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Showing papers by "University of Perugia published in 2012"


Journal ArticleDOI
TL;DR: In this paper, results from searches for the standard model Higgs boson in proton-proton collisions at 7 and 8 TeV in the CMS experiment at the LHC, using data samples corresponding to integrated luminosities of up to 5.8 standard deviations.

8,857 citations


Journal ArticleDOI
TL;DR: Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation.
Abstract: Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.

4,116 citations


Journal ArticleDOI
P. L. Nolan1, A. A. Abdo2, A. A. Abdo3, Markus Ackermann  +290 moreInstitutions (53)
TL;DR: The second Fermi-LAT catalog (2FGL) as mentioned in this paper includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and spectral fits in terms either power-law, exponentially cutoff power law, or log-normal forms.
Abstract: We present the second catalog of high-energy γ-ray sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi), derived from data taken during the first 24 months of the science phase of the mission, which began on 2008 August 4. Source detection is based on the average flux over the 24 month period. The second Fermi-LAT catalog (2FGL) includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and spectral fits in terms of power-law, exponentially cutoff power-law, or log-normal forms. Also included are flux measurements in five energy bands and light curves on monthly intervals for each source. Twelve sources in the catalog are modeled as spatially extended. We provide a detailed comparison of the results from this catalog with those from the first Fermi-LAT catalog (1FGL). Although the diffuse Galactic and isotropic models used in the 2FGL analysis are improved compared to the 1FGL catalog, we attach caution flags to 162 of the sources to indicate possible confusion with residual imperfections in the diffuse model. The 2FGL catalog contains 1873 sources detected and characterized in the 100 MeV to 100 GeV range of which we consider 127 as being firmly identified and 1171 as being reliably associated with counterparts of known or likely γ-ray-producing source classes.

1,541 citations


Journal ArticleDOI
TL;DR: This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate.
Abstract: Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.

1,471 citations


Journal ArticleDOI
TL;DR: In this article, the authors outline the principles for landslide mapping, and review the conventional methods for the preparation of landslide maps, including geomorphological, event, seasonal, and multi-temporal inventories.

1,290 citations


Journal ArticleDOI
TL;DR: Extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytic cells, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor
Abstract: The S100 protein family consists of 24 members functionally distributed into three main subgroups: those that only exert intracellular regulatory effects, those with intracellular and extracellular functions and those which mainly exert extracellular regulatory effects. S100 proteins are only expressed in vertebrates and show cell-specific expression patterns. In some instances, a particular S100 protein can be induced in pathological circumstances in a cell type that does not express it in normal physiological conditions. Within cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors and nucleic acids. Some S100 proteins are secreted or released and regulate cell functions in an autocrine and paracrine manner via activation of surface receptors (e.g. the receptor for advanced glycation end-products and toll-like receptor 4), G-protein-coupled receptors, scavenger receptors, or heparan sulfate proteoglycans and N-glycans. Extracellular S100A4 and S100B also interact with epidermal growth factor and basic fibroblast growth factor, respectively, thereby enhancing the activity of the corresponding receptors. Thus, extracellular S100 proteins exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytes, Schwann cells, epithelial cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell migration and chemotaxis, tissue development and repair, and leukocyte and tumor cell invasion.

1,042 citations


Journal ArticleDOI
29 Mar 2012
TL;DR: In this article, the authors reported results from searches for the standard model Higgs boson in proton-proton collisions at square root(s) = 7 TeV in five decay modes: gamma pair, b-quark pair, tau lepton pair, W pair, and Z pair.
Abstract: Combined results are reported from searches for the standard model Higgs boson in proton-proton collisions at sqrt(s)=7 TeV in five Higgs boson decay modes: gamma pair, b-quark pair, tau lepton pair, W pair, and Z pair. The explored Higgs boson mass range is 110-600 GeV. The analysed data correspond to an integrated luminosity of 4.6-4.8 inverse femtobarns. The expected excluded mass range in the absence of the standard model Higgs boson is 118-543 GeV at 95% CL. The observed results exclude the standard model Higgs boson in the mass range 127-600 GeV at 95% CL, and in the mass range 129-525 GeV at 99% CL. An excess of events above the expected standard model background is observed at the low end of the explored mass range making the observed limits weaker than expected in the absence of a signal. The largest excess, with a local significance of 3.1 sigma, is observed for a Higgs boson mass hypothesis of 124 GeV. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-600 (110-145) GeV is estimated to be 1.5 sigma (2.1 sigma). More data are required to ascertain the origin of this excess.

