bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro
Activity of Ceftaroline against a Broad Spectrum of Recent Clinical Anaerobic Isolates
Authors: Snydman David R. , Jacobus Nilda V. , McDermott Laura A.
Published: November 2010

The
in vitro
activity of ceftaroline was compared with those of ceftriaxone, clindamycin, imipenem, metronidazole, moxifloxacin, tigecycline, and vancomycin against 514 clinical anaerobic isolates using Clinical and Laboratory Standards Institute (CLSI) standard methodology. Ceftaroline demonstrated good to excellent activity against Gram-positive anaerobic pathogens and limited activity against Gram-negative pathogens, particularly
Bacteroides fragilis
group isolates.
Genetic Predisposition Favors the Acquisition of Stable Artemisinin Resistance in Malaria Parasites
Authors: Beez Dorothee , Sanchez Cecilia P. , Stein Wilfred D. , Lanzer Michael
Published: November 2010

The emergence of artemisinin-resistantPlasmodium falciparummalaria jeopardizes efforts to control this infectious disease. To identify factors contributing to reduced artemisinin susceptibility, we have employed a classical genetic approach by analyzing artemisinin responses in the F1 progeny of a genetic cross. Our data show that reduced artemisinin susceptibility is a multifactorial trait, withpfmdr1and two additional loci (on chromosomes 12 and 13) contributing to it. We further show that the different artemisinin susceptibilities of the progeny strains affect their responses to selection with increasing concentrations of artemisinin. Stable, high-levelin vitroartemisinin resistance rapidly arose in those parasites that were the least artemisinin susceptible among the F1 progeny, whereas progeny that were highly artemisinin susceptible did not acquire stable artemisinin resistance. These data suggest that genetic predisposition favors the acquisition of high-level artemisinin resistance.In vitro-induced artemisinin resistance did not result in cross-resistance to artesunate or artemether, suggesting that resistance to one derivative does not necessarily render the entire drug class ineffective.
Novel Insights into the Mode of Inhibition of Class A SHV-1 β-Lactamases Revealed by Boronic Acid Transition State Inhibitors
Authors: Ke Wei , Sampson Jared M. , Ori Claudia , Prati Fabio , Drawz Sarah M. , Bethel Christopher R. , Bonomo Robert A. , van den Akker Focco
Published: November 2010

Boronic acid transition state inhibitors (BATSIs) are potent class A and C β-lactamase inactivators and are of particular interest due to their reversible nature mimicking the transition state. Here, we present structural and kinetic data describing the inhibition of the SHV-1 β-lactamase, a clinically important enzyme found in
Klebsiella pneumoniae
, by BATSI compounds possessing the R1 side chains of ceftazidime and cefoperazone and designed variants of the latter, compounds 1 and 2. The ceftazidime and cefoperazone BATSI compounds inhibit the SHV-1 β-lactamase with micromolar affinity that is considerably weaker than their inhibition of other β-lactamases. The solved crystal structures of these two BATSIs in complex with SHV-1 reveal a possible reason for SHV-1's relative resistance to inhibition, as the BATSIs adopt a deacylation transition state conformation compared to the usual acylation transition state conformation when complexed to other β-lactamases. Active-site comparison suggests that these conformational differences might be attributed to a subtle shift of residue A237 in SHV-1. The ceftazidime BATSI structure revealed that the carboxyl-dimethyl moiety is positioned in SHV-1's carboxyl binding pocket. In contrast, the cefoperazone BATSI has its R1 group pointing away from the active site such that its phenol moiety moves residue Y105 from the active site via end-on stacking interactions. To work toward improving the affinity of the cefoperazone BATSI, we synthesized two variants in which either one or two extra carbons were added to the phenol linker. Both variants yielded improved affinity against SHV-1, possibly as a consequence of releasing the strain of its interaction with the unusual Y105 conformation.
Identification of Diverse OXA-40 Group Carbapenemases, Including a Novel Variant, OXA-160, fromAcinetobacter baumanniiin Pennsylvania
Authors: Tian Guo-Bao , Adams-Haduch Jennifer M. , Bogdanovich Tatiana , Pasculle Anthony W. , Quinn John P. , Wang Hong-Ning , Doi Yohei
Published: November 2010

ThreeAcinetobacter baumanniiisolates that possess OXA-40 group carbapenemase genes were identified. They belonged to novel sequence types (ST122, ST123, and ST124) and harboredblaOXA-160,blaOXA-72, andblaOXA-40, respectively. OXA-160 is a novel variant of OXA-40 with a P227S substitution. An isogenicEscherichia coliclone producing OXA-160 was more susceptible to carbapenems than a clone producing OXA-40. The genetic environment ofblaOXA-160andblaOXA-40beyond the putative XerC/XerD recombination sites was distinct from the scaffold reported previously.
Cytomegalovirus UL97 Mutations Affecting Cyclopropavir and Ganciclovir Susceptibility
Authors: Chou Sunwen , Bowlin Terry L.
Published: November 2010

