bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thread Friction Torque in Bolted Joints
Authors: Nassar Sayed A. , Matin Payam H. , Barber Gary C. 
Published: October 2005

Abstract
In this paper, formulas are developed for the calculation of the effective thread friction radius in fasteners, in order to determine the thread friction torque component. Due to the lack of exact formulas in the literature, current practice uses the average value of the minor and major thread radii, as an approximation, for determining the thread friction torque component. Results provided by these formulas are compared with those given by the current practice that uses the average value of the minor and major thread radii, instead of the exact value. It is well known that the torque-tension relationship in threaded fastener applications is highly sensitive to the friction torque components: between threads, and under the turning fastener head or nut. Even moderate variations or inaccuracies in determining the friction torque components would significantly impact the fastener tension and the joint clamp load. High accuracy in the estimation of the friction torque components is critical, as it directly affects the reliability, safety, and the quality of bolted assemblies. This analysis focuses on the thread friction torque component. The new formulas for the thread friction radius are developed for a mathematical model of a bolted joint using five assumed scenarios of the contact pressure between male and female threads. Because of the fact that the variation in the sliding speed of various points on a thread surface is insignificant, a uniform thread friction coefficient is used in the analysis. However, a contact area weighted average value is used for the thread friction coefficient. Numerical results and error analysis are presented in terms of a single nondimensional variable, namely, the ratio between the major and minor thread radii.
Antibiotic Abscess Penetration: Fosfomycin Levels Measured in Pus and Simulated Concentration-Time Profiles
Authors: Sauermann Robert , Karch Rudolf , Langenberger Herbert , Kettenbach Joachim , Mayer-Helm Bernhard , Petsch Martina , Wagner Claudia , Sautner Thomas , Gattringer Rainer , Karanikas Georgios , Joukhadar Christian 
Published: October 2005

ABSTRACTThe present study was performed to evaluate the ability of fosfomycin, a broad-spectrum antibiotic, to penetrate into abscess fluid. Twelve patients scheduled for surgical or computer tomography-guided abscess drainage received a single intravenous dose of 8 g of fosfomycin. The fosfomycin concentrations in plasma over time and in pus upon drainage were determined. A pharmacokinetic model was developed to estimate the concentration-time profile of fosfomycin in pus. Individual fosfomycin concentrations in abscess fluid at drainage varied substantially, ranging from below the limit of detection up to 168 mg/liter. The fosfomycin concentrations in pus of the study population correlated neither with plasma levels nor with the individual ratios of abscess surface area to volume. This finding was attributed to highly variable abscess permeability. The average concentration in pus was calculated to be 182 ± 64 mg/liter at steady state, exceeding the MIC50/90s of several bacterial species which are commonly involved in abscess formation, such as streptococci, staphylococci, andEscherichia coli. Hereby, the exceptionally long mean half-life of fosfomycin of 32 ± 39 h in abscess fluid may favor its antimicrobial effect because fosfomycin exerts time-dependent killing. After an initial loading dose of 10 to 12 g, fosfomycin should be administered at doses of 8 g three times per day to reach sufficient concentrations in abscess fluid and plasma. Applying this dosing regimen, fosfomycin levels in abscess fluid are expected to be effective after multiple doses in most patients.
Fitness Cost Due to Mutations in the 16S rRNA Associated with Spectinomycin Resistance in
Chlamydia psittaci
6BC
Authors: Binet Rachel , Maurelli Anthony T. 
Published: October 2005

