Flush communication channels: Effective implementation and verification

Flush communication channels, or F-channels, generalize more conventional asynchronous communication paradigms. A distributed system which uses an F-channel allows a programmer to define the delivery order of each message in relation to other messages transmitted on the channel. Unreliable datagrams and FIFO (first-in-first-out) communication channels have strictly defined delivery semantics. No restrictions are allowed on message delivery order with unreliable datagrams--message delivery is completely unordered. FIFO channels, on the other hand, insist messages are delivered in the order of their transmission. Flush channels can provide either of these delivery order semantics; in addition, F-channels allow the user to define the delivery of a message to be after the delivery of all messages previously transmitted or before the delivery of all messages subsequently transmitted or both. A system which communicates with a flush channel has a message delivery order that is a partial order.;Dynamically specifying a partial message delivery order complicates many aspects of how we implement and reason about the communication channel. From the system\u27s perspective, we develop a feasible implementation protocol and prove its correctness. The protocol effectively handles the partially ordered message delivery. From the user\u27s perspective, we derive an axiomatic verification methodology for flush applications. The added flexibility of defining the delivery order dynamically slightly increases the complexity for the application programmer. Our verification work helps the user effectively deal with the partially ordered message delivery in flush communication

Flush communication channels: Effective implementation and verification

Flush communication channels, or F-channels, generalize more conventional asynchronous communication paradigms. A distributed system which uses an F-channel allows a programmer to define the delivery order of each message in relation to other messages transmitted on the channel. Unreliable datagrams and FIFO (first-in-first-out) communication channels have strictly defined delivery semantics. No restrictions are allowed on message delivery order with unreliable datagrams--message delivery is completely unordered. FIFO channels, on the other hand, insist messages are delivered in the order of their transmission. Flush channels can provide either of these delivery order semantics; in addition, F-channels allow the user to define the delivery of a message to be after the delivery of all messages previously transmitted or before the delivery of all messages subsequently transmitted or both. A system which communicates with a flush channel has a message delivery order that is a partial order.;Dynamically specifying a partial message delivery order complicates many aspects of how we implement and reason about the communication channel. From the system\u27s perspective, we develop a feasible implementation protocol and prove its correctness. The protocol effectively handles the partially ordered message delivery. From the user\u27s perspective, we derive an axiomatic verification methodology for flush applications. The added flexibility of defining the delivery order dynamically slightly increases the complexity for the application programmer. Our verification work helps the user effectively deal with the partially ordered message delivery in flush communication

Comparative genomics-based investigation of resequencing targets in Vibrio fischeri: Focus on point miscalls and artefactual expansions

<p>Abstract</p> <p>Background</p> <p>Sequence closure often represents the end-point of a genome project, without a system in place for subsequent improvement and refinement. Building on the genome project of <it>Vibrio fischeri </it>ES114, we used a comparative approach to identify and investigate genes that had a high likelihood of sequence error.</p> <p>Results</p> <p>Comparison of the <it>V. fischeri </it>ES114 genome with that of conspecific strain MJ11 identified 82 target loci in ES114 as containing likely errors, and thus of high-priority for resequencing. Analysis of the targets identified 75 loci in which an error had occurred, resulting in the correction of 10,457 base pairs to generate the new ES114 genomic sequence. A majority of the inaccurate loci involved frameshift errors, correction of which fused adjacent ORFs. Although insertions/deletions are thought to be rare in microbial genome assemblies, fourteen of the loci contained extraneous sequence of over 300 bp, likely due to imperfect contig ends that were misassembled in tandem rather than as overlapping segments. Additionally we updated the entire genome annotation with 113 new features including previously uncalled protein-coding genes, regulatory RNA genes and operon leader peptides, and we analyzed the transcriptional apparatus encoded by ES114.</p> <p>Conclusion</p> <p>We demonstrate that errors in microbial genome sequences, thought to largely be confined to point mutations, may also consist of other prevalent large-scale rearrangements such as insertions. Ongoing genome quality control and annotation programs are necessary to accompany technological advancements in data generation. These updates further advance <it>V. fischeri </it>as an important model for understanding intercellular communication and colonization of animal tissue.</p

Domestic chickens activate a piRNA defense against avian leukosis virus

PIWI-interacting RNAs (piRNAs) protect the germ line by targeting transposable elements (TEs) through the base-pair complementarity. We do not know how piRNAs co-evolve with TEs in chickens. Here we reported that all active TEs in the chicken germ line are targeted by piRNAs, and as TEs lose their activity, the corresponding piRNAs erode away. We observed de novo piRNA birth as host responds to a recent retroviral invasion. Avian leukosis virus (ALV) has endogenized prior to chicken domestication, remains infectious, and threatens poultry industry. Domestic fowl produce piRNAs targeting ALV from one ALV provirus that was known to render its host ALV resistant. This proviral locus does not produce piRNAs in undomesticated wild chickens. Our findings uncover rapid piRNA evolution reflecting contemporary TE activity, identify a new piRNA acquisition modality by activating a pre-existing genomic locus, and extend piRNA defense roles to include the period when endogenous retroviruses are still infectious. DOI: http://dx.doi.org/10.7554/eLife.24695.00

