bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleation and Initial-Growth Behavior of Thin-Film Deposits
Authors: Lewis B. , Campbell D. S. 
Published: July 2002

This paper gives a theoretical and experimental treatment of the subject. It is shown that the capture of single atoms can be related to catchment areas associated with stable and critical nuclei. It is then shown that for the materials and conditions used in evaporation work the size of the smallest stable cluster is normally a pair.
Two equations describing the initial stages of growth are then derived dependent on whether the lifetime of single atoms is determined by reevaporation or by capture. For the reevaporation case, it is predicted that nucleation proceeds exponentially to a saturation density Ns of islands, and that Ns increases with temperature T and is independent of incidence rate R. For the capture case, condensation is initially complete and Ns increases with R and decreases with T. Experimental results with gold on vacuum cleaved rocksalt show reasonable agreement with the predicted behavior. Modified growth conditions are also examined experimentally, and the results are interpreted in terms of the parameters of the theoretical expressions. Growth using gold ejected from a sputtered single crystal suggests an increased effective condensate temperature. Normal evaporation with simultaneous electron bombardment of the substrate gives results which can be ascribed to lower mobility of migrating atoms.
Field emission from structures with quantum wells
Authors: Litovchenko V. G. , Kryuchenko Yu. V. 
Published: July 2002

Computer simulation studies of the properties of some novel types of field emitters have been carried out in the framework of the theory of quantum disc effects. The following cases have been analyzed in detail. (1) Emission from the field surface states (SS) exhibiting both discrete and continuous energy spectra. This case resembles the known effect of the work-function deterioration ΔW∼(Ec−ESS), yet, here, prior to the emission into vacuum, the SS electrons must be excited the conductivity band via the Pool–Frenkel mechanism: ne≂C exp(aEs1/2/kT), or some other. (2) Emission from the δ-doped structures via the internal field ionization of filled states, deposited near to surface in semiconductor or in super-thin insulator layer. (3) Emission from the two-dimensional (2D) quantum well (QW) surface space charge regions. In this case, the bottom of a subsurface c band is shifted by the quantization value E=Ec−Ei with Ei=(ℏ2/2m*)1/3 [3/2πeEs(i+3/4)]2/3∼Es2/3. Here Es=4π/2eNs is the strength of the surface electric field and i stands for the number of a quantum well (or a 2D subband). In contrast with the three-dimensional (3D) case, the electron concentration in the ith 2D degenerate subband is given bt a step function Ns=(m*/πℏ2)kT ln{1+exp[(Ec−Ei)/kT]}. With m*=0.01 me, the difference E=(Ei−Ec) greatly increases in pretty high applied fields (Es∼10 V cm−1) and, thus, may give rise to a pronounced increase of the field emission current. Moreover, with growing Es, subsequent bands are being filed and, due to the steplike dependence of NSS, an additional growth of the emission current may occur, together with emerging collisions on the Fowler–Nordheim differential curve. (4) Emission from very sharp tips containing 2D-conducting layer (QW space charge), when τ tip is comparable to the low thickness of QW layer.
Here we have so-called zero-size (zero-dimensional) systems, when the dependence ΔW on ES becomes even sharper. (%) emission from the tips covered by very thin films with quantized conducting electrons. For these, narrow-band or semimetallic materials (such as Bi) with very low effective mass (HgCdTe, InSb, PbSTe, etc.) may be used. Discrete Q levels Ei govern the current oscillations with the increasing Es, when Ei is filled by the applied field. For the transversal current (in the direction of the electron localization) to appear, necessary determine or ionization 2D quasilocalized electron to more high, 3D subbands, or due to different scattering processes (including oscillation in QW).
Mitochondria and Apoptosis
Authors: Green Douglas R. , Reed John C. 
Published: July 2002

REVIEW
A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins. The different signals that converge on mitochondria to trigger or inhibit these events and their downstream effects delineate several major pathways in physiological cell death.
Deregulation of the Arginine Deiminase (
arc
) Operon in Penicillin-Tolerant Mutants of
Streptococcus gordonii
Authors: Caldelari I. , Loeliger B. , Langen H. , Glauser M. P. , Moreillon P. 
Published: July 2002

