Inflammatory Cytokines in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin affecting virtually all organ systems. Beyond genetic and environmental factors, cytokine imbalances contribute to immune dysfunction, trigger inflammation, and induce organ damage. The key cytokine that is involved in SLE pathogenesis is interferon alpha. Interferon secretion is induced by immune complexes and leads to upregulation of several inflammatory proteins, which account for the so-called IFN signature that can be found in the majority of SLE PBMCs. Additionally IL-6 and IFN-y as well as T-cell-derived cytokines like IL-17, IL-21, and IL-2 are dysregulated in SLE. The latter induce a T-cell phenotype that is characterized by enhanced B-cell help and enhanced secretion of proinflammatory cytokines but reduced induction of suppressive T cells and activation-induced cell death. This paper will focus on these cytokines and highlights pathophysiological approaches and therapeutic potential

Noncommutative Solitons of Gravity

We investigate a three-dimensional gravitational theory on a noncommutative space which has a cosmological constant term only. We found various kinds of nontrivial solutions, by applying a similar technique which was used to seek noncommutative solitons in noncommutative scalar field theories. Some of those solutions correspond to bubbles of spacetimes, or represent dimensional reduction. The solution which interpolates $G_{\mu\nu}=0$ and Minkowski metric is also found. All solutions we obtained are non-perturbative in the noncommutative parameter $\theta$, therefore they are different from solutions found in other contexts of noncommutative theory of gravity and would have a close relation to quantum gravity.Comment: 29 pages, 5 figures. v2: minor corrections done in Section 3.1 and Appendix, references added. v3, v4: typos correcte

Perception of categories: from coding efficiency to reaction times

Reaction-times in perceptual tasks are the subject of many experimental and theoretical studies. With the neural decision making process as main focus, most of these works concern discrete (typically binary) choice tasks, implying the identification of the stimulus as an exemplar of a category. Here we address issues specific to the perception of categories (e.g. vowels, familiar faces, ...), making a clear distinction between identifying a category (an element of a discrete set) and estimating a continuous parameter (such as a direction). We exhibit a link between optimal Bayesian decoding and coding efficiency, the latter being measured by the mutual information between the discrete category set and the neural activity. We characterize the properties of the best estimator of the likelihood of the category, when this estimator takes its inputs from a large population of stimulus-specific coding cells. Adopting the diffusion-to-bound approach to model the decisional process, this allows to relate analytically the bias and variance of the diffusion process underlying decision making to macroscopic quantities that are behaviorally measurable. A major consequence is the existence of a quantitative link between reaction times and discrimination accuracy. The resulting analytical expression of mean reaction times during an identification task accounts for empirical facts, both qualitatively (e.g. more time is needed to identify a category from a stimulus at the boundary compared to a stimulus lying within a category), and quantitatively (working on published experimental data on phoneme identification tasks)

A tool box for implementing supersymmetric models

We present a framework for performing a comprehensive analysis of a large class of supersymmetric models, including spectrum calculation, dark matter studies and collider phenomenology. To this end, the respective model is defined in an easy and straightforward way using the \Mathematica package SARAH. SARAH then generates model files for CalcHep which can be used with MicrOmegas as well as model files for WHIZARD and OMEGA. In addition, Fortran source code for SPheno is created which facilitates the determination of the particle spectrum using two-loop renormalization group equations and one-loop corrections to the masses. As an additional feature, the generated SPheno code can write out input files suitable for use with HiggsBounds to apply bounds coming from the Higgs searches to the model. Combining all program provides a closed chain from model building to phenomenology.Comment: 68 pages, 7 figure

Chemokine receptorâ 7 (CCR7) deficiency leads to delayed development of joint damage and functional deficits in a murine model of osteoarthritis

