bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on Friction and Formation of Transfer Layer in HCP Metals
Authors: Menezes Pradeep L. , Kishore  , Kailas Satish V. , Lovell Michael R.
Published: June 2009

Surface texture plays an important role in the frictional behavior and transfer layer formation of contacting surfaces. In the present investigation, basic experiments were conducted using an inclined pin-on-plate sliding apparatus to better understand the role of surface texture on the coefficient of friction and the formation of a transfer layer. In the experiments, soft HCP materials such as pure Mg and pure Zn were used for the pins and a hardened 080 M40 steel was used for the plate. Two surface parameters of the steel plates—roughness and texture—were varied in tests that were conducted at a sliding speed of 2 mm/s in ambient conditions under both dry and lubricated conditions. The morphologies of the worn surfaces of the pins and the formation of the transfer layer on the counter surfaces were observed using a scanning electron microscope. In the experiments, the occurrence of stick-slip motion, the formation of a transfer layer, and the value of friction were recorded. With respect to the friction, both adhesion and plowing components were analyzed. Based on the experimental results, the effect of surface texture on the friction was attributed to differences in the amount of plowing. Both the plowing component of friction and the amplitude of stick-slip motion were determined to increase surface textures that promote plane strain conditions and decrease the textures that favor plane stress conditions.
Continuum Modeling and Analysis of the Frictional Interaction Between a CNT and a Substrate During Dragging
Authors: Adams George G. , Nagappan Palaniappan , McGruer Nicol E.
Published: June 2009

A simple method to determine the frictional interaction between a carbon nanotube (CNT) and a substrate is analyzed for feasibility. In this technique an atomic force microscope (AFM) tip is used to drag a CNT along a substrate. Then the deformed shape of the CNT can be viewed either with the AFM or in a scanning electron microscope. An analysis of the steady-state deformed shape allows the determination of the frictional interactions, which occurred during dragging. It is important to quantify these interactions in a variety of potential applications of nanotechnology. In one such example, a CNT based nanoswitch consists of a CNT bridging over a trench. Actuation of the CNT causes it to stretch and can lead to partial slip at the interface. This slip causes hysteresis, which has been observed in the mechanical actuation of a CNT bridge. In this paper continuum level modeling of the frictional interaction is used to determine the relationship between the steady-state deformed shape of the CNT and the frictional interaction, which occurred between the CNT and substrate during dragging. The model and analysis indicate that this method should be feasible for CNTs with aspect ratios approximately in the 100–250 range.
Cytochrome P450 3A Inhibition by Atazanavir and Ritonavir, but Not Demography or Drug Formulation, Influences Saquinavir Population Pharmacokinetics in Human Immunodeficiency Virus Type 1-Infected Adults
Authors: von Hentig Nils , Lötsch Jörn
Published: June 2009

Inadequate concentrations of the human immunodeficiency virus (HIV) protease inhibitor saquinavir jeopardize individual therapy success or produce side effects despite treatment according to the current guidelines. We performed a population pharmacokinetic analysis with NONMEM and determined that the steady-state pharmacokinetics of saquinavir in 136 HIV type 1-infected adults was modulated by a decrease in saquinavir CL following coadministration of the cytochrome P450 3A inhibitors ritonavir and atazanavir. In contrast, age, sex, weight, pregnancy, and the pharmaceutical formulation exerted only minor, nonsignificant effects.
New Semiphysiological Absorption Model To Assess the Pharmacodynamic Profile of Cefuroxime Axetil Using Nonparametric and Parametric Population Pharmacokinetics
Authors: Bulitta J. B. , Landersdorfer C. B. , Kinzig M. , Holzgrabe U. , Sorgel F.
Published: June 2009

Cefuroxime axetil is widely used to treat respiratory tract infections. We are not aware of a population pharmacokinetic (PK) model for cefuroxime axetil. Our objectives were to develop a semiphysiological population PK model and evaluate the pharmacodynamic profile for cefuroxime axetil. Twenty-four healthy volunteers received 250 mg oral cefuroxime as a suspension after a standardized breakfast. Liquid chromatography-tandem mass spectrometry was used for drug analysis, NONMEM and S-ADAPT (results reported) were used for parametric population PK modeling, and NPAG was used for nonparametric population PK modeling. Monte Carlo simulations were used to predict the duration for which the non-protein-bound-plasma concentration was above the MIC (
f
T
>MIC
). A model with one disposition compartment, a saturable and time-dependent drug release from the stomach, and fast drug absorption from the intestine yielded precise (
r
> 0.992) and unbiased curve fits and an excellent predictive performance. The apparent clearance was 21.7 liters/h (19.8% coefficient of variation [CV]) and the volume of distribution 38.7 liters (18.3% CV). Robust (≥90%) probabilities of target attainment (PTAs) were achieved by 250 mg cefuroxime given every 12 h (q12h) or q8h for MICs of ≤0.375 mg/liter or ≤0.5 mg/liter, respectively, for the bacteriostasis target
f
T
>MIC
of ≥40% and for MICs of ≤0.094 mg/liter or ≤0.375 mg/liter, respectively, for the near-maximal-killing target
f
T
>MIC
of ≥65%. For the ≥40%
f
T
>MIC
target, the PTAs for 250 mg cefuroxime q12h were ≥97.8% for
S
treptococcus pyogenes
and penicillin-susceptible
S
treptococcus pneumoniae
. Cefuroxime at 250 mg q12h or q8h achieved PTAs below 73% or 92%, respectively, for
H
aemophilus influenzae
,
M
oraxella catarrhalis
, and penicillin-intermediate
S. pneumoniae
for susceptibility data from various countries. Depending on the MIC distribution, 250 mg oral cefuroxime q8h instead of q12h should be considered, especially for more-severe infections that require near-maximal killing by cefuroxime.
Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy Subjects
Authors: Ginsberg Ann M. , Laurenzi Martino W. , Rouse Doris J. , Whitney Karl D. , Spigelman Melvin K.
Published: June 2009

PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant
Mycobacterium tuberculosis
. The compound's MIC is between 0.015 and 0.25 μg/ml for drug-sensitive strains and between 0.03 and 0.53 μg/ml for drug-resistant strains. In addition, it is active against nonreplicating anaerobic
Mycobacterium tuberculosis
. The safety, tolerability, and pharmacokinetics of PA-824 were evaluated in two escalating-dose clinical studies, one a single-dose study and the other a multiple-dose study (up to 7 days of daily dosing). In 58 healthy subjects dosed with PA-824 in these studies, the drug candidate was well tolerated, with no significant or serious adverse events. In both studies, following oral administration PA-824 reached maximal plasma levels in 4 to 5 h independently of the dose. Maximal blood levels averaged approximately 3 μg/ml (1,500-mg dose) in the single-dose study and 3.8 μg/ml (600-mg dose) in the multiple-dose study. Steady state was achieved after 5 to 6 days of daily dosing, with an accumulation ratio of approximately 2. The elimination half-life averaged 16 to 20 h. Overall, PA-824 was well tolerated following oral doses once daily for up to 7 days, and pharmacokinetic parameters were consistent with a once-a-day regimen. The results of these studies, combined with the demonstrated activity of PA-824 against drug-sensitive and multidrug-resistant
Mycobacterium tuberculosis
, support the investigation of this novel compound for the treatment of tuberculosis.
In Vitro Activity of TR-700, the Active Ingredient of the Antibacterial Prodrug TR-701, a Novel Oxazolidinone Antibacterial Agent
Authors: Schaadt Ronda , Sweeney Debora , Shinabarger Dean , Zurenko Gary
Published: June 2009

TR-701 is the prodrug of the microbiologically active molecule TR-700, a novel orally and intravenously administered oxazolidinone antibacterial agent. The in vitro activity of TR-700 was evaluated against 1,063 bacterial clinical isolates including staphylococci, enterococci, streptococci,
Moraxella catarrhalis
,
Haemophilus influenzae
, and a variety of anaerobic bacterial species. The test strains were recent (2005 to 2008) clinical isolates from diverse U.S. (80%) and non-U.S. (20%) sites. MIC assays were conducted using reference broth microdilution and agar dilution methods with the principal comparators linezolid and vancomycin. TR-700 was four- to eightfold more potent than linezolid against staphylococci and generally fourfold more potent against enterococci and streptococci. TR-700 was less active against
M. catarrhalis
and
H. influenzae
but was twofold more active than linezolid. Against anaerobic species, the activity of TR-700 was equivalent to or up to fourfold higher than that of linezolid. These results indicate that TR-700 is a promising new oxazolidinone antibacterial agent with greater in vitro potency than linezolid against clinically important gram-positive bacteria.
Efficacy of Combination Antifungal Therapy with Intraperitoneally Administered Micafungin and Aerosolized Liposomal Amphotericin B against Murine Invasive Pulmonary Aspergillosis
Authors: Takazono Takahiro , Izumikawa Koichi , Mihara Tomo , Kosai Kosuke , Saijo Tomomi , Imamura Yoshifumi , Miyazaki Taiga , Seki Masafumi , Kakeya Hiroshi , Yamamoto Yoshihiro , Yanagihara Katsunori , Kohno Shigeru
Published: June 2009

Targeted intrapulmonary delivery of drugs may reduce systemic toxicity and improve treatment efficacy. In the current study, we evaluated the effects of a combination treatment consisting of inhalation of aerosolized liposomal amphotericin B (L-AMB) with intraperitoneal administration of micafungin (MCFG) against murine invasive pulmonary aspergillosis. The combination of aerosolized L-AMB with intraperitoneal MCFG significantly improved the survival rate, and the fungal burdens and histopathology findings after this treatment were superior to those of the control and both monotherapy groups.
Genetics of Chromosomally Mediated Intermediate Resistance to Ceftriaxone and Cefixime in
Neisseria gonorrhoeae
Authors: Zhao Shuqing , Duncan Margaret , Tomberg Joshua , Davies Christopher , Unemo Magnus , Nicholas Robert A.
Published: June 2009

All strains of
Neisseria gonorrhoeae
with reduced susceptibility to ceftriaxone and cefixime (cephalosporin-intermediate-resistant [Ceph
i
] strains) contain a mosaic
penA
allele encoding penicillin-binding protein 2 (PBP 2) with nearly 60 amino acid differences compared to the sequence of wild-type PBP 2, together with a set of resistance determinants (i.e.,
mtrR
,
penB
, and/or
ponA1
) that are required for high-level penicillin resistance. To define the individual contributions of these determinants to reduced susceptibility to ceftriaxone and cefixime, we created isogenic strains containing the mosaic
penA
allele from the Ceph
i
strain 35/02 (
penA35
) together with one or more of the other resistance determinants and determined the MICs of penicillin G, ceftriaxone, and cefixime. The majority of cefixime resistance is conferred by the
penA35
allele, with only a small contribution coming from
mtrR
and
penB
, whereas ceftriaxone resistance is nearly equally dependent upon
mtrR
and
penB
. Unlike high-level penicillin resistance, the
ponA1
allele does not appear to be important for Ceph
i
. A strain containing all four determinants has increased resistance to ceftriaxone and cefixime but not to the levels that the donor Ceph
i
strain does, suggesting that Ceph
i
strains, similar to high-level-penicillin-resistant strains, contain an additional unknown determinant that is required to reach donor levels of resistance. Our data also suggest that the original Ceph
i
strains arose from the transformation of
penA
genes from commensal
Neisseria
species into a penicillin-resistant strain already harboring
mtrR
,
penB
,
ponA1
, and the unknown gene(s) involved in high-level penicillin resistance.
VanA-Type
Staphylococcus aureus
Strain VRSA-7 Is Partially Dependent on Vancomycin for Growth
Authors: Moubareck Carole , Meziane-Cherif Djalal , Courvalin Patrice , Périchon Bruno
Published: June 2009

