bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamical virial masses of Lyman-break galaxy haloes at z = 3
Authors: Weatherley Stephen J. , Warren Stephen J. 
Published: September 2005

Abstract
We improve on our earlier dynamical estimate of the virial masses of the haloes of Lyman-break galaxies (LBGs) at redshift z= 3 by accounting for the effects of seeing, slit width and observational uncertainties. From an analysis of the small number of available rotation curves for LBGs we determine a relation Vc7= (1.9 ± 0.2)σ between circular velocity at a radius of 7 kpc, Vc7, and central line velocity width, σ. We use this relation to transform the measured velocity widths of 32 LBGs to the distribution of circular velocities, Vc7, for the population of LBGs brighter than . We compare this distribution against the predicted distribution for the ‘massive-halo’ model in which LBGs pinpoint all of the highest mass dark matter haloes at that epoch. The observed LBG circular velocities are smaller than the predicted circular velocities by a factor of &gt;1.4 ± 0.15. This is a lower limit, as we have ignored any increase of circular velocity caused by baryonic dissipation. The massive-halo model predicts a median halo virial mass of 1012.3 M⊙, and a small spread of circular velocities, Vc7. Our median estimated dynamical mass is &lt;1011.6±0.3 M⊙, which is significantly smaller; furthermore, the spread of our derived circular velocities is much larger than the massive-halo prediction. These results are consistent with a picture which leaves some of the most massive haloes available for occupation by other populations which do not meet the LBG selection criteria. Our new dynamical mass limit is a factor of 3 larger than our earlier estimate which neglected the effects of seeing and slit width. The median halo mass recently estimated by Adelberger et al. from the measured clustering of LBGs is 1011.86±0.3 M⊙. Our dynamical analysis appears to favour lower masses and to be more in line with the median mass predicted by the collisional starburst model of Somerville et al., which is 1011.3 M⊙.
Effect of Ribavirin on Intracellular and Plasma Pharmacokinetics of Nucleoside Reverse Transcriptase Inhibitors in Patients with Human Immunodeficiency Virus-Hepatitis C Virus Coinfection: Results of a Randomized Clinical Study
Authors: Rodriguez-Torres M. , Torriani F. J. , Soriano V. , Borucki M. J. , Lissen E. , Sulkowski M. , Dieterich D. , Wang K. , Gries J.-M. , Hoggard P. G. , Back D. 
Published: September 2005

ABSTRACTThe intracellular triphosphorylation and plasma pharmacokinetics of lamivudine (3TC), stavudine (d4T), and zidovudine (ZDV) were assessed in a pharmacokinetic substudy, in 56 human immunodeficiency virus-hepatitis C virus (HIV-HCV) coinfected patients receiving peginterferon alfa-2a (40KD) 180 μg/week plus either placebo or ribavirin (RBV) 800 mg/day in the AIDS PEGASYS Ribavirin International Coinfection Trial. There were no significant differences between patients treated with RBV and placebo in plasma pharmacokinetics parameters for the nucleoside reverse transcriptase inhibitors (NRTIs) at steady state (weeks 8 to 12): ratios of least squares mean of area under the plasma concentration-time curve (AUC0-12 h) were 1.17 (95% confidence interval, 0.91 to 1.51) for 3TC, 1.44 (95% confidence interval, 0.58 to 3.60) for d4T and 0.85 (95% confidence interval, 0.50 to 1.45) for ZDV, and ratios of least squares mean plasmaCmaxwere 1.33 (95% confidence interval, 0.99 to 1.78), 1.06 (95% confidence interval, 0.68 to 1.65), and 0.84 (95% confidence interval, 0.46 to 1.53), respectively. Concentrations of NRTI triphosphate (TP) metabolites in relation to those of the triphosphates of endogenous deoxythymidine-triphosphate (dTTP) and deoxcytidine-triphosphate (dCTP) were similar in the RBV and placebo groups. Differences (RBV to placebo) in least squares mean ratios of AUC0-12 hat steady state were 0.274 (95% confidence interval, −0.37 to 0.91) for 3TC-TP:dCTP, 0.009 (95% confidence interval, −0.06 to 0.08) for d4T-TP:dTTP, and −0.081 (95% confidence interval, −0.40 to 0.24) for ZDV-TP:dTTP. RBV did not adversely affect HIV-1 replication. In summary, RBV 800 mg/day administered in combination with peginterferon alfa-2a (40KD) does not significantly affect the intracellular phosphorylation or plasma pharmacokinetics of 3TC, d4T, and ZDV in HIV-HCV-coinfected patients.
Evaluating Ciprofloxacin Dosing for
Pseudomonas aeruginosa
Infection by Using Clinical Outcome-Based Monte Carlo Simulations
Authors: Zelenitsky Sheryl , Ariano Robert , Harding Godfrey , Forrest Alan 
Published: September 2005

