bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model of dynamic side‐chain–side‐chain interactions in the α‐lactalbumin molten globule
Authors: Bai Ping , Song Jianxing , Luo Li , Peng Zheng‐Yu 
Published: July 2002

AbstractProteins in the molten globule state contain high levels of secondary structure, as well as a rudimentary, nativelike tertiary topology. Thus, the structural similarity between the molten globule and native proteins may have a significant bearing in understanding the protein‐folding problem. To explore the nature of side‐chain–side‐chain interactions in the α‐lactalbumin (α‐LA) molten globule, we determined the effective concentration for formation of the 28–111 disulfide bond in 14 double‐mutant proteins, each containing two hydrophobic core residues replaced by alanine. We compared our results with those of single‐alanine substitutions using the framework of double‐mutant cycle analysis and found that, in the majority of cases, the effects of two alanine substitutions are additive. Based on these results, we propose a model of side‐chain–side‐chain interactions in the α‐LA molten globule, which takes into consideration the dynamic nature of this partially folded species.
Direct comparison of binding equilibrium, thermodynamic, and rate constants determined by surface‐ and solution‐based biophysical methods
Authors: Day Yasmina S.N. , Baird Cheryl L. , Rich Rebecca L. , Myszka David G. 
Published: July 2002

AbstractThe binding interactions of small molecules with carbonic anhydrase II were used as model systems to compare the reaction constants determined from surface‐ and solution‐based biophysical methods. Interaction data were collected for two arylsulfonamide compounds, 4‐carboxybenzenesulfonamide (CBS) and 5‐dimethyl‐amino‐1‐naphthalene‐sulfonamide (DNSA), binding to the enzyme using surface plasmon resonance, isothermal titration calorimetry, and stopped‐flow fluorescence. We demonstrate that when the surface plasmon resonance biosensor experiments are performed with care, the equilibrium, thermodynamic, and kinetic constants determined from this surface‐based technique match those acquired in solution. These results validate the use of biosensor technology to collect reliable data on small molecules binding to immobilized macromolecular targets. Binding kinetics were shown to provide more detailed information about complex formation than equilibrium constants alone. For example, although carbonic anhydrase II bound DNSA with twofold higher affinity than CBS, kinetic analysis revealed that CBS had a fourfold slower dissociation rate. Analysis of the binding and transition state thermodynamics also revealed significant differences in the enthalpy and entropy of complex formation. The lack of labeling requirements, high information content, and high throughput of surface plasmon resonance biosensors will make this technology an important tool for characterizing the interactions of small molecules with enzymes and receptors.
Differential Diagnosis of Gear and Bearing Faults
Authors: Antoni J. , Randall R. B. 
Published: July 2002

Abstract
This paper deals with the vibration-based diagnosis of rolling element bearings in the presence of strong interfering gear signals, such as is typical of helicopter gearboxes. The key idea consists in recognizing gear signals as purely periodic, whereas bearing signals experience some randomness and are close to cyclostationary, i.e. with a periodic bivariate autocorrelation function. This assertion is demonstrated by introducing a comprehensive model for the vibration generating process of bearing faults: distinctions are made between localized and distributed faults, between cyclostationary and pseudo-cyclostationary processes, and between additive and multiplicative interactions with gear signals. Finally, an original diagnostic procedure is proposed and its performance illustrated using simulated, experimental and actual cases.
Two-Dimensional Transient Analysis of Absorbing Thin Films in Laser
Treatments
Authors: Bianco N. , Manca O. 
Published: July 2002

Abstract
In this paper the transient coupled conductive-radiative field, due to a laser heat source impinging on a thin film deposited on a substrate, has been solved in the hypothesis of one dimensionality of the optical field and of two dimensionality of the thermal field. Results have been obtained with the matrix method for the optical field and the finite volume method for the thermal field. The results show that when the investigation is localized to the center of the spot, the one-dimensional model describes the thermal field quite well. Instead, if knowledge of the temperature is required elsewhere, the two-dimensional model is needed. The investigation herein presented shows that for low-conductivity materials (a–Si) the temperature peaks are placed inside the thin film for the absorption function distribution, determined by interference phenomena. [S0022-1481(00)01301-3]
Dynamics of the interaction of ethane with Ir(110)-(1×2)
Authors: Mullins C. B. , Weinberg W. H. 
Published: July 2002

