bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and Molecular Characterization of β-Lactamase-Negative Ampicillin-Resistant
Haemophilus influenzae
with Unusually High Resistance to Ampicillin
Authors: Kaczmarek Frank S. , Gootz Thomas D. , Dib-Hajj Fadia , Shang Wenchi , Hallowell Shawn , Cronan Melissa 
Published: April 2004

ABSTRACT

Previous studies with beta-lactamase-negative, ampicillin-resistant (BLNAR)
Haemophilus influenzae
from Japan, France, and North America indicate that mutations in
ftsI
encoding PBP3 confer ampicillin MICs of 1 to 4 μg/ml. Several BLNAR strains with ampicillin MICs of 4 to 16 μg/ml recently isolated from North America were studied. Pulsed-field gel electrophoresis identified 12 unique BLNAR strains; sequencing of their
ftsI
transpeptidase domains identified 1 group I and 11 group II mutants, as designated previously (K. Ubukata, Y. Shibasaki, K. Yamamoto, N. Chiba, K. Hasegawa, Y. Takeuchi, K. Sunakawa, M. Inoue, and M. Konno, Antimicrob. Agents Chemother.
45:
1693-1699, 2001). Geometric mean ampicillin MICs for several clinical isolates were 8 to 10.56 μg/ml. Replacement of the
ftsI
gene in
H. influenzae
Rd with the intact
ftsI
from several clinical isolates resulted in integrants with typical BLNAR geometric mean ampicillin MICs of 1.7 to 2.2 μg/ml. Cloning and purification of His-tagged PBP3 from three clinical BLNAR strains showed significantly reduced Bocillin binding compared to that of PBP3 from strain Rd. Based on these data, changes in PBP3 alone could not account for the high ampicillin MICs observed for these BLNAR isolates. In an effort to determine the presence of additional mechanism(s) of ampicillin resistance, sequencing of the transpeptidase regions of
pbp1a
, -
1b
, and -
2
was performed. While numerous changes were observed compared to the sequences from Rd, no consistent pattern correlating with high-level ampicillin resistance was apparent. Additional analysis of the resistant BLNAR strains revealed frame shift insertions in
acrR
for all four high-level, ampicillin-resistant isolates.
acrR
was intact for all eight low-level ampicillin-resistant and four ampicillin-susceptible strains tested. A knockout of
acrB
made in one clinical isolate (initial mean ampicillin MIC of 10.3 μg/ml) lowered the ampicillin MIC to 3.67 μg/ml, typical for BLNAR strains. These studies illustrate that BLNAR strains with high ampicillin MICs exist that have combined resistance mechanisms in PBP3 and in the AcrAB efflux pump.
Bis-Anthracycline Antibiotics Inhibit Human Immunodeficiency Virus Type 1 Transcription
Authors: Kutsch Olaf , Levy David N. , Bates Paula J. , Decker Julie , Kosloff Barry R. , Shaw George M. , Priebe W. , Benveniste Etty N. 
Published: April 2004

ABSTRACT
The increasing numbers of human immunodeficiency virus type 1 (HIV-1) strains that exhibit resistance to antiretroviral agents used at present require the development of new effective antiretroviral compounds. Tat transactivation was recognized early on as an attractive target for drug interference. To screen for and analyze the effects of compounds that interfere with Tat transactivation, we developed several cell-based reporter systems in which enhanced green fluorescence protein is a direct and quantitative marker of HIV-1 expression or Tat-dependent long terminal repeat activity. Using these reporter cell lines, we found that the bis-anthracycline WP631, a recently developed DNA intercalator, efficiently inhibits HIV-1 expression at subcytotoxic concentrations. WP631 also abrogated acute HIV-1 replication in peripheral blood mononuclear cells infected with various primary virus isolates. We demonstrate that WP631-mediated HIV-1 inhibition is caused by the inhibition of Tat transactivation. The data presented suggest that WP631 could serve as a lead compound for a new type of HIV-1 inhibitor.
In Vivo Efficacy and Pharmacokinetics of AC98-6446, a Novel Cyclic Glycopeptide, in Experimental Infection Models
Authors: Weiss William J. , Murphy Timothy , Lenoy Eileen , Young Mairead 
Published: April 2004