Among the 7 most common UL97 mutations encountered in ganciclovir-resistant clinical cytomegalovirus isolates, the associated cyclopropavir cross-resistance varies from insignificant (L595S) to substantial (M460I and H520Q) as determined by recombinant phenotyping. Mutations M460I and H520Q were preferentially selected
in vitro
under cyclopropavir and conferred 12- to 20-fold increases in 50% effective concentration (EC
50
) values, while M460V, C592G, A594V, and C603W conferred 3- to 5-fold increases. Uncommon mutations M460T and C603R increased cyclopropavir EC
50
s by 8- to 10-fold.
Coevolution of TH1, TH2, and TH17 Responses during Repeated Pulmonary Exposure toAspergillus fumigatusConidia
Authors: Murdock Benjamin J. , Shreiner Andrew B. , McDonald Roderick A. , Osterholzer John J. , White Eric S. , Toews Galen B. , Huffnagle Gary B.
Published: November 2010

Aspergillus fumigatus, a ubiquitous airborne fungus, can cause invasive infection in immunocompromised individuals but also triggers allergic bronchopulmonary aspergillosis in a subset of otherwise healthy individuals repeatedly exposed to the organism. This study addresses a critical gap in our understanding of the immunoregulation in response to repeated exposure toA. fumigatusconidia. C57BL/6 mice were challenged intranasally withA. fumigatusconidia weekly, and leukocyte composition, activation, and cytokine production were examined after two, four, and eight challenges. Approximately 99% ofA. fumigatusconidia were cleared within 24 h after inoculation, and repeated exposure toA. fumigatusconidia did not result in hyphal growth or accumulation of conidia with time. After 2 challenges, there was an early influx of neutrophils and regulatory T (Treg) cells into the lungs but minimal inflammation. Repeated exposure promoted sustained expansion of the draining lymph nodes, while the influx of eosinophils and other myeloid cells into the lungs peaked after four exposures and then decreased despite continuedA. fumigatuschallenges. Goblet cell metaplasia and low-level fibrosis were evident during the response. Repeated exposure toA. fumigatusconidia induced T cell activation in the lungs and the codevelopment by four exposures of TH1, TH2, and TH17 responses in the lungs, which were maintained through eight exposures. Changes in CD4 T cell polarization or Tregnumbers did not account for the reduction in myeloid cell numbers later in the response, suggesting a non-T-cell regulatory pathway involved in dampening inflammation during repeated exposure toA. fumigatusconidia.
Genome-Wide Identification ofStreptococcus pneumoniaeGenes Essential for Bacterial Replication during Experimental Meningitis
Authors: Molzen T. E. , Burghout P. , Bootsma H. J. , Brandt C. T. , van der Gaast-de Jongh Christa E. , Eleveld M. J. , Verbeek M. M. , Frimodt-Møller N. , Østergaard C. , Hermans P. W. M.
Published: November 2010

Meningitis is the most serious of invasive infections caused by the Gram-positive bacteriumStreptococcus pneumoniae. Vaccines protect only against a limited number of serotypes, and evolving bacterial resistance to antimicrobials impedes treatment. Further insight into the molecular pathogenesis of invasive pneumococcal disease is required in order to enable the development of new or adjunctive treatments and/or pneumococcal vaccines that are efficient across serotypes. We applied genomic array footprinting (GAF) in the search forS. pneumoniaegenes that are essential during experimental meningitis. A total of 6,000 independent TIGR4marinerT7transposon mutants distributed over four libraries were injected intracisternally into rabbits, and cerebrospinal fluid (CSF) was collected after 3, 9, and 15 h. Microarray analysis of mutant-specific probes from CSF samples and inocula identified 82 and 11 genes mutants of which had become attenuated or enriched, respectively, during infection. The results point to essential roles for capsular polysaccharides, nutrient uptake, and amino acid biosynthesis in bacterial replication during experimental meningitis. The GAF phenotype of a subset of identified targets was followed up by detailed studies of directed mutants in competitive and noncompetitive infection models of experimental rat meningitis. It appeared that adenylosuccinate synthetase, flavodoxin, and LivJ, the substrate binding protein of a branched-chain amino acid ABC transporter, are relevant as targets for future therapy and prevention of pneumococcal meningitis, since their mutants were attenuated in both models of infection as well as in competitive growth in human cerebrospinal fluidin vitro.
Older Adults Have a Low Capacity To Opsonize Pneumococci Due to Low IgM Antibody Response to Pneumococcal Vaccinations
Authors: Park Saeyoung , Nahm Moon H.
Published: November 2010

Since the 23-valent pneumococcal polysaccharide vaccine (PPV23) is less effective for older adults than for young adults, it is important to investigate the immunologic basis for the reduced efficacy of PPV23 among older adults. We determined the effectiveness of PPV23 among young (n= 55) and older (n= 44) adults by measuring the serum IgG, IgM, and IgA concentrations and opsonic capacities against serotypes 14, 18C, and 23F. While young and older adults showed no difference in levels of IgG antibodies against pneumococcal polysaccharide (PPS), older adults had lower IgA and IgM antibody levels than young adults for all three serotypes. In both age groups, anti-PPS IgA or IgM antibody levels were much lower than anti-PPS IgG antibody levels. Young adults showed higher opsonic capacities than older adults for serotypes 14 and 23F. In order to determine the effects of anti-PPS IgA or IgM antibodies on the functional difference between young and older adults, anti-PPS IgA or IgM antibodies were removed from immune sera by affinity chromatography. The difference in opsonic capacity between young and older adults disappeared for serotypes 14 and 23F (but not for serotype 18C) when IgM antibody was removed. However, there was no significant difference between the two age groups when IgA antibody was removed. In conclusion, even though anti-PPS IgG antibody levels are high compared with anti-PPS IgM antibody levels, the low levels of anti-PPS IgM antibody alone can explain the functional difference observed between young and older adults immunized with PPV23 with regard to some pneumococcal serotypes.
Porphyromonas gingivalis
Virulence in a
Drosophila melanogaster
Model
Authors: Igboin Christina O. , Moeschberger Melvin L. , Griffen Ann L. , Leys Eugene J.
Published: November 2010