Elevated chemokine receptor Ccr7 is observed in knee osteoarthritis (OA) and associated with severity of symptoms. In this study, we confirmed that CCR7 protein expression is elevated in synovial tissue from OA patients by immunohistochemical staining. We then investigated whether Ccr7 deficiency impacted structural and functional joint degeneration utilizing a murine model of OA. OAâ like disease was induced in male C57BL/6 and Ccr7â deficient (Ccr7â /â ) mice by destabilization of the medial meniscus (DMM). Functional deficits were measured by computer integrated monitoring of spontaneous activity every 4 weeks after DMM surgery up 16 weeks. Joint degeneration was evaluated at 6 and 19 weeks postâ surgery by histopathology, and subchondral bone changes analyzed by microCT. Results showed reduction in locomotor activities in DMMâ operated C57BL/6 mice by 8 weeks, while activity decreases in Ccr7â /â mice were delayed until 16 weeks. Histopathologic evaluation showed minimal protection from early cartilage degeneration (pâ =â 0.06) and osteophytosis (pâ =â 0.04) in Ccr7â /â mice 6 weeks postâ DMM compared to C57BL/6 controls, but not at 19 weeks. However, subchondral bone mineral density (pâ =â 0.03) and histologic sclerosis (pâ =â 0.02) increased in response to surgery in C57BL/6 mice at 6 weeks, while Ccr7â /â mice were protected from these changes. Our results are the first to demonstrate a role for Ccr7 in early development of functional deficits and subchondral bone changes in the DMM model. Understanding the mechanism of Ccr7 receptor signaling in the initiation of joint pathology and disability will inform the development of innovative therapies to slow symptomatic OA development after injury. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res 36:864â 875, 2018.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143717/1/jor23671.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143717/2/jor23671_am.pd

Evaluation of Internal Reference Genes for Quantitative Expression Analysis by Real-Time PCR in Ovine Whole Blood

The use of reference genes is commonly accepted as the most reliable approach to normalize qRT-PCR and to reduce possible errors in the quantification of gene expression. The most suitable reference genes in sheep have been identified for a restricted range of tissues, but no specific data on whole blood are available. The aim of this study was to identify a set of reference genes for normalizing qRT-PCR from ovine whole blood. We designed 11 PCR assays for commonly employed reference genes belonging to various functional classes and then determined their expression stability in whole blood samples from control and disease-stressed sheep. SDHA and YWHAZ were considered the most suitable internal controls as they were stably expressed regardless of disease status according to both geNorm and NormFinder software; furthermore, geNorm indicated SDHA/HPRT, YWHAZ/GAPDH and SDHA/YWHAZ as the best reference gene combinations in control, disease-stressed and combined sheep groups, respectively. Our study provides a validated panel of optimal control genes which may be useful for the identification of genes differentially expressed by qRT-PCR in a readily accessible tissue, with potential for discovering new physiological and disease markers and as a tool to improve production traits (e.g., by identifying expression Quantitative Trait Loci). An additional outcome of the study is a set of intron-spanning primer sequences suitable for gene expression experiments employing SYBR Green chemistry on other ovine tissues and cells

Search for charged Higgs decays of the top quark using hadronic tau decays

We present the result of a search for charged Higgs decays of the top quark, produced in $p\bar{p}$ collisions at $\surd s =$ 1.8 TeV. When the charged Higgs is heavy and decays to a tau lepton, which subsequently decays hadronically, the resulting events have a unique signature: large missing transverse energy and the low-charged-multiplicity tau. Data collected in the period 1992-1993 at the Collider Detector at Fermilab, corresponding to 18.7$\pm$0.7~pb$^{-1}$, exclude new regions of combined top quark and charged Higgs mass, in extensions to the standard model with two Higgs doublets.Comment: uuencoded, gzipped tar file of LaTeX and 6 Postscript figures; 11 pp; submitted to Phys. Rev.

Inclusive jet cross section in pˉp{\bar p p} collisions at s=1.8\sqrt{s}=1.8 TeV

The inclusive jet differential cross section has been measured for jet transverse energies, $E_T$, from 15 to 440 GeV, in the pseudorapidity region 0.1$\leq | \eta| \leq$0.7. The results are based on 19.5 pb$^{-1}$ of data collected by the CDF collaboration at the Fermilab Tevatron collider. The data are compared with QCD predictions for various sets of parton distribution functions. The cross section for jets with $E_T>200$ GeV is significantly higher than current predictions based on O($\alpha_s^3$) perturbative QCD calculations. Various possible explanations for the high-$E_T$ excess are discussed.Comment: 8 pages with 2 eps uu-encoded figures Submitted to Physical Review Letter