bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Peptide Ligands of RGS4 from a Focused One‐Bead, One‐Compound Library
Authors: Roof Rebecca A. , Sobczyk‐Kojiro Katarzyna , Turbiak Anjanette J. , Roman David L. , Pogozheva Irina D. , Blazer Levi L. , Neubig Richard R. , Mosberg Henry I. 
Published: July 2008

Regulators of G protein signaling accelerate GTP hydrolysis by Gα subunits and profoundly inhibit signaling by G protein‐coupled receptors. The distinct expression patterns and pathophysiologic regulation of regulators of G protein signaling proteins suggest that inhibitors may have therapeutic potential. We previously reported the design, mechanistic evaluation, and structure–activity relationships of a disulfide‐containing cyclic peptide inhibitor of RGS4,YJ34(Ac‐Val‐Lys‐c[Cys‐Thr‐Gly‐Ile‐Cys]‐Glu‐NH2, S‐S) (Roofet al., Chem Biol Drug Des, 67, 2006, 266). Using a focused one‐bead, one‐compound peptide library that contains features known to be necessary for the activity ofYJ34, we now identify peptides that bind to RGS4. Six peptides showed confirmed binding to RGS4 by flow cytometry. Two analogs of peptide2(Gly‐Thr‐c[Cys‐Phe‐Gly‐Thr‐Cys]‐Trp‐NH2, S‐S with a free or acetylatedN‐terminus) inhibited RGS4‐stimulated GαoGTPase activity at 25–50 μm. They selectively inhibit RGS4 but not RGS7, RGS16, and RGS19. Their inhibition of RGS4 does not depend on cysteine‐modification of RGS4, as they do not lose activity when all cysteines are removed from RGS4. Peptide2has been modeled to fit in the same binding pocket predicted forYJ34but in the reverse orientation.
A preliminary pressure–impact analysis applied in the Pinios river basin (Thessaly, Central Greece)
Authors: Ioannou Alexis , Chatzinikolaou Yorgos , Lazaridou Maria 
Published: July 2008

AbstractGreece has not yet undertaken one of the first and most important tasks required by the Water Framework Directive (WFD: the integrated review of the impact of human activity on the status of surface waters for each river basin – the IMPRESS analysis. Owing to the lack of a national methodology, a preliminary analysis was carried out for the Pinios river basin, applying a combination of different methodologies refined to suit the particularities of the Greek freshwater environment and to accommodate the limited availability of data. Pressures caused by the main pollution sources, point and nonpoint, were quantified in terms of pollution loads with the use of emission factors. The existing limited biological and physicochemical monitoring data were used to assess impacts. Additionally, we identified pressures caused by alterations from land‐use data; we carried out a River Habitat Survey (RHS) and estimated the hydromorphological impacts through the calculation of a Habitat Modification Score (HMS). Our results suggest that the probability of the Pinios river basin failing to achieve good ecological quality by 2015 due to pollution is high, and due to hydromorphological pressures is moderate.
Gene Expression Profiles of Meningiomas are Associated with Tumor Cytogenetics and Patient Outcome
Authors: Tabernero Maria Dolores , Maillo Angel , Gil‐Bellosta Carlos J. , Castrillo Abel , Sousa Pablo , Merino Marta , Orfao Alberto 
Published: July 2008

AbstractCytogenetic analysis is a powerful tool for predicting recurrence in meningiomas, even among histologically benign/grade I tumors. Despite this, no study has been reported in which the impact of tumor cytogenetics on the gene expression profiles (GEP) has been analyzed in meningiomas. Here, we analyzed the GEP of 47 tumors and correlated them with the most clinical relevant cytogenetic subgroups of meningiomas, as confirmed through the analysis of 172 patients. Additionally three normal meningeal samples were also studied.Overall, our results show a clear association between the clinically relevant cytogenetic subgroups of meningiomas including diploid tumors (n = 18), isolated −22/22q− (n = 12), del(1p36) alone (n = 4) and complex karyotypes associated with del(1p36) and/or −14q (n = 13) and their GEP. Accordingly, based on the expression of 85 genes (40 of which were coded in the altered chromosomes used for patient stratification) the cytogenetic class of the tumor could be predicted with an error of <1%, a clear association being found between the GEP and patient outcome (P = 0.03) but not tumor histopathology.In summary, we show a clear association between GEP of neoplastic cells and clinically relevant cytogenetic subgroups of meningiomas.
Comparative analysis of G‐CSFR and GM‐CSFR expressions on CD34+ cells in patients with aplastic anemia and myelodysplastic syndrome
Authors: XU H. , LI A. , YU Y. , LI J. , LIU X. , WANG X. , WANG X. , XU G. 
Published: July 2008

SummaryThe aim of this article was to explore the pathogenetic differences, as well as to provide a new way for the differential diagnosis of these two diseases by comparative analysis of CD34+ cells numbers and their surface expression of granulocyte colony‐stimulating factor receptor (G‐CSFR) and granulocyte‐macrophage colony‐stimulating factor receptor (GM‐CSFR) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). Twenty‐seven patients with AA, 45 patients with MDS, and 20 normal controls were enrolled in this study. The ratio of CD34+ cells and their surface expression of G‐CSFR and GM‐CSFR were detected by flow cytometry (FCM). The ratio of CD34+ cells in BMMNC of AA, MDS patients and controls were 0.2438 ± 0.1129%, 2.1677 ± 1.1345% and 1.0792 ± 0.3221%, respectively. Compared with normal controls as well as MDS patients, the ratio of CD34+ cells in BMMNC of AA was significantly reduced (P < 0.05). The ratio of CD34+ cells in MDS was significantly elevated than controls (P < 0.05). The ratio of CD34+ cells in BMMNC of MDS‐RA and MDS‐RAEB patients were 1.2821 ± 0.4658% and 3.7729 ± 2.3360%, respectively. Compared with normal controls and MDS‐RA patients, the ratio of CD34+ cells in MDS‐RAEB was significantly elevated (P < 0.05). The ratio of CD34+ cells in MDS‐RA was significantly elevated than AA patients (P < 0.05). The surface expression of G‐CSFR on CD34+ cells of AA, MDS patients and controls were 34.402 ± 21.8357%, 26.376 ± 15.2895% and 21.443 ± 7.4465%, respectively. The surface expression of G‐CSFR on CD34+ cells of MDS‐RA and MDS‐RAEB patients were 22.788 ± 14.7628% and 30.682 ± 15.5346%. The surface expression of GM‐CSFR on CD34+ cells of AA, MDS patients and controls were 6.5961 ± 4.4322%, 18.2737 ± 10.9841% and 4.2753 ± 2.6249%, respectively. Compared with AA and controls, the expression of GM‐CSFR in MDS patients was significantly elevated (P < 0.05). The surface expression of GM‐CSFR on CD34+ cells of MDS‐RA and MDS‐RAEB patients were 16.1625 ± 6.9487% and 22.1003 ± 14.2983%. In AA patients, the ratio of CD34+ cells in BMMNC less than 0.1% accounts for 75% (6/8) SAA patients, compared with 10.55% (2/19) in CAA (P < 0.05). The detection of CD34+ cells and their surface expression of granulocyte (macrophage) colony‐stimulating factor receptors G (M)‐CSFR in AA and MDS are helpful in the differential diagnosis or prognosis of these two disorders.
Power Law Velocity and Temperature Profiles in a Fully Developed
Turbulent Channel Flow
Authors: Seena Abu , Afzal Noor 
Published: July 2008

