bluuebunny/crossref_metadata_2025 huggingface dataset:
CHARACTERIZATION OF LYMPHOMATOUS LYMPH NODES IN DOGS USING CONTRAST HARMONIC AND POWER DOPPLER ULTRASOUND
Authors: Salwei Rochelle M. , O'Brien Robert T. , Matheson Jodi S.
Published: September 2005

Doppler ultrasound has been used in humans to determine angioarchitecture of lymph nodes as the criterion for the determination of malignancy. We hypothesized that the vascular and perfusion patterns of a canine malignant lymph node could be characterized with intravenous microbubble ultrasound contrast media and that contrast harmonic ultrasound could provide better conspicuity of the angioarchitecture when compared with Power Doppler ultrasound. In this study, 11 peripheral lymph nodes in dogs with histologically verified malignant lymphoma were imaged with fundamental ultrasound, Power Doppler ultrasound, and three contrast harmonic pulse sequences to characterize the vascular pattern and perfusion. Vascular imaging was greatly enhanced in these nodes with 2.13 times more vessels seen with contrast harmonic ultrasound compared with Power Doppler ultrasound (P<0.01). The angioarchitecture of lymphomatous lymph nodes of dogs in this study were similar to those previously described in malignant superficial lymph nodes in human patients; 45.5% of the nodes had displacement of the central hilar vessel, 45.5% had aberrant vessels, 63.6% had pericapsular vessels, 36.4% had subcapsular vessels, and 81.8% had loss of the central hyperechoic band in fundamental sonography. Poor perfusion, indicated by a lower mean pixel intensity increase between pre‐ and postcontrast administration images, was seen in 36.4% of the lymph nodes while 63.6% had fair to good perfusion. The perfusion patterns in nine of the 11 lymph nodes were homogenous and two showed focal hypoperfused regions. We conclude that Power Doppler and contrast harmonic ultrasound are beneficial in accurately depicting angioarchitechture and can provide additional information in determining the presence of malignant vascular characteristics within lymphomatous nodes in dogs.
COMPARISON OF GLOMERULAR NUMBER AND SPECIMEN LENGTH OBTAINED FROM 100 DOGS VIA PERCUTANEOUS ECHO‐ASSISTED RENAL BIOPSY USING TWO DIFFERENT NEEDLES
Authors: Zatelli Andrea , D'Ippolito Paola , Zini Eric
Published: September 2005

Our objective was to evaluate possible differences in the number of glomeruli and length of renal biopsies collected in canine subjects by two different types of biopsy needles: a semiautomatic 18‐gauge Trucut and an automated 18‐gauge Jamshidi modified (Biopince). One hundred biopsy samples obtained from dogs of different ages and gender affected by different nephropathies were evaluated retrospectively. All animals were biopsied using one of the two different needles. Biopsies were performed under ultrasound guidance and evaluated by a single pathologist. Statistical analysis was performed to evaluate possible differences in the number of glomeruli and length of renal biopsies collected comparisons were determined between subgroups of dogs with or without the identification of renal interstitial infiltrates and/or fibrosis. Neither the mean difference of the number of glomeruli nor the length of tissue sample collected with the different needles was significantly different. Likewise, the average biopsy length did not differ in dogs with or without renal interstitial infiltrate in animals biopsied with either biopsy needle. Both the Biopince and the Trucut devices provide diagnostically adequate biopsy renal specimens using ultrasound‐guidance.
ORAL SIZE PERCEPTION OF PARTICLES: EFFECT OF SIZE, TYPE, VISCOSITY AND METHOD
Authors: ENGELEN LINA , VAN DER BILT ANDRIES , SCHIPPER MARIA , BOSMAN FRITS
Published: September 2005

We investigated how different parameters affect oral size perception of small particles of SiO

2

and polystyrene particles of varying sizes (2–230 μm). Eighteen healthy subjects assessed the size of the particles by rubbing the sample between the tongue and the palate. The importance of size and type were studied by direct scaling and forced choice ranking and the results of the two methods were compared. To assess the relative importance of the tongue and the palate in oral size perception topical anesthesia was applied. The size and characteristics of particles are of importance for perception of particle size, where hard and irregular particles are perceived as larger than soft and round particles of similar size. The two methods of size perception, direct scaling and forced ranking produce very similar results on oral size perception. Topical anesthesia of either the tongue or the palate had no significant effect.
TEXTURAL CHARACTERISTICS OF PASTA MADE FROM RICE FLOUR SUPPLEMENTED WITH PROTEINS AND HYDROCOLLOIDS
Authors: RAINA C.S. , SINGH S. , BAWA A.S. , SAXENA D.C.
Published: September 2005

Broken pieces of three indigenous rice cultivars were utilized for the formulation of tube type pasta (Ziti‐cut) using four levels each of vital gluten and guar gum. The rice flours were modified by pregelatinization and the pregelatinized flour was found suitable for pasta preparation based on instrumental and sensory texture analysis. The cooking time for pasta was reduced from 10 to 6 min by using pregelatinized rice flour. The textural quality of pasta was analyzed using texture analyzer (TAXT‐2i) and descriptive sensory analysis techniques. A protein level of 16% was found suitable for production of rice pasta, which was comparable to commercial semolina sample whereas a gum level of 1.5% supplemented to pregelatinized rice flour containing 14% protein was judged the best on the basis of instrumental as well as sensory textural characteristics.
Abnormal Tribological Behavior of Multiwalled Nanotube Rafts Part II: Inclined Rafts
Authors: Yang Wei , Wang Hongtao , Huang Y.
Published: September 2005

