626 research outputs found
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
ANOCA, INOCA, MINOCA: The New Frontier of Coronary Syndromes.
Abstract: The growing prevalence in the diagnosis of INOCA (Ischemia with Non-
Obstructive Coronary Arteries), ANOCA (Angina with Non-Obstructive Coronary Arteries),
and MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries)
highlights the need to reassess their clinical relevance. Historically regarded as benign
syndromes, emerging evidence suggests that these conditions may cause serious cardiovascular events and considerable long-term disability. Additionally, emerging studies
suggest that non-obstructive coronary artery disease (CAD) may have a higher prevalence
compared to traditional obstructive forms of CAD. This leads to the need to better clarify
the underlying pathogenic mechanisms as well as the risk factors associated with these
syndromes. This is precisely the aim of this review, which focuses on the complex and heterogeneous mechanisms underlying these syndromes as well as the associated risk factors. This review also sums up the diagnostic steps necessary to achieve an accurate diagnosis, along with the interventional and pharmacological approaches to be implemented in light of the latest evidence
Measurement of the t¯tZ and t¯tW cross sections in proton-proton collisions at √s=13 TeV with the ATLAS detector
A measurement of the associated production of a top-quark pair (t¯t) with a vector boson (W, Z) in proton-proton collisions at a center-of-mass energy of 13 TeV is presented, using 36.1 fb−1 of integrated luminosity collected by the ATLAS detector at the Large Hadron Collider. Events are selected in channels with two same- or opposite-sign leptons (electrons or muons), three leptons or four leptons, and each channel is further divided into multiple regions to maximize the sensitivity of the measurement. The t¯tZ and t¯tW production cross sections are simultaneously measured using a combined fit to all regions. The best-fit values of the production cross sections are σt¯tZ=0.95±0.08stat±0.10syst pb and σt¯tW=0.87±0.13stat±0.14syst pb in agreement with the Standard Model predictions. The measurement of the t¯tZ cross section is used to set constraints on effective field theory operators which modify the t¯tZ vertex
Search for large missing transverse momentum in association with one top-quark in proton-proton collisions at √s = 13 TeV with the ATLAS detector
This paper describes a search for events with one top-quark and large missing transverse momentum in the final state. Data collected during 2015 and 2016 by the ATLAS experiment from 13 TeV proton–proton collisions at the LHC corresponding to an integrated luminosity of 36.1 fb−1 are used. Two channels are considered, depending on the leptonic or the hadronic decays of the W boson from the top quark. The obtained results are interpreted in the context of simplified models for dark-matter production and for the single production of a vector-like T quark. In the absence of significant deviations from the Standard Model background expectation, 95% confidence-level upper limits on the corresponding production cross-sections are obtained and these limits are translated into constraints on the parameter space of the models considered
Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.
Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim
of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases
Differential viral accessibility (DIVA) identifies alterations in chromatin architecture through large-scale mapping of lentiviral integration sites.
Alterations in chromatin structure play a major role in the epigenetic regulation of gene expression. Here, we describe a step-by-step protocol for differential viral accessibility (DIVA), a method for identifying changes in chromatin accessibility genome-wide. Commonly used methods for mapping accessible genomic loci have strong preferences toward detecting 'open' chromatin found at regulatory regions but are not well suited to studying chromatin accessibility in gene bodies and intergenic regions. DIVA overcomes this limitation, enabling a broader range of sites to be interrogated. Conceptually, DIVA is similar to ATAC-seq in that it relies on the integration of exogenous DNA into the genome to map accessible chromatin, except that chromatin architecture is probed through mapping integration sites of exogenous lentiviruses. An isogenic pair of cell lines are transduced with a lentiviral vector, followed by PCR amplification and Illumina sequencing of virus-genome junctions; the resulting sequences define a set of unique lentiviral integration sites, which are compared to determine whether genomic loci exhibit significantly altered accessibility between experimental and control cells. Experienced researchers will take 6 d to generate lentiviral stocks and transduce the target cells, a further 5 d to prepare the Illumina sequencing libraries and a few hours to perform the bioinformatic analysis
Comparison of different methods involved in the planning of clinical crown lengthening surgery
