bluuebunny/crossref_metadata_2025 huggingface dataset:
Partial Safety Factors and Characteristic Values for Combined Extreme Wind and Wave Load Effects
Authors: Tarp-Johansen Niels Jacob
Published: April 2005

Background: The present paper regards the concerted action of wind and wave loads on offshore wind turbines in the extreme storm event. The load combination problem involves the definition of the characteristic loads and safety factors. In wind engineering and offshore engineering well established practices for the definition of characteristic values and safety factors for wind and wave loads separately exist. The aim is to investigate the possibility of making a simple merger of these existing practices into a possibly conservative design rule. Method of Approach: The paper applies a simplified probabilistic approach giving an understanding of how the merging can possibly be established and finally gives first guidance on the choice of characteristic values and safety factors. Results and conclusions: Under the assumptions made herein, it is made probable that a simple combination rule can be established.
Peak and Post-Peak Power Aerodynamics from Phase VI NASA Ames Wind Turbine Data
Authors: Gerber Brandon S. , Tangler James L. , Duque Earl P. N. , Kocurek J. David
Published: April 2005

Constant speed/pitch rotor operation lacks adequate theory for predicting peak and post-peak power. The objective of this study was to identify and quantify how measured blade element performance characteristics from the Phase VI NASA Ames 24m×36m80ft×120ft wind tunnel test of a two-bladed, tapered, twisted rotor relate to the prediction of peak and post-peak rotor power. The performance prediction code, NREL’s Lifting Surface Prescribed Wake code (LSWT), was used to study the flow physics along the blade. Airfoil lift and drag coefficients along the blade were derived using the predicted angle of attack distribution from LSWT and Phase VI measured normal and tangential force coefficients. Through successive iterations, the local lift and drag coefficients were modified until agreement was achieved between the predicted and Phase VI measured normal and tangential force coefficients along the blade. This agreement corresponded to an LSWT angle of attack distribution and modified airfoil data table that reflected the measured three-dimensional aerodynamics. This effort identified five aerodynamic events important to the prediction of peak and post-peak power. The most intriguing event was a rapid increase in drag that corresponds with the occurrence of peak power. This is not currently modeled in engineering performance prediction methods.
An Experimental Study of Cutting Forces in High-Speed End Milling and Implications for Dynamic Force Modeling
Authors: Mativenga P. T. , Hon K. K. B.
Published: April 2005

The characteristics of high-speed machining (HSM) dynamic milling forces was investigated. Recent studies in chip segmentation are discussed. A Mikron 700 High-Speed Machining Center was used in the end-milling of AISI H13 tool steel using PVD TiN coated two flute micrograin carbide tools. Dynamic force signals were studied using a real-time data acquisition system for spindle speeds from 3,750 to 31,500 rpm for a 6 mm dia tool. Frequency domain studies were also carried out for a larger tool of 12 mm dia for spindle speeds between 10,000 and 40,000 rpm. The trend and frequency domain aspects of the dynamic forces were evaluated and discussed. The fundamental concept of modeling cutting forces based on chip morphology is revisited. A new basis for modeling dynamic forces from the static component and harmonic contributions is presented. This approach for modeling the dynamic HSM force signal accounts for secondary harmonics.
Localized Material and Processing Aspects Related to Enhanced Recycled Material Utilization Through Vibration-Assisted Injection Molding
Authors: Kikuchi Akihisa , Coulter John P. , Angstadt David , Pinarbasi Ahmet
Published: April 2005

With society focusing more and more on environmental issues, the recycling of materials of all types has become an important concern. As a result of previous processing and usage, the properties of recycled materials are often significantly inferior when compared to their unrecycled counterparts. Recycled polymeric materials, for example, have lowered molecular weights caused by previous thermal and/or shear histories. Thus, the scope of application for recycled materials has traditionally been very limited. With the aid of a new processing concept known as vibration-assisted injection molding (VAIM), the mechanical properties of products containing recycled polymeric materials could be dramatically improved. The current paper presents the results of an initial experimental investigation into the application of VAIM for recycled polystyrene (Recycled-PS) products. A number of recycled/new material blends were studied, and in all cases significant product mechanical property enhancements were realized through the use of VAIM. It was concluded that VAIM molded products containing as much as 50% low-grade recycled material could be made stronger than products made using traditional molding with 100% new polymer. Detailed results are presented in the paper, along with some insight into the likely fundamental mechanism underlying the utility of the VAIM technique.
Wind Turbine Performance Predictions Using a Differential Actuator-Lifting Disk Model
Authors: Leclerc Christophe , Masson Christian
Published: April 2005

This paper presents a method based on the imposition of velocity discontinuities to model flow perturbation due to the existence of vortical structures. The proposed method uses actuator-disk and lifting line concepts in order to provide a framework of analysis that respects conservation laws for momentum, energy, and vorticity, which is not always the case for engineering methods used in the wind industry. The flow field is described by the Euler equations. In the proposed mathematical model, the attitude toward flow determination is entirely linked to the vorticity structure of the flow, which is modeled by velocity discontinuities. The numerical method has been applied to four wind turbines: NREL phases II, IV, and VI rotors, as well as to the Tjaereborg rotor, and has shown satisfactory predictions compared to measurements up to peak power. Comparisons have also been undertaken with the results of a previous method, developed by the same authors, where the velocity field is not allowed to be discontinuous and the actuator disk is analyzed as a source of external forces only. In the stall regime of the turbine, the relative differences in power output between the two methods have been evaluated at 5% on the average.
Relationship between Mutations in the
gyrA
Gene and Quinolone Resistance in Clinical Isolates of
Corynebacterium striatum
and
Corynebacterium amycolatum
Authors: Sierra Josep M. , Martinez-Martinez Luis , Vázquez Fernando , Giralt Ernest , Vila Jordi
Published: April 2005

Quinolone susceptibility was analyzed in 17 clinical isolates of
Corynebacterium striatum
and 9 strains of
Corynebacterium amycolatum
by the E-test method in Mueller-Hinton agar plates. The
C. striatum
ATCC 6940 strain was used as a control strain. The amplified quinolone resistance determining regions of the
gyrA
genes of
C. amycolatum
and
C. striatum
were characterized. Four in vitro quinolone-resistant mutants of
C. amycolatum
were selected and analyzed. Both in vivo and in vitro quinolone-resistant strains of
C. amycolatum
showed high levels of fluoroquinolone resistance in strains with a double mutation leading to an amino acid change in positions 87 and 91 or positions 87 and 88 (unusual mutation) of GyrA, whereas the same concomitant mutations at amino acid positions 87 and 91 in GyrA of
C. striatum
produced high levels of resistance to ciprofloxacin and levofloxacin but only showed a moderate increase in the MIC of moxifloxacin, suggesting that other mechanism(s) of quinolone resistance could be involved in moxifloxacin resistance in
C. amycolatum
. Moreover, a PCR-RFLP-NcoI of the
gyrA
gene was developed to distinguish between
C. amycolatum
and
C. striatum
species.
Virological and Pharmacological Parameters Predicting the Response to Lopinavir-Ritonavir in Heavily Protease Inhibitor-Experienced Patients
Authors: Marcelin Anne-Geneviève , Cohen-Codar Isabelle , King Martin S. , Colson Philippe , Guillevic Emmanuel , Descamps Diane , Lamotte Claire , Schneider Véronique , Ritter Jacques , Segondy Michel , Peigue-Lafeuille Hélène , Morand-Joubert Laurence , Schmuck Anne , Ruffault Annick , Palmer Pierre , Chaix Marie-Laure , Mackiewicz Vincent , Brodard Véronique , Izopet Jacques , Cottalorda Jacqueline , Kohli Evelyne , Chauvin Jean-Pierre , Kempf Dale J. , Peytavin Gilles , Calvez Vincent
Published: April 2005

The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of −1.50 log10copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-stateCminconcentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.
Immunomodulatory Activities of Small Host Defense Peptides
Authors: Bowdish Dawn M. E. , Davidson Donald J. , Scott Monisha G. , Hancock Robert E. W.
Published: April 2005

Recent studies have demonstrated that in addition to their antimicrobial activity, cationic host defense peptides, like the human cathelicidin LL-37, perform many activities relating to innate immunity, including the induction or modulation of chemokine and cytokine production, alteration of gene expression in host cells, and inhibition of proinflammatory responses of host cells to bacterial components such as lipopolysaccharide (LPS) in vitro and in vivo. To investigate if these properties are shared by smaller peptides, two cathelicidin peptides derived from bovine neutrophils, the 13-mer indolicidin and Bac2A, a linear 12-amino-acid derivative of bactenecin, were compared to the 37-amino-acid peptide LL-37. Indolicidin, like LL-37, inhibited LPS-induced tumor necrosis factor alpha (TNF-α) secretion, even when added up to an hour after the addition of
Escherichia coli
O111:B4 LPS to the human macrophage/monocyte-like THP-1 cell line. In contrast, Bac2A demonstrated no significant antiendotoxin activity. At low concentrations, indolicidin and LL-37 acted synergistically to suppress LPS-induced production of TNF-α. Indolicidin was analogous to LL-37 in its ability to induce the production of the chemokine interleukin-8 (IL-8) in a human bronchial cell line, 16HBE14o
−
, but it was unable to induce production of IL-8 in THP-1 cells. In contrast, Bac2A was unable to induce IL-8 in either cell type. Conversely, Bac2A was chemotactic for THP-1 cells at concentrations between 10 and 100 μg/ml, while indolicidin and LL-37 were not chemotactic at these concentrations for THP-1 cells. This indicates that in addition to the potential for direct microbicidal activity, cationic host defense peptides may have diverse and complementary abilities to modulate the innate immune response.
Candida albicans
Zinc Cluster Protein Upc2p Confers Resistance to Antifungal Drugs and Is an Activator of Ergosterol Biosynthetic Genes
Authors: MacPherson Sarah , Akache Bassel , Weber Sandra , De Deken Xavier , Raymond Martine , Turcotte Bernard
Published: April 2005

The human pathogen
Candida albicans
is responsible for a large proportion of infections in immunocompromised individuals, and the emergence of drug-resistant strains is of medical concern. Resistance to antifungal azole compounds is often due to an increase in drug efflux or an alteration of the pathway for synthesis of ergosterol, an important plasma membrane component in fungi. However, little is known about the transcription factors that mediate drug resistance. In
Saccharomyces cerevisiae
, two highly related transcriptional activators, Upc2p and Ecm22p, positively regulate the expression of genes involved in ergosterol synthesis (
ERG
genes). We have identified a homologue in
C. albicans
of the
S. cerevisiae UPC2
/
ECM22
genes and named it
UPC2
. Deletion of this gene impaired growth under anaerobic conditions and rendered cells highly susceptible to the antifungal drugs ketoconazole and fluconazole. Conversely, overexpression of Upc2p increased resistance to ketoconazole, fluconazole, and fluphenazine. Azole-induced expression of the
ERG
genes was abolished in a Δ
upc2
strain, while basal levels of these mRNAs remained unchanged. Importantly, the purified DNA binding domain of Upc2p bound in vitro to putative sterol response elements in the
ERG2
promoter, suggesting that Upc2p increases the expression of the
ERG
genes by directly binding to their promoters. These results provide an important link between changes in the ergosterol biosynthetic pathway and azole resistance in this opportunistic fungal species.
In Vitro Assessment of the Further Potential for Development of Fluoroquinolone Resistance in
Neisseria meningitidis
Authors: Shultz Tiffany R. , White Peter A. , Tapsall John W.
Published: April 2005

We examined the potential for the development of fluoroquinolone resistance in
Neisseria meningitidis
by cultivating two clinical isolates of meningococci in the presence of concentrations of ciprofloxacin at and about the predetermined MIC. The quinolone resistance determining regions (QRDRs) of
gyrA
and
parC
of 50 stable quinolone-resistant mutants derived in vitro were sequenced and compared with QRDR alterations reported in clinical isolates of quinolone-resistant meningococci and gonococci. MICs to ciprofloxacin and trovafloxacin were determined and sequence changes were correlated with quinolone MICs. Ciprofloxacin and trovafloxacin MICs of the in vitro-derived quinolone-resistant mutants ranged up to 16 mg/liter. Single GyrA alterations were the first change detected and were accompanied by raised MICs, followed by double GyrA changes and still higher MICs. MICs increased further as single ParC substitutions appeared and these were always in the presence of a single or double GyrA change. GyrA changes occurred at positions 91 and 95 with substitutions of Asp-95→Asn and Thr-91→Ala and Ile. Changes in the
parC
QRDR occurred at positions 85, 86, and 91 with four substitutions, Gly-85→Asp, Asp-86→Asn, Glu-91→Gly, and Glu-91→Lys, detected. The nature of the individual QRDR substitution appeared to influence the level of quinolone resistance expressed, and this varied with the quinolone agent examined. Close similarities occurred between the sequence and nature of QRDR changes in clinical and in vitro-generated quinolone-resistant mutants and with those previously reported for clinical and in vitro-generated quinolone-resistant gonococci. This suggests that quinolone resistance in meningococci may arise in the same manner and reach similar levels in vivo to those seen in quinolone-resistant
Neisseria gonorrhoeae
.
Bactericidal Activity of First-Choice Antibiotics against Gamma Interferon-Induced Persistent Infection of Human Epithelial Cells by
Chlamydia trachomatis
Authors: Reveneau Nathalie , Crane Deborah D. , Fischer Elizabeth , Caldwell Harlan D.
Published: April 2005

Chlamydia trachomatis
is responsible for clinically important chronic inflammatory diseases of humans, including trachoma and pelvic inflammatory disease. Persistent infection of mucosal sites may contribute to the development of these chronic inflammatory diseases. Standard clinical therapy results in satisfactory cure rates of acute infections; however, chronic infection associated with persistence has been suggested to be less responsive to antibiotic therapy. We report the efficiency of two first-line chlamydial antibiotics, azithromycin and doxycycline, under conditions of eradication of
C. trachomatis
persistent infection using the in vitro model of gamma interferon (IFN-γ)-mediated persistence and reactivation from persistence. Doxycycline was superior in eradicating acute (minimal bactericidal concentration [MBC]
100
= 2.5 to 5.0 μg/ml) compared to persistent (MBC
100
= 10 to 50 μg/ml) infection. In contrast, azithromycin was significantly more effective in eradicating persistent infection (MBC
100
= 2.5 to 5.0 μg/ml) than acute infection (MBC
100
= 10 to 50 μg/ml). The superior bactericidal effect of azithromycin against persistent infection was found to correlate with the enhanced uptake of the drug by IFN-γ-treated infected epithelial cells. Based on these findings, we hypothesize that azithromycin should be a particularly efficacious anti-infective agent for the eradication of IFN-γ-induced chlamydial persistent infection in vivo.
Growth Cycle-Dependent Pharmacodynamics of Antichlamydial Drugs
Authors: Siewert Katrin , Rupp Jan , Klinger Matthias , Solbach Werner , Gieffers Jens
Published: April 2005

Chlamydiae are obligate intracellular pathogens that exhibit an extensive intracellular developmental cycle in vivo. Clinical treatment of chlamydial infection is typically initiated upon occurrence of symptomatology and is directed against an asynchronous population of different chlamydial developmental forms. Pharmacodynamics of antichlamydial drugs are predominantly characterized by MICs; however, in vitro determinations of MIC may not reflect differential susceptibilities of the developmental cycle. In this study, we correlated the antichlamydial effect of erythromycin, rifampin, doxycycline, and ciprofloxacin with the developmental stage of a fast-replicating and a slow-replicating chlamydial species. In addition, we describe the influence of concentration on killing. Extracellular elementary bodies and very-early-phase and late-phase chlamydiae were refractory to all tested antibiotics except rifampin, which was very effective against early-cycle chlamydiae. Rifampin was the most effective antibiotic overall, killed in a dose dependent matter, and exhibited moderate synergism with erythromycin. These considerations provide important information on chlamydial biology and antimicrobial susceptibility. A combinational therapy of rifampin and a macrolide should be considered in therapy-refractory infections.
Measurement of Intracellular Didanosine and Tenofovir Phosphorylated Metabolites and Possible Interaction of the Two Drugs in Human Immunodeficiency Virus-Infected Patients
Authors: Pruvost Alain , Negredo Eugènia , Benech Henri , Theodoro Frédéric , Puig Jordi , Grau Eulàlia , García Elisabet , Moltó José , Grassi Jacques , Clotet Bonaventura
Published: April 2005

