bluuebunny/crossref_metadata_2025 huggingface dataset:
The Periodical Shear Environment of a Cone-and-Plate Bioreactor
Authors: Chung C. A. , Weng C. S. , Tu M. Z.
Published: March 2006

We investigate theoretically the periodic shear environment of a cone-and-plate bioreactor. The imposed frequency is designated to reflect the periodic nature of mammalian cardiac cycles. The working formula obtained for the distribution of shear stresses shall be of substantial interest for applying periodic shear stresses to cell cultures in vitro.
Analysis of the Sutton Model for Aero-Optical Properties of Compressible Boundary Layers
Authors: Tromeur Eric , Garnier Eric , Sagaut Pierre
Published: March 2006

In order to assess the capability of the Sutton model to evaluate aero-optical effects in a turbulent boundary layer, large-eddy simulation (LES) evolving spatially and Reynolds averaged Navier-Stokes (RANS) computations are carried out at Mach number equal to 0.9. First aerodynamic fields are proved to compare favorably with theoretical and experimental results. Once validated, the characteristics of the boundary layer allow us to obtain information concerning optical beam degradation. On the one hand, the density field is used to compute phase distortion directly and, on the other hand, by means of the Sutton model. Therefore, LES and RANS simulations allow us to study optical models and the validity of their assumptions. Finally, LES is proved to be considered as a reference tool to evaluate aero-optical effects.
Optimization of Plasma Spray Processing Parameters for Deposition of Nanostructured Powders for Coating Formation
Authors: Ahmed I. , Bergman T. L.
Published: March 2006

When nanostructured powder particles are used for thermal spray coatings, the retention of the original nanostructure that is engineered into the raw stock is a principal objective, along with production of some molten material in order to adhere the sprayed material to the surface being coated. Therefore, in contrast with spraying conventional powders, complete melting of the nanostructured raw stock is to be avoided. In this study, the melting and resolidification of sprayed material is correlated to a spray processing parameter that has been introduced in the literature by some of the spray processing practitioners. Using computer modeling, processing of zirconia agglomerates with plasma spraying has been simulated. Transition regions for the phase change response of the sprayed material to the thermal processing conditions are identified. The retained nanostructure content and liquid fraction of the sprayed material are correlated to particle diameters, injection velocities, as well as this thermal spray processing parameter. Finally, a novel method to produce desired coatings composed of partially molten material using a bimodal particle size distribution of the sprayed powder is suggested.
A Method to Predict Cavitation Inception Using Large-Eddy Simulation and its Application to the Flow Past a Square Cylinder
Authors: Wienken W. , Stiller J. , Keller A.
Published: March 2006

A new method to predict traveling bubble cavitation inception is devised. The crux of the method consists in combining the enhanced predictive capabilities of large-eddy-simulation (LES) for flow computation with a simple but carefully designed stability criterion for the cavitation nuclei. For LES a second-order accurate finite element model based on the Galerkin/least-squares method with Runge-Kutta time integration is applied. The incoming nucleus’ spectrum is approximated by a Weibull distribution. Moreover, it is shown that under typical conditions the stability of the nuclei can be evaluated with an algebraic criterion emerging from the Rayleigh-Plesset equation. This criterion can be expressed as modified critical Thoma number and fits well into the LES approach. The method was applied to study cavitation inception in a flow past a square cylinder. A good agreement with experimental results was achieved. Furthermore, the principal advantage over statistical (time-averaged) methods could be clearly demonstrated, even though the spatial resolution and application of the LES were restricted by limited computational resources. As the latter keep on growing, a wider range of applications will become accessible methods for cavitation prediction based on algebraic stability criteria combined with LES.
Identification of a Dynamic Atmosphere at Enceladus with the Cassini Magnetometer
Authors: Dougherty M. K. , Khurana K. K. , Neubauer F. M. , Russell C. T. , Saur J. , Leisner J. S. , Burton M. E.
Published: March 2006

The Cassini magnetometer has detected the interaction of the magnetospheric plasma of Saturn with an atmospheric plume at the icy moon Enceladus. This unanticipated finding, made on a distant flyby, was subsequently confirmed during two follow-on flybys, one very close to Enceladus. The magnetometer data are consistent with local outgassing activity via a plume from the surface of the moon near its south pole, as confirmed by other Cassini instruments.
Enceladus' Varying Imprint on the Magnetosphere of Saturn
Authors: Jones G. H. , Roussos E. , Krupp N. , Paranicas C. , Woch J. , Lagg A. , Mitchell D. G. , Krimigis S. M. , Dougherty M. K.
Published: March 2006

