bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of the amyloidogenicity of a protein by specific binding of ligands to the native conformation
Authors: Chiti Fabrizio , Taddei Niccolò , Stefani Massimo , Dobson Christopher M. , Ramponi Giampietro 
Published: July 2002

AbstractIt is known that human muscle acylphosphatase (AcP) is able, under appropriate conditions in vitro, to aggregate and form amyloid fibrils of the type associated with human diseases. A number of compounds were tested for their ability to bind specifically to the native conformation of AcP under conditions favoring denaturation and subsequent aggregation and fibril formation. Compounds displaying different binding affinities for AcP were selected and their ability to inhibit protein fibrillization in vitro was evaluated. We found that compounds displaying a relatively high affinity for AcP are able to significantly delay protein fibrillization, mimicking the effect of stabilizing mutations; in addition, the effectiveness of such outcome correlates positively to both ligand concentration and affinity to the native state of AcP. By contrast, the inhibitory effect of ligands on AcP aggregation disappears in a mutant protein in which such binding affinity is lost. These results indicate that the stabilization of the native conformation of amyloidogenic proteins by specific ligand binding can be a strategy of general interest to inhibit amyloid formation in vivo.
Rotor/Seal Experimental and Analytical Study on Full Annular Rub
Authors: Yu J. J. , Goldman P. , Bently D. E. , Muzynska A. 
Published: July 2002

AbstractRotor/seal full annular rub, including synchronous (forward) and reverse (backward) precessions, has been investigated both experimentally and analytically. Of particular interest is the finding of reverse precessional full annular rub (dry whip) that occurs repeatedly in small clearance cases without any outside disturbance. The experimental results include rub triggering mechanism, mass unbalance, and rotative speed effects. A simplified mathematical model is used to interpret experimental results. Nonlinear solutions for both synchronous and reverse precessions are obtained along with instability zones. Mass unbalance effect on shifting from synchronous response to reverse rub and destabilizing factors such as dry friction, rotor damping, and seal stiffness, are discussed.
Synchronous Response Estimation in Rotating Machinery
Authors: Maslen E. H. , Sortore C. K. , Vázquez J. A. , Knospe C. R. 
Published: July 2002

AbstractSynchronous response estimation attempts to determine the forced response (displacement) of a rotor at critical points which cannot be measured directly. This type of prediction, if accurate and reliable, has broad potential use in the rotating machinery industry. Many machines have close clearance points on their shafts, such as seals, which can easily be damaged by excess vibration. Accurate estimates of the actual level of vibration at these points could usefully assist machine operators in troubleshooting and in protecting the equipment from expensive damage. This type of response information can be used both to generate less conservative alarm limits and, if magnetic bearings are available, to directly guide the bearing controllers in restricting the rotor motion at these critical points. It is assumed that the disturbance forces acting upon the rotor are predominantly synchronous. The response estimate is constructed using the measurable response in conjunction with an estimator gain matrix derived from a model of the transmissibilities of the rotor system. A fundamental performance bound is established based on the single-speed set of measurements by bounding the response to the unmeasurable component of the disturbance force. Acknowledging that some model uncertainty will always exist, a robust performance analysis is developed using structured singular value (μ) analysis techniques. Assuming some reasonable levels of uncertainty for the model parameters (natural frequencies, modal dampings, mode shapes, bearing stiffnesses, and dampings) the results of the estimator construction and analysis establish feasibility of the proposed estimation. Two reference rotor models that are representative of industrially sized machines are used to demonstrate and evaluate the estimation. The unmeasurable response estimation errors consistently lie below 25 μm for the examples examined.
Modal Reduction of a Nonlinear Rotating Beam Through Nonlinear Normal Modes
Authors: Pesheck Eric , Pierre Christophe , Shaw Steven W. 
Published: July 2002

Abstract
A method for determining reduced-order models for rotating beams is presented. The approach is based on the construction of nonlinear normal modes that are defined in terms of invariant manifolds that exist for the system equations of motion. The beam considered is an idealized model for a rotor blade whose motions are dominated by transverse vibrations in the direction perpendicular to the plane of rotation (known as flapping). The mathematical model for the rotating beam is relatively simple, but contains the nonlinear coupling that exists between transverse and axial deflections. When one employs standard modal expansion or finite element techniques to this system, this nonlinearity causes slow convergence, leading to models that require many degrees of freedom in order to achieve accurate dynamical representations. In contrast, the invariant manifold approach systematically accounts for the nonlinear coupling between linear modes, thereby providing models with very few degrees of freedom that accurately capture the essential dynamics of the system. Models with one and two nonlinear modes are considered, the latter being able to handle systems with internal resonances. Simulation results are used to demonstrate the validity of the approach and to exhibit features of the nonlinear modal responses.
Three-Dimensional Sintering of Two-Component Metal Powders With Stationary and Moving Laser Beams
Authors: Zhang Yuwen , Faghri A. , Buckley C. W. , Bergman T. L. 
Published: July 2002

