bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Situ Matrix Shear Response Using Torsional Test
Data of Fiber Reinforced Unidirectional Polymer Composites
Authors: Yerramalli Chandra S. , Waas Anthony M. 
Published: July 2002

Abstract
The in situ shear response of the matrix in polymer matrix composites (PMC) has been studied. Torsion tests were performed on solid cylinders of unidirectional glass fiber reinforced/vinylester and unidirectional carbon fiber reinforced/vinylester composites. The composite specimens were subjected to a uniform rate of twist. From the composite stress-strain curve, a plot of tangent shear modulus vs shear strain was derived. Then, using the Halpin-Tsai equations, the in situ matrix shear modulus was determined. The in situ matrix properties obtained from glass/vinylester and carbon/vinylester composites were found to be different. In addition, the properties of the in situ matrix were found to be a function of fiber volume fraction and the elastic properties of the reinforcing fiber. The behavior of the in situ matrix as a function of the fiber volume fraction was explained by using a three cylinder interphase model. The validity of the interphase model in predicting the composite shear modulus was studied by comparison of results against a conventional 2 cylinder model.
Continuous Model for the Transverse Vibration of Cracked Timoshenko
Beams
Authors: Carneiro Sergio H. S. , Inman Daniel J. 
Published: July 2002

Abstract
A continuous model for the transverse vibrations of cracked beams including the effect of shear deformation is derived. Partial differential equations of motion and associated boundary conditions are obtained via the Hu-Washizu-Barr variational principle, which allows simultaneous and independent assumptions on the displacement, stress and strain fields. The stress and strain concentration caused by the presence of a crack are represented by so-called crack disturbance functions, which modify the kinematic assumptions used in the variational procedure. For the shear stress/strain fields, a quadratic distribution over the beam depth is assumed, which is a refinement of the typical constant shear stress distribution implicit in the Timoshenko model for uncracked beams. The resulting equations of motion are solved by a Galerkin method using local B-splines as test functions. As a numerical verification, natural frequencies of the linear, open-crack model are computed and the results are compared to analytical results from similar models based on Euler-Bernoulli assumptions and experimental results found in the literature. For short beams, results from a 2-D finite element model are used to confirm the advantages of the proposed model when compared with previous formulations.
Fluid Flow and Heat Transfer in a Rotating Two-Pass Square Duct With In-Line 90-deg Ribs
Authors: Liou Tong-Miin , Chen Meng-Yu , Tsai Meng-Hsiun 
Published: July 2002

Abstract
Laser-doppler velocimetry and transient thermochromic liquid crystal measurements are presented to understand local fluid flow and surface heat transfer distributions in a rotating ribbed duct with a 180 deg sharp turn. The in-line 90-deg ribs were arranged on the leading and trailing walls with rib height-to-hydraulic diameter ratio and pitch-to-height ratio of 0.136 and 10, respectively. The Reynolds number, based on duct hydraulic diameter and bulk mean velocity, was fixed at 1.0×104 whereas the rotational number varied from 0 to 0.2. Results are compared with those of the rotating smooth duct flow in terms of maximum streamwise mean velocities Umax/Ub and turbulence intensities u′max/Ub, skewness of mean velocity profiles, secondary flow pattern, turn-induced separation bubble, and turbulence anisotropy. Nusselt number ratio mappings are also provided on the leading and trailing walls. The relationships between the fluid flow and local heat transfer enhancement are also documented. It is found that the rotating ribbed duct flow provides higher Umax/Ub,u′max/Ub, and stronger total averaged secondary flow and, hence heat transfer is enhanced. Comparisons with heat transfer data published by other research groups are also made. Furthermore, simple linear correlations between regional averaged Nusselt number ratio and rotation number are developed.
Comparative Pharmacodynamic Analysis of Q-T Interval Prolongation Induced by the Macrolides Clarithromycin, Roxithromycin, and Azithromycin in Rats
Authors: Ohtani Hisakazu , Taninaka Chieko , Hanada Erika , Kotaki Hajime , Sato Hitoshi , Sawada Yasufumi , Iga Tatsuji 
Published: July 2002

