195 research outputs found
New Upper Limit of Terrestrial Equivalence Principle Test for Rotating Extended Bodies
Improved terrestrial experiment to test the equivalence principle for
rotating extended bodies is presented, and a new upper limit for the violation
of the equivalence principle is obtained at the level of 1.6, which is limited by the friction of the rotating gyroscope. It
means the spin-gravity interaction between the extended bodies has not been
observed at this level.Comment: 4 page
Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.
Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies
The Nab Experiment: A Precision Measurement of Unpolarized Neutron Beta Decay
Neutron beta decay is one of the most fundamental processes in nuclear
physics and provides sensitive means to uncover the details of the weak
interaction. Neutron beta decay can evaluate the ratio of axial-vector to
vector coupling constants in the standard model, , through
multiple decay correlations. The Nab experiment will carry out measurements of
the electron-neutrino correlation parameter with a precision of and the Fierz interference term to
in unpolarized free neutron beta decay. These results, along with a more
precise measurement of the neutron lifetime, aim to deliver an independent
determination of the ratio with a precision of that will allow an evaluation of and sensitively
test CKM unitarity, independent of nuclear models. Nab utilizes a novel, long
asymmetric spectrometer that guides the decay electron and proton to two large
area silicon detectors in order to precisely determine the electron energy and
an estimation of the proton momentum from the proton time of flight. The Nab
spectrometer is being commissioned at the Fundamental Neutron Physics Beamline
at the Spallation Neutron Source at Oak Ridge National Lab. We present an
overview of the Nab experiment and recent updates on the spectrometer,
analysis, and systematic effects.Comment: Presented at PPNS201
Resilience trinity: Safeguarding ecosystem functioning and services across three different time horizons and decision contexts
Ensuring ecosystem resilience is an intuitive approach to safeguard the functioning of ecosystems and hence the future provisioning of ecosystem services (ES). However, resilience is a multi‐faceted concept that is difficult to operationalize. Focusing on resilience mechanisms, such as diversity, network architectures or adaptive capacity, has recently been suggested as means to operationalize resilience. Still, the focus on mechanisms is not specific enough. We suggest a conceptual framework, resilience trinity, to facilitate management based on resilience mechanisms in three distinctive decision contexts and time‐horizons: 1) reactive, when there is an imminent threat to ES resilience and a high pressure to act, 2) adjustive, when the threat is known in general but there is still time to adapt management and 3) provident, when time horizons are very long and the nature of the threats is uncertain, leading to a low willingness to act. Resilience has different interpretations and implications at these different time horizons, which also prevail in different disciplines. Social ecology, ecology and engineering are often implicitly focussing on provident, adjustive or reactive resilience, respectively, but these different notions of resilience and their corresponding social, ecological and economic tradeoffs need to be reconciled. Otherwise, we keep risking unintended consequences of reactive actions, or shying away from provident action because of uncertainties that cannot be reduced. The suggested trinity of time horizons and their decision contexts could help ensuring that longer‐term management actions are not missed while urgent threats to ES are given priority
Trocar-guided total tension-free vaginal mesh repair of post-hysterectomy vaginal vault prolapse
Contains fulltext :
81076.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The objective of this study was to report 1 year anatomical and functional outcomes of trocar-guided total tension-free vaginal mesh (Prolift) repair for post-hysterectomy vaginal vault prolapse with one continuous piece of polypropylene mesh. METHODS: We conducted a prospective observational cohort study of 46 patients. A minimum sample size of 35 patients was needed to detect a recurrence rate of less than 20% at 12 months. Instruments of measurement used were pelvic organ prolapse quantification and validated questionnaires. RESULTS: Overall anatomical success was 91% (95% confidence interval 83-99), with significant improvement in experienced bother and quality of life. Mesh exposure occurred in seven patients (15%). No adverse effects on sexual function could be detected. CONCLUSIONS: Trocar-guided total tension-free vaginal mesh (Prolift) repair with one continuous piece of mesh for post-hysterectomy vaginal vault prolapse is well tolerated and anatomically and functionally highly effective. Results of controlled trials will determine its position in the operative armamentarium
The fundamental constants and their variation: observational status and theoretical motivations
This article describes the various experimental bounds on the variation of
the fundamental constants of nature. After a discussion on the role of
fundamental constants, of their definition and link with metrology, the various
constraints on the variation of the fine structure constant, the gravitational,
weak and strong interactions couplings and the electron to proton mass ratio
are reviewed. This review aims (1) to provide the basics of each measurement,
