22 research outputs found

    Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

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    A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

    International AIDS Society global scientific strategy: towards an HIV cure 2016

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    Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy

    A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

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    The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

    Journal of Biophotonics / Reshaping a multimode laser beam into a constructed Gaussian beam for generating a thin light sheet

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    Based on the modal analysis method, we developed a model that describes the output beam of a diodepumped solid state (DPSS) laser emitting a multimode beam. Measuring the output beam profile in the near field and at the constructed far field the individual modes, their respective contributions, and their optical parameters are determined. Using this information, the beam is optically reshaped into a quasiGaussian beam by the interference and superposition of the various modes. This process is controlled by a mode modulator unit that includes different mesoaspheric elements and a softaperture. The converted beam is guided into a second optical unit comprising achromaticaspheric elements to produce a thin light sheet for ultramicroscopy. We found that this light sheet is markedly thinner and exhibits less side shoulders compared with a light sheet directly generated from the output of a DPSS multimode laser.(VLID)481827

    Democratizing knowledge representation with BioCypher

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    International audienceStandardising the representation of biomedical knowledge among allresearchers is an insurmountable task, hindering the effectiveness of manycomputational methods. To facilitate harmonisation and interoperability despitethis fundamental challenge, we propose to standardise the framework ofknowledge graph creation instead. We implement this standardisation inBioCypher, a FAIR (findable, accessible, interoperable, reusable) framework totransparently build biomedical knowledge graphs while preserving provenances ofthe source data. Mapping the knowledge onto biomedical ontologies helps tobalance the needs for harmonisation, human and machine readability, and ease ofuse and accessibility to non-specialist researchers. We demonstrate the usefulnessof the framework on a variety of use cases, from maintenance of task-specificknowledge stores, to interoperability between biomedical domains, to on-demandbuilding of task-specific knowledge graphs for federated learning. BioCypher(https://biocypher.org) thus facilitates automating knowledge-based biomedicalresearch, and we encourage the community to further develop and use it

    ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma

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    Clinical management of melanomas with NRAS mutations is challenging. Targeting MAPK signaling is only beneficial to a small subset of patients due to resistance that arises through genetic, transcriptional, and metabolic adaptation. Identification of targetable vulnerabilities in NRAS-mutated melanoma could help improve patient treatment. Here, we used multiomics analyses to reveal that NRAS-mutated melanoma cells adopt a mesenchymal phenotype with a quiescent metabolic program to resist cellular stress induced by MEK inhibition. The metabolic alterations elevated baseline reactive oxygen species (ROS) levels, leading these cells to become highly sensitive to ROS induction. In vivo xenograft experiments and single-cell RNA sequencing demonstrated that intratumor heterogeneity necessitates the combination of a ROS inducer and a MEK inhibitor to inhibit both tumor growth and metastasis. Ex vivo pharmacoscopy of 62 human metastatic melanomas confirmed that MEK inhibitor-resistant tumors significantly benefited from the combination therapy. Finally, oxidative stress response and translational suppression corresponded with ROS-inducer sensitivity in 486 cancer cell lines, independent of cancer type. These findings link transcriptional plasticity to a metabolic phenotype that can be inhibited by ROS inducers in melanoma and other cancers. Significance: Metabolic reprogramming in drug-resistant NRAS-mutated melanoma cells confers sensitivity to ROS induction, which suppresses tumor growth and metastasis in combination with MAPK pathway inhibitors
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