The analysis in part I of this series is extended to the case of inclined and randomly distributed multiwall carbon nanotube (MWCNT) rafts that are brought into contact. The MWCNTs are modeled by elastic and cylindrically anisotropic materials. The JKR theory of adhesion is adopted. With the incorporation of three-dimensional contact configuration that features the inclined contact, we are able to show that the abnormal tribological behavior, in drastic contrast to the classical Amonton’s law, persists for both inclined and randomly oriented rafts.
Growth and Ordering of Si-Ge Quantum Dots on Strain Patterned Substrates
Authors: Ramasubramaniam A. , Shenoy V. B.
Published: September 2005

Manipulating the strain distribution along the surface of a substrate has been shown experimentally to promote spatial ordering of self-assembled nanostructures in heteroepitaxial film growth without having to resort to expensive nanolithographic techniques. We present here numerical studies of three-dimensional modeling of self-assembly in Si-Ge systems with the aim of understanding the effect of spatially varying mismatch strain-fields on the growth and ordering of quantum dots. We use a continuum model based on the underlying physics of crystallographic surface steps in our calculations. Using appropriate parameters from atomistic studies, the (100) orientation is found to be unstable under compressive strain; the surface energy now develops a new minimum at an orientation that may be interpreted as the (105) facet observed in SiGe∕Si systems. This form of surface energy allows for the nucleationless growth of quantum dots which start off via a surface instability as shallow stepped mounds whose sidewalls evolve continuously toward their low-energy orientations. The interaction of the surface instability with one- and two-dimensional strain modulations is considered in detail as a function of the growth rate. One-dimensional strain modulations lead to the formation of rows of dots in regions of low mismatch—there is some ordering within these rows owing to elastic interactions between dots but this is found to depend strongly upon the kinetics of the growth process. Two-dimensional strain modulations are found to provide excellent ordering within the island array, the growth kinetics being less influential in this case. For purposes of comparison, we also consider self-assembly of dots for an isotropic surface energy. While the results do not differ significantly from those for the anisotropic surface energy with the two-dimensional strain variation, the one-dimensional strain variation produces profoundly different behavior. The surface instability is seen to start off initially as stripes in regions of low mismatch. However, since stripes are less effective at relaxing the mismatch strain they eventually break up into islands. The spacing of these islands is determined by the wavelength of the fastest growing mode of the Asaro-Tiller-Grinfeld instability. However, the fact that such a growth mode is not observed experimentally indicates the importance of accounting for surface energy anisotropy in growth models.
A Thermodynamic Framework for Viscoplasticity Based on Overstress (VBO)
Authors: Hall Richard B.
Published: September 2005

A thermodynamic framework is presented for the theory of Viscoplasticity Based on Overstress (VBO) developed by Krempl and co-workers (Krempl, E., and Ho, K., 2001, in Lemaitre Handbook of Materials Behavior Models, Academic Press, New York, pp. 336–348; 2000, in Time Dependent and Nonlinear Effects in Polymers and Composites, ASTM STP 1357, Schapery, R. A., and Sun, C. T., eds., ASTM, West Conshohocken, PA, pp. 118–137; Cernocky, E. P., and Krempl, E., 1979, Int. J. Non-Linear Mech., 14, pp. 183–203; Gomaa et al., 2004, Int. J. Solids Struct., 41, pp. 3607–3624), for anisotropic materials and small deformations. A Caratheodory-based approach is applied to demonstrate the existence of entropy and absolute temperature, as previously described by Hall (2000, Compos. Sci. Technol., 60, pp. 2581–2599). The present framework indicates that the stress rate-dependent term in the established growth law for the equilibrium stress cannot contribute to the dissipation, and is therefore referred to here as the elastic equilibrium stress rate. A new temperature rate-dependent term is obtained for the same growth law, which is also required to be dissipationless. These terms are therefore identified with dissipationless changes of the stored energy and∕or entropy. In general, the traditional, and thermodynamically justified, forms for the potential functions that arise in the present nonequilibrium treatment lead to dissipationless contributions from internal variable growth law terms that are linear in the rates of the controllable variables. Similar indications, without first establishing entropy and absolute temperature existence, were noted in the modeling of Lehmann (1984, in The Constitutive Law in Thermoplasticity, T. Lehmann, ed., Springer, New York).
Coherent Structures In Open-Channel Flows Over a Fixed Dune
Authors: Yue Wusi , Lin Ching-Long , Patel Virendra C.
Published: September 2005

Turbulent open-channel flow over a two-dimensional laboratory-scale dune is studied using large eddy simulation. Free surface motion is simulated using level set method. Two subgrid scale models, namely, dynamic Smagorinsky model and dynamic two-parameter model, are employed for assessing model effects on the free surface flow. The present numerical predictions of mean flow field and turbulence statistics are in good agreement with experimental data. The mean flow can be divided into two zones, an inner zone where turbulence strongly depends on the dune bed geometry and an outer layer free from the direct influence of the bed geometry. Streaky structures are observed in the wall layer after flow reattachment. Quadrant two events are found to prevail in near-wall and near-surface motions, indicating the predominance of turbulence ejections in open-channel flows. Large-scale coherent structures are produced behind the dune crest by a strong shear layer riding over the recirculation zone. These quasistreamwise tubelike vortical structures are transported downstream with the mean flow and most are destructed before arriving at the next crest. Free surface deformation is visualized, demonstrating complex patterns of upwelling and downdraft.
Implication of Mismatch Between Stress and Strain-Rate in Turbulence Subjected to Rapid Straining and Destraining on Dynamic LES Models
Authors: Chen Jun , Katz Joseph , Meneveau Charles
Published: September 2005

