A Comparison of Operator Utility Measures for On-Line Operator Selection in Local Search

This paper investigates the adaptive selection of operators in the context of Local Search. The utility of each operator is computed from the solution quality and distance of the candidate solution from the search trajectory. A number of utility measures based on the Pareto dominance relationship and the relative distances between the operators are proposed and evaluated on QAP instances using an implied or static target balance between exploitation and exploration. A refined algorithm with an adaptive target balance is then examined

An Exploration-exploitation Compromise-based Adaptive Operator Selection for Local Search

This paper deals with the adaptive selection of operators in the context of local search (LS). In evolutionary algorithms, diversity is a key concept. We consider a related idea: the similarity between the candidate solution and the solutions in the search trajectory. This notion, together with the solution quality, is used to evaluate the performance of each operator. A new utility measure for LS operators, evaluating relative distances between the operators, is introduced. It is compared with an existing measure based on the Pareto dominance relationship using some basic selection schemes. An adaptive version of the algorithm is also examined. The proposed methods are tested on the Quadratic Assignment Problem and Asymmetric Traveling Salesman Problem

Synthesis and biological activity of α-glucosyl C24:0 and C20:2 ceramides

a-Glucosyl ceramides 4 and 5 have been synthesised and evaluated for their ability to stimulate the activation and expansion of human iNKT cells. The key challenge in the synthesis of both target molecules was the stereoselective synthesis of the a-glycosidic linkage. Of the methods examined, glycosylation using per-TMS-protected glucosyl iodide 16 was completely a-selective and provided gram quantities of amine 11, from which a-glucosyl ceramides 4 and 5 were obtained by N-acylation. a-GlcCer 4, containing a C24 saturated acyl chain, stimulated a marked proliferation and expansion of human circulating iNKT cells in short-term cultures. a-GlcCer 5, which contains a C20 11,14-cis-diene acyl chain (C20:2),induced extremely similar levels of iNKT cell activation and expansion

A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial

Clinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1–7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy. Methods and results A multi-centre phase II randomized, double-blind, and placebo-controlled trial. One hundred patients with anterior AMI and significant regional wall motion abnormality were randomized to receive either intracoronary infusion of BMC or placebo (1:1) within 24 h of successful primary percutaneous intervention (PPCI). The primary endpoint was the change in left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging. At 1 year, although LVEF increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: −0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0–0.20; P = 0.048). Major adverse events were rare in both treatment groups. Conclusion The early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage.UK Stem Cells Foundation, the Heart Cells Foundation, and Barts and the London Charity. Funding to pay the Open Access publication charges for this article was provided by the Barts Cardiovascular Biomedical Research Unit (CVBRU)

Ottawa 2020 consensus statements for programmatic assessment 2: Implementation and practice

INTRODUCTION: Programmatic assessment is a longitudinal, developmental approach that fosters and harnesses the learning function of assessment. Yet the implementation, a critical step to translate theory into practice, can be challenging. As part of the Ottawa 2020 consensus statement on programmatic assessment, we sought to provide descriptions of the implementation of the 12 principles of programmatic assessment and to gain insight into enablers and barriers across different institutions and contexts. METHODS: After the 2020 Ottawa conference, we surveyed 15 Health Profession Education programmes from six different countries about the implementation of the 12 principles of programmatic assessment. Survey responses were analysed using a deductive thematic analysis. RESULTS AND DISCUSSION: A wide range of implementations were reported although the principles remained, for the most part, faithful to the original enunciation and rationale. Enablers included strong leadership support, ongoing faculty development, providing students with clear expectations about assessment, simultaneous curriculum renewal and organisational commitment to change. Most barriers were related to the need for a paradigm shift in the culture of assessment. Descriptions of implementations in relation to the theoretical principles, across multiple educational contexts, coupled with explanations of enablers and barriers, provided new insights and a clearer understanding of the strategic and operational considerations in the implementation of programmatic assessment. Future research is needed to further explore how contextual and cultural factors affect implementation

Saposins utilize two strategies for lipid transfer and CD1 antigen presentation

Funding: We are grateful to A.N. Odyniec, M. Brigl, G.F.M. Watts, and T.Y. Cheng for suggestions and excellent technical assistance. This work was supported by National Institutes of Health (NIH) Grants AI028973 and AI063428 (to M.B.B.), DK36729 and NS36681 (to G.A.G.), and AR048632 and AI049313 (to D.B.M. and A.K.); a Howard Hughes Medical Institute Gilliam Fellowship (to L.L.); the Burroughs Wellcome Fund (D.B.M. and A.K.); a Personal Research Chair from Mr. James Bardrick (to V.B., N.V., and G.S.B.); a Royal Society Wolfson Research Merit Award (to V.B., N.V., and G.S.B.); the Medical Research Council (V.B., N.V., and G.S.B.); Wellcome Trust Grant 084923/B/08/Z (to V.B., N.V., and G.S.B.); and a Netherlands Organization for Scientific Research Grant (to A.J.M.Transferring lipid antigens from membranes into CD1 antigen-presenting proteins represents a major molecular hurdle necessary for T-cell recognition. Saposins facilitate this process, but the mechanisms used are not well understood. We found that saposin B forms soluble saposin protein-lipid complexes detected by native gel electrophoresis that can directly load CD1 proteins. Because saposin B must bind lipids directly to function, we found it could not accommodate long acyl chain containing lipids. In contrast, saposin C facilitates CD1 lipid loading in a different way. It uses a stable, membrane-associated topology and was capable of loading lipid antigens without forming soluble saposin-lipid antigen complexes. These findings reveal how saposins use different strategies to facilitate transfer of structurally diverse lipid antigens.publishersversionpublishe