bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract: Temperature profiles of targets bombarded by electron beams
Authors: El-Kareh A. B. , Moravan K. Y. Y. 
Published: July 2002

A detailed theoretical calculation is presented of the relationship between the spot size and temperature as a function of the physical properties of a target material when it is bombarded by an electron beam. As a result of this analysis, it is possible to determine the desired characteristics of materials which are suitable for application in mass-storage devices.
The thermal problem can be analyzed by solving the appropriate radial heat-flow equation. The electron beam heating of the target can be determined within certain limitations by assuming that the heat is generated uniformly in a spot of hemispherical shape whose radius is given by the effective range of electron penetration. This range is determined by making use of the universal curve of the normalized Bohr–Bethe range obtained by Everhart and Hoff.
From the above calculation, the properties of suitable targets can be obtained. It is found that to have a small spot, a high mass density of the target is desirable. The requirement that the equilibrium temperature to be greater than the boiling temperature of the target sets an upper limit for the conductivity of the target. In order for the rise time (the time needed for temperature at the center of the spot to reach a significant portion of the equilibrium temperature value) to be of the same order as the machining time, a lower limit for conductivity and the inter-relationship between heat capacity, conductivity, and mass density can be obtained. A set of curves are given to show the space and time dependence of the temperature of the spot being machined for different beam powers. It can be seen that both higher temperature and better resolution can be obtained for electron-beam powers between 2.5 and 10 keV than for above 10 keV.
Abstract: Scanning microspot Auger spectroscopy and microscopy as a device diagnostic technique
Authors: Christou A. , Day H. M. 
Published: July 2002

Auger spectroscopy with a focused electron beam in the scanning electron microscope (SEM) has been applied as a diagnostic technique for solid state devices. The focused electron beam in a SEM allows one to determine the surface topography (SEM mode) of the specimen and then determine the Auger spectra of selected areas. In addition, a scanning Auger image may be obtained by using the amplitudes of the Auger peaks for intensity or amplitude modulation of the cathode ray tube. In the present system, a SEM designed with a dry-pump UHV system and equipped with an Auger electron detector and sputter etching capability has been applied to device failure diagnostics. Vacuum levels of 3×10−9 Torr (4×10−7 Pa) at the specimen stage have been obtained with an electro-ion-titanium sublimation pumping system. A secondary electron image resolution of less than 2000 Å with Auger spectra of features less than 1 μm have been attained. Gray-scale images from Auger electrons have been obtained at beam currents of 10−6 to 10−8 A. The Auger electron detector used has an energy resolution of 0.5% and transmission of 10%. A sputter-etching capability for sputter cleaning of specimen surfaces prior to analysis is provided.
The energy source of the SEM is a triode electron gun with a high-emission filament (3.5×105 A cm−2 sr−1 at 20 kV). The relationship between probe current and diameter for a fixed working distance was measured in order to determine the optimum spatial resolution for AES. For optimum conditions and high beam currents (10−6 A) spatial resolution is essentially determined by the probe diameter. For low beam currents, it is shown that parameters such as escape depth, atomic number, surface area, and beam energy affect spatial resolution. AES recording time and its variation with signal-to-noise ratio has also been determined.
The normal modes for microspot AES investigations in the SEM include spot analysis, line scan, and Auger electron imaging. For Auger imaging the vacuum levels and probe currents are shown to be the critical parameters since the time to record such an image is usually greater than five minutes.
RNA Polymerase Inhibitors with Activity against Rifampin-Resistant Mutants of
Staphylococcus aureus
Authors: O'Neill Alexander , Oliva Brunello , Storey Christopher , Hoyle Anthony , Fishwick Colin , Chopra Ian 
Published: July 2002

