58 research outputs found

    Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives

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    [EN] We introduce a simulation framework for the transport of high and low energy electrons in xenon-based optical time projection chambers (OTPCs). The simulation relies on elementary cross sections (electron-atom and electron-molecule) and incorporates, in order to compute the gas scintillation, the reaction/quenching rates (atom-atom and atom-molecule) of the first 41 excited states of xenon and the relevant associated excimers, together with their radiative cascade. The results compare positively with observations made in pure xenon and its mixtures with CO2 and CF4 in a range of pressures from 0.1 to 10 bar. This work sheds some light on the elementary processes responsible for the primary and secondary xenon-scintillation mechanisms in the presence of additives, that are of interest to the OTPC technology.DGD is supported by the Ramon y Cajal program (Spain) under contract number RYC-2015-18820. The authors want to acknowledge the RD51 collaboration for encouragement and support during the elaboration of this work, and in particular discussions with F. Resnati, A. Milov, V. Peskov, M. Suzuki and A. F. Borghesani. The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the Ministerio de Economia y Competitividad of Spain under grants FIS2014-53371-C04 and the Severo Ochoa Program SEV-2014-0398; the GVA of Spain under grant PROM-ETEO/2016/120; the Portuguese FCT and FEDER through the program COMPETE, project PTDC/FIS-NUC/2525/2014 and UID/FIS/04559/2013; the U.S. Department of Energy under contracts number DE-AC02-07CH11359 (Fermi National Accelerator Laboratory) and DE-FG02-13ER42020 (Texas A& and the University of Texas at Arlington.Azevedo, C.; Gonzalez-Diaz, D.; Biagi, SF.; Oliveira, CAB.; Henriques, CAO.; Escada, J.; Monrabal, F.... (2018). Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives. Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment. 877:157-172. https://doi.org/10.1016/j.nima.2017.08.049S15717287

    Designing a broad-spectrum integrative approach for cancer prevention and treatment

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    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

    The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

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    More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease
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