Recent work has demonstrated the existence of a systemic interaction between didanosine (ddI) and tenofovir disoproxyl fumarate (TDF) that leads to a significant increase in plasma ddI levels when coadministered with TDF (40 to 50% increase). These two drugs are, respectively, nucleoside and nucleotide analogues of adenosine and efficiently inhibit the human immunodeficiency virus (HIV) reverse transcriptase when transformed to their triphosphate moieties in the intracellular (IC) medium (ddA-TP and TFV-DP, respectively). Since ddI and TDF partly share the same IC metabolic pathway leading to the active triphosphates, we investigated a putative IC interaction. We used high-performance liquid chromatography-tandem mass spectrometry techniques to determine ddA-TP and TFV-DP IC levels in HIV-infected patients cotreated with both drugs, in comparison with patients treated with just one of the two drugs. These measurements revealed no significant differences in IC levels of the corresponding triphosphates when ddI (250 mg, once a day [QD]) was coadministered with TDF (300 mg, QD) compared to ddI 400 mg (QD) administered without TDF, thus supporting the dose adaptation proposed for this combination. However, we observed that both ddA-TP and TFV-DP have very long IC half-lives, resulting in unusual IC pharmacokinetic profiles with no significant changes in triphosphate concentrations between two dosings. In the case of TFV-DP, thist1/2of elimination was roughly estimated to be 180 h (7.5 days). This characteristic is certainly interesting in terms of efficacy but could have some drawbacks in terms of virus resistance for patients discontinuing these drugs.
Global Transcriptional Response of
Bacillus subtilis
to Treatment with Subinhibitory Concentrations of Antibiotics That Inhibit Protein Synthesis
Authors: Lin Janine T. , Connelly Mariah Bindel , Amolo Chris , Otani Suzie , Yaver Debbie S.
Published: April 2005

Global
gene expression patterns of
Bacillus subtilis
in response to
subinhibitory concentrations of protein synthesis inhibitors
(chloramphenicol, erythromycin, and gentamicin) were studied by DNA
microarray analysis.
B. subtilis
cultures were treated with
subinhibitory concentrations of protein synthesis inhibitors for 5, 15,
30, and 60 min, and transcriptional patterns were measured throughout
the time course. Three major classes of genes were affected by the
protein synthesis inhibitors: genes encoding transport/binding
proteins, genes involved in protein synthesis, and genes involved in
the metabolism of carbohydrates and related molecules. Similar
expression patterns for a few classes of genes were observed due to
treatment with chloramphenicol (0.4× MIC) or erythromycin
(0.5× MIC), whereas expression patterns of gentamicin-treated
cells were distinct. Expression of genes involved in metabolism of
amino acids was altered by treatment with chloramphenicol and
erythromycin but not by treatment with gentamicin. Heat shock genes
were induced by gentamicin but repressed by chloramphenicol. Other
genes induced by the protein synthesis inhibitors included the
yheIH
operon encoding ABC transporter-like proteins, with
similarity to multidrug efflux proteins, and the
ysbAB
operon
encoding homologs of LrgAB that function to inhibit cell wall cleavage
(murein hydrolase activity) and convey penicillin tolerance in
Staphylococcus
aureus
.
OXA-46, a New Class D β-Lactamase of Narrow Substrate Specificity Encoded by ablaVIM-1-Containing Integron from aPseudomonas aeruginosaClinical Isolate
Authors: Giuliani Francesco , Docquier Jean-Denis , Riccio Maria Letizia , Pagani Laura , Rossolini Gian Maria
Published: April 2005

A novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette inserted into a class 1 integron from a multidrug-resistantPseudomonas aeruginosaclinical isolate. The variable region of the integron also contained ablaVIM-1metallo-β-lactamase cassette and a duplicatedaacA4aminoglycoside acetyltransferase cassette. OXA-46 belongs to the OXA-2 lineage of class D β-lactamases. It exhibits 78% sequence identity with OXA-2 and the highest similarity (around 92% identity) with another OXA-type enzyme detected in clinical isolates ofBurkholderia cepaciaand in unidentified bacteria from a wastewater plant. Expression ofblaOXA-46inEscherichia colidecreased susceptibility to penicillins and narrow-spectrum cephalosporins but not to extended-spectrum cephalosporins, cefsulodin, aztreonam, or carbapenems. The enzyme was overproduced inE. coliand purified by two anion-exchange chromatography steps (approximate yield, 6 mg/liter). OXA-46 was made of a 28.5-kDa polypeptide and exhibited an alkaline pI (7.8). In its native form OXA-46 appeared to be dimeric, and the oligomerization state was not affected by EDTA. Kinetic analysis of OXA-46 revealed a specificity for narrow-spectrum substrates, including oxacillin, other penicillins (but not temocillin), and narrow-spectrum cephalosporins. The enzyme apparently did not interact with temocillin, oxyimino-cephalosporins, or aztreonam. OXA-46 was inactivated by tazobactam and carbapenems and, although less efficiently, also by clavulanic acid. Enzyme activity was not affected either by EDTA or by divalent cations and exhibited low susceptibility to NaCl. These findings underscore the functional and structural diversity that can be encountered among class D β-lactamases.
Benznidazole Therapy inTrypanosoma cruzi-Infected Mice Blocks Thymic Involution and Apoptosis of CD4+CD8+Double-Positive Thymocytes
Authors: Olivieri B. P. , Farias-De-Oliveira D. A. , Araujo-Jorge T. C. , Cotta-de-Almeida V.
Published: April 2005

