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Sample records for selected virulence models

  1. Processing plant persistent strains of Listeria monocytogenes appear to have a lower virulence potential than clinical strains in selected virulence models

    DEFF Research Database (Denmark)

    Jensen, Anne; Thomsen, L.E.; Jørgensen, R.L.

    2008-01-01

    cell line, Caco-2; time to death in a nematode model, Caenorhabditis elegans and in a fruit fly model, Drosophila melanogaster and fecal shedding in a guinea pig model. All strains adhered to and grew in Caco-2 cells in similar levels. When exposed to 10(6) CFU/ml, two strains representing......% killed C elegans worms was longer (110 h) for the RAPD type 9 strains than for the other four strains (80 h). The Scott A strain and one RAPD type 9 strain were suspended in whipping cream before being fed to guinea pigs and the persistent RAPD type 9 strain was isolated from feces in a lower level...... to contaminate food products, and it is important to determine their virulence potential to evaluate risk to consumers. We compared the behaviour of food processing persistent and clinical L. monocytogenes strains in four virulence models: Adhesion, invasion and intracellular growth was studied in an epithelial...

  2. Natural Selection in Virulence Genes of Francisella tularensis.

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    Gunnell, Mark K; Robison, Richard A; Adams, Byron J

    2016-06-01

    A fundamental tenet of evolution is that alleles that are under negative selection are often deleterious and confer no evolutionary advantage. Negatively selected alleles are removed from the gene pool and are eventually extinguished from the population. Conversely, alleles under positive selection do confer an evolutionary advantage and lead to an increase in the overall fitness of the organism. These alleles increase in frequency until they eventually become fixed in the population. Francisella tularensis is a zoonotic pathogen and a potential biothreat agent. The most virulent type of F. tularensis, Type A, is distributed across North America with Type A.I occurring mainly in the east and Type A.II appearing mainly in the west. F. tularensis is thought to be a genome in decay (losing genes) because of the relatively large number of pseudogenes present in its genome. We hypothesized that the observed frequency of gene loss/pseudogenes may be an artifact of evolution in response to a changing environment, and that genes involved in virulence should be under strong positive selection. To test this hypothesis, we sequenced and compared whole genomes of Type A.I and A.II isolates. We analyzed a subset of virulence and housekeeping genes from several F. tularensis subspecies genomes to ascertain the presence and extent of positive selection. Eleven previously identified virulence genes were screened for positive selection along with 10 housekeeping genes. Analyses of selection yielded one housekeeping gene and 7 virulence genes which showed significant evidence of positive selection at loci implicated in cell surface structures and membrane proteins, metabolism and biosynthesis, transcription, translation and cell separation, and substrate binding and transport. Our results suggest that while the loss of functional genes through disuse could be accelerated by negative selection, the genome decay in Francisella could also be the byproduct of adaptive evolution

  3. The animal model determines the results of Aeromonas virulence factors

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    Alejandro Romero

    2016-10-01

    Full Text Available The selection of an experimental animal model is of great importance in the study of bacterial virulence factors. Here, a bath infection of zebrafish larvae is proposed as an alternative model to study the virulence factors of A. hydrophila. Intraperitoneal infections in mice and trout were compared with bath infections in zebrafish larvae using specific mutants. The great advantage of this model is that bath immersion mimics the natural route of infection, and injury to the tail also provides a natural portal of entry for the bacteria. The implication of T3SS in the virulence of A. hydrophila was analysed using the AH-1::aopB mutant. This mutant was less virulent than the wild-type strain when inoculated into zebrafish larvae, as described in other vertebrates. However, the zebrafish model exhibited slight differences in mortality kinetics only observed using invertebrate models. Infections using the mutant AH-1∆vapA lacking the gene coding for the surface S-layer suggested that this protein was not totally necessary to the bacteria once it was inside the host, but it contributed to the inflammatory response. Only when healthy zebrafish larvae were infected did the mutant produce less mortality than the wild type. Variations between models were evidenced using the AH-1∆rmlB, which lacks the O-antigen lipopolysaccharide (LPS, and the AH-1∆wahD, which lacks the O-antigen LPS and part of the LPS outer-core. Both mutants showed decreased mortality in all of the animal models, but the differences between them were only observed in injured zebrafish larvae, suggesting that residues from the LPS outer core must be important for virulence. The greatest differences were observed using the AH-1ΔFlaB-J (lacking polar flagella and unable to swim and the AH-1::motX (non-motile but producing flagella. They were as pathogenic as the wild-type strain when injected into mice and trout, but no mortalities were registered in zebrafish larvae. This study

  4. [Virulence of Sporothrix globosa in murine models].

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    Cruz Choappa, Rodrigo; Pérez Gaete, Salomón; Rodríguez Badilla, Valentina; Vieille Oyarzo, Peggy; Opazo Sanchez, Héctor

    The sporothricosis disease is an infection caused by species included in Sporothrix schenkii complex. Verify the virulence of a strain of S. globosa using two different concentrations of inoculum by intraperitoneally and subcutaneously, into a mouse model. Nonrandomized pilot study, in murine inoculated with a strain of S. globosa (CBS 14.076M) by intraperitoneally and subcutaneously with inoculum concentrations of 0.5 and 4 McFarland. For this purpose 18 rodents CF-1 (ISP, Santiago, Chile) were used. The studied strain did not induce illness or injury on animals, they all survived and neither the tissue culture nor the histopathological analysis showed fungal growth or suggestive infection by organ abnormalities. The S. globosa strain did not present any virulence enough to cause disease at 0.5 and 4.0 McFarland concentration inoculum when inoculated in both intraperitoneally and subcutaneously, in murine models. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Inhibitors of Mycobacterium marinum virulence identified in a Dictyostelium discoideum host model.

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    Hajer Ouertatani-Sakouhi

    Full Text Available Tuberculosis remains one of the major threats to public health worldwide. Given the prevalence of multi drug resistance (MDR in Mycobacterium tuberculosis strains, there is a strong need to develop new anti-mycobacterial drugs with modes of action distinct from classical antibiotics. Inhibitors of mycobacterial virulence might target new molecular processes and may represent a potential new therapeutic alternative. In this study, we used a Dictyostelium discoideum host model to assess virulence of Mycobacterium marinum and to identify compounds inhibiting mycobacterial virulence. Among 9995 chemical compounds, we selected 12 inhibitors of mycobacterial virulence that do not inhibit mycobacterial growth in synthetic medium. Further analyses revealed that 8 of them perturbed functions requiring an intact mycobacterial cell wall such as sliding motility, bacterial aggregation or cell wall permeability. Chemical analogs of two compounds were analyzed. Chemical modifications altered concomitantly their effect on sliding motility and on mycobacterial virulence, suggesting that the alteration of the mycobacterial cell wall caused the loss of virulence. We characterized further one of the selected compounds and found that it inhibited the ability of mycobacteria to replicate in infected cells. Together these results identify new antimycobacterial compounds that represent new tools to unravel the molecular mechanisms controlling mycobacterial pathogenicity. The isolation of compounds with anti-virulence activity is the first step towards developing new antibacterial treatments.

  6. Novel genetic tools for diaminopimelic acid selection in virulence studies of Yersinia pestis.

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    David M Bland

    2011-03-01

    Full Text Available Molecular studies of bacterial virulence are enhanced by expression of recombinant DNA during infection to allow complementation of mutants and expression of reporter proteins in vivo. For highly pathogenic bacteria, such as Yersinia pestis, these studies are currently limited because deliberate introduction of antibiotic resistance is restricted to those few which are not human treatment options. In this work, we report the development of alternatives to antibiotics as tools for host-pathogen research during Yersinia pestis infections focusing on the diaminopimelic acid (DAP pathway, a requirement for cell wall synthesis in eubacteria. We generated a mutation in the dapA-nlpB(dapX operon of Yersinia pestis KIM D27 and CO92 which eliminated the expression of both genes. The resulting strains were auxotrophic for diaminopimelic acid and this phenotype was complemented in trans by expressing dapA in single and multi-copy. In vivo, we found that plasmids derived from the p15a replicon were cured without selection, while selection for DAP enhanced stability without detectable loss of any of the three resident virulence plasmids. The dapAX mutation rendered Y. pestis avirulent in mouse models of bubonic and septicemic plague which could be complemented when dapAX was inserted in single or multi-copy, restoring development of disease that was indistinguishable from the wild type parent strain. We further identified a high level, constitutive promoter in Y. pestis that could be used to drive expression of fluorescent reporters in dapAX strains that had minimal impact to virulence in mouse models while enabling sensitive detection of bacteria during infection. Thus, diaminopimelic acid selection for single or multi-copy genetic systems in Yersinia pestis offers an improved alternative to antibiotics for in vivo studies that causes minimal disruption to virulence.

  7. Novel genetic tools for diaminopimelic acid selection in virulence studies of Yersinia pestis.

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    Bland, David M; Eisele, Nicholas A; Keleher, Lauren L; Anderson, Paul E; Anderson, Deborah M

    2011-03-02

    Molecular studies of bacterial virulence are enhanced by expression of recombinant DNA during infection to allow complementation of mutants and expression of reporter proteins in vivo. For highly pathogenic bacteria, such as Yersinia pestis, these studies are currently limited because deliberate introduction of antibiotic resistance is restricted to those few which are not human treatment options. In this work, we report the development of alternatives to antibiotics as tools for host-pathogen research during Yersinia pestis infections focusing on the diaminopimelic acid (DAP) pathway, a requirement for cell wall synthesis in eubacteria. We generated a mutation in the dapA-nlpB(dapX) operon of Yersinia pestis KIM D27 and CO92 which eliminated the expression of both genes. The resulting strains were auxotrophic for diaminopimelic acid and this phenotype was complemented in trans by expressing dapA in single and multi-copy. In vivo, we found that plasmids derived from the p15a replicon were cured without selection, while selection for DAP enhanced stability without detectable loss of any of the three resident virulence plasmids. The dapAX mutation rendered Y. pestis avirulent in mouse models of bubonic and septicemic plague which could be complemented when dapAX was inserted in single or multi-copy, restoring development of disease that was indistinguishable from the wild type parent strain. We further identified a high level, constitutive promoter in Y. pestis that could be used to drive expression of fluorescent reporters in dapAX strains that had minimal impact to virulence in mouse models while enabling sensitive detection of bacteria during infection. Thus, diaminopimelic acid selection for single or multi-copy genetic systems in Yersinia pestis offers an improved alternative to antibiotics for in vivo studies that causes minimal disruption to virulence.

  8. Life history trade-offs and relaxed selection can decrease bacterial virulence in environmental reservoirs.

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    Lauri Mikonranta

    Full Text Available Pathogen virulence is usually thought to evolve in reciprocal selection with the host. While this might be true for obligate pathogens, the life histories of opportunistic pathogens typically alternate between within-host and outside-host environments during the infection-transmission cycle. As a result, opportunistic pathogens are likely to experience conflicting selection pressures across different environments, and this could affect their virulence through life-history trait correlations. We studied these correlations experimentally by exposing an opportunistic bacterial pathogen Serratia marcescens to its natural protist predator Tetrahymena thermophila for 13 weeks, after which we measured changes in bacterial traits related to both anti-predator defence and virulence. We found that anti-predator adaptation (producing predator-resistant biofilm caused a correlative attenuation in virulence. Even though the direct mechanism was not found, reduction in virulence was most clearly connected to a predator-driven loss of a red bacterial pigment, prodigiosin. Moreover, life-history trait evolution was more divergent among replicate populations in the absence of predation, leading also to lowered virulence in some of the 'predator absent' selection lines. Together these findings suggest that the virulence of non-obligatory, opportunistic bacterial pathogens can decrease in environmental reservoirs through life history trade-offs, or random accumulation of mutations that impair virulence traits under relaxed selection.

  9. Transient virulence of emerging pathogens.

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    Bolker, Benjamin M; Nanda, Arjun; Shah, Dharmini

    2010-05-06

    Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution.

  10. A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence.

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    Tannistha Nandi

    2010-04-01

    Full Text Available Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence". To understand this process, we compared eleven isolate genomes of Burkholderia pseudomallei (Bp, a tropical soil microbe and causative agent of the human and animal disease melioidosis. We found evidence for the existence of several new genes in the Bp reference genome, identifying 282 novel genes supported by at least two independent lines of supporting evidence (mRNA transcripts, database homologs, and presence of ribosomal binding sites and 81 novel genes supported by all three lines. Within the Bp core genome, 211 genes exhibited significant levels of positive selection (4.5%, distributed across many cellular pathways including carbohydrate and secondary metabolism. Functional experiments revealed that certain positively selected genes might enhance mammalian virulence by interacting with host cellular pathways or utilizing host nutrients. Evolutionary modifications improving Bp environmental fitness may thus have indirectly facilitated the ability of Bp to colonize and survive in mammalian hosts. These findings improve our understanding of the pathogenesis of melioidosis, and establish Bp as a model system for studying the genetics of accidental virulence.

  11. Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii.

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    Hussein M Abkallo

    2015-02-01

    Full Text Available In endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. It has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. This competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. It has also been argued that within-host competition could lead to selection for more virulent parasites. Here we use the rodent malaria parasite Plasmodium yoelii to assess the consequences of mixed strain infections on disease severity and parasite fitness. Three isogenic strains with dramatically different growth rates (and hence virulence were maintained in mice in single infections or in mixed strain infections with a genetically distinct strain. We compared the virulence (defined as harm to the mammalian host of mixed strain infections with that of single infections, and assessed whether competition impacted on parasite fitness, assessed by transmission potential. We found that mixed infections were associated with a higher degree of disease severity and a prolonged infection time. In the mixed infections, the strain with the slower growth rate was often responsible for the competitive exclusion of the faster growing strain, presumably through host immune-mediated mechanisms. Importantly, and in contrast to previous work conducted with Plasmodium chabaudi, we found no correlation between parasite virulence and transmission potential to mosquitoes, suggesting that within-host competition would not drive the evolution of parasite virulence in P. yoelii.

  12. Galleria mellonella model identifies highly virulent strains among all major molecular types of Cryptococcus gattii.

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    Carolina Firacative

    Full Text Available Cryptococcosis is mainly caused by Cryptococcus neoformans. However, the number of cases due to C. gattii is increasing, affecting mainly immunocompetent hosts. C. gattii is divided into four major molecular types, VGI to VGIV, which differ in their host range, epidemiology, antifungal susceptibility and geographic distribution. Besides studies on the Vancouver Island outbreak strains, which showed that the subtype VGIIa is highly virulent compared to the subtype VGIIb, little is known about the virulence of the other major molecular types. To elucidate the virulence potential of the major molecular types of C. gattii, Galleria mellonella larvae were inoculated with ten globally selected strains per molecular type. Survival rates were recorded and known virulence factors were studied. One VGII, one VGIII and one VGIV strain were more virulent (p 0.05, 21 (five VGI, five VGII, four VGIII and seven VGIV were less virulent (p <0.05 while one strain of each molecular type were avirulent. Cell and capsule size of all strains increased markedly during larvae infection (p <0.001. No differences in growth rate at 37°C were observed. Melanin synthesis was directly related with the level of virulence: more virulent strains produced more melanin than less virulent strains (p <0.05. The results indicate that all C. gattii major molecular types exhibit a range of virulence, with some strains having the potential to be more virulent. The study highlights the necessity to further investigate the genetic background of more and less virulent strains in order to recognize critical features, other than the known virulence factors (capsule, melanin and growth at mammalian body temperature, that maybe crucial for the development and progression of cryptococcosis.

  13. Differences in Virulence Between Legionella pneumophila Isolates From Human and Non-human Sources Determined in Galleria mellonella Infection Model

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    Patrícia S. Sousa

    2018-04-01

    Full Text Available Legionella pneumophila is a ubiquitous bacterium in freshwater environments and in many man-made water systems capable of inducing pneumonia in humans. Despite its ubiquitous character most studies on L. pneumophila virulence focused on clinical strains and isolates from man-made environments, so little is known about the nature and extent of virulence variation in strains isolated from natural environments. It has been established that clinical isolates are less diverse than man-made and natural environmental strains, suggesting that only a subset of environmental isolates is specially adapted to infect humans. In this work we intended to determine if unrelated L. pneumophila strains, isolated from different environments and with distinct virulence-related genetic backgrounds, displayed differences in virulence, using the Wax Moth Galleria mellonella infection model. We found that all tested strains were pathogenic in G. mellonella, regardless of their origin. Indeed, a panoply of virulence-related phenotypes was observed sustaining the existence of significant differences on the ability of L. pneumophila strains to induce disease. Taken together our results suggest that the occurrence of human infection is not related with the increased capability of some strains to induce disease since we also found a concentration threshold above which L. pneumophila strains are equally able to cause disease. In addition, no link could be established between the sequence-type (ST and L. pneumophila pathogenicity. We envision that in man-made water distribution systems environmental filtering selection and biotic competition acts structuring L. pneumophila populations by selecting more resilient and adapted strains that can rise to high concentration if no control measures are implemented. Therefore, public health strategies based on the sequence based typing (STB scheme analysis should take into account that the major disease-associated clones of L

  14. A theoretical model of the evolution of virulence in sexually transmitted HIV/AIDS

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    FAB Coutinho

    1999-08-01

    Full Text Available INTRODUCTION: The evolution of virulence in host-parasite relationships has been the subject of several publications. In the case of HIV virulence, some authors suggest that the evolution of HIV virulence correlates with the rate of acquisition of new sexual partners. In contrast some other authors argue that the level of HIV virulence is independent of the sexual activity of the host population. METHODS: Provide a mathematical model for the study of the potential influence of human sexual behaviour on the evolution of virulence of HIV is provided. RESULTS: The results indicated that, when the probability of acquisition of infection is a function both of the sexual activity and of the virulence level of HIV strains, the evolution of HIV virulence correlates positively with the rate of acquisition of new sexual partners. CONCLUSION: It is concluded that in the case of a host population with a low (high rate of exchange of sexual partners the evolution of HIV virulence is such that the less (more virulent strain prevails.

  15. A theoretical model of the evolution of virulence in sexually transmitted HIV/AIDS

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    Coutinho FAB

    1999-01-01

    Full Text Available INTRODUCTION: The evolution of virulence in host-parasite relationships has been the subject of several publications. In the case of HIV virulence, some authors suggest that the evolution of HIV virulence correlates with the rate of acquisition of new sexual partners. In contrast some other authors argue that the level of HIV virulence is independent of the sexual activity of the host population. METHODS: Provide a mathematical model for the study of the potential influence of human sexual behaviour on the evolution of virulence of HIV is provided. RESULTS: The results indicated that, when the probability of acquisition of infection is a function both of the sexual activity and of the virulence level of HIV strains, the evolution of HIV virulence correlates positively with the rate of acquisition of new sexual partners. CONCLUSION: It is concluded that in the case of a host population with a low (high rate of exchange of sexual partners the evolution of HIV virulence is such that the less (more virulent strain prevails.

  16. The δ subunit of RNA polymerase guides promoter selectivity and virulence in Staphylococcus aureus.

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    Weiss, Andy; Ibarra, J Antonio; Paoletti, Jessica; Carroll, Ronan K; Shaw, Lindsey N

    2014-04-01

    In Gram-positive bacteria, and particularly the Firmicutes, the DNA-dependent RNA polymerase (RNAP) complex contains an additional subunit, termed the δ factor, or RpoE. This enigmatic protein has been studied for more than 30 years for various organisms, but its function is still not well understood. In this study, we investigated its role in the major human pathogen Staphylococcus aureus. We showed conservation of important structural regions of RpoE in S. aureus and other species and demonstrated binding to core RNAP that is mediated by the β and/or β' subunits. To identify the impact of the δ subunit on transcription, we performed transcriptome sequencing (RNA-seq) analysis and observed 191 differentially expressed genes in the rpoE mutant. Ontological analysis revealed, quite strikingly, that many of the downregulated genes were known virulence factors, while several mobile genetic elements (SaPI5 and prophage SA3usa) were strongly upregulated. Phenotypically, the rpoE mutant had decreased accumulation and/or activity of a number of key virulence factors, including alpha toxin, secreted proteases, and Panton-Valentine leukocidin (PVL). We further observed significantly decreased survival of the mutant in whole human blood, increased phagocytosis by human leukocytes, and impaired virulence in a murine model of infection. Collectively, our results demonstrate that the δ subunit of RNAP is a critical component of the S. aureus transcription machinery and plays an important role during infection.

  17. Time resolved bovine host reponse to virulence factors mapped in milk by selected reaction monitoring

    DEFF Research Database (Denmark)

    Bislev, Stine Lønnerup; Kusebauch, Ulrike; Codrea, Marius Cosmin

    . In this study, we present a sensitive selected reaction monitoring (SRM) proteomics approach, targeting proteins suggested to play key roles in the bovine host response to mastitis. 17 biomarker candidates related to inflammatory response and mastitis were selected. The 17 candidate proteins were quantified......TIME RESOLVED BOVINE HOST RESPONSE TO VIRULENCE FACTORS, MAPPED IN MILK BY SELECTED REACTION MONITORING S.L. Bislev1, U. Kusebauch2, M.C. Codrea1, R. Moritz2, C.M. Røntved1, E. Bendixen1 1 Department of Animal Science, Faculty of Science and Technology, Aarhus University, Tjele, Denmark; 2...... Institute for Systems Biology, Seattle, Washington, USA Mastitis is beyond doubt the largest health problem in modern milk production. Many different pathogens can cause infections in the mammary gland, and give rise to severe toll on animal welfare, economic gain as well as on excessive use of antibiotics...

  18. Evidence for positive selection in putative virulence factors within the Paracoccidioides brasiliensis species complex.

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    Daniel R Matute

    Full Text Available Paracoccidioides brasiliensis is a dimorphic fungus that is the causative agent of paracoccidioidomycosis, the most important prevalent systemic mycosis in Latin America. Recently, the existence of three genetically isolated groups in P. brasiliensis was demonstrated, enabling comparative studies of molecular evolution among P. brasiliensis lineages. Thirty-two gene sequences coding for putative virulence factors were analyzed to determine whether they were under positive selection. Our maximum likelihood-based approach yielded evidence for selection in 12 genes that are involved in different cellular processes. An in-depth analysis of four of these genes showed them to be either antigenic or involved in pathogenesis. Here, we present evidence indicating that several replacement mutations in gp43 are under positive balancing selection. The other three genes (fks, cdc42 and p27 show very little variation among the P. brasiliensis lineages and appear to be under positive directional selection. Our results are consistent with the more general observations that selective constraints are variable across the genome, and that even in the genes under positive selection, only a few sites are altered. We present our results within an evolutionary framework that may be applicable for studying adaptation and pathogenesis in P. brasiliensis and other pathogenic fungi.

  19. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    Kaman, W.E.; Hawkey, S.; Kleij, D. van der; Broekhuijsen, M.P.; Silman, N.J.; Bikker, F.J.

    2011-01-01

    We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all

  20. Examining the virulence of Candida albicans transcription factor mutants using Galleria mellonella and mouse infection models

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    Sara eAmorim-Vaz

    2015-05-01

    Full Text Available The aim of the present study was to identify C. albicans transcription factors (TF involved in virulence. Although mice are considered the gold-standard model to study fungal virulence, mini-host infection models have been increasingly used. Here, barcoded TF mutants were first screened in mice by pools of strains and fungal burdens quantified in kidneys. Mutants of unannotated genes which generated a kidney fungal burden significantly different from that of wild-type were selected and individually examined in G. mellonella. In addition, mutants that could not be detected in mice were also tested in G. mellonella. Only 25 % of these mutants displayed matching phenotypes in both hosts, highlighting a significant discrepancy between the two models. To address the basis of this difference (pool or host effects, a set of 19 mutants tested in G. mellonella were also injected individually into mice. Matching fungal burden phenotypes were observed in 50 % of the cases, highlighting the bias due to host effects. In contrast, 33.4 % concordance was observed between pool and single strain infections in mice, thereby highlighting the bias introduced by the pool effect. After filtering the results obtained from the two infection models, mutants for MBF1 and ZCF6 were selected. Independent marker-free mutants were subsequently tested in both hosts to validate previous results. The MBF1 mutant showed impaired infection in both models, while the ZCF6 mutant was only significant in mice infections. The two mutants showed no obvious in vitro phenotypes compared with the wild-type, indicating that these genes might be specifically involved in in vivo adaptation.

  1. Effects of selection pressure and genetic association on the relationship between antibiotic resistance and virulence in Escherichia coli.

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    Zhang, Lixin; Levy, Karen; Trueba, Gabriel; Cevallos, William; Trostle, James; Foxman, Betsy; Marrs, Carl F; Eisenberg, Joseph N S

    2015-11-01

    Antibiotic selection pressure and genetic associations may lead to the cooccurrence of resistance and virulence in individual pathogens. However, there is a lack of rigorous epidemiological evidence that demonstrates the cooccurrence of resistance and virulence at the population level. Using samples from a population-based case-control study in 25 villages in rural Ecuador, we characterized resistance to 12 antibiotics among pathogenic (n = 86) and commensal (n = 761) Escherichia coli isolates, classified by the presence or absence of known diarrheagenic virulence factor genes. The prevalences of resistance to single and multiple antibiotics were significantly higher for pathogenic isolates than for commensal isolates. Using a generalized estimating equation, antibiotic resistance was independently associated with virulence factor carriage, case status, and antibiotic use (for these respective factors: odds ratio [OR] = 3.0, with a 95% confidence interval [CI] of 1.7 to 5.1; OR = 2.0, with a 95% CI of 1.3 to 3.0; and OR = 1.5, with a 95% CI of 0.9 to 2.5). Virulence factor carriage was more strongly related to antibiotic resistance than antibiotic use for all antibiotics examined, with the exception of fluoroquinolones, gentamicin, and cefotaxime. This study provides epidemiological evidence that antibiotic resistance and virulence factor carriage are linked in E. coli populations in a community setting. Further, these data suggest that while the cooccurrence of resistance and virulence in E. coli is partially due to antibiotic selection pressure, it is also genetically determined. These findings should be considered in developing strategies for treating infections and controlling for antibiotic resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Virulence of Klebsiella pneumoniae isolates harboring bla KPC-2 carbapenemase gene in a Caenorhabditis elegans model.

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    Jean-Philippe Lavigne

    Full Text Available Klebsiella pneumoniae carbapenemase (KPC is a carbapenemase increasingly reported worldwide in Enterobacteriaceae. The aim of this study was to analyze the virulence of several KPC-2-producing K. pneumoniae isolates. The studied strains were (i five KPC-2 clinical strains from different geographical origins, belonging to different ST-types and possessing plasmids of different incompatibility groups; (ii seven transformants obtained after electroporation of either these natural KPC plasmids or a recombinant plasmid harboring only the bla KPC-2 gene into reference strains K. pneumoniae ATCC10031/CIP53153; and (iii five clinical strains cured of plasmids. The virulence of K. pneumoniae isolates was evaluated in the Caenorhabditis elegans model. The clinical KPC producers and transformants were significantly less virulent (LT50: 5.5 days than K. pneumoniae reference strain (LT50: 4.3 days (p<0.01. However, the worldwide spread KPC-2 positive K. pneumoniae ST258 strains and reference strains containing plasmids extracted from K. pneumoniae ST258 strains had a higher virulence than KPC-2 strains belonging to other ST types (LT50: 5 days vs. 6 days, p<0.01. The increased virulence observed in cured strains confirmed this trend. The bla KPC-2 gene itself was not associated to increased virulence.

  3. Virulence genes and subclone status as markers of experimental virulence in a murine sepsis model among Escherichia coli sequence type 131 clinical isolates from Spain.

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    Irene Merino

    Full Text Available To assess experimental virulence among sequence type 131 (ST131 Escherichia coli bloodstream isolates in relation to virulence genotype and subclone.We analysed 48 Spanish ST131 bloodstream isolates (2010 by PCR for ST131 subclone status (H30Rx, H30 non-Rx, or non-H30, virulence genes (VGs, and O-type. Then we compared these traits with virulence in a murine sepsis model, as measured by illness severity score (ISS and rapid lethality (mean ISS ≥ 4.Of the 48 study isolates, 65% were H30Rx, 21% H30 non-Rx, and 15% non-H30; 44% produced ESBLs, 98% were O25b, and 83% qualified as extraintestinal pathogenic E. coli (ExPEC. Of 49 VGs, ibeA and iss were associated significantly with non-H30 isolates, and sat, iha and malX with H30 isolates. Median VG scores differed by subclone, i.e., 12 (H30Rx, 10 (H30 non-Rx, and 11 (non-H30 (p < 0.01. Nearly 80% of isolates represented a described virotype. In mice, H30Rx and non-H30 isolates were more virulent than H30 non-Rx isolates (according to ISS [p = 0.03] and rapid lethality [p = 0.03], as were ExPEC isolates compared with non-ExPEC isolates (median ISS, 4.3 vs. 2.7: p = 0.03. In contrast, most individual VGs, VG scores, VG profiles, and virotypes were not associated with mouse virulence.ST131 subclone and ExPEC status, but not individual VGs, VG scores or profiles, or virotypes, predicted mouse virulence. Given the lower virulence of non-Rx H30 isolates, hypervirulence probably cannot explain the ST131-H30 clade's epidemic emergence.

  4. The worm has turned--microbial virulence modeled in Caenorhabditis elegans.

    Science.gov (United States)

    Sifri, Costi D; Begun, Jakob; Ausubel, Frederick M

    2005-03-01

    The nematode Caenorhabditis elegans is emerging as a facile and economical model host for the study of evolutionarily conserved mechanisms of microbial pathogenesis and innate immunity. A rapidly growing number of human and animal microbial pathogens have been shown to injure and kill nematodes. In many cases, microbial genes known to be important for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity in nematodes. C. elegans has been used in mutation-based screening systems to identify novel virulence-related microbial genes and immune-related host genes, many of which have been validated in mammalian models of disease. C. elegans-based pathogenesis systems hold the potential to simultaneously explore the molecular genetic determinants of both pathogen virulence and host defense.

  5. Evaluating Different Virulence Traits of Klebsiella pneumoniae Using Dictyostelium discoideum and Zebrafish Larvae as Host Models

    Directory of Open Access Journals (Sweden)

    Andrés E. Marcoleta

    2018-02-01

    Full Text Available Multiresistant and invasive hypervirulent Klebsiella pneumoniae strains have become one of the most urgent bacterial pathogen threats. Recent analyses revealed a high genomic plasticity of this species, harboring a variety of mobile genetic elements associated with virulent strains, encoding proteins of unknown function whose possible role in pathogenesis have not been addressed. K. pneumoniae virulence has been studied mainly in animal models such as mice and pigs, however, practical, financial, ethical and methodological issues limit the use of mammal hosts. Consequently, the development of simple and cost-effective experimental approaches with alternative host models is needed. In this work we described the use of both, the social amoeba and professional phagocyte Dictyostelium discoideum and the fish Danio rerio (zebrafish as surrogate host models to study K. pneumoniae virulence. We compared three K. pneumoniae clinical isolates evaluating their resistance to phagocytosis, intracellular survival, lethality, intestinal colonization, and innate immune cells recruitment. Optical transparency of both host models permitted studying the infective process in vivo, following the Klebsiella-host interactions through live-cell imaging. We demonstrated that K. pneumoniae RYC492, but not the multiresistant strains 700603 and BAA-1705, is virulent to both host models and elicits a strong immune response. Moreover, this strain showed a high resistance to phagocytosis by D. discoideum, an increased ability to form biofilms and a more prominent and irregular capsule. Besides, the strain 700603 showed the unique ability to replicate inside amoeba cells. Genomic comparison of the K. pneumoniae strains showed that the RYC492 strain has a higher overall content of virulence factors although no specific genes could be linked to its phagocytosis resistance, nor to the intracellular survival observed for the 700603 strain. Our results indicate that both zebrafish

  6. Specific selection for virulent urinary tract infectious Escherichia coli strains during catheter-associated biofilm formation

    DEFF Research Database (Denmark)

    Ferrieres, Lionel; Hancock, Viktoria; Klemm, Per

    2007-01-01

    microorganisms can attach. Urinary tract infectious (UTI) Escherichia coli range in pathogenicity and the damage they cause - from benign asymptomatic bacteriuria (ABU) strains, which inflict no or few problems to the host, to uropathogenic E. coli (UPEC) strains, which are virulent and often cause severe...... for and promote biofilm formation of the most virulent group of UTI E. coli strains, hardly a desirable situation for the catheterized patient....

  7. The Streptococcus sanguinis competence regulon is not required for infective endocarditis virulence in a rabbit model.

    Directory of Open Access Journals (Sweden)

    Jill E Callahan

    Full Text Available Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon in addition to DNA uptake, including virulence. We investigated this possibility in S. sanguinis. Strains deleted for the comCDE or comX master regulatory genes were created. Using a rabbit endocarditis model in conjunction with a variety of virulence assays, we determined that both mutants possessed infectivity equivalent to that of a virulent control strain, and that measures of disease were similar in rabbits infected with each strain. These results suggest that the com regulon is not required for S. sanguinis infective endocarditis virulence in this model. We propose that the different roles of the S. sanguinis, S. pneumoniae, and S. mutans com regulons in virulence can be understood in relation to the pathogenic mechanisms employed by each species.

  8. The Streptococcus sanguinis competence regulon is not required for infective endocarditis virulence in a rabbit model.

    Science.gov (United States)

    Callahan, Jill E; Munro, Cindy L; Kitten, Todd

    2011-01-01

    Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon in addition to DNA uptake, including virulence. We investigated this possibility in S. sanguinis. Strains deleted for the comCDE or comX master regulatory genes were created. Using a rabbit endocarditis model in conjunction with a variety of virulence assays, we determined that both mutants possessed infectivity equivalent to that of a virulent control strain, and that measures of disease were similar in rabbits infected with each strain. These results suggest that the com regulon is not required for S. sanguinis infective endocarditis virulence in this model. We propose that the different roles of the S. sanguinis, S. pneumoniae, and S. mutans com regulons in virulence can be understood in relation to the pathogenic mechanisms employed by each species.

  9. Decrease of Staphylococcus aureus Virulence by Helcococcus kunzii in a Caenorhabditis elegans Model.

    Science.gov (United States)

    Ngba Essebe, Christelle; Visvikis, Orane; Fines-Guyon, Marguerite; Vergne, Anne; Cattoir, Vincent; Lecoustumier, Alain; Lemichez, Emmanuel; Sotto, Albert; Lavigne, Jean-Philippe; Dunyach-Remy, Catherine

    2017-01-01

    Social bacterial interactions are considered essential in numerous infectious diseases, particularly in wounds. Foot ulcers are a common complication in diabetic patients and these ulcers become frequently infected. This infection is usually polymicrobial promoting cell-to-cell communications. Staphylococcus aureus is the most prevalent pathogen isolated. Its association with Helcococcus kunzii , commensal Gram-positive cocci, is frequently described. The aim of this study was to assess the impact of co-infection on virulence of both H. kunzii and S. aureus strains in a Caenorhabditis elegans model. To study the host response, qRT-PCRs targeting host defense genes were performed. We observed that H. kunzii strains harbored a very low (LT50: 5.7 days ± 0.4) or an absence of virulence (LT50: 6.9 days ± 0.5). In contrast, S. aureus strains (LT50: 2.9 days ± 0.4) were significantly more virulent than all H. kunzii ( P aureus strains were associated, H. kunzii significantly reduced the virulence of the S. aureus strain in nematodes (LT50 between 4.4 and 5.2 days; P aureus led to a strong induction of defense genes ( lys-5, sodh-1 , and cyp-37B1 ) while H. kunzii did not. No statistical difference of host response genes expression was observed when C. elegans were infected with either S. aureus alone or with S. aureus + H. kunzii . Moreover, two well-characterized virulence factors ( hla and agr ) present in S. aureus were down-regulated when S. aureus were co-infected with H. kunzii . This study showed that H. kunzii decreased the virulence of S. aureus without modifying directly the host defense response. Factor(s) produced by this bacterium modulating the staphylococci virulence must be investigated.

  10. Economic Game Theory to Model the Attenuation of Virulence of an Obligate Intracellular Bacterium.

    Science.gov (United States)

    Tago, Damian; Meyer, Damien F

    2016-01-01

    Diseases induced by obligate intracellular pathogens have a large burden on global human and animal health. Understanding the factors involved in the virulence and fitness of these pathogens contributes to the development of control strategies against these diseases. Based on biological observations, a theoretical model using game theory is proposed to explain how obligate intracellular bacteria interact with their host. The equilibrium in such a game shows that the virulence and fitness of the bacterium is host-triggered and by changing the host's defense system to which the bacterium is confronted, an evolutionary process leads to an attenuated strain. Although, the attenuation procedure has already been conducted in practice in order to develop an attenuated vaccine (e.g., with Ehrlichia ruminantium), there was a lack of understanding of the theoretical basis behind this process. Our work provides a model to better comprehend the existence of different phenotypes and some underlying evolutionary mechanisms for the virulence of obligate intracellular bacteria.

  11. Assessment of Listeria monocytogenes virulence in the Galleria mellonella insect larvae model.

    Science.gov (United States)

    Rakic Martinez, Mira; Wiedmann, Martin; Ferguson, Martine; Datta, Atin R

    2017-01-01

    Several animal models have been used to understand the molecular basis of the pathogenicity, infectious dose and strain to strain variation of Listeria monocytogenes. The greater wax worm Galleria mellonella, as an alternative model, provides some useful advantages not available with other models and has already been described as suitable for the virulence assessment of various pathogens including L. monocytogenes. The objectives of this study are: 1) confirming the usefulness of this model with a wide panel of Listeria spp. including non-pathogenic L. innocua, L. seeligeri, L. welshimeri and animal pathogen L. ivanovii; 2) assessment of virulence of several isogenic in-frame deletion mutants in virulence and stress related genes of L. monocytogenes and 3) virulence assessment of paired food and clinical isolates of L. monocytogenes from 14 major listeriosis outbreaks occurred worldwide between 1980 and 2015. Larvae injected with different concentrations of Listeria were incubated at 37°C and monitored over seven days for time needed to kill 50% of larvae (LT50) and to determine change of bacterial population in G. mellonella, 2 and 24 hours post-inoculation. Non-pathogenic members of Listeria and L. ivanovii showed significantly (P monocytogenes strains. Isogenic mutants of L. monocytogenes with the deletions in prfA, plcA, hly, actA and virR genes, also showed significantly (P monocytogenes strains related to non-invasive (gastroenteritis) outbreaks of listeriosis showed significantly (P < 0.05) lower virulence than isolates of the same serotype obtained from outbreaks with invasive symptoms. The difference, however, was dose and strain- dependent. No significant differences in virulence were observed among the serotype tested in this study.

  12. Technologies and Approaches to Elucidate and Model the Virulence Program of Salmonella.

    Energy Technology Data Exchange (ETDEWEB)

    McDermott, Jason E.; Yoon, Hyunjin; Nakayasu, Ernesto S.; Metz, Thomas O.; Hyduke, Daniel R.; Kidwai, Afshan S.; Palsson, Bernhard O.; Adkins, Joshua N.; Heffron, Fred

    2011-04-01

    Salmonella is a primary cause of enteric diseases in a variety of animals. During its evolution into a pathogenic bacterium, Salmonella acquired an elaborate regulatory network that responds to multiple environmental stimuli within host animals and integrates them resulting in fine regulation of the virulence program. The coordinated action by this regulatory network involves numerous virulence regulators, necessitating genome-wide profiling analysis to assess and combine efforts from multiple regulons. In this review we discuss recent high-throughput analytic approaches to understand the regulatory network of Salmonella that controls virulence processes. Application of high-throughput analyses have generated a large amount of data and driven development of computational approaches required for data integration. Therefore, we also cover computer-aided network analyses to infer regulatory networks, and demonstrate how genome-scale data can be used to construct regulatory and metabolic systems models of Salmonella pathogenesis. Genes that are coordinately controlled by multiple virulence regulators under infectious conditions are more likely to be important for pathogenesis. Thus, reconstructing the global regulatory network during infection or, at the very least, under conditions that mimic the host cellular environment not only provides a bird’s eye view of Salmonella survival strategy in response to hostile host environments but also serves as an efficient means to identify novel virulence factors that are essential for Salmonella to accomplish systemic infection in the host.

  13. Assessment of Listeria monocytogenes virulence in the Galleria mellonella insect larvae model.

    Directory of Open Access Journals (Sweden)

    Mira Rakic Martinez

    Full Text Available Several animal models have been used to understand the molecular basis of the pathogenicity, infectious dose and strain to strain variation of Listeria monocytogenes. The greater wax worm Galleria mellonella, as an alternative model, provides some useful advantages not available with other models and has already been described as suitable for the virulence assessment of various pathogens including L. monocytogenes. The objectives of this study are: 1 confirming the usefulness of this model with a wide panel of Listeria spp. including non-pathogenic L. innocua, L. seeligeri, L. welshimeri and animal pathogen L. ivanovii; 2 assessment of virulence of several isogenic in-frame deletion mutants in virulence and stress related genes of L. monocytogenes and 3 virulence assessment of paired food and clinical isolates of L. monocytogenes from 14 major listeriosis outbreaks occurred worldwide between 1980 and 2015. Larvae injected with different concentrations of Listeria were incubated at 37°C and monitored over seven days for time needed to kill 50% of larvae (LT50 and to determine change of bacterial population in G. mellonella, 2 and 24 hours post-inoculation. Non-pathogenic members of Listeria and L. ivanovii showed significantly (P < 0.05 higher LT50 (lower virulence than the wild type L. monocytogenes strains. Isogenic mutants of L. monocytogenes with the deletions in prfA, plcA, hly, actA and virR genes, also showed significantly (P < 0.05 higher LT50 than the wild type strain at the inoculum of 106CFU/larva. Food isolates had significantly (P < 0.05 lower virulence than the paired clinical isolates, at all three inoculum concentrations. L. monocytogenes strains related to non-invasive (gastroenteritis outbreaks of listeriosis showed significantly (P < 0.05 lower virulence than isolates of the same serotype obtained from outbreaks with invasive symptoms. The difference, however, was dose and strain- dependent. No significant differences in

  14. Virulence of six capsular serotypes of Porphyromonas gingivalis in a mouse model

    NARCIS (Netherlands)

    Laine, ML; van Winkelhoff, AJ

    1998-01-01

    Capsular structures of Porphyromonas gingivalis have been correlated to the pathogenicity in animal models. Six polysaccharide capsular serotypes have recently been described in P. gingivalis. In the present study, virulence of the P. gingivalis strains of the six capsular serotypes was compared

  15. Critical role of LuxS in the virulence of Campylobacter jejuni in a guinea pig model of abortion.

    Science.gov (United States)

    Plummer, Paul; Sahin, Orhan; Burrough, Eric; Sippy, Rachel; Mou, Kathy; Rabenold, Jessica; Yaeger, Mike; Zhang, Qijing

    2012-02-01

    Previous studies on Campylobacter jejuni have demonstrated the role of LuxS in motility, cytolethal distending toxin production, agglutination, and intestinal colonization; however, its direct involvement in virulence has not been reported. In this study, we demonstrate a direct role of luxS in the virulence of C. jejuni in two different animal hosts. The IA3902 strain, a highly virulent sheep abortion strain recently described by our laboratory, along with its isogenic luxS mutant and luxS complement strains, was inoculated by the oral route into both a pregnant guinea pig virulence model and a chicken colonization model. In both cases, the IA3902 luxS mutant demonstrated a complete loss of ability to colonize the intestinal tract. In the pregnant model, the mutant also failed to induce abortion, while the wild-type strain was highly abortifacient. Genetic complementation of the luxS gene fully restored the virulent phenotype in both models. Interestingly, when the organism was inoculated into guinea pigs by the intraperitoneal route, no difference in virulence (abortion induction) was observed between the luxS mutant and the wild-type strain, suggesting that the defect in virulence following oral inoculation is likely associated with a defect in colonization and/or translocation of the organism out of the intestine. These studies provide the first direct evidence that LuxS plays an important role in the virulence of C. jejuni using an in vivo model of natural disease.

  16. Evolution of viral virulence: empirical studies

    Science.gov (United States)

    Kurath, Gael; Wargo, Andrew R.

    2016-01-01

    The concept of virulence as a pathogen trait that can evolve in response to selection has led to a large body of virulence evolution theory developed in the 1980-1990s. Various aspects of this theory predict increased or decreased virulence in response to a complex array of selection pressures including mode of transmission, changes in host, mixed infection, vector-borne transmission, environmental changes, host vaccination, host resistance, and co-evolution of virus and host. A fundamental concept is prediction of trade-offs between the costs and benefits associated with higher virulence, leading to selection of optimal virulence levels. Through a combination of observational and experimental studies, including experimental evolution of viruses during serial passage, many of these predictions have now been explored in systems ranging from bacteriophage to viruses of plants, invertebrates, and vertebrate hosts. This chapter summarizes empirical studies of viral virulence evolution in numerous diverse systems, including the classic models myxomavirus in rabbits, Marek's disease virus in chickens, and HIV in humans. Collectively these studies support some aspects of virulence evolution theory, suggest modifications for other aspects, and show that predictions may apply in some virus:host interactions but not in others. Finally, we consider how virulence evolution theory applies to disease management in the field.

  17. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    W.E. Kaman (Wendy); S. Hawkey; D. van der Kleij (Desiree); M.P. Broekhuijsen; N.J. Silman; F.J. Bikker (Floris)

    2011-01-01

    textabstractWe determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The

  18. Correlates between Models of Virulence for Mycobacterium tuberculosis among Isolates of the Central Asian Lineage: a Case for Lysozyme Resistance Testing?

    Science.gov (United States)

    Casali, Nicola; Clark, Simon O.; Hooper, Richard; Williams, Ann; Velji, Preya; Gonzalo, Ximena

    2015-01-01

    Virulence factors (VFs) contribute to the emergence of new human Mycobacterium tuberculosis strains, are lineage dependent, and are relevant to the development of M. tuberculosis drugs/vaccines. VFs were sought within M. tuberculosis lineage 3, which has the Central Asian (CAS) spoligotype. Three isolates were selected from clusters previously identified as dominant in London, United Kingdom. Strain-associated virulence was studied in guinea pig, monocyte-derived macrophage, and lysozyme resistance assays. Whole-genome sequencing, single nucleotide polymorphism (SNP) analysis, and a literature review contributed to the identification of SNPs of interest. The animal model revealed borderline differences in strain-associated pathogenicity. Ex vivo, isolate C72 exhibited statistically significant differences in intracellular growth relative to C6 and C14. SNP candidates inducing lower fitness levels included 123 unique nonsynonymous SNPs, including three located in genes (lysX, caeA, and ponA2) previously identified as VFs in the laboratory-adapted reference strain H37Rv and shown to confer lysozyme resistance. C72 growth was most affected by lysozyme in vitro. A BLAST search revealed that all three SNPs of interest (C35F, P76Q, and P780R) also occurred in Tiruvallur, India, and in Uganda. Unlike C72, however, no single isolate identified through BLAST carried all three SNPs simultaneously. CAS isolates representative of three medium-sized human clusters demonstrated differential outcomes in models commonly used to estimate strain-associated virulence, supporting the idea that virulence varies within, not just across, M. tuberculosis lineages. Three VF SNPs of interest were identified in two additional locations worldwide, which suggested independent selection and supported a role for these SNPs in virulence. The relevance of lysozyme resistance to strain virulence remains to be established. PMID:25776753

  19. Interplay among Resistance Profiles, High-Risk Clones, and Virulence in the Caenorhabditis elegans Pseudomonas aeruginosa Infection Model.

    Science.gov (United States)

    Sánchez-Diener, Irina; Zamorano, Laura; López-Causapé, Carla; Cabot, Gabriel; Mulet, Xavier; Peña, Carmen; Del Campo, Rosa; Cantón, Rafael; Doménech-Sánchez, Antonio; Martínez-Martínez, Luis; Arcos, Susana C; Navas, Alfonso; Oliver, Antonio

    2017-12-01

    The increasing prevalence of nosocomial infections produced by multidrug-resistant (MDR) or extensively drug-resistant (XDR) Pseudomonas aeruginosa is frequently linked to widespread international strains designated high-risk clones. In this work, we attempted to decipher the interplay between resistance profiles, high-risk clones, and virulence, testing a large ( n = 140) collection of well-characterized P. aeruginosa isolates from different sources (bloodstream infections, nosocomial outbreaks, cystic fibrosis, and the environment) in a Caenorhabditis elegans infection model. Consistent with previous data, we documented a clear inverse correlation between antimicrobial resistance and virulence in the C. elegans model. Indeed, the lowest virulence was linked to XDR profiles, which were typically linked to defined high-risk clones. However, virulence varied broadly depending on the involved high-risk clone; it was high for sequence type 111 (ST111) and ST235 but very low for ST175. The highest virulence of ST235 could be attributed to its exoU + type III secretion system (TTSS) genotype, which was found to be linked with higher virulence in our C. elegans model. Other markers, such as motility or pigment production, were not essential for virulence in the C. elegans model but seemed to be related with the higher values of the statistical normalized data. In contrast to ST235, the ST175 high-risk clone, which is widespread in Spain and France, seems to be associated with a particularly low virulence in the C. elegans model. Moreover, the previously described G154R AmpR mutation, prevalent in ST175, was found to contribute to the reduced virulence, although it was not the only factor involved. Altogether, our results provide a major step forward for understanding the interplay between P. aeruginosa resistance profiles, high-risk clones, and virulence. Copyright © 2017 American Society for Microbiology.

  20. Virulence Inhibitors from Brazilian Peppertree Block Quorum Sensing and Abate Dermonecrosis in Skin Infection Models

    Science.gov (United States)

    Muhs, Amelia; Lyles, James T.; Parlet, Corey P.; Nelson, Kate; Kavanaugh, Jeffery S.; Horswill, Alexander R.; Quave, Cassandra L.

    2017-01-01

    Widespread antibiotic resistance is on the rise and current therapies are becoming increasingly limited in both scope and efficacy. Methicillin-resistant Staphylococcus aureus (MRSA) represents a major contributor to this trend. Quorum sensing controlled virulence factors include secreted toxins responsible for extensive damage to host tissues and evasion of the immune system response; they are major contributors to morbidity and mortality. Investigation of botanical folk medicines for wounds and infections led us to study Schinus terebinthifolia (Brazilian Peppertree) as a potential source of virulence inhibitors. Here, we report the inhibitory activity of a flavone rich extract “430D-F5” against all S. aureus accessory gene regulator (agr) alleles in the absence of growth inhibition. Evidence for this activity is supported by its agr-quenching activity (IC50 2–32 μg mL−1) in transcriptional reporters, direct protein outputs (α-hemolysin and δ-toxin), and an in vivo skin challenge model. Importantly, 430D-F5 was well tolerated by human keratinocytes in cell culture and mouse skin in vivo; it also demonstrated significant reduction in dermonecrosis following skin challenge with a virulent strain of MRSA. This study provides an explanation for the anti-infective activity of peppertree remedies and yields insight into the potential utility of non-biocide virulence inhibitors in treating skin infections. PMID:28186134

  1. C. elegans as a virulence model for E. coli strain 042

    OpenAIRE

    Kjærbo, Rasmus E. R.; Godballe, Troels; Hansen, Klaus G.; Petersen, Pernille D.; Tikander, Emil

    2010-01-01

    During the last decade the nematode Caenorhabditis elegans has been used to model the pathogenesis of several bacterial species. The emerging pathogen enteroaggregative Escherichia coli (EAEC) is a considerable cause of both acute and persistent diarrhea worldwide. Travellers to developing countries, immunocompromised people and young children are high-risk groups prone to infection. Virulence models using C. elegans might provide valuable information about the host-pathogen interactions whic...

  2. The Galleria mellonella larvae as an in vivo model for evaluation of Shigella virulence.

    Science.gov (United States)

    Barnoy, Shoshana; Gancz, Hanan; Zhu, Yuewei; Honnold, Cary L; Zurawski, Daniel V; Venkatesan, Malabi M

    2017-07-04

    Shigella spp. causing bacterial diarrhea and dysentery are human enteroinvasive bacterial pathogens that are orally transmitted through contaminated food and water and cause bacillary dysentery. Although natural Shigella infections are restricted to humans and primates, several smaller animal models are used to analyze individual steps in pathogenesis. No animal model fully duplicates the human response and sustaining the models requires expensive animals, costly maintenance of animal facilities, veterinary services and approved animal protocols. This study proposes the development of the caterpillar larvae of Galleria mellonella as a simple, inexpensive, informative, and rapid in-vivo model for evaluating virulence and the interaction of Shigella with cells of the insect innate immunity. Virulent Shigella injected through the forelegs causes larvae death. The mortality rates were dependent on the Shigella strain, the infectious dose, and the presence of the virulence plasmid. Wild-type S. flexneri 2a, persisted and replicated within the larvae, resulting in haemocyte cell death, whereas plasmid-cured mutants were rapidly cleared. Histology of the infected larvae in conjunction with fluorescence, immunofluorescence, and transmission electron microscopy indicate that S. flexneri reside within a vacuole of the insect haemocytes that ultrastructurally resembles vacuoles described in studies with mouse and human macrophage cell lines. Some of these bacteria-laden vacuoles had double-membranes characteristic of autophagosomes. These results suggest that G. mellonella larvae can be used as an easy-to-use animal model to understand Shigella pathogenesis that requires none of the time and labor-consuming procedures typical of other systems.

  3. Selected lactic acid-producing bacterial isolates with the capacity to reduce Salmonella translocation and virulence gene expression in chickens.

    Directory of Open Access Journals (Sweden)

    Xiaojian Yang

    Full Text Available BACKGROUND: Probiotics have been used to control Salmonella colonization/infection in chickens. Yet the mechanisms of probiotic effects are not fully understood. This study has characterized our previously-selected lactic acid-producing bacterial (LAB isolates for controlling Salmonella infection in chickens, particularly the mechanism underlying the control. METHODOLOGY/PRINCIPAL FINDINGS: In vitro studies were conducted to characterize 14 LAB isolates for their tolerance to low pH (2.0 and high bile salt (0.3-1.5% and susceptibility to antibiotics. Three chicken infection trials were subsequently carried out to evaluate four of the isolates for reducing the burden of Salmonella enterica serovar Typhimurium in the broiler cecum. Chicks were gavaged with LAB cultures (10(6-7 CFU/chick or phosphate-buffered saline (PBS at 1 day of age followed by Salmonella challenge (10(4 CFU/chick next day. Samples of cecal digesta, spleen, and liver were examined for Salmonella counts on days 1, 3, or 4 post-challenge. Salmonella in the cecum from Trial 3 was also assessed for the expression of ten virulence genes located in its pathogenicity island-1 (SPI-1. These genes play a role in Salmonella intestinal invasion. Tested LAB isolates (individuals or mixed cultures were unable to lower Salmonella burden in the chicken cecum, but able to attenuate Salmonella infection in the spleen and liver. The LAB treatments also reduced almost all SPI-1 virulence gene expression (9 out of 10 in the chicken cecum, particularly at the low dose. In vitro treatment with the extracellular culture fluid from a LAB culture also down-regulated most SPI-1 virulence gene expression. CONCLUSIONS/SIGNIFICANCE: The possible correlation between attenuation of Salmonella infection in the chicken spleen and liver and reduction of Salmonella SPI-1 virulence gene expression in the chicken cecum by LAB isolates is a new observation. Suppression of Salmonella virulence gene expression in

  4. The putative thiosulfate sulfurtransferases PspE and GlpE contribute to virulence of Salmonella Typhimurium in the mouse model of systemic disease

    DEFF Research Database (Denmark)

    Wallrodt, Inke; Jelsbak, Lotte; Thorndahl, Lotte

    2013-01-01

    contribute to S. Typhimurium virulence, as a glpE and pspE double deletion strain showed significantly decreased virulence in a mouse model of systemic infection. However, challenge of cultured epithelial cells and macrophages did not reveal any virulence-associated phenotypes. We hypothesized...

  5. Virulence variations in Shigella and enteroinvasive Escherichia coli using the Caenorhabditis elegans model.

    Science.gov (United States)

    Fung, Crystal Ching; Octavia, Sophie; Mooney, Anne-Marie; Lan, Ruiting

    2015-01-01

    Shigella species and enteroinvasive Escherichia coli (EIEC) belong to the same species genetically, with remarkable phenotypic and genomic similarities. Shigella is the main cause of bacillary dysentery with around 160 million annual cases, while EIEC generally induces a milder disease compared to Shigella. This study aimed to determine virulence variations between Shigella and EIEC using the nematode Caenorhabditis elegans as a model host. Caenorhabditis elegans killing- and bacterial colonization assays were performed to examine the potential difference in virulence between Shigella and EIEC strains. Statistically significant difference in the survival rates of nematodes was demonstrated, with Shigella causing death at 88.24 ± 1.20% and EIEC at 94.37 ± 0.70%. The intestinal load of bacteria in the nematodes was found to be 7.65 × 10(4) ± 8.83 × 10(3) and 2.92 × 10(4) ± 6.26 × 10(3) CFU ml(-1) per nematode for Shigella and EIEC, respectively. Shigella dysenteriae serotype 1 which carries the Shiga toxin showed the lowest nematode survival rate at 82.6 ± 3.97% and highest bacterial colonization of 1.75 × 10(5) ± 8.17 × 10(4) CFU ml(-1), whereas a virulence plasmid-negative Shigella strain demonstrated 100 ± 0% nematode survival and lowest bacterial accumulation of 1.02 × 10(4) ± 7.23 × 10(2) CFU ml(-1). This study demonstrates C. elegans as an effective model for examining and comparing Shigella and EIEC virulence variation. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Distinct virulence of Rift Valley fever phlebovirus strains from different genetic lineages in a mouse model.

    Directory of Open Access Journals (Sweden)

    Tetsuro Ikegami

    Full Text Available Rift Valley fever phlebovirus (RVFV causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Mice were intraperitoneally infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains. Among them, mice infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2-3 dpi. Recombinant SA51 (rSA51 and Zinga (rZinga strains were recovered by reverse genetics, and their virulence was also tested in CD1 mice. The rSA51 strain reproduced peracute RVF disease in mice, whereas the rZinga strain showed a similar virulence with that of rZH501 strain. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development as well as pathological studies.

  7. A theoretical model of the evolution of virulence in sexually transmitted HIV/AIDS Modelo teórico da evolucão da virulência do HIV/AIDS transmitido sexualmente

    Directory of Open Access Journals (Sweden)

    FAB Coutinho

    1999-08-01

    Full Text Available INTRODUCTION: The evolution of virulence in host-parasite relationships has been the subject of several publications. In the case of HIV virulence, some authors suggest that the evolution of HIV virulence correlates with the rate of acquisition of new sexual partners. In contrast some other authors argue that the level of HIV virulence is independent of the sexual activity of the host population. METHODS: Provide a mathematical model for the study of the potential influence of human sexual behaviour on the evolution of virulence of HIV is provided. RESULTS: The results indicated that, when the probability of acquisition of infection is a function both of the sexual activity and of the virulence level of HIV strains, the evolution of HIV virulence correlates positively with the rate of acquisition of new sexual partners. CONCLUSION: It is concluded that in the case of a host population with a low (high rate of exchange of sexual partners the evolution of HIV virulence is such that the less (more virulent strain prevails.INTRODUÇÃO: A evolução da virulência na relação hospedeiro-parasita tem sido objeto de várias publicações. No caso do HIV, alguns autores sugerem que a evolução da virulência do HIV correlaciona-se com a taxa de aquisição de novos parceiros sexuais. Por outro lado, outros autores argumentam que o nível de virulência do HIV é independente da atividade sexual da população hospedeira. MÉTODOS: Propõe-se um modelo matemático para estudar a influência potencial que o comportamento sexual humano possa ter na evolução da virulência do HIV. RESULTADOS: Os resultados indicam que, quando a probabilidade de aquisição da infecção pelo HIV é uma função tanto da atividade sexual da população humana quanto da virulência das cepas de HIV, a evolução da virulência do HIV correlaciona-se positivamente com a taxa de aquisição de novos parceiros sexuais. CONCLUSÃO: Concluiu-se que no caso de uma popula

  8. Linking Genomo- and Pathotype: Exploiting the Zebrafish Embryo Model to Investigate the Divergent Virulence Potential among Cronobacter spp.

    Directory of Open Access Journals (Sweden)

    Athmanya K Eshwar

    Full Text Available Bacteria belonging to the genus Cronobacter have been recognized as causative agents of life-threatening systemic infections primarily in premature, low-birth weight and immune-compromised neonates. Apparently not all Cronobacter species are linked to infantile infections and it has been proposed that virulence varies among strains. Whole genome comparisons and in silico analysis have proven to be powerful tools in elucidating potential virulence determinants, the presence/absence of which may explain the differential virulence behaviour of strains. However, validation of these factors has in the past been hampered by the availability of a suitable neonatal animal model. In the present study we have used zebrafish embryos to model Cronobacter infections in vivo using wild type and genetically engineered strains. Our experiments confirmed the role of the RepF1B-like plasmids as "virulence plasmids" in Cronobacter and underpinned the importantce of two putative virulence factors-cpa and zpx-in in vivo pathogenesis. We propose that by using this model in vivo infection studies are now possible on a large scale level which will boost the understanding on the virulence strategies employed by these pathogens.

  9. All Yersinia enterocolitica are pathogenic: virulence of phylogroup 1 Y. enterocolitica in a Galleria mellonella infection model.

    Science.gov (United States)

    Alenizi, Dhahi; Ringwood, Tamara; Redhwan, Alya; Bouraha, Bouchra; Wren, Brendan W; Prentice, Michael; McNally, Alan

    2016-08-01

    Yersinia enterocolitica is a zoonotic pathogen and a common cause of gastroenteritis in humans. The species is composed of six diverse phylogroups, of which strains of phylogroup 1 are considered non-pathogenic to mammals due to the lack of the major virulence plasmid pYV, and their lack of virulence in a mouse infection model. In the present report we present data examining the pathogenicity of strains of Y. enterocolitica across all six phylogroups in a Galleria mellonellla model. We have demonstrated that in this model strains of phylogroup 1 exhibit severe pathogenesis with a lethal dose of as low as 10 c.f.u., that this virulence is an active process and that flagella play a major role in the virulence phenotype. We have also demonstrated that the complete lack of virulence in Galleria of the mammalian pathogenic phylogroups is not due to carriage of the pYV virulence plasmid. Our data suggest that all Y. enterocolitica can be pathogenic, which may be a reflection of the true natural habitat of the species, and that we may need to reconsider the eco-evo perspective of this important bacterial species.

  10. Correlation of Klebsiella pneumoniae comparative genetic analyses with virulence profiles in a murine respiratory disease model.

    Directory of Open Access Journals (Sweden)

    Ramy A Fodah

    Full Text Available Klebsiella pneumoniae is a bacterial pathogen of worldwide importance and a significant contributor to multiple disease presentations associated with both nosocomial and community acquired disease. ATCC 43816 is a well-studied K. pneumoniae strain which is capable of causing an acute respiratory disease in surrogate animal models. In this study, we performed sequencing of the ATCC 43816 genome to support future efforts characterizing genetic elements required for disease. Furthermore, we performed comparative genetic analyses to the previously sequenced genomes from NTUH-K2044 and MGH 78578 to gain an understanding of the conservation of known virulence determinants amongst the three strains. We found that ATCC 43816 and NTUH-K2044 both possess the known virulence determinant for yersiniabactin, as well as a Type 4 secretion system (T4SS, CRISPR system, and an acetonin catabolism locus, all absent from MGH 78578. While both NTUH-K2044 and MGH 78578 are clinical isolates, little is known about the disease potential of these strains in cell culture and animal models. Thus, we also performed functional analyses in the murine macrophage cell lines RAW264.7 and J774A.1 and found that MGH 78578 (K52 serotype was internalized at higher levels than ATCC 43816 (K2 and NTUH-K2044 (K1, consistent with previous characterization of the antiphagocytic properties of K1 and K2 serotype capsules. We also examined the three K. pneumoniae strains in a novel BALB/c respiratory disease model and found that ATCC 43816 and NTUH-K2044 are highly virulent (LD50<100 CFU while MGH 78578 is relatively avirulent.

  11. Adaptation of Listeria monocytogenes in a simulated cheese medium: effects on virulence using the Galleria mellonella infection model.

    Science.gov (United States)

    Schrama, D; Helliwell, N; Neto, L; Faleiro, M L

    2013-06-01

    The aim of this study was to evaluate the effect of the acid and salt adaptation in a cheese-based medium on the virulence potential of Listeria monocytogenes strains isolated from cheese and dairy processing environment using the Galleria mellonella model. Four L. monocytogenes strains were exposed to a cheese-based medium in conditions of induction of an acid tolerance response and osmotolerance response (pH 5·5 and 3·5% w/v NaCl) and injected in G. mellonella insects. The survival of insects and the L. monocytogenes growth kinetics in insects were evaluated. The gene expression of hly, actA and inlA genes was determined by real-time PCR. The adapted cells of two dairy strains showed reduced insect mortality (P 0·05) was found between adapted and nonadapted cells. The gene expression results evidenced an overexpression of virulence genes in cheese-based medium, but not in simulated insect-induced conditions. Our results suggest that adaptation to low pH and salt in a cheese-based medium can affect the virulence of L. monocytogenes, but this effect is strain dependent. In this study, the impact of adaptation to low pH and salt in a cheese-based medium on L. monocytogenes virulence was tested using the Wax Moth G. mellonella model. This model allowed the differentiation of the virulence potential between the L. monocytogenes strains. The effect of adaptation on virulence is strain dependent. The G. mellonella model revealed to be a prompt method to test food-related factors on L. monocytogenes virulence. © 2013 The Society for Applied Microbiology.