Porphyromonas gingivalis
has been implicated in the etiology of adult periodontitis. In this study, we examined the viability of
Drosophila melanogaster
as a new model for examining
P. gingivalis
-host interactions.
P. gingivalis
(W83) infection of
Drosophila
resulted in a systemic infection that killed in a dose-dependent manner. Differences in the virulence of several clinically prevalent
P. gingivalis
strains were observed in the
Drosophila
killing model, and the results correlated well with studies in mammalian infection models and human epidemiologic studies.
P. gingivalis
pathobiology in
Drosophila
did not result from uncontrolled growth of the bacterium in the
Drosophila
hemolymph (blood) or overt damage to
Drosophila
tissues.
P. gingivalis
killing of
Drosophila
was multifactorial, involving several bacterial factors that are also involved in virulence in mammals. The results from this study suggest that many aspects of
P. gingivalis
pathogenesis in mammals are conserved in
Drosophila
, and thus the
Drosophila
killing model should be useful for characterizing
P. gingivalis
-host interactions and, potentially, polymicrobe-host interactions.
Porphyromonas gingivalis-Host Interactions in aDrosophila melanogasterModel
Authors: Igboin Christina O. , Tordoff Kevin P. , Moeschberger Melvin L. , Griffen Ann L. , Leys Eugene J.
Published: November 2010

Porphyromonas gingivalisis a Gram-negative obligate anaerobe that has been implicated in the etiology of adult periodontitis. We recently introduced aDrosophila melanogasterkilling model for examination ofP. gingivalis-host interactions. In the current study, theDrosophilakilling model was used to characterize the host response toP. gingivalisinfection by identifying host components that play a role during infection.Drosophilaimmune response gene mutants were screened for altered susceptibility to killing byP. gingivalis. The Imd signaling pathway was shown to be important for the survival ofDrosophilainfected by nonencapsulatedP. gingivalisstrains but was dispensable for the survival ofDrosophilainfected by encapsulatedP. gingivalisstrains. TheP. gingivaliscapsule was shown to mediate resistance to killing byDrosophilaantimicrobial peptides (Imd pathway-regulated cecropinA and drosocin) and human beta-defensin 3.Drosophilathiol-ester protein II (Tep II) and Tep IV and the tumor necrosis factor (TNF) homolog Eiger were also involved in the immune response againstP. gingivalisinfection, while the scavenger receptors Eater and Croquemort played no roles in the response toP. gingivalisinfection. This study demonstrates that theDrosophilakilling model is a useful high-throughput model for characterizing the host response toP. gingivalisinfection and uncovering novel interactions between the bacterium and the host.
Burkholderia pseudomalleiProteins Presented by Monocyte-Derived Dendritic Cells Stimulate Human Memory T CellsIn Vitro
Authors: Tippayawat Patcharaporn , Pinsiri Maneerat , Rinchai Darawan , Riyapa Donporn , Romphruk Amornrat , Gan Yunn-Hwen , Houghton Raymond L. , Felgner Philip L. , Titball Richard W. , Stevens Mark P. , Galyov Edouard E. , Bancroft Gregory J. , Lertmemongkolchai Ganjana
Published: November 2010

Melioidosis is a severe infectious disease caused by the saprophytic facultative intracellular pathogenBurkholderia pseudomallei. The disease is endemic in Southeast Asia and Northern Australia, and no effective vaccine exists. To describe human cell-mediated immune responses toB. pseudomalleiand to identify candidate antigens for vaccine development, the ability of antigen-pulsed monocyte-derived dendritic cells (moDCs) to trigger autologous T-cell responses toB. pseudomalleiand its products was tested. moDCs were prepared from healthy individuals exposed or not exposed toB. pseudomallei, based on serological evidence. These were pulsed with heat-killedB. pseudomalleior purified antigens, including ABC transporters (LolC, OppA, and PotF), Bsa type III secreted proteins (BipD and BopE), tandem repeat sequence-containing proteins (Rp1 and Rp2), flagellin, and heat shock proteins (Hsp60 and Hsp70), prior to being mixed with autologous T-cell populations. After pulsing of cells with either heat-killedB. pseudomallei, LolC, or Rp2, coculturing the antigen-pulsed moDCs with T cells elicited gamma interferon production from CD4+T cells from seropositive donors at levels greater than those for seronegative donors. These antigens also induced granzyme B (cytotoxic) responses from CD8+T cells. Activation of antigen-specific CD4+T cells required direct contact with moDCs and was therefore not dependent on soluble mediators. Rp peptide epitopes recognized by T cells in healthy individuals were identified. Our study provides valuable novel data on the induction of human cell-mediated immune responses toB. pseudomalleiand its protein antigens that may be exploited in the rational development of vaccines to combat melioidosis.
ThefbpABCOperon Is Required for Ton-Independent Utilization of Xenosiderophores byNeisseria gonorrhoeaeStrain FA19
Authors: Strange Heather R. , Zola Tracey A. , Cornelissen Cynthia Nau
Published: November 2010

