bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical Framework to Define Product Architecture
Authors: Manohar Karthik , Abell Jeffrey , Beiter Kurt , Gonzales Dennis
Published: March 2011

Product design over the past few decades has moved towards shorter life cycles, shorter design cycles while simultaneously having to satisfy multiple market segments. Global companies have responded to this challenge by designing products based on architectures, to meet these new market requirements. However, designing products based on architecture levies a significant tradeoff penalty on the derivative variants when compared to custom requirement-specific design. All derivative variants sharing the common architecture will have to carry the engineering weight of the variant with the most stringent performance requirements. This makes architecture definition a crucial step in achieving market success. The architecture definition process has three primary steps: architecture bandwidth definition, determining the number of variants and definition of the bandwidth of each variant. A study of the current architecture definition process in a large automobile manufacturer determined that the bandwidth and variant decision making process was entirely manual and dependant on the skill & experience of the personnel involved. This paper defines a math-based framework to define, determine and visualize the entire solution space of product variants in an individual architecture. A case study was built around a midsize vehicle architecture; with elemental physics and dynamics determining the performance attributes of each variant solution. A commercial simulation solution provided the marketshare simulation, for all the potential virtual vehicles in the solution space, providing a connection for engineering requirements to market performance. This paper begins with a brief overview of the architecture design space, walks through an analytical framework to define product architecture, and finally, future steps for this line of research.
Quantitative study on the enhancement of sidewall coverage of sputter-deposited film by partially tapering the sidewall of via holes
Authors: Kim Chang-Gyu , Lee Won-Jong
Published: March 2011

As the aspect ratio of a via increases, the film sputter-deposited inside the via suffers from poor step coverage. In this study, the authors introduced a partially tapered via and simulated the thickness profile of sputter-deposited film inside it. For the simulation, the directionality factor k was introduced to the Monte Carlo method to consider the angular directionality of depositing atoms. The optimum partially tapered via, which has a maximum sidewall coverage, was obtained for various via dimensions (i.e., aspect ratios and bottom-to-entrance size ratios) and directionality factors of depositing atoms. The enhancement effect of the sidewall coverage by introducing an optimum partially tapered via was investigated quantitatively. The enhancement factor of an optimum partially tapered via is always greater than that of a fully tapered via. To achieve high sidewall coverage for high aspect ratio vias, it is suggested to deposit a film inside an optimum partially tapered via under the condition with high directionality.
CD69: An Unexpected Regulator of T
H
17 Cell–Driven Inflammatory Responses
Authors: Martín Pilar , Sánchez-Madrid Francisco
Published: March 2011

CD69 deficiency promotes differentiation of inflammatory T
H
17 cells and exacerbates autoimmune diseases in mice.
Retinol Gets In on the Act
Authors: Foley John F.
Published: March 2011

The binding of vitamin A to its uptake receptor activates JAK-STAT signaling and gene expression.
Activating CatSper
Authors: Adler Elizabeth M.
Published: March 2011

Progesterone stimulates calcium influx in human sperm through the CatSper channel.
Chromatin-Associated PKC
Authors: Gough Nancy R.
Published: March 2011

Protein kinase C-θ acts directly at gene promoters to participate in inducible gene expression.
The Brain’s Alarm Clock
Authors: Hines Pamela J.
Published: March 2011

Neurons in the brain that boost the morning response of the circadian rhythm are themselves directly responsive to light.
Limiting Heart Hypertrophy
Authors: Gough Nancy R.
Published: March 2011

Reducing the abundance of follistatin-like 3, a secreted antagonist of members of the transforming growth factor–β family, reduces cardiac hypertrophy.
OXA-163, an OXA-48-Related Class D β-Lactamase with Extended Activity Toward Expanded-Spectrum Cephalosporins
Authors: Poirel Laurent , Castanheira Mariana , Carrër Amélie , Rodriguez Carla Parada , Jones Ronald N. , Smayevsky Jorgelina , Nordmann Patrice
Published: March 2011

Two
bla
OXA-48
-like-positive isolates (
Klebsiella pneumoniae
and
Enterobacter cloacae
) were recovered in Argentina in 2008 as part of a large-scale survey focused on multidrug resistance in
Enterobacteriaceae
. In both cases, sequencing identified β-lactamase OXA-163, differing from OXA-48 by a single amino substitution and a 4-amino-acid deletion. OXA-163 hydrolyzed penicillins, ceftazidime, and cefotaxime, whereas OXA-48 did not. However, OXA-163 had a much lower ability to hydrolyze carbapenems than OXA-48, therefore barely being considered a carbapenemase. In both isolates, the
bla
OXA-163
gene was located on plasmids that differed in structure and size. However, a detailed genetic analysis revealed a similar genetic context in those isolates, with the
bla
OXA-163
gene being bracketed by novel transposase genes, making this genetic environment different from that reported for the
bla
OXA-48
gene. This study identified the first class D β-lactamase compromising both extended-spectrum cephalosporin and carbapenem activities.
Quorum Sensing Inhibitors Increase the Susceptibility of Bacterial Biofilms to Antibiotics In Vitro and In Vivo
Authors: Brackman Gilles , Cos Paul , Maes Louis , Nelis Hans J. , Coenye Tom
Published: March 2011