ABSTRACT

The fitness cost of a resistance determinant is the primary parameter that determines its frequency in vivo. As a model for analysis of the impact of drug resistance mutations on the intracellular life cycle of
Chlamydia
spp., we studied the growth of four genetically defined spectinomycin-resistant (Spc
r
) clonal variants of
Chlamydia psittaci
6BC isolated in the plaque assay. The development of each variant was monitored over 46 h postinfection in the absence of drug, either in pure culture or in 1:1 competition with the parent strain. Spc
r
mutations in the 16S rRNA gene at positions 1191 and 1193 were associated with a marked impairment of
C.psittaci
biological fitness, and the bacteria were severely outcompeted by the wild-type parent. In contrast, mutations at position 1192 had minor effects on the bacterial life cycle, allowing the resistant isolates to compete more efficiently with the wild-type strain. Thus, mutations with a wide range of fitness costs can be selected in the plaque assay, providing a new strategy for prediction and monitoring of the emergence of antibiotic resistance in chlamydiae. So far, drug resistance has not been a serious threat for the treatment of chlamydial infections. Tetracycline is an effective antichlamydial drug that targets 16S rRNA. Attempts to isolate spontaneous tetracycline-resistant mutants of
C. psittaci
6BC revealed a frequency <3 × 10
−9
. We suggest that the rarity of genotypic antibiotic resistance among chlamydial clinical isolates reflects the deleterious effects of such mutations on the fitness of these obligate intracellular bacteria in the host.
Novel Acquired Metallo-β-Lactamase Gene,blaSIM-1, in a Class 1 Integron fromAcinetobacter baumanniiClinical Isolates from Korea
Authors: Lee Kyungwon , Yum Jong Hwa , Yong Dongeun , Lee Hyuk Min , Kim Heung Dong , Docquier Jean-Denis , Rossolini Gian Maria , Chong Yunsop 
Published: October 2005

ABSTRACTCarbapenem resistance mediated by acquired carbapenemase genes has been increasingly reported, particularly for clinical isolates ofPseudomonas aeruginosaandAcinetobacterspp. Of 1,234 nonduplicate isolates of carbapenem-resistantPseudomonasspp. andAcinetobacterspp. isolated at a tertiary-care hospital in Seoul, Korea, 211 (17%) were positive for metallo-β-lactamase (MBL). Of these, 204 (96%) had either theblaIMP-1orblaVIM-2allele. In addition, sevenAcinetobacter baumanniiisolates were found to have a novel MBL gene, which was designatedblaSIM-1. The SIM-1 protein has a pI of 7.2, is a new member of subclass B1, and exhibits 64 to 69% identity with the IMP-type MBLs, which are its closest relatives. All SIM-1-producing isolates exhibited relatively low imipenem and meropenem MICs (8 to 16 μg/ml) and had a multidrug resistance phenotype. Expression of the clonedblaSIM-1gene inEscherichia colirevealed that the encoded enzyme is capable of hydrolyzing a broad array of β-lactams, including penicillins, narrow- to expanded-spectrum cephalosporins, and carbapenems. TheblaSIM-1gene was carried on a gene cassette inserted into a class 1 integron, which included three additional cassettes (arr-3,catB3, andaadA1). The strains were isolated from sputum and urine specimens from patients with pneumonia and urinary tract infections, respectively. All patients had various underlying diseases. Pulsed-field gel electrophoresis of SmaI-digested genomic DNAs showed that the strains belonged to two different clonal lineages, indicating that horizontal transfer of this gene had occurred and suggesting the possibility of further spread of resistance in the future.
Randomized, Placebo-Controlled Trial of Nonpegylated and Pegylated Forms of Recombinant Human Alpha Interferon 2a for Suppression of Dengue Virus Viremia in Rhesus Monkeys
Authors: Ajariyakhajorn C. , Mammen M. P. , Endy T. P. , Gettayacamin M. , Nisalak A. , Nimmannitya S. , Libraty D. H. 
Published: October 2005