Several alterations involving peripheral lymphoid organs have been extensively described after experimentalTrypanosoma cruziinfection. Thymic involution occurs as well in infected mice, with both structural and functional alterations in the organ. Despite these abnormalities, specific immune response proceeds to control parasitemia and the participation of T lymphocytes is essential. However, there are relatively few studies on the impact of benznidazole (N-benzyl-2-nitroimidazole acetamide) upon this response. In this present work, we decided to evaluate the impact of benznidazole treatment upon the thymus involution following acuteT. cruziinfection in mice. We have provided evidence that benznidazole treatment controls the severe abnormalities seen in the thymus due toT. cruziinfection. The thymocyte loss related to the depletion of double-positive CD4+CD8+thymocytes was clearly prevented, corroborating the idea that the mechanism responsible for the prevention of thymus involution is related to the decrease of apoptosis rate in this subset after benznidazole treatment. Furthermore, we demonstrated the prevention of enhanced extracellular matrix deposition in the thymus. In conclusion, the preservation of thymus homeostasis, even though partial, was accomplished after benznidazole treatment. Our data are consistent with the notion that different outcomes ofT. cruziinfection may be linked to differences in the parasite load concomitant to fine tuning of the host immune response.
Lethality of Quinolones against
Mycobacterium smegmatis
in the Presence or Absence of Chloramphenicol
Authors: Malik Muhammad , Lu Tao , Zhao Xilin , Singh Anubha , Hattan Christopher M. , Domagala John , Kerns Robert , Drlica Karl
Published: April 2005

Quinolones were examined for rapid lethal activity against
Mycobacterium smegmatis
in the presence and absence of chloramphenicol, an inhibitor of protein synthesis. C-8 methoxy, C-6 fluorine, and particular C-7 ring substituents enhanced rapid killing. With the surprising exception of moxifloxacin, higher quinolone concentrations were required for lethal activity in the presence of chloramphenicol than in its absence. Moxifloxacin was also unusual in lacking the time lag characteristic of fluoroquinolone lethality. Several fluoroquinolone dimers, which represent quinolones with large C-7 substituents, showed modest bacteriostatic activity. Unlike other quinolones, the dimers failed to display lethal activity. The insensitivity of moxifloxacin to chloramphenicol has not been observed with other bacteria and may therefore reflect unique aspects of mycobacterial gyrase.
Pharmacokinetics of Tenofovir in Breast Milk of Lactating Rhesus Macaques
Authors: Van Rompay Koen K. A. , Hamilton Marta , Kearney Brian , Bischofberger Norbert
Published: April 2005

To study tenofovir transfer into milk, two lactating macaques were given a subcutaneous dose of tenofovir (30 mg/kg of body weight). Peak concentrations and area under the curve values of tenofovir in milk were ∼3 and ∼20% of those detected in serum, respectively.
Identification of a Progenitor of the CTX-M-9 Group of Extended-Spectrum β-Lactamases from
Kluyvera georgiana
Isolated in Guyana
Authors: Olson Adam B. , Silverman M. , Boyd David A. , McGeer Allison , Willey Barbara M. , Pong-Porter V. , Daneman N. , Mulvey Michael R.
Published: April 2005

Chromosomal β-lactamase genes (
bla
KLUY
) from six
Kluyvera georgiana
strains isolated in Guyana were cloned and expressed in
Escherichia coli
. KLUY-1 exhibited 100% amino acid identity with the extended-spectrum β-lactamase CTX-M-14. We also show that a 2.7-kb
Kluyvera
chromosomal region exhibits 99% nucleotide identity to a portion of In60 that includes
bla
CTX-M-9
.
High Genetic Diversity of Ciprofloxacin-Nonsusceptible Isolates of
Streptococcus pneumoniae
in Poland
Authors: Sadowy Ewa , Izdebski Radosław , Skoczyńska Anna , Gniadkowski Marek , Hryniewicz Waleria
Published: April 2005

We have analyzed the susceptibility to ciprofloxacin of 697 pneumococcal isolates collected in 1998-2002 in Poland from patients with respiratory tract diseases. Thirty-one ciprofloxacin-nonsusceptible isolates (MICs, ≥4 μg/ml) were identified, of which two were resistant to levofloxacin (MIC, 8 μg/ml). Serotyping, pulsed-field gel electrophoresis, multilocus sequence typing, and the analysis of resistance determinants showed their great genetic diversity.
NONLOCALITY OF ACCELERATED SYSTEMS
Authors: MASHHOON BAHRAM
Published: April 2005