ABSTRACTAC98-6446 is a novel semisynthetic derivative of a natural product related to the mannopeptimycins produced byStreptomyces hygroscopicus. Naturally occurring esterified mannopeptimycins exhibited excellent in vitro activity but only moderate in vivo efficacy against staphylococcal infection. The in vivo efficacy and pharmacokinetics of AC98-6446 were investigated in murine acute lethal, bacterial thigh and rat endocarditis infections. Pharmacokinetics were performed in mice, rats, monkeys, and dogs. Acute lethal infections were performed with several gram-positive isolates:Staphylococcus aureus(methicillin-susceptible and methicillin-resistant staphylococci), vancomycin-resistantEnterococcus faecalis, and penicillin-susceptible and -resistantStreptococcus pneumoniae. The 50% effective dose for all isolates tested ranged from 0.05 to 0.39 mg/kg of body weight after intravenous (i.v.) administration. Vancomycin was more than fivefold less efficacious against all of these same infections. Results of the thigh infection withS. aureusshowed a static dose for AC98-6446 of 0.4 mg/kg by i.v. administration. Reduction of counts in the thigh of >2 log10CFU were achieved with doses of 1 mg/kg. i.v. administration of 3 mg/kg twice a day for 3 days resulted in a >3 log10reduction in bacterial counts of vancomycin-susceptible and -resistantE. faecalisin a rat endocarditis model. Pharmacokinetics of AC98-6446 showed an increase in exposure (area under the concentration-time curve) from mouse to dog species. The i.v. half-life (t1/2) increased threefold between rodents and the higher species dosed. Efficacy of AC98-6446 has been demonstrated in several models of infection with resistant gram-positive pathogens. This glycopeptide exhibited bactericidal activity in these models, resulting in efficacy at low doses with reduction in bacterial load.
Natural Polymorphism of Cytomegalovirus DNA Polymerase Lies in Two Nonconserved Regions Located between Domains Delta-C and II and between Domains III and I
Authors: Fillet Anne-Marie , Auray Laetitia , Alain Sophie , Gourlain Karine , Imbert Berthe Marie , Najioullah Fatiha , Champier Gael , Gouarin Stéphanie , Carquin Jocelyne , Houhou Nadhira , Garrigue Isabelle , Ducancelle Alexandra , Thouvenot Danielle , Mazeron Marie-Christine 
Published: April 2004

ABSTRACT
We described the natural polymorphism of cytomegalovirus DNA polymerase in 42 unrelated isolates susceptible to ganciclovir, foscarnet, and cidofovir. All variations, including an eight-amino-acid deletion, were located between domains delta-C and II and between domains III and I, suggesting that these specific residues are not involved in enzymatic functions.
Rapid Colorimetric Assay for Antimicrobial Susceptibility Testing of
Pseudomonas aeruginosa
Authors: Tunney Michael M. , Ramage Gordon , Field Tyler R. , Moriarty Thomas F. , Storey Douglas G. 
Published: April 2004

ABSTRACT

A colorimetric assay based on the reduction of a tetrazolium salt {2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT)} for rapidly determining the susceptibility of
Pseudomonas aeruginosa
isolates to bactericidal antibiotics is described. There was excellent agreement between the tobramycin and ofloxacin MICs determined after 5 h using the XTT assay and after 18 h using conventional methods. The data suggests that an XTT-based assay could provide a useful method for rapidly determining the susceptibility of
P. aeruginosa
to bactericidal antibiotics.
GAUSSIAN PROCESSES FOR MACHINE LEARNING
Authors: SEEGER MATTHIAS 
Published: April 2004