ABSTRACT

A collection of rifampin-resistant mutants of
Staphylococcus aureus
with characterized RNA polymerase β-subunit (
rpoB
) gene mutations was cross-screened against a number of other RNA polymerase inhibitors to correlate susceptibility with specific
rpoB
genotypes. The
rpoB
mutants were cross-resistant to streptolydigin and sorangicin A. In contrast, thiolutin, holomycin, corallopyronin A, and ripostatin A retained activity against the
rpoB
mutants. The second group of inhibitors may be of interest as drug development candidates.
Characterization of a Divergent
vanD
-Type Resistance Element from the First Glycopeptide-Resistant Strain of
Enterococcus faecium
Isolated in Brazil
Authors: Dalla Costa Libera M. , Reynolds Peter E. , Souza Helena A. P. H. M. , Souza Dilair C. , Palepou Marie-France I. , Woodford Neil 
Published: July 2002

ABSTRACT

Enterococcus faecium
10/96A from Brazil was resistant to vancomycin (MIC, 256 μg/ml) but gave no amplification products with primers specific for known
van
genotypes. A 2,368-bp fragment of a
van
cluster contained one open reading frame encoding a peptide with 83% amino acid identity to VanH
D
, and a second encoding a
d
-alanine-
d
-lactate ligase with 83 to 85% identity to VanD. The divergent glycopeptide resistance phenotype was designated VanD4.
A Population Pharmacokinetic Model for Vancomycin in Pediatric Patients and Its Predictive Value in a Naive Population
Authors: Lamarre Patrice , Lebel Denis , Ducharme Murray P. 
Published: July 2002

ABSTRACT

The objectives of this study were to (i) construct a population pharmacokinetic (PK) model able to describe vancomycin (VAN) concentrations in serum in pediatric patients, (ii) determine VAN PK parameters in this population, and (iii) validate the predictive ability of this model in a naive pediatric population. Data used in this study were obtained from 78 pediatric patients (under 18 years old). PK analyses were performed using compartmental methods. The most appropriate model was chosen based on the evaluation of pertinent graphics and calculation of the Akaike information criterion test. The population PK analysis was performed using an iterative two-stage method. A two-compartment PK model using age, sex, weight, and serum creatinine as covariates was determined to be the most appropriate one to describe serum VAN concentrations. The quality of fit was very good, and the distribution of weighted residuals was found to be homoscedastic (Wilcoxon signed rank test). Fitted population PK parameters (mean ± standard deviation) were as follows: central clearance (0.1 ± 0.05 liter/h/kg), central volume of distribution (0.27 ± 0.07 liter/kg), peripheral volume of distribution (0.16 ± 0.07 liter/kg), and distributional clearance (0.16 ± 0.07 liter/kg). The predictive ability of the developed model (including the above-mentioned covariates) was evaluated in a naive population of 19 pediatric patients. The predictability was very good. Precision (±95% confidence interval [CI]) (peak, 4.1 [±1.4], and trough, 2.2 [±0.7]) and bias (±95% CI) (peak, −0.58 [±2.2], and trough, 0.63 [±1.1] mg/liter) were significantly (
P
< 0.05) superior to those obtained using a conventional method (precision [±95% CI]: peak, 8.03 [±2.46], and trough, 2.7 [±0.74]; bias: peak, −7.1 [±2.9], and trough, −1.35 [±1.2] mg/liter). We propose the use of this population PK model to optimize VAN clinical therapies in our institution and others with similar patient population characteristics.
A Double-Blind Placebo-Controlled Study of an Infusion of Lexipafant (Platelet-Activating Factor Receptor Antagonist) in Patients with Severe Sepsis
Authors: Suputtamongkol Yupin , Intaranongpai Sunanta , Smith Michael D. , Angus Brian , Chaowagul Wipada , Permpikul Chairat , Simpson Julie A. , Leelarasamee Amorn , Curtis Lloyd , White Nicholas J. 
Published: July 2002

