Algorithm Engineering in Robust Optimization

Robust optimization is a young and emerging field of research having received a considerable increase of interest over the last decade. In this paper, we argue that the the algorithm engineering methodology fits very well to the field of robust optimization and yields a rewarding new perspective on both the current state of research and open research directions. To this end we go through the algorithm engineering cycle of design and analysis of concepts, development and implementation of algorithms, and theoretical and experimental evaluation. We show that many ideas of algorithm engineering have already been applied in publications on robust optimization. Most work on robust optimization is devoted to analysis of the concepts and the development of algorithms, some papers deal with the evaluation of a particular concept in case studies, and work on comparison of concepts just starts. What is still a drawback in many papers on robustness is the missing link to include the results of the experiments again in the design

Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways

Cyclosporine A (CSA) is an immunosuppressive agent that specifically targets T cells and also increases the percentage of pro-tolerogenic CD4+Foxp3+ regulatory T cells (Treg) through unknown mechanisms. We previously reported that CD44, a receptor for the extracellular matrix glycosaminoglycan hyaluronan (HA), promotes Treg stability in IL-2-low environments. Here, we asked whether CD44 signaling also promotes Treg resistance to CSA. We found that CD44 cross-linking promoted Foxp3 expression and Treg viability in the setting of CSA treatment. This effect was IL-2 independent but could be suppressed using sc-355979, an inhibitor of Stat5-phosphorylation. Moreover, we found that inhibition of HA synthesis impairs Treg homeostasis but that this effect could be overcome with exogenous IL-2 or CD44-cross-linking. Together, these data support a model whereby CD44 cross-linking by HA promotes IL-2-independent Foxp3 expression and Treg survival in the face of CSA

Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide

An association has previously been shown between antibiotic-refractory Lyme arthritis, the human histocompatibility leukocyte antigen (HLA)–DR4 molecule, and T cell recognition of an epitope of Borrelia burgdorferi outer-surface protein A (OspA163–175). We studied the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes in 121 patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis and correlated these frequencies with in vitro binding of the OspA163–175 peptide to 14 DRB molecules. Among the 121 patients, the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes were similar to those in control subjects. However, when stratified by antibiotic response, the frequencies of DRB1 alleles in the 71 patients with antibiotic-refractory arthritis differed significantly from those in the 50 antibiotic-responsive patients (log likelihood test, P = 0.006; exact test, P = 0.008; effect size, Wn = 0.38). 7 of the 14 DRB molecules (DRB1*0401, 0101, 0404, 0405, DRB5*0101, DRB1*0402, and 0102) showed strong to weak binding of OspA163–175, whereas the other seven showed negligible or no binding of the peptide. Altogether, 79% of the antibiotic-refractory patients had at least one of the seven known OspA peptide–binding DR molecules compared with 46% of the antibiotic-responsive patients (odds ratio = 4.4; P < 0.001). We conclude that binding of a single spirochetal peptide to certain DRB molecules is a marker for antibiotic-refractory Lyme arthritis and might play a role in the pathogenesis of the disease

The insulin A-chain epitope recognized by human T cells is posttranslationally modified

The autoimmune process that destroys the insulin-producing pancreatic β cells in type 1 diabetes (T1D) is targeted at insulin and its precursor, proinsulin. T cells that recognize the proximal A-chain of human insulin were identified recently in the pancreatic lymph nodes of subjects who had T1D. To investigate the specificity of proinsulin-specific T cells in T1D, we isolated human CD4+ T cell clones to proinsulin from the blood of a donor who had T1D. The clones recognized a naturally processed, HLA DR4–restricted epitope within the first 13 amino acids of the A-chain (A1–13) of human insulin. T cell recognition was dependent on the formation of a vicinal disulfide bond between adjacent cysteine residues at A6 and A7, which did not alter binding of the peptide to HLA DR4. CD4+ T cell clones that recognized this epitope were isolated from an HLA DR4+ child with autoantibodies to insulin, and therefore, at risk for T1D, but not from two healthy HLA DR4+ donors. We define for the first time a novel posttranslational modification that is required for T cell recognition of the insulin A-chain in T1D

Semileptonic B decays into excited charmed mesons from QCD sum rules

Exclusive semileptonic $B$ decays into excited charmed mesons are studied with QCD sum rules in the leading order of heavy quark effective theory. Two universal Isgur-Wise functions \tau and \zeta for semileptonic B decays into four lowest lying excited $D$ mesons ($D_1$, $D_2^*$, $D'_0$, and $D'_1$) are determined. The decay rates and branching ratios for these processes are calculated.Comment: RevTeX, 17 pages including 2 figure

Enacting informal science learning: exploring the battle for informal learning

Informal Science Learning (ISL) is a policy narrative of interest in the UK and abroad. This paper explores how a group of English secondary school science teachers, enacted ISL science clubs through employing the Periodic Table of Videos (PTOV). It examines how these teachers ‘battled’ to enact ISL policy in performative (Lyotard, 1979) conditions at the micro-scale, and how this battle reflected macro-scale epistemological and political considerations. Data from the study suggests that for some, ISL was low-stakes as it was seen to have negligible impact upon performance data. As a result, there was some resistance toward enacting ISL and conflict between the formal and informal curriculum processes. Nonetheless, analysis indicates that the informants highly valued ISL despite the requirement for them to justify it over more formal and ‘effective’ approaches to learning science

Scoring Federal Legislation for Equity: Definition, Framework, and Potential Application

Federal legislation is fundamental to building a nation in which all can participate, prosper, and reach their full potential. Since our nation's founding, in many ways, federal legislation has created and exacerbated racial inequities, leaving one-third of the population experiencing material poverty and preventing our democracy from realizing the promise of equity. To ensure the federal government serves us all, we must accurately understand and assess whether every policy advances or impedes equity. The Equity Scoring Initiative (ESI) exists to establish the foundation for a new legislative scoring regime. By scoring for equity, we can begin to create an accountable, responsive democracy

Generation of nonclassical biphoton states through cascaded quantum walks on a nonlinear chip

We demonstrate a nonlinear optical chip that generates photons with reconfigurable nonclassical spatial correlations. We employ a quadratic nonlinear waveguide array, where photon pairs are generated through spontaneous parametric down-conversion and simultaneously spread through quantum walks between the waveguides. Because of the quantum interference of these cascaded quantum walks, the emerging photons can become entangled over multiple waveguide positions. We experimentally observe highly nonclassical photon-pair correlations, confirming the high fidelity of on-chip quantum interference. Furthermore, we demonstrate biphoton-state tunability by spatial shaping and frequency tuning of the classical pump beam