bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACT

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

ABSTRACT
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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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.
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.
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.
FastTrack
Authors: Flanagan Cormac , Freund Stephen N. 
Published: June 2009

\begin{abstract}
Multithreaded programs are notoriously prone to race conditions. Prior work on dynamic race detectors includes fast but imprecise race detectors that report false alarms, as well as slow but precise race detectors that never report false alarms. The latter typically use expensive vector clock operations that require time linear in the number of program threads.
This paper exploits the insight that the full generality of vector clocks is unnecessary in most cases. That is, we can replace heavyweight vector clocks with an adaptive lightweight representation that, for almost all operations of the target program, requires only constant space and supports constant-time operations. This representation change significantly improves time and space performance, with no loss in precision.

Experimental results on Java benchmarks including the Eclipse development environment show that our
FastTrack
race detector is an order of magnitude faster than a traditional vector-clock race detector, and roughly twice as fast as the high-performance DJIT+ algorithm.
FastTrack
is even comparable in speed to
Eraser
on our Java benchmarks, while never reporting false alarms.