ABSTRACT

Penicillin tolerance is an incompletely understood phenomenon that allows bacteria to resist drug-induced killing. Tolerance was studied with independent
Streptococcus gordonii
mutants generated by cyclic exposure to 500 times the MIC of penicillin. Parent cultures lost 4 to 5 log
10
CFU/ml of viable counts/24 h. In contrast, each of four independent mutant cultures lost ≤2 log
10
CFU/ml/24 h. The mutants had unchanged penicillin-binding proteins but contained increased amounts of two proteins with respective masses of ca. 50 and 45 kDa. One mutant (Tol1) was further characterized. The two proteins showing increased levels were homologous to the arginine deiminase and ornithine carbamoyl transferase of other gram-positive bacteria and were encoded by an operon that was >80% similar to the arginine-deiminase (
arc
) operon of these organisms. Partial nucleotide sequencing and insertion inactivation of the
S. gordonii arc
locus indicated that tolerance was not a direct consequence of
arc
alteration. On the other hand, genetic transformation of tolerance by Tol1 DNA always conferred
arc
deregulation. In nontolerant recipients,
arc
was repressed during exponential growth and up-regulated during postexponential growth. In tolerant transformants,
arc
was constitutively expressed. Tol1 DNA transformed tolerance at the same rate as transformation of a point mutation (10
−2
to 10
−3
). The tolerance mutation mapped on a specific chromosomal fragment but was physically distant from
arc
. Importantly,
arc
deregulation was observed in most (6 of 10) of additional independent penicillin-tolerant mutants. Thus, although not exclusive, the association between
arc
deregulation and tolerance was not fortuitous. Since penicillin selection mimicked the antibiotic pressure operating in the clinical environment,
arc
deregulation might be an important correlate of naturally occurring tolerance and help in understanding the mechanism(s) underlying this clinically problematic phenotype.
Effects of Antiviral Usage on Transmission Dynamics of Herpes Simplex Virus Type 1 and on Antiviral Resistance: Predictions of Mathematical Models
Authors: Lipsitch Marc , Bacon Teresa H. , Leary Jeffry J. , Antia Rustom , Levin Bruce R. 
Published: July 2002

ABSTRACTHerpes simplex virus type 1 (HSV-1) causes recurrent herpes labialis (RHL), a common disease afflicting up to 40% of adults worldwide. Mathematical models are used to analyze the effect of antiviral treatment on the transmission of, and the prevalence of drug resistance in, HSV-1 in the United States. Three scenarios are analyzed: no antiviral use, the current level of use, and a substantial increase in nucleoside analogue use, such as might occur if topical penciclovir were available over-the-counter for the treatment of RHL. A basic model predicts that present level of nucleoside analogue use has a negligible effect on HSV-1 transmission and that even if use of topical penciclovir for (RHL) increased substantially, the overall prevalence of infectious HSV-1 is unlikely to be reduced by more than 5%. An expanded model, which allows for acquired resistance and includes immunocompromised hosts and other more realistic features, predicts that current antiviral use is unlikely to lead to any noticeable increase in resistance. If antiviral use increases, the resulting rise in resistance in the population will depend primarily on the probability that immunocompetent hosts will acquire permanent resistance upon treatment. This probability is known to be small, but its exact value remains uncertain. If acquired resistance occurs less than once per 2,500 treated episodes, then in the community at large, the frequency of HSV-1 resistance is predicted to increase slowly, if at all (remaining below 0.5% for >50 years), even with extensive nucleoside analogue use. If acquired resistance emerges in 1 of 625 treated episodes (the maximum of an approximate 95% confidence interval derived from the results of several studies of resistance in treated hosts), then the prevalence of infection with resistant HSV-1 could rise from about 0.2% to 1.5 to 3% within 50 years. The limitations of existing data on acquired resistance and the potential impact of acquired resistance if it occurs are discussed, and strategies are suggested for enhancing information on acquired resistance. The predictions of this model contrast with the more rapid increases in antimicrobial resistance anticipated by models and observed for other pathogenic bacteria and viruses. The reasons for these contrasting predictions are discussed.
Cloning and Characterization of SmeDEF, a Novel Multidrug Efflux Pump from
Stenotrophomonas maltophilia
Authors: Alonso Ana , Martínez José L. 
Published: July 2002