ABSTRACTDengue fever and dengue hemorrhagic fever are caused by infection with any one of the four dengue viruses (DVs) and are significant public health burdens throughout the tropics. Higher viremia levels are associated with greater dengue disease severity. A therapeutic intervention to suppress viremia early in DV infection could potentially ameliorate severe disease. Recombinant alpha interferon 2a (rIFN-α-2a, Roferon-A) suppressed DV replication in human peripheral blood mononuclear cells in vitro. We therefore examined the effects of rIFN-α-2a and pegylated recombinant IFN-α-2a (PEG-rIFN-α-2a, PEGASYS) on DV serotype 2 (DV-2) viremia in rhesus monkeys. Flavivirus-naïve monkeys were inoculated with DV-2 and randomized to receive a single dose of rIFN-α-2a (10 million international units/m2) versus placebo or PEG-rIFN-α-2a (6 μg/kg) versus placebo 1 day after the onset of viremia. Serial daily viremia levels were measured, and convalescent-phase DV-2 neutralizing antibody titers were determined. Compared to placebo, a single injection of rIFN-α-2a temporarily suppressed DV-2 replication and delayed the time to peak viremia by a median of 3 days. However, measures of total viral burden were not different between the two groups. A single injection of PEG-rIFN-α-2a significantly lowered daily viremia levels and improved virus clearance, starting 48 h after administration. There were no significant differences in DV-2 neutralizing antibody titers between the treatment and placebo groups at 30 and 90 days postinfection. Based on their individual effects, future studies should investigate a combination of rIFN-α-2a and PEG-rIFN-α-2a for suppression of dengue virus viremia and as a potential therapeutic intervention.
Use of Ribotyping To Retrospectively Identify Methicillin-Resistant
Staphylococcus aureus
Isolates from Phase 3 Clinical Trials for Tigecycline That Are Genotypically Related to Community-Associated Isolates
Authors: McAleese Fionnuala , Murphy Ellen , Babinchak Timothy , Singh Guy , Said-Salim Battouli , Kreiswirth Barry , Dunman Paul , O'Connell John , Projan Steven J. , Bradford Patricia A. 
Published: October 2005

ABSTRACT

A retrospective study was performed to identify methicillin-resistant
Staphylococcus aureus
(MRSA) isolates obtained from patients enrolled in phase 3 clinical trials for tigecycline that were genotypically similar to known community-associated MRSA (CA-MRSA) strains. The clinical trials were double-blind comparator studies for complicated skin and skin structure infections or complicated intra-abdominal infections. We obtained 85% of the MRSA isolates from patients with complicated skin and skin structure infections. Using ribotyping, MRSA isolates were compared with well-characterized North American CA-MRSA strains and negative-control hospital-associated (HA) MRSA strains by cluster analysis; 91 of the 173 isolates clustered with two groups of known CA-MRSA strains, 60% of which shared an indistinguishable ribotype. These isolates were subsequently tested for the presence of SCC
mec
type IV and the Panton-Valentine leukocidin (PVL)-encoding genes as well as susceptibility to clindamycin, characteristics that are typically associated with CA-MRSA; 89 of the 91 isolates carried the type IV SCC
mec
element and 76 were also positive for the PVL-encoding genes; 73 of these isolates were susceptible to clindamycin. A similar analysis performed on 26 nonclustering isolates identified only four with these characteristics; 89 of the 91 clustering isolates were inhibited by tigecycline at MICs of ≤0.5 μg/ml. On the basis of clustering information and preliminary genetic characterization, it appears that ribotyping is a useful tool in identifying potential CA-MRSA isolates and 76 MRSA isolates from patients enrolled in the tigecycline phase 3 trials have genetic markers typically associated with CA-MRSA.
Gene Expression Analysis of the Mechanism of Natural Sb(V) Resistance in
Leishmania donovani
Isolates from Nepal
Authors: Decuypere Saskia , Rijal Suman , Yardley Vanessa , De Doncker Simonne , Laurent Thierry , Khanal Basudha , Chappuis François , Dujardin Jean-Claude 
Published: October 2005