Experimentally determined values of the initial adsorption probability of ethane on Ir(110)-(1×2) are presented which probe the dynamics of the interaction. The data were obtained from supersonic molecular beam measurements with an incident kinetic energy Ei ranging between 1.2 and 24 kcal/mol, surface temperatures TS between 77 and 550 K, and incident angle θi between 0° and 45°. Experimentally determined values of the initial trapping probability ζ0 of ethane into a physically adsorbed state at TS=77 K as a function of Ei and θi and experimentally determined values of the initial probability of dissociative chemisorption S0 as a function of Ei,θi, and TS are presented. The value of ζ0 is found to decrease with increasing Ei consistent with the fact that an increasingly larger fraction of the incident kinetic energy must be dissipated in order for the molecule to physically adsorb.
The initial trapping probability has a relatively weak dependence on θi such that the value of ζ0 is found empirically to scale as Ei cos0.5 θi. Two distinct mechanisms of dissociative chemisorption on the bare surface are revealed. At low Ei a temperature-dependent trapping-mediated chemisorption mechanism dominates, while at relatively high Ei a temperature-independent direct mechanism dominates. For Ei less than 13.4 kcal/mol, the value of S0 decreases rapidly with increasing TS, consistent with a trapping-mediated mechanism. For a surface temperature of 154 K, S0 decreases with increasing Ei for 1.2≤Ei≤13.4 kcal/mol, in a manner similar to that for the molecular trapping probability. The data in the low Ei regime also support quantitatively a kinetic model consistent with a trapping-mediated chemisorption mechanism. The difference in the activation energies for desorption and chemisorption from the physically adsorbed, trapped state Ed−Ec is 2.2±0.2 kcal/mol. In the trapping-mediated chemisorption regime, the value of S0 is found to be rather insensitive to incident angle, scaling with Ei cos0.5 θi just as for trapping of molecular ethane into a physically adsorbed state. For a normal energy Ei cos2 θi greater than 8 kcal/mol, chemisorption via a direct mechanism becomes significant and increases with increasing Ei. Values of S0 in the direct chemisorption regime scale with normal energy and are independent of TS over the range from 350 to 1350 K.
Estimation of Particulate Organic Carbon in the Ocean from Satellite Remote Sensing
Authors: Stramski Dariusz , Reynolds Rick A. , Kahru Mati , Mitchell B. Greg 
Published: July 2002

Measurements from the Southern Ocean show that particulate organic carbon (POC) concentration is well correlated with the optical backscattering by particles suspended in seawater. This relation, in conjunction with retrieval of the backscattering coefficient from remote-sensing reflectance, provides an algorithm for estimating surface POC from satellite data of ocean color. Satellite imagery from SeaWiFS reveals the seasonal progression of POC, with a zonal band of elevated POC concentrations in December coinciding with the Antarctic Polar Front Zone. At that time, the POC pool within the top 100 meters of the entire Southern Ocean south of 40°S exceeded 0.8 gigatons.
Evidence for an Efflux Pump Mediating Multiple Antibiotic Resistance in
Salmonella enterica
Serovar Typhimurium
Authors: Piddock Laura J. V. , White David G. , Gensberg Karl , Pumbwe Lilian , Griggs Deborah J. 
Published: July 2002

ABSTRACT

The mechanism of multiple antibiotic resistance in six isolates of
Salmonella enterica
serovar Typhimurium recovered from a patient treated with ciprofloxacin was studied to investigate the role of efflux in the resistance phenotype. Compared to the patient's pretherapy isolate (L3), five of six isolates accumulated less ciprofloxacin, three of six isolates accumulated less chloramphenicol, and all six accumulated less tetracycline. The accumulation of one or more antibiotics was increased by carbonyl cyanide
m
-chlorophenylhydrazone to concentrations similar to those accumulated by L3 for all isolates except one, in which accumulation of all three agents remained approximately half that of L3. All isolates had the published wild-type sequences of
marO
and
marR
. No increased expression of
marA
,
tolC
, or
soxS
was observed by Northern blotting; however, three isolates showed increased expression of
acrB
, which was confirmed by quantitative competitive reverse transcription-PCR. However, there were no mutations within
acrR
or the promoter region of
acrAB
in any of the isolates.
Activities of an Intravenous Formulation of Itraconazole in Experimental DisseminatedAspergillus,Candida, andCryptococcusInfections
Authors: Odds Frank C. , Oris Michel , Van Dorsselaer Pascal , Van Gerven Frans 
Published: July 2002

ABSTRACTAn intravenous (i.v.) formulation of itraconazole was evaluated in disseminated fungal infection models in guinea pigs. In acute disseminatedCandida albicansandAspergillus fumigatusinfections, treatment at 5 mg/kg of body weight twice a day (b.i.d.) significantly prolonged survival. In these models and in animals with chronic disseminated cryptococcosis, itraconazole given i.v. at 2.5 and 5 mg/kg b.i.d. greatly reduced the proportions of organs with culture-detectable fungal burdens. The efficacy of i.v. itraconazole in these animal models justifies its further investigation for the treatment of life-threatening mycoses in humans.
Candidacidal Activities of Human Lactoferrin Peptides Derived from the N Terminus
Authors: Lupetti Antonella , Paulusma-Annema Akke , Welling Mick M. , Senesi Sonia , van Dissel Jaap T. , Nibbering Peter H. 
Published: July 2002

ABSTRACTIn light of the need for new antifungal agents, the candidacidal activities of human lactoferrin (hLF) and synthetic peptides representing the first, hLF(1-11), and second, hLF(21-31), cationic domains of its N terminus were compared. The results revealed that hLF(1-11) was more effective in killing fluconazole-resistantCandida albicansthan hLF(21-31) and much more effective than lactoferrin, as determined microbiologically and by propidium iodide (PI) staining. By using hLF(1-11) and various derivatives, it was found that the second and third residues of the N terminus of hLF(1-11) were critical for its candidacidal activity. Detailed investigation to elucidate the mechanism of action of hLF(1-11) revealed a dose-dependent release of ATP byCandidaupon exposure to hLF(1-11). Our observations that sodium azide reduced the PI uptake and candidacidal activity of hLF(1-11) and that, upon exposure to hLF(1-11), the fluorescent dye rhodamine 123 first accumulated inside the mitochondria and later was released into the cytoplasm indicate that the peptide triggers the energized mitochondrion. Furthermore, oxidized ATP, which interferes with the interaction of ATP with its extracellular receptors, blocked the candidacidal action of hLF(1-11), as measured microbiologically and by PI staining. Addition of ATP (or analogues) was not a sufficient stimulus to killC. albicansor to act synergistically with suboptimal concentrations of the peptide. The main conclusions are that the first two arginines at the N terminus of hLF are critical in the candidacidal activity of hLF(1-11) and that extracellular ATP is essential but not sufficient for the peptide to exert its candidacidal activity.
Characterization of Spontaneous, In Vitro-Selected, Rifampin-Resistant Mutants of
Mycobacterium tuberculosis
Strain H37Rv
Authors: Morlock Glenn P. , Plikaytis Bonnie B. , Crawford Jack T. 
Published: July 2002

ABSTRACT

Resistance to rifampin in
Mycobacterium tuberculosis
results from mutations in the gene coding for the beta subunit of RNA polymerase (
rpoB
). At least 95% of rifampin-resistant isolates have mutations in
rpoB
, and the mutations are clustered in a small region. About 40 distinct point mutations and in-frame insertions and deletions in
rpoB
have been identified, but point mutations in two codons, those coding for Ser
531
and His
526
, are seen in about 70% of rifampin-resistant clinical isolates, with Ser
531
-to-Leu (TCG-to-TGG) mutations being by far the most common. To explore this phenomenon, we isolated independent, spontaneous, rifampin-resistant mutant versions of well-characterized
M. tuberculosis
laboratory strain H37Rv by plating 100 separate cultures, derived from a single low-density inoculum, onto rifampin-containing medium. Rifampin-resistant mutants were obtained from 64 of these cultures. Although we anticipated that the various point mutations would occur with approximately equal frequencies, sequencing the
rpoB
gene from one colony per plate revealed that 39 (60.9%) were Ser
531
to Leu. We conclude that, for unknown reasons, the associated
rpoB
mutation occurs at a substantially higher rate than other
rpoB
mutations. This higher mutation rate may contribute to the high percentage of this mutation seen in clinical isolates.
Salivary Histatin 5 and Human Neutrophil Defensin 1 Kill
Candida albicans
via Shared Pathways
Authors: Edgerton Mira , Koshlukova Svetlana E. , Araujo Marcelo W. B. , Patel Rashmi C. , Dong Jin , Bruenn Jeremy A. 
Published: July 2002