786 citations


Journal ArticleDOI
TL;DR: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage.
Abstract: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).

690 citations


Journal ArticleDOI
Markus Ackermann, Marco Ajello1, W. B. Atwood2, Luca Baldini3  +176 moreInstitutions (36)
TL;DR: In this paper, a grid of models is created by varying within observational limits the distribution of cosmic-ray sources, the size of the cosmicray confinement volume (halo), and distribution of interstellar gas.
Abstract: The gamma-ray sky >100 MeV is dominated by the diffuse emissions from interactions of cosmic rays with the interstellar gas and radiation fields of the Milky Way. Observations of these diffuse emissions provide a tool to study cosmic-ray origin and propagation, and the interstellar medium. We present measurements from the first 21 months of the Fermi-LAT mission and compare with models of the diffuse gamma-ray emission generated using the GALPROP code. The models are fitted to cosmic-ray data and incorporate astrophysical input for the distribution of cosmic-ray sources, interstellar gas and radiation fields. To assess uncertainties associated with the astrophysical input, a grid of models is created by varying within observational limits the distribution of cosmic-ray sources, the size of the cosmic-ray confinement volume (halo), and the distribution of interstellar gas. An all-sky maximum-likelihood fit is used to determine the Xco-factor, the ratio between integrated CO-line intensity and molecular hydrogen column density, the fluxes and spectra of the gamma-ray point sources from the first Fermi-LAT catalogue, and the intensity and spectrum of the isotropic background including residual cosmic rays that were misclassified as gamma rays, all of which have some dependency on the assumed diffuse emission model. The models are compared on the basis of their maximum likelihood ratios as well as spectra, longitude, and latitude profiles. We also provide residual maps for the data following subtraction of the diffuse emission models. The models are consistent with the data at high and intermediate latitudes but under-predict the data in the inner Galaxy for energies above a few GeV. Possible explanations for this discrepancy are discussed, including the contribution by undetected point source populations and spectral variations of cosmic rays throughout the Galaxy.

686 citations


Journal ArticleDOI
TL;DR: In this article, a comparison of selected non-isothermal methods for analyzing solid-state kinetics data is presented, and the results of the kinetic study can be used in modeling devolatilization process through computational fluid dynamics (CFDs) to simulate mass and energy balances.

663 citations


Journal ArticleDOI
J. P. Lees1, V. Poireau1, V. Tisserand1, J. Garra Tico2  +362 moreInstitutions (77)
TL;DR: In this article, the BaBar data sample was used to investigate the sensitivity of BaBar ratios to new physics contributions in the form of a charged Higgs boson in the type II two-Higgs doublet model.
Abstract: Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.

Journal ArticleDOI
Markus Ackermann1, Marco Ajello1, Alice Allafort1, W. B. Atwood2  +155 moreInstitutions (31)
TL;DR: The Fermi Large Area Telescope measured separate cosmic-ray electron and positron spectra to distinguish the two species by exploiting Earth's shadow, and it is confirmed that the fraction rises with energy in the 20-100 GeV range.
Abstract: We measured separate cosmic-ray electron and positron spectra with the Fermi Large Area Telescope. Because the instrument does not have an onboard magnet, we distinguish the two species by exploiting the Earth's shadow, which is offset in opposite directions for opposite charges due to the Earth's magnetic field. We estimate and subtract the cosmic-ray proton background using two different methods that produce consistent results. We report the electron-only spectrum, the positron-only spectrum, and the positron fraction between 20 GeV and 200 GeV. We confirm that the fraction rises with energy in the 20--100 GeV range and determine for the first time that it continues to rise between 100 and 200 GeV.

Journal ArticleDOI
Markus Ackermann, Marco Ajello1, Andrea Albert2, Alice Allafort1  +220 moreInstitutions (42)
TL;DR: The Fermi Large Area Telescope (Fermi-LAT, hereafter LAT), the primary instrument on the FermI Gamma-ray Space Telescope (fermi) mission, is an imaging, wide field-of-view, high-energy \gamma-ray telescope, covering the energy range from 20 MeV to more than 300 GeV as discussed by the authors.
Abstract: The Fermi Large Area Telescope (Fermi-LAT, hereafter LAT), the primary instrument on the Fermi Gamma-ray Space Telescope (Fermi) mission, is an imaging, wide field-of-view, high-energy \gamma-ray telescope, covering the energy range from 20 MeV to more than 300 GeV. During the first years of the mission the LAT team has gained considerable insight into the in-flight performance of the instrument. Accordingly, we have updated the analysis used to reduce LAT data for public release as well as the Instrument Response Functions (IRFs), the description of the instrument performance provided for data analysis. In this paper we describe the effects that motivated these updates. Furthermore, we discuss how we originally derived IRFs from Monte Carlo simulations and later corrected those IRFs for discrepancies observed between flight and simulated data. We also give details of the validations performed using flight data and quantify the residual uncertainties in the IRFs. Finally, we describe techniques the LAT team has developed to propagate those uncertainties into estimates of the systematic errors on common measurements such as fluxes and spectra of astrophysical sources.