VanA-type
Staphylococcus aureus
strain VRSA-7 was partially dependent on glycopeptides for growth. The
vanA
gene cluster, together with the
erm
(A) and the
ant(9)-Ia
resistance genes, was carried by the ca. 35- to 40-kb conjugative plasmid pIP848 present at five copies per cell. The chromosomal
ddl
gene had a mutation that led to a N
308
K substitution in the
d
-Ala:
d
-Ala ligase that resulted in a 1,000-fold decrease in activity relative to that of strain VRSA-6. Strain VRSA-7 grown in the absence or in the presence of vancomycin mainly synthesized precursors ending in
d
-Ala-
d
-Lac, indicating that the strain relied on the vancomycin resistance pathway for peptidoglycan synthesis. Greatly enhanced growth in the presence of glycopeptides and the absence of mutations in the genes for VanR and VanS indicated the inducible expression of resistance. Thus, a combination of loose regulation of the
vanA
operon by the two-component system and a gene dosage effect accounts for the partial glycopeptide dependence of VRSA-7. Since peptidoglycan precursors ending in
d
-Ala-
d
-Lac are not processed by PBP 2′, the strain was fully susceptible to oxacillin, despite the production of a wild-type PBP 2′.
Simple, Rapid, and Inexpensive Detection of
Neisseria gonorrhoeae
Resistance Mechanisms Using Heat-Denatured Isolates and SYBR Green-Based Real-Time PCR
Authors: Kugelman Gayle , Tapsall John W. , Goire Namraj , Syrmis Melanie W. , Limnios Athena , Lambert Stephen B. , Nissen Michael D. , Sloots Theo P. , Whiley David M.
Published: June 2009

Neisseria gonorrhoeae
has developed resistance to multiple classes of antimicrobials. There is now growing concern that without the availability of appropriate public health strategies to combat this problem, gonorrhea could become untreatable. For this reason, surveillance for gonococcal antimicrobial resistance must be optimal both in terms of obtaining a representative sample of gonococcal isolates and in terms of having the appropriate tools to identify resistance. To aid with this surveillance, molecular tools are increasingly being used. In the present study, we investigated the use of a simple heat denaturation protocol for isolate DNA preparation combined with SYBR green-based real-time PCR for the identification of mutations associated with
N. gonorrhoeae
antimicrobial resistance. A total of 109 clinical gonococcal isolates were tested by high-resolution melting (HRM) curve analysis for chromosomal mutations associated with gonococcal resistance to beta-lactam antibiotics: a
penA
345A insertion,
ponA
L421P,
mtrR
G45D, substitutions at positions 120 and 121 in
porB1b
, and an adenine deletion in the
mtrR
promoter. An allele-specific PCR assay was also investigated for its ability to detect the adenine deletion in the
mtrR
promoter. The results were compared to those obtained by DNA sequencing. Our HRM assays provided the accurate discrimination of heat-treated isolates in which the sequence types differed in GC content, including isolates with the
penA
345A insertion and the
ponA
L421P and
mtrR
G45D mutations. The allele-specific PCR assay accurately identified isolates with the adenine deletion in the
mtrR
promoter. Heat-denatured DNA combined with SYBR green-based real-time PCR offers a simple, rapid, and inexpensive means of detecting gonococcal resistance mechanisms. These methods may have broader application in the detection of polymorphisms associated with phenotypes of interest.
Synergistic Interaction between Silver Nanoparticles and Membrane-Permeabilizing Antimicrobial Peptides
Authors: Ruden Serge , Hilpert Kai , Berditsch Marina , Wadhwani Parvesh , Ulrich Anne S.
Published: June 2009

Silver nanoparticles, as well as antimicrobial peptides (AMPs), can be used to fight infectious diseases. Since AMPs are known to permeabilize bacterial membranes and might therefore help silver nanoparticles to access internal target sites, we investigated their combined activities and showed synergistic effects between polymyxin B and silver nanoparticles for gram-negative bacteria.
Pharmacodynamic Profiling of Ceftobiprole for Treatment of Complicated Skin and Skin Structure Infections
Authors: Kimko Holly , Xu Xu , Nandy Partha , Samtani Mahesh N. , Strauss Richard S. , Bagchi Partha , Noel Gary J.
Published: June 2009

Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin (meticillin)-resistant staphylococci, was statistically noninferior to a combination of vancomycin plus ceftazidime in patients with complicated skin and skin structure infections (cSSSI). This analysis used data from this clinical trial to determine the relationship between therapeutic outcome and the percentage of time that the unbound ceftobiprole concentration exceeds the MIC (percent T>MIC). From the trial of ceftobiprole (500 mg every 8 h, 2-h infusion) for cSSSI due to gram-positive and/or gram-negative bacteria, data from 309 patients in the microbiological intent-to-treat analysis set with measured ceftobiprole concentrations and baseline MICs were used to assess the relationship between percent T>MIC and therapeutic outcome. Individual pharmacokinetic (PK) profiles were obtained from a three-compartment population PK model. The relationship between percent T>MIC and a clinical cure was determined. For the clinical trial dosing regimen, individual percent T>MICs were used to calculate fractional target attainment rates (TARs) for ≥30 and ≥50% T>MIC targets at various MICs. There was a statistically significant relationship between achieving a ≥30 or ≥50% T>MIC and a clinical cure (
P
= 0.003 and
P
= 0.007, respectively; Pearson's χ
2
test). The fractional TAR was greater than 90% at a MIC of ≤4 mg/liter for patients with normal renal function. A relationship between percent T>MIC and a clinical cure with ceftobiprole was demonstrated. A ceftobiprole regimen of 500 mg every 8 h as a 2-h infusion has a high probability of achieving a target of ≥30 or ≥50% T>MIC for patients with cSSSI due to gram-positive and gram-negative pathogens.
Pharmacokinetics and Ex Vivo Pharmacodynamic Antimalarial Activity of Dihydroartemisinin-Piperaquine in Patients with Uncomplicated Falciparum Malaria in Vietnam
Authors: Nguyen Dao Van Hoang , Nguyen Quoc Phuc , Nguyen Ngoa Dang , Le Thuy Thi Thanh , Nguyen The Duy , Dinh Duy Ngoc , Nguyen Thanh Xuan , Bui Dai , Chavchich Marina , Edstein Michael D.
Published: June 2009

Compared to healthy subjects, malaria patients show a reduction in the mean oral clearance (1.19 versus 5.87 liters/h/kg of body weight) and apparent volume of distribution (1.47 versus 8.02 liters/kg) of dihydroartemisinin in Vietnamese patients following treatment with dihydroartemisinin-piperaquine (Artekin) for uncomplicated
Plasmodium falciparum
. Dihydroartemisinin is responsible for most of the ex vivo antimalarial activity of dihydroartemisinin-piperaquine.
Transcriptional Profiling Identifies the Metabolic Phenotype of Gonococcal Biofilms
Authors: Falsetta Megan L. , Bair Thomas B. , Ku Shan Chi , vanden Hoven Rachel N. , Steichen Christopher T. , McEwan Alastair G. , Jennings Michael P. , Apicella Michael A.
Published: June 2009

Neisseria gonorrhoeae
, the etiologic agent of gonorrhea, is frequently asymptomatic in women, often leading to chronic infections. One factor contributing to this may be biofilm formation.
N. gonorrhoeae
can form biofilms on glass and plastic surfaces. There is also evidence that biofilm formation may occur during natural cervical infection. To further study the mechanism of gonococcal biofilm formation, we compared transcriptional profiles of
N. gonorrhoeae
biofilms to planktonic profiles. Biofilm RNA was extracted from
N. gonorrhoeae
1291 grown for 48 h in continuous-flow chambers over glass. Planktonic RNA was extracted from the biofilm runoff. In comparing biofilm with planktonic growth, 3.8% of the genome was differentially regulated. Genes that were highly upregulated in biofilms included
aniA
,
norB
, and
ccp
. These genes encode enzymes that are central to anaerobic respiratory metabolism and stress tolerance. Downregulated genes included members of the
nuo
gene cluster, which encodes the proton-translocating NADH dehydrogenase. Furthermore, it was observed that
aniA
,
ccp
, and
norB
insertional mutants were attenuated for biofilm formation on glass and transformed human cervical epithelial cells. These data suggest that biofilm formation by the gonococcus may represent a response that is linked to the control of nitric oxide steady-state levels during infection of cervical epithelial cells.
Novel Chimpanzee/Human Monoclonal Antibodies That Neutralize Anthrax Lethal Factor, and Evidence for Possible Synergy with Anti-Protective Antigen Antibody
Authors: Chen Zhaochun , Moayeri Mahtab , Crown Devorah , Emerson Suzanne , Gorshkova Inna , Schuck Peter , Leppla Stephen H. , Purcell Robert H.
Published: June 2009

Three chimpanzee Fabs reactive with lethal factor (LF) of anthrax toxin were isolated and converted into complete monoclonal antibodies (MAbs) with human γ1 heavy-chain constant regions. In a macrophage toxicity assay, two of the MAbs, LF10E and LF11H, neutralized lethal toxin (LT), a complex of LF and anthrax protective antigen (PA). LF10E has the highest reported affinity for a neutralizing MAb against LF (dissociation constant of 0.69 nM). This antibody also efficiently neutralized LT in vitro, with a 50% effective concentration (EC
50
) of 0.1 nM, and provided 100% protection of rats against toxin challenge with a 0.5 submolar ratio relative to LT. LF11H, on the other hand, had a slightly lower binding affinity to LF (dissociation constant of 7.4 nM) and poor neutralization of LT in vitro (EC
50
of 400 nM) and offered complete protection in vivo only at an equimolar or higher ratio to toxin. Despite this, LF11H, but not LF10E, provided robust synergistic protection when combined with MAb W1, which neutralizes PA. Epitope mapping and binding assays indicated that both LF10E and LF11H recognize domain I of LF (amino acids 1 to 254). Although domain I is responsible for binding to PA, neither MAb prevented LF from binding to activated PA. Although two unique MAbs could protect against anthrax when used alone, even more efficient and broader protection should be gained by combining them with anti-PA MAbs.
Contribution of Autolysin and Sortase A during
Enterococcus faecalis
DNA-Dependent Biofilm Development
Authors: Guiton Pascale S. , Hung Chia S. , Kline Kimberly A. , Roth Robyn , Kau Andrew L. , Hayes Ericka , Heuser John , Dodson Karen W. , Caparon Michael G. , Hultgren Scott J.
Published: June 2009

Biofilm production is a major attribute of
Enterococcus faecalis
clinical isolates. Although some factors, such as sortases, autolysin, and extracellular DNA (eDNA), have been associated with
E. faecalis
biofilm production, the mechanisms underlying the contributions of these factors to this process have not been completely elucidated yet. In this study we define important roles for the major
E. faecalis
autolysin (Atn), eDNA, and sortase A (SrtA) during the developmental stages of biofilm formation under static and hydrodynamic conditions. Deletion of
srtA
affects the attachment stage and results in a deficiency in biofilm production. Atn-deficient mutants are delayed in biofilm development due to defects in primary adherence and DNA release, which we show to be particularly important during the accumulative phase for maturation and architectural stability of biofilms. Confocal laser scanning and freeze-dry electron microscopy of biofilms grown under hydrodynamic conditions revealed that
E. faecalis
produces a DNase I-sensitive fibrous network, which is important for biofilm stability and is absent in
atn
-deficient mutant biofilms. This study establishes the stage-specific requirements for SrtA and Atn and demonstrates a role for Atn in the pathway leading to DNA release during biofilm development in
E. faecalis
.
Accelerated Type III Secretion System 2-Dependent Enteropathogenesis by a
Salmonella enterica
Serovar Enteritidis PT4/6 Strain
Authors: Suar Mrutyunjay , Periaswamy Balamurugan , Songhet Pascal , Misselwitz Benjamin , Müller Andreas , Käppeli Rina , Kremer Marcus , Heikenwalder Mathias , Hardt Wolf-Dietrich
Published: June 2009

Salmonella enterica
subsp. I serovars Typhimurium and Enteritidis are major causes of enteric disease. The pathomechanism of enteric infection by serovar Typhimurium has been studied in detail. Serovar Typhimurium employs two pathways in parallel for triggering disease, i.e., the “classical” pathway, triggered by type III secretion system 1 (TTSS-1), and the “alternative” pathway, mediated by TTSS-2. It had remained unclear whether these two pathways would also explain the enteropathogenesis of strains from other serovars. We chose the isolate P125109 of the epidemic serovar Enteritidis PT4/6, generated isogenic mutants, and studied their virulence. Using in vitro and in vivo infection experiments, a dendritic cell depletion strategy, and MyD88
−/−
knockout mice, we found that P125109 employs both the “classical” and “alternative” pathways for triggering mucosal inflammation. The “classical” pathway was phenotypically similar in serovar Typhimurium strain SL1344 and in P125109. However, the kinetics of the “alternative” pathway differed significantly. Via TTSS-2, P125109 colonized the gut tissue more efficiently and triggered mucosal inflammation approximately 1 day faster than SL1344 did. In conclusion, our data demonstrate that different
Salmonella
spp. can differ in their capacity to trigger mucosal inflammation via the “alternative” pathway in vivo.
The Meningococcal ABC-Type
l
-Glutamate Transporter GltT Is Necessary for the Development of Experimental Meningitis in Mice
Authors: Colicchio Roberta , Ricci Susanna , Lamberti Florentia , Pagliarulo Caterina , Pagliuca Chiara , Braione Velia , Braccini Tiziana , Talà Adelfia , Montanaro Donatella , Tripodi Sergio , Cintorino Marcella , Troncone Giancarlo , Bucci Cecilia , Pozzi Gianni , Bruni Carmelo B. , Alifano Pietro , Salvatore Paola
Published: June 2009

Experimental animal models of bacterial meningitis are useful to study the host-pathogen interactions occurring at the cerebral level and to analyze the pathogenetic mechanisms behind this life-threatening disease. In this study, we have developed a mouse model of meningococcal meningitis based on the intracisternal inoculation of bacteria. Experiments were performed with mouse-passaged serogroup C
Neisseria meningitidis.
Survival and clinical parameters of infected mice and microbiological and histological analysis of the brain demonstrated the establishment of meningitis with features comparable to those of the disease in humans. When using low bacterial inocula, meningococcal replication in the brain was very efficient, with a 1,000-fold increase of viable counts in 18 h. Meningococci were also found in the blood, spleens, and livers of infected mice, and bacterial loads in different organs were dependent on the infectious dose. As glutamate uptake from the host has been implicated in meningococcal virulence, mice were infected intracisternally with an isogenic strain deficient in the ABC-type
l
-glutamate transporter GltT. Noticeably, the mutant was attenuated in virulence in mixed infections, indicating that wild-type bacteria outcompeted the GltT-deficient meningococci. The data show that the GltT transporter plays a role in meningitis and concomitant systemic infection, suggesting that meningococci may use
l
-glutamate as a nutrient source and as a precursor to synthesize the antioxidant glutathione.
Evidence for Horizontal Gene Transfer of Two Antigenically Distinct O Antigens in
Bordetella bronchiseptica
Authors: Buboltz Anne M. , Nicholson Tracy L. , Karanikas Alexia T. , Preston Andrew , Harvill Eric T.
Published: June 2009