Although the exact role of quorum sensing (QS) in various stages of biofilm formation, maturation, and dispersal and in biofilm resistance is not entirely clear, the use of QS inhibitors (QSI) has been proposed as a potential antibiofilm strategy. We have investigated whether QSI enhance the susceptibility of bacterial biofilms to treatment with conventional antimicrobial agents. The QSI used in our study target the acyl-homoserine lactone-based QS system present inPseudomonas aeruginosaandBurkholderia cepaciacomplex organisms (baicalin hydrate, cinnamaldehyde) or the peptide-based system present inStaphylococcus aureus(hamamelitannin). The effect of tobramycin (P. aeruginosa,B. cepaciacomplex) and clindamycin or vancomycin (S. aureus), alone or in combination with QSI, was evaluated in variousin vitroandin vivobiofilm model systems, including two invertebrate models and one mouse pulmonary infection model.In vitrothe combined use of an antibiotic and a QSI generally resulted in increased killing compared to killing by an antibiotic alone, although reductions were strain and model dependent. A significantly higher fraction of infectedGalleria mellonellalarvae andCaenorhabditis eleganssurvived infection following combined treatment, compared to treatment with an antibiotic alone. Finally, the combined use of tobramycin and baicalin hydrate reduced the microbial load in the lungs of BALB/c mice infected withBurkholderia cenocepaciamore than tobramycin treatment alone. Our data suggest that QSI may increase the success of antibiotic treatment by increasing the susceptibility of bacterial biofilms and/or by increasing host survival following infection.
Chemical Characterization and Biological Properties of NVC-422, a Novel, Stable
N
-Chlorotaurine Analog
Authors: Wang Lu , Belisle Barbara , Bassiri Mansour , Xu Ping , Debabov Dmitri , Celeri Chris , Alvarez Nichole , Robson Martin C. , Payne Wyatt G. , Najafi Ramin , Khosrovi Behzad
Published: March 2011

During oxidative burst, neutrophils selectively generate HOCl to destroy invading microbial pathogens. Excess HOCl reacts with taurine, a semi-essential amino acid, resulting in the formation of the longer-lived biogenerated broad-spectrum antimicrobial agent,
N
-chlorotaurine (NCT). In the presence of an excess of HOCl or under moderately acidic conditions, NCT can be further chlorinated, or it can disproportionate to produce
N
,
N
-dichlorotaurine (NNDCT). In the present study, 2,2-dimethyltaurine was used to prepare a more stable
N
-chlorotaurine, namely,
N
,
N
-dichloro-2,2-dimethyltaurine (NVC-422). In addition, we report on the chemical characterization,
in vitro
antimicrobial properties, and cytotoxicity of this compound. NVC-422 was shown effectively to kill all 17 microbial strains tested, including antibiotic-resistant
Staphylococcus aureus
and
Enterococcus faecium
. The minimum bactericidal concentration of NVC-422 against Gram-negative and Gram-positive bacteria ranged from 0.12 to 4 μg/ml. The minimum fungicidal concentrations against
Candida albicans
and
Candida glabrata
were 32 and 16 μg/ml, respectively. NVC-422 has an
in vitro
cytotoxicity (50% cytotoxicity = 1,440 μg/ml) similar to that of NNDCT. Moreover, our data showed that this agent possesses rapid, pH-dependent antimicrobial activity. At pH 4, NVC-422 completely killed both
Escherichia coli
and
S. aureus
within 5 min at a concentration of 32 μg/ml. Finally, the effect of NVC-422 in the treatment of an
E. coli
-infected granulating wound rat model was evaluated. Treatment of the infected granulating wound with NVC-422 resulted in significant reduction of the bacterial tissue burden and faster wound healing compared to a saline-treated control. These findings suggest that NVC-422 could have potential application as a topical antimicrobial.
Synergistic Effect of 14-Alpha-Lipoyl Andrographolide and Various Antibiotics on the Formation of Biofilms and Production of Exopolysaccharide and Pyocyanin by Pseudomonas aeruginosa
Authors: Zeng Xiangping , Liu Xiangyang , Bian Jiang , Pei Gang , Dai Huanqin , Polyak Steven W. , Song Fuhang , Ma Li , Wang Yuqiang , Zhang Lixin
Published: March 2011

Pseudomonas aeruginosa
produces a biofilm that provides the bacteria with an effective barrier against antibiotics. Here, we investigated the synergy of various antibiotics with 14-alpha-lipoyl andrographolide (AL-1), focusing upon synthesis of the biofilm. AL-1 also inhibited the production of the exopolysaccharide and pyocyanin components. We propose that AL-1 may potentially serve as a cotherapy to combat
P. aeruginosa
.
Effect of Antibiotic Treatment on Establishment and Elimination of Intestinal Colonization by KPC-Producing Klebsiella pneumoniae in Mice
Authors: Perez Federico , Pultz Michael J. , Endimiani Andrea , Bonomo Robert A. , Donskey Curtis J.
Published: March 2011