ABSTRACT
In order to evaluate the arrhythmogenic potency of macrolide antibiotics in a quantitative manner, we analyzed the influence of clarithromycin (CAM), roxithromycin (RXM), and azithromycin (AZM) on Q-T intervals from pharmacokinetic and pharmacodynamic points of view and in comparison with the potency of erythromycin (EM) previously reported by us for rats. Male Sprague-Dawley rats were anesthetized, and CAM (6.6, 21.6, and 43.2 mg/kg of body weight/h), RXM (20 and 40 mg/kg/h), and AZM (40 and 100 mg/kg/h) were intravenously injected for 90 min to obtain the time courses of drug concentrations in plasma and the changes in the Q-T intervals during and after the drug injections. Distinct Q-T interval prolongation of up to 10 ms was observed with CAM at its clinical concentrations. RXM and AZM evoked Q-T interval prolongation at concentrations higher than their clinical ranges. The potencies for Q-T interval prolongation, assessed as the slope of the concentration-response relationship, were 6.09, 0.536, and 0.989 ms · ml/μg for CAM, RXM, and AZM, respectively. There was hysteresis between the change in the Q-T intervals and the time course of the plasma concentration of each drug. The rank order of clinical arrhythmogenicity was estimated to be EM > CAM > RXM > AZM, as assessed from the present results and our previous report for EM. In conclusion, RXM and AZM were estimated to be less potent at provoking arrhythmia than EM and CAM. These results should be useful for making a safer choice of an appropriate agent for patients with electrocardiographic risk factors.
Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues
Authors: Frossard Martin , Joukhadar Christian , Erovic Boban M. , Dittrich Peter , Mrass Paulus E. , Van Houte Michael , Burgmann Heinz , Georgopoulos Apostolos , Müller Markus 
Published: July 2002

ABSTRACT

Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. For this purpose fosfomycin concentrations in vivo in the fluid of the interstitial space of human soft tissues were measured by microdialysis following intravenous infusion of 4 or 8 g of fosfomycin (
n
= 6). Subsequently, bacterial isolates with relevance for soft tissue infections were exposed to concentrations according to the in vivo pharmacokinetic profile in the interstitial space fluid obtained by microdialysis. Our experiments indicated a high degree of soft tissue penetration for fosfomycin, with ratios of the area under the concentration-time curve from 0 to 8 h for muscle (AUC

0–8
muscle

)/AUC

0–8
serum

of 0.48 ± 0.08 and 0.53 ± 0.04 and ratios of AUC

0–8
adipose tissue

/AUC

0–8
serum

of 0.74 ± 0.12 and 0.71 ± 0.11 following administration of 4 and 8 g, respectively. In corresponding in vitro simulation experiments with selected isolates of
Staphylococcus aureus
,
Enterobacter cloacae
, and
Serratia marcescens
for which MICs were 16 μg/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.
Itraconazole-Amphotericin B Antagonism in
Aspergillus fumigatus
: an E-Test-Based Strategy
Authors: Kontoyiannis Dimitrios P. , Lewis Russell E. , Sagar Namita , May Gregory , Prince Randall A. , Rolston Kenneth V. I. 
Published: July 2002

ABSTRACT

We examined an E-test-based strategy for testing the combination of itraconazole and amphotericin B, the latter given either sequentially or concomitantly, in isolates of
Aspergillus fumigatus
. An antagonistic interaction between the two drugs was noted, especially with the sequential administration of amphotericin B. This in vitro antagonism was reversible.
In Vitro Activities of Novel
trans
-3,5-Disubstituted Pyrrolidinylthio-1β-Methylcarbapenems with Potent Activities against Methicillin-Resistant
Staphylococcus aureus
and
Pseudomonas aeruginosa
Authors: Nagano Rie , Shibata Kaneyoshi , Adachi Yuka , Imamura Hideaki , Hashizume Terutaka , Morishima Hajime 
Published: July 2002

ABSTRACT

The in vitro activities of the novel 1β-methylcarbapenems J-111,225, J-114,870, and J-114,871, which have a structurally unique side chain that consists of a
trans
-3,5-disubstituted 5-arylpyrrolidin-3-ylthio moiety at the C-2 position, were compared with those of reference antibiotics. Among isolates of both methicillin-resistant
Staphylococcus aureus
(MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS), 90% were inhibited by J-111,347 (prototype), J-111,225, J-114,870, and J-114,871 at concentrations of 2, 4, 4, and 4 μg/ml (MICs at which 90% of isolates are inhibited [MIC
90
s]), respectively, indicating that these agents were 32- to 64-fold more potent than imipenem, which has an MIC
90
of 128 μg/ml. Although these drugs were less active in vitro than vancomycin, which had MIC
90
s of 1 and 2 μg/ml for MRSA and MRCoNS, respectively, the new carbapenems displayed better killing kinetics than vancomycin. The potent anti-MRSA activity was ascribed to the excellent affinities of the new carbapenems for penicillin-binding protein 2a of MRSA. Since the new carbapenems also exhibited good activity against gram-positive and -negative bacteria including clinically important pathogens such as penicillin-resistant
Streptococcus pneumoniae
,
Haemophilus influenzae
, members of the family
Enterobacteriaceae
,
Pseudomonas aeruginosa
, and
Clostridium difficile
, as well as MRSA, the novel carbapenems are worthy of further evaluation.
vanC
Cluster of Vancomycin-Resistant
Enterococcus gallinarum
BM4174
Authors: Arias Cesar A. , Courvalin Patrice , Reynolds Peter E. 
Published: July 2002

