bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystallization and preliminary diffraction studies of a truncated form of a novel protease from spores of Bacillus megaterium
Authors: Ponnuraj Karthe , Kelly Stephen , Nessi Claudio , Setlow Peter , Jedrzejas Mark J. 
Published: July 2002

During germination of spores of Bacillus species, a novel protease termed GPR initiates the degradation of a group of small acid-soluble spore proteins which protect the dormant spore's DNA from damage. Trypsin digestion of the zymogen of B. megaterium GPR removes ∼15 kDa from the C-terminal end of the 46 kDa zymogen subunit, leaving a 30 kDa subunit. Single crystals of this truncated form of GPR have been obtained by the vapor-diffusion method using PEG 4000 as a precipitating agent. The crystals belong to the monoclinic space group P21, with unit-cell parameters a = 67.99, b = 105.34, c = 108.63 Å, β = 95.68°. The cryofrozen crystals diffract X-rays to about 3.3 Å using synchrotron radiation.
Present Status and Performance of SPring-8 Front Ends
Authors: Sakurai Y. , Oura M. , Takahashi S. , Hayashi Y. , Aoyagi H. , Shiwaku H. , Kudo T. , Mochizuki T. , Oikawa Y. , Takahasi M. , Yoshii K. , Kitamura H. 
Published: July 2002

SPring-8 front ends have a novel structure which makes it easy to rearrange them and exchange the components. The structure has a common support for all the components except X-ray beam-position monitors and lead collimators. The alignment of the common support as well as the components was carried out with an accuracy of 0.25 mm in the vertical and horizontal directions. Replaceable pumping systems have also been placed on the common support and have achieved a vacuum of 2 × 10−8 Pa at the upstream part of the front ends without synchrotron radiation. During the commissioning with synchrotron radiation, the pumping systems displayed good pumping-down characteristics. Commissioning has been successfully performed for four standard in-vacuum X-ray undulators and three bending-magnet-beamline front ends up to July 1997. Measurements of temperature rise show that absorber, pre-slits and XY slits can handle the anticipated maximum heat load at a ring current of 100 mA.
cis-Aquabis(2,2′-bipyridine-N,N′)[dichromato(2–)-O1]nickel(II)
Authors: Fernández-González Nélida , González-Silgo Cristina , González-Platas Javier , Gili Pedro , Martín-Zarza Pedro 
Published: July 2002

The molecular structure of the title compound, [Ni(C10H8N2)2(H2O){Cr2O7}], contains an NiIIatom with a distortedcis-octahedral coordination formed by two chelating bipyridine (bipy) ligands [mean Ni—Nbipy = 2.068 (3) Å], one water molecule [Ni—O = 2.086 (3) Å] and an O atom of the dichromate anion [Ni—O = 2.083 (2) Å]. One of the water H atoms is involved in the intramolecular hydrogen bond with the terminal O atom of the dichromate ligand [O...O 2.743 (5) Å], whereas its second H atom participates in the intermolecular hydrogen bonding [O...O 2.688 (4) Å]; the latter is responsible for the formation of the infinite chains stretching along the polarcaxis of the crystal.
Understanding thermostability in cytochrome P450 by combinatorial mutagenesis
Authors: Maves Shelley A. , Sligar Stephen G. 
Published: July 2002

AbstractThe cytochromes P450 are an important class of mono‐oxygenases involved in xenobiotic metabolism and steroid biosynthesis in a diverse set of life forms. Discovery of CYP‐119, a P450 from the archea Sulfolobus solfataricus has provided a means for understanding nature's method of stabilizing this important protein superfamily. To identify classes of stabilizing interactions used by CYP‐119, we have generated a randomized library of point mutants and screened for mutants that are less thermostable than the wild type by monitoring the characteristic Soret band in the visible region of the cell lysis. The selected mutants were characterized by differential scanning calorimetry to compare the temperatures of the melting transitions of the various mutants. The identified mutations suggested that electrostatic interactions involving salt links and charge–charge interactions, as well as contributions from other interactions such as aromatic stacking, and side chain volume of hydrophobic residues contribute to enhanced thermostability in this cytochrome P450.
Contact Stresses in Dovetail Attachments: Physical Modeling
Authors: Sinclair G. B. , Cormier N. G. 
Published: July 2002