SNPdetector: A Software Tool for Sensitive and Accurate SNP Detection

Identification of single nucleotide polymorphisms (SNPs) and mutations is important for the discovery of genetic predisposition to complex diseases. PCR resequencing is the method of choice for de novo SNP discovery. However, manual curation of putative SNPs has been a major bottleneck in the application of this method to high-throughput screening. Therefore it is critical to develop a more sensitive and accurate computational method for automated SNP detection. We developed a software tool, SNPdetector, for automated identification of SNPs and mutations in fluorescence-based resequencing reads. SNPdetector was designed to model the process of human visual inspection and has a very low false positive and false negative rate. We demonstrate the superior performance of SNPdetector in SNP and mutation analysis by comparing its results with those derived by human inspection, PolyPhred (a popular SNP detection tool), and independent genotype assays in three large-scale investigations. The first study identified and validated inter- and intra-subspecies variations in 4,650 traces of 25 inbred mouse strains that belong to either the Mus musculus species or the M. spretus species. Unexpected heterozgyosity in CAST/Ei strain was observed in two out of 1,167 mouse SNPs. The second study identified 11,241 candidate SNPs in five ENCODE regions of the human genome covering 2.5 Mb of genomic sequence. Approximately 50% of the candidate SNPs were selected for experimental genotyping; the validation rate exceeded 95%. The third study detected ENU-induced mutations (at 0.04% allele frequency) in 64,896 traces of 1,236 zebra fish. Our analysis of three large and diverse test datasets demonstrated that SNPdetector is an effective tool for genome-scale research and for large-sample clinical studies. SNPdetector runs on Unix/Linux platform and is available publicly (http://lpg.nci.nih.gov)

Stochastic bounds in fork-join queueing systems under full and partial mapping

In a Fork-Join (FJ) queueing system an upstream fork station splits incoming jobs into N tasks to be further processed by N parallel servers, each with its own queue; the response time of one job is determined, at a downstream join station, by the maximum of the corresponding tasks’ response times. This queueing system is useful to the modelling of multi-service systems subject to synchronization constraints, such as MapReduce clusters or multipath routing. Despite their apparent simplicity, FJ systems are hard to analyze. This paper provides the first computable stochastic bounds on the waiting and response time distributions in FJ systems under full (bijective) and partial (injective) mapping of tasks to servers. We consider four practical scenarios by combining 1a) renewal and 1b) non-renewal arrivals, and 2a) non-blocking and 2b) blocking servers. In the case of non-blocking servers we prove that delays scale as O(log N), a law which is known for first moments under renewal input only. In the case of blocking servers, we prove that the same factor of log N dictates the stability region of the system. Simulation results indicate that our bounds are tight, especially at high utilizations, in all four scenarios. A remarkable insight gained from our results is that, at moderate to high utilizations, multipath routing “makes sense” from a queueing perspective for two paths only, i.e., response times drop the most when N = 2; the technical explanation is that the resequencing (delay) price starts to quickly dominate the tempting gain due to multipath transmissions

An Ultra-High-Density, Transcript-Based, Genetic Map of Lettuce.

We have generated an ultra-high-density genetic map for lettuce, an economically important member of the Compositae, consisting of 12,842 unigenes (13,943 markers) mapped in 3696 genetic bins distributed over nine chromosomal linkage groups. Genomic DNA was hybridized to a custom Affymetrix oligonucleotide array containing 6.4 million features representing 35,628 unigenes of Lactuca spp. Segregation of single-position polymorphisms was analyzed using 213 F7:8 recombinant inbred lines that had been generated by crossing cultivated Lactuca sativa cv. Salinas and L. serriola acc. US96UC23, the wild progenitor species of L. sativa The high level of replication of each allele in the recombinant inbred lines was exploited to identify single-position polymorphisms that were assigned to parental haplotypes. Marker information has been made available using GBrowse to facilitate access to the map. This map has been anchored to the previously published integrated map of lettuce providing candidate genes for multiple phenotypes. The high density of markers achieved in this ultradense map allowed syntenic studies between lettuce and Vitis vinifera as well as other plant species

Clonal propagation history shapes the intra-cultivar genetic diversity in Malbec grapevines

Grapevine (Vitis vinifera L.) cultivars are clonally propagated to preserve their varietal 26 attributes. However, novel genetic variation still accumulates due to somatic mutations. Aiming 27 to study the potential impact of clonal propagation history on grapevines intra-cultivar genetic 28 diversity, we have focused on ‘Malbec’. This cultivar is appreciated for red wines elaboration, 29 it was originated in Southwestern France and introduced into Argentina during the 1850s. Here, 30 we generated whole-genome resequencing data for four ‘Malbec’ clones with different 31 historical backgrounds. A stringent variant calling procedure was established to identify reliable 32 clonal polymorphisms, additionally corroborated by Sanger sequencing. This analysis retrieved 33 941 single nucleotide variants (SNVs), occurring among the analyzed clones. Based on a set of 34 validated SNVs, a genotyping experiment was custom-designed to survey ‘Malbec’ genetic 35 diversity. We successfully genotyped 214 samples and identified 14 different clonal genotypes, 36 that clustered into two genetically divergent groups. Group-Ar was driven by clones with a long 37 history of clonal propagation in Argentina, while Group-Fr was driven by clones that have 38 longer remained in Europe. Findings show the ability of such approaches for clonal genotypes 39 identification in grapevines. In particular, we provide evidence on how human actions may have 40 shaped ‘Malbec’ extant genetic diversity pattern.Fil: Calderón, Pablo Luciano Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Mauri, Nuria. Consejo Superior de Investigaciones Científicas; EspañaFil: Muñoz, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; ArgentinaFil: Carbonell Bejerano, Pablo. Max Planck Institute for Biology of Ageing; AlemaniaFil: Bree, Laura. No especifíca;Fil: Sola, Cristobal. No especifíca;Fil: Gómez Talquenca, Sebastián. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Royo, Carolina. Consejo Superior de Investigaciones Científicas; EspañaFil: Ibañez, Javier. Consejo Superior de Investigaciones Científicas; EspañaFil: Martinez-Zapater, José Miguel. Consejo Superior de Investigaciones Científicas; EspañaFil: Lijavetzky, Diego Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Biología Agrícola de Mendoza. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Instituto de Biología Agrícola de Mendoza; Argentin