Journal ArticleDOI
TL;DR: In this article, the performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at the LHC in 2010.
Abstract: The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta)<2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.

Journal ArticleDOI
TL;DR: Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in therisk of major bleeding.
Abstract: In this multicenter, investigator-initiated, double-blind study, patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism, and major bleeding was the primary safety outcome. Results Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups. Conclusions Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding. (Funded by the University of Perugia and others; WARFASA ClinicalTrials.gov number, NCT00222677.)

Journal ArticleDOI
TL;DR: SIR2011, the successor of SIR2004, is the latest program of the SIR suite and can solve ab initio crystal structures of small- and medium-size molecules, as well as protein structures, using X-ray or electron diffraction data.
Abstract: SIR2011, the successor of SIR2004, is the latest program of the SIR suite. It can solve ab initio crystal structures of small- and medium-size molecules, as well as protein structures, using X-ray or electron diffraction data. With respect to the predecessor the program has several new abilities: e.g. a new phasing method (VLD) has been implemented, it is able to exploit prior knowledge of the molecular geometry via simulated annealing techniques, it can use molecular replacement methods for solving proteins, it includes new tools like free lunch and new approaches for electron diffraction data, and it visualizes three-dimensional electron density maps. The graphical interface has been further improved and allows the straightforward use of the program even in difficult cases.

Journal ArticleDOI
TL;DR: In this paper, the authors used cellulose nanocrystals (CNCs) and surfactant modified (s-CNC) and silver (Ag) nanoparticles in the polylactic acid (PLA) matrix using mel...

Journal ArticleDOI
TL;DR: Semuloparin reduces the incidence of thromboembolic events in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding.
Abstract: Background Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism. Limited data support the clinical benefit of antithrombotic prophylaxis. Methods In this double-blind, multicenter trial, we evaluated the efficacy and safety of the ultra-low-molecular-weight heparin semuloparin for prevention of venous thromboembolism in patients receiving chemotherapy for cancer. Patients with metastatic or locally advanced solid tumors who were beginning to receive a course of chemotherapy were randomly assigned to receive subcutaneous semuloparin, 20 mg once daily, or placebo until there was a change of chemotherapy regimen. The primary efficacy outcome was the composite of any symptomatic deep-vein thrombosis, any nonfatal pulmonary embolism, and death related to venous thromboembolism. Clinically relevant bleeding (major and nonmajor) was the main safety outcome. Results The median treatment duration was 3.5 months. Venous thromboembolism occurred in 20 of 1608 patients (1.2%) re...

Journal ArticleDOI
TL;DR: The transverse momentum spectra of charged particles have been measured in pp and PbPb collisions at 2.76 TeV by the CMS experiment at the LHC as mentioned in this paper.
Abstract: The transverse momentum spectra of charged particles have been measured in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV by the CMS experiment at the LHC. In the transverse momentum range pt = 5-10 GeV/c, the charged particle yield in the most central PbPb collisions is suppressed by up to a factor of 5 compared to the pp yield scaled by the number of incoherent nucleon-nucleon collisions. At higher pt, this suppression is significantly reduced, approaching roughly a factor of 2 for particles with pt in the range pt=40-100 GeV/c.

Journal ArticleDOI
TL;DR: Evaluated small-molecule inhibitors of poly-ADP-ribose polymerase (PARP) family proteins showed that the majority of PARP inhibitors bind multiple targets, providing insight into the design of new inhibitors.
Abstract: Inhibitors of poly-ADP-ribose polymerase (PARP) family proteins are currently in clinical trials as cancer therapeutics, yet the specificity of many of these compounds is unknown. Here we evaluated a series of 185 small-molecule inhibitors, including research reagents and compounds being tested clinically, for the ability to bind to the catalytic domains of 13 of the 17 human PARP family members including the tankyrases, TNKS1 and TNKS2. Many of the best-known inhibitors, including TIQ-A, 6(5H)-phenanthridinone, olaparib, ABT-888 and rucaparib, bound to several PARP family members, suggesting that these molecules lack specificity and have promiscuous inhibitory activity. We also determined X-ray crystal structures for five TNKS2 ligand complexes and four PARP14 ligand complexes. In addition to showing that the majority of PARP inhibitors bind multiple targets, these results provide insight into the design of new inhibitors.