Neisseria gonorrhoeaeproduces no known siderophores but can employ host-derived, iron-binding proteins, including transferrin and lactoferrin, as iron sources. Given the propensity of this pathogen to hijack rather than synthesize iron-sequestering molecules, we hypothesized that the ability to use siderophores produced by other bacteria, or xenosiderophores, may also play a role in the survival of the gonococcus. Among a panel of diverse siderophores, only the catecholate xenosiderophores enterobactin and salmochelin promoted growth of gonococcal strain FA19. Surprisingly, the internalization pathway was independent of TonB or any of the TonB-dependent transporters. Xenosiderophore-mediated growth was similarly independent of the pilin-extruding secretin formed by PilQ and of the hydrophobic-agent efflux system composed of MtrCDE. ThefbpABCoperon encodes a periplasmic-binding-protein-dependent ABC transport system that enables the gonococcus to transport iron into the cell subsequent to outer membrane translocation. We hypothesized that the FbpABC proteins, required for ferric iron transport from transferrin and lactoferrin, might also contribute to the utilization of xenosiderophores as iron sources. We created mutants that conditionally expressed FbpABC from an IPTG-inducible promoter. We determined that expression of FbpABC was required for growth of gonococcal strain FA19 in the presence of enterobactin and salmochelin. The monomeric component of enterobactin, dihydroxybenzoylserine (DHBS), and the S2 form of salmochelin specifically promoted FbpABC-dependent growth of FA19. This study demonstrated that the gonococcal FbpABC transport system is required for utilization of some xenosiderophores as iron sources and that growth promotion by these ferric siderophores can occur in the absence of TonB or individual TonB-dependent transporters.
Persistence of
Plasmodium falciparum
Parasites in Infected Pregnant Mozambican Women after Delivery
Authors: Serra-Casas Elisa , Menéndez Clara , Dobaño Carlota , Bardají Azucena , Quintó Llorençc , Ordi Jaume , Sigauque Betuel , Cisteró Pau , Mandomando Inacio , Alonso Pedro L. , Mayor Alfredo
Published: November 2010

Pregnant women are susceptible to
Plasmodium falciparum
parasites that sequester in the placenta. The massive accumulation of infected erythrocytes in the placenta has been suggested to trigger the deleterious effects of malaria in pregnant women and their offspring. The risk of malaria is also high during the postpartum period, although mechanisms underlying this susceptibility are not known. Here, we aimed to identify host factors contributing to the risk of postpartum infections and to determine the origin of postpartum parasites by comparing their genotypes with those present at the time of delivery. To address this, blood samples were collected at delivery (
n
= 402) and postpartum (
n
= 354) from Mozambican women enrolled in a trial of intermittent preventive treatment in pregnancy (IPTp).
P. falciparum
was detected by real-time quantitative PCR (qPCR), and the parasite merozoite surface protein 1 (
msp-1
) and
msp-2
genes were genotyped. Fifty-seven out of 354 (16%) women were infected postpartum as assessed by qPCR, whereas prevalence by optical microscopy was only 4%. Risk of postpartum infection was lower in older women (odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.15 to 0.81) and higher in women with a placental infection at delivery (OR = 4.20, 95% CI = 2.19 to 8.08). Among 24 women with matched infections, 12 (50%) were infected postpartum with at least one parasite strain that was also present in their placentas. These results suggest that parasites infecting pregnant women persist after delivery and increase the risk of malaria during the postpartum period. Interventions that reduce malaria during pregnancy may translate into a lower risk of postpartum infection.
Quantitative PCR-Based Competitive Index for High-Throughput Screening of
Salmonella
Virulence Factors
Authors: Yoon Hyunjin , Gros Phillipe , Heffron Fred
Published: November 2010

Salmonella enterica
serovar Typhimurium is an intracellular pathogen and a main cause of food-borne illness. In this study, a quantitative PCR (qPCR)-based competitive index (CI) method was developed to simultaneously compare the growth of multiple
Salmonella
strains. This method was applied to a mixture of 17
Salmonella
mutants lacking regulator genes, and their survival ratios were compared based on expression of natural resistance-associated macrophage protein 1 (Nramp1). Nramp1, as a major host innate immune component, controls the intracellular replication of pathogens. Deletion strains containing unique DNA barcodes in place of regulator genes were mixed with the parental control, and the bacteria were inoculated into congenic mice differing only at Nramp1. Most of the deletion strains were outcompeted by wild-type bacteria in either mouse strain, and the lack of Nramp1 didn't increase the tested strain/parent control replication ratios. When the same collection of mutants was tested in congenic mouse-derived primary macrophages, a major Nramp1-expressing cell type, six strains (Δ
himD
, Δ
phoP
/
phoQ
, Δ
rpoE
, Δ
rpoS
, Δ
ompR
/
envZ
, and Δ
hfq
strains) grew better in Nramp1
−/−
than in Nramp1
+/+
macrophages, suggesting that these six regulators may play roles in overcoming Nramp1-mediated bactericidal activity in primary macrophages. The discrepancy in survival of macrophages and that of mice suggests either that there are differences in macrophage populations or that other cell types expressing Nramp1 control
Salmonella
proliferation in the host. The method described allows competitive infection analysis to be carried out on complex mixtures of bacteria and provides high reproducibility from independent biological replicates.
Role of Purine Biosynthesis inBacillus anthracisPathogenesis and Virulence
Authors: Jenkins Amy , Cote Christopher , Twenhafel Nancy , Merkel Tod , Bozue Joel , Welkos Susan
Published: November 2010

Bacillus anthracis, the etiological agent of anthrax, is a spore-forming, Gram-positive bacterium and a category A biothreat agent. Screening of a library of transposon-mutagenizedB. anthracisspores identified a mutant displaying an altered phenotype that harbored a mutated gene encoding the purine biosynthetic enzyme PurH. PurH is a bifunctional protein that catalyzes the final steps in the biosynthesis of the purine IMP. We constructed and characterized definedpurHmutants of the virulentB. anthracisAmes strain. The virulence of thepurHmutants was assessed in guinea pigs, mice, and rabbits. The spores of thepurHmutants were as virulent as wild-type spores in mouse intranasal and rabbit subcutaneous infection models but were partially attenuated in a mouse intraperitoneal model. In contrast, thepurHmutant spores were highly attenuated in guinea pigs regardless of the administration route. The reduced virulence in guinea pigs was not due solely to a germination defect, since both bacilli and toxins were detectedin vivo, suggesting that the significant attenuation was associated with a growth defectin vivo. We hypothesize that an intact purine biosynthetic pathway is required for the virulence ofB. anthracisin guinea pigs.
Upper respiratory tract infection is reduced in physically fit and active adults
Authors: Nieman David C , Henson Dru A , Austin Melanie D , Sha Wei
Published: November 2010

Objective

Limited data imply an inverse relationship between physical activity or fitness level and the rates of upper respiratory tract infection (URTI). The purpose of this study was to monitor URTI symptoms and severity in a heterogeneous group of community adults and contrast across tertiles of physical activity and fitness levels while adjusting for potential confounders.

Design

A group of 1002 adults (ages 18–85 years, 60% female, 40% male) were followed for 12 weeks during the winter and fall seasons while monitoring URTI symptoms and severity using the Wisconsin Upper Respiratory Symptom Survey. Subjects reported frequency of aerobic activity, and rated their physical fitness level using a 10-point Likert scale. A general linear model, with adjustment for seven confounders, was used to examine the effect of exercise frequency and fitness level on the number of days with URTI and severity of symptoms.

Results

The number of days with URTI during the 12-week period was significantly reduced, 43% in subjects reporting ≥5 days/week aerobic exercise compared to those who were largely sedentary (≤1 day/week) and 46% when comparing subjects in the high versus low fitness tertile. URTI severity and symptomatology were also reduced 32% to 41% between high and low aerobic activity and physical fitness tertiles.

Conclusions

Perceived physical fitness and frequency of aerobic exercise are important correlates of reduced days with URTI and severity of symptoms during the winter and fall common cold seasons.
STOCHASTIC BIFURCATION OF AN ASYMMETRIC SINGLE-WELL POTENTIAL DUFFING OSCILLATOR UNDER BOUNDED NOISE EXCITATION
Authors: YUE XIAOLE , XU WEI
Published: November 2010

The stochastic bifurcation, defined as the collision of a stochastic attractor with a stochastic saddle, of an asymmetric single-well potential Duffing oscillator subject to bounded noise excitation is studied by means of the modified digraph cell mapping method. The vivid evolution of stochastic bifurcation is described in detail. Meanwhile, the invariant manifolds of the system accompanied by the stochastic bifurcation are also obtained by this method. Furthermore, the relationship between unstable manifold and the growth direction in the shape and size of the stochastic attractor and stochastic saddle as the system parameter is varied, is given through our analysis.
FAILURE PREDICTION OF RAIL CONSIDERING ROLLING CONTACT FATIGUE
Authors: PATRA AMBIKA PRASAD , BIDHAR SUJIT , KUMAR UDAY
Published: November 2010

Rolling Contact Fatigue (RCF) is a major cause of rail failure leading to replacement of rails. RCF defects are caused by a combination of high normal and tangential stresses between the wheel and rail. In this study, a methodology has been proposed to evaluate P-F (Potential failure-functional failure) interval of RCF defects based on RCF defect rate distribution and fatigue design life distribution. For estimating fatigue design life distribution, load under variable amplitude has been considered which is a case in the mixed traffic scenario. Stochastic S-N curve has been considered to account for probabilistic nature of fatigue life. The stress history can be calculated from the actual load history. RCF defect distribution can be estimated from the probability density function of the defects from the actual field data. The proper estimation of P-F interval will help the infrastructure managers to define rail inspection interval scientifically.
STOCHASTIC DIFFERENTIAL EQUATION BASED SRGM FOR ERRORS OF DIFFERENT SEVERITY WITH TESTING-EFFORT
Authors: KAPUR P. K. , BASIRZADEH MASHAALLAH , INOUE SHINJI , YAMADA SHIGERU
Published: November 2010

Models that describe the failure phenomenon and consequent enhancement in reliability due to fault removal are termed as Software Reliability Growth Models (SRGM). As the size of software system is large and the number of faults detected during the testing phase becomes large, so the change of the number of faults that are detected and removed through each debugging becomes sufficiently small compared with the initial fault content at the beginning of the testing phase. In such a situation, we can model the software fault detection process as a stochastic process with continuous-state space. Several continuous-state space SRGM based on stochastic differential equations of [Formula: see text] type to assess software reliability for large scale software systems have been proposed in the literature so far. However these continuous-state space SRGM have seldom taken the effect of testing-effort into consideration. The resources, such as manpower used for fault detection/removal, number of executed test-cases and CPU hours spent in executing software under test, are well-known as one of the most important factors related to the software reliability growth process. Some of the existing SRGM define errors of different severity. Severity of a failure or fault is the impact it has on the operation of a software-based system. Different faults may require different amount of testing efforts and testing strategy for their removal from the software. The aim of this paper is to determine the type of faults and their proportion present in the software. We have also assumed that learning of removal team grows as testing progresses due to experience and have incorporated the logistic removal rate during modeling of different types of faults with testing-effort by applying a mathematical technique of stochastic differential equations of [Formula: see text] type. Finally, a goodness-of-fit comparison between proposed models and existing continuous-state space SRGM using stochastic differential equations has been conducted.
ON THE DEVELOPMENT OF UNIFIED SCHEME FOR DISCRETE SOFTWARE RELIABILITY GROWTH MODELING
Authors: KAPUR P. K. , AGGARWAL ANU G. , SHATNAWI OMAR , KUMAR RAVI
Published: November 2010

The importance of Software Reliability Growth Models to control the testing process and for quantitative assessment of software reliability is a well established fact. However, difficulties created by their underlying assumptions, their relevance and validity to real testing environment have made the selection of appropriate model an uphill task. Recently, new dimensions have been added to software reliability engineering with the development of unified modeling schemes. These schemes have proved seminal in the development of the general theory, partially because of their simplicity and mathematical tractability. In this paper, we propose a unified scheme for discrete software reliability growth modeling using the fault detection/correction rate function. Standard probability distributions have been used to model the fault correction and detection times. Initially, we have formulated the unified scheme when the fault correction is immediate to the failure observation and later we extend it to the cases where removal is a two stage process namely failure observation followed by fault detection/correction. The use of fault detection/correction rate or else known as hazard rate to represent stage wise removal of fault during testing highlights the importance of the proposed framework. Convolution of probability distribution functions has been used to represent Stage-wise removal of fault i.e. failure observation, fault detection/fault correction. Few Discrete models have been derived using the proposed methodology. Parameter estimation on two real software failure datasets has been worked out. The results obtained are fairly accurate and quite encouraging.
INTEGRATION OF BLACK-BOX AND WHITE-BOX MODELING APPROACHES FOR SOFTWARE RELIABILITY ESTIMATION
Authors: KRISHNA MOHAN K. , VERMA A. K. , SRIVIDYA A. , PAPIC LJUBISA
Published: November 2010

Quality of a software product should be tracked during the software lifecycle right from the architectural phase to its operational phase. Heterogeneous systems consist of several globally distributed components, thus rendering their reliability evaluation more complex with respect to the conventional methods. The objective of our work is to expand the evaluation process for effective reliability analysis by using both white box and black box approaches at prototype and at module/component level before the actual development. In this paper the, Black box testing is based on non-functional requirements for early quantitative analysis for the reliability estimation of the application development based on the output results of the prototype development. White box testing is based on inter-component interactions which deal with probabilistic software behavior. It uses an internal perspective of the system to design test cases based on internal structure at requirements and design phases. This paper has been applied for evolution of effective reliability quantification analysis at prototype level of a financial application case study with both non functional test data of software Development Life cycle (SDLC) phases captured from defect consolidation table in the form orthogonal defect classification as well functional requirements at requirement and design phases captured through software architectural modeling paradigms.
MEMBERSHIP-VALUE-BASED HOMOGENIZATION FOR A DESCRIPTIVE MULTIFACTOR MULTIVARIATE DATA ANALYSIS: EXAMPLE FEATURING QUANTITATIVE AND QUALITATIVE TIME VARIABLES IN CAR DRIVING
Authors: LOSLEVER PIERRE , YOUNSI KARINE , POPIEUL JEAN-CHRISTOPHE , SIMON PHILIPPE
Published: November 2010

This paper explains the pivotal part played by space windowing within Preliminary Data Analysis originating from MultiFactor and MultiVariate databases (PDA-MFMV). The explanation is based on the general case of a database featuring a hyperparallelepipedic structure in which the directions correspond to the factors and where the measurement variables may be either quantitative or qualitative, temporal or non-temporal, and objective or subjective. The space windowing (SW) approach hereby described in this article is less information reducing than most basic summarizing procedures without windowing using usual statistical indicators. First, the data in each cell of the hyperparallelepiped is transformed into membership values to be averaged over factors, such as time or individuals. Then, several graphic techniques can be made use of in order to investigate membership values. In this paper, Multiple Correspondence Analysis (MCA) has been chosen. A didactic example concerning car driving with four factors and 11 time variables (one being qualitative) is used in order to illustrate the widespread use of the " SW/MCA" pair, fuzzy time windowing being also considered. From the results yielded by this pair, some suggestions about statistical tests are made aiming at a more explanatory analysis. The discussion then weighs out the pros and cons of resorting to space windowing to perform a PDA-MFMV.
IMPROVING PURCHASING BEHAVIOR PREDICTIONS BY DATA AUGMENTATION WITH SITUATIONAL VARIABLES
Authors: BAECKE PHILIPPE , VAN DEN POEL DIRK
Published: November 2010