AbstractMelting and resolidification of a mixture of two metal powders with significantly different melting points under irradiation of a stationary or a moving Gaussian laser beam were investigated numerically and experimentally. The liquid motion driven by capillary and gravity forces as well as the shrinkage of the powder bed caused by the overall density change were taken into account in the physical model. The liquid flow was formulated by using Darcy’s law, and the energy equation was given using a temperature transforming model. Prediction were compared with experimental results obtained with nickel braze and AISI 1018 steel powder. The effects of laser properties and the scanning velocity on the laser sintering process were also investigated. An empirical correlation that can be used to predict the cross-sectional area of the heat affected zone is proposed. [S0022-1481(00)70201-5]
SME-Type Carbapenem-Hydrolyzing Class A β-Lactamases from Geographically Diverse
Serratia marcescens
Strains
Authors: Queenan Anne Marie , Torres-Viera Carlos , Gold Howard S. , Carmeli Yehuda , Eliopoulos George M. , Moellering Robert C. , Quinn John P. , Hindler Janet , Medeiros Antone A. , Bush Karen 
Published: July 2002

ABSTRACT

Three sets of carbapenem-resistant
Serratia marcescens
isolates have been identified in the United States: 1 isolate in Minnesota in 1985 (before approval of carbapenems for clinical use), 5 isolates in Los Angeles (University of California at Los Angeles [UCLA]) in 1992, and 19 isolates in Boston from 1994 to 1999. All isolates tested produced two β-lactamases, an AmpC-type enzyme with pI values of 8.6 to 9.0 and one with a pI value of approximately 9.5. The enzyme with the higher pI in each strain hydrolyzed carbapenems and was not inhibited by EDTA, similar to the chromosomal class A SME-1 β-lactamase isolated from the 1982 London strain
S. marcescens
S6. The genes encoding the carbapenem-hydrolyzing enzymes were cloned in
Escherichia coli
and sequenced. The enzyme from the Minnesota isolate had an amino acid sequence identical to that of SME-1. The isolates from Boston and UCLA produced SME-2, an enzyme with a single amino acid change relative to SME-1, a substitution from valine to glutamine at position 207. Purified SME enzymes from the U.S. isolates had β-lactam hydrolysis profiles similar to that of the London SME-1 enzyme. Pulsed-field gel electrophoresis analysis revealed that the isolates showed some similarity but differed by at least three genetic events. In conclusion, a family of rare class A carbapenem-hydrolyzing β-lactamases first described in London has now been identified in
S. marcescens
isolates across the United States.
Candida albicansMutants Deficient in Respiration Are Resistant to the Small Cationic Salivary Antimicrobial Peptide Histatin 5
Authors: Gyurko Csilla , Lendenmann Urs , Troxler Robert F. , Oppenheim Frank G. 
Published: July 2002

ABSTRACTHistatins are a group of small cationic peptides in human saliva which are well known for their antibacterial and antifungal activities. In a previous study we demonstrated that histatin 5 kills both blastoconidia and germ tubes ofCandida albicansin a time- and concentration-dependent manner at 37°C, whereas no killing was detected at 4°C. This indicated that killing activity depends on cellular energy. To test histatin 5 killing activity at lower cellular ATP levels at 37°C, respiratory mutants, or so-called petite mutants, ofC. albicanswere prepared. These mutants are deficient in respiration due to mutations in mitochondrial DNA. Mutants were initially identified by their small colony size and were further characterized with respect to colony morphology, growth characteristics, respiratory activity, and cytochrome spectra. The killing activity of histatin 5 at the highest concentration was only 28 to 30% against respiratory mutants, whereas 98% of the wild-type cells were killed. Furthermore, histatin 5 killing activity was also tested on wild-type cells in the presence of the respiratory inhibitor sodium azide or, alternatively, the uncoupler carbonyl cyanidem-chlorophenylhydrazone. In both cases histatin 5 killing activity was significantly reduced. Additionally, supernatants and pellets of cells incubated with histatin 5 in the presence or absence of inhibitors of mitochondrial ATP synthesis were analyzed by sodium dodecyl sulfate gel electrophoresis. It was observed that wild-type cells accumulated large amounts of histatin 5, while wild-type cells treated with inhibitors or petite mutants did not accumulate significant amounts of the peptide. These data showed first that cellular accumulation of histatin 5 is necessary for killing activity and second that accumulation of histatin 5 depends on the availability of cellular energy. Therefore, mitochondrial ATP synthesis is required for effective killing activity of histatin 5.
In Vivo Characterization of the Pharmacodynamics of Flucytosine in a Neutropenic Murine Disseminated Candidiasis Model
Authors: Andes D. , van Ogtrop M. 
Published: July 2002