  12. Recruiter Selection Model

    National Research Council Canada - National Science Library

    Halstead, John B

    2006-01-01

    .... The research uses a combination of statistical learning, feature selection methods, and multivariate statistics to determine the better prediction function approximation with features obtained...

  13. Virulence Studies of Different Sequence Types and Geographical Origins of Streptococcus suis Serotype 2 in a Mouse Model of Infection

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Auger

    2016-07-01

    Full Text Available Multilocus sequence typing previously identified three predominant sequence types (STs of Streptococcus suis serotype 2: ST1 strains predominate in Eurasia while North American (NA strains are generally ST25 and ST28. However, ST25/ST28 and ST1 strains have also been isolated in Asia and NA, respectively. Using a well-standardized mouse model of infection, the virulence of strains belonging to different STs and different geographical origins was evaluated. Results demonstrated that although a certain tendency may be observed, S. suis serotype 2 virulence is difficult to predict based on ST and geographical origin alone; strains belonging to the same ST presented important differences of virulence and did not always correlate with origin. The only exception appears to be NA ST28 strains, which were generally less virulent in both systemic and central nervous system (CNS infection models. Persistent and high levels of bacteremia accompanied by elevated CNS inflammation are required to cause meningitis. Although widely used, in vitro tests such as phagocytosis and killing assays require further standardization in order to be used as predictive tests for evaluating virulence of strains. The use of strains other than archetypal strains has increased our knowledge and understanding of the S. suis serotype 2 population dynamics.

  14. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

    Science.gov (United States)

    Mylonakis, Eleftherios; Casadevall, Arturo; Ausubel, Frederick M

    2007-07-27

    Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

  15. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

    Directory of Open Access Journals (Sweden)

    Eleftherios Mylonakis

    2007-07-01

    Full Text Available Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

  16. Staphylococcus aureus virulence factors identified by using a high-throughput Caenorhabditis elegans-killing model.

    Science.gov (United States)

    Begun, Jakob; Sifri, Costi D; Goldman, Samuel; Calderwood, Stephen B; Ausubel, Frederick M

    2005-02-01

    Staphylococcus aureus is an important human pathogen that is also able to kill the model nematode Caenorhabditis elegans. We constructed a 2,950-member Tn917 transposon insertion library in S. aureus strain NCTC 8325. Twenty-one of these insertions exhibited attenuated C. elegans killing, and of these, 12 contained insertions in different genes or chromosomal locations. Ten of these 12 insertions showed attenuated killing phenotypes when transduced into two different S. aureus strains, and 5 of the 10 mutants correspond to genes that have not been previously identified in signature-tagged mutagenesis studies. These latter five mutants were tested in a murine renal abscess model, and one mutant harboring an insertion in nagD exhibited attenuated virulence. Interestingly, Tn917 was shown to have a very strong bias for insertions near the terminus of DNA replication.

  17. LPS structure and PhoQ activity are important for Salmonella Typhimurium virulence in the Galleria mellonella infection model [corrected].

    Directory of Open Access Journals (Sweden)

    Jennifer K Bender

    Full Text Available The larvae of the wax moth, Galleria mellonella, have been used experimentally to host a range of bacterial and fungal pathogens. In this study we evaluated the suitability of G. mellonella as an alternative animal model of Salmonella infection. Using a range of inoculum doses we established that the LD₅₀ of SalmonellaTyphimurium strain NCTC 12023 was 3.6 × 10³ bacteria per larva. Further, a set of isogenic mutant strains depleted of known virulence factors was tested to identify determinants essential for S. Typhimurium pathogenesis. Mutants depleted of one or both of the type III secretion systems encoded by Salmonella Pathogenicity Islands 1 and 2 showed no virulence defect. In contrast, we observed reduced pathogenic potential of a phoQ mutant indicating an important role for the PhoPQ two-component signal transduction system. Lipopolysaccharide (LPS structure was also shown to influence Salmonella virulence in G. mellonella. A waaL(rfaL mutant, which lacks the entire O-antigen (OAg, was virtually avirulent, while a wzz(ST/wzz(fepE double mutant expressing only a very short OAg was highly attenuated for virulence. Furthermore, shortly after infection both LPS mutant strains showed decreased replication when compared to the wild type in a flow cytometry-based competitive index assay. In this study we successfully established a G. mellonella model of S. Typhimurium infection. By identifying PhoQ and LPS OAg length as key determinants of virulence in the wax moth larvae we proved that there is an overlap between this and other animal model systems, thus confirming that the G. mellonella infection model is suitable for assessing aspects of Salmonella virulence function.

  18. Diverse protist grazers select for virulence-related traits in Legionella

    Science.gov (United States)

    Amaro, Francisco; Wang, Wen; Gilbert, Jack A; Roger Anderson, O; Shuman, Howard A

    2015-01-01

    It is generally accepted that selection for resistance to grazing by protists has contributed to the evolution of Legionella pneumophila as a pathogen. Grazing resistance is becoming more generally recognized as having an important role in the ecology and evolution of bacterial pathogenesis. However, selection for grazing resistance presupposes the existence of protist grazers that provide the selective pressure. To determine whether there are protists that graze on pathogenic Legionella species, we investigated the existence of such organisms in a variety of environmental samples. We isolated and characterized diverse protists that graze on L. pneumophila and determined the effects of adding L. pneumophila on the protist community structures in microcosms made from these environmental samples. Several unrelated organisms were able to graze efficiently on L. pneumophila. The community structures of all samples were markedly altered by the addition of L. pneumophila. Surprisingly, some of the Legionella grazers were closely related to species that are known hosts for L. pneumophila, indicating the presence of unknown specificity determinants for this interaction. These results provide the first direct support for the hypothesis that protist grazers exert selective pressure on Legionella to acquire and retain adaptations that contribute to survival, and that these properties are relevant to the ability of the bacteria to cause disease in people. We also report a novel mechanism of killing of amoebae by one Legionella species that requires an intact Type IV secretion system but does not involve intracellular replication. We refer to this phenomenon as ‘food poisoning'. PMID:25575308

  19. Model selection in periodic autoregressions

    NARCIS (Netherlands)

    Ph.H.B.F. Franses (Philip Hans); R. Paap (Richard)

    1994-01-01

    textabstractThis paper focuses on the issue of period autoagressive time series models (PAR) selection in practice. One aspect of model selection is the choice for the appropriate PAR order. This can be of interest for the valuation of economic models. Further, the appropriate PAR order is important

  20. Candidate Targets for New Anti-Virulence Drugs: Selected Cases of Bacterial Adhesion and Biofilm Formation

    DEFF Research Database (Denmark)

    Klemm, Per; Hancock, Viktoria; Kvist, Malin

    2007-01-01

    is particularly problematic in medical contexts because biofilm-associated bacteria are particularly hard to eradicate. Several promising candidate drugs that target bacterial adhesion and biofilm formation are being developed. Some of these might be valuable weapons for fighting infectious diseases in the future...... formation are highly attractive targets for new drugs. Specific adhesion provides bacteria with target selection and prevents removal by hydrodynamic flow forces. Bacterial adhesion is of paramount importance for bacterial pathogenesis. Adhesion is also the first step in biofilm formation. Biofilm formation...

  1. Modeling Natural Selection

    Science.gov (United States)

    Bogiages, Christopher A.; Lotter, Christine

    2011-01-01

    In their research, scientists generate, test, and modify scientific models. These models can be shared with others and demonstrate a scientist's understanding of how the natural world works. Similarly, students can generate and modify models to gain a better understanding of the content, process, and nature of science (Kenyon, Schwarz, and Hug…

  2. Models selection and fitting

    International Nuclear Information System (INIS)

    Martin Llorente, F.

    1990-01-01

    The models of atmospheric pollutants dispersion are based in mathematic algorithms that describe the transport, diffusion, elimination and chemical reactions of atmospheric contaminants. These models operate with data of contaminants emission and make an estimation of quality air in the area. This model can be applied to several aspects of atmospheric contamination

  3. Selected System Models

    Science.gov (United States)

    Schmidt-Eisenlohr, F.; Puñal, O.; Klagges, K.; Kirsche, M.

    Apart from the general issue of modeling the channel, the PHY and the MAC of wireless networks, there are specific modeling assumptions that are considered for different systems. In this chapter we consider three specific wireless standards and highlight modeling options for them. These are IEEE 802.11 (as example for wireless local area networks), IEEE 802.16 (as example for wireless metropolitan networks) and IEEE 802.15 (as example for body area networks). Each section on these three systems discusses also at the end a set of model implementations that are available today.

  4. The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models.

    Directory of Open Access Journals (Sweden)

    Paul J Converse

    2010-04-01

    Full Text Available It has been hypothesized that the virulence of lab-passaged Mycobacterium tuberculosis and recombinant M. tuberculosis mutants might be reduced due to multiple in vitro passages, and that virulence might be augmented by passage of these strains through mice before quantitative virulence testing in the mouse or guinea pig aerosol models.By testing three M. tuberculosis H37Rv samples, one deletion mutant, and one recent clinical isolate for survival by the quantitative organ CFU counting method in mouse or guinea pig aerosol or intravenous infection models, we could discern no increase in bacterial fitness as a result of passaging of M. tuberculosis strains in mice prior to quantitative virulence testing in two animal models. Surface lipid expression as assessed by neutral red staining and thin-layer chromatography for PDIM analysis also failed to identify virulence correlates.These results indicate that animal passaging of M. tuberculosis strains prior to quantitative virulence testing in mouse or guinea pig models does not enhance or restore potency to strains that may have lost virulence due to in vitro passaging. It is critical to verify virulence of parental strains before genetic manipulations are undertaken and comparisons are made.

  5. Launch vehicle selection model

    Science.gov (United States)

    Montoya, Alex J.

    1990-01-01

    Over the next 50 years, humans will be heading for the Moon and Mars to build scientific bases to gain further knowledge about the universe and to develop rewarding space activities. These large scale projects will last many years and will require large amounts of mass to be delivered to Low Earth Orbit (LEO). It will take a great deal of planning to complete these missions in an efficient manner. The planning of a future Heavy Lift Launch Vehicle (HLLV) will significantly impact the overall multi-year launching cost for the vehicle fleet depending upon when the HLLV will be ready for use. It is desirable to develop a model in which many trade studies can be performed. In one sample multi-year space program analysis, the total launch vehicle cost of implementing the program reduced from 50 percent to 25 percent. This indicates how critical it is to reduce space logistics costs. A linear programming model has been developed to answer such questions. The model is now in its second phase of development, and this paper will address the capabilities of the model and its intended uses. The main emphasis over the past year was to make the model user friendly and to incorporate additional realistic constraints that are difficult to represent mathematically. We have developed a methodology in which the user has to be knowledgeable about the mission model and the requirements of the payloads. We have found a representation that will cut down the solution space of the problem by inserting some preliminary tests to eliminate some infeasible vehicle solutions. The paper will address the handling of these additional constraints and the methodology for incorporating new costing information utilizing learning curve theory. The paper will review several test cases that will explore the preferred vehicle characteristics and the preferred period of construction, i.e., within the next decade, or in the first decade of the next century. Finally, the paper will explore the interaction

  6. A Heckman Selection- t Model

    KAUST Repository

    Marchenko, Yulia V.

    2012-03-01

    Sample selection arises often in practice as a result of the partial observability of the outcome of interest in a study. In the presence of sample selection, the observed data do not represent a random sample from the population, even after controlling for explanatory variables. That is, data are missing not at random. Thus, standard analysis using only complete cases will lead to biased results. Heckman introduced a sample selection model to analyze such data and proposed a full maximum likelihood estimation method under the assumption of normality. The method was criticized in the literature because of its sensitivity to the normality assumption. In practice, data, such as income or expenditure data, often violate the normality assumption because of heavier tails. We first establish a new link between sample selection models and recently studied families of extended skew-elliptical distributions. Then, this allows us to introduce a selection-t (SLt) model, which models the error distribution using a Student\\'s t distribution. We study its properties and investigate the finite-sample performance of the maximum likelihood estimators for this model. We compare the performance of the SLt model to the conventional Heckman selection-normal (SLN) model and apply it to analyze ambulatory expenditures. Unlike the SLNmodel, our analysis using the SLt model provides statistical evidence for the existence of sample selection bias in these data. We also investigate the performance of the test for sample selection bias based on the SLt model and compare it with the performances of several tests used with the SLN model. Our findings indicate that the latter tests can be misleading in the presence of heavy-tailed data. © 2012 American Statistical Association.

  7. Infection in a rat model reactivates attenuated virulence after long-term axenic culture of Acanthamoeba spp

    Directory of Open Access Journals (Sweden)

    Carolina De Marco Verissimo

    2013-11-01

    Full Text Available Prolonged culturing of many microorganisms leads to the loss of virulence and a reduction of their infective capacity. However, little is known about the changes in the pathogenic strains of Acanthamoeba after long culture periods. Our study evaluated the effect of prolonged culturing on the invasiveness of different isolates of Acanthamoeba in an in vivo rat model. ATCC strains of Acanthamoeba, isolates from the environment and clinical cases were evaluated. The in vivo model was effective in establishing the infection and differentiating the pathogenicity of the isolates and re-isolates. The amoebae cultured in the laboratory for long periods were less virulent than those that were recently isolated, confirming the importance of passing Acanthamoeba strains in animal models.

  8. Virulence of invasive Salmonella Typhimurium ST313 in animal models of infection.

    Directory of Open Access Journals (Sweden)

    Girish Ramachandran

    2017-08-01

    Full Text Available Salmonella Typhimurium sequence type (ST 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve these differences, we tested clinical Salmonella Typhimurium ST313 and ST19 strains in murine and rhesus macaque infection models. The 50% lethal dose (LD50 was determined for three Salmonella Typhimurium ST19 and ST313 strains in mice. For dissemination studies, bacterial burden in organs was determined at various time-points post-challenge. Indian rhesus macaques were infected with one ST19 and one ST313 strain. Animals were monitored for clinical signs and bacterial burden and pathology were determined. The LD50 values for ST19 and ST313 infected mice were not significantly different. However, ST313-infected BALB/c mice had significantly higher bacterial numbers in blood at 24 h than ST19-infected mice. ST19-infected rhesus macaques exhibited moderate-to-severe diarrhea while ST313-infected monkeys showed no-to-mild diarrhea. ST19-infected monkeys had higher bacterial burden and increased inflammation in tissues. Our data suggest that Salmonella Typhimurium ST313 invasiveness may be investigated using mice. The non-human primate results are consistent with clinical data, suggesting that ST313 strains do not cause diarrhea.

  9. Virulence of invasive Salmonella Typhimurium ST313 in animal models of infection.

    Science.gov (United States)

    Ramachandran, Girish; Panda, Aruna; Higginson, Ellen E; Ateh, Eugene; Lipsky, Michael M; Sen, Sunil; Matson, Courtney A; Permala-Booth, Jasnehta; DeTolla, Louis J; Tennant, Sharon M

    2017-08-01

    Salmonella Typhimurium sequence type (ST) 313 produces septicemia in infants in sub-Saharan Africa. Although there are known genetic and phenotypic differences between ST313 strains and gastroenteritis-associated ST19 strains, conflicting data about the in vivo virulence of ST313 strains have been reported. To resolve these differences, we tested clinical Salmonella Typhimurium ST313 and ST19 strains in murine and rhesus macaque infection models. The 50% lethal dose (LD50) was determined for three Salmonella Typhimurium ST19 and ST313 strains in mice. For dissemination studies, bacterial burden in organs was determined at various time-points post-challenge. Indian rhesus macaques were infected with one ST19 and one ST313 strain. Animals were monitored for clinical signs and bacterial burden and pathology were determined. The LD50 values for ST19 and ST313 infected mice were not significantly different. However, ST313-infected BALB/c mice had significantly higher bacterial numbers in blood at 24 h than ST19-infected mice. ST19-infected rhesus macaques exhibited moderate-to-severe diarrhea while ST313-infected monkeys showed no-to-mild diarrhea. ST19-infected monkeys had higher bacterial burden and increased inflammation in tissues. Our data suggest that Salmonella Typhimurium ST313 invasiveness may be investigated using mice. The non-human primate results are consistent with clinical data, suggesting that ST313 strains do not cause diarrhea.

  10. Poly-N-acetylglucosamine production in Staphylococcus aureus is essential for virulence in murine models of systemic infection.

    Science.gov (United States)

    Kropec, Andrea; Maira-Litran, Tomas; Jefferson, Kimberly K; Grout, Martha; Cramton, Sarah E; Götz, Friedrich; Goldmann, Donald A; Pier, Gerald B

    2005-10-01

    The contribution of the Staphylococcus aureus surface polysaccharide poly-N-acetylglucosamine (PNAG) to virulence was evaluated in three mouse models of systemic infection: bacteremia, renal abscess formation, and lethality following high-dose intraperitoneal (i.p.) infection. Deletion of the intercellular adhesin (ica) locus that encodes the biosynthetic enzymes for PNAG production in S. aureus strains Mn8, Newman, and NCTC 10833 resulted in mutant strains with significantly reduced abilities to maintain bacterial levels in blood following intravenous or i.p. injection, to spread systemically to the kidneys following i.p. injection, or to induce a moribund/lethal state following i.p. infection. In the bacteremia model, neither growth phase nor growth medium used to prepare the S. aureus inoculum affected the conclusion that PNAG production was needed for full virulence. As the SarA regulatory protein has been shown to affect ica transcription, PNAG synthesis, and biofilm formation, we also evaluated S. aureus strains Mn8 and 10833 deleted for the sarA gene in the renal infection model. A decrease in PNAG production was seen in sarA mutants using immunoblots of cell surface extracts but was insufficient to reduce the virulence of sarA-deleted strains in this model. S. aureus strains deleted for the ica genes were much more susceptible to antibody-independent opsonic killing involving human peripheral blood leukocytes and rabbit complement. Thus, PNAG confers on S. aureus resistance to killing mediated by these innate host immune mediators. Overall, PNAG production by S. aureus appears to be a critical virulence factor as assessed in murine models of systemic infection.

  11. Generation of a convalescent model of virulent Francisella tularensis infection for assessment of host requirements for survival of tularemia.

    Directory of Open Access Journals (Sweden)

    Deborah D Crane

    Full Text Available Francisella tularensis is a facultative intracellular bacterium and the causative agent of tularemia. Development of novel vaccines and therapeutics for tularemia has been hampered by the lack of understanding of which immune components are required to survive infection. Defining these requirements for protection against virulent F. tularensis, such as strain SchuS4, has been difficult since experimentally infected animals typically die within 5 days after exposure to as few as 10 bacteria. Such a short mean time to death typically precludes development, and therefore assessment, of immune responses directed against virulent F. tularensis. To enable identification of the components of the immune system that are required for survival of virulent F. tularensis, we developed a convalescent model of tularemia in C57Bl/6 mice using low dose antibiotic therapy in which the host immune response is ultimately responsible for clearance of the bacterium. Using this model we demonstrate αβTCR(+ cells, γδTCR(+ cells, and B cells are necessary to survive primary SchuS4 infection. Analysis of mice deficient in specific soluble mediators shows that IL-12p40 and IL-12p35 are essential for survival of SchuS4 infection. We also show that IFN-γ is required for survival of SchuS4 infection since mice lacking IFN-γR succumb to disease during the course of antibiotic therapy. Finally, we found that both CD4(+ and CD8(+ cells are the primary producers of IFN-γand that γδTCR(+ cells and NK cells make a minimal contribution toward production of this cytokine throughout infection. Together these data provide a novel model that identifies key cells and cytokines required for survival or exacerbation of infection with virulent F. tularensis and provides evidence that this model will be a useful tool for better understanding the dynamics of tularemia infection.

  12. A Heckman Selection- t Model

    KAUST Repository

    Marchenko, Yulia V.; Genton, Marc G.

    2012-01-01

    for sample selection bias based on the SLt model and compare it with the performances of several tests used with the SLN model. Our findings indicate that the latter tests can be misleading in the presence of heavy-tailed data. © 2012 American Statistical

  13. Invasion thresholds and the evolution of nonequilibrium virulence.

    Science.gov (United States)

    Bull, James J; Ebert, Dieter

    2008-02-01

    The enterprise of virulence management attempts to predict how social practices and other factors affect the evolution of parasite virulence. These predictions are often based on parasite optima or evolutionary equilibria derived from models of host-parasite dynamics. Yet even when such models accurately capture the parasite optima, newly invading parasites will typically not be at their optima. Here we show that parasite invasion of a host population can occur despite highly nonoptimal virulence. Fitness improvements soon after invasion may proceed through many steps with wide changes in virulence, because fitness depends on transmission as well as virulence, and transmission improvements can overwhelm nonoptimal virulence. This process is highly sensitive to mutation supply and the strength of selection. Importantly, the same invasion principle applies to the evolution of established parasites, whenever mutants arise that overcome host immunity/resistance. A host population may consequently experience repeated invasions of new parasite variants and possible large shifts in virulence as it evolves in an arms race with the parasite. An experimental study of phage lysis time and examples of mammalian viruses matching some of these characteristics are reviewed.

  14. Effects of contact structure on the transient evolution of HIV virulence.

    Directory of Open Access Journals (Sweden)

    Sang Woo Park

    2017-03-01

    Full Text Available Early in an epidemic, high densities of susceptible hosts select for relatively high parasite virulence; later in the epidemic, lower susceptible densities select for lower virulence. Thus over the course of a typical epidemic the average virulence of parasite strains increases initially, peaks partway through the epidemic, then declines again. However, precise quantitative outcomes, such as the peak virulence reached and its timing, may depend sensitively on epidemiological details. Fraser et al. proposed a model for the eco-evolutionary dynamics of HIV that incorporates the tradeoffs between transmission and virulence (mediated by set-point viral load, SPVL and their heritability between hosts. Their model used implicit equations to capture the effects of partnership dynamics that are at the core of epidemics of sexually transmitted diseases. Our models combine HIV virulence tradeoffs with a range of contact models, explicitly modeling partnership formation and dissolution and allowing for individuals to transmit disease outside of partnerships. We assess summary statistics such as the peak virulence (corresponding to the maximum value of population mean log10 SPVL achieved throughout the epidemic across models for a range of parameters applicable to the HIV epidemic in sub-Saharan Africa. Although virulence trajectories are broadly similar across models, the timing and magnitude of the virulence peak vary considerably. Previously developed implicit models predicted lower virulence and slower progression at the peak (a maximum of 3.5 log10 SPVL compared both to more realistic models and to simple random-mixing models with no partnership structure at all (both with a maximum of ≈ 4.7 log10 SPVL. In this range of models, the simplest random-mixing structure best approximates the most realistic model; this surprising outcome occurs because the dominance of extra-pair contact in the realistic model swamps the effects of partnership structure.

  15. Variations in virulence of avian pathogenic Escherichia coli demonstrated by the use of a new in vivo infection model

    DEFF Research Database (Denmark)

    Pors, Susanne Elisabeth; Olsen, Rikke Heidemann; Christensen, Jens Peter

    2014-01-01

    , E. coli was found in pure culture from one or more positions in the oviduct and the liver. Birds receiving sterile broth did not culture positive and demonstrated no gross lesions. Subsequently, 19 birds were inoculated with an isolate of E. coli ST95 and 20 birds with an isolate of E. coli ST141....... Major variation in virulence was observed between the two isolates used in relation to clinical signs, gross lesions and histopathology. In contrast to E. coli ST141, E. coli ST95 caused severe clinical signs, epithelial necrosis of the oviduct and purulent salpingitis. The results of the study show...... the potential of the model in studies of the pathogenesis of infections and virulence of bacteria of the oviduct....

  16. The evolution of intermediate castration virulence and ant coexistence in a spatially structured environment.

    Science.gov (United States)

    Szilágyi, András; Scheuring, István; Edwards, David P; Orivel, Jerome; Yu, Douglas W

    2009-12-01

    Theory suggests that spatial structuring should select for intermediate levels of virulence in parasites, but empirical tests are rare and have never been conducted with castration (sterilizing) parasites. To test this theory in a natural landscape, we construct a spatially explicit model of the symbiosis between the ant-plant Cordia nodosa and its two, protecting ant symbionts, Allomerus and Azteca. Allomerus is also a castration parasite, preventing fruiting to increase colony fecundity. Limiting the dispersal of Allomerus and host plant selects for intermediate castration virulence. Increasing the frequency of the mutualist, Azteca, selects for higher castration virulence in Allomerus, because seeds from Azteca-inhabited plants are a public good that Allomerus exploits. These results are consistent with field observations and, to our knowledge, provide the first empirical evidence supporting the hypothesis that spatial structure can reduce castration virulence and the first such evidence in a natural landscape for either mortality or castration virulence.

  17. Virulence of geographically different Cryptosporidium parvum isolates in experimental animal model

    Science.gov (United States)

    Sayed, Fatma G.; Hamza, Amany I.; Galal, Lamia A.; Sayed, Douaa M.; Gaber, Mona

    2016-10-01

    Cryptosporidium parvum is a coccidian parasite which causes gastrointestinal disease in humans and a variety of other mammalian species. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The study aimed to investigate infectivity and virulence of two Cryptosporidium parvum “Iowa isolate” (CpI) and a “local water isolate” (CpW). Thirty-three Swiss albino mice have been divided into three groups: Negative control Group (C), the CpI group infected with “Iowa isolate “and the CpW group infected with C. parvum oocysts isolated from a local water supply. Infectivity and virulence have been measured by evaluating clinical, parasitological and histological aspects of infection. Significant differences were detected regarding oocysts shedding rate, clinical outcomes, and the histopathological picture of the intestine, lung, and brain. It was concluded that the local water isolate is significantly more virulent than the exported one.

  18. The putative thiosulfate sulfurtransferases PspE and GlpE contribute to virulence of Salmonella Typhimurium in the mouse model of systemic disease.

    Directory of Open Access Journals (Sweden)

    Inke Wallrodt

    Full Text Available The phage-shock protein PspE and GlpE of the glycerol 3-phosphate regulon of Salmonella enterica serovar Typhimurium are predicted to belong to the class of thiosulfate sulfurtransferases, enzymes that traffic sulfur between molecules. In the present study we demonstrated that the two genes contribute to S. Typhimurium virulence, as a glpE and pspE double deletion strain showed significantly decreased virulence in a mouse model of systemic infection. However, challenge of cultured epithelial cells and macrophages did not reveal any virulence-associated phenotypes. We hypothesized that their contribution to virulence could be in sulfur metabolism or by contributing to resistance to nitric oxide, oxidative stress, or cyanide detoxification. In vitro studies demonstrated that glpE but not pspE was important for resistance to H2O2. Since the double mutant, which was the one affected in virulence, was not affected in this assay, we concluded that resistance to oxidative stress and the virulence phenotype was most likely not linked. The two genes did not contribute to nitric oxid stress, to synthesis of essential sulfur containing amino acids, nor to detoxification of cyanide. Currently, the precise mechanism by which they contribute to virulence remains elusive.

  19. Selection, assessment of virulence to Alphitobius diaperinus, and Pr1 enzyme production of Beauveria bassiana (Bals. Vuill. isolates cultured at stress temperatures

    Directory of Open Access Journals (Sweden)

    Kelly Christiane Constanski

    2015-12-01

    Full Text Available The entomopathogenic fungus Beauveria bassiana is a promising agent for use in insect control. Its pathogenic activity, as well as other factors such as temperature that can interfere with its development, should be assessed, thus, establishing the foundations for B. bassiana use in biological control programs. The objective of this study was to select and induce tolerance of B. bassiana isolates to high and low temperatures and to assess their virulence before and after exposure to those temperatures. A pre-selection test was performed, in which the tolerance of isolates to stress temperatures was tested and compared to the ideal growth temperature of 25 °C for this organism. For the isolates/temperature combinations resulting in growth, conidia germination and colony-forming units (CFUs were assessed. The isolates Unioeste 4 and Unioeste 40 exhibited >95% germinated conidia at 16 and 31 °C. Thereafter, they underwent four consecutive passages at maximum and minimum tolerated temperatures (10 and 37 °C. A significant difference in germination was observed between the two isolates at all temperatures tested. More CFUs were observed for Unioeste 4 compared to Unioeste 40 at all temperatures, and in the case of the latter, there was no difference in CFU formation at 10 and 25 °C. For both isolates, decreased vegetative growth was observed at 37 °C. Recovery of virulence was observed in both isolates, as determined by insect mortality. No relationship was observed between production of the enzyme Pr1 and the virulence of the isolates.

  20. Genomic characterization of Burkholderia pseudomallei isolates selected for medical countermeasures testing: comparative genomics associated with differential virulence.

    Directory of Open Access Journals (Sweden)

    Jason W Sahl

    Full Text Available Burkholderia pseudomallei is the causative agent of melioidosis and a potential bioterrorism agent. In the development of medical countermeasures against B. pseudomallei infection, the US Food and Drug Administration (FDA animal Rule recommends using well-characterized strains in animal challenge studies. In this study, whole genome sequence data were generated for 6 B. pseudomallei isolates previously identified as candidates for animal challenge studies; an additional 5 isolates were sequenced that were associated with human inhalational melioidosis. A core genome single nucleotide polymorphism (SNP phylogeny inferred from a concatenated SNP alignment from the 11 isolates sequenced in this study and a diverse global collection of isolates demonstrated the diversity of the proposed Animal Rule isolates. To understand the genomic composition of each isolate, a large-scale blast score ratio (LS-BSR analysis was performed on the entire pan-genome; this demonstrated the variable composition of genes across the panel and also helped to identify genes unique to individual isolates. In addition, a set of ~550 genes associated with pathogenesis in B. pseudomallei were screened against the 11 sequenced genomes with LS-BSR. Differential gene distribution for 54 virulence-associated genes was observed between genomes and three of these genes were correlated with differential virulence observed in animal challenge studies using BALB/c mice. Differentially conserved genes and SNPs associated with disease severity were identified and could be the basis for future studies investigating the pathogenesis of B. pseudomallei. Overall, the genetic characterization of the 11 proposed Animal Rule isolates provides context for future studies involving B. pseudomallei pathogenesis, differential virulence, and efficacy to therapeutics.

  1. Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

    Directory of Open Access Journals (Sweden)

    Sinem Oktem-Okullu

    Full Text Available The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1, IL-17 (Th17, and FOXP3 (Treg expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

  2. Multiplex-PCR-Based Screening and Computational Modeling of Virulence Factors and T-Cell Mediated Immunity in Helicobacter pylori Infections for Accurate Clinical Diagnosis.

    Science.gov (United States)

    Oktem-Okullu, Sinem; Tiftikci, Arzu; Saruc, Murat; Cicek, Bahattin; Vardareli, Eser; Tozun, Nurdan; Kocagoz, Tanil; Sezerman, Ugur; Yavuz, Ahmet Sinan; Sayi-Yazgan, Ayca

    2015-01-01

    The outcome of H. pylori infection is closely related with bacteria's virulence factors and host immune response. The association between T cells and H. pylori infection has been identified, but the effects of the nine major H. pylori specific virulence factors; cagA, vacA, oipA, babA, hpaA, napA, dupA, ureA, ureB on T cell response in H. pylori infected patients have not been fully elucidated. We developed a multiplex- PCR assay to detect nine H. pylori virulence genes with in a three PCR reactions. Also, the expression levels of Th1, Th17 and Treg cell specific cytokines and transcription factors were detected by using qRT-PCR assays. Furthermore, a novel expert derived model is developed to identify set of factors and rules that can distinguish the ulcer patients from gastritis patients. Within all virulence factors that we tested, we identified a correlation between the presence of napA virulence gene and ulcer disease as a first data. Additionally, a positive correlation between the H. pylori dupA virulence factor and IFN-γ, and H. pylori babA virulence factor and IL-17 was detected in gastritis and ulcer patients respectively. By using computer-based models, clinical outcomes of a patients infected with H. pylori can be predicted by screening the patient's H. pylori vacA m1/m2, ureA and cagA status and IFN-γ (Th1), IL-17 (Th17), and FOXP3 (Treg) expression levels. Herein, we report, for the first time, the relationship between H. pylori virulence factors and host immune responses for diagnostic prediction of gastric diseases using computer-based models.

  3. The ovine mammary gland as an experimental model to determine the virulence of animal ureaplasmas.

    OpenAIRE

    Ball, H. J.; Mackie, D. P.

    1985-01-01

    As an estimate of their virulence, the ability of ovine, bovine, canine, feline and simian ureaplasma strains to cause mastitis in the ovine mammary gland was investigated. Five ovine ureaplasmas produced a clinical mastitis. Broth cultures of seven bovine ureaplasmas were unable to infect the ovine gland, but two of these strains plus one other were able to do so following passage through the bovine udder. One of two canine strains and a feline strain both caused mastitis, but the simian str...

  4. The Streptococcus sanguinis Competence Regulon Is Not Required for Infective Endocarditis Virulence in a Rabbit Model

    OpenAIRE

    Callahan, Jill E.; Munro, Cindy L.; Kitten, Todd

    2011-01-01

    Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon in addition to DNA uptake, including virulence. We investigated this possibility i...

  5. Selected Tether Applications Cost Model

    Science.gov (United States)

    Keeley, Michael G.

    1988-01-01

    Diverse cost-estimating techniques and data combined into single program. Selected Tether Applications Cost Model (STACOM 1.0) is interactive accounting software tool providing means for combining several independent cost-estimating programs into fully-integrated mathematical model capable of assessing costs, analyzing benefits, providing file-handling utilities, and putting out information in text and graphical forms to screen, printer, or plotter. Program based on Lotus 1-2-3, version 2.0. Developed to provide clear, concise traceability and visibility into methodology and rationale for estimating costs and benefits of operations of Space Station tether deployer system.

  6. Inhibition of Pseudomonas aeruginosa virulence: characterization of the AprA-AprI interface and species selectivity.

    Science.gov (United States)

    Bardoel, Bart W; van Kessel, Kok P M; van Strijp, Jos A G; Milder, Fin J

    2012-01-20

    Pseudomonas aeruginosa secretes the virulence factor alkaline protease (AprA) to enhance its survival. AprA cleaves one of the key microbial recognition molecules, monomeric flagellin, and thereby diminishes Toll-like receptor 5 activation. In addition, AprA degrades host proteins such as complement proteins and cytokines. P. aeruginosa encodes a highly potent inhibitor of alkaline protease (AprI) that is solely located in the periplasm where it is presumed to protect periplasmic proteins against secreted AprA. We set out to study the enzyme-inhibitor interactions in more detail in order to provide a basis for future drug development. Structural and mutational studies reveal that the conserved N-terminal residues of AprI occupy the protease active site and are essential for inhibitory activity. We constructed peptides mimicking the N-terminus of AprI; however, these were incapable of inhibiting AprA-mediated flagellin cleavage. Furthermore, we expressed and purified AprI of P. aeruginosa and the homologous (37% sequence identity) AprI of Pseudomonas syringae, which remarkably show species specificity for their cognate protease. Exchange of the first five N-terminal residues between AprI of P. syringae and P. aeruginosa did not affect the observed specificity, whereas exchange of only six residues located at the AprI surface that contacts the protease did abolish specificity. These findings are elementary steps toward the design of molecules derived from the natural inhibitor of the virulence factor AprA and their use in therapeutic applications in Pseudomonas and other Gram-negative infections. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Macrophage and Galleria mellonella infection models reflect the virulence of naturally occurring isolates of B. pseudomallei, B. thailandensis and B. oklahomensis

    Directory of Open Access Journals (Sweden)

    Michell Stephen L

    2011-01-01

    Full Text Available Abstract Background Burkholderia pseudomallei is the causative agent of melioidosis, a tropical disease of humans with a variable and often fatal outcome. In murine models of infection, different strains exhibit varying degrees of virulence. In contrast, two related species, B. thailandensis and B. oklahomensis, are highly attenuated in mice. Our aim was to determine whether virulence in mice is reflected in macrophage or wax moth larvae (Galleria mellonella infection models. Results B. pseudomallei strains 576 and K96243, which have low median lethal dose (MLD values in mice, were able to replicate and induce cellular damage in macrophages and caused rapid death of G. mellonella. In contrast, B. pseudomallei strain 708a, which is attenuated in mice, showed reduced replication in macrophages, negligible cellular damage and was avirulent in G. mellonella larvae. B. thailandensis isolates were less virulent than B. pseudomallei in all of the models tested. However, we did record strain dependent differences. B. oklahomensis isolates were the least virulent isolates. They showed minimal ability to replicate in macrophages, were unable to evoke actin-based motility or to form multinucleated giant cells and were markedly attenuated in G. mellonella compared to B. thailandensis. Conclusions We have shown that the alternative infection models tested here, namely macrophages and Galleria mellonella, are able to distinguish between strains of B. pseudomallei, B. thailandensis and B. oklahomensis and that these differences reflect the observed virulence in murine infection models. Our results indicate that B. oklahomensis is the least pathogenic of the species investigated. They also show a correlation between isolates of B. thailandensis associated with human infection and virulence in macrophage and Galleria infection models.

  8. RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis.

    Directory of Open Access Journals (Sweden)

    Trung Anh Trieu

    2017-01-01

    Full Text Available Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies.

  9. Role of the Helicobacter pylori virulence factors vacuolating cytotoxin, CagA, and urease in a mouse model of disease.

    Science.gov (United States)

    Ghiara, P; Marchetti, M; Blaser, M J; Tummuru, M K; Cover, T L; Segal, E D; Tompkins, L S; Rappuoli, R

    1995-10-01

    The pathogenic role of Helicobacter pylori virulence factors has been studied with a mouse model of gastric disease. BALB/c mice were treated orally with different amounts of sonic extracts of cytotoxic H. pylori strains (NCTC 11637, 60190, 84-183, and 87A300 [CagA+/Tox+]). The pathological effects on histological sections of gastric mucosae were assessed and were compared with the effects of treatments with extracts from noncytotoxic strains (G21 and G50 [CagA-/Tox-]) and from strains that express either CagA alone (D931 [CagA+/Tox-]) or the cytotoxin alone (G104 [CagA-/Tox+]). The treatment with extracts from cytotoxic strains induced various epithelial lesions (vacuolation, erosions, and ulcerations), recruitment of inflammatory cells in the lamina propria, and a marked reduction of the mucin layer. Extracts of noncytotoxic strains induced mucin depletion but no other significant pathology. Crude extracts of strain D931, expressing CagA alone, caused only mild infiltration of inflammatory cells, whereas extracts of strain G104, expressing cytotoxin alone, induced extensive epithelial damage but little inflammatory reaction. Loss of the mucin layer was not associated with a cytotoxic phenotype, since this loss was observed in mice treated with crude extracts of all strains. The pathogenic roles of CagA, cytotoxin, and urease were further assessed by using extracts of mutant strains of H. pylori defective in the expression of each of these virulence factors. The results obtained suggest that (i) urease activity does not play a significant role in inducing the observed gastric damage, (ii) cytotoxin has an important role in the induction of gastric epithelial cell lesions but not in eliciting inflammation, and (iii) other components present in strains which carry the cagA gene, but distinct from CagA itself, are involved in eliciting the inflammatory response.

  10. The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus.

    Science.gov (United States)

    Hodille, Elisabeth; Rose, Warren; Diep, Binh An; Goutelle, Sylvain; Lina, Gerard; Dumitrescu, Oana

    2017-10-01

    Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation. The reported mechanisms underlying S. aureus virulence modulation by antibiotics were reviewed. The relevance of in vitro observations is discussed in relation to animal model data and to clinical evidence extracted from case reports and recommendations on the management of toxin-related staphylococcal diseases. Most in vitro data point to a decreased level of virulence expression upon treatment with ribosomally active antibiotics (linezolid and clindamycin), while cell wall-active antibiotics (beta-lactams) mainly increase exotoxin production. In vivo studies confirmed the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization as a valuable management strategy to improve patient outcomes in cases of toxin-associated staphylococcal disease. Copyright © 2017 American Society for Microbiology.

  11. Virulence of Mycobacterium avium Subsp. hominissuis Human Isolates in an in vitro Macrophage Infection Model

    Directory of Open Access Journals (Sweden)

    Laura Rindi

    2018-01-01

    Full Text Available Background: Mycobacterium avium subsp. hominissuis (MAH is an environmental opportunistic pathogen for humans and swine worldwide; in humans, the vast majority of MAH infections is due to strains belonging to specific genotypes, such as the internal transcribed spacer (ITS-sequevars Mav-A and Mav-B that mostly cause pulmonary infections in elderly patients and severe disseminated infections in acquired immunodeficiency syndrome patients, respectively. To test whether the different types of infections in distinct patients' populations might reflect a different virulence of the infecting genotypes, MAH human isolates, genotyped by ITS sequencing and MIRU-VNTR minisatellite analysis, were studied for the capacity to infect and replicate in human macrophages in vitro. Methods: Cultures of human peripheral blood mononuclear cells and phagocytic human leukemic cell line THP-1 cells were infected with each MAH isolate and intracellular colony-forming units (CFU were determined. Results: At 2 h after infection, i.e., immediately after cell entry, the numbers of intracellular bacteria did not differ between Mav-A and Mav-B organisms in both phagocytic cell types. At 5 days, Mav-A organisms, sharing highly related VNTR-MIRU genotypes, yielded numbers of intracellular CFUs significantly higher than Mav-B organisms in both phagocytic cell types. MIRU-VNTR-based minimum spanning tree analysis of the MAH isolates showed a divergent phylogenetic pathway of Mav-A and Mav-B organisms. Conclusion: Mav-A and Mav-B sequevars might have evolved different pathogenetic properties that might account for their association with different human infections.

  12. Selected sports talent development models

    Directory of Open Access Journals (Sweden)

    Michal Vičar

    2017-06-01

    Full Text Available Background: Sports talent in the Czech Republic is generally viewed as a static, stable phenomena. It stands in contrast with widespread praxis carried out in Anglo-Saxon countries that emphasise its fluctuant nature. This is reflected in the current models describing its development. Objectives: The aim is to introduce current models of talent development in sport. Methods: Comparison and analysing of the following models: Balyi - Long term athlete development model, Côté - Developmental model of sport participation, Csikszentmihalyi - The flow model of optimal expertise, Bailey and Morley - Model of talent development. Conclusion: Current models of sport talent development approach talent as dynamic phenomenon, varying in time. They are based in particular on the work of Simonton and his Emergenic and epigenic model and of Gagné and his Differentiated model of giftedness and talent. Balyi's model is characterised by its applicability and impications for practice. Côté's model highlights the role of family and deliberate play. Both models describe periodization of talent development. Csikszentmihalyi's flow model explains how the athlete acquires experience and develops during puberty based on the structure of attention and flow experience. Bailey and Morley's model accents the situational approach to talent and development of skills facilitating its growth.

  13. Aureusimines in Staphylococcus aureus are not involved in virulence.

    Science.gov (United States)

    Sun, Fei; Cho, Hoonsik; Jeong, Do-Won; Li, Chunling; He, Chuan; Bae, Taeok

    2010-12-29

    Recently, dipeptide aureusimines were reported to activate expression of staphylococcal virulence genes, such as alpha-hemolysin, and increase S. aureus virulence. Surprisingly, most of the virulence genes affected by aureusimines form part of the regulon of the SaeRS two component system (TCS), raising the possibility that SaeRS might be directly or indirectly involved in the aureusimine-dependent signaling process. Using HPLC analyses, we confirmed that a transposon mutant of ausA, the gene encoding the aureusimine dipeptide synthesis enzyme, does not produce dipeptides. However, the transposon mutant showed normal hemolysis activity and alpha-hemolysin/SaeP production. Furthermore, the P1 promoter of the sae operon, one of the targets of the SaeRS TCS, showed normal transcription activity. Moreover, in contrast to the original report, the ausA transposon mutant did not exhibit attenuated virulence in an animal infection model. DNA sequencing revealed that the ausA deletion mutant used in the original study has an 83 nt-duplication in saeS. Hemolysis activity of the original mutant was restored by a plasmid carrying the sae operon. A mutant of the sae operon showed elevated resistance to chloramphenicol and erythromycin, two antibiotics widely used during staphylococcal mutagenesis. At 43°C in the presence of erythromycin and aeration, the conditions typically employed for staphylococcal mutagenesis, an saeR transposon mutant grew much faster than a control mutant and the saeR mutant was highly enriched in a mixed culture experiment. Our results show that the previously reported roles of aureusimines in staphylococcal gene regulation and virulence were due to an unintended mutation in saeS, which was likely selected due to elevated resistance of the mutant to environmental stresses. Thus, there is no evidence indicating that the dipeptide aureusimines play a role in sae-mediated virulence factor production or contribute to staphylococcal virulence.

  14. Aureusimines in Staphylococcus aureus are not involved in virulence.

    Directory of Open Access Journals (Sweden)

    Fei Sun

    2010-12-01

    Full Text Available Recently, dipeptide aureusimines were reported to activate expression of staphylococcal virulence genes, such as alpha-hemolysin, and increase S. aureus virulence. Surprisingly, most of the virulence genes affected by aureusimines form part of the regulon of the SaeRS two component system (TCS, raising the possibility that SaeRS might be directly or indirectly involved in the aureusimine-dependent signaling process.Using HPLC analyses, we confirmed that a transposon mutant of ausA, the gene encoding the aureusimine dipeptide synthesis enzyme, does not produce dipeptides. However, the transposon mutant showed normal hemolysis activity and alpha-hemolysin/SaeP production. Furthermore, the P1 promoter of the sae operon, one of the targets of the SaeRS TCS, showed normal transcription activity. Moreover, in contrast to the original report, the ausA transposon mutant did not exhibit attenuated virulence in an animal infection model. DNA sequencing revealed that the ausA deletion mutant used in the original study has an 83 nt-duplication in saeS. Hemolysis activity of the original mutant was restored by a plasmid carrying the sae operon. A mutant of the sae operon showed elevated resistance to chloramphenicol and erythromycin, two antibiotics widely used during staphylococcal mutagenesis. At 43°C in the presence of erythromycin and aeration, the conditions typically employed for staphylococcal mutagenesis, an saeR transposon mutant grew much faster than a control mutant and the saeR mutant was highly enriched in a mixed culture experiment.Our results show that the previously reported roles of aureusimines in staphylococcal gene regulation and virulence were due to an unintended mutation in saeS, which was likely selected due to elevated resistance of the mutant to environmental stresses. Thus, there is no evidence indicating that the dipeptide aureusimines play a role in sae-mediated virulence factor production or contribute to staphylococcal

  15. Selected sports talent development models

    OpenAIRE

    Michal Vičar

    2017-01-01

    Background: Sports talent in the Czech Republic is generally viewed as a static, stable phenomena. It stands in contrast with widespread praxis carried out in Anglo-Saxon countries that emphasise its fluctuant nature. This is reflected in the current models describing its development. Objectives: The aim is to introduce current models of talent development in sport. Methods: Comparison and analysing of the following models: Balyi - Long term athlete development model, Côté - Developmen...

  16. MODEL SELECTION FOR SPECTROPOLARIMETRIC INVERSIONS

    International Nuclear Information System (INIS)

    Asensio Ramos, A.; Manso Sainz, R.; Martínez González, M. J.; Socas-Navarro, H.; Viticchié, B.; Orozco Suárez, D.

    2012-01-01

    Inferring magnetic and thermodynamic information from spectropolarimetric observations relies on the assumption of a parameterized model atmosphere whose parameters are tuned by comparison with observations. Often, the choice of the underlying atmospheric model is based on subjective reasons. In other cases, complex models are chosen based on objective reasons (for instance, the necessity to explain asymmetries in the Stokes profiles) but it is not clear what degree of complexity is needed. The lack of an objective way of comparing models has, sometimes, led to opposing views of the solar magnetism because the inferred physical scenarios are essentially different. We present the first quantitative model comparison based on the computation of the Bayesian evidence ratios for spectropolarimetric observations. Our results show that there is not a single model appropriate for all profiles simultaneously. Data with moderate signal-to-noise ratios (S/Ns) favor models without gradients along the line of sight. If the observations show clear circular and linear polarization signals above the noise level, models with gradients along the line are preferred. As a general rule, observations with large S/Ns favor more complex models. We demonstrate that the evidence ratios correlate well with simple proxies. Therefore, we propose to calculate these proxies when carrying out standard least-squares inversions to allow for model comparison in the future.

  17. Masking of the contribution of V protein to sendai virus pathogenesis in an infection model with a highly virulent field isolate

    International Nuclear Information System (INIS)

    Sakaguchi, Takemasa; Kiyotani, Katsuhiro; Watanabe, Hitoshi; Huang Cheng; Fukuhara, Noriko; Fujii, Yutaka; Shimazu, Yukie; Sugahara, Fumihiro; Nagai, Yoshiyuki; Yoshida, Tetsuya

    2003-01-01

    Sendai virus V protein is not essential for virus replication in cultured cells but is essential for efficient virus replication and pathogenesis in mice, indicating that the V protein has a luxury function to facilitate virus propagation in mice. This was discovered in the Z strain, an egg-adapted avirulent laboratory strain. In the present study, we reexamined the function of Sendai virus V protein by generating a V-knockout Sendai virus derived from the Hamamatsu strain, a virulent field isolate, which is an appropriate model for studying the natural course of Sendai virus infection in mice. We unexpectedly found that the V-knockout virus propagated efficiently in mice and was as virulent as the wild-type virus. Switching of the functionally important V unique region demonstrated that this region of the Hamamatsu strain was also functional in a Z strain background. It thus appears that the V protein is nonsense in a field isolate of Sendai virus. However, the V protein was required for virus growth and pathogenesis of the Hamamatsu strain in mice when the virulence of the virus was attenuated by introducing mutations that had been found in an egg-adapted, avirulent virus. The V protein therefore seems to be potentially functional in the highly virulent Hamamatsu strain and to be prominent if virus replication is restricted

  18. Genome-wide identification of Pseudomonas aeruginosa virulence-related genes using a Caenorhabditis elegans infection model.

    Directory of Open Access Journals (Sweden)

    Rhonda L Feinbaum

    Full Text Available Pseudomonas aeruginosa strain PA14 is an opportunistic human pathogen capable of infecting a wide range of organisms including the nematode Caenorhabditis elegans. We used a non-redundant transposon mutant library consisting of 5,850 clones corresponding to 75% of the total and approximately 80% of the non-essential PA14 ORFs to carry out a genome-wide screen for attenuation of PA14 virulence in C. elegans. We defined a functionally diverse 180 mutant set (representing 170 unique genes necessary for normal levels of virulence that included both known and novel virulence factors. Seven previously uncharacterized virulence genes (ABC transporters PchH and PchI, aminopeptidase PepP, ATPase/molecular chaperone ClpA, cold shock domain protein PA0456, putative enoyl-CoA hydratase/isomerase PA0745, and putative transcriptional regulator PA14_27700 were characterized with respect to pigment production and motility and all but one of these mutants exhibited pleiotropic defects in addition to their avirulent phenotype. We examined the collection of genes required for normal levels of PA14 virulence with respect to occurrence in P. aeruginosa strain-specific genomic regions, location on putative and known genomic islands, and phylogenetic distribution across prokaryotes. Genes predominantly contributing to virulence in C. elegans showed neither a bias for strain-specific regions of the P. aeruginosa genome nor for putatively horizontally transferred genomic islands. Instead, within the collection of virulence-related PA14 genes, there was an overrepresentation of genes with a broad phylogenetic distribution that also occur with high frequency in many prokaryotic clades, suggesting that in aggregate the genes required for PA14 virulence in C. elegans are biased towards evolutionarily conserved genes.

  19. Genome-wide identification of Pseudomonas aeruginosa virulence-related genes using a Caenorhabditis elegans infection model.

    Science.gov (United States)

    Feinbaum, Rhonda L; Urbach, Jonathan M; Liberati, Nicole T; Djonovic, Slavica; Adonizio, Allison; Carvunis, Anne-Ruxandra; Ausubel, Frederick M

    2012-01-01

    Pseudomonas aeruginosa strain PA14 is an opportunistic human pathogen capable of infecting a wide range of organisms including the nematode Caenorhabditis elegans. We used a non-redundant transposon mutant library consisting of 5,850 clones corresponding to 75% of the total and approximately 80% of the non-essential PA14 ORFs to carry out a genome-wide screen for attenuation of PA14 virulence in C. elegans. We defined a functionally diverse 180 mutant set (representing 170 unique genes) necessary for normal levels of virulence that included both known and novel virulence factors. Seven previously uncharacterized virulence genes (ABC transporters PchH and PchI, aminopeptidase PepP, ATPase/molecular chaperone ClpA, cold shock domain protein PA0456, putative enoyl-CoA hydratase/isomerase PA0745, and putative transcriptional regulator PA14_27700) were characterized with respect to pigment production and motility and all but one of these mutants exhibited pleiotropic defects in addition to their avirulent phenotype. We examined the collection of genes required for normal levels of PA14 virulence with respect to occurrence in P. aeruginosa strain-specific genomic regions, location on putative and known genomic islands, and phylogenetic distribution across prokaryotes. Genes predominantly contributing to virulence in C. elegans showed neither a bias for strain-specific regions of the P. aeruginosa genome nor for putatively horizontally transferred genomic islands. Instead, within the collection of virulence-related PA14 genes, there was an overrepresentation of genes with a broad phylogenetic distribution that also occur with high frequency in many prokaryotic clades, suggesting that in aggregate the genes required for PA14 virulence in C. elegans are biased towards evolutionarily conserved genes.

  20. A Computational Model of Selection by Consequences

    Science.gov (United States)

    McDowell, J. J.

    2004-01-01

    Darwinian selection by consequences was instantiated in a computational model that consisted of a repertoire of behaviors undergoing selection, reproduction, and mutation over many generations. The model in effect created a digital organism that emitted behavior continuously. The behavior of this digital organism was studied in three series of…

  1. A computational model of selection by consequences.

    OpenAIRE

    McDowell, J J

    2004-01-01

    Darwinian selection by consequences was instantiated in a computational model that consisted of a repertoire of behaviors undergoing selection, reproduction, and mutation over many generations. The model in effect created a digital organism that emitted behavior continuously. The behavior of this digital organism was studied in three series of computational experiments that arranged reinforcement according to random-interval (RI) schedules. The quantitative features of the model were varied o...

  2. Bayesian Model Selection under Time Constraints

    Science.gov (United States)

    Hoege, M.; Nowak, W.; Illman, W. A.

    2017-12-01

    Bayesian model selection (BMS) provides a consistent framework for rating and comparing models in multi-model inference. In cases where models of vastly different complexity compete with each other, we also face vastly different computational runtimes of such models. For instance, time series of a quantity of interest can be simulated by an autoregressive process model that takes even less than a second for one run, or by a partial differential equations-based model with runtimes up to several hours or even days. The classical BMS is based on a quantity called Bayesian model evidence (BME). It determines the model weights in the selection process and resembles a trade-off between bias of a model and its complexity. However, in practice, the runtime of models is another weight relevant factor for model selection. Hence, we believe that it should be included, leading to an overall trade-off problem between bias, variance and computing effort. We approach this triple trade-off from the viewpoint of our ability to generate realizations of the models under a given computational budget. One way to obtain BME values is through sampling-based integration techniques. We argue with the fact that more expensive models can be sampled much less under time constraints than faster models (in straight proportion to their runtime). The computed evidence in favor of a more expensive model is statistically less significant than the evidence computed in favor of a faster model, since sampling-based strategies are always subject to statistical sampling error. We present a straightforward way to include this misbalance into the model weights that are the basis for model selection. Our approach follows directly from the idea of insufficient significance. It is based on a computationally cheap bootstrapping error estimate of model evidence and is easy to implement. The approach is illustrated in a small synthetic modeling study.

  3. A Dynamic Model for Limb Selection

    NARCIS (Netherlands)

    Cox, R.F.A; Smitsman, A.W.

    2008-01-01

    Two experiments and a model on limb selection are reported. In Experiment 1 left-handed and right-handed participants (N = 36) repeatedly used one hand for grasping a small cube. After a clear switch in the cube’s location, perseverative limb selection was revealed in both handedness groups. In

  4. Nectin-4 Interactions Govern Measles Virus Virulence in a New Model of Pathogenesis, the Squirrel Monkey (Saimiri sciureus).

    Science.gov (United States)

    Delpeut, Sébastien; Sawatsky, Bevan; Wong, Xiao-Xiang; Frenzke, Marie; Cattaneo, Roberto; von Messling, Veronika

    2017-06-01

    In addition to humans, only certain nonhuman primates are naturally susceptible to measles virus (MeV) infection. Disease severity is species dependent, ranging from mild to moderate for macaques to severe and even lethal for certain New World monkey species. To investigate if squirrel monkeys ( Saimiri sciureus ), which are reported to develop a course of disease similar to humans, may be better suited than macaques for the identification of virulence determinants or the evaluation of therapeutics, we infected them with a green fluorescent protein-expressing MeV. Compared to cynomolgus macaques ( Macaca fascicularis ) infected with the same virus, the squirrel monkeys developed more-severe immunosuppression, higher viral load, and a broader range of clinical signs typical for measles. In contrast, infection with an MeV unable to interact with the epithelial receptor nectin-4, while causing immunosuppression, resulted in only a mild and transient rash and a short-lived elevation of the body temperature. Similar titers of the wild-type and nectin-4-blind MeV were detected in peripheral blood mononuclear cells and lymph node homogenates, but only the wild-type virus was found in tracheal lavage fluids and urine. Thus, our study demonstrates the importance of MeV interactions with nectin-4 for clinical disease in the new and better-performing S. sciureus model of measles pathogenesis. IMPORTANCE The characterization of mechanisms underlying measles virus clinical disease has been hampered by the lack of an animal model that reproduces the course of disease seen in human patients. Here, we report that infection of squirrel monkeys ( Saimiri sciureus ) fulfills these requirements. Comparative infection with wild-type and epithelial cell receptor-blind viruses demonstrated the importance of epithelial cell infection for clinical disease, highlighting the spread to epithelia as an attractive target for therapeutic strategies. Copyright © 2017 American Society for

  5. Virulence regulation in Staphylococcus aureus: the need for in vivo analysis of virulence factor regulation.

    Science.gov (United States)

    Pragman, Alexa A; Schlievert, Patrick M

    2004-10-01

    Staphylococcus aureus is a pathogenic microorganism that is responsible for a wide variety of clinical infections. These infections can be relatively mild, but serious, life-threatening infections may result from the expression of staphylococcal virulence factors that are coordinated by virulence regulators. Much work has been done to characterize the actions of staphylococcal virulence regulators in broth culture. Recently, several laboratories showed that transcriptional analyses of virulence regulators in in vivo animal models or in human infection did not correlate with transcriptional analyses accomplished in vitro. In describing the differences between in vitro and in vivo transcription of staphylococcal virulence regulators, we hope to encourage investigators to study virulence regulators using infection models whenever possible.

  6. A Gambler's Model of Natural Selection.

    Science.gov (United States)

    Nolan, Michael J.; Ostrovsky, David S.

    1996-01-01

    Presents an activity that highlights the mechanism and power of natural selection. Allows students to think in terms of modeling a biological process and instills an appreciation for a mathematical approach to biological problems. (JRH)

  7. Review and selection of unsaturated flow models

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, M.; Baker, N.A.; Duguid, J.O. [INTERA, Inc., Las Vegas, NV (United States)

    1994-04-04

    Since the 1960`s, ground-water flow models have been used for analysis of water resources problems. In the 1970`s, emphasis began to shift to analysis of waste management problems. This shift in emphasis was largely brought about by site selection activities for geologic repositories for disposal of high-level radioactive wastes. Model development during the 1970`s and well into the 1980`s focused primarily on saturated ground-water flow because geologic repositories in salt, basalt, granite, shale, and tuff were envisioned to be below the water table. Selection of the unsaturated zone at Yucca Mountain, Nevada, for potential disposal of waste began to shift model development toward unsaturated flow models. Under the US Department of Energy (DOE), the Civilian Radioactive Waste Management System Management and Operating Contractor (CRWMS M&O) has the responsibility to review, evaluate, and document existing computer models; to conduct performance assessments; and to develop performance assessment models, where necessary. This document describes the CRWMS M&O approach to model review and evaluation (Chapter 2), and the requirements for unsaturated flow models which are the bases for selection from among the current models (Chapter 3). Chapter 4 identifies existing models, and their characteristics. Through a detailed examination of characteristics, Chapter 5 presents the selection of models for testing. Chapter 6 discusses the testing and verification of selected models. Chapters 7 and 8 give conclusions and make recommendations, respectively. Chapter 9 records the major references for each of the models reviewed. Appendix A, a collection of technical reviews for each model, contains a more complete list of references. Finally, Appendix B characterizes the problems used for model testing.

  8. Review and selection of unsaturated flow models

    International Nuclear Information System (INIS)

    Reeves, M.; Baker, N.A.; Duguid, J.O.

    1994-01-01

    Since the 1960's, ground-water flow models have been used for analysis of water resources problems. In the 1970's, emphasis began to shift to analysis of waste management problems. This shift in emphasis was largely brought about by site selection activities for geologic repositories for disposal of high-level radioactive wastes. Model development during the 1970's and well into the 1980's focused primarily on saturated ground-water flow because geologic repositories in salt, basalt, granite, shale, and tuff were envisioned to be below the water table. Selection of the unsaturated zone at Yucca Mountain, Nevada, for potential disposal of waste began to shift model development toward unsaturated flow models. Under the US Department of Energy (DOE), the Civilian Radioactive Waste Management System Management and Operating Contractor (CRWMS M ampersand O) has the responsibility to review, evaluate, and document existing computer models; to conduct performance assessments; and to develop performance assessment models, where necessary. This document describes the CRWMS M ampersand O approach to model review and evaluation (Chapter 2), and the requirements for unsaturated flow models which are the bases for selection from among the current models (Chapter 3). Chapter 4 identifies existing models, and their characteristics. Through a detailed examination of characteristics, Chapter 5 presents the selection of models for testing. Chapter 6 discusses the testing and verification of selected models. Chapters 7 and 8 give conclusions and make recommendations, respectively. Chapter 9 records the major references for each of the models reviewed. Appendix A, a collection of technical reviews for each model, contains a more complete list of references. Finally, Appendix B characterizes the problems used for model testing

  9. Metabolite cross-feeding enhances virulence in a model polymicrobial infection.

    Directory of Open Access Journals (Sweden)

    Matthew M Ramsey

    2011-03-01

    Full Text Available Microbes within polymicrobial infections often display synergistic interactions resulting in enhanced pathogenesis; however, the molecular mechanisms governing these interactions are not well understood. Development of model systems that allow detailed mechanistic studies of polymicrobial synergy is a critical step towards a comprehensive understanding of these infections in vivo. In this study, we used a model polymicrobial infection including the opportunistic pathogen Aggregatibacter actinomycetemcomitans and the commensal Streptococcus gordonii to examine the importance of metabolite cross-feeding for establishing co-culture infections. Our results reveal that co-culture with S. gordonii enhances the pathogenesis of A. actinomycetemcomitans in a murine abscess model of infection. Interestingly, the ability of A. actinomycetemcomitans to utilize L-lactate as an energy source is essential for these co-culture benefits. Surprisingly, inactivation of L-lactate catabolism had no impact on mono-culture growth in vitro and in vivo suggesting that A. actinomycetemcomitans L-lactate catabolism is only critical for establishing co-culture infections. These results demonstrate that metabolite cross-feeding is critical for A. actinomycetemcomitans to persist in a polymicrobial infection with S. gordonii supporting the idea that the metabolic properties of commensal bacteria alter the course of pathogenesis in polymicrobial communities.

  10. Model Selection with the Linear Mixed Model for Longitudinal Data

    Science.gov (United States)

    Ryoo, Ji Hoon

    2011-01-01

    Model building or model selection with linear mixed models (LMMs) is complicated by the presence of both fixed effects and random effects. The fixed effects structure and random effects structure are codependent, so selection of one influences the other. Most presentations of LMM in psychology and education are based on a multilevel or…

  11. An evolutionary algorithm for model selection

    Energy Technology Data Exchange (ETDEWEB)

    Bicker, Karl [CERN, Geneva (Switzerland); Chung, Suh-Urk; Friedrich, Jan; Grube, Boris; Haas, Florian; Ketzer, Bernhard; Neubert, Sebastian; Paul, Stephan; Ryabchikov, Dimitry [Technische Univ. Muenchen (Germany)

    2013-07-01

    When performing partial-wave analyses of multi-body final states, the choice of the fit model, i.e. the set of waves to be used in the fit, can significantly alter the results of the partial wave fit. Traditionally, the models were chosen based on physical arguments and by observing the changes in log-likelihood of the fits. To reduce possible bias in the model selection process, an evolutionary algorithm was developed based on a Bayesian goodness-of-fit criterion which takes into account the model complexity. Starting from systematically constructed pools of waves which contain significantly more waves than the typical fit model, the algorithm yields a model with an optimal log-likelihood and with a number of partial waves which is appropriate for the number of events in the data. Partial waves with small contributions to the total intensity are penalized and likely to be dropped during the selection process, as are models were excessive correlations between single waves occur. Due to the automated nature of the model selection, a much larger part of the model space can be explored than would be possible in a manual selection. In addition the method allows to assess the dependence of the fit result on the fit model which is an important contribution to the systematic uncertainty.

  12. Genetic search feature selection for affective modeling

    DEFF Research Database (Denmark)

    Martínez, Héctor P.; Yannakakis, Georgios N.

    2010-01-01

    Automatic feature selection is a critical step towards the generation of successful computational models of affect. This paper presents a genetic search-based feature selection method which is developed as a global-search algorithm for improving the accuracy of the affective models built....... The method is tested and compared against sequential forward feature selection and random search in a dataset derived from a game survey experiment which contains bimodal input features (physiological and gameplay) and expressed pairwise preferences of affect. Results suggest that the proposed method...

  13. Strain-specific virulence phenotypes of Streptococcus pneumoniae assessed using the Chinchilla laniger model of otitis media.