Gaussian processes (GPs) are natural generalisations of multivariate Gaussian random variables to infinite (countably or continuous) index sets. GPs have been applied in a large number of fields to a diverse range of ends, and very many deep theoretical analyses of various properties are available. This paper gives an introduction to Gaussian processes on a fairly elementary level with special emphasis on characteristics relevant in machine learning. It draws explicit connections to branches such as spline smoothing models and support vector machines in which similar ideas have been investigated.Gaussian process models are routinely used to solve hard machine learning problems. They are attractive because of their flexible non-parametric nature and computational simplicity. Treated within a Bayesian framework, very powerful statistical methods can be implemented which offer valid estimates of uncertainties in our predictions and generic model selection procedures cast as nonlinear optimization problems. Their main drawback of heavy computational scaling has recently been alleviated by the introduction of generic sparse approximations.13,78,31The mathematical literature on GPs is large and often uses deep concepts which are not required to fully understand most machine learning applications. In this tutorial paper, we aim to present characteristics of GPs relevant to machine learning and to show up precise connections to other "kernel machines" popular in the community. Our focus is on a simple presentation, but references to more detailed sources are provided.
Penetration and Metabolism of Topical Retinoids in ex vivo Organ-Cultured Full-Thickness Human Skin Explants
Authors: Antille C. , Tran C. , Sorg O. , Saurat J.-H. 
Published: April 2004

The human epidermis contains endogenous retinoids [retinol (vitamin A) and retinyl esters] and carotenoids (mostly β-carotene). Previous studies in the mouse have shown that the enzymes involved in retinoid metabolism are present in the epidermis. In this study, we wanted to assess the skin penetration and metabolism of topical retinoids in the human. To do this, fresh surgically excised human abdominal skin was mounted on Franz perfusion cells. Topical retinoic acid, retinal, retinol and retinyl palmitate were applied at 2.5 mg/cm<sup>2</sup> in oil-in-water creams containing 0.05% retinoids on the donor compartment, while the receptor compartment was filled with culture medium. The skin was incubated for 24 h at 37°C, then epidermal retinoid concentrations were determined by HPLC. The same experiment was performed with mouse back skin mounted on Franz cells. Finally, topical retinoids were applied on the back of hairless mice for 24 h; then the mice were sacrificed and retinoid concentrations were assayed in the epidermis. In all three models, retinol and its esters were found to be endogenous, as was the case in previous studies in the mouse in vivo. The four applied retinoids penetrated well into the epidermis. Topical retinoic acid did not increase endogenous retinoids, whereas the latter were greatly increased following topical retinal in the mouse. Retinal was also metabolized into retinoic acid, unlike topical retinol and retinyl palmitate, which only increased endogenous retinoids. Topical retinal and retinol did undergo a higher metabolism in both mouse models than in human skin. In summary, the penetration and metabolism patterns of topical retinoids were quite similar in the two mouse models used, indicating that the Franz cells appear to be a good model to predict in vivo metabolism of topical retinoids. When applying this concept to our results obtained in Franz cells with human skin, we conclude that topical retinol and retinal load human skin with both storage and functional vitamin A.
1 Corinthians 6:5: a Proposal
Authors: Kloha Jeffrey 
Published: April 2004

AbstractInterpreters have considered the phrase ν μ σoν τo δελo α τo (1 Cor. 6:5) to be an ellipse or abbreviation. The several parallels that have been adduced for this conclusion are analyzed, with the result that none may continue to be regarded as a genuine parallel. In addition, patristic writers and the versions show various attempts to resolve the difficulty, which supports the conclusion that the Greek text, as it stands, is impossible. Several conjectures are proposed, any of which may have been lost early in the transmission history of the text by homoioteleuton.
Modeling of Heat Transfer and Void Dynamics for the Thermoplastic Composite Tow-Placement Process
Authors: Tierney John , Gillespie John W. 
Published: April 2004

Thermoplastic composite tow-placement technology is a nonautoclave consolidation process that offers the potential to significantly reduce fabrication costs by using in situ consolidation as a method for manufacturing large composite components. The temperature history and resulting degree of consolidation directly control the final part quality and are directly affected by the process set points. In this work, series of integrated submodels are developed for predicting the heat transfer and void dynamics within the laminate. The final through thickness void fraction is predicted as a function of process parameters. Experiments are carried out to validate these results for a wide variety of process conditions. The model is used to quantify the relationships between variation of quality of incoming material (e.g., void content ranges 3.1 and 5.5% and final void content gradients. It was found that significant gradients in final void content exist through the thickness and is directly related to processing conditions. Recommendations for process optimization are discussed.
Sparsity: Optimization Framework for Sparse Matrix Kernels
Authors: Im Eun-Jin , Yelick Katherine , Vuduc Richard 
Published: April 2004