The conceptual basis for the nonlocality of accelerated systems is presented. The non-local theory of accelerated observers and its consequences are briefly described. Nonlocal field equations are developed for the case of the electrodynamics of linearly accelerated systems.
PHENOMENOLOGY FOR AN EXTRA DIMENSION FROM GRAVITATIONAL WAVES PROPAGATION ON A KALUZA–KLEIN SPACE–TIME
Authors: ALESCI EMANUELE , MONTANI GIOVANNI
Published: April 2005

In the present work we analyze the behavior of 5-dimensional (5-d) gravitational waves propagating on a Kaluza–Klein background. We face separately the two cases in which the waves are generated before and after the process of dimensional compactification respectively. We show that if the waves are originated on a 5-d space–time which fulfills the principle of general relativity, then the process of compactification cannot reduce the dynamics to the pure 4-d scalar, vector and tensor degrees of freedom. In particular, while the electromagnetic waves evolve independently, the scalar and tensor fields couple to each other; this feature appears because when the gauge conditions are split, the presence of the scalar ripple prevents the 4-d gravitational waves from becoming traceless. The phenomenological issue of this scheme consists of an anomalous relative amplitude of the two independent polarizations which characterize the 4-d gravitational waves. Such profile of polarization amplitudes, if detected, would outline the extra dimension in a very reliable way, because a wave with non-zero trace cannot arise from ordinary matter sources. We discuss the above mentioned phenomenon either in the case of a unit constant value of the background scalar component (when the geodesic deviation is treated with precise outputs), or assuming such background field as a dynamical degree. Only qualitative conclusion are provided here, because the details of the polarization amplitudes depend on the choice of specific metric forms. Finally, we perturb a real Kaluza–Klein theory showing that in this context, while the electromagnetic waves propagate independently, the 4-d gravitational waves preserve their ordinary structure, while the scalar plays for the role of source.
QUASINORMAL MODES, QUANTIZED BLACK HOLES, AND CORRESPONDENCE PRINCIPLE
Authors: KHRIPLOVICH I. B.
Published: April 2005

Contrary to the wide-spread belief, the correspondence principle does not dictate any relation between the asymptotics of quasinormal modes and the spectrum of quantized black holes. Moreover, this belief is in conflict with simple physical arguments.
INTERACTION OF ELECTROMAGNETIC WAVES WITH THIN ROTATING CYLINDRICAL SHELL OF CONDUCTOR IN VICINITY OF WEAKLY GRAVITATING STRING
Authors: MUMINOV A. T.
Published: April 2005

The boundary value problem for electromagnetic waves interaction with thin rotating cylindrical shell of conductor in static cylindrical metric with weakly gravitating string has been solved analytically. Influence of line mass density on the string to the process under consideration is studied. It is shown that the increase of line mass density of the string diminishes effect of amplification of cylindrical electromagnetic wave under reflecting off conducting cylindrical rotating body in non-wave zone.
A formulation of combinatorial auction via reverse convex programming
Authors: Schellhorn Henry
Published: April 2005

In combinatorial auctions, buyers and sellers bid not only for single items but also for combinations (or “bundles”, or “baskets”) of items. Clearing the auction is in general an NP-hard problem; it is usually solved with integer linear programming. We proposed in an earlier paper a continuous approximation
of this problem, where orders are aggregated and integrality constraints are relaxed. It was proved that this problem could be solved efficiently in two steps by calculating two fixed points, first the fixed point of a contraction mapping, and then of a set-valued function. In this paper, we generalize the problem to incorporate constraints on maximum price changes between two auction rounds. This generalized problem cannot be solved by the aforementioned methods and necessitates reverse convex programming techniques.
Monitoring of Bone Marrow Cell Homing Into the Infarcted Human Myocardium
Authors: Hofmann Michael , Wollert Kai C. , Meyer Gerd P. , Menke Alix , Arseniev Lubomir , Hertenstein Bernd , Ganser Arnold , Knapp Wolfram H. , Drexler Helmut
Published: April 2005

Background—

Intracoronary transfer of autologous bone marrow cells (BMCs) promotes recovery of left ventricular systolic function in patients with acute myocardial infarction. Although the mechanisms of this effect remain to be established, homing of BMCs into the infarcted myocardium is probably a critical early event.

Methods and Results—

We determined BMC biodistribution after therapeutic application in patients with a first ST-segment–elevation myocardial infarction who had undergone stenting of the infarct-related artery. Unselected BMCs were radiolabeled with 100 MBq 2-[
18
F]-fluoro-2-deoxy-
d
-glucose (
18
F-FDG) and infused into the infarct-related coronary artery (intracoronary; n=3 patients) or injected via an antecubital vein (intravenous; n=3 patients). In 3 additional patients, CD34-positive (CD34
+
) cells were immunomagnetically enriched from unselected BMCs, labeled with
18
F-FDG, and infused intracoronarily. Cell transfer was performed 5 to 10 days after stenting. More than 99% of the infused total radioactivity was cell bound. Nucleated cell viability, comparable in all preparations, ranged from 92% to 96%. Fifty to 75 minutes after cell transfer, all patients underwent 3D PET imaging. After intracoronary transfer, 1.3% to 2.6% of
18
F-FDG–labeled unselected BMCs were detected in the infarcted myocardium; the remaining activity was found primarily in liver and spleen. After intravenous transfer, only background activity was detected in the infarcted myocardium. After intracoronary transfer of
18
F-FDG–labeled CD34-enriched cells, 14% to 39% of the total activity was detected in the infarcted myocardium. Unselected BMCs engrafted in the infarct center and border zone; homing of CD34-enriched cells was more pronounced in the border zone.