The bombardment of Saturn's moon Enceladus by >20–kiloelectron volt magnetospheric particles causes particle flux depletions in regions magnetically connected to its orbit. Irrespective of magnetospheric activity, proton depletions are persistent, whereas electron depletions are quickly erased by magnetospheric processes. Observations of these signatures by Cassini's Magnetospheric Imaging Instrument allow remote monitoring of Enceladus' gas and dust environments. This reveals substantial outgassing variability at the moon and suggests increased dust concentrations at its Lagrange points. The characteristics of the particle depletions additionally provide key radial diffusion coefficients for energetic electrons and an independent measure of the inner magnetosphere's rotation velocity.
Composition and Physical Properties of Enceladus' Surface
Authors: Brown Robert H. , Clark Roger N. , Buratti Bonnie J. , Cruikshank Dale P. , Barnes Jason W. , Mastrapa Rachel M. E. , Bauer J. , Newman S. , Momary T. , Baines K. H. , Bellucci G. , Capaccioni F. , Cerroni P. , Combes M. , Coradini A. , Drossart P. , Formisano V. , Jaumann R. , Langevin Y. , Matson D. L. , McCord T. B. , Nelson R. M. , Nicholson P. D. , Sicardy B. , Sotin C.
Published: March 2006

Observations of Saturn's satellite Enceladus using Cassini's Visual and Infrared Mapping Spectrometer instrument were obtained during three flybys of Enceladus in 2005. Enceladus' surface is composed mostly of nearly pure water ice except near its south pole, where there are light organics, CO
2
, and amorphous and crystalline water ice, particularly in the region dubbed the âtiger stripes.â An upper limit of 5 precipitable nanometers is derived for CO in the atmospheric column above Enceladus, and 2% for NH
3
in global surface deposits. Upper limits of 140 kelvin (for a filled pixel) are derived for the temperatures in the tiger stripes.
Enceladus' Water Vapor Plume
Authors: Hansen Candice J. , Esposito L. , Stewart A. I. F. , Colwell J. , Hendrix A. , Pryor W. , Shemansky D. , West R.
Published: March 2006

The Cassini spacecraft flew close to Saturn's small moon Enceladus three times in 2005. Cassini's UltraViolet Imaging Spectrograph observed stellar occultations on two flybys and confirmed the existence, composition, and regionally confined nature of a water vapor plume in the south polar region of Enceladus. This plume provides an adequate amount of water to resupply losses from Saturn's E ring and to be the dominant source of the neutral OH and atomic oxygen that fill the Saturnian system.
Cassini Ion and Neutral Mass Spectrometer: Enceladus Plume Composition and Structure
Authors: Waite J. Hunter , Combi Michael R. , Ip Wing-Huen , Cravens Thomas E. , McNutt Ralph L. , Kasprzak Wayne , Yelle Roger , Luhmann Janet , Niemann Hasso , Gell David , Magee Brian , Fletcher Greg , Lunine Jonathan , Tseng Wei-Ling
Published: March 2006

The Cassini spacecraft passed within 168.2 kilometers of the surface above the southern hemisphere at 19:55:22 universal time coordinated on 14 July 2005 during its closest approach to Enceladus. Before and after this time, a substantial atmospheric plume and coma were observed, detectable in the Ion and Neutral Mass Spectrometer (INMS) data set out to a distance of over 4000 kilometers from Enceladus. INMS data indicate that the atmospheric plume and coma are dominated by water, with significant amounts of carbon dioxide, an unidentified species with a mass-to-charge ratio of 28 daltons (either carbon monoxide or molecular nitrogen), and methane. Trace quantities (<1%) of acetylene and propane also appear to be present. Ammonia is present at a level that does not exceed 0.5%. The radial and angular distributions of the gas density near the closest approach, as well as other independent evidence, suggest a significant contribution to the plume from a source centered near the south polar cap, as distinct from a separately measured more uniform and possibly global source observed on the outbound leg of the flyby.
Diffusive Separation of the Lower Atmosphere
Authors: Adachi Yosuke , Kawamura Kenji , Armi Laurence , Keeling Ralph F.
Published: March 2006

