bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluations of Unformulated and FormulatedDendrimer-Based Microbicide Candidates in Mouse and Guinea PigModels of GenitalHerpes
Authors: Bernstein D. I. , Stanberry L. R. , Sacks S. , Ayisi N. K. , Gong Y. H. , Ireland J. , Mumper R. J. , Holan G. , Matthews B. , McCarthy T. , Bourne N. 
Published: November 2003

ABSTRACT

Prevention
of sexually transmitted infections is a priority in developed and
developing countries. One approach to prevention is the use of topical
microbicides, and one promising approach is the use of dendrimers,
highly branched macromolecules synthesized from a polyfunctional core.
Three new dendrimer products developed to provide stable and
cost-efficient microbicides were initially evaluated in vitro for
anti-herpes simplex virus activity and then in vivo by using a mouse
model of genital herpes. From these experiments one product, SPL7013,
was chosen for further evaluation to define the dose and duration of
protection. Unformulated SPL7013 provided significant protection from
genital herpes disease and infection at concentrations as low as 1
mg/ml and for at least 1 h following topical (intravaginal)
administration of 10 mg/ml. This compound was then formulated into
three vehicles and further evaluated in mouse and guinea pig models of
genital herpes infection. In the murine evaluations each of the
formulations provided significant protection at concentrations of 10
and 50 mg/ml. Formulated compounds provided protection for at least
1 h at a concentration of 10 mg/ml. From these experiments
formulation 2V was chosen for dose ranging experiments using the guinea
pig model of genital herpes. The guinea pig evaluations suggested that
doses of 30 to 50 mg/ml were required for optimal protection. From
these studies a lead compound and formulation (2V of SPL7013) was
chosen for ongoing evaluations in primate models of simian
immunodeficiency virus and
Chlamydia trachomatis
infection.
aph(3′)-IIb
, a Gene Encoding anAminoglycoside-Modifying Enzyme, Is under the Positive Control ofSurrogate RegulatorHpaA
Authors: Zeng Lin , Jin Shouguang 
Published: November 2003

ABSTRACT

Pseudomonas
aeruginosa
harbors a chromosomal aminoglycoside phosphotransferase
gene,
aph(3′)-IIb
, which confers
P.
aeruginosa
resistance to several important aminoglycoside
antibiotics, including kanamycin A and B, neomycin B and C, butirosin,
and seldomycin F5. The
aph(3′)-IIb
gene has been found
to be regulated by an AraC-type transcriptional regulator (HpaA)
encoded by a gene located upstream of the
aph(3′)-IIb
gene. In the presence of 4-hydroxyphenylacetic acid (4-HPA), HpaA
activates the expression of
aph(3′)-IIb
as well as
that of the
hpa
regulon which encodes metabolic enzymes for
the utilization of 4-HPA.
hpaA
and
aph(3′)-IIb
form an operon, and in response to the
presence of 4-HPA, the wild-type
P. aeruginosa
strain PAK (but
not its
hpaA
mutant strain) displays increased resistance to
neomycin. A survey of 39 clinical and 19 environmental isolates of
P. aeruginosa
demonstrated in all of them the presence of an
hpaA-aph
gene cluster, while 56 out of the 58 isolates are
able to utilize the 4-HPA as a sole carbon source, suggesting a feature
common to
P. aeruginosa
strains. Interestingly, a larger
portion of clinical isolates than environmental isolates showed
4-HPA-induced resistance to neomycin. The
aph(3′)-IIb
gene product is likely to function as a metabolic enzyme which has a
cross-reactivity with aminoglycosides. These findings provide new
insight into the possible mechanism of
P. aeruginosa
antibiotic
resistance.
Carbapenem-Resistant Strain of
Klebsiellaoxytoca
Harboring Carbapenem-Hydrolyzingβ-LactamaseKPC-2
Authors: Yigit Hesna , Queenan Anne Marie , Rasheed J. Kamile , Biddle James W. , Domenech-Sanchez Antonio , Alberti Sebastian , Bush Karen , Tenover Fred C. 
Published: November 2003