Planar straining and destraining of turbulence is an idealized form of turbulence-meanflow interaction that is representative of many complex engineering applications. This paper studies experimentally the response of turbulence subjected to a process involving planar straining, a brief relaxation and destraining. Subsequent analysis quantifies the impact of the applied distortions on model coefficients of various eddy viscosity subgrid-scale models. The data are obtained using planar particle image velocimetry (PIV) in a water tank, in which high Reynolds number turbulence with very low mean velocity is generated by an array of spinning grids. Planar straining and destraining mean flows are produced by pushing and pulling a rectangular piston towards and away from the bottom wall of the tank. The velocity distributions are processed to yield the time evolution of mean subgrid dissipation rate, the Smagorinsky and dynamic model coefficients, as well as the mean subgrid-scale momentum flux during the entire process. It is found that the Smagorinsky coefficient is strongly scale dependent during periods of straining and destraining. The standard dynamic approach overpredicts the dissipation based Smagorinsky coefficient, with the model coefficient at scale Δ in the standard dynamic Smagorinsky model being close to the dissipation based Smagorinsky coefficient at scale 2Δ. The scale-dependent Smagorinsky model, which is designed to compensate for such discrepancies, yields unsatisfactory results due to subtle phase lags between the responses of the subgrid-scale stress and strain-rate tensors to the applied strains. Time lags are also observed for the SGS momentum flux at the larger filter scales considered. The dynamic and scale-dependent dynamic nonlinear mixed models do not show a significant improvement. These potential problems of SGS models suggest that more research is needed to further improve and validate SGS models in highly unsteady flows.
Investigation of the Large-Scale Flow Structures in the Cooling Jets Used in the Blown Film Manufacturing Process
Authors: Gao Nan , Ewing Dan
Published: September 2005

The development of the flow field produced by concentric jets used in the blown-film manufacturing process was studied experimentally using hot wire anemometry. It was found that the inner jet was entrained into the outer jet before the outer jet attached to the wall. The inner shear layer of the outer jet attached to the surface 3H to 5H downstream of the jet exit, and the outside shear layer of the outer jet attaches to the surface further downstream of the jet exit. The distribution and spectra of the fluctuating wall pressure was measured using microphones. The pressure fluctuations were largest where the outer jet attached to the surface, and had characteristic frequencies of 100to900Hz. Measurements of two-point and two-time correlation of the fluctuating pressure were used to characterize the development of the large-scale structures that caused these pressure fluctuations. It was found that the structures were convected along the surface at 0.45 to 0.7 of the outer jet velocity for different ratios between inner and outer jet velocities. The convection velocity of the large scale structures in the region farther than 10H downstream of the jet exit was determined by the upper jet velocity.
Index of Resolution Quality for Large Eddy Simulations
Authors: Celik I. B. , Cehreli Z. N. , Yavuz I.
Published: September 2005

In the light of rapidly increasing applications of large-eddy simulations (LES), it is deemed necessary to impose some quality assessment measures for such studies. The verification of LES calculations is difficult because of the fact that both the subgrid scale (SGS) model contribution and numerical discretization errors are functions of the grid resolution. In this study, various indexes of quality measures, hereafter referred to as LES̱IQ, are proposed. The recommended LES̱IQ is based on the Richardson extrapolation concept. This method has been applied to various cases and the calculated LES̱IQ results are compared with the relative total experimental and direct numerical simulation (DNS) error, defined as IQ̱EX and IQ̱DNS, respectively. It is postulated that in practical applications of LES, numerical dissipation will always be a significant part of the overall dissipation, and it must be accounted for in any assessment of the quality of LES. It is further suggested that LES̱IQ of 75% to 85% can be considered adequate for most engineering applications that typically occur at high Reynolds numbers; the proposed index is an indicator of good resolution (i.e., verification), but not necessarily a good or accurate model (i.e., validation).
Computational Study of the Wake and Contaminant Transport of a Walking Human
Authors: Edge Brian A. , Paterson Eric G. , Settles Gary S.
Published: September 2005

The unsteady aerodynamic wake of a human is studied using a time-accurate computational fluid dynamics simulation. Transport of a scalar contaminant, which originates on the body, is also considered. An existing Reynolds-averaged Navier-Stokes solver is modified to include energy, scalar-transport, and thermal buoyancy effects. Structured overset grids are used to discretize the geometry and the flow field. Results indicate two distinct wake regions: an unsteady bluff-body wake behind the torso which is characterized by a mean recirculation zone, and a region of unsteady vortex shedding behind the legs which is dominated by a “jet” of air formed between the legs. A significant downwash occurs behind the body which has the effect of laterally spreading the lower portions of the wake. The magnitude of the scalar contaminant is shown to decay exponentially within the wake and is found to be highly dependent upon the source location.
Evaluation of Thermal Aging Embrittlement in Directionally Solidified Ni-Base Superalloy by Small Punch Test
Authors: Komazaki Shin-ichi , Shoji Tetsuo , Takamura Kazumune
Published: September 2005

