Combined Bulk and Surface Radiation Damage Effects at Very High Fluences in Silicon Detectors: Measurements and TCAD Simulations

In this work we propose a new combined TCAD radiation damage modelling scheme, featuring both bulk and surface radiation damage effects, for the analysis of silicon detectors aimed at the High Luminosity LHC. In particular, a surface damage model has been developed by introducing the relevant parameters (NOX, NIT) extracted from experimental measurements carried out on p-type substrate test structures after gamma irradiations at doses in the range 10-500 Mrad(Si). An extended bulk model, by considering impact ionization and deep-level cross-sections variation, was included as well. The model has been validated through the comparison of the simulation findings with experimental measurements carried out at very high fluences (2 10^16 1 MeV equivalent n/cm^2) thus fostering the application of this TCAD approach for the design and optimization of the new generation of silicon detectors to be used in future HEP experiments.Comment: 8 pages, 14 figures. arXiv admin note: text overlap with arXiv:1611.1013

Fabrication of a hydrogenated amorphous silicon detector in 3-d geometry and preliminary test on planar prototypes

Hydrogenated amorphous silicon (a-Si:H) can be produced by plasma-enhanced chemical vapor deposition (PECVD) of SiH4 (silane) mixed with hydrogen. The resulting material shows outstanding radiation hardness properties and can be deposited on a wide variety of substrates. Devices employing a-Si:H technologies have been used to detect many different kinds of radiation, namely, minimum ionizing particles (MIPs), X-rays, neutrons, and ions, as well as low-energy protons and alphas. However, the detection of MIPs using planar a-Si:H diodes has proven difficult due to their unsatisfactory S/N ratio arising from a combination of high leakage current, high capacitance, and limited charge collection efficiency (50% at best for a 30 µm planar diode). To overcome these limitations, the 3D-SiAm collaboration proposes employing a 3D detector geometry. The use of vertical electrodes allows for a small collection distance to be maintained while preserving a large detector thickness for charge generation. The depletion voltage in this configuration can be kept below 400 V with a consequent reduction in the leakage current. In this paper, following a detailed description of the fabrication process, the results of the tests performed on the planar p-i-n structures made with ion implantation of the dopants and with carrier selective contacts are illustrated

Synthesis, molecular docking and antibacterial activity of an oxadiazole-based lipoteichoic acid inhibitor and its metabolites

Amongst drug resistant Gram-positive bacteria, Staphylococcus aureus is a pathogen of great concern as it is the leading cause of life-threatening nosocomial and community acquired infections which are often associated with implanted medical devices. The biosynthesis of lipotheicoic acid (LTA) by S. aureus has been recognized as a promising antibacterial target, owing its critical role in the growth and survival of Gram-positive bacteria. Here we report for the first time the chemical synthesis and characterisation of an oxadiazole based compound (1771), previously described as an inhibitor of LTA biosynthesis by targeting Lta synthase enzyme (LtaS). To investigate its controversial mode of action, we also performed molecular docking studies, which indicated that 1771 behaves as a competitive inhibitor against LtaS. We also synthesised and evaluated the antimicrobial activity of 1771 metabolites which we have identified from its decomposition in mouse serum, proving that the biological activity was caused by intact 1771

HLA class II DNA typing in a large series of European patients with systemic lupus erythematosus: correlations with clinical and autoantibody subsets

We conducted this study to determine the HLA class II allele associations in a large cohort of patients of homogeneous ethnic derivation with systemic lupus erythematosus (SLE). The large sample size allowed us to stratify patients according to their clinical and serologic characteristics. We studied 577 European Caucasian patients with SLE. Antinuclear antibodies (Hep-2 cells), anti-dsDNA antibodies (Crithidia luciliae), and antibodies to extractable nuclear antigens Ro (SS-A), La (SS-B), U1-RNP, Sm, Jo1, SCL70, and PCNA, were detected in all patients. Molecular typing of HLA-DRB1, DRB3, DQA1, and DQB1 loci was performed by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. We found a significantly increased frequency of DRB1*03, DRB1*15, DRB1*16, DQA1*0102, DQB1*0502, DQB1*0602, DQB1*0201, DQB1*0303, and DQB1*0304 in lupus patients as compared with healthy controls. In addition, DRB1*03 was associated with anti-Ro, anti-La, pleuritis, and involvement of lung, kidney, and central nervous system. DRB1*15 and DQB1*0602 were associated with anti-dsDNA antibodies; DQB1*0201 with anti-Ro and anti-La, leukopenia, digital skin vasculitis, and pleuritis; and DQB1*0502 was associated with anti-Ro, renal involvement, discoid lupus, and livedo reticularis. In conclusion, our study shows some new HLA clinical and serologic associations in SLE and further confirms that the role of MHC genes is mainly to predispose to particular serologic and clinical manifestations of this disease

Serological epitope profile of anti-Ro52-positive patients with systemic autoimmune rheumatic diseases