ABSTRACT

Pseudomonas aeruginosa
causes serious infections whose outcome is highly dependent on antimicrobial therapy. The goal of this study was to predict the relative efficacies of three ciprofloxacin dosing regimens for
P. aeruginosa
infection using clinical outcome-based Monte Carlo simulations (MCS) with “real patient” demographics, pharmacokinetics, MICs, and pharmacodynamics (PDs). Each cohort consisted of 1,000 simulated study subjects. Three ciprofloxacin dosing regimens were studied, including (i) the recommended standard dose of 400 mg given intravenously (i.v.) every 12 h (q12h), (ii) the recommended high dose of 400 mg i.v. q8h, and (iii) a novel, PD-targeted regimen to attain a ƒAUC/MIC value of >86. Probability of target attainment (PTA) and probability of cure (POC) were determined for each regimen. POC with the standard dose was at least 0.90 if pathogen MICs were ≤0.25 μg/ml but only 0.59 or 0.27 if MICs were 0.5 or 1 μg/ml, respectively. Predicted cure rates in these MIC categories were significantly higher at 0.72 and 0.40 with the high dose and 0.91 and 0.72 with the PD-targeted regimen(
P
< 0.0001). Analyses based on the local susceptibility profile produced PTA and POC estimates of 0.44 and 0.74 with the standard ciprofloxacin dose, 0.58 and 0.81 with the high dose, and 0.84 and 0.93 with the PD-targeted regimen, respectively. In conclusion, as demonstrated by clinical outcome-based MCSs, the highest recommended ciprofloxacin dose of 400 mg i.v. q8h should be used in the treatment of
P. aeruginosa
infection to improve PD target attainment and clinical cure. However, even this appears ineffective if pathogen MICs are 1 μg/ml, warranting the consideration of a lower MIC breakpoint, ≤0.5 μg/ml.
Efficient Intermittent Rifapentine-Moxifloxacin-Containing Short-Course Regimen for Treatment of Tuberculosis in Mice
Authors: Veziris N. , Lounis N. , Chauffour A. , Truffot-Pernot C. , Jarlier V. 
Published: September 2005

ABSTRACT

Long-half-life drugs raise the hope of once-a-week administration of antituberculous treatment. In a previous study with the murine model of tuberculosis, the most active intermittent regimen which contained rifapentine (RFP), isoniazid (INH), and moxifloxacin (MXF) given once a week during 5.5 months, preceded by 2 weeks of daily treatment with INH, rifampin (RIF), pyrazinamide (PZA), and MXF, was less active than the standard 6-month daily RIF-INH-PZA regimen. We evaluated with the same model similar regimens in which we increased the dosing of rifapentine from 10 to 15 mg/kg of body weight and of moxifloxacin from 100 to 400 mg/kg. Mice infected intravenously by 6.2 ×10
6
CFU of
Mycobacterium tuberculosis
H37Rv were treated 2 weeks later when infection was established. After 6 months of treatment, all mice had negative lung culture. After 3 months of follow-up, no relapse occurred in the two groups that received moxifloxacin at 400 mg/kg, whatever the dosage of RFP, and in the group receiving the standard RIF-INH-PZA control regimen. In contrast, in the two groups receiving moxifloxacin at a lower dosage, the relapse rate was significantly higher (13% in mice receiving RFP at 15 mg/kg and 27% in those receiving RFP at 10 mg/kg). Finally, the fully intermittent once-a-week regimen (26 drug ingestions) of INH, RFP (15 mg/kg), and MXF (400 mg/kg) led to a relapse rate of 11%. In conclusion, when used at high dosage, rifapentine and moxifloxacin are very efficient when combined with isoniazid in a once-a-week treatment in mouse tuberculosis.
Open-Label Randomized Trial of Oral Trimethoprim-Sulfamethoxazole, Doxycycline, and Chloramphenicol Compared with Trimethoprim-Sulfamethoxazole and Doxycycline for Maintenance Therapy of Melioidosis
Authors: Chaowagul Wipada , Chierakul Wirongrong , Simpson Andrew J. , Short Jennifer M. , Stepniewska Kasia , Maharjan Bina , Rajchanuvong Adul , Busarawong Duangkaew , Limmathurotsakul Direk , Cheng Allen C. , Wuthiekanun Vanaporn , Newton Paul N. , White Nicholas J. , Day Nicholas P. J. , Peacock Sharon J. 
Published: September 2005

