Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles

Several new HLA-B (B8, B51, Bw62)- and HLA-C (Cw6, Cw7)-specific genes were isolated either as genomic cosmid or cDNA clones to study the diversity of HLA antigens. The allele specificities were identified by sequence analysis in comparison with published HLAB and -C sequences, by transfection experiments, and Southern and northern blot analysis using oligonucleotide probes. Comparison of the classical HLA-A, -B, and -C sequences reveals that allele-specific substitutions seem to be rare events. HLA-B51 codes only for one allelespecific residue: arginine at position 81 located on the cd helix, pointing toward the antigen binding site. HLA-B8 contains an acidic substitution in amino acid position 9 on the first central/3 sheet which might affect antigen binding capacity, perhaps in combination with the rare replacement at position 67 (F) on the Alpha-l helix. HLA-B8 shows greatest homology to HLA-Bw42, -Bw41, -B7, and -Bw60 antigens, all of which lack the conserved restriction sites Pst I at position 180 and Sac I at position 131. Both sites associated with amino acid replacements seem to be genetic markers of an evolutionary split of the HLA-B alleles, which is also observed in the leader sequences. HLA-Cw7 shows 98% sequence identity to the JY328 gene. In general, the HLA-C alleles display lower levels of variability in the highly polymorphic regions of the Alpha 1 and Alpha 2 domains, and have more distinct patterns of locusspecific residues in the transmembrane and cytoplasmic domains. Thus we propose a more recent origin for the HLA-C locus

What About the Children? - FDA's Response to Pediatric Drug Testing

The Federal Food and Drug Administration (FDA) has played a critical role in the protection of human subjects in research. Most recently, FDA enacted an interim final rule regarding protection of children in clinical investigations. FDA’s interim rule represents its most current policy on human subject protection. Current events illuminate FDA’s policies and how FDA has chosen to respond to debates over pediatric drug testing. This paper will provide a brief history of FDA’s participation in human subject protection. This paper will then focus on FDA’s policies for pediatric research, its interim rule, and how the interim rule relates to current events. Finally, this paper will make a comment about how FDA balances its competing duties of protecting the public but also of promoting research

Metaheuristics for the Order Batching Problem in Manual Order Picking Systems

In manual order picking systems, order pickers walk or drive through a distribution warehouse in order to collect items which are requested by (internal or external) customers. In order to perform these operations effciently, it is usually required that customer orders are combined into (more substantial) picking orders of limited size. The Order Batching Problem considered in this paper deals with the question of how a given set of customer orders should be combined such that the total length of all tours is minimized which are necessary to collect all items. The authors introduce two metaheuristic approaches for the solution of this problem; the rst one is based on Iterated Local Search, the second one on Ant Colony Optimization. In a series of extensive numerical experiments, the newly developed approaches are benchmarked against classic solution methods. It is demonstrated that the proposed methods are not only superior to existing methods, but provide solutions which may allow for operating distribution warehouses signicantly more effcient.Warehouse Management, Order Picking, Order Batching, Iterated Local Search, Ant Colony Optimization

Reports of the Scientific, Technical and Economic Committee for Fisheries - Special request for evaluating Baltic cod additional measures (STECF-16-23)

Commission Decision of 25 February 2016 setting up a Scientific, Technical and Economic Committee for Fisheries, C(2016) 1084, OJ C 74, 26.2.2016, p. 4–10. The Commission may consult the group on any matter relating to marine and fisheries biology, fishing gear technology, fisheries economics, fisheries governance, ecosystem effects of fisheries, aquaculture or similar disciplines. This report deals with a special request for evaluating Baltic cod additional measures.JRC.D.2 - Water and Marine Resource

Scientific, Technical and Economic Committee for Fisheries (STECF) - Opinion by Written Procedure - Evaluations of Slovenian and Spanish Management Plans (STECF-OWP-12-02)

The STECF Expert Working Group EWG-11-20, which was held 16-20 January 2012 in Madrid (Spain), conducted evaluations of Slovenian and Spanish Management Plans. STECF then reviewed the EWG-11-20 evaluations by written procedure in March 2012.JRC.G.4 - Maritime affair

Frequency-Multiplexed bias and readout of a 16-pixel Superconducting Nanowire Single-Photon Detector Array

We demonstrate a 16-pixel array of radio-frequency superconducting nanowire single-photon detectors with an integrated and scalable frequency-division multiplexing architecture, reducing the required bias and readout lines to a single microwave feed line. The electrical behavior of the photon-sensitive nanowires, embedded in a resonant circuit, as well as the optical performance and timing jitter of the single detectors is discussed. Besides the single pixel measurements we also demonstrate the operation of the 16-pixel array with a temporal, spatial and photon-number resolution