Conclusions—

18
F-FDG labeling and 3D PET imaging can be used to monitor myocardial homing and biodistribution of BMCs after therapeutic application in patients.
Control of Hypertension in Adults With Chronic Kidney Disease in the United States
Authors: Peralta Carmen A. , Hicks Leroi S. , Chertow Glenn M. , Ayanian John Z. , Vittinghoff Eric , Lin Feng , Shlipak Michael G.
Published: April 2005

Although improved control of hypertension is known to attenuate progression of chronic kidney disease (CKD), little is known about the adequacy of hypertension treatment in adults with CKD in the United States. Using data from the Fourth National Health and Nutrition Survey, we assessed adherence to national hypertension guideline targets for patients with CKD (blood pressure <130/80 mm Hg), we assessed control of systolic (<130 mm Hg) and diastolic (<80 mm Hg) blood pressure, and we evaluated determinants of adequate blood pressure control. Presence of CKD was defined as glomerular filtration rate <60 mL/min per 1.73 m
2
or presence of albuminuria (albumin:creatinine ratio >30 μg/mg). Multivariable logistic regression with appropriate weights was used to determine predictors of inadequate hypertension control and related outcomes. Among 3213 participants with CKD, 37% had blood pressure <130/80 mm Hg (95% confidence interval [CI], 34.5% to 41.8%). Of those with inadequate blood pressure control, 59% (95% CI, 54% to 64%) had systolic >130 mm Hg, with diastolic ≤80 mm Hg, whereas only 7% (95% CI, 3.9 to 9.8%) had a diastolic pressure >80 mm Hg, with systolic blood pressure ≤130 mm Hg. Non-Hispanic black race (odds ratio [OR], 2.4; 95% CI, 1.5 to 3.9), age >75 years (OR, 4.7; 95% CI, 2.7 to 8.2), and albuminuria (OR, 2.4; 95% CI, 1.4 to 4.1) were independently associated with inadequate blood pressure control. We conclude that control of hypertension is poor in participants with CKD and that lack of control is primarily attributable to systolic hypertension. Future guidelines and antihypertensive therapies for patients with CKD should target isolated systolic hypertension.
Quantitative Coronary Angiogram Analysis
Authors: Shinoda Eiji , Yui Yoshiki , Kodama Kazuhisa , Hirayama Atsushi , Nonogi Hiroshi , Haze Kazuo , Sumiyoshi Tetsuya , Hosoda Saichi , Kawai Chuichi
Published: April 2005

This study was performed to compare the effects of nifedipine retard and angiotensin-converting enzyme (ACE) inhibitors on the progression of coronary atherosclerosis by means of quantitative coronary angiogram. Coronary angiogram was performed before the start of the study and during the 3-year treatment period. This study was conducted on the assumption that possible coronary vasodilation, which may be caused by nifedipine, was excluded by administration of sufficient isosorbide dinitrate. The changes from the baseline in the minimum lumen diameter of the coronary artery in all measured segments were negligible in the nifedipine group (+0.02±0.27 mm;
P
=0.543), whereas they were significantly reduced in the ACE inhibitor group (−0.12±0.27 mm;
P
<0.001), with a significant difference observed between the groups (
P
=0.002). The number of progressors in the nifedipine group was significantly lower than that in the ACE inhibitor group (
P
=0.019), and there was also a significant difference between the groups in the number of patients in whom ≥1 lesion developed after treatment (
P
=0.040). However, the changes of minimum lumen diameter stratified by baseline percent diameter stenosis demonstrated that progression of coronary atherosclerosis was suppressed in the nifedipine group for lesions with a percent diameter stenosis of ≤40 but was suppressed in both groups for those with a percent diameter stenosis of ≥41. This study suggests that nifedipine retard and ACE inhibitors may be effective in suppression of progression of coronary atherosclerosis, and that nifedipine in particular may be effective for mild to moderate stenosis.
Spike Timing Precision and Neural Error Correction: Local Behavior
Authors: Stiber Michael
Published: April 2005

The effects of spike timing precision and dynamical behavior on error correction in spiking neurons were investigated. Stationary discharges—phase locked, quasiperiodic, or chaotic—were induced in a simulated neuron by presenting pacemaker presynaptic spike trains across a model of a prototypical inhibitory synapse. Reduced timing precision was modeled by jittering presynaptic spike times. Aftereffects of errors—in this communication, missed presynaptic spikes—were determined by comparing postsynaptic spike times between simulations identical except for the presence or absence of errors. Results show that the effects of an error vary greatly depending on the ongoing dynamical behavior. In the case of phase lockings, a high degree of presynaptic spike timing precision can provide significantly faster error recovery. For nonlocked behaviors, isolated missed spikes can have little or no discernible aftereffects (or even serve to paradoxically reduce uncertainty in postsynaptic spike timing), regardless of presynaptic imprecision. This suggests two possible categories of error correction: high-precision locking with rapid recovery and low-precision nonlocked with error immunity.
A Discontinuous Galerkin Transport Scheme on the Cubed Sphere
Authors: Nair Ramachandran D. , Thomas Stephen J. , Loft Richard D.
Published: April 2005

