bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycoplasma genitalium-Encoded MG309 Activates NF-κB via Toll-Like Receptors 2 and 6 To Elicit Proinflammatory Cytokine Secretion from Human Genital Epithelial Cells
Authors: McGowin Chris L. , Ma Liang , Martin David H. , Pyles Richard B.
Published: December 2008

Mycoplasma genitaliumhas been implicated in several important reproductive tract syndromes in women, including pelvic inflammatory disease, cervicitis, and tubal factor infertility. The mechanisms of immune activation are unclear, and we sought to determine whetherM. genitaliumwas capable of activating innate immune responses through ligation of highly expressed Toll-like receptors (TLR) of the genital tract. Using HEK293 cells expressing specific human TLR, viableM. genitaliumand the recombinant C-terminal portion of the immunogenic protein MG309 (rMG309c) were shown to activate NF-κB via TLR2/6. These data provided a putative mechanism for activation of the innate response in genital tissues. Genital epithelial cells (EC) are the first responders to sexually transmitted pathogens and express high levels of TLR2 and -6. Following exposure to purified rMG309c, vaginal and ecto- and endocervical EC secreted proinflammatory cytokines, including interleukin-6 (IL-6) and IL-8. Vaginal EC were less responsive than cervical EC. The capacity of rMG309c to bind TLR2/6 and elicit inflammation was sensitive to proteinase K digestion and independent of traditional N-terminal lipoylation. Furthermore, the immunostimulatory capacity of rMG309c was localized specifically to a 91-amino-acid subfragment of the recombinant protein, suggesting that TLR activation is likely amino acid based. Together, these data indicated that human vaginal and cervical EC are immunologically responsive toM. genitaliumand to purified rMG309c via highly expressed TLR of the genital tract. These findings provide valuable insights into the mechanisms for activation of acute-phase inflammatory responses and suggest thatM. genitaliumcolonization of reproductive tract tissues may result in inflammatory sequelae.
The H35A Mutated Alpha-Toxin Interferes with Cytotoxicity of Staphylococcal Alpha-Toxin
Authors: Liang Xudong , Yan Meiying , Ji Yinduo
Published: December 2008

Staphylococcal alpha-toxin is an important virulence factor for
Staphylococcus aureus
to cause severe infections. In this study, we explored whether the toxoid of alpha-toxin may be utilized to block the toxicity of wild-type alpha-toxin. We created a series of H35A mutated alpha-toxin expression strains and revealed that the H35A mutation eliminates the activity of alpha-toxin using a human lung epithelial cell line (A549). More importantly, we found that either the pretreatment or simultaneous treatment of the epithelial cells with alpha-toxin-H35A completely disrupted the cytotoxicity of alpha-toxin. Specifically, we demonstrated that alpha-toxin-H35A can effectively interfere with the pore formation and the internalization of alpha-toxin using cytotoxicity and immunofluorescence assays. In addition, we found that the removal of either the 30-amino-acid (aa) or 99-aa C-terminal region of alpha-toxin-H35A reactivated its cytotoxicity, indicating that interactions between the alanine residue at position 35 and these C-terminal regions may be associated with interrupting the toxic activity of alpha-toxin-H35A. Taken together, these results suggest that the alpha-toxin-H35A protein may be developed as a potential alternative therapeutic agent for treating early stages of
S. aureus
infections.
Role of Melanin Pigment in Expression of
Vibrio cholerae
Virulence Factors
Authors: Valeru Soni Priya , Rompikuntal Pramod Kumar , Ishikawa Takahiko , Vaitkevicius Karolis , Sjöling Åsa , Dolganov Nadia , Zhu Jun , Schoolnik Gary , Wai Sun Nyunt
Published: December 2008

We identified the mutated gene locus in a pigment-overproducing
Vibrio cholerae
mutant of strain A1552. The deduced gene product is suggested to be an oxidoreductase based on partial homology to putative homogentisate 1,2-dioxygenase in
Pseudomonas aeruginosa
and
Mesorhizobium loti
, and we propose that the gene VC1345 in the
V. cholerae
genome be denoted
hmgA
in accordance with the nomenclature for other species. The
hmgA
::mini-Tn
5
mutant showed a nonpigmented phenotype after complementation with a plasmid clone carrying the WT
hmgA
+
locus. Microarray transcription analysis revealed that expression of
hmgA
and the neighboring genes encoding a postulated two-component sensor system was growth phase dependent. Results from quantitative reverse transcription-PCR analysis showed that
hmgA
operon expression was reduced in the
rpoS
mutant, but pigment production by the WT
V. cholerae
or the
hmgA
mutant was not detectably influenced by the stationary-phase regulator RpoS. The pigmented mutant showed increased UV resistance in comparison with the WT strain. Interestingly, the pigment-producing mutant expressed more toxin-coregulated pilus and cholera toxin than WT
V. cholerae
. Moreover, the
hmgA
mutant showed a fivefold increase in the ability to colonize the intestines of infant mice. A possible mechanism by which pigment production might cause induction of the ToxR regulon due to generation of hydrogen peroxide was supported by results from tests showing that externally supplied H
2
O
2
led to higher TcpA levels. Taken together, our findings suggest that melanin pigment formation may play a role in
V. cholerae
virulence factor expression.
TheYersinia pestis caf1M1A1Fimbrial Capsule Operon Promotes Transmission by Flea Bite in a Mouse Model of Bubonic Plague
Authors: Sebbane Florent , Jarrett Clayton , Gardner Donald , Long Daniel , Hinnebusch B. Joseph
Published: December 2008