Nowadays, an increasing number of information technology tools are implemented in order to support decision making about marketing strategies and improve customer relationship management (CRM). Consequently, an improvement in CRM can be obtained by enhancing the databases on which these information technology tools are based. This study shows that data augmentation with situational variables of the purchase occasion can significantly improve purchasing behavior predictions for a home vending company. Three dimensions of situational variables are examined: physical surroundings, temporal perspective and social surroundings respectively represented by weather, time, and salesperson variables. The smallest, but still significant, increase in predictive performance was measured by enhancing the model with time variables. Besides the moment of the day, this study shows that the incorporation of weather variables, and more specifically sunshine, can also improve the accuracy of a CRM model. Finally, the best improvement in purchasing behavior predictions was obtained by taking the salesperson effect into account using a multilevel model.
UNSUPERVISED LEARNING BASED DISTRIBUTED DETECTION OF GLOBAL ANOMALIES
Authors: ZHOU JUNLIN , LAZAREVIC ALEKSANDAR , HSU KUO-WEI , SRIVASTAVA JAIDEEP , FU YAN , WU YUE
Published: November 2010

Anomaly detection has recently become an important problem in many industrial and financial applications. Very often, the databases from which anomalies have to be found are located at multiple local sites and cannot be merged due to privacy reasons or communication overhead. In this paper, a novel general framework for distributed anomaly detection is proposed. The proposed method consists of three steps: (i) building local models for distributed data sources with unsupervised anomaly detection methods and computing quality measure of local models; (ii) transforming local unsupervised local models into sharing models; and (iii) reusing sharing models for new data and combining their results by considering both quality and diversity of them to detect anomalies in a global view. In experiments performed on synthetic and real-life large data set, the proposed distributed anomaly detection method achieved prediction performance comparable or even slightly better than the global anomaly detection algorithm applied on the data set obtained when all distributed data set were merged.
IMAGE AND AUDIO-SPEECH DENOISING BASED ON HIGHER-ORDER STATISTICAL MODELING OF WAVELET COEFFICIENTS AND LOCAL VARIANCE ESTIMATION
Authors: KITTISUWAN PICHID , CHANWIMALUANG THITIPORN , MARUKATAT SANPARITH , ASDORNWISED WIDHYAKORN
Published: November 2010

At first, this paper is concerned with wavelet-based image denoising using Bayesian technique. In conventional denoising process, the parameters of probability density function (PDF) are usually calculated from the first few moments, mean and variance. In the first part of our work, a new image denoising algorithm based on Pearson Type VII random vectors is proposed. This PDF is used because it allows higher-order moments to be incorporated into the noiseless wavelet coefficients' probabilistic model. One of the cruxes of the Bayesian image denoising algorithms is to estimate the variance of the clean image. Here, maximum a posterior (MAP) approach is employed for not only noiseless wavelet-coefficient estimation but also local observed variance acquisition. For the local observed variance estimation, the selection of noisy wavelet-coefficient model, either a Laplacian or a Gaussian distribution, is based upon the corrupted noise power where Gamma distribution is used as a prior for the variance. Evidently, our selection of prior is motivated by analytical and computational tractability. In our experiments, our proposed method gives promising denoising results with moderate complexity. Eventually, our image denoising method can be simply extended to audio/speech processing by forming matrix representation whose rows are formed by time segments of digital speech waveforms. This way, the use of our image denoising methods can be exploited to improve the performance of various audio/speech tasks, e.g., denoised enhancement of voice activity detection to capture voiced speech, significantly needed for speech coding and voice conversion applications. Moreover, one of the voice abnormality detections, called oropharyngeal dysphagia classification, is also required denoising method to improve the signal quality in elderly patients. We provide simple speech examples to demonstrate the prospects of our techniques.
HIGH APPROXIMATION ORDER BIORTHOGONAL MULTISCALING FUNCTIONS WITH DILATION FACTOR a
Authors: XIE CHANGZHEN
Published: November 2010

An algorithm is presented for constructing a pair of high approximation order biorthogonal multiscaling function with dilation factor a in terms of any given pair of biorthogonal multiscaling function. The special case that a = 2 is discussed. If the dilation factor a = 2, then a biorthogonal multiwavelet pair is constructed explicitly. Finally, examples are given.
RADIAL BASIS FUNCTION COLLOCATION FOR THE CHEMICAL MASTER EQUATION
Authors: ZHANG JINGWEI , WATSON LAYNE T. , BEATTIE CHRISTOPHER A. , CAO YANG
Published: November 2010

The chemical master equation (CME), formulated from the Markov assumption of stochastic processes, offers an accurate description of general chemical reaction systems. This paper proposes a collocation method using radial basis functions to numerically approximate the solution to the CME. Numerical results for some systems biology problems show that the collocation approximation method has good potential for solving large-scale CMEs.
MINIMIZING THE GROSS-PITAEVSKII ENERGY FUNCTIONAL WITH THE SOBOLEV GRADIENT — ANALYTICAL AND NUMERICAL RESULTS
Authors: KAZEMI PARIMAH , ECKART MICHAEL
Published: November 2010

In this contribution, we prove the global existence and uniqueness of a trajectory that globally converges to the minimizer of the Gross-Pitaevskii energy functional for a large class of external potentials. Using the method of Sobolev gradients, we can provide an explicit construction of this minimizing sequence.

