A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED

RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes. METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement. RESULTS: 9 GSVA signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper type 2 (Th-2) cytokines and lack of corticosteroid response (Group 1 and Group 3). Group 1 had the highest submucosal eosinophils, high exhaled nitric oxide (FeNO) levels, exacerbation rates and oral corticosteroid (OCS) use whilst Group 3 patients showed the highest levels of sputum eosinophils and had a high BMI. In contrast, Group 2 and Group 4 patients had an 86% and 64% probability of having non-eosinophilic inflammation. Using machine-learning tools, we describe an inference scheme using the currently-available inflammatory biomarkers sputum eosinophilia and exhaled nitric oxide levels along with OCS use that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity. CONCLUSION: This analysis demonstrates the usefulness of a transcriptomic-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target Th2-mediated inflammation and/or corticosteroid insensitivity

Studies of the Response of the Prototype CMS Hadron Calorimeter, Including Magnetic Field Effects, to Pion, Electron, and Muon Beams

We report on the response of a prototype CMS hadron calorimeter module to charged particle beams of pions, muons, and electrons with momenta up to 375 GeV/c. The data were taken at the H2 and H4 beamlines at CERN in 1995 and 1996. The prototype sampling calorimeter used copper absorber plates and scintillator tiles with wavelength shifting fibers for readout. The effects of a magnetic field of up to 3 Tesla on the response of the calorimeter to muons, electrons, and pions are presented, and the effects of an upstream lead tungstate crystal electromagnetic calorimeter on the linearity and energy resolution of the combined calorimetric system to hadrons are evaluated. The results are compared with Monte Carlo simulations and are used to optimize the choice of total absorber depth, sampling frequency, and longitudinal readout segmentation.Comment: 89 pages, 41 figures, to be published in NIM, corresponding author: P de Barbaro, [email protected]

Radiation hardness qualification of PbWO4 scintillation crystals for the CMS Electromagnetic Calorimeter

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPEnsuring the radiation hardness of PbWO4 crystals was one of the main priorities during the construction of the electromagnetic calorimeter of the CMS experiment at CERN. The production on an industrial scale of radiation hard crystals and their certification over a period of several years represented a difficult challenge both for CMS and for the crystal suppliers. The present article reviews the related scientific and technological problems encountered

A New Biology: A Modern Perspective on the Challenge of Closing the Gap between the Islands of Knowledge

This paper discusses the rebirth of the old quest for the principles of biology along the discourse line of machine-organism disanalogy and within the context of biocomputation from a modern perspective. It reviews some new attempts to revise the existing body of research and enhance it with new developments in some promising fields of mathematics and computation. The major challenge is that the latter are expected to also answer the need for a new framework, a new language and a new methodology capable of closing the existing gap between the different levels of complex system organization

Performance of a spaghetti calorimeter prototype with tungsten absorber and garnet crystal fibres

A spaghetti calorimeter (SPACAL) prototype with scintillating crystal fibres was assembled and tested with electron beams of energy from 1 to 5 GeV. The prototype comprised radiation-hard Cerium-doped GdAlGaO (GAGG:Ce) and YAlO (YAG:Ce) embedded in a pure tungsten absorber. The energy resolution was studied as a function of the incidence angle of the beam and found to be of the order of 10%/E⊕1%, in line with the LHCb Shashlik technology. The time resolution was measured with metal channel dynode photomultipliers placed in contact with the fibres or coupled via a light guide, additionally testing an optical tape to glue the components. Time resolution of a few tens of picosecond was achieved for all the energies reaching down to (18.5 ± 0.2) ps at 5 GeV.We acknowledge support by the CERN Strategic Programme on Technologies for Future Experiments, https://ep-rnd.web.cern.ch/, by the MCIN/AEI, GenCat and GVA (Spain), and by the NSFC (China) under grant Nos. 12175005, 12061141007. The measurements were performed at the Test Beam Facility at DESY Hamburg (Germany), a member of the Helmholtz Association (HGF). The authors would like to thank T. Schneider, H. Gerwig, N. Siegrist, and D. Deyrail (CERN) for their help in designing and assembling the prototype and the set-up, A. Barnyakov, Budker Institute of Nuclear Physics (BINP), Novosibirsk, for kindly providing the MCPs, and the ITEP ATLAS group for the DWCs

Levi-Civita,Tullio

International audienceTullio Levi-Civita (29 March 1873 to 29 December 1941) has been an Italian mathematician and mathematical physicist, known above all for his work on the absolute differential calculus. Levi-Civita came from a rigorous and creative school of mathematical physicists and was a pupil of Gregorio Ricci-Curbastro. LeviCivita’s work included outstanding results in pure and applied mathematics and in celestial and analytic mechanics but also celebrated textbooks. These last, even those written in Italian, have influenced mathematical physicists all over the world.Levi-Civita has perfected some conceptual tools of great importance in modern science, particularly in general relativity, number theory, and continuum mechanics

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Ly6Chi monocyte recruitment is responsible for Th2 associated host-protective macrophage accumulation in liver inflammation due to schistosomiasis

Accumulation of M2 macrophages in the liver, within the context of a strong Th2 response, is a hallmark of infection with the parasitic helminth, Schistosoma mansoni, but the origin of these cells is unclear. To explore this, we examined the relatedness of macrophages to monocytes in this setting. Our data show that both monocyte-derived and resident macrophages are engaged in the response to infection. Infection caused CCR2-dependent increases in numbers of Ly6Chi monocytes in blood and liver and of CX3CR1+ macrophages in diseased liver. Ly6Chi monocytes recovered from liver had the potential to differentiate into macrophages when cultured with M-CSF. Using pulse chase BrdU labeling, we found that most hepatic macrophages in infected mice arose from monocytes. Consistent with this, deletion of monocytes led to the loss of a subpopulation of hepatic CD11chi macrophages that was present in infected but not naïve mice. This was accompanied by a reduction in the size of egg-associated granulomas and significantly exacerbated disease. In addition to the involvement of monocytes and monocyte-derived macrophages in hepatic inflammation due to infection, we observed increased incorporation of BrdU and expression of Ki67 and MHC II in resident macrophages, indicating that these cells are participating in the response. Expression of both M2 and M1 marker genes was increased in liver from infected vs. naive mice. The M2 fingerprint in the liver was not accounted for by a single cell type, but rather reflected expression of M2 genes by various cells including macrophages, neutrophils, eosinophils and monocytes. Our data point to monocyte recruitment as the dominant process for increasing macrophage cell numbers in the liver during schistosomiasis

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets