bluuebunny/crossref_metadata_2025 huggingface dataset:
Genotypic Profile of the Outer Membrane Proteins BabA and BabB in Clinical Isolates of
Helicobacter pylori
Authors: Colbeck Jeffrey C. , Hansen Lori M. , Fong Julie M. , Solnick Jay V.
Published: June 2006

Helicobacter pylori
BabA is the ABO blood group antigen binding adhesin, which has a closely related paralogue (BabB) whose function is unknown. PCR and DNA sequence analysis showed extensive genotypic diversity in
babA
and
babB
across different strains, as well as within a strain colonizing an individual patient. We hypothesize that diverse profiles of
babA
and
babB
reflect selective pressures for adhesion, which may differ across different hosts and within an individual over time.
Identification and Characterization of an Antigen I/II Family Protein Produced by Group AStreptococcus
Authors: Zhang Shizhen , Green Nicole M. , Sitkiewicz Izabela , LeFebvre Rance B. , Musser James M.
Published: June 2006

Group AStreptococcus(GAS) is a gram-positive human bacterial pathogen that causes infections ranging in severity from pharyngitis to life-threatening invasive disease, such as necrotizing fasciitis. Serotype M28 strains are consistently isolated from invasive infections, particularly puerperal sepsis, a severe infection that occurs during or after childbirth. We recently sequenced the genome of a serotype M28 GAS strain and discovered a novel 37.4-kb foreign genetic element designated region of difference 2 (RD2). RD2 is similar in gene content and organization to genomic islands found in group B streptococci (GBS), the major cause of neonatal infections. RD2 encodes seven proteins with conventional gram-positive secretion signal sequences, six of which have not been characterized. Herein, we report that one of these six proteins (M28_Spy1325; Spy1325) is a member of the antigen I/II family of cell surface-anchored molecules produced by oral streptococci. PCR and DNA sequence analysis found that Spy1325 is very well conserved in GAS strains of distinct M protein serotypes. As assessed by real-time TaqMan quantitative PCR, the Spy1325 gene was expressed in vitro, and Spy1325 protein was present in culture supernatants and on the GAS cell surface. Western immunoblotting and enzyme-linked immunosorbent assays indicated that Spy1325 was produced by GAS in infected mice and humans. Importantly, the immunization of mice with recombinant Spy1325 fragments conferred protection against GAS-mediated mortality. Similar to other antigen I/II proteins, recombinant Spy1325 bound purified human salivary agglutinin glycoprotein. Spy1325 may represent a shared virulence factor among GAS, GBS, and oral streptococci.
Pneumococcal Neuraminidases A and B Both Have Essential Roles during Infection of the Respiratory Tract and Sepsis
Authors: Manco Sonia , Hernon Fidelma , Yesilkaya Hasan , Paton James C. , Andrew Peter W. , Kadioglu Aras
Published: June 2006

We examined the role of the neuraminidases NanA and NanB in colonization and infection in the upper and lower respiratory tract by
Streptococcus pneumoniae
, as well as the role of these neuraminidases in the onset and development of septicemia following both intranasal and intravenous infection. We demonstrated for the first time using outbred MF1 mouse models of infection that both NanA and NanB were essential for the successful colonization and infection of the upper and lower respiratory tract, respectively, as well as pneumococcal survival in nonmucosal sites, such as the blood. Our studies have shown that in vivo a neuraminidase A mutant is cleared from the nasopharynx, trachea, and lungs within 12 h postinfection, while a neuraminidase B mutant persists but does not increase in either the nasopharynx, trachea, or lungs. We also demonstrated both neuraminidase mutants were unable to cause sepsis following intranasal infections. When administered intravenously, however, both mutants survived initially but were unable to persist in the blood beyond 48 h postinfection and were progressively cleared. The work presented here demonstrates the importance of pneumococcal neuraminidase A and for the first time neuraminidase B in the development of upper and lower respiratory tract infection and sepsis.
Escherichia coli
Cytotoxic Necrotizing Factor 1 Blocks Cell Cycle G
2
/M Transition in Uroepithelial Cells
Authors: Falzano Loredana , Filippini Perla , Travaglione Sara , Miraglia Alessandro Giamboi , Fabbri Alessia , Fiorentini Carla
Published: June 2006

Evidence is accumulating that a growing number of bacterial toxins act by modulating the eukaryotic cell cycle machinery. In this context, we provide evidence that a protein toxin named cytotoxic necrotizing factor 1 (CNF1) from uropathogenic
Escherichia coli
is able to block cell cycle G
2
/M transition in the uroepithelial cell line T24. CNF1 permanently activates the small GTP-binding proteins of the Rho family that, beside controlling the actin cytoskeleton organization, also play a pivotal role in a large number of other cellular processes, including cell cycle regulation. The results reported here show that CNF1 is able to induce the accumulation of cells in the G
2
/M phase by sequestering cyclin B1 in the cytoplasm and down-regulating its expression. The possible role played by the Rho GTPases in the toxin-induced cell cycle deregulation has been investigated and discussed. The activity of CNF1 on cell cycle progression can offer a novel view of
E. coli
pathogenicity.
Toxoplasma gondiiInhibits Toll-Like Receptor 4 Ligand-Induced Mobilization of Intracellular Tumor Necrosis Factor Alpha to the Surface of Mouse Peritoneal Neutrophils
Authors: Bennouna Soumaya , Sukhumavasi Woraporn , Denkers Eric Y.
Published: June 2006