    Directory of Open Access Journals (Sweden)

    Michael L Forbes

    2008-04-01

    Full Text Available Streptococcus pneumoniae [Sp] infection is associated with local and systemic disease. Our current understanding of the differential contributions of genetic strain variation, serotype, and host response to disease phenotype is incomplete. Using the chinchilla model of otitis media [OM] we investigated the disease phenotype generated by the laboratory strain TIGR4 and each of thirteen clinical strains (BS68-75, BS290, BS291, BS293, BS436 and BS437; eleven of the thirteen strains have been genomically sequenced.For each strain 100 colony forming units were injected bilaterally into the tympanic bullae of 6 young adult chinchillas under general anesthesia. All animals were examined daily for local and systemic disease by a blinded observer. Pneumatic otoscopy was used to evaluate local disease, and behavioral assessments served as the measure of systemic disease. Virulence scoring was performed using a 4-point scale to assess four clinical parameters [severity and rapidity of local disease onset; and severity and rapidity of systemic disease onset] during a 10-day evaluation period. Highly significant variation was observed among the strains in their ability to cause disease and moribundity.As expected, there was a significant correlation between the rapidity of systemic disease onset and severity of systemic disease; however, there was little correlation between the severity of otoscopic changes and severity of systemic disease. Importantly, it was observed that different strains of the same serotype produced as broad an array of disease phenotypes as did strains of different serotypes. We attribute these phenotypic differences among the strains to the high degree of genomic plasticity that we have previously documented.

  14. The effect of E coli virulence on bacterial translocation and systemic sepsis in the neonatal rabbit model.

    Science.gov (United States)

    Jackson, R J; Smith, S D; Wadowsky, R M; DePudyt, L; Rowe, M I

    1991-04-01

    In the surgical neonate, three factors that promote bacterial translocation and systemic infection are: (1) intestinal bacterial colonization and overgrowth; (2) compromised host defenses; and (3) disruption of the mucosal epithelial barrier. The newborn rabbit provides an excellent model to study these factors. Like the human, there is early closure of the gut mucosa to macromolecules, and nutrition can be maintained by breast or formula feeding. This study examines translocation and systemic sepsis after colonization with virulent K1 and avirulent K100 strains of Escherichia coli. New Zealand white rabbit pups (2 to 5 days old) were studied. The gastrointestinal tracts of 12 were colonized with K1 E coli; 14 were colonized with K100 E coli; 12 control animals were not inoculated. Mesenteric lymph node (MLN), liver, spleen, and colon homogenate were cultured 72 hours postinoculation. No bacteria were isolated from the colons of all but one control animal. Translocation or systemic sepsis did not occur. Translocation to the MLN was significantly increased (P less than .03) in K1 (50%) and K100 (36%) groups compared with controls (0%). Translocation to liver and spleen (systemic sepsis) was significantly increased (P less than .03) in K1 animals (67%) compared with K100 (0%) or controls (0%). Colonization by both strains of E coli led to translocation to the MLN, but only K1 E coli caused systemic sepsis. This suggests that although colonization by E coli in the newborn leads to translocation to the MLN, progression to systemic sepsis is the result of characteristics of the bacteria and/or neonatal host responses.

  15. Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions.

    NARCIS (Netherlands)

    Limmer, S.; Quintin, J.; Hetru, C.; Ferrandon, D.

    2011-01-01

    To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens

  16. A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

    NARCIS (Netherlands)

    Kaman, W.E.; Hawkey, S.; van der Kleij, D.; Broekhuijsen, M.P.; Silman, N.J.; Bikker, F.J.

    2011-01-01

    Yersinia pestis, the Gram-negative bacterial agent of plague, is a zoonotic pathogen that primarily infects wild rodents and is transmitted by fleas. Y. pestis is one of the most invasive and virulent bacterial pathogens and has caused devastating pandemics, including the Black Death of 14th century

  17. Comparative transcript profiling of Candida albicans and Candida dubliniensis identifies SFL2, a C. albicans gene required for virulence in a reconstituted epithelial infection model.

    LENUS (Irish Health Repository)

    Spiering, Martin J

    2010-02-01

    Candida albicans and Candida dubliniensis are closely related species displaying differences in virulence and genome content, therefore providing potential opportunities to identify novel C. albicans virulence genes. C. albicans gene arrays were used for comparative analysis of global gene expression in the two species in reconstituted human oral epithelium (RHE). C. albicans (SC5314) showed upregulation of hypha-specific and virulence genes within 30 min postinoculation, coinciding with rapid induction of filamentation and increased RHE damage. C. dubliniensis (CD36) showed no detectable upregulation of hypha-specific genes, grew as yeast, and caused limited RHE damage. Several genes absent or highly divergent in C. dubliniensis were upregulated in C. albicans. One such gene, SFL2 (orf19.3969), encoding a putative heat shock factor, was deleted in C. albicans. DeltaDeltasfl2 cells failed to filament under a range of hypha-inducing conditions and exhibited greatly reduced RHE damage, reversed by reintroduction of SFL2 into the DeltaDeltasfl2 strain. Moreover, SFL2 overexpression in C. albicans triggered hyphal morphogenesis. Although SFL2 deletion had no apparent effect on host survival in the murine model of systemic infection, DeltaDeltasfl2 strain-infected kidney tissues contained only yeast cells. These results suggest a role for SFL2 in morphogenesis and an indirect role in C. albicans pathogenesis in epithelial tissues.

  18. Melody Track Selection Using Discriminative Language Model

    Science.gov (United States)

    Wu, Xiao; Li, Ming; Suo, Hongbin; Yan, Yonghong

    In this letter we focus on the task of selecting the melody track from a polyphonic MIDI file. Based on the intuition that music and language are similar in many aspects, we solve the selection problem by introducing an n-gram language model to learn the melody co-occurrence patterns in a statistical manner and determine the melodic degree of a given MIDI track. Furthermore, we propose the idea of using background model and posterior probability criteria to make modeling more discriminative. In the evaluation, the achieved 81.6% correct rate indicates the feasibility of our approach.

  19. Model selection for Gaussian kernel PCA denoising

    DEFF Research Database (Denmark)

    Jørgensen, Kasper Winther; Hansen, Lars Kai

    2012-01-01

    We propose kernel Parallel Analysis (kPA) for automatic kernel scale and model order selection in Gaussian kernel PCA. Parallel Analysis [1] is based on a permutation test for covariance and has previously been applied for model order selection in linear PCA, we here augment the procedure to also...... tune the Gaussian kernel scale of radial basis function based kernel PCA.We evaluate kPA for denoising of simulated data and the US Postal data set of handwritten digits. We find that kPA outperforms other heuristics to choose the model order and kernel scale in terms of signal-to-noise ratio (SNR...

  20. Expert System Model for Educational Personnel Selection

    Directory of Open Access Journals (Sweden)

    Héctor A. Tabares-Ospina

    2013-06-01

    Full Text Available The staff selection is a difficult task due to the subjectivity that the evaluation means. This process can be complemented using a system to support decision. This paper presents the implementation of an expert system to systematize the selection process of professors. The management of software development is divided into 4 parts: requirements, design, implementation and commissioning. The proposed system models a specific knowledge through relationships between variables evidence and objective.

  1. Automated sample plan selection for OPC modeling

    Science.gov (United States)

    Casati, Nathalie; Gabrani, Maria; Viswanathan, Ramya; Bayraktar, Zikri; Jaiswal, Om; DeMaris, David; Abdo, Amr Y.; Oberschmidt, James; Krause, Andreas

    2014-03-01

    It is desired to reduce the time required to produce metrology data for calibration of Optical Proximity Correction (OPC) models and also maintain or improve the quality of the data collected with regard to how well that data represents the types of patterns that occur in real circuit designs. Previous work based on clustering in geometry and/or image parameter space has shown some benefit over strictly manual or intuitive selection, but leads to arbitrary pattern exclusion or selection which may not be the best representation of the product. Forming the pattern selection as an optimization problem, which co-optimizes a number of objective functions reflecting modelers' insight and expertise, has shown to produce models with equivalent quality to the traditional plan of record (POR) set but in a less time.

  2. Variable selection and model choice in geoadditive regression models.

    Science.gov (United States)

    Kneib, Thomas; Hothorn, Torsten; Tutz, Gerhard

    2009-06-01

    Model choice and variable selection are issues of major concern in practical regression analyses, arising in many biometric applications such as habitat suitability analyses, where the aim is to identify the influence of potentially many environmental conditions on certain species. We describe regression models for breeding bird communities that facilitate both model choice and variable selection, by a boosting algorithm that works within a class of geoadditive regression models comprising spatial effects, nonparametric effects of continuous covariates, interaction surfaces, and varying coefficients. The major modeling components are penalized splines and their bivariate tensor product extensions. All smooth model terms are represented as the sum of a parametric component and a smooth component with one degree of freedom to obtain a fair comparison between the model terms. A generic representation of the geoadditive model allows us to devise a general boosting algorithm that automatically performs model choice and variable selection.

  3. Model Selection in Data Analysis Competitions

    DEFF Research Database (Denmark)

    Wind, David Kofoed; Winther, Ole

    2014-01-01

    The use of data analysis competitions for selecting the most appropriate model for a problem is a recent innovation in the field of predictive machine learning. Two of the most well-known examples of this trend was the Netflix Competition and recently the competitions hosted on the online platform...... performers from Kaggle and use previous personal experiences from competing in Kaggle competitions. The stated hypotheses about feature engineering, ensembling, overfitting, model complexity and evaluation metrics give indications and guidelines on how to select a proper model for performing well...... Kaggle. In this paper, we will state and try to verify a set of qualitative hypotheses about predictive modelling, both in general and in the scope of data analysis competitions. To verify our hypotheses we will look at previous competitions and their outcomes, use qualitative interviews with top...

  4. Adverse selection model regarding tobacco consumption

    Directory of Open Access Journals (Sweden)

    Dumitru MARIN

    2006-01-01

    Full Text Available The impact of introducing a tax on tobacco consumption can be studied trough an adverse selection model. The objective of the model presented in the following is to characterize the optimal contractual relationship between the governmental authorities and the two type employees: smokers and non-smokers, taking into account that the consumers’ decision to smoke or not represents an element of risk and uncertainty. Two scenarios are run using the General Algebraic Modeling Systems software: one without taxes set on tobacco consumption and another one with taxes set on tobacco consumption, based on an adverse selection model described previously. The results of the two scenarios are compared in the end of the paper: the wage earnings levels and the social welfare in case of a smoking agent and in case of a non-smoking agent.

  5. Genetic and Virulent Difference Between Pigmented and Non-pigmented Staphylococcus aureus.

    Science.gov (United States)

    Zhang, Jing; Suo, Yujuan; Zhang, Daofeng; Jin, Fangning; Zhao, Hang; Shi, Chunlei

    2018-01-01

    Staphyloxanthin (STX), a golden carotenoid pigment produced by Staphylococcus aureus , is suggested to act as an important virulence factor due to its antioxidant properties. Restraining biosynthesis of STX was considered as an indicator of virulence decline in pigmented S. aureus isolates. However, it is not clear whether natural non-pigmented S. aureus isolates have less virulence than pigmented ones. In this study, it is aimed to compare the pigmented and non-pigmented S. aureus isolates to clarify the genetic and virulent differences between the two groups. Here, 132 S. aureus isolates were divided into two phenotype groups depending on the absorbance (OD 450 ) of the extracted carotenoids. Then, all isolates were subjected to spa typing and multilocus sequence typing (MLST), and then the detection of presence of 30 virulence factors and the gene integrity of crtN and crtM . Furthermore, 24 typical S. aureus isolates and 4 S. argenteus strains were selected for the murine infection assay of in vivo virulence, in which the histological observation and enumeration of CFUs were carried out. These isolates were distributed in 26 sequence types (STs) and 49 spa types. The pigmented isolates were scattered in 25 STs, while the non-pigmented isolates were more centralized, which mainly belonged to ST20 (59%) and ST25 (13%). Among the 54 non-pigmented isolates, about 20% carried intact crtN and crtM genes. The in vivo assay suggested that comparing with pigmented S. aureus , non-pigmented S. aureus and S. argenteus strains did not show a reduced virulence in murine sepsis models. Therefore, it suggested that there were no significant genetic and virulent differences between pigmented and non-pigmented S. aureus .

  6. Genetic and Virulent Difference Between Pigmented and Non-pigmented Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2018-04-01

    Full Text Available Staphyloxanthin (STX, a golden carotenoid pigment produced by Staphylococcus aureus, is suggested to act as an important virulence factor due to its antioxidant properties. Restraining biosynthesis of STX was considered as an indicator of virulence decline in pigmented S. aureus isolates. However, it is not clear whether natural non-pigmented S. aureus isolates have less virulence than pigmented ones. In this study, it is aimed to compare the pigmented and non-pigmented S. aureus isolates to clarify the genetic and virulent differences between the two groups. Here, 132 S. aureus isolates were divided into two phenotype groups depending on the absorbance (OD450 of the extracted carotenoids. Then, all isolates were subjected to spa typing and multilocus sequence typing (MLST, and then the detection of presence of 30 virulence factors and the gene integrity of crtN and crtM. Furthermore, 24 typical S. aureus isolates and 4 S. argenteus strains were selected for the murine infection assay of in vivo virulence, in which the histological observation and enumeration of CFUs were carried out. These isolates were distributed in 26 sequence types (STs and 49 spa types. The pigmented isolates were scattered in 25 STs, while the non-pigmented isolates were more centralized, which mainly belonged to ST20 (59% and ST25 (13%. Among the 54 non-pigmented isolates, about 20% carried intact crtN and crtM genes. The in vivo assay suggested that comparing with pigmented S. aureus, non-pigmented S. aureus and S. argenteus strains did not show a reduced virulence in murine sepsis models. Therefore, it suggested that there were no significant genetic and virulent differences between pigmented and non-pigmented S. aureus.

  7. Review and selection of unsaturated flow models

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-09-10

    Under the US Department of Energy (DOE), the Civilian Radioactive Waste Management System Management and Operating Contractor (CRWMS M&O) has the responsibility to review, evaluate, and document existing computer ground-water flow models; to conduct performance assessments; and to develop performance assessment models, where necessary. In the area of scientific modeling, the M&O CRWMS has the following responsibilities: To provide overall management and integration of modeling activities. To provide a framework for focusing modeling and model development. To identify areas that require increased or decreased emphasis. To ensure that the tools necessary to conduct performance assessment are available. These responsibilities are being initiated through a three-step process. It consists of a thorough review of existing models, testing of models which best fit the established requirements, and making recommendations for future development that should be conducted. Future model enhancement will then focus on the models selected during this activity. Furthermore, in order to manage future model development, particularly in those areas requiring substantial enhancement, the three-step process will be updated and reported periodically in the future.

  8. Expatriates Selection: An Essay of Model Analysis

    Directory of Open Access Journals (Sweden)

    Rui Bártolo-Ribeiro

    2015-03-01

    Full Text Available The business expansion to other geographical areas with different cultures from which organizations were created and developed leads to the expatriation of employees to these destinations. Recruitment and selection procedures of expatriates do not always have the intended success leading to an early return of these professionals with the consequent organizational disorders. In this study, several articles published in the last five years were analyzed in order to identify the most frequently mentioned dimensions in the selection of expatriates in terms of success and failure. The characteristics in the selection process that may increase prediction of adaptation of expatriates to new cultural contexts of the some organization were studied according to the KSAOs model. Few references were found concerning Knowledge, Skills and Abilities dimensions in the analyzed papers. There was a strong predominance on the evaluation of Other Characteristics, and was given more importance to dispositional factors than situational factors for promoting the integration of the expatriates.

  9. Post-model selection inference and model averaging

    Directory of Open Access Journals (Sweden)

    Georges Nguefack-Tsague

    2011-07-01

    Full Text Available Although model selection is routinely used in practice nowadays, little is known about its precise effects on any subsequent inference that is carried out. The same goes for the effects induced by the closely related technique of model averaging. This paper is concerned with the use of the same data first to select a model and then to carry out inference, in particular point estimation and point prediction. The properties of the resulting estimator, called a post-model-selection estimator (PMSE, are hard to derive. Using selection criteria such as hypothesis testing, AIC, BIC, HQ and Cp, we illustrate that, in terms of risk function, no single PMSE dominates the others. The same conclusion holds more generally for any penalised likelihood information criterion. We also compare various model averaging schemes and show that no single one dominates the others in terms of risk function. Since PMSEs can be regarded as a special case of model averaging, with 0-1 random-weights, we propose a connection between the two theories, in the frequentist approach, by taking account of the selection procedure when performing model averaging. We illustrate the point by simulating a simple linear regression model.

  10. Skewed factor models using selection mechanisms

    KAUST Repository

    Kim, Hyoung-Moon

    2015-12-21

    Traditional factor models explicitly or implicitly assume that the factors follow a multivariate normal distribution; that is, only moments up to order two are involved. However, it may happen in real data problems that the first two moments cannot explain the factors. Based on this motivation, here we devise three new skewed factor models, the skew-normal, the skew-tt, and the generalized skew-normal factor models depending on a selection mechanism on the factors. The ECME algorithms are adopted to estimate related parameters for statistical inference. Monte Carlo simulations validate our new models and we demonstrate the need for skewed factor models using the classic open/closed book exam scores dataset.

  11. Skewed factor models using selection mechanisms

    KAUST Repository

    Kim, Hyoung-Moon; Maadooliat, Mehdi; Arellano-Valle, Reinaldo B.; Genton, Marc G.

    2015-01-01

    Traditional factor models explicitly or implicitly assume that the factors follow a multivariate normal distribution; that is, only moments up to order two are involved. However, it may happen in real data problems that the first two moments cannot explain the factors. Based on this motivation, here we devise three new skewed factor models, the skew-normal, the skew-tt, and the generalized skew-normal factor models depending on a selection mechanism on the factors. The ECME algorithms are adopted to estimate related parameters for statistical inference. Monte Carlo simulations validate our new models and we demonstrate the need for skewed factor models using the classic open/closed book exam scores dataset.

  12. Model structure selection in convolutive mixtures

    DEFF Research Database (Denmark)

    Dyrholm, Mads; Makeig, S.; Hansen, Lars Kai

    2006-01-01

    The CICAAR algorithm (convolutive independent component analysis with an auto-regressive inverse model) allows separation of white (i.i.d) source signals from convolutive mixtures. We introduce a source color model as a simple extension to the CICAAR which allows for a more parsimonious represent......The CICAAR algorithm (convolutive independent component analysis with an auto-regressive inverse model) allows separation of white (i.i.d) source signals from convolutive mixtures. We introduce a source color model as a simple extension to the CICAAR which allows for a more parsimonious...... representation in many practical mixtures. The new filter-CICAAR allows Bayesian model selection and can help answer questions like: ’Are we actually dealing with a convolutive mixture?’. We try to answer this question for EEG data....

  13. Virulence phenotypes of low-passage clinical isolates of Nontypeable Haemophilus influenzae assessed using the chinchilla laniger model of otitis media

    Directory of Open Access Journals (Sweden)

    Hogg Justin

    2007-06-01

    Full Text Available Abstract Background The nontypeable Haemophilus influenzae (NTHi are associated with a spectrum of respiratory mucosal infections including: acute otitis media (AOM; chronic otitis media with effusion (COME; otorrhea; locally invasive diseases such as mastoiditis; as well as a range of systemic disease states, suggesting a wide range of virulence phenotypes. Genomic studies have demonstrated that each clinical strain contains a unique genic distribution from a population-based supragenome, the distributed genome hypothesis. These diverse clinical and genotypic findings suggest that each NTHi strain possesses a unique set of virulence factors that contributes to the course of the disease. Results The local and systemic virulence patterns of ten genomically characterized low-passage clinical NTHi strains (PittAA – PittJJ obtained from children with COME or otorrhea were stratified using the chinchilla model of otitis media (OM. Each isolate was used to bilaterally inoculate six animals and thereafter clinical assessments were carried out daily for 8 days by blinded observers. There was no statistical difference in the time it took for any of the 10 NTHi strains to induce otologic (local disease with respect to any or all of the other strains, however the differences in time to maximal local disease and the severity of local disease were both significant between the strains. Parameters of systemic disease indicated that the strains were not all equivalent: time to development of the systemic disease, maximal systemic scores and mortality were all statistically different among the strains. PittGG induced 100% mortality while PittBB, PittCC, and PittEE produced no mortality. Overall Pitt GG, PittII, and Pitt FF produced the most rapid and most severe local and systemic disease. A post hoc determination of the clinical origins of the 10 NTHi strains revealed that these three strains were of otorrheic origin, whereas the other 7 were from patients

  14. Outer membrane protein P4 is not required for virulence in the human challenge model of Haemophilus ducreyi infection.

    Science.gov (United States)

    Janowicz, Diane M; Zwickl, Beth W; Fortney, Kate R; Katz, Barry P; Bauer, Margaret E

    2014-06-24

    Bacterial lipoproteins often play important roles in pathogenesis and can stimulate protective immune responses. Such lipoproteins are viable vaccine candidates. Haemophilus ducreyi, which causes the sexually transmitted disease chancroid, expresses a number of lipoproteins during human infection. One such lipoprotein, OmpP4, is homologous to the outer membrane lipoprotein e (P4) of H. influenzae. In H. influenzae, e (P4) stimulates production of bactericidal and protective antibodies and contributes to pathogenesis by facilitating acquisition of the essential nutrients heme and nicotinamide adenine dinucleotide (NAD). Here, we tested the hypothesis that, like its homolog, H. ducreyi OmpP4 contributes to virulence and stimulates production of bactericidal antibodies. We determined that OmpP4 is broadly conserved among clinical isolates of H. ducreyi. We next constructed and characterized an isogenic ompP4 mutant, designated 35000HPompP4, in H. ducreyi strain 35000HP. To test whether OmpP4 was necessary for virulence in humans, eight healthy adults were experimentally infected. Each subject was inoculated with a fixed dose of 35000HP on one arm and three doses of 35000HPompP4 on the other arm. The overall parent and mutant pustule formation rates were 52.4% and 47.6%, respectively (P = 0.74). These results indicate that expression of OmpP4 in not necessary for H. ducreyi to initiate disease or progress to pustule formation in humans. Hyperimmune mouse serum raised against purified, recombinant OmpP4 did not promote bactericidal killing of 35000HP or phagocytosis by J774A.1 mouse macrophages in serum bactericidal and phagocytosis assays, respectively. Our data suggest that, unlike e (P4), H. ducreyi OmpP4 is not a suitable vaccine candidate. OmpP4 may be dispensable for virulence because of redundant mechanisms in H. ducreyi for heme acquisition and NAD utilization.

  15. Detection of Alpha-Toxin and Other Virulence Factors in Biofilms of Staphylococcus aureus on Polystyrene and a Human Epidermal Model.

    Science.gov (United States)

    den Reijer, P M; Haisma, E M; Lemmens-den Toom, N A; Willemse, J; Koning, R I; Koning, R A; Demmers, J A A; Dekkers, D H W; Rijkers, E; El Ghalbzouri, A; Nibbering, P H; van Wamel, W

    2016-01-01

    The ability of Staphylococcus aureus to successfully colonize (a)biotic surfaces may be explained by biofilm formation and the actions of virulence factors. The aim of the present study was to establish the presence of 52 proteins, including virulence factors such as alpha-toxin, during biofilm formation of five different (methicillin resistant) S. aureus strains on Leiden human epidermal models (LEMs) and polystyrene surfaces (PS) using a competitive Luminex-based assay. All five S. aureus strains formed biofilms on PS, whereas only three out of five strains formed biofilms on LEMs. Out of the 52 tested proteins, six functionally diverse proteins (ClfB, glucosaminidase, IsdA, IsaA, SACOL0688 and nuclease) were detected in biofilms of all strains on both PS and LEMs. At the same time, four toxins (alpha-toxin, gamma-hemolysin B and leukocidins D and E), two immune modulators (formyl peptide receptor-like inhibitory protein and Staphylococcal superantigen-like protein 1), and two other proteins (lipase and LytM) were detectable in biofilms by all five S. aureus strains on LEMs, but not on PS. In contrast, fibronectin-binding protein B (FnbpB) was detectable in biofilms by all S. aureus biofilms on PS, but not on LEMs. These data were largely confirmed by the results from proteomic and transcriptomic analyses and in case of alpha-toxin additionally by GFP-reporter technology. Functionally diverse virulence factors of (methicillin-resistant) S. aureus are present during biofilm formation on LEMs and PS. These results could aid in identifying novel targets for future treatment strategies against biofilm-associated infections.

  16. Vitamin A deficiency impairs adaptive B and T cell responses to a prototype monovalent attenuated human rotavirus vaccine and virulent human rotavirus challenge in a gnotobiotic piglet model.

    Directory of Open Access Journals (Sweden)

    Kuldeep S Chattha

    Full Text Available Rotaviruses (RV are a major cause of gastroenteritis in children. Widespread vitamin A deficiency is associated with reduced efficacy of vaccines and higher incidence of diarrheal infections in children in developing countries. We established a vitamin A deficient (VAD gnotobiotic piglet model that mimics subclinical vitamin A deficiency in children to study its effects on an oral human rotavirus (HRV vaccine and virulent HRV challenge. Piglets derived from VAD and vitamin A sufficient (VAS sows were orally vaccinated with attenuated HRV or mock, with/without supplemental vitamin A and challenged with virulent HRV. Unvaccinated VAD control piglets had significantly lower hepatic vitamin A, higher severity and duration of diarrhea and HRV fecal shedding post-challenge as compared to VAS control pigs. Reduced protection coincided with significantly higher innate (IFNα cytokine and CD8 T cell frequencies in the blood and intestinal tissues, higher pro-inflammatory (IL12 and 2-3 fold lower anti-inflammatory (IL10 cytokines, in VAD compared to VAS control pigs. Vaccinated VAD pigs had higher diarrhea severity scores compared to vaccinated VAS pigs, which coincided with lower serum IgA HRV antibody titers and significantly lower intestinal IgA antibody secreting cells post-challenge in the former groups suggesting lower anamnestic responses. A trend for higher serum HRV IgG antibodies was observed in VAD vs VAS vaccinated groups post-challenge. The vaccinated VAD (non-vitamin A supplemented pigs had significantly higher serum IL12 (PID2 and IFNγ (PID6 compared to vaccinated VAS groups suggesting higher Th1 responses in VAD conditions. Furthermore, regulatory T-cell responses were compromised in VAD pigs. Supplemental vitamin A in VAD pigs did not fully restore the dysregulated immune responses to AttHRV vaccine or moderate virulent HRV diarrhea. Our findings suggest that that VAD in children in developing countries may partially contribute to more

  17. Behavioral optimization models for multicriteria portfolio selection

    Directory of Open Access Journals (Sweden)

    Mehlawat Mukesh Kumar

    2013-01-01

    Full Text Available In this paper, behavioral construct of suitability is used to develop a multicriteria decision making framework for portfolio selection. To achieve this purpose, we rely on multiple methodologies. Analytical hierarchy process technique is used to model the suitability considerations with a view to obtaining the suitability performance score in respect of each asset. A fuzzy multiple criteria decision making method is used to obtain the financial quality score of each asset based upon investor's rating on the financial criteria. Two optimization models are developed for optimal asset allocation considering simultaneously financial and suitability criteria. An empirical study is conducted on randomly selected assets from National Stock Exchange, Mumbai, India to demonstrate the effectiveness of the proposed methodology.

  18. Robust inference in sample selection models

    KAUST Repository

    Zhelonkin, Mikhail; Genton, Marc G.; Ronchetti, Elvezio

    2015-01-01

    The problem of non-random sample selectivity often occurs in practice in many fields. The classical estimators introduced by Heckman are the backbone of the standard statistical analysis of these models. However, these estimators are very sensitive to small deviations from the distributional assumptions which are often not satisfied in practice. We develop a general framework to study the robustness properties of estimators and tests in sample selection models. We derive the influence function and the change-of-variance function of Heckman's two-stage estimator, and we demonstrate the non-robustness of this estimator and its estimated variance to small deviations from the model assumed. We propose a procedure for robustifying the estimator, prove its asymptotic normality and give its asymptotic variance. Both cases with and without an exclusion restriction are covered. This allows us to construct a simple robust alternative to the sample selection bias test. We illustrate the use of our new methodology in an analysis of ambulatory expenditures and we compare the performance of the classical and robust methods in a Monte Carlo simulation study.

  19. Robust inference in sample selection models

    KAUST Repository

    Zhelonkin, Mikhail

    2015-11-20

    The problem of non-random sample selectivity often occurs in practice in many fields. The classical estimators introduced by Heckman are the backbone of the standard statistical analysis of these models. However, these estimators are very sensitive to small deviations from the distributional assumptions which are often not satisfied in practice. We develop a general framework to study the robustness properties of estimators and tests in sample selection models. We derive the influence function and the change-of-variance function of Heckman\\'s two-stage estimator, and we demonstrate the non-robustness of this estimator and its estimated variance to small deviations from the model assumed. We propose a procedure for robustifying the estimator, prove its asymptotic normality and give its asymptotic variance. Both cases with and without an exclusion restriction are covered. This allows us to construct a simple robust alternative to the sample selection bias test. We illustrate the use of our new methodology in an analysis of ambulatory expenditures and we compare the performance of the classical and robust methods in a Monte Carlo simulation study.

  20. Efficiently adapting graphical models for selectivity estimation

    DEFF Research Database (Denmark)

    Tzoumas, Kostas; Deshpande, Amol; Jensen, Christian S.

    2013-01-01

    cardinality estimation without making the independence assumption. By carefully using concepts from the field of graphical models, we are able to factor the joint probability distribution over all the attributes in the database into small, usually two-dimensional distributions, without a significant loss...... in estimation accuracy. We show how to efficiently construct such a graphical model from the database using only two-way join queries, and we show how to perform selectivity estimation in a highly efficient manner. We integrate our algorithms into the PostgreSQL DBMS. Experimental results indicate...

  1. [Virulence and its relationship to antibiotic resistance].

    Science.gov (United States)

    Joly-Guillou, M L

    1998-12-01

    PATHOGENIC ISLANDS: Certain DNA blocks inserted into the chromosome of most Gram negative bacteria originated in pathogens found in plants. VIRULENCE-ANTIBIOTIC INTERACTIONS: During the invasive phase, the bacterial cell covers itself with adhesins which facilitate its adherence to tissues. The bacterial cell produces a fibronectin which protects its defense systems. Antibiotics favor bacterial resistance by increasing the expression of surface adhesins and fibronectin production. PENICILLIN RESISTANT PNEUMOCOCCI: Experimental models have demonstrated that mortality in mice and host resistance to pneumococcal infection are related to the type of capsule and not to antibiotic resistance. QUORUM SENSING: The bacterial inoculum regulates the production of virulence factors in vivo via quorum sensing. This regulation can play an important role in Pseudomonas aeruginosa infections. ACINETOBACTER BAUMANNI VIRULENCE: Long poorly understood, factors favoring A. baumanni virulence appear to result from bacterial production of IROMPs in the extracellular growth medium in response to iron depletion during the exponential growth phase.

  2. Virulence patterns in a murine sepsis model of ST131 Escherichia coli clinical isolates belonging to serotypes O25b:H4 and O16:H5 are associated to specific virotypes.

    Directory of Open Access Journals (Sweden)

    Azucena Mora

    Full Text Available Escherichia coli sequence type (ST131 is an emerging disseminated public health threat implicated in multidrug-resistant extraintestinal infections worldwide. Although the majority of ST131 isolates belong to O25b:H4 serotype, new variants with different serotypes, STs using the discriminative multilocus sequence typing scheme of Pasteur Institute, and virulence-gene profiles (virotypes have been reported with unknown implications on the pattern of spread, persistence and virulence. The aim of the present study was to compare virulence in a mouse subcutaneous sepsis model of representative ST131 clinical isolates belonging to 2 serotypes (O25b:H4, O16:H5 and nine virotypes and subtypes (A, B, C, D1, D2, D3, D4, D5 and E. Fourteen out of the 23 ST131 isolates tested (61% killed 90 to 100% of mice challenged, and 18 of 23 (78% at least 50%. Interestingly, different virulence patterns in association with virotypes were observed, from highly rapid lethality (death in less than 24 h to low final lethality (death at 7 days but with presence of an acute inflammation. This is the first study to assess virulence of ST131 isolates belonging to serotype O16:H5, which exhibited virotype C. In spite of their low virulence-gene score, O16:H5 isolates did not show significant differences in final lethality compared with highly virulent O25b:H4 isolates of virotypes A, B and C, but killed mice less rapidly. Significant differences were found, however, between virotypes A, B, C (final lethality ≥80% of mice challenged and virotypes D, E. Particularly unexpected was the low lethality of the newly assigned virotype E taking into account that it exhibited high virulence-gene score, and the same clonotype H30 as highly virulent O25b:H4 isolates of virotypes A, B and C. In vivo virulence diversity reported in this study would reflect the genetic variability within ST131 clonal group evidenced by molecular typing.

  3. Synthetic Peptides to Target Stringent Response-Controlled Virulence in a Pseudomonas aeruginosa Murine Cutaneous Infection Model

    Directory of Open Access Journals (Sweden)

    Daniel Pletzer

    2017-09-01

    Full Text Available Microorganisms continuously monitor their surroundings and adaptively respond to environmental cues. One way to cope with various stress-related situations is through the activation of the stringent stress response pathway. In Pseudomonas aeruginosa this pathway is controlled and coordinated by the activity of the RelA and SpoT enzymes that metabolize the small nucleotide secondary messenger molecule (pppGpp. Intracellular ppGpp concentrations are crucial in mediating adaptive responses and virulence. Targeting this cellular stress response has recently been the focus of an alternative approach to fight antibiotic resistant bacteria. Here, we examined the role of the stringent response in the virulence of P. aeruginosa PAO1 and the Liverpool epidemic strain LESB58. A ΔrelA/ΔspoT double mutant showed decreased cytotoxicity toward human epithelial cells, exhibited reduced hemolytic activity, and caused down-regulation of the expression of the alkaline protease aprA gene in stringent response mutants grown on blood agar plates. Promoter fusions of relA or spoT to a bioluminescence reporter gene revealed that both genes were expressed during the formation of cutaneous abscesses in mice. Intriguingly, virulence was attenuated in vivo by the ΔrelA/ΔspoT double mutant, but not the relA mutant nor the ΔrelA/ΔspoT complemented with either gene. Treatment of a cutaneous P. aeruginosa PAO1 infection with anti-biofilm peptides increased animal welfare, decreased dermonecrotic lesion sizes, and reduced bacterial numbers recovered from abscesses, resembling the phenotype of the ΔrelA/ΔspoT infection. It was previously demonstrated by our lab that ppGpp could be targeted by synthetic peptides; here we demonstrated that spoT promoter activity was suppressed during cutaneous abscess formation by treatment with peptides DJK-5 and 1018, and that a peptide-treated relA complemented stringent response double mutant strain exhibited reduced peptide

  4. A molecular beacon based on DNA-templated silver nanoclusters for the highly sensitive and selective multiplexed detection of virulence genes.

    Science.gov (United States)

    Han, Dan; Wei, Chunying

    2018-05-01

    In this work, we develop a fluorescent molecular beacon based on the DNA-templated silver nanoclusters (DNA-Ag NCs). The skillfully designed molecular beacon can be conveniently used for detection of diverse virulence genes as long as the corresponding recognition sequences are embedded. Importantly, the constructed detection system allows simultaneous detection of multiple nucleic acids, which is attributed to non-overlapping emission spectra of the as-synthesized silver nanoclusters. Based on the target-induced fluorescence enhancement, three infectious disease-related genes HIV, H1N1, and H5N1 are detected, and the corresponding detection limits are 3.53, 0.12 and 3.95nM, respectively. This design allows specific, versatile and simultaneous detection of diverse targets with easy operation and low cost. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Item selection via Bayesian IRT models.

    Science.gov (United States)

    Arima, Serena

    2015-02-10

    With reference to a questionnaire that aimed to assess the quality of life for dysarthric speakers, we investigate the usefulness of a model-based procedure for reducing the number of items. We propose a mixed cumulative logit model, which is known in the psychometrics literature as the graded response model: responses to different items are modelled as a function of individual latent traits and as a function of item characteristics, such as their difficulty and their discrimination power. We jointly model the discrimination and the difficulty parameters by using a k-component mixture of normal distributions. Mixture components correspond to disjoint groups of items. Items that belong to the same groups can be considered equivalent in terms of both difficulty and discrimination power. According to decision criteria, we select a subset of items such that the reduced questionnaire is able to provide the same information that the complete questionnaire provides. The model is estimated by using a Bayesian approach, and the choice of the number of mixture components is justified according to information criteria. We illustrate the proposed approach on the basis of data that are collected for 104 dysarthric patients by local health authorities in Lecce and in Milan. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Real-time PCR expression profiling of genes encoding potential virulence factors in Candida albicans biofilms: identification of model-dependent and -independent gene expression

    Directory of Open Access Journals (Sweden)

    Řičicová Markéta

    2010-04-01

    Full Text Available Abstract Background Candida albicans infections are often associated with biofilm formation. Previous work demonstrated that the expression of HWP1 (hyphal wall protein and of genes belonging to the ALS (agglutinin-like sequence, SAP (secreted aspartyl protease, PLB (phospholipase B and LIP (lipase gene families is associated with biofilm growth on mucosal surfaces. We investigated using real-time PCR whether genes encoding potential virulence factors are also highly expressed in biofilms associated with abiotic surfaces. For this, C. albicans biofilms were grown on silicone in microtiter plates (MTP or in the Centres for Disease Control (CDC reactor, on polyurethane in an in vivo subcutaneous catheter rat (SCR model, and on mucosal surfaces in the reconstituted human epithelium (RHE model. Results HWP1 and genes belonging to the ALS, SAP, PLB and LIP gene families were constitutively expressed in C. albicans biofilms. ALS1-5 were upregulated in all model systems, while ALS9 was mostly downregulated. ALS6 and HWP1 were overexpressed in all models except in the RHE and MTP, respectively. The expression levels of SAP1 were more pronounced in both in vitro models, while those of SAP2, SAP4 and SAP6 were higher in the in vivo model. Furthermore, SAP5 was highly upregulated in the in vivo and RHE models. For SAP9 and SAP10 similar gene expression levels were observed in all model systems. PLB genes were not considerably upregulated in biofilms, while LIP1-3, LIP5-7 and LIP9-10 were highly overexpressed in both in vitro models. Furthermore, an elevated lipase activity was detected in supernatans of biofilms grown in the MTP and RHE model. Conclusions Our findings show that HWP1 and most of the genes belonging to the ALS, SAP and LIP gene families are upregulated in C. albicans biofilms. Comparison of the fold expression between the various model systems revealed similar expression levels for some genes, while for others model-dependent expression

  7. Factors influencing creep model equation selection

    International Nuclear Information System (INIS)

    Holdsworth, S.R.; Askins, M.; Baker, A.; Gariboldi, E.; Holmstroem, S.; Klenk, A.; Ringel, M.; Merckling, G.; Sandstrom, R.; Schwienheer, M.; Spigarelli, S.

    2008-01-01

    During the course of the EU-funded Advanced-Creep Thematic Network, ECCC-WG1 reviewed the applicability and effectiveness of a range of model equations to represent the accumulation of creep strain in various engineering alloys. In addition to considering the experience of network members, the ability of several models to describe the deformation characteristics of large single and multi-cast collations of ε(t,T,σ) creep curves have been evaluated in an intensive assessment inter-comparison activity involving three steels, 21/4 CrMo (P22), 9CrMoVNb (Steel-91) and 18Cr13NiMo (Type-316). The choice of the most appropriate creep model equation for a given application depends not only on the high-temperature deformation characteristics of the material under consideration, but also on the characteristics of the dataset, the number of casts for which creep curves are available and on the strain regime for which an analytical representation is required. The paper focuses on the factors which can influence creep model selection and model-fitting approach for multi-source, multi-cast datasets

  8. Salmonella-secreted Virulence Factors

    Energy Technology Data Exchange (ETDEWEB)

    Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

    2011-05-01

    In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

  9. Inactivation of the spxA1 or spxA2 gene of Streptococcus mutans decreases virulence in the rat caries model

    Science.gov (United States)

    Galvão, Lívia C.C.; Rosalen, Pedro L.; Rivera-Ramos, Isamar; Franco, Gilson C.N.; Kajfasz, Jessica K; Abranches, Jacqueline; Bueno-Silva, Bruno; Koo, Hyun; Lemos, José A.

    2016-01-01

    SUMMARY In oral biofilms, the major environmental challenges encountered by Streptococcus mutans are acid and oxidative stresses. Previously, we showed that the transcriptional regulators SpxA1 and SpxA2 are involved in general stress survival of S. mutans with SpxA1 playing a primary role in activation of antioxidant and detoxification strategies whereas SpxA2 serves as a back up activator of oxidative stress genes. We have also found that spxA1 mutant strains (ΔspxA1 and ΔspxA1ΔspxA2) are outcompeted by peroxigenic oral streptococci in vitro and have impaired abilities to colonize the teeth of rats fed a highly cariogenic diet. Here, we show that the Spx proteins can also exert regulatory roles in the expression of additional virulence attributes of S. mutans. Competence activation is significantly impaired in Δspx strains and the production of mutacin IV and V is virtually abolished in ΔspxA1 strains. Unexpectedly, the ΔspxA2 strain showed increased production of glucans from sucrose, without affecting the total amount of bacteria within biofilms when compared to the parent strain. By using the rat caries model, we showed that the capacity of the ΔspxA1 and ΔspxA2 strains to cause caries on smooth tooth surfaces is significantly impaired. The ΔspxA2 strain also formed fewer lesions on sulcal surfaces. This report reveals that global regulation via Spx contributes to the cariogenic potential of S. mutans and highlights the essentiality of animal models in the characterization of bacterial traits implicated in virulence. PMID:27037617

  10. Inactivation of the spxA1 or spxA2 gene of Streptococcus mutans decreases virulence in the rat caries model.

    Science.gov (United States)

    Galvão, L C C; Rosalen, P L; Rivera-Ramos, I; Franco, G C N; Kajfasz, J K; Abranches, J; Bueno-Silva, B; Koo, H; Lemos, J A

    2017-04-01

    In oral biofilms, the major environmental challenges encountered by Streptococcus mutans are acid and oxidative stresses. Previously, we showed that the transcriptional regulators SpxA1 and SpxA2 are involved in general stress survival of S. mutans with SpxA1 playing a primary role in activation of antioxidant and detoxification strategies whereas SpxA2 serves as a back up activator of oxidative stress genes. We have also found that spxA1 mutant strains (∆spxA1 and ∆spxA1∆spxA2) are outcompeted by peroxigenic oral streptococci in vitro and have impaired abilities to colonize the teeth of rats fed a highly cariogenic diet. Here, we show that the Spx proteins can also exert regulatory roles in the expression of additional virulence attributes of S. mutans. Competence activation is significantly impaired in Δspx strains and the production of mutacin IV and V is virtually abolished in ΔspxA1 strains. Unexpectedly, the ∆spxA2 strain showed increased production of glucans from sucrose, without affecting the total amount of bacteria within biofilms when compared with the parent strain. By using the rat caries model, we showed that the capacity of the ΔspxA1 and ΔspxA2 strains to cause caries on smooth tooth surfaces is significantly impaired. The ∆spxA2 strain also formed fewer lesions on sulcal surfaces. This report reveals that global regulation via Spx contributes to the cariogenic potential of S. mutans and highlights that animal models are essential in the characterization of bacterial traits implicated in virulence. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. High-dimensional model estimation and model selection

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    I will review concepts and algorithms from high-dimensional statistics for linear model estimation and model selection. I will particularly focus on the so-called p>>n setting where the number of variables p is much larger than the number of samples n. I will focus mostly on regularized statistical estimators that produce sparse models. Important examples include the LASSO and its matrix extension, the Graphical LASSO, and more recent non-convex methods such as the TREX. I will show the applicability of these estimators in a diverse range of scientific applications, such as sparse interaction graph recovery and high-dimensional classification and regression problems in genomics.

  12. Halo models of HI selected galaxies

    Science.gov (United States)

    Paul, Niladri; Choudhury, Tirthankar Roy; Paranjape, Aseem

    2018-06-01

    Modelling the distribution of neutral hydrogen (HI) in dark matter halos is important for studying galaxy evolution in the cosmological context. We use a novel approach to infer the HI-dark matter connection at the massive end (m_H{I} > 10^{9.8} M_{⊙}) from radio HI emission surveys, using optical properties of low-redshift galaxies as an intermediary. In particular, we use a previously calibrated optical HOD describing the luminosity- and colour-dependent clustering of SDSS galaxies and describe the HI content using a statistical scaling relation between the optical properties and HI mass. This allows us to compute the abundance and clustering properties of HI-selected galaxies and compare with data from the ALFALFA survey. We apply an MCMC-based statistical analysis to constrain the free parameters related to the scaling relation. The resulting best-fit scaling relation identifies massive HI galaxies primarily with optically faint blue centrals, consistent with expectations from galaxy formation models. We compare the Hi-stellar mass relation predicted by our model with independent observations from matched Hi-optical galaxy samples, finding reasonable agreement. As a further application, we make some preliminary forecasts for future observations of HI and optical galaxies in the expected overlap volume of SKA and Euclid/LSST.

  13. Selecting a model of supersymmetry breaking mediation

    International Nuclear Information System (INIS)

    AbdusSalam, S. S.; Allanach, B. C.; Dolan, M. J.; Feroz, F.; Hobson, M. P.

    2009-01-01

    We study the problem of selecting between different mechanisms of supersymmetry breaking in the minimal supersymmetric standard model using current data. We evaluate the Bayesian evidence of four supersymmetry breaking scenarios: mSUGRA, mGMSB, mAMSB, and moduli mediation. The results show a strong dependence on the dark matter assumption. Using the inferred cosmological relic density as an upper bound, minimal anomaly mediation is at least moderately favored over the CMSSM. Our fits also indicate that evidence for a positive sign of the μ parameter is moderate at best. We present constraints on the anomaly and gauge mediated parameter spaces and some previously unexplored aspects of the dark matter phenomenology of the moduli mediation scenario. We use sparticle searches, indirect observables and dark matter observables in the global fit and quantify robustness with respect to prior choice. We quantify how much information is contained within each constraint.

  14. Selective Oxidation of Lignin Model Compounds.

    Science.gov (United States)

    Gao, Ruili; Li, Yanding; Kim, Hoon; Mobley, Justin K; Ralph, John

    2018-05-02

    Lignin, the planet's most abundant renewable source of aromatic compounds, is difficult to degrade efficiently to welldefined aromatics. We developed a microwave-assisted catalytic Swern oxidation system using an easily prepared catalyst, MoO 2 Cl 2 (DMSO) 2 , and DMSO as the solvent and oxidant. It demonstrated high efficiency in transforming lignin model compounds containing the units and functional groups found in native lignins. The aromatic ring substituents strongly influenced the selectivity of β-ether phenolic dimer cleavage to generate sinapaldehyde and coniferaldehyde, monomers not usually produced by oxidative methods. Time-course studies on two key intermediates provided insight into the reaction pathway. Owing to the broad scope of this oxidation system and the insight gleaned with regard to its mechanism, this strategy could be adapted and applied in a general sense to the production of useful aromatic chemicals from phenolics and lignin. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Impact of Resistance to Fluconazole on Virulence and Morphological Aspects of Cryptococcus neoformans and Cryptococcus gattii Isolates.

    Directory of Open Access Journals (Sweden)

    Suélen Andreia eRossi

    2016-02-01

    Full Text Available Cryptococcus spp. are responsible for around one million cases of meningitis every year. Fluconazole (FLU is commonly used in the treatment of cryptococcosis, mainly in immunocompromised patients and the resistance is usually reported after long periods of treatment. In this study, the morphological characterization and virulence profile of FLU-susceptible and FLU-resistant clinical and environmental isolates of C. neoformans and C. gattii were performed both in vitro and in vivo using the Galleria mellonella model. FLU-susceptible isolates from C. neoformans were significantly more virulent than the FLU-resistant isolates. FLU-susceptible C. gattii isolates showed a different virulence profile from C. neoformans isolates where only the environmental isolate, CL, was more virulent compared with the resistant isolates. Cell morphology and capsule size were analyzed and the FLU-resistant isolates did not change significantly compared with the most sensitive isolates. Growth at 37°C was also evaluated and in both species, the resistant isolates showed a reduced growth at this temperature, indicating that FLU resistance can affect their growth. Based on the results obtained is possible suggest that FLU resistance can influence the morphology of the isolates and consequently changed the virulence profiles. The most evident results were observed for C. neoformans showing that the adaptation of isolates to antifungal selective pressure influenced the loss of virulence.

  16. Genome-wide screen of Pseudomonas aeruginosa In Saccharomyces cerevisiae identifies new virulence factors

    Directory of Open Access Journals (Sweden)

    Rafat eZrieq

    2015-11-01

    Full Text Available Pseudomonas aeruginosa is a human opportunistic pathogen that causes mortality in cystic fibrosis and immunocompromised patients. While many virulence factors of this pathogen have already been identified, several remain to be discovered. In this respect we set an unprecedented genome-wide screen of a P. aeruginosa expression library based on a yeast growth phenotype. 51 candidates were selected in a three-round screening process. The robustness of the screen was validated by the selection of three well known secreted proteins including one demonstrated virulence factor, the protease LepA. Further in silico sorting of the 51 candidates highlighted three potential new Pseudomonas effector candidates (Pec. By testing the cytotoxicity of wild type P. aeruginosa vs pec mutants towards macrophages and the virulence in the Caenorhabditis elegans model, we demonstrated that the three selected Pecs are novel virulence factors of P. aeruginosa. Additional cellular localization experiments in the host revealed specific localization for Pec1 and Pec2 that could inform about their respective functions.

  17. Estimation of a multivariate mean under model selection uncertainty

    Directory of Open Access Journals (Sweden)

    Georges Nguefack-Tsague

    2014-05-01

    Full Text Available Model selection uncertainty would occur if we selected a model based on one data set and subsequently applied it for statistical inferences, because the "correct" model would not be selected with certainty.  When the selection and inference are based on the same dataset, some additional problems arise due to the correlation of the two stages (selection and inference. In this paper model selection uncertainty is considered and model averaging is proposed. The proposal is related to the theory of James and Stein of estimating more than three parameters from independent normal observations. We suggest that a model averaging scheme taking into account the selection procedure could be more appropriate than model selection alone. Some properties of this model averaging estimator are investigated; in particular we show using Stein's results that it is a minimax estimator and can outperform Stein-type estimators.

  18. Hidden Markov Model for Stock Selection

    Directory of Open Access Journals (Sweden)

    Nguyet Nguyen

    2015-10-01

    Full Text Available The hidden Markov model (HMM is typically used to predict the hidden regimes of observation data. Therefore, this model finds applications in many different areas, such as speech recognition systems, computational molecular biology and financial market predictions. In this paper, we use HMM for stock selection. We first use HMM to make monthly regime predictions for the four macroeconomic variables: inflation (consumer price index (CPI, industrial production index (INDPRO, stock market index (S&P 500 and market volatility (VIX. At the end of each month, we calibrate HMM’s parameters for each of these economic variables and predict its regimes for the next month. We then look back into historical data to find the time periods for which the four variables had similar regimes with the forecasted regimes. Within those similar periods, we analyze all of the S&P 500 stocks to identify which stock characteristics have been well rewarded during the time periods and assign scores and corresponding weights for each of the stock characteristics. A composite score of each stock is calculated based on the scores and weights of its features. Based on this algorithm, we choose the 50 top ranking stocks to buy. We compare the performances of the portfolio with the benchmark index, S&P 500. With an initial investment of $100 in December 1999, over 15 years, in December 2014, our portfolio had an average gain per annum of 14.9% versus 2.3% for the S&P 500.

  19. Psyche Mission: Scientific Models and Instrument Selection

    Science.gov (United States)

    Polanskey, C. A.; Elkins-Tanton, L. T.; Bell, J. F., III; Lawrence, D. J.; Marchi, S.; Park, R. S.; Russell, C. T.; Weiss, B. P.

    2017-12-01

    NASA has chosen to explore (16) Psyche with their 14th Discovery-class mission. Psyche is a 226-km diameter metallic asteroid hypothesized to be the exposed core of a planetesimal that was stripped of its rocky mantle by multiple hit and run collisions in the early solar system. The spacecraft launch is planned for 2022 with arrival at the asteroid in 2026 for 21 months of operations. The Psyche investigation has five primary scientific objectives: A. Determine whether Psyche is a core, or if it is unmelted material. B. Determine the relative ages of regions of Psyche's surface. C. Determine whether small metal bodies incorporate the same light elements as are expected in the Earth's high-pressure core. D. Determine whether Psyche was formed under conditions more oxidizing or more reducing than Earth's core. E. Characterize Psyche's topography. The mission's task was to select the appropriate instruments to meet these objectives. However, exploring a metal world, rather than one made of ice, rock, or gas, requires development of new scientific models for Psyche to support the selection of the appropriate instruments for the payload. If Psyche is indeed a planetary core, we expect that it should have a detectable magnetic field. However, the strength of the magnetic field can vary by orders of magnitude depending on the formational history of Psyche. The implications of both the extreme low-end and the high-end predictions impact the magnetometer and mission design. For the imaging experiment, what can the team expect for the morphology of a heavily impacted metal body? Efforts are underway to further investigate the differences in crater morphology between high velocity impacts into metal and rock to be prepared to interpret the images of Psyche when they are returned. Finally, elemental composition measurements at Psyche using nuclear spectroscopy encompass a new and unexplored phase space of gamma-ray and neutron measurements. We will present some end

  20. High-throughput, signature-tagged mutagenic approach to identify novel virulence factors of Yersinia pestis CO92 in a mouse model of infection.

    Science.gov (United States)

    Ponnusamy, Duraisamy; Fitts, Eric C; Sha, Jian; Erova, Tatiana E; Kozlova, Elena V; Kirtley, Michelle L; Tiner, Bethany L; Andersson, Jourdan A; Chopra, Ashok K

    2015-05-01

    The identification of new virulence factors in Yersinia pestis and understanding their molecular mechanisms during an infection process are necessary in designing a better vaccine or to formulate an appropriate therapeutic intervention. By using a high-throughput, signature-tagged mutagenic approach, we created 5,088 mutants of Y. pestis strain CO92 and screened them in a mouse model of pneumonic plague at a dose equivalent to 5 50% lethal doses (LD50) of wild-type (WT) CO92. From this screen, we obtained 118 clones showing impairment in disseminating to the spleen, based on hybridization of input versus output DNA from mutant pools with 53 unique signature tags. In the subsequent screen, 20/118 mutants exhibited attenuation at 8 LD50 when tested in a mouse model of bubonic plague, with infection by 10/20 of the aforementioned mutants resulting in 40% or higher survival rates at an infectious dose of 40 LD50. Upon sequencing, six of the attenuated mutants were found to carry interruptions in genes encoding hypothetical proteins or proteins with putative functions. Mutants with in-frame deletion mutations of two of the genes identified from the screen, namely, rbsA, which codes for a putative sugar transport system ATP-binding protein, and vasK, a component of the type VI secretion system, were also found to exhibit some attenuation at 11 or 12 LD50 in a mouse model of pneumonic plague. Likewise, among the remaining 18 signature-tagged mutants, 9 were also attenuated (40 to 100%) at 12 LD50 in a pneumonic plague mouse model. Previously, we found that deleting genes encoding Braun lipoprotein (Lpp) and acyltransferase (MsbB), the latter of which modifies lipopolysaccharide function, reduced the virulence of Y. pestis CO92 in mouse models of bubonic and pneumonic plague. Deletion of rbsA and vasK genes from either the Δlpp single or the Δlpp ΔmsbB double mutant augmented the attenuation to provide 90 to 100% survivability to mice in a pneumonic plague model at 20

  1. A new Russell model for selecting suppliers

    NARCIS (Netherlands)

    Azadi, Majid; Shabani, Amir; Farzipoor Saen, Reza

    2014-01-01

    Recently, supply chain management (SCM) has been considered by many researchers. Supplier evaluation and selection plays a significant role in establishing an effective SCM. One of the techniques that can be used for selecting suppliers is data envelopment analysis (DEA). In some situations, to

  2. Virulence factors of the Mycobacterium tuberculosis complex

    Science.gov (United States)

    Forrellad, Marina A.; Klepp, Laura I.; Gioffré, Andrea; Sabio y García, Julia; Morbidoni, Hector R.; Santangelo, María de la Paz; Cataldi, Angel A.; Bigi, Fabiana

    2013-01-01

    The Mycobacterium tuberculosis complex (MTBC) consists of closely related species that cause tuberculosis in both humans and animals. This illness, still today, remains to be one of the leading causes of morbidity and mortality throughout the world. The mycobacteria enter the host by air, and, once in the lungs, are phagocytated by macrophages. This may lead to the rapid elimination of the bacillus or to the triggering of an active tuberculosis infection. A large number of different virulence factors have evolved in MTBC members as a response to the host immune reaction. The aim of this review is to describe the bacterial genes/proteins that are essential for the virulence of MTBC species, and that have been demonstrated in an in vivo model of infection. Knowledge of MTBC virulence factors is essential for the development of new vaccines and drugs to help manage the disease toward an increasingly more tuberculosis-free world. PMID:23076359

  3. Macrophage replication screen identifies a novel Francisella hydroperoxide resistance protein involved in virulence.

    Directory of Open Access Journals (Sweden)

    Anna C Llewellyn

    Full Text Available Francisella tularensis is a gram-negative facultative intracellular pathogen and the causative agent of tularemia. Recently, genome-wide screens have identified Francisella genes required for virulence in mice. However, the mechanisms by which most of the corresponding proteins contribute to pathogenesis are still largely unknown. To further elucidate the roles of these virulence determinants in Francisella pathogenesis, we tested whether each gene was required for replication of the model pathogen F. novicida within macrophages, an important virulence trait. Fifty-three of the 224 genes tested were involved in intracellular replication, including many of those within the Francisella pathogenicity island (FPI, validating our results. Interestingly, over one third of the genes identified are annotated as hypothetical, indicating that F. novicida likely utilizes novel virulence factors for intracellular replication. To further characterize these virulence determinants, we selected two hypothetical genes to study in more detail. As predicted by our screen, deletion mutants of FTN_0096 and FTN_1133 were attenuated for replication in macrophages. The mutants displayed differing levels of attenuation in vivo, with the FTN_1133 mutant being the most attenuated. FTN_1133 has sequence similarity to the organic hydroperoxide resistance protein Ohr, an enzyme involved in the bacterial response to oxidative stress. We show that FTN_1133 is required for F. novicida resistance to, and degradation of, organic hydroperoxides as well as resistance to the action of the NADPH oxidase both in macrophages and mice. Furthermore, we demonstrate that F. holarctica LVS, a strain derived from a highly virulent human pathogenic species of Francisella, also requires this protein for organic hydroperoxide resistance as well as replication in macrophages and mice. This study expands our knowledge of Francisella's largely uncharacterized intracellular lifecycle and

  4. An integrated model for supplier selection process

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    In today's highly competitive manufacturing environment, the supplier selection process becomes one of crucial activities in supply chain management. In order to select the best supplier(s) it is not only necessary to continuously tracking and benchmarking performance of suppliers but also to make a tradeoff between tangible and intangible factors some of which may conflict. In this paper an integration of case-based reasoning (CBR), analytical network process (ANP) and linear programming (LP) is proposed to solve the supplier selection problem.

  5. Dealing with selection bias in educational transition models

    DEFF Research Database (Denmark)

    Holm, Anders; Jæger, Mads Meier

    2011-01-01

    This paper proposes the bivariate probit selection model (BPSM) as an alternative to the traditional Mare model for analyzing educational transitions. The BPSM accounts for selection on unobserved variables by allowing for unobserved variables which affect the probability of making educational tr...... account for selection on unobserved variables and high-quality data are both required in order to estimate credible educational transition models.......This paper proposes the bivariate probit selection model (BPSM) as an alternative to the traditional Mare model for analyzing educational transitions. The BPSM accounts for selection on unobserved variables by allowing for unobserved variables which affect the probability of making educational...... transitions to be correlated across transitions. We use simulated and real data to illustrate how the BPSM improves on the traditional Mare model in terms of correcting for selection bias and providing credible estimates of the effect of family background on educational success. We conclude that models which...

  6. The effect of mutation on Rhodococcus equi virulence plasmid gene expression and mouse virulence.

    Science.gov (United States)

    Ren, Jun; Prescott, John F

    2004-11-15

    An 81 kb virulence plasmid containing a pathogenicity island (PI) plays a crucial role in the pathogenesis of Rhodococcus equi pneumonia in foals but its specific function in virulence and regulation of plasmid-encoded virulence genes is unclear. Using a LacZ selection marker developed for R. equi in this study, in combination with an apramycin resistance gene, an efficient two-stage homologous recombination targeted gene mutation procedure was used to mutate three virulence plasmid genes, a LysR regulatory gene homologue (ORF4), a ResD-like two-component response regulator homologue (ORF8), and a gene (ORF10) of unknown function that is highly expressed by R. equi inside macrophages, as well as the chromosomal gene operon, phoPR. Virulence testing by liver clearance after intravenous injection in mice showed that the ORF4 and ORF8 mutants were fully attenuated, that the phoPR mutant was hypervirulent, and that virulence of the ORF10 mutant remained unchanged. A virulence plasmid DNA microarray was used to compare the plasmid gene expression profile of each of the four gene-targeted mutants against the parental R. equi strain. Changes were limited to PI genes and gene induction was observed for all mutants, suggesting that expression of virulence plasmid genes is dominated by a negative regulatory network. The finding of attenuation of ORF4 and ORF8 mutants despite enhanced transcription of vapA suggests that factors other than VapA are important for full expression of virulence. ORF1, a putative Lsr antigen gene, was strongly and similarly induced in all mutants, implying a common regulatory pathway affecting this gene for all four mutated genes. ORF8 is apparently the centre of this common pathway. Two distinct highly correlated gene induction patterns were observed, that of the ORF4 and ORF8 mutants, and that of the ORF10 and phoPR mutants. The gene induction pattern distinguishing these two groups paralleled their virulence in mice.

  7. A Bayesian random effects discrete-choice model for resource selection: Population-level selection inference

    Science.gov (United States)

    Thomas, D.L.; Johnson, D.; Griffith, B.

    2006-01-01

    Modeling the probability of use of land units characterized by discrete and continuous measures, we present a Bayesian random-effects model to assess resource selection. This model provides simultaneous estimation of both individual- and population-level selection. Deviance information criterion (DIC), a Bayesian alternative to AIC that is sample-size specific, is used for model selection. Aerial radiolocation data from 76 adult female caribou (Rangifer tarandus) and calf pairs during 1 year on an Arctic coastal plain calving ground were used to illustrate models and assess population-level selection of landscape attributes, as well as individual heterogeneity of selection. Landscape attributes included elevation, NDVI (a measure of forage greenness), and land cover-type classification. Results from the first of a 2-stage model-selection procedure indicated that there is substantial heterogeneity among cow-calf pairs with respect to selection of the landscape attributes. In the second stage, selection of models with heterogeneity included indicated that at the population-level, NDVI and land cover class were significant attributes for selection of different landscapes by pairs on the calving ground. Population-level selection coefficients indicate that the pairs generally select landscapes with higher levels of NDVI, but the relationship is quadratic. The highest rate of selection occurs at values of NDVI less than the maximum observed. Results for land cover-class selections coefficients indicate that wet sedge, moist sedge, herbaceous tussock tundra, and shrub tussock tundra are selected at approximately the same rate, while alpine and sparsely vegetated landscapes are selected at a lower rate. Furthermore, the variability in selection by individual caribou for moist sedge and sparsely vegetated landscapes is large relative to the variability in selection of other land cover types. The example analysis illustrates that, while sometimes computationally intense, a

  8. Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model.

    Directory of Open Access Journals (Sweden)

    Jing Luo

    Full Text Available The quorum sensing (QS circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS-controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has remained controversial due to emerging drug resistance; therefore, screening diverse compounds for anti-biofilm or anti-QS activities is important. This study demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. In addition, baicalin exerted dose-dependent inhibitory effects on virulence phenotypes (LasA protease, LasB elastase, pyocyanin, rhamnolipid, motilities and exotoxin A regulated by QS in Pseudomonas aeruginosa. Moreover, the expression levels of QS-regulatory genes, including lasI, lasR, rhlI, rhlR, pqsR and pqsA, were repressed after sub-MIC baicalin treatment, resulting in significant decreases in the QS signaling molecules 3-oxo-C12-HSL and C4-HSL, confirming the ability of baicalin-mediated QS inhibition to alter gene and protein expression. In vivo experiments indicated that baicalin treatment reduces Pseudomonas aeruginosa pathogenicity in Caenorhabditis elegans. Greater worm survival in the baicalin-treated group manifested as an increase in the LT50 from 24 to 96 h. In a mouse peritoneal implant infection model, baicalin treatment enhanced the clearance of Pseudomonas aeruginosa from the implants of mice infected with Pseudomonas aeruginosa compared with the control group. Moreover, the combination of baicalin and antibiotics significantly reduced the numbers of colony-forming units in the implants to a significantly greater degree than antibiotic treatment alone. Pathological and histological analyses revealed

  9. The effects of modeled microgravity on growth kinetics, antibiotic susceptibility, cold growth, and the virulence potential of a Yersinia pestis ymoA-deficient mutant and its isogenic parental strain.

