A Community Resource Benchmarking Predictions of Peptide Binding to MHC-I Molecules

Recognition of peptides bound to major histocompatibility complex (MHC) class I molecules by T lymphocytes is an essential part of immune surveillance. Each MHC allele has a characteristic peptide binding preference, which can be captured in prediction algorithms, allowing for the rapid scan of entire pathogen proteomes for peptide likely to bind MHC. Here we make public a large set of 48,828 quantitative peptide-binding affinity measurements relating to 48 different mouse, human, macaque, and chimpanzee MHC class I alleles. We use this data to establish a set of benchmark predictions with one neural network method and two matrix-based prediction methods extensively utilized in our groups. In general, the neural network outperforms the matrix-based predictions mainly due to its ability to generalize even on a small amount of data. We also retrieved predictions from tools publicly available on the internet. While differences in the data used to generate these predictions hamper direct comparisons, we do conclude that tools based on combinatorial peptide libraries perform remarkably well. The transparent prediction evaluation on this dataset provides tool developers with a benchmark for comparison of newly developed prediction methods. In addition, to generate and evaluate our own prediction methods, we have established an easily extensible web-based prediction framework that allows automated side-by-side comparisons of prediction methods implemented by experts. This is an advance over the current practice of tool developers having to generate reference predictions themselves, which can lead to underestimating the performance of prediction methods they are not as familiar with as their own. The overall goal of this effort is to provide a transparent prediction evaluation allowing bioinformaticians to identify promising features of prediction methods and providing guidance to immunologists regarding the reliability of prediction tools

Circulating TNF-like protein 1A (TL1A) is elevated early in rheumatoid arthritis and depends on TNF

Abstract Background The tumor necrosis factor (TNF) superfamily cytokine TNF-like protein 1A (TL1A) and its receptor DR3 are essential for diverse animal models of autoimmune disease and may be pathogenic in rheumatoid arthritis (RA). However, the relationship of TL1A to disease duration, activity, and response to anti-TNF and other therapies in RA is not clear. Methods We measured soluble TL1A in synovial fluid (SF), serum, or plasma from RA first-degree relatives (FDRs) and in early RA and established disease. We measured the effects of anti-TNF and methotrexate (MTX) therapy on circulating TL1A from multiple independent RA treatment trials. We also determined the ability of a blocking anti-TL1A antibody to inhibit clinical disease and articular bone destruction in the murine collagen-induced arthritis (CIA) model of human RA. Results Soluble TL1A was specifically elevated in the blood and SF of patients with RA compared to patients with other diseases and was elevated early in disease and in at-risk anti-cyclic citrullinated peptide (CCP) (+) first-degree relatives (FDRs). Therapeutic TNF inhibition reduced serum TL1A in both responders and non-responders, whereas TL1A declined following MTX treatment only in responders. In murine CIA, TL1A blockade was clinically efficacious and reduced bone erosions. Conclusions TL1A is specifically elevated in RA from early in the disease course and in at-risk FDRs. The decline in TL1A after TNF blockade suggests that TL1A levels may be a useful biomarker for TNF activity in RA. These results support the further investigation of the relationship between TL1A and TNF and TL1A blockade as a potential therapeutic strategy in RA

THE EFFECT OF SEQUENTIAL VARIABLES ON PERFORMANCE USING ATTITUDINAL STIMULI

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an Analysis of Identity Checks in Paris

Law enforcement officers in France are often accused of carrying out identity checks on the basis of physical appearance (contrôles au faciès), singling out particular ethnic groups, or “visible minorities”. To show that discrimination is taking place, it is not enough simply to demonstrate that police stops affect one group more than another. It also has to be shown that this group is disproportionately targeted in relation to the population present in the relevant geographical area. This is a particularly difficult task. Fabien JOBARD, René LÉVY, John LAMBERTH and Sophie NÉVANEN report on a survey of identity checks carried out in Paris in 2007-2008 and describe the relatively complex methodology that was used. They first conducted a “census ” of the population available to be stopped, and recorded some of their visible features. They then unobtrusively monitored police stops and their targets, noting their characteristics based on the same set of features. By this means, the researchers were able to demonstrate that the “stop population ” differed from the “benchmark population ” not just in terms of visible ethnicity, but also of age, sex and style of clothing. Contrôle au faciès, or “identity check on the basis of physical appearance”, is a familiar yet polemical expression in France, where it refers to what is known in European legal language and the specialist literature as “racial ” or “ethnic profiling”. It means that instead of stopping individuals on the basis of operational briefings, suspect descriptions, or specific acts leading them to suspect that an offence has been committed or is about to be committed, law enforcement officers decide which people to stop mainly according to their * Centre for Sociological Research on Law and Criminal Justice Institutions (CESDIP)

Mesurer les discriminations selon l'apparence : une analyse des contrôles d'identité à Paris

International audienceLes contrôles d'identité effectués par la police en France sont souvent accusés d'être effectués " au faciès " et de viser plus particulièrement certaines populations issues de l'immigration, les minorités " visibles ". Pour établir l'existence d'une discrimination, il ne suffit pas de constater que les contrôles de police atteignent une population particulière, il faut démontrer que cela aboutit à une surreprésentation de la catégorie visée par rapport à son importance dans l'espace géographique concerné, ce qui est particulièrement difficile. Fabien Jobard, René Lévy, John Lamberth et Sophie NévaNeN rendent compte d'une enquête sur les contrôles d'identité effectués à Paris en 2007 et 2008. Ils exposent ici la méthodologie assez complexe de cette enquête : " recensement " de la population exposée aux contrôles et de quelques-unes de ses caractéristiques apparentes, puis observation discrète des contrôles et des personnes contrôlées selon ces mêmes caractéristiques. Ils parviennent ainsi à démontrer que la population des contrôlés ne présente pas la même composition que la population présente, non seulement par l'" apparence ethnique " mais aussi par l'âge, le sexe, ou la manière de s'habiller

Measuring Appareance-Based Discrimination. An Analysis of Identity Checks in Paris

International audienc

Measuring Appareance-Based Discrimination. An Analysis of Identity Checks in Paris

International audienc

Jumping Performance of Elite NCAA Division 1 Student-athletes: The Effect of Basketball Shoe Design – Part I

Background: Assessment of basketball shoes as personal protection equipment (PPE) at the collegiate level is unique. Objective: The purpose of Part I in this pilot study was to examine the effect of shoe design on jump height in elite male and female National Collegiate Athletic Association (NCAA) Division 1 basketball student-athletes. Method: Each team selected two pairs of AdidasTM branded shoes. The male student-athletes selected the AdidasTM Harden Vol. 3 and the AdidasTM SM Pro basketball shoes. The female student-athletes selected the AdidasTM Harden Vol. 3 and the AdidasTM Captain Marvel basketball shoes. A total of sixteen basketball student-athletes (six males, ten females) performed an acute series of four styled basketball jumps on two ForceDecksTM Force Platforms while trying to maximize jump height by tapping VertecTM Jump Vanes. Two trials were performed in each shoe and for each type of jump which included a countermovement jump, drop jump from 30cm, step and jump, and a series of plyometric jumps. Results: The results of this pilot study indicated a non-significant effect of basketball shoe design on jump height while performing an acute series of basketball style jumps for either the male or female basketball student-athletes. However, there were significant differences in jump height and peak power between the male and female basketball student-athletes (p = 0.001). Conclusion: In addition to the results, the use of quantitative performance testing on the effectiveness of basketball shoe designs as PPE may assist in the mitigation of non-contact ankle and lower limb injuries

Effect of Curcumin Supplementation on Exercise-Induced Oxidative Stress, Inflammation, Muscle Damage, and Muscle Soreness.

Curcumin has been shown to reduce exercise-induced oxidative stress (OS) and inflammation. The purpose of this investigation was to examine the effects of curcumin supplementation on OS, inflammation, muscle damage, and muscle soreness. Nineteen males participated in a randomized, double-blinded, placebo-controlled trial to examine the effects of curcumin supplementation (1.5 g/day) compared to a placebo (PLA) following a muscle-damaging protocol (MDP) on OS, inflammation, muscle damage, and soreness. Participants were randomized to two groups, curcumin or placebo group. The MDP was performed before and after supplementation (28 days). Blood was sampled pre- and post-exercise and 60 min, 24 h, and 48 h post-exercise and analyzed for total antioxidant capacity (TAC), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and creatine kinase (CK). In addition, a visual analog scale (VAS) was used on each blood sample to measure perceived muscle soreness. After supplementation, curcumin significantly blunted CK levels (199.62 U/L) compared to the placebo (287.03 U/L), overall (p \u3c 0.0001). In addition, curcumin resulted in decreased muscle soreness, overall (VAS scale 2.88), when compared to the placebo (VAS scale 3.36) (p = 0.0120). There were no differences found in TAC, TNF-α, or MDA. Curcumin may reduce muscle damage and perceived muscle soreness without negatively impacting a natural inflammatory response following exercise. Future research should investigate chronic curcumin supplementation and its mechanistic effects on muscle recovery from exercise