Neutrophils are well-known to rapidly respond to infection through chemotactic infiltration at sites of inflammation, followed by rapid release of microbicidal molecules, chemokines, and proinflammatory cytokines. For tumor necrosis factor alpha (TNF-α), we recently found that neutrophils contain intracellular pools of the cytokine and display the capacity to upregulate transcriptional activity of the gene during lipopolysaccharide (LPS) stimulation. We now show that triggering of mouse peritoneal neutrophils with Toll-like receptor 2 (TLR2), TLR4, and TLR9 ligands, but not ligands of TLR3, induces upregulation of surface membrane TNF-α. However, neutrophils infected with the protozoanToxoplasma gondiidisplayed an inability to respond fully in terms of TLR ligand-induced increases in membrane TNF-α expression. Infected neutrophils failed to display decreased levels of intracellular TNF-α upon LPS exposure. In contrast to intermediate inhibitory effects in nontreated neutrophils,T. gondiiinduced a complete blockade in LPS-induced surface TNF-α expression in the presence of the protein synthesis inhibitor cycloheximide. Despite these inhibitory effects, the parasite did not affect LPS-induced upregulation of TNF-α gene transcription. Collectively, the results show thatToxoplasmaprevents TLR ligand-triggered mobilization of TNF-α to the neutrophil surface, revealing a novel immunosuppressive activity of the parasite.
Exploitation of the Endocytic Pathway by
Orientia tsutsugamushi
in Nonprofessional Phagocytes
Authors: Chu Hyuk , Lee Jung-Hee , Han Seung-Hoon , Kim Se-Yoon , Cho Nam-Hyuk , Kim Ik-Sang , Choi Myung-Sik
Published: June 2006

Orientia tsutsugamushi
, a causative agent of scrub typhus, is an obligate intracellular bacterium that requires the exploitation of the endocytic pathway in the host cell. We observed the localization of
O. tsutsugamushi
with clathrin or adaptor protein 2 within 30 min after the infection of nonprofessional phagocytes. We have further confirmed that the infectivity of
O. tsutsugamushi
is significantly reduced by drugs that block clathrin-mediated endocytosis but not by filipin III, an inhibitor that blocks caveola-mediated endocytosis. In the present study, with a confocal microscope,
O. tsutsugamushi
was sequentially colocalized with the early and late endosomal markers EEA1 and LAMP2, respectively, within 1 h after infection. The colocalization of
O. tsutsugamushi
organisms with EEA1 and LAMP2 gradually disappeared until 2 h postinfection, and then free
O. tsutsugamushi
organisms were found in the cytoplasm. When the acidification of endocytic vesicles was blocked by treating the cells with NH
4
Cl or bafilomycin A, the escape of
O. tsutsugamushi
organisms from the endocytic pathway was severely impaired, and the infectivity of
O. tsutsugamushi
was drastically reduced. To our knowledge, this is the first report that the invasion of
O. tsutsugamushi
is dependent on the clathrin-dependent endocytic pathway and the acidification process of the endocytic vesicles in nonprofessional phagocytes.
TheActinobacillus actinomycetemcomitansRibose Binding Protein RbsB Interacts with Cognate and Heterologous Autoinducer 2 Signals
Authors: James DeAnna , Shao HanJuan , Lamont Richard J. , Demuth Donald R.
Published: June 2006

Autoinducer 2 (AI-2) produced by the oral pathogenActinobacillus actinomycetemcomitansinfluences growth of the organism under iron limitation and regulates the expression of iron uptake genes. However, the cellular components that mediate the response ofA. actinomycetemcomitansto AI-2 have not been fully characterized. Analysis of the complete genome sequence ofA. actinomycetemcomitans(www.oralgen.lanl.gov) indicated that the RbsB protein was related to LuxP, the AI-2 receptor ofVibrio harveyi. To determine if RbsB interacts with AI-2, the bioluminescence of the reporter strainV. harveyiBB170 (sensor 1−, sensor 2+) was determined after stimulation with partially purified AI-2 fromA. actinomycetemcomitansor conditioned medium fromV. harveyicultures in the presence and absence of purified six-His-tagged RbsB. RbsB efficiently inhibitedV. harveyibioluminescence induced by bothA. actinomycetemcomitansAI-2 andV. harveyiAI-2 in a dose-dependent manner, suggesting that RbsB competes with LuxP for AI-2. Fifty percent inhibition occurred with approximately 0.3 nM RbsB forA. actinomycetemcomitansAI-2 and 15 nM RbsB forV. harveyiAI-2. RbsB-mediated inhibition ofV. harveyibioluminescence was reversed by the addition of 50 mM ribose, suggesting thatA. actinomycetemcomitansAI-2 and ribose bind at the same site of RbsB. The RbsB/AI-2 complex was thermostable sinceA. actinomycetemcomitansAI-2 could not be recovered by heating. This was not due to heat inactivation ofA. actinomycetemcomitansAI-2 since signal activity was unaffected by heating in the absence of RbsB. Furthermore, an isogenicA. actinomycetemcomitansmutant that was unable to expressrbsBwas deficient in depletingA. actinomycetemcomitansAI-2 from solution relative to the wild-type organism. Inactivation ofrbsBalso influenced the ability of the organism to grow under iron-limiting conditions. The mutant strain attained a cell density of approximately 30% that of the wild-type organism under iron limitation. In addition, real-time PCR showed that the expression ofafuABC, encoding a major ferric ion transporter, was reduced by approximately eightfold in therbsBmutant. This phenotype was similar to that of a LuxS-deficient mutant ofA. actinomycetemcomitansthat is unable to produce AI-2. Together, our results suggest that RbsB may play a role in the response ofA. actinomycetemcomitansto AI-2.
Cell Activation by Ligands of the Toll-Like Receptor and Interleukin-1 Receptor Family Depends on the Function of the Large-Conductance Potassium Channel MaxiK in Human Macrophages
Authors: Scheel Olaf , Papavlassopoulos Martin , Blunck Rikard , Gebert Andreas , Hartung Thomas , Zähringer Ulrich , Seydel Ulrich , Schromm Andra B.
Published: June 2006

Performing patch-clamp experiments on human macrophages, we show that the K
+
channel MaxiK is activated by lipopolysaccharide, peptidoglycan, and interleukin-1. Cytokine production initiated by several Toll-like receptor (TLR) ligands and by interleukin-1 is inhibited by MaxiK blockade. This provides evidence for functional association of the MaxiK channel and TLR signaling complexes.
Type III Secretion-Dependent Modulation of Innate Immunity as One of Multiple Factors Regulated byPseudomonas aeruginosaRetS
Authors: Zolfaghar Irandokht , Evans David J. , Ronaghi Reza , Fleiszig Suzanne M. J.
Published: June 2006

Mutation ofretS(rtsM) ofPseudomonas aeruginosastrain PA103 reduces its virulence in both ocular and respiratory murine models of infection. In vitro,retSmutants exhibit loss of the ExsA-regulated type III secretion system (TTSS), reduced twitching motility, and a decrease in association with, invasion of, and survival within corneal epithelial cells. In addition, transcription of multiple other virulence genes is positively and negatively affected byretSmutation. Since our published data show that ExoU and ExoT, the two TTSS effectors encoded by strain PA103, each confer virulence in this corneal model, we hypothesized that loss of virulence ofretSmutants follows loss of type III secretion. Corneal pathology, bacterial colonization, and phagocyte infiltration were compared for wild-type PA103,retSmutants, and various TTSS mutants after infection with ∼106CFU bacteria. Results showed that either aretSor anexsA(TTSS) mutation delayed disease progression, as illustrated by reduced severity scores and colonization levels during the first 48 h postinfection. Surprisingly,retSmutant infections then became more severe than those involvingexsAmutants. By day 7, colonization levels ofretSmutants even surpassed those of wild-type bacteria (more than twofold,P = 0.028). AlthoughretSmutants caused more severe opacification of central corneas than both the wild type and theexsAmutants, neither mutant caused the peripheral ring opacity commonly associated with wild-type infection, suggesting that the TTSS was involved. Histological experiments withretSand various TTSS mutants showed that ring opacification required ExoU but not ExoT and that it consisted of dense polymorphonuclear phagocyte infiltration at the corneal periphery and the absence of any cell type in the central cornea. These data suggest that theseP. aeruginosaTTSS effectors have different effects on innate immunity and that RetS influences virulence beyond its effects on the TTSS.
The Animal Pathogen-Like Type III Secretion System Is Required for the Intracellular Survival of
Burkholderia mallei
within J774.2 Macrophages
Authors: Ribot Wilson J. , Ulrich Ricky L.
Published: June 2006

Burkholderia mallei
is a highly infectious gram-negative pathogen and is the causative agent of human and animal glanders. By generating polar mutations (disruption of
bsaQ
and
bsaZ
) in the
B. mallei
ATCC 23344 animal pathogen-like type III secretion system (TTS), we demonstrate that this bacterial protein delivery system is required for intracellular growth of
B. mallei
in J774.2 cells, formation of macrophage membrane protrusions, actin polymerization, and phagosomal escape. These findings suggest that TTS plays a role in the intracellular trafficking of
B. mallei
and may facilitate cell-to-cell spread via actin-based motility.
Doxycycline Reduces Mortality and Injury to the Brain and Cochlea in Experimental Pneumococcal Meningitis
Authors: Meli Damian N. , Coimbra Roney S. , Erhart Dominik G. , Loquet Gerard , Bellac Caroline L. , Täuber Martin G. , Neumann Ulf , Leib Stephen L.
Published: June 2006

Bacterial meningitis is characterized by an inflammatory reaction to the invading pathogens that can ultimately lead to sensorineural hearing loss, permanent brain injury, or death. The matrix metalloproteinases (MMPs) and tumor necrosis factor alpha-converting enzyme (TACE) are key mediators that promote inflammation, blood-brain barrier disruption, and brain injury in bacterial meningitis. Doxycycline is a clinically used antibiotic with anti-inflammatory effects that lead to reduced cytokine release and the inhibition of MMPs. Here, doxycycline inhibited TACE with a 50% inhibitory dose of 74 μM in vitro and reduced the amount of tumor necrosis factor alpha released into the cerebrospinal fluid by 90% in vivo. In an infant rat model of pneumococcal meningitis, a single dose of doxycycline (30 mg/kg) given as adjuvant therapy in addition to ceftriaxone 18 h after infection significantly reduced the mortality, the blood-brain barrier disruption, and the extent of cortical brain injury. Adjuvant doxycycline (30 mg/kg given subcutaneously once daily for 4 days) also attenuated hearing loss, as assessed by auditory brainstem response audiometry, and neuronal death in the cochlear spiral ganglion at 3 weeks after infection. Thus, doxycycline, probably as a result of its anti-inflammatory properties, had broad beneficial effects in the brain and the cochlea and improved survival in this model of pneumococcal meningitis in infant rats.
Identification of
Francisella tularensis
Genes Affected by Iron Limitation
Authors: Deng Kaiping , Blick Robert J. , Liu Wei , Hansen Eric J.
Published: June 2006

