227 research outputs found

    Variable frame based Max-Weight algorithms for networks with switchover delay

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    This paper considers the scheduling problem for networks with interference constraints and switchover delays, where it takes a nonzero time to reconfigure each service schedule. Switchover delay occurs in many telecommunication applications such as satellite, optical or delay tolerant networks (DTNs). Under zero switchover delay it is well known that the Max-Weight algorithm is throughput-optimal without requiring knowledge of the arrival rates. However, we show that this property of Max-Weight no longer holds when there is a nonzero switchover delay. We propose a class of variable frame based Max-Weight (VFMW) algorithms which employ the Max-Weight schedule corresponding to the beginning of the frame during an interval of duration dependent on the queue sizes. The VFMW algorithms dynamically adapt the frame sizes to the stochastic arrivals and provide throughput-optimality without requiring knowledge of the arrival rates. Numerical results regarding the application of the VFMW algorithms to DTN and optical networks demonstrate a good delay performance.National Science Foundation (U.S.) (NSF grant CNS-0626781)National Science Foundation (U.S.) (NSF grant CNS-0915988)United States. Army Research Office (ARO Muri grant number W911NF-08-1-0238

    An overlay architecture for throughput optimal multipath routing

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    Legacy networks are often designed to operate with simple single-path routing, like shortest-path, which is known to be throughput suboptimal. On the other hand, previously proposed throughput optimal policies (i.e., backpressure) require every device in the network to make dynamic routing decisions. In this work, we study an overlay architecture for dynamic routing such that only a subset of devices (overlay nodes) need to make dynamic routing decisions. We determine the essential collection of nodes that must bifurcate traffic for achieving the maximum multicommodity network throughput. We apply our optimal node placement algorithm to several graphs and the results show that a small fraction of overlay nodes is sufficient for achieving maximum throughput. Finally, we propose a heuristic policy (OBP), which dynamically controls traffic bifurcations at overlay nodes. In all studied simulation scenarios, OBP not only achieves full throughput, but also reduces delay in comparison to the throughput optimal backpressure routing.United States. Air Force (Contract FA8721-05-C-0002)National Science Foundation (U.S.) (Grant CNS-0915988)United States. Office of Naval Research (Grant N00014-12-1-0064)United States. Army Research Office. Multidisciplinary University Research Initiative (Grant W911NF-08-1-0238)European Social Fund (WiNC Project of the Action:Supporting Postdoctoral Researchers

    A clonal Plasmodium falciparum population in an isolated outbreak of malaria in the Republic of Cabo Verde

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    We present the first parasitological, molecular and longitudinal analysis of an isolated outbreak of malaria. This outbreak occurred on Santiago Island (Republic of Cabo Verde), a region where malaria is hypoendemic and controlled, and thus the population is considered non-immune. Blood samples were collected from the inhabitants over 1 month and during cross-sectional surveys in the following year. The presence and nature of the parasites was determined by PCR. Plasmodium falciparum was the only species detected. Genetic analysis revealed that the circulating parasites were genetically homogeneous, and probably clonal. Gametocytes were found throughout this period. Our data suggest that this represented a focal outbreak, resulting in the infection of at least 40% of the villagers with a clonal parasite line. Thus, P. falciparum infections can persist for at least 1 year in a substantial proportion (10%) of the hosts. Implications for malaria control and the interpretation of epidemiological data are discussed

    Genome landscapes and bacteriophage codon usage

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    Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.Comment: 9 Color Figures, 5 Tables, 53 Reference

    Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed

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    The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors

    Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations

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    An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due to their high frequency of occurrence. Through this survey the CFTR has become the most exhaustively studied gene for its coding sequence variability and, though to a lesser extent, for its noncoding sequence variability as well. Interestingly, most variation was associated with the M470 allele, while the V470 allele showed an 'extended haplotype homozygosity' (EHH). These findings make us suggest a role for selection acting either on the M470V itself or through an hitchhiking mechanism involving a second site. The possible ancient origin of the V allele in an 'out of Africa' time frame is discussed

    Antitumour necrosis factor-α therapy for hidradenitis suppurativa: results from a national cohort study between 2000 and 2013

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    International audienceHidradenitis suppurativa (HS) is a frequent chronic inflammatory skin disease typically characterized by recurrent painful, deep inflammatory nodules of the axillary, breast, groin and gluteal areas. European recommendations are mainly based on expert opinion. Drug treatments are heterogenous (e.g., antibiotics, corticosteroids, retinoids) and lack consensus among expert centres. The most severe disease forms or those failing to respond to conventional drugs may be associated with worsened functional prognosis. Anti-tumor necrosis factor α (anti-TNFα) drugs have been prescribed in these cases. The results of randomized controlled trials (RCTs) are discordant. Three RCTs concluded to the efficacy of adalimumab (ADA), and two others did not detect any difference between infliximab (IFX) or etanercept (ETA) and placebo. Finally, data from the literature and reported experiences do not conclude on the efficacy of anti-TNFα drugs for HS. This article is protected by copyright. All rights reserve

    Haemoglobin C and S Role in Acquired Immunity against Plasmodium falciparum Malaria

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    A recently proposed mechanism of protection for haemoglobin C (HbC; ÎČ6Glu→Lys) links an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, on the surface of HbC infected erythrocytes together with the observation of reduced cytoadhesion of parasitized erythrocytes and impaired rosetting in vitro. We investigated the impact of this hypothesis on the development of acquired immunity against Plasmodium falciparum variant surface antigens (VSA) encoding PfEMP1 in HbC in comparison with HbA and HbS carriers of Burkina Faso. We measured: i) total IgG against a single VSA, A4U, and against a panel of VSA from severe malaria cases in human sera from urban and rural areas of Burkina Faso of different haemoglobin genotypes (CC, AC, AS, SC, SS); ii) total IgG against recombinant proteins of P. falciparum asexual sporozoite, blood stage antigens, and parasite schizont extract; iii) total IgG against tetanus toxoid. Results showed that the reported abnormal cell-surface display of PfEMP1 on HbC infected erythrocytes observed in vitro is not associated to lower anti- PfEMP1 response in vivo. Higher immune response against the VSA panel and malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the ÎČ-globin genotype. These findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. The enhanced immune reactivity in both HbC and HbS carriers supports the hypothesis that the protection against malaria of these adaptive genotypes might be at least partially mediated by acquired immunity against malaria
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