Sparse matrix–vector multiplication is an important computational kernel that performs poorly on most modern processors due to a low compute-to-memory ratio and irregular memory access patterns. Optimization is difficult because of the complexity of cache-based memory systems and because performance is highly dependent on the non-zero structure of the matrix. The SPARSITY system is designed to address these problems by allowing users to automatically build sparse matrix kernels that are tuned to their matrices and machines. SPARSITY combines traditional techniques such as loop transformations with data structure transformations and optimization heuristics that are specific to sparse matrices. It provides a novel framework for selecting optimization parameters, such as block size, using a combination of performance models and search. In this paper we discuss the optimization of two operations: a sparse matrix times a dense vector and a sparse matrix times a set of dense vectors. Our experience indicates that register level optimizations are effective for matrices arising in certain scientific simulations, in particular finite-element problems. Cache level optimizations are important when the vector used in multiplication is larger than the cache size, especially for matrices in which the non-zero structure is random. For applications involving multiple vectors, reorganizing the computation to perform the entire set of multiplications as a single operation produces significant speedups. We describe the different optimizations and parameter selection techniques and evaluate them on several machines using over 40 matrices taken from a broad set of application domains. Our results demonstrate speedups of up to 4× for the single vector case and up to 10× for the multiple vector case.
Warrior Charisma and the Spiritualization of Violence
Authors: Turner Bryan 
Published: April 2004

Norbert Elias (2001) produced one of the most influential theories on the history of violence in human societies in terms of &lsquo;the civilizing process&rsquo;. With the transformation of feudalism, the rise of bourgeois society and the development of the modern state, interpersonal violence was increasingly regulated by social norms that emphasized self-restraint and personal discipline. His theory was a moral pedagogics of the body in which the &lsquo;passions&rsquo; are self-regulated through detailed social regimes. While his theory is influential, it has also been the subject of systematic criticism. I examine three obvious lacunae in Elias&rsquo; theory. First, his theory does not provide an adequate account of the role of religion in the civilizing process, particularly with respect to controlling human violence, and I examine Elias&rsquo; theory through a commentary on charisma and the sacred in human society, namely the role of sacred violence. Second, Elias had relatively little to say about the interaction between military technology and interpersonal norms. Modern technology has made it possible, both in peace and war, for the state and modern military institutions to gain control of forms of mass violence that were unimaginable in less civilized societies. We could accept Elias&rsquo; proposition about constraint in terms of interpersonal violence, but argue that modern technology has obviously enhanced the capacity of the means of violence in society. This &lsquo;de-personalization&rsquo; of violence is consistent with aspects of Elias&rsquo; civilization theory. However, the theme of technology was completely understated. Third, apart from Elias&rsquo; interest in art and society as a consequence of his teaching appointment in Ghana (1962&ndash;4), his theory was primarily concerned to explain aspects of social change in European society. An exploration of the evolution of military violence and charisma among American Plains Indians, especially the Cheyenne, is intended as an elaboration of the debate around Elias&rsquo; &lsquo;figurational sociology&rsquo;. Through an examination of the training of warriors in nomadic Plains culture, their mode of warfare is defined as a form of spiritual violence, because warfare was bound up with religious norms of conduct and their military interaction was highly ritualized. These spiritual technologies are an important illustration of military technologies of self-creation. My account concludes with an examination of the nature of modern conflict between professional armies within an international human rights framework. The democratization of warfare results in the routinization of military charisma and the charismatic hero survives primarily in popular culture as a celebrity.
Preservation of reproductive behaviors during modest cooling: rapid cold-hardening fine-tunes organismal response
Authors: Shreve Scott M. , Kelty Jonathan D. , Lee Richard E. 
Published: April 2004