    Science.gov (United States)

    Lawal, Abidat; Kirtley, Michelle L; van Lier, Christina J; Erova, Tatiana E; Kozlova, Elena V; Sha, Jian; Chopra, Ashok K; Rosenzweig, Jason A

    2013-09-01

    Previously, we reported that there was no enhancement in the virulence potential (as measured by cell culture infections) of the bacterial pathogen Yersinia pestis (YP) following modeled microgravity/clinorotation growth. We have now further characterized the effects of clinorotation (CR) on YP growth kinetics, antibiotic sensitivity, cold growth, and YP's virulence potential in a murine model of infection. Surprisingly, none of the aforementioned phenotypes were altered. To better understand why CR did not enhance YP's virulence potential as it did for other bacterial pathogens, a YP ΔymoA isogenic mutant in the KIM/D27 background strain that is unable to produce the histone-like YmoA protein and influences DNA topography was used in both cell culture and murine models of infection. YmoA represses type three secretion system (T3SS) virulence gene expression in the yersiniae. Similar to our CR-grown parental YP strain data, the CR-grown ΔymoA mutant induced reduced HeLa cell cytotoxicity with concomitantly decreased Yersinia outer protein E (YopE) and low calcium response V (LcrV) antigen production and secretion. Important, however, were our findings that, although no significant differences were observed in survival of mice infected intraperitoneally with either normal gravity (NG)- or CR-grown parental YP, the ΔymoA mutant induced significantly more mortality in infected mice than did the parental strain following CR growth. Taken together, our data demonstrate that CR did enhance the virulence potential of the YP ΔymoA mutant in a murine infection model (relative to the CR-grown parental strain), despite inducing less HeLa cell rounding in our cell culture infection assay due to reduced T3SS activity. Therefore, CR, which induces a unique type of bacterial stress, might be enhancing YP's virulence potential in vivo through a T3SS-independent mechanism when the histone-like YmoA protein is absent.

  10. Virulence of a Klebsiella pneumoniae strain carrying the New Delhi metallo-beta-lactamase-1 (NDM-1)

    DEFF Research Database (Denmark)

    Fuursted, Kurt; Schøler, Lone; Hansen, Frank

    2011-01-01

    , and in vitro virulence by assessing various virulence factors. The NDM-1 carrying K. pneumoniae isolate was the most virulent in the murine sepsis model but there was no clear cut correlation to in vitro virulence factors or killing in C. elegans. It is concluded that K. pneumoniae carrying NDM-1 have......The aim of the study was to compare and evaluate virulence in five strains of Klebsiella pneumoniae, including an isolate carrying New Delhi metallo-beta-lactamase-1 (NDM-1). In vivo virulence was assessed using a murine sepsis model and using the nematode Caenorhabditis elegans killing model...

  11. Plasmid-cured Chlamydia caviae activates TLR2-dependent signaling and retains virulence in the guinea pig model of genital tract infection.

    Science.gov (United States)

    Frazer, Lauren C; Darville, Toni; Chandra-Kuntal, Kumar; Andrews, Charles W; Zurenski, Matthew; Mintus, Margaret; AbdelRahman, Yasser M; Belland, Robert J; Ingalls, Robin R; O'Connell, Catherine M

    2012-01-01

    Loss of the conserved "cryptic" plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL) in C. caviae. However, 2-deoxyglucose (2DG) treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains.

  12. Plasmid-cured Chlamydia caviae activates TLR2-dependent signaling and retains virulence in the guinea pig model of genital tract infection.

    Directory of Open Access Journals (Sweden)

    Lauren C Frazer

    Full Text Available Loss of the conserved "cryptic" plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL in C. caviae. However, 2-deoxyglucose (2DG treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains.

  13. Uncertainty associated with selected environmental transport models

    International Nuclear Information System (INIS)

    Little, C.A.; Miller, C.W.

    1979-11-01

    A description is given of the capabilities of several models to predict accurately either pollutant concentrations in environmental media or radiological dose to human organs. The models are discussed in three sections: aquatic or surface water transport models, atmospheric transport models, and terrestrial and aquatic food chain models. Using data published primarily by model users, model predictions are compared to observations. This procedure is infeasible for food chain models and, therefore, the uncertainty embodied in the models input parameters, rather than the model output, is estimated. Aquatic transport models are divided into one-dimensional, longitudinal-vertical, and longitudinal-horizontal models. Several conclusions were made about the ability of the Gaussian plume atmospheric dispersion model to predict accurately downwind air concentrations from releases under several sets of conditions. It is concluded that no validation study has been conducted to test the predictions of either aquatic or terrestrial food chain models. Using the aquatic pathway from water to fish to an adult for 137 Cs as an example, a 95% one-tailed confidence limit interval for the predicted exposure is calculated by examining the distributions of the input parameters. Such an interval is found to be 16 times the value of the median exposure. A similar one-tailed limit for the air-grass-cow-milk-thyroid for 131 I and infants was 5.6 times the median dose. Of the three model types discussed in this report,the aquatic transport models appear to do the best job of predicting observed concentrations. However, this conclusion is based on many fewer aquatic validation data than were availaable for atmospheric model validation

  14. Comparison of antibiotic resistance, virulence gene profiles, and pathogenicity of methicillin-resistant and methicillin-susceptible Staphylococcus aureus using a Caenorhabditis elegans infection model

    Science.gov (United States)

    Thompson, Terissa; Brown, Paul D

    2014-01-01

    Objectives: This study compared the presence of 35 virulence genes, resistance phenotypes to 11 anti-staphylococcal antibiotics, and pathogenicity in methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). Methods: Multiplex PCR analysis was used to differentiate Staphylococcus aureus isolates (n = 102) based on characterization of the Staphylococcal Cassette Chromosome mec (SCCmec). Singleplex and multiplex PCR assays targeting 35 virulence determinants were used to analyze the virulence repertoire of S. aureus. In vitro activities of the antibiotics were determined by the disk-diffusion method. The pathogenicity of representative isolates was assessed using Caenorhabditis elegans survival assays. Significance in virulence distribution and antibiotic resistance phenotypes was assessed using the Chi-squared tests. Kaplan–Meier survival estimates were used to analyze nematode survival and significance of survival rates evaluated using the log-rank test. Results: Except for sei (staphylococcal enterotoxin I) (P  =  0.027), all other virulence genes were not significantly associated with MRSA. Resistance to clindamycin (P  =  0.03), tetracycline (P  =  0.048), trimethoprim/sulfamethoxazole (P  =  0.038), and oxacillin (P  =  0.004) was significantly associated with MRSA. Survival assay showed MSSA having a lower median lifespan of 3 days than MRSA that had a median lifespan of 6 days. The difference in the killing time of MRSA and MSSA was significant (P virulence genes. The quicker killing potential of MSSA compared to MRSA suggests that carriage of virulence determinants per se does not determine pathogenicity in S. aureus. Pathogenicity is impacted by other factors, possibly antibiotic resistance. PMID:25319852

  15. Quality Quandaries- Time Series Model Selection and Parsimony

    DEFF Research Database (Denmark)

    Bisgaard, Søren; Kulahci, Murat

    2009-01-01

    Some of the issues involved in selecting adequate models for time series data are discussed using an example concerning the number of users of an Internet server. The process of selecting an appropriate model is subjective and requires experience and judgment. The authors believe an important...... consideration in model selection should be parameter parsimony. They favor the use of parsimonious mixed ARMA models, noting that research has shown that a model building strategy that considers only autoregressive representations will lead to non-parsimonious models and to loss of forecasting accuracy....

  16. Toxin-independent virulence of Bacillus anthracis in rabbits.

    Directory of Open Access Journals (Sweden)

    Haim Levy

    Full Text Available The accepted paradigm states that anthrax is both an invasive and toxinogenic disease and that the toxins play a major role in pathogenicity. In the guinea pig (GP model we have previously shown that deletion of all three toxin components results in a relatively moderate attenuation in virulence, indicating that B. anthracis possesses an additional toxin-independent virulence mechanism. To characterize this toxin-independent mechanism in anthrax disease, we developed a new rabbit model by intravenous injection (IV of B. anthracis encapsulated vegetative cells, artificially creating bacteremia. Using this model we were able to demonstrate that also in rabbits, B. anthracis mutants lacking the toxins are capable of killing the host within 24 hours. This virulent trait depends on the activity of AtxA in the presence of pXO2, as, in the absence of the toxin genes, deletion of either component abolishes virulence. Furthermore, this IV virulence depends mainly on AtxA rather than the whole pXO1. A similar pattern was shown in the GP model using subcutaneous (SC administration of spores of the mutant strains, demonstrating the generality of the phenomenon. The virulent strains showed higher bacteremia levels and more efficient tissue dissemination; however our interpretation is that tissue dissemination per se is not the main determinant of virulence whose exact nature requires further elucidation.

  17. The Central Metabolism Regulator EIIAGlc Switches Salmonella from Growth Arrest to Acute Virulence through Activation of Virulence Factor Secretion

    Directory of Open Access Journals (Sweden)

    Alain Mazé

    2014-06-01

    Full Text Available The ability of Salmonella to cause disease depends on metabolic activities and virulence factors. Here, we show that a key metabolic protein, EIIAGlc, is absolutely essential for acute infection, but not for Salmonella survival, in a mouse typhoid fever model. Surprisingly, phosphorylation-dependent EIIAGlc functions, including carbohydrate transport and activation of adenylate cyclase for global regulation, do not explain this virulence phenotype. Instead, biochemical studies, in vitro secretion and translocation assays, and in vivo genetic epistasis experiments suggest that EIIAGlc binds to the type three secretion system 2 (TTSS-2 involved in systemic virulence, stabilizes its cytoplasmic part including the crucial TTSS-2 ATPase, and activates virulence factor secretion. This unexpected role of EIIAGlc reveals a striking direct link between central Salmonella metabolism and a crucial virulence mechanism.

  18. Selection of Hydrological Model for Waterborne Release

    International Nuclear Information System (INIS)

    Blanchard, A.

    1999-01-01

    This evaluation will aid in determining the potential impacts of liquid releases to downstream populations on the Savannah River. The purpose of this report is to evaluate the two available models and determine the appropriate model for use in following waterborne release analyses. Additionally, this report will document the Design Basis and Beyond Design Basis accidents to be used in the future study

  19. Application of Bayesian Model Selection for Metal Yield Models using ALEGRA and Dakota.

    Energy Technology Data Exchange (ETDEWEB)

    Portone, Teresa; Niederhaus, John Henry; Sanchez, Jason James; Swiler, Laura Painton

    2018-02-01

    This report introduces the concepts of Bayesian model selection, which provides a systematic means of calibrating and selecting an optimal model to represent a phenomenon. This has many potential applications, including for comparing constitutive models. The ideas described herein are applied to a model selection problem between different yield models for hardened steel under extreme loading conditions.

  20. Astrophysical Model Selection in Gravitational Wave Astronomy

    Science.gov (United States)

    Adams, Matthew R.; Cornish, Neil J.; Littenberg, Tyson B.

    2012-01-01

    Theoretical studies in gravitational wave astronomy have mostly focused on the information that can be extracted from individual detections, such as the mass of a binary system and its location in space. Here we consider how the information from multiple detections can be used to constrain astrophysical population models. This seemingly simple problem is made challenging by the high dimensionality and high degree of correlation in the parameter spaces that describe the signals, and by the complexity of the astrophysical models, which can also depend on a large number of parameters, some of which might not be directly constrained by the observations. We present a method for constraining population models using a hierarchical Bayesian modeling approach which simultaneously infers the source parameters and population model and provides the joint probability distributions for both. We illustrate this approach by considering the constraints that can be placed on population models for galactic white dwarf binaries using a future space-based gravitational wave detector. We find that a mission that is able to resolve approximately 5000 of the shortest period binaries will be able to constrain the population model parameters, including the chirp mass distribution and a characteristic galaxy disk radius to within a few percent. This compares favorably to existing bounds, where electromagnetic observations of stars in the galaxy constrain disk radii to within 20%.

  1. A model for selecting leadership styles.

    Science.gov (United States)

    Perkins, V J

    1992-01-01

    Occupational therapists lead a variety of groups during their professional activities. Such groups include therapy groups, treatment teams and management meetings. Therefore it is important for each therapist to understand theories of leadership and be able to select the most effective style for him or herself in specific situations. This paper presents a review of leadership theory and research as well as therapeutic groups. It then integrates these areas to assist students and new therapists in identifying a style that is effective for a particular group.

  2. Caenorhabditis elegans reveals novel Pseudomonas aeruginosa virulence mechanism

    NARCIS (Netherlands)

    Utari, Putri Dwi; Quax, Wim J.

    The susceptibility of Caenorhabditis elegans to different virulent phenotypes of Pseudomonas aeruginosa makes the worms an excellent model for studying host-pathogen interactions. Including the recently described liquid killing, five different killing assays are now available offering superb

  3. On Optimal Input Design and Model Selection for Communication Channels

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yanyan [ORNL; Djouadi, Seddik M [ORNL; Olama, Mohammed M [ORNL

    2013-01-01

    In this paper, the optimal model (structure) selection and input design which minimize the worst case identification error for communication systems are provided. The problem is formulated using metric complexity theory in a Hilbert space setting. It is pointed out that model selection and input design can be handled independently. Kolmogorov n-width is used to characterize the representation error introduced by model selection, while Gel fand and Time n-widths are used to represent the inherent error introduced by input design. After the model is selected, an optimal input which minimizes the worst case identification error is shown to exist. In particular, it is proven that the optimal model for reducing the representation error is a Finite Impulse Response (FIR) model, and the optimal input is an impulse at the start of the observation interval. FIR models are widely popular in communication systems, such as, in Orthogonal Frequency Division Multiplexing (OFDM) systems.

  4. Deficiency of double-strand DNA break repair does not impair Mycobacterium tuberculosis virulence in multiple animal models of infection.

    Science.gov (United States)

    Heaton, Brook E; Barkan, Daniel; Bongiorno, Paola; Karakousis, Petros C; Glickman, Michael S

    2014-08-01

    Mycobacterium tuberculosis persistence within its human host requires mechanisms to resist the effector molecules of host immunity, which exert their bactericidal effects through damaging pathogen proteins, membranes, and DNA. Substantial evidence indicates that bacterial pathogens, including M. tuberculosis, require DNA repair systems to repair the DNA damage inflicted by the host during infection, but the role of double-strand DNA break (DSB) repair systems is unclear. Double-strand DNA breaks are the most cytotoxic form of DNA damage and must be repaired for chromosome replication to proceed. M. tuberculosis elaborates three genetically distinct DSB repair systems: homologous recombination (HR), nonhomologous end joining (NHEJ), and single-strand annealing (SSA). NHEJ, which repairs DSBs in quiescent cells, may be particularly relevant to M. tuberculosis latency. However, very little information is available about the phenotype of DSB repair-deficient M. tuberculosis in animal models of infection. Here we tested M. tuberculosis strains lacking NHEJ (a Δku ΔligD strain), HR (a ΔrecA strain), or both (a ΔrecA Δku strain) in C57BL/6J mice, C3HeB/FeJ mice, guinea pigs, and a mouse hollow-fiber model of infection. We found no difference in bacterial load, histopathology, or host mortality between wild-type and DSB repair mutant strains in any model of infection. These results suggest that the animal models tested do not inflict DSBs on the mycobacterial chromosome, that other repair pathways can compensate for the loss of NHEJ and HR, or that DSB repair is not required for M. tuberculosis pathogenesis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  5. Invasion thresholds and the evolution of nonequilibrium virulence

    OpenAIRE

    Bull, J. J.; Ebert, D.

    2008-01-01

    Abstract The enterprise of virulence management attempts to predict how social practices and other factors affect the evolution of parasite virulence. These predictions are often based on parasite optima or evolutionary equilibria derived from models of host-parasite dynamics. Yet even when such models accurately capture the parasite optima, newly invading parasites will typically not be at their optima. Here we show that parasite invasion of a host population can occur despite highly nonopti...

  6. Model selection in kernel ridge regression

    DEFF Research Database (Denmark)

    Exterkate, Peter

    2013-01-01

    Kernel ridge regression is a technique to perform ridge regression with a potentially infinite number of nonlinear transformations of the independent variables as regressors. This method is gaining popularity as a data-rich nonlinear forecasting tool, which is applicable in many different contexts....... The influence of the choice of kernel and the setting of tuning parameters on forecast accuracy is investigated. Several popular kernels are reviewed, including polynomial kernels, the Gaussian kernel, and the Sinc kernel. The latter two kernels are interpreted in terms of their smoothing properties......, and the tuning parameters associated to all these kernels are related to smoothness measures of the prediction function and to the signal-to-noise ratio. Based on these interpretations, guidelines are provided for selecting the tuning parameters from small grids using cross-validation. A Monte Carlo study...

  7. Model Selection in Kernel Ridge Regression

    DEFF Research Database (Denmark)

    Exterkate, Peter

    Kernel ridge regression is gaining popularity as a data-rich nonlinear forecasting tool, which is applicable in many different contexts. This paper investigates the influence of the choice of kernel and the setting of tuning parameters on forecast accuracy. We review several popular kernels......, including polynomial kernels, the Gaussian kernel, and the Sinc kernel. We interpret the latter two kernels in terms of their smoothing properties, and we relate the tuning parameters associated to all these kernels to smoothness measures of the prediction function and to the signal-to-noise ratio. Based...... on these interpretations, we provide guidelines for selecting the tuning parameters from small grids using cross-validation. A Monte Carlo study confirms the practical usefulness of these rules of thumb. Finally, the flexible and smooth functional forms provided by the Gaussian and Sinc kernels makes them widely...

  8. Methods for model selection in applied science and engineering.

    Energy Technology Data Exchange (ETDEWEB)

    Field, Richard V., Jr.

    2004-10-01

    Mathematical models are developed and used to study the properties of complex systems and/or modify these systems to satisfy some performance requirements in just about every area of applied science and engineering. A particular reason for developing a model, e.g., performance assessment or design, is referred to as the model use. Our objective is the development of a methodology for selecting a model that is sufficiently accurate for an intended use. Information on the system being modeled is, in general, incomplete, so that there may be two or more models consistent with the available information. The collection of these models is called the class of candidate models. Methods are developed for selecting the optimal member from a class of candidate models for the system. The optimal model depends on the available information, the selected class of candidate models, and the model use. Classical methods for model selection, including the method of maximum likelihood and Bayesian methods, as well as a method employing a decision-theoretic approach, are formulated to select the optimal model for numerous applications. There is no requirement that the candidate models be random. Classical methods for model selection ignore model use and require data to be available. Examples are used to show that these methods can be unreliable when data is limited. The decision-theoretic approach to model selection does not have these limitations, and model use is included through an appropriate utility function. This is especially important when modeling high risk systems, where the consequences of using an inappropriate model for the system can be disastrous. The decision-theoretic method for model selection is developed and applied for a series of complex and diverse applications. These include the selection of the: (1) optimal order of the polynomial chaos approximation for non-Gaussian random variables and stationary stochastic processes, (2) optimal pressure load model to be

  9. Brucella, nitrogen and virulence.

    Science.gov (United States)

    Ronneau, Severin; Moussa, Simon; Barbier, Thibault; Conde-Álvarez, Raquel; Zuniga-Ripa, Amaia; Moriyon, Ignacio; Letesson, Jean-Jacques

    2016-08-01

    The brucellae are α-Proteobacteria causing brucellosis, an important zoonosis. Although multiplying in endoplasmic reticulum-derived vacuoles, they cause no cell death, suggesting subtle but efficient use of host resources. Brucellae are amino-acid prototrophs able to grow with ammonium or use glutamate as the sole carbon-nitrogen source in vitro. They contain more than twice amino acid/peptide/polyamine uptake genes than the amino-acid auxotroph Legionella pneumophila, which multiplies in a similar vacuole, suggesting a different nutritional strategy. During these two last decades, many mutants of key actors in nitrogen metabolism (transporters, enzymes, regulators, etc.) have been described to be essential for full virulence of brucellae. Here, we review the genomic and experimental data on Brucella nitrogen metabolism and its connection with virulence. An analysis of various aspects of this metabolism (transport, assimilation, biosynthesis, catabolism, respiration and regulation) has highlighted differences and similarities in nitrogen metabolism with other α-Proteobacteria. Together, these data suggest that, during their intracellular life cycle, the brucellae use various nitrogen sources for biosynthesis, catabolism and respiration following a strategy that requires prototrophy and a tight regulation of nitrogen use.

  10. Selection of Hydrological Model for Waterborne Release

    International Nuclear Information System (INIS)

    Blanchard, A.

    1999-01-01

    Following a request from the States of South Carolina and Georgia, downstream radiological consequences from postulated accidental aqueous releases at the three Savannah River Site nonreactor nuclear facilities will be examined. This evaluation will aid in determining the potential impacts of liquid releases to downstream populations on the Savannah River. The purpose of this report is to evaluate the two available models and determine the appropriate model for use in following waterborne release analyses. Additionally, this report will document the accidents to be used in the future study

  11. Random effect selection in generalised linear models

    DEFF Research Database (Denmark)

    Denwood, Matt; Houe, Hans; Forkman, Björn

    We analysed abattoir recordings of meat inspection codes with possible relevance to onfarm animal welfare in cattle. Random effects logistic regression models were used to describe individual-level data obtained from 461,406 cattle slaughtered in Denmark. Our results demonstrate that the largest...

  12. Adapting AIC to conditional model selection

    NARCIS (Netherlands)

    T. van Ommen (Thijs)

    2012-01-01

    textabstractIn statistical settings such as regression and time series, we can condition on observed information when predicting the data of interest. For example, a regression model explains the dependent variables $y_1, \\ldots, y_n$ in terms of the independent variables $x_1, \\ldots, x_n$.

  13. A Permutation Approach for Selecting the Penalty Parameter in Penalized Model Selection

    Science.gov (United States)

    Sabourin, Jeremy A; Valdar, William; Nobel, Andrew B

    2015-01-01

    Summary We describe a simple, computationally effcient, permutation-based procedure for selecting the penalty parameter in LASSO penalized regression. The procedure, permutation selection, is intended for applications where variable selection is the primary focus, and can be applied in a variety of structural settings, including that of generalized linear models. We briefly discuss connections between permutation selection and existing theory for the LASSO. In addition, we present a simulation study and an analysis of real biomedical data sets in which permutation selection is compared with selection based on the following: cross-validation (CV), the Bayesian information criterion (BIC), Scaled Sparse Linear Regression, and a selection method based on recently developed testing procedures for the LASSO. PMID:26243050

  14. The extracytoplasmic function sigma factor SigV plays a key role in the original model of lysozyme resistance and virulence of Enterococcus faecalis.

    Directory of Open Access Journals (Sweden)

    André Le Jeune

    Full Text Available BACKGROUND: Enterococcus faecalis is one of the leading agents of nosocomial infections. To cause diseases, pathogens or opportunistic bacteria have to adapt and survive to the defense systems encountered in the host. One of the most important compounds of the host innate defense response against invading microorganisms is lysozyme. It is found in a wide variety of body fluids, as well as in cells of the innate immune system. Lysozyme could act either as a muramidase and/or as a cationic antimicrobial peptide. Like Staphylococcus aureus, E. faecalis is one of the few bacteria that are completely lysozyme resistant. RESULTS: This study revealed that oatA (O-acetyl transferase and dlt (D-Alanylation of lipoteicoic acids genes contribute only partly to the lysozyme resistance of E. faecalis and that a specific transcriptional regulator, the extracytoplasmic function SigV sigma factor plays a key role in this event. Indeed, the sigV single mutant is as sensitive as the oatA/dltA double mutant, and the sigV/oatA/dltA triple mutant displays the highest level of lysozyme sensitivity suggesting synergistic effects of these genes. In S. aureus, mutation of both oatA and dlt genes abolishes completely the lysozyme resistance, whereas this is not the case in E. faecalis. Interestingly SigV does not control neither oatA nor dlt genes. Moreover, the sigV mutants clearly showed a reduced capacity to colonize host tissues, as they are significantly less recovered than the parental JH2-2 strain from organs of mice subjected to intravenous or urinary tract infections. CONCLUSIONS: This work led to the discovery of an original model of lysozyme resistance mechanism which is obviously more complex than those described for other Gram positive pathogens. Moreover, our data provide evidences for a direct link between lysozyme resistance and virulence of E. faecalis.

  15. The genealogy of samples in models with selection.

    Science.gov (United States)

    Neuhauser, C; Krone, S M

    1997-02-01

    We introduce the genealogy of a random sample of genes taken from a large haploid population that evolves according to random reproduction with selection and mutation. Without selection, the genealogy is described by Kingman's well-known coalescent process. In the selective case, the genealogy of the sample is embedded in a graph with a coalescing and branching structure. We describe this graph, called the ancestral selection graph, and point out differences and similarities with Kingman's coalescent. We present simulations for a two-allele model with symmetric mutation in which one of the alleles has a selective advantage over the other. We find that when the allele frequencies in the population are already in equilibrium, then the genealogy does not differ much from the neutral case. This is supported by rigorous results. Furthermore, we describe the ancestral selection graph for other selective models with finitely many selection classes, such as the K-allele models, infinitely-many-alleles models. DNA sequence models, and infinitely-many-sites models, and briefly discuss the diploid case.

  16. Modeling shape selection of buckled dielectric elastomers

    Science.gov (United States)

    Langham, Jacob; Bense, Hadrien; Barkley, Dwight

    2018-02-01

    A dielectric elastomer whose edges are held fixed will buckle, given a sufficiently applied voltage, resulting in a nontrivial out-of-plane deformation. We study this situation numerically using a nonlinear elastic model which decouples two of the principal electrostatic stresses acting on an elastomer: normal pressure due to the mutual attraction of oppositely charged electrodes and tangential shear ("fringing") due to repulsion of like charges at the electrode edges. These enter via physically simplified boundary conditions that are applied in a fixed reference domain using a nondimensional approach. The method is valid for small to moderate strains and is straightforward to implement in a generic nonlinear elasticity code. We validate the model by directly comparing the simulated equilibrium shapes with the experiment. For circular electrodes which buckle axisymetrically, the shape of the deflection profile is captured. Annular electrodes of different widths produce azimuthal ripples with wavelengths that match our simulations. In this case, it is essential to compute multiple equilibria because the first model solution obtained by the nonlinear solver (Newton's method) is often not the energetically favored state. We address this using a numerical technique known as "deflation." Finally, we observe the large number of different solutions that may be obtained for the case of a long rectangular strip.

  17. Polyamines Are Required for Virulence in Salmonella enterica Serovar Typhimurium

    DEFF Research Database (Denmark)

    Jelsbak, Lotte; Thomsen, Line Elnif; Wallrodt, Inke

    2012-01-01

    for studying typhoid fever. Central to its virulence are two major virulence loci Salmonella Pathogenicity Island 1 and 2 (SPI1 and SPI2). SPI1 promotes invasion of epithelial cells, whereas SPI2 enables S. Typhimurium to survive and proliferate within specialized compartments inside host cells. In this study......, we show that an S. Typhimurium polyamine mutant is defective for invasion, intracellular survival, killing of the nematode Caenorhabditis elegans and systemic infection of the mouse model of typhoid fever. Virulence of the mutant could be restored by genetic complementation, and invasion...

  18. Modeling HIV-1 drug resistance as episodic directional selection.

    Science.gov (United States)

    Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L; Scheffler, Konrad

    2012-01-01

    The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

  19. Modeling HIV-1 drug resistance as episodic directional selection.

    Directory of Open Access Journals (Sweden)

    Ben Murrell

    Full Text Available The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

  20. Multilevel and kin selection in a connected world

    DEFF Research Database (Denmark)

    Wade, Michael J; Wilson, David S; Goodnight, Charles

    2010-01-01

    in the opposition of two processes: within-group and among-group selection. This distinction is important in light of the current controversy among evolutionary biologists in which some continue to affirm that natural selection centres only and always at the level of the individual organism or gene, despite......Wild et al. argue that the evolution of reduced virulence can be understood from the perspective of inclusive fitness, obviating the need to evoke group selection as a contributing causal factor. Although they acknowledge the mathematical equivalence of the inclusive fitness and multilevel...... selection approaches, they conclude that reduced virulence can be viewed entirely as an individual-level adaptation by the parasite. Here we show that their model is a well-known special case of the more general theory of multilevel selection, and that the cause of reduced virulence resides...

  1. Variable selection for mixture and promotion time cure rate models.

    Science.gov (United States)

    Masud, Abdullah; Tu, Wanzhu; Yu, Zhangsheng

    2016-11-16

    Failure-time data with cured patients are common in clinical studies. Data from these studies are typically analyzed with cure rate models. Variable selection methods have not been well developed for cure rate models. In this research, we propose two least absolute shrinkage and selection operators based methods, for variable selection in mixture and promotion time cure models with parametric or nonparametric baseline hazards. We conduct an extensive simulation study to assess the operating characteristics of the proposed methods. We illustrate the use of the methods using data from a study of childhood wheezing. © The Author(s) 2016.

  2. Two-step variable selection in quantile regression models

    Directory of Open Access Journals (Sweden)

    FAN Yali

    2015-06-01

    Full Text Available We propose a two-step variable selection procedure for high dimensional quantile regressions, in which the dimension of the covariates, pn is much larger than the sample size n. In the first step, we perform ℓ1 penalty, and we demonstrate that the first step penalized estimator with the LASSO penalty can reduce the model from an ultra-high dimensional to a model whose size has the same order as that of the true model, and the selected model can cover the true model. The second step excludes the remained irrelevant covariates by applying the adaptive LASSO penalty to the reduced model obtained from the first step. Under some regularity conditions, we show that our procedure enjoys the model selection consistency. We conduct a simulation study and a real data analysis to evaluate the finite sample performance of the proposed approach.

  3. Virulence characterisation of Salmonella enterica isolates of differing antimicrobial resistance recovered from UK livestock and imported meat samples.

    Directory of Open Access Journals (Sweden)

    Roderick eCard

    2016-05-01

    Full Text Available Salmonella enterica is a foodborne zoonotic pathogen of significant public health concern. We have characterised the virulence and antimicrobial resistance gene content of 95 Salmonella isolates from 11 serovars by DNA microarray recovered from UK livestock or imported meat. Genes encoding resistance to sulphonamides (sul1, sul2, tetracycline (tet(A, tet(B, streptomycin (strA, strB, aminoglycoside (aadA1, aadA2, beta-lactam (blaTEM, and trimethoprim (dfrA17 were common. Virulence gene content differed between serovars; S. Typhimurium formed two subclades based on virulence plasmid presence. Thirteen isolates were selected by their virulence profile for pathotyping using the Galleria mellonella pathogenesis model. Infection with a chicken invasive S. Enteritidis or S. Gallinarum isolate, a multidrug resistant S. Kentucky, or a S. Typhimurium DT104 isolate resulted in high mortality of the larvae; notably presence of the virulence plasmid in S. Typhimurium was not associated with increased larvae mortality. Histopathological examination showed that infection caused severe damage to the Galleria gut structure. Enumeration of intracellular bacteria in the larvae 24 hours post-infection showed increases of up to 7 log above the initial inoculum and transmission electron microscopy (TEM showed bacterial replication in the haemolymph. TEM also revealed the presence of vacuoles containing bacteria in the haemocytes, similar to Salmonella containing vacuoles observed in mammalian macrophages; although there was no evidence from our work of bacterial replication within vacuoles. This work shows that microarrays can be used for rapid virulence genotyping of S. enterica and that the Galleria animal model replicates some aspects of Salmonella infection in mammals. These procedures can be used to help inform on the pathogenicity of isolates that may be antibiotic resistant and have scope to aid the assessment of their potential public and animal health risk.

  4. Partner Selection Optimization Model of Agricultural Enterprises in Supply Chain

    OpenAIRE

    Feipeng Guo; Qibei Lu

    2013-01-01

    With more and more importance of correctly selecting partners in supply chain of agricultural enterprises, a large number of partner evaluation techniques are widely used in the field of agricultural science research. This study established a partner selection model to optimize the issue of agricultural supply chain partner selection. Firstly, it constructed a comprehensive evaluation index system after analyzing the real characteristics of agricultural supply chain. Secondly, a heuristic met...

  5. Effect of Model Selection on Computed Water Balance Components

    NARCIS (Netherlands)

    Jhorar, R.K.; Smit, A.A.M.F.R.; Roest, C.W.J.

    2009-01-01

    Soil water flow modelling approaches as used in four selected on-farm water management models, namely CROPWAT. FAIDS, CERES and SWAP, are compared through numerical experiments. The soil water simulation approaches used in the first three models are reformulated to incorporate ail evapotranspiration

  6. Ensembling Variable Selectors by Stability Selection for the Cox Model

    Directory of Open Access Journals (Sweden)

    Qing-Yan Yin

    2017-01-01

    Full Text Available As a pivotal tool to build interpretive models, variable selection plays an increasingly important role in high-dimensional data analysis. In recent years, variable selection ensembles (VSEs have gained much interest due to their many advantages. Stability selection (Meinshausen and Bühlmann, 2010, a VSE technique based on subsampling in combination with a base algorithm like lasso, is an effective method to control false discovery rate (FDR and to improve selection accuracy in linear regression models. By adopting lasso as a base learner, we attempt to extend stability selection to handle variable selection problems in a Cox model. According to our experience, it is crucial to set the regularization region Λ in lasso and the parameter λmin properly so that stability selection can work well. To the best of our knowledge, however, there is no literature addressing this problem in an explicit way. Therefore, we first provide a detailed procedure to specify Λ and λmin. Then, some simulated and real-world data with various censoring rates are used to examine how well stability selection performs. It is also compared with several other variable selection approaches. Experimental results demonstrate that it achieves better or competitive performance in comparison with several other popular techniques.

  7. Validation of elk resource selection models with spatially independent data

    Science.gov (United States)

    Priscilla K. Coe; Bruce K. Johnson; Michael J. Wisdom; John G. Cook; Marty Vavra; Ryan M. Nielson

    2011-01-01

    Knowledge of how landscape features affect wildlife resource use is essential for informed management. Resource selection functions often are used to make and validate predictions about landscape use; however, resource selection functions are rarely validated with data from landscapes independent of those from which the models were built. This problem has severely...

  8. A Working Model of Natural Selection Illustrated by Table Tennis

    Science.gov (United States)

    Dinc, Muhittin; Kilic, Selda; Aladag, Caner

    2013-01-01

    Natural selection is one of the most important topics in biology and it helps to clarify the variety and complexity of organisms. However, students in almost every stage of education find it difficult to understand the mechanism of natural selection and they can develop misconceptions about it. This article provides an active model of natural…

  9. Augmented Self-Modeling as an Intervention for Selective Mutism

    Science.gov (United States)

    Kehle, Thomas J.; Bray, Melissa A.; Byer-Alcorace, Gabriel F.; Theodore, Lea A.; Kovac, Lisa M.

    2012-01-01

    Selective mutism is a rare disorder that is difficult to treat. It is often associated with oppositional defiant behavior, particularly in the home setting, social phobia, and, at times, autism spectrum disorder characteristics. The augmented self-modeling treatment has been relatively successful in promoting rapid diminishment of selective mutism…

  10. Response to selection in finite locus models with nonadditive effects

    NARCIS (Netherlands)

    Esfandyari, Hadi; Henryon, Mark; Berg, Peer; Thomasen, Jørn Rind; Bijma, Piter; Sørensen, Anders Christian

    2017-01-01

    Under the finite-locus model in the absence of mutation, the additive genetic variation is expected to decrease when directional selection is acting on a population, according to quantitative-genetic theory. However, some theoretical studies of selection suggest that the level of additive

  11. Elementary Teachers' Selection and Use of Visual Models

    Science.gov (United States)

    Lee, Tammy D.; Gail Jones, M.

    2018-02-01

    As science grows in complexity, science teachers face an increasing challenge of helping students interpret models that represent complex science systems. Little is known about how teachers select and use models when planning lessons. This mixed methods study investigated the pedagogical approaches and visual models used by elementary in-service and preservice teachers in the development of a science lesson about a complex system (e.g., water cycle). Sixty-seven elementary in-service and 69 elementary preservice teachers completed a card sort task designed to document the types of visual models (e.g., images) that teachers choose when planning science instruction. Quantitative and qualitative analyses were conducted to analyze the card sort task. Semistructured interviews were conducted with a subsample of teachers to elicit the rationale for image selection. Results from this study showed that both experienced in-service teachers and novice preservice teachers tended to select similar models and use similar rationales for images to be used in lessons. Teachers tended to select models that were aesthetically pleasing and simple in design and illustrated specific elements of the water cycle. The results also showed that teachers were not likely to select images that represented the less obvious dimensions of the water cycle. Furthermore, teachers selected visual models more as a pedagogical tool to illustrate specific elements of the water cycle and less often as a tool to promote student learning related to complex systems.

  12. Target Selection Models with Preference Variation Between Offenders

    NARCIS (Netherlands)

    Townsley, Michael; Birks, Daniel; Ruiter, Stijn; Bernasco, Wim; White, Gentry

    2016-01-01

    Objectives: This study explores preference variation in location choice strategies of residential burglars. Applying a model of offender target selection that is grounded in assertions of the routine activity approach, rational choice perspective, crime pattern and social disorganization theories,

  13. COPS model estimates of LLEA availability near selected reactor sites

    International Nuclear Information System (INIS)

    Berkbigler, K.P.

    1979-11-01

    The COPS computer model has been used to estimate local law enforcement agency (LLEA) officer availability in the neighborhood of selected nuclear reactor sites. The results of these analyses are presented both in graphic and tabular form in this report

  14. Molecular modelling of a chemodosimeter for the selective detection ...

    Indian Academy of Sciences (India)

    Wintec

    Molecular modelling of a chemodosimeter for the selective detection of. As(III) ion in water. † ... high levels of arsenic cause severe skin diseases in- cluding skin cancer ..... Special Attention to Groundwater in SE Asia (eds) D. Chakraborti, A ...

  15. Stenotrophomonas maltophilia isolated from patients exposed to invasive devices in a university hospital in Argentina: molecular typing, susceptibility and detection of potential virulence factors.

    Science.gov (United States)

    Alcaraz, Eliana; Garcia, Carlos; Papalia, Mariana; Vay, Carlos; Friedman, Laura; Passerini de Rossi, Beatriz

    2018-05-25

    The aim of this work was to investigate the presence of selected potential virulence factors, susceptibility and clonal relatedness among 63 Stenotrophomonas maltophilia isolates recovered from patients exposed to invasive devices in a university hospital in Argentina between January 2004 and August 2012. Genetic relatedness was assessed by enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and pulsed-field gel electrophoresis (PFGE). Isolates were characterized by antimicrobial resistance, the presence and/or expression of potential virulence determinants, and virulence in the Galleria mellonella model.Results/Key findings. ERIC-PCR generated 52 fingerprints, and PFGE added another pattern. Resistance to trimethoprim-sulfamethoxazole (6.35 %), levofloxacin (9.52 %) and ciprofloxacin (23.80 %) was detected. All isolates were susceptible to minocycline. All isolates were lipase, protease and siderophore producers, while all but Sm61 formed biofilms. However, 11/63 isolates did not amplify the major extracellular protease-coding gene (stmPr1). Sm61 is an stmPr1-negative isolate, and showed (as did Sm13 and the reference strain K279a) strong proteolysis and siderophore production, and high resistance to hydrogen peroxide. The three isolates were virulent in the G. mellonella model, while Sm10, a low-resistance hydrogen peroxide stmPr1-negative isolate, and weak proteolysis and siderophore producer, was not virulent. This is the first epidemiological study of the clonal relatedness of S. maltophilia clinical isolates in Argentina. Great genomic diversity was observed, and only two small clusters of related S. maltophilia types were found. Minocycline and trimethoprim-sulfamethoxazole were the most active agents. S. maltophilia virulence in the G. mellonella model is multifactorial, and further studies are needed to elucidate the role of each potential virulence factor.

  16. Model Selection in Continuous Test Norming With GAMLSS.

    Science.gov (United States)

    Voncken, Lieke; Albers, Casper J; Timmerman, Marieke E

    2017-06-01

    To compute norms from reference group test scores, continuous norming is preferred over traditional norming. A suitable continuous norming approach for continuous data is the use of the Box-Cox Power Exponential model, which is found in the generalized additive models for location, scale, and shape. Applying the Box-Cox Power Exponential model for test norming requires model selection, but it is unknown how well this can be done with an automatic selection procedure. In a simulation study, we compared the performance of two stepwise model selection procedures combined with four model-fit criteria (Akaike information criterion, Bayesian information criterion, generalized Akaike information criterion (3), cross-validation), varying data complexity, sampling design, and sample size in a fully crossed design. The new procedure combined with one of the generalized Akaike information criterion was the most efficient model selection procedure (i.e., required the smallest sample size). The advocated model selection procedure is illustrated with norming data of an intelligence test.

  17. Selection Criteria in Regime Switching Conditional Volatility Models

    Directory of Open Access Journals (Sweden)

    Thomas Chuffart

    2015-05-01

    Full Text Available A large number of nonlinear conditional heteroskedastic models have been proposed in the literature. Model selection is crucial to any statistical data analysis. In this article, we investigate whether the most commonly used selection criteria lead to choice of the right specification in a regime switching framework. We focus on two types of models: the Logistic Smooth Transition GARCH and the Markov-Switching GARCH models. Simulation experiments reveal that information criteria and loss functions can lead to misspecification ; BIC sometimes indicates the wrong regime switching framework. Depending on the Data Generating Process used in the experiments, great care is needed when choosing a criterion.

  18. The Use of Evolution in a Central Action Selection Model

    Directory of Open Access Journals (Sweden)

    F. Montes-Gonzalez

    2007-01-01

    Full Text Available The use of effective central selection provides flexibility in design by offering modularity and extensibility. In earlier papers we have focused on the development of a simple centralized selection mechanism. Our current goal is to integrate evolutionary methods in the design of non-sequential behaviours and the tuning of specific parameters of the selection model. The foraging behaviour of an animal robot (animat has been modelled in order to integrate the sensory information from the robot to perform selection that is nearly optimized by the use of genetic algorithms. In this paper we present how selection through optimization finally arranges the pattern of presented behaviours for the foraging task. Hence, the execution of specific parts in a behavioural pattern may be ruled out by the tuning of these parameters. Furthermore, the intensive use of colour segmentation from a colour camera for locating a cylinder sets a burden on the calculations carried out by the genetic algorithm.

  19. A Hybrid Multiple Criteria Decision Making Model for Supplier Selection

    Directory of Open Access Journals (Sweden)

    Chung-Min Wu

    2013-01-01

    Full Text Available The sustainable supplier selection would be the vital part in the management of a sustainable supply chain. In this study, a hybrid multiple criteria decision making (MCDM model is applied to select optimal supplier. The fuzzy Delphi method, which can lead to better criteria selection, is used to modify criteria. Considering the interdependence among the selection criteria, analytic network process (ANP is then used to obtain their weights. To avoid calculation and additional pairwise comparisons of ANP, a technique for order preference by similarity to ideal solution (TOPSIS is used to rank the alternatives. The use of a combination of the fuzzy Delphi method, ANP, and TOPSIS, proposing an MCDM model for supplier selection, and applying these to a real case are the unique features of this study.

  20. Variable selection in Logistic regression model with genetic algorithm.

    Science.gov (United States)

    Zhang, Zhongheng; Trevino, Victor; Hoseini, Sayed Shahabuddin; Belciug, Smaranda; Boopathi, Arumugam Manivanna; Zhang, Ping; Gorunescu, Florin; Subha, Velappan; Dai, Songshi

    2018-02-01

    Variable or feature selection is one of the most important steps in model specification. Especially in the case of medical-decision making, the direct use of a medical database, without a previous analysis and preprocessing step, is often counterproductive. In this way, the variable selection represents the method of choosing the most relevant attributes from the database in order to build a robust learning models and, thus, to improve the performance of the models used in the decision process. In biomedical research, the purpose of variable selection is to select clinically important and statistically significant variables, while excluding unrelated or noise variables. A variety of methods exist for variable selection, but none of them is without limitations. For example, the stepwise approach, which is highly used, adds the best variable in each cycle generally producing an acceptable set of variables. Nevertheless, it is limited by the fact that it commonly trapped in local optima. The best subset approach can systematically search the entire covariate pattern space, but the solution pool can be extremely large with tens to hundreds of variables, which is the case in nowadays clinical data. Genetic algorithms (GA) are heuristic optimization approaches and can be used for variable selection in multivariable regression models. This tutorial paper aims to provide a step-by-step approach to the use of GA in variable selection. The R code provided in the text can be extended and adapted to other data analysis needs.

  1. Applying Four Different Risk Models in Local Ore Selection

    International Nuclear Information System (INIS)

    Richmond, Andrew

    2002-01-01

    Given the uncertainty in grade at a mine location, a financially risk-averse decision-maker may prefer to incorporate this uncertainty into the ore selection process. A FORTRAN program risksel is presented to calculate local risk-adjusted optimal ore selections using a negative exponential utility function and three dominance models: mean-variance, mean-downside risk, and stochastic dominance. All four methods are demonstrated in a grade control environment. In the case study, optimal selections range with the magnitude of financial risk that a decision-maker is prepared to accept. Except for the stochastic dominance method, the risk models reassign material from higher cost to lower cost processing options as the aversion to financial risk increases. The stochastic dominance model usually was unable to determine the optimal local selection

  2. Statistical model selection with “Big Data”

    Directory of Open Access Journals (Sweden)

    Jurgen A. Doornik

    2015-12-01

    Full Text Available Big Data offer potential benefits for statistical modelling, but confront problems including an excess of false positives, mistaking correlations for causes, ignoring sampling biases and selecting by inappropriate methods. We consider the many important requirements when searching for a data-based relationship using Big Data, and the possible role of Autometrics in that context. Paramount considerations include embedding relationships in general initial models, possibly restricting the number of variables to be selected over by non-statistical criteria (the formulation problem, using good quality data on all variables, analyzed with tight significance levels by a powerful selection procedure, retaining available theory insights (the selection problem while testing for relationships being well specified and invariant to shifts in explanatory variables (the evaluation problem, using a viable approach that resolves the computational problem of immense numbers of possible models.

  3. Virulence Factors Associated with Enterococcus Faecalis Infective Endocarditis

    DEFF Research Database (Denmark)

    Madsen, Kristian T; Skov, Marianne N; Gill, Sabine

    2017-01-01

    INTRODUCTION: The enterococci are accountable for up to 20% of all cases of infective endocarditis, with Enterococcus faecalis being the primary causative isolate. Infective endocarditis is a life-threatening infection of the endocardium that results in the formation of vegetations. Based...... on a literature review, this paper provides an overview of the virulence factors associated with E. faecalis infective endocarditis. Furthermore, it reports the effects of active or passive immunization against some of these involved factors. INDIVIDUAL VIRULENCE FACTORS: Nine virulence factors have in particular...... been associated with E. faecalis infective endocarditis. Absence of these factors entailed attenuation of strains in both mixed- and mono-bacterial infection endocarditis models as well as in in vitro and ex vivo assays when compared to their virulence factor expressing parental strains. PATHOGENESIS...

  4. Selection, calibration, and validation of models of tumor growth.

    Science.gov (United States)

    Lima, E A B F; Oden, J T; Hormuth, D A; Yankeelov, T E; Almeida, R C

    2016-11-01

    This paper presents general approaches for addressing some of the most important issues in predictive computational oncology concerned with developing classes of predictive models of tumor growth. First, the process of developing mathematical models of vascular tumors evolving in the complex, heterogeneous, macroenvironment of living tissue; second, the selection of the most plausible models among these classes, given relevant observational data; third, the statistical calibration and validation of models in these classes, and finally, the prediction of key Quantities of Interest (QOIs) relevant to patient survival and the effect of various therapies. The most challenging aspects of this endeavor is that all of these issues often involve confounding uncertainties: in observational data, in model parameters, in model selection, and in the features targeted in the prediction. Our approach can be referred to as "model agnostic" in that no single model is advocated; rather, a general approach that explores powerful mixture-theory representations of tissue behavior while accounting for a range of relevant biological factors is presented, which leads to many potentially predictive models. Then representative classes are identified which provide a starting point for the implementation of OPAL, the Occam Plausibility Algorithm (OPAL) which enables the modeler to select the most plausible models (for given data) and to determine if the model is a valid tool for predicting tumor growth and morphology ( in vivo ). All of these approaches account for uncertainties in the model, the observational data, the model parameters, and the target QOI. We demonstrate these processes by comparing a list of models for tumor growth, including reaction-diffusion models, phase-fields models, and models with and without mechanical deformation effects, for glioma growth measured in murine experiments. Examples are provided that exhibit quite acceptable predictions of tumor growth in laboratory

  5. Comparison of climate envelope models developed using expert-selected variables versus statistical selection

    Science.gov (United States)

    Brandt, Laura A.; Benscoter, Allison; Harvey, Rebecca G.; Speroterra, Carolina; Bucklin, David N.; Romañach, Stephanie; Watling, James I.; Mazzotti, Frank J.

    2017-01-01

    Climate envelope models are widely used to describe potential future distribution of species under different climate change scenarios. It is broadly recognized that there are both strengths and limitations to using climate envelope models and that outcomes are sensitive to initial assumptions, inputs, and modeling methods Selection of predictor variables, a central step in modeling, is one of the areas where different techniques can yield varying results. Selection of climate variables to use as predictors is often done using statistical approaches that develop correlations between occurrences and climate data. These approaches have received criticism in that they rely on the statistical properties of the data rather than directly incorporating biological information about species responses to temperature and precipitation. We evaluated and compared models and prediction maps for 15 threatened or endangered species in Florida based on two variable selection techniques: expert opinion and a statistical method. We compared model performance between these two approaches for contemporary predictions, and the spatial correlation, spatial overlap and area predicted for contemporary and future climate predictions. In general, experts identified more variables as being important than the statistical method and there was low overlap in the variable sets (0.9 for area under the curve (AUC) and >0.7 for true skill statistic (TSS). Spatial overlap, which compares the spatial configuration between maps constructed using the different variable selection techniques, was only moderate overall (about 60%), with a great deal of variability across species. Difference in spatial overlap was even greater under future climate projections, indicating additional divergence of model outputs from different variable selection techniques. Our work is in agreement with other studies which have found that for broad-scale species distribution modeling, using statistical methods of variable

  6. CRISPR interference can prevent natural transformation and virulence acquisition during in vivo bacterial infection.

    Science.gov (United States)

    Bikard, David; Hatoum-Aslan, Asma; Mucida, Daniel; Marraffini, Luciano A

    2012-08-16

    Pathogenic bacterial strains emerge largely due to transfer of virulence and antimicrobial resistance genes between bacteria, a process known as horizontal gene transfer (HGT). Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci of bacteria and archaea encode a sequence-specific defense mechanism against bacteriophages and constitute a programmable barrier to HGT. However, the impact of CRISPRs on the emergence of virulence is unknown. We programmed the human pathogen Streptococcus pneumoniae with CRISPR sequences that target capsule genes, an essential pneumococcal virulence factor, and show that CRISPR interference can prevent transformation of nonencapsulated, avirulent pneumococci into capsulated, virulent strains during infection in mice. Further, at low frequencies bacteria can lose CRISPR function, acquire capsule genes, and mount a successful infection. These results demonstrate that CRISPR interference can prevent the emergence of virulence in vivo and that strong selective pressure for virulence or antibiotic resistance can lead to CRISPR loss in bacterial pathogens. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Models of microbiome evolution incorporating host and microbial selection.

    Science.gov (United States)

    Zeng, Qinglong; Wu, Steven; Sukumaran, Jeet; Rodrigo, Allen

    2017-09-25

    Numerous empirical studies suggest that hosts and microbes exert reciprocal selective effects on their ecological partners. Nonetheless, we still lack an explicit framework to model the dynamics of both hosts and microbes under selection. In a previous study, we developed an agent-based forward-time computational framework to simulate the neutral evolution of host-associated microbial communities in a constant-sized, unstructured population of hosts. These neutral models allowed offspring to sample microbes randomly from parents and/or from the environment. Additionally, the environmental pool of available microbes was constituted by fixed and persistent microbial OTUs and by contributions from host individuals in the preceding generation. In this paper, we extend our neutral models to allow selection to operate on both hosts and microbes. We do this by constructing a phenome for each microbial OTU consisting of a sample of traits that influence host and microbial fitnesses independently. Microbial traits can influence the fitness of hosts ("host selection") and the fitness of microbes ("trait-mediated microbial selection"). Additionally, the fitness effects of traits on microbes can be modified by their hosts ("host-mediated microbial selection"). We simulate the effects of these three types of selection, individually or in combination, on microbiome diversities and the fitnesses of hosts and microbes over several thousand generations of hosts. We show that microbiome diversity is strongly influenced by selection acting on microbes. Selection acting on hosts only influences microbiome diversity when there is near-complete direct or indirect parental contribution to the microbiomes of offspring. Unsurprisingly, microbial fitness increases under microbial selection. Interestingly, when host selection operates, host fitness only increases under two conditions: (1) when there is a strong parental contribution to microbial communities or (2) in the absence of a strong

  8. Virulence Factors of Streptococcus mutans.

    Science.gov (United States)

    1986-08-01

    763512/715242 Final Report U VIRULENCE FACTORS OF STREPTOCOCCUS MUTANS U Samuel Rosen Department of Oral Biology For the Period April 1, 1983 - June 30...00 FINAL REPORT VIRULENCE FACTORS OF STREPTOCOCCUS MUTANS Sam Rosen, Irving Shklair, E. X. Beck and F. M. Beck Ohio State University Columbus,Oh and...206-212. Johnson CP, Gorss S, Hillman JD (1978). Cariogenic properties of LDH deficient mutants of streptococcus mutans . J Dent Res 57, Special Issue

  9. Development of an Environment for Software Reliability Model Selection

    Science.gov (United States)

    1992-09-01

    now is directed to other related problems such as tools for model selection, multiversion programming, and software fault tolerance modeling... multiversion programming, 7. Hlardware can be repaired by spare modules, which is not. the case for software, 2-6 N. Preventive maintenance is very important

  10. Fuzzy Investment Portfolio Selection Models Based on Interval Analysis Approach

    Directory of Open Access Journals (Sweden)

    Haifeng Guo

    2012-01-01

    Full Text Available This paper employs fuzzy set theory to solve the unintuitive problem of the Markowitz mean-variance (MV portfolio model and extend it to a fuzzy investment portfolio selection model. Our model establishes intervals for expected returns and risk preference, which can take into account investors' different investment appetite and thus can find the optimal resolution for each interval. In the empirical part, we test this model in Chinese stocks investment and find that this model can fulfill different kinds of investors’ objectives. Finally, investment risk can be decreased when we add investment limit to each stock in the portfolio, which indicates our model is useful in practice.

  11. Diversified models for portfolio selection based on uncertain semivariance

    Science.gov (United States)

    Chen, Lin; Peng, Jin; Zhang, Bo; Rosyida, Isnaini

    2017-02-01

    Since the financial markets are complex, sometimes the future security returns are represented mainly based on experts' estimations due to lack of historical data. This paper proposes a semivariance method for diversified portfolio selection, in which the security returns are given subjective to experts' estimations and depicted as uncertain variables. In the paper, three properties of the semivariance of uncertain variables are verified. Based on the concept of semivariance of uncertain variables, two types of mean-semivariance diversified models for uncertain portfolio selection are proposed. Since the models are complex, a hybrid intelligent algorithm which is based on 99-method and genetic algorithm is designed to solve the models. In this hybrid intelligent algorithm, 99-method is applied to compute the expected value and semivariance of uncertain variables, and genetic algorithm is employed to seek the best allocation plan for portfolio selection. At last, several numerical examples are presented to illustrate the modelling idea and the effectiveness of the algorithm.

  12. A Primer for Model Selection: The Decisive Role of Model Complexity

    Science.gov (United States)

    Höge, Marvin; Wöhling, Thomas; Nowak, Wolfgang

    2018-03-01

    Selecting a "best" model among several competing candidate models poses an often encountered problem in water resources modeling (and other disciplines which employ models). For a modeler, the best model fulfills a certain purpose best (e.g., flood prediction), which is typically assessed by comparing model simulations to data (e.g., stream flow). Model selection methods find the "best" trade-off between good fit with data and model complexity. In this context, the interpretations of model complexity implied by different model selection methods are crucial, because they represent different underlying goals of modeling. Over the last decades, numerous model selection criteria have been proposed, but modelers who primarily want to apply a model selection criterion often face a lack of guidance for choosing the right criterion that matches their goal. We propose a classification scheme for model selection criteria that helps to find the right criterion for a specific goal, i.e., which employs the correct complexity interpretation. We identify four model selection classes which seek to achieve high predictive density, low predictive error, high model probability, or shortest compression of data. These goals can be achieved by following either nonconsistent or consistent model selection and by either incorporating a Bayesian parameter prior or not. We allocate commonly used criteria to these four classes, analyze how they represent model complexity and what this means for the model selection task. Finally, we provide guidance on choosing the right type of criteria for specific model selection tasks. (A quick guide through all key points is given at the end of the introduction.)

  13. Selection of climate change scenario data for impact modelling

    DEFF Research Database (Denmark)

    Sloth Madsen, M; Fox Maule, C; MacKellar, N

    2012-01-01

    Impact models investigating climate change effects on food safety often need detailed climate data. The aim of this study was to select climate change projection data for selected crop phenology and mycotoxin impact models. Using the ENSEMBLES database of climate model output, this study...... illustrates how the projected climate change signal of important variables as temperature, precipitation and relative humidity depends on the choice of the climate model. Using climate change projections from at least two different climate models is recommended to account for model uncertainty. To make...... the climate projections suitable for impact analysis at the local scale a weather generator approach was adopted. As the weather generator did not treat all the necessary variables, an ad-hoc statistical method was developed to synthesise realistic values of missing variables. The method is presented...

  14. A SUPPLIER SELECTION MODEL FOR SOFTWARE DEVELOPMENT OUTSOURCING

    Directory of Open Access Journals (Sweden)

    Hancu Lucian-Viorel

    2010-12-01

    Full Text Available This paper presents a multi-criteria decision making model used for supplier selection for software development outsourcing on e-marketplaces. This model can be used in auctions. The supplier selection process becomes complex and difficult on last twenty years since the Internet plays an important role in business management. Companies have to concentrate their efforts on their core activities and the others activities should be realized by outsourcing. They can achieve significant cost reduction by using e-marketplaces in their purchase process and by using decision support systems on supplier selection. In the literature were proposed many approaches for supplier evaluation and selection process. The performance of potential suppliers is evaluated using multi criteria decision making methods rather than considering a single factor cost.

  15. Adverse Selection Models with Three States of Nature

    Directory of Open Access Journals (Sweden)

    Daniela MARINESCU

    2011-02-01

    Full Text Available In the paper we analyze an adverse selection model with three states of nature, where both the Principal and the Agent are risk neutral. When solving the model, we use the informational rents and the efforts as variables. We derive the optimal contract in the situation of asymmetric information. The paper ends with the characteristics of the optimal contract and the main conclusions of the model.

  16. Comparing the staffing models of outsourcing in selected companies

    OpenAIRE

    Chaloupková, Věra

    2010-01-01

    This thesis deals with problems of takeover of employees in outsourcing. The capital purpose is to compare the staffing model of outsourcing in selected companies. To compare in selected companies I chose multi-criteria analysis. This thesis is dividend into six chapters. The first charter is devoted to the theoretical part. In this charter describes the basic concepts as outsourcing, personal aspects, phase of the outsourcing projects, communications and culture. The rest of thesis is devote...

  17. ERP Software Selection Model using Analytic Network Process

    OpenAIRE

    Lesmana , Andre Surya; Astanti, Ririn Diar; Ai, The Jin

    2014-01-01

    During the implementation of Enterprise Resource Planning (ERP) in any company, one of the most important issues is the selection of ERP software that can satisfy the needs and objectives of the company. This issue is crucial since it may affect the duration of ERP implementation and the costs incurred for the ERP implementation. This research tries to construct a model of the selection of ERP software that are beneficial to the company in order to carry out the selection of the right ERP sof...

  18. Economic assessment model architecture for AGC/AVLIS selection

    International Nuclear Information System (INIS)

    Hoglund, R.L.

    1984-01-01

    The economic assessment model architecture described provides the flexibility and completeness in economic analysis that the selection between AGC and AVLIS demands. Process models which are technology-specific will provide the first-order responses of process performance and cost to variations in process parameters. The economics models can be used to test the impacts of alternative deployment scenarios for a technology. Enterprise models provide global figures of merit for evaluating the DOE perspective on the uranium enrichment enterprise, and business analysis models compute the financial parameters from the private investor's viewpoint

  19. IT vendor selection model by using structural equation model & analytical hierarchy process

    Science.gov (United States)

    Maitra, Sarit; Dominic, P. D. D.

    2012-11-01

    Selecting and evaluating the right vendors is imperative for an organization's global marketplace competitiveness. Improper selection and evaluation of potential vendors can dwarf an organization's supply chain performance. Numerous studies have demonstrated that firms consider multiple criteria when selecting key vendors. This research intends to develop a new hybrid model for vendor selection process with better decision making. The new proposed model provides a suitable tool for assisting decision makers and managers to make the right decisions and select the most suitable vendor. This paper proposes a Hybrid model based on Structural Equation Model (SEM) and Analytical Hierarchy Process (AHP) for long-term strategic vendor selection problems. The five steps framework of the model has been designed after the thorough literature study. The proposed hybrid model will be applied using a real life case study to assess its effectiveness. In addition, What-if analysis technique will be used for model validation purpose.

  20. Model Selection in Historical Research Using Approximate Bayesian Computation

    Science.gov (United States)

    Rubio-Campillo, Xavier

    2016-01-01

    Formal Models and History Computational models are increasingly being used to study historical dynamics. This new trend, which could be named Model-Based History, makes use of recently published datasets and innovative quantitative methods to improve our understanding of past societies based on their written sources. The extensive use of formal models allows historians to re-evaluate hypotheses formulated decades ago and still subject to debate due to the lack of an adequate quantitative framework. The initiative has the potential to transform the discipline if it solves the challenges posed by the study of historical dynamics. These difficulties are based on the complexities of modelling social interaction, and the methodological issues raised by the evaluation of formal models against data with low sample size, high variance and strong fragmentation. Case Study This work examines an alternate approach to this evaluation based on a Bayesian-inspired model selection method. The validity of the classical Lanchester’s laws of combat is examined against a dataset comprising over a thousand battles spanning 300 years. Four variations of the basic equations are discussed, including the three most common formulations (linear, squared, and logarithmic) and a new variant introducing fatigue. Approximate Bayesian Computation is then used to infer both parameter values and model selection via Bayes Factors. Impact Results indicate decisive evidence favouring the new fatigue model. The interpretation of both parameter estimations and model selection provides new insights into the factors guiding the evolution of warfare. At a methodological level, the case study shows how model selection methods can be used to guide historical research through the comparison between existing hypotheses and empirical evidence. PMID:26730953

  1. Sample selection and taste correlation in discrete choice transport modelling

    DEFF Research Database (Denmark)

    Mabit, Stefan Lindhard

    2008-01-01

    explain counterintuitive results in value of travel time estimation. However, the results also point at the difficulty of finding suitable instruments for the selection mechanism. Taste heterogeneity is another important aspect of discrete choice modelling. Mixed logit models are designed to capture...... the question for a broader class of models. It is shown that the original result may be somewhat generalised. Another question investigated is whether mode choice operates as a self-selection mechanism in the estimation of the value of travel time. The results show that self-selection can at least partly...... of taste correlation in willingness-to-pay estimation are presented. The first contribution addresses how to incorporate taste correlation in the estimation of the value of travel time for public transport. Given a limited dataset the approach taken is to use theory on the value of travel time as guidance...

  2. Short-Run Asset Selection using a Logistic Model

    Directory of Open Access Journals (Sweden)

    Walter Gonçalves Junior

    2011-06-01

    Full Text Available Investors constantly look for significant predictors and accurate models to forecast future results, whose occasional efficacy end up being neutralized by market efficiency. Regardless, such predictors are widely used for seeking better (and more unique perceptions. This paper aims to investigate to what extent some of the most notorious indicators have discriminatory power to select stocks, and if it is feasible with such variables to build models that could anticipate those with good performance. In order to do that, logistical regressions were conducted with stocks traded at Bovespa using the selected indicators as explanatory variables. Investigated in this study were the outputs of Bovespa Index, liquidity, the Sharpe Ratio, ROE, MB, size and age evidenced to be significant predictors. Also examined were half-year, logistical models, which were adjusted in order to check the potential acceptable discriminatory power for the asset selection.

  3. Uncertain programming models for portfolio selection with uncertain returns

    Science.gov (United States)

    Zhang, Bo; Peng, Jin; Li, Shengguo

    2015-10-01

    In an indeterminacy economic environment, experts' knowledge about the returns of securities consists of much uncertainty instead of randomness. This paper discusses portfolio selection problem in uncertain environment in which security returns cannot be well reflected by historical data, but can be evaluated by the experts. In the paper, returns of securities are assumed to be given by uncertain variables. According to various decision criteria, the portfolio selection problem in uncertain environment is formulated as expected-variance-chance model and chance-expected-variance model by using the uncertainty programming. Within the framework of uncertainty theory, for the convenience of solving the models, some crisp equivalents are discussed under different conditions. In addition, a hybrid intelligent algorithm is designed in the paper to provide a general method for solving the new models in general cases. At last, two numerical examples are provided to show the performance and applications of the models and algorithm.

  4. The Properties of Model Selection when Retaining Theory Variables

    DEFF Research Database (Denmark)

    Hendry, David F.; Johansen, Søren

    Economic theories are often fitted directly to data to avoid possible model selection biases. We show that embedding a theory model that specifies the correct set of m relevant exogenous variables, x{t}, within the larger set of m+k candidate variables, (x{t},w{t}), then selection over the second...... set by their statistical significance can be undertaken without affecting the estimator distribution of the theory parameters. This strategy returns the theory-parameter estimates when the theory is correct, yet protects against the theory being under-specified because some w{t} are relevant....

  5. The expression and evolution of virulence in multiple infections: the role of specificity, relative virulence and relative dose.