ABSTRACT

Stenotrophomonas maltophilia
is a nosocomial bacterial pathogen intrinsically resistant to several antibiotics. The mechanisms involved in this intrinsic multiresistance phenotype are poorly understood. A library of chromosomal DNA from a spontaneous multidrug-resistant
S. maltophilia
D457R mutant (A. Alonso and J. L. Martinez, Antimicrob. Agents Chemother. 41:1140–1142, 1997) was screened for complementation of erythromycin susceptibility on an antibiotic-hypersusceptible
Escherichia coli ΔacrAB
strain. Cloning and further analysis revealed that a 6-kbp region constituting a transcriptional unit was capable of complementing the antibiotic-susceptible phenotype of an
E. coli ΔacrAB
strain. We identified three open reading frames,
smeD
,
smeE
and
smeF
, which code for members of the membrane fusion protein, resistance nodulation division, and outer membrane factor families, respectively. Drug susceptibility assays indicated that the SmeDEF system cloned in
E. coli
mediates resistance to a wide range of antibiotics. Ethidium bromide and norfloxacin accumulation experiments in the presence and in the absence of carbonyl cyanide
m
-chlorophenylhydrazone showed that this system constitutes a drug efflux pump dependent on the membrane proton motive force. The presence of high levels of
smeDEF
mRNA in the multiresistant D457R mutant was consistent with the high levels of SmeF (formerly Omp54) observed in the same strain. In contrast, transcription levels of
smeDEF
in the D457 strain were tiny, which correlates with the low levels of SmeF observed for this strain. Also, for both the D457 and D457R strains, we observed growth phase-dependent regulation in which the highest level of transcription corresponded to early exponential phase, with transcription decreasing throughout the growth curve to undetectable levels at 24 h.
Effect of Ceftazidime on Systemic Cytokine Concentrations in Rats
Authors: Alkharfy Khalid M. , Kellum John A. , Frye Reginald F. , Matzke Gary R. 
Published: July 2002

ABSTRACT
The effect of a single dose of ceftazidime on circulating concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in a rat model of sepsis was studied. IL-6 concentrations were significantly elevated (100 to 200 times the baseline) 6 h after ceftazidime administration in both septic and nonseptic (control) rats. TNF-α concentrations increased significantly in nonseptic (∼40 times the baseline) rats but not septic (∼2 to 3 times the baseline) rats. Ceftazidime administration was not associated with an increase in endotoxin concentrations. These findings suggest that ceftazidime modulation of proinflammatory cytokine concentrations may be independent of its antimicrobial properties.
Discovery of Novel Antifungal (1,3)-β-
d
-Glucan Synthase Inhibitors
Authors: Onishi J. , Meinz M. , Thompson J. , Curotto J. , Dreikorn S. , Rosenbach M. , Douglas C. , Abruzzo G. , Flattery A. , Kong L. , Cabello A. , Vicente F. , Pelaez F. , Diez M. T. , Martin I. , Bills G. , Giacobbe R. , Dombrowski A. , Schwartz R. , Morris S. , Harris G. , Tsipouras A. , Wilson K. , Kurtz M. B. 
Published: July 2002

ABSTRACT

The increasing incidence of life-threatening fungal infections has driven the search for new, broad-spectrum fungicidal agents that can be used for treatment and prophylaxis in immunocompromised patients. Natural-product inhibitors of cell wall (1,3)-β-
d
-glucan synthase such as lipopeptide pneumocandins and echinocandins as well as the glycolipid papulacandins have been evaluated as potential therapeutics for the last two decades. As a result, MK-0991 (caspofungin acetate; Cancidas), a semisynthetic analogue of pneumocandin B
o
, is being developed as a broad-spectrum parenteral agent for the treatment of aspergillosis and candidiasis. This and other lipopeptide antifungal agents have limited oral bioavailability. Thus, we have sought new chemical structures with the mode of action of lipopeptide antifungal agents but with the potential for oral absorption. Results of natural-product screening by a series of newly developed methods has led to the identification of four acidic terpenoid (1,3)-β-
d
-glucan synthase inhibitors. Of the four compounds, the in vitro antifungal activity of one, enfumafungin, is comparable to that of L-733560, a close analogue of MK-0991. Like the lipopeptides, enfumafungin specifically inhibits glucan synthesis in whole cells and in (1,3)-β-
d
-glucan synthase assays, alters the morphologies of yeasts and molds, and produces a unique response in
Saccharomyces cerevisiae
strains with point mutations in
FKS1
, the gene which encodes the large subunit of glucan synthase.
Efficacy of FK463, a New Lipopeptide Antifungal Agent, in Mouse Models of Pulmonary Aspergillosis
Authors: Matsumoto Satoru , Wakai Yoshimi , Nakai Toru , Hatano Kazuo , Ushitani Tomoe , Ikeda Fumiaki , Tawara Shuichi , Goto Toshio , Matsumoto Fumio , Kuwahara Shogo 
Published: July 2002