Cells of an attenuated live vaccine strain (LVS) of
F. tularensis
grown under iron-restricted conditions were found to contain increased quantities of several proteins relative to cells of this same strain grown under iron-replete conditions. Mass spectrometric analysis identified two of these proteins as IglC and PdpB, both of which are encoded by genes located in a previously identified pathogenicity island in
F. tularensis
LVS. Regions with homology to the consensus Fur box sequence were located immediately in front of the
iglC
and
pdpB
open reading frames (ORFs), and in silico analysis of the
F. tularensis
Schu4 genome detected a number of predicted 5′ untranslated regions that contained putative Fur boxes. The putative Fur box preceding
Francisella
iron-regulated gene A (
figA
) had the highest degree of identity with the consensus Fur box sequence. DNA microarray analysis showed that nearly 80 of the genes in the
F. tularensis
LVS genome were up- or down-regulated at least twofold under iron-restricted growth conditions. When tested for possible siderophore production by means of the Chrome Azurol S assay, a wild-type
F. novicida
strain produced a large reaction zone whereas its
figA
mutant produced very little reactivity in this assay. In addition, a cross-feeding experiment demonstrated that this siderophore-like activity produced by the wild-type
F. novicida
strain could enhance the ability of the
F. novicida figA
mutant to grow under iron-restricted conditions. This study provides the first identification of iron-regulated genes in
F. tularensis
LVS and evidence for the production of a siderophore-like molecule by
F. novicida
.
Role of Sigma E-Regulated Genes in
Escherichia coli
Uropathogenesis
Authors: Redford Peter , Welch Rodney A.
Published: June 2006

The sigma E regulon encodes proteins for maintenance and repair of the
Escherichia coli
cell envelope. Previously, we observed that an antirepressor of sigma E, DegS, is essential for uropathogenic
E. coli
virulence. Here we use a mouse urinary tract infection model to assay the virulence of mutants of
E. coli
genes described as sigma E dependent. Deletion mutants of candidate genes were made in the uropathogenic
E. coli
strain CFT073. Swiss Webster female mice were inoculated with a mixture of mutant and wild-type strains. Bladder and kidney homogenates were cultured 2 days after infection, and CFU of the wild type and mutant were compared. Eleven mutants were assayed, and two, CFT073
degP
and CFT073
skp
, showed significantly diminished survival compared to wild type. DegP is a chaperone and degradase active in the periplasm. Skp is also a periplasmic chaperone. The virulence of the
skp
deletion mutant could not be restored by complementation with
skp
. The virulence of the
degP
deletion mutant, in contrast, could be restored. However, complementation with a
degP
allele encoding a serine-to-alanine (S210A) mutation at the protease active site fails to restore virulence. Unlike
degP
mutants in other bacteria, the
E. coli degP
mutant is tolerant of oxidative stress. It disappears abruptly from bladder and kidney cultures between 6 and 12 hours after inoculation. A mutant of
degQ
, a close homolog of
degP
, was not attenuated in mice. This is the first report that the DegP degradase is an
E. coli
virulence factor in an animal infection model.
Mucosal Immunity to Asymptomatic
Entamoeba histolytica
and
Entamoeba dispar
Infection Is Associated with a Peak Intestinal Anti-Lectin Immunoglobulin A Antibody Response
Authors: Abd-Alla Mohamed D. , Jackson Terry F. G. H. , Rogers Tyson , Reddy Selvan , Ravdin Jonathan I.
Published: June 2006

We monitored 93 subjects cured of amebic liver abscess (ALA) and 963 close associate controls in Durban, South Africa, and determined by enzyme-linked immunosorbent assay that the intestinal immunoglobulin A (IgA) antibody response to the
Entamoeba histolytica
galactose-inhibitable adherence lectin is most accurately represented by a complex pattern of transitory peaks. One or more intestinal anti-lectin IgA antibody peaks occurred in 85.9% of ALA subjects over 36 months compared to 41.6% of controls (
P
< 0.0001). ALA subjects exhibited a greater number of anti-lectin IgA antibody peaks (
P
< 0.0001) than controls. In addition, their peak optical density values were higher (peak numbers 1 to 3,
P
< 0.003), peaks were of longer duration (for peaks 1 and 2,
P
≤ 0.0054), and there was a shorter time interval between peaks (between 1 and 2 or 2 and 3,
P
≤ 0.0106) than observed for control subjects. A prior
E. histolytica
infection was associated with the occurrence of an anti-lectin IgA antibody peak (79.1%,
P
< 0.0001) more so than for
Entamoeba dispar
infection (57.2%,
P
< 0.001). The annual number of anti-lectin IgA antibody peaks in ALA subjects was 0.71 per year, compared to just 0.22 in controls (
P
<0.0001), indicating a higher rate of exposure to the parasite than previously appreciated. Anti-lectin IgA antibody peaks were of higher amplitude following a
E. histolytica
infection compared to
E. dispar
(
P
= 0.01) and, for either, were of greater height in ALA subjects than controls (
P
< 0.01). ALA subjects demonstrated greater clearance of amebic infection after an anti-lectin IgA antibody peak compared to controls, and only 14.3% remained with a positive culture after the peak, compared to 38.9% in controls (
P
= 0.035). In summary, this prospective controlled longitudinal study elucidated the dynamic nature of the human intestinal IgA antibody response to
E. histolytica
and
E. dispar
infection and revealed that ALA subjects exhibit heightened intestinal anti-lectin IgA antibody peaks that are associated with clearance of
E. histolytica
and
E. dispar
infection.
LeishmaniaInfection Impairs β1-Integrin Function and Chemokine Receptor Expression in Mononuclear Phagocytes
Authors: Pinheiro Nathanael F. , Hermida Micely D. R. , Macedo Mariana P. , Mengel José , Bafica Andre , dos-Santos Washington L. C.
Published: June 2006

