286 research outputs found

    A Novel Electrical Method to Measure Wire Tensions for Time Projection Chambers

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    We present a novel electrical technique to measure the tension of wires in multi-wire drift chambers. We create alternating electric fields by biasing adjacent wires on both sides of a test wire with a superposition of positive and negative DC voltages on an AC signal (VAC±VDCV_{\rm AC} \pm V_{\rm DC}). The resulting oscillations of the wire will display a resonance at its natural frequency, and the corresponding change of the capacitance will lead to a measurable current. This scheme is scalable to multiple wires and therefore enables us to precisely measure the tension of a large number of wires in a short time. This technique can also be applied at cryogenic temperatures making it an attractive solution for future large time-projection chambers such as the DUNE detector. We present the concept, an example implementation and its performance in a real-world scenario and discuss the limitations of the sensitivity of the system in terms of voltage and wire length.Comment: 7 pages, 8 figures. Accepted by NIM

    Pharmacokinetics and safety of capmatinib with food in patients with MET-dysregulated advanced solid tumors

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    Purpose: In the Phase II GEOMETRY mono-1 study, the potent and selective mesenchymal-epithelial transition (MET) inhibitor capmatinib exhibited considerable efficacy in MET exon 14 skipping (METex14)–mutated metastatic non–small cell lung cancer at a dose of 400 mg BID. The current recommended dose is 400 mg BID in tablet formulation, with or without food. This article reports the pharmacokinetic (PK) profile, safety, and tolerability of capmatinib 300 and 400 mg BID given with food in MET-dysregulated advanced solid tumors. Methods: This multicenter, open-label, Phase I study enrolled adult patients with MET-dysregulated advanced solid tumors. In the dose escalation phase, capmatinib tablets were orally administered at a dose of 300 mg BID with food; if tolerated, the dose escalation cohort of 400 mg BID was to be opened to enrollment. In the expansion phase, patients were to be enrolled at the higher of the tolerated doses. Tablets were taken within 30 minutes of an unrestricted meal type, except on cycle 1 day 1 (C1D1) and cycle 1 day 7 (C1D7), when they were given with a high-fat meal. The primary objectives were to determine the higher of the tolerated study doses and assess PK variables, with a secondary objective of safety. Findings: Overall, 35 patients (300 mg BID, n = 8; 400 mg BID, n = 27) with MET-dysregulated advanced solid tumors were enrolled; all patients had received prior antineoplastic therapy, and the most common primary site was lung (45.7%). Among PK-evaluable patients, the median T for capmatinib after administration with a high-fat meal (on C1D1/C1D7) was 4.0 to 5.6 hours across doses. At steady state (C1D7), capmatinib accumulation was low across dose levels (geometric mean of accumulation ratios, 1.29–1.69), with an increase in exposure (AUC and C ) from 300 to 400 mg BID. There were no occurrences of dose-limiting toxicity. All patients experienced at least 1 adverse event, and treatment-related adverse events occurred in 28 patients (80%; 300 mg BID, n = 6; 400 mg BID, n = 22), the most frequent of which were fatigue (37.1%) and nausea (34.3%). Implications: Capmatinib tablet formulation at a dose of up to 400 mg BID with food is well tolerated in patients with MET-dysregulated advanced solid tumors, with safety observations consistent with the existing profile under fasted conditions. These findings support the capmatinib dosing recommendation of 400 mg BID with or without food. ClinicalTrials.gov identifier: NCT02925104

    First Measurement of Electron Neutrino Scattering Cross Section on Argon

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    We report the first electron neutrino cross section measurements on argon, based on data collected by the ArgoNeuT experiment running in the GeV-scale NuMI beamline at Fermilab. A flux-averaged νe+ν‾e\nu_e + \overline{\nu}_e total and a lepton angle differential cross section are extracted using 13 νe\nu_e and ν‾e\overline{\nu}_e events identified with fully-automated selection and reconstruction. We employ electromagnetic-induced shower characterization and analysis tools developed to identify νe/ν‾e\nu_e/\overline{\nu}_e-like events among complex interaction topologies present in ArgoNeuT data (⟨Eνˉe⟩=4.3\langle E_{\bar{\nu}_e} \rangle = 4.3 GeV and ⟨Eνe⟩=10.5\langle E_{\nu_e} \rangle = 10.5 GeV). The techniques are widely applicable to searches for electron-flavor appearance at short- and long-baseline using liquid argon time projection chamber technology. Notably, the data-driven studies of GeV-scale νe/ν‾e\nu_e/\overline{\nu}_e interactions presented in this Letter probe an energy regime relevant for future DUNE oscillation physics.Comment: added acknowledgement

    Ulcerogenic Helicobacter pylori Strains Isolated from Children: A Contribution to Get Insight into the Virulence of the Bacteria

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    Infection with Helicobacter pylori is the major cause for the development of peptic ulcer disease (PUD). In children, with no other etiology for the disease, this rare event occurs shortly after infection. In these young patients, habits of smoking, diet, consumption of alcohol and non-steroid anti-inflammatory drugs and stress, in addition to the genetic susceptibility of the patient, represent a minor influence. Accordingly, the virulence of the implicated H. pylori strain should play a crucial role in the development of PUD. Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins. To uncover virulence features, we compared the proteome of these two groups of H. pylori strains. Two-dimensional gel electrophoresis followed by mass-spectrometry allowed us to detect 27 differentially expressed proteins between them. In addition to the presence of genes encoding well established virulence factors, namely cagA, vacAs1, oipA “on” status, homB and jhp562 genes, the pediatric ulcerogenic strains shared a proteome profile characterized by changes in the abundance of: motility-associated proteins, accounting for higher motility; antioxidant proteins, which may confer increased resistance to inflammation; and enzymes involved in key steps in the metabolism of glucose, amino acids and urea, which may be advantageous to face fluctuations of nutrients. In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors

    Self-bias and the emotionality of foreign languages

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    Article first published online: June 13, 2018Foreign language contexts impose a relative psychological and emotional distance in bilinguals. In our previous studies, we demonstrated that the use of a foreign language changes the strength of the seemingly automatic emotional responses in the self-paradigm, showing a robust asymmetry in the self-bias effect in a native and a foreign language context. Namely, larger effects were found in the native language, suggesting an emotional blunting in the foreign language context. In the present study, we investigated the source of these effects by directly comparing whether they stem from a language’s foreignness versus its non-nativeness. We employed the same self-paradigm (a simple perceptual matching task of associating simple geometric shapes with the labels “you,” “friend,” and “other”), testing unbalanced Spanish–Basque–English trilinguals. We applied the paradigm to three language contexts: native, non-native but contextually present (i.e., non-native local), and non-native foreign. Results showed a smaller self-bias only in the foreign language pointing to the foreign-language-induced psychological/emotional distance as the necessary prerequisite for foreign language effects. Furthermore, we explored whether perceived emotional distance towards foreign languages in Spanish–English bilinguals modulates foreign language effects. Results suggest that none of the different indices of emotional distance towards the foreign language obtained via questionnaires modulated the self-biases in the foreign language contexts. Our results further elucidate the deeply rooted and automatic nature of foreign-language-driven differential emotional processing.This research has been partially funded by grants PSI2015-65689-P and SEV-2015-0490 from the Spanish Government, AThEME-613465 from the European Union, and a 2016 BBVA Foundation Grant for Researchers and Cultural Creators awarded to the last author (J.A.D.)
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