ABSTRACT

Melioidosis (infection caused by
Burkholderia pseudomallei
) requires a prolonged course of oral antibiotics following initial intravenous therapy to reduce the risk of relapse after cessation of treatment. The current recommendation is a four-drug regimen (trimethoprim [TMP], sulfamethoxazole [SMX], doxycycline, and chloramphenicol) and a total treatment time of 12 to 20 weeks. Drug side effects are common; the aim of this study was to compare the efficacy and tolerance of the four-drug regimen with a three-drug regimen (TMP-SMX and doxycycline). An open-label, randomized trial was conducted in northeast Thailand. A total of 180 adult Thai patients were enrolled, of which 91 were allocated to the four-drug regimen and 89 to the three-drug regimen. The trial was terminated early due to poor drug tolerance, particularly of the four-drug regimen. The culture-confirmed relapse rates at 1 year were 6.6% and 5.6% for the four- and three-drug regimens, respectively (
P
= 0.79). The three-drug regimen was better tolerated than the four-drug regimen; 36% of patients receiving four drugs and 19% of patients receiving three drugs required a switch in therapy due to side effects (
P
= 0.01). The duration of oral therapy was significantly associated with relapse; after adjustment for confounders, patients receiving less than 12 weeks of oral therapy had a 5.7-fold increase of relapse or death. A combination of TMP-SMX and doxycycline is as effective as and better tolerated than the conventional four-drug regimen for the oral treatment phase of melioidosis.
Susceptibility Patterns and Molecular Identification of
Trichosporon
Species
Authors: Rodriguez-Tudela Juan L. , Diaz-Guerra Teresa M. , Mellado Emilia , Cano Virginia , Tapia Cecilia , Perkins Alexander , Gomez-Lopez Alicia , Rodero Laura , Cuenca-Estrella Manuel 
Published: September 2005

ABSTRACT

The physiological patterns, the sequence polymorphisms of the internal transcriber spacer (ITS), and intergenic spacer regions (IGS) of the rRNA genes and the antifungal susceptibility profile were evaluated for their ability to identify
Trichosporon
spp. and their specificity for the identification of 49 clinical isolates of
Trichosporon
spp. Morphological and biochemical methodologies were unable to differentiate among the
Trichosporon
species. ITS sequencing was also unable to differentiate several species. However, IGS1 sequencing unambiguously identified all
Trichosporon
isolates. Following the results of DNA-based identification,
Trichosporon asahii
was the species most frequently isolated from deep sites (15 of 25 strains; 60%). In the main, other
Trichosporon
species were recovered from cutaneous samples. The majority of
T. asahii
,
T. faecale
, and
T. coremiiforme
clinical isolates exhibited resistance in vitro to amphotericin B, with geometric mean (GM) MICs >4 μg/ml. The other species of
Trichosporon
did not show high MICs of amphotericin B, and GM MICs were <1 μg/ml. Azole agents were active in vitro against the majority of clinical strains. The most potent compound in vitro was voriconazole, with a GM MIC ≤0.14 μg/ml. The sequencing of IGS correctly identified
Trichosporon
isolates; however, this technique is not available in many clinical laboratories, and strains should be dispatched to reference centers where these complex methods are available. Therefore, it seems to be more practical to perform antifungal susceptibility testing of all isolates belonging to
Trichosporon
spp., since correct identification could take several weeks, delaying the indication of an antifungal agent which exhibits activity against the infectious strain.
Comparative Efficacies of Quinupristin-Dalfopristin, Linezolid, Vancomycin, and Ciprofloxacin in Treatment, Using the Antibiotic-Lock Technique, of Experimental Catheter-Related Infection Due to
Staphylococcus aureus
Authors: Giacometti Andrea , Cirioni Oscar , Ghiselli Roberto , Orlando Fiorenza , Mocchegiani Federico , Silvestri Carmela , Licci Alberto , De Fusco Matteo , Provinciali Mauro , Saba Vittorio , Scalise Giorgio 
Published: September 2005