    Science.gov (United States)

    Ben-Ami, Frida; Routtu, Jarkko

    2013-05-03

    Multiple infections of the same host by different strains of the same microparasite species are believed to play a crucial role during the evolution of parasite virulence. We investigated the role of specificity, relative virulence and relative dose in determining the competitive outcome of multiple infections in the Daphnia magna-Pasteuria ramosa host-parasite system. We found that infections by P. ramosa clones (single genotype) were less virulent and produced more spores than infections by P. ramosa isolates (possibly containing multiple genotypes). We also found that two similarly virulent isolates of P. ramosa differed considerably in their within-host competitiveness and their effects on host offspring production when faced with coinfecting P. ramosa isolates and clones. Although the relative virulence of a P. ramosa isolate/clone appears to be a good indicator of its competitiveness during multiple infections, the relative dose may alter the competitive outcome. Moreover, spore counts on day 20 post-infection indicate that the competitive outcome is largely decided early in the parasite's growth phase, possibly mediated by direct interference or apparent competition. Our results emphasize the importance of epidemiology as well as of various parasite traits in determining the outcome of within-host competition. Incorporating realistic epidemiological and ecological conditions when testing theoretical models of multiple infections, as well as using a wider range of host and parasite genotypes, will enable us to better understand the course of virulence evolution.

  6. Fixation probability in a two-locus intersexual selection model.

    Science.gov (United States)

    Durand, Guillermo; Lessard, Sabin

    2016-06-01

    We study a two-locus model of intersexual selection in a finite haploid population reproducing according to a discrete-time Moran model with a trait locus expressed in males and a preference locus expressed in females. We show that the probability of ultimate fixation of a single mutant allele for a male ornament introduced at random at the trait locus given any initial frequency state at the preference locus is increased by weak intersexual selection and recombination, weak or strong. Moreover, this probability exceeds the initial frequency of the mutant allele even in the case of a costly male ornament if intersexual selection is not too weak. On the other hand, the probability of ultimate fixation of a single mutant allele for a female preference towards a male ornament introduced at random at the preference locus is increased by weak intersexual selection and weak recombination if the female preference is not costly, and is strong enough in the case of a costly male ornament. The analysis relies on an extension of the ancestral recombination-selection graph for samples of haplotypes to take into account events of intersexual selection, while the symbolic calculation of the fixation probabilities is made possible in a reasonable time by an optimizing algorithm. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Spatial Fleming-Viot models with selection and mutation

    CERN Document Server

    Dawson, Donald A

    2014-01-01

    This book constructs a rigorous framework for analysing selected phenomena in evolutionary theory of populations arising due to the combined effects of migration, selection and mutation in a spatial stochastic population model, namely the evolution towards fitter and fitter types through punctuated equilibria. The discussion is based on a number of new methods, in particular multiple scale analysis, nonlinear Markov processes and their entrance laws, atomic measure-valued evolutions and new forms of duality (for state-dependent mutation and multitype selection) which are used to prove ergodic theorems in this context and are applicable for many other questions and renormalization analysis for a variety of phenomena (stasis, punctuated equilibrium, failure of naive branching approximations, biodiversity) which occur due to the combination of rare mutation, mutation, resampling, migration and selection and make it necessary to mathematically bridge the gap (in the limit) between time and space scales.

  8. Uniform design based SVM model selection for face recognition

    Science.gov (United States)

    Li, Weihong; Liu, Lijuan; Gong, Weiguo

    2010-02-01

    Support vector machine (SVM) has been proved to be a powerful tool for face recognition. The generalization capacity of SVM depends on the model with optimal hyperparameters. The computational cost of SVM model selection results in application difficulty in face recognition. In order to overcome the shortcoming, we utilize the advantage of uniform design--space filling designs and uniformly scattering theory to seek for optimal SVM hyperparameters. Then we propose a face recognition scheme based on SVM with optimal model which obtained by replacing the grid and gradient-based method with uniform design. The experimental results on Yale and PIE face databases show that the proposed method significantly improves the efficiency of SVM model selection.

  9. How Many Separable Sources? Model Selection In Independent Components Analysis

    DEFF Research Database (Denmark)

    Woods, Roger P.; Hansen, Lars Kai; Strother, Stephen

    2015-01-01

    among potential model categories with differing numbers of Gaussian components. Based on simulation studies, the assumptions and approximations underlying the Akaike Information Criterion do not hold in this setting, even with a very large number of observations. Cross-validation is a suitable, though....../Principal Components Analysis (mixed ICA/PCA) model described here accommodates one or more Gaussian components in the independent components analysis model and uses principal components analysis to characterize contributions from this inseparable Gaussian subspace. Information theory can then be used to select from...... might otherwise be questionable. Failure of the Akaike Information Criterion in model selection also has relevance in traditional independent components analysis where all sources are assumed non-Gaussian....

  10. Selecting an optimal mixed products using grey relationship model

    Directory of Open Access Journals (Sweden)

    Farshad Faezy Razi

    2013-06-01

    Full Text Available This paper presents an integrated supplier selection and inventory management using grey relationship model (GRM as well as multi-objective decision making process. The proposed model of this paper first ranks different suppliers based on GRM technique and then determines the optimum level of inventory by considering different objectives. To show the implementation of the proposed model, we use some benchmark data presented by Talluri and Baker [Talluri, S., & Baker, R. C. (2002. A multi-phase mathematical programming approach for effective supply chain design. European Journal of Operational Research, 141(3, 544-558.]. The preliminary results indicate that the proposed model of this paper is capable of handling different criteria for supplier selection.

  11. Model selection and inference a practical information-theoretic approach

    CERN Document Server

    Burnham, Kenneth P

    1998-01-01

    This book is unique in that it covers the philosophy of model-based data analysis and an omnibus strategy for the analysis of empirical data The book introduces information theoretic approaches and focuses critical attention on a priori modeling and the selection of a good approximating model that best represents the inference supported by the data Kullback-Leibler information represents a fundamental quantity in science and is Hirotugu Akaike's basis for model selection The maximized log-likelihood function can be bias-corrected to provide an estimate of expected, relative Kullback-Leibler information This leads to Akaike's Information Criterion (AIC) and various extensions and these are relatively simple and easy to use in practice, but little taught in statistics classes and far less understood in the applied sciences than should be the case The information theoretic approaches provide a unified and rigorous theory, an extension of likelihood theory, an important application of information theory, and are ...

  12. Working covariance model selection for generalized estimating equations.

    Science.gov (United States)

    Carey, Vincent J; Wang, You-Gan

    2011-11-20

    We investigate methods for data-based selection of working covariance models in the analysis of correlated data with generalized estimating equations. We study two selection criteria: Gaussian pseudolikelihood and a geodesic distance based on discrepancy between model-sensitive and model-robust regression parameter covariance estimators. The Gaussian pseudolikelihood is found in simulation to be reasonably sensitive for several response distributions and noncanonical mean-variance relations for longitudinal data. Application is also made to a clinical dataset. Assessment of adequacy of both correlation and variance models for longitudinal data should be routine in applications, and we describe open-source software supporting this practice. Copyright © 2011 John Wiley & Sons, Ltd.

  13. Evidence accumulation as a model for lexical selection.

    Science.gov (United States)

    Anders, R; Riès, S; van Maanen, L; Alario, F X

    2015-11-01

    We propose and demonstrate evidence accumulation as a plausible theoretical and/or empirical model for the lexical selection process of lexical retrieval. A number of current psycholinguistic theories consider lexical selection as a process related to selecting a lexical target from a number of alternatives, which each have varying activations (or signal supports), that are largely resultant of an initial stimulus recognition. We thoroughly present a case for how such a process may be theoretically explained by the evidence accumulation paradigm, and we demonstrate how this paradigm can be directly related or combined with conventional psycholinguistic theory and their simulatory instantiations (generally, neural network models). Then with a demonstrative application on a large new real data set, we establish how the empirical evidence accumulation approach is able to provide parameter results that are informative to leading psycholinguistic theory, and that motivate future theoretical development. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Integrated model for supplier selection and performance evaluation

    Directory of Open Access Journals (Sweden)

    Borges de Araújo, Maria Creuza

    2015-08-01

    Full Text Available This paper puts forward a model for selecting suppliers and evaluating the performance of those already working with a company. A simulation was conducted in a food industry. This sector has high significance in the economy of Brazil. The model enables the phases of selecting and evaluating suppliers to be integrated. This is important so that a company can have partnerships with suppliers who are able to meet their needs. Additionally, a group method is used to enable managers who will be affected by this decision to take part in the selection stage. Finally, the classes resulting from the performance evaluation are shown to support the contractor in choosing the most appropriate relationship with its suppliers.

  15. Attention-based Memory Selection Recurrent Network for Language Modeling

    OpenAIRE

    Liu, Da-Rong; Chuang, Shun-Po; Lee, Hung-yi

    2016-01-01

    Recurrent neural networks (RNNs) have achieved great success in language modeling. However, since the RNNs have fixed size of memory, their memory cannot store all the information about the words it have seen before in the sentence, and thus the useful long-term information may be ignored when predicting the next words. In this paper, we propose Attention-based Memory Selection Recurrent Network (AMSRN), in which the model can review the information stored in the memory at each previous time ...

  16. Phages can constrain protist predation-driven attenuation of Pseudomonas aeruginosa virulence in multienemy communities

    Science.gov (United States)

    Friman, Ville-Petri; Buckling, Angus

    2014-01-01

    The coincidental theory of virulence predicts that bacterial pathogenicity could be a by-product of selection by natural enemies in environmental reservoirs. However, current results are ambiguous and the simultaneous impact of multiple ubiquitous enemies, protists and phages on virulence evolution has not been investigated previously. Here we tested experimentally how Tetrahymena thermophila protist predation and PNM phage parasitism (bacteria-specific virus) alone and together affect the evolution of Pseudomonas aeruginosa PAO1 virulence, measured in wax moth larvae. Protist predation selected for small colony types, both in the absence and presence of phage, which showed decreased edibility to protists, reduced growth in the absence of enemies and attenuated virulence. Although phage selection alone did not affect the bacterial phenotype, it weakened protist-driven antipredatory defence (biofilm formation), its associated pleiotropic growth cost and the correlated reduction in virulence. These results suggest that protist selection can be a strong coincidental driver of attenuated bacterial virulence, and that phages can constrain this effect owing to effects on population dynamics and conflicting selection pressures. Attempting to define causal links such as these might help us to predict the cold and hot spots of coincidental virulence evolution on the basis of microbial community composition of environmental reservoirs. PMID:24671085

  17. The Selection of ARIMA Models with or without Regressors

    DEFF Research Database (Denmark)

    Johansen, Søren; Riani, Marco; Atkinson, Anthony C.

    We develop a $C_{p}$ statistic for the selection of regression models with stationary and nonstationary ARIMA error term. We derive the asymptotic theory of the maximum likelihood estimators and show they are consistent and asymptotically Gaussian. We also prove that the distribution of the sum...

  18. Model selection for contingency tables with algebraic statistics

    NARCIS (Netherlands)

    Krampe, A.; Kuhnt, S.; Gibilisco, P.; Riccimagno, E.; Rogantin, M.P.; Wynn, H.P.

    2009-01-01

    Goodness-of-fit tests based on chi-square approximations are commonly used in the analysis of contingency tables. Results from algebraic statistics combined with MCMC methods provide alternatives to the chi-square approximation. However, within a model selection procedure usually a large number of

  19. Computationally efficient thermal-mechanical modelling of selective laser melting

    NARCIS (Netherlands)

    Yang, Y.; Ayas, C.; Brabazon, Dermot; Naher, Sumsun; Ul Ahad, Inam

    2017-01-01

    The Selective laser melting (SLM) is a powder based additive manufacturing (AM) method to produce high density metal parts with complex topology. However, part distortions and accompanying residual stresses deteriorates the mechanical reliability of SLM products. Modelling of the SLM process is

  20. Multivariate time series modeling of selected childhood diseases in ...

    African Journals Online (AJOL)

    This paper is focused on modeling the five most prevalent childhood diseases in Akwa Ibom State using a multivariate approach to time series. An aggregate of 78,839 reported cases of malaria, upper respiratory tract infection (URTI), Pneumonia, anaemia and tetanus were extracted from five randomly selected hospitals in ...

  1. Rank-based model selection for multiple ions quantum tomography

    International Nuclear Information System (INIS)

    Guţă, Mădălin; Kypraios, Theodore; Dryden, Ian

    2012-01-01

    The statistical analysis of measurement data has become a key component of many quantum engineering experiments. As standard full state tomography becomes unfeasible for large dimensional quantum systems, one needs to exploit prior information and the ‘sparsity’ properties of the experimental state in order to reduce the dimensionality of the estimation problem. In this paper we propose model selection as a general principle for finding the simplest, or most parsimonious explanation of the data, by fitting different models and choosing the estimator with the best trade-off between likelihood fit and model complexity. We apply two well established model selection methods—the Akaike information criterion (AIC) and the Bayesian information criterion (BIC)—two models consisting of states of fixed rank and datasets such as are currently produced in multiple ions experiments. We test the performance of AIC and BIC on randomly chosen low rank states of four ions, and study the dependence of the selected rank with the number of measurement repetitions for one ion states. We then apply the methods to real data from a four ions experiment aimed at creating a Smolin state of rank 4. By applying the two methods together with the Pearson χ 2 test we conclude that the data can be suitably described with a model whose rank is between 7 and 9. Additionally we find that the mean square error of the maximum likelihood estimator for pure states is close to that of the optimal over all possible measurements. (paper)

  2. Harbouring public good mutants within a pathogen population can increase both fitness and virulence.

    Science.gov (United States)

    Lindsay, Richard J; Kershaw, Michael J; Pawlowska, Bogna J; Talbot, Nicholas J; Gudelj, Ivana

    2016-12-28

    Existing theory, empirical, clinical and field research all predict that reducing the virulence of individuals within a pathogen population will reduce the overall virulence, rendering disease less severe. Here, we show that this seemingly successful disease management strategy can fail with devastating consequences for infected hosts. We deploy cooperation theory and a novel synthetic system involving the rice blast fungus Magnaporthe oryzae . In vivo infections of rice demonstrate that M. oryzae virulence is enhanced, quite paradoxically, when a public good mutant is present in a population of high-virulence pathogens. We reason that during infection, the fungus engages in multiple cooperative acts to exploit host resources. We establish a multi-trait cooperation model which suggests that the observed failure of the virulence reduction strategy is caused by the interference between different social traits. Multi-trait cooperative interactions are widespread, so we caution against the indiscriminant application of anti-virulence therapy as a disease-management strategy.

  3. Measures and limits of models of fixation selection.

    Directory of Open Access Journals (Sweden)

    Niklas Wilming

    Full Text Available Models of fixation selection are a central tool in the quest to understand how the human mind selects relevant information. Using this tool in the evaluation of competing claims often requires comparing different models' relative performance in predicting eye movements. However, studies use a wide variety of performance measures with markedly different properties, which makes a comparison difficult. We make three main contributions to this line of research: First we argue for a set of desirable properties, review commonly used measures, and conclude that no single measure unites all desirable properties. However the area under the ROC curve (a classification measure and the KL-divergence (a distance measure of probability distributions combine many desirable properties and allow a meaningful comparison of critical model performance. We give an analytical proof of the linearity of the ROC measure with respect to averaging over subjects and demonstrate an appropriate correction of entropy-based measures like KL-divergence for small sample sizes in the context of eye-tracking data. Second, we provide a lower bound and an upper bound of these measures, based on image-independent properties of fixation data and between subject consistency respectively. Based on these bounds it is possible to give a reference frame to judge the predictive power of a model of fixation selection. We provide open-source python code to compute the reference frame. Third, we show that the upper, between subject consistency bound holds only for models that predict averages of subject populations. Departing from this we show that incorporating subject-specific viewing behavior can generate predictions which surpass that upper bound. Taken together, these findings lay out the required information that allow a well-founded judgment of the quality of any model of fixation selection and should therefore be reported when a new model is introduced.

  4. Generalized Selectivity Description for Polymeric Ion-Selective Electrodes Based on the Phase Boundary Potential Model.

    Science.gov (United States)

    Bakker, Eric

    2010-02-15

    A generalized description of the response behavior of potentiometric polymer membrane ion-selective electrodes is presented on the basis of ion-exchange equilibrium considerations at the sample-membrane interface. This paper includes and extends on previously reported theoretical advances in a more compact yet more comprehensive form. Specifically, the phase boundary potential model is used to derive the origin of the Nernstian response behavior in a single expression, which is valid for a membrane containing any charge type and complex stoichiometry of ionophore and ion-exchanger. This forms the basis for a generalized expression of the selectivity coefficient, which may be used for the selectivity optimization of ion-selective membranes containing electrically charged and neutral ionophores of any desired stoichiometry. It is shown to reduce to expressions published previously for specialized cases, and may be effectively applied to problems relevant in modern potentiometry. The treatment is extended to mixed ion solutions, offering a comprehensive yet formally compact derivation of the response behavior of ion-selective electrodes to a mixture of ions of any desired charge. It is compared to predictions by the less accurate Nicolsky-Eisenman equation. The influence of ion fluxes or any form of electrochemical excitation is not considered here, but may be readily incorporated if an ion-exchange equilibrium at the interface may be assumed in these cases.

  5. Fisher-Wright model with deterministic seed bank and selection.

    Science.gov (United States)

    Koopmann, Bendix; Müller, Johannes; Tellier, Aurélien; Živković, Daniel

    2017-04-01

    Seed banks are common characteristics to many plant species, which allow storage of genetic diversity in the soil as dormant seeds for various periods of time. We investigate an above-ground population following a Fisher-Wright model with selection coupled with a deterministic seed bank assuming the length of the seed bank is kept constant and the number of seeds is large. To assess the combined impact of seed banks and selection on genetic diversity, we derive a general diffusion model. The applied techniques outline a path of approximating a stochastic delay differential equation by an appropriately rescaled stochastic differential equation. We compute the equilibrium solution of the site-frequency spectrum and derive the times to fixation of an allele with and without selection. Finally, it is demonstrated that seed banks enhance the effect of selection onto the site-frequency spectrum while slowing down the time until the mutation-selection equilibrium is reached. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Forecasting house prices in the 50 states using Dynamic Model Averaging and Dynamic Model Selection

    DEFF Research Database (Denmark)

    Bork, Lasse; Møller, Stig Vinther

    2015-01-01

    We examine house price forecastability across the 50 states using Dynamic Model Averaging and Dynamic Model Selection, which allow for model change and parameter shifts. By allowing the entire forecasting model to change over time and across locations, the forecasting accuracy improves substantia......We examine house price forecastability across the 50 states using Dynamic Model Averaging and Dynamic Model Selection, which allow for model change and parameter shifts. By allowing the entire forecasting model to change over time and across locations, the forecasting accuracy improves...

  7. How Many Separable Sources? Model Selection In Independent Components Analysis

    Science.gov (United States)

    Woods, Roger P.; Hansen, Lars Kai; Strother, Stephen

    2015-01-01

    Unlike mixtures consisting solely of non-Gaussian sources, mixtures including two or more Gaussian components cannot be separated using standard independent components analysis methods that are based on higher order statistics and independent observations. The mixed Independent Components Analysis/Principal Components Analysis (mixed ICA/PCA) model described here accommodates one or more Gaussian components in the independent components analysis model and uses principal components analysis to characterize contributions from this inseparable Gaussian subspace. Information theory can then be used to select from among potential model categories with differing numbers of Gaussian components. Based on simulation studies, the assumptions and approximations underlying the Akaike Information Criterion do not hold in this setting, even with a very large number of observations. Cross-validation is a suitable, though computationally intensive alternative for model selection. Application of the algorithm is illustrated using Fisher's iris data set and Howells' craniometric data set. Mixed ICA/PCA is of potential interest in any field of scientific investigation where the authenticity of blindly separated non-Gaussian sources might otherwise be questionable. Failure of the Akaike Information Criterion in model selection also has relevance in traditional independent components analysis where all sources are assumed non-Gaussian. PMID:25811988

  8. A model for the sustainable selection of building envelope assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Huedo, Patricia, E-mail: huedo@uji.es [Universitat Jaume I (Spain); Mulet, Elena, E-mail: emulet@uji.es [Universitat Jaume I (Spain); López-Mesa, Belinda, E-mail: belinda@unizar.es [Universidad de Zaragoza (Spain)

    2016-02-15

    The aim of this article is to define an evaluation model for the environmental impacts of building envelopes to support planners in the early phases of materials selection. The model is intended to estimate environmental impacts for different combinations of building envelope assemblies based on scientifically recognised sustainability indicators. These indicators will increase the amount of information that existing catalogues show to support planners in the selection of building assemblies. To define the model, first the environmental indicators were selected based on the specific aims of the intended sustainability assessment. Then, a simplified LCA methodology was developed to estimate the impacts applicable to three types of dwellings considering different envelope assemblies, building orientations and climate zones. This methodology takes into account the manufacturing, installation, maintenance and use phases of the building. Finally, the model was validated and a matrix in Excel was created as implementation of the model. - Highlights: • Method to assess the envelope impacts based on a simplified LCA • To be used at an earlier phase than the existing methods in a simple way. • It assigns a score by means of known sustainability indicators. • It estimates data about the embodied and operating environmental impacts. • It compares the investment costs with the costs of the consumed energy.

  9. A model for the sustainable selection of building envelope assemblies

    International Nuclear Information System (INIS)

    Huedo, Patricia; Mulet, Elena; López-Mesa, Belinda

    2016-01-01

    The aim of this article is to define an evaluation model for the environmental impacts of building envelopes to support planners in the early phases of materials selection. The model is intended to estimate environmental impacts for different combinations of building envelope assemblies based on scientifically recognised sustainability indicators. These indicators will increase the amount of information that existing catalogues show to support planners in the selection of building assemblies. To define the model, first the environmental indicators were selected based on the specific aims of the intended sustainability assessment. Then, a simplified LCA methodology was developed to estimate the impacts applicable to three types of dwellings considering different envelope assemblies, building orientations and climate zones. This methodology takes into account the manufacturing, installation, maintenance and use phases of the building. Finally, the model was validated and a matrix in Excel was created as implementation of the model. - Highlights: • Method to assess the envelope impacts based on a simplified LCA • To be used at an earlier phase than the existing methods in a simple way. • It assigns a score by means of known sustainability indicators. • It estimates data about the embodied and operating environmental impacts. • It compares the investment costs with the costs of the consumed energy.

  10. On selection of optimal stochastic model for accelerated life testing

    International Nuclear Information System (INIS)

    Volf, P.; Timková, J.

    2014-01-01

    This paper deals with the problem of proper lifetime model selection in the context of statistical reliability analysis. Namely, we consider regression models describing the dependence of failure intensities on a covariate, for instance, a stressor. Testing the model fit is standardly based on the so-called martingale residuals. Their analysis has already been studied by many authors. Nevertheless, the Bayes approach to the problem, in spite of its advantages, is just developing. We shall present the Bayes procedure of estimation in several semi-parametric regression models of failure intensity. Then, our main concern is the Bayes construction of residual processes and goodness-of-fit tests based on them. The method is illustrated with both artificial and real-data examples. - Highlights: • Statistical survival and reliability analysis and Bayes approach. • Bayes semi-parametric regression modeling in Cox's and AFT models. • Bayes version of martingale residuals and goodness-of-fit test

  11. Model building strategy for logistic regression: purposeful selection.

    Science.gov (United States)

    Zhang, Zhongheng

    2016-03-01

    Logistic regression is one of the most commonly used models to account for confounders in medical literature. The article introduces how to perform purposeful selection model building strategy with R. I stress on the use of likelihood ratio test to see whether deleting a variable will have significant impact on model fit. A deleted variable should also be checked for whether it is an important adjustment of remaining covariates. Interaction should be checked to disentangle complex relationship between covariates and their synergistic effect on response variable. Model should be checked for the goodness-of-fit (GOF). In other words, how the fitted model reflects the real data. Hosmer-Lemeshow GOF test is the most widely used for logistic regression model.

  12. Statistical modelling in biostatistics and bioinformatics selected papers

    CERN Document Server

    Peng, Defen

    2014-01-01

    This book presents selected papers on statistical model development related mainly to the fields of Biostatistics and Bioinformatics. The coverage of the material falls squarely into the following categories: (a) Survival analysis and multivariate survival analysis, (b) Time series and longitudinal data analysis, (c) Statistical model development and (d) Applied statistical modelling. Innovations in statistical modelling are presented throughout each of the four areas, with some intriguing new ideas on hierarchical generalized non-linear models and on frailty models with structural dispersion, just to mention two examples. The contributors include distinguished international statisticians such as Philip Hougaard, John Hinde, Il Do Ha, Roger Payne and Alessandra Durio, among others, as well as promising newcomers. Some of the contributions have come from researchers working in the BIO-SI research programme on Biostatistics and Bioinformatics, centred on the Universities of Limerick and Galway in Ireland and fu...

  13. Modeling and Solving the Liner Shipping Service Selection Problem

    DEFF Research Database (Denmark)

    Karsten, Christian Vad; Balakrishnan, Anant

    We address a tactical planning problem, the Liner Shipping Service Selection Problem (LSSSP), facing container shipping companies. Given estimated demand between various ports, the LSSSP entails selecting the best subset of non-simple cyclic sailing routes from a given pool of candidate routes...... to accurately model transshipment costs and incorporate routing policies such as maximum transit time, maritime cabotage rules, and operational alliances. Our hop-indexed arc flow model is smaller and easier to solve than path flow models. We outline a preprocessing procedure that exploits both the routing...... requirements and the hop limits to reduce problem size, and describe techniques to accelerate the solution procedure. We present computational results for realistic problem instances from the benchmark suite LINER-LIB....

  14. Variable Selection for Regression Models of Percentile Flows

    Science.gov (United States)

    Fouad, G.

    2017-12-01

    Percentile flows describe the flow magnitude equaled or exceeded for a given percent of time, and are widely used in water resource management. However, these statistics are normally unavailable since most basins are ungauged. Percentile flows of ungauged basins are often predicted using regression models based on readily observable basin characteristics, such as mean elevation. The number of these independent variables is too large to evaluate all possible models. A subset of models is typically evaluated using automatic procedures, like stepwise regression. This ignores a large variety of methods from the field of feature (variable) selection and physical understanding of percentile flows. A study of 918 basins in the United States was conducted to compare an automatic regression procedure to the following variable selection methods: (1) principal component analysis, (2) correlation analysis, (3) random forests, (4) genetic programming, (5) Bayesian networks, and (6) physical understanding. The automatic regression procedure only performed better than principal component analysis. Poor performance of the regression procedure was due to a commonly used filter for multicollinearity, which rejected the strongest models because they had cross-correlated independent variables. Multicollinearity did not decrease model performance in validation because of a representative set of calibration basins. Variable selection methods based strictly on predictive power (numbers 2-5 from above) performed similarly, likely indicating a limit to the predictive power of the variables. Similar performance was also reached using variables selected based on physical understanding, a finding that substantiates recent calls to emphasize physical understanding in modeling for predictions in ungauged basins. The strongest variables highlighted the importance of geology and land cover, whereas widely used topographic variables were the weakest predictors. Variables suffered from a high

  15. Studies on the virulence and attenuation of Trypanosoma cruzi using immunodeficient animals

    Directory of Open Access Journals (Sweden)

    Basombrío Miguel Ángel

    2000-01-01

    Full Text Available Tissue invasion and pathology by Trypanosoma cruzi result from an interaction between parasite virulence and host immunity. Successive in vivo generations of the parasite select populations with increasing ability to invade the host. Conversely, prolonged in vitro selection of the parasite produces attenuated sublines with low infectivity for mammals. One such subline (TCC clone has been extensively used in our laboratory as experimental vaccine and tested in comparative experiments with its virulent ancestor (TUL. The experiments here reviewed aimed at the use of immunodeficient mice for testing the infectivity of TCC parasites. It has not been possible to obtain virulent, revertant sublines by prolonged passaged in such mice.

  16. Numerical Model based Reliability Estimation of Selective Laser Melting Process

    DEFF Research Database (Denmark)

    Mohanty, Sankhya; Hattel, Jesper Henri

    2014-01-01

    Selective laser melting is developing into a standard manufacturing technology with applications in various sectors. However, the process is still far from being at par with conventional processes such as welding and casting, the primary reason of which is the unreliability of the process. While...... of the selective laser melting process. A validated 3D finite-volume alternating-direction-implicit numerical technique is used to model the selective laser melting process, and is calibrated against results from single track formation experiments. Correlation coefficients are determined for process input...... parameters such as laser power, speed, beam profile, etc. Subsequently, uncertainties in the processing parameters are utilized to predict a range for the various outputs, using a Monte Carlo method based uncertainty analysis methodology, and the reliability of the process is established....

  17. Modelling Technical and Economic Parameters in Selection of Manufacturing Devices

    Directory of Open Access Journals (Sweden)

    Naqib Daneshjo

    2017-11-01

    Full Text Available Sustainable science and technology development is also conditioned by continuous development of means of production which have a key role in structure of each production system. Mechanical nature of the means of production is complemented by controlling and electronic devices in context of intelligent industry. A selection of production machines for a technological process or technological project has so far been practically resolved, often only intuitively. With regard to increasing intelligence, the number of variable parameters that have to be considered when choosing a production device is also increasing. It is necessary to use computing techniques and decision making methods according to heuristic methods and more precise methodological procedures during the selection. The authors present an innovative model for optimization of technical and economic parameters in the selection of manufacturing devices for industry 4.0.

  18. Bacterial Prostatitis: Bacterial Virulence, Clinical Outcomes, and New Directions.

    Science.gov (United States)

    Krieger, John N; Thumbikat, Praveen

    2016-02-01

    Four prostatitis syndromes are recognized clinically: acute bacterial prostatitis, chronic bacterial prostatitis, chronic prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatitis. Because Escherichia coli represents the most common cause of bacterial prostatitis, we investigated the importance of bacterial virulence factors and antimicrobial resistance in E. coli strains causing prostatitis and the potential association of these characteristics with clinical outcomes. A structured literature review revealed that we have limited understanding of the virulence-associated characteristics of E. coli causing acute prostatitis. Therefore, we completed a comprehensive microbiological and molecular investigation of a unique strain collection isolated from healthy young men. We also considered new data from an animal model system suggesting certain E. coli might prove important in the etiology of chronic prostatitis/chronic pelvic pain syndrome. Our human data suggest that E. coli needs multiple pathogenicity-associated traits to overcome anatomic and immune responses in healthy young men without urological risk factors. The phylogenetic background and accumulation of an exceptional repertoire of extraintestinal pathogenic virulence-associated genes indicate that these E. coli strains belong to a highly virulent subset of uropathogenic variants. In contrast, antibiotic resistance confers little added advantage to E. coli strains in these healthy outpatients. Our animal model data also suggest that certain pathogenic E. coli may be important in the etiology of chronic prostatitis/chronic pelvic pain syndrome through mechanisms that are dependent on the host genetic background and the virulence of the bacterial strain.

  19. Selection of Models for Ingestion Pathway and Relocation Radii Determination

    International Nuclear Information System (INIS)

    Blanchard, A.

    1998-01-01

    The distance at which intermediate phase protective actions (such as food interdiction and relocation) may be needed following postulated accidents at three Savannah River Site nonreactor nuclear facilities will be determined by modeling. The criteria used to select dispersion/deposition models are presented. Several models were considered, including ARAC, MACCS, HOTSPOT, WINDS (coupled with PUFF-PLUME), and UFOTRI. Although ARAC and WINDS are expected to provide more accurate modeling of atmospheric transport following an actual release, analyses consistent with regulatory guidance for planning purposes may be accomplished with comparatively simple dispersion models such as HOTSPOT and UFOTRI. A recommendation is made to use HOTSPOT for non-tritium facilities and UFOTRI for tritium facilities

  20. Selection of Models for Ingestion Pathway and Relocation

    International Nuclear Information System (INIS)

    Blanchard, A.; Thompson, J.M.

    1998-01-01

    The area in which intermediate phase protective actions (such as food interdiction and relocation) may be needed following postulated accidents at three Savannah River Site nonreactor nuclear facilities will be determined by modeling. The criteria used to select dispersion/deposition models are presented. Several models are considered, including ARAC, MACCS, HOTSPOT, WINDS (coupled with PUFF-PLUME), and UFOTRI. Although ARAC and WINDS are expected to provide more accurate modeling of atmospheric transport following an actual release, analyses consistent with regulatory guidance for planning purposes may be accomplished with comparatively simple dispersion models such as HOTSPOT and UFOTRI. A recommendation is made to use HOTSPOT for non-tritium facilities and UFOTRI for tritium facilities. The most recent Food and Drug Administration Derived Intervention Levels (August 1998) are adopted as evaluation guidelines for ingestion pathways

  1. Selection of Models for Ingestion Pathway and Relocation

    International Nuclear Information System (INIS)

    Blanchard, A.; Thompson, J.M.

    1999-01-01

    The area in which intermediate phase protective actions (such as food interdiction and relocation) may be needed following postulated accidents at three Savannah River Site nonreactor nuclear facilities will be determined by modeling. The criteria used to select dispersion/deposition models are presented. Several models are considered, including ARAC, MACCS, HOTSPOT, WINDS (coupled with PUFF-PLUME), and UFOTRI. Although ARAC and WINDS are expected to provide more accurate modeling of atmospheric transport following an actual release, analyses consistent with regulatory guidance for planning purposes may be accomplished with comparatively simple dispersion models such as HOTSPOT and UFOTRI. A recommendation is made to use HOTSPOT for non-tritium facilities and UFOTRI for tritium facilities. The most recent Food and Drug Administration Derived Intervention Levels (August 1998) are adopted as evaluation guidelines for ingestion pathways

  2. Predicting artificailly drained areas by means of selective model ensemble

    DEFF Research Database (Denmark)

    Møller, Anders Bjørn; Beucher, Amélie; Iversen, Bo Vangsø

    . The approaches employed include decision trees, discriminant analysis, regression models, neural networks and support vector machines amongst others. Several models are trained with each method, using variously the original soil covariates and principal components of the covariates. With a large ensemble...... out since the mid-19th century, and it has been estimated that half of the cultivated area is artificially drained (Olesen, 2009). A number of machine learning approaches can be used to predict artificially drained areas in geographic space. However, instead of choosing the most accurate model....... The study aims firstly to train a large number of models to predict the extent of artificially drained areas using various machine learning approaches. Secondly, the study will develop a method for selecting the models, which give a good prediction of artificially drained areas, when used in conjunction...

  3. ASYMMETRIC PRICE TRANSMISSION MODELING: THE IMPORTANCE OF MODEL COMPLEXITY AND THE PERFORMANCE OF THE SELECTION CRITERIA

    Directory of Open Access Journals (Sweden)

    Henry de-Graft Acquah

    2013-01-01

    Full Text Available Information Criteria provides an attractive basis for selecting the best model from a set of competing asymmetric price transmission models or theories. However, little is understood about the sensitivity of the model selection methods to model complexity. This study therefore fits competing asymmetric price transmission models that differ in complexity to simulated data and evaluates the ability of the model selection methods to recover the true model. The results of Monte Carlo experimentation suggest that in general BIC, CAIC and DIC were superior to AIC when the true data generating process was the standard error correction model, whereas AIC was more successful when the true model was the complex error correction model. It is also shown that the model selection methods performed better in large samples for a complex asymmetric data generating process than with a standard asymmetric data generating process. Except for complex models, AIC's performance did not make substantial gains in recovery rates as sample size increased. The research findings demonstrate the influence of model complexity in asymmetric price transmission model comparison and selection.

  4. Sporangiospore size dimorphism is linked to virulence of Mucor circinelloides.

    Science.gov (United States)

    Li, Charles H; Cervantes, Maria; Springer, Deborah J; Boekhout, Teun; Ruiz-Vazquez, Rosa M; Torres-Martinez, Santiago R; Heitman, Joseph; Lee, Soo Chan

    2011-06-01

    Mucor circinelloides is a zygomycete fungus and an emerging opportunistic pathogen in immunocompromised patients, especially transplant recipients and in some cases otherwise healthy individuals. We have discovered a novel example of size dimorphism linked to virulence. M. circinelloides is a heterothallic fungus: (+) sex allele encodes SexP and (-) sex allele SexM, both of which are HMG domain protein sex determinants. M. circinelloides f. lusitanicus (Mcl) (-) mating type isolates produce larger asexual sporangiospores that are more virulent in the wax moth host compared to (+) isolates that produce smaller less virulent sporangiospores. The larger sporangiospores germinate inside and lyse macrophages, whereas the smaller sporangiospores do not. sexMΔ mutants are sterile and still produce larger virulent sporangiospores, suggesting that either the sex locus is not involved in virulence/spore size or the sexP allele plays an inhibitory role. Phylogenetic analysis supports that at least three extant subspecies populate the M. circinelloides complex in nature: Mcl, M. circinelloides f. griseocyanus, and M. circinelloides f. circinelloides (Mcc). Mcc was found to be more prevalent among clinical Mucor isolates, and more virulent than Mcl in a diabetic murine model in contrast to the wax moth host. The M. circinelloides sex locus encodes an HMG domain protein (SexP for plus and SexM for minus mating types) flanked by genes encoding triose phosphate transporter (TPT) and RNA helicase homologs. The borders of the sex locus between the three subspecies differ: the Mcg sex locus includes the promoters of both the TPT and the RNA helicase genes, whereas the Mcl and Mcc sex locus includes only the TPT gene promoter. Mating between subspecies was restricted compared to mating within subspecies. These findings demonstrate that spore size dimorphism is linked to virulence of M. circinelloides species and that plasticity of the sex locus and adaptations in pathogenicity have

  5. An Improved Nested Sampling Algorithm for Model Selection and Assessment

    Science.gov (United States)

    Zeng, X.; Ye, M.; Wu, J.; WANG, D.

    2017-12-01

    Multimodel strategy is a general approach for treating model structure uncertainty in recent researches. The unknown groundwater system is represented by several plausible conceptual models. Each alternative conceptual model is attached with a weight which represents the possibility of this model. In Bayesian framework, the posterior model weight is computed as the product of model prior weight and marginal likelihood (or termed as model evidence). As a result, estimating marginal likelihoods is crucial for reliable model selection and assessment in multimodel analysis. Nested sampling estimator (NSE) is a new proposed algorithm for marginal likelihood estimation. The implementation of NSE comprises searching the parameters' space from low likelihood area to high likelihood area gradually, and this evolution is finished iteratively via local sampling procedure. Thus, the efficiency of NSE is dominated by the strength of local sampling procedure. Currently, Metropolis-Hasting (M-H) algorithm and its variants are often used for local sampling in NSE. However, M-H is not an efficient sampling algorithm for high-dimensional or complex likelihood function. For improving the performance of NSE, it could be feasible to integrate more efficient and elaborated sampling algorithm - DREAMzs into the local sampling. In addition, in order to overcome the computation burden problem of large quantity of repeating model executions in marginal likelihood estimation, an adaptive sparse grid stochastic collocation method is used to build the surrogates for original groundwater model.

  6. Stochastic isotropic hyperelastic materials: constitutive calibration and model selection

    Science.gov (United States)

    Mihai, L. Angela; Woolley, Thomas E.; Goriely, Alain

    2018-03-01

    Biological and synthetic materials often exhibit intrinsic variability in their elastic responses under large strains, owing to microstructural inhomogeneity or when elastic data are extracted from viscoelastic mechanical tests. For these materials, although hyperelastic models calibrated to mean data are useful, stochastic representations accounting also for data dispersion carry extra information about the variability of material properties found in practical applications. We combine finite elasticity and information theories to construct homogeneous isotropic hyperelastic models with random field parameters calibrated to discrete mean values and standard deviations of either the stress-strain function or the nonlinear shear modulus, which is a function of the deformation, estimated from experimental tests. These quantities can take on different values, corresponding to possible outcomes of the experiments. As multiple models can be derived that adequately represent the observed phenomena, we apply Occam's razor by providing an explicit criterion for model selection based on Bayesian statistics. We then employ this criterion to select a model among competing models calibrated to experimental data for rubber and brain tissue under single or multiaxial loads.

  7. Modeling selective pressures on phytoplankton in the global ocean.

    Directory of Open Access Journals (Sweden)

    Jason G Bragg

    Full Text Available Our view of marine microbes is transforming, as culture-independent methods facilitate rapid characterization of microbial diversity. It is difficult to assimilate this information into our understanding of marine microbe ecology and evolution, because their distributions, traits, and genomes are shaped by forces that are complex and dynamic. Here we incorporate diverse forces--physical, biogeochemical, ecological, and mutational--into a global ocean model to study selective pressures on a simple trait in a widely distributed lineage of picophytoplankton: the nitrogen use abilities of Synechococcus and Prochlorococcus cyanobacteria. Some Prochlorococcus ecotypes have lost the ability to use nitrate, whereas their close relatives, marine Synechococcus, typically retain it. We impose mutations for the loss of nitrogen use abilities in modeled picophytoplankton, and ask: in which parts of the ocean are mutants most disadvantaged by losing the ability to use nitrate, and in which parts are they least disadvantaged? Our model predicts that this selective disadvantage is smallest for picophytoplankton that live in tropical regions where Prochlorococcus are abundant in the real ocean. Conversely, the selective disadvantage of losing the ability to use nitrate is larger for modeled picophytoplankton that live at higher latitudes, where Synechococcus are abundant. In regions where we expect Prochlorococcus and Synechococcus populations to cycle seasonally in the real ocean, we find that model ecotypes with seasonal population dynamics similar to Prochlorococcus are less disadvantaged by losing the ability to use nitrate than model ecotypes with seasonal population dynamics similar to Synechococcus. The model predictions for the selective advantage associated with nitrate use are broadly consistent with the distribution of this ability among marine picocyanobacteria, and at finer scales, can provide insights into interactions between temporally varying

  8. Modeling selective pressures on phytoplankton in the global ocean.

    Science.gov (United States)

    Bragg, Jason G; Dutkiewicz, Stephanie; Jahn, Oliver; Follows, Michael J; Chisholm, Sallie W

    2010-03-10

    Our view of marine microbes is transforming, as culture-independent methods facilitate rapid characterization of microbial diversity. It is difficult to assimilate this information into our understanding of marine microbe ecology and evolution, because their distributions, traits, and genomes are shaped by forces that are complex and dynamic. Here we incorporate diverse forces--physical, biogeochemical, ecological, and mutational--into a global ocean model to study selective pressures on a simple trait in a widely distributed lineage of picophytoplankton: the nitrogen use abilities of Synechococcus and Prochlorococcus cyanobacteria. Some Prochlorococcus ecotypes have lost the ability to use nitrate, whereas their close relatives, marine Synechococcus, typically retain it. We impose mutations for the loss of nitrogen use abilities in modeled picophytoplankton, and ask: in which parts of the ocean are mutants most disadvantaged by losing the ability to use nitrate, and in which parts are they least disadvantaged? Our model predicts that this selective disadvantage is smallest for picophytoplankton that live in tropical regions where Prochlorococcus are abundant in the real ocean. Conversely, the selective disadvantage of losing the ability to use nitrate is larger for modeled picophytoplankton that live at higher latitudes, where Synechococcus are abundant. In regions where we expect Prochlorococcus and Synechococcus populations to cycle seasonally in the real ocean, we find that model ecotypes with seasonal population dynamics similar to Prochlorococcus are less disadvantaged by losing the ability to use nitrate than model ecotypes with seasonal population dynamics similar to Synechococcus. The model predictions for the selective advantage associated with nitrate use are broadly consistent with the distribution of this ability among marine picocyanobacteria, and at finer scales, can provide insights into interactions between temporally varying ocean processes and

  9. Modeling selective attention using a neuromorphic analog VLSI device.

    Science.gov (United States)

    Indiveri, G

    2000-12-01

    Attentional mechanisms are required to overcome the problem of flooding a limited processing capacity system with information. They are present in biological sensory systems and can be a useful engineering tool for artificial visual systems. In this article we present a hardware model of a selective attention mechanism implemented on a very large-scale integration (VLSI) chip, using analog neuromorphic circuits. The chip exploits a spike-based representation to receive, process, and transmit signals. It can be used as a transceiver module for building multichip neuromorphic vision systems. We describe the circuits that carry out the main processing stages of the selective attention mechanism and provide experimental data for each circuit. We demonstrate the expected behavior of the model at the system level by stimulating the chip with both artificially generated control signals and signals obtained from a saliency map, computed from an image containing several salient features.

  10. Genomic Selection in Plant Breeding: Methods, Models, and Perspectives.

    Science.gov (United States)

    Crossa, José; Pérez-Rodríguez, Paulino; Cuevas, Jaime; Montesinos-López, Osval; Jarquín, Diego; de Los Campos, Gustavo; Burgueño, Juan; González-Camacho, Juan M; Pérez-Elizalde, Sergio; Beyene, Yoseph; Dreisigacker, Susanne; Singh, Ravi; Zhang, Xuecai; Gowda, Manje; Roorkiwal, Manish; Rutkoski, Jessica; Varshney, Rajeev K

    2017-11-01

    Genomic selection (GS) facilitates the rapid selection of superior genotypes and accelerates the breeding cycle. In this review, we discuss the history, principles, and basis of GS and genomic-enabled prediction (GP) as well as the genetics and statistical complexities of GP models, including genomic genotype×environment (G×E) interactions. We also examine the accuracy of GP models and methods for two cereal crops and two legume crops based on random cross-validation. GS applied to maize breeding has shown tangible genetic gains. Based on GP results, we speculate how GS in germplasm enhancement (i.e., prebreeding) programs could accelerate the flow of genes from gene bank accessions to elite lines. Recent advances in hyperspectral image technology could be combined with GS and pedigree-assisted breeding. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. A Model of Social Selection and Successful Altruism

    Science.gov (United States)

    1989-10-07

    D., The evolution of social behavior. Annual Reviews of Ecological Systems, 5:325-383 (1974). 2. Dawkins , R., The selfish gene . Oxford: Oxford...alive and well. it will be important to re- examine this striking historical experience,-not in terms o, oversimplified models of the " selfish gene ," but...Darwinian Analysis The acceptance by many modern geneticists of the axiom that the basic unit of selection Is the " selfish gene " quickly led to the

  12. Pareto-Optimal Model Selection via SPRINT-Race.

    Science.gov (United States)

    Zhang, Tiantian; Georgiopoulos, Michael; Anagnostopoulos, Georgios C

    2018-02-01

    In machine learning, the notion of multi-objective model selection (MOMS) refers to the problem of identifying the set of Pareto-optimal models that optimize by compromising more than one predefined objectives simultaneously. This paper introduces SPRINT-Race, the first multi-objective racing algorithm in a fixed-confidence setting, which is based on the sequential probability ratio with indifference zone test. SPRINT-Race addresses the problem of MOMS with multiple stochastic optimization objectives in the proper Pareto-optimality sense. In SPRINT-Race, a pairwise dominance or non-dominance relationship is statistically inferred via a non-parametric, ternary-decision, dual-sequential probability ratio test. The overall probability of falsely eliminating any Pareto-optimal models or mistakenly returning any clearly dominated models is strictly controlled by a sequential Holm's step-down family-wise error rate control method. As a fixed-confidence model selection algorithm, the objective of SPRINT-Race is to minimize the computational effort required to achieve a prescribed confidence level about the quality of the returned models. The performance of SPRINT-Race is first examined via an artificially constructed MOMS problem with known ground truth. Subsequently, SPRINT-Race is applied on two real-world applications: 1) hybrid recommender system design and 2) multi-criteria stock selection. The experimental results verify that SPRINT-Race is an effective and efficient tool for such MOMS problems. code of SPRINT-Race is available at https://github.com/watera427/SPRINT-Race.

  13. Establishment of selected acute pulmonary thromboembolism model in experimental sheep

    International Nuclear Information System (INIS)

    Fan Jihai; Gu Xiulian; Chao Shengwu; Zhang Peng; Fan Ruilin; Wang Li'na; Wang Lulu; Wang Ling; Li Bo; Chen Taotao

    2010-01-01

    Objective: To establish a selected acute pulmonary thromboembolism model in experimental sheep suitable for animal experiment. Methods: By using Seldinger's technique the catheter sheath was placed in both the femoral vein and femoral artery in ten sheep. Under C-arm DSA guidance the catheter was inserted through the catheter sheath into the pulmonary artery. Via the catheter appropriate amount of sheep autologous blood clots was injected into the selected pulmonary arteries. The selected acute pulmonary thromboembolism model was thus established. Pulmonary angiography was performed to check the results. The pulmonary arterial pressure, femoral artery pressure,heart rates and partial pressure of oxygen in arterial blood (PaO 2 ) were determined both before and after the treatment. The above parameters obtained after the procedure were compared with the recorded parameters measured before the procedure, and the sheep model quality was evaluated. Results: The baseline of pulmonary arterial pressure was (27.30 ± 9.58) mmHg,femoral artery pressure was (126.4 ± 13.72) mmHg, heart rate was (103 ± 15) bpm and PaO 2 was (87.7 ± 12.04) mmHg. Sixty minutes after the injection of (30 ± 5) ml thrombotic agglomerates, the pulmonary arterial pressures rose to (52 ± 49) mmHg, femoral artery pressures dropped to (100 ± 21) mmHg. The heart rates went up to (150 ± 26) bpm. The PaO 2 fell to (25.3 ± 11.2) mmHg. After the procedure the above parameters were significantly different from that measured before the procedure in all ten animals (P < 0.01). The pulmonary arteriography clearly demonstrated that the selected pulmonary arteries were successfully embolized. Conclusion: The anatomy of sheep's femoral veins,vena cava system, pulmonary artery and right heart system are suitable for the establishment of the catheter passage, for this reason, selected acute pulmonary thromboembolism model can be easily created in experimental sheep. The technique is feasible and the model

  14. Selection of key terrain attributes for SOC model

    DEFF Research Database (Denmark)

    Greve, Mogens Humlekrog; Adhikari, Kabindra; Chellasamy, Menaka

    As an important component of the global carbon pool, soil organic carbon (SOC) plays an important role in the global carbon cycle. SOC pool is the basic information to carry out global warming research, and needs to sustainable use of land resources. Digital terrain attributes are often use...... was selected, total 2,514,820 data mining models were constructed by 71 differences grid from 12m to 2304m and 22 attributes, 21 attributes derived by DTM and the original elevation. Relative importance and usage of each attributes in every model were calculated. Comprehensive impact rates of each attribute...

  15. A decision model for energy resource selection in China

    International Nuclear Information System (INIS)

    Wang Bing; Kocaoglu, Dundar F.; Daim, Tugrul U.; Yang Jiting

    2010-01-01

    This paper evaluates coal, petroleum, natural gas, nuclear energy and renewable energy resources as energy alternatives for China through use of a hierarchical decision model. The results indicate that although coal is still the major preferred energy alternative, it is followed closely by renewable energy. The sensitivity analysis indicates that the most critical criterion for energy selection is the current energy infrastructure. A hierarchical decision model is used, and expert judgments are quantified, to evaluate the alternatives. Criteria used for the evaluations are availability, current energy infrastructure, price, safety, environmental impacts and social impacts.

  16. Empirical support for optimal virulence in a castrating parasite.

    Directory of Open Access Journals (Sweden)

    Knut Helge Jensen

    2006-07-01

    Full Text Available The trade-off hypothesis for the evolution of virulence predicts that parasite transmission stage production and host exploitation are balanced such that lifetime transmission success (LTS is maximised. However, the experimental evidence for this prediction is weak, mainly because LTS, which indicates parasite fitness, has been difficult to measure. For castrating parasites, this simple model has been modified to take into account that parasites convert host reproductive resources into transmission stages. Parasites that kill the host too early will hardly benefit from these resources, while postponing the killing of the host results in diminished returns. As predicted from optimality models, a parasite inducing castration should therefore castrate early, but show intermediate levels of virulence, where virulence is measured as time to host killing. We studied virulence in an experimental system where a bacterial parasite castrates its host and produces spores that are not released until after host death. This permits estimating the LTS of the parasite, which can then be related to its virulence. We exposed replicate individual Daphnia magna (Crustacea of one host clone to the same amount of bacterial spores and followed individuals until their death. We found that the parasite shows strong variation in the time to kill its host and that transmission stage production peaks at an intermediate level of virulence. A further experiment tested for the genetic basis of variation in virulence by comparing survival curves of daphniids infected with parasite spores obtained from early killing versus late killing infections. Hosts infected with early killer spores had a significantly higher death rate as compared to those infected with late killers, indicating that variation in time to death was at least in part caused by genetic differences among parasites. We speculate that the clear peak in lifetime reproductive success at intermediate killing times

  17. Bacterial proteases and virulence

    DEFF Research Database (Denmark)

    Frees, Dorte; Brøndsted, Lone; Ingmer, Hanne

    2013-01-01

    signalling to short-circuit host cell processes. Common to both intra- and extracellular proteases is the tight control of their proteolytic activities. In general, substrate recognition by the intracellular proteases is highly selective which is, in part, attributed to the chaperone activity associated...... tolerance to adverse conditions such as those experienced in the host. In the membrane, HtrA performs similar functions whereas the extracellular proteases, in close contact with host components, pave the way for spreading infections by degrading host matrix components or interfering with host cell...... with the proteases either encoded within the same polypeptide or on separate subunits. In contrast, substrate recognition by extracellular proteases is less selective and therefore these enzymes are generally expressed as zymogens to prevent premature proteolytic activity that would be detrimental to the cell...

  18. Covariate selection for the semiparametric additive risk model

    DEFF Research Database (Denmark)

    Martinussen, Torben; Scheike, Thomas

    2009-01-01

    This paper considers covariate selection for the additive hazards model. This model is particularly simple to study theoretically and its practical implementation has several major advantages to the similar methodology for the proportional hazards model. One complication compared...... and study their large sample properties for the situation where the number of covariates p is smaller than the number of observations. We also show that the adaptive Lasso has the oracle property. In many practical situations, it is more relevant to tackle the situation with large p compared with the number...... of observations. We do this by studying the properties of the so-called Dantzig selector in the setting of the additive risk model. Specifically, we establish a bound on how close the solution is to a true sparse signal in the case where the number of covariates is large. In a simulation study, we also compare...

  19. Optimal foraging in marine ecosystem models: selectivity, profitability and switching

    DEFF Research Database (Denmark)

    Visser, Andre W.; Fiksen, Ø.

    2013-01-01

    ecological mechanics and evolutionary logic as a solution to diet selection in ecosystem models. When a predator can consume a range of prey items it has to choose which foraging mode to use, which prey to ignore and which ones to pursue, and animals are known to be particularly skilled in adapting...... to the preference functions commonly used in models today. Indeed, depending on prey class resolution, optimal foraging can yield feeding rates that are considerably different from the ‘switching functions’ often applied in marine ecosystem models. Dietary inclusion is dictated by two optimality choices: 1...... by letting predators maximize energy intake or more properly, some measure of fitness where predation risk and cost are also included. An optimal foraging or fitness maximizing approach will give marine ecosystem models a sound principle to determine trophic interactions...

  20. Selection of productivity improvement techniques via mathematical modeling

    Directory of Open Access Journals (Sweden)

    Mahassan M. Khater

    2011-07-01

    Full Text Available This paper presents a new mathematical model to select an optimal combination of productivity improvement techniques. The proposed model of this paper considers four-stage cycle productivity and the productivity is assumed to be a linear function of fifty four improvement techniques. The proposed model of this paper is implemented for a real-world case study of manufacturing plant. The resulted problem is formulated as a mixed integer programming which can be solved for optimality using traditional methods. The preliminary results of the implementation of the proposed model of this paper indicate that the productivity can be improved through a change on equipments and it can be easily applied for both manufacturing and service industries.

  1. An Introduction to Model Selection: Tools and Algorithms

    Directory of Open Access Journals (Sweden)

    Sébastien Hélie

    2006-03-01

    Full Text Available Model selection is a complicated matter in science, and psychology is no exception. In particular, the high variance in the object of study (i.e., humans prevents the use of Popper’s falsification principle (which is the norm in other sciences. Therefore, the desirability of quantitative psychological models must be assessed by measuring the capacity of the model to fit empirical data. In the present paper, an error measure (likelihood, as well as five methods to compare model fits (the likelihood ratio test, Akaike’s information criterion, the Bayesian information criterion, bootstrapping and cross-validation, are presented. The use of each method is illustrated by an example, and the advantages and weaknesses of each method are also discussed.

  2. Frequency of Fimbrial Virulence Genes (fim, pap, sfa in Escherichia Coli Isolated from the Patients with Urinary Tract Infections from selective hospitals of Tehran, Boroujerd and Sanandej City in 2015-2016

    Directory of Open Access Journals (Sweden)

    mohsen mirzaee

    2017-02-01

    Full Text Available Introduction: Urinary tract infection (UTI caused by E coli is one of the most common diseases in community. Colonization of E. coli and its attachment to the uroepithelium are mediated by adhesions such as P, Fim and S fimbriae. The present study was aimed to evaluate the prevalence of fimbrial virulence genes in Escherichia coli (E. coli isolates from the patients with urinary tract infection in Tehran, Boroujerd and Sanandaj cities, Iran. Methods: In this descriptive cross sectional study, 150 clinical isolates of uropathogenic E.coli were collected from the patients with urinary tract infection. All bacterial isolates were identified by standard biochemical laboratory methods; the fim, pap and sfa genes were detected using the PCR and Multiplex-PCR methods. Results: One hundred forty-five (96.66% isolates were positive for fim gene, one hundred forty (93.33% isolates were positive for pap gene and seven (4.66 isolates were positive for sfa gene. Whole of the isolates were possessed at least one of the three virulence genes. Six (4% isolates were positive for all genes. Conclusion: The findings of this study showed the high frequency of fim and P fimbriae among uropathogenic E.coli isolates from the patients with urinary tract infection. Because of the higher prevalence of UTI in the presence of these genes, detection of the genes in urine samples may help in more suspicious and rapid management of UTI.

  3. The link between morphotype transition and virulence in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Linqi Wang

    Full Text Available Cryptococcus neoformans is a ubiquitous human fungal pathogen. This pathogen can undergo morphotype transition between the yeast and the filamentous form and such morphological transition has been implicated in virulence for decades. Morphotype transition is typically observed during mating, which is governed by pheromone signaling. Paradoxically, components specific to the pheromone signaling pathways play no or minimal direct roles in virulence. Thus, the link between morphotype transition and virulence and the underlying molecular mechanism remain elusive. Here, we demonstrate that filamentation can occur independent of pheromone signaling and mating, and both mating-dependent and mating-independent morphotype transition require the transcription factor Znf2. High expression of Znf2 is necessary and sufficient to initiate and maintain sex-independent filamentous growth under host-relevant conditions in vitro and during infection. Importantly, ZNF2 overexpression abolishes fungal virulence in murine models of cryptococcosis. Thus, Znf2 bridges the sex-independent morphotype transition and fungal pathogenicity. The impacts of Znf2 on morphological switch and pathogenicity are at least partly mediated through its effects on cell adhesion property. Cfl1, a Znf2 downstream factor, regulates morphogenesis, cell adhesion, biofilm formation, and virulence. Cfl1 is the first adhesin discovered in the phylum Basidiomycota of the Kingdom Fungi. Together with previous findings in other eukaryotic pathogens, our findings support a convergent evolution of plasticity in morphology and its impact on cell adhesion as a critical adaptive trait for pathogenesis.

  4. The Impact of Varied Discrimination Parameters on Mixed-Format Item Response Theory Model Selection

    Science.gov (United States)

    Whittaker, Tiffany A.; Chang, Wanchen; Dodd, Barbara G.

    2013-01-01

    Whittaker, Chang, and Dodd compared the performance of model selection criteria when selecting among mixed-format IRT models and found that the criteria did not perform adequately when selecting the more parameterized models. It was suggested by M. S. Johnson that the problems when selecting the more parameterized models may be because of the low…

  5. Wind scatterometry with improved ambiguity selection and rain modeling

    Science.gov (United States)

    Draper, David Willis

    Although generally accurate, the quality of SeaWinds on QuikSCAT scatterometer ocean vector winds is compromised by certain natural phenomena and retrieval algorithm limitations. This dissertation addresses three main contributors to scatterometer estimate error: poor ambiguity selection, estimate uncertainty at low wind speeds, and rain corruption. A quality assurance (QA) analysis performed on SeaWinds data suggests that about 5% of SeaWinds data contain ambiguity selection errors and that scatterometer estimation error is correlated with low wind speeds and rain events. Ambiguity selection errors are partly due to the "nudging" step (initialization from outside data). A sophisticated new non-nudging ambiguity selection approach produces generally more consistent wind than the nudging method in moderate wind conditions. The non-nudging method selects 93% of the same ambiguities as the nudged data, validating both techniques, and indicating that ambiguity selection can be accomplished without nudging. Variability at low wind speeds is analyzed using tower-mounted scatterometer data. According to theory, below a threshold wind speed, the wind fails to generate the surface roughness necessary for wind measurement. A simple analysis suggests the existence of the threshold in much of the tower-mounted scatterometer data. However, the backscatter does not "go to zero" beneath the threshold in an uncontrolled environment as theory suggests, but rather has a mean drop and higher variability below the threshold. Rain is the largest weather-related contributor to scatterometer error, affecting approximately 4% to 10% of SeaWinds data. A simple model formed via comparison of co-located TRMM PR and SeaWinds measurements characterizes the average effect of rain on SeaWinds backscatter. The model is generally accurate to within 3 dB over the tropics. The rain/wind backscatter model is used to simultaneously retrieve wind and rain from SeaWinds measurements. The simultaneous

  6. Selection of Representative Models for Decision Analysis Under Uncertainty

    Science.gov (United States)

    Meira, Luis A. A.; Coelho, Guilherme P.; Santos, Antonio Alberto S.; Schiozer, Denis J.

    2016-03-01

    The decision-making process in oil fields includes a step of risk analysis associated with the uncertainties present in the variables of the problem. Such uncertainties lead to hundreds, even thousands, of possible scenarios that are supposed to be analyzed so an effective production strategy can be selected. Given this high number of scenarios, a technique to reduce this set to a smaller, feasible subset of representative scenarios is imperative. The selected scenarios must be representative of the original set and also free of optimistic and pessimistic bias. This paper is devoted to propose an assisted methodology to identify representative models in oil fields. To do so, first a mathematical function was developed to model the representativeness of a subset of models with respect to the full set that characterizes the problem. Then, an optimization tool was implemented to identify the representative models of any problem, considering not only the cross-plots of the main output variables, but also the risk curves and the probability distribution of the attribute-levels of the problem. The proposed technique was applied to two benchmark cases and the results, evaluated by experts in the field, indicate that the obtained solutions are richer than those identified by previously adopted manual approaches. The program bytecode is available under request.

  7. Multilevel selection in a resource-based model

    Science.gov (United States)

    Ferreira, Fernando Fagundes; Campos, Paulo R. A.

    2013-07-01

    In the present work we investigate the emergence of cooperation in a multilevel selection model that assumes limiting resources. Following the work by R. J. Requejo and J. Camacho [Phys. Rev. Lett.0031-900710.1103/PhysRevLett.108.038701 108, 038701 (2012)], the interaction among individuals is initially ruled by a prisoner's dilemma (PD) game. The payoff matrix may change, influenced by the resource availability, and hence may also evolve to a non-PD game. Furthermore, one assumes that the population is divided into groups, whose local dynamics is driven by the payoff matrix, whereas an intergroup competition results from the nonuniformity of the growth rate of groups. We study the probability that a single cooperator can invade and establish in a population initially dominated by defectors. Cooperation is strongly favored when group sizes are small. We observe the existence of a critical group size beyond which cooperation becomes counterselected. Although the critical size depends on the parameters of the model, it is seen that a saturation value for the critical group size is achieved. The results conform to the thought that the evolutionary history of life repeatedly involved transitions from smaller selective units to larger selective units.

  8. METHODS OF SELECTING THE EFFECTIVE MODELS OF BUILDINGS REPROFILING PROJECTS

    Directory of Open Access Journals (Sweden)

    Александр Иванович МЕНЕЙЛЮК

    2016-02-01

    Full Text Available The article highlights the important task of project management in reprofiling of buildings. It is expedient to pay attention to selecting effective engineering solutions to reduce the duration and cost reduction at the project management in the construction industry. This article presents a methodology for the selection of efficient organizational and technical solutions for the reconstruction of buildings reprofiling. The method is based on a compilation of project variants in the program Microsoft Project and experimental statistical analysis using the program COMPEX. The introduction of this technique in the realigning of buildings allows choosing efficient models of projects, depending on the given constraints. Also, this technique can be used for various construction projects.

  9. Applying a Hybrid MCDM Model for Six Sigma Project Selection

    Directory of Open Access Journals (Sweden)

    Fu-Kwun Wang

    2014-01-01

    Full Text Available Six Sigma is a project-driven methodology; the projects that provide the maximum financial benefits and other impacts to the organization must be prioritized. Project selection (PS is a type of multiple criteria decision making (MCDM problem. In this study, we present a hybrid MCDM model combining the decision-making trial and evaluation laboratory (DEMATEL technique, analytic network process (ANP, and the VIKOR method to evaluate and improve Six Sigma projects for reducing performance gaps in each criterion and dimension. We consider the film printing industry of Taiwan as an empirical case. The results show that our study not only can use the best project selection, but can also be used to analyze the gaps between existing performance values and aspiration levels for improving the gaps in each dimension and criterion based on the influential network relation map.