Background: Ro52 is an interferon-inducible protein of the tripartite motif family. Antibodies against Ro52 have been described in patients with different autoimmune diseases, such as systemic lupus erythematosus and Sj\uf6gren's syndrome, that are often associated with anti-Ro60 antibodies. The Ro52 autoantigen is extraordinarily immunogenic, and its autoantibodies are directed against both linear and conformational epitopes. The aim of this study was to evaluate the prevalence of antibodies to the five Ro52 domains, as well as to Ro52 176- to 196-amino acid (aa) and 200-239-aa peptides, in different systemic autoimmune rheumatic diseases (SARDs). We also aimed to verify whether antibodies to a single domain or domain association could increase their diagnostic specificity for any SARD. Methods: Serum samples were obtained from 100 anti-Ro52 antibody-positive patients with SARDs and from 68 controls (50 healthy donors and 18 patients with other autoimmune or allergic diseases). A special line immunoassay was created containing a full-length Ro52 antigen expressed in insect cells using the baculovirus system, five recombinant Ro52 antigen fragments [Ro52-1, Ro52-2, Ro52-3, Ro52-4 (partly overlapping Ro52-1 and Ro52-2), and Ro52-5 (partly overlapping Ro52-2 and Ro52-3)], and two Ro52 peptides (176-196 aa and 200-239 aa), all expressed in Escherichia coli. Results: In patients with SARDs, fragment prevalence rates were as follows: Ro52-1 = 3 %, Ro52-2 = 97 %, Ro52-3 = 0 %, Ro52-4 = 9 %, Ro52-5 = 28 %, Ro52 175-196-aa peptide = 6 %, and Ro52 200-239-aa peptide = 74 %. All control samples were negative for the full-length Ro52 and for the five fragments tested. Conclusions: The main epitope of the Ro52 antigen was localized on fragment 2 (aa 125-267), and the majority (97 %) of SARD sera had antibodies that target this fragment. As most of the samples were positive for fragment 2 and only some for fragments 4 or 5, which partially overlap fragment 2, it seems that the target epitope is localized in the middle of fragment 2 or in the area between fragments 4 and 5. No antibody against a single epitope or a combination of epitopes was linked to any of the single SARDs

Clinical Significance of Cartilage Biomarkers for Monitoring Structural Joint Damage in Rheumatoid Arthritis Patients Treated with Anti-TNF Therapy

PURPOSE: With the current use of biologics in rheumatoid arthritis (RA), there is a need to monitor ongoing structural joint damage due to the dissociation of articular cartilage damage from disease activity of RA. This study longitudinally analyzed levels of serum cartilage biomarkers during 54 weeks of infliximab therapy, to evaluate the feasibility of biomarkers for monitoring structural joint damage. METHODS: Subjects comprised 33 patients with early RA and 33 patients with established RA. All patients received 3 mg/kg of infliximab and methotrexate for 54 weeks. Levels of the following serum cartilage markers were measured at baseline and at weeks 14, 22, and 54: hyaluronan (HA); cartilage oligometric matrix protein (COMP); type II collagen (CII)-related neoepitope (C2C); type II procollagen carboxy-propeptide (CPII); and keratin sulfate (KS). Time courses for each biomarker were assessed, and relationships between these biomarkers and clinical or radiographic parameters generally used for RA were investigated. RESULTS: Levels of CRP, MMP-3, DAS28-CRP, and annual progression of TSS were improved to similar degrees in both groups at week 54. HA and C2C/CPII were significantly decreased compared to baseline in the early RA group (p<0.001), whereas HA and COMP, but not C2C/CPII, were decreased in the established RA group. Strikingly, serum C2C/CPII levels were universally improved in early RA, regardless of EULAR response grade. Both ΔHA and ΔC2C/CPII from baseline to week 54 correlated significantly with not only ΔCRP, but also ΔDAS28 in early RA. Interestingly, when partial correlation coefficients were calculated by standardizing CRP levels, the significant correlation of ΔHA to ΔDAS28 disappeared, whereas correlations of ΔC2C/CPII to ΔDAS28, ΔJNS, and ΔHAQ remained significant. These results suggest a role of ΔC2C/CPII as a marker of ongoing structural joint damage with the least association with CRP, and that irreversible cartilage damage in established RA limits restoration of the C2C/CPII level, even with tight control of joint inflammation. CONCLUSION: The temporal course of C2C/CPII level during anti-TNF therapy indicates that CII turnover shifts toward CII synthesis in early RA, but not in established RA, potentially due to irreversible cartilage damage. ΔC2C/CPII appears to offer a useful marker reflecting ongoing structural joint damage, dissociated from inflammatory indices such as CRP and MMP-3

Progress in Diamond Detector Development

Detectors based on Chemical Vapor Deposition (CVD) diamond have been used successfully in Luminosity and Beam Condition Monitors (BCM) in the highest radiation areas of the LHC. Future experiments at CERN will accumulate an order of magnitude larger fluence. As a result, an enormous effort is underway to identify detector materials that can operate under fluences of 1 · 1016 n cm−2 and 1 · 1017 n cm−2. Diamond is one candidate due to its large displacement energy that enhances its radiation tolerance. Over the last 30 years the RD42 collaboration has constructed diamond detectors in CVD diamond with a planar geometry and with a 3D geometry to extend the material's radiation tolerance. The 3D cells in these detectors have a size of 50 µm×50 µm with columns of 2.6 µm in diameter and 100 µm×150 µm with columns of 4.6 µm in diameter. Here we present the latest beam test results from planar and 3D diamond pixel detectors