Journal ArticleDOI
TL;DR: The migration level of the studied nano-biocomposites was below the overall migration limits required by the current normative for food packaging materials in both non-polar and polar simulants.

Journal ArticleDOI
Markus Ackermann, Marco Ajello1, Alice Allafort1, Luca Baldini2  +157 moreInstitutions (37)
TL;DR: In this paper, the authors examined a sample of 69 dwarf, spiral, and luminous and ultraluminous infrared galaxies at photon energies 0.1-100 GeV using 3 years of data collected by the LAT on the Fermi Gamma-ray Space Telescope (Fermi).
Abstract: Recent detections of the starburst galaxies M82 and NGC 253 by gamma-ray telescopes suggest that galaxies rapidly forming massive stars are more luminous at gamma-ray energies compared to their quiescent relatives. Building upon those results, we examine a sample of 69 dwarf, spiral, and luminous and ultraluminous infrared galaxies at photon energies 0.1-100 GeV using 3 years of data collected by the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope (Fermi). Measured fluxes from significantly detected sources and flux upper limits for the remaining galaxies are used to explore the physics of cosmic rays in galaxies.We find further evidence for quasi-linear scaling relations between gamma-ray luminosity and both radio continuum luminosity and total infrared luminosity which apply both to quiescent galaxies of the Local Group and low-redshift starburst galaxies (conservative P-values 0.05 accounting for statistical and systematic uncertainties). The normalizations of these scaling relations correspond to luminosity ratios of log(L0.1-100 GeV/L1.4 GHz) = 1.7 ± 0.1(statistical) ± 0.2(dispersion) and log(L0.1-100 GeV/L8-1000μm) = −4.3 ± 0.1(statistical) ± 0.2(dispersion) for a galaxy with a star formation rate of 1M yr−1, assuming a Chabrier initial mass function. Using the relationship between infrared luminosity and gamma-ray luminosity, the collective intensity of unresolved star-forming galaxies at redshifts 0 < z < 2.5 above 0.1 GeV is estimated to be 0.4-2.4 ×10−6 ph cm−2 s−1 sr−1 (4%-23% of the intensity of the isotropic diffuse component measured with the LAT).We anticipate that∼10 galaxies could be detected by their cosmic-ray-induced gamma-ray emission during a 10 year Fermi mission.

Journal ArticleDOI
TL;DR: This data indicates that in patients with unprovoked venous thromboembolism, the optimal duration of anticoagulation is anchored on estimating the risk of disease recurrence, and this work contributes to this understanding.

Journal ArticleDOI
TL;DR: The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid, and the proportion of adverse events was significantly higher when the lineZolid daily dosage exceeded 600 mg.
Abstract: Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure). Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤ 600 mg versus >600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg. The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.

Journal ArticleDOI
TL;DR: Notch2 mutations represent the most frequent lesion in splenic marginal zone lymphoma and are associated with atypical granuloma-like lesions.
Abstract: Splenic marginal zone lymphoma (SMZL) is a B cell malignancy of unknown pathogenesis, and thus an orphan of targeted therapies. By integrating whole-exome sequencing and copy-number analysis, we show that the SMZL exome carries at least 30 nonsilent gene alterations. Mutations in NOTCH2, a gene required for marginal-zone (MZ) B cell development, represent the most frequent lesion in SMZL, accounting for ~20% of cases. All NOTCH2 mutations are predicted to cause impaired degradation of the NOTCH2 protein by eliminating the C-terminal PEST domain, which is required for proteasomal recruitment. Among indolent B cell lymphoproliferative disorders, NOTCH2 mutations are restricted to SMZL, thus representing a potential diagnostic marker for this lymphoma type. In addition to NOTCH2, other modulators or members of the NOTCH pathway are recurrently targeted by genetic lesions in SMZL; these include NOTCH1, SPEN, and DTX1. We also noted mutations in other signaling pathways normally involved in MZ B cell development, suggesting that deregulation of MZ B cell development pathways plays a role in the pathogenesis of ~60% SMZL. These findings have direct implications for the treatment of SMZL patients, given the availability of drugs that can target NOTCH, NF-kB, and other pathways deregulated in this disease.