Plague is a zoonosis transmitted by fleas and caused by the gram-negative bacteriumYersinia pestis. During infection, the plasmidiccaf1M1A1operon that encodes theY. pestisF1 protein capsule is highly expressed, and anti-F1 antibodies are protective. Surprisingly, the capsule is not required for virulence after injection of cultured bacteria, even though it is an antiphagocytic factor and capsule-deficientY. pestisstrains are rarely isolated. We found that acaf-negativeY. pestismutant was not impaired in either flea colonization or virulence in mice after intradermal inoculation of cultured bacteria. In contrast, absence of thecafoperon decreased bubonic plague incidence after a flea bite. Successful development of plague in mice infected by flea bite with thecaf-negative mutant required a higher number of infective bites per challenge. In addition, the mutant displayed a highly autoaggregative phenotype in infected liver and spleen. The results suggest that acquisition of thecaflocus via horizontal transfer by an ancestralY. pestisstrain increased transmissibility and the potential for epidemic spread. In addition, our data support a model in which atypicalcaf-negative strains could emerge during climatic conditions that favor a high flea burden. Human infection with such strains would not be diagnosed by the standard clinical tests that detect F1 antibody or antigen, suggesting that more comprehensive surveillance for atypicalY. pestisstrains in plague foci may be necessary. The results also highlight the importance of studyingY. pestispathogenesis in the natural context of arthropod-borne transmission.
Defects in Innate Immunity Predispose C57BL/6J-Leprdb/LeprdbMice to Infection byStaphylococcus aureus
Authors: Park Sunny , Rich Jeremy , Hanses Frank , Lee Jean C.
Published: December 2008

Foot and ankle infections are the most common cause of hospitalization among diabetic patients, andStaphylococcus aureusis a major pathogen implicated in these infections. Patients with insulin-resistant (type 2) diabetes are more susceptible to bacterial infections than nondiabetic subjects, but the pathogenesis of these infections is poorly understood. C57BL/6J-Leprdb/Leprdb(hereafter,db/db) mice develop type 2 diabetes due to a recessive, autosomal mutation in the leptin receptor. We established aS. aureushind paw infection in diabeticdb/dband nondiabeticLepr+/+(+/+) mice to investigate host factors that predispose diabetic mice to infection. Nondiabetic +/+ mice resolved theS. aureushind paw infection within 10 days, whereasdb/dbmice with persistent hyperglycemia developed a chronic infection associated with a high bacterial burden. Diabeticdb/dbmice showed a more robust neutrophil infiltration to the infection site and higher levels of chemokines in the infected tissue than +/+ mice. Blood from +/+ mice killedS. aureusin vitro, whereasdb/dbblood was defective in bacterial killing. Compared with peripheral blood neutrophils from +/+ mice,db/dbneutrophils demonstrated a diminished respiratory burst when stimulated withS. aureus. However, bone marrow-derived neutrophils from +/+ anddb/dbmice showed comparable phagocytosis and bactericidal activity. Our results indicate that diabeticdb/dbmice are more susceptible to staphylococcal infection than their nondiabetic littermates and that persistent hyperglycemia modulates innate immunity in the diabetic host.
GbdR Regulates
Pseudomonas aeruginosa plcH
and
pchP
Transcription in Response to Choline Catabolites
Authors: Wargo Matthew J. , Ho Tiffany C. , Gross Maegan J. , Whittaker Laurie A. , Hogan Deborah A.
Published: December 2008

Pseudomonas aeruginosa
hemolytic phospholipase C, PlcH, can degrade phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and extracellular PC in lung surfactant. Numerous studies implicate PlcH in
P. aeruginosa
virulence. The phosphorylcholine released by PlcH activity on phospholipids is hydrolyzed by a periplasmic phosphorylcholine phosphatase, PchP. Both
plcH
gene expression and PchP enzyme activity are positively regulated by phosphorylcholine degradation products, including glycine betaine. Here we report that the induction of
plcH
and
pchP
transcription by glycine betaine is mediated by GbdR, an AraC family transcription factor. Mutants that lack
gbdR
are unable to induce
plcH
and
pchP
in media containing glycine betaine or choline and in phosphatidylcholine-rich environments, such as lung surfactant or mouse lung lavage fluid. In T broth containing choline, the
gbdR
mutant exhibited a 95% reduction in PlcH activity. In electrophoretic mobility shift assays, a GbdR-maltose binding protein fusion bound specifically to both the
plcH
and
pchP
promoters. Promoter mapping, alignment of GbdR-regulated promoter sequences, and analysis of targeted promoter mutants that lack GbdR-dependent induction of transcription were used to identify a region necessary for GbdR-dependent transcriptional activation. GbdR also plays a significant role in
plcH
and
pchP
regulation within the mouse lung. Our studies suggest that GbdR is the primary regulator of
plcH
and
pchP
expression in PC-rich environments, such as the lung, and that
pchP
and other genes involved in phosphorylcholine catabolism are necessary to stimulate the GbdR-mediated positive feedback induction of
plcH
.
Role of Neutrophils in Response toBordetella pertussisInfection in Mice
Authors: Andreasen Charlotte , Carbonetti Nicholas H.
Published: December 2008

Pertussis is an acute respiratory disease caused by the bacteriumBordetella pertussis, for which humans are the only known reservoir. During infection,B. pertussisreleases several toxins, including pertussis toxin (PT) and adenylate cyclase toxin (ACT), which have both been shown to play roles in promoting bacterial growth during early infection in a mouse model. Furthermore, in vitro and in vivo studies suggest that PT and ACT affect neutrophil chemotaxis and/or function, thereby altering the innate immune response. In this study we depleted animals of neutrophils to investigate whether neutrophils play a protective role duringB. pertussisinfection in mice. In addition, by infection with toxin-deficient strains, we investigated whether neutrophils are the main targets for PT and/or ACT activity in promoting bacterial growth. Surprisingly, we found no role for neutrophils duringB. pertussisinfection in naïve mice. However, in previously infected (immune) mice or in mice receiving immune serum, we observed a significant role for neutrophils during infection. Furthermore, in this immune mouse model our evidence indicates that neutrophils appear to be the main target cells for ACT, but not for PT.
Proinflammatory Response of Human Osteoblastic Cell Lines and Osteoblast-Monocyte Interaction upon Infection withBrucellaspp
Authors: Delpino M. Victoria , Fossati Carlos A. , Baldi Pablo C.
Published: December 2008

The ability ofBrucellaspp. to infect human osteoblasts and the cytokine response of these cells to infection were investigated in vitro.Brucella abortus, B. suis, B. melitensis, andB. caniswere able to infect the SaOS-2 and MG-63 osteoblastic cell lines, and the first three species exhibited intracellular replication.B. abortusinternalization was not significantly affected by pretreatment of cells with cytochalasin D but was inhibited up to 92% by colchicine. AvirB10mutant ofB. abortuscould infect but not replicate within osteoblasts, suggesting a role for the type IV secretion system in intracellular survival. Infected osteoblasts produced low levels of chemokines (interleukin-8 [IL-8] and macrophage chemoattractant protein 1 [MCP-1]) and did not produce proinflammatory cytokines (IL-1β, IL-6, and tumor necrosis factor alpha [TNF-α]). However, osteoblasts stimulated with culture supernatants fromBrucella-infected human monocytes (THP-1 cell line) produced chemokines at levels 12-fold (MCP-1) to 17-fold (IL-8) higher than those of infected osteoblasts and also produced IL-6. In the inverse experiment, culture supernatants fromBrucella-infected osteoblasts induced the production of IL-8, IL-1β, IL-6, and TNF-α by THP-1 cells. The induction of TNF-α and IL-1β was largely due to granulocyte-macrophage colony-stimulating factor produced by infected osteoblasts, as demonstrated by inhibition with a specific neutralizing antibody. This study shows thatBrucellacan invade and replicate within human osteoblastic cell lines, which can directly and indirectly mount a proinflammatory response. Both phenomena may have a role in the chronic inflammation and bone and joint destruction observed in osteoarticular brucellosis.
Retentive Memory of Bacteria: Long-Term Regulation of Dehalorespiration in
Sulfurospirillum multivorans
Authors: John Markus , Rubick Raffael , Schmitz Roland P. H. , Rakoczy Jana , Schubert Torsten , Diekert Gabriele
Published: December 2008

The gram-negative, strictly anaerobic epsilonproteobacterium
Sulfurospirillum multivorans
is able to gain energy from dehalorespiration with tetrachloroethene (perchloroethylene [PCE]) as a terminal electron acceptor. The organism can also utilize fumarate as an electron acceptor. Prolonged subcultivation of
S. multivorans
in the absence of PCE with pyruvate as an electron donor and fumarate as an electron acceptor resulted in a decrease of PCE dehalogenase (PceA) activity. Concomitantly, the
pceA
transcript level equally decreased as shown by reverse transcriptase PCR. After 35 subcultivations (approximately 105 generations), a
pceA
transcript was not detectable and the PceA protein and activity were completely absent. In such long-term subcultivated
S. multivorans
cells, the biosynthesis of catalytically active PceA was restored to the initial level within about 50 h (approximately three generations) by the addition of PCE or trichloroethene. Single colonies obtained from PceA-depleted cultures were able to induce PCE dechlorination, indicating that long-term subcultured cells still contained the functional
pceA
gene. The results point to a novel type of long-term regulation of PCE dehalogenase gene expression in
S. multivorans
.
Allosteric Coupling between the Lid and Interdomain Linker in DnaK Revealed by Inhibitor Binding Studies
Authors: Liebscher Markus , Roujeinikova Anna
Published: December 2008

The molecular chaperone DnaK assists protein folding and refolding, translocation across membranes, and regulation of the heat shock response. InEscherichia coli, the protein is a target for insect-derived antimicrobial peptides, pyrrhocoricins. We present here the X-ray crystallographic analysis of theE. coliDnaK substrate-binding domain in complex with pyrrhocoricin-derived peptide inhibitors. The structures show that pyrrhocoricins act as site-specific, dual-mode (competitive and allosteric) inhibitors, occupying the substrate-binding tunnel and disrupting the latch between the lid and the β-sandwich. Our structural analysis revealed an allosteric coupling between the movements of the lid and the interdomain linker, identifying a previously unknown mechanism of the lid-mediated regulation of the chaperone cycle.
Bacteriocin Activity of
Streptococcus pneumoniae
Is Controlled by the Serine Protease HtrA via Posttranscriptional Regulation
Authors: Dawid Suzanne , Sebert Michael E. , Weiser Jeffrey N.
Published: December 2008

The
blp
locus of a type 6A strain of
Streptococcus pneumoniae
encodes a two-peptide bacteriocin, pneumocin MN, which mediates intraspecies competition during mouse nasopharyngeal colonization. This locus is regulated by a quorum-sensing mechanism consisting of a dedicated two-component regulatory system and a peptide pheromone. Like most clinical isolates, this type 6A strain can be separated into opaque and transparent colony variants, each playing a different role during pneumococcal infection. In this study, we show that the
blp
locus is differentially regulated at the posttranscriptional level in pneumococcal opacity variants. Transparent and opaque variants produce equivalent amounts of
blpMNPO
transcript when stimulated with a synthetic pheromone, but transparent variants have no pneumocin MN-mediated inhibitory activity while opaque variants produce large zones of inhibitory activity. The differential regulation in opacity variants is driven by the two-component regulatory system CiaRH via its regulation of the serine protease HtrA. Transparent mutants deficient in CiaH or HtrA show increased pneumocin MN-mediated inhibition. In addition, these mutants demonstrate alterations in their dose response to a synthetic peptide pheromone, suggesting that HtrA activity impacts pneumocin MN production at the level of signaling. This, in addition to its known effects on competence, suggests that HtrA is a pleiotropic regulator whose protease activity affects several important bacterial pathways. The complex regulation of pneumocins may allow the pneumococcus to reserve the secretion of active peptides for situations where the benefit of their inhibitory activity outweighs the cost of their production.
Identification of a Divided Genome for VSH-1, the Prophage-Like Gene Transfer Agent of
Brachyspira hyodysenteriae
Authors: Stanton Thaddeus B. , Humphrey Samuel B. , Bayles Darrell O. , Zuerner Richard L.
Published: December 2008

The
Brachyspira hyodysenteriae
B204 genome sequence revealed three VSH-1 tail genes,
hvp31
,
hvp60
, and
hvp37
, in a 3.6-kb cluster. The location and transcription direction of these genes relative to those of the previously described VSH-1 16.3-kb gene operon indicate that the gene transfer agent VSH-1 has a noncontiguous, divided genome.
A
Campylobacter jejuni znuA
Orthologue Is Essential for Growth in Low-Zinc Environments and Chick Colonization
Authors: Davis Lindsay M. , Kakuda Tsutomu , DiRita Victor J.
Published: December 2008

Campylobacter jejuni
infection is a leading cause of bacterial gastroenteritis in the United States and is acquired primarily through the ingestion of contaminated poultry products. Here, we describe the
C. jejuni
orthologue of ZnuA in other gram-negative bacteria. ZnuA (Cj0143c) is the periplasmic component of a putative zinc ABC transport system and is encoded on a zinc-dependent operon with Cj0142c and Cj0141c, which encode the other two likely components of the transport system of
C. jejuni
. Transcription of these genes is zinc dependent. A mutant lacking Cj0143c is growth deficient in zinc-limiting media, as well as in the chick gastrointestinal tract. The protein is glycosylated at asparagine 28, but this modification is dispensable for zinc-limited growth and chick colonization. Affinity-purified FLAG-tagged Cj0143c binds zinc in vitro. Based on our findings and on its homology to
E. coli
ZnuA, we conclude that Cj0143c encodes the
C. jejuni
orthologue of ZnuA.
Hypomodification of the Wobble Base in tRNA
Glu
, tRNA
Lys
, and tRNA
Gln
Suppresses the Temperature-Sensitive Phenotype Caused by Mutant Release Factor 1
Authors: Isak Georgina , Rydén-Aulin Monica
Published: December 2008

In
Escherichia coli
, release factor 1 (RF1) is one of two RFs that mediate termination; it specifically recognizes UAA and UAG stop codons. A mutant allele,
prfA1
, coding for an RF1 that causes temperature-sensitive (Ts) growth at 42°C, was used to select for temperature-resistant (Ts
+
) suppressors. This study describes one such suppressor that is the result of an IS
10
insertion into the
cysB
gene, giving a Cys
−
phenotype. CysB is a transcription factor regulating the
cys
regulon, mainly as an activator, which explains the Cys
−
phenotype. We have found that suppression is a consequence of the lost ability to donate sulfur to enzymes involved in the synthesis of thiolated nucleosides. From genetic analyses we conclude that it is the lack of the 5-methylaminomethyl-2-thiouridine (mnm
5
s
2
U) modification of the wobble base of tRNA
Glu
, tRNA
Lys
, and/or tRNA
Gln
that causes the suppressor phenotype.
Comparative Proteomic Analysis of the
Haemophilus ducreyi
Porin-Deficient Mutant 35000HP::P2AB
Authors: Davie Jeremiah J. , Campagnari Anthony A.
Published: December 2008

Haemophilus ducreyi
is an obligate human pathogen and the causative agent of the sexually transmitted, genital ulcerative disease chancroid. The genome of strain 35000HP contains two known porin proteins, OmpP2A and OmpP2B. Loss of OmpP2A and OmpP2B expression in the mutant 35000HP::P2AB resulted in no obvious growth defect or phenotype. Comparison of outer membrane profiles indicated increased expression of the 58.5-kDa chaperone, GroEL, in the porin-deficient mutant. A proteomics-based comparison resulted in the identification of 231 proteins present in membrane-associated protein samples, of which a subset of 56 proteins was differentially expressed at a level of 1.5-fold or greater in the porin-deficient strain 35000HP::P2AB relative to that in 35000HP. Twenty of the differentially expressed proteins were selected for real-time PCR, resulting in the validation of 90% of the selected subgroup. Proteins identified in these studies suggested a decreased membrane stability phenotype, which was verified by disk diffusion assay. Loss of OmpP2A and OmpP2B resulted in global protein expression changes which appear to compensate for the absence of porin expression in 35000HP::P2AB.
sarZ
, a
sarA
Family Gene, Is Transcriptionally Activated by MgrA and Is Involved in the Regulation of Genes Encoding Exoproteins in
Staphylococcus aureus
Authors: Ballal Anand , Ray Binata , Manna Adhar C.
Published: December 2008

The expression of genes involved in the pathogenesis of
Staphylococcus aureus
is controlled by global regulatory loci, including two-component regulatory systems and transcriptional regulators (e.g.,
sar
family genes). Most members of the SarA family have been partially characterized and shown to regulate a large numbers of target genes. Here, we describe the characterization of
sarZ
, a
sarA
paralog from
S. aureus
, and its regulatory relationship with other members of its family. Expression of
sarZ
was growth phase dependent with maximal expression in the early exponential phase of growth. Transcription of
sarZ
was reduced in an
mgrA
mutant and returned to a normal level in a complemented
mgrA
mutant strain, which suggests that
mgrA
acts as an activator of
sarZ
transcription. Purified MgrA protein bound to the
sarZ
promoter region, as determined by gel shift assays. Among the
sarA
family of genes analyzed, inactivation of
sarZ
increased
sarS
transcription, while it decreased
agr
transcription. The expression of potential target genes involved in virulence was evaluated in single and double mutants of
sarZ
with
mgrA
,
sarX
, and
agr
. Northern and zymogram analyses indicated that the
sarZ
gene product played a role in regulating several virulence genes, particularly those encoding exoproteins. Gel shift assays demonstrated nonspecific binding of purified SarZ protein to the promoter regions of the
sarZ
-regulated target genes. These results demonstrate the important role played by SarZ in controlling regulatory and virulence gene expression in
S. aureus
.
Conditional Essentiality of thecsrAGene inEscherichia coli
Authors: Timmermans Johan , Van Melderen Laurence
Published: December 2008

CsrA is a global posttranscriptional regulator of numerous physiological processes, such as glycogenesis and glycolysis. Here, we show that thecsrAgene ofEscherichia coliis essential for growth on LB and on synthetic medium containing glycolytic carbon sources. However,csrAis not necessary for growth on synthetic medium containing pyruvate, showing that the Krebs cycle is functional in thecsrA::catdeletion mutant. Deletion of theglgCAPoperon in thecsrA::catmutant restored the ability to grow on LB and on synthetic medium containing glycolytic carbon sources, showing that growth inhibition is due to an excess of glycogen synthesis.
The relationship between local clean indoor air policies and smoking behaviours in Minnesota youth
Authors: Klein E G , Forster J L , Erickson D J , Lytle L A , Schillo B
Published: December 2008

Background:

While clean indoor air (CIA) policies are intended to reduce exposure to second-hand smoke in the workplace, restrictions in public workplaces have the potential to discourage youth smoking. There is growing evidence from cross-sectional and ecological studies, but limited evidence from longitudinal studies that this is so.

Objective:

To evaluate the association between local CIA policies and smoking behaviours among Minnesota youth over time.

Design, setting and subjects:

A cohort of 4233 Minnesota youths, ages 11 to 16 at baseline, was interviewed via telephone for 6 years (2000–2006). Individual, family and community level variables were collected from participants every 6 months. A generalised estimating equation (GEE) logistic regression was used to assess the relationship between CIA policies and past-month smoking in youth over time. The analysis was controlled for potential confounders at individual and community levels.

Results:

There was not significant association between CIA policies and youth smoking behaviours in the multivariate analyses. At the individual level, parental smoking significantly increased the odds of smoking nearly 40% and close friend smoking increased the odds of past-month smoking by nearly 100% for each close friend. Banning smoking in the home was significantly associated with a 12% reduction in the odds of past-month smoking.

Conclusion:

After accounting for other community and individual level factors known to be associated with youth smoking, there was no significant association between CIA policies and past-month smoking for youth over time.
ON IMPROVED HOMOGENEOUS BALANCE METHOD, AUTO-BÄCKLUND TRANSFORMATION AND MULTI-SOLITONIC SOLUTIONS OF A VARIABLE-COEFFICIENT BURGERS EQUATION
Authors: SABRY R.
Published: December 2008

An improved homogeneous balance (IHB) method is introduced. On using the IHB method, a new auto-Bäcklund transformation and multi-solitonic solutions were obtained for a generalized variable-coefficient Burgers equation. The obtained solitary waves were found to propagate with a variable propagating speed which depends on the coefficients of the studied model. Also, fusion of two single solitary waves into a one-resonant solitary wave is pointed out.
A PARALLEL THERMAL LATTICE BOLTZMANN MODEL WITH FLUX LIMITERS FOR MICROSCALE FLOW
Authors: BOTTI M. , GONNELLA G. , LAMURA A. , MASSAIOLI F. , SOFONEA V.
Published: December 2008

We propose a thermal lattice Boltzmann model to study gaseous flow in microcavities. The model relies on the use of a finite difference scheme to solve the set of evolution equations. By adopting diffuse reflection boundary conditions to deal with flows in the slip regime, we study the micro-Couette flow in order to select the best numerical scheme in terms of accuracy. The scheme based on flux limiters is then used to simulate a micro-lid-driven cavity flow by using an efficient and parallel implementation. The numerical results are in very good agreement with the available results recovered with different methods.
DEGREE AND WEIGHTED PROPERTIES OF THE DIRECTED CHINA RAILWAY NETWORK
Authors: GUO LONG , CAI XU
Published: December 2008

As well known, many real complex systems are directed and weighted ones. For understanding the topology structure of the directed China Railway Network (CRN) further, we analyze the degree properties of the directed CRN and propose a new method to measure the weight of station (i.e., the utilized efficiency of station) in CRN according to how CRN works really. Rigorous analysis of the existing CRN data shows that the CRN is an assortative network with scale-free degree distribution in space L. On the other hand, the cumulative distribution of station's relative weight, the cumulative distribution of the shortest path length between stations, and the relationship between relative weight and in-(out-)degree have been studied. Our present work provides a new perspective to define the weight of transport complex network, which will be helpful for studying the dynamics of CRN.
A POSTERIORI TESTS OF ONE-EQUATION LES MODELING OF ROTATING TURBULENCE
Authors: LU HAO , RUTLAND CHRISTOPHER J. , SMITH LESLIE M.
Published: December 2008

Eight subgrid-scale (SGS) models were evaluated using two flow configurations: homogeneous decaying turbulence, and rotating turbulence forced at large or intermediate scales. Testing was performed for the first configuration through a systematic comparison between direct numerical simulation results and large eddy simulation results of many characteristics, including resolved kinetic energy, SGS energy production, molecular dissipation, and kinetic energy spectrum. The new models, which are based on dynamic structure model and satisfy the consistency of material frame indifference with the SGS stress, showed more accurate results than traditional models. In the forced testing, the new models were better able to capture essential features of rotating turbulence, including cyclonic/anti-cyclonic asymmetry, quasi-2D at large scales, and reverse kinetic energy transfer from small to large scales.
THE MULTISCALE VTCR APPROACH APPLIED TO ACOUSTICS PROBLEMS
Authors: RIOU HERVÉ , LADEVEZE PIERRE , SOURCIS BENJAMIN
Published: December 2008

An approach, called the "Variational Theory of Complex Rays," was proposed recently for calculating the vibrations of slightly damped elastic structures in the medium-frequency range. One key feature of this approach is the use of a new variational formulation of the vibration problem which allows the shape functions to be discontinuous across element boundaries, thus giving this strategy great flexibility and robustness. This method was fully developed for structural vibrations. In this paper, we apply it to acoustics problems. Examples of two-dimensional Helmholtz problems show that this method is very robust and accurate yet requires much less computational effort than the finite element method, which enables one to use it up to much higher frequencies.
DFT MODAL ANALYSIS OF SPECTRAL ELEMENT METHODS FOR ACOUSTIC WAVE PROPAGATION
Authors: SERIANI GÉZA , OLIVEIRA SAULO POMPONET
Published: December 2008

Spectral element methods are now widely used for wave propagation simulations. They are appreciated for their high order of accuracy, but are still used on a heuristic basis. In this work we present the numerical dispersion of spectral elements, which allows us to assess their error limits and to devise efficient numerical simulations, particularly for 2D and 3D problems. We propose a novel approach based on a discrete Fourier transform of both the probing plane waves and the discrete wave operators. The underlying dispersion relation is estimated by the Rayleigh quotients of the plane waves with respect to the discrete operator. Together with the Kronecker product properties, this approach delivers numerical dispersion estimates for 1D operators as well as for 2D and 3D operators, and is well suited for spectral element methods, which use nonequidistant collocation points such as Gauss–Lobatto–Chebyshev and Gauss–Lobatto–Legendre points. We illustrate this methodology with dispersion and anisotropy graphs for spectral elements with polynomial degrees from 4 to 12. These graphs confirm the rule of thumb that spectral element methods reach a safe level of accuracy at about four grid points per wavelength.
A FOURTH-ORDER ACCURATE SCHEME FOR SOLVING ONE-DIMENSIONAL HIGHLY NONLINEAR STANDING WAVE EQUATION IN DIFFERENT THERMOVISCOUS FLUIDS
Authors: NABAVI MAJID , SIDDIQUI M. H. KAMRAN , DARGAHI JAVAD
Published: December 2008

Combination of a fourth-order Padé compact finite difference discretization in space and a fourth-order Runge–Kutta time stepping scheme is shown to yield an effective method for solving highly nonlinear standing waves in a thermoviscous medium. This accurate and fast-solver numerical scheme can predict the pressure, particle velocity, and density along the standing wave resonator filled with a thermoviscous fluid from linear to strongly nonlinear levels of the excitation amplitude. The stability analysis is performed to determine the stability region of the scheme. Beside the fourth-order accuracy in both time and space, another advantage of the given numerical scheme is that no additional attenuation is required to get numerical stability. As it is well known, the results show that the pressure and particle velocity waveforms for highly nonlinear waves are significantly different from that of the linear waves, in both time and space. For highly nonlinear waves, the results also indicate the presence of a wavefront that travels along the resonator with very high pressure and velocity gradients. Two gases, air and CO 2, are considered. It is observed that the slopes of the traveling velocity and pressure gradients are higher for CO 2 than those for air. For highly nonlinear waves, the results also indicate the higher asymmetry in pressure for CO 2 than that for air.
Use of municipal solid waste incinerator bottom ash as aggregate in concrete
Authors: Rübner K. , Haamkens F. , Linde O.
Published: December 2008