  10. A Reliability Based Model for Wind Turbine Selection

    Directory of Open Access Journals (Sweden)

    A.K. Rajeevan

    2013-06-01

    Full Text Available A wind turbine generator output at a specific site depends on many factors, particularly cut- in, rated and cut-out wind speed parameters. Hence power output varies from turbine to turbine. The objective of this paper is to develop a mathematical relationship between reliability and wind power generation. The analytical computation of monthly wind power is obtained from weibull statistical model using cubic mean cube root of wind speed. Reliability calculation is based on failure probability analysis. There are many different types of wind turbinescommercially available in the market. From reliability point of view, to get optimum reliability in power generation, it is desirable to select a wind turbine generator which is best suited for a site. The mathematical relationship developed in this paper can be used for site-matching turbine selection in reliability point of view.

  11. Automation of Endmember Pixel Selection in SEBAL/METRIC Model

    Science.gov (United States)

    Bhattarai, N.; Quackenbush, L. J.; Im, J.; Shaw, S. B.

    2015-12-01

    The commonly applied surface energy balance for land (SEBAL) and its variant, mapping evapotranspiration (ET) at high resolution with internalized calibration (METRIC) models require manual selection of endmember (i.e. hot and cold) pixels to calibrate sensible heat flux. Current approaches for automating this process are based on statistical methods and do not appear to be robust under varying climate conditions and seasons. In this paper, we introduce a new approach based on simple machine learning tools and search algorithms that provides an automatic and time efficient way of identifying endmember pixels for use in these models. The fully automated models were applied on over 100 cloud-free Landsat images with each image covering several eddy covariance flux sites in Florida and Oklahoma. Observed land surface temperatures at automatically identified hot and cold pixels were within 0.5% of those from pixels manually identified by an experienced operator (coefficient of determination, R2, ≥ 0.92, Nash-Sutcliffe efficiency, NSE, ≥ 0.92, and root mean squared error, RMSE, ≤ 1.67 K). Daily ET estimates derived from the automated SEBAL and METRIC models were in good agreement with their manual counterparts (e.g., NSE ≥ 0.91 and RMSE ≤ 0.35 mm day-1). Automated and manual pixel selection resulted in similar estimates of observed ET across all sites. The proposed approach should reduce time demands for applying SEBAL/METRIC models and allow for their more widespread and frequent use. This automation can also reduce potential bias that could be introduced by an inexperienced operator and extend the domain of the models to new users.

  12. Neutropenia restores virulence to an attenuated Cu,Zn superoxide dismutase-deficient Haemophilus ducreyi strain in the swine model of chancroid.

    Science.gov (United States)

    San Mateo, L R; Toffer, K L; Orndorff, P E; Kawula, T H

    1999-10-01

    Haemophilus ducreyi causes chancroid, a sexually transmitted cutaneous genital ulcer disease associated with increased heterosexual transmission of human immunodeficiency virus. H. ducreyi expresses a periplasmic copper-zinc superoxide dismutase (Cu, Zn SOD) that protects the bacterium from killing by exogenous superoxide in vitro. We hypothesized that the Cu,Zn SOD would protect H. ducreyi from immune cell killing, enhance survival, and affect ulcer development in vivo. In order to test this hypothesis and study the role of the Cu,Zn SOD in H. ducreyi pathogenesis, we compared a Cu,Zn SOD-deficient H. ducreyi strain to its isogenic wild-type parent with respect to survival and ulcer development in immunocompetent and immunosuppressed pigs. The Cu,Zn SOD-deficient strain was recovered from significantly fewer inoculated sites and in significantly lower numbers than the wild-type parent strain or a merodiploid (sodC+ sodC) strain after infection of immunocompetent pigs. In contrast, survival of the wild-type and Cu,Zn SOD-deficient strains was not significantly different in pigs that were rendered neutropenic by treatment with cyclophosphamide. Ulcer severity in pigs was not significantly different between sites inoculated with wild type and sites inoculated with Cu,Zn SOD-deficient H. ducreyi. Our data suggest that the periplasmic Cu,Zn SOD is an important virulence determinant in H. ducreyi, protecting the bacterium from host immune cell killing and contributing to survival and persistence in the host.

  13. Fuzzy Goal Programming Approach in Selective Maintenance Reliability Model

    Directory of Open Access Journals (Sweden)

    Neha Gupta

    2013-12-01

    Full Text Available 800x600 In the present paper, we have considered the allocation problem of repairable components for a parallel-series system as a multi-objective optimization problem and have discussed two different models. In first model the reliability of subsystems are considered as different objectives. In second model the cost and time spent on repairing the components are considered as two different objectives. These two models is formulated as multi-objective Nonlinear Programming Problem (MONLPP and a Fuzzy goal programming method is used to work out the compromise allocation in multi-objective selective maintenance reliability model in which we define the membership functions of each objective function and then transform membership functions into equivalent linear membership functions by first order Taylor series and finally by forming a fuzzy goal programming model obtain a desired compromise allocation of maintenance components. A numerical example is also worked out to illustrate the computational details of the method.  Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4

  14. Development of Solar Drying Model for Selected Cambodian Fish Species

    Science.gov (United States)

    Hubackova, Anna; Kucerova, Iva; Chrun, Rithy; Chaloupkova, Petra; Banout, Jan

    2014-01-01

    A solar drying was investigated as one of perspective techniques for fish processing in Cambodia. The solar drying was compared to conventional drying in electric oven. Five typical Cambodian fish species were selected for this study. Mean solar drying temperature and drying air relative humidity were 55.6°C and 19.9%, respectively. The overall solar dryer efficiency was 12.37%, which is typical for natural convection solar dryers. An average evaporative capacity of solar dryer was 0.049 kg·h−1. Based on coefficient of determination (R 2), chi-square (χ 2) test, and root-mean-square error (RMSE), the most suitable models describing natural convection solar drying kinetics were Logarithmic model, Diffusion approximate model, and Two-term model for climbing perch and Nile tilapia, swamp eel and walking catfish and Channa fish, respectively. In case of electric oven drying, the Modified Page 1 model shows the best results for all investigated fish species except Channa fish where the two-term model is the best one. Sensory evaluation shows that most preferable fish is climbing perch, followed by Nile tilapia and walking catfish. This study brings new knowledge about drying kinetics of fresh water fish species in Cambodia and confirms the solar drying as acceptable technology for fish processing. PMID:25250381

  15. Development of Solar Drying Model for Selected Cambodian Fish Species

    Directory of Open Access Journals (Sweden)

    Anna Hubackova

    2014-01-01

    Full Text Available A solar drying was investigated as one of perspective techniques for fish processing in Cambodia. The solar drying was compared to conventional drying in electric oven. Five typical Cambodian fish species were selected for this study. Mean solar drying temperature and drying air relative humidity were 55.6°C and 19.9%, respectively. The overall solar dryer efficiency was 12.37%, which is typical for natural convection solar dryers. An average evaporative capacity of solar dryer was 0.049 kg·h−1. Based on coefficient of determination (R2, chi-square (χ2 test, and root-mean-square error (RMSE, the most suitable models describing natural convection solar drying kinetics were Logarithmic model, Diffusion approximate model, and Two-term model for climbing perch and Nile tilapia, swamp eel and walking catfish and Channa fish, respectively. In case of electric oven drying, the Modified Page 1 model shows the best results for all investigated fish species except Channa fish where the two-term model is the best one. Sensory evaluation shows that most preferable fish is climbing perch, followed by Nile tilapia and walking catfish. This study brings new knowledge about drying kinetics of fresh water fish species in Cambodia and confirms the solar drying as acceptable technology for fish processing.

  16. Continuum model for chiral induced spin selectivity in helical molecules

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Ernesto [Centro de Física, Instituto Venezolano de Investigaciones Científicas, 21827, Caracas 1020 A (Venezuela, Bolivarian Republic of); Groupe de Physique Statistique, Institut Jean Lamour, Université de Lorraine, 54506 Vandoeuvre-les-Nancy Cedex (France); Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287 (United States); González-Arraga, Luis A. [IMDEA Nanoscience, Cantoblanco, 28049 Madrid (Spain); Finkelstein-Shapiro, Daniel; Mujica, Vladimiro [Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287 (United States); Berche, Bertrand [Centro de Física, Instituto Venezolano de Investigaciones Científicas, 21827, Caracas 1020 A (Venezuela, Bolivarian Republic of); Groupe de Physique Statistique, Institut Jean Lamour, Université de Lorraine, 54506 Vandoeuvre-les-Nancy Cedex (France)

    2015-05-21

    A minimal model is exactly solved for electron spin transport on a helix. Electron transport is assumed to be supported by well oriented p{sub z} type orbitals on base molecules forming a staircase of definite chirality. In a tight binding interpretation, the spin-orbit coupling (SOC) opens up an effective π{sub z} − π{sub z} coupling via interbase p{sub x,y} − p{sub z} hopping, introducing spin coupled transport. The resulting continuum model spectrum shows two Kramers doublet transport channels with a gap proportional to the SOC. Each doubly degenerate channel satisfies time reversal symmetry; nevertheless, a bias chooses a transport direction and thus selects for spin orientation. The model predicts (i) which spin orientation is selected depending on chirality and bias, (ii) changes in spin preference as a function of input Fermi level and (iii) back-scattering suppression protected by the SO gap. We compute the spin current with a definite helicity and find it to be proportional to the torsion of the chiral structure and the non-adiabatic Aharonov-Anandan phase. To describe room temperature transport, we assume that the total transmission is the result of a product of coherent steps.

  17. Selection of models to calculate the LLW source term

    International Nuclear Information System (INIS)

    Sullivan, T.M.

    1991-10-01

    Performance assessment of a LLW disposal facility begins with an estimation of the rate at which radionuclides migrate out of the facility (i.e., the source term). The focus of this work is to develop a methodology for calculating the source term. In general, the source term is influenced by the radionuclide inventory, the wasteforms and containers used to dispose of the inventory, and the physical processes that lead to release from the facility (fluid flow, container degradation, wasteform leaching, and radionuclide transport). In turn, many of these physical processes are influenced by the design of the disposal facility (e.g., infiltration of water). The complexity of the problem and the absence of appropriate data prevent development of an entirely mechanistic representation of radionuclide release from a disposal facility. Typically, a number of assumptions, based on knowledge of the disposal system, are used to simplify the problem. This document provides a brief overview of disposal practices and reviews existing source term models as background for selecting appropriate models for estimating the source term. The selection rationale and the mathematical details of the models are presented. Finally, guidance is presented for combining the inventory data with appropriate mechanisms describing release from the disposal facility. 44 refs., 6 figs., 1 tab

  18. Selection Strategies for Social Influence in the Threshold Model

    Science.gov (United States)

    Karampourniotis, Panagiotis; Szymanski, Boleslaw; Korniss, Gyorgy

    The ubiquity of online social networks makes the study of social influence extremely significant for its applications to marketing, politics and security. Maximizing the spread of influence by strategically selecting nodes as initiators of a new opinion or trend is a challenging problem. We study the performance of various strategies for selection of large fractions of initiators on a classical social influence model, the Threshold model (TM). Under the TM, a node adopts a new opinion only when the fraction of its first neighbors possessing that opinion exceeds a pre-assigned threshold. The strategies we study are of two kinds: strategies based solely on the initial network structure (Degree-rank, Dominating Sets, PageRank etc.) and strategies that take into account the change of the states of the nodes during the evolution of the cascade, e.g. the greedy algorithm. We find that the performance of these strategies depends largely on both the network structure properties, e.g. the assortativity, and the distribution of the thresholds assigned to the nodes. We conclude that the optimal strategy needs to combine the network specifics and the model specific parameters to identify the most influential spreaders. Supported in part by ARL NS-CTA, ARO, and ONR.

  19. A Dual-Stage Two-Phase Model of Selective Attention

    Science.gov (United States)

    Hubner, Ronald; Steinhauser, Marco; Lehle, Carola

    2010-01-01

    The dual-stage two-phase (DSTP) model is introduced as a formal and general model of selective attention that includes both an early and a late stage of stimulus selection. Whereas at the early stage information is selected by perceptual filters whose selectivity is relatively limited, at the late stage stimuli are selected more efficiently on a…

  20. Estimation and variable selection for generalized additive partial linear models

    KAUST Repository

    Wang, Li

    2011-08-01

    We study generalized additive partial linear models, proposing the use of polynomial spline smoothing for estimation of nonparametric functions, and deriving quasi-likelihood based estimators for the linear parameters. We establish asymptotic normality for the estimators of the parametric components. The procedure avoids solving large systems of equations as in kernel-based procedures and thus results in gains in computational simplicity. We further develop a class of variable selection procedures for the linear parameters by employing a nonconcave penalized quasi-likelihood, which is shown to have an asymptotic oracle property. Monte Carlo simulations and an empirical example are presented for illustration. © Institute of Mathematical Statistics, 2011.

  1. Quantitative modeling of selective lysosomal targeting for drug design

    DEFF Research Database (Denmark)

    Trapp, Stefan; Rosania, G.; Horobin, R.W.

    2008-01-01

    log K ow. These findings were validated with experimental results and by a comparison to the properties of antimalarial drugs in clinical use. For ten active compounds, nine were predicted to accumulate to a greater extent in lysosomes than in other organelles, six of these were in the optimum range...... predicted by the model and three were close. Five of the antimalarial drugs were lipophilic weak dibasic compounds. The predicted optimum properties for a selective accumulation of weak bivalent bases in lysosomes are consistent with experimental values and are more accurate than any prior calculation...

  2. Genes involved in virulence of the entomopathogenic fungus Beauveria bassiana.

    Science.gov (United States)

    Valero-Jiménez, Claudio A; Wiegers, Harm; Zwaan, Bas J; Koenraadt, Constantianus J M; van Kan, Jan A L

    2016-01-01

    Pest insects cause severe damage to global crop production and pose a threat to human health by transmitting diseases. Traditionally, chemical pesticides (insecticides) have been used to control such pests and have proven to be effective only for a limited amount of time because of the rapid spread of genetic insecticide resistance. The basis of this resistance is mostly caused by (co)dominant mutations in single genes, which explains why insecticide use alone is an unsustainable solution. Therefore, robust solutions for insect pest control need to be sought in alternative methods such as biological control agents for which single-gene resistance is less likely to evolve. The entomopathogenic fungus Beauveria bassiana has shown potential as a biological control agent of insects, and insight into the mechanisms of virulence is essential to show the robustness of its use. With the recent availability of the whole genome sequence of B. bassiana, progress in understanding the genetics that constitute virulence toward insects can be made more quickly. In this review we divide the infection process into distinct steps and provide an overview of what is currently known about genes and mechanisms influencing virulence in B. bassiana. We also discuss the need for novel strategies and experimental methods to better understand the infection mechanisms deployed by entomopathogenic fungi. Such knowledge can help improve biocontrol agents, not only by selecting the most virulent genotypes, but also by selecting the genotypes that use combinations of virulence mechanisms for which resistance in the insect host is least likely to develop. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A Neuronal Network Model for Pitch Selectivity and Representation.

    Science.gov (United States)

    Huang, Chengcheng; Rinzel, John

    2016-01-01

    Pitch is a perceptual correlate of periodicity. Sounds with distinct spectra can elicit the same pitch. Despite the importance of pitch perception, understanding the cellular mechanism of pitch perception is still a major challenge and a mechanistic model of pitch is lacking. A multi-stage neuronal network model is developed for pitch frequency estimation using biophysically-based, high-resolution coincidence detector neurons. The neuronal units respond only to highly coincident input among convergent auditory nerve fibers across frequency channels. Their selectivity for only very fast rising slopes of convergent input enables these slope-detectors to distinguish the most prominent coincidences in multi-peaked input time courses. Pitch can then be estimated from the first-order interspike intervals of the slope-detectors. The regular firing pattern of the slope-detector neurons are similar for sounds sharing the same pitch despite the distinct timbres. The decoded pitch strengths also correlate well with the salience of pitch perception as reported by human listeners. Therefore, our model can serve as a neural representation for pitch. Our model performs successfully in estimating the pitch of missing fundamental complexes and reproducing the pitch variation with respect to the frequency shift of inharmonic complexes. It also accounts for the phase sensitivity of pitch perception in the cases of Schroeder phase, alternating phase and random phase relationships. Moreover, our model can also be applied to stochastic sound stimuli, iterated-ripple-noise, and account for their multiple pitch perceptions.

  4. On the selection of ordinary differential equation models with application to predator-prey dynamical models.

    Science.gov (United States)

    Zhang, Xinyu; Cao, Jiguo; Carroll, Raymond J

    2015-03-01

    We consider model selection and estimation in a context where there are competing ordinary differential equation (ODE) models, and all the models are special cases of a "full" model. We propose a computationally inexpensive approach that employs statistical estimation of the full model, followed by a combination of a least squares approximation (LSA) and the adaptive Lasso. We show the resulting method, here called the LSA method, to be an (asymptotically) oracle model selection method. The finite sample performance of the proposed LSA method is investigated with Monte Carlo simulations, in which we examine the percentage of selecting true ODE models, the efficiency of the parameter estimation compared to simply using the full and true models, and coverage probabilities of the estimated confidence intervals for ODE parameters, all of which have satisfactory performances. Our method is also demonstrated by selecting the best predator-prey ODE to model a lynx and hare population dynamical system among some well-known and biologically interpretable ODE models. © 2014, The International Biometric Society.

  5. Acute leukemia classification by ensemble particle swarm model selection.

    Science.gov (United States)

    Escalante, Hugo Jair; Montes-y-Gómez, Manuel; González, Jesús A; Gómez-Gil, Pilar; Altamirano, Leopoldo; Reyes, Carlos A; Reta, Carolina; Rosales, Alejandro

    2012-07-01

    Acute leukemia is a malignant disease that affects a large proportion of the world population. Different types and subtypes of acute leukemia require different treatments. In order to assign the correct treatment, a physician must identify the leukemia type or subtype. Advanced and precise methods are available for identifying leukemia types, but they are very expensive and not available in most hospitals in developing countries. Thus, alternative methods have been proposed. An option explored in this paper is based on the morphological properties of bone marrow images, where features are extracted from medical images and standard machine learning techniques are used to build leukemia type classifiers. This paper studies the use of ensemble particle swarm model selection (EPSMS), which is an automated tool for the selection of classification models, in the context of acute leukemia classification. EPSMS is the application of particle swarm optimization to the exploration of the search space of ensembles that can be formed by heterogeneous classification models in a machine learning toolbox. EPSMS does not require prior domain knowledge and it is able to select highly accurate classification models without user intervention. Furthermore, specific models can be used for different classification tasks. We report experimental results for acute leukemia classification with real data and show that EPSMS outperformed the best results obtained using manually designed classifiers with the same data. The highest performance using EPSMS was of 97.68% for two-type classification problems and of 94.21% for more than two types problems. To the best of our knowledge, these are the best results reported for this data set. Compared with previous studies, these improvements were consistent among different type/subtype classification tasks, different features extracted from images, and different feature extraction regions. The performance improvements were statistically significant

  6. Host-Nonspecific Iron Acquisition Systems and Virulence in the Zoonotic Serovar of Vibrio vulnificus

    Science.gov (United States)

    Pajuelo, David; Lee, Chung-Te; Roig, Francisco J.; Lemos, Manuel L.; Hor, Lien-I

    2014-01-01

    The zoonotic serovar of Vibrio vulnificus (known as biotype 2 serovar E) is the etiological agent of human and fish vibriosis. The aim of the present work was to discover the role of the vulnibactin- and hemin-dependent iron acquisition systems in the pathogenicity of this zoonotic serovar under the hypothesis that both are host-nonspecific virulence factors. To this end, we selected three genes for three outer membrane receptors (vuuA, a receptor for ferric vulnibactin, and hupA and hutR, two hemin receptors), obtained single and multiple mutants as well as complemented strains, and tested them in a series of in vitro and in vivo assays, using eels and mice as animal models. The overall results confirm that hupA and vuuA, but not hutR, are host-nonspecific virulence genes and suggest that a third undescribed host-specific plasmid-encoded system could also be used by the zoonotic serovar in fish. hupA and vuuA were expressed in the internal organs of the animals in the first 24 h of infection, suggesting that they may be needed to achieve the population size required to trigger fatal septicemia. vuuA and hupA were sequenced in strains representative of the genetic diversity of this species, and their phylogenies were reconstructed by multilocus sequence analysis of selected housekeeping and virulence genes as a reference. Given the overall results, we suggest that both genes might form part of the core genes essential not only for disease development but also for the survival of this species in its natural reservoir, the aquatic environment. PMID:24478087

  7. Radial Domany-Kinzel models with mutation and selection

    Science.gov (United States)

    Lavrentovich, Maxim O.; Korolev, Kirill S.; Nelson, David R.

    2013-01-01

    We study the effect of spatial structure, genetic drift, mutation, and selective pressure on the evolutionary dynamics in a simplified model of asexual organisms colonizing a new territory. Under an appropriate coarse-graining, the evolutionary dynamics is related to the directed percolation processes that arise in voter models, the Domany-Kinzel (DK) model, contact process, and so on. We explore the differences between linear (flat front) expansions and the much less familiar radial (curved front) range expansions. For the radial expansion, we develop a generalized, off-lattice DK model that minimizes otherwise persistent lattice artifacts. With both simulations and analytical techniques, we study the survival probability of advantageous mutants, the spatial correlations between domains of neutral strains, and the dynamics of populations with deleterious mutations. “Inflation” at the frontier leads to striking differences between radial and linear expansions. For a colony with initial radius R0 expanding at velocity v, significant genetic demixing, caused by local genetic drift, occurs only up to a finite time t*=R0/v, after which portions of the colony become causally disconnected due to the inflating perimeter of the expanding front. As a result, the effect of a selective advantage is amplified relative to genetic drift, increasing the survival probability of advantageous mutants. Inflation also modifies the underlying directed percolation transition, introducing novel scaling functions and modifications similar to a finite-size effect. Finally, we consider radial range expansions with deflating perimeters, as might arise from colonization initiated along the shores of an island.

  8. Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.

    Science.gov (United States)

    Kerr, P J; Perkins, H D; Inglis, B; Stagg, R; McLaughlin, E; Collins, S V; Van Leeuwen, B H

    2004-06-20

    Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization.

  9. Developing a conceptual model for selecting and evaluating online markets

    Directory of Open Access Journals (Sweden)

    Sadegh Feizollahi

    2013-04-01

    Full Text Available There are many evidences, which emphasis on the benefits of using new technologies of information and communication in international business and many believe that E-Commerce can help satisfy customer explicit and implicit requirements. Internet shopping is a concept developed after the introduction of electronic commerce. Information technology (IT and its applications, specifically in the realm of the internet and e-mail promoted the development of e-commerce in terms of advertising, motivating and information. However, with the development of new technologies, credit and financial exchange on the internet websites were constructed so to facilitate e-commerce. The proposed study sends a total of 200 questionnaires to the target group (teachers - students - professionals - managers of commercial web sites and it manages to collect 130 questionnaires for final evaluation. Cronbach's alpha test is used for measuring reliability and to evaluate the validity of measurement instruments (questionnaires, and to assure construct validity, confirmatory factor analysis is employed. In addition, in order to analyze the research questions based on the path analysis method and to determine markets selection models, a regular technique is implemented. In the present study, after examining different aspects of e-commerce, we provide a conceptual model for selecting and evaluating online marketing in Iran. These findings provide a consistent, targeted and holistic framework for the development of the Internet market in the country.

  10. Ensemble Prediction Model with Expert Selection for Electricity Price Forecasting

    Directory of Open Access Journals (Sweden)

    Bijay Neupane

    2017-01-01

    Full Text Available Forecasting of electricity prices is important in deregulated electricity markets for all of the stakeholders: energy wholesalers, traders, retailers and consumers. Electricity price forecasting is an inherently difficult problem due to its special characteristic of dynamicity and non-stationarity. In this paper, we present a robust price forecasting mechanism that shows resilience towards the aggregate demand response effect and provides highly accurate forecasted electricity prices to the stakeholders in a dynamic environment. We employ an ensemble prediction model in which a group of different algorithms participates in forecasting 1-h ahead the price for each hour of a day. We propose two different strategies, namely, the Fixed Weight Method (FWM and the Varying Weight Method (VWM, for selecting each hour’s expert algorithm from the set of participating algorithms. In addition, we utilize a carefully engineered set of features selected from a pool of features extracted from the past electricity price data, weather data and calendar data. The proposed ensemble model offers better results than the Autoregressive Integrated Moving Average (ARIMA method, the Pattern Sequence-based Forecasting (PSF method and our previous work using Artificial Neural Networks (ANN alone on the datasets for New York, Australian and Spanish electricity markets.

  11. A Network Analysis Model for Selecting Sustainable Technology

    Directory of Open Access Journals (Sweden)

    Sangsung Park

    2015-09-01

    Full Text Available Most companies develop technologies to improve their competitiveness in the marketplace. Typically, they then patent these technologies around the world in order to protect their intellectual property. Other companies may use patented technologies to develop new products, but must pay royalties to the patent holders or owners. Should they fail to do so, this can result in legal disputes in the form of patent infringement actions between companies. To avoid such situations, companies attempt to research and develop necessary technologies before their competitors do so. An important part of this process is analyzing existing patent documents in order to identify emerging technologies. In such analyses, extracting sustainable technology from patent data is important, because sustainable technology drives technological competition among companies and, thus, the development of new technologies. In addition, selecting sustainable technologies makes it possible to plan their R&D (research and development efficiently. In this study, we propose a network model that can be used to select the sustainable technology from patent documents, based on the centrality and degree of a social network analysis. To verify the performance of the proposed model, we carry out a case study using actual patent data from patent databases.

  12. Cliff-edge model of obstetric selection in humans.

    Science.gov (United States)

    Mitteroecker, Philipp; Huttegger, Simon M; Fischer, Barbara; Pavlicev, Mihaela

    2016-12-20

    The strikingly high incidence of obstructed labor due to the disproportion of fetal size and the mother's pelvic dimensions has puzzled evolutionary scientists for decades. Here we propose that these high rates are a direct consequence of the distinct characteristics of human obstetric selection. Neonatal size relative to the birth-relevant maternal dimensions is highly variable and positively associated with reproductive success until it reaches a critical value, beyond which natural delivery becomes impossible. As a consequence, the symmetric phenotype distribution cannot match the highly asymmetric, cliff-edged fitness distribution well: The optimal phenotype distribution that maximizes population mean fitness entails a fraction of individuals falling beyond the "fitness edge" (i.e., those with fetopelvic disproportion). Using a simple mathematical model, we show that weak directional selection for a large neonate, a narrow pelvic canal, or both is sufficient to account for the considerable incidence of fetopelvic disproportion. Based on this model, we predict that the regular use of Caesarean sections throughout the last decades has led to an evolutionary increase of fetopelvic disproportion rates by 10 to 20%.

  13. Evidence for acquisition of virulence effectors in pathogenic chytrids

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    Summers Kyle

    2011-07-01

    Full Text Available Abstract Background The decline in amphibian populations across the world is frequently linked to the infection of the chytrid fungus Batrachochytrium dendrobatidis (Bd. This is particularly perplexing because Bd was only recently discovered in 1999 and no chytrid fungus had previously been identified as a vertebrate pathogen. Results In this study, we show that two large families of known virulence effector genes, crinkler (CRN proteins and serine peptidases, were acquired by Bd from oomycete pathogens and bacteria, respectively. These two families have been duplicated after their acquisition by Bd. Additional selection analyses indicate that both families evolved under strong positive selection, suggesting that they are involved in the adaptation of Bd to its hosts. Conclusions We propose that the acquisition of virulence effectors, in combination with habitat disruption and climate change, may have driven the Bd epidemics and the decline in amphibian populations. This finding provides a starting point for biochemical investigations of chytridiomycosis.

  14. Addressing selected problems of the modelling of digital control systems

    International Nuclear Information System (INIS)

    Sedlak, J.

    2004-12-01

    The introduction of digital systems to practical activities at nuclear power plants brings about new requirements for their modelling for the purposes of reliability analyses required for plant licensing as well as for inclusion into PSA studies and subsequent use in applications for the assessment of events, limits and conditions, and risk monitoring. It is very important to assess, both qualitatively and quantitatively, the effect of this change on operational safety. The report describes selected specific features of reliability analysis of digital system and recommends methodological procedures. The chapters of the report are as follows: (1) Flexibility and multifunctionality of the system. (2) General framework of reliability analyses (Understanding the system; Qualitative analysis; Quantitative analysis; Assessment of results, comparison against criteria; Documenting system reliability analyses; Asking for comments and their evaluation); and (3) Suitable reliability models (Reliability models of basic events; Monitored components with repair immediately following defect or failure; Periodically tested components; Constant unavailability (probability of failure to demand); Application of reliability models for electronic components; Example of failure rate decomposition; Example modified for diagnosis successfulness; Transfer of reliability analyses to PSA; Common cause failures - CCF; Software backup and CCF type failures, software versus hardware). (P.A.)

  15. A CONCEPTUAL MODEL FOR IMPROVED PROJECT SELECTION AND PRIORITISATION

    Directory of Open Access Journals (Sweden)

    P. J. Viljoen

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT: Project portfolio management processes are often designed and operated as a series of stages (or project phases and gates. However, the flow of such a process is often slow, characterised by queues waiting for a gate decision and by repeated work from previous stages waiting for additional information or for re-processing. In this paper the authors propose a conceptual model that applies supply chain and constraint management principles to the project portfolio management process. An advantage of the proposed model is that it provides the ability to select and prioritise projects without undue changes to project schedules. This should result in faster flow through the system.

    AFRIKAANSE OPSOMMING: Prosesse om portefeuljes van projekte te bestuur word normaalweg ontwerp en bedryf as ’n reeks fases en hekke. Die vloei deur so ’n proses is dikwels stadig en word gekenmerk deur toue wat wag vir besluite by die hekke en ook deur herwerk van vorige fases wat wag vir verdere inligting of vir herprosessering. In hierdie artikel word ‘n konseptuele model voorgestel. Die model berus op die beginsels van voorsieningskettings sowel as van beperkingsbestuur, en bied die voordeel dat projekte geselekteer en geprioritiseer kan word sonder onnodige veranderinge aan projekskedules. Dit behoort te lei tot versnelde vloei deur die stelsel.

  16. Helicobacter pylori virulence and cancer pathogenesis.

    Science.gov (United States)

    Yamaoka, Yoshio; Graham, David Y

    2014-06-01

    Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

  17. Selection of an appropriately simple storm runoff model

    Directory of Open Access Journals (Sweden)

    A. I. J. M. van Dijk

    2010-03-01

    Full Text Available An appropriately simple event runoff model for catchment hydrological studies was derived. The model was selected from several variants as having the optimum balance between simplicity and the ability to explain daily observations of streamflow from 260 Australian catchments (23–1902 km2. Event rainfall and runoff were estimated from the observations through a combination of baseflow separation and storm flow recession analysis, producing a storm flow recession coefficient (kQF. Various model structures with up to six free parameters were investigated, covering most of the equations applied in existing lumped catchment models. The performance of alternative structures and free parameters were expressed in Aikake's Final Prediction Error Criterion (FPEC and corresponding Nash-Sutcliffe model efficiencies (NSME for event runoff totals. For each model variant, the number of free parameters was reduced in steps based on calculated parameter sensitivity. The resulting optimal model structure had two or three free parameters; the first describing the non-linear relationship between event rainfall and runoff (Smax, the second relating runoff to antecedent groundwater storage (CSg, and a third that described initial rainfall losses (Li, but which could be set at 8 mm without affecting model performance too much. The best three parameter model produced a median NSME of 0.64 and outperformed, for example, the Soil Conservation Service Curve Number technique (median NSME 0.30–0.41. Parameter estimation in ungauged catchments is likely to be challenging: 64% of the variance in kQF among stations could be explained by catchment climate indicators and spatial correlation, but corresponding numbers were a modest 45% for CSg, 21% for Smax and none for Li, respectively. In gauged catchments, better

  18. Impact of selected troposphere models on Precise Point Positioning convergence

    Science.gov (United States)

    Kalita, Jakub; Rzepecka, Zofia

    2016-04-01

    The Precise Point Positioning (PPP) absolute method is currently intensively investigated in order to reach fast convergence time. Among various sources that influence the convergence of the PPP, the tropospheric delay is one of the most important. Numerous models of tropospheric delay are developed and applied to PPP processing. However, with rare exceptions, the quality of those models does not allow fixing the zenith path delay tropospheric parameter, leaving difference between nominal and final value to the estimation process. Here we present comparison of several PPP result sets, each of which based on different troposphere model. The respective nominal values are adopted from models: VMF1, GPT2w, MOPS and ZERO-WET. The PPP solution admitted as reference is based on the final troposphere product from the International GNSS Service (IGS). The VMF1 mapping function was used for all processing variants in order to provide capability to compare impact of applied nominal values. The worst case initiates zenith wet delay with zero value (ZERO-WET). Impact from all possible models for tropospheric nominal values should fit inside both IGS and ZERO-WET border variants. The analysis is based on data from seven IGS stations located in mid-latitude European region from year 2014. For the purpose of this study several days with the most active troposphere were selected for each of the station. All the PPP solutions were determined using gLAB open-source software, with the Kalman filter implemented independently by the authors of this work. The processing was performed on 1 hour slices of observation data. In addition to the analysis of the output processing files, the presented study contains detailed analysis of the tropospheric conditions for the selected data. The overall results show that for the height component the VMF1 model outperforms GPT2w and MOPS by 35-40% and ZERO-WET variant by 150%. In most of the cases all solutions converge to the same values during first

  19. On model selections for repeated measurement data in clinical studies.

    Science.gov (United States)

    Zou, Baiming; Jin, Bo; Koch, Gary G; Zhou, Haibo; Borst, Stephen E; Menon, Sandeep; Shuster, Jonathan J

    2015-05-10

    Repeated measurement designs have been widely used in various randomized controlled trials for evaluating long-term intervention efficacies. For some clinical trials, the primary research question is how to compare two treatments at a fixed time, using a t-test. Although simple, robust, and convenient, this type of analysis fails to utilize a large amount of collected information. Alternatively, the mixed-effects model is commonly used for repeated measurement data. It models all available data jointly and allows explicit assessment of the overall treatment effects across the entire time spectrum. In this paper, we propose an analytic strategy for longitudinal clinical trial data where the mixed-effects model is coupled with a model selection scheme. The proposed test statistics not only make full use of all available data but also utilize the information from the optimal model deemed for the data. The performance of the proposed method under various setups, including different data missing mechanisms, is evaluated via extensive Monte Carlo simulations. Our numerical results demonstrate that the proposed analytic procedure is more powerful than the t-test when the primary interest is to test for the treatment effect at the last time point. Simulations also reveal that the proposed method outperforms the usual mixed-effects model for testing the overall treatment effects across time. In addition, the proposed framework is more robust and flexible in dealing with missing data compared with several competing methods. The utility of the proposed method is demonstrated by analyzing a clinical trial on the cognitive effect of testosterone in geriatric men with low baseline testosterone levels. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Computationally efficient thermal-mechanical modelling of selective laser melting

    Science.gov (United States)

    Yang, Yabin; Ayas, Can

    2017-10-01

    The Selective laser melting (SLM) is a powder based additive manufacturing (AM) method to produce high density metal parts with complex topology. However, part distortions and accompanying residual stresses deteriorates the mechanical reliability of SLM products. Modelling of the SLM process is anticipated to be instrumental for understanding and predicting the development of residual stress field during the build process. However, SLM process modelling requires determination of the heat transients within the part being built which is coupled to a mechanical boundary value problem to calculate displacement and residual stress fields. Thermal models associated with SLM are typically complex and computationally demanding. In this paper, we present a simple semi-analytical thermal-mechanical model, developed for SLM that represents the effect of laser scanning vectors with line heat sources. The temperature field within the part being build is attained by superposition of temperature field associated with line heat sources in a semi-infinite medium and a complimentary temperature field which accounts for the actual boundary conditions. An analytical solution of a line heat source in a semi-infinite medium is first described followed by the numerical procedure used for finding the complimentary temperature field. This analytical description of the line heat sources is able to capture the steep temperature gradients in the vicinity of the laser spot which is typically tens of micrometers. In turn, semi-analytical thermal model allows for having a relatively coarse discretisation of the complimentary temperature field. The temperature history determined is used to calculate the thermal strain induced on the SLM part. Finally, a mechanical model governed by elastic-plastic constitutive rule having isotropic hardening is used to predict the residual stresses.

  1. Identification of genes preferentially expressed by highly virulent piscine Streptococcus agalactiae upon interaction with macrophages.

    Directory of Open Access Journals (Sweden)

    Chang-Ming Guo

    Full Text Available Streptococcus agalactiae, long recognized as a mammalian pathogen, is an emerging concern with regard to fish. In this study, we used a mouse model and in vitro cell infection to evaluate the pathogenetic characteristics of S. agalactiae GD201008-001, isolated from tilapia in China. This bacterium was found to be highly virulent and capable of inducing brain damage by migrating into the brain by crossing the blood-brain barrier (BBB. The phagocytosis assays indicated that this bacterium could be internalized by murine macrophages and survive intracellularly for more than 24 h, inducing injury to macrophages. Further, selective capture of transcribed sequences (SCOTS was used to investigate microbial gene expression associated with intracellular survival. This positive cDNA selection technique identified 60 distinct genes that could be characterized into 6 functional categories. More than 50% of the differentially expressed genes were involved in metabolic adaptation. Some genes have previously been described as associated with virulence in other bacteria, and four showed no significant similarities to any other previously described genes. This study constitutes the first step in further gene expression analyses that will lead to a better understanding of the molecular mechanisms used by S. agalactiae to survive in macrophages and to cross the BBB.

  2. Identification of Genes Preferentially Expressed by Highly Virulent Piscine Streptococcus agalactiae upon Interaction with Macrophages

    Science.gov (United States)

    Guo, Chang-Ming; Chen, Rong-Rong; Kalhoro, Dildar Hussain; Wang, Zhao-Fei; Liu, Guang-Jin; Lu, Cheng-Ping; Liu, Yong-Jie

    2014-01-01

    Streptococcus agalactiae, long recognized as a mammalian pathogen, is an emerging concern with regard to fish. In this study, we used a mouse model and in vitro cell infection to evaluate the pathogenetic characteristics of S. agalactiae GD201008-001, isolated from tilapia in China. This bacterium was found to be highly virulent and capable of inducing brain damage by migrating into the brain by crossing the blood–brain barrier (BBB). The phagocytosis assays indicated that this bacterium could be internalized by murine macrophages and survive intracellularly for more than 24 h, inducing injury to macrophages. Further, selective capture of transcribed sequences (SCOTS) was used to investigate microbial gene expression associated with intracellular survival. This positive cDNA selection technique identified 60 distinct genes that could be characterized into 6 functional categories. More than 50% of the differentially expressed genes were involved in metabolic adaptation. Some genes have previously been described as associated with virulence in other bacteria, and four showed no significant similarities to any other previously described genes. This study constitutes the first step in further gene expression analyses that will lead to a better understanding of the molecular mechanisms used by S. agalactiae to survive in macrophages and to cross the BBB. PMID:24498419

  3. Multicriteria decision group model for the selection of suppliers

    Directory of Open Access Journals (Sweden)

    Luciana Hazin Alencar

    2008-08-01

    Full Text Available Several authors have been studying group decision making over the years, which indicates how relevant it is. This paper presents a multicriteria group decision model based on ELECTRE IV and VIP Analysis methods, to those cases where there is great divergence among the decision makers. This model includes two stages. In the first, the ELECTRE IV method is applied and a collective criteria ranking is obtained. In the second, using criteria ranking, VIP Analysis is applied and the alternatives are selected. To illustrate the model, a numerical application in the context of the selection of suppliers in project management is used. The suppliers that form part of the project team have a crucial role in project management. They are involved in a network of connected activities that can jeopardize the success of the project, if they are not undertaken in an appropriate way. The question tackled is how to select service suppliers for a project on behalf of an enterprise that assists the multiple objectives of the decision-makers.Vários autores têm estudado decisão em grupo nos últimos anos, o que indica a relevância do assunto. Esse artigo apresenta um modelo multicritério de decisão em grupo baseado nos métodos ELECTRE IV e VIP Analysis, adequado aos casos em que se tem uma grande divergência entre os decisores. Esse modelo é composto por dois estágios. No primeiro, o método ELECTRE IV é aplicado e uma ordenação dos critérios é obtida. No próximo estágio, com a ordenação dos critérios, o método VIP Analysis é aplicado e as alternativas são selecionadas. Para ilustrar o modelo, uma aplicação numérica no contexto da seleção de fornecedores em projetos é realizada. Os fornecedores que fazem parte da equipe do projeto têm um papel fundamental no gerenciamento de projetos. Eles estão envolvidos em uma rede de atividades conectadas que, caso não sejam executadas de forma apropriada, podem colocar em risco o sucesso do

  4. Improving permafrost distribution modelling using feature selection algorithms

    Science.gov (United States)

    Deluigi, Nicola; Lambiel, Christophe; Kanevski, Mikhail

    2016-04-01

    The availability of an increasing number of spatial data on the occurrence of mountain permafrost allows the employment of machine learning (ML) classification algorithms for modelling the distribution of the phenomenon. One of the major problems when dealing with high-dimensional dataset is the number of input features (variables) involved. Application of ML classification algorithms to this large number of variables leads to the risk of overfitting, with the consequence of a poor generalization/prediction. For this reason, applying feature selection (FS) techniques helps simplifying the amount of factors required and improves the knowledge on adopted features and their relation with the studied phenomenon. Moreover, taking away irrelevant or redundant variables from the dataset effectively improves the quality of the ML prediction. This research deals with a comparative analysis of permafrost distribution models supported by FS variable importance assessment. The input dataset (dimension = 20-25, 10 m spatial resolution) was constructed using landcover maps, climate data and DEM derived variables (altitude, aspect, slope, terrain curvature, solar radiation, etc.). It was completed with permafrost evidences (geophysical and thermal data and rock glacier inventories) that serve as training permafrost data. Used FS algorithms informed about variables that appeared less statistically important for permafrost presence/absence. Three different algorithms were compared: Information Gain (IG), Correlation-based Feature Selection (CFS) and Random Forest (RF). IG is a filter technique that evaluates the worth of a predictor by measuring the information gain with respect to the permafrost presence/absence. Conversely, CFS is a wrapper technique that evaluates the worth of a subset of predictors by considering the individual predictive ability of each variable along with the degree of redundancy between them. Finally, RF is a ML algorithm that performs FS as part of its

  5. A Model for Selection of Eyespots on Butterfly Wings.

    Science.gov (United States)

    Sekimura, Toshio; Venkataraman, Chandrasekhar; Madzvamuse, Anotida

    2015-01-01

    The development of eyespots on the wing surface of butterflies of the family Nympalidae is one of the most studied examples of biological pattern formation.However, little is known about the mechanism that determines the number and precise locations of eyespots on the wing. Eyespots develop around signaling centers, called foci, that are located equidistant from wing veins along the midline of a wing cell (an area bounded by veins). A fundamental question that remains unsolved is, why a certain wing cell develops an eyespot, while other wing cells do not. We illustrate that the key to understanding focus point selection may be in the venation system of the wing disc. Our main hypothesis is that changes in morphogen concentration along the proximal boundary veins of wing cells govern focus point selection. Based on previous studies, we focus on a spatially two-dimensional reaction-diffusion system model posed in the interior of each wing cell that describes the formation of focus points. Using finite element based numerical simulations, we demonstrate that variation in the proximal boundary condition is sufficient to robustly select whether an eyespot focus point forms in otherwise identical wing cells. We also illustrate that this behavior is robust to small perturbations in the parameters and geometry and moderate levels of noise. Hence, we suggest that an anterior-posterior pattern of morphogen concentration along the proximal vein may be the main determinant of the distribution of focus points on the wing surface. In order to complete our model, we propose a two stage reaction-diffusion system model, in which an one-dimensional surface reaction-diffusion system, posed on the proximal vein, generates the morphogen concentrations that act as non-homogeneous Dirichlet (i.e., fixed) boundary conditions for the two-dimensional reaction-diffusion model posed in the wing cells. The two-stage model appears capable of generating focus point distributions observed in

  6. A Model for Selection of Eyespots on Butterfly Wings.

    Directory of Open Access Journals (Sweden)

    Toshio Sekimura

    Full Text Available The development of eyespots on the wing surface of butterflies of the family Nympalidae is one of the most studied examples of biological pattern formation.However, little is known about the mechanism that determines the number and precise locations of eyespots on the wing. Eyespots develop around signaling centers, called foci, that are located equidistant from wing veins along the midline of a wing cell (an area bounded by veins. A fundamental question that remains unsolved is, why a certain wing cell develops an eyespot, while other wing cells do not.We illustrate that the key to understanding focus point selection may be in the venation system of the wing disc. Our main hypothesis is that changes in morphogen concentration along the proximal boundary veins of wing cells govern focus point selection. Based on previous studies, we focus on a spatially two-dimensional reaction-diffusion system model posed in the interior of each wing cell that describes the formation of focus points. Using finite element based numerical simulations, we demonstrate that variation in the proximal boundary condition is sufficient to robustly select whether an eyespot focus point forms in otherwise identical wing cells. We also illustrate that this behavior is robust to small perturbations in the parameters and geometry and moderate levels of noise. Hence, we suggest that an anterior-posterior pattern of morphogen concentration along the proximal vein may be the main determinant of the distribution of focus points on the wing surface. In order to complete our model, we propose a two stage reaction-diffusion system model, in which an one-dimensional surface reaction-diffusion system, posed on the proximal vein, generates the morphogen concentrations that act as non-homogeneous Dirichlet (i.e., fixed boundary conditions for the two-dimensional reaction-diffusion model posed in the wing cells. The two-stage model appears capable of generating focus point distributions

  7. Multiphysics modeling of selective laser sintering/melting

    Science.gov (United States)

    Ganeriwala, Rishi Kumar

    A significant percentage of total global employment is due to the manufacturing industry. However, manufacturing also accounts for nearly 20% of total energy usage in the United States according to the EIA. In fact, manufacturing accounted for 90% of industrial energy consumption and 84% of industry carbon dioxide emissions in 2002. Clearly, advances in manufacturing technology and efficiency are necessary to curb emissions and help society as a whole. Additive manufacturing (AM) refers to a relatively recent group of manufacturing technologies whereby one can 3D print parts, which has the potential to significantly reduce waste, reconfigure the supply chain, and generally disrupt the whole manufacturing industry. Selective laser sintering/melting (SLS/SLM) is one type of AM technology with the distinct advantage of being able to 3D print metals and rapidly produce net shape parts with complicated geometries. In SLS/SLM parts are built up layer-by-layer out of powder particles, which are selectively sintered/melted via a laser. However, in order to produce defect-free parts of sufficient strength, the process parameters (laser power, scan speed, layer thickness, powder size, etc.) must be carefully optimized. Obviously, these process parameters will vary depending on material, part geometry, and desired final part characteristics. Running experiments to optimize these parameters is costly, energy intensive, and extremely material specific. Thus a computational model of this process would be highly valuable. In this work a three dimensional, reduced order, coupled discrete element - finite difference model is presented for simulating the deposition and subsequent laser heating of a layer of powder particles sitting on top of a substrate. Validation is provided and parameter studies are conducted showing the ability of this model to help determine appropriate process parameters and an optimal powder size distribution for a given material. Next, thermal stresses upon

  8. Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage

    DEFF Research Database (Denmark)

    Yang, Ziheng; Nielsen, Rasmus

    2008-01-01

    Current models of codon substitution are formulated at the levels of nucleotide substitution and do not explicitly consider the separate effects of mutation and selection. They are thus incapable of inferring whether mutation or selection is responsible for evolution at silent sites. Here we impl...... codon usage in mammals. Estimates of selection coefficients nevertheless suggest that selection on codon usage is weak and most mutations are nearly neutral. The sensitivity of the analysis on the assumed mutation model is discussed.......Current models of codon substitution are formulated at the levels of nucleotide substitution and do not explicitly consider the separate effects of mutation and selection. They are thus incapable of inferring whether mutation or selection is responsible for evolution at silent sites. Here we...... implement a few population genetics models of codon substitution that explicitly consider mutation bias and natural selection at the DNA level. Selection on codon usage is modeled by introducing codon-fitness parameters, which together with mutation-bias parameters, predict optimal codon frequencies...

  9. Responsiveness to acidity via metal ion regulators mediates virulence in the gastric pathogen Helicobacter pylori.

    Science.gov (United States)

    Bury-Moné, Stéphanie; Thiberge, Jean-Michel; Contreras, Monica; Maitournam, Aboubakar; Labigne, Agnès; De Reuse, Hilde

    2004-07-01

    The virulence of pathogenic bacteria is dependent on their adaptation to and survival in the stressful conditions encountered in their hosts. Helicobacter pylori exclusively colonizes the acid stomach of primates, making it an ideal study model. Little is known about how H. pylori responds to the moderately acidic conditions encountered at its colonization site, the gastric mucus layer. Thus, we compared gene expression profiles of H. pylori 26695 grown at neutral and acidic pH, and validated the data for a selection of genes by real-time polymerase chain reaction, dot-blots or enzymatic assays. During growth in acidic conditions, 56 genes were upregulated and 45 genes downregulated. We found that acidity is a signal modulating the expression of several virulence factors. Regulation of genes related to metal ion homeostasis suggests protective mechanisms involving diminished transport and enhanced storage. Genes encoding subunits of the F0F1 ATPase and of a newly identified Na+/H+ antiporter (NhaC-HP0946) were downregulated, revealing that this bacterium uses original mechanisms to control proton entry. Five of the upregulated genes encoded proteins controlling intracellular ammonia synthesis, including urease, amidase and formamidase, underlining the major role of this buffering compound in the protection against acidity in H. pylori. Regulatory networks and transcriptome analysis as well as enzymatic assays implicated two metal-responsive transcriptional regulators (NikR and Fur) and an essential two-component response regulator (HP0166, OmpR-like) as effectors of the H. pylori acid response. Finally, a nikR-fur mutant is attenuated in the mouse model, emphasizing the link between response to acidity, metal metabolism and virulence in this gastric pathogen.

  10. Cystic fibrosis-niche adaptation of Pseudomonas aeruginosa reduces virulence in multiple infection hosts.

    Directory of Open Access Journals (Sweden)

    Nicola Ivan Lorè

    Full Text Available The opportunistic pathogen Pseudomonas aeruginosa is able to thrive in diverse ecological niches and to cause serious human infection. P. aeruginosa environmental strains are producing various virulence factors that are required for establishing acute infections in several host organisms; however, the P. aeruginosa phenotypic variants favour long-term persistence in the cystic fibrosis (CF airways. Whether P. aeruginosa strains, which have adapted to the CF-niche, have lost their competitive fitness in the other environment remains to be investigated. In this paper, three P. aeruginosa clonal lineages, including early strains isolated at the onset of infection, and late strains, isolated after several years of chronic lung infection from patients with CF, were analysed in multi-host model systems of acute infection. P. aeruginosa early isolates caused lethality in the three non-mammalian hosts, namely Caenorhabditis elegans, Galleria mellonella, and Drosophila melanogaster, while late adapted clonal isolates were attenuated in acute virulence. When two different mouse genetic background strains, namely C57Bl/6NCrl and Balb/cAnNCrl, were used as acute infection models, early P. aeruginosa CF isolates were lethal, while late isolates exhibited reduced or abolished acute virulence. Severe histopathological lesions, including high leukocytes recruitment and bacterial load, were detected in the lungs of mice infected with P. aeruginosa CF early isolates, while late isolates were progressively cleared. In addition, systemic bacterial spread and invasion of epithelial cells, which were detected for P. aeruginosa CF early strains, were not observed with late strains. Our findings indicate that niche-specific selection in P. aeruginosa reduced its ability to cause acute infections across a broad range of hosts while maintaining the capacity for chronic infection in the CF host.

  11. Consistency in Estimation and Model Selection of Dynamic Panel Data Models with Fixed Effects

    Directory of Open Access Journals (Sweden)

    Guangjie Li

    2015-07-01

    Full Text Available We examine the relationship between consistent parameter estimation and model selection for autoregressive panel data models with fixed effects. We find that the transformation of fixed effects proposed by Lancaster (2002 does not necessarily lead to consistent estimation of common parameters when some true exogenous regressors are excluded. We propose a data dependent way to specify the prior of the autoregressive coefficient and argue for comparing different model specifications before parameter estimation. Model selection properties of Bayes factors and Bayesian information criterion (BIC are investigated. When model uncertainty is substantial, we recommend the use of Bayesian Model Averaging to obtain point estimators with lower root mean squared errors (RMSE. We also study the implications of different levels of inclusion probabilities by simulations.

  12. Hyperopt: a Python library for model selection and hyperparameter optimization

    Science.gov (United States)

    Bergstra, James; Komer, Brent; Eliasmith, Chris; Yamins, Dan; Cox, David D.

    2015-01-01

    Sequential model-based optimization (also known as Bayesian optimization) is one of the most efficient methods (per function evaluation) of function minimization. This efficiency makes it appropriate for optimizing the hyperparameters of machine learning algorithms that are slow to train. The Hyperopt library provides algorithms and parallelization infrastructure for performing hyperparameter optimization (model selection) in Python. This paper presents an introductory tutorial on the usage of the Hyperopt library, including the description of search spaces, minimization (in serial and parallel), and the analysis of the results collected in the course of minimization. This paper also gives an overview of Hyperopt-Sklearn, a software project that provides automatic algorithm configuration of the Scikit-learn machine learning library. Following Auto-Weka, we take the view that the choice of classifier and even the choice of preprocessing module can be taken together to represent a single large hyperparameter optimization problem. We use Hyperopt to define a search space that encompasses many standard components (e.g. SVM, RF, KNN, PCA, TFIDF) and common patterns of composing them together. We demonstrate, using search algorithms in Hyperopt and standard benchmarking data sets (MNIST, 20-newsgroups, convex shapes), that searching this space is practical and effective. In particular, we improve on best-known scores for the model space for both MNIST and convex shapes. The paper closes with some discussion of ongoing and future work.

  13. Model catalysis by size-selected cluster deposition

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Scott [Univ. of Utah, Salt Lake City, UT (United States)

    2015-11-20

    This report summarizes the accomplishments during the last four years of the subject grant. Results are presented for experiments in which size-selected model catalysts were studied under surface science and aqueous electrochemical conditions. Strong effects of cluster size were found, and by correlating the size effects with size-dependent physical properties of the samples measured by surface science methods, it was possible to deduce mechanistic insights, such as the factors that control the rate-limiting step in the reactions. Results are presented for CO oxidation, CO binding energetics and geometries, and electronic effects under surface science conditions, and for the electrochemical oxygen reduction reaction, ethanol oxidation reaction, and for oxidation of carbon by water.

  14. Quantitative genetic models of sexual selection by male choice.

    Science.gov (United States)

    Nakahashi, Wataru

    2008-09-01

    There are many examples of male mate choice for female traits that tend to be associated with high fertility. I develop quantitative genetic models of a female trait and a male preference to show when such a male preference can evolve. I find that a disagreement between the fertility maximum and the viability maximum of the female trait is necessary for directional male preference (preference for extreme female trait values) to evolve. Moreover, when there is a shortage of available male partners or variance in male nongenetic quality, strong male preference can evolve. Furthermore, I also show that males evolve to exhibit a stronger preference for females that are more feminine (less resemblance to males) than the average female when there is a sexual dimorphism caused by fertility selection which acts only on females.

  15. Analytical Modelling Of Milling For Tool Design And Selection

    International Nuclear Information System (INIS)

    Fontaine, M.; Devillez, A.; Dudzinski, D.

    2007-01-01

    This paper presents an efficient analytical model which allows to simulate a large panel of milling operations. A geometrical description of common end mills and of their engagement in the workpiece material is proposed. The internal radius of the rounded part of the tool envelope is used to define the considered type of mill. The cutting edge position is described for a constant lead helix and for a constant local helix angle. A thermomechanical approach of oblique cutting is applied to predict forces acting on the tool and these results are compared with experimental data obtained from milling tests on a 42CrMo4 steel for three classical types of mills. The influence of some tool's geometrical parameters on predicted cutting forces is presented in order to propose optimisation criteria for design and selection of cutting tools

  16. The LuxS/AI-2 Quorum-Sensing System of Streptococcus pneumoniae Is Required to Cause Disease, and to Regulate Virulence- and Metabolism-Related Genes in a Rat Model of Middle Ear Infection

    Directory of Open Access Journals (Sweden)

    Mukesh K. Yadav

    2018-05-01

    DNA replication and repair, ATP synthesis, capsule biosynthesis, cell division, the cell cycle, signal transduction, transcription regulation, competence, virulence, and carbohydrate metabolism were downregulated in the absence of LuxS/AI-2.Conclusion: The S. pneumoniae LuxS/AI-2 quorum-sensing system is necessary for biofilm formation and the colonization of the ear epithelium, and caused middle ear infection in the rat model. LuxS/AI-2 regulates the expression of the genes involved in virulence and bacterial fitness during pneumococcal biofilm formation.

  17. ModelMage: a tool for automatic model generation, selection and management.

    Science.gov (United States)

    Flöttmann, Max; Schaber, Jörg; Hoops, Stephan; Klipp, Edda; Mendes, Pedro

    2008-01-01

    Mathematical modeling of biological systems usually involves implementing, simulating, and discriminating several candidate models that represent alternative hypotheses. Generating and managing these candidate models is a tedious and difficult task and can easily lead to errors. ModelMage is a tool that facilitates management of candidate models. It is designed for the easy and rapid development, generation, simulation, and discrimination of candidate models. The main idea of the program is to automatically create a defined set of model alternatives from a single master model. The user provides only one SBML-model and a set of directives from which the candidate models are created by leaving out species, modifiers or reactions. After generating models the software can automatically fit all these models to the data and provides a ranking for model selection, in case data is available. In contrast to other model generation programs, ModelMage aims at generating only a limited set of models that the user can precisely define. ModelMage uses COPASI as a simulation and optimization engine. Thus, all simulation and optimization features of COPASI are readily incorporated. ModelMage can be downloaded from http://sysbio.molgen.mpg.de/modelmage and is distributed as free software.

  18. Identification of Burkholderia cenocepacia strain H111 virulence factors using nonmammalian infection hosts

    DEFF Research Database (Denmark)

    Schwager, Stephan; Agnoli, Kirsty; Köthe, Manuela

    2013-01-01

    Burkholderia cenocepacia H111, a strain isolated from a cystic fibrosis patient, has been shown to effectively kill the nematode Caenorhabditis elegans. We used the C. elegans model of infection to screen a mini-Tn5 mutant library of B. cenocepacia H111 for attenuated virulence....... Of the approximately 5,500 B. cenocepacia H111 random mini-Tn5 insertion mutants that were screened, 22 showed attenuated virulence in C. elegans. Except for the quorum-sensing regulator cepR, none of the mutated genes coded for the biosynthesis of classical virulence factors such as extracellular proteases...... or siderophores. Instead, the mutants contained insertions in metabolic and regulatory genes. Mutants attenuated in virulence in the C. elegans infection model were also tested in the Drosophila melanogaster pricking model, and those also attenuated in this model were further tested in Galleria mellonella. Six...

  19. Within-host selection of drug resistance in a mouse model reveals dose-dependent selection of atovaquone resistance mutations

    NARCIS (Netherlands)

    Nuralitha, Suci; Murdiyarso, Lydia S.; Siregar, Josephine E.; Syafruddin, Din; Roelands, Jessica; Verhoef, Jan; Hoepelman, Andy I.M.; Marzuki, Sangkot

    2017-01-01

    The evolutionary selection of malaria parasites within an individual host plays a critical role in the emergence of drug resistance. We have compared the selection of atovaquone resistance mutants in mouse models reflecting two different causes of failure of malaria treatment, an inadequate

  20. A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae.

    Science.gov (United States)

    Atack, John M; Srikhanta, Yogitha N; Fox, Kate L; Jurcisek, Joseph A; Brockman, Kenneth L; Clark, Tyson A; Boitano, Matthew; Power, Peter M; Jen, Freda E-C; McEwan, Alastair G; Grimmond, Sean M; Smith, Arnold L; Barenkamp, Stephen J; Korlach, Jonas; Bakaletz, Lauren O; Jennings, Michael P

    2015-07-28

    Non-typeable Haemophilus influenzae contains an N(6)-adenine DNA-methyltransferase (ModA) that is subject to phase-variable expression (random ON/OFF switching). Five modA alleles, modA2, modA4, modA5, modA9 and modA10, account for over two-thirds of clinical otitis media isolates surveyed. Here, we use single molecule, real-time (SMRT) methylome analysis to identify the DNA-recognition motifs for all five of these modA alleles. Phase variation of these alleles regulates multiple proteins including vaccine candidates, and key virulence phenotypes such as antibiotic resistance (modA2, modA5, modA10), biofilm formation (modA2) and immunoevasion (modA4). Analyses of a modA2 strain in the chinchilla model of otitis media show a clear selection for ON switching of modA2 in the middle ear. Our results indicate that a biphasic epigenetic switch can control bacterial virulence, immunoevasion and niche adaptation in an animal model system.

  1. CHAIN-WISE GENERALIZATION OF ROAD NETWORKS USING MODEL SELECTION

    Directory of Open Access Journals (Sweden)

    D. Bulatov

    2017-05-01

    Full Text Available Streets are essential entities of urban terrain and their automatized extraction from airborne sensor data is cumbersome because of a complex interplay of geometric, topological and semantic aspects. Given a binary image, representing the road class, centerlines of road segments are extracted by means of skeletonization. The focus of this paper lies in a well-reasoned representation of these segments by means of geometric primitives, such as straight line segments as well as circle and ellipse arcs. We propose the fusion of raw segments based on similarity criteria; the output of this process are the so-called chains which better match to the intuitive perception of what a street is. Further, we propose a two-step approach for chain-wise generalization. First, the chain is pre-segmented using circlePeucker and finally, model selection is used to decide whether two neighboring segments should be fused to a new geometric entity. Thereby, we consider both variance-covariance analysis of residuals and model complexity. The results on a complex data-set with many traffic roundabouts indicate the benefits of the proposed procedure.

  2. A computational neural model of goal-directed utterance selection.

    Science.gov (United States)

    Klein, Michael; Kamp, Hans; Palm, Guenther; Doya, Kenji

    2010-06-01

    It is generally agreed that much of human communication is motivated by extra-linguistic goals: we often make utterances in order to get others to do something, or to make them support our cause, or adopt our point of view, etc. However, thus far a computational foundation for this view on language use has been lacking. In this paper we propose such a foundation using Markov Decision Processes. We borrow computational components from the field of action selection and motor control, where a neurobiological basis of these components has been established. In particular, we make use of internal models (i.e., next-state transition functions defined on current state action pairs). The internal model is coupled with reinforcement learning of a value function that is used to assess the desirability of any state that utterances (as well as certain non-verbal actions) can bring about. This cognitive architecture is tested in a number of multi-agent game simulations. In these computational experiments an agent learns to predict the context-dependent effects of utterances by interacting with other agents that are already competent speakers. We show that the cognitive architecture can account for acquiring the capability of deciding when to speak in order to achieve a certain goal (instead of performing a non-verbal action or simply doing nothing), whom to address and what to say. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. Molecular Characterization of Putative Virulence Determinants in Burkholderia pseudomallei

    Directory of Open Access Journals (Sweden)

    Suat Moi Puah

    2014-01-01

    Full Text Available The Gram-negative saprophyte Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease which is endemic in Southeast Asia and northern Australia. This bacterium possesses many virulence factors which are thought to contribute to its survival and pathogenicity. Using a virulent clinical isolate of B. pseudomallei and an attenuated strain of the same B. pseudomallei isolate, 6 genes BPSL2033, BP1026B_I2784, BP1026B_I2780, BURPS1106A_A0094, BURPS1106A_1131, and BURPS1710A_1419 were identified earlier by PCR-based subtractive hybridization. These genes were extensively characterized at the molecular level, together with an additional gene BPSL3147 that had been identified by other investigators. Through a reverse genetic approach, single-gene knockout mutants were successfully constructed by using site-specific insertion mutagenesis and were confirmed by PCR. BPSL2033::Km and BURPS1710A_1419::Km mutants showed reduced rates of survival inside macrophage RAW 264.7 cells and also low levels of virulence in the nematode infection model. BPSL2033::Km demonstrated weak statistical significance (P=0.049 at 8 hours after infection in macrophage infection study but this was not seen in BURPS1710A_1419::Km. Nevertheless, complemented strains of both genes were able to partially restore the gene defects in both in vitro and in vivo studies, thus suggesting that they individually play a minor role in the virulence of B. pseudomallei.

  4. Selection Bias in Educational Transition Models: Theory and Empirical Evidence

    DEFF Research Database (Denmark)

    Holm, Anders; Jæger, Mads

    variables. This paper, first, explains theoretically how selection on unobserved variables leads to waning coefficients and, second, illustrates empirically how selection leads to biased estimates of the effect of family background on educational transitions. Our empirical analysis using data from...

  5. Verification Techniques for Parameter Selection and Bayesian Model Calibration Presented for an HIV Model

    Science.gov (United States)

    Wentworth, Mami Tonoe

    Uncertainty quantification plays an important role when making predictive estimates of model responses. In this context, uncertainty quantification is defined as quantifying and reducing uncertainties, and the objective is to quantify uncertainties in parameter, model and measurements, and propagate the uncertainties through the model, so that one can make a predictive estimate with quantified uncertainties. Two of the aspects of uncertainty quantification that must be performed prior to propagating uncertainties are model calibration and parameter selection. There are several efficient techniques for these processes; however, the accuracy of these methods are often not verified. This is the motivation for our work, and in this dissertation, we present and illustrate verification frameworks for model calibration and parameter selection in the context of biological and physical models. First, HIV models, developed and improved by [2, 3, 8], describe the viral infection dynamics of an HIV disease. These are also used to make predictive estimates of viral loads and T-cell counts and to construct an optimal control for drug therapy. Estimating input parameters is an essential step prior to uncertainty quantification. However, not all the parameters are identifiable, implying that they cannot be uniquely determined by the observations. These unidentifiable parameters can be partially removed by performing parameter selection, a process in which parameters that have minimal impacts on the model response are determined. We provide verification techniques for Bayesian model calibration and parameter selection for an HIV model. As an example of a physical model, we employ a heat model with experimental measurements presented in [10]. A steady-state heat model represents a prototypical behavior for heat conduction and diffusion process involved in a thermal-hydraulic model, which is a part of nuclear reactor models. We employ this simple heat model to illustrate verification

  6. Anaerobiosis induced virulence of Salmonella typhi

    DEFF Research Database (Denmark)

    Kapoor, Sarika; Singh, R D; Sharma, P C

    2002-01-01

    , we examined the effect of anaerobiosis on the virulence of Salmonella Typhi, a Gram negative bacteria which invades through the gut mucosa and is responsible for typhoid fever. METHODS: Salmonella Typhi (ty2) was cultured in aerobic and anaerobic conditions to compare its virulence by rabbit ileal...