SUMMARY
The primary objectives of this study were to determine (1) whether rapid cold-hardening (RCH) preserves reproductive behaviors during modest cooling,(2) whether increased mating success at a lower temperature comes at the cost of decreased performance at a higher temperature and (3) whether RCH is associated with an elevated metabolic rate. Drosophila melanogaster(Diptera: Drosphilidae) were rapidly cold-hardened by a 2-h exposure to 16°C prior to experiments. A temperature decrease of only 7°C(23°C to 16°C) prevented half (11/22) of the control pairs of D. melanogaster from engaging in any courtship activity. By contrast, most RCH pairs courted (17/20). Additionally, the 7°C transfer prevented mating in every pair of control flies, whereas more than half (11/20) of the RCH pairs mated. There was no evidence of impaired courtship or mating performance when RCH pairs were tested at 23°C. Finally, RCH is apparently not an energy-demanding process because no increase in the metabolic rate was detected during its induction. Overall, these data demonstrate that RCH serves to constantly fine-tune an insect's physiological state to match slight changes in environmental temperature. Furthermore, the RCH response is not restricted to cryoprotection and survival in the cold but also preserves more subtle behaviors, such as courtship, at moderate to high temperatures throughout the year.
Echolocation clicks of two free-ranging, oceanic delphinids with different food preferences: false killer whales Pseudorca crassidensand Risso's dolphins Grampus griseus
Authors: Madsen P. T. , Kerr I. , Payne R. 
Published: April 2004

SUMMARY
Toothed whales (Odontoceti, Cetacea) navigate and locate prey by means of active echolocation. Studies on captive animals have accumulated a large body of knowledge concerning the production, reception and processing of sound in odontocete biosonars, but there is little information about the properties and use of biosonar clicks of free-ranging animals in offshore habitats. This study presents the first source parameter estimates of biosonar clicks from two free-ranging oceanic delphinids, the opportunistically foraging Pseudorca crassidens and the cephalopod eating Grampus griseus. Pseudorca produces short duration (30 μs), broadband(Q=2–3) signals with peak frequencies around 40 kHz, centroid frequencies of 30–70 kHz, and source levels between 201–225 dB re. 1 μPa (peak to peak, pp). Grampus also produces short (40 μs),broadband (Q=2–3) signals with peak frequencies around 50 kHz,centroid frequencies of 60–90 kHz, and source levels between 202 and 222 dB re. 1 μPa (pp). On-axis clicks from both species had centroid frequencies in the frequency range of most sensitive hearing, and lower peak frequencies and higher source levels than reported from captive animals. It is demonstrated that sound production in these two free-ranging echolocators is dynamic, and that free-ranging animals may not always employ biosonar signals comparable to the extreme signal properties reported from captive animals in long-range detection tasks. Similarities in source parameters suggest that evolutionary factors other than prey type determine the properties of biosonar signals of the two species. Modelling shows that interspecific detection ranges of prey types differ from 80 to 300 m for Grampus and Pseudorca, respectively.
Comparison of Specific Gravity and Creatinine for Normalizing Urinary Reproductive Hormone Concentrations
Authors: Miller Rebecca C , Brindle Eleanor , Holman Darryl J , Shofer Jane , Klein Nancy A , Soules Michael R , O’Connor Kathleen A 
Published: April 2004

AbstractBackground: Specific gravity (SG) may perform as well as creatinine (CR) correction for adjusting urinary hormone concentrations, as well as offer some advantages. We compared the two methods and applied them to US and Bangladeshi specimens to evaluate their use in different populations.Methods: Pearson correlations between serum concentrations and SG, CR, and uncorrected urinary concentrations were compared using paired daily urine and serum specimens from one menstrual cycle from 30 US women. Corrected urinary estrone conjugate and pregnanediol glucuronide concentrations were compared with serum estradiol and progesterone. Urine specimens across one menstrual cycle from 13 Bangladeshi women were used to evaluate the applicability of both methods to a nonindustrialized population. Linear mixed-effects models were used to compare CR and SG values in the Bangladeshi vs US specimens.Results: There was no significant difference between SG-corrected vs serum and CR-corrected vs serum correlations for either assay. Usable CR results were obtained for all US specimens, but 37% of the Bangladeshi specimens were below the CR assay limit of detection. The Bangladeshi sample had significantly lower CR and higher inter- and intrasubject CR variability than the US sample.Conclusions: SG is a potentially useful alternative to CR correction for normalizing urinary steroid hormone concentrations, particularly in settings where CR values are highly variable or unusually low.