In order to develop a procedure for evaluating the degradation of impact toughness in directionally solidified Ni-base superalloy CM247LC, which is commonly used for advanced gas turbine blades, the change in small punch (SP) fracture energy due to thermal aging has been investigated. The SP testing technique has been applied to materials aged under various aging conditions, and correlation with the results of Charpy V-notch impact tests has been examined. The experimental results reveal that SP fracture energy at room temperature decreases with aging at 800 °C and is uniquely correlated with high-temperature Charpy impact toughness. The current experiment has shown that the SP testing technique is useful in evaluating the degree of thermal aging embrittlement, one of the parameters required for remaining-life prediction of aged components.
Noise in Gene Expression: Origins, Consequences, and Control
Authors: Raser Jonathan M. , O'Shea Erin K.
Published: September 2005

Genetically identical cells and organisms exhibit remarkable diversity even when they have identical histories of environmental exposure. Noise, or variation, in the process of gene expression may contribute to this phenotypic variability. Recent studies suggest that this noise has multiple sources, including the stochastic or inherently random nature of the biochemical reactions of gene expression. In this review, we summarize noise terminology and comment on recent investigations into the sources, consequences, and control of noise in gene expression.
An Aneuploid Mouse Strain Carrying Human Chromosome 21 with Down Syndrome Phenotypes
Authors: O'Doherty Aideen , Ruf Sandra , Mulligan Claire , Hildreth Victoria , Errington Mick L. , Cooke Sam , Sesay Abdul , Modino Sonie , Vanes Lesley , Hernandez Diana , Linehan Jacqueline M. , Sharpe Paul T. , Brandner Sebastian , Bliss Timothy V. P. , Henderson Deborah J. , Nizetic Dean , Tybulewicz Victor L. J. , Fisher Elizabeth M. C.
Published: September 2005

Aneuploidies are common chromosomal defects that result in growth and developmental deficits and high levels of lethality in humans. To gain insight into the biology of aneuploidies, we manipulated mouse embryonic stem cells and generated a trans-species aneuploid mouse line that stably transmits a freely segregating, almost complete human chromosome 21 (Hsa21). This âtranschromosomicâ mouse line, Tc1, is a model of trisomy 21, which manifests as Down syndrome (DS) in humans, and has phenotypic alterations in behavior, synaptic plasticity, cerebellar neuronal number, heart development, and mandible size that relate to human DS. Transchromosomic mouse lines such as Tc1 may represent useful genetic tools for dissecting other human aneuploidies.
Dating of Multistage Fluid Flow in Sandstones
Authors: Mark Darren F. , Parnell John , Kelley Simon P. , Lee Martin , Sherlock Sarah C. , Carr Andrew
Published: September 2005

Through ultraviolet laser argon-argon dating of potassium feldspar cements containing fluid inclusions, we determined temperature-composition-time data for paleofluids in a sedimentary basin, including data for an evolving episode of fluid flow recorded in distinct phases of cement. The fluid evolved from mixed aqueous oil 83 million years ago to purely aqueous by 76 million years ago, thus dating the time of oil charge in this reservoir.
Genetic Engineering of Terpenoid Metabolism Attracts Bodyguards to
Arabidopsis
Authors: Kappers Iris F. , Aharoni Asaph , van Herpen Teun W. J. M. , Luckerhoff Ludo L. P. , Dicke Marcel , Bouwmeester Harro J.
Published: September 2005

Herbivore-damaged plants release complex mixtures of volatiles that attract natural enemies of the herbivore. To study the relevance of individual components of these mixtures for predator attraction, we manipulated herbivory-induced volatiles through genetic engineering. Metabolic engineering of terpenoids, which dominate the composition of many induced plant volatile bouquets, holds particular promise. By switching the subcellular localization of the introduced sesquiterpene synthase to the mitochondria, we obtained transgenic
Arabidopsis thaliana
plants emitting two new isoprenoids. These altered plants attracted carnivorous predatory mites (
Phytoseiulus persimilis
) that aid the plants' defense mechanisms.
Jumping Nanodroplets
Authors: Habenicht A. , Olapinski M. , Burmeister F. , Leiderer P. , Boneberg J.
Published: September 2005

Flat gold nanostructures on inert substrates like glass or graphite were illuminated by single intensive laser pulses with fluences above the gold melting threshold. The liquid structures produced in this way are far from their equilibrium shape, and a dewetting process sets in. On a time scale of a few nanoseconds, the liquid contracted toward a sphere. During this contraction, the center of mass moved upward, which could lead to detachment of droplets from the surface due to inertia. The resulting velocities were on the order of 10 meters per second for droplets with radii in the range of 100 nanometers.
Regulation of Mammalian Tooth Cusp Patterning by Ectodin
Authors: Kassai Yoshiaki , Munne Pauliina , Hotta Yuhei , Penttilä Enni , Kavanagh Kathryn , Ohbayashi Norihiko , Takada Shinji , Thesleff Irma , Jernvall Jukka , Itoh Nobuyuki
Published: September 2005