An understanding of the impact of antibiotics on the intestinal reservoir of KPC carbapenemase-producing
Klebsiella pneumoniae
(KPC-Kp) is important to prevent its emergence. We used a mouse model to examine the effect of antibiotic treatment on the establishment and elimination of intestinal colonization with KPC-Kp. Mice (10 per group) received subcutaneous antibiotics daily for 8 days. On day 3 of treatment, 10
3
CFU of KPC-Kp was given orogastrically, and concentrations of KPC-Kp in stool were monitored. Additional experiments assessed the effects of antibiotic treatment on concentrations of total anaerobes and
Bacteroides
spp. in stool and the efficacy of orogastric gentamicin and polymyxin E in suppressing KPC-Kp colonization. Of four antibiotics with minimal activity against the KPC-Kp test strain (MIC ≥ 16 μg/ml), those that suppressed total anaerobes and bacteroides (i.e., clindamycin and piperacillin-tazobactam) promoted colonization by KPC-Kp (
P
< 0.001), whereas agents that did not suppress total anaerobes or bacteroides (i.e., ciprofloxacin and cefepime) did not (
P
= 0.35). Of two agents with moderate activity against the KPC-Kp test strain, ertapenem (MIC, 4 μg/ml) did not promote colonization by KPC-Kp, whereas tigecycline (MIC, 3 μg/ml) did (
P
< 0.001), despite not reducing levels of total anaerobes or bacteroides. Orogastric treatment with gentamicin and polymyxin E suppressed KPC-Kp to undetectable levels in the majority of mice. These data suggest that antibiotics that disturb the intestinal anaerobic microflora and lack significant activity against KPC-Kp promote colonization by this organism. The administration of nonabsorbed oral antibiotics may be an effective strategy to suppress colonization with KPC-Kp.
Multiple Origins of Plasmodium falciparum Dihydropteroate Synthetase Mutant Alleles Associated with Sulfadoxine Resistance in India
Authors: Lumb Vanshika , Das Manoj K. , Singh Neeru , Dev Vas , Khan Wajihullah , Sharma Yagya D.
Published: March 2011

With the spread of chloroquine (CQ)-resistant malaria in India, sulfadoxine-pyrimethamine (SP) alone or in combination with artesunate is used as an alternative antimalarial drug. Due to continuous drug pressure, the
Plasmodium falciparum
parasite is exhibiting resistance to antifolates because of mutations in candidate genes dihydrofolate reductase (
dhfr
) and dihydropteroate synthetase (
dhps
). Our earlier study on flanking microsatellite markers of
dhfr
mutant alleles from India had shown a single origin of the pyrimethamine resistance and some minor haplotypes which shared haplotypes with Southeast Asian (Thailand) strains. In the present study, we have analyzed 193 of these Indian
P. falciparum
isolates for 15 microsatellite loci around
dhps
to investigate the genetic lineages of the mutant
dhps
alleles in different parts of the country. Eighty-one of these samples had mutant
dhps
alleles, of which 62 were from Andaman and Nicobar Islands and the remaining 19 were from mainland India. Of 112 isolates with a wild-type
dhps
allele, 109 were from mainland India and only 3 were from Andaman and Nicobar Islands. Consistent with the model of selection, the mean expected heterozygosity (

H
e

) around mutant
dhps
alleles (

H
e

= 0.55;
n
= 81) associated with sulfadoxine resistance was lower (
P
≤ 0.05) than the mean

H
e

around the wild-type
dhps
allele (

H
e

= 0.80;
n
= 112). There was more genetic diversity in flanking microsatellites of
dhps
than
dhfr
among these isolates, which confirms the assertion that
dhps
mutations are at a very early stage of fixation in the parasite population. Microsatellite haplotypes around various mutant
dhps
alleles suggest that the resistant
dhps
alleles have multiple independent origins in India, especially in Andaman and Nicobar Islands. Determining the genetic lineages of the resistant
dhps
alleles on Andaman and Nicobar Islands and mainland India is significant, given the role of Asia in the intercontinental spread of chloroquine- and pyrimethamine-resistant parasites in the past.
First Report of Klebsiella oxytoca Strain Coproducing KPC-2 and IMP-8 Carbapenemases
Authors: Li Bin , Sun Jing-Yong , Liu Qing-Zhong , Han Li-Zhong , Huang Xin-Hong , Ni Yu-Xing
Published: March 2011

The study shows for the first time the presence of the
Klebsiella oxytoca
strain fp10 coproducing plasmid-mediated KPC-2 and IMP-8 carbapenemases. The strain was obtained from the fecal sample of an inpatient and showed high-level resistance to imipenem and ertapenem (MICs > 32 μg/ml). Conjugation experiments demonstrated the transferability of the carbapenem-resistant determinants. The results of plasmid analysis and Southern hybridization revealed that the
bla
KPC-2
gene was located on transferable plasmid pFP10-1 (∼54 kb), whereas the
bla
IMP-8
gene was on transferable plasmid pFP10-2 (∼180 kb). Analysis of the genetic environment of these two genes has demonstrated that IS
Kpn6
and IS
Kpn8
are involved in the spread of the
bla
KPC-2
gene, while the transposable elements IS
26
,
intI1
, and
tniC
might contribute to the dissemination of the
bla
IMP-8
gene. The chimera of several transposon-associated elements indicated a novel genetic environment of IMP-type metallo-β-lactamase gene in
Enterobacteriaceae
from China.
Mutation in the
sdeS
Gene Promotes Expression of the
sdeAB
Efflux Pump Genes and Multidrug Resistance in Serratia marcescens
Authors: Maseda Hideaki , Hashida Yumiko , Shirai Akihiro , Omasa Takeshi , Nakae Taiji
Published: March 2011

Serratia marcescens
gained resistance to both biocides and antibiotics on expressing the SdeAB efflux pump, following exposure to increasingly higher concentrations of a biocide (H. Maseda et al., Antimicrob. Agents Chemother. 53:5230–5235, 2009). To reveal the regulatory mechanism of
sdeAB
expression, wild-type cells were subjected to transposon-mediated random mutagenesis, and a mutant with antibiotic resistance, which mimicked the phenotype of the previous biocide-resistant cells, was obtained. The transposon element was found in the chromosomal DNA downstream of the
sdeAB
operon. Sequencing revealed the presence of an open reading frame (ORF) encoding a protein with 159 amino acid residues that is highly similar to the BadM-type transcriptional repressor, designated
sdeS
. The level of
sdeB
::
xylE
reporter gene expression, undetectable in the wild-type cells, appeared to be fully comparable to that in the biocide-resistant cells. Nucleotide sequencing of the mutant revealed
sdeS
to have a single G-to-A base substitution at position 269 that converted Trp90 to a stop codon. Introduction of a plasmid-borne intact
sdeS
into the mutant cells and the biocide-resistant cells resulted in a reduction in
sdeB
::
xylE
reporter activity to an undetectable level. These results suggested that SdeS functions as a repressor of the
sdeAB
operon. It was concluded that the original biocide-resistant cells had an impaired
sdeS
and, therefore, a derepressed level of the SdeAB efflux pump.
Steady-State Plasma Pharmacokinetics of Oral Voriconazole in Obese Adults
Authors: Pai Manjunath P. , Lodise Thomas P.
Published: March 2011