Abstract
The power law temperature distribution in a fully developed turbulent channel flow for large Peclet numbers has been proposed in the present work. The analysis of the power law velocity profile in a fully developed mean turbulent channel flow would be used for carrying out the analysis of the power law temperature profile. The Reynolds mean thermal energy equation in a fully developed mean turbulent channel flow has been analyzed. The mean turbulent thermal flow is divided in the inner and outer thermal layers that have been matched by Izakson–Millikan–Kolmogorov hypothesis to get the power law temperature profiles and the power law heat transfer law in the overlap region, in addition to traditional log laws for temperature profiles and heat transfer. It has been shown that the envelope of the heat transfer power law gives the heat transfer log law. Further, it is shown that the temperature power law index and prefactor are functions of the friction Peclet number, as well as function of an alternate variable, the nondimensional friction temperature. It is shown that for large Peclet numbers the power law temperature profile is equivalent to the log law temperature profile. The direct numerical simulation velocity profile data of fully developed turbulent flow provide good support for the power law temperature profile theory.
Ventilation
of Wind-Permeable Clothed Cylinder Subject to Periodic Swinging Motion: Modeling and
Experimentation
Authors: Ghaddar N. , Ghali K. , Jreije B. 
Published: July 2008

Abstract
A theoretical and experimental study has been performed to determine the ventilation induced by swinging motion and external wind for a fabric-covered cylinder of finite length representing a limb. The estimated ventilation rates are important in determining local thermal comfort. A model is developed to estimate the external pressure distribution resulting from the relative wind around the swinging clothed cylinder. A mass balance equation of the microclimate air layer is reduced to a pressure equation assuming laminar flow in axial and angular directions and that the air layer is lumped in the radial direction. The ventilation model predicts the total renewal rate during the swinging cycle. A good agreement was found between the predicted ventilation rates at swinging frequencies between 40rpm and 60rpm and measured values from experiments conducted in a controlled environmental chamber (air velocity is less than 0.05m∕s) and in a low speed wind tunnel (for air speed between 2m∕s and 6m∕s) using the tracer gas method to measure the total ventilation rate induced by the swinging motion of a cylinder covered with a cotton fabric for both closed and open aperture cases. A parametric study using the current model is performed on a cotton fabric to study the effect of wind on ventilation rates for a nonmoving clothed limb at wind speeds ranging from 0.5m∕sto8m∕s, the effect of a swinging limb in stagnant air at frequencies up to 80rpm, and the combined effect of wind and swinging motion on the ventilation rate. For a nonmoving limb, ventilation rate increases with external wind. In the absence of wind, the ventilation rate increases with increased swinging frequency.
Lack of a Significant Drug Interaction between Raltegravir and Tenofovir
Authors: Wenning Larissa A. , Friedman Evan J. , Kost James T. , Breidinger Sheila A. , Stek Jon E. , Lasseter Kenneth C. , Gottesdiener Keith M. , Chen Joshua , Teppler Hedy , Wagner John A. , Stone Julie A. , Iwamoto Marian 
Published: July 2008

ABSTRACT

Raltegravir is a novel human immunodeficiency virus type 1 (HIV-1) integrase inhibitor with potent in vitro activity (95% inhibitory concentration of 31 nM in 50% human serum). This article reports the results of an open-label, sequential, three-period study of healthy subjects. Period 1 involved raltegravir at 400 mg twice daily for 4 days, period 2 involved tenofovir disoproxil fumarate (TDF) at 300 mg once daily for 7 days, and period 3 involved raltegravir at 400 mg twice daily plus TDF at 300 mg once daily for 4 days. Pharmacokinetic profiles were also determined in HIV-1-infected patients dosed with raltegravir monotherapy versus raltegravir in combination with TDF and lamivudine. There was no clinically significant effect of TDF on raltegravir. The raltegravir area under the concentration time curve from 0 to 12 h (AUC
0-12
) and peak plasma drug concentration (
C
max
) were modestly increased in healthy subjects (geometric mean ratios [GMRs], 1.49 and 1.64, respectively). There was no substantial effect of TDF on raltegravir concentration at 12 h postdose (
C
12
) in healthy subjects (GMR [TDF plus raltegravir-raltegravir alone], 1.03; 90% confidence interval [CI], 0.73 to 1.45), while a modest increase (GMR, 1.42; 90% CI, 0.89 to 2.28) was seen in HIV-1-infected patients. Raltegravir had no substantial effect on tenofovir pharmacokinetics:
C
24
, AUC, and
C
max
GMRs were 0.87, 0.90, and 0.77, respectively. Coadministration of raltegravir and TDF does not change the pharmacokinetics of either drug to a clinically meaningful degree. Raltegravir and TDF may be coadministered without dose adjustments.
In Vitro Profiling of Ceftaroline against a Collection of Recent Bacterial Clinical Isolates from across the United States
Authors: Ge Yigong , Biek Donald , Talbot George H. , Sahm Daniel F. 
Published: July 2008