ABSTRACT

Salivary histatins are a family of basic histidine-rich proteins in which therapeutic potential as drugs against oral candidiasis is apparent, considering their potent in vitro antifungal activity and lack of toxicity to humans. Histatin 5 (Hst 5) kills the fungal pathogen
Candida albicans
via a mechanism that involves binding to specific sites on the yeast cell membrane and subsequent release of cellular ATP in the absence of cytolysis. We explored the killing pathway activated by Hst 5 and compared it to those activated by other antifungal agents. The candidacidal activity of human neutrophil defensin 1 (HNP-1) shared very similar features to Hst 5 cytotoxic action with respect to active concentrations and magnitude of induction of nonlytic ATP efflux, depletion of intracellular ATP pools, and inhibitor profile. Hst 5 and HNP-1 are basic proteins of about 3 kDa; however, they have unique primary sequences and solution structures that cannot explain how these two molecules act so similarly on
C. albicans
to induce cell death. Our finding that HNP-1 prevented Hst 5 binding to the candidal Hst 5 binding protein suggests that the basis for the overlapping actions of these two naturally occurring antimicrobial proteins may involve interactions with shared yeast components.
Nasal Carriage in Vietnamese Children of
Streptococcus pneumoniae
Resistant to Multiple Antimicrobial Agents
Authors: Parry Christopher M. , Diep To Song , Wain John , Hoa Nguyen Thi Tuyet , Gainsborough Mary , Nga Diem , Davies Catrin , Phu Nguyen Hoan , Hien Tran Tinh , White Nicholas J. , Farrar Jeremy J. 
Published: July 2002

ABSTRACT

Resistance to antimicrobial agents in
Streptococcus pneumoniae
is increasing rapidly in many Asian countries. There is little recent information concerning resistance levels in Vietnam. A prospective study of pneumococcal carriage in 911 urban and rural Vietnamese children, of whom 44% were nasal carriers, was performed. Carriage was more common in children <5 years old than in those ≥5 years old (192 of 389 [49.4%] versus 212 of 522 [40.6%];
P
, 0.01). A total of 136 of 399 isolates (34%) had intermediate susceptibility to penicillin (MIC, 0.1 to 1 mg/liter), and 76 of 399 isolates (19%) showed resistance (MIC, >1.0 mg/liter). A total of 54 of 399 isolates (13%) had intermediate susceptibility to ceftriaxone, and 3 of 399 isolates (1%) were resistant. Penicillin resistance was 21.7 (95% confidence interval, 7.0 to 67.6) times more common in urban than in rural children (35 versus 2%;
P
, <0.001). More than 40% of isolates from urban children were also resistant to erythromycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Penicillin resistance was independently associated with an urban location when the age of the child was controlled for. Multidrug resistance (resistance to three or more antimicrobial agent groups) was present in 32% of isolates overall but in 39% of isolates with intermediate susceptibility to penicillin and 86% of isolates with penicillin resistance. The predominant serotypes of the
S. pneumoniae
isolates were 19, 23, 14, 6, and 18. Almost half of the penicillin-resistant isolates serotyped were serotype 23, and these isolates were often multidrug resistant. This study suggests that resistance to penicillin and other antimicrobial agents is common in carriage isolates of
S. pneumoniae
from children in Vietnam.
A Dose-Response Study of Antibiotic Resistance in
Pseudomonas aeruginosa
Biofilms
Authors: Brooun Alexei , Liu Songhua , Lewis Kim 
Published: July 2002

ABSTRACT

Bacterial biofilms show enormous levels of antibiotic resistance, but little is known about the underlying molecular mechanisms. Multidrug resistance pumps (MDRs) are responsible for the extrusion of chemically unrelated antimicrobials from the bacterial cell. Contribution of the MDR-mediated efflux to antibiotic resistance of
Pseudomonas aeruginosa
biofilms was examined by using strains overexpressing and lacking the MexAB-OprM pump. Resistance of
P. aeruginosa
biofilms to ofloxacin was dependent on the expression of MexAB-OprM but only in the low concentration range. Unexpectedly, biofilm resistance to ciprofloxacin, another substrate of MexAB-OprM, did not depend on the presence of this pump. Dose-dependent killing indicated the presence of a small “superresistant” cell fraction. This fraction was primarily responsible for very high resistance of
P. aeruginosa
biofilms to quinolones. Bacterial cells recovered from a biofilm and tested under nongrowing conditions with tobramycin exhibited higher resistance levels than planktonic cells but lower levels than cells of an intact biofilm.
Characterization of the
fomA
and
fomB
Gene Products from
Streptomyces wedmorensis
, Which Confer Fosfomycin Resistance on
Escherichia coli
Authors: Kobayashi Seiji , Kuzuyama Tomohisa , Seto Haruo 
Published: July 2002