ABSTRACT

Glycopeptide-resistant enterococci of the VanC type synthesize UDP-muramyl-pentapeptide[
d
-Ser] for cell wall assembly and prevent synthesis of peptidoglycan precursors ending in
d
-Ala. The
vanC
cluster of
Enterococcus gallinarum
BM4174 consists of five genes:
vanC-1
,

vanXY
C

,
vanT
,

vanR
C

, and

vanS
C

. Three genes are sufficient for resistance:
vanC-1
encodes a ligase that synthesizes the dipeptide
d
-Ala-
d
-Ser for addition to UDP-MurNAc-tripeptide,

vanXY
C

encodes a
d
,
d
-dipeptidase–carboxypeptidase that hydrolyzes
d
-Ala-
d
-Ala and removes
d
-Ala from UDP-MurNAc-pentapeptide[
d
-Ala], and
vanT
encodes a membrane-bound serine racemase that provides
d
-Ser for the synthetic pathway. The three genes are clustered: the start codons of

vanXY
C

and
vanT
overlap the termination codons of
vanC-1
and

vanXY
C

, respectively. Two genes which encode proteins with homology to the VanS-VanR two-component regulatory system were present downstream from the resistance genes. The predicted amino acid sequence of VanR
C
exhibited 50% identity to VanR and 33% identity to VanR
B
. VanS
C
had 40% identity to VanS over a region of 308 amino acids and 24% identity to VanS
B
over a region of 285 amino acids. All residues with important functions in response regulators and histidine kinases were conserved in VanR
C
and VanS
C
, respectively. Induction experiments based on the determination of
d
,
d
-carboxypeptidase activity in cytoplasmic extracts confirmed that the genes were expressed constitutively. Using a promoter-probing vector, regions upstream from the resistance and regulatory genes were identified that have promoter activity.
Antiviral Therapy Reduces Viral Burden but Does Not Prevent Thymic Involution in Young Cats Infected with Feline Immunodeficiency Virus
Authors: Hayes Kathleen A. , Phipps Andrew J. , Francke Sabine , Mathes Lawrence E. 
Published: July 2002

ABSTRACT
The thymus is a major target organ in human immunodeficiency virus type 1 (HIV-1)-infected children and feline immunodeficiency virus (FIV)-infected young cats (G. A. Dean and N. C. Pedersen, J. Virol. 72:9436–9440, 1998; J. L. Heeney, Immunol. Today 16:515–520, 1995; S. M. Schnittman et al., Proc. Natl. Acad. Sci. USA 87:7727–7731, 1990; T. A. Seemayer et al., Hum. Pathol. 15:469–474, 1984; H.-J. Shuurn et al., Am. J. Pathol. 134:1329–1338, 1989; J. C. Woo et al., J. Virol. 71:8632–8641, 1997; J. C. Woo et al., AIDS Res. Hum. Retrovir. 15:1377–1388, 1999). It is likely that the accelerated disease process in children and cats is due to infection of the thymus during the time when generation of naive T lymphocytes is needed for development of the mature immune system. Zidovudine (ZDV) monotherapy, which is used to prevent and treat perinatal HIV-1 infection (R. Sperling, Infect. Dis. Obstet. Gynecol. 6:197–203, 1998), previously had been shown to reduce viral burden in FIV-infected young cats (K. A. Hayes et al., J. Acquir. Immune Defic. Syndr. 6:127–134, 1993). The purpose of this study was to evaluate the effect of drug-induced reduction of viral burden in the thymus on virus-mediated thymic involution and peripheral blood CD4 decline using FIV-infected cats as a model for pediatric HIV-1 infection. Eight-week-old cats were randomly assigned to uninfected, saline-treated; uninfected, ZDV-treated; FIV-infected, saline-treated; and FIV-infected, ZDV-treated groups. Parameters measured included blood lymphocyte numbers, viral load in blood and thymic tissue, and thymic histopathology. While the viral burden was significantly reduced by ZDV monotherapy in peripheral blood lymphocytes, plasma, and thymus, thymic lesions were similar for the treated and untreated FIV-infected cats. Further, markedly lowering the viral burden did not increase blood CD4 lymphocyte numbers or prevent their decline. The data suggest that an inflammatory process continued in spite of reduced virus replication. These observations imply that reducing virus load and limiting thymic inflammation are separate factors that must be addressed when considering therapeutic strategies aimed at preserving thymic function.
Molecular Modeling Approach to Understanding the Mode of Action ofl-Nucleosides as Antiviral Agents
Authors: Lee Kyeong , Chu Chung K. 
Published: July 2002

