Jonathan Arnold

Quality of Service for Workflows and Web Service Processes

Workflow management systems (WfMSs) have been used to support various types of business processes for more than a decade now. In workflows or Web processes for e-commerce and Web service applications, suppliers and customers define a binding agreement or contract between the two parties, specifying Quality of Service (QoS) items such as products or services to be delivered, deadlines, quality of products, and cost of services. The management of QoS metrics directly impacts the success of organizations participating in e-commerce. Therefore, when services or products are created or managed using workflows or Web processes, the underlying workflow engine must accept the specifications and be able to estimate, monitor, and control the QoS rendered to customers. In this paper, we present a predictive QoS model that makes it possible to compute the quality of service for workflows automatically based on atomic task QoS attributes. We also present the implementation of our QoS model for the METEOR workflow system. We describe the components that have been changed or added, and discuss how they interact to enable the management of QoS.

Demographic influences on mitochondrial DNA lineage survivorship in animal populations

SummaryProbability models of branching processes and computer simulations of these models are used to examine stochastic survivorship of female lineages under a variety of demographic scenarios. A parameter II, defined as the probability of survival of two or more independent lineages over G generations, is monitored as a function of founding size of a population, population size at carrying capacity, and the frequency distributions of surviving progeny.Stochastic lineage extinction can be very rapid under certain biologically plausible demographic conditions. For stable-sized populations initiated by n females and/or regulated about carrying capacity k=n, it is highly probable that within about 4n generations all descendants will trace their ancestries to a single founder female. For a given mean family size, increased variance decreases lineage survivorship. In expanding populations, however, lineage extinction is dramatically slowed, and the final k value is a far more important determinant of II than is the size of the population at founding. The results are discussed in the context of recent empirical observations of low mitochondrial DNA (mtDNA) sequence heterogeneity in humans and expected distributions of asexually transmitted traits among sexually reproducing species.

Comparison of the nucleotide sequence of soybean 18S rRNA with the sequences of other small-subunit rRNAs

SummaryWe present the sequence of the nuclearencoded ribosomal small-subunit RNA from soybean. The soybean 18S rRNA sequence of 1807 nucleotides (nt) is contained in a gene family of approximately 800 closely related members per haploid genome. This sequence is compared with the ribosomal small-subunit RNAs of maize (1805 nt), yeast (1789 nt),Xenopus (1825 nt), rat (1869 nt), andEscherichia coli (1541 nt). Significant sequence homology is observed among the eukaryotic small-subunit rRNAs examined, and some sequence homology is observed between eukaryotic and prokaryotic small-subunit rRNAs. Conserved regions are found to be interspersed among highly diverged sequences. The significance of these comparisons is evaluated using computer simulation of a random sequence model. A tentative model of the secondary structure of soybean 18S rRNA is presented and discussed in the context of the functions of the various conserved regions within the sequence. On the basis of this model, the short basepaired sequences defining the four structural and functional domains of all 18S rRNAs are seen to be well conserved. The potential roles of other conserved soybean 18S rRNA sequences in protein synthesis are discussed.

IntelliGEN: A Distributed Workflow System for Discovering Protein-Protein Interactions

A large genomics project involves a significant number of researchers and technicians performing dozens of tasks, either manual (e.g. performing laboratory experiments), computer assisted (e.g. looking for genes in the GENBANK database), or sometimes performed entirely automatically by the computer (e.g. sequence assembly). It has become apparent that managing such projects poses overwhelming problems and may lead to results of lower or even unacceptable quality, or possibly drastically increased project costs. In this paper, we present a design and an initial implementation of a distributed workflow system created to schedule and support activities in a genomics laboratory. The focus of the activities in the laboratory is the discovery of protein-protein interactions of fungi, specifically Neurospora crassa. We present our approach of developing, adapting and applying workflow technology in the genomics lab and illustrate it using one distinct part of a larger workflow to discover protein-protein interactions. Novel features of our system include the ability to monitor the quality and timeliness of the results and if necessary, suggesting and incorporating changes to the selected tasks and their scheduling.

An ensemble method for identifying regulatory circuits with special reference to the qa gene cluster of Neurospora crassa

A chemical reaction network for the regulation of the quinic acid (qa) gene cluster of Neurospora crassa is proposed. An efficient Monte Carlo method for walking through the parameter space of possible chemical reaction networks is developed to identify an ensemble of deterministic kinetics models with rate constants consistent with RNA and protein profiling data. This method was successful in identifying a model ensemble fitting available RNA profiling data on the qa gene cluster.

Systems biology of the clock in Neurospora crassa.