Host immunity is a major driving force of antigenic diversity, resulting in pathogens that can evade immunity induced by closely related strains. Here we show that two
Bordetella bronchiseptica
strains, RB50 and 1289, express two antigenically distinct O-antigen serotypes (O1 and O2, respectively). When 18 additional
B. bronchiseptica
strains were serotyped, all were found to express either the O1 or O2 serotype. Comparative genomic hybridization and PCR screening showed that the expression of either the O1 or O2 serotype correlated with the strain containing either the classical or alternative O-antigen locus, respectively. Multilocus sequence typing analysis of 49
B. bronchiseptica
strains was used to build a phylogenetic tree, which revealed that the two O-antigen loci did not associate with a particular lineage, evidence that these loci are horizontally transferred between
B. bronchiseptica
strains. From experiments using mice vaccinated with purified lipopolysaccharide from strain RB50 (O1), 1289 (O2), or RB50Δ
wbm
(O antigen deficient), our data indicate that these O antigens do not confer cross-protection in vivo. The lack of cross-immunity between O-antigen serotypes appears to contribute to inefficient antibody-mediated clearance between strains. Together, these data are consistent with the idea that the O-antigen loci of
B. bronchiseptica
are horizontally transferred between strains and encode antigenically distinct serotypes, resulting in inefficient cross-immunity.
Emergency department-initiated tobacco control: a randomised controlled trial in an inner city university hospital
Authors: Neuner B , Weiss-Gerlach E , Miller P , Martus P , Hesse D , Spies C
Published: June 2009

Objectives:

Emergency department (ED) patients show high smoking rates. The effects of ED-initiated tobacco control (ETC) on 7-day abstinence at 12 months were investigated.

Methods:

A randomised controlled intention-to-treat trial (trials registry no.: ISRCTN41527831) was conducted with 1044 patients in an urban ED. ETC consisted of on-site counselling plus up to four telephone booster sessions. Controls received usual care. Analysis was by logistic regression.

Results:

In all, 630 (60.7%) participants were males, the median age was 30 years (range 18–81) and the median smoking intensity was 15 (range 1–60) cigarettes per day. Overall, 580 study participants (55.6%) were unmotivated, 331 (31.7%) were ambivalent and 133 (12.7%) were motivated smokers. ETC (median time 30 (range 1–99) min) was administered to 472 (91.7% out of 515) randomised study participants. At follow-up, 685 study participants (65.6% of 1044) could be contacted. In the ETC group, 73 out of 515 (14.2%) in the ETC group were abstinent, whereas 60 out of 529 (11.3%) controls were abstinent (OR adjusted for age and gender = 1.31 (95% CI 0.91 to 1.89, p = 0.15). Stratified for motivation to change behaviour, the adjusted ORs for ETC versus usual care were OR = 1.00 (95% CI 0.57 to 1.76) in unmotivated smokers, respectively OR = 1.37 (95% CI 0.73 to 2.58) in ambivalent smokers and OR = 2.19 (95% CI 0.98 to 4.89) in motivated smokers, p for trend = 0.29.

Conclusions:

ETC, in the form of on-site counselling with up to four telephone booster sessions, showed no overall effect on tobacco abstinence after 12 months. A non-significant trend for a better performance of ETC in more motivated smokers was observed.
Regulatory assessment of brand changes in the commercial tobacco product market
Authors: Wayne G Ferris , Connolly G N
Published: June 2009

Background:

Regulatory oversight of tobacco product design has gained momentum in the US and internationally. Appropriate standards for assessing commercial brands and characterising product features must be considered a priority. An area of potential concern is in-market design changes adopted within a single commercial brand over time.

Methods:

Internal tobacco industry documents were identified and used to assess internal discussion of product guidelines and practices regarding in-market brand changes.

Results:

Commercial tobacco products undergo a constant process of revision in-market, beginning at the most basic level of physical product characteristics and components, and including every aspect of design. These revisions commonly exceed guidelines for acceptable product variance adopted within the industry. While consumer and market testing is conducted to ensure that products remain acceptable to users, explicit marketing often may not accompany brand changes. In the absence of such marketing, it should not be assumed that a brand remains unchanged.

Conclusions:

For manufacturers, assessment of competitor brands includes identification and analysis of non-routine changes; that is, those changes likely to significantly alter the character of a given brand. Regulators must adopt a similar practice in determining standards for product evaluation in the face of ongoing commercial product revision.
THE APPROXIMATE ANALYTICAL SOLUTIONS OF THE KLEIN–GORDON EQUATION WITH THE SECOND PÖSCHL–TELLER LIKE POTENTIAL FOR NONZERO ANGULAR MOMENTUM
Authors: CHEN WEN-LI , WEI GAO-FENG , QIANG WEN-CHAO
Published: June 2009

The approximate analytical bound and scattering state solutions of the arbitrary l-wave Klein–Gordon equation for the second Pöschl–Teller like potential are carried out by a new approximation to the centrifugal term. The analytical radial wave functions of the l-wave Klein–Gordon equation with the second Pöschl–Teller like potential are presented and the corresponding energy equations for bound states and phase shifts for scattering states are derived. It is well shown that the poles of S-matrix in the complex energy plane correspond to bound states for real poles and scattering states for complex poles in the lower half of the energy plane. Some numerical results are calculated to show the improved accuracy of our results and the special case for s-wave is also studied briefly.
A FRAMEWORK FOR ACTIVELY SELECTING VIEWPOINTS IN OBJECT RECOGNITION
Authors: DEINZER FRANK , DERICHS CHRISTIAN , NIEMANN HEINRICH , DENZLER JOACHIM
Published: June 2009

Object recognition problems in computer vision are often based on single image data processing. In various applications this processing can be extended to a complete sequence of images, usually received passively. In contrast, we propose a method for active object recognition, where a camera is selectively moved around a considered object. Doing so, we aim at reliable classification results with a clearly reduced amount of necessary views by optimizing the camera movement for the access of new viewpoints (viewpoint selection). Therefore, the optimization criterion is the gain of class discriminative information when observing the appropriate next image.