Mammalian tooth crowns have precise functional requirements but cannot be substantially remodeled after eruption. In developing teeth, epithelial signaling centers, the enamel knots, form at future cusp positions and are the first signs of cusp patterns that distinguish species. We report that
ectodin
, a secreted bone morphogenetic protein (BMP) inhibitor, is expressed as a “negative” image of mouse enamel knots. Furthermore, we show that
ectodin
-deficient mice have enlarged enamel knots, highly altered cusp patterns, and extra teeth. Unlike in normal teeth, excess BMP accelerates patterning in
ectodin
-deficient teeth. We propose that
ectodin
is critical for robust spatial delineation of enamel knots and cusps.
Voyager 1 in the Foreshock, Termination Shock, and Heliosheath
Authors: Decker R. B. , Krimigis S. M. , Roelof E. C. , Hill M. E. , Armstrong T. P. , Gloeckler G. , Hamilton D. C. , Lanzerotti L. J.
Published: September 2005

Voyager 1 (V1) began measuring precursor energetic ions and electrons from the heliospheric termination shock (TS) in July 2002. During the ensuing 2.5 years, average particle intensities rose as V1 penetrated deeper into the energetic particle foreshock of the TS. Throughout 2004, V1 observed even larger, fluctuating intensities of ions from 40 kiloelectron volts (keV) to ≥50 megaelectron volts per nucleon and of electrons from >26 keV to ≥350 keV. On day 350 of 2004 (2004/350), V1 observed an intensity spike of ions and electrons that was followed by a sustained factor of 10 increase at the lowest energies and lesser increases at higher energies, larger than any intensities since V1 was at 15 astronomical units in 1982. The estimated solar wind radial flow speed was positive (outward) at ∼+100 kilometers per second (km s–1) from 2004/352 until 2005/018, when the radial flows became predominantly negative (sunward) and fluctuated between ∼–50 and 0 km s–1until about 2005/110; they then became more positive, with recent values (2005/179) of ∼+50 km s–1. The energetic proton spectrum averaged over the postshock period is apparently dominated by strongly heated interstellar pickup ions. We interpret these observations as evidence that V1 was crossed by the TS on 2004/351 (during a tracking gap) at 94.0 astronomical units, evidently as the shock was moving radially inward in response to decreasing solar wind ram pressure, and that V1 has remained in the heliosheath until at least mid-2005.
P-DCFOLD OR HOW TO PREDICT ALL KINDS OF PSEUDOKNOTS IN RNA SECONDARY STRUCTURES
Authors: TAHI FARIZA , STEFAN ENGELEN , REGNIER MIREILLE
Published: September 2005

Pseudoknots play important roles in many RNAs. But for computational reasons, pseudoknots are usually excluded from the definition of RNA secondary structures. Indeed, prediction of pseudoknots increase very highly the complexities in time of the algorithms, knowing that all existing algorithms for RNA secondary structure prediction have complexities at least of O(n3). Some algorithms have been developed for searching pseudoknots, but all of them have very high complexities, and consider generally particular kinds of pseudoknots.

We present an algorithm, called P-DCFold based on the comparative approach, for the prediction of RNA secondary structures including all kinds of pseudoknots. The helices are searched recursively using the "Divide and Conquer" approach, searching the helices from the "most significant" to the "less significant". A selected helix subdivide the sequence into two sub-sequences, the internal one and a concatenation of the two externals. This approach is used to search non-interleaved helices and allows to limit the space of searching. To search for pseudoknots, the processing is reiterated. Therefore, each helix of the pseudoknot is selected in a different step.

P-DCFold has been applied to several RNA sequences. In less than two seconds, their respective secondary structures, including their pseudoknots, have been recovered very efficiently.
STOCHASTIC RESONANCE AND NOISE-ENHANCED FISHER INFORMATION
Authors: WANG YOUGUO , WU LENAN
Published: September 2005

We discuss the signal estimation that can be finished on a signal buried in generalized Gaussian noise based on the quantized version provided by a summing array of threshold devices. In the estimation, the Fisher information contained in the array output about the input signal is investigated. We show that the Fisher information can be improved as the noise intensity increases in the summing array and that a noise with a thinner tail in its distribution can lead to a better improvement, i.e., the fatter tail in the noise distribution may neutralize the beneficial role of noise. These results prove that the phenomenon of stochastic resonance (SR) or supra-threshold stochastic resonance (SSR) exists based on Fisher information in the summing array of threshold devices for generalized Gaussian noise, and that the noise distribution has an effect on the efficacy of SR or SSR. These above results also extend the applicability of the nonlinear phenomenon of SR or SSR in signal estimation.
WHAT WORKS, AND WHAT REMAINS TO BE DONE, IN HIV PREVENTION IN THE UNITED STATES
Authors: Holtgrave David R. , Curran James W.
Published: September 2005

▪ Abstract  Since the beginning of the HIV epidemic in the United States, HIV prevention programs have prevented hundreds of thousands of HIV infections, and the investment in these programs has actually been cost-saving to society in terms of medical costs averted. A substantial body of evidence exists (including randomized controlled trials and careful meta-analyses) which demonstrates that various HIV prevention services are effective; an increasingly large body of data also demonstrates the cost-effectiveness of these interventions. However, the efforts to utilize these interventions in a comprehensive HIV prevention program are hampered by insufficient funding, imperfect targeting strategies, and a problematic policy environment that creates barriers to the use of some of these life-saving interventions. Progress toward reducing new HIV infections will likely be as much a function of improvements in funding and policies as it will in the development of new tools for HIV prevention.
AID TO PEOPLE WITH DISABILITIES: Medicaid's Growing Role
Authors: Carbaugh Alicia L. , Elias Risa , Rowland Diane
Published: September 2005