ABSTRACT

We
investigated a
Klebsiella oxytoca
isolate demonstrating
resistance to imipenem, meropenem, extended-spectrum cephalosporins,
and aztreonam. The MICs of both imipenem and meropenem were 32μ
g/ml. The β-lactamase activity against imipenem and
meropenem was inhibited in the presence of clavulanic acid. Isoelectric
focusing studies demonstrated five β-lactamases with pIs of 8.2
(SHV-46), 6.7 (KPC-2), 6.5 (unknown), 6.4 (probable OXY-2), and 5.4
(TEM-1). The presence of the
bla
SHV
and
bla
TEM
genes was confirmed by specific PCR assays
and DNA sequence analysis. Transformation and conjugation studies with
Escherichia coli
showed that the β-lactamase with a pI
of 6.7,
Klebsiella pneumoniae
carbapenemase-2 (KPC-2), was
encoded on an approximately 70-kb conjugative plasmid that also carried
SHV-46, TEM-1, and the β-lactamase with a pI of 6.5. The
bla
KPC-2
determinant was cloned in
E. coli
and conferred resistance to imipenem, meropenem, extended-spectrum
cephalosporins, and aztreonam. The amino acid sequence of KPC-2 showed
a single amino acid difference, S174G, when compared with KPC-1,
another carbapenem-hydrolyzing β-lactamase from
K.
pneumoniae
1534. Hydrolysis studies showed that purified KPC-2
hydrolyzed not only carbapenems but also penicillins, cephalosporins,
and aztreonam. KPC-2 had the highest affinity for meropenem. The
kinetic studies revealed that KPC-2 was inhibited by clavulanic acid
and tazobactam. An examination of the outer membrane proteins of the
parent
K. oxytoca
strain demonstrated that it expressed
detectable levels of OmpK36 (the homolog of OmpC) and a
higher-molecular-weight OmpK35 (the homolog of OmpF). Thus, carbapenem
resistance in
K. oxytoca
3127 is due to production of the Bush
group 2f, class A, carbapenem-hydrolyzing β-lactamase KPC-2.
This β-lactamase is likely located on a transposon that is part
of a conjugative plasmid and thus has a very high potential for
dissemination.
Molecular Diagnostics
Authors: Braziel Rita M. , Shipp Margaret A. , Feldman Andrew L. , Espina Virginia , Winters Mary , Jaffe Elaine S. , Petricoin Emanuel F. , Liotta Lance A. 
Published: November 2003

Abstract
It is increasingly evident that molecular diagnostics, that is, the use of diagnostic testing to understand the molecular mechanisms of an individual patient’s disease, will be pivotal in the delivery of safe and effective therapy for many diseases in the future. A huge body of new information on the genetic, genomic and proteomic profiles of different hematopoietic diseases is accumulating. This chapter focuses on new technologies and advancements in understanding the molecular basis of hematologic disorders, providing an overview of new information and its significance to patient care.
In Section I, Dr. Braziel discusses the impact of new genetic information and research technologies on the actual practice of diagnostic molecular hematopathology. Recent and projected changes in methodologies and analytical strategies used by clinical molecular diagnostics laboratories for the evaluation of hematologic disorders will be discussed, and some of the challenges to clinical implementation of new molecular information and techniques will be highlighted.
In Section II, Dr. Shipp provides an update on current scientific knowledge in the genomic profiling of malignant lymphomas, and describes some of the technical aspects of gene expression profiling. Analysis methods and the actual and potential clinical and therapeutic applications of information obtained from genomic profiling of malignant lymphomas are discussed.
In Section III, Dr. Liotta presents an update on proteomic analysis, a new and very active area of research in hematopoietic malignancies. He describes new technologies for rapid identification of different important proteins and protein networks, and the potential therapeutic and prognostic value of the elucidation of these proteins and protein pathways in the clinical care of patients with malignant lymphomas.
Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes
Authors: Turhan Aslihan , Jenab Pegah , Bruhns Pierre , Ravetch Jeffrey V. , Coller Barry S. , Frenette Paul S. 
Published: November 2003

Abstract
Sickle cell vaso-occlusion is a complex multistep process likely involving heterotypic interactions among sickle erythrocytes (red blood cells [RBCs]), leukocytes (white blood cells [WBCs]), and endothelial cells. Recent data using intravital microscopy in a sickle cell mouse model suggest that adherent leukocytes in postcapillary venules play a critical role in vaso-occlusion by capturing circulating sickle RBCs. In the course of studies to investigate the adhesion receptors mediating sickle RBC-WBC interactions, we found that control nonspecific immunoglobulin G (IgG) preparations displayed significant inhibitory activity. As a result, we studied the effects of commercial intravenous human immune globulin (IVIG) preparations and found that IVIG inhibits RBC-WBC interactions in cremasteric venules in a dose-dependent manner. IVIG of at least 200 mg/kg dramatically reduced these interactions, even after tumor necrosis factor-α (TNF-α) stimulation, and not only increased microcirculatory blood flow but also improved survival of sickle cell mice. These data raise the possibility that IVIG may have a beneficial effect on sickle cell–associated vaso-occlusion.
Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: a randomized, double-blind controlled trial [ISRCTN43755713]
Authors: Muellejans Bernd , López Angel , Cross Michael H , Bonome César , Morrison Lachlan , Kirkham Andrew JT 
Published: November 2003

Abstract
Introduction
This double-blind, randomized, multicentre study was conducted to compare the efficacy and safety of remifentanil and fentanyl for intensive care unit (ICU) sedation and analgesia.

Methods
Intubated cardiac, general postsurgical or medical patients (aged ≥ 18 years), who were mechanically ventilated for 12–72 hours, received remifentanil (9 μg/kg per hour; n = 77) or fentanyl (1.5 μg/kg per hour; n = 75). Initial opioid titration was supplemented with propofol (0.5 mg/kg per hour), if required, to achieve optimal sedation (i.e. a Sedation–Agitation Scale score of 4).

Results
The mean percentages of time in optimal sedation were 88.3% for remifentanil and 89.3% for fentanyl (not significant). Patients with a Sedation–Agitation Scale score of 4 exhibited significantly less between-patient variability in optimal sedation on remifentanil (variance ratio of fentanyl to remifentanil 1.84; P = 0.009). Of patients who received fentanyl 40% required propofol, as compared with 35% of those who received remifentanil (median total doses 683 mg and 378 mg, respectively; P = 0.065). Recovery was rapid (median time to extubation: 1.1 hours for remifentanil and 1.3 hours for fentanyl; not significant). Remifentanil patients who experienced pain did so for significantly longer during extubation (6.5% of the time versus 1.4%; P = 0.013), postextubation (10.2% versus 3.6%; P = 0.001) and post-treatment (13.5% versus 5.1%; P = 0.001), but they exhibited similar haemodynamic stability with no significant differences in adverse event incidence.

Conclusion
Analgesia based sedation with remifentanil titrated to response provided effective sedation and rapid extubation without the need for propofol in most patients. Fentanyl was similar, probably because the dosing algorithm demanded frequent monitoring and adjustment, thereby preventing over-sedation. Rapid offset of analgesia with remifentanil resulted in a greater incidence of pain, highlighting the need for proactive pain management when transitioning to longer acting analgesics, which is difficult within a double-blind study but would be quite possible under normal circumstances.
Offset of pharmacodynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment
Authors: Breen Des , Wilmer Alexander , Bodenham Andrew , Bach Vagn , Bonde Jan , Kessler Paul , Albrecht Sven , Shaikh Soraya 
Published: November 2003

Abstract
Introduction
This open label, multicentre study was conducted to assess the times to offset of the pharmacodynamic effects and the safety of remifentanil in patients with varying degrees of renal impairment requiring intensive care.

Methods
A total of 40 patients, who were aged 18 years or older and had normal/mildly impaired renal function (estimated creatinine clearance ≥ 50 ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine clearance <50 ml/min; n = 30), were entered into the study. Remifentanil was infused for up to 72 hours (initial rate 6–9 μg/kg per hour), with propofol administered if required, to achieve a target Sedation–Agitation Scale score of 2–4, with no or mild pain.

