New transcriptional-based insights into the pathogenesis of desmoplastic small round cell tumors (DSRCTs).

To gain new insights into desmoplastic small round cell tumors (DSRCTs) by means of gene expression profiling (GEP). Formalin-fixed, paraffin-embedded surgical specimens obtained from seven pretreated DSRCT patients were interrogated using GEP complemented by immunohistochemistry, a cancer stem cell array, and miRNA in situ hybridisation, including the combined chimera modules miRNA-200/ZEB1 and miRNA-34/SLUG. The chimera modules divided the cases into three classes that respectively recapitulated the traits of mesenchymal epithelial reverse transition (MErT), epithelial mesenchymal transition (EMT), and hybrid/partial EMT. This indicates a close correlation between the reprogramming governed by EMT regulators and DSRCT biology, which was further confirmed by miRNA-21 and is consistent with the broad morphological spectrum of DSRCTs. Starting from the miRNA-200/ZEB1 axis, we also found that DSRCTs carry a signature of immunological ignorance that is not responsive to PD--L1 blockade. Evidence that the up-regulation of miRNA-200 and E-cadherin, and quite a high level of miRNA-21 expression segregate with the MErT supports the idea that, in addition to the hybrid/partial state, MErT is also enriched in stemness: the androgen-positive cases, whose stemness traits were confirmed by stem cell arrays, all fell into these two classes. Our findings also confirmed that tumoral cell PDGFRA expression correlates with desmoplasia, and demonstrated the co-expression of PDGFRA and ISLR/Meflin, another marker of pluripotency. Despite the limited number of cases, these findings provide unexpectedly relevant information concerning the pathogenesis of DSRCTs, and prove the validity of miRNA-based chimera circuit modelling in the clinico-pathological setting

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Aligning the CMS Muon Chambers with the Muon Alignment System during an Extended Cosmic Ray Run

Peer reviewe

Search for dark matter candidates and large extra dimensions in events with a jet and missing transverse momentum with the ATLAS detector

Open Access, Copyright CERN, for the benefit of the ATLAS collaboration. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited

A three-dimensional model of human lung development and disease from pluripotent stem cells

Author ManuscriptRecapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. Infection in vitro with respiratory syncytial virus, which causes small airway obstruction and bronchiolitis in infants, led to swelling, detachment and shedding of infected cells into the organoid lumens, similar to what has been observed in human lungs. Introduction of mutation in HPS1, which causes an early-onset form of intractable pulmonary fibrosis, led to accumulation of extracellular matrix and mesenchymal cells, suggesting the potential use of this model to recapitulate fibrotic lung disease in vitro. LBOs therefore recapitulate lung development and may provide a useful tool to model lung disease.NIH HL120046-01 (H.-W.S.), 1U01HL134760-01 (H.-W.S.) RO1 AI031971 (A.M.), and RO1 AI114736 (A.M.), as well as a sponsored research and agreement from Northern Biologics Inc. (H.-W.S.), and funding from the Thomas R Kully IPF Research Fund (H.-W.S.). RUES2-HPS1 cells were generated by the Columbia Stem Cell Core Facility. We thank NYULMC OCS Microscopy core C. Petzold and K. Dancel for their assistance with transmission electron microscopy. We thank M. Peeples (Ohio State University) for providing the original recombinant RSV. Flow cytometry was performed in the CCTI Flow Cytometry Core, supported in part by the Office of the Director, National Institutes of Health under awards S10RR027050 and S10OD02005

Electrochemical copolymerization of N-methylpyrrole and 2,2′-bithitiophene; characterization, micro-capacitor study, and equivalent circuit model evaluation

N-methylpyrrole (N-MPy) and 2,2'-bithiophene (BTh) were electrocopolymerized in 0 center dot 2 M acetonitrile-sodium perchlorate solvent-electrolyte couple on a glassy carbon electrode (GCE) by cyclic voltammetry (CV). The resulting homopolymers and copolymers in different initial feed ratios of [N-MPy](0)/[BTh](0) = 1/1, 1/2, 1/5 and 1/10 were characterized by CV, Fourier-transform infrared reflectance attenuated transmittance (FTIR-ATR), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX) and electrochemical impedance spectroscopy (EIS). The capacitive behaviours of the modified electrodes were defined via Nyquist, Bode-magnitude, Bode-phase and admittance plots. The equivalent circuit model of R(C(R)(QR)(CR)) was performed to fit theoretical and experimental data. The highest low-frequency capacitance (C (LF)) were obtained as C (LF) = similar to 1 center dot 23 x 10 (-4) mF cm (-2) for P(N-MPy), C (LF) = similar to 2 center dot 09 x 10 (-4) mF cm(-2) for P(BTh) and C (LF) = similar to 5 center dot 54 x 10 (-4) mF cm(-2) for copolymer in the inital feed ratio of [N-MPy](0)/[BTh] (0) = 1/2.Research Foundation of Namik Kemal University, TurkeyNamik Kemal University [NKUBAP.00.10.YL.12.02]Financial support for this work by the Research Foundation of Namik Kemal University, Turkey, (project number: NKUBAP.00.10.YL.12.02), is gratefully acknowledged

Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older

A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229.)