ABSTRACT

The efficacy of FK463, a novel water-soluble lipopeptide, was evaluated in mouse models of pulmonary aspergillosis and was compared with that of amphotericin B (AMPH-B). In the pulmonary aspergillosis models induced by intranasal inoculation, FK463 exhibited good efficacy, with 50% effective doses in the range of 0.26 to 0.51 mg/kg of body weight; these values were comparable to those of AMPH-B. In an
Aspergillus
target organ assay with immunosuppressed mice, under conditions of constant plasma levels of FK463, using a subcutaneously implanted osmotic pressure pump, a significant reduction in viable fungal cells was observed at plasma FK463 levels of 0.55 to 0.80 μg/ml or higher. We conclude that FK463 is highly effective in the treatment of pulmonary aspergillosis in this animal model. These results indicate that FK463 may be a potent parenterally administered antifungal agent for pulmonary aspergillosis.
Potent and Selective Activity of a Combination of Thymidine and 1843U89, a Folate-Based Thymidylate Synthase Inhibitor, against
Plasmodium falciparum
Authors: Jiang Lei , Lee Pei-Chieh , White John , Rathod Pradipsinh K. 
Published: July 2002

ABSTRACT

Unlike mammalian cells, malarial parasites are completely dependent on the de novo pyrimidine pathway and lack the enzymes to salvage preformed pyrimidines. In the present study, first, it is shown that 1843U89, even without polyglutamylation, is a potent folate-based inhibitor of purified malarial parasite thymidylate synthase. The binding was noncompetitive with respect to methylenetetrahydrofolate, and 1843U89 had a

K
i

of 1 nM. The compound also had potent antimalarial activity in vitro.
Plasmodium falciparum
cells in culture were inhibited by 1843U89, with a 50% inhibitory concentration of about 70 nM. The compound was effective against drug-sensitive as well as drug-resistant clones of
P. falciparum
. As predicted by the biochemistry of the parasite, the potent inhibition of parasite proliferation by 1843U89 could not be reversed with 10 μM thymidine. In contrast, in the presence of 10 μM thymidine, mammalian cells were unaffected by 1843U89 even at concentrations as high as 0.1 mM, thus offering a selectivity window of more than 1,000-fold. On this basis, folate-based thymidylate synthase inhibitors may represent a powerful additional tool that can be used to combat drug-resistant malaria.
Concentrations of Chloroquine and Malaria Parasites in Blood in Nigerian Children
Authors: Mockenhaupt Frank P. , May Jürgen , Bergqvist Yngve , Ademowo Olusegun G. , Olumese Peter E. , Falusi Adeyinka G. , Großterlinden Lars , Meyer Christian G. , Bienzle Ulrich 
Published: July 2002

ABSTRACT

Consumption of chloroquine (CQ) and subtherapeutic drug levels in blood are considered to be widespread in areas where malaria is endemic. A cross-sectional study was performed with 405 Nigerian children to assess factors associated with the presence of CQ in blood and to examine correlations of drug levels with malaria parasite species and densities. Infections with
Plasmodium
species and parasite densities were determined by microscopy and PCR assays. Whole-blood CQ concentrations were measured by high-performance liquid chromatography.
Plasmodium falciparum
,
P. malariae
, and
P. ovale
were observed in 80, 16, and 9% of the children, respectively, and CQ was detected in 52% of the children. CQ concentrations were >17 and <100 nmol/liter in 25% of the children, 100 to 499 nmol/liter in 14% of the children, and ≥500 nmol/liter in 13% of the children. Young age, attendance at health posts, and absence of parasitemia were factors independently associated with CQ in blood. With increasing concentrations of CQ, the prevalence of
P. falciparum
infection and parasite densities decreased. However, at concentrations corresponding to those usually attained during regular prophylaxis (≥500 nmol/liter), 62% of children were still harboring
P. falciparum
parasites. In contrast, no infection with
P. malariae
and only one infection with
P. ovale
were observed in children with CQ concentrations of ≥100 nmol/liter. These data show the high prevalence of subcurative CQ concentrations in Nigerian children and confirm the considerable degree of CQ resistance in that country. Subtherapeutic drug levels are likely to further promote CQ resistance and may impair the development and maintenance of premunition in areas where malaria is endemic.
Enhanced Extracellular Production of Aspartyl Proteinase, a Virulence Factor, by
Candida albicans
Isolates following Growth in Subinhibitory Concentrations of Fluconazole
Authors: Wu Tao , Wright Katherine , Hurst Steven F. , Morrison Christine J. 
Published: July 2002