ABSTRACT

In vivo pharmacodynamic parameters have been characterized for a variety of antibacterial agents. These parameters have been studied in correlation with in vivo outcomes in order to determine (i) which dosing parameter is predictive of outcome and (ii) the magnitude of that parameter associated with efficacy. Very little is known of the pharmacodynamics of antifungal agents. We used a neutropenic murine model of disseminated candidiasis to correlate the pharmacodynamic parameters (percentage of time above the MIC, area under the concentration-time curve [AUC]/MIC and peak level/MIC) for flucytosine (5-FC) in vivo with efficacy as measured by organism number in homogenized kidney cultures after 24 h of therapy. The pharmacokinetics of 5-FC in infected mice were linear. Serum half-lives ranged from 0.36 to 0.43 h. Infection was achieved by intravenous inoculation of 10
6
CFU of yeast cells per ml via the lateral tail vein of neutropenic mice. Groups of mice were treated with fourfold escalating total doses of 5-FC ranging from 1.56 to 400 mg/kg of body weight/day divided into one, two, four, or eight doses over 24 h. Increasing doses produced minimal concentration-dependent killing ranging from 0 to 0.9 log
10
CFU/kidneys. 5-FC did, however, produce a dose-dependent suppression of growth after levels in serum had fallen below the MIC. The fungistatic dose increased from 6 to 8 mg/kg with dosing every 3 and 6 h to 70 mg/kg at with dosing every 24 h. Nonlinear regression analysis was used to determine which pharmacodynamic parameter best correlated with efficacy. Time above the MIC was the parameter best predictive of outcome, while AUC/MIC was only slightly less predictive (time above MIC,
R
2
= 85%; AUC/MIC,
R
2
= 77%; peak level/MIC,
R
2
= 53%). Maximal efficacy was observed when levels exceeded the MIC for only 20 to 25% of the dosing interval. If one considers drug kinetics in humans, these results suggest reevaluation of current dosing regimens.
Aminoglycoside-Streptothricin Resistance Gene Cluster
aadE–sat4–aphA-3
Disseminated among Multiresistant Isolates of
Enterococcus faecium
Authors: Werner Guido , Hildebrandt Bianca , Witte Wolfgang 
Published: July 2002

ABSTRACT

Seventy-two
Enterococcus faecium
isolates of different origins highly resistant to nourseothricin and streptomycin were studied. Sequencing of a genomic fragment from two isolates identified a gene cluster,
aadE–
sat4
–
aphA-3
, which has been isolated recently in staphylococci and
Campylobacter coli
. Patterns of digested PCR products of
aadE–sat4–aphA-3
were identical for all isolates.
Antifungal Activity and Pharmacokinetics of Posaconazole (SCH 56592) in Treatment and Prevention of Experimental Invasive Pulmonary Aspergillosis: Correlation with Galactomannan Antigenemia
Authors: Petraitiene Ruta , Petraitis Vidmantas , Groll Andreas H. , Sein Tin , Piscitelli Stephen , Candelario Myrna , Field-Ridley Aida , Avila Nilo , Bacher John , Walsh Thomas J. 
Published: July 2002