Voriconazole is an antifungal agent that is currently used as primary therapy for invasive aspergillosis and as a potential treatment for systemic candidiasis. Data on the dosing of voriconazole in obese patients are not available, which is problematic given the increased prevalence of this special population. To address this limitation, we evaluated the steady-state plasma pharmacokinetics of voriconazole through a two-way, crossover design in a cohort of eight healthy volunteers with class II obesity or greater. The median (minimum, maximum) age, weight, and body mass index of obese subjects were 43 (22, 48) years, 133 (105, 155) kg, and 46.2 (38.4, 53.7) kg/m
2
, respectively. The geometric mean ratios (90% confidence intervals) for the area under the curve from time zero to 12 h (dosing interval; AUC
0–τ
), maximum concentration (
C
max
), minimum concentration at 12 h (
C
min
), and time to
C
max
(
T
max
) of the 300-mg to 200-mg dosing regimens were 2.0 (1.5, 2.7), 1.8 (1.4, 2.2), 2.2 (1.6, 2.9), and 1.6 (1.0, 2.4) in obese subjects, respectively. The AUC
0–τ
values observed in obese subjects were comparable to those from a historical data set of nonobese subjects. Voriconazole dose-normalized AUC
0–τ
values had a modestly better correlation with lean body weight (
r
2
= 0.42) than total body weight (
r
2
= 0.14). An excellent linear relationship (
r
2
= 0.96) was identified between
C
min
values and AUC
0–τ
values. Adjustment of voriconazole doses in individuals with class II obesity or greater does not appear to be necessary on the basis of body weight.
Loss of Heterozygosity of
FCY2
Leading to the Development of Flucytosine Resistance in Candida tropicalis
Authors: Chen Yen-Ning , Lo Hsiu-Jung , Wu Chia-Chen , Ko Hui-Ching , Chang Te-Pin , Yang Yun-Liang
Published: March 2011

As fluconazole resistance becomes an emerging issue for treating infections caused by
Candida tropicalis
, searching for alternative becomes a prominent task. In the present study, 97 clinical isolates of
C. tropicalis
were tested for the susceptibilities to flucytosine (5FC) with the Etest method. Although only one isolate was resistant to 5FC, 30 susceptible isolates could produce resistant progeny after exposure to the drug. Interestingly, 22 of these 30 clinical isolates had a heterozygous G/T at the 145th position on
FCY2
, encoding purine-cytosine permease, whereas their progeny recovered from within the inhibitory ellipses had homozygous T/T, resulting in null alleles for both copies of the gene and produced only truncated proteins, effecting the 5FC resistance. Furthermore, we found that two major fluconazole-resistant clinical clones, diploid sequence type 98 (DST98) and DST140, had a homozygous G/G at the 145th position, and neither was able to produce 5FC-resistant progeny within the inhibitory ellipses. Hence, strains of
C. tropicalis
containing heterozygous alleles may develop 5FC resistance readily, whereas those with homozygous G/G wild-type alleles can be treated with 5FC. Subsequently, a combination of 5FC and another antifungal drug is applicable for treating infections of
C. tropicalis
.
The Interaction between Candida krusei and Murine Macrophages Results in Multiple Outcomes, Including Intracellular Survival and Escape from Killing
Authors: García-Rodas Rocío , González-Camacho Fernando , Rodríguez-Tudela Juan Luis , Cuenca-Estrella Manuel , Zaragoza Oscar
Published: March 2011

Candida kruseiis a fungal pathogen of interest for the scientific community for its intrinsic resistance to fluconazole. Little is known about the interaction of this yeast with host immune cells. In this work, we have characterized the outcome of the interaction betweenC. kruseiand murine macrophages. OnceC. kruseiwas internalized, we observed different phenomena. In a macrophage-like cell line,C. kruseisurvived in a significant number of macrophages and induced filamentation and macrophage explosion. Phagocytosis ofC. kruseiled to actin polymerization around the yeast cells at the site of entry. Fluorescent specific staining with anti-Lamp1 and LysoTracker indicated that after fungal internalization, there was a phagolysosome maturation defect, a phenomenon that was more efficient when the macrophages phagocytosed killed yeast cells. Using cell line macrophages, we also observed macrophage fusion after cell division. When we used primary resident peritoneal macrophages in addition to macrophage explosion, we also observed a strong chemotaxis of uninfected macrophages to regions whereC. krusei-infected macrophages were present. We also noticed yeast transfer phenomena between infected macrophages. Primary macrophages inhibited pseudohypha elongation more efficiently than the macrophage-like cell line, suggesting thatC. kruseiinfection was better controlled by the former macrophages. Primary macrophages induced more tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) than the macrophage-like cell line. Our results demonstrate thatC. kruseican exploit the macrophages for replication, although other different outcomes are also possible, indicating that the interaction of this pathogen with phagocytic cells is very complex and regulated by multiple factors.
Identification of
In Vivo
-Induced Antigens Including an RTX Family Exoprotein Required for Uropathogenic Escherichia coli Virulence
Authors: Vigil Patrick D. , Alteri Christopher J. , Mobley Harry L. T.
Published: March 2011