ABSTRACT

We examined the production of secreted aspartyl proteinase (Sap), a putative virulence factor of
Candida albicans
, by a series of 17 isolates representing a single strain obtained from the oral cavity of an AIDS patient before and after the development of clinical and in vitro resistance to fluconazole. Isolates were grown in Sap-inducing yeast carbon base-bovine serum albumin medium containing 0, 0.25, 0.5, or 1 MIC of fluconazole, and cultures were sampled daily for 14 days to determine extracellular Sap activity by enzymatic degradation of bovine serum albumin. Extracellular Sap activity was significantly decreased in a dose-dependent manner for the most fluconazole-susceptible isolate (MIC, 1.0 μg/ml) and significantly increased in a dose-dependent manner for the most fluconazole-resistant isolate (MIC, >64 μg/ml). Enhanced extracellular Sap production could not be attributed to cell death or nonspecific release of Sap, because there was no reduction in the number of CFU and no significant release of enolase, a constitutive enzyme of the glycolytic pathway. Conversely, intracellular Sap concentrations were significantly increased in a dose-dependent manner in the most fluconazole-susceptible isolate and decreased in the most fluconazole-resistant isolate. Enhanced Sap production correlated with the overexpression of a gene encoding a multidrug resistance (
MDR1
) efflux pump occurring in these isolates. These data indicate that exposure to subinhibitory concentrations of fluconazole can result in enhanced extracellular production of Sap by isolates with the capacity to overexpress
MDR1
and imply that patients infected with these isolates and subsequently treated with suboptimal doses of fluconazole may experience enhanced
C. albicans
virulence in vivo.
Serotype Distribution and Antimicrobial Resistance of
Streptococcus pneumoniae
Isolates from Pediatric Patients in Singapore
Authors: Soh Shirlena Wee-Ling , Poh Chit Laa , Lin Raymond V. Tzer Pin 
Published: July 2002

ABSTRACT

One hundred eighty
Streptococcus pneumoniae
strains isolated from children at a pediatric hospital in Singapore from 1997 to 1999 were serotyped and their antimicrobial susceptibility patterns were determined. Sixty-three percent of the isolates were resistant to penicillin. Significantly large numbers of the strains investigated were resistant to trimethoprim-sulfamethoxazole (87.8%), tetracycline (71.7%), erythromycin (67.8%), and chloramphenicol (40%). Penicillin and multidrug resistance was mostly associated with the frequently isolated
S. pneumoniae
isolates of serotypes (serotypes 19F, 23F, 6B, and 14). Isolates of serotype 19F, the serotype most commonly encountered in Singapore (41.1%), had the highest prevalence of penicillin (78.4%) and multidrug resistance (94.6%). Most of the invasive
S. pneumoniae
isolates (8 of 17; 47.1%) were of serotype 14.
Bacteriostatic and Bactericidal Activities of Moxifloxacin against
Coxiella burnetii
Authors: Rolain Jean-Marc , Maurin Max , Raoult Didier 
Published: July 2002

ABSTRACT

The in vitro activity of moxifloxacin against
Coxiella burnetii
was compared to those of pefloxacin, ofloxacin, and doxycycline. MICs of moxifloxacin ranged from 0.5 to 1 μg/ml for the Nine Mile, Priscilla, and Q212 strains. Moxifloxacin was not bactericidal against
C. burnetii
at 4 μg/ml.