AbstractSimple physical models for the stresses in dovetail attachments are developed. These models address: to slip or not to slip, nominal stresses during loading up, peak contact and shear stresses during loading up, hoop stresses during loading up, peak contact and shear stresses during unloading, and hoop stresses during unloading. Comparisons are made with a previous paper on companion finite element modeling. Generally there is good agreement between the simple physical models and the finite element analysis. Together the two identify a pinching mechanism as leading to large fluctuations in hoop stresses at the edges of contact. These fluctuating hoop stresses can be expected to be a major contributor to the fatigue of dovetail attachments.
Review of inverse analysis for indirect measurement of impact
force
Authors: Inoue Hirotsugu , Harrigan John J , Reid Stephen R 
Published: July 2002

Abstract
When dealing with the mechanics of deformable bodies, the variation of the applied force is one of the most important factors to be considered. The mechanical force acting on a body cannot be measured directly. If a body is loaded quasi-statically and if the body deforms linear-elastically, the deformation at any point of the body is proportional to the applied force. Therefore, the variation of the force can be measured indirectly by measuring the variation of the deformation. However, this principle cannot be applied when a body is subjected to an impulsive force. In this case, the propagation of stress waves inside the body cannot be neglected so that the variation of the deformation at any point of the body is no longer the same as the variation of the applied force. Therefore, impact force is much more difficult to measure than quasi-static force. In order to overcome this difficulty, inverse analysis methods to estimate variations of impact force from measured responses of a body have been studied extensively during the last two decades. This article presents a review of methods of inverse analysis for the indirect measurement of impact force.
Mechanical Behavior of a Cu-Al-Be Shape Memory Alloy Under Multiaxial
Proportional and Nonproportional Loadings
Authors: Bouvet Christophe , Calloch Sylvain , Lexcellent Christian 
Published: July 2002

Abstract
This paper is concerned with the mechanical behavior of a Cu-Al-Be Shape Memory Alloy (SMA). A large experimental database, made of tension-internal pressure tests and biaxial compressive tests, is reported. Particular attention is paid to the behavior of the material under multiaxial proportional and nonproportional loadings. Moreover, these two types of complementary tests allow for the determination, on the one hand, of the shape of the initial surface of transformation onset and, on the other hand, of the initial direction of the transformation strain rate. A generalized macroscopic J2-J3 criterion to describe the transformation onset is proposed and identified.
Vibration Instability in Rolling Mills: Modeling and Experimental Results
Authors: Meehan Paul A. 
Published: July 2002

Abstract
Models for the occurrence of the vibrational instability during rolling known as third octave chatter are presented and discussed. An analysis of rolling mill chatter was performed for the purpose of identifying characteristics of the vibrations and to determine any dependency on the rolling schedule. In particular, a stability criterion for the critical rolling speed is used to predict the maximum rolling speed without chatter instability on schedules from a 5 stand tandem mill rolling thin steel product. The results correlate well with measurements of critical speed occurring on the mill using a vibration monitor. This research provides significant insights into the chatter phenomena and has been used to investigate control methods for suppression of the instability.
Analytical Solutions to H∞ and H2 Optimization of Dynamic Vibration Absorbers Attached to Damped Linear Systems
Authors: Asami Toshihiko , Nishihara Osamu , Baz Amr M. 
Published: July 2002

AbstractH ∞ and H2 optimization problems of the Voigt type dynamic vibration absorber (DVA) are classical optimization problems, which have been already solved for a special case when the primary system has no damping. However, for the general case including a damped primary system, no one has solved these problems by algebraic approaches. Only the numerical solutions have been proposed until now. This paper presents the analytical solutions for the H∞ and H2 optimization of the DVA attached to the damped primary systems. In the H∞ optimization the DVA is designed such that the maximum amplitude magnification factor of the primary system is minimized; whereas in the H2 optimization the DVA is designed such that the squared area under the response curve of the primary system is minimized. We found a series solution for the H∞ optimization and a closed-form algebraic solution for the H2 optimization. The series solution is then compared with the numerical solution in order to check the accuracy in connection with the truncation error of the series. The exact solution presented in this paper is too complicated to handle by a hand-held calculator, so we proposed an approximate solution for the practical object.
Comparison of Three Methods of Determining MICs for Filamentous Fungi Using Different End Point Criteria and Incubation Periods
Authors: Llop C. , Pujol I. , Aguilar C. , Sala J. , Riba D. , Guarro J. 
Published: July 2002