  7. Virulence, serotype and phylogenetic groups of diarrhoeagenic ...

    African Journals Online (AJOL)

    Dr DADIE Thomas

    2014-02-17

    Feb 17, 2014 ... The virulence, serotype and phylogenetic traits of diarrhoeagenic Escherichia coli were detected in 502 strains isolated during digestive infections. Molecular detection of the target virulence genes, rfb gene of operon O and phylogenetic grouping genes Chua, yjaA and TSPE4.C2 was performed.

  8. Molecular epidemiology and virulence assessment of Aspergillus fumigatus isolates from white stork chicks and their environment.

    Science.gov (United States)

    Olias, Philipp; Gruber, Achim D; Hafez, Hafez M; Lierz, Michael; Slesiona, Silvia; Brock, Matthias; Jacobsen, Ilse D

    2011-03-24

    Aspergillus fumigatus is a common pathogen in poultry and captive wild birds and an emerging opportunistic fungal pathogen in immunocompromised humans. Although invasive aspergillosis is frequently reported in free-ranging wild birds, the incidence and epidemiology of the disease in a natural setting is unknown. We recently reported endemic outbreaks of invasive aspergillosis at white stork nesting sites close to human habitation in Germany with significant subsequent breeding losses. Therefore, we hypothesized that A. fumigatus strains with higher virulence in birds may have evolved in this environment and performed the first epidemiological analysis of invasive aspergillosis in free-ranging wild birds. Sixty-one clinical and environmental A. fumigatus isolates from six affected nesting sites were genotyped by microsatellite analysis using the STRAf-assay. The isolates showed a remarkable high genomic diversity and, contrary to the initial hypothesis, clinical and environmental isolates did not cluster significantly. Interestingly, storks were infected with two to four different genotypes and in most cases both mating types MAT-1.1 and MAT-1.2 were present within the same specimen. The majority of selected clinical and environmental strains exhibited similar virulence in an in vivo infection model using embryonated chicken eggs. Noteworthy, virulence was not associated with one distinct fungal mating type. These results further support the assumption that the majority of A. fumigatus strains have the potential to cause disease in susceptible hosts. In white storks, immaturity of the immune system during the first three weeks of age may enhance susceptibility to invasive aspergillosis. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Reduced Set of Virulence Genes Allows High Accuracy Prediction of Bacterial Pathogenicity in Humans

    Science.gov (United States)

    Iraola, Gregorio; Vazquez, Gustavo; Spangenberg, Lucía; Naya, Hugo

    2012-01-01

    Although there have been great advances in understanding bacterial pathogenesis, there is still a lack of integrative information about what makes a bacterium a human pathogen. The advent of high-throughput sequencing technologies has dramatically increased the amount of completed bacterial genomes, for both known human pathogenic and non-pathogenic strains; this information is now available to investigate genetic features that determine pathogenic phenotypes in bacteria. In this work we determined presence/absence patterns of different virulence-related genes among more than finished bacterial genomes from both human pathogenic and non-pathogenic strains, belonging to different taxonomic groups (i.e: Actinobacteria, Gammaproteobacteria, Firmicutes, etc.). An accuracy of 95% using a cross-fold validation scheme with in-fold feature selection is obtained when classifying human pathogens and non-pathogens. A reduced subset of highly informative genes () is presented and applied to an external validation set. The statistical model was implemented in the BacFier v1.0 software (freely available at ), that displays not only the prediction (pathogen/non-pathogen) and an associated probability for pathogenicity, but also the presence/absence vector for the analyzed genes, so it is possible to decipher the subset of virulence genes responsible for the classification on the analyzed genome. Furthermore, we discuss the biological relevance for bacterial pathogenesis of the core set of genes, corresponding to eight functional categories, all with evident and documented association with the phenotypes of interest. Also, we analyze which functional categories of virulence genes were more distinctive for pathogenicity in each taxonomic group, which seems to be a completely new kind of information and could lead to important evolutionary conclusions. PMID:22916122

  10. Association between virulence and triazole tolerance in the phytopathogenic fungus Mycosphaerella graminicola.

    Directory of Open Access Journals (Sweden)

    Lina Yang

    Full Text Available Host resistance and synthetic antimicrobials such as fungicides are two of the main approaches used to control plant diseases in conventional agriculture. Although pathogens often evolve to overcome host resistance and antimicrobials, the majority of reports have involved qualitative host - pathogen interactions or antimicrobials targeting a single pathogen protein or metabolic pathway. Studies that consider jointly the evolution of virulence, defined as the degree of damage caused to a host by parasite infection, and antimicrobial resistance are rare. Here we compared virulence and fungicide tolerance in the fungal pathogen Mycosphaerella graminicola sampled from wheat fields across three continents and found a positive correlation between virulence and tolerance to a triazole fungicide. We also found that quantitative host resistance selected for higher pathogen virulence. The possible mechanisms responsible for these observations and their consequences for sustainable disease management are discussed.

  11. Uropathogenic Escherichia coli virulence genes: invaluable approaches for designing DNA microarray probes.

    Science.gov (United States)

    Jahandeh, Nadia; Ranjbar, Reza; Behzadi, Payam; Behzadi, Elham

    2015-01-01

    The pathotypes of uropathogenic Escherichia coli (UPEC) cause different types of urinary tract infections (UTIs). The presence of a wide range of virulence genes in UPEC enables us to design appropriate DNA microarray probes. These probes, which are used in DNA microarray technology, provide us with an accurate and rapid diagnosis and definitive treatment in association with UTIs caused by UPEC pathotypes. The main goal of this article is to introduce the UPEC virulence genes as invaluable approaches for designing DNA microarray probes. Main search engines such as Google Scholar and databases like NCBI were searched to find and study several original pieces of literature, review articles, and DNA gene sequences. In parallel with in silico studies, the experiences of the authors were helpful for selecting appropriate sources and writing this review article. There is a significant variety of virulence genes among UPEC strains. The DNA sequences of virulence genes are fabulous patterns for designing microarray probes. The location of virulence genes and their sequence lengths influence the quality of probes. The use of selected virulence genes for designing microarray probes gives us a wide range of choices from which the best probe candidates can be chosen. DNA microarray technology provides us with an accurate, rapid, cost-effective, sensitive, and specific molecular diagnostic method which is facilitated by designing microarray probes. Via these tools, we are able to have an accurate diagnosis and a definitive treatment regarding UTIs caused by UPEC pathotypes.

  12. Main functions and taxonomic distribution of virulence genes in Brucella melitensis 16 M.

    Directory of Open Access Journals (Sweden)

    Aniel Jessica Leticia Brambila-Tapia

    Full Text Available Many virulence genes have been detected in attenuated mutants of Brucella melitensis 16 M; nevertheless, a complete report of these genes, including the main Cluster of Orthologous Groups (COG represented as well as the taxonomical distribution among all complete bacterial and archaeal genomes, has not been analyzed. In this work a total of 160 virulence genes that have been reported in attenuated mutants in B. melitensis were included and analyzed. Additionally, we obtained 250 B. melitensis randomly selected genes as a reference group for the taxonomical comparisons. The COGs and the taxonomical distribution profile for 789 nonredundant bacterial and archaeal genomes were obtained and compared with the whole-genome COG distribution and with the 250 randomly selected genes, respectively. The main COGs associated with virulence genes corresponded to the following: intracellular trafficking, secretion and vesicular transport (U; cell motility (N; nucleotide transport and metabolism (F; transcription (K; and cell wall/membrane/envelope biogenesis (M. In addition, we found that virulence genes presented a higher proportion of orthologs in the Euryarchaeota and Proteobacteria phyla, with a significant decrease in Chlamydiae, Bacteroidetes, Tenericutes, Firmicutes and Thermotogae. In conclusion, we found that genes related to specific functions are more relevant to B. melitensis virulence, with the COG U the most significant. Additionally, the taxonomical distribution of virulence genes highlights the importance of these genes in the related Proteobacteria, being less relevant in distant groups of organisms with the exception of Euryarchaeota.

  13. Production Of Some Virulence Factors Under Different Growth ...

    African Journals Online (AJOL)

    Production Of Some Virulence Factors Under Different Growth Conditions And Antibiotic Susceptibility Pattern Of ... Animal Research International ... Keywords: Virulence, Haemolytic activity, Susceptibility, Antibiotics, Aeromonas hydrophila

  14. Host age modulates parasite infectivity, virulence and reproduction.

    Science.gov (United States)

    Izhar, Rony; Ben-Ami, Frida

    2015-07-01

    Host age is one of the most striking differences among hosts within most populations, but there is very little data on how age-dependent effects impact ecological and evolutionary dynamics of both the host and the parasite. Here, we examined the influence of host age (juveniles, young and old adults) at parasite exposure on host susceptibility, fecundity and survival as well as parasite transmission, using two clones of the water flea Daphnia magna and two clones of its bacterial parasite Pasteuria ramosa. Younger D. magna were more susceptible to infection than older ones, regardless of host or parasite clone. Also, younger-infected D. magna became castrated faster than older hosts, but host and parasite clone effects contributed to this trait as well. Furthermore, the early-infected D. magna produced considerably more parasite transmission stages than late-infected ones, while host age at exposure did not affect virulence as it is defined in models (host mortality). When virulence is defined more broadly as the negative effects of infection on host fitness, by integrating the parasitic effects on host fecundity and mortality, then host age at exposure seems to slide along a negative relationship between host and parasite fitness. Thus, the virulence-transmission trade-off differs strongly among age classes, which in turn affects predictions of optimal virulence. Age-dependent effects on host susceptibility, virulence and parasite transmission could pose an important challenge for experimental and theoretical studies of infectious disease dynamics and disease ecology. Our results present a call for a more explicit stage-structured theory for disease, which will incorporate age-dependent epidemiological parameters. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

  15. Heat transfer modelling and stability analysis of selective laser melting

    International Nuclear Information System (INIS)

    Gusarov, A.V.; Yadroitsev, I.; Bertrand, Ph.; Smurov, I.

    2007-01-01

    The process of direct manufacturing by selective laser melting basically consists of laser beam scanning over a thin powder layer deposited on a dense substrate. Complete remelting of the powder in the scanned zone and its good adhesion to the substrate ensure obtaining functional parts with improved mechanical properties. Experiments with single-line scanning indicate, that an interval of scanning velocities exists where the remelted tracks are uniform. The tracks become broken if the scanning velocity is outside this interval. This is extremely undesirable and referred to as the 'balling' effect. A numerical model of coupled radiation and heat transfer is proposed to analyse the observed instability. The 'balling' effect at high scanning velocities (above ∼20 cm/s for the present conditions) can be explained by the Plateau-Rayleigh capillary instability of the melt pool. Two factors stabilize the process with decreasing the scanning velocity: reducing the length-to-width ratio of the melt pool and increasing the width of its contact with the substrate

  16. Influenza A virus NS1 gene mutations F103L and M106I increase replication and virulence

    Directory of Open Access Journals (Sweden)

    Ping Jihui

    2011-01-01

    Full Text Available Abstract Background To understand the evolutionary steps required for a virus to become virulent in a new host, a human influenza A virus (IAV, A/Hong Kong/1/68(H3N2 (HK-wt, was adapted to increased virulence in the mouse. Among eleven mutations selected in the NS1 gene, two mutations F103L and M106I had been previously detected in the highly virulent human H5N1 isolate, A/HK/156/97, suggesting a role for these mutations in virulence in mice and humans. Results To determine the selective advantage of these mutations, reverse genetics was used to rescue viruses containing each of the NS1 mouse adapted mutations into viruses possessing the HK-wt NS1 gene on the A/PR/8/34 genetic backbone. Both F103L and M106I NS1 mutations significantly enhanced growth in vitro (mouse and canine cells and in vivo (BALB/c mouse lungs as well as enhanced virulence in the mouse. Only the M106I NS1 mutation enhanced growth in human cells. Furthermore, these NS1 mutations enhanced early viral protein synthesis in MDCK cells and showed an increased ability to replicate in mouse interferon β (IFN-β pre-treated mouse cells relative to rPR8-HK-NS-wt NS1. The double mutant, rPR8-HK-NS-F103L + M106I, demonstrated growth attenuation late in infection due to increased IFN-β induction in mouse cells. We then generated a rPR8 virus possessing the A/HK/156/97 NS gene that possesses 103L + 106I, and then rescued the L103F + I106M mutant. The 103L + 106I mutations increased virulence by >10 fold in BALB/c mice. We also inserted the avian A/Ck/Beijing/1/95 NS1 gene (the source lineage of the A/HK/156/97 NS1 gene that possesses 103L + 106I, onto the A/WSN/33 backbone and then generated the L103F + I106M mutant. None of the H5N1 and H9N2 NS containing viruses resulted in increased IFN-β induction. The rWSN-A/Ck/Beijing/1/95-NS1 gene possessing 103L and 106I demonstrated 100 fold enhanced growth and >10 fold enhanced virulence that was associated with increased tropism for lung

  17. The OmpA-like protein Loa22 is essential for leptospiral virulence.

    Directory of Open Access Journals (Sweden)

    Paula Ristow

    2007-07-01

    Full Text Available Pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetic manipulations of pathogenic species. In this study, we characterized a mutant obtained by insertion of the transposon Himar1 into a gene encoding a putative lipoprotein, Loa22, which has a predicted OmpA domain based on sequence identity. The resulting mutant did not express Loa22 and was attenuated in virulence in the guinea pig and hamster models of leptospirosis, whereas the genetically complemented strain was restored in Loa22 expression and virulence. Our results show that Loa22 was expressed during host infection and exposed on the cell surface. Loa22 is therefore necessary for virulence of L. interrogans in the animal model and represents, to our knowledge, the first genetically defined virulence factor in Leptospira species.

  18. Equilibrium and nonequilibrium attractors for a discrete, selection-migration model

    Science.gov (United States)

    James F. Selgrade; James H. Roberds

    2003-01-01

    This study presents a discrete-time model for the effects of selection and immigration on the demographic and genetic compositions of a population. Under biologically reasonable conditions, it is shown that the model always has an equilibrium. Although equilibria for similar models without migration must have real eigenvalues, for this selection-migration model we...

  19. The effect of immunodeficiency on the evolution of virulence: an experimental test with the rodent malaria Plasmodium chabaudi.

    Science.gov (United States)

    Barclay, Victoria C; Kennedy, David A; Weaver, Veronika C; Sim, Derek; Lloyd-Smith, James O; Read, Andrew F

    2014-08-01

    Host immunity plays an important role in the evolution of pathogen virulence and disease emergence. There is increasing theoretical and empirical evidence that enhanced immunity through vaccination may have the unfortunate side effect of selecting for more virulent parasites, but the effect of host immune suppression on pathogen evolution is less clear. Here, we use serial passage experiments in mice to test how immune-suppressed hosts may alter pathogen virulence evolution. We passaged Plasmodium chabaudi through CD4(+) T cell-depleted or control mice every 7 days for 20 weeks and then measured virulence differences during infection of immunologically normal mice. We found that those parasites that had been selected through CD4(+) T cell-depleted mice were more virulent than parasites selected through control mice. Virulence increases during serial passage are believed to be caused by pathogen adaptation to the passage host. These data suggest that immune-suppressed hosts could provide a within-host environment that lowers the barrier to parasite adaptation and promotes the evolution of virulence.

  20. Performance Measurement Model for the Supplier Selection Based on AHP

    Directory of Open Access Journals (Sweden)

    Fabio De Felice

    2015-10-01

    Full Text Available The performance of the supplier is a crucial factor for the success or failure of any company. Rational and effective decision making in terms of the supplier selection process can help the organization to optimize cost and quality functions. The nature of supplier selection processes is generally complex, especially when the company has a large variety of products and vendors. Over the years, several solutions and methods have emerged for addressing the supplier selection problem (SSP. Experience and studies have shown that there is no best way for evaluating and selecting a specific supplier process, but that it varies from one organization to another. The aim of this research is to demonstrate how a multiple attribute decision making approach can be effectively applied for the supplier selection process.

  1. Diminished Virulence of an Alpha-Toxin Mutant of Staphylococcus aureus in Experimental Brain Abscesses

    OpenAIRE

    Kielian, Tammy; Cheung, Ambrose; Hickey, William F.

    2001-01-01

    Staphylococcus aureus is one of the major etiologic agents of brain abscesses in humans, occasionally leading to focal neurological deficits and even death. The objective of the present study was to identify key virulence determinants contributing to the pathogenesis of S. aureus in the brain using a murine brain abscess model. The importance of virulence factor production in disease development was demonstrated by the inability of heat-inactivated S. aureus to induce proinflammatory cytokine...

  2. Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity.

    Science.gov (United States)

    Bertels, Frederic; Marzel, Alex; Leventhal, Gabriel; Mitov, Venelin; Fellay, Jacques; Günthard, Huldrych F; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Battegay, Manuel; Rauch, Andri; Cavassini, Matthias; Calmy, Alexandra; Bernasconi, Enos; Schmid, Patrick; Scherrer, Alexandra U; Müller, Viktor; Bonhoeffer, Sebastian; Kouyos, Roger; Regoes, Roland R

    2018-01-01

    Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as "per-parasite pathogenicity". Using viral load and CD4+ T-cell measures from 2014 HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence-measured as the rate of decline of CD4+ T cells-and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T-cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T-cell decline is 17% (5-30%), and that of the per-parasite pathogenicity is 17% (4-29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12-46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T-cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genotype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  3. Development of virulence to Meloidogyne incognita on resistant pepper rootstocks

    Energy Technology Data Exchange (ETDEWEB)

    Ros-Ibanez, C.; Robertson, L.; Martinez-Lluch, M. C.; Cano-Garcia, A.; Lacasa-Plasencia, A.

    2014-06-01

    The root-knot nematode (RKN) Meloidogyne incognita is a major soil parasite of pepper crops in greenhouses in Southeast Spain. Due to the limitations of the use of soil fumigants, grafting plants on resistant rootstocks (R-rootstocks) has become an important alternative to chemical nematicides. The repeated use of R-rootstocks can bring about the selection of virulent populations capable of overcoming resistance. We carried out a six-year investigation on resistant rootstocks in a naturally M. incognita infested greenhouse, and found that two successive years of growing plants grafted on R-rootstocks Atlante (ATL) were sufficient to overcome resistance (galling index 1.5 and 5.6 in the first and second years respectively). A large variability was observed between several R-rootstocks. Two R-rootstocks (C19 and Snooker) behaved like ATL while two others (Terrano and DRO 8801) were not infected by RKN. Laboratory studies with the same R-rootstocks, inoculated with two nematode isolates (avirulent and virulent against ATL) confirmed the greenhouse results, indicating that some rootstocks may be infested by virulent populations and others may not. It suggests that different R-genes, which are differentially overcome by RKN, have been introgressed into the rootstocks. This may have consequences for the management of resistant rootstocks in the field. (Author)

  4. Exploring virulence and immunogenicity in the emerging pathogen Sporothrix brasiliensis.

    Science.gov (United States)

    Della Terra, Paula Portella; Rodrigues, Anderson Messias; Fernandes, Geisa Ferreira; Nishikaku, Angela Satie; Burger, Eva; de Camargo, Zoilo Pires

    2017-08-01

    Sporotrichosis is a polymorphic chronic infection of humans and animals classically acquired after traumatic inoculation with soil and plant material contaminated with Sporothrix spp. propagules. An alternative and successful route of transmission is bites and scratches from diseased cats, through which Sporothrix yeasts are inoculated into mammalian tissue. The development of a murine model of subcutaneous sporotrichosis mimicking the alternative route of transmission is essential to understanding disease pathogenesis and the development of novel therapeutic strategies. To explore the impact of horizontal transmission in animals (e.g., cat-cat) and zoonotic transmission on Sporothrix fitness, the left hind footpads of BALB/c mice were inoculated with 5×106 yeasts (n = 11 S. brasiliensis, n = 2 S. schenckii, or n = 1 S. globosa). Twenty days post-infection, our model reproduced both the pathophysiology and symptomology of sporotrichosis with suppurating subcutaneous nodules that progressed proximally along lymphatic channels. Across the main pathogenic members of the S. schenckii clade, S. brasiliensis was usually more virulent than S. schenckii and S. globosa. However, the virulence in S. brasiliensis was strain-dependent, and we demonstrated that highly virulent isolates disseminate from the left hind footpad to the liver, spleen, kidneys, lungs, heart, and brain of infected animals, inducing significant and chronic weight loss (losing up to 15% of their body weight). The weight loss correlated with host death between 2 and 16 weeks post-infection. Histopathological features included necrosis, suppurative inflammation, and polymorphonuclear and mononuclear inflammatory infiltrates. Immunoblot using specific antisera and homologous exoantigen investigated the humoral response. Antigenic profiles were isolate-specific, supporting the hypothesis that different Sporothrix species can elicit a heterogeneous humoral response over time, but cross reaction was observed

  5. Selecting representative climate models for climate change impact studies : An advanced envelope-based selection approach

    NARCIS (Netherlands)

    Lutz, Arthur F.; ter Maat, Herbert W.; Biemans, Hester; Shrestha, Arun B.; Wester, Philippus; Immerzeel, Walter W.|info:eu-repo/dai/nl/290472113

    2016-01-01

    Climate change impact studies depend on projections of future climate provided by climate models. The number of climate models is large and increasing, yet limitations in computational capacity make it necessary to compromise the number of climate models that can be included in a climate change

  6. Selecting representative climate models for climate change impact studies: an advanced envelope-based selection approach

    NARCIS (Netherlands)

    Lutz, Arthur F.; Maat, ter Herbert W.; Biemans, Hester; Shrestha, Arun B.; Wester, Philippus; Immerzeel, Walter W.

    2016-01-01

    Climate change impact studies depend on projections of future climate provided by climate models. The number of climate models is large and increasing, yet limitations in computational capacity make it necessary to compromise the number of climate models that can be included in a climate change

  7. Evaluation of phytochemicals from medicinal plants of Myrtaceae family on virulence factor production by Pseudomonas aeruginosa.

    Science.gov (United States)

    Musthafa, Khadar Syed; Sianglum, Wipawadee; Saising, Jongkon; Lethongkam, Sakkarin; Voravuthikunchai, Supayang Piyawan

    2017-05-01

    Virulence factors regulated by quorum sensing (QS) play a critical role in the pathogenesis of an opportunistic human pathogen, Pseudomonas aeruginosa in causing infections to the host. Hence, in the present work, the anti-virulence potential of the medicinal plant extracts and their derived phytochemicals from Myrtaceae family was evaluated against P. aeruginosa. In the preliminary screening of the tested medicinal plant extracts, Syzygium jambos and Syzygium antisepticum demonstrated a maximum inhibition in QS-dependent violacein pigment production by Chromobacterium violaceum DMST 21761. These extracts demonstrated an inhibitory activity over a virulence factor, pyoverdin, production by P. aeruginosa ATCC 27853. Gas chromatography-mass spectrometric (GC-MS) analysis revealed the presence of 23 and 12 phytochemicals from the extracts of S. jambos and S. antisepticum respectively. Three top-ranking phytochemicals, including phytol, ethyl linoleate and methyl linolenate, selected on the basis of docking score in molecular docking studies lowered virulence factors such as pyoverdin production, protease and haemolytic activities of P. aeruginosa to a significant level. In addition, the phytochemicals reduced rhamnolipid production by the organism. The work demonstrated an importance of plant-derived compounds as anti-virulence drugs to conquer P. aeruginosa virulence towards the host. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  8. Virulence and genomic feature of multidrug resistant Campylobacter jejuni isolated from broiler chicken

    Directory of Open Access Journals (Sweden)

    Haihong Hao

    2016-10-01

    Full Text Available The aim of this study was to reveal the molecular mechanism involved in multidrug resistance and virulence of Campylobacter jejuni isolated from broiler chickens. The virulence of six multidrug resistant C. jejuni was determined by in vitro and in vivo methods. The de novo whole genome sequencing technology and molecular biology methods were used to analyze the genomic features associated with the multidrug resistance and virulence of a selected isolate (C. jejuni 1655. The comparative genomic analyses revealed a large number of single nucleotide polymorphisms, deletions, rearrangements, and inversions in C. jejuni 1655 compared to reference C. jejuni genomes. The co-emergence of Thr-86-Ile mutation in gyrA gene, A2075G mutation in 23S rRNA gene, tetO, aphA and aadE genes and pTet plasmid in C. jejuni 1655 contributed its multidrug resistance to fluoroquinolones, macrolides, tetracycline and aminoglycosides. The combination of multiple virulence genes may work together to confer the relative higher virulence in C. jejuni 1655. The co-existence of mobile gene elements (e.g. pTet and CRISPR-Cas system in C. jejuni 1655 may play an important role in the gene transfer and immune defense. The present study provides basic information of phenotypic and genomic features of C. jejuni 1655, a strain recently isolated from a chicken displaying multidrug resistance and relatively high level of virulence.

  9. Use of Metarhizium anisopliae Chitinase Genes for Genotyping and Virulence Characterization

    Directory of Open Access Journals (Sweden)

    Saliou Niassy

    2013-01-01

    Full Text Available Virulence is the primary factor used for selection of entomopathogenic fungi (EPF for development as biopesticides. To understand the genetic mechanisms underlying differences in virulence of fungal isolates on various arthropod pests, we compared the chitinase genes, chi2 and chi4, of 8 isolates of Metarhizium anisopliae. The clustering of the isolates showed various groups depending on their virulence. However, the analysis of their chitinase DNA sequences chi2 and chi4 did not reveal major divergences. Although their protein translates have been implicated in fungal virulence, the predicted protein structure of chi2 was identical for all isolates. Despite the critical role of chitin digestion in fungal infection, we conclude that chi2 and chi4 genes cannot serve as molecular markers to characterize observed variations in virulence among M. anisopliae isolates as previously suggested. Nevertheless, processes controlling the efficient upregulation of chitinase expression might be responsible for different virulence characteristics. Further studies using comparative “in vitro” chitin digestion techniques would be more appropriate to compare the quality and the quantity of chitinase production between fungal isolates.

  10. An Integrated DEMATEL-QFD Model for Medical Supplier Selection

    OpenAIRE

    Mehtap Dursun; Zeynep Şener

    2014-01-01

    Supplier selection is considered as one of the most critical issues encountered by operations and purchasing managers to sharpen the company’s competitive advantage. In this paper, a novel fuzzy multi-criteria group decision making approach integrating quality function deployment (QFD) and decision making trial and evaluation laboratory (DEMATEL) method is proposed for supplier selection. The proposed methodology enables to consider the impacts of inner dependence among supplier assessment cr...

  11. National HIV prevalence estimates for sub-Saharan Africa: controlling selection bias with Heckman-type selection models

    Science.gov (United States)

    Hogan, Daniel R; Salomon, Joshua A; Canning, David; Hammitt, James K; Zaslavsky, Alan M; Bärnighausen, Till

    2012-01-01

    Objectives Population-based HIV testing surveys have become central to deriving estimates of national HIV prevalence in sub-Saharan Africa. However, limited participation in these surveys can lead to selection bias. We control for selection bias in national HIV prevalence estimates using a novel approach, which unlike conventional imputation can account for selection on unobserved factors. Methods For 12 Demographic and Health Surveys conducted from 2001 to 2009 (N=138 300), we predict HIV status among those missing a valid HIV test with Heckman-type selection models, which allow for correlation between infection status and participation in survey HIV testing. We compare these estimates with conventional ones and introduce a simulation procedure that incorporates regression model parameter uncertainty into confidence intervals. Results Selection model point estimates of national HIV prevalence were greater than unadjusted estimates for 10 of 12 surveys for men and 11 of 12 surveys for women, and were also greater than the majority of estimates obtained from conventional imputation, with significantly higher HIV prevalence estimates for men in Cote d'Ivoire 2005, Mali 2006 and Zambia 2007. Accounting for selective non-participation yielded 95% confidence intervals around HIV prevalence estimates that are wider than those obtained with conventional imputation by an average factor of 4.5. Conclusions Our analysis indicates that national HIV prevalence estimates for many countries in sub-Saharan African are more uncertain than previously thought, and may be underestimated in several cases, underscoring the need for increasing participation in HIV surveys. Heckman-type selection models should be included in the set of tools used for routine estimation of HIV prevalence. PMID:23172342

  12. Species Identification and Virulence Attributes of Saccharomyces boulardii (nom. inval.)

    Science.gov (United States)

    McCullough, Michael J.; Clemons, Karl V.; McCusker, John H.; Stevens, David A.

    1998-01-01

    Saccharomyces boulardii (nom. inval.) has been used for the treatment of several types of diarrhea. Recent studies have confirmed that S. boulardii is effective in the treatment of diarrhea, in particular chronic or recurrent diarrhea, and furthermore that it is a safe and well-tolerated treatment. The aim of the present study was to identify strains of S. boulardii to the species level and assess their virulence in established murine models. Three strains of S. boulardii were obtained from commercially available products in France and Italy. The three S. boulardii strains did not form spores upon repeated testing. Therefore, classical methods used for the identification of Saccharomyces spp. could not be undertaken. Typing by using the restriction fragment length polymorphisms (RFLPs) of the PCR-amplified intergenic transcribed spacer regions (including the 5.8S ribosomal DNA) showed that the three isolates of S. boulardii were not separable from authentic isolates of Saccharomyces cerevisiae with any of the 10 restriction endonucleases assessed, whereas 9 of the 10 recognized species of Saccharomyces could be differentiated. RFLP analysis of cellular DNA with EcoRI showed that all three strains of S. boulardii had identical patterns and were similar to other authentic S. cerevisiae isolates tested. Therefore, the commercial strains of S. boulardii available to us cannot be genotypically distinguished from S. cerevisiae. Two S. boulardii strains were tested in CD-1 and DBA/2N mouse models of systemic disease and showed intermediate virulence compared with virulent and avirulent strains of S. cerevisiae. The results of the present study show that these S. boulardii strains are asporogenous strains of the species S. cerevisiae, not representatives of a distinct and separate species, and possess moderate virulence in murine models of systemic infection. Therefore, caution should be advised in the clinical use of these strains in immunocompromised patients until

  13. Spontaneous Loss of Virulence in Natural Populations of Listeria monocytogenes.

    Science.gov (United States)

    Maury, Mylène M; Chenal-Francisque, Viviane; Bracq-Dieye, Hélène; Han, Lei; Leclercq, Alexandre; Vales, Guillaume; Moura, Alexandra; Gouin, Edith; Scortti, Mariela; Disson, Olivier; Vázquez-Boland, José A; Lecuit, Marc

    2017-11-01

    The pathogenesis of Listeria monocytogenes depends on the ability of this bacterium to escape from the phagosome of the host cells via the action of the pore-forming toxin listeriolysin O (LLO). Expression of the LLO-encoding gene ( hly ) requires the transcriptional activator PrfA, and both hly and prfA genes are essential for L. monocytogenes virulence. Here, we used the hemolytic activity of LLO as a phenotypic marker to screen for spontaneous virulence-attenuating mutations in L. monocytogenes Sixty nonhemolytic isolates were identified among a collection of 57,820 confirmed L. monocytogenes strains isolated from a variety of sources (0.1%). In most cases (56/60; 93.3%), the nonhemolytic phenotype resulted from nonsense, missense, or frameshift mutations in prfA Five strains carried hly mutations leading to a single amino acid substitution (G299V) or a premature stop codon causing strong virulence attenuation in mice. In one strain, both hly and gshF (encoding a glutathione synthase required for full PrfA activity) were missing due to genomic rearrangements likely caused by a transposable element. The PrfA/LLO loss-of-function (PrfA - /LLO - ) mutants belonged to phylogenetically diverse clades of L. monocytogenes , and most were identified among nonclinical strains (57/60). Consistent with the rare occurrence of loss-of-virulence mutations, we show that prfA and hly are under purifying selection. Although occurring at a low frequency, PrfA - /LLO - mutational events in L. monocytogenes lead to niche restriction and open an evolutionary path for obligate saprophytism in this facultative intracellular pathogen. Copyright © 2017 Maury et al.

  14. Genes under positive selection in a model plant pathogenic fungus, Botrytis.

    Science.gov (United States)

    Aguileta, Gabriela; Lengelle, Juliette; Chiapello, Hélène; Giraud, Tatiana; Viaud, Muriel; Fournier, Elisabeth; Rodolphe, François; Marthey, Sylvain; Ducasse, Aurélie; Gendrault, Annie; Poulain, Julie; Wincker, Patrick; Gout, Lilian

    2012-07-01

    The rapid evolution of particular genes is essential for the adaptation of pathogens to new hosts and new environments. Powerful methods have been developed for detecting targets of selection in the genome. Here we used divergence data to compare genes among four closely related fungal pathogens adapted to different hosts to elucidate the functions putatively involved in adaptive processes. For this goal, ESTs were sequenced in the specialist fungal pathogens Botrytis tulipae and Botrytis ficariarum, and compared with genome sequences of Botrytis cinerea and Sclerotinia sclerotiorum, responsible for diseases on over 200 plant species. A maximum likelihood-based analysis of 642 predicted orthologs detected 21 genes showing footprints of positive selection. These results were validated by resequencing nine of these genes in additional Botrytis species, showing they have also been rapidly evolving in other related species. Twenty of the 21 genes had not previously been identified as pathogenicity factors in B. cinerea, but some had functions related to plant-fungus interactions. The putative functions were involved in respiratory and energy metabolism, protein and RNA metabolism, signal transduction or virulence, similarly to what was detected in previous studies using the same approach in other pathogens. Mutants of B. cinerea were generated for four of these genes as a first attempt to elucidate their functions. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Evaluation of uncertainties in selected environmental dispersion models

    International Nuclear Information System (INIS)

    Little, C.A.; Miller, C.W.

    1979-01-01

    Compliance with standards of radiation dose to the general public has necessitated the use of dispersion models to predict radionuclide concentrations in the environment due to releases from nuclear facilities. Because these models are only approximations of reality and because of inherent variations in the input parameters used in these models, their predictions are subject to uncertainty. Quantification of this uncertainty is necessary to assess the adequacy of these models for use in determining compliance with protection standards. This paper characterizes the capabilities of several dispersion models to predict accurately pollutant concentrations in environmental media. Three types of models are discussed: aquatic or surface water transport models, atmospheric transport models, and terrestrial and aquatic food chain models. Using data published primarily by model users, model predictions are compared to observations

  16. Effect Of Spaceflight On Microbial Gene Expression And Virulence: Preliminary Results From Microbe Payload Flown On-Board STS-115

    Science.gov (United States)

    Wilson, J. W.; HonerzuBentrup, K,; Schurr, M. J.; Buchanan, K.; Morici, L.; Hammond, T.; Allen, P.; Baker, C.; Ott, C. M.; Nelman-Gonzalez M.; hide

    2007-01-01

    Human presence in space, whether permanent or temporary, is accompanied by the presence of microbes. However, the extent of microbial changes in response to spaceflight conditions and the corresponding changes to infectious disease risk is unclear. Previous studies have indicated that spaceflight weakens the immune system in humans and animals. In addition, preflight and in-flight monitoring of the International Space Station (ISS) and other spacecraft indicates the presence of opportunistic pathogens and the potential of obligate pathogens. Altered antibiotic resistance of microbes in flight has also been shown. As astronauts and cosmonauts live for longer periods in a closed environment, especially one using recycled water and air, there is an increased risk to crewmembers of infectious disease events occurring in-flight. Therefore, understanding how the space environment affects microorganisms and their disease potential is critically important for spaceflight missions and requires further study. The goal of this flight experiment, operationally called MICROBE, is to utilize three model microbial pathogens, Salmonella typhimurium, Pseudomonas aeruginosa, and Candida albicans to examine the global effects of spaceflight on microbial gene expression and virulence attributes. Specifically, the aims are (1) to perform microarray-mediated gene expression profiling of S. typhimurium, P. aeruginosa, and C. albicans, in response to spaceflight in comparison to ground controls and (2) to determine the effect of spaceflight on the virulence potential of these microorganisms immediately following their return from spaceflight using murine models. The model microorganisms were selected as they have been isolated from preflight or in-flight monitoring, represent different degrees of pathogenic behavior, are well characterized, and have sequenced genomes with available microarrays. In particular, extensive studies of S. typhimurium by the Principal Investigator, Dr. Nickerson

  17. Bayesian model selection of template forward models for EEG source reconstruction.

    Science.gov (United States)

    Strobbe, Gregor; van Mierlo, Pieter; De Vos, Maarten; Mijović, Bogdan; Hallez, Hans; Van Huffel, Sabine; López, José David; Vandenberghe, Stefaan

    2014-06-01

    Several EEG source reconstruction techniques have been proposed to identify the generating neuronal sources of electrical activity measured on the scalp. The solution of these techniques depends directly on the accuracy of the forward model that is inverted. Recently, a parametric empirical Bayesian (PEB) framework for distributed source reconstruction in EEG/MEG was introduced and implemented in the Statistical Parametric Mapping (SPM) software. The framework allows us to compare different forward modeling approaches, using real data, instead of using more traditional simulated data from an assumed true forward model. In the absence of a subject specific MR image, a 3-layered boundary element method (BEM) template head model is currently used including a scalp, skull and brain compartment. In this study, we introduced volumetric template head models based on the finite difference method (FDM). We constructed a FDM head model equivalent to the BEM model and an extended FDM model including CSF. These models were compared within the context of three different types of source priors related to the type of inversion used in the PEB framework: independent and identically distributed (IID) sources, equivalent to classical minimum norm approaches, coherence (COH) priors similar to methods such as LORETA, and multiple sparse priors (MSP). The resulting models were compared based on ERP data of 20 subjects using Bayesian model selection for group studies. The reconstructed activity was also compared with the findings of previous studies using functional magnetic resonance imaging. We found very strong evidence in favor of the extended FDM head model with CSF and assuming MSP. These results suggest that the use of realistic volumetric forward models can improve PEB EEG source reconstruction. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Exploring potential virulence regulators in Paracoccidioides brasiliensis isolates of varying virulence through quantitative proteomics.

    Science.gov (United States)

    Castilho, Daniele G; Chaves, Alison F A; Xander, Patricia; Zelanis, André; Kitano, Eduardo S; Serrano, Solange M T; Tashima, Alexandre K; Batista, Wagner L

    2014-10-03

    Few virulence factors have been identified for Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis. In this study, we quantitatively evaluated the protein composition of P. brasiliensis in the yeast phase using minimal and rich media to obtain a better understanding of its virulence and to gain new insights into pathogen adaptation strategies. This analysis was performed on two isolates of the Pb18 strain showing distinct infection profiles in B10.A mice. Using liquid chromatography/tandem mass spectrometry (LC-MS/MS) analysis, we identified and quantified 316 proteins in minimal medium, 29 of which were overexpressed in virulent Pb18. In rich medium, 29 out of 295 proteins were overexpressed in the virulent fungus. Three proteins were found to be up-regulated in both media, suggesting the potential roles of these proteins in virulence regulation in P. brasiliensis. Moreover, genes up-regulated in virulent Pb18 showed an increase in its expression after the recovery of virulence of attenuated Pb18. Proteins up-regulated in both isolates were grouped according to their functional categories. Virulent Pb18 undergoes metabolic reorganization and increased expression of proteins involved in fermentative respiration. This approach allowed us to identify potential virulence regulators and provided a foundation for achieving a molecular understanding of how Paracoccidioides modulates the host-pathogen interaction to its advantage.

  19. Virulence Factors IN Fungi OF Systemic Mycoses

    Directory of Open Access Journals (Sweden)

    KUROKAWA Cilmery Suemi

    1998-01-01

    Full Text Available Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.

  20. Global economic consequences of selected surgical diseases: a modelling study.

    Science.gov (United States)

    Alkire, Blake C; Shrime, Mark G; Dare, Anna J; Vincent, Jeffrey R; Meara, John G

    2015-04-27

    The surgical burden of disease is substantial, but little is known about the associated economic consequences. We estimate the global macroeconomic impact of the surgical burden of disease due to injury, neoplasm, digestive diseases, and maternal and neonatal disorders from two distinct economic perspectives. We obtained mortality rate estimates for each disease for the years 2000 and 2010 from the Institute of Health Metrics and Evaluation Global Burden of Disease 2010 study, and estimates of the proportion of the burden of the selected diseases that is surgical from a paper by Shrime and colleagues. We first used the value of lost output (VLO) approach, based on the WHO's Projecting the Economic Cost of Ill-Health (EPIC) model, to project annual market economy losses due to these surgical diseases during 2015-30. EPIC attempts to model how disease affects a country's projected labour force and capital stock, which in turn are related to losses in economic output, or gross domestic product (GDP). We then used the value of lost welfare (VLW) approach, which is conceptually based on the value of a statistical life and is inclusive of non-market losses, to estimate the present value of long-run welfare losses resulting from mortality and short-run welfare losses resulting from morbidity incurred during 2010. Sensitivity analyses were performed for both approaches. During 2015-30, the VLO approach projected that surgical conditions would result in losses of 1·25% of potential GDP, or $20·7 trillion (2010 US$, purchasing power parity) in the 128 countries with data available. When expressed as a proportion of potential GDP, annual GDP losses were greatest in low-income and middle-income countries, with up to a 2·5% loss in output by 2030. When total welfare losses are assessed (VLW), the present value of economic losses is estimated to be equivalent to 17% of 2010 GDP, or $14·5 trillion in the 175 countries assessed with this approach. Neoplasm and injury account

  1. Expression of Haemophilus ducreyi collagen binding outer membrane protein NcaA is required for virulence in swine and human challenge models of chancroid.

    Science.gov (United States)

    Fulcher, Robert A; Cole, Leah E; Janowicz, Diane M; Toffer, Kristen L; Fortney, Kate R; Katz, Barry P; Orndorff, Paul E; Spinola, Stanley M; Kawula, Thomas H

    2006-05-01

    Haemophilus ducreyi, the etiologic agent of the sexually transmitted genital ulcer disease chancroid, has been shown to associate with dermal collagen fibers within infected skin lesions. Here we describe NcaA, a previously uncharacterized outer membrane protein that is important for H. ducreyi collagen binding and host colonization. An H. ducreyi strain lacking the ncaA gene was impaired in adherence to type I collagen but not fibronectin (plasma or cellular form) or heparin. The mutation had no effect on serum resistance or binding to HaCaT keratinocytes or human foreskin fibroblasts in vitro. Escherichia coli expressing H. ducreyi NcaA bound to type I collagen, demonstrating that NcaA is sufficient to confer collagen attachment. The importance of NcaA in H. ducreyi pathogenesis was assessed using both swine and human experimental models of chancroid. In the swine model, 20% of lesions from sites inoculated with the ncaA mutant were culture positive for H. ducreyi 7 days after inoculation, compared to 73% of wild-type-inoculated sites. The average number of CFU recovered from mutant-inoculated lesions was also significantly reduced compared to that recovered from wild-type-inoculated sites at both 2 and 7 days after inoculation. In the human challenge model, 8 of 30 sites inoculated with wild-type H. ducreyi progressed to the pustular stage, compared to 0 of 30 sites inoculated with the ncaA mutant. Together these results demonstrate that the collagen binding protein NcaA is required for H. ducreyi infection.

  2. 78 FR 20148 - Reporting Procedure for Mathematical Models Selected To Predict Heated Effluent Dispersion in...

    Science.gov (United States)

    2013-04-03

    ... procedure acceptable to the NRC staff for providing summary details of mathematical modeling methods used in... NUCLEAR REGULATORY COMMISSION [NRC-2013-0062] Reporting Procedure for Mathematical Models Selected... Regulatory Guide (RG) 4.4, ``Reporting Procedure for Mathematical Models Selected to Predict Heated Effluent...

  3. Virulence Factors of Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Paul Sinclair

    1991-01-01

    environment with respect to pH. The spiral shape of the cells and their flagellar motility allow them to wind themselves into the mucous layer of the stomach. Some evidence exists for the production of strong proteolytic activity, hence degrading the mucous barrier and increasing permeability for the organism. Cyroroxin excreted by the bacteria may have some effect on the surrounding cells, with the possible lysis and release of bacterial growth factors. There is evidence that a chemotactic response is present due to these growth factors and their higher concentration in the intracellular spaces. The presence of specific and nonspecific adhesion has also been demonstrated, thus allowing the bacterium, once at the epithelial cell surface, to attach and avoid being washed off by movement within the stomach. Although treatment with antimicrobials eradicates the organism and improves symptoms of peptic ulcer patients, there is no indication that the same occurs in nonulcer dyspepsia patients. Further work is essential to describe the virulence mechanisms of H pylori and the possible pathogenic role of the organism.

  4. Bootstrap-after-bootstrap model averaging for reducing model uncertainty in model selection for air pollution mortality studies.

    Science.gov (United States)

    Roberts, Steven; Martin, Michael A

    2010-01-01

    Concerns have been raised about findings of associations between particulate matter (PM) air pollution and mortality that have been based on a single "best" model arising from a model selection procedure, because such a strategy may ignore model uncertainty inherently involved in searching through a set of candidate models to find the best model. Model averaging has been proposed as a method of allowing for model uncertainty in this context. To propose an extension (double BOOT) to a previously described bootstrap model-averaging procedure (BOOT) for use in time series studies of the association between PM and mortality. We compared double BOOT and BOOT with Bayesian model averaging (BMA) and a standard method of model selection [standard Akaike's information criterion (AIC)]. Actual time series data from the United States are used to conduct a simulation study to compare and contrast the performance of double BOOT, BOOT, BMA, and standard AIC. Double BOOT produced estimates of the effect of PM on mortality that have had smaller root mean squared error than did those produced by BOOT, BMA, and standard AIC. This performance boost resulted from estimates produced by double BOOT having smaller variance than those produced by BOOT and BMA. Double BOOT is a viable alternative to BOOT and BMA for producing estimates of the mortality effect of PM.

  5. Model-independent plot of dynamic PET data facilitates data interpretation and model selection.

    Science.gov (United States)

    Munk, Ole Lajord

    2012-02-21

    When testing new PET radiotracers or new applications of existing tracers, the blood-tissue exchange and the metabolism need to be examined. However, conventional plots of measured time-activity curves from dynamic PET do not reveal the inherent kinetic information. A novel model-independent volume-influx plot (vi-plot) was developed and validated. The new vi-plot shows the time course of the instantaneous distribution volume and the instantaneous influx rate. The vi-plot visualises physiological information that facilitates model selection and it reveals when a quasi-steady state is reached, which is a prerequisite for the use of the graphical analyses by Logan and Gjedde-Patlak. Both axes of the vi-plot have direct physiological interpretation, and the plot shows kinetic parameter in close agreement with estimates obtained by non-linear kinetic modelling. The vi-plot is equally useful for analyses of PET data based on a plasma input function or a reference region input function. The vi-plot is a model-independent and informative plot for data exploration that facilitates the selection of an appropriate method for data analysis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Short-sighted evolution of virulence in parasitic honeybee workers ( Apis mellifera capensis Esch.)

    Science.gov (United States)

    Moritz, Robin F. A.; Pirk, Christian W. W.; Hepburn, H. Randall; Neumann, Peter

    2008-06-01

    The short-sighted selection hypothesis for parasite virulence predicts that winners of within-host competition are poorer at transmission to new hosts. Social parasitism by self-replicating, female-producing workers occurs in the Cape honeybee Apis mellifera capensis, and colonies of other honeybee subspecies are susceptible hosts. We found high within-host virulence but low transmission rates in a clone of social parasitic A. m. capensis workers invading the neighbouring subspecies A. m. scutellata. In contrast, parasitic workers from the endemic range of A. m. capensis showed low within-host virulence but high transmission rates. This suggests a short-sighted selection scenario for the host-parasite co-evolution in the invasive range of the Cape honeybee, probably facilitated by beekeeping-assisted parasite transmission in apiaries.

  7. The Selection of Turbulence Models for Prediction of Room Airflow

    DEFF Research Database (Denmark)

    Nielsen, Peter V.

    This paper discusses the use of different turbulence models and their advantages in given situations. As an example, it is shown that a simple zero-equation model can be used for the prediction of special situations as flow with a low level of turbulence. A zero-equation model with compensation...

  8. Stem biomass and volume models of selected tropical tree species ...

    African Journals Online (AJOL)

    Stem biomass and stem volume were modelled as a function of diameter (at breast height; Dbh) and stem height (height to the crown base). Logarithmic models are presented that utilise Dbh and height data to predict tree component biomass and stem volumes. Alternative models are given that afford prediction based on ...

  9. Model selection criteria : how to evaluate order restrictions

    NARCIS (Netherlands)

    Kuiper, R.M.

    2012-01-01

    Researchers often have ideas about the ordering of model parameters. They frequently have one or more theories about the ordering of the group means, in analysis of variance (ANOVA) models, or about the ordering of coefficients corresponding to the predictors, in regression models.A researcher might

  10. The Living Dead: Transformative Experiences in Modelling Natural Selection

    Science.gov (United States)

    Petersen, Morten Rask

    2017-01-01

    This study considers how students change their coherent conceptual understanding of natural selection through a hands-on simulation. The results show that most students change their understanding. In addition, some students also underwent a transformative experience and used their new knowledge in a leisure time activity. These transformative…

  11. Modelling the negative effects of landscape fragmentation on habitat selection

    NARCIS (Netherlands)

    Langevelde, van F.

    2015-01-01

    Landscape fragmentation constrains movement of animals between habitat patches. Fragmentation may, therefore, limit the possibilities to explore and select the best habitat patches, and some animals may have to cope with low-quality patches due to these movement constraints. If so, these individuals

  12. Lightweight Graphical Models for Selectivity Estimation Without Independence Assumptions

    DEFF Research Database (Denmark)

    Tzoumas, Kostas; Deshpande, Amol; Jensen, Christian S.

    2011-01-01

    the attributes in the database into small, usually two-dimensional distributions. We describe several optimizations that can make selectivity estimation highly efficient, and we present a complete implementation inside PostgreSQL’s query optimizer. Experimental results indicate an order of magnitude better...

  13. Selection bias in species distribution models: An econometric approach on forest trees based on structural modeling

    Science.gov (United States)

    Martin-StPaul, N. K.; Ay, J. S.; Guillemot, J.; Doyen, L.; Leadley, P.

    2014-12-01

    Species distribution models (SDMs) are widely used to study and predict the outcome of global changes on species. In human dominated ecosystems the presence of a given species is the result of both its ecological suitability and human footprint on nature such as land use choices. Land use choices may thus be responsible for a selection bias in the presence/absence data used in SDM calibration. We present a structural modelling approach (i.e. based on structural equation modelling) that accounts for this selection bias. The new structural species distribution model (SSDM) estimates simultaneously land use choices and species responses to bioclimatic variables. A land use equation based on an econometric model of landowner choices was joined to an equation of species response to bioclimatic variables. SSDM allows the residuals of both equations to be dependent, taking into account the possibility of shared omitted variables and measurement errors. We provide a general description of the statistical theory and a set of applications on forest trees over France using databases of climate and forest inventory at different spatial resolution (from 2km to 8km). We also compared the outputs of the SSDM with outputs of a classical SDM (i.e. Biomod ensemble modelling) in terms of bioclimatic response curves and potential distributions under current climate and climate change scenarios. The shapes of the bioclimatic response curves and the modelled species distribution maps differed markedly between SSDM and classical SDMs, with contrasted patterns according to species and spatial resolutions. The magnitude and directions of these differences were dependent on the correlations between the errors from both equations and were highest for higher spatial resolutions. A first conclusion is that the use of classical SDMs can potentially lead to strong miss-estimation of the actual and future probability of presence modelled. Beyond this selection bias, the SSDM we propose represents

  14. Model selection for integrated pest management with stochasticity.

    Science.gov (United States)

    Akman, Olcay; Comar, Timothy D; Hrozencik, Daniel

    2018-04-07

    In Song and Xiang (2006), an integrated pest management model with periodically varying climatic conditions was introduced. In order to address a wider range of environmental effects, the authors here have embarked upon a series of studies resulting in a more flexible modeling approach. In Akman et al. (2013), the impact of randomly changing environmental conditions is examined by incorporating stochasticity into the birth pulse of the prey species. In Akman et al. (2014), the authors introduce a class of models via a mixture of two birth-pulse terms and determined conditions for the global and local asymptotic stability of the pest eradication solution. With this work, the authors unify the stochastic and mixture model components to create further flexibility in modeling the impacts of random environmental changes on an integrated pest management system. In particular, we first determine the conditions under which solutions of our deterministic mixture model are permanent. We then analyze the stochastic model to find the optimal value of the mixing parameter that minimizes the variance in the efficacy of the pesticide. Additionally, we perform a sensitivity analysis to show that the corresponding pesticide efficacy determined by this optimization technique is indeed robust. Through numerical simulations we show that permanence can be preserved in our stochastic model. Our study of the stochastic version of the model indicates that our results on the deterministic model provide informative conclusions about the behavior of the stochastic model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Leukocyte Motility Models Assessed through Simulation and Multi-objective Optimization-Based Model Selection.

    Directory of Open Access Journals (Sweden)

    Mark N Read

    2016-09-01

    Full Text Available The advent of two-photon microscopy now reveals unprecedented, detailed spatio-temporal data on cellular motility and interactions in vivo. Understanding cellular motility patterns is key to gaining insight into the development and possible manipulation of the immune response. Computational simulation has become an established technique for understanding immune processes and evaluating hypotheses in the context of experimental data, and there is clear scope to integrate microscopy-informed motility dynamics. However, determining which motility model best reflects in vivo motility is non-trivial: 3D motility is an intricate process requiring several metrics to characterize. This complicates model selection and parameterization, which must be performed against several metrics simultaneously. Here we evaluate Brownian motion, Lévy walk and several correlated random walks (CRWs against the motility dynamics of neutrophils and lymph node T cells under inflammatory conditions by simultaneously considering cellular translational and turn speeds, and meandering indices. Heterogeneous cells exhibiting a continuum of inherent translational speeds and directionalities comprise both datasets, a feature significantly improving capture of in vivo motility when simulated as a CRW. Furthermore, translational and turn speeds are inversely correlated, and the corresponding CRW simulation again improves capture of our in vivo data, albeit to a lesser extent. In contrast, Brownian motion poorly reflects our data. Lévy walk is competitive in capturing some aspects of neutrophil motility, but T cell directional persistence only, therein highlighting the importance of evaluating models against several motility metrics simultaneously. This we achieve through novel application of multi-objective optimization, wherein each model is independently implemented and then parameterized to identify optimal trade-offs in performance against each metric. The resultant Pareto

  16. Role and regulation of the Flp/Tad pilus in the virulence of Pectobacterium atrosepticum SCRI1043 and Pectobacterium wasabiae SCC3193.

    Science.gov (United States)

    Nykyri, Johanna; Mattinen, Laura; Niemi, Outi; Adhikari, Satish; Kõiv, Viia; Somervuo, Panu; Fang, Xin; Auvinen, Petri; Mäe, Andres; Palva, E Tapio; Pirhonen, Minna

    2013-01-01

    In this study, we characterized a putative Flp/Tad pilus-encoding gene cluster, and we examined its regulation at the transcriptional level and its role in the virulence of potato pathogenic enterobacteria of the genus Pectobacterium. The Flp/Tad pilus-encoding gene clusters in Pectobacterium atrosepticum, Pectobacterium wasabiae and Pectobacterium aroidearum were compared to previously characterized flp/tad gene clusters, including that of the well-studied Flp/Tad pilus model organism Aggregatibacter actinomycetemcomitans, in which this pilus is a major virulence determinant. Comparative analyses revealed substantial protein sequence similarity and open reading frame synteny between the previously characterized flp/tad gene clusters and the cluster in Pectobacterium, suggesting that the predicted flp/tad gene cluster in Pectobacterium encodes a Flp/Tad pilus-like structure. We detected genes for a novel two-component system adjacent to the flp/tad gene cluster in Pectobacterium, and mutant analysis demonstrated that this system has a positive effect on the transcription of selected Flp/Tad pilus biogenesis genes, suggesting that this response regulator regulate the flp/tad gene cluster. Mutagenesis of either the predicted regulator gene or selected Flp/Tad pilus biogenesis genes had a significant impact on the maceration ability of the bacterial strains in potato tubers, indicating that the Flp/Tad pilus-encoding gene cluster represents a novel virulence determinant in Pectobacterium. Soft-rot enterobacteria in the genera Pectobacterium and Dickeya are of great agricultural importance, and an investigation of the virulence of these pathogens could facilitate improvements in agricultural practices, thus benefiting farmers, the potato industry and consumers.

  17. Comparison of the virulence of three H3N2 canine influenza virus isolates from Korea and China in mouse and Guinea pig models.

    Science.gov (United States)

    Xie, Xing; Na, Woonsung; Kang, Aram; Yeom, Minjoo; Yuk, Heejun; Moon, Hyoungjoon; Kim, Sung-Jae; Kim, Hyun-Woo; Kim, Jeong-Ki; Pang, Maoda; Wang, Yongshan; Liu, Yongjie; Song, Daesub

    2018-05-02

    Avian-origin H3N2 canine influenza virus (CIV) has been the most common subtype in Korea and China since 2007. Here, we compared the pathogenicity and transmissibility of three H3N2 CIV strains [Chinese CIV (JS/10), Korean CIV (KR/07), and Korean recombinant CIV between the classic H3N2 CIV and the pandemic H1N1 virus (MV/12)] in BALB/c mouse and guinea pig models. The pandemic H1N1 (CA/09) strain served as the control. BALB/c mice infected with H1N1 had high mortality and obvious body weight loss, whereas no overt disease symptoms were observed in mice inoculated with H3N2 CIV strains. The viral titers were higher in the group MV/12 than those in groups JS/10 and KR/07, while the mice infected with JS/10 showed higher viral titers in all tissues (except for the lung) than the mice infected with KR/07. The data obtained in guinea pigs also demonstrated that group MV/12 presented the highest loads in most of the tissues, followed by group JS/10 and KR/07. Also, direct contact transmissions of all the three CIV strains could be observed in guinea pigs, and for the inoculated and the contact groups, the viral titer of group MV/12 and KR/07 was higher than that of group JS/10 in nasal swabs. These findings indicated that the matrix (M) gene obtained from the pandemic H1N1 may enhance viral replication of classic H3N2 CIV; JS/10 has stronger viral replication ability in tissues as compared to KR/07, whereas KR/07 infected guinea pigs have more viral shedding than JS/10 infected guinea pigs. There exists a discrepancy in pathobiology among CIV isolates. Reverse genetics regarding the genomes of CIV isolates will be helpful to further explain the virus characteristics.

  18. Evaluating virulence of waterborne and clinical Aeromonas isolates using gene expression and mortality in neonatal mice followed by assessing cell culture’s ability to predict virulence based on transcriptional response

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, S L; Rodgers, M R; Lye, D J; Stelma, G N; McKinstry, Craig A.; Malard, Joel M.; Vesper, Sephen J.

    2007-10-01

    Aims: To assess the virulence of Aeromonas spp. using two models, a neonatal mouse assay and a mouse intestinal cell culture. Methods and Results: After artificial infection with a variety of Aeromonas spp., mRNA extracts from the two models were processed and hydridized to murine microarrays to determine host gene response. Definition of virulence was determined based on host mRNA production in murine neonatal intestinal tissue and mortality of infected animals. Infections of mouse intestinal cell cultures were then performed to determine whether this simpler model system’s mRNA responses correlated to neonatal results and therefore be predictive of virulence of Aeromonas spp. Virulent aeromonads up-regulated transcripts in both models including multiple host defense gene products (chemokines, regulation of transcription and apoptosis and cell signalling). Avirulent species exhibited little or no host response in neonates. Mortality results correlated well with both bacterial dose and average fold change of up-regulated transcripts in the neonatal mice. Conclusions: Cell culture results were less discriminating but showed promise as potentially being able to be predictive of virulence. Jun oncogene up-regulation in murine cell culture is potentially predictive of Aeromonas virulence. Significance and Impact of the Study: Having the ability to determine virulence of waterborne pathogens quickly would potentially assist public health officials to rapidly assess exposure risks.

  19. Survival and virulence of copper- and chlorine-stressed Yersinia enterocolitica in Experimentally infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Singh, A.; McFeters, G.A.

    1987-08-01

    The effect of gastric pH on the viability and virulence of Yersinia enterocolitica 0:8 after exposure to sublethal concentrations of copper and chlorine was determined in mice. Viability and injury were assessed with a nonselective TLY agar and two selective media, TLYD agar and CIN agar. Both copper and chlorine caused injury which was manifested by the inability of the cells to grow on selective media. CIN agar was more restrictive to the growth of injured cells than TLYD agar. Injury of the exposed cells was further enhanced in the gastric environment of mice. Besides injury, the low gastric pH caused extensive loss of viability in copper-exposed cells. Lethality in the chlorine-exposed cells was less extensive, and a portion of the inoculum reached the small intestine 5 min postinoculation. No adverse effect on the injured cells was apparent in the small intestine, and a substantial revival of the injury occurred in 3 to 4 h after intraluminal inoculation. The virulence of chlorine-stressed Y. enterocolitica in orally inoculated mice was similar to that of the control culture, but copper-stressed cells showed reduced virulence. Virulence was partly restored by oral administration of sodium bicarbonate before the inoculation of copper-exposed cells. Neutralization of gastric acidity had no effect on the virulence of the control of chlorine-stressed cells.

  20. Selected Constitutive Models for Simulating the Hygromechanical Response of Wood

    DEFF Research Database (Denmark)

    Frandsen, Henrik Lund

    , the boundary conditions are discussed based on discrepancies found for similar research on moisture transport in paper stacks. Paper III: A new sorption hysteresis model suitable for implementation into a numerical method is developed. The prevailing so-called scanning curves are modeled by closed......-form expressions, which only depend on the current relative humidity of the air and current moisture content of the wood. Furthermore, the expressions for the scanning curves are formulated independent of the temperature and species-dependent boundary curves. Paper IV: The sorption hysteresis model developed...... are discussed. The constitutive moisture transport models are coupled with a heat transport model yielding terms that describe the so-called Dufour and Sorret effects, however, with multiple phases and hysteresis included. Paper VII: In this paper the modeling of transverse couplings in creep of wood...

  1. Sequential Markov chain Monte Carlo filter with simultaneous model selection for electrocardiogram signal modeling.

    Science.gov (United States)

    Edla, Shwetha; Kovvali, Narayan; Papandreou-Suppappola, Antonia

    2012-01-01

    Constructing statistical models of electrocardiogram (ECG) signals, whose parameters can be used for automated disease classification, is of great importance in precluding manual annotation and providing prompt diagnosis of cardiac diseases. ECG signals consist of several segments with different morphologies (namely the P wave, QRS complex and the T wave) in a single heart beat, which can vary across individuals and diseases. Also, existing statistical ECG models exhibit a reliance upon obtaining a priori information from the ECG data by using preprocessing algorithms to initialize the filter parameters, or to define the user-specified model parameters. In this paper, we propose an ECG modeling technique using the sequential Markov chain Monte Carlo (SMCMC) filter that can perform simultaneous model selection, by adaptively choosing from different representations depending upon the nature of the data. Our results demonstrate the ability of the algorithm to track various types of ECG morphologies, including intermittently occurring ECG beats. In addition, we use the estimated model parameters as the feature set to classify between ECG signals with normal sinus rhythm and four different types of arrhythmia.

  2. Selected Aspects of Computer Modeling of Reinforced Concrete Structures

    Directory of Open Access Journals (Sweden)

    Szczecina M.

    2016-03-01

    Full Text Available The paper presents some important aspects concerning material constants of concrete and stages of modeling of reinforced concrete structures. The problems taken into account are: a choice of proper material model for concrete, establishing of compressive and tensile behavior of concrete and establishing the values of dilation angle, fracture energy and relaxation time for concrete. Proper values of material constants are fixed in simple compression and tension tests. The effectiveness and correctness of applied model is checked on the example of reinforced concrete frame corners under opening bending moment. Calculations are performed in Abaqus software using Concrete Damaged Plasticity model of concrete.

  3. cipC is important for Aspergillus fumigatus virulence.

    Science.gov (United States)

    Canela, Heliara Maria Spina; Takami, Luciano Akira; da Silva Ferreira, Márcia Eliana

    2017-02-01

    Aspergillus fumigatus is the main causative agent of invasive aspergillosis, a disease that affects immunocompromised patients and has a high mortality rate. We previously observed that the transcription of a cipC-like gene was increased when A. fumigatus encountered an increased CO 2 concentration, as occurs during the infection process. CipC is a protein of unknown function that might be associated with fungal pathogenicity. In this study, the cipC gene was disrupted in A. fumigatus to evaluate its importance for fungal pathogenicity. The gene was replaced, and the germination, growth phenotype, stress responses, and virulence of the resultant mutant were assessed. Although cipC was not essential, its deletion attenuated A. fumigatus virulence in a low-dose murine infection model, suggesting the involvement of the cipC gene in the virulence of this fungus. This study is the first to disrupt the cipC gene in A. fumigatus. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  4. Virulence of Flavobacterium columnare genomovars in rainbow trout Oncorhynchus mykiss.