▪ Abstract  Medicaid is the nation's largest health care program providing assistance with health and long-term care services for millions of low-income Americans, including people with chronic illness and severe disabilities. This article traces the evolution of Medicaid's now-substantial role for people with disabilities; assesses Medicaid's contributions over the last four decades to improving health insurance coverage, access to care, and the delivery of care; and examines the program's future challenges as a source of assistance to children and adults with disabilities. Medicaid has shown that it is an important source of health insurance coverage for this population, people for whom private coverage is often unavailable or unaffordable, substantially expanding coverage and helping to reduce the disparities in access to care between the low-income population and the privately insured.
Endothelial actin cytoskeleton remodeling during mechanostimulation with fluid shear stress
Authors: Osborn Eric A. , Rabodzey Aleksandr , Dewey C. Forbes , Hartwig John H.
Published: September 2005

Fluid shear stress stimulation induces endothelial cells to elongate and align in the direction of applied flow. Using the complementary techniques of photoactivation of fluorescence and fluorescence recovery after photobleaching, we have characterized endothelial actin cytoskeleton dynamics during the alignment process in response to steady laminar fluid flow and have correlated these results to motility. Alignment requires 24 h of exposure to fluid flow, but the cells respond within minutes to flow and diminish their movement by 50%. Although movement slows, the actin filament turnover rate increases threefold and the percentage of total actin in the polymerized state decreases by 34%, accelerating actin filament remodeling in individual cells within a confluent endothelial monolayer subjected to flow to levels used by dispersed nonconfluent cells under static conditions for rapid movement. Temporally, the rapid decrease in filamentous actin shortly after flow stimulation is preceded by an increase in actin filament turnover, revealing that the earliest phase of the actin cytoskeletal response to shear stress is net cytoskeletal depolymerization. However, unlike static cells, in which cell motility correlates positively with the rate of filament turnover and negatively with the amount polymerized actin, the decoupling of enhanced motility from enhanced actin dynamics after shear stress stimulation supports the notion that actin remodeling under these conditions favors cytoskeletal remodeling for shape change over locomotion. Hours later, motility returned to pre-shear stress levels but actin remodeling remained highly dynamic in many cells after alignment, suggesting continual cell shape optimization. We conclude that shear stress initiates a cytoplasmic actin-remodeling response that is used for endothelial cell shape change instead of bulk cell translocation.
Distinct roles for ANG II and ANG-(1–7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytes
Authors: Gallagher Patricia E. , Chappell Mark C. , Ferrario Carlos M. , Tallant E. Ann
Published: September 2005

Angiotensin-converting enzyme 2 (ACE2) is a homolog of ACE that preferentially forms angiotensin-(1–7) [ANG-(1–7)] from angiotensin II (ANG II). Incubation of neonatal rat cerebellar or medullary astrocytes with ANG II reduced ACE2 mRNA by ∼60%, suggesting transcriptional regulation of the enzyme. In contrast, ANG II had no effect on ACE mRNA in astrocytes isolated from either brain region, demonstrating a differential regulation of the two enzymes by ANG II. The ANG II-mediated reduction in ACE2 mRNA was blocked by the angiotensin type 1 (AT1) receptor antagonists losartan or valsartan; the angiotensin type 2 (AT2) antagonist PD123319 was ineffective. The reduction in ACE2 mRNA by ANG II also was associated with a 50% decrease in cerebellar and medullary ACE2 protein, which was blocked by losartan. Treatment of medullary astrocytes with ANG-(1–7), the product of ACE2 hydrolysis of ANG II, did not affect ACE2 mRNA; however, ANG-(1–7) prevented the ANG II-mediated reduction in ACE2 mRNA. The addition of [d-Ala7]-ANG-(1–7), a selective AT(1–7) receptor antagonist, blocked the inhibitory actions of ANG-(1–7). These data are the first to demonstrate transcriptional regulation of ACE2 by ANG II and ANG-(1–7). Because ACE2 preferentially converts ANG II to ANG-(1–7), downregulation of the enzyme by ANG II constitutes a novel positive feed-forward system within the brain that may favor ANG II-mediated neural responses. Furthermore, the modulatory role of ANG-(1–7) in the transcriptional regulation of ACE2 by ANG II suggests a complex interplay between these peptides that is mediated by distinct receptor systems.
Two-step Ca2+ intracellular release underlies excitation-contraction coupling in mouse urinary bladder myocytes
Authors: Morimura Kozo , Ohi Yoshiaki , Yamamura Hisao , Ohya Susumu , Muraki Katsuhiko , Imaizumi Yuji
Published: September 2005

The relative contributions of Ca2+-induced Ca2+ release (CICR) versus Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs) to excitation-contraction coupling has not been defined in most smooth muscle cells (SMCs). The present study was undertaken to address this issue in mouse urinary bladder (UB) smooth muscle cells (UBSMCs). Confocal Ca2+ images were obtained under voltage- or current-clamp conditions. When UBSMCs were activated by a 30-ms depolarization to 0 mV, intracellular Ca2+ concentration ([Ca2+]i) increased in several small, discrete areas just beneath the cell membrane. These Ca2+ “hot spots” then spread slowly through the myoplasm as Ca2+ waves, which continued even after repolarization. Shorter depolarizations (5 ms) elicited only a few Ca2+ sparks, which declined quickly. The number of Ca2+ sparks, or hot spots, was closely related to the depolarization duration in the range of ∼5–20 ms. There was an apparent threshold depolarization duration of ∼10 ms within which to induce enough Ca2+ transients to spread globally and then induce a contraction. Application of 100 μM ryanodine to the pipette solution did not change the resting [Ca2+]i or the VDCC current, but it did abolish Ca2+ hot spots elicited by depolarization. Application of 3 μM xestospongin C reduced ACh-induced Ca2+ release but did not affect depolarization-induced Ca2+ events. The addition of 100 μM ryanodine to tissue segments markedly reduced the amplitude of contractions triggered by direct electrical stimulation. In conclusion, global [Ca2+]i rise triggered by a single action potential is not due mainly to Ca2+ influx through VDCCs but is attributable to the subsequent two-step CICR.
Increased cross-bridge cycling rate in stunned myocardium
Authors: Gao Wei Dong , Dai Tieying , Nyhan Daniel
Published: September 2005

