7 research outputs found

    Ab initio optical properties of Si(100)

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    We compute the linear optical properties of different reconstructions of the clean and hydrogenated Si(100) surface within DFT-LDA, using norm-conserving pseudopotentials. The equilibrium atomic geometries of the surfaces, determined from self-consistent total energy calculations within the Car-Parrinello scheme, strongly influence Reflectance Anisotropy Spectra (RAS), showing differences between the p(2x2) and c(4x2)reconstructions. The Differential Reflectivity spectrum for the c(4x2) reconstruction shows a positive peak at energies < 1 eV, in agreement with experimental results.Comment: fig. 2 correcte

    Molecular profiling of long-term IDH-wildtype glioblastoma survivors

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    Background: Glioblastoma (GBM) represents an aggressive cancer type with a median survival of only 14 months. With fewer than 5% of patients surviving 5 years, comprehensive profiling of these rare patients could elucidate prognostic biomarkers that may confer better patient outcomes. We utilized multiple molecular approaches to characterize the largest patient cohort of isocitrate dehydrogenase (IDH)-wildtype GBM long-term survivors (LTS) to date. Methods: Retrospective analysis was performed on 49 archived formalin-fixed paraffin embedded tumor specimens from patients diagnosed with GBM at the Mayo Clinic between December 1995 and September 2013. These patient samples were subdivided into 2 groups based on survival (12 LTS, 37 short-term survivors [STS]) and subsequently examined by mutation sequencing, copy number analysis, methylation profiling, and gene expression. Results: Of the 49 patients analyzed in this study, LTS were younger at diagnosis (P = 0.016), more likely to be female (P = 0.048), and MGMT promoter methylated (UniD, P = 0.01). IDH-wildtype STS and LTS demonstrated classic GBM mutations and copy number changes. Pathway analysis of differentially expressed genes showed LTS enrichment for sphingomyelin metabolism, which has been linked to decreased GBM growth, invasion, and angiogenesis. STS were enriched for DNA repair and cell cycle control networks. Conclusions: While our findings largely report remarkable similarity between these LTS and more typical STS, unique attributes were observed in regard to altered gene expression and pathway enrichment. These attributes may be valuable prognostic markers and are worth further examination. Importantly, this study also underscores the limitations of existing biomarkers and classification methods in predicting patient prognosis

    Selection of the InSight Landing Site

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    The selection of the Discovery Program InSight landing site took over four years from initial identification of possible areas that met engineering constraints, to downselection via targeted data from orbiters (especially Mars Reconnaissance Orbiter (MRO) Context Camera (CTX) and High-Resolution Imaging Science Experiment (HiRISE) images), to selection and certification via sophisticated entry, descent and landing (EDL) simulations. Constraints on elevation (≀−2.5 km for sufficient atmosphere to slow the lander), latitude (initially 15°S–5°N and later 3°N–5°N for solar power and thermal management of the spacecraft), ellipse size (130 km by 27 km from ballistic entry and descent), and a load bearing surface without thick deposits of dust, severely limited acceptable areas to western Elysium Planitia. Within this area, 16 prospective ellipses were identified, which lie ∌600 km north of the Mars Science Laboratory (MSL) rover. Mapping of terrains in rapidly acquired CTX images identified especially benign smooth terrain and led to the downselection to four northern ellipses. Acquisition of nearly continuous HiRISE, additional Thermal Emission Imaging System (THEMIS), and High Resolution Stereo Camera (HRSC) images, along with radar data confirmed that ellipse E9 met all landing site constraints: with slopes \u3c15° at 84 m and 2 m length scales for radar tracking and touchdown stability, low rock abundance (\u3c10 %) to avoid impact and spacecraft tip over, instrument deployment constraints, which included identical slope and rock abundance constraints, a radar reflective and load bearing surface, and a fragmented regolith ∌5 m thick for full penetration of the heat flow probe. Unlike other Mars landers, science objectives did not directly influence landing site selection

    Effect of celecoxib vs placebo as adjuvant therapy on disease-free survival among patients with breast cancer

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    Importance: Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking. Objective: To evaluate the role of celecoxib as an addition to conventional therapy for women with ERBB2 (formerly HER2)-negative primary breast cancer. Design, Setting, and Participants: The Randomized European Celecoxib Trial (REACT) was a phase 3, randomized, double-blind study conducted in 160 centers across the UK and Germany testing 2 years of adjuvant celecoxib vs placebo among 2639 patients recruited between January 19, 2007, and November 1, 2012, with follow-up 10 years after treatment completion. Eligible patients had completely resected breast cancer with local and systemic therapy according to local practice. Patients with ERBB2-positive or node-negative and T1, grade 1 tumors were not eligible. Randomization was in a 2:1 ratio between celecoxib or placebo. Statistical analysis was performed from May 5, 2019, to March 5, 2020. Interventions: Patients received celecoxib, 400 mg, or placebo once daily for 2 years. Main Outcomes and Measures: The primary end point was disease-free survival (DFS), analyzed in the intention-to-treat population using Cox proportional hazards regression and log-rank analysis. Follow-up is complete. Results: A total of 2639 patients (median age, 55.2 years [range, 26.8-86.0 years]) were recruited; 1763 received celecoxib, and 876 received placebo. Most patients' tumors (1930 [73%]) were estrogen receptor positive or progesterone receptor positive and ERBB2 negative. A total of 1265 patients (48%) had node-positive disease, and 1111 (42%) had grade 3 tumors. At a median follow-up of 74.3 months (interquartile range, 61.4-93.6 years), DFS events had been reported for 487 patients (19%): 18% for those who received celecoxib (n = 323; 5-year DFS rate = 84%) vs 19% for those who received placebo (n = 164; 5-year DFS rate = 83%); the unadjusted hazard ratio was 0.97 (95% CI, 0.80-1.17; log-rank P =.75). Rates of toxic effects were low across both treatment groups, with no evidence of a difference. Conclusions and Relevance: In this randomized clinical trial, patients showed no evidence of a DFS benefit for 2 years' treatment with celecoxib compared with placebo as adjuvant treatment of ERBB2-negative breast cancer. Longer-term treatment or use of a higher dose of celecoxib may lead to a DFS benefit, but further studies would be required to test this possibility. Trial Registration: ClinicalTrials.gov Identifier: NCT02429427 and isrctn.org Identifier: ISRCTN48254013

    Selenium Donors at the Junction of Inflammatory Diseases

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