Leishmaniaspp. are intracellular parasites that cause lesions in the skin, mucosa, and viscera. We have previously shown thatLeishmaniainfection reduces mononuclear phagocyte adhesion to inflamed connective tissue. In this study, we examined the role of adhesion molecules and chemokines in this process. Infection rate (r= −0.826,P= 0.003) and parasite burden (r= −0.917,P= 0.028) negatively correlated to mouse phagocyte adhesion. The decrease (58.7 to 75.0% inhibition,P= 0.005) in phagocyte adhesion to connective tissue, induced byLeishmania, occurred as early as 2 h after infection and was maintained for at least 24 h. Interestingly, impairment of cell adhesion was sustained by phagocyte infection, since it was not observed following phagocytosis of killed parasites (cell adhesion varied from 15.2% below to 24.0% above control levels,P> 0.05). In addition,Leishmaniainfection diminished cell adhesion to fibronectin (54.1 to 96.2%,P< 0.01), collagen (15.7 to 83.7%,P< 0.05), and laminin (59.1 to 82.2%,P< 0.05). The CD11bhisubpopulation was highly infected (49.6 to 97.3%). Calcium and Mg2+replacement by Mn2+, a treatment that is known to induce integrins to a high state of affinity for their receptors, reverted the inhibition in adhesion caused byLeishmania. This reversion was completely blocked by anti-VLA4 antibodies. Furthermore, expression of CCR4 and CCR5, two chemokine receptors implicated in cell adhesion, was found to be downregulated 16 h after infection (2.8 to 4.1 times and 1.9 to 2.8 times, respectively). Together, these results suggest that mechanisms regulating integrin function are implicated in the change of macrophage adhesion in leishmaniasis.
Why are manual workers at high risk of upper limb disorders? The role of physical work factors in a random sample of workers in France (the Pays de la Loire study)
Authors: Melchior M , Roquelaure Y , Evanoff B , Chastang J-F , Ha C , Imbernon E , Goldberg M , Leclerc A
Published: June 2006

Objective:To investigate the reasons for the excess risk of upper limb musculoskeletal disorders among manual workers compared with other workers in a random sample of 2656 French men and women (20–59 years old) participating in a study on the prevalence of work related upper limb disorders conducted by France’s National Institute of Health Surveillance.

Methods:Prevalence ratios (PR) of physician-diagnosed musculoskeletal disorders of the shoulder, elbow, wrist, and hand (any of six leading disorders, rotator cuff syndrome, carpal tunnel syndrome) in manual versus non-manual workers were calculated using Cox regression models with a constant time of follow up and robust variance.

Results:11.3% of men and 15.1% of women were diagnosed with an upper limb disorder. The risk was especially high in manual workers (PRs: 1.40 to 2.10). Physical work factors accounted for over 50% of occupational disparities overall, 62% (men) to 67% (women) for rotator cuff syndrome, and 96% (women) for carpal tunnel syndrome. The authors calculated that under lower levels of physical work exposures, up to 31% of cases among manual workers could have been prevented.

Conclusions:In working men and women, upper limb musculoskeletal disorders are frequent. Physical work exposures, such as repetitive and forceful movements, are an important source of risk and in particular account for a large proportion of excess morbidity among manual workers.
ESTIMATORS OF THE RETRIAL RATE IN M/G/1 RETRIAL QUEUES
Authors: RODRIGO ANTONIO
Published: June 2006

In this article we analyze the M/G/1 retrial queue from a statistical viewpoint. Assuming that retrials are exponentially distributed we focus on the estimation of the retrial parameter for constant and non-constant retrial policies, including the non-ergodic case. We consider different estimators and compare their asymptotic variances. We test numerically the accuracy of the proposed estimators.
A HYBRID HEURISTIC FOR THE MINIMUM WEIGHT VERTEX COVER PROBLEM
Authors: SINGH ALOK , GUPTA ASHOK KUMAR
Published: June 2006

Given an undirected graph with weights associated with its vertices, the minimum weight vertex cover problem seeks a subset of vertices with minimum sum of weights such that each edge of the graph has at least one endpoint belonging to the subset. In this paper, we propose a hybrid approach, combining a steady-state genetic algorithm and a greedy heuristic, for the minimum weight vertex cover problem. The genetic algorithm generates vertex cover, which is then reduced to minimal weight vertex cover by the heuristic. We have evaluated the performance of our algorithm on several test problems of varying sizes. Computational results show the effectiveness of our approach in solving the minimum weight vertex cover problem.
A DISCRETE-TIME Geo/G/1 RETRIAL QUEUE WITH SERVER BREAKDOWNS
Authors: ATENCIA IVAN , MORENO PILAR
Published: June 2006

This paper discusses a discrete-time Geo/G/1 retrial queue with the server subject to breakdowns and repairs. The customer just being served before server breakdown completes his remaining service when the server is fixed. The server lifetimes are assumed to be geometrical and the server repair times are arbitrarily distributed. We study the Markov chain underlying the considered queueing system and present its stability condition as well as some performance measures of the system in steady-state. Then, we derive a stochastic decomposition law and as an application we give bounds for the proximity between the steady-state distributions of our system and the corresponding system without retrials. Also, we introduce the concept of generalized service time and develop a recursive procedure to obtain the steady-state distributions of the orbit and system size. Finally, we prove the convergence to the continuous-time counterpart and show some numerical results.
DOES SIZE MATTER? FINDING THE PROFITABILITY AND MARKETABILITY BENCHMARK OF FINANCIAL HOLDING COMPANIES
Authors: LO SHIH-FANG , LU WEN-MIN
Published: June 2006