A model-driven discovery process, Computing Life, is used to identify an ensemble of genetic networks that describe the biological clock. A clock mechanism involving the genes white-collar-1 and white-collar-2 (wc-1 and wc-2) that encode a transcriptional activator (as well as a blue-light receptor) and an oscillator frequency (frq) that encodes a cyclin that deactivates the activator is used to guide this discovery process through three cycles of microarray experiments. Central to this discovery process is a new methodology for the rational design of a Maximally Informative Next Experiment (MINE), based on the genetic network ensemble. In each experimentation cycle, the MINE approach is used to select the most informative new experiment in order to mine for clock-controlled genes, the outputs of the clock. As much as 25% of the N. crassa transcriptome appears to be under clock-control. Clock outputs include genes with products in DNA metabolism, ribosome biogenesis in RNA metabolism, cell cycle, protein metabolism, transport, carbon metabolism, isoprenoid (including carotenoid) biosynthesis, development, and varied signaling processes. Genes under the transcription factor complex WCC ( = WC-1/WC-2) control were resolved into four classes, circadian only (612 genes), light-responsive only (396), both circadian and light-responsive (328), and neither circadian nor light-responsive (987). In each of three cycles of microarray experiments data support that wc-1 and wc-2 are auto-regulated by WCC. Among 11,000 N. crassa genes a total of 295 genes, including a large fraction of phosphatases/kinases, appear to be under the immediate control of the FRQ oscillator as validated by 4 independent microarray experiments. Ribosomal RNA processing and assembly rather than its transcription appears to be under clock control, suggesting a new mechanism for the post-transcriptional control of clock-controlled genes.

Selection for resistance to Bacillus thuringiensis subspecies israelensis in field and laboratory populations of the mosquito Aedes aegypti.

Abstract One laboratory and two wild populations of the yellow fever mosquito, Aedes aegypti , were used in an attempt to artificially select for resistance to Bacillus thuringiensis subsp. israelensis . After 14 generations of LC 50 selection pressure, a small but statistically significant shift (twofold increase) in response was observed in the F 15 generation of one wild strain only. Regression lines, LC 50 values, and slopes of parental populations between strains did not differ significantly.

Towards understanding the evolution of the human commensal yeast Candida albicans

Allelic frequencies and relationships for one dimorphic locus and three unlinked polymorphic loci have been determined for 114 unrelated isolates of Candida albicans, including 14 laboratory reference strains and 50 strains from each of two geographic regions. Although there was no indication of geographical partitioning, there were significant correlations for specific allelic pairs among loci and little evidence that any alleles were in Hardy-Weinberg equilibrium. This gives additional support for the concept that the primary mode of genetic inheritance in this species is clonal, with other intracellular genetic events playing a lesser role in the creation of genomic diversity. Through inference of this and other known attributes of closely related Candida species, such as sequence analysis of IS1 and the ITS2 (internal transcribed spacer 2) region of the rDNA cistron, the deduced phylogeny suggests an evolutionarily recent origin for many frequently isolated strains. This finding will be of interest in the context of understanding pathogenicity and drug resistance in this human commensal yeast.

HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging.

The search for longevity‐determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity.

Transcriptome of Pneumocystis carinii during Fulminate Infection: Carbohydrate Metabolism and the Concept of a Compatible Parasite

Members of the genus Pneumocystis are fungal pathogens that cause pneumonia in a wide variety of mammals with debilitated immune systems. Little is known about their basic biological functions, including life cycle, since no species can be cultured continuously outside the mammalian lung. To better understand the pathological process, about 4500 ESTS derived from sequencing of the poly(A) tail ends of P. carinii mRNAs during fulminate infection were annotated and functionally characterized as unassembled reads, and then clustered and reduced to a unigene set with 1042 members. Because of the presence of sequences from other microbial genomes and the rat host, the analysis and compression to a unigene set was necessarily an iterative process. BLASTx analysis of the unassembled reads (UR) vs. the Uni-Prot and TREMBL databases revealed 56% had similarities to existing polypeptides at E values of≤10−6, with the remainder lacking any significant homology. The most abundant transcripts in the UR were associated with stress responses, energy production, transcription and translation. Most (70%) of the UR had similarities to proteins from filamentous fungi (e.g., Aspergillus, Neurospora) and existing P. carinii gene products. In contrast, similarities to proteins of the yeast-like fungi, Schizosaccharomyces pombe and Saccharomyces cerevisiae, predominated in the unigene set. Gene Ontology analysis using BLAST2GO revealed P. carinii dedicated most of its transcripts to cellular and physiological processes (∼80%), molecular binding and catalytic activities (∼70%), and were primarily derived from cell and organellar compartments (∼80%). KEGG Pathway mapping showed the putative P. carinii genes represented most standard metabolic pathways and cellular processes, including the tricarboxylic acid cycle, glycolysis, amino acid biosynthesis, cell cycle and mitochondrial function. Several gene homologs associated with mating, meiosis, and sterol biosynthesis in fungi were identified. Genes encoding the major surface glycoprotein family (MSG), heat shock (HSP70), and proteases (PROT/KEX) were the most abundantly expressed of known P. carinii genes. The apparent presence of many metabolic pathways in P. carinii, sexual reproduction within the host, and lack of an invasive infection process in the immunologically intact host suggest members of the genus Pneumocystis may be adapted parasites and have a compatible relationship with their mammalian hosts. This study represents the first characterization of the expressed genes of a non-culturable fungal pathogen of mammals during the infective process.