ABSTRACT
Platelet-activating factor (PAF) is a potent endogenous proinflammatory mediator implicated in the pathogenesis of septic shock. A double-blind randomized placebo-controlled trial of an intravenous PAF receptor antagonist (lexipafant) was conducted with 131 adult Thai patients with suspected severe sepsis (66 of whom had positive blood cultures). Detailed serial clinical, biochemical, and cytokine measurements were performed. Lexipafant treatment was well tolerated. The 28-day mortality in the lexipafant group (61.4%) was similar to that in the placebo group (62.6%). There was also no evidence that lexipafant affected clinical or biochemical measures of disease severity or the profile of sequentially measured plasma cytokine levels. PAF may not have an important role in the pathogenesis of severe sepsis.
Horizontal Transfer of
parC
and
gyrA
in Fluoroquinolone-Resistant Clinical Isolates of
Streptococcus pneumoniae
Authors: Ferrándiz María José , Fenoll Asunción , Liñares Josefina , De La Campa Adela G. 
Published: July 2002

ABSTRACT

We have analyzed genetically three clinical isolates (3180, 3870, and 1244) of
Streptococcus pneumoniae
with high-level ciprofloxacin resistance. Isolates 3180 and 3870 were atypical because of their insolubility in deoxycholate. However, they hybridized specifically with pneumococcal autolysin and pneumolysin gene probes and have typical pneumococcal
atpC
and
atpA
gene sequences. Analysis of the complete sequences of the
parC
and
gyrA
genes revealed total variations of 8 and 8.7% (isolate 3180) and 7.4 and 3.6% (isolate 3870), respectively, compared to the wild-type strain R6 sequence. The variations observed between the sequences of R6 and isolate 1244 were less than 0.9%. The structure of the
gyrA
and
parC
genes from isolates 3180 and 3870 was organized in sequence blocks that show different levels of divergence, suggesting a pattern of recombination. These results are evidence for recombination at the fluoroquinolone target genes in clinical isolates of
S. pneumoniae
. The genetically related viridans group streptococci could act as a reservoir for fluoroquinolone resistance genes.
Role of P Glycoprotein in the Course and Treatment of
Encephalitozoon
Microsporidiosis
Authors: Leitch Gordon J. , Scanlon Mary , Shaw Andrew , Visvesvara Govinda S. 
Published: July 2002

ABSTRACT

Encephalitozoon
microsporidia are obligate intracellular protozoan parasites that proliferate and differentiate within a parasitophorous vacuole inside host cells that are usually epithelial in nature. Isolates of the three species of the
Encephalitozoon
microsporidia,
E. cuniculi
,
E. hellem
, and
E. intestinalis
, were obtained from AIDS patients and cultured in green monkey (E6) kidney cells. Anti-P-glycoprotein (anti-Pgp) and anti-multidrug resistance-associated protein (anti-MRP) monoclonal antibodies were used to probe for multidrug resistance (MDR) pump epitopes and verapamil- or cyclosporin A- and probenecid-modulated intracellular calcein fluorescence were used to assess the expression of Pgp and MRP respectively in uninfected and infected cells. Pgp, but not MRP, was detected immunocytochemically and by verapamil- and cyclosporin A-potentiated intracellular fluorescence in both host cells and parasite developing stages. When an in vitro infection assay was employed, verapamil and cyclosporin A acted as chemosensitizing agents for the antiparasitic drug albendazole. These observations suggest that inhibiting host cell and perhaps parasite MDR pumps may increase the efficacy of antiparasitic agents in these and other microsporidia species.
Genetic Analysis of Multiple Loci Suggests that Mutations in the
Pneumocystis carinii
f. sp.
hominis
Dihydropteroate Synthase Gene Arose Independently in Multiple Strains
Authors: Ma Liang , Kovacs Joseph A. 
Published: July 2002

ABSTRACT

To determine if mutations in the dihydropteroate synthase (DHPS) gene of
Pneumocystis carinii
f. sp.
hominis
arose in a single strain that was subsequently widely disseminated, we examined four genomic regions of 22
P. carinii
clinical isolates selected based on the absence or presence of mutations in the DHPS gene. By single-strand conformation polymorphism and DNA sequencing, we found varying genotypes for each of the four regions in isolates with DHPS mutations, suggesting that these mutations occurred independently in multiple strains of
P. carinii
. This suggests that exposure to sulfa will select for these mutations in diverse strains.
In Vitro and In Vivo Activities of Sitafloxacin against
Chlamydia
spp
Authors: Miyashita Naoyuki , Niki Yoshihito , Matsushima Toshiharu 
Published: July 2002