ABSTRACTA series of unnaturall-nucleosides such as 3TC, FTC andl-FMAU have been found to be potent antiviral agents. The mode of action ofl-nucleosides has been found to be similar to that ofd-nucleosides as antiviral agents, despite their unnatural stereochemistry, that is, nucleotide formation by kinases followed by interaction with the reverse transcriptase (RT) of HIV or DNA polymerase. To date, the mode of action of nucleoside inhibitors at the molecular level with respect to the active conformations of the 5′-triphosphates as well as the interaction with the RT is not known. Recently, the X-ray crystal structure of the RT-DNA-dTTP catalytic complex has been reported. Computer modeling has been performed for several pairs ofd- andl-nucleoside inhibitors using the HIV-1 RT model and crystal coordinate data from a subset of the protein surrounding the deoxynucleoside triphosphate (dNTP) binding pocket region. Results from our modeling studies ofd-/l-zidovudine,d-/l-3TC,d-/l-dideoxycytosine triphosphates, dTTP and dCTP show that their binding energies correlate with the reported 50% effective concentrations. Modeling results are also discussed with respect to favorable conformations of each inhibitor at the dNTP site in the polymerization process. Additionally, the clinically important M184V mutation, which confers resistance against 3TC and FTC, was studied with our modeling system. The binding energy patterns of nucleoside inhibitors at the M184V mutation site correlate with the reported antiviral data.
Pharmacodynamics of Fluoroquinolones against
Streptococcus pneumoniae
in Patients with Community-Acquired Respiratory Tract Infections
Authors: Ambrose Paul G. , Grasela Dennis M. , Grasela Thaddeus H. , Passarell Julie , Mayer Howard B. , Pierce Phillip F. 
Published: July 2002

ABSTRACT

Fluoroquinolone antibiotic agents have demonstrated efficacy in the treatment of respiratory tract infections. This analysis was designed to examine the relationship between drug exposure, as measured by the free-drug area under the concentration-time curve at 24 h (AUC
24
)/MIC ratio, and clinical and microbiological responses in patients with community-acquired respiratory tract infections involving
Streptococcus pneumoniae
. The study population included 58 adult patients (34 males, 24 females) who were enrolled in either of two phase III, randomized, multicenter, double-blind studies of levofloxacin versus gatifloxacin for the treatment of community-acquired pneumonia or acute exacerbation of chronic bronchitis. Clearance equations from previously published population pharmacokinetic models were used in conjunction with dose and adjusted for protein binding to estimate individual patient free-drug AUC
24
s. In vitro susceptibility was determined in a central laboratory by broth microdilution in accordance with NCCLS guidelines. Pharmacodynamic analyses were performed on data from all evaluable patients with documented
S. pneumoniae
infection using univariate and multivariable logistic regression; pharmacodynamic breakpoints were estimated using Classification and Regression Tree analysis. A statistically significant (
P
= 0.013) relationship between microbiological response and the free-drug AUC
24
/MIC ratio was detected. At a free-drug AUC
24
/MIC ratio of <33.7, the probability of a microbiological response was 64%, and at a free-drug AUC
24
/MIC ratio of >33.7, it was 100% (
P
< 0.01). These findings may provide a minimum target free-drug AUC
24
/MIC ratio for the treatment of infections involving
S. pneumoniae
with fluoroquinolone antibiotics and provide a paradigm for the selection of fluoroquinolones to be brought forward from drug discovery into clinical development and dose selection for clinical trials. Further, when target free-drug AUC
24
/MIC ratios are used in conjunction with stochastic modeling techniques, these findings may be used to support susceptibility breakpoints for fluoroquinolone antibiotics and
S.
pneumoniae
.
In Vitro Anti-
Helicobacter pylori
Activity of the Probiotic Strain
Bacillus subtilis
3 Is Due to Secretion of Antibiotics
Authors: Pinchuk Irina V. , Bressollier Philippe , Verneuil Bernard , Fenet Bernard , Sorokulova Irina B. , Mégraud Francis , Urdaci Maria C. 
Published: July 2002