ABSTRACT

We performed in vitro studies to elucidate the bactericidal activity of the antibiotics in an adherent-cell biofilm model. Efficacy studies were performed in a staphylococcal central venous catheter (CVC) infection rat model. Silastic catheters were implanted into the superior cava. Via the CVC the rats were challenged with 1.0 × 10
6
CFU of a live
Staphylococcus aureus
strain. Twenty-four hours later, the antibiotic-lock technique was started. All animals were randomized to receive daily isotonic sodium chloride solution, quinupristin-dalfopristin (Q/D), linezolid, vancomycin, or ciprofloxacin at the minimal bactericidal concentration (MBC) and at 1,024 μg/ml in a volume of 0.1 ml that filled the CVC. The main outcome measures were MICs and MBCs for both planktonic and adherent cells, quantitative culture of the catheters and surrounding venous tissues, and quantitative peripheral blood cultures. The killing activities of all antibiotics against the adherent bacteria were at least fourfold lower than those against freely growing cells, with the exception of Q/D, which showed comparable activities against both adherent and planktonic organisms. Overall, Q/D at 1,024 μg/ml produced the greatest reduction in the number of cells recovered from the catheters, while at the same concentration, Q/D and vancomycin demonstrated higher activities than ciprofloxacin or linezolid in reducing the number of organisms recovered from the blood cultures. This study points out that treatment outcome of device-related infections cannot be predicted by the results of a standard susceptibility test such as the MIC. Our findings suggest that the clinically used antibiotics cannot eradicate the CVC infection through the antibiotic-lock technique, even at a concentration of 1,024 μg/ml.
Antiviral Activity of GW678248, a Novel Benzophenone Nonnucleoside Reverse Transcriptase Inhibitor
Authors: Ferris Robert G. , Hazen Richard J. , Roberts Grace B. , St. Clair Marty H. , Chan Joseph H. , Romines Karen R. , Freeman George A. , Tidwell Jeffrey H. , Schaller Lee T. , Cowan Jill R. , Short Steven A. , Weaver Kurt L. , Selleseth Dean W. , Moniri Kelly R. , Boone Lawrence R. 
Published: September 2005

ABSTRACT

The compound GW678248 is a novel benzophenone nonnucleoside reverse transcriptase inhibitor (NNRTI). Preclinical assessment of GW678248 indicates that this compound potently inhibits wild-type (WT) and mutant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase in biochemical assays, with 50% inhibitory concentrations (IC
50
s) between 0.8 and 6.8 nM. In HeLa CD4 MAGI cell culture virus replication assays, GW678248 has an IC
50
of ≤21 nM against HIV-1 isogenic strains with single or double mutations known to be associated with NNRTI resistance, including L100I, K101E, K103N, V106A/I/M, V108I, E138K, Y181C, Y188C, Y188L, G190A/E, P225H, and P236L and various combinations. An IC
50
of 86 nM was obtained with a mutant virus having V106I, E138K, and P236L mutations that resulted from serial passage of WT virus in the presence of GW678248. The presence of 45 mg/ml human serum albumin plus 1 mg/ml α-1 acid glycoprotein increased the IC
50
approximately sevenfold. Cytotoxicity studies with GW678248 indicate that the 50% cytotoxicity concentration is greater than the level of compound solubility and provides a selectivity index of >2,500-fold for WT, Y181C, or K103N HIV-1. This compound exhibits excellent preclinical antiviral properties and, as a prodrug designated GW695634, is being developed as a new generation of NNRTI for the treatment of HIV-1 in combination with other antiretroviral agents.
Aptamers That Preferentially Bind Type IVB Pili and Inhibit Human Monocytic-Cell Invasion by
Salmonella enterica
Serovar Typhi
Authors: Pan Qin , Zhang Xiao-Lian , Wu Hong-Yan , He Pan-Wen , Wang Fubin , Zhang Ming-Sheng , Hu Jian-Ming , Xia Bing , Wu Jianguo 
Published: September 2005

ABSTRACT

Salmonella enterica
serovar Typhi is an important pathogen exclusively for humans and causes typhoid or enteric fever. It has been shown that type IVB pili, encoded by the
S. enterica
serovar Typhi
pil
operon located in
Salmonella
pathogenicity island 7, are important in the pathogenic process. In this study, by using both an adhesion-invasion assay and fluorescence quantitative PCR analysis, we demonstrated that the entry of type IVB piliated
S. enterica
serovar Typhi A21-6 (
pil
+
Km
r
) into human THP-1 monocytic cells was greater than that of a nonpiliated
S. enterica
serovar Typhi
pilS
::Km
r
(
pil
mutant) strain. We have applied a systematic evolution of ligands by exponential enrichment approach to select oligonucleotides (aptamers) as ligands that specifically bind to type IVB pili. Using this approach, we identified a high-affinity single-stranded RNA aptamer (S-PS
8.4
) as a type IVB pilus-specific ligand and further found that the selected aptamer (S-PS
8.4
) could significantly inhibit the entry of the piliated strain (but not that of the nonpiliated strain) into human THP-1 cells. The binding affinities between aptamers and pre-PilS (structural protein of type IVB pili) were determined by nitrocellulose filter-binding assays, and the

