Effect of Mn and Mg dopants on vacancy defect formation in ammonothermal GaN

We have applied positron annihilation spectroscopy to study the formation of Ga vacancy related defects in Mg and Mn doped bulk GaN crystals grown by the ammonothermal method. We show that Mn doping has little or no effect on the formation of Ga vacancies, while Mg doping strongly suppresses their formation, in spite of both dopants leading to highly resistive material. We suggest the differences are primarily due to the hydrogen-dopant interactions. Further investigations are called for to draw a detailed picture of the atomic scale phe-nomena in the synthesis of ammonothermal GaN.Peer reviewe

SPECTROSCOPY OF DEFECTS IN NEUTRON IRRADIATED AMMONO-THERMAL GaN BY COMBINING PHOTOIONIZATION, PHOTOLUMINESCENCE AND POSITRON ANNIHILATION TECHNIQUES

In this work, pulsed photoionization as well as photoluminescence and positron annihilation spectroscopy were combined to detect different species of defects. The GaN crystals, grown by the ammono-thermal method, doped with Mn as well as Mg impurities and irradiated with different fluences of reactor neutrons, were examined to clarify the role of the technological and radiation defects. The evolution of the prevailing photoactive centres was examined by pulsed photoionization spectroscopy. Positron annihilation spectroscopy was applied to reveal vacancy-type defects.Peer reviewe

Study of variations of the carrier recombination and charge transport parameters during proton irradiation of silicon pin diode structures

Peer reviewe

Tenascin expression in normal and pathological conditions of the musculoskeletal system

Tenascin is an extracellular matrix protein with highly regulated expression and uncertain functions. It is prominently expressed during musculoskeletal embryogenesis. The pattern of distribution of tenascin in healthy adult musculoskeletal tissues is spatially and temporally restricted. It can be only detected in a small amount in the muscle-tendon junctions, tendons, perichondrium, periosteum, endosteum, the superficial layer of articular cartilage and the subintimal connective tissue of synovium. Elevated tenascin expression is found in inflammatory, degenerative and neoplastic lesions of the musculoskeletal system. The peculiar pattern of tenascin expression suggests it may play a role in the regulation of cell behavior at the interfaces between different elements of the musculoskeletal system and in various pathological processes, in particular those involving attachment and or detachment of cells from the extracellular matrix and their proliferation and collagenase secretion.Biomedical Reviews 1996; 6: 83-94

Identifying Mechanisms by Which Escherichia coli O157:H7 Subverts Interferon-γ Mediated Signal Transducer and Activator of Transcription-1 Activation

Enterohemorrhagic Escherichia coli serotype O157:H7 is a food borne enteric bacterial pathogen that causes significant morbidity and mortality in both developing and industrialized nations. E. coli O157:H7 infection of host epithelial cells inhibits the interferon gamma pro-inflammatory signaling pathway, which is important for host defense against microbial pathogens, through the inhibition of Stat-1 tyrosine phosphorylation. The aim of this study was to determine which bacterial factors are involved in the inhibition of Stat-1 tyrosine phosphorylation. Human epithelial cells were challenged with either live bacteria or bacterial-derived culture supernatants, stimulated with interferon-gamma, and epithelial cell protein extracts were then analyzed by immunoblotting. The results show that Stat-1 tyrosine phosphorylation was inhibited by E. coli O157:H7 secreted proteins. Using sequential anion exchange and size exclusion chromatography, YodA was identified, but not confirmed to mediate subversion of the Stat-1 signaling pathway using isogenic mutants. We conclude that E. coli O157:H7 subverts Stat-1 tyrosine phosphorylation in response to interferon-gamma through a still as yet unidentified secreted bacterial protein

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Methods for high-dimensonal analysis of cells dissociated from cyropreserved synovial tissue

Background: Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples. Methods: Multiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface protein preservation for cell sorting and mass cytometry, as well as for reproducibility in RNA sequencing (RNA-seq). Cryopreserved synovial samples were collectively analyzed at a central processing site by a custom-designed and validated 35-marker mass cytometry panel. In parallel, each sample was flow sorted into fibroblast, T-cell, B-cell, and macrophage suspensions for bulk population RNA-seq and plate-based single-cell CEL-Seq2 RNA-seq. Results: Upon dissociation, cryopreserved synovial tissue fragments yielded a high frequency of viable cells, comparable to samples undergoing immediate processing. Optimization of synovial tissue dissociation across six clinical collection sites with ~ 30 arthroplasty and ~ 20 biopsy samples yielded a consensus digestion protocol using 100 μg/ml of Liberase™ TL enzyme preparation. This protocol yielded immune and stromal cell lineages with preserved surface markers and minimized variability across replicate RNA-seq transcriptomes. Mass cytometry analysis of cells from cryopreserved synovium distinguished diverse fibroblast phenotypes, distinct populations of memory B cells and antibody-secreting cells, and multiple CD4+ and CD8+ T-cell activation states. Bulk RNA-seq of sorted cell populations demonstrated robust separation of synovial lymphocytes, fibroblasts, and macrophages. Single-cell RNA-seq produced transcriptomes of over 1000 genes/cell, including transcripts encoding characteristic lineage markers identified. Conclusions: We have established a robust protocol to acquire viable cells from cryopreserved synovial tissue with intact transcriptomes and cell surface phenotypes. A centralized pipeline to generate multiple high-dimensional analyses of synovial tissue samples collected across a collaborative network was developed. Integrated analysis of such datasets from large patient cohorts may help define molecular heterogeneity within RA pathology and identify new therapeutic targets and biomarkers

Effect of Mn and Mg dopants on vacancy defect formation in ammonothermal GaN

We have applied positron annihilation spectroscopy to study the formation of Ga vacancy related defects in Mg and Mn doped bulk GaN crystals grown by the ammonothermal method. We show that Mn doping has little or no effect on the formation of Ga vacancies, while Mg doping strongly suppresses their formation, in spite of both dopants leading to highly resistive material. We suggest the differences are primarily due to the hydrogen-dopant interactions. Further investigations are called for to draw a detailed picture of the atomic scale phenomena in the synthesis of ammonothermal GaN.Peer reviewe