ABSTRACT
Three different methods were used to determine the in vitro activities of amphotericin B, ketoconazole, itraconazole, and flucytosine against 30 isolates of different genera of filamentous fungi. MICs were determined visually, with or without agitation, and spectrophotometrically by using a broth microdilution method. For amphotericin B, there was one end point reading criterion (the minimum concentration of antifungal that inhibited 100% of growth), but for azoles and flucytosine there were two (the minimum concentrations that inhibited 50 and 75% of fungal growth, respectively) after 48 and 72 h of incubation. All tests were performed in triplicate. An intraclass correlation coefficient (ICC) was used to evaluate the reproducibility of each of the methods and the correlation among them. The reproducibility of the three methods was very high (ICC of 0.808 to 0.992), particularly in the case of azoles and flucytosine. In general, the degree of reproducibility was highest for azoles and amphotericin B after 72 h of incubation and for flucytosine after 48 h of incubation. The degree of correlation among the three methods was very high (ICC of >0.98) with all of the antifungals under all the conditions tested. The end point reading criteria and the time of incubation affected neither the reproducibility of the methods nor their correlation, and their effect on MICs was statistically significant.
Genes for Production of the Enediyne Antitumor Antibiotic C-1027 in
Streptomyces globisporus
Are Clustered with the
cagA
Gene That Encodes the C-1027 Apoprotein
Authors: Liu Wen , Shen Ben 
Published: July 2002

ABSTRACT

C-1027, the most potent member of the enediyne antitumor antibiotic family, is produced by
Streptomyces globisporus
C-1027 and consists of an apoprotein (encoded by the
cagA
gene) and a nonpeptidic chromophore. The C-1027 chromophore could be viewed as being derived biosynthetically from a benzoxazolinate, a deoxyamino hexose, a β-amino acid, and an enediyne core. By adopting a strategy for cloning of the C-1027 biosynthesis gene cluster by mapping a putative dNDP-glucose 4,6-dehydratase (NGDH) gene to
cagA
, we have localized 75 kb of contiguous DNA from
S. globisporus
. DNA sequence analysis of two regions of the cloned gene cluster revealed two genes,
sgcA
and
sgcB
, that encode an NGDH enzyme and a transmembrane efflux protein, respectively, and confirmed that the
cagA
gene resides approximately 14 kb upstream of the
sgcAB
locus. The involvement of the cloned gene cluster in C-1027 biosynthesis was demonstrated by disrupting the
sgcA
gene to generate C-1027-nonproducing mutants and by complementing the
sgcA
mutants in vivo to restore C-1027 production. These results represent the first cloning of a gene cluster for enediyne antitumor antibiotic biosynthesis and provide a starting point for future genetic and biochemical investigations of C-1027 biosynthesis.
A Canadian National Surveillance Study of Urinary Tract Isolates from Outpatients: Comparison of the Activities of Trimethoprim-Sulfamethoxazole, Ampicillin, Mecillinam, Nitrofurantoin, and Ciprofloxacin
Authors: Zhanel George G. , Karlowsky James A. , Harding Godfrey K. M. , Carrie Anita , Mazzulli Tony , Low Donald E. ,   The Canadian Urinary Isolate Study Group, Hoban Daryl J. 
Published: July 2002

ABSTRACT

Ampicillin, trimethoprim-sulfamethoxazole, mecillinam, nitrofurantoin, and ciprofloxacin mean resistance rates for 2,000 urinary tract isolates collected from outpatients across Canada in 1998 were 41.1, 19.2, 14.7, 5.0, and 1.8%, respectively. For
Escherichia coli
isolates alone (
n
= 1,681) comparable rates were 41.0, 18.9, 7.4, 0.1, and 1.2%, respectively. The majority of
E. coli
isolates resistant to ampicillin, trimethoprim-sulfamethoxazole, or ciprofloxacin were susceptible (MIC, <16 μg/ml) to mecillinam.
Population Pharmacokinetics and Pharmacodynamic Modeling of Abacavir (1592U89) from a Dose-Ranging, Double-Blind, Randomized Monotherapy Trial with Human Immunodeficiency Virus-Infected Subjects
Authors: Weller Stephen , Radomski Kristine M. , Lou Yu , Stein Daniel S. 
Published: July 2002