ABSTRACT

The in vitro and in vivo antichlamydial activity of sitafloxacin was investigated. The MICs and minimal chlamydiacidal concentrations of sitafloxacin for various species of chlamydia ranged from 0.031 to 0.125 μg/ml. Sitafloxacin had an excellent therapeutic effect on experimental
Chlamydia psittaci
pneumonia and was more potent than tosufloxacin, ofloxacin, and ciproflxacin, although slightly less potent than sparfloxacin.
rho
Is Not Essential for Viability or Virulence in
Staphylococcus aureus
Authors: Washburn Robert S. , Marra Andrea , Bryant Alexander P. , Rosenberg Martin , Gentry Daniel R. 
Published: July 2002

ABSTRACT

We have identified the gene for transcription termination factor Rho in
Staphylococcus aureus
. Deletion of
rho
in
S. aureus
reveals that it is not essential for viability or virulence. We also searched the available bacterial genomic sequences for homologs of Rho and found that it is broadly distributed and highly conserved. Exceptions include
Streptococcus pneumoniae
,
Streptococcus pyogenes
,
Mycoplasma genitalium, Mycoplasma pneumoniae, Ureaplasma urealyticum,
and
Synechocystis
sp. strain PCC6803, all of which appear not to possess a Rho homolog. Complementation studies indicate that
S. aureus
Rho possesses the same activity as
Escherichia coli
Rho and that the Rho inhibitor bicyclomycin is active against
S. aureus
Rho. Our results explain the lack of activity of bicyclomycin against many gram-positive bacteria and raise the possibility that the essentiality of
rho
may be the exception rather than the rule.
Efficacy of Teicoplanin-Gentamicin Given Once a Day on the Basis of Pharmacokinetics in Humans for Treatment of Enterococcal Experimental Endocarditis
Authors: López Pedro , Gavaldà Joan , Martin M. Teresa , Almirante Benito , Gomis Xavier , Azuaje Carlos , Borrell Nuria , Pou Leonor , Falcó Vicenç , Pigrau Carles , Pahissa Albert 
Published: July 2002

ABSTRACT

With the aim of investigating home therapy for enterococcal endocarditis, we compared the efficacy of teicoplanin combined with gentamicin given once a day or in three daily doses (t.i.d.) with the standard treatment, ampicillin plus gentamicin administered t.i.d., for treating experimental enterococcal endocarditis. The antibiotics were administered by using “human-like pharmacokinetics” (H-L), i.e, pharmacokinetics like those in humans, that simulated the profiles of these drugs in human serum. Animals with catheter-induced endocarditis were infected intravenously with 10
8
CFU of
Enterococcus faecalis
EF91 (MICs and MBCs of ampicillin, gentamicin, and teicoplanin, 0.5 and 32, 16 and 32, and 0.5 and 1 μg/ml, respectively) and were treated for 3 days with ampicillin H-L at 2 g every 4 h plus gentamicin H-L at 1 mg/kg every 8 h, or teicoplanin H-L at 10 mg/kg every 24 h, alone or combined with gentamicin, administered at dose of H-L at 1 mg/kg every 8 h or H-L at 4.5 mg/kg every 24 h. The results of therapy for experimental endocarditis due to EF91 showed that teicoplanin alone was as effective as ampicillin alone in reducing the bacterial load (
P
> 0.05). The combination of ampicillin or teicoplanin with gentamicin was more effective than the administration of both drugs alone in reducing the log
10
CFU/gram of aortic vegetation (
P
< 0.01 and
P
< 0.05, respectively). Teicoplanin plus gentamicin H-L at 4.5 mg/kg, both administered every 24 h, showed an efficacy equal to the “gold standard,” ampicillin plus gentamicin H-L at 1 mg/kg t.i.d. (
P
> 0.05). Increasing the interval of administration of gentamicin to a single daily dose combined with teicoplanin resulted in a reduction of bacteria in the vegetations equivalent to that achieved with the recommended regimen of ampicillin plus thrice-daily gentamicin in the treatment of experimental endocarditis due to
E. faecalis
. Teicoplanin plus gentamicin, both administered once a day, may be useful home therapy for selected cases of enterococcal endocarditis.
Multidrug Efflux Pumps: Expression Patterns and Contribution to Antibiotic Resistance in
Pseudomonas aeruginosa
Biofilms
Authors: De Kievit Teresa R. , Parkins Michael D. , Gillis Richard J. , Srikumar Ramakrishnan , Ceri Howard , Poole Keith , Iglewski Barbara H. , Storey Douglas G. 
Published: July 2002