Results
There was no evidence of increased offset time with increased duration of exposure to remifentanil in either group. The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours during scheduled down-titrations of the infusion) were more variable and were statistically significantly longer in the moderate/severe group than in the normal/mild group at 24 hours and 72 hours. These observed differences were not clinically significant (the difference in mean offset at 72 hours was only 16.5 min). Propofol consumption was lower with the remifentanil based technique than with hypnotic based sedative techniques. There were no statistically significant differences between the renal function groups in the incidence of adverse events, and no deaths were attributable to remifentanil use.

Conclusion
Remifentanil was well tolerated, and the offset of pharmacodynamic effects was not prolonged either as a result of renal dysfunction or prolonged infusion up to 72 hours.
Velocity‐porosity relationships, 1: Accurate velocity model for clean consolidated sandstones
Authors: Knackstedt Mark A. , Arns Christoph H. , Pinczewski W. Val 
Published: November 2003

We use numerical simulations to derive the elastic properties of model monomineralic consolidated sandstones. The model morphology is based on overlapping spheres of a mineral phase. We consider model quartzose and feldspathic sands. We generate moduli‐porosity relationships for both the dry and water‐saturated states. The ability to control pore space structure and mineralogy results in numerical data sets which exhibit much less noise than corresponding experimental data. The numerical data allows us to quantitatively analyze the effects of porosity and the properties of the mineral phase on the elastic properties of porous rocks. The agreement between the numerical results and available experimental data for clean consolidated sandstones is encouraging.We compare our numerical data to commonly used theoretical and empirical moduli‐porosity relationships. The self‐consistent method gives the best theoretical fit to the numerical data. We find that the empirical relationship of Krief et al. is successful at describing the numerical data for dry shear modulus and that the recent empirical method of Arns et al. gives a good match to the numerical data for Poisson's ratio or Vp/Vsratio of dry rock. The Raymer equation is the best of the velocity‐porosity models for the water‐saturated systems. Gassmann's relations are shown to accurately map between the dry and fluid‐saturated states.Based on these results, we propose a new empirical method, based solely on a knowledge of the mineral modulus, to estimate the full velocity‐porosity relationship for monomineralic consolidated sands under dry and fluid‐saturated states. The method uses the equation of Krief et al. for the dry shear modulus and the empirical equation of Arns et al. for the dry Poisson's ratio. Gassmann's relations are applied to obtain the fluid‐saturated states. The agreement between the new empirical method, the numerical data and available experimental data for dry and water‐saturated states is encouraging.
Predicting seismic velocity and other rock properties from clay content only
Authors: Pratson Lincoln F. , Stroujkova Anastasia , Herrick Damian , Boadu Fred , Malin Peter 
Published: November 2003

It has been shown that accurate predictions of compressional and shear‐wave velocities can be derived from measurements of clay content, porosity, and bulk density. In this paper, we test the efficacy of using a sequence of established petrophysical formulations to go a step further and predict porosity and bulk density as well as velocity from clay content alone. Other variables, like grain and pore‐fluid properties, are assumed to be constant, while empirical relationships are used to model such behaviors as grain packing and compaction.The sequence of formulations, referred to as the “model,” is evaluated using well‐log and core data from the Amazon Fan collected during Ocean Drilling Program Leg 155. Clay contents are estimated from the borehole gamma‐ray logs. These are input to the model, which in turn predicts observed porosities to a rms error of <20%, and bulk densities and compressional velocities to rms errors of ≤10%. The results suggest that with better measurements of clay content and improvements to the model, even more accurate predictions of velocity might be achieved for unconsolidated sediments.
Simultaneous 1D inversion of loop–loop electromagnetic data for magnetic susceptibility and electrical conductivity
Authors: Farquharson Colin G. , Oldenburg Douglas W. , Routh Partha S. 
Published: November 2003