ABSTRACT

A limited number of antibiotics can be used against
Helicobacter pylori
infection, and resistance jeopardizes the success of treatment. Therefore, a search for new agents is warranted. The use of probiotics to enhance gastrointestinal health has been proposed for many years, but the scientific basis of the prophylactic and therapeutic actions of probiotics has not yet been clearly delineated. Probiotic strain
Bacillus subtilis
3, whose safety has previously been demonstrated, is known to have antagonistic properties against species of the family
Enterobacteriaceae
. In the present study, it was also found to inhibit
H. pylori
. The anti-
H. pylori
activity present in the cell-free supernatant was not related to pH or organic acid concentration. It was heat stable and protease insensitive. At least two antibiotics, detected by thin-layer chromatography (

R
f

values, 0.47 and 0.85, respectively) and confirmed by high-performance liquid chromatographic analysis, were found to be responsible for this anti-
H. pylori
activity. All
H. pylori
strains tested were sensitive to both compounds. One of these compounds was identified as amicoumacin A, an antibiotic with anti-inflammatory properties. MICs for
H. pylori
determined in solid and liquid media ranged between 1.7 and 6.8 μg/ml and 0.75 and 2.5 μg/ml, respectively. The underestimation of MICs determined in solid medium may be due to physicochemical instability of the antibiotic under these test conditions. An additive effect between amicoumacin A and the nonamicoumacin antibiotic against
H. pylori
was demonstrated.
Comparison of the Activities of Zanamivir, Oseltamivir, and RWJ-270201 against Clinical Isolates of Influenza Virus and Neuraminidase Inhibitor-Resistant Variants
Authors: Gubareva Larisa V. , Webster Robert G. , Hayden Frederick G. 
Published: July 2002

ABSTRACTRWJ-270201 is a novel cyclopentane inhibitor of influenza A and B virus neuraminidases (NAs). We compared the ability of RWJ-270201 to inhibit NA activity of clinical influenza isolates and viruses with defined resistance mutations with that of zanamivir and oseltamivir carboxylate. In NA inhibition assays with influenza A viruses, the median 50% inhibitory concentration (IC50) of RWJ-270201 (approximately 0.34 nM) was comparable to that of oseltamivir carboxylate (0.45 nM) but lower than that of zanamivir (0.95 nM). For influenza B virus isolates, the IC50of RWJ-270201 (1.36 nM) was comparable to that of zanamivir (2.7 nM) and less than that of oseltamivir carboxylate (8.5 nM). A zanamivir-resistant variant bearing a Glu119-to-Gly (Glu119→Gly) or Glu119→Ala substitution in an NA (N2) remained susceptible to RWJ-270201 and oseltamivir carboxylate. However, a zanamivir-selected variant with an Arg292→Lys substitution in an NA (N2) showed a moderate level of resistance to RWJ-270201 (IC50= 30 nM) and zanamivir (IC50= 20 nM) and a high level of resistance to oseltamivir carboxylate (IC50> 3,000 nM). The zanamivir-resistant influenza B virus variant bearing an Arg152→Lys substitution was resistant to each NA inhibitor (IC50= 100 to 750 nM). The oseltamivir-selected variant (N1) with the His274→Tyr substitution exhibited resistance to oseltamivir carboxylate (IC50= 400 nM) and to RWJ-270201 (IC50= 40 nM) but retained full susceptibility to zanamivir (IC50= 1.5 nM). Thus, drug-resistant variants with substitutions in framework residues 119 or 274 can retain susceptibility to other NA inhibitors, whereas replacement of functional residue 152 or 292 leads to variable levels of cross-resistance. We conclude that RWJ-270201 is a potent inhibitor of NAs of wild-type and some zanamivir-resistant or oseltamivir-resistant influenza A and B virus variants.
Newer Macrolides as Empiric Treatment for Acute Q Fever Infection
Authors: Gikas Achilleas , Kofteridis Diamantis P. , Manios Andreas , Pediaditis John , Tselentis Yiannis 
Published: July 2002

ABSTRACT

The effectiveness of newer macrolides in acute Q fever for 113 patients was recorded. The mean times to defervescence were 2.9 days for doxycycline and 3.3, 3.9, 3.9, and 6.4 days for clarithromycin, roxithromycin, erythromycin, and β-lactams, respectively (
P
< 0.01 for macrolides versus β-lactams). We conclude that macrolides may be an adequate empirical antibiotic therapy for acute Q fever.