A conservative transport scheme based on the discontinuous Galerkin (DG) method has been developed for the cubed sphere. Two different central projection methods, equidistant and equiangular, are employed for mapping between the inscribed cube and the sphere. These mappings divide the spherical surface into six identical subdomains, and the resulting grid is free from singularities. Two standard advection tests, solid-body rotation and deformational flow, were performed to evaluate the DG scheme. Time integration relies on a third-order total variation diminishing (TVD) Runge–Kutta scheme without a limiter. The numerical solutions are accurate and neither exhibit shocks nor discontinuities at cube-face edges and vertices. The numerical results are either comparable or better than a standard spectral element method. In particular, it was found that the standard relative error metrics are significantly smaller for the equiangular as opposed to the equidistant projection.
Mixed Parallel–Sequential-Split Schemes for Time-Stepping Multiple Physical Parameterizations
Authors: Dubal Mark , Wood Nigel , Staniforth Andrew
Published: April 2005

Split schemes for time-stepping physical parameterizations in numerical weather prediction and climate models are investigated within the context of simplified model equations. A symmetrized-splitting technique is applied to various parameterized systems containing fast and slow physics processes. The physics processes are represented by time-dependent forcing terms and linear damping/oscillatory terms. Finite-difference schemes, obtained from the splitting procedures, are examined to determine their stability properties, degree of splitting error, and truncation error. This analysis provides insight into the advantages and disadvantages of different splitting procedures across a range of possible parameterization scenarios. Many schemes obtained via splitting have time-step-dependent splitting errors, which can lead to inaccurate solutions when fast processes are present and the time step is large. Some splitting combinations, however, are more useful than others. The symmetrized-splitting procedure considered in this paper can produce stable first- and second-order accurate schemes, which have either no significant splitting errors or acceptably small errors relative to a steady-state solution. The consequences of this analysis for physics coupling strategies in realistic numerical weather prediction and climate models are noted.
Formation of Extreme Cold-Air Pools in Elevated Sinkholes: An Idealized Numerical Process Study
Authors: Zängl Günther
Published: April 2005

High-resolution numerical simulations with the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) are presented to investigate the processes leading to the formation of extreme cold-air pools in elevated sinkholes. The simulations are idealized in the sense that they are conducted with idealized model topography and with idealized large-scale conditions representing an undisturbed wintertime high pressure situation. After a number of model modifications, the temperature fields, radiative cooling rates, and sensible heat fluxes simulated by the model were in good agreement with the available observations, giving confidence that the model is suitable for this process study.

The model results indicate a number of necessary preconditions for the formation of an extreme cold-air pool in a sinkhole. Apart from undisturbed clear weather, a small heat conductivity of the ground and an effective mechanism drying the low-level air during the cooling process are required. The importance of the heat conductivity results from the fact that the net cooling of the ground is only a small residual between the net radiative heat loss and the ground heat flux. As a consequence, extreme cooling events are strongly favored by the presence of freshly fallen powder snow. The necessity of a drying mechanism is related to the strong temperature dependence of the saturation vapor pressure, decreasing by a factor of about 2.5 per 10 K temperature decrease at temperatures below −20°C. Except in cases of very dry ambient air, a nocturnal cooling by 25 or 30 K (as observed in extreme cases) must be accompanied by an order-of-magnitude reduction of the water vapor mixing ratio to prevent the formation of fog. According to the simulations, the most effective drying mechanism is provided by the formation of ice clouds and the subsequent sedimentation of the ice particles. Near the surface, direct deposition of water vapor at the ground also seems to play a significant role.
Using Probability Density Functions to Derive Consistent Closure Relationships among Higher-Order Moments
Authors: Larson Vincent E. , Golaz Jean-Christophe
Published: April 2005

Parameterizations of turbulence often predict several lower-order moments and make closure assumptions for higher-order moments. In principle, the low- and high-order moments share the same probability density function (PDF). One closure assumption, then, is the shape of this family of PDFs. When the higher-order moments involve both velocity and thermodynamic scalars, often the PDF shape has been assumed to be a double or triple delta function. This is equivalent to assuming a mass-flux model with no subplume variability. However, PDF families other than delta functions can be assumed. This is because the assumed PDF methodology is fairly general.

This paper proposes closures for several third- and fourth-order moments. To derive the closures, the moments are assumed to be consistent with a particular PDF family, namely, a mixture of two trivariate Gaussians. (This PDF is also called a double Gaussian or binormal PDF by some authors.) Separately from the PDF assumption, the paper also proposes a simplified relationship between scalar and velocity skewnesses. This PDF family and skewness relationship are simple enough to yield simple, analytic closure formulas relating the moments. If certain conditions hold, this set of moments is specifically realizable. By this it is meant that the set of moments corresponds to a real Gaussian-mixture PDF, one that is normalized and nonnegative everywhere.

This paper compares the new closure formulas with both large eddy simulations (LESs) and closures based on double and triple delta PDFs. This paper does not implement the closures in a single-column model and test them interactively. Rather, the comparisons are diagnostic; that is, low-order moments are extracted from the LES and treated as givens that are input into the closures. This isolates errors in the closures from errors in a single-column model. The test cases are three atmospheric boundary layers: a trade wind cumulus layer, a stratocumulus layer, and a clear convective case. The new closures have shortcomings, but nevertheless are superior to the double or triple delta closures in most of the cases tested.