The separation of atmospheric constituents by gravity has been proposed theoretically for almost two centuries. However, turbulent mixing has prevented the detection of this phenomenon in the lower atmosphere. By using precise measurements of the Ar/N2 ratio of air samples taken under strong nocturnal inversions, we have detected such separation in near-surface layers. The effect is shown to be consistent with combined influence of thermal and gravimetric separation, with the thermal contribution being more important.
A Major Ecosystem Shift in the Northern Bering Sea
Authors: Grebmeier Jacqueline M. , Overland James E. , Moore Sue E. , Farley Ed V. , Carmack Eddy C. , Cooper Lee W. , Frey Karen E. , Helle John H. , McLaughlin Fiona A. , McNutt S. Lyn
Published: March 2006

Until recently, northern Bering Sea ecosystems were characterized by extensive seasonal sea ice cover, high water column and sediment carbon production, and tight pelagic-benthic coupling of organic production. Here, we show that these ecosystems are shifting away from these characteristics. Changes in biological communities are contemporaneous with shifts in regional atmospheric and hydrographic forcing. In the past decade, geographic displacement of marine mammal population distributions has coincided with a reduction of benthic prey populations, an increase in pelagic fish, a reduction in sea ice, and an increase in air and ocean temperatures. These changes now observed on the shallow shelf of the northern Bering Sea should be expected to affect a much broader portion of the Pacific-influenced sector of the Arctic Ocean.
Cassini Dust Measurements at Enceladus and Implications for the Origin of the E Ring
Authors: Spahn Frank , Schmidt Jürgen , Albers Nicole , Hörning Marcel , Makuch Martin , Seiß Martin , Kempf Sascha , Srama Ralf , Dikarev Valeri , Helfert Stefan , Moragas-Klostermeyer Georg , Krivov Alexander V. , Sremčević Miodrag , Tuzzolino Anthony J. , Economou Thanasis , Grün Eberhard
Published: March 2006

During Cassini's close flyby of Enceladus on 14 July 2005, the High Rate Detector of the Cosmic Dust Analyzer registered micron-sized dust particles enveloping this satellite. The dust impact rate peaked about 1 minute before the closest approach of the spacecraft to the moon. This asymmetric signature is consistent with a locally enhanced dust production in the south polar region of Enceladus. Other Cassini experiments revealed evidence for geophysical activities near Enceladus' south pole: a high surface temperature and a release of water gas. Production or release of dust particles related to these processes may provide the dominant source of Saturn's E ring.
Opposing Effects of Native and Exotic Herbivores on Plant Invasions
Authors: Parker John D. , Burkepile Deron E. , Hay Mark E.
Published: March 2006

Exotic species are widely assumed to thrive because they lack natural enemies in their new ranges. However, a meta-analysis of 63 manipulative field studies including more than 100 exotic plant species revealed that native herbivores suppressed exotic plants, whereas exotic herbivores facilitated both the abundance and species richness of exotic plants. Both outcomes suggest that plants are especially susceptible to novel, generalist herbivores that they have not been selected to resist. Thus, native herbivores provide biotic resistance to plant invasions, but the widespread replacement of native with exotic herbivores eliminates this ecosystem service, facilitates plant invasions, and triggers an invasional “meltdown.”
Structure and Mechanism of the Lantibiotic Cyclase Involved in Nisin Biosynthesis
Authors: Li Bo , Yu John Paul J. , Brunzelle Joseph S. , Moll Gert N. , van der Donk Wilfred A. , Nair Satish K.
Published: March 2006

Nisin is a posttranslationally modified antimicrobial peptide that is widely used as a food preservative. It contains five cyclic thioethers of varying sizes that are installed by a single enzyme, NisC. Reported here are the in vitro reconstitution of the cyclization process and the x-ray crystal structure of the NisC enzyme. The structure reveals similarities in fold and substrate activation with mammalian farnesyl transferases, suggesting that human homologs of NisC posttranslationally modify a cysteine of a protein substrate.
Cassini Encounters Enceladus: Background and the Discovery of a South Polar Hot Spot
Authors: Spencer J. R. , Pearl J. C. , Segura M. , Flasar F. M. , Mamoutkine A. , Romani P. , Buratti B. J. , Hendrix A. R. , Spilker L. J. , Lopes R. M. C.
Published: March 2006