Uncomplicated urinary tract infections (UTI) are caused most commonly by uropathogenic
Escherichia coli
(UPEC). Whole-genome screening approaches, including transcriptomic, proteomic, and signature-tagged mutagenesis, have shown that UPEC highly expresses or requires genes for translational machinery, capsule, lipopolysaccharide, type 1 fimbriae, and iron acquisition systems during UTI. To identify additional genes expressed by UPEC during UTI, an immunoscreening approach termed
in vivo
-induced antigen technology (IVIAT) was employed to identify antigens produced during experimental infection that are not produced during
in vitro
culture. An inducible protein expression library, constructed from genomic DNA isolated from UPEC strain CFT073, was screened using exhaustively adsorbed pooled sera from 20 chronically infected female CBA/J mice. Using this approach, we identified 93 antigens induced by UPEC
in vivo
. A representative subset of these genes was tested by quantitative PCR for expression by CFT073
in vivo
and during growth in human urine or LB medium
in vitro
;
proWX
,
narJI
,
lolA
,
lolD
,
tosA
(
upxA
), c2432,
katG
,
ydhX
,
kpsS
, and
yddQ
were poorly expressed
in vitro
but highly expressed
in vivo
. Of these,
tosA
, a gene encoding a predicted repeat-in-toxin family member, was expressed exclusively during UTI. Deletion of
tosA
in UPEC strain CFT073 resulted in significant attenuation in bladder and kidney infections during ascending UTI. By screening for
in vivo
-induced antigens, we identified a novel UPEC virulence factor and additional proteins that could be useful as potential vaccine targets.
Deletion of a Cation Transporter Promotes Lysis in Streptococcus pneumoniae
Authors: Neef Jolanda , Andisi Vahid Farshchi , Kim Kwang S. , Kuipers Oscar P. , Bijlsma Jetta J. E.
Published: March 2011

Streptococcus pneumoniaeis a significant human pathogen which causes respiratory and serious invasive diseases. Mg2+is essential for life, and its concentration varies throughout the human body. Magnesium uptake plays an important role in the virulence of many bacterial pathogens. To study the Mg2+uptake ofS. pneumoniaestrain D39, a mutant was generated in SPD1383, a P-type ATPase with homology to theSalmonellaMg2+transporter MgtA, which has also been shown to be a Ca2+exporter in strain TIGR4. Under low-Ca2+conditions, mutation led to a growth defect in complex medium and the gene was nearly essential for growth under low-Mg2+conditions. Addition of Mg2+restored the normal growth of the mutant in all cases, but the addition of other divalent cations had no effect. Addition of Ca2+, Mn2+, and Zn2+in the presence of high Mg2+concentrations inhibited restoration of growth. The mutant was unable to proliferate in blood, which was also alleviated by the addition of Mg2+. The protein was located in the membrane and produced in variousS. pneumoniaestrains and pathogenic streptococcal species. Surprisingly, mutation of the gene led to an elevated toxicity for endothelial cells. This was caused by an increased amount of pneumolysin in the medium, mediated by elevated lysis of the mutant. Thus, in this study, we uncovered a role for SPD1383 in Mg2+uptake and hypothesize that the protein is a Mg2+/Ca2+antiporter. Furthermore, a disturbance in Mg2+homeostasis seems to promote lysis ofS. pneumoniae.
The Staphylococcus aureus KdpDE Two-Component System Couples Extracellular K
+
Sensing and Agr Signaling to Infection Programming
Authors: Xue Ting , You Yibo , Hong De , Sun Haipeng , Sun Baolin
Published: March 2011

The Kdp system is widely distributed among bacteria. In
Escherichia coli
, the Kdp-ATPase is a high-affinity K
+
uptake system and its expression is activated by the KdpDE two-component system in response to K
+
limitation or salt stress. However, information about the role of this system in many bacteria still remains obscure. Here we demonstrate that KdpFABC in
Staphylococcus aureus
is not a major K
+
transporter and that the main function of KdpDE is not associated with K
+
transport but that instead it regulates transcription for a series of virulence factors through sensing external K
+
concentrations, indicating that this bacterium might modulate its infectious status through sensing specific external K
+
stimuli in different environments. Our results further reveal that
S. aureus
KdpDE is upregulated by the Agr/RNAIII system, which suggests that KdpDE may be an important virulence regulator coordinating the external K
+
sensing and Agr signaling during pathogenesis in this bacterium.
Genotype and Phenotypes of an Intestine-Adapted Escherichia coli K-12 Mutant Selected by Animal Passage for Superior Colonization
Authors: Fabich Andrew J. , Leatham Mary P. , Grissom Joe E. , Wiley Graham , Lai Hongshing , Najar Fares , Roe Bruce A. , Cohen Paul S. , Conway Tyrrell
Published: March 2011