ABSTRACT

Control of visceral leishmaniasis (VL) is being challenged by the emergence of natural resistance against the first line of treatment, pentavalent antimonials [Sb(V)]. An insight into the mechanism of natural Sb(V) resistance is required for the development of efficient strategies to monitor the emergence and spreading of Sb(V) resistance in countries where VL is endemic. In this work, we have focused on the mechanism of natural Sb(V) resistance emerging in Nepal, a site where anthroponotic VL is endemic. Based on the current knowledge of Sb(V) metabolism and of the in vitro trivalent antimonial [Sb(III)] models of resistance to
Leishmania
spp., we selected nine genes for a comparative transcriptomic study on natural Sb(V)-resistant and -sensitive
Leishmania donovani
isolates. Differential gene expression patterns were observed for the genes coding for 2-thiol biosynthetic enzymes, gamma-glutamylcysteine synthetase (GCS) and ornithine decarboxylase (ODC), and for the Sb(III) transport protein aquaglyceroporin 1 (AQP1). The results indicate that the mechanism for natural Sb(V) resistance partially differs from the mechanism reported for in vitro Sb(III) resistance. More specifically, we hypothesize that natural Sb(V) resistance results from (i) a changed thiol metabolism, possibly resulting in inhibition of Sb(V) activation in amastigotes, and (ii) decreased uptake of the active drug Sb(III) by amastigotes.
Inhibitory Activities of Epidermal Growth Factor Receptor Tyrosine Kinase-Targeted Dihydroxyisoflavone and Trihydroxydeoxybenzoin Derivatives on
Sarcocystis neurona
,
Neospora caninum
, and
Cryptosporidium parvum
Development
Authors: Gargala G. , Baishanbo A. , Favennec L. , François A. , Ballet J. J. , Rossignol J.-F. 
Published: October 2005

ABSTRACT

Several gene sequences of parasitic protozoa belonging to protein kinase gene families and epidermal growth factor (EGF)-like peptides, which act via binding to receptor tyrosine kinases of the EGF receptor (EGFR) family, appear to mediate host-protozoan interactions. As a clue to EGFR protein tyrosine kinase (PTK) mediation and a novel approach for identifying anticoccidial agents, activities against
Sarcocystis neurona
,
Neospora caninum
, and
Cryptosporidium parvum
grown in BM and HCT-8 cell cultures of 52 EGFR PTK inhibitor isoflavone analogs (dihydroxyisoflavone and trihydroxydeoxybenzoine derivatives) were investigated. Their cytotoxicities against host cells were either absent, mild, or moderate by a nitroblue tetrazolium test. At concentrations ranging from 5 to 10 μg/ml, 20 and 5 analogs, including RM-6427 and RM-6428, exhibited an in vitro inhibitory effect of ≥95% against at least one parasite or against all three, respectively. In immunosuppressed
Cryptosporidium parvum
-infected Mongolian gerbils orally treated with either 200 or 400 mg of agent RM-6427/kg of body weight/day for 8 days, fecal microscopic oocyst shedding was abolished in 6/10 animals (
P
of <0.001 versus untreated controls) and mean shedding was reduced by 90.5% (
P
of <0.0001) and 92.0% (
P
of <0.0001), respectively, higher levels of inhibition than after nitazoxanide (200 mg/kg/day for 8 days) or paromomycin (100 mg/kg/day for 8 days) treatment (55.0%,
P
of <0.001, and 17.5%,
P
of >0.05, respectively). After RM-6427 therapy (200 mg/kg/day for 8 days), the reduction in the ratio of animals with intracellular parasites was nearly significant in ileum (
P
= 0.067) and more marked in the biliary tract (
P
< 0.0013) than after nitazoxanide or paromomycin treatment (0.05 <
P
< 0.004). RM-6428 treatment at a regimen of 400 mg/kg/day for 12 days inhibited oocyst shedding, measured using flow cytometry from day 4 (
P
< 0.05) to day 12 (
P
< 0.02) of therapy, when 2/15 animals had no shedding (
P
< 0.0001) and 11/15 were free of gut and/or biliary tract parasites (
P
< 0.01). No mucosal alteration was microscopically observed for treated or untreated infected gerbils. To our knowledge, this report is the first to suggest that the isoflavone class of agents has the potential for anticoccidial therapy.
Horizontal Transfer of Iturin A Operon,
itu
, to
Bacillus subtilis
168 and Conversion into an Iturin A Producer
Authors: Tsuge Kenji , Inoue Satoka , Ano Takashi , Itaya Mitsuhiro , Shoda Makoto 
Published: October 2005