Journal ArticleDOI
T. Accadia1, Fausto Acernese2, M. Alshourbagy3, P. Amico4  +338 moreInstitutions (20)
TL;DR: Virgo as discussed by the authors is a very large Michelson interferometer with 3 km-long arms, built at Cascina, near Pisa (Italy), with a detailed description of all its different elements is given.
Abstract: This paper presents a complete description of Virgo, the French-Italian gravitational wave detector. The detector, built at Cascina, near Pisa (Italy), is a very large Michelson interferometer, with 3 km-long arms. In this paper, following a presentation of the physics requirements, leading to the specifications for the construction of the detector, a detailed description of all its different elements is given. These include civil engineering infrastructures, a huge ultra-high vacuum (UHV) chamber (about 6000 cubic metres), all of the optical components, including high quality mirrors and their seismic isolating suspensions, all of the electronics required to control the interferometer and for signal detection. The expected performances of these different elements are given, leading to an overall sensitivity curve as a function of the incoming gravitational wave frequency. This description represents the detector as built and used in the first data-taking runs. Improvements in different parts have been and continue to be performed, leading to better sensitivities. These will be detailed in a forthcoming paper.

Journal ArticleDOI
TL;DR: The consensus reached on preanalytical issues and the recommendations put forward during the Alzheimer's Biomarkers Standardization Initiative (ABSI) consensus meetings are presented in this paper.
Abstract: Background Numerous studies show that the cerebrospinal fluid biomarkers total tau (T-tau), tau phosphorylated at threonine 181 (P-tau 181P ), and amyloid-β (1-42) (Aβ 1–42 ) have high diagnostic accuracy for Alzheimer's disease. Variability in concentrations for Aβ 1–42 , T-tau, and P-tau 181P drives the need for standardization. Methods Key issues were identified and discussed before the first meeting of the members of the Alzheimer's Biomarkers Standardization Initiative (ABSI). Subsequent ABSI consensus meetings focused on preanalytical issues. Results Consensus was reached on preanalytical issues such as the effects of fasting, different tube types, centrifugation, time and temperature before storage, storage temperature, repeated freeze/thaw cycles, and length of storage on concentrations of Aβ 1–42 , T-tau, and P-tau 181P in cerebrospinal fluid. Conclusions The consensus reached on preanalytical issues and the recommendations put forward during the ABSI consensus meetings are presented in this paper.

Journal ArticleDOI
TL;DR: Two previous consensus guidelines for preanalytical confounding factors for CSF biomarkers are merged to achieve one exhaustive guideline updated with new evidence for Aβ42, total tau and phosphorylated tau, and α-synuclein.
Abstract: Early diagnosis of neurodegenerative disorders such as Alzheimer’s (AD) or Parkinson’s disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging due to the high variability found between centers in the concentrations of both AD CSF biomarkers (Aβ42, total tau and phosphorylated tau) and PD CSF biomarker (a-synuclein). Such a variability has been partially attributed to different preanalytical procedures between laboratories, thus highlighting the need to establish standardized operating procedures. Here, we merge two previous consensus guidelines for preanalytical confounding factors in order to achieve one exhaustive guideline updated with new evidence for Aβ42, total tau and phosphorylated tau, and a-synuclein. The proposed standardized operating procedures are applicable not only to novel CSF biomarkers in AD and PD, but also to biomarkers for other neurodegenerative disorders.

Journal ArticleDOI
Markus Ackermann, Marco Ajello1, Marco Ajello2, Alice Allafort1  +169 moreInstitutions (36)
30 Nov 2012-Science
TL;DR: In this paper, an absorption feature was observed in the combined spectra of a sample of gamma-ray blazars out to a redshift of z ∼ 1.6.
Abstract: The light emitted by stars and accreting compact objects through the history of the universe is encoded in the intensity of the extragalactic background light (EBL). Knowledge of the EBL is important to understand the nature of star formation and galaxy evolution, but direct measurements of the EBL are limited by galactic and other foreground emissions. Here, we report an absorption feature seen in the combined spectra of a sample of gamma-ray blazars out to a redshift of z ∼ 1.6. This feature is caused by attenuation of gamma rays by the EBL at optical to ultraviolet frequencies and allowed us to measure the EBL flux density in this frequency band.