Magnetic susceptibility affects electromagnetic (EM) loop–loop observations in ways that cannot be replicated by conductive, nonsusceptible earth models. The most distinctive effects are negative in‐phase values at low frequencies. Inverting data contaminated by susceptibility effects for conductivity alone can give misleading models: the observations strongly influenced by susceptibility will be underfit, and those less strongly influenced will be overfit to compensate, leading to artifacts in the model. Simultaneous inversion for both conductivity and susceptibility enables reliable conductivity models to be constructed and can give useful information about the distribution of susceptibility in the earth. Such information complements that obtained from the inversion of static magnetic data because EM measurements are insensitive to remanent magnetization.We present an algorithm that simultaneously inverts susceptibility‐affected data for 1D conductivity and susceptibility models. The solution is obtained by minimizing an objective function comprised of a sum‐of‐squares measure of data misfit and sum‐of‐squares measures of the amounts of structure in the conductivity and susceptibility models. Positivity of the susceptibilities is enforced by including a logarithmic barrier term in the objective function. The trade‐off parameter is automatically estimated using the generalized cross validation (GCV) criterion. This enables an appropriate fit to the observations to be achieved even if good noise estimates are not available. As well as synthetic examples, we show the results of inverting airborne data sets from Australia and Heath Steele Stratmat, New Brunswick.
Automated anomaly picking from broadband electromagnetic data in an unexploded ordnance (UXO) survey
Authors: Huang Hoaping , Won I. J. 
Published: November 2003

We present automated anomaly‐picking methods for detecting unexploded ordnance (UXO) from broadband electromagnetic (EM) data. Using data consisting of in‐phase and quadrature responses at multiple (typically 10) frequencies, a detector function attempts to detect all metal objects but to suppress false alarms caused by geology, variations in sensor height, and sensor motions in the earth's magnetic field.Promising detector functions considered here are (1) the sum of all quadrature responses, Qsum, (2) the sum of all differences among the in‐phase or quadrature components, Ispreador Qspread, (3) the sum of the Ispreadand Qspreads, Tspread, (4) the weighted total apparent conductivity (TAC) from all frequencies, and (5) the apparent magnetic susceptibility (AMS) derived from the lowest frequency of a survey. These detector functions favor metallic objects and are relatively insensitive to geologic variations and motion‐induced noise, which are common with a handheld or cart‐mounted sensor in rough terrain. We discuss the properties of these detector functions, apply them to field data from two sites, and compare the results with limited ground truths. Based on the theoretic study and test on the real data, the total apparent conductivity is the best detector function for picking and classifying anomalies, which shows more distinct anomalies and quieter background than other detector functions.
2D modeling and inversion of gravity data using density contrast varying with depth and source–basement geometry described by the Fourier series
Authors: García‐Abdeslem Juan 
Published: November 2003

A method is developed for 2D forward modeling and nonlinear inversion of gravity data. The forward modeling calculates the gravity anomaly caused by a 2D source body with an assumed depth‐dependent density contrast given by a cubic polynomial. The source body is bounded at depth by a smooth, curvilinear surface given by the Fourier series, which represents the basement. The weighted and damped discrete nonlinear inverse method presented here can invert gravity data to infer the geometry of the source body. The use of the Fourier series to define the basement geometry allows the interpreter to reconstruct a broad variety of geometries for the geologic structures using a small number of free parameters. Both modeling and inversion methods are illustrated with examples using field gravity data across the San Jacinto graben in southern California and across the Sayula basin in Jalisco, Mexico. The inversion of the San Jacinto graben residual Bouguer gravity data yields results compatible with those from previous interpretations of the same data set, suggesting that this geologic structure accommodates about 2.5 km of sediments. The inversion of the residual Bouguer gravity data across the Sayula basin suggests a maximum of 1‐km‐thick sedimentary infill.
A new method for continuation of 3D potential fields to a horizontal plane
Authors: Xu Shi‐zhe , Yang Chieh‐Hou , Dai Shikun , Zhang Dahai 
Published: November 2003

A 3D potential on a 3D topography is approximately regarded as a potential on an imaginary horizontal plane. A fast Fourier transform (FFT) is applied to calculate the outward normal derivative of the potential on the horizontal plane. An approximation can be made such that the calculated derivative is used as the outward normal derivative of the potential on the 3D topographic surface. Based on the potential and the approximated normal derivative on the topography, Green's formula is used to obtain the potential at an arbitrary point above the topography. When the potential at a flat level above the topography is obtained, an FFT is used again to determine the potential at other levels above the source of the potential. A model test shows that the results from this method compare well with analytic solutions. The method has high computation speed and can be used for continuation of 3D potential fields for large data sets, e.g., aeromagnetic data.