ABSTRACT

Iturin A and its derivatives are lipopeptide antibiotics produced by
Bacillus subtilis
and several closely related bacteria. Three
iturin group operons (i.e., iturin A, mycosubtilin, and bacillomycin D) of those antibiotic-producing strains have been cloned and sequenced
thus far, strongly implying the horizontal transfer of these operons. To examine the nature of such horizontal transfer in terms of antibiotic production, a 42-kb region of the
B. subtilis
RB14 genome, which contains a complete 38-kb iturin A operon, was
transferred via competent cell transformation to the genome of a non-iturin A producer,
B. subtilis
168, using a method based on double-crossover homologous recombination with two short landing pad sequences (LPSs) in the genome. The recombinant was positively selected
by confirming the elimination of the
c
I repressor gene, which was localized between the two LPSs and substituted by the transferred
segment. The iturin A operon-transferred strain 168 was then converted into an iturin A producer by the introduction of an
sfp
gene,
which encodes 4′-phosphopantetheinyl transferase and is mutated in strain 168. By inserting the pleiotropic regulator
degQ
, the productivity of iturin A increased sevenfold and was restored to about half that of the donor strain RB14, without the transfer of
additional genes, such as regulatory or self-resistance genes.
Safety and Efficacy of Tigecycline in Treatment of Skin and Skin Structure Infections: Results of a Double-Blind Phase 3 Comparison Study with Vancomycin-Aztreonam
Authors: Breedt Johannes , Teras Jüri , Gardovskis Janis , Maritz Frans Jacobus , Vaasna Tiit , Ross Douglas Patrick , Gioud-Paquet Martine , Dartois Nathalie , Ellis-Grosse Evelyn J. , Loh Evan 
Published: October 2005

ABSTRACTIn a randomized, double-blind, controlled trial, 546 patients with complicated skin and skin structure infections received tigecycline 100 mg/day (a 100-mg initial dose and then 50 mg intravenously twice daily) or the combination of vancomycin 2 g/day (1 g intravenously twice daily) and aztreonam 4 g/day (2 g intravenously twice daily) for up to 14 days. The primary end point was the clinical response in the clinical modified intent-to-treat (c-mITT) and clinically evaluable (CE) populations at the test-of-cure visit 12 to 92 days after the last dose. The microbiologic response at the test-of-cure visit was also assessed. Safety was assessed by physical examination, laboratory results, and adverse event reporting. Five hundred twenty patients were included in the c-mITT population (tigecycline group,n= 261; combination group,n= 259), and 436 were clinically evaluable (tigecycline group,n= 223; combination group,n= 213). The clinical responses in the tigecycline and the combination vancomycin and aztreonam groups were similar in the c-mITT population (84.3% versus 86.9%; difference, −2.6% [95% confidence interval, −9.0, 3.8];P= 0.4755) and the CE population (89.7% versus 94.4%; difference, −4.7% [95% confidence interval, −10.2, 0.8];P= 0.1015). Microbiologic eradication (documented or presumed) occurred in 84.8% of the patients receiving tigecycline and 93.2% of the patients receiving vancomycin and aztreonam (difference, −8.5 [95% confidence interval, −16.0, −1.0];P= 0.0243). The numbers of patients reporting adverse events were similar in the two groups, with increased nausea and vomiting rates in the tigecycline group and an increased incidence of rash and increases in alanine aminotransferase and aspartate aminotransferase levels in the combination vancomycin and aztreonam group. Tigecycline was shown to be safe and effective for the treatment of complicated skin and skin structure infections.
Combination Therapy with Terbinafine and Amphotericin B in a Rabbit Model of Experimental Invasive Aspergillosis
Authors: Kirkpatrick William R. , Vallor Ana C. , McAtee Robert K. , Ryder Neil S. , Fothergill Annette W. , Rinaldi Michael G. , Patterson Thomas F. 
Published: October 2005

