Throughput Optimization in Mobile Backbone Networks

This paper describes new algorithms for throughput optimization in a mobile backbone network. This hierarchical communication framework combines mobile backbone nodes, which have superior mobility and communication capability, with regular nodes, which are constrained in mobility and communication capability. An important quantity of interest in mobile backbone networks is the number of regular nodes that can be successfully assigned to mobile backbone nodes at a given throughput level. This paper develops a novel technique for maximizing this quantity in networks of fixed regular nodes using mixed-integer linear programming (MILP). The MILP-based algorithm provides a significant reduction in computation time compared to existing methods and is computationally tractable for problems of moderate size. An approximation algorithm is also developed that is appropriate for large-scale problems. This paper presents a theoretical performance guarantee for the approximation algorithm and also demonstrates its empirical performance. Finally, the mobile backbone network problem is extended to include mobile regular nodes, and exact and approximate solution algorithms are presented for this extension.United States. Air Force Office of Scientific Research (AFOSR grant FA9550- 04-1-0458)National Science Foundation (U.S.) (grant CCR-0325401)National Science Foundation (U.S.) (grant CNS-091598)National Science Foundation (U.S.) (Graduate Fellowship

Distributed CSMA with pairwise coding

We consider distributed strategies for joint routing, scheduling, and network coding to maximize throughput in wireless networks. Network coding allows for an increase in network throughput under certain routing conditions. We previously developed a centralized control policy to jointly optimize for routing and scheduling combined with a simple network coding strategy using max-weight scheduling (MWS) [9]. In this work we focus on pairwise network coding and develop a distributed carrier sense multiple access (CSMA) policy that supports all arrival rates allowed by the network subject to the pairwise coding constraint. We extend our scheme to optimize for packet overhearing to increase the number of beneficial coding opportunities. Simulation results show that the CSMA strategy yields the same throughput as the optimal centralized policy of [9], but at the cost of increased delay. Moreover, overhearing provides up to an additional 25% increase in throughput on random topologies.United States. Dept. of Defense. Assistant Secretary of Defense for Research & EngineeringUnited States. Air Force (Air Force Contract FA8721-05-C-0002

Natural polymorphism in the thrombospondin-related adhesive protein of Plasmodium falciparum

We have developed a typing system using natural sequence variation in the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum. This method permits a haplotype to be assigned to any particular TRAP gene. We have applied this method to a hospital-based, case control-study in Mali. Previous sequence variation and conservation in TRAP has been confirmed. Particular TRAP haplotypes can be used as geographic hallmarks. Because of the high level of conflict between characters, we have examined the phylogenetic relationships between parasites using a network approach. Having received patient samples from urban and periurban areas of Bamako, the majority of haplotypes were closely related and distinct from TRAP sequences present in other continents. This suggests that the structure of TRAP can only tolerate a limited number of sequence variations to preserve its function but that this is sufficient to allow the parasite to evade the host's immune system until a long-lived immune response can be maintained. It may also reflect host genetics in that certain variants may escape the host immune response more efficiently than others. For vaccine design, sequences from the major regional variants may need to be considered in the production of effective subunit vaccines

Optimal routing and scheduling for a simple network coding scheme

We consider jointly optimal routing, scheduling, and network coding strategies to maximize throughput in wireless networks. While routing and scheduling techniques for wireless networks have been studied for decades, network coding is a relatively new technique that allows for an increase in throughput under certain topological and routing conditions. In this work we introduce k-tuple coding, a generalization of pairwise coding with next-hop decodability, and fully characterize the region of arrival rates for which the network queues can be stabilized under this coding strategy. We propose a dynamic control policy for routing, scheduling, and k-tuple coding, and prove that our policy is throughput optimal subject to the k-tuple coding constraint. We provide analytical bounds on the coding gain of our policy, and present numerical results to support our analytical findings. We show that most of the gains are achieved with pairwise coding, and that the coding gain is greater under 2-hop than 1-hop interference. Simulations show that under 2-hop interference our policy yields median throughput gains of 31% beyond optimal scheduling and routing on random topologies with 16 nodes.National Science Foundation (U.S.) (grant CNS-0915988)United States. Office of Naval Research (grant N00014-12-1-0064)United States. Office of Naval Research. Multidisciplinary University Research Initiative (grant number W911NF-08-1-0238)United States. Air ForceUnited States. Dept. of Defense (Contract No. FA8721-05-C-0002

The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa

Transthyretin (TTR) pV142I (rs76992529-A) is one of the 113 variants in the human TTR gene associated with systemic amyloidosis. It results from a G to A transition at a CG dinucleotide in the codon for amino acid 122 of the mature protein (TTR V122I). The allele frequency is 0.0173 in African Americans

An overlay architecture for throughput optimal multipath routing

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

Genome landscapes and bacteriophage codon usage

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

Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study

Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative

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

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