distinct observed endpoints, almost always attributable to \widetilde{\chi}_{2,3,4}^0 \to \widetilde{\chi}_1^0 \ell^+\ell^- decays, which can be utilized to determine a great deal of information about the neutralino and slepton mass spectra and related MSSM input parameters. Wedge and double-wedge patterns are seen in wedgebox plots in another region of higher \mu and M_2 values, denoted as the`upper island.' Here the pattern is simpler and more stable as one moves across the (\mu, M_2) input parameter space.Comment: 28 pages (LaTeX), 8 figures (encapsulated postscript

Probing neutrino masses with future galaxy redshift surveys

We perform a new study of future sensitivities of galaxy redshift surveys to the free-streaming effect caused by neutrino masses, adding the information on cosmological parameters from measurements of primary anisotropies of the cosmic microwave background (CMB). Our reference cosmological scenario has nine parameters and three different neutrino masses, with a hierarchy imposed by oscillation experiments. Within the present decade, the combination of the Sloan Digital Sky Survey (SDSS) and CMB data from the PLANCK experiment will have a 2-sigma detection threshold on the total neutrino mass close to 0.2 eV. This estimate is robust against the inclusion of extra free parameters in the reference cosmological model. On a longer term, the next generation of experiments may reach values of order sum m_nu = 0.1 eV at 2-sigma, or better if a galaxy redshift survey significantly larger than SDSS is completed. We also discuss how the small changes on the free-streaming scales in the normal and inverted hierarchy schemes are translated into the expected errors from future cosmological data.Comment: 14 pages, 7 figures. Added results with the KAOS proposal and 1 referenc

Dynamical mu Term in Gauge Mediation

We address the mu problem of gauge mediation by considering a singlet chiral superfield coupled to the Higgs and messenger fields. We compute the soft terms generated below the messenger scale and study the phenomenological consequences of the model. The experimental bound on the Higgs mass provides a severe constraint that identifies three special regions of parameters where the mass spectrum and the collider signatures can be distinct from ordinary gauge mediation.Comment: 24 pages, 3 figures. v2: reference added, version to appear in Phys.Lett.

Axes determination for segmented true-coaxial HPGe detectors

A fast method to determine the crystallographic axes of segmented true-coaxial high-purity germanium detectors is presented. It is based on the analysis of segment-occupancy patterns obtained by irradiation with radioactive sources. The measured patterns are compared to predictions for different axes orientations. The predictions require a simulation of the trajectories of the charge carriers taking the transverse anisotropy of their drift into account.Comment: 18 pages, 1 table, 31 figures; included background contribution to the occupancy patterns and systematic uncertainties, results slightly change

Sustained VWF‐ADAMTS‐13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction

Background Prolonged recovery is common after acute SARS-CoV-2 infection; however, the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF/ADAMTS-13 imbalance, dysregulated angiogenesis, and immunothrombosis are hallmarks of acute COVID-19. We hypothesized that VWF/ADAMTS-13 imbalance persists in convalescence together with endothelial cell (EC) activation and angiogenic disturbance. Additionally, we postulate that ongoing immune cell dysfunction may be linked to sustained EC and coagulation activation. Patients and methods Fifty patients were reviewed at a minimum of 6 weeks following acute COVID-19. ADAMTS-13, Weibel Palade Body (WPB) proteins, and angiogenesis-related proteins were assessed and clinical evaluation and immunophenotyping performed. Comparisons were made with healthy controls (n = 20) and acute COVID-19 patients (n = 36). Results ADAMTS-13 levels were reduced (p = 0.009) and the VWF-ADAMTS-13 ratio was increased in convalescence (p = 0.0004). Levels of platelet factor 4 (PF4), a putative protector of VWF, were also elevated (p = 0.0001). A non-significant increase in WPB proteins Angiopoietin-2 (Ang-2) and Osteoprotegerin (OPG) was observed in convalescent patients and WPB markers correlated with EC parameters. Enhanced expression of 21 angiogenesis-related proteins was observed in convalescent COVID-19. Finally, immunophenotyping revealed significantly elevated intermediate monocytes and activated CD4+ and CD8+ T cells in convalescence, which correlated with thrombin generation and endotheliopathy markers, respectively. Conclusion Our data provide insights into sustained EC activation, dysregulated angiogenesis, and VWF/ADAMTS-13 axis imbalance in convalescent COVID-19. In keeping with the pivotal role of immunothrombosis in acute COVID-19, our findings support the hypothesis that abnormal T cell and monocyte populations may be important in the context of persistent EC activation and hemostatic dysfunction during convalescence

Asymptotic Fourier Coefficients for a C ∞ Bell (Smoothed-“Top-Hat”) & the Fourier Extension Problem

In constructing local Fourier bases and in solving differential equations with nonperiodic solutions through Fourier spectral algorithms, it is necessary to solve the Fourier Extension Problem. This is the task of extending a nonperiodic function, defined on an interval , to a function which is periodic on the larger interval . We derive the asymptotic Fourier coefficients for an infinitely differentiable function which is one on an interval , identically zero for , and varies smoothly in between. Such smoothed “top-hat” functions are “bells” in wavelet theory. Our bell is (for x ≥ 0) where where . By applying steepest descents to approximate the coefficient integrals in the limit of large degree j , we show that when the width L is fixed, the Fourier cosine coefficients a j of on are proportional to where Λ( j ) is an oscillatory factor of degree given in the text. We also show that to minimize error in a Fourier series truncated after the N th term, the width should be chosen to increase with N as . We derive similar asymptotics for the function f ( x )= x as extended by a more sophisticated scheme with overlapping bells; this gives an even faster rate of Fourier convergencePeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43417/1/10915_2005_Article_9010.pd