(2) to show as clearly as possible why it constrains a given constant and (3)
to point out the underlying hypotheses. Such an investigation is of importance
to compare the different results, particularly in view of understanding the
recent claims of the detections of a variation of the fine structure constant
and of the electron to proton mass ratio in quasar absorption spectra. The
theoretical models leading to the prediction of such variation are also
reviewed, including Kaluza-Klein theories, string theories and other
alternative theories and cosmological implications of these results are
discussed. The links with the tests of general relativity are emphasized.Comment: 56 pages, l7 figures, submitted to Rev. Mod. Phy
Association of Common Polymorphisms in GLUT9 Gene with Gout but Not with Coronary Artery Disease in a Large Case-Control Study
BACKGROUND: Serum uric acid (UA) levels have recently been shown to be genetically influenced by common polymorphisms in the GLUT9 gene in two genome-wide association analyses of Italian and British populations. Elevated serum UA levels are often found in conjunction with the metabolic syndrome. Hyperuricemia is the major risk factor for gout and has been associated with increased cardiovascular morbidity and mortality. The aim of the present study was to further elucidate the association of polymorphisms in GLUT9 with gout and coronary artery disease (CAD) or myocardial infarction (MI). To test our hypotheses, we performed two large case-control association analyses of individuals from the German MI Family Study. METHODS AND FINDINGS: First, 665 patients with gout and 665 healthy controls, which were carefully matched for age and gender, were genotyped for four single nucleotide polymorphisms (SNPs) within or near the GLUT9 gene. All four SNPs demonstrated highly significant association with gout. SNP rs6855911, located within intron 7 of GLUT9, showed the strongest signal with a protective effect of the minor allele with an allelic odds ratio of 0.62 (95% confidence interval 0.52-0.75; p = 3.2*10(-7)). Importantly, this finding was not influenced by adjustment for components of the metabolic syndrome or intake of diuretics. Secondly, 1,473 cases with severe CAD or MI and 1,241 healthy controls were tested for the same four GLUT9 SNPs. The analyses revealed, however, no significant association with CAD or with MI. Additional screening of genome-wide association data sets showed no signal for CAD or MI within the GLUT9 gene region. CONCLUSION: Thus, our results provide compelling evidence that common genetic variations within the GLUT9 gene strongly influence the risk for gout but are unlikely to have a major effect on CAD or MI in a German population
METhodological RadiomICs Score (METRICS): a quality scoring tool for radiomics research endorsed by EuSoMII
Purpose: To propose a new quality scoring tool, METhodological RadiomICs Score (METRICS), to assess and improve research quality of radiomics studies. Methods: We conducted an online modified Delphi study with a group of international experts. It was performed in three consecutive stages: Stage#1, item preparation; Stage#2, panel discussion among EuSoMII Auditing Group members to identify the items to be voted; and Stage#3, four rounds of the modified Delphi exercise by panelists to determine the items eligible for the METRICS and their weights. The consensus threshold was 75%. Based on the median ranks derived from expert panel opinion and their rank-sum based conversion to importance scores, the category and item weights were calculated. Result: In total, 59 panelists from 19 countries participated in selection and ranking of the items and categories. Final METRICS tool included 30 items within 9 categories. According to their weights, the categories were in descending order of importance: study design, imaging data, image processing and feature extraction, metrics and comparison, testing, feature processing, preparation for modeling, segmentation, and open science. A web application and a repository were developed to streamline the calculation of the METRICS score and to collect feedback from the radiomics community. Conclusion: In this work, we developed a scoring tool for assessing the methodological quality of the radiomics research, with a large international panel and a modified Delphi protocol. With its conditional format to cover methodological variations, it provides a well-constructed framework for the key methodological concepts to assess the quality of radiomic research papers. Critical relevance statement: A quality assessment tool, METhodological RadiomICs Score (METRICS), is made available by a large group of international domain experts, with transparent methodology, aiming at evaluating and improving research quality in radiomics and machine learning. Key points: • A methodological scoring tool, METRICS, was developed for assessing the quality of radiomics research, with a large international expert panel and a modified Delphi protocol. • The proposed scoring tool presents expert opinion-based importance weights of categories and items with a transparent methodology for the first time. • METRICS accounts for varying use cases, from handcrafted radiomics to entirely deep learning-based pipelines. • A web application has been developed to help with the calculation of the METRICS score (https://metricsscore.github.io/metrics/METRICS.html) and a repository created to collect feedback from the radiomics community (https://github.com/metricsscore/metrics). Graphical Abstract: [Figure not available: see fulltext.
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