ABSTRACT

This study evaluated the in vitro activity of ceftaroline, a novel cephalosporin with broad-spectrum activity against gram-negative and -positive pathogens, against 4,151 recent clinical isolates collected in the United States. Ceftaroline was very potent against bacteria found in community- and hospital-acquired infections, including methicillin-resistant
Staphylococcus aureus
, multidrug-resistant
Streptococcus pneumoniae
, and common
Enterobacteriaceae
spp.
Pharmacokinetics of High-Dose Lopinavir-Ritonavir with and without Saquinavir or Nonnucleoside Reverse Transcriptase Inhibitors in Human Immunodeficiency Virus-Infected Pediatric and Adolescent Patients Previously Treated with Protease Inhibitors
Authors: Robbins Brian L. , Capparelli Edmund V. , Chadwick Ellen G. , Yogev Ram , Serchuck Leslie , Worrell Carol , Smith Mary Elizabeth , Alvero Carmelita , Fenton Terence , Heckman Barbara , Pelton Stephen I. , Aldrovandi Grace , Borkowsky William , Rodman John , Havens Peter L. 
Published: July 2008

ABSTRACTHuman immunodeficiency virus (HIV)-infected children and adolescents who are failing antiretrovirals may have a better virologic response when drug exposures are increased, using higher protease inhibitor doses or ritonavir boosting. We studied the pharmacokinetics and safety of high-dose lopinavir-ritonavir (LPV/r) in treatment-experienced patients, using an LPV/r dose of 400/100 mg/m2orally every 12 h (p.o. q12h) (without nonnucleoside reverse transcriptase inhibitor [NNRTI]), or 480/120 mg/m2p.o. q12h (with NNRTI). We calculated the LPV inhibitory quotient (IQ), and when the IQ was <15, saquinavir (SQV) 750 mg/m2p.o. q12h was added to the regimen. We studied 26 HIV-infected patients. The median age was 15 years (range, 7 to 17), with 11.5 prior antiretroviral medications, 197 CD4 cells/ml, viral load of 75,577 copies/ml, and a 133-fold change in LPV resistance. By treatment week 2, 14 patients had a viral-load decrease of >0.75 log10, with a median maximal decrease in viral load of −1.57 log10copies/ml at week 8. At week 2, 19 subjects showed a median LPV area under the concentration-time curve (AUC) of 157.2 (range, 62.8 to 305.5) μg·h/ml and median LPV trough concentration (Ctrough) of 10.8 (range, 4.1 to 25.3) μg/ml. In 16 subjects with SQV added, the SQV median AUC was 33.7 (range, 4.4 to 76.5) μg·h/ml and the median SQVCtroughwas 2.1 (range, 0.2 to 4.1) μg/ml. At week 24, 18 of 26 (69%) subjects remained in the study. Between weeks 24 and 48, one subject withdrew for nonadherence and nine withdrew for persistently high virus load. In antiretroviral-experienced children and adolescents with HIV, high doses of LPV/r with or without SQV offer safe options for salvage therapy, but the modest virologic response and the challenge of adherence to a regimen with a high pill burden may limit the usefulness of this approach.
Increasing Trends in Antimicrobial Resistance among Clinically Important Anaerobes and
Bacteroides fragilis
Isolates Causing Nosocomial Infections: Emerging Resistance to Carbapenems
Authors: Liu Chia-Ying , Huang Yu-Tsung , Liao Chun-Hsing , Yen Li-Ching , Lin Hsiu-Ying , Hsueh Po-Ren 
Published: July 2008

ABSTRACT

This study reports data on the susceptibilities to five commonly used antianaerobic agents of five clinically frequently encountered anaerobes from 2000 to 2007 and to
Bacteroides fragilis
isolates causing nosocomial infections from 1990 to 2006. There was a trend of decreasing susceptibilities of these anaerobes to ampicillin-sulbactam, cefmetazole, chloramphenicol, and clindamycin with time during the study period. The rates of susceptibility to clindamycin and cefmetazole for all clinical isolates of
Bacteroides fragilis
isolates were higher than those of isolates associated with nosocomial infections. The MICs of 207 anaerobic blood isolates collected in 2006 to 14 antimicrobial agents were determined by the agar dilution method. The rates of nonsusceptibility to imipenem and meropenem were 7% and 12% for
B. fragilis
isolates (
n
= 60), 7% and 3% for
Bacteroides thetaiotamicron
isolates (
n
= 30), 4% and 4% for
Fusobacterium
species (
n
= 27), 6% and 0% for
Prevotella
species (
n
= 16), 15% and 0% for
Clostridium
species (
n
= 28), and 0% and 0% for
Peptostreptococcus
species (
n
= 32). The rates of susceptibility to moxifloxacin were 90% for
B. fragilis
isolates, 87% for
B. thetaiotaomicron
isolates, 81% for
Fusobacterium
species, 75% for
Prevotella
species, 93% for
Clostridium
species, and 78% for
Peptostreptococcus
species. Thirty-six percent of
Clostridium
species and 12% of
Peptostreptococcus
species were not susceptible to metronidazole. Comparison of the data with the data from a previous survey from the same institute in 2002 revealed higher rates of nonsusceptibility to carbapenems, especially for
B. fragilis
,
Fusobacterium
species, and
Prevotella
species isolates. The high rates of nonsusceptibility to commonly used antianaerobic agents mandate our attention, and periodic monitoring of the trend of the resistance is crucial.
Efficacy of Quinoxaline-2-Carboxylate 1,4-Di-
N
-Oxide Derivatives in Experimental Tuberculosis
Authors: Vicente Esther , Villar Raquel , Burguete Asunción , Solano Beatriz , Pérez-Silanes Silvia , Aldana Ignacio , Maddry Joseph A. , Lenaerts Anne J. , Franzblau Scott G. , Cho Sang-hyun , Monge Antonio , Goldman Robert C. 
Published: July 2008

ABSTRACT

This study extends earlier reports regarding the in vitro efficacies of the 1,4-di-
N
-oxide quinoxaline derivatives against
Mycobacterium tuberculosis
and has led to the discovery of a derivative with in vivo efficacy in the mouse model of tuberculosis. Quinoxaline-2-carboxylate 1,4-di-
N
-oxide derivatives were tested in vitro against a broad panel of single-drug-resistant
M. tuberculosis
strains. The susceptibilities of these strains to some compounds were comparable to those of strain H
37
Rv, as indicated by the ratios of MICs for resistant and nonresistant strains, supporting the premise that 1,4-di-
N
-oxide quinoxaline derivatives have a novel mode of action unrelated to those of the currently used antitubercular drugs. Specific derivatives were further evaluated in a series of in vivo assays, including evaluations of the maximum tolerated doses, the levels of oral bioavailability, and the efficacies in a low-dose aerosol model of tuberculosis in mice. One compound, ethyl 7-chloro-3-methylquinoxaline-2-carboxylate 1,4-dioxide, was found to be (i) active in reducing CFU counts in both the lungs and spleens of infected mice following oral administration, (ii) active against PA-824-resistant
Mycobacterium bovis
, indicating that the pathway of bioreduction/activation is different from that of PA-824 (a bioreduced nitroimidazole that is in clinical trials), and (iii) very active against nonreplicating bacteria adapted to low-oxygen conditions. These data indicate that 1,4-di-
N
-oxide quinoxalines hold promise for the treatment of tuberculosis.
Cell Density and Cell Aging as Factors Modulating Antifungal Resistance ofCandida albicansBiofilms
Authors: Seneviratne C. J. , Jin L. J. , Samaranayake Y. H. , Samaranayake L. P. 
Published: July 2008