The aim of this paper is to explore the efficiency and the benchmarks of financial holding companies (FHCs) for a small open economy, Taiwan. We employ a two-stage production process including profitability and marketability performance using a non-parametric frontier method — data envelopment analysis (DEA). Furthermore, the factor-specific measure and BCC (Banker–Charnes–Cooper) model are combined together not only to identify the inputs/outputs that are most important but also to distinguish those FHCs which can be treated as benchmarks. Our empirical result shows that (1) big-sized FHCs are generally more efficient than small-sized ones; (2) FHCs with the main body of insurance averagely perform better than the other two types (banks and securities); (3) while small efficient FHCs are easily to become benchmarks, big efficient FHCs are deemed as competitive niche players; (4) further mergers and acquisitions among FHCs should be considered so as to achieve economies of scale. The profitability/marketability matrix of FHCs is also presented.
AN ANALYTIC METHOD OF DESCRIBING R-RELATED QUANTITIES IN QCD
Authors: MILTON K. A. , SOLOVTSOV I. L. , SOLOVTSOVA O. P.
Published: June 2006

A model based on the analytic approach to QCD, involving a summation of threshold singularities and taking into account the nonperturbative character of the light quark masses, is applied to find hadronic contributions to different physical quantities. It is shown that the suggested model allows us to describe well such objects as the hadronic contribution to the anomalous magnetic moment of the muon, the ratio of hadronic to leptonic τ-decay widths in the vector channel, the Adler D-function, the smeared RΔ-function, and the hadronic contribution to the evolution of the fine structure constant.
MAXIMIZING WELFARE THROUGH COOPERATIVE NEGOTIATION IN A MULTI-AGENT INTERNET ECONOMY
Authors: DASGUPTA PRITHVIRAJ , MELLIAR-SMITH P. MICHAEL , MOSER LOUISE E.
Published: June 2006

E-commerce over the Internet has become an attractive means of conducting business in today's world. However, the principles of classical economics demand a fresh insight before they can be adapted to the market structure presented by the Internet. Here, we investigate markets for goods that are characterized by an experience-limited supply curve. We propose an algorithm that maximizes the welfare in the e-market by maximizing the combined profit of the buyers and sellers. For this, the buyers and sellers must reveal their value and cost curves to a trusted intermediary who can determine the transaction that maximizes their joint welfare. We show that accurate revelation of hidden profits offers better incentives, both to the buyers and the sellers, than inaccurate or incomplete revelation.
IDENTIFICATION OF RIVER WATER EXCESSIVE POLLUTION SOURCES
Authors: KACHIASHVILI K. J. , MELIKDZHANIAN D. I.
Published: June 2006

The program package for identification of river water excessive pollution sources located between two controlled cross-sections of the river is described in this paper. The software has been developed by the authors on the basis of mathematical models of pollutant transport in the rivers and statistical hypotheses checking methods. The identification algorithms were elaborated with the supposition that the pollution sources discharge different compositions of pollutants or (at the identical composition) different proportions of pollutants into the rivers.
SOCIO-ECONOMIC FACTORS AND THEIR INFLUENCE ON THE ADOPTION OF E-COMMERCE BY COMSUMERS IN SINGAPORE
Authors: SIYAL M. Y. , CHOWDHRY B. S. , RAJPUT A. Q.
Published: June 2006

For the past few years, a steady growth has been observed in the Internet-based commerce activities in Singapore and Asia-Pacific region. However, there has been very limited study that empirically investigates the socio-economic factors and their influence on the adoption of electronic commerce (e-commerce) by consumers in Singapore. This study seeks to fill some of the gaps in this area. Viewing such a medium as a form of new innovation, the five socio-economic characters namely gender, age, income level, education level and the exposure to the Internet were hypothesized to see whether there was any relationship between these five factors and the consumer's willingness to adopt e-commerce. The results indicate that income level; education level and exposure to the Internet were significant predictors in explaining the rate of adoption of e-commerce. However, contrary to general beliefs, this study showed that the gender and the age of consumers are not important factors for the adoption of e-commerce in Singapore. This study may help the e-merchants and policy makers to better understand consumer behavior and attitude towards e-commerce so that suitable changes can be made to make e-commerce more attractive and popular in Singapore and the Asia-Pacific region.
INFORMATION IN AN EIA PROCESS AND THE INFLUENCE THEREOF ON PUBLIC OPINION
Authors: PETERLIN MONIKA , KROSS BURTON C. , KONTIC BRANKO
Published: June 2006

Environmental issues can only be solved by coherent action at local, national and international levels, therefore understanding of the factors that influence the information exchange process is very important. The subject of investigation in this research is the influence of environmental information provided in the Environmental Impact Assessment (EIA) process on the level of knowledge concerning environmental issues in the local community. A survey of public opinion of the environmental impacts of the Port of Koper in Slovenia was performed.