The Cassini spacecraft completed three close flybys of Saturn's enigmatic moon Enceladus between February and July 2005. On the third and closest flyby, on 14 July 2005, multiple Cassini instruments detected evidence for ongoing endogenic activity in a region centered on Enceladus' south pole. The polar region is the source of a plume of gas and dust, which probably emanates from prominent warm troughs seen on the surface. Cassini's Composite Infrared Spectrometer (CIRS) detected 3 to 7 gigawatts of thermal emission from the south polar troughs at temperatures up to 145 kelvin or higher, making Enceladus only the third known solid planetary body—after Earth and Io—that is sufficiently geologically active for its internal heat to be detected by remote sensing. If the plume is generated by the sublimation of water ice and if the sublimation source is visible to CIRS, then sublimation temperatures of at least 180 kelvin are required.
Engineering Cooperativity in Biomotor-Protein Assemblies
Authors: Diehl Michael R. , Zhang Kechun , Lee Heun Jin , Tirrell David A.
Published: March 2006

A biosynthetic approach was developed to control and probe cooperativity in multiunit biomotor assemblies by linking molecular motors to artificial protein scaffolds. This approach provides precise control over spatial and elastic coupling between motors. Cooperative interactions between monomeric kinesin-1 motors attached to protein scaffolds enhance hydrolysis activity and microtubule gliding velocity. However, these interactions are not influenced by changes in the elastic properties of the scaffold, distinguishing multimotor transport from that powered by unorganized monomeric motors. These results highlight the role of supramolecular architecture in determining mechanisms of collective transport.
Ultrafast Interfacial Proton-Coupled Electron Transfer
Authors: Li Bin , Zhao Jin , Onda Ken , Jordan Kenneth D. , Yang Jinlong , Petek Hrvoje
Published: March 2006

The coupling of electron and nuclear motions in ultrafast charge transfer at molecule-semiconductor interfaces is central to many phenomena, including catalysis, photocatalysis, and molecular electronics. By using femtosecond laser excitation, we transferred electrons from a rutile titanium dioxide (110) surface into a CH
3
OH overlayer state that is 2.3 ± 0.2 electron volts above the Fermi level. The redistributed charge was stabilized within 30 femtoseconds by the inertial motion of substrate ions (polaron formation) and, more slowly, by adsorbate molecules (solvation). According to a pronounced deuterium isotope effect (CH
3
OD), this motion of heavy atoms transforms the reverse charge transfer from a purely electronic process (nonadiabatic) to a correlated response of electrons and protons.
Cassini Observes the Active South Pole of Enceladus
Authors: Porco C. C. , Helfenstein P. , Thomas P. C. , Ingersoll A. P. , Wisdom J. , West R. , Neukum G. , Denk T. , Wagner R. , Roatsch T. , Kieffer S. , Turtle E. , McEwen A. , Johnson T. V. , Rathbun J. , Veverka J. , Wilson D. , Perry J. , Spitale J. , Brahic A. , Burns J. A. , DelGenio A. D. , Dones L. , Murray C. D. , Squyres S.
Published: March 2006

Cassini has identified a geologically active province at the south pole of Saturn's moon Enceladus. In images acquired by the Imaging Science Subsystem (ISS), this region is circumscribed by a chain of folded ridges and troughs at â¼55Â°S latitude. The terrain southward of this boundary is distinguished by its albedo and color contrasts, elevated temperatures, extreme geologic youth, and narrow tectonic rifts that exhibit coarse-grained ice and coincide with the hottest temperatures measured in the region. Jets of fine icy particles that supply Saturn's E ring emanate from this province, carried aloft by water vapor probably venting from subsurface reservoirs of liquid water. The shape of Enceladus suggests a possible intense heating epoch in the past by capture into a 1:4 secondary spin/orbit resonance.
Genome-Wide Prediction of
C. elegans
Genetic Interactions
Authors: Zhong Weiwei , Sternberg Paul W.
Published: March 2006

To obtain a global view of functional interactions among genes in a metazoan genome, we computationally integrated interactome data, gene expression data, phenotype data, and functional annotation data from three model organisms—
Saccharomyces cerevisiae, Caenorhabditis elegans
, and
Drosophila melanogaster
—and predicted genome-wide genetic interactions in
C. elegans
. The resulting genetic interaction network (consisting of 18,183 interactions) provides a framework for system-level understanding of gene functions. We experimentally tested the predicted interactions for two human disease-related genes and identified 14 new modifiers.
Signatures of H
2
CO Photodissociation from Two Electronic States
Authors: Yin H. M. , Kable S. H. , Zhang X. , Bowman J. M.
Published: March 2006