K
d

value was determined to be 8.56 nM for the S-PS
8.4
aptamer alone. As an example of an aptamer against type IVB pili of
S. enterica
serovar Typhi, the aptamer S-PS
8.4
can serve as a tool for analysis of bacterial type IVB pilus-host cell interactions and may yield information for the development of putative new drugs against
S. enterica
serovar Typhi bacterial infections, useful both in prevention of infection and in therapeutic treatment.
Neuraminidase Inhibitor-Resistant Influenza Viruses May Differ Substantially in Fitness and Transmissibility
Authors: Yen Hui-Ling , Herlocher Louise M. , Hoffmann Erich , Matrosovich Mikhail N. , Monto Arnold S. , Webster Robert G. , Govorkova Elena A. 
Published: September 2005

ABSTRACT
Mutations of the conserved residues of influenza virus neuraminidase (NA) that are associated with NA inhibitor (NAI) resistance decrease the sialidase activity and/or stability of the NA, thus compromising viral fitness. In fact, clinically derived NAI-resistant variants with different NA mutations have shown different transmissibilities in ferrets (M. L. Herlocher, R. Truscon, S. Elias, H. Yen, N. A. Roberts, S. E. Ohmit, and A. S. Monto, J. Infect. Dis. 190:1627-1630, 2004). Molecular characterization of mutant viruses that have a homogeneous genetic background is required to determine the effect of single mutations at conserved NA residues. We generated recombinant viruses containing either the wild-type NA (RG WT virus) or a single amino acid change at NA residue 119 (RG E119V-NA virus) or 292 (RG R292K-NA virus) in the A/Wuhan/359/95 (H3N2) influenza virus background by reverse genetics. Both mutants showed decreased sensitivity to oseltamivir carboxylate, and the RG R292K-NA virus showed cross-resistance to zanamivir. We also observed differences between the two mutants in NA enzymatic activity and thermostability. The R292K mutation caused greater reduction of sialidase activity and thermostability than the E119V mutation. The NA defect caused by the R292K mutation was associated with compromised growth and transmissibility, whereas the growth and transmissibility of the RG E119V-NA virus were comparable to those of RG WT virus. Our results suggest that NAI-resistant influenza virus variants may differ substantially in fitness and transmissibility, depending on different levels of NA functional loss.
Atomic Force Microscopy Study of the Effect of Antimicrobial Peptides on the Cell Envelope of
Escherichia coli
Authors: Meincken M. , Holroyd D. L. , Rautenbach M. 
Published: September 2005

ABSTRACT

The influences of the antibacterial magainin 2 and PGLa from the African clawed frog (
Xenopus laevis
) and the hemolytic bee venom melittin on
Escherichia coli
as the target cell were studied by atomic force microscopy (AFM). Nanometer-scale images of the effects of the peptides on this gram-negative bacterium's cell envelope were obtained in situ without the use of fixing agents. These high-resolution AFM images of the surviving and intact target cells before and after peptide treatment showed distinct changes in cell envelope morphology as a consequence of peptide action. Although all three peptides are lytic to
E. coli
, it is clear from this AFM study that each peptide causes distinct morphological changes in the outer membrane and in some cases the inner membrane, probably as a consequence of different mechanisms of action.
Sophorolipids, Microbial Glycolipids with Anti-Human Immunodeficiency Virus and Sperm-Immobilizing Activities
Authors: Shah Vishal , Doncel Gustavo F. , Seyoum Theodoros , Eaton Kristin M. , Zalenskaya Irina , Hagver Rena , Azim Abul , Gross Richard 
Published: September 2005

ABSTRACT

The increased incidence of human immunodeficiency virus (HIV)/AIDS disease in women aged 15 to 49 years has identified the urgent need for a female-controlled, efficacious, and safe vaginal topical microbicide. To meet this challenge, sophorolipid (SL) produced by
Candida bombicola
and its structural analogs have been studied in this report for their spermicidal, anti-HIV, and cytotoxic activities. The sophorolipid diacetate ethyl ester derivative is the most potent spermicidal and virucidal agent of the series of SLs studied. Its virucidal activity against HIV and sperm-immobilizing activity against human semen are similar to those of nonoxynol-9. However, it also induced enough vaginal cell toxicity to raise concerns about its applicability for long-term microbicidal contraception. Its structure-activity relationship has been established for creating new analogs with less cytotoxicity and higher activity.