Decreased Ca2+ responsiveness of the myofilaments underlies myocardial stunning. Given that cross-bridge cycling is a major determinant of myofilament behavior, we quantified cross-bridge cycling rate in stunned myocardium. After stabilization, rat hearts were subjected to 20 min of no-flow global ischemia and 30 min of reperfusion at 37°C. Control hearts were perfused continuously at 37°C for 60 min. Trabeculae were dissected and chemically skinned with 1% Triton X-100. The muscles were then activated with solutions of varied Ca2+ concentration ([Ca2+]). Force-[Ca2+] relations, rate of force redevelopment after release ( ktr), muscle stiffness ( km), and myofilament ATP consumption were determined. Maximal Ca2+-activated force (Fmax) was depressed in stunned myocardium (49 ± 5 vs. 82 ± 5 mN/mm2, P < 0.01). Western immunoblotting showed degradation of troponin I in stunned myocardium. The ktr at Fmax was significantly increased in stunned muscles (19.82 ± 2.74 vs. 13.19 ± 0.96 s−1, 22°C, P < 0.01; 7.49 ± 0.52 vs. 5.81 ± 0.54 s−1, 10°C, P < 0.05). The ratio of km measured at 100 Hz over that at 1 Hz, during Fmax, is lower in stunned muscles (8.22 ± 1.56 vs. 12.94 ± 0.71, P < 0.05). In comparison with km at rigor, km at Fmax is significantly lower in the stunned group (78.82 ± 6.11 vs. 93.27 ± 3.03%, P < 0.05). Myofilament ATP consumption at Fmax did not change in stunned muscles (5,901 ± 952 vs. 5,596 ± 972 pmol·μl−1·min−1, P = 0.49). These results show that cross-bridge cycling is increased in stunned myocardium. Such increases are likely the result of increased transition rate from force-generating states to non-force-generating states. Thus stunned myocardium still maintains ATP consumption in spite of lower force development, rationalizing the long-standing paradox of decreased force but unchanged oxygen consumption in the postischemic heart.
Coronary occlusion and reperfusion promote early afterdepolarizations and ventricular tachycardia in a canine tissue model of type 3 long QT syndrome
Authors: Ueda Norihiro , Zipes Douglas P. , Wu Jiashin
Published: September 2005

Although long QT syndrome (LQTS) and coronary occlusion-reperfusion (O/R) are arrhythmogenic, they affect ventricular action potential duration (APD) differently. In contrast to the prolonged APD in LQTS, ischemia abbreviates APD after a transient prolongation. Thus we hypothesized that the dynamic interactive effects of ischemia and LQTS on APD and its dispersion would affect ventricular arrhythmogenicity. We mapped transmural distribution of action potentials in 6 groups of 10 isolated wedges of canine ventricular walls: LQTS-O/R, LQTS only, and O/R only, with separate groups for pacing cycle lengths (PCL) of 1,000 and 2,000 ms. We created type 3 LQTS with anemone toxin (ATX) II followed >30 min later by arterial occlusion (40 min) and reperfusion (>100 min). Arterial occlusion initially (first 4 min) prolonged and then shortened APD. Early afterdepolarizations (EADs) occurred during the initial 4 min of occlusion in 4 of the 10 LQTS-O/R wedges at PCL of 2,000 ms but not in the other groups. Reperfusion restored APD in the O/R-only groups but caused APD to overshoot its original duration, indicating depressed repolarization reserve, in the LQTS-O/R group. Reperfusion increased the dispersion of APDs and initiated ventricular tachycardia-fibrillation in 7 of 10 and 6 of 10 LQTS-O/R wedges and in 2 of 10 and 1 of 10 O/R-only wedges at PCLs of 1,000 and 2,000 ms, respectively. The LQTS-only wedges exhibited neither EADs nor ventricular tachycardia. We conclude that coronary O/R increased the arrhythmogenicity of LQTS via cumulative prolongation of APD, increase in repolarization dispersion, and suppression of repolarization reserve.
Putative role of the NTS in alterations in neural control of the circulation following exercise training in rats
Authors: Mueller Patrick J. , Hasser Eileen M.
Published: September 2005