As a result of their chemical and mineralogical characteristics, bottom ashes from municipal solid waste incinerators can, in principle, be used as aggregates in the production of normal strength concrete. However, because the ashes contain concrete-damaging components, such as chlorides, sulphates and organic compounds, or excessive quantities of fines, aluminium and waste glass, recycling becomes problematic. In particular, inclusions of aluminium in the ash particles and a glass content of about 15% cause considerable cracks and spalling in concrete specimens within a very short time. The harmful substances can be reduced or removed by additional treatments, such as upstream sieving and washing, waste glass separation, and lye treatment with sodium hydroxide solution. Tests on concretes with 2–32 mm bottom ash as coarse aggregates indicate that the quality of the ash is actually improved by the additional processing. Thus concretes with a compressive strength of C20/25 can easily be produced. Similar to concretes made with recycled aggregates, these concretes exhibit 15% lower compressive strength and E-modulus but twice the porosity of control specimens containing exclusively natural sand and gravel. However, only those concretes that were made with ash with a low aluminium content as a result of lye treatment remained free of damage.
Groundwater flow in the South Wales coalfield: historical data informing 3D modelling
Authors: Robins N.S. , Davies J. , Dumpleton S.
Published: December 2008

The South Wales Coalfield is structurally and lithologically complex. Attempts to understand the regional groundwater flow system have been largely piecemeal, focusing on single collieries or groups of collieries. Inspection of both historical data, gathered during the active mine dewatering phase of the coalfield, and of contemporary post-mining groundwater rebound data, allows a picture of the whole groundwater flow system to be derived, along with the regional water balance. The assessment is aided by application of a 3D visualization model of the geological framework, which includes the piezometry during and after the mining phase and pumping and yield data. Other valuable historical information, which can no longer be replicated, are the analyses of samples of groundwater that entered working mines from specified horizons, rather than present-day analyses of acid mine drainage. It is found that there is little deep regional groundwater flow across the basin, for example towards the sea, and most groundwater flow is of river catchment scale draining to the main rivers that traverse the coalfield. This analysis of the coalfield and the 3D model provide a foundation for future investigation into issues such as dewatering of new opencast pits,
in situ
gasification or anthracite mining.
Groundwater recharge to a fractured limestone aquifer overlain by glacial till in County Monaghan, Ireland
Authors: Misstear B.D.R. , Brown L. , Williams N. Hunter
Published: December 2008

Obstractions from the Knockatallon aquifer in County Monaghan, Ireland, caused groundwater levels to fall substantially over a 20 year period. The aquifer consists of two formations of fractured limestone and other Carboniferous rocks. The aquifer is overlain by up to 53 m of low-permeability glacial tills. The presence of this overburden inhibits direct recharge to the aquifer. Recharge was investigated using a combination of approaches: soil moisture budget, water balance, environmental tracers, through flow analysis and river baseflow analysis. The study showed that the proportion of effective rainfall that replenishes the aquifer as direct recharge through the till is very low (less than 5%), and thus that the presence of the till has a major impact on recharge. The study also highlighted the importance of applying several approaches when trying to quantify recharge, as any single approach on its own is unlikely to give satisfactory results.
Sound and complete relevance assessment for XML retrieval
Authors: Piwowarski Benjamin , Trotman Andrew , Lalmas Mounia
Published: December 2008

In information retrieval research, comparing retrieval approaches requires test collections consisting of documents, user requests and relevance assessments. Obtaining relevance assessments that are as sound and complete as possible is crucial for the comparison of retrieval approaches. In XML retrieval, the problem of obtaining sound and complete relevance assessments is further complicated by the structural relationships between retrieval results.

A major difference between XML retrieval and flat document retrieval is that the relevance of elements (the retrievable units) is not independent of that of related elements. This has major consequences for the gathering of relevance assessments. This article describes investigations into the creation of sound and complete relevance assessments for the evaluation of content-oriented XML retrieval as carried out at INEX, the evaluation campaign for XML retrieval. The campaign, now in its seventh year, has had three substantially different approaches to gather assessments and has finally settled on a highlighting method for marking relevant passages within documents—even though the objective is to collect assessments at element level. The different methods of gathering assessments at INEX are discussed and contrasted. The highlighting method is shown to be the most reliable of the methods.
Trusting spam reporters
Authors: Zheleva Elena , Kolcz Aleksander , Getoor Lise
Published: December 2008