ABSTRACT

The antifungal efficacy, safety, and pharmacokinetics of posaconazole (SCH 56592) (POC) were investigated in treatment and prophylaxis of primary pulmonary aspergillosis due to
Aspergillus fumigatus
in persistently neutropenic rabbits. Antifungal therapy consisted of POC at 2, 6, and 20 mg/kg of body weight per os; itraconazole (ITC) at 2, 6, and 20 mg/kg per os; or amphotericin B (AMB) at 1 mg/kg intravenously. Rabbits treated with POC showed a significant improvement in survival and significant reductions in pulmonary infarct scores, total lung weights, numbers of pulmonary CFU per gram, numbers of computerized-tomography-monitored pulmonary lesions, and levels of galactomannan antigenemia. AMB and POC had comparable therapeutic efficacies by all parameters. By comparison, animals treated with ITC had no significant changes in outcome variables in comparison to those of untreated controls (UC). Rabbits receiving prophylactic POC at all dosages showed a significant reduction in infarct scores, total lung weights, and organism clearance from lung tissue in comparison to results for UC (
P
< 0.01). There was dosage-dependent microbiological clearance of
A. fumigatus
from lung tissue in response to POC. Serum creatinine levels were greater (
P
< 0.01) in AMB-treated animals than in UC and POC- or ITC-treated rabbits. There was no elevation of serum hepatic transaminase levels in POC- or ITC-treated rabbits. The pharmacokinetics of POC and ITC in plasma demonstrated dose dependency after multiple dosing. The 2-, 6-, and 20-mg/kg dosages of POC maintained plasma drug levels above the MICs for the entire 24-h dosing interval. In summary, POC at ≥6 mg/kg/day per os generated sustained concentrations in plasma of ≥1 μg/ml that were as effective in the treatment and prevention of invasive pulmonary aspergillosis as AMB at 1 mg/kg/day and more effective than cyclodextrin ITC at ≥6 mg/kg/day per os in persistently neutropenic rabbits.
Multicenter Survey of the Changing In Vitro Antimicrobial Susceptibilities of Clinical Isolates of
Bacteroides fragilis
Group,
Prevotella, Fusobacterium, Porphyromonas
, and
Peptostreptococcus
Species
Authors: Aldridge Kenneth E. , Ashcraft Deborah , Cambre Karl , Pierson Carl L. , Jenkins Stephen G. , Rosenblatt Jon E. 
Published: July 2002

ABSTRACT

In vitro surveys of antimicrobial resistance among clinically important anaerobes are an important source of information that can be used for clinical decisions in the choice of empiric antimicrobial therapy. This study surveyed the susceptibilities of 556 clinical anaerobic isolates from four large medical centers using a broth microdilution method. Piperacillin-tazobactam was the only antimicrobial agent to which all the isolates were susceptible. Similarly, imipenem, meropenem, and metronidazole were highly active (resistance, <0.5%), whereas the lowest susceptibility rates were noted for penicillin G, ciprofloxacin, and clindamycin. For most antibiotics, blood isolates were less susceptible than isolates from intra-abdominal, obstetric-gynecologic, and other sources. All isolates of the
Bacteroides fragilis
group were susceptible to piperacillin-tazobactam and metronidazole, while resistance to imipenem and meropenem was low (<2%). For these same isolates, resistance rates (intermediate and resistant MICs) to ampicillin-sulbactam, cefoxitin, trovafloxacin, and clindamycin were 11, 8, 7, and 29%, respectively. Among the individual species of the
B. fragilis
group, the highest resistance rates were noted among the following organism-drug combinations: for clindamycin,
Bacteroides distasonis
and
Bacteroides ovatus
; for cefoxitin,
Bacteroides thetaiotaomicron, B. distasonis
, and
Bacteroides uniformis;
for ampicillin-sulbactam,
B. distasonis, B. ovatus
, and
B. uniformis
; and for trovafloxacin,
Bacteroides vulgatus
. For the carbapenens, imipenem resistance was noted among
B. fragilis
and meropenem resistance was seen among
B. fragilis, B. vulgatus
, and
B. uniformis
. With few exceptions all antimicrobial agents were highly active against isolates of
Prevotella, Fusobacterium, Porphyromonas
, and
Peptostreptococcus
. These data further establish and confirm that clinically important anaerobes can vary widely in their antimicrobial susceptibilities. Fortunately most antimicrobial agents were active against the test isolates. However, concern is warranted for what appears to be a significant increases in resistance to ampicillin-sulbactam and clindamycin.
In Vitro and In Vivo Activities of Amikacin, Cefepime, Amikacin plus Cefepime, and Imipenem against an SHV-5 Extended-Spectrum β-Lactamase-ProducingKlebsiella pneumoniaeStrain
Authors: Szabó Dóra , Máthé András , Filetóth Zsolt , Anderlik Piroska , Rókusz László , Rozgonyi Ferenc 
Published: July 2002

ABSTRACTThe in vitro and in vivo effectiveness of amikacin, cefepime, and imipenem was studied using a high inoculum of an extended-spectrum β-lactamase-producingKlebsiella pneumoniaestrain. An in vitro susceptibility test at the standard inoculum predicted the in vivo outcome of amikacin or imipenem while it did not do so for cefepime due to the inoculum effect.
Thalidomide Inhibits Granulocyte Responses in Healthy Humans after Ex Vivo Stimulation with Bacterial Antigens
Authors: Juffermans Nicole P. , Verbon Annelies , Schultz Marc J. , Hack C. Erik , van Deventer Sander J. H. , Speelman Peter , van der Poll Tom 
Published: July 2002

