217 research outputs found

    The Primary Cosmic Ray Electron Spectrum near Solar Minimum

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    Primary cosmic ray electron spectrum near solar minimu

    The flux and energy spectrum of primary cosmic ray electrons

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    Experiment giving approximate energy spectrum of electron component in primary cosmic radiatio

    The primary cosmic ray electron spectrum in the energy range from 300 MeV to 4 BeV from 1964 to 1966

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    Primary cosmic ray electron spectrum in energy range from 300 MeV to 4 Be

    Study of helium transfer technology for STICCR: Fluid management

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    The Space Infrared Telescope Facility (SIRTF) is a long life cryogenically cooled space based telescope for infrared astronomy from 2 to 700 microns currently under study and planned for launch in the mid 90's. SIRTF will operate as a multi-user facility, initially carrying 3 instruments at the focal plane. It will be cooled to below 2 K by superfluid liquid helium to achieve radiometric sensitivity limited only by the statistical fluctuations in the natural infrared background radiation over most of its spectral range. The lifetime of the mission will be limited by the lifetime of the liquid helium supply, and is currently baselined to be 2 years. Candidates are reviewed for a liquid management device to be used in the resupply of liquid helium, and for the selection of an appropriate candidate

    The development of a high energy cosmic ray detector for Spacelab-2

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    A large cosmic ray detector aimed at measurements of the energy spectra and of the elemental abundances of cosmic ray nuclei at very high energies, up to several TeV/nucleon was constructed. The instrument is an electronic counter telescope with a geometric factor of 5 sq ster. It accomplishes measurements of the particle energies through the use of gas Cerenkov counters and of transition radiation detectors. The solutions of a number of technological problems that are encountered when developing such instrumentation for Shuttle missions are discussed

    Olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer patients without a germline BRCA1/BRCA2 mutation: OPINION primary analysis

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    Maintenance; Olaparib; Ovarian cancerManteniment; Olaparib; Càncer d'ovarisMantenimiento; Olaparib; Cáncer de ovariosObjective The phase IIIb OPINION trial (NCT03402841) investigated olaparib maintenance monotherapy in patients without a deleterious or suspected deleterious germline BRCA1/BRCA2 mutation (gBRCAm) who had platinum-sensitive relapsed ovarian cancer (PSROC) and had received ≥2 previous lines of platinum-based chemotherapy. Methods In this single-arm, open-label, international study, patients who had responded to platinum-based chemotherapy received maintenance olaparib tablets (300 mg twice daily) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival (PFS) (modified RECIST version 1.1). A key secondary endpoint was PFS by homologous recombination deficiency (HRD) and somatic BRCAm (sBRCAm) status. The primary analysis of PFS was planned for 18 months after the last patient received their first dose. Results Two hundred and seventy-nine patients were enrolled and received olaparib. At data cutoff (October 2, 2020), 210 PFS events had occurred (75.3% maturity) and median PFS was 9.2 months (95% confidence interval [CI], 7.6–10.9) in the overall population. At 12 and 18 months, 38.5% and 24.3% of patients were progression-free, respectively. In the predefined biomarker subgroups, median PFS was 16.4, 11.1, 9.7, and 7.3 months in sBRCAm, HRD-positive including sBRCAm, HRD-positive excluding sBRCAm, and HRD-negative patients, respectively. The most common treatment-emergent adverse events (TEAEs) were nausea (48.4%) and fatigue/asthenia (44.1%). TEAEs led to dose interruption, dose reduction, and treatment discontinuation in 47.0%, 22.6%, and 7.5% of patients, respectively. Conclusion Maintenance olaparib demonstrated clinical benefit in patients without a gBRCAm, and across all subgroups, compared with historical placebo controls. There were no new safety signals.This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

    Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: Clinical and molecular characterization

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    Purpose: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. Experimental Design: A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted. LT response was defined as response to olaparib/placebo > 2 years, ST as < 3 months. Molecular analyses included germline BRCA1/2 status, three-biomarker homologous recombination deficiency (HRD) score, BRCA1 methylation, and mutational profiling. Another olaparib maintenance study (Study 41; NCT01081951) was used as an additional cohort. Results: Thirty-seven LT (32 olaparib) and 61 ST (21 olaparib) patients were identified. Treatment was significantly associated with outcome (P < 0.0001), with more LT patients on olaparib (60.4%) than placebo (11.1%). LT sensitivity to olaparib correlated with complete response to chemotherapy (P < 0.05). In the olaparib LT group, 244 genetic alterations were detected, with TP53, BRCA1, and BRCA2 mutations being most common (90%, 25%, and 35%, respectively). BRCA2 mutations were enriched among the LT responders. BRCA methylation was not associated with response duration. High myriad HRD score (>42) and/or BRCA1/2 mutation was associated with LT response to olaparib. Study 41 confirmed the correlation of LT response with olaparib and BRCA1/2 mutation. Conclusions: Findings show that LT response to olaparib may be multifactorial and related to homologous recombination repair deficiency, particularly BRCA1/2 defects. The type of BRCA1/2 mutation warrants further investigation. (C) 2017 AACR
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