We previously isolated a spontaneous mutant of
Escherichia coli
K-12, strain MG1655, following passage through the streptomycin-treated mouse intestine, that has colonization traits superior to the wild-type parent strain (M. P. Leatham et al., Infect. Immun.
73:
8039–8049, 2005). This intestine-adapted strain (
E. coli
MG1655*) grew faster on several different carbon sources than the wild type and was nonmotile due to deletion of the
flhD
gene. We now report the results of several high-throughput genomic analysis approaches to further characterize
E. coli
MG1655*. Whole-genome pyrosequencing did not reveal any changes on its genome, aside from the deletion at the
flhDC
locus, that could explain the colonization advantage of
E. coli
MG1655*. Microarray analysis revealed modest yet significant induction of catabolic gene systems across the genome in both
E. coli
MG1655* and an isogenic
flhD
mutant constructed in the laboratory. Catabolome analysis with Biolog GN2 microplates revealed an enhanced ability of both
E. coli
MG1655* and the isogenic
flhD
mutant to oxidize a variety of carbon sources. The results show that intestine-adapted
E. coli
MG1655* is more fit than the wild type for intestinal colonization, because loss of FlhD results in elevated expression of genes involved in carbon and energy metabolism, resulting in more efficient carbon source utilization and a higher intestinal population. Hence, mutations that enhance metabolic efficiency confer a colonization advantage.
Phagocytic Receptors Dictate Phagosomal Escape and Intracellular Proliferation of Francisella tularensis
Authors: Geier Henriette , Celli Jean
Published: March 2011

Francisella tularensis, the causative agent of tularemia, survives and proliferates within macrophages of the infected host as part of its pathogenic strategy, through an intracellular life cycle that includes phagosomal escape and extensive proliferation within the macrophage cytosol. Variousin vitromodels ofFrancisella-macrophage interactions have been developed, using either opsonic or nonopsonic phagocytosis, and have generated discrepant results on the timing and extent ofFrancisellaphagosomal escape. Here we have investigated whether either complement or antibody opsonization of the virulent prototypical type A strainFrancisella tularensissubsp.tularensisSchu S4 affects its intracellular cycle within primary murine bone marrow-derived macrophages. Opsonization of Schu S4 with either human serum or purified IgG enhanced phagocytosis but restricted phagosomal escape and intracellular proliferation. Opsonization of Schu S4 with either fresh serum or purified antibodies redirected bacteria from the mannose receptor (MR) to the complement receptor CR3, the scavenger receptor A (SRA), and the Fcγ receptor (FcγR), respectively. CR3-mediated uptake delayed maturation of the earlyFrancisella-containing phagosome (FCP) and restricted phagosomal escape, while FcγR-dependent phagocytosis was associated with superoxide production in the early FCP and restricted phagosomal escape and intracellular growth in an NADPH oxidase-dependent manner. Taken together, these results demonstrate that opsonophagocytic receptors alter the intracellular fate ofFrancisellaby delivering bacteria through phagocytic pathways that restrict phagosomal escape and intracellular proliferation.
Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species
Authors: Mital Jeffrey , Hackstadt Ted
Published: March 2011

Chlamydiae are well known for their species specificity and tissue tropism, and yet the individual species and strains show remarkable genomic synteny and share an intracellular developmental cycle unique in the microbial world. Only a relatively few chlamydial genes have been linked to specific disease or tissue tropism. Here we show that chlamydial species associated with human infections,
Chlamydia trachomatis
and
C. pneumoniae
, exhibit unique requirements for Src-family kinases throughout their developmental cycle. Utilization of Src-family kinases by
C. trachomatis
includes tyrosine phosphorylation of the secreted effector Tarp during the entry process, a functional role in microtubule-dependent trafficking to the microtubule organizing center, and a requirement for Src-family kinases for successful initiation of development. Nonhuman chlamydial species
C. caviae
and
C. muridarum
show none of these requirements and, instead, appear to be growth restricted by the activities of Src-family kinases. Depletion of Src-family kinases triggers a more rapid development of
C. caviae
with up to an 800% increase in infectious progeny production. Collectively, the results suggest that human chlamydial species have evolved requirements for tyrosine phosphorylation by Src-family kinases that are not seen in other chlamydial species. The requirement for Src-family kinases thus represents a fundamental distinction between chlamydial species that would not be readily apparent in genomic comparisons and may provide insights into chlamydial disease association and species specificity.

IMPORTANCE
Chlamydiae are well known for their species specificity and tissue tropism as well as their association with unique diseases. A paradox in the field relates to the remarkable genomic synteny shown among chlamydiae and the very few chlamydial genes linked to specific diseases. We have found that different chlamydial species exhibit unique requirements for Src-family kinases. These differing requirements for Src-family kinases would not be apparent in genomic comparisons and appear to be a previously unrecognized distinction that may provide insights to guide research in chlamydial pathogenesis.
‘forbidden Points— in Pregnancy: Do They Exist?
Authors: da Silva André V Guerreiro , Nakamura Mary Uchiyama , da Silva João Bosco Guerreiro
Published: March 2011

Acupuncture has been used in numerous diseases and for many types of symptoms. It has been also used for obstetric complaints, such as nausea and vomiting, insomnia and low back and girdle pain. There has long been concern that some points—called forbidden—might harm pregnancy owing to a potential abortifacient effect, but it is difficult to confirm this proposition. The small number of available publications on this topic seems to show that this is not correct. Animal research examining possible harmful effects and a systematic review would be welcome to throw some light on this question.
Paediatric road traffic injuries in urban Ghana: a population-based study
Authors: Guerrero Alejandro , Amegashie Justice , Obiri-Yeboah May , Appiah Noble , Zakariah Ahmed
Published: March 2011

Objective/setting

To provide a population-based analysis of childhood road traffic injuries (RTI) in two communities of the greater Accra region of Ghana, with the goal of establishing an RTI incidence baseline in these communities and to identify RTI characteristics in order to model a targeted injury prevention programme.

Study design

Geographical cluster sampling was performed in two separate communities with household surveys administered in person to determine a denominator. The guardian responsible for any household members below the age of 15 years involved in an RTI within the previous 12 months received an in-depth questionnaire. Demographics, incident characteristics, medical attention, injuries and disability days were noted. These are described and compared with injury severity and age-specific tendencies.

