BAFF Index and CXCL13 levels in the cerebrospinal fluid associate respectively with intrathecal IgG synthesis and cortical atrophy in multiple sclerosis at clinical onset

Abstract Background B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS. Methods Paired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh). Results Compared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes ( p \u2009<\u20090.01), lower values of BAFF Index (11.9\u2009\ub1\u20096.1 vs 17.5\u2009\ub1\u20095.2, p \u2009<\u20090.01), and higher CSF CXCL13 levels (27.7\u2009\ub1\u200933.5 vs 0.9\u2009\ub1\u20091.5, p \u2009<\u20090.005). In these patients, BAFF Index but not CSF CXCL13 levels inversely correlated with the intrathecal IgG synthesis ( r \u2009>\u20090.5 and p \u2009<\u20090.05 for all correlations). CSF leukocyte counts were significantly higher in IgGOB+ compared to IgGOB\u2212 ( p \u2009<\u20090.05) and HC ( p \u2009<\u20090.01), and correlated to CSF CXCL13 concentrations ( r 0.77, p \u2009<\u20090.001). The gCTh was significantly lower in patients with higher CSF CXCL13 levels (2.41\u2009\ub1\u20090.1 vs 2.49\u2009\ub1\u20090.1\ua0mm, p \u2009<\u20090.05), while no difference in MRI parameters of WM and GM pathology was observed between IgGOB+ and IgGOB\u2212. Conclusions The intrathecal IgG synthesis inversely correlated with BAFF Index and showed no correlation with CSF CXCL13. These findings seem to indicate that intrathecally synthesized IgG are produced by long-term PCs that have entered the CNS from the peripheral blood, rather than produced by PCs developed in the meningeal follicle-like structures (FLS). In this study, CXCL13 identifies a subgroup of MS patients characterized by ..

Development and Manufacture of the Coil End Spacers of the LHC Pre-series Dipoles

The coil end spacers play an important role in the performance of superconducting coils, as their shape and location determine the mechanical stability of the conductors in the coil ends (and hence the overall coil training performance) and the local field quality. The dipole end spacers are often of a size and a geometry difficult to be industrially series manufactured and measured. Efficiency of the production and related costs are a key issue to achieve the required production rate of the LHC main dipoles at an affordable price. For the latter reasons, a design approach integrating state-of-the-art CAD/CAM optimization techniques allowing to considerably decrease design and machining time was implemented. This paper gives examples and describes the design criteria, the computation methods, the machining and measuring procedures adopted to carry out the pre-series production

Spinning Loop Black Holes

In this paper we construct four Kerr-like spacetimes starting from the loop black hole Schwarzschild solutions (LBH) and applying the Newman-Janis transformation. In previous papers the Schwarzschild LBH was obtained replacing the Ashtekar connection with holonomies on a particular graph in a minisuperspace approximation which describes the black hole interior. Starting from this solution, we use a Newman-Janis transformation and we specialize to two different and natural complexifications inspired from the complexifications of the Schwarzschild and Reissner-Nordstrom metrics. We show explicitly that the space-times obtained in this way are singularity free and thus there are no naked singularities. We show that the transformation move, if any, the causality violating regions of the Kerr metric far from r=0. We study the space-time structure with particular attention to the horizons shape. We conclude the paper with a discussion on a regular Reissner-Nordstrom black hole derived from the Schwarzschild LBH and then applying again the Newmann-Janis transformation.Comment: 18 pages, 18 figure

The EPRL intertwiners and corrected partition function

Do the SU(2) intertwiners parametrize the space of the EPRL solutions to the simplicity constraint? What is a complete form of the partition function written in terms of this parametrization? We prove that the EPRL map is injective for n-valent vertex in case when it is a map from SO(3) into SO(3)xSO(3) representations. We find, however, that the EPRL map is not isometric. In the consequence, in order to be written in a SU(2) amplitude form, the formula for the partition function has to be rederived. We do it and obtain a new, complete formula for the partition function. The result goes beyond the SU(2) spin-foam models framework.Comment: RevTex4, 15 pages, 5 figures; theorem of injectivity of EPRL map correcte

Single-cell gene network analysis and transcriptional landscape of MYCN-amplified neuroblastoma cell lines