Results show that respondents did not find the EIA presentations effective and received more information from TV, newspapers and radio. The EIA process did not fulfil its' potential, since respondents express the highest trust in expert information, but the effectiveness of the expert part of the presentation is considered to be low, not reaching the media. By improving the presentations effectiveness in the EIA process, further efforts in informing public and employees could theoretically bring the opinions of both groups to a similar level of understanding.
AN INTEGRATED MANAGEMENT APPROACH TO DESIGNING SUSTAINABLE BUILDINGS
Authors: HASSAN OSAMA A. B.
Published: June 2006

This article advances building sustainability theory by relating quality and environmental methodologies to building construction. The sustainability criteria and indicators are first defined and then linked to the integration problem. For designing for sustainability, widely-used methodologies, such as total quality management (TQM), life cycle analysis (LCA), life-cycle cost analysis (LCCA), value-focused thinking (VFT), benchmarking, and others are presented. Key concepts that contribute to sustainable building design and construction are found. These concepts are arranged by construction stages and activities, and the common areas for integration are discussed at the level of specific products and processes as well as at the construction company level.
WORKSHOP APPROACH TO DEVELOPING OBJECTIVES, TARGETS AND INDICATORS FOR USE IN SEA
Authors: DONNELLY ALISON , JENNINGS ELEANOR , MOONEY PETER , FINNAN JOHN , LYNN DEIRDRE , JONES MIKE , O'MAHONY TADHG , THÉRIVEL RIKI , BYRNE GERRY
Published: June 2006

Strategic Environmental Assessment (SEA) is the process through which the impacts of plans and programmes on the environment are assessed. Objectives, targets and indicators are the tools through which these environmental impacts can be measured. The same objectives, targets and indicators may be used for all planning levels but it is also necessary to identify additional plan specific ones. We used a workshop based approach to provide an interface between planners and environmental scientists and to give examples of objectives, targets and indicators for biodiversity, water, air and climatic factors, which could be used in SEA for national, regional and local plans. In addition, we highlight the need for careful consideration during the selection process of these variables which will result in a more rigorous and robust SEA. This is a challenging process but once completed will maximise resources and reduce the workload later in the SEA process.
IN IT TOGETHER: ORGANIZATIONAL LEARNING THROUGH PARTICIPATION IN ENVIRONMENTAL ASSESSMENT
Authors: FITZPATRICK PATRICIA
Published: June 2006

This research explores opportunities for organizational learning through participation in environmental assessment (EA). The study examines information sharing, information interpretation, organizational memory and learning outcomes of organizations involved in two concurrent but geographically separate EAs: the Wuskwatim generation station and transmission lines projects (Manitoba) and the Snap Lake project (Northwest Territories). Primary data collection included semi-structured interviews with EA participants, and a review of documentation generated through each EA. Data were analyzed based on criteria derived from organizational learning literature. Findings indicate that organizations have a variety of structures that facilitate learning. Learning outcomes by state actors emphasized "single-loop learning", activities designed to improve performance within the existing EA process. Public actors, however, identified a wider range of outcomes centred on changing the EA process, termed "double-loop learning". These learning outcomes provide invaluable information about strengthening project specific EA, and provide insight into improving resource management.
Characterization and regulation of the gene expression of amino acid transport system A (SNAT2) in rat mammary gland
Authors: López Adriana , Torres Nimbe , Ortiz Victor , Alemán Gabriela , Hernández-Pando Rogelio , Tovar Armando R.
Published: June 2006

Amino acid transport via system A plays an important role during lactation, promoting the uptake of small neutral amino acids, mainly alanine and glutamine. However, the regulation of gene expression of system A [sodium-coupled neutral amino acid transporter (SNAT)2] in mammary gland has not been studied. The aim of the present work was to understand the possible mechanisms of regulation of SNAT2 in the rat mammary gland. Incubation of gland explants in amino acid-free medium induced the expression of SNAT2, and this response was repressed by the presence of small neutral amino acids or by actinomycin D but not by large neutral or cationic amino acids. The half-life of SNAT2 mRNA was 67 min, indicating a rapid turnover. In addition, SNAT2 expression in the mammary gland was induced by forskolin and PMA, inducers of PKA and PKC signaling pathways, respectively. Inhibitors of PKA and PKC pathways partially prevented the upregulation of SNAT2 mRNA during adaptive regulation. Interestingly, SNAT2 mRNA was induced during pregnancy and to a lesser extent at peak lactation. β-Estradiol stimulated the expression of SNAT2 in mammary gland explants; this stimulation was prevented by the estrogen receptor inhibitor ICI-182780. Our findings clearly demonstrated that the SNAT2 gene is regulated by multiple pathways, indicating that the expression of this amino acid transport system is tightly controlled due to its importance for the mammary gland during pregnancy and lactation to prepare the gland for the transport of amino acids during lactation.
Laser-Doppler flowmetry reveals rapid perfusion changes in adipose tissue of lean and obese females
Authors: Wellhöner P. , Rolle D. , Lönnroth P. , Strindberg L. , Elam M. , Dodt C.
Published: June 2006

The present study aimed to evaluate adipose tissue blood flow (ATBF) by means of laser-Doppler flowmetry (LDF) in humans. Lower body negative pressure (LBNP) and straining known to affect epidermal blood flow through the autonomic nervous system were performed in 11 lean and 11 obese female volunteers. ATBF changes were compared between both groups and also discriminated from skin blood flow (SBF) responses of the immediate vicinity. Additionally, LDF measurements were compared with flow measurements using133xenon washout in 10 lean subjects during whole body cooling. LDF estimations of SBF and ATBF showed a positive correlation to133Xe during cooling. SBF and ATBF were reduced to the same extent in both lean and obese subjects during LBNP. Straining induced divergent changes in SBF and ATBF: initially SBF decreased while ATBF increased, but toward the end of straining SBF increased above baseline and ATBF returned down to baseline level. Those changes were similar in both weight groups. Interestingly, only in obese subjects, both LBNP and straining were followed by ATBF augmentation, while SBF levels remained stable. In conclusion, LDF compares with133Xe washout in monitoring ATBF during tonic perfusion changes. Its strength, however, lies in the detection of rapid flow alterations within the subcutaneous tissue, allowing the evaluation of reflex responses of the subcutaneous microcirculation. Interestingly, those rapid changes in SBF and ATBF can be both concordant and discordant. With regard to ATBF, vasoconstrictor components of the reflex responses were similar in lean and obese subjects, whereas vasodilatory responses were more pronounced in obese volunteers.
Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation
Authors: Shibata Eiji , Powers Robert W. , Rajakumar Augustine , von Versen-Höynck Frauke , Gallaher Marcia J. , Lykins David L. , Roberts James M. , Hubel Carl A.
Published: June 2006