We show how to apply an unsupervised reinforcement learning algorithm to that problem. Specifically, we focus on the modeling of continuous states, continuous actions and supporting rewards for an optimized recognition. We also present an algorithm for the sequential fusion of gathered image information and we combine all these components into a single framework.

The experimental evaluations are split into results for synthetic and real objects with one- or two-dimensional camera actions, respectively. This allows the systematic evaluation of the theoretical correctness as well as the practical applicability of the proposed method. Our experiments showed that the proposed combined viewpoint selection and viewpoint fusion approach is able to significantly improve the recognition rates compared to passive object recognition with randomly chosen views.
REPRESENTATIONS OF THE RENNER MONOID
Authors: LI ZHUO , LI ZHENHENG , CAO YOU'AN
Published: June 2009

We describe irreducible representations and character formulas of the Renner monoids for reductive monoids, which generalize the Munn–Solomon representation theory of rook monoids to any Renner monoids. The type map and polytope associated with reductive monoids play a crucial role in our work. It turns out that the irreducible representations of certain parabolic subgroups of the Weyl groups determine the complete set of irreducible representations of the Renner monoids. An analogue of the Munn–Solomon formula for calculating the character of the Renner monoids, in terms of the characters of the parabolic subgroups, is shown.
SELF-SIMILAR COSMOLOGIES IN 5D: SPATIALLY FLAT ANISOTROPIC MODELS
Authors: PONCE DE LEON J.
Published: June 2009

In the context of theories of the Kaluza–Klein type, with a large extra dimension, we study self-similar cosmological models in 5D that are homogeneous, anisotropic and spatially flat. The "ladder" to go between the physics in 5D and in 4D is provided by Campbell–Maagard's embedding theorems. We show that the 5D field equations RAB = 0 determine the form of the similarity variable. There are three different possibilities: homothetic, conformal and "wavelike" solutions in 5D. We derive the most general homothetic and conformal solutions to the 5D field equations. They require the extra dimension to be spacelike, and are given in terms of one arbitrary function of the similarity variable and three parameters. The Riemann tensor in 5D is not zero, except in the isotropic limit, which corresponds to the case where the parameters are equal to each other. The solutions can be used as 5D embeddings for a great variety of 4D homogeneous cosmological models, with and without matter, including the Kasner universe. Since the extra dimension is spacelike, the 5D solutions are invariant under the exchange of spatial coordinates. Therefore they also embed a family of spatially inhomogeneous models in 4D. We show that these models can be interpreted as vacuum solutions in braneworld theory. Our work (I) generalizes the 5D embeddings used for FLRW models; (II) shows that anisotropic cosmologies are, in general, curved in 5D, in contrast with FLRW models, which can always be embedded in a 5D Riemann-flat (Minkowski) manifold; and (III) reveals that anisotropic cosmologies can be curved and devoid of matter, both in 5D and in 4D, even when the metric in 5D explicitly depends on the extra coordinate, which is quite different from the isotropic case.
COPRIME CONJUGACY CLASS SIZES
Authors: Camina A. R. , Camina R. D.
Published: June 2009

We consider finite groups in which every triple of distinct conjugacy class sizes greater than one has a pair which is coprime. We prove such a group is soluble and has conjugate rank at most three.
Out on the town
Authors: Paay Jeni , Kjeldskov Jesper , Howard Steve , Dave Bharat
Published: June 2009

As urban environments become increasingly hybridized, mixing the social, built, and digital in interesting ways, designing for computing in the city presents new challenges—how do we understand such hybridization, and then respond to it as designers? Here we synthesize earlier work in human-computer interaction, sociology and architecture in order to deliberately influence the design of digital systems with an understanding of their built and social context of use. We propose, illustrate, and evaluate a multidisciplinary approach combining rapid ethnography, architectural analysis, design sketching, and paper prototyping. Following the approach we are able to provide empirically grounded representations of the socio-physical context of use, in this case people socializing in urban spaces. We then use this understanding to influence the design of a context aware system to be used while out on the town. We believe that the approach is of value more generally, particularly when achieving powerfully situated interactions is the design ambition.
Rapid prototyping and evaluation of in-vehicle interfaces
Authors: Salvucci Dario D.
Published: June 2009

As driver distraction from in-vehicle devices becomes an increasingly critical issue, researchers have aimed to establish better scientific understanding of distraction along with better engineering tools to build less distracting devices. This article presents a new system, Distract-R, that allows designers to rapidly prototype and evaluate new in-vehicle interfaces. The core engine of the system relies on a rigorous cognitive model of driver behavior which, when integrated with models of task behavior on the prototyped interfaces, generate predictions of driver performance and distraction. Distract-R allows a designer to prototype basic interfaces, demonstrate possible tasks on these interfaces, specify relevant driver characteristics and driving scenarios, and finally simulate, visualize, and analyze the resulting behavior as generated by the cognitive model. The article includes three modeling studies that demonstrate the system's ability to account for various aspects of driver performance for several types of in-vehicle interfaces. More generally, Distract-R illustrates how cognitive models can be used as internal simulation engines for design tools intended for nonmodelers, with the ultimate goal of helping to understand and predict user behavior in multitasking environments.
Kansuke
Authors: Tanaka-Ishii Kumiko , Godon Julian
Published: June 2009