ABSTRACT

Pseudomonas aeruginosa
biofilms are intrinsically resistant to antimicrobial chemotherapies. At present, very little is known about the physiological changes that occur during the transition from the planktonic to biofilm mode of growth. The resistance of
P. aeruginosa
biofilms to numerous antimicrobial agents that are substrates subject to active efflux from planktonic cells suggests that efflux pumps may substantially contribute to the innate resistance of biofilms. In this study, we investigated the expression of genes associated with two multidrug resistance (MDR) efflux pumps, MexAB-OprM and MexCD-OprJ, throughout the course of biofilm development. Using fusions to
gfp
, we were able to analyze spatial and temporal expression of
mexA
and
mexC
in the developing biofilm. Remarkably, expression of
mexAB-oprM
and
mexCD-oprJ
was not upregulated but rather decreased over time in the developing biofilm. Northern blot analysis confirmed that these pumps were not hyperexpressed in the biofilm. Furthermore, spatial differences in
mexAB-oprM
and
mexCD-oprJ
expression were observed, with maximal activity occurring at the biofilm substratum. Using a series of MDR mutants, we assessed the contribution of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY efflux pumps to
P. aeruginosa
biofilm resistance. These analyses led to the surprising discovery that the four characterized efflux pumps do not play a role in the antibiotic-resistant phenotype of
P. aeruginosa
biofilms.
Growth and Development of Tetracycline-Resistant
Chlamydia suis
Authors: Lenart J. , Andersen A. A. , Rockey D. D. 
Published: July 2002

ABSTRACT

Tetracycline (TET) is a front-line antibiotic for the treatment of chlamydial infections in both humans and animals, and the emergence of TET-resistant (Tet
r
)
Chlamydia
is of significant clinical importance. Recently, several Tet
r
chlamydial strains have been isolated from swine (
Sus scrofa)
raised in production facilities in Nebraska. Here, the intracellular development of two Tet
r
strains, R19 and R27, is characterized through the use of tissue culture and immunofluorescence. The strains grow in concentrations of up to 4 μg of TET/ml, while a TET-sensitive (Tet
s
) swine strain (S45) and a strain of the human serovar L2 (LGV-434) grow in up to 0.1 μg of TET/ml. Although inclusions form in the presence of TET, many contain large aberrant reticulate bodies (RBs) that do not differentiate into infectious elementary bodies. The percentage of inclusions containing typical developmental forms decreases with increasing TET concentrations, and at 3 μg of TET/ml 100% of inclusions contain aberrant RBs. However, upon removal of TET the aberrant RBs revert to typical RBs, and a productive developmental cycle ensues. In addition, inclusions were found that contained both
C. suis
R19 and
Chlamydia trachomatis
L2 after sequential infection, demonstrating that two biologically distinct chlamydial strains could both develop within a single inclusion.
Pharmacodynamics of Gatifloxacin against
Streptococcus pneumoniae
in an In Vitro Pharmacokinetic Model: Impact of Area under the Curve/MIC Ratios on Eradication
Authors: Lister Philip D. 
Published: July 2002