ABSTRACT

Together, the
fomA
and
fomB
genes in the fosfomycin biosynthetic gene cluster of
Streptomyces wedmorensis
confer high-level fosfomycin resistance on
Escherichia coli
. To elucidate their functions, the
fomA
and
fomB
genes were overexpressed in
E. coli
and the gene products were characterized. The recombinant FomA protein converted fosfomycin to fosfomycin monophosphate, which was inactive on
E. coli
, in the presence of a magnesium ion and ATP. On the other hand, the recombinant FomB protein did not inactivate fosfomycin. However, a reaction mixture containing FomA and FomB proteins converted fosfomycin to fosfomycin monophosphate and fosfomycin diphosphate in the presence of ATP and a magnesium ion, indicating that FomA and FomB catalyzed phosphorylations of fosfomycin and fosfomycin monophosphate, respectively. These results suggest that the self-resistance mechanism of the fosfomycin-producing organism
S. wedmorensis
is mono- and diphosphorylation of the phosphonate function of fosfomycin catalyzed by FomA and FomB.
Intracellular Metabolism of β-
l
-2′,3′-Dideoxyadenosine: Relevance to Its Limited Antiviral Activity
Authors: Placidi Laurent , Cretton-Scott Erika , Gosselin Gilles , Pierra Claire , Schinazi Raymond F. , Imbach Jean-Louis , el Kouni Mahmoud H. , Sommadossi Jean-Pierre 
Published: July 2002

ABSTRACT

The intracellular metabolism of the β-
l
- enantiomer of 2′,3′-dideoxyadenosine (β-
l
-ddA) was investigated in HepG2 cells, human peripheral blood mononuclear cells (PBMC), and primary cultured human hepatocytes in an effort to understand the metabolic basis of its limited activity on the replication of human immunodeficiency virus and hepatitis B virus. Incubation of cells with 10 μM [2′,3′,8-
3
H]-β-
l
-ddA resulted in an increased intracellular concentration of β-
l
-ddA with time, demonstrating that these cells were able to transport β-
l
-ddA. However, it did not result in the phosphorylation of β-
l
-ddA to its pharmacologically active 5′-triphosphate (β-
l
-ddATP). Five other intracellular metabolites were detected and identified as β-
l
-2′,3′-dideoxyribonolactone, hypoxanthine, inosine, ADP, and ATP, with the last being the predominant metabolite, reaching levels as high as 5.14 ± 0.95, 8.15 ± 2.64, and 15.60 ± 1.74 pmol/10
6
cells at 8, 4, and 2 h in HepG2 cells, PBMC, and hepatocytes, respectively. In addition, a β-glucuronic derivative of β-
l
-ddA was detected in cultured hepatocytes, accounting for 12.5% of the total metabolite pool. Coincubation of hepatocytes in primary culture with β-
l
-ddA in the presence of increasing concentrations of 5′-methylthioadenosine resulted in decreased phosphorolysis of β-
l
-ddA and formation of associated metabolites. These results indicate that the limited antiviral activity of β-
l
-ddA is the result of its inadequate phosphorylation to the nucleotide level due to phosphorolysis and catabolism of β-
l
-ddA by methylthioadenosine phosphorylase (EC
2.4.2.28
).
Distribution and Content of Class 1 Integrons in Different
Vibrio cholerae
O-Serotype Strains Isolated in Thailand
Authors: Dalsgaard Anders , Forslund Anita , Serichantalergs Oralak , Sandvang Dorthe 
Published: July 2002

ABSTRACT

In this study, 176 clinical and environmental
Vibrio cholerae
strains of different O serotypes isolated in Thailand from 1982 to 1995 were selected and studied for the presence of class 1 integrons, a new group of genetic elements which carry antibiotic resistance genes. Using PCR and DNA sequencing, we found that 44 isolates contained class 1 integrons harboring the
aadB
,
aadA2
,
blaP1
,
dfrA1
, and
dfrA15
gene cassettes, which encode resistance to gentamicin, kanamycin, and tobramycin; streptomycin and spectinomycin; β-lactams; and trimethoprim, respectively. Each cassette array contained only a single antibiotic resistance gene. Although resistance genes in class 1 integrons were found in strains from the same epidemic, as well as in unrelated non-O1, non-O139 strains isolated from children with diarrhea, they were found to encode only some of the antibiotic resistance expressed by the strains. Serotype O139 strains did not contain class 1 integrons. However, the appearance and disappearance of the O139 serotype in the coastal city Samutsakorn in 1992 and 1993 were associated with the emergence of a distinct
V. cholerae
O1 strain which contained the
aadA2
resistance gene cassette. A 150-kb self-transmissible plasmid found in three O1 strains isolated in 1982 contained the
aadB
gene cassette. Surprisingly, several strains harbored two integrons containing different cassettes. Thus, class 1 integrons containing various resistance gene cassettes are distributed among different
V. cholerae
O serotypes of mainly clinical origin in Thailand.