In-situ Magnesium Diboride Superconducting Thin Films grown by Pulsed Laser Deposition

Superconducting thin films of MgB2 were deposited by Pulsed Laser Deposition on magnesium oxide and sapphire substrates. Samples grown at 450C in an argon buffer pressure of about 10-2 mbar by using a magnesium enriched target resulted to be superconducting with a transition temperature of about 25 K. Film deposited from a MgB2 sintered pellet target in ultra high vacuum conditions showed poor metallic or weak semiconducting behavior and they became superconducting only after an ex-situ annealing in Mg vapor atmosphere. Up to now, no difference in the superconducting properties of the films obtained by these two procedures has been evidenced.Comment: 10 pages, 4 figure

In situ epitaxial MgB2 thin films for superconducting electronics

A thin film technology compatible with multilayer device fabrication is critical for exploring the potential of the 39-K superconductor magnesium diboride for superconducting electronics. Using a Hybrid Physical-Chemical Vapor Deposition (HPCVD) process, it is shown that the high Mg vapor pressure necessary to keep the MgB$_2$ phase thermodynamically stable can be achieved for the {\it in situ} growth of MgB$_2$ thin films. The films grow epitaxially on (0001) sapphire and (0001) 4H-SiC substrates and show a bulk-like $T_c$ of 39 K, a $J_c$(4.2K) of $1.2 \times 10^7$ A/cm$^2$ in zero field, and a $H_{c2}(0)$ of 29.2 T in parallel magnetic field. The surface is smooth with a root-mean-square roughness of 2.5 nm for MgB$_2$ films on SiC. This deposition method opens tremendous opportunities for superconducting electronics using MgB$_2$

Adenovirus Vector Vaccination Impacts NK Cell Rheostat Function following Lymphocytic Choriomeningitis Virus Infection

ABSTRACT Natural killer (NK) cells respond rapidly as a first line of defense against infectious pathogens. In addition, NK cells may provide a “rheostat” function and have been shown to reduce the magnitude of antigen-specific T cell responses following infection to avoid immunopathology. However, it remains unknown whether NK cells similarly modulate vaccine-elicited T cell responses following virus challenge. We used the lymphocytic choriomeningitis virus (LCMV) clone 13 infection model to address whether NK cells regulate T cell responses in adenovirus vector-vaccinated mice following challenge. As expected, NK cell depletion in unvaccinated mice resulted in increased virus-specific CD4+ and CD8+ T cell responses and immunopathology following LCMV challenge. In contrast, NK cell depletion had minimal to no impact on antigen-specific T cell responses in mice that were vaccinated with an adenovirus serotype 5 (Ad5)-GP vector prior to LCMV challenge. Moreover, NK cell depletion in vaccinated mice prior to challenge did not result in immunopathology and did not compromise protective efficacy. These data suggest that adenovirus vaccine-elicited T cells may be less sensitive to NK cell rheostat regulation than T cells primed by LCMV infection. IMPORTANCE: Recent data have shown that NK cell depletion leads to enhanced virus-elicited T cell responses that can result in severe immunopathology following LCMV infection in mice. In this study, we observed that NK cells exerted minimal to no impact on vaccine-elicited T cells following LCMV challenge, suggesting that adenovirus vaccine-elicited T cells may be less subject to NK cell regulation. These data contribute to our understanding of NK cell regulatory functions and T cell-based vaccines

High-Resolution Mapping of Gene Expression Using Association in an Outbred Mouse Stock

Quantitative trait locus (QTL) analysis is a powerful tool for mapping genes for complex traits in mice, but its utility is limited by poor resolution. A promising mapping approach is association analysis in outbred stocks or different inbred strains. As a proof of concept for the association approach, we applied whole-genome association analysis to hepatic gene expression traits in an outbred mouse population, the MF1 stock, and replicated expression QTL (eQTL) identified in previous studies of F2 intercross mice. We found that the mapping resolution of these eQTL was significantly greater in the outbred population. Through an example, we also showed how this precise mapping can be used to resolve previously identified loci (in intercross studies), which affect many different transcript levels (known as eQTL “hotspots”), into distinct regions. Our results also highlight the importance of correcting for population structure in whole-genome association studies in the outbred stock

Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles (“immunoallertypes”), were determined. Measurements and Main Results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. “Sensitized bronchiectasis” was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a “treatable trait” permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionSupported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award NMRC/TA/0048/2016 (S.H.C.) and Changi General Hospital Research grant CHF2016.03-P (T.B.L.). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and National Medical Research Council grants N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, and NMRC/1150/2008 (F.T.C.); J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research

