Source Reconstruction as an Inverse Problem

Inverse Problem techniques offer powerful tools which deal naturally with marginal data and asymmetric or strongly smoothing kernels, in cases where parameter-fitting methods may be used only with some caution. Although they are typically subject to some bias, they can invert data without requiring one to assume a particular model for the source. The Backus-Gilbert method in particular concentrates on the tradeoff between resolution and stability, and allows one to select an optimal compromise between them. We use these tools to analyse the problem of reconstructing features of the source star in a microlensing event, show that it should be possible to obtain useful information about the star with reasonably obtainable data, and note that the quality of the reconstruction is more sensitive to the number of data points than to the quality of individual ones.Comment: 8 pages, 3 figures. To be published in "Microlensing 2000, A New Era of Microlensing Astrophysics", eds., J.W. Menzies and P.D. Sackett, ASP Conference Serie

An interactive triangle approach to student learning

Report of a CELT project on enhancing learning and teaching through innovation and research.Discusses the findings of a research project designed to improve student performance through innovative learning and teaching methods. The traditional format of the Human Physiology module (a core module in the Biomedical Science portfolio) comprising a weekly programme of two lectures and one tutorial was replaced by converting lectures into an on-line form and hosting them on the University's virtual learning environment (WOLF), linking these to key texts, on-line resources and computer software packages. Workshops and drop-in sessions provided additional support and an opportunity for lecturers to diagnose areas of difficulty and provide strategies for resolving them

Gravitational Microlensing of Extended Objects

Gravitational microlensing is an important tool in the search for Galactic dark matter. This thesis investigates how microlensing can be used to infer astrophysically interesting information about the structure of extended objects, as well as the feasibility of using extended source effects to improve the estimates of the lens parameters

The myriad positive impacts of the Virtual Learning Environment, from LabSims to Smart Worksheets (a 17 year journey)

PROBLEM Introducing a virtual learning environment (VLE) in support of practical teaching in Chemistry is not trivial. In this study we identify keys areas which are essential for successful implementation based on 17 years of experience. PLAN We have analysed a range of metrics from first initiating a VLE in the Centre for Excellence in Teaching and Learning (CETL) called Bristol CemLabS in 2006 and compare and contrast a similar implementation in the Faculty of Natural Sciences at The University of the Western Cape in South Africa in 2020. ACTION There are strong similarities in both environments following implementation of a VLE. Raising of confidence of students in using instruments and carrying out techniques found in an undergraduate chemistry laboratory is clear, increasing students understanding of the theory behind techniques and their real appreciation of health and safety. For demonstrators, their role changes from one where they are giving instruction to one where they are discussing the development of the practical investigation with the students. For academics, the transformation in ability of students, and long-term impacts on practical ability and final year projects that can be undertaken are noted. REFLECTION The transformation in both case studies was pretty much instant and irreversible for the students. Key elements required are strong IT support, strong collaboration between staff, demonstrators and technical staff. The main question to ask is why did we take so long to do this

Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: integrated analysis of data from Study 10 and ARIEL2

Objective: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). Methods: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600 mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600 mg BID, irrespective of BRCA1/2 mutation status and prior treatments. Results: In the efficacy population (n = 106), ORR was 53.8% (95% confidence interval [CI], 43.8–63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2 months (95% CI, 6.6–11.6). In the safety population (n = 377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥ 3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. Conclusions: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile

Commencement Program, June (1939)

https://red.mnstate.edu/commencement/1056/thumbnail.jp

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations