Extended morphometric analysis of neuronal cells with Minkowski valuations

Minkowski valuations provide a systematic framework for quantifying different aspects of morphology. In this paper we apply vector- and tensor-valued Minkowski valuations to neuronal cells from the cat's retina in order to describe their morphological structure in a comprehensive way. We introduce the framework of Minkowski valuations, discuss their implementation for neuronal cells and show how they can discriminate between cells of different types.Comment: 14 pages, 18 postscript figure

Identification of the TeV Gamma-ray Source ARGO J2031+4157 with the Cygnus Cocoon

The extended TeV gamma-ray source ARGO J2031+4157 (or MGRO J2031+41) is positionally consistent with the Cygnus Cocoon discovered by $Fermi$-LAT at GeV energies in the Cygnus superbubble. Reanalyzing the ARGO-YBJ data collected from November 2007 to January 2013, the angular extension and energy spectrum of ARGO J2031+4157 are evaluated. After subtracting the contribution of the overlapping TeV sources, the ARGO-YBJ excess map is fitted with a two-dimensional Gaussian function in a square region of $10^{\circ}\times 10^{\circ}$, finding a source extension $\sigma_{ext}$= 1$^{\circ}$.8$\pm$0$^{\circ}$.5. The observed differential energy spectrum is $dN/dE =(2.5\pm0.4) \times 10^{-11}(E/1 TeV)^{-2.6\pm0.3}$ photons cm$^{-2}$ s$^{-1}$ TeV$^{-1}$, in the energy range 0.2-10 TeV. The angular extension is consistent with that of the Cygnus Cocoon as measured by $Fermi$-LAT, and the spectrum also shows a good connection with the one measured in the 1-100 GeV energy range. These features suggest to identify ARGO J2031+4157 as the counterpart of the Cygnus Cocoon at TeV energies. The Cygnus Cocoon, located in the star-forming region of Cygnus X, is interpreted as a cocoon of freshly accelerated cosmic rays related to the Cygnus superbubble. The spectral similarity with Supernova Remnants indicates that the particle acceleration inside a superbubble is similar to that in a SNR. The spectral measurements from 1 GeV to 10 TeV allows for the first time to determine the possible spectrum slope of the underlying particle distribution. A hadronic model is adopted to explain the spectral energy distribution.Comment: 16 pages, 3 figures, has been accepted by ApJ for publicatio

Electric and magnetic form factors of strange baryons

Predictions for the electromagnetic form factors of the Lambda$, Sigma and Xi hyperons are presented. The numerical calculations are performed within the framework of the fully relativistic constituent-quark model developed by the Bonn group. The computed magnetic moments compare favorably with the experimentally known values. Most magnetic form factors G_M(Q^2) can be parametrized in terms of a dipole with cutoff masses ranging from 0.79 to 1.14 GeV.Comment: 15 pages, 8 figures, 3 tables, submitted to Eur. Phys. J.

BEAM DECOHERENCE DUE TO COMBINATION OF WAKE FORCE AND NONLINEARITY IN SP-RING-8 STORAGE RING

Abstract To understand particle behavior from a beam injection state to equilibrium state determined by radiation effects, we have performed a simple experiment to observe the beam decoherence, i.e., temporal variation of the damping of beam coherent motion generated by a single horizontal kicker. We found that the beam decoherence much depends on chromaticities, the sign of amplitudedependent tune shift and beam current. This suggests that short-range wake force and nonlinearity of ring parameters play important roles in the observed phenomena. Simulations with transverse wake fields show good agreements with the measurements

Fine mapping seronegative and seropositive rheumatoid arthritis to shared and distinct HLA alleles by adjusting for the effects of heterogeneity

Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA(+)) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA(-)) RA has been challenging because of clinical heterogeneity within clinical cohorts. We imputed 8,961 classical HLA alleles, amino acids, and SNPs from Immunochip data in a discovery set of 2,406 ACPA(-) RA case and 13,930 control individuals. We developed a statistical approach to identify and adjust for clinical heterogeneity within ACPA(-) RA and observed independent associations for serine and leucine at position 11 in HLA-DRbeta1 (p = 1.4 x 10(-13), odds ratio [OR] = 1.30) and for aspartate at position 9 in HLA-B (p = 2.7 x 10(-12), OR = 1.39) within the peptide binding grooves. These amino acid positions induced associations at HLA-DRB1( *)03 (encoding serine at 11) and HLA-B( *)08 (encoding aspartate at 9). We validated these findings in an independent set of 427 ACPA(-) case subjects, carefully phenotyped with a highly sensitive ACPA assay, and 1,691 control subjects (HLA-DRbeta1 Ser11+Leu11: p = 5.8 x 10(-4), OR = 1.28; HLA-B Asp9: p = 2.6 x 10(-3), OR = 1.34). Although both amino acid sites drove risk of ACPA(+) and ACPA(-) disease, the effects of individual residues at HLA-DRbeta1 position 11 were distinct (p \u3c 2.9 x 10(-107)). We also identified an association with ACPA(+) RA at HLA-A position 77 (p = 2.7 x 10(-8), OR = 0.85) in 7,279 ACPA(+) RA case and 15,870 control subjects. These results contribute to mounting evidence that ACPA(+) and ACPA(-) RA are genetically distinct and potentially have separate autoantigens contributing to pathogenesis. We expect that our approach might have broad applications in analyzing clinical conditions with heterogeneity at both major histocompatibility complex (MHC) and non-MHC regions

HMGB1 in health and disease

Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed high-mobility group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhibitors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localization, structure, post-translational modification, and identification of additional partners will undoubtedly uncover additional secrets regarding HMGB1\u27s multiple functions. (C) 2014 Elsevier Ltd. All rights reserved

Validation of the lupus nephritis clinical indices in childhood-onset systemic lupus erythematosus

OBJECTIVE: To validate clinical indices of lupus nephritis (LN) activity and damage when used in children against the criterion standard of kidney biopsy findings. METHODS: In 83 children requiring kidney biopsy the SLE Disease Activity Index Renal Domain (SLEDAI-R); British Isles Lupus Assessment Group index Renal Domain (BILAG-R), Systemic Lupus International Collaborating Clinics Renal Activity (SLICC-RAS) and Damage Index Renal Domain (SDI-R) were measured. Fixed effect and logistic models were done to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low/moderate vs. high LN-activity [NIH Activity Index (NIH-AI) score:10; Tubulointerstitial Activity Index (TIAI) score:5) or the absence vs. presence of LN chronicity [NIH Chronicity Index (NIH-CI) score: 0 vs. \u3e/= 1]. RESULTS: There were 10, 50 and 23 patients with class I/II, III/IV and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with LN-activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between LN-activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture LN chronicity was 23.5% and 91.7%, respectively. Despite designed to measure LN-activity, SLICC-RAS and SLEDAI-R scores significantly differed with LN chronicity status. CONCLUSION: Current clinical indices of LN fail to discriminate ISN/RPS Class in children. Despite its shortcomings, the SLEDAI-R appears to best for measuring LN activity in a clinical setting. The SDI-R is a poor correlate of LN chronicity. This article is protected by copyright. All rights reserved