Exercise training (ExTr) has been associated with alterations in neural control of the circulation, including effects on arterial baroreflex function. The nucleus tractus solitarius (NTS) is the primary termination site of cardiovascular afferents and critical in the regulation of baroreflex-mediated changes in heart rate (HR) and sympathetic nervous system outflow. The purpose of the present study was to determine whether ExTr is associated with alterations in neurotransmitter regulation of neurons involved in control of cardiovascular function at the level of the NTS. We hypothesized that ExTr would increase glutamatergic and reduce GABAergic transmission in the NTS and that, collectively, these changes would result in a greater overall sympathoinhibitory drive from the NTS in ExTr animals. To test these hypotheses, male Sprague-Dawley rats were treadmill trained or maintained under sedentary conditions for 8–10 wk. NTS microinjections were performed in Inactin-anesthetized animals instrumented to record mean arterial pressure (MAP), HR, and lumbar sympathetic nerve activity (LSNA). Generalized activation of the NTS with unilateral microinjections of glutamate (1–10 mM, 30 nl) produced dose-dependent decreases in MAP, HR, and LSNA that were unaffected by ExTr. Bilateral inhibition of NTS with the GABAA agonist muscimol (1 mM, 90 nl) produced increases in MAP and LSNA that were blunted by ExTr. In contrast, pressor and sympathoexcitatory responses to bilateral microinjections of the ionotropic glutamate receptor antagonist, kynurenate (40 mM, 90 nl), were similar between groups. Bradycardic responses to bilateral microinjections of the GABAA antagonist bicuculline (0.1 mM, 90 nl) were attenuated by ExTr. These data indicate that alterations in neurotransmission at the level of the NTS contribute importantly to regulation of HR and LSNA in ExTr animals. In addition to alterations at NTS, these experiments suggest indirectly that changes in other cardiovascular nuclei contribute to the observed alterations in neural control of the circulation following ExTr.
Hypoxia-Inducible Factor 1α Expression as an Intrinsic Marker of Hypoxia
Authors: Hutchison Gillian J. , Valentine Helen R. , Loncaster Juliette A. , Davidson Susan E. , Hunter Robert D. , Roberts Stephen A. , Harris Adrian L. , Stratford Ian J. , Price Patricia M. , West Catharine M. L.
Published: September 2005

Purpose: Hypoxia-inducible factor (HIF)-1α expression was studied retrospectively in locally advanced carcinoma of the cervix in relation to other methods for measuring/assessing tumor hypoxia and outcome after radiotherapy.

Experimental Design: HIF-1α expression was examined in formalin-fixed tumor biopsies using a semiquantitative scoring system and correlated with measurements of hypoxia obtained using oxygen electrodes, pimonidazole staining, and carbonic anhydrase 9.

Results: High HIF-1α expression showed a weak correlation with low pO2 (r = −0.26; P = 0.030; n = 72). Weak significant correlations were found between HIF-1α and pimonidazole staining (r = 0.34; P = 0.040; n = 36) and carbonic anhydrase IX (r = 0.27; P = 0.001; n = 160). There was no relationship with surviving fraction at 2 Gy. The relationship between HIF-1α expression and radiotherapy outcome was examined in 99 patients. HIF-1α expression did not correlate with disease stage, grade, tumor size, and patient age. HIF-1α alone was not a significant prognostic factor for disease-free survival, metastasis-free survival, or local recurrence-free survival. High HIF-1α expression tended to be associated with poor outcome in small tumors but good outcome in large tumors, with statistically significant interactions between HIF-1α and tumor size for survival (P = 0.046) and local control (P = 0.009).

Conclusions: In this study, HIF-1α had no prognostic significance in locally advanced carcinoma of the cervix. The possible switch in large tumors for an association between high HIF-1α expression and good outcome might relate to tumor size-related changes in the balance of genes up-regulated by HIF-1α. Whereas angiogenesis-promoting genes might be preferentially up-regulated in small tumors, proapoptotic genes might be induced in large tumors. This hypothesis needs testing in future work.
Molecular Profiling and Classification of Sporadic Renal Cell Carcinoma by Quantitative Methylation Analysis
Authors: Gonzalgo Mark L. , Yegnasubramanian Srinivasan , Yan Gai , Rogers Craig G. , Nicol Theresa L. , Nelson William G. , Pavlovich Christian P.
Published: September 2005

Purpose: Preoperative histologic classification of solid renal masses remains limited with current technology. We determine the utility of molecular profiling based on quantitative methylation analysis for characterization of sporadic renal cell carcinoma.

Experimental Design: Primary renal cell carcinomas representing three different histologic subtypes were obtained from a total of 38 patients who underwent radical nephrectomy for suspected malignant disease. Genomic DNA was isolated from tumors and was subjected to sodium bisulfite modification. The normalized index of methylation (NIM) for each sample was determined by quantitative real-time methylation-specific PCR at 17 different gene promoters. Hierarchical cluster analysis was performed by using an unsupervised neural network with binary tree topology.

Results: The majority of gene promoters that were analyzed in this study demonstrated very low levels of methylation (NIM <1.0). The RASSF1A gene promoter, however, was methylated in 30 of 38 (79%) cases. The frequency of RASSF1A methylation in papillary, clear-cell, and oncocytoma subtypes was 100, 90, and 25%, respectively. The highest levels of RASSF1A methylation were observed in the papillary (mean NIM = 78.9) and clear-cell (mean NIM = 13.4) subtypes. The vast majority of oncocytomas were completely unmethylated, and none demonstrated >1% methylation (mean NIM = 0.11). Hierarchical cluster analysis based on quantitative methylation levels resulted in stratification of sporadic renal cell carcinomas into their discrete histologic subtypes.

Conclusions: Classification of sporadic renal cell carcinomas into histologic subtypes can be accomplished via multigene quantitative methylation profiling. Validation of this approach and selection of appropriate methylation markers may ultimately lead to use of this technology in the preoperative assessment of suspicious renal masses.