We have developed a method that makes it easier for language novices to look up Japanese and Chinese logographs. Instead of using the arbitrary conventions of logographs, this method is based on three simple prototypes: horizontal, vertical, and other strokes. For example, the code for the logograph ⊞ (
ta
, meaning rice field) is 3-3-0, indicating the logograph consists of three horizontal strokes and three vertical strokes. Such codes allow a novice to look up logographs even with no knowledge of the logographic conventions used by native speakers. To make the search easier, a complex logograph can be looked up via the components making up the logograph. We conducted a user evaluation of this system and found that novices could look up logographs with fewer failures with our system than with conventional methods.
Automation Schemes for FPGA Implementation of Wave-Pipelined Circuits
Authors: Seetharaman G. , Venkataramani B.
Published: June 2009

Operating frequencies of combinational logic circuits can be increased using Wave-Pipelining (WP), by adjusting the clock periods and clock skews. In this article, Built-In Self-Test (BIST) and System-on-Chip (SOC) approaches are proposed for automating this adjustment and they are evaluated by implementation of filters using a Distributed Arithmetic Algorithm (DAA) and sinewave generator using the COordinate Rotation DIgital Computer (CORDIC). Both the circuits are studied by adopting three schemes: wave-pipelining, pipelining, and nonpipelining. Xilinx Spartan II and Altera Cyclone II FPGAs with Nios II soft-core processor are used for implementation of the circuits with the BIST and SOC approaches, respectively. The proposed schemes increase the speed of the WP circuits by a factor of 1.19--2.6 compared to nonpipelined circuits. The pipelined circuits achieve higher speed than the WP circuits by a factor of 1.13--3.27 at the cost of increase in area and power. When both pipelined and WP circuits are operated at the same frequency, the former dissipates more power for circuits with higher word sizes and for moderate logic depths. The observation regarding the dependence of the superiority of the WP circuits with regard to power dissipation on the logic depth is one of the major contributions of this article.
Vector Processing as a Soft Processor Accelerator
Authors: Yu Jason , Eagleston Christopher , Chou Christopher Han-Yu , Perreault Maxime , Lemieux Guy
Published: June 2009

Current FPGA soft processor systems use dedicated hardware modules or accelerators to speed up data-parallel applications. This work explores an alternative approach of using a soft vector processor as a general-purpose accelerator. The approach has the benefits of a purely software-oriented development model, a fixed ISA allowing parallel software and hardware development, a single accelerator that can accelerate multiple applications, and scalable performance from the same source code. With no hardware design experience needed, a software programmer can make area-versus-performance trade-offs by scaling the number of functional units and register file bandwidth with a single parameter. A soft vector processor can be further customized by a number of secondary parameters to add or remove features for a specific application to optimize resource utilization. This article introduces VIPERS, a soft vector processor architecture that maps efficiently into an FPGA and provides a scalable amount of performance for a reasonable amount of area. Compared to a Nios II/s processor, instances of VIPERS with 32 processing lanes achieve up to 44× speedup using up to 26× the area.
CEAL
Authors: Hammer Matthew A. , Acar Umut A. , Chen Yan
Published: June 2009

Self-adjusting computation offers a language-centric approach to writing programs that can automatically respond to modifications to their data (e.g., inputs). Except for several domain-specific implementations, however, all previous implementations of self-adjusting computation assume mostly functional, higher-order languages such as Standard ML. Prior to this work, it was not known if self-adjusting computation can be made to work with low-level, imperative languages such as C without placing undue burden on the programmer.

We describe the design and implementation of CEAL: a C-based language for self-adjusting computation. The language is fully general and extends C with a small number of primitives to enable writing self-adjusting programs in a style similar to conventional C programs. We present efficient compilation techniques for translating CEAL programs into C that can be compiled with existing C compilers using primitives supplied by a run-time library for self-adjusting computation. We implement the proposed compiler and evaluate its effectiveness. Our experiments show that CEAL is effective in practice: compiled self-adjusting programs respond to small modifications to their data by orders of magnitude faster than recomputing from scratch while slowing down a from-scratch run by a moderate constant factor. Compared to previous work, we measure significant space and time improvements.
Lightweight annotations for controlling sharing in concurrent data structures
Authors: Anderson Zachary R. , Gay David , Naik Mayur
Published: June 2009

SharC is a recently developed system for checking data-sharing in multithreaded programs. Programmers specify sharing rules (read-only, protected by a lock, etc.) for individual objects, and the SharC compiler enforces these rules using static and dynamic checks. Violations of these rules indicate unintended data sharing, which is the underlying cause of harmful data-races. Additionally, SharC allows programmers to change the sharing rules for a specific object using a
sharing cast
, to capture the fact that sharing rules for an object often change during the object's lifetime. SharC was successfully applied to a number of multi-threaded C programs.

However, many programs are not readily checkable using SharC because their sharing rules, and changes to sharing rules, effectively apply to whole data structures rather than to individual objects. We have developed a system called
Shoal
to address this shortcoming. In addition to the sharing rules and sharing cast of SharC, our system includes a new concept that we call
groups
. A group is a collection of objects all having the same sharing mode. Each group has a distinguished member called the
group leader
. When the sharing mode of the group leader changes by way of a sharing cast, the sharing mode of all members of the group also changes. This operation is made sound by maintaining the invariant that at the point of a sharing cast, the only external pointer into the group is the pointer to the group leader. The addition of groups allows checking safe concurrency at the level of data structures rather than at the level of individual objects.

We demonstrate the necessity and practicality of groups by applying Shoal to a wide range of concurrent C programs (the largest approaching a million lines of code). In all benchmarks groups entail low annotation burden and no significant additional performance overhead.