Reduced transport of amino acids from mother to fetus can lead to fetal intrauterine growth restriction (IUGR). The activities of several amino acid transport systems, including system A, are decreased in placental syncytiotrophoblast of IUGR pregnancies. Na+-K+-ATPase activity provides an essential driving force for Na+-coupled system A transport, is decreased in the placenta of IUGR pregnancies, and is decreased by angiotensin II in several tissues. Several reports have shown activation of the fetoplacental renin-angiotensin system (RAS) in IUGR. We investigated the effect of angiotensin II on placental system A transport and Na+-K+-ATPase activity in placental villi. Placental system A activity in single primary villous fragments was measured as the Na+-dependent uptake of α-(methylamino)isobutyric acid, and Na+/K+ ATPase activity was measured as ouabain-sensitive uptake of 86rubidium. Angiotensin II decreased system A activity in a concentration-dependent fashion (10–500 nmol/l). Angiotensin II type 1 receptor (AT1-R) antagonists losartan and AT1-R anti-peptide blocked the angiotensin II effect, but the angiotensin II type 2 receptor antagonist PD-123319 was without effect. System A activity was not altered by preincubation with AT1-R-independent vasoconstrictors, and antioxidants did not prevent the decrease in activity mediated by angiotensin II. Angiotensin II decreased Na+-K+-ATPase activity by an AT1-R dependent mechanism, and inhibition of Na+-K+-ATPase activity decreased system A activity in a dose-response fashion. These data suggest that angiotensin II, via AT1-R signaling, decreases system A activity by suppressing Na+-K+-ATPase in human placental villi, consistent with possible adverse effects of enhanced placental RAS on fetal growth.
Long-lived αMUPA transgenic mice exhibit pronounced circadian rhythms
Authors: Froy Oren , Chapnik Nava , Miskin Ruth
Published: June 2006

Robust biological rhythms have been shown to affect life span. Biological clocks can be entrained by two feeding regimens, restricted feeding (RF) and caloric restriction (CR). RF restricts the time of food availability, whereas CR restricts the amount of calories with temporal food consumption. CR is known to retard aging and extend life span of animals via yet-unknown pathways. We hypothesize that resetting the biological clock could be one possible mechanism by which CR extends life span. Because it is experimentally difficult to uncouple calorie reduction from temporal food consumption, we took advantage of the murine urokinase-like plasminogen activator (αMUPA) transgenic mice overexpressing a serine protease implicated in brain development and plasticity; they exhibit spontaneously reduced eating and increased life span. Quantitative real-time PCR analysis revealed that αMUPA mice exhibit robust expression of the clock genes mPer1, mPer2, mClock, and mCry1 but not mBmal1 in the liver. We also found changes in the circadian amplitude and/or phase of clock-controlled output systems, such as feeding behavior, body temperature, and enteric cryptdin expression. A change in the light-dark regimen led to modified clock gene expression and abrogated circadian patterns of food intake in wild-type (WT) and αMUPA mice. Consequently, food consumption of WT mice increased, whereas that of αMUPA mice remained the same, indicating that reduced food intake occurs upstream and independently of the biological clock. Thus we surmise that CR could lead to pronounced and synchronized biological rhythms. Because the biological clock controls mitochondrial, hormonal, and physiological parameters, system synchronicity could lead to extended life span.
Dodecanedioic acid overcomes metabolic inflexibility in type 2 diabetic subjects
Authors: Salinari Serenella , Bertuzzi Alessandro , Gandolfi Alberto , Greco Aldo V. , Scarfone Antonino , Manco Melania , Mingrone Geltrude
Published: June 2006

Metabolically healthy skeletal muscle possesses the ability to switch easily between glucose and fat oxidation in response to homeostatic signals. In type 2 diabetes mellitus and obesity, the skeletal muscle shows a great reduction in this metabolic flexibility. A substrate like dodecanedioic acid (C-12), able to increase skeletal muscle glycogen stores via succinyl-CoA formation, might both postpone the fatigue and increase fatty acid utilization, since it does not affect insulin secretion. In healthy volunteers and in type 2 diabetic subjects, the effect of an oral C-12 load was compared with a glucose or water load during prolonged, moderate-intensity, physical exercise. C-12 metabolism was analyzed by a mathematical model. After C-12, diabetics were able to complete the 2 h of exercise. Nonesterified fatty acids increased both during and after the exercise in the C-12 session. C-12 oxidation provided 14% of total energy expenditure, and the sum of C-12 plus lipids oxidized after the C-12 meal was significantly greater than lipids oxidized after the glucose meal ( P < 0.025). The fraction of C-12 that entered the central compartment was 47% of that ingested. During the first phase of the exercise (∼60 min), the mean C-12 clearance from the central compartment toward tissues was 2.57 and 1.30 l/min during the second phase of the exercise. In conclusion, C-12 seems to be a suitable energy substrate during exercise, since it reduces muscle fatigue, is rapidly oxidized, and does not stimulate insulin secretion, which implies that lipolysis is not inhibited as reported after glucose ingestion.