ABSTRACT
Antagonistic effects of combination therapy using amphotericin B (AmB) with agents which block ergosterol synthesis are a concern. Terbinafine was evaluated with AmB to assess antagonism or synergy in a rabbit model of invasive aspergillosis. Terbinafine had relatively little activity but did not demonstrate antagonism against AmB in our model.
TLA-2, a Novel Ambler Class A Expanded-Spectrum β-Lactamase
Authors: Girlich Delphine , Poirel Laurent , Schlüter Andreas , Nordmann Patrice 
Published: October 2005

ABSTRACT

β-Lactamase TLA-2 is encoded by a 47-kb plasmid isolated from an unidentified bacterial strain from a wastewater treatment plant. TLA-2 is an Ambler class A β-lactamase that shares 52% amino acid identity with CGA-1 from
Chryseobacterium gleum
and 51% with TLA-1 from
Escherichia coli
. The enzyme hydrolyzes mostly cephalosporins.
mmpL7
Gene of
Mycobacterium tuberculosis
Is Responsible for Isoniazid Efflux in
Mycobacterium smegmatis
Authors: Pasca Maria R. , Guglierame Paola , De Rossi Edda , Zara Francesca , Riccardi Giovanna 
Published: October 2005

ABSTRACT

The
Mycobacterium tuberculosis mmpL7
gene, encoding a hypothetical resistance nodulation division transporter, confers a high resistance level to isoniazid when overexpressed in
Mycobacterium smegmatis
. The resistance level decreased in the presence of the efflux pump inhibitors reserpine and CCCP (carbonyl cyanide
m
-chlorophenylhydrazone). Energy-dependent efflux of isoniazid from
M. smegmatis
cells expressing the
mmpL7
gene was observed.
Analysis of the Contribution of
Salmonella
Pathogenicity Islands 1 and 2 to Enteric Disease Progression Using a Novel Bovine Ileal Loop Model and a Murine Model of Infectious Enterocolitis
Authors: Coombes Brian K. , Coburn Bryan A. , Potter Andrew A. , Gomis Susantha , Mirakhur Kuldip , Li Yuling , Finlay B. Brett 
Published: October 2005

ABSTRACT

We have developed a novel ileal loop model for use in calves to analyze the contribution of
Salmonella enterica
serovar Typhimurium type III secretion systems to disease processes in vivo. Our model involves constructing ileal loops with end-to-end anastamoses to restore the patency of the small intestine, thereby allowing experimental animals to convalesce following surgery for the desired number of days. This model overcomes the time constraint imposed by ligated ileal loop models that have precluded investigation of
Salmonella
virulence factors during later stages of the infection process. Here, we have used this model to examine the enteric disease process at 24 h and 5 days following infection with wild-type
Salmonella
and mutants lacking the virulence-associated
Salmonella
pathogenicity island 1 (SPI-1) or SPI-2 type III secretion systems. We show that SPI-2 mutants are dramatically attenuated at 5 days following infection and report a new phenotype for SPI-1 mutants, which induce intestinal pathology in calves similar to wild-type
Salmonella
in the 5-day ileal loop model. Both of these temporal phenotypes for SPI-1 and SPI-2 mutants were corroborated in a second animal model of enteric disease using streptomycin-pretreated mice. These data delineate novel phenotypes for SPI-1 and SPI-2 mutants in the intestinal phase of bovine and murine salmonellosis and provide working models to further investigate the effector contribution to these pathologies.