Results

5128 children were interviewed in 60 clusters. Of them, 172 were involved in an RTI within the previous 12 months. This resulted in a rate of 34 RTI/1000 person-years, and 43 RTI/1000 person-years in the 5–14-year-old age group. RTI involving a mini-bus taxi, as a pedestrian, correlated with a disability of greater than 30 days, as did fractures. 35.8% of injuries occurred at sunset. Most RTI occurred on a highway and involved the lower extremities. There were two deaths resulting in an incidence of 39.0/100 000 person-years.

Conclusion

Childhood RTI in this urban west African setting are a major source of disability. Specific injury circumstances are reviewed in detail. This study provides baseline incidence data that may be used to measure injury prevention efforts and to validate secondary data sources.
Chlamydia screening by community pharmacists: a qualitative study: Table 1
Authors: Dabrera Gavin , Pinson David , Whiteman Steve
Published: March 2011

Background and methodology

The National Chlamydia Screening Programme offers opportunistic screening for genitalChlamydia trachomatisinfection to young people aged 15–24 years in England. Screening packs are available in many different settings, including community sexual health clinics, colleges and community pharmacies. This article focuses on screening through community pharmacies. Currently, pharmacies provide only a small proportion of screening nationally despite the assumption that community pharmacies are an ideal location to undertake chlamydia screening. This article reports on semistructured interviews undertaken with a sample of 10 pharmacists offering chlamydia screening in Greenwich, London, UK in order to understand the issues facing pharmacists in offering chlamydia screening.

Results

Participants had good awareness of the importance of chlamydia infection and the need for screening. The majority were supportive of it, although some were concerned about approaching some younger individuals. Many pharmacists only raised opportunistically the provision of free chlamydia screening when customers were attending for emergency hormonal contraception. The pharmacists felt it was more difficult to discuss the subject of chlamydia screening with customers attending for non-sexual health-related services. The local chlamydia screening programme had undertaken other initiatives including mail outs. Some pharmacists had broached the subject of chlamydia screening but had discovered customers already had a screening pack at home.

Discussion and conclusions

These findings have highlighted challenges in opportunistically offering chlamydia screening to young people in community pharmacies. These challenges can be overcome through a combination of training and service innovation, in order to capitalise on the potential of community pharmacies to contribute to this important sexual health service.
Attitudes towards human papillomavirus vaccination: a qualitative study of vaccinated and unvaccinated girls aged 17–18 years
Authors: Williams Kate , Forster Alice , Marlow Laura , Waller Jo
Published: March 2011

Background and methodology

This study explored knowledge about human papillomavirus (HPV) and attitudes towards HPV vaccination among girls who were part of the ‘catch-up’ vaccination programme. Interviews were carried out between March and May 2009 with girls (aged 17–18 years) who had received HPV vaccine (n=5) and girls who had opted not to receive HPV vaccine (n=5). Interviews lasted approximately 25 minutes, were recorded and transcribed verbatim. The data were analysed qualitatively using framework analysis.

Results

Most girls were aware that HPV is sexually transmitted, but beyond this had limited understanding of HPV and HPV vaccination, and expressed a desire for further information. Girls were uncertain about the need for the vaccine both in terms of perceived risk (e.g. because they were not sexually active) and because of its novelty. Some had concerns about the efficacy and safety of the vaccine, while others were mistrusting of the information provided. Being embarrassed about discussing the vaccine with parents and practical barriers to vaccination were also discussed.

Discussion and conclusions

Understanding of HPV was poor, despite participants having been offered the vaccine. School-based interventions might be a useful supplement to leaflets, and should focus on improving knowledge of HPV and awareness of the purpose of HPV vaccination.
Comparison of varying injection rates of saline chasers on intravascular contrast enhancement for dynamic CT in cattle
Authors: Lee K. , Ikeo S. , Iwasaki T. , Yamada K.
Published: March 2011

Dynamic CT was performed in five normal Holstein calves to investigate the effect of saline chasers on intravascular contrast enhancement when administered at three different rates. The five calves were imaged using dynamic CT in a crossover study design. Group A was administered only contrast medium (600 mg iodine/kg, 4 ml/s), while groups B, C and D were administered contrast medium at 30 per cent reduction followed by saline chasers injected at 2, 4 and 8 ml/s, respectively. Attenuation values were obtained from the right and left maxillary arteries and dorsal sagittal sinus. Maximum enhancement value and mean value of the enhancement plateau obtained from the maxillary arteries were significantly lower in group B than in the other groups. The duration of the enhancement plateau was longer in group C than in groups B and D (P<0.05).
TWO ATTACKS ON A TWO-FACTOR USER AUTHENTICATION IN WIRELESS SENSOR NETWORKS
Authors: LEE CHENG-CHI , LI CHUN-TA , CHEN SHUN-DER
Published: March 2011

Recently, a secure two-factor user authentication scheme for wireless sensor networks (WSN) was proposed by Das. The proposed scheme can resist many logged in users with the same login identity, stolen-verifier, guessing, impersonation and replay threats. In this paper we study the two-factor user authentication scheme for WSN and find that the scheme is insecure against the masquerade attacks. With our masquerade attacks, an attacker can masquerade as any legal user to login the gateway node without knowing the user's password or can masquerade as a gateway node to communicate with the legal user at anytime.
THE HAMILTON–JACOBI ANALYSIS OF OPTICAL WAVEGUIDES
Authors: NAWAFLEH KHALED I.
Published: March 2011