ABSTRACT

Previous studies have demonstrated that fluoroquinolone area under the curve (AUC)/MIC ratios of 30 to 50 are sufficient to eradicate pneumococci from in vitro pharmacokinetic models (IVPMs). However, more systematic studies of the impact of AUC/MIC ratios on the antipneumococcal activities of fluoroquinolones are needed. In the present study, a two-compartment IVPM was used to evaluate the impact of AUC/MIC ratios on the pharmacodynamics of gatifloxacin against four strains of
Streptococcus pneumoniae
. Gatifloxacin MICs were 0.4 to 1 μg/ml, whereas levofloxacin MICs were 1.8 to 3.2 μg/ml. Since both peak concentration/MIC (peak/MIC) and AUC/MIC ratios affect fluoroquinolone pharmacodynamics, logarithmic-phase cultures (5 × 10
7
CFU/ml) were exposed to gatifloxacin at constant peak/MIC ratios of 2:1 to 3:1 at 0 and 24 h, elimination half-lives were varied to provide a range of AUC/MIC ratios, and changes in viable counts were measured over 30 h. As a comparison, levofloxacin was evaluated at similar peak/MIC ratios and at AUC/MIC ratios of 30 to 38. For each strain, killing rates through 4 to 8 h were similar since peak/MIC ratios were kept constant. However, continued killing and eradication were observed only when gatifloxacin AUC/MIC ratios were 27 to 48. Levofloxacin also provided eradication. In contrast, substantial regrowth was observed in most experiments when gatifloxacin AUC/MIC ratios were 9 to 24. These data provide further support that fluoroquinolone AUC/MIC ratios of approximately 30 or higher can be sufficient for eradication of pneumococci from IVPMs. Furthermore, the overall impact of the AUC/MIC ratio was not influenced by the strain evaluated or its susceptibility to gatifloxacin. Further studies with other fluoroquinolones and pneumococci that exhibit wider ranges of susceptibilities are warranted. In addition, similar studies with higher peak/MIC ratios are needed to better define the impact of AUC/MIC ratios and peak/MIC ratios on the antipneumococcal pharmacodynamics of fluoroquinolones.
Molecular Analysis of Rifampin Resistance in
Bacillus anthracis
and
Bacillus cereus
Authors: Vogler Amy J. , Busch Joseph D. , Percy-Fine Stephanie , Tipton-Hunton Christine , Smith Kimothy L. , Keim Paul 
Published: July 2002

ABSTRACT

Rifampin-resistant mutants were selected from UV-light-treated
Bacillus cereus
(20 mutants) and attenuated
B. anthracis
(23 mutants). In addition, spontaneous rifampin-resistant mutants were also isolated in attenuated
B. anthracis
(22 mutants). The rifampin resistance clusters of the
rpoB
gene were sequenced for all 65 mutants. Mutations associated with resistance were consistent with those from other bacteria, though two novel changes were observed. The spontaneous rate of resistance was estimated at 1.57 × 10
−9
mutations/generation by a Luria-Delbrück fluctuation test.
Efficacy of Ravuconazole in Treatment of Systemic Murine Histoplasmosis
Authors: Clemons K. V. , Martinez M. , Calderon L. , Stevens D. A. 
Published: July 2002

ABSTRACT

Ravuconazole (RCZ) was evaluated for efficacy in comparison to fluconazole (FCZ) and itraconazole (ITZ) in murine models of disseminated histoplasmosis. All regimens tested prolonged survival (
P
< 0.05 to 0.0001). At equivalent doses of 50 mg/kg of body weight, RCZ and ITZ were equally effective and RCZ was more effective than FCZ (
P
= 0.02). Clearance of fungal burden from the livers and spleens of mice showed RCZ and ITZ at doses of 50 mg/kg to be efficacious but not curative. These data indicate that RCZ should be studied further.