There is little material in the literature that compares biological width measurements in periapical and bite-wings radiographs with clinical measurements. The purpose of this study was to compare measurements of biological width taken by three different methods which are frequently used for planning periodontal surgery - periapical radiograph, bite-wing radiograph and transperiodontal probing - with the trans-surgical measurements. Thirty-four sites from twenty-one subjects were analyzed. The intra-class correlation coefficients between measurements obtained trans-surgically (gold standard) and those obtained by transperiodontal probing, periapical radiography and bite-wing radiography were determined. Average measurements were compared using the Wilcoxon test at a significance level of 0.05. Also, the frequency distribution of differences between test measurements and the gold standard was calculated. The results showed that transperiodontal probing (mean 2.05 mm) was the most accurate measurement, as compared to the gold standard (mean 1.97 mm), with no statistically significant difference observed. On the other hand, periapical and bite-wing radiographic mean values (1.56 mm and 1.72 mm, respectively) were smaller than the gold standard, with statistically significant differences (p < 0.05). It was concluded that transperiodontal probing was the most accurate measurement, as compared to the gold standard, followed by that obtained with the bite-wing radiograph. The clinical relevance of these results could be that planning for crown lengthening surgery should, preferably, include transperiodontal probing
New CUORICINO Results On the Way to CUORE
CUORE is a 0.75 ton experiment to search for neutrinoless double beta decay of Te130 using 988 TeO2 bolometers. It aims at reaching a sensitivity on the effective neutrino mass of the order of few tens of meV. CUORICINO, a single CUORE tower running since 2003, plays an important role as a stand alone experiment and for developing the future CUORE setup. Present results already achieved and studies that are underway are here presented and discussed
MicroRNA-199b-5p Impairs Cancer Stem Cells through Negative Regulation of HES1 in Medulloblastoma
BACKGROUND: Through negative regulation of gene expression, microRNAs (miRNAs) can function in cancers as oncosuppressors, and they can show altered expression in various tumor types. Here we have investigated medulloblastoma tumors (MBs), which arise from an early impairment of developmental processes in the cerebellum, where Notch signaling is involved in many cell-fate-determining stages. MBs occur bimodally, with the peak incidence seen between 3-4 years and 8-9 years of age, although it can also occur in adults. Notch regulates a subset of the MB cells that have stem-cell-like properties and can promote tumor growth. On the basis of this evidence, we hypothesized that miRNAs targeting the Notch pathway can regulated these phenomena, and can be used in anti-cancer therapies. METHODOLOGY/PRINCIPAL FINDINGS: In a screening of MB cell lines, the miRNA miR-199b-5p was seen to be a regulator of the Notch pathway through its targeting of the transcription factor HES1. Down-regulation of HES1 expression by miR-199b-5p negatively regulates the proliferation rate and anchorage-independent growth of MB cells. MiR-199b-5p over-expression blocks expression of several cancer stem-cell genes, impairs the engrafting potential of MB cells in the cerebellum of athymic/nude mice, and of particular interest, decreases the MB stem-cell-like (CD133+) subpopulation of cells. In our analysis of 61 patients with MB, the expression of miR-199b-5p in the non-metastatic cases was significantly higher than in the metastatic cases (P = 0.001). Correlation with survival for these patients with high levels of miR-199b expression showed a positive trend to better overall survival than for the low-expressing patients. These data showing the down-regulation of miR-199b-5p in metastatic MBs suggest a potential silencing mechanism through epigenetic or genetic alterations. Upon induction of de-methylation using 5-aza-deoxycytidine, lower miR-199b-5p expression was seen in a panel of MB cell lines, supported an epigenetic mechanism of regulation. Furthermore, two cell lines (Med8a and UW228) showed significant up-regulation of miR-199b-5p upon treatment. Infection with MB cells in an induced xenograft model in the mouse cerebellum and the use of an adenovirus carrying miR-199b-5p indicate a clinical benefit through this negative influence of miR-199b-5p on tumor growth and on the subset of MB stem-cell-like cells, providing further proof of concept. CONCLUSIONS/SIGNIFICANCE: Despite advances in our understanding of the pathogenesis of MB, one-third of these patients remain incurable and current treatments can significantly damage long-term survivors. Here we show that miR-199b-5p expression correlates with metastasis spread, identifying a new molecular marker for a poor-risk class in patients with MB. We further show that in a xenograft model, MB tumor burden can be reduced, indicating the use of miR199b-5p as an adjuvant therapy after surgery, in combination with radiation and chemotherapy, for the improvement of anti-cancer MB therapies and patient quality of life. To date, this is the first report that expression of a miRNA can deplete the tumor stem cells, indicating an interesting therapeutic approach for the targeting of these cells in brain tumors
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