Based upon this theoretical framework we numerically apply these results to a specific realization of the external potential and illustrate the main benefits of the method of Sobolev gradients, which are high numerical stability and rapid convergence toward the minimizer.
ON FORMAL AND COGNITIVE SEMANTICS FOR SEMANTIC COMPUTING
Authors: WANG YINGXU
Published: November 2010

Semantics is the meaning of symbols, notations, concepts, functions, and behaviors, as well as their relations that can be deduced onto a set of predefined entities and/or known concepts. Semantic computing is an emerging computational methodology that models and implements computational structures and behaviors at semantic or knowledge level beyond that of symbolic data. In semantic computing, formal semantics can be classified into the categories of to be, to have, and to do semantics. This paper presents a comprehensive survey of formal and cognitive semantics for semantic computing in the fields of computational linguistics, software science, computational intelligence, cognitive computing, and denotational mathematics. A set of novel formal semantics, such as deductive semantics, concept-algebra-based semantics, and visual semantics, is introduced that forms a theoretical and cognitive foundation for semantic computing. Applications of formal semantics in semantic computing are presented in case studies on semantic cognition of natural languages, semantic analyses of computing behaviors, behavioral semantics of human cognitive processes, and visual semantic algebra for image and visual object manipulations.
GUIDELINES FOR REUSING ONTOLOGIES ON THE SEMANTIC WEB
Authors: SIMPERL ELENA
Published: November 2010

The ability to efficiently and effectively reuse ontologies is commonly acknowledged to play a crucial role in the large scale dissemination of ontologies and ontology-driven technology, being thus a pre-requisite for the ongoing realization of the Semantic Web. In this article, we give an account of ontology reuse from a process point of view. We present a methodology that can be utilized to systematize and monitor ontology engineering processes in scenarios reusing available ontological knowledge in the context of a particular application. Notably, and by contrast to existing approaches in this field, our aim is to provide means to overcome the poor reusability of existing resources — rather than to solve the more general issue of building new, more reusable knowledge components. To do so we investigate the impact of the application context of an ontology — in terms of tasks this ontology has been created for and will be utilized in — has on the feasibility of a reuse-oriented ontology development strategy and provide guidelines that take these aspects into account. The applicability of the methodology is demonstrated through a case study performed in collaboration with an international eRecruitment solution provider.
Approximate Bayesian Computation in Evolution and Ecology
Authors: Beaumont Mark A.
Published: November 2010

In the past 10years a statistical technique, approximate Bayesian computation (ABC), has been developed that can be used to infer parameters and choose between models in the complicated scenarios that are often considered in the environmental sciences. For example, based on gene sequence and microsatellite data, the method has been used to choose between competing models of human demographic history as well as to infer growth rates, times of divergence, and other parameters. The method fits naturally in the Bayesian inferential framework, and a brief overview is given of the key concepts. Three main approaches to ABC have been developed, and these are described and compared. Although the method arose in population genetics, ABC is increasingly used in other fields, including epidemiology, systems biology, ecology, and agent-based modeling, and many of these applications are briefly described.
Biodiversity and Climate Change: Integrating Evolutionary and Ecological Responses of Species and Communities
Authors: Lavergne Sébastien , Mouquet Nicolas , Thuiller Wilfried , Ronce Ophélie
Published: November 2010

Today's scientists are facing the enormous challenge of predicting how climate change will affect species distributions and species assemblages. To do so, ecologists are widely using phenomenological models of species distributions that mainly rely on the concept of species niche and generally ignore species' demography, species' adaptive potential, and biotic interactions. This review examines the potential role of the emerging synthetic discipline of evolutionary community ecology in improving our understanding of how climate change will alter future distribution of biodiversity. We review theoretical and empirical advances about the role of niche evolution, interspecific interactions, and their interplay in altering species geographic ranges and community assembly. We discuss potential ways to integrate complex feedbacks between ecology and evolution in ecological forecasting. We also point at a number of caveats in our understanding of the eco-evolutionary consequences of climate change and highlight several challenges for future research.
Changing Geographic Distributions of Human Pathogens
Authors: Smith Katherine F. , Guégan Jean-François
Published: November 2010

Since the rise of modern humans, changes in demography and land use and frequent contact with wildlife and domesticated animals have created ongoing opportunities for pathogen loss, gain, and evolution in the human population. Early transportation networks and population expansion created a world where many human-specific pathogens are now ubiquitous, yet zoonoses continue to emerge as humans encroach into the last remaining wild areas, increase livestock production, and plug into vast global trade networks. Pathogens are exploiting almost any change in human ecology that provides new opportunities for transmission, the most recent being rampant use of antibiotics resulting in new multidrug-resistant pathogens. Public health advances have benefitted some nations, but others continue to suffer from pathogens long eradicated by developed nations. Generalities of pathogen occurrence aid in disease prediction, but a systemic approach incorporating ecology, biogeography, public health, and conservation biology is ultimately necessary to fully comprehend the changing geographic distributions of human pathogens.