ABSTRACTIngestion of thalidomide was associated with a reduction in the upregulation of the granulocyte activation marker CD11b and a reduced capacity to release elastase and lactoferrin after stimulation with lipopolysaccharide or lipoteichoic acid. A single oral dose of thalidomide attenuates neutrophil activation upon ex vivo stimulation with bacterial antigens.
Prospective Study of
Candida
Species in Patients at a Comprehensive Cancer Center
Authors: Safdar Amar , Chaturvedi Vishnu , Cross Emily W. , Park Steven , Bernard Edward M. , Armstrong Donald , Perlin David S. 
Published: July 2002

ABSTRACT

Since most nosocomial systemic yeast infections arise from the endogenous flora of the patient, we prospectively evaluated the species stratification and antifungal susceptibility profile of
Candida
spp. associated with heavy colonization and systemic infection in patients at Memorial Sloan-Kettering Cancer Center in New York. A total of 349
Candida
isolates were obtained from 223 patients during the later half of 1998. Cancer was the most common underlying disease, occurring in 91% of the patients, including 61.8% with organ and 23.7% with hematological malignancies; 4.4% of the patients had AIDS.
Candida albicans
was the predominant species (67.3%); among 114 non-
albicans Candida
spp.,
C. glabrata
(45.6%) was the most frequent, followed by
C. tropicalis
(18.4%),
C. parapsilosis
(16.6%), and
C. krusei
(9.6%). The overall resistance to triazole-based agents among all yeast isolates was 9.4 and 10.8% for fluconazole and itraconazole, respectively. A total of 5% of
C. albicans
strains were resistant to triazole antifungals, whereas 30.8 and 46.2% of
C. glabrata
strains were resistant to fluconazole (MIC ≥ 64 μg/ml) and itraconazole (MIC ≥ 1 μg/ml), respectively. A significant association was observed between prior treatment with triazole and isolation of fluconazole-resistant
C. albicans
(
P
= 0.005, OR 36), although this relationship was not seen in
C. glabrata
isolates (
P
= 0.4). This study reinforces the importance of periodic, prospective surveillance of clinical fungal isolates to determine appropriate prophylactic, empiric, and preemptive antifungal therapy for the highly susceptible patient population.
In Vitro Susceptibilities of Wild-Type or Drug-Resistant Hepatitis B Virus to (−)-β-d-2,6-Diaminopurine Dioxolane and 2′-Fluoro-5-Methyl-β-l-Arabinofuranosyluracil
Authors: Chin Ruth , Shaw Tim , Torresi Joseph , Sozzi Vittina , Trautwein Christian , Bock Thomas , Manns Michael , Isom Harriet , Furman Phil , Locarnini Stephen 
Published: July 2002

ABSTRACTProlonged treatment of chronic hepatitis B virus (HBV) infection with lamivudine ([−]-β-l-2′,3′-dideoxy-3′ thiacytidine) or famciclovir may select for viral mutants that are drug resistant due to point mutations in the polymerase gene. Determining whether such HBV mutants are sensitive to new antiviral agents is therefore important. We used a transient transfection system to compare the sensitivities of wild-type HBV and four lamivudine- and/or famciclovir-resistant HBV mutants to adefovir [9-(2-phosphonyl-methoxyethyl)-adenine; PMEA] and the nucleoside analogues (−)-β-d-2, 6-diaminopurine dioxolane (DAPD) and 2′-fluoro-5-methyl-β-l-arabinofuranosyluracil (l-FMAU). The drug-resistant mutants contained amino acid substitutions in the polymerase protein. We found that the M550I and M550V plus L526M substitutions, which confer lamivudine resistance, did not confer cross-resistance to adefovir or DAPD, but conferred cross-resistance tol-FMAU. The M550V substitution in isolation conferred a similar phenotype to M550I, except that it did not confer significant resistance tol-FMAU. The L526M substitution, which is associated with famciclovir resistance, conferred cross-resistance tol-FMAU but not to adefovir or DAPD. Inhibition of HBV secretion by DAPD,l-FMAU, and adefovir did not always correlate with inhibition of the generation of intracellular HBV replicative intermediates, suggesting that these analogs may preferentially inhibit specific stages of the viral replication cycle.