Spam is a growing problem; it interferes with valid email and burdens both email users and service providers. In this work, we propose a reactive spam-filtering system based on reporter reputation for use in conjunction with existing spam-filtering techniques. The system has a trust-maintenance component for users, based on their spam-reporting behavior. The challenge that we consider is that of maintaining a reliable system, not vulnerable to malicious users, that will provide early spam-campaign detection to reduce the costs incurred by users and systems. We report on the utility of a reputation system for spam filtering that makes use of the feedback of trustworthy users. We evaluate our proposed framework, using actual complaint feedback from a large population of users, and validate its spam-filtering performance on a collection of real email traffic over several weeks. To test the broader implication of the system, we create a model of the behavior of malicious reporters, and we simulate the system under various assumptions using a synthetic dataset.
Extended probabilistic HAL with close temporal association for psychiatric query document retrieval
Authors: Yeh Jui-Feng , Wu Chung-Hsien , Yu Liang-Chih , Lai Yu-Sheng
Published: December 2008

Psychiatric query document retrieval can assist individuals to locate query documents relevant to their depression-related problems efficiently and effectively. By referring to relevant documents, individuals can understand how to alleviate their depression-related symptoms according to recommendations from health professionals. This work presents an extended probabilistic
Hyperspace Analog to Language
(
epHAL
) model to achieve this aim. The epHAL incorporates the close temporal associations between words in query documents to represent word cooccurrence relationships in a high-dimensional context space. The information flow mechanism further combines the query words in the epHAL space to infer related words for effective information retrieval. The language model perplexity is considered as the criterion for model optimization. Finally, the epHAL is adopted for psychiatric query document retrieval, and indicates its superiority in information retrieval over traditional approaches.
combinFormation
Authors: Kerne Andruid , Koh Eunyee , Smith Steven M. , Webb Andrew , Dworaczyk Blake
Published: December 2008

combinFormation is a mixed-initiative creativity support tool for searching, browsing, organizing, and integrating information. Images and text are connected to represent surrogates (enhanced bookmarks), optimizing the use of human cognitive facilities. Composition, an alternative to lists and spatial hypertext, is used to represent a collection of surrogates as a connected whole, using principles from art and design. This facilitates the creative process ofinformation discovery, in which humans develop new ideas while finding and collecting information. To provoke the user to think about the large space of potentially relevant information resources, a generative agent proactively engages in collecting information resources, forming image and text surrogates, and composing them visually. The agent develops the collection and its visual representation over time, enabling the user to see ideas and relationships. To keep the human in control, we develop interactive mechanisms for authoring the composition and directing the agent. In a field study in an interdisciplinary course on The Design Process, over a hundred students alternated using combinFormation and Google+Word to collect prior work on information discovery invention assignments. The students that used combinFormation's mixed-initiative composition of image and text surrogates performed better.
Toward automatic facet analysis and need negotiation
Authors: Lin Jimmy , Wu Philip , Abels Eileen
Published: December 2008

This work explores the hypothesis that interactions between a trained human search intermediary and an information seeker can inform the design of interactive IR systems. We discuss results from a controlled Wizard-of-Oz case study, set in the context of the TREC 2005 HARD track evaluation, in which a trained intermediary executed an integrated search and interaction strategy based on conceptual facet analysis and informed by need negotiation techniques common in reference interviews. Having a human “in the loop” yielded large improvements over fully automated systems as measured by standard ranked-retrieval metrics, demonstrating the value of mediated search. We present a detailed analysis of the intermediary's actions to gain a deeper understanding of what worked and why. One contribution is a taxonomy of clarification types informed both by empirical results and existing theories in library and information science. We discuss how these findings can guide the development of future systems. Overall, this work illustrates how studying human information-seeking processes can lead to better information retrieval applications.
Calculating the future
Authors: Lindley David
Published: December 2008

Climate researchers have no shortage of scientific issues on which to expend computer power. The biggest problem is choosing which one to tackle first.
The universe in your computer
Authors: Kanipe Jeff
Published: December 2008

Two virtual astronomical telescopes promise to transform the way people view and study the cosmos.
Law and technologyThe end of the generative internet
Authors: Zittrain Jonathan
Published: December 2008

Exploring the expectations and implications for version 2.0 of the Net's new gated communities.
The business of softwareThe ontology of paper
Authors: Armour Phillip G.
Published: December 2008

The next generation of software engineering will involve designing systems without using paper-based formats, instead using software to develop software.
Eventually consistent
Authors: Vogels Werner
Published: December 2008

Building reliable distributed systems at a worldwide scale demands trade-offs between consistency and availability.
Voyagers and voyeurs
Authors: Heer Jeffrey , Viégas Fernanda B. , Wattenberg Martin
Published: December 2008

This article describes mechanisms for asynchronous collaboration in the context of information visualization, recasting visualizations as not just analytic tools, but social spaces. We contribute the design and implementation of
sense.us
, a Web site supporting asynchronous collaboration across a variety of visualization types. The site supports view sharing, discussion, graphical annotation, and social navigation and includes novel interaction elements. We report the results of user studies of the system, observing emergent patterns of social data analysis, including cycles of observation and hypothesis, and the complementary roles of social navigation and data-driven exploration.
A pioneer woman
Authors: Ross Michael
Published: December 2008

Programmer Jean Bartik is inducted into the Computer History Museum's Hall of Fellows.
Controlling Proteins Through Molecular Springs
Authors: Zocchi Giovanni
Published: December 2008

We argue that the mechanical control of proteins—the notion of controlling chemical reactions and processes by mechanics—is conceptually interesting. We give a brief review of the main accomplishments so far, leading to our present approach of using DNA molecular springs to exert controlled stresses on proteins. Our focus is on the physical principles that underlie both artificial mechanochemical devices and natural mechanisms of allostery.