ABSTRACT

Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other antiretroviral agents. The population pharmacokinetics and pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected, antiretroviral naive adults with baseline CD4
+
cell counts of ≥100/mm
3
and plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained from patients who received randomized, blinded monotherapy with abacavir at 100, 300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir concentrations from sparse sampling were analyzed by standard population pharmacokinetic methods, and the effects of dose, combination therapy, gender, weight, and age on parameter estimates were investigated. Bayesian pharmacokinetic parameter estimates were calculated to determine the peak concentration of abacavir in plasma (
C
max
) and the area under the concentration-time curve from time zero to infinity (AUC
0–∞
) for individual subjects. The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg dose range and were unaffected by any covariates. No significant correlations were observed between the incidence of the five most common adverse events (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC
0–∞
. A significant correlation was observed between
C
max
and nausea by categorical analysis (
P
= 0.019), but this was of borderline significance by logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32). The log
10
time-averaged AUC
0–∞
minus baseline (AAUCMB) values for HIV-1 RNA and CD4
+
cell count correlated significantly with
C
max
and AUC
0–∞
, but with better model fits for AUC
0–∞
. The increase in AAUCMB values for CD4
+
cell count plateaued early for drug exposures that were associated with little change in AAUCMB values for plasma HIV-1 RNA. There was less than a 0.4 log
10
difference over 12 weeks in the HIV-1 RNA levels with the doubling of the abacavir AUC
0–∞
from 300 to 600 mg BID dosing. In conclusion, pharmacodynamic modeling supports the selection of abacavir 300 mg twice-daily dosing.
Use of Preclinical Data for Selection of a Phase II/III Dose for Evernimicin and Identification of a Preclinical MIC Breakpoint
Authors: Drusano G. L. , Preston S. L. , Hardalo C. , Hare R. , Banfield C. , Andes D. , Vesga O. , Craig W. A. 
Published: July 2002

ABSTRACT

One of the most challenging issues in the design of phase II/III clinical trials of antimicrobial agents is dose selection. The choice is often based on preclinical data from pharmacokinetic (PK) studies with animals and healthy volunteers but is rarely linked directly to the target organisms except by the MIC, an in vitro measure of antimicrobial activity with many limitations. It is the thesis of this paper that rational dose-selection decisions can be made on the basis of the pharmacodynamics (PDs) of the test agent predicted by a mathematical model which uses four data sets: (i) the distribution of MICs for clinical isolates, (ii) the distribution of the values of the PK parameters for the test drug in the population, (iii) the PD target(s) developed from animal models of infection, and (iv) the protein binding characteristics of the test drug. In performing this study with the new anti-infective agent evernimicin, we collected a large number (
n
= 4,543) of recent clinical isolates of gram-positive pathogens (
Streptococcus pneumoniae
,
Enterococcus faecalis
and
Enterococcus faecium
, and
Staphylococcus aureus
) and determined the MICs using E-test methods (AB Biodisk, Stockholm, Sweden) for susceptibility to evernimicin. Population PK data were collected from healthy volunteers (
n
= 40) and patients with hypoalbuminemia (
n
= 12), and the data were analyzed by using NPEM III. PD targets were developed with a neutropenic murine thigh infection model with three target pathogens:
S. pneumoniae
(
n
= 5),
E. faecalis
(
n
= 2), and
S. aureus
(
n
= 4). Drug exposure or the ratio of the area under the concentration-time curve/MIC (AUC/MIC) was found to be the best predictor of microbiological efficacy. There were three possible microbiological results: stasis of the initial inoculum at 24 h (10
7
CFU), log killing (pathogen dependent, ranging from 1 to 3 log
10
), or 90% maximal killing effect (90%
E
max
). The levels of protein binding in humans and mice were similar. The PK and PD of 6 and 9 mg of evernimicin per kg of body weight were compared; the population values for the model parameters and population covariance matrix were used to generate five Monte Carlo simulations with 200 subjects each. The fractional probability of attaining the three PD targets was calculated for each dose and for each of the three pathogens. All differences in the fractional probability of attaining the target AUC/MIC in this PD model were significant. For
S. pneumoniae
, the probability of attaining all three PD targets was high for both doses. For
S. aureus
and enterococci, there were increasing differences between the 6- and 9-mg/kg evernimicin doses for reaching the 2 log killing (
S. aureus
), 1 log killing (enterococci), or 90%
E
max
AUC/MIC targets. This same approach may also be used to set preliminary in vitro MIC breakpoints.
Prevalence of Molecular Mechanisms of Resistance to Azole Antifungal Agents in
Candida albicans
Strains Displaying High-Level Fluconazole Resistance Isolated from Human Immunodeficiency Virus-Infected Patients
Authors: Perea Sofia , López-Ribot José L. , Kirkpatrick William R. , McAtee Robert K. , Santillán Rebecca A. , Martı́nez Marcos , Calabrese David , Sanglard Dominique , Patterson Thomas F. 
Published: July 2002