ABSTRACTBiofilm formation is a major virulence attribute ofCandidapathogenicity which contributes to higher antifungal resistance. We investigated the roles of cell density and cellular aging on the relative antifungal susceptibility of planktonic, biofilm, and biofilm-derived planktonic modes ofCandida. A reference and a wild-type strain ofCandida albicanswere used to evaluate the MICs of caspofungin (CAS), amphotericin B (AMB), nystatin (NYT), ketoconazole (KTC), and flucytosine (5FC). Standard, NCCLS, and European Committee on Antibiotic Susceptibility Testing methods were used for planktonic MIC determination.Candidabiofilms were then developed on polystyrene wells, and MICs were determined with a standard 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide assay. Subsequently, antifungal susceptibility testing was performed for greater inoculum concentrations and 24- and 48-h-old cultures of planktonicCandida. Furthermore,Candidabiofilm-derived planktonic cells (BDPC) were also subjected to antifungal susceptibility testing. The MICs for bothC.albicansstrains in the planktonic mode were low, although on increasing the inoculum concentration (up to 1 × 108cells/ml), a variable MIC was noted. On the contrary, forCandidabiofilms, the MICs of antifungals were 15- to >1,000-fold higher. Interestingly, the MICs for BDPC were lower and were similar to those for planktonic-mode cells, particularly those of CAS and AMB. Our data indicate that higher antifungal resistance ofCandidabiofilms is an intrinsic feature possibly related to the biofilm architecture rather than cellular density or cellular aging.
Surveillance for Neuraminidase Inhibitor Resistance among Human Influenza A and B Viruses Circulating Worldwide from 2004 to 2008
Authors: Sheu Tiffany G. , Deyde Varough M. , Okomo-Adhiambo Margaret , Garten Rebecca J. , Xu Xiyan , Bright Rick A. , Butler Eboneé N. , Wallis Teresa R. , Klimov Alexander I. , Gubareva Larisa V. 
Published: July 2008

ABSTRACTThe surveillance of seasonal influenza virus susceptibility to neuraminidase (NA) inhibitors was conducted using an NA inhibition assay. The 50% inhibitory concentration values (IC50s) of 4,570 viruses collected globally from October 2004 to March 2008 were determined. Based on mean IC50s, A(H3N2) viruses (0.44 nM) were more sensitive to oseltamivir than A(H1N1) viruses (0.91 nM). The opposite trend was observed with zanamivir: 1.06 nM for A(H1N1) and 2.54 nM for A(H3N2). Influenza B viruses exhibited the least susceptibility to oseltamivir (3.42 nM) and to zanamivir (3.87 nM). To identify potentially resistant viruses (outliers), a threshold of a mean IC50value + 3 standard deviations was defined for type/subtype and drug. Sequence analysis of outliers was performed to identify NA changes that might be associated with reduced susceptibility. Molecular markers of oseltamivir resistance were found in six A(H1N1) viruses (H274Y) and one A(H3N2) virus (E119V) collected between 2004 and 2007. Some outliers contained previously reported mutations (e.g., I222T in the B viruses), while other mutations [e.g., R371K and H274Y in B viruses and H274N in A(H3N2) viruses) were novel. The R371K B virus outlier exhibited high levels of resistance to both inhibitors (>100 nM). A substantial variance at residue D151 was observed among A(H3N2) zanamivir-resistant outliers. The clinical relevance of newly identified NA mutations is unknown. A rise in the incidence of oseltamivir resistance in A(H1N1) viruses carrying the H274Y mutation was detected in the United States and in other countries in the ongoing 2007 to 2008 season. As of March 2008, the frequency of resistance among A(H1N1) viruses in the United States was 8.6% (50/579 isolates). The recent increase in oseltamivir resistance among A(H1N1) viruses isolated from untreated patients raises public health concerns and necessitates close monitoring of resistance to NA inhibitors.