Neuroblastoma (NBL) is a pediatric cancer responsible for more than 15% of cancer deaths in children, with 800 new cases each year in the United States alone. Genomic amplification of the MYC oncogene family member MYCN characterizes a subset of high-risk pediatric neuroblastomas. Several cellular models have been implemented to study this disease over the years. Two of these, SK-N-BE-2-C (BE2C) and Kelly, are amongst the most used worldwide as models of MYCN-Amplified human NBL. Here, we provide a transcriptome-wide quantitative measurement of gene expression and transcriptional network activity in BE2C and Kelly cell lines at an unprecedented single-cell resolution. We obtained 1105 Kelly and 962 BE2C unsynchronized cells, with an average number of mapped reads/cell of roughly 38,000. The single-cell data recapitulate gene expression signatures previously generated from bulk RNA-Seq. We highlight low variance for commonly used housekeeping genes between different cells (ACTB, B2M and GAPDH), while showing higher than expected variance for metallothionein transcripts in Kelly cells. The high number of samples, despite the relatively low read coverage of single cells, allowed for robust pathway enrichment analysis and master regulator analysis (MRA), both of which highlight the more mesenchymal nature of BE2C cells as compared to Kelly cells, and the upregulation of TWIST1 and DNAJC1 transcriptional networks. We further defined master regulators at the single cell level and showed that MYCN is not constantly active or expressed within Kelly and BE2C cells, independently of cell cycle phase. The dataset, alongside a detailed and commented programming protocol to analyze it, is fully shared and reusable

Photoelectrochemical oxidation of glycerol on hematite: thermal effects, in situ FTIR and long-term HPLC product analysis

Photoelectrochemical (PEC) oxidation of biomass is a profitable approach to produce hydrogen by substituting the water oxidation reaction in the electrolyzers’ photoanodes. Among the biomass-derived molecules, glycerol is an interesting alternative to water since its standard thermodynamic potential is considerably lower than that of water and because it is widely produced in the biodiesel industry. Herein, we performed a fundamental study of the PEC oxidation of glycerol on hematite. In situ FTIR experiments and long-term electrolysis followed by HPLC analysis revealed C1, C2 and C3 oxidation products showing the low selectivity of the reaction under these conditions. We explained this lack of selectivity by an electrooxidation mechanism involving highly reactive radicals as intermediates. [Figure not available: see fulltext.]

Euclidean three-point function in loop and perturbative gravity

We compute the leading order of the three-point function in loop quantum gravity, using the vertex expansion of the Euclidean version of the new spin foam dynamics, in the region of gamma<1. We find results consistent with Regge calculus in the limit gamma->0 and j->infinity. We also compute the tree-level three-point function of perturbative quantum general relativity in position space, and discuss the possibility of directly comparing the two results.Comment: 16 page

Asymptotics of the Wigner 9j symbol

We present the asymptotic formula for the Wigner 9j-symbol, valid when all quantum numbers are large, in the classically allowed region. As in the Ponzano-Regge formula for the 6j-symbol, the action is expressed in terms of lengths of edges and dihedral angles of a geometrical figure, but the angles require care in definition. Rules are presented for converting spin networks into the associated geometrical figures. The amplitude is expressed as the determinant of a 2x2 matrix of Poisson brackets. The 9j-symbol possesses caustics associated with the fold and elliptic and hyperbolic umbilic catastrophes. The asymptotic formula obeys the exact symmetries of the 9j-symbol.Comment: 17 pages, 7 figure

Myocardial Scar on Surface ECG: Selvester Score, but Not Fragmentation, Predicts Response to CRT

Purpose. Myocardial scar is directly related to the response to CRT after implantation. The extent of myocardial scar can be detected not only by cardiac magnetic resonance but also by two electrocardiographic scores: fragmented QRS (fQRS) and Selvester score (SSc). The aim of our study is to compare the role of baseline SSc and fQRS in predicting response to CRT in a cohort of heart failure patients with true left bundle branch block (LBBB). As a secondary endpoint, we assessed the association of both scores with overall and cardiac mortality, heart failure hospitalizations, ventricular arrhythmias requiring ICD intervention, and major adverse cardiovascular event (MACE). Methods. We evaluated fQRS and SSc of 178 consecutive HF patients with severe systolic dysfunction (LVEF ≤ 35%), NYHA class II-III despite optimal medical treatment, and true-LBBB. Response to CRT was defined as the improvement of LVEF of at least 10% or as the reduction of LVESV of at least 15% at a 6-month follow-up. Each endpoint was related to fQRS and SSc. Results. SSc ≥7 was significantly associated with the absence of echocardiographic response to CRT (OR: 0.327; 95% C.I. 0.155-0.689; p=0.003), while the presence of fQRS at baseline ECG was not (OR: 1.133; 95% C.I. 0.539-2.381; p=0.742). No correlation was found between SSc and overall mortality, cardiac death, ventricular arrhythmias, hospitalizations due to heart failure, or for MACE. Similar results were observed between fQRS and all secondary endpoints. Conclusion. In HF patients with true-LBBB and LVEF ≤35% eligible for CRT, myocardial scar assessed by calculating the SSc on preimplant ECG is an independent predictor of nonresponse after multiple adjustments. Neither SSc nor fQRS is associated with overall and cardiac death, ventricular arrhythmias, or hospitalization for heart failure at a 24-month follow-up