ABSTRACT

Molecular mechanisms of azole resistance in
Candida albicans
, including alterations in the target enzyme and increased efflux of drug, have been described, but the epidemiology of the resistance mechanisms has not been established. We have investigated the molecular mechanisms of resistance to azoles in
C. albicans
strains displaying high-level fluconazole resistance (MICs, ≥64 μg/ml) isolated from human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis. The levels of expression of genes encoding lanosterol 14α-demethylase (
ERG11
) and efflux transporters (
MDR1
and CDR) implicated in azole resistance were monitored in matched sets of susceptible and resistant isolates. In addition,
ERG11
genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. The analysis confirmed the multifactorial nature of azole resistance and the prevalence of these mechanisms of resistance in
C. albicans
clinical isolates exhibiting frank fluconazole resistance, with a predominance of overexpression of genes encoding efflux pumps, detected in 85% of all resistant isolates, being found. Alterations in the target enzyme, including functional amino acid substitutions and overexpression of the gene that encodes the enzyme, were detected in 65 and 35% of the isolates, respectively. Overall, multiple mechanisms of resistance were combined in 75% of the isolates displaying high-level fluconazole resistance. These results may help in the development of new strategies to overcome the problem of resistance as well as new treatments for this condition.
Inhibition of Trypsin-Like Cysteine Proteinases (Gingipains) fromPorphyromonas gingivalisby Tetracycline and Its Analogues
Authors: Imamura Takahisa , Matsushita Kenji , Travis James , Potempa Jan 
Published: July 2002

ABSTRACTExtracellular cysteine proteinases, referred to as gingipains, are considered important virulence factors forPorphyromonas gingivalis, a bacterium recognized as a major etiologic agent of chronic periodontitis. We investigated the effect of tetracycline and its analogues, doxycycline and minocycline, on the enzymatic activities of gingipains. Tetracyclines at 100 μM totally inhibited the amidolytic activity of arginine-specific gingipains (HRgpA and RgpB). In contrast, inhibition of Kgp was less efficient and required a somewhat higher concentration of the antibiotic to achieve the same effect. Among tetracycline derivatives, the most potent gingipain inhibitor was doxycycline, followed by tetracycline and minocycline. RgpB was inhibited by doxycycline in an uncompetitive and reversible manner with a 50% inhibitory concentration of 3 μM. Significantly, inhibition was unaffected by calcium, excluding the chelating activity of tetracyclines as the mechanism of gingipain inactivation. In contrast, the inhibitory activities of the tetracyclines were reduced by cysteine, a reducing agent, suggesting an interference of the drug at the oxidative region with the catalytic system of the enzyme. Doxycycline, at 10 μM, significantly inhibited the RgpB-mediated production of vascular permeability-enhancing activity from human plasma, thus proving an effective inhibition of gingipain in vivo. These results indicate a new activity of tetracyclines as cysteine proteinase inhibitors and may explain the therapeutic efficiency of these antibiotics in the treatment of periodontitis.