A propofol binding site on mammalian GABAA receptors identified by photolabeling

Propofol is the most important intravenous general anesthetic in current clinical use. It acts by potentiating GABA(A) receptors, but where it binds to this receptor is not known and has been a matter of some controversy. We have synthesized a novel propofol analogue photolabeling reagent that has a biological activity very similar to that of propofol. We confirmed that this reagent labeled known propofol binding sites in human serum albumin which have been identified using X-ray crystallography. Using a combination of the protiated label and a deuterated version, and mammalian receptors labeled in intact membranes, we have identified a novel binding site for propofol in GABA(A) receptors consisting of both β(3) homopentamers and α(1)β(3) heteropentamers. The binding site is located within the β subunit, at the interface between the transmembrane domains and the extracellular domain, and lies close to known determinants of anesthetic sensitivity in transmembrane segments TM1 and TM2

Predictions for cold nuclear matter effects in p plus Pb collisions at root SNN =8.16 TeV

Predictions for cold nuclear matter effects on charged hadrons, identified light hadrons, quarkonium and heavy flavor hadrons, Drell-Yan dileptons, jets, photons, gauge bosons and top quark pairs produced in p+Pb collisions at, root S-NN = 8.16 TeV are compiled and, where possible, compared to each other. Predictions of the normalized ratios of p+Pb to p+ p cross sections are also presented for most of the observables, providing new insights into the expected role of cold nuclear matter effects. In particular, the role of nuclear parson distribution functions on particle production can now be probed over a wider range of phase space than ever before. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

Expression of Bmi-1 is a prognostic marker in bladder cancer

<p>Abstract</p> <p>Background</p> <p>The molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer.</p> <p>Methods</p> <p>We examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis.</p> <p>Results</p> <p>Expression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (<it>P </it>< 0.01). By immunohistochemical examination, five of 30 adjacent normal bladder specimens (16.7%) versus 75 of 137 bladder cancers (54.3%) showed Bmi-1 protein expression (<it>P </it>< 0.05). Bmi-1 protein expression was intense in 20.6%, 54.3%, and 78.8% of tumors of histopathological stages G1, G2, and G3, respectively (<it>P </it>< 0.05). Expression of Bmi-1 protein was greater in invasive bladder cancers than in superficial bladder cancers (81.5% versus 32.5%, <it>P </it>< 0.05). In invasive bladder cancers, the expression of Bmi-1 protein in progression-free cancers was similar to that of cancers that have progressed (80.0% versus 82.4%, <it>P </it>> 0.5). In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, <it>P </it>< 0.05). Bmi-1 expression was positively correlated with tumor classification and TNM stage (<it>P </it>< 0.05), but not with tumor number (<it>P </it>> 0.05). Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (<it>P </it>< 0.05). Patients with higher Bmi-1 expression had shorter survival time, whereas patients with lower Bmi-1 expression had longer survival time (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>Expression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.</p

Epithelial to Mesenchymal Transition of a Primary Prostate Cell Line with Switches of Cell Adhesion Modules but without Malignant Transformation

Background: Epithelial to mesenchymal transition (EMT) has been connected with cancer progression in vivo and the generation of more aggressive cancer cell lines in vitro. EMT has been induced in prostate cancer cell lines, but has previously not been shown in primary prostate cells. The role of EMT in malignant transformation has not been clarified. Methodology/Principal Findings: In a transformation experiment when selecting for cells with loss of contact inhibition, the immortalized prostate primary epithelial cell line, EP156T, was observed to undergo EMT accompanied by loss of contact inhibition after about 12 weeks in continuous culture. The changed new cells were named EPT1. EMT of EPT1 was characterized by striking morphological changes and increased invasion and migration compared with the original EP156T cells. Gene expression profiling showed extensively decreased epithelial markers and increased mesenchymal markers in EPT1 cells, as well as pronounced switches of gene expression modules involved in cell adhesion and attachment. Transformation assays showed that EPT1 cells were sensitive to serum or growth factor withdrawal. Most importantly, EPT1 cells were not able to grow in an anchorage-independent way in soft agar, which is considered a critical feature of malignant transformation. Conclusions/Significance: This work for the first time established an EMT model from primary prostate cells. The results show that EMT can be activated as a coordinated gene expression program in association with early steps of transformation. The model allows a clearer identification of the molecular mechanisms of EMT and its potential role in malignant transformation