In this paper, the Hamilton–Jacobi method for solving differential equations of wave propagation is investigated. It is shown that when a wave propagates through a background medium that varies slowly on the scale of the wavelength, the trajectory of the light particle follows the usual rule of refraction.
STRINGENT VERIFICATION OF THIRD ORDER + SECOND ORDER PERTURBATION DENSITY FUNCTION THEORY: BASED ON SHORT-RANGE SQUARE WELL POTENTIAL
Authors: XIANG YUANTAO , JAMNIK A.
Published: March 2011

A recently proposed third order + second order perturbation density functional theory (DFT) approach is made self-contained by using a virial pressure from the Ornstein–Zernike integral equation theory as input to determine the numerical value of an associated physical parameter. An exacting examination is formulated by applying the self-contained perturbation DFT approach to a short-range square well fluid of low temperatures subject to various external fields and comparing the theoretical results for density profiles to the corresponding grand canonical ensemble Monte Carlo simulation results. The comparison seems favorable for the third order + second order perturbation DFT approach as a self-contained and accurate predictive approach. It is surprisingly found that this self-contained third order + second order perturbation DFT approach is displayed outstandingly even if a deep SW perturbation term is being accounted for by a second order perturbation expansion. A discussion is presented about potential opportunity for this perturbation scheme.
PHASE DIAGRAM OF THE ONE-DIMENSIONAL t–U–J MODEL WITH ON-BOND REPULSION AT HALF FILLING
Authors: DING HANQIN , WANG YANSHEN
Published: March 2011

By using the bosonization approach and the renormalization group (RG) technique, we study the half-filled band one-dimensional t–U–J model with additional on-bond repulsion (W>0) in the weak-coupling regime. The presence of on-bond repulsion is responsible for realization of a metallic phase in the system, and the phase diagram is strongly controlled by the symmetry of the model. By analyzing the RG flow diagram and comparing order parameters, the phase boundaries are determined and the structure of the phase diagram is clarified. In the case of SU (2) ⊗ SU (2) symmetry, the phase diagram consists of a metallic phase characterized by a Luttinger liquid (LL) and two insulting phases characterized by the degenerate spin-density-wave (SDW) and the bond-charge-density-wave (BCDW). In the SU (2) ⊗ U(1)-symmetric case, the phase diagram contains two metallic phases: a LL and a Luther–Emery phase, and three insulating phases: the transverse SDW ( SDW ±), the longitudinal SDW ( SDW z) and the dimerized BCDW. The insulating charge-density-wave and bond-spin-density-wave (BSDW) phases are always suppressed in the ground state. In addition, the system show a long-ranged order in the BCDW and SDW z phases.
GENERATING TEST CASES OF COMPOSITE SERVICES BASED ON OWL-S AND EH-CPN
Authors: LI BIXIN , JI SHUNHUI , QIU DONG , CAI JU
Published: March 2011

In web service times, the techniques for composing services are based on service reuse and automatic integration. A new web service will be generated by composing some existing web services. These web services cooperate with each other to provide a new more complex function. It is necessary and very important to test the interaction behavior between any two web services during composition. In this paper, a kind of enhanced hierarchical color petri-net (or EH-CPN) is introduced to generate test cases for testing the interaction, where EH-CPN is transformed from OWL-S document, and both control flow and data flow information in EH-CPN are analyzed and used to generate an executable test sequence, and further test cases are created by combining the test sequence and test data in an XML file.
REASONING UNDER UNCERTAINTY FOR SHILL DETECTION IN ONLINE AUCTIONS USING DEMPSTER–SHAFER THEORY
Authors: DONG FEI , SHATZ SOL M. , XU HAIPING
Published: March 2011

This paper describes the design of a decision support system for shill detection in online auctions. To assist decision making, each bidder is associated with a type of certification, namely shill, shill suspect, or trusted bidder, at the end of each auction's bidding cycle. The certification level is determined on the basis of a bidder's bidding behaviors including shilling behaviors and normal bidding behaviors, and thus fraudulent bidders can be identified. In this paper, we focus on representing knowledge about bidders from different aspects in online auctions, and reasoning on bidders' trustworthiness under uncertainties using Dempster–Shafer theory of evidence. To demonstrate the feasibility of our approach, we provide a case study using real auction data from eBay. The analysis results show that our approach can be used to detect shills effectively and efficiently. By applying Dempster–Shafer theory to combine multiple sources of evidence for shill detection, the proposed approach can significantly reduce the number of false positive results in comparison to approaches using a single source of evidence.
A FINE GRAINED ASPECT COORDINATION MECHANISM
Authors: ZAMBRANO ARTURO , GORDILLO SILVIA , FABRY JOHAN
Published: March 2011

Aspect interactions and conflicts are an important issue for AOSD. Aspectual conflicts are difficult to manage and, specifically semantic ones remain an open issue for AOSD. In this work, we present a simple mechanism for handling semantic conflicts at the granularity of aspect and advice in the resource awareness domain. We also analyze the impact of such coordination mechanism on some important properties of software (some of the so called ilities). We found that aspects can effectively be coordinated and remain independent, improving their reusability, modularity and evolvability.
GROWTH MODE OF Sn ON A AU(111) SUBSTRATE
Authors: CANZIAN A. , MOSCA H. O. , BOZZOLO G.
Published: March 2011

Atomistic simulations of low coverage Sn growth on Au(111) using the Bozzolo–Ferrante–Smith (BFS) method for alloys are presented. Simulated annealing and atom-by-atom analysis of the energetics explains the close competition between the experimentally observed surface alloying and layer-by-layer growth.