    Science.gov (United States)

    Evenhuis, Jason P; LaFrentz, Benjamin R

    2016-08-09

    Flavobacterium columnare is the causative agent of columnaris disease and is responsible for significant economic losses in aquaculture. F. columnare is a Gram-negative bacterium, and 5 genetic types or genomovars have been described based on restriction fragment length polymorphism of the 16S rRNA gene. Previous research has suggested that genomovar II isolates are more virulent than genomovar I isolates to multiple species of fish, including rainbow trout Oncorhynchus mykiss. In addition, improved genotyping methods have shown that some isolates previously classified as genomovar I, and used in challenge experiments, were in fact genomovar III. Our objective was to confirm previous results with respect to genomovar II virulence, and to determine the susceptibility of rainbow trout to other genomovars. The virulence of 8 genomovar I, 4 genomovar II, 3 genomovar II-B, and 5 genomovar III isolates originating from various sources was determined through 3 independent challenges in rainbow trout using an immersion challenge model. Mean cumulative percent mortality (CPM) of ~49% for genomovar I isolates, ~1% for genomovar II, ~5% for the II-B isolates, and ~7% for the III isolates was observed. The inability of genomovar II isolates to produce mortalities in rainbow trout was unanticipated based on previous studies, but may be due to a number of factors including rainbow trout source and water chemistry. The source of fish and/or the presence of sub-optimal environment may influence the susceptibility of rainbow trout to different F. columnare genomovars.

  5. Bayesian model selection validates a biokinetic model for zirconium processing in humans

    Science.gov (United States)

    2012-01-01

    Background In radiation protection, biokinetic models for zirconium processing are of crucial importance in dose estimation and further risk analysis for humans exposed to this radioactive substance. They provide limiting values of detrimental effects and build the basis for applications in internal dosimetry, the prediction for radioactive zirconium retention in various organs as well as retrospective dosimetry. Multi-compartmental models are the tool of choice for simulating the processing of zirconium. Although easily interpretable, determining the exact compartment structure and interaction mechanisms is generally daunting. In the context of observing the dynamics of multiple compartments, Bayesian methods provide efficient tools for model inference and selection. Results We are the first to apply a Markov chain Monte Carlo approach to compute Bayes factors for the evaluation of two competing models for zirconium processing in the human body after ingestion. Based on in vivo measurements of human plasma and urine levels we were able to show that a recently published model is superior to the standard model of the International Commission on Radiological Protection. The Bayes factors were estimated by means of the numerically stable thermodynamic integration in combination with a recently developed copula-based Metropolis-Hastings sampler. Conclusions In contrast to the standard model the novel model predicts lower accretion of zirconium in bones. This results in lower levels of noxious doses for exposed individuals. Moreover, the Bayesian approach allows for retrospective dose assessment, including credible intervals for the initially ingested zirconium, in a significantly more reliable fashion than previously possible. All methods presented here are readily applicable to many modeling tasks in systems biology. PMID:22863152

  6. A model selection support system for numerical simulations of nuclear thermal-hydraulics

    International Nuclear Information System (INIS)

    Gofuku, Akio; Shimizu, Kenji; Sugano, Keiji; Yoshikawa, Hidekazu; Wakabayashi, Jiro

    1990-01-01

    In order to execute efficiently a dynamic simulation of a large-scaled engineering system such as a nuclear power plant, it is necessary to develop intelligent simulation support system for all phases of the simulation. This study is concerned with the intelligent support for the program development phase and is engaged in the adequate model selection support method by applying AI (Artificial Intelligence) techniques to execute a simulation consistent with its purpose and conditions. A proto-type expert system to support the model selection for numerical simulations of nuclear thermal-hydraulics in the case of cold leg small break loss-of-coolant accident of PWR plant is now under development on a personal computer. The steps to support the selection of both fluid model and constitutive equations for the drift flux model have been developed. Several cases of model selection were carried out and reasonable model selection results were obtained. (author)

  7. Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

    Science.gov (United States)

    Gillette, Devyn D.; Curry, Heather M.; Cremer, Thomas; Ravneberg, David; Fatehchand, Kavin; Shah, Prexy A.; Wewers, Mark D.; Schlesinger, Larry S.; Butchar, Jonathan P.; Tridandapani, Susheela; Gavrilin, Mikhail A.

    2014-01-01

    Background: Human monocyte inflammatory responses differ between virulent and attenuated Francisella infection. Results: A mixed infection model showed that the virulent F. tularensis Schu S4 can attenuate inflammatory cytokine responses to the less virulent F. novicida in human monocytes. Conclusion: F. tularensis dampens inflammatory response by an active process. Significance: This suppression may contribute to enhanced pathogenicity of F. tularensis. Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity. PMID:24783062

  8. Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens

    Directory of Open Access Journals (Sweden)

    de Rochefort Anna

    2009-10-01

    Full Text Available Abstract Background New and improved antimicrobial countermeasures are urgently needed to counteract increased resistance to existing antimicrobial treatments and to combat currently untreatable or new emerging infectious diseases. We demonstrate that computational comparative genomics, together with experimental screening, can identify potential generic (i.e., conserved across multiple pathogen species and novel virulence-associated genes that may serve as targets for broad-spectrum countermeasures. Results Using phylogenetic profiles of protein clusters from completed microbial genome sequences, we identified seventeen protein candidates that are common to diverse human pathogens and absent or uncommon in non-pathogens. Mutants of 13 of these candidates were successfully generated in Yersinia pseudotuberculosis and the potential role of the proteins in virulence was assayed in an animal model. Six candidate proteins are suggested to be involved in the virulence of Y. pseudotuberculosis, none of which have previously been implicated in the virulence of Y. pseudotuberculosis and three have no record of involvement in the virulence of any bacteria. Conclusion This work demonstrates a strategy for the identification of potential virulence factors that are conserved across a number of human pathogenic bacterial species, confirming the usefulness of this tool.

  9. Optimal selection of Orbital Replacement Unit on-orbit spares - A Space Station system availability model

    Science.gov (United States)

    Schwaab, Douglas G.

    1991-01-01

    A mathematical programing model is presented to optimize the selection of Orbital Replacement Unit on-orbit spares for the Space Station. The model maximizes system availability under the constraints of logistics resupply-cargo weight and volume allocations.

  10. Assessing the accuracy and stability of variable selection methods for random forest modeling in ecology

    Science.gov (United States)

    Random forest (RF) modeling has emerged as an important statistical learning method in ecology due to its exceptional predictive performance. However, for large and complex ecological datasets there is limited guidance on variable selection methods for RF modeling. Typically, e...

  11. Hybrid nested sampling algorithm for Bayesian model selection applied to inverse subsurface flow problems

    KAUST Repository

    Elsheikh, Ahmed H.; Wheeler, Mary Fanett; Hoteit, Ibrahim

    2014-01-01

    A Hybrid Nested Sampling (HNS) algorithm is proposed for efficient Bayesian model calibration and prior model selection. The proposed algorithm combines, Nested Sampling (NS) algorithm, Hybrid Monte Carlo (HMC) sampling and gradient estimation using

  12. Variable selection models for genomic selection using whole-genome sequence data and singular value decomposition.

    Science.gov (United States)

    Meuwissen, Theo H E; Indahl, Ulf G; Ødegård, Jørgen

    2017-12-27

    Non-linear Bayesian genomic prediction models such as BayesA/B/C/R involve iteration and mostly Markov chain Monte Carlo (MCMC) algorithms, which are computationally expensive, especially when whole-genome sequence (WGS) data are analyzed. Singular value decomposition (SVD) of the genotype matrix can facilitate genomic prediction in large datasets, and can be used to estimate marker effects and their prediction error variances (PEV) in a computationally efficient manner. Here, we developed, implemented, and evaluated a direct, non-iterative method for the estimation of marker effects for the BayesC genomic prediction model. The BayesC model assumes a priori that markers have normally distributed effects with probability [Formula: see text] and no effect with probability (1 - [Formula: see text]). Marker effects and their PEV are estimated by using SVD and the posterior probability of the marker having a non-zero effect is calculated. These posterior probabilities are used to obtain marker-specific effect variances, which are subsequently used to approximate BayesC estimates of marker effects in a linear model. A computer simulation study was conducted to compare alternative genomic prediction methods, where a single reference generation was used to estimate marker effects, which were subsequently used for 10 generations of forward prediction, for which accuracies were evaluated. SVD-based posterior probabilities of markers having non-zero effects were generally lower than MCMC-based posterior probabilities, but for some regions the opposite occurred, resulting in clear signals for QTL-rich regions. The accuracies of breeding values estimated using SVD- and MCMC-based BayesC analyses were similar across the 10 generations of forward prediction. For an intermediate number of generations (2 to 5) of forward prediction, accuracies obtained with the BayesC model tended to be slightly higher than accuracies obtained using the best linear unbiased prediction of SNP

  13. Varying Coefficient Panel Data Model in the Presence of Endogenous Selectivity and Fixed Effects

    OpenAIRE

    Malikov, Emir; Kumbhakar, Subal C.; Sun, Yiguo

    2013-01-01

    This paper considers a flexible panel data sample selection model in which (i) the outcome equation is permitted to take a semiparametric, varying coefficient form to capture potential parameter heterogeneity in the relationship of interest, (ii) both the outcome and (parametric) selection equations contain unobserved fixed effects and (iii) selection is generalized to a polychotomous case. We propose a two-stage estimator. Given consistent parameter estimates from the selection equation obta...

  14. Required experimental accuracy to select between supersymmetrical models

    Science.gov (United States)

    Grellscheid, David

    2004-03-01

    We will present a method to decide a priori whether various supersymmetrical scenarios can be distinguished based on sparticle mass data alone. For each model, a scan over all free SUSY breaking parameters reveals the extent of that model's physically allowed region of sparticle-mass-space. Based on the geometrical configuration of these regions in mass-space, it is possible to obtain an estimate of the required accuracy of future sparticle mass measurements to distinguish between the models. We will illustrate this algorithm with an example. This talk is based on work done in collaboration with B C Allanach (LAPTH, Annecy) and F Quevedo (DAMTP, Cambridge).

  15. Development of Solar Drying Model for Selected Cambodian Fish Species

    OpenAIRE

    Hubackova, Anna; Kucerova, Iva; Chrun, Rithy; Chaloupkova, Petra; Banout, Jan

    2014-01-01

    A solar drying was investigated as one of perspective techniques for fish processing in Cambodia. The solar drying was compared to conventional drying in electric oven. Five typical Cambodian fish species were selected for this study. Mean solar drying temperature and drying air relative humidity were 55.6°C and 19.9%, respectively. The overall solar dryer efficiency was 12.37%, which is typical for natural convection solar dryers. An average evaporative capacity of solar dryer was 0.049 kg·h...

  16. Identification of landscape features influencing gene flow: How useful are habitat selection models?

    Science.gov (United States)

    Gretchen H. Roffler; Michael K. Schwartz; Kristine Pilgrim; Sandra L. Talbot; George K. Sage; Layne G. Adams; Gordon Luikart

    2016-01-01

    Understanding how dispersal patterns are influenced by landscape heterogeneity is critical for modeling species connectivity. Resource selection function (RSF) models are increasingly used in landscape genetics approaches. However, because the ecological factors that drive habitat selection may be different from those influencing dispersal and gene flow, it is...

  17. Optimal covariance selection for estimation using graphical models

    OpenAIRE

    Vichik, Sergey; Oshman, Yaakov

    2011-01-01

    We consider a problem encountered when trying to estimate a Gaussian random field using a distributed estimation approach based on Gaussian graphical models. Because of constraints imposed by estimation tools used in Gaussian graphical models, the a priori covariance of the random field is constrained to embed conditional independence constraints among a significant number of variables. The problem is, then: given the (unconstrained) a priori covariance of the random field, and the conditiona...

  18. A Neuronal Network Model for Pitch Selectivity and Representation

    OpenAIRE

    Huang, Chengcheng; Rinzel, John

    2016-01-01

    Pitch is a perceptual correlate of periodicity. Sounds with distinct spectra can elicit the same pitch. Despite the importance of pitch perception, understanding the cellular mechanism of pitch perception is still a major challenge and a mechanistic model of pitch is lacking. A multi-stage neuronal network model is developed for pitch frequency estimation using biophysically-based, high-resolution coincidence detector neurons. The neuronal units respond only to highly coincident input among c...

  19. Fuzzy Multicriteria Model for Selection of Vibration Technology

    Directory of Open Access Journals (Sweden)

    María Carmen Carnero

    2016-01-01

    Full Text Available The benefits of applying the vibration analysis program are well known and have been so for decades. A large number of contributions have been produced discussing new diagnostic, signal treatment, technical parameter analysis, and prognosis techniques. However, to obtain the expected benefits from a vibration analysis program, it is necessary to choose the instrumentation which guarantees the best results. Despite its importance, in the literature, there are no models to assist in taking this decision. This research describes an objective model using Fuzzy Analytic Hierarchy Process (FAHP to make a choice of the most suitable technology among portable vibration analysers. The aim is to create an easy-to-use model for processing, manufacturing, services, and research organizations, to guarantee adequate decision-making in the choice of vibration analysis technology. The model described recognises that judgements are often based on ambiguous, imprecise, or inadequate information that cannot provide precise values. The model incorporates judgements from several decision-makers who are experts in the field of vibration analysis, maintenance, and electronic devices. The model has been applied to a Health Care Organization.

  20. Calcineurin Targets Involved in Stress Survival and Fungal Virulence.

    Directory of Open Access Journals (Sweden)

    Hee-Soo Park

    2016-09-01

    Full Text Available Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. Calcineurin is activated by increased Ca2+ levels caused by stress, and transduces signals by dephosphorylating protein substrates. Herein, we identified and characterized calcineurin substrates in C. neoformans by employing phosphoproteomic TiO2 enrichment and quantitative mass spectrometry. The identified targets include the transactivator Crz1 as well as novel substrates whose functions are linked to P-bodies/stress granules (PBs/SGs and mRNA translation and decay, such as Pbp1 and Puf4. We show that Crz1 is a bona fide calcineurin substrate, and Crz1 localization and transcriptional activity are controlled by calcineurin. We previously demonstrated that thermal and other stresses trigger calcineurin localization to PBs/SGs. Several calcineurin targets localized to PBs/SGs, including Puf4 and Pbp1, contribute to stress resistance and virulence individually or in conjunction with Crz1. Moreover, Pbp1 is also required for sexual development. Genetic epistasis analysis revealed that Crz1 and the novel targets Lhp1, Puf4, and Pbp1 function in a branched calcineurin pathway that orchestrates stress survival and virulence. These findings support a model whereby calcineurin controls stress and virulence, at the transcriptional level via Crz1, and post-transcriptionally by localizing to PBs/SGs and acting on targets involved in mRNA metabolism. The calcineurin targets identified in this study share little overlap with known calcineurin substrates, with the exception of Crz1. In particular, the mRNA binding proteins and PBs/SGs residents comprise a cohort of novel calcineurin targets that have not been previously linked to calcineurin in mammals or in Saccharomyces cerevisiae. This study suggests either extensive evolutionary rewiring of the calcineurin pathway, or alternatively that these novel calcineurin targets have yet

  1. Multi-Criteria Decision Making For Determining A Simple Model of Supplier Selection

    Science.gov (United States)

    Harwati

    2017-06-01

    Supplier selection is a decision with many criteria. Supplier selection model usually involves more than five main criteria and more than 10 sub-criteria. In fact many model includes more than 20 criteria. Too many criteria involved in supplier selection models sometimes make it difficult to apply in many companies. This research focuses on designing supplier selection that easy and simple to be applied in the company. Analytical Hierarchy Process (AHP) is used to weighting criteria. The analysis results there are four criteria that are easy and simple can be used to select suppliers: Price (weight 0.4) shipment (weight 0.3), quality (weight 0.2) and services (weight 0.1). A real case simulation shows that simple model provides the same decision with a more complex model.

  2. Calibration model maintenance in melamine resin production: Integrating drift detection, smart sample selection and model adaptation.

    Science.gov (United States)

    Nikzad-Langerodi, Ramin; Lughofer, Edwin; Cernuda, Carlos; Reischer, Thomas; Kantner, Wolfgang; Pawliczek, Marcin; Brandstetter, Markus

    2018-07-12

    selection of samples by active learning (AL) used for subsequent model adaptation is advantageous compared to passive (random) selection in case that a drift leads to persistent prediction bias allowing more rapid adaptation at lower reference measurement rates. Fully unsupervised adaptation using FLEXFIS-PLS could improve predictive accuracy significantly for light drifts but was not able to fully compensate for prediction bias in case of significant lack of fit w.r.t. the latent variable space. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Selecting a climate model subset to optimise key ensemble properties

    Directory of Open Access Journals (Sweden)

    N. Herger

    2018-02-01

    Full Text Available End users studying impacts and risks caused by human-induced climate change are often presented with large multi-model ensembles of climate projections whose composition and size are arbitrarily determined. An efficient and versatile method that finds a subset which maintains certain key properties from the full ensemble is needed, but very little work has been done in this area. Therefore, users typically make their own somewhat subjective subset choices and commonly use the equally weighted model mean as a best estimate. However, different climate model simulations cannot necessarily be regarded as independent estimates due to the presence of duplicated code and shared development history. Here, we present an efficient and flexible tool that makes better use of the ensemble as a whole by finding a subset with improved mean performance compared to the multi-model mean while at the same time maintaining the spread and addressing the problem of model interdependence. Out-of-sample skill and reliability are demonstrated using model-as-truth experiments. This approach is illustrated with one set of optimisation criteria but we also highlight the flexibility of cost functions, depending on the focus of different users. The technique is useful for a range of applications that, for example, minimise present-day bias to obtain an accurate ensemble mean, reduce dependence in ensemble spread, maximise future spread, ensure good performance of individual models in an ensemble, reduce the ensemble size while maintaining important ensemble characteristics, or optimise several of these at the same time. As in any calibration exercise, the final ensemble is sensitive to the metric, observational product, and pre-processing steps used.

  4. Selecting a climate model subset to optimise key ensemble properties

    Science.gov (United States)

    Herger, Nadja; Abramowitz, Gab; Knutti, Reto; Angélil, Oliver; Lehmann, Karsten; Sanderson, Benjamin M.

    2018-02-01

    End users studying impacts and risks caused by human-induced climate change are often presented with large multi-model ensembles of climate projections whose composition and size are arbitrarily determined. An efficient and versatile method that finds a subset which maintains certain key properties from the full ensemble is needed, but very little work has been done in this area. Therefore, users typically make their own somewhat subjective subset choices and commonly use the equally weighted model mean as a best estimate. However, different climate model simulations cannot necessarily be regarded as independent estimates due to the presence of duplicated code and shared development history. Here, we present an efficient and flexible tool that makes better use of the ensemble as a whole by finding a subset with improved mean performance compared to the multi-model mean while at the same time maintaining the spread and addressing the problem of model interdependence. Out-of-sample skill and reliability are demonstrated using model-as-truth experiments. This approach is illustrated with one set of optimisation criteria but we also highlight the flexibility of cost functions, depending on the focus of different users. The technique is useful for a range of applications that, for example, minimise present-day bias to obtain an accurate ensemble mean, reduce dependence in ensemble spread, maximise future spread, ensure good performance of individual models in an ensemble, reduce the ensemble size while maintaining important ensemble characteristics, or optimise several of these at the same time. As in any calibration exercise, the final ensemble is sensitive to the metric, observational product, and pre-processing steps used.

  5. Differences in virulence and sporulation of Phytophthora kernoviae isolates originating from two distinct geographical regions

    Science.gov (United States)

    Phytophthora kernoviae has only been isolated from the United Kingdom (U.K.) and New Zealand. To understand what differences may exist between isolates from these two distinct geographical regions, virulence studies on three host plants and sporulation on host leaves were conducted on select isolat...

  6. Bmh1p (14-3-3) mediates pathways associated with virulence in Candida albicans.

    Science.gov (United States)

    Kelly, Michelle N; Johnston, Douglas A; Peel, Bethany A; Morgan, Timothy W; Palmer, Glen E; Sturtevant, Joy E

    2009-05-01

    The ability of the pathogenic fungus Candida albicans to cause disease requires rapid adaptation to changes in the host environment and to an evolving host immune response. The identification of 'virulence factors' using in vitro characterization of mutant strains has traditionally relied on a common set of phenotypic and biochemical assays (most often performed at 30 degrees C) and the subsequent correlation with their corresponding virulence in mouse models of disease. Utilizing a panel of isogenic mutants for the multifunctional signal-modulating 14-3-3 protein (Bmh1p), we have found that specific mutations affect a variety of different pathways currently associated with virulence, including those involved with the formation of filaments, as well as interaction with host immune cells. Surprisingly, our studies revealed that deficiencies in many of these pathways do not always correlate with virulence in a mouse model of disseminated infection. Mutations within the binding pocket of Bmh1p that affect the ability of the protein to efficiently bind ligand had varying effects on the results of a number of in vitro and in vivo assays. The capability, in vitro, to filament in embedment conditions, and to filament and form chlamydospores under microaerophilic conditions on cornmeal agar, does not correlate with virulence. It is likely that only a subset of hyphal signalling pathways is actually required for the establishment of infection in the disseminated mouse model. Most importantly, our results suggest that the delayed onset of log-phase [corrected] growth in vitro at 37 degrees C, and not at 30 degrees C, results in an inability of these mutants to rapidly adjust to environmental changes in vivo and may be responsible for their increased clearance and reduced virulence. It is critical, therefore, that future in vitro studies of putative virulence factors in C. albicans include careful characterization at physiological temperatures.

  7. Selected developments and applications of Leontief models in industrial ecology

    International Nuclear Information System (INIS)

    Stroemman, Anders Hammer

    2005-01-01

    Thesis Outline: This thesis investigates issues of environmental repercussions on processes of three spatial scales; a single process plant, a regional value chain and the global economy. The first paper investigates environmental repercussions caused by a single process plant using an open Leontief model with combined physical and monetary units in what is commonly referred to as a hybrid life cycle model. Physical capital requirements are treated as any other good. Resources and environmental stressors, thousands in total, are accounted for and assessed by aggregation using standard life cycle impact assessment methods. The second paper presents a methodology for establishing and combining input-output matrices and life-cycle inventories in a hybrid life cycle inventory. Information contained within different requirements matrices are combined and issues of double counting that arise are addressed and methods for eliminating these are developed and presented. The third paper is an extension of the first paper. Here the system analyzed is increased from a single plant and component in the production network to a series of nodes, constituting a value chain. The hybrid framework proposed in paper two is applied to analyze the use of natural gas, methanol and hydrogen as transportation fuels. The fourth paper presents the development of a World Trade Model with Bilateral Trade, an extension of the World Trade Model (Duchin, 2005). The model is based on comparative advantage and is formulated as a linear program. It endogenously determines the regional output of sectors and bilateral trade flows between regions. The model may be considered a Leontief substitution model where substitution of production is allowed between regions. The primal objective of the model requires the minimization of global factor costs. The fifth paper demonstrates how the World Trade Model with Bilateral Trade can be applied to address questions relevant for industrial ecology. The model is

  8. Model validity and frequency band selection in operational modal analysis

    Science.gov (United States)

    Au, Siu-Kui

    2016-12-01

    Experimental modal analysis aims at identifying the modal properties (e.g., natural frequencies, damping ratios, mode shapes) of a structure using vibration measurements. Two basic questions are encountered when operating in the frequency domain: Is there a mode near a particular frequency? If so, how much spectral data near the frequency can be included for modal identification without incurring significant modeling error? For data with high signal-to-noise (s/n) ratios these questions can be addressed using empirical tools such as singular value spectrum. Otherwise they are generally open and can be challenging, e.g., for modes with low s/n ratios or close modes. In this work these questions are addressed using a Bayesian approach. The focus is on operational modal analysis, i.e., with 'output-only' ambient data, where identification uncertainty and modeling error can be significant and their control is most demanding. The approach leads to 'evidence ratios' quantifying the relative plausibility of competing sets of modeling assumptions. The latter involves modeling the 'what-if-not' situation, which is non-trivial but is resolved by systematic consideration of alternative models and using maximum entropy principle. Synthetic and field data are considered to investigate the behavior of evidence ratios and how they should be interpreted in practical applications.

  9. Selecting salient frames for spatiotemporal video modeling and segmentation.

    Science.gov (United States)

    Song, Xiaomu; Fan, Guoliang

    2007-12-01

    We propose a new statistical generative model for spatiotemporal video segmentation. The objective is to partition a video sequence into homogeneous segments that can be used as "building blocks" for semantic video segmentation. The baseline framework is a Gaussian mixture model (GMM)-based video modeling approach that involves a six-dimensional spatiotemporal feature space. Specifically, we introduce the concept of frame saliency to quantify the relevancy of a video frame to the GMM-based spatiotemporal video modeling. This helps us use a small set of salient frames to facilitate the model training by reducing data redundancy and irrelevance. A modified expectation maximization algorithm is developed for simultaneous GMM training and frame saliency estimation, and the frames with the highest saliency values are extracted to refine the GMM estimation for video segmentation. Moreover, it is interesting to find that frame saliency can imply some object behaviors. This makes the proposed method also applicable to other frame-related video analysis tasks, such as key-frame extraction, video skimming, etc. Experiments on real videos demonstrate the effectiveness and efficiency of the proposed method.

  10. Statistical mechanics of sparse generalization and graphical model selection

    International Nuclear Information System (INIS)

    Lage-Castellanos, Alejandro; Pagnani, Andrea; Weigt, Martin

    2009-01-01

    One of the crucial tasks in many inference problems is the extraction of an underlying sparse graphical model from a given number of high-dimensional measurements. In machine learning, this is frequently achieved using, as a penalty term, the L p norm of the model parameters, with p≤1 for efficient dilution. Here we propose a statistical mechanics analysis of the problem in the setting of perceptron memorization and generalization. Using a replica approach, we are able to evaluate the relative performance of naive dilution (obtained by learning without dilution, following by applying a threshold to the model parameters), L 1 dilution (which is frequently used in convex optimization) and L 0 dilution (which is optimal but computationally hard to implement). Whereas both L p diluted approaches clearly outperform the naive approach, we find a small region where L 0 works almost perfectly and strongly outperforms the simpler to implement L 1 dilution

  11. Selection of References in Wind Turbine Model Predictive Control Design

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Hovgaard, Tobias

    2015-01-01

    a model predictive controller for a wind turbine. One of the important aspects for a tracking control problem is how to setup the optimal reference tracking problem, as it might be relevant to track, e.g., the three concurrent references: optimal pitch angle, optimal rotational speed, and optimal power......Lowering the cost of energy is one of the major focus areas in the wind turbine industry. Recent research has indicated that wind turbine controllers based on model predictive control methods can be useful in obtaining this objective. A number of design considerations have to be made when designing....... The importance if the individual references differ depending in particular on the wind speed. In this paper we investigate the performance of a reference tracking model predictive controller with two different setups of the used optimal reference signals. The controllers are evaluated using an industrial high...

  12. SELECT NUMERICAL METHODS FOR MODELING THE DYNAMICS SYSTEMS

    Directory of Open Access Journals (Sweden)

    Tetiana D. Panchenko

    2016-07-01

    Full Text Available The article deals with the creation of methodical support for mathematical modeling of dynamic processes in elements of the systems and complexes. As mathematical models ordinary differential equations have been used. The coefficients of the equations of the models can be nonlinear functions of the process. The projection-grid method is used as the main tool. It has been described iterative method algorithms taking into account the approximate solution prior to the first iteration and proposed adaptive control computing process. The original method of estimation error in the calculation solutions as well as for a given level of error of the technique solutions purpose adaptive method for solving configuration parameters is offered. A method for setting an adaptive method for solving the settings for a given level of error is given. The proposed method can be used for distributed computing.

  13. Mathematical Model of the Emissions of a selected vehicle

    Directory of Open Access Journals (Sweden)

    Matušů Radim

    2014-10-01

    Full Text Available The article addresses the quantification of exhaust emissions from gasoline engines during transient operation. The main targeted emissions are carbon monoxide and carbon dioxide. The result is a mathematical model describing the production of individual emissions components in all modes (static and dynamic. It also describes the procedure for the determination of emissions from the engine’s operating parameters. The result is compared with other possible methods of measuring emissions. The methodology is validated using the data from an on-road measurement. The mathematical model was created on the first route and validated on the second route.

  14. An Optimization Model For Strategy Decision Support to Select Kind of CPO’s Ship

    Science.gov (United States)

    Suaibah Nst, Siti; Nababan, Esther; Mawengkang, Herman

    2018-01-01

    The selection of marine transport for the distribution of crude palm oil (CPO) is one of strategy that can be considered in reducing cost of transport. The cost of CPO’s transport from one area to CPO’s factory located at the port of destination may affect the level of CPO’s prices and the number of demands. In order to maintain the availability of CPO a strategy is required to minimize the cost of transporting. In this study, the strategy used to select kind of charter ships as barge or chemical tanker. This study aims to determine an optimization model for strategy decision support in selecting kind of CPO’s ship by minimizing costs of transport. The select of ship was done randomly, so that two-stage stochastic programming model was used to select the kind of ship. Model can help decision makers to select either barge or chemical tanker to distribute CPO.

  15. The Optimal Portfolio Selection Model under g-Expectation

    Directory of Open Access Journals (Sweden)

    Li Li

    2014-01-01

    complicated and sophisticated, the optimal solution turns out to be surprisingly simple, the payoff of a portfolio of two binary claims. Also I give the economic meaning of my model and the comparison with that one in the work of Jin and Zhou, 2008.

  16. An ecosystem model for tropical forest disturbance and selective logging

    Science.gov (United States)

    Maoyi Huang; Gregory P. Asner; Michael Keller; Joseph A. Berry

    2008-01-01

    [1] A new three-dimensional version of the Carnegie-Ames-Stanford Approach (CASA) ecosystem model (CASA-3D) was developed to simulate regional carbon cycling in tropical forest ecosystems after disturbances such as logging. CASA-3D has the following new features: (1) an alternative approach for calculating absorbed photosynthetically active radiation (APAR) using new...

  17. Process chain modeling and selection in an additive manufacturing context

    DEFF Research Database (Denmark)

    Thompson, Mary Kathryn; Stolfi, Alessandro; Mischkot, Michael

    2016-01-01

    This paper introduces a new two-dimensional approach to modeling manufacturing process chains. This approach is used to consider the role of additive manufacturing technologies in process chains for a part with micro scale features and no internal geometry. It is shown that additive manufacturing...... evolving fields like additive manufacturing....

  18. Selecting Tools to Model Integer and Binomial Multiplication

    Science.gov (United States)

    Pratt, Sarah Smitherman; Eddy, Colleen M.

    2017-01-01

    Mathematics teachers frequently provide concrete manipulatives to students during instruction; however, the rationale for using certain manipulatives in conjunction with concepts may not be explored. This article focuses on area models that are currently used in classrooms to provide concrete examples of integer and binomial multiplication. The…

  19. Modeling Selected Climatic Variables in Ibadan, Oyo State, Nigeria ...

    African Journals Online (AJOL)

    PROF. O. E. OSUAGWU

    2013-09-01

    Sep 1, 2013 ... The aim of this study was fitting the modified generalized burr density function to total rainfall and temperature data obtained from the meteorological unit in the Department of. Environmental Modelling and Management of the Forestry Research Institute of Nigeria. (FRIN) in Ibadan, Oyo State, Nigeria.

  20. Parameter Estimation and Model Selection for Mixtures of Truncated Exponentials

    DEFF Research Database (Denmark)

    Langseth, Helge; Nielsen, Thomas Dyhre; Rumí, Rafael

    2010-01-01

    Bayesian networks with mixtures of truncated exponentials (MTEs) support efficient inference algorithms and provide a flexible way of modeling hybrid domains (domains containing both discrete and continuous variables). On the other hand, estimating an MTE from data has turned out to be a difficul...

  1. THERMODYNAMIC MODEL AND VISCOSITY OF SELECTED ZIRCONIA CONTAINING SILICATE GLASSES

    Directory of Open Access Journals (Sweden)

    MÁRIA CHROMČÍKOVÁ

    2013-03-01

    Full Text Available The compositional dependence of viscosity, and viscous flow activation energy of glasses with composition xNa2O∙(15-x K2O∙yCaO∙(10-yZnO∙zZrO2∙(75-zSiO2 (x = 0, 7.5, 15; y = 0, 5, 10; z = 0, 1, 3, 5, 7 was analyzed. The studied glasses were described by the thermodynamic model of Shakhmatkin and Vedishcheva considering the glass as an equilibrium ideal solution of species with stoichiometry given by the composition of stable crystalline phases of respective glass forming system. Viscosity-composition relationships were described by the regression approach considering the viscous flow activation energy and the particular isokome temperature as multilinear function of equilibrium molar amounts of system components. The classical approach where the mole fractions of individual oxides are considered as independent variables was compared with the thermodynamic model. On the basis of statistical analysis there was proved that the thermodynamic model is able to describe the composition property relationships with higher reliability. Moreover, due its better physical justification, thermodynamic model can be even used for predictive purposes.

  2. Model Selection and Accounting for Model Uncertainty in Graphical Models Using OCCAM’s Window

    Science.gov (United States)

    1991-07-22

    mental work; C, strenuous physical work; D, systolic blood pressure: E. ratio of 13 and Qt proteins; F, family anamnesis of coronary heart disease...of F, family anamnesis . The models are shown in Figure 4. 12 Table 1: Risk factors for Coronary lfeart Disea:W B No Yes A No Yes No Yes F E D C...a link from smoking (A) to systolic blood pressure (D). There is decisive evidence in favour of the marginal independence of family anamnesis of

  3. On a Robust MaxEnt Process Regression Model with Sample-Selection

    Directory of Open Access Journals (Sweden)

    Hea-Jung Kim

    2018-04-01

    Full Text Available In a regression analysis, a sample-selection bias arises when a dependent variable is partially observed as a result of the sample selection. This study introduces a Maximum Entropy (MaxEnt process regression model that assumes a MaxEnt prior distribution for its nonparametric regression function and finds that the MaxEnt process regression model includes the well-known Gaussian process regression (GPR model as a special case. Then, this special MaxEnt process regression model, i.e., the GPR model, is generalized to obtain a robust sample-selection Gaussian process regression (RSGPR model that deals with non-normal data in the sample selection. Various properties of the RSGPR model are established, including the stochastic representation, distributional hierarchy, and magnitude of the sample-selection bias. These properties are used in the paper to develop a hierarchical Bayesian methodology to estimate the model. This involves a simple and computationally feasible Markov chain Monte Carlo algorithm that avoids analytical or numerical derivatives of the log-likelihood function of the model. The performance of the RSGPR model in terms of the sample-selection bias correction, robustness to non-normality, and prediction, is demonstrated through results in simulations that attest to its good finite-sample performance.

  4. A BAYESIAN NONPARAMETRIC MIXTURE MODEL FOR SELECTING GENES AND GENE SUBNETWORKS.

    Science.gov (United States)

    Zhao, Yize; Kang, Jian; Yu, Tianwei

    2014-06-01

    It is very challenging to select informative features from tens of thousands of measured features in high-throughput data analysis. Recently, several parametric/regression models have been developed utilizing the gene network information to select genes or pathways strongly associated with a clinical/biological outcome. Alternatively, in this paper, we propose a nonparametric Bayesian model for gene selection incorporating network information. In addition to identifying genes that have a strong association with a clinical outcome, our model can select genes with particular expressional behavior, in which case the regression models are not directly applicable. We show that our proposed model is equivalent to an infinity mixture model for which we develop a posterior computation algorithm based on Markov chain Monte Carlo (MCMC) methods. We also propose two fast computing algorithms that approximate the posterior simulation with good accuracy but relatively low computational cost. We illustrate our methods on simulation studies and the analysis of Spellman yeast cell cycle microarray data.

  5. A model of directional selection applied to the evolution of drug resistance in HIV-1.

    Science.gov (United States)

    Seoighe, Cathal; Ketwaroo, Farahnaz; Pillay, Visva; Scheffler, Konrad; Wood, Natasha; Duffet, Rodger; Zvelebil, Marketa; Martinson, Neil; McIntyre, James; Morris, Lynn; Hide, Winston

    2007-04-01

    Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.

  6. Potential drivers of virulence evolution in aquaculture

    Science.gov (United States)

    Kennedy, David A.; Kurath, Gael; Brito, Ilana L.; Purcell, Maureen K.; Read, Andrew F.; Winton, James R.; Wargo, Andrew R.

    2016-01-01

    Infectious diseases are economically detrimental to aquaculture, and with continued expansion and intensification of aquaculture, the importance of managing infectious diseases will likely increase in the future. Here, we use evolution of virulence theory, along with examples, to identify aquaculture practices that might lead to the evolution of increased pathogen virulence. We identify eight practices common in aquaculture that theory predicts may favor evolution toward higher pathogen virulence. Four are related to intensive aquaculture operations, and four others are related specifically to infectious disease control. Our intention is to make aquaculture managers aware of these risks, such that with increased vigilance, they might be able to detect and prevent the emergence and spread of increasingly troublesome pathogen strains in the future.

  7. Parameter Selection and Performance Analysis of Mobile Terminal Models Based on Unity3D

    Institute of Scientific and Technical Information of China (English)

    KONG Li-feng; ZHAO Hai-ying; XU Guang-mei

    2014-01-01

    Mobile platform is now widely seen as a promising multimedia service with a favorable user group and market prospect. To study the influence of mobile terminal models on the quality of scene roaming, a parameter setting platform of mobile terminal models is established to select the parameter selection and performance index on different mobile platforms in this paper. This test platform is established based on model optimality principle, analyzing the performance curve of mobile terminals in different scene models and then deducing the external parameter of model establishment. Simulation results prove that the established test platform is able to analyze the parameter and performance matching list of a mobile terminal model.

  8. Evaluation and comparison of alternative fleet-level selective maintenance models

    International Nuclear Information System (INIS)

    Schneider, Kellie; Richard Cassady, C.

    2015-01-01

    Fleet-level selective maintenance refers to the process of identifying the subset of maintenance actions to perform on a fleet of repairable systems when the maintenance resources allocated to the fleet are insufficient for performing all desirable maintenance actions. The original fleet-level selective maintenance model is designed to maximize the probability that all missions in a future set are completed successfully. We extend this model in several ways. First, we consider a cost-based optimization model and show that a special case of this model maximizes the expected value of the number of successful missions in the future set. We also consider the situation in which one or more of the future missions may be canceled. These models and the original fleet-level selective maintenance optimization models are nonlinear. Therefore, we also consider an alternative model in which the objective function can be linearized. We show that the alternative model is a good approximation to the other models. - Highlights: • Investigate nonlinear fleet-level selective maintenance optimization models. • A cost based model is used to maximize the expected number of successful missions. • Another model is allowed to cancel missions if reliability is sufficiently low. • An alternative model has an objective function that can be linearized. • We show that the alternative model is a good approximation to the other models

  9. Modulation of Replicative Lifespan in Cryptococcus neoformans: Implications for Virulence

    Science.gov (United States)

    Bouklas, Tejas; Jain, Neena; Fries, Bettina C.

    2017-01-01

    The fungal pathogen, Cryptococcus neoformans, has been shown to undergo replicative aging. Old cells are characterized by advanced generational age and phenotypic changes that appear to mediate enhanced resistance to host and antifungal-based killing. As a consequence of this age-associated resilience, old cells accumulate during chronic infection. Based on these findings, we hypothesized that shifting the generational age of a pathogenic yeast population would alter its vulnerability to the host and affect its virulence. SIR2 is a well-conserved histone deacetylase, and a pivotal target for the development of anti-aging drugs. We tested its effect on C. neoformans’ replicative lifespan (RLS). First, a mutant C. neoformans strain (sir2Δ) was generated, and confirmed a predicted shortened RLS in sir2Δ cells consistent with its known role in aging. Next, RLS analysis showed that treatment of C. neoformans with Sir2p-agonists resulted in a significantly prolonged RLS, whereas treatment with a Sir2p-antagonist shortened RLS. RLS modulating effects were dependent on SIR2 and not observed in sir2Δ cells. Because SIR2 loss resulted in a slightly impaired fitness, effects of genetic RLS modulation on virulence could not be compared with wild type cells. Instead we chose to chemically modulate RLS, and investigated the effect of Sir2p modulating drugs on C. neoformans cells in a Galleria mellonella infection model. Consistent with our hypothesis that shifts in the generational age of the infecting yeast population alters its vulnerability to host cells, we observed decreased virulence of C. neoformans in the Galleria host when RLS was prolonged by treatment with Sir2p agonists. In contrast, treatment with a Sir2p antagonist, which shortens RLS enhanced virulence in Galleria. In addition, combination of Sir2p agonists with antifungal therapy enhanced the antifungal’s effect. Importantly, no difference in virulence was observed with drug treatment when sir2Δ cells

  10. Model-supported selection of distribution coefficients for performance assessment

    International Nuclear Information System (INIS)

    Ochs, M.; Lothenbach, B.; Shibata, Hirokazu; Yui, Mikazu

    1999-01-01

    A thermodynamic speciation/sorption model is used to illustrate typical problems encountered in the extrapolation of batch-type K d values to repository conditions. For different bentonite-groundwater systems, the composition of the corresponding equilibrium solutions and the surface speciation of the bentonite is calculated by treating simultaneously solution equilibria of soluble components of the bentonite as well as ion exchange and acid/base reactions at the bentonite surface. K d values for Cs, Ra, and Ni are calculated by implementing the appropriate ion exchange and surface complexation equilibria in the bentonite model. Based on this approach, hypothetical batch experiments are contrasted with expected conditions in compacted backfill. For each of these scenarios, the variation of K d values as a function of groundwater composition is illustrated for Cs, Ra, and Ni. The applicability of measured, batch-type K d values to repository conditions is discussed. (author)

  11. Glucose starvation boosts Entamoeba histolytica virulence.

    Directory of Open Access Journals (Sweden)

    Ayala Tovy

    2011-08-01

    Full Text Available The unicellular parasite, Entamoeba histolytica, is exposed to numerous adverse conditions, such as nutrient deprivation, during its life cycle stages in the human host. In the present study, we examined whether the parasite virulence could be influenced by glucose starvation (GS. The migratory behaviour of the parasite and its capability to kill mammalian cells and to lyse erythrocytes is strongly enhanced following GS. In order to gain insights into the mechanism underlying the GS boosting effects on virulence, we analyzed differences in protein expression levels in control and glucose-starved trophozoites, by quantitative proteomic analysis. We observed that upstream regulatory element 3-binding protein (URE3-BP, a transcription factor that modulates E.histolytica virulence, and the lysine-rich protein 1 (KRiP1 which is induced during liver abscess development, are upregulated by GS. We also analyzed E. histolytica membrane fractions and noticed that the Gal/GalNAc lectin light subunit LgL1 is up-regulated by GS. Surprisingly, amoebapore A (Ap-A and cysteine proteinase A5 (CP-A5, two important E. histolytica virulence factors, were strongly down-regulated by GS. While the boosting effect of GS on E. histolytica virulence was conserved in strains silenced for Ap-A and CP-A5, it was lost in LgL1 and in KRiP1 down-regulated strains. These data emphasize the unexpected role of GS in the modulation of E.histolytica virulence and the involvement of KRiP1 and Lgl1 in this phenomenon.

  12. Selected bibliography on the modeling and control of plant processes

    Science.gov (United States)

    Viswanathan, M. M.; Julich, P. M.

    1972-01-01

    A bibliography of information pertinent to the problem of simulating plants is presented. Detailed simulations of constituent pieces are necessary to justify simple models which may be used for analysis. Thus, this area of study is necessary to support the Earth Resources Program. The report sums up the present state of the problem of simulating vegetation. This area holds the hope of major benefits to mankind through understanding the ecology of a region and in improving agricultural yield.

  13. Fuzzy Multicriteria Model for Selection of Vibration Technology

    OpenAIRE

    María Carmen Carnero

    2016-01-01

    The benefits of applying the vibration analysis program are well known and have been so for decades. A large number of contributions have been produced discussing new diagnostic, signal treatment, technical parameter analysis, and prognosis techniques. However, to obtain the expected benefits from a vibration analysis program, it is necessary to choose the instrumentation which guarantees the best results. Despite its importance, in the literature, there are no models to assist in taking this...

  14. Functional genomic characterization of virulence factors from necrotizing fasciitis-causing strains of Aeromonas hydrophila.

    Science.gov (United States)

    Grim, Christopher J; Kozlova, Elena V; Ponnusamy, Duraisamy; Fitts, Eric C; Sha, Jian; Kirtley, Michelle L; van Lier, Christina J; Tiner, Bethany L; Erova, Tatiana E; Joseph, Sandeep J; Read, Timothy D; Shak, Joshua R; Joseph, Sam W; Singletary, Ed; Felland, Tracy; Baze, Wallace B; Horneman, Amy J; Chopra, Ashok K

    2014-07-01

    The genomes of 10 Aeromonas isolates identified and designated Aeromonas hydrophila WI, Riv3, and NF1 to NF4; A. dhakensis SSU; A. jandaei Riv2; and A. caviae NM22 and NM33 were sequenced and annotated. Isolates NF1 to NF4 were from a patient with necrotizing fasciitis (NF). Two environmental isolates (Riv2 and -3) were from the river water from which the NF patient acquired the infection. While isolates NF2 to NF4 were clonal, NF1 was genetically distinct. Outside the conserved core genomes of these 10 isolates, several unique genomic features were identified. The most virulent strains possessed one of the following four virulence factors or a combination of them: cytotoxic enterotoxin, exotoxin A, and type 3 and 6 secretion system effectors AexU and Hcp. In a septicemic-mouse model, SSU, NF1, and Riv2 were the most virulent, while NF2 was moderately virulent. These data correlated with high motility and biofilm formation by the former three isolates. Conversely, in a mouse model of intramuscular infection, NF2 was much more virulent than NF1. Isolates NF2, SSU, and Riv2 disseminated in high numbers from the muscular tissue to the visceral organs of mice, while NF1 reached the liver and spleen in relatively lower numbers on the basis of colony counting and tracking of bioluminescent strains in real time by in vivo imaging. Histopathologically, degeneration of myofibers with significant infiltration of polymorphonuclear cells due to the highly virulent strains was noted. Functional genomic analysis provided data that allowed us to correlate the highly infectious nature of Aeromonas pathotypes belonging to several different species with virulence signatures and their potential ability to cause NF. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  15. Organization And Financing Models Of Health Service In Selected Countries

    Directory of Open Access Journals (Sweden)

    Branimir Marković

    2009-07-01

    Full Text Available The introductory part of the work gives a short theoretical presentation regarding possible financing models of health services in the world. In the applicative part of the work we shall present the basic practical models of financing health services in the countries that are the leaders of classic methods of health services financing, e. g. the USA, Great Britain, Germany and Croatia. Working out the applicative part of the work we gave the greatest significance to analysis of some macroeconomic indicators in health services (tendency of total health consumption in relation to GDP, average consumption per insured person etc., to structure analysis of health insurance and just to the scheme of health service organization and financing. We presume that each model of health service financing contains certain limitations that can cause problem (weak organization, increase of expenses etc.. This is the reason why we, in the applicative part of the work, paid a special attention to analysis of financial difficulties in the health sector and pointed to the needs and possibilities of solving them through possible reform measures. The end part of the work aims to point out to advantages and disadvantages of individual financing sources through the comparison method (budgetary – taxes or social health insurance – contributions.

  16. A Model for Service Life Control of Selected Device Systems

    Directory of Open Access Journals (Sweden)

    Zieja Mariusz

    2014-04-01

    Full Text Available This paper presents a way of determining distribution of limit state exceedence time by a diagnostic parameter which determines accuracy of maintaining zero state. For calculations it was assumed that the diagnostic parameter is deviation from nominal value (zero state. Change of deviation value occurs as a result of destructive processes which occur during service. For estimation of deviation increasing rate in probabilistic sense, was used a difference equation from which, after transformation, Fokker-Planck differential equation was obtained [4, 11]. A particular solution of the equation is deviation increasing rate density function which was used for determining exceedance probability of limit state. The so-determined probability was then used to determine density function of limit state exceedance time, by increasing deviation. Having at disposal the density function of limit state exceedance time one determined service life of a system of maladjustment. In the end, a numerical example based on operational data of selected aircraft [weapon] sights was presented. The elaborated method can be also applied to determining residual life of shipboard devices whose technical state is determined on the basis of analysis of values of diagnostic parameters.

  17. Probabilistic wind power forecasting with online model selection and warped gaussian process

    International Nuclear Information System (INIS)

    Kou, Peng; Liang, Deliang; Gao, Feng; Gao, Lin

    2014-01-01

    Highlights: • A new online ensemble model for the probabilistic wind power forecasting. • Quantifying the non-Gaussian uncertainties in wind power. • Online model selection that tracks the time-varying characteristic of wind generation. • Dynamically altering the input features. • Recursive update of base models. - Abstract: Based on the online model selection and the warped Gaussian process (WGP), this paper presents an ensemble model for the probabilistic wind power forecasting. This model provides the non-Gaussian predictive distributions, which quantify the non-Gaussian uncertainties associated with wind power. In order to follow the time-varying characteristics of wind generation, multiple time dependent base forecasting models and an online model selection strategy are established, thus adaptively selecting the most probable base model for each prediction. WGP is employed as the base model, which handles the non-Gaussian uncertainties in wind power series. Furthermore, a regime switch strategy is designed to modify the input feature set dynamically, thereby enhancing the adaptiveness of the model. In an online learning framework, the base models should also be time adaptive. To achieve this, a recursive algorithm is introduced, thus permitting the online updating of WGP base models. The proposed model has been tested on the actual data collected from both single and aggregated wind farms

  18. Models for MOX fuel behaviour. A selective review

    International Nuclear Information System (INIS)

    Massih, Ali R.

    2006-01-01

    This report reviews the basic physical properties of light water reactor mixed-oxide (MOX) fuel comprising nuclear characteristics, thermal properties such as melting temperature, thermal conductivity, thermal expansion, and heat capacity, and compares these with properties of conventional UO 2 fuel. These properties are generally well understood for MOX fuel and are well described by appropriate models developed for engineering analysis. Moreover, certain modelling approaches of MOX fuel in-reactor behaviour, regarding densification, swelling, fission product gas release, helium release, fuel creep and grain growth, are evaluated and compared with the models for UO 2 . In MOX fuel the presence of plutonium rich agglomerates adds to the complexity of fuel behaviour on the micro scale. In addition, we survey the recent fuel performance experience and post irradiation examinations on several types of MOX fuel types. We discuss the data from these examinations, regarding densification, swelling, fission product gas release and the evolution of the microstructure during irradiation. The results of our review indicate that in general MOX fuel has a higher fission gas release and helium release than UO 2 fuel. Part of this increase is due to the higher operating temperatures of MOX fuel relative to UO 2 fuel due to the lower thermal conductivity of MOX material. But this effect by itself seems to be insufficient to make for the difference in the observed fission gas release of UO 2 vs. MOX fuel. Furthermore, the irradiation induced creep rate of MOX fuel is higher than that of UO 2 . This effect can reduce the pellet-clad interaction intensity in fuel rods. Finally, we suggest that certain physical based approaches discussed in the report are implemented in the fuel performance code to account for the behaviour of MOX fuel during irradiation

  19. Models for MOX fuel behaviour. A selective review

    Energy Technology Data Exchange (ETDEWEB)

    Massih, Ali R. [Quantum Technologies AB, Uppsala Science Park (Sweden)

    2006-12-15

    This report reviews the basic physical properties of light water reactor mixed-oxide (MOX) fuel comprising nuclear characteristics, thermal properties such as melting temperature, thermal conductivity, thermal expansion, and heat capacity, and compares these with properties of conventional UO{sub 2} fuel. These properties are generally well understood for MOX fuel and are well described by appropriate models developed for engineering analysis. Moreover, certain modelling approaches of MOX fuel in-reactor behaviour, regarding densification, swelling, fission product gas release, helium release, fuel creep and grain growth, are evaluated and compared with the models for UO{sub 2}. In MOX fuel the presence of plutonium rich agglomerates adds to the complexity of fuel behaviour on the micro scale. In addition, we survey the recent fuel performance experience and post irradiation examinations on several types of MOX fuel types. We discuss the data from these examinations, regarding densification, swelling, fission product gas release and the evolution of the microstructure during irradiation. The results of our review indicate that in general MOX fuel has a higher fission gas release and helium release than UO{sub 2} fuel. Part of this increase is due to the higher operating temperatures of MOX fuel relative to UO{sub 2} fuel due to the lower thermal conductivity of MOX material. But this effect by itself seems to be insufficient to make for the difference in the observed fission gas release of UO{sub 2} vs. MOX fuel. Furthermore, the irradiation induced creep rate of MOX fuel is higher than that of UO{sub 2}. This effect can reduce the pellet-clad interaction intensity in fuel rods. Finally, we suggest that certain physical based approaches discussed in the report are implemented in the fuel performance code to account for the behaviour of MOX fuel during irradiation.

  20. Causal Inference and Model Selection in Complex Settings

    Science.gov (United States)

    Zhao, Shandong

    Propensity score methods have become a part of the standard toolkit for applied researchers who wish to ascertain causal effects from observational data. While they were originally developed for binary treatments, several researchers have proposed generalizations of the propensity score methodology for non-binary treatment regimes. In this article, we firstly review three main methods that generalize propensity scores in this direction, namely, inverse propensity weighting (IPW), the propensity function (P-FUNCTION), and the generalized propensity score (GPS), along with recent extensions of the GPS that aim to improve its robustness. We compare the assumptions, theoretical properties, and empirical performance of these methods. We propose three new methods that provide robust causal estimation based on the P-FUNCTION and GPS. While our proposed P-FUNCTION-based estimator preforms well, we generally advise caution in that all available methods can be biased by model misspecification and extrapolation. In a related line of research, we consider adjustment for posttreatment covariates in causal inference. Even in a randomized experiment, observations might have different compliance performance under treatment and control assignment. This posttreatment covariate cannot be adjusted using standard statistical methods. We review the principal stratification framework which allows for modeling this effect as part of its Bayesian hierarchical models. We generalize the current model to add the possibility of adjusting for pretreatment covariates. We also propose a new estimator of the average treatment effect over the entire population. In a third line of research, we discuss the spectral line detection problem in high energy astrophysics. We carefully review how this problem can be statistically formulated as a precise hypothesis test with point null hypothesis, why a usual likelihood ratio test does not apply for problem of this nature, and a doable fix to correctly

  1. On extended liability in a model of adverse selection

    OpenAIRE

    Dieter Balkenborg

    2004-01-01

    We consider a model where a judgment-proof firm needs finance to realize a project. This project might cause an environmental hazard with a probability that is the private knowledge of the firm. Thus there is asymmetric information with respect to the environmental riskiness of the project. We consider the implications of a simple joint and strict liability rule on the lender and the firm where, in case of a damage, the lender is responsible for that part of the liability which the judgment-p...

  2. Antibiotic modulation of capsular exopolysaccharide and virulence in Acinetobacter baumannii.

    Directory of Open Access Journals (Sweden)

    Edward Geisinger

    2015-02-01

    Full Text Available Acinetobacter baumannii is an opportunistic pathogen of increasing importance due to its propensity for intractable multidrug-resistant infections in hospitals. All clinical isolates examined contain a conserved gene cluster, the K locus, which determines the production of complex polysaccharides, including an exopolysaccharide capsule known to protect against killing by host serum and to increase virulence in animal models of infection. Whether the polysaccharides determined by the K locus contribute to intrinsic defenses against antibiotics is unknown. We demonstrate here that mutants deficient in the exopolysaccharide capsule have lowered intrinsic resistance to peptide antibiotics, while a mutation affecting sugar precursors involved in both capsule and lipopolysaccharide synthesis sensitizes the bacterium to multiple antibiotic classes. We observed that, when grown in the presence of certain antibiotics below their MIC, including the translation inhibitors chloramphenicol and erythromycin, A. baumannii increases production of the K locus exopolysaccharide. Hyperproduction of capsular exopolysaccharide is reversible and non-mutational, and occurs concomitantly with increased resistance to the inducing antibiotic that is independent of the presence of the K locus. Strikingly, antibiotic-enhanced capsular exopolysaccharide production confers increased resistance to killing by host complement and increases virulence in a mouse model of systemic infection. Finally, we show that augmented capsule production upon antibiotic exposure is facilitated by transcriptional increases in K locus gene expression that are dependent on a two-component regulatory system, bfmRS. These studies reveal that the synthesis of capsule, a major pathogenicity determinant, is regulated in response to antibiotic stress. Our data are consistent with a model in which gene expression changes triggered by ineffectual antibiotic treatment cause A. baumannii to transition

  3. Efficient nonparametric and asymptotic Bayesian model selection methods for attributed graph clustering

    KAUST Repository

    Xu, Zhiqiang

    2017-02-16

    Attributed graph clustering, also known as community detection on attributed graphs, attracts much interests recently due to the ubiquity of attributed graphs in real life. Many existing algorithms have been proposed for this problem, which are either distance based or model based. However, model selection in attributed graph clustering has not been well addressed, that is, most existing algorithms assume the cluster number to be known a priori. In this paper, we propose two efficient approaches for attributed graph clustering with automatic model selection. The first approach is a popular Bayesian nonparametric method, while the second approach is an asymptotic method based on a recently proposed model selection criterion, factorized information criterion. Experimental results on both synthetic and real datasets demonstrate that our approaches for attributed graph clustering with automatic model selection significantly outperform the state-of-the-art algorithm.

  4. Efficient nonparametric and asymptotic Bayesian model selection methods for attributed graph clustering

    KAUST Repository

    Xu, Zhiqiang; Cheng, James; Xiao, Xiaokui; Fujimaki, Ryohei; Muraoka, Yusuke

    2017-01-01

    Attributed graph clustering, also known as community detection on attributed graphs, attracts much interests recently due to the ubiquity of attributed graphs in real life. Many existing algorithms have been proposed for this problem, which are either distance based or model based. However, model selection in attributed graph clustering has not been well addressed, that is, most existing algorithms assume the cluster number to be known a priori. In this paper, we propose two efficient approaches for attributed graph clustering with automatic model selection. The first approach is a popular Bayesian nonparametric method, while the second approach is an asymptotic method based on a recently proposed model selection criterion, factorized information criterion. Experimental results on both synthetic and real datasets demonstrate that our approaches for attributed graph clustering with automatic model selection significantly outperform the state-of-the-art algorithm.

  5. Incidence and virulence characteristics of Aeromonas spp. in fish

    Directory of Open Access Journals (Sweden)

    Ashraf M. Abd-El-Malek

    2017-01-01

    Full Text Available Aim: This study was conducted to evaluate the presence of Aeromonas spp. in raw and ready-to-eat (RTE fish commonly consumed in Assiut city, Egypt, and to determine virulence factors due to they play a key role in their pathogenicity. Materials and Methods: A total of 125 samples of raw and RTE fish samples were taken from different fish markets and fish restaurants in Assiut Governorate and screened for the presence of Aeromonas spp. by enrichment on tryptic soy broth then incubated at 30°C for 24 h. Plating unto the sterile Petri dishes containing Aeromonas agar base to which Aeromonas selective supplement was added. The plates were incubated at 37°C for 24 h. Presumptive Aeromonas colonies were biochemically confirmed and analyzed for pathogenicity by hemolysin production, protease, and lipase detection. Results: The results indicated that raw fish were contaminated with Aeromonas spp. (40% in wild and 36% in cultured Nile tilapia. Regarding RTE, Aeromonas spp. could be isolated with the percentage of 16%, 28% and 20% in fried Bolti, grilled Bolti and fried Bayad, respectively. Out of 35 isolates obtained, 22 were categorized as Aeromonas hydrophila, 12 were classified as Aeromonas sobria and Aeromonas caviae were found in only one isolate. The virulence factors of Aeromonas spp. were detected and the results showed that all isolates produced of hemolysin (91.4%, protease (77.1%, and lipase enzyme (17.1%. Conclusion: This study indicates that the presence of A. hydrophila with virulence potential in fresh and RTE fish may be a major threat to public health.

  6. SU-F-R-10: Selecting the Optimal Solution for Multi-Objective Radiomics Model

    International Nuclear Information System (INIS)

    Zhou, Z; Folkert, M; Wang, J

    2016-01-01

    Purpose: To develop an evidential reasoning approach for selecting the optimal solution from a Pareto solution set obtained by a multi-objective radiomics model for predicting distant failure in lung SBRT. Methods: In the multi-objective radiomics model, both sensitivity and specificity are considered as the objective functions simultaneously. A Pareto solution set with many feasible solutions will be resulted from the multi-objective optimization. In this work, an optimal solution Selection methodology for Multi-Objective radiomics Learning model using the Evidential Reasoning approach (SMOLER) was proposed to select the optimal solution from the Pareto solution set. The proposed SMOLER method used the evidential reasoning approach to calculate the utility of each solution based on pre-set optimal solution selection rules. The solution with the highest utility was chosen as the optimal solution. In SMOLER, an optimal learning model coupled with clonal selection algorithm was used to optimize model parameters. In this study, PET, CT image features and clinical parameters were utilized for predicting distant failure in lung SBRT. Results: Total 126 solution sets were generated by adjusting predictive model parameters. Each Pareto set contains 100 feasible solutions. The solution selected by SMOLER within each Pareto set was compared to the manually selected optimal solution. Five-cross-validation was used to evaluate the optimal solution selection accuracy of SMOLER. The selection accuracies for five folds were 80.00%, 69.23%, 84.00%, 84.00%, 80.00%, respectively. Conclusion: An optimal solution selection methodology for multi-objective radiomics learning model using the evidential reasoning approach (SMOLER) was proposed. Experimental results show that the optimal solution can be found in approximately 80% cases.

  7. SU-F-R-10: Selecting the Optimal Solution for Multi-Objective Radiomics Model

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Z; Folkert, M; Wang, J [UT Southwestern Medical Center, Dallas, TX (United States)

    2016-06-15

    Purpose: To develop an evidential reasoning approach for selecting the optimal solution from a Pareto solution set obtained by a multi-objective radiomics model for predicting distant failure in lung SBRT. Methods: In the multi-objective radiomics model, both sensitivity and specificity are considered as the objective functions simultaneously. A Pareto solution set with many feasible solutions will be resulted from the multi-objective optimization. In this work, an optimal solution Selection methodology for Multi-Objective radiomics Learning model using the Evidential Reasoning approach (SMOLER) was proposed to select the optimal solution from the Pareto solution set. The proposed SMOLER method used the evidential reasoning approach to calculate the utility of each solution based on pre-set optimal solution selection rules. The solution with the highest utility was chosen as the optimal solution. In SMOLER, an optimal learning model coupled with clonal selection algorithm was used to optimize model parameters. In this study, PET, CT image features and clinical parameters were utilized for predicting distant failure in lung SBRT. Results: Total 126 solution sets were generated by adjusting predictive model parameters. Each Pareto set contains 100 feasible solutions. The solution selected by SMOLER within each Pareto set was compared to the manually selected optimal solution. Five-cross-validation was used to evaluate the optimal solution selection accuracy of SMOLER. The selection accuracies for five folds were 80.00%, 69.23%, 84.00%, 84.00%, 80.00%, respectively. Conclusion: An optimal solution selection methodology for multi-objective radiomics learning model using the evidential reasoning approach (SMOLER) was proposed. Experimental results show that the optimal solution can be found in approximately 80% cases.

  8. Genomic comparison of virulent and non-virulent Streptococcus agalactiae in fish.

    Science.gov (United States)

    Delannoy, C M J; Zadoks, R N; Crumlish, M; Rodgers, D; Lainson, F A; Ferguson, H W; Turnbull, J; Fontaine, M C

    2016-01-01

    Streptococcus agalactiae infections in fish are predominantly caused by beta-haemolytic strains of clonal complex (CC) 7, notably its namesake sequence type (ST) 7, or by non-haemolytic strains of CC552, including the globally distributed ST260. In contrast, CC23, including its namesake ST23, has been associated with a wide homeothermic and poikilothermic host range, but never with fish. The aim of this study was to determine whether ST23 is virulent in fish and to identify genomic markers of fish adaptation of S. agalactiae. Intraperitoneal challenge of Nile tilapia, Oreochromis niloticus (Linnaeus), showed that ST260 is lethal at doses down to 10(2) cfu per fish, whereas ST23 does not cause disease at 10(7) cfu per fish. Comparison of the genome sequence of ST260 and ST23 with those of strains derived from fish, cattle and humans revealed the presence of genomic elements that are unique to subpopulations of S. agalactiae that have the ability to infect fish (CC7 and CC552). These loci occurred in clusters exhibiting typical signatures of mobile genetic elements. PCR-based screening of a collection of isolates from multiple host species confirmed the association of selected genes with fish-derived strains. Several fish-associated genes encode proteins that potentially provide fitness in the aquatic environment. © 2014 John Wiley & Sons Ltd.

  9. Selective Cooperation in Early Childhood - How to Choose Models and Partners.

    Directory of Open Access Journals (Sweden)

    Jonas Hermes

    Full Text Available Cooperation is essential for human society, and children engage in cooperation from early on. It is unclear, however, how children select their partners for cooperation. We know that children choose selectively whom to learn from (e.g. preferring reliable over unreliable models on a rational basis. The present study investigated whether children (and adults also choose their cooperative partners selectively and what model characteristics they regard as important for cooperative partners and for informants about novel words. Three- and four-year-old children (N = 64 and adults (N = 14 saw contrasting pairs of models differing either in physical strength or in accuracy (in labeling known objects. Participants then performed different tasks (cooperative problem solving and word learning requiring the choice of a partner or informant. Both children and adults chose their cooperative partners selectively. Moreover they showed the same pattern of selective model choice, rega