Even in small molecules, the influence of electronic state on rotational and vibrational product energies is not well understood. Here, we use experiments and theory to address this issue in photodissociation of formaldehyde, H
2
CO, to the radical products H + HCO. These products result from dissociation from the singlet ground electronic state or the first excited triplet state (
T
1
) of H
2
CO. Fluorescence spectra reveal a sudden decrease in the HCO rotational energy with increasing photolysis energy accompanied by substantial HCO vibrational excitation. Calculations of the rotational distribution using an ab initio potential energy surface for the
T
1
state are in very good agreement with experiment and strongly support dominance of the
T
1
state in the dynamics at the higher photolysis energies.
Laonastes
and the "Lazarus Effect" in Recent Mammals
Authors: Dawson Mary R. , Marivaux Laurent , Li Chuan-kui , Beard K. Christopher , Métais Grégoire
Published: March 2006

The living Laotian rodent
Laonastes aenigmamus
, first described in early 2005, has been interpreted as the sole member of the new family Laonastidae on the basis of its distinctive morphology and apparent phylogenetic isolation from other living rodents. Here we show that
Laonastes
is actually a surviving member of the otherwise extinct rodent family Diatomyidae, known from early Oligocene to late Miocene sites in Pakistan, India, Thailand, China, and Japan.
Laonastes
is a particularly striking example of the “Lazarus effect” in Recent mammals, whereby a taxon that was formerly thought to be extinct is rediscovered in the extant biota, in this case after a temporal gap of roughly 11 million years.
Does Enceladus Govern Magnetospheric Dynamics at Saturn?
Authors: Kivelson Margaret Galland
Published: March 2006

Instruments on the Cassini spacecraft reveal that a heat source within Saturn's moon Enceladus powers a great plume of water ice particles and dust grains, a geyser that jets outward from the south polar regions and most likely serves as the dominant source of Saturn's E ring. The interaction of flowing magnetospheric plasma with the plume modifies the particle and field environment of Enceladus. The structure of Saturn's magnetosphere, the extended region of space threaded by magnetic-field lines linked to the planet, is shaped by the ion source at Enceladus, and magnetospheric dynamics may be affected by the rate at which fresh ions are created.
Enceladus: Cosmic Gymnast, Volatile Miniworld
Authors: Kargel Jeffrey S.
Published: March 2006

The exploration of Saturn by the Cassini/Huygens mission has yielded a rich collection of data about the planet and its rings and moons, in particular its small satellite Enceladus and giant satellite Titan. Once believed too small to be active, Enceladus has been found to be one of the most geologically dynamic objects in the solar system. Among the surprises are a watery, gaseous plume; a south polar hot spot; and a surface marked by deep canyons and thick flows.
Humanity Usurps Nature
Authors: Chameides Bill
Published: March 2006

The Weather Makers
. How Man Is Changing the Climate and What It Means for Life on Earth.
By Tim Flanner

Atlantic Monthly Press, New York, 2006. 381 pp. $24. ISBN 0-87113-935-9.

The Weather Makers
. The History and Future Impact of Climate Change . Allen Lane, London, 2006. £N 0-713-99921-7.

Besides offering an accessible overview of the history, science, and politics of climate change, the author suggests what must be done to restrain global warming.
Synthesis and Crystal Structures of Dinuclear Trichloro(tetramethylcyclopentadienyl)titanium Complexes
Authors: Lukešová Lenka , Gyepes Róbert , Varga Vojtech , Pinkas Jiří , Horáček Michal , Kubišta Jiří , Mach Karel
Published: March 2006

Dinuclear half-sandwich complexes [{TiCl3(η5-C5Me4)}2SiMe2] (2) and [{TiCl3(η5-C5Me4SiMe2CH2)}2] (4) were prepared by synproportionation of ansa-titanocene dichlorides [TiCl2{(η5-C5Me4)2SiMe2}] (1) and [TiCl2(η5-C5Me4SiMe2CH2)2] (3), respectively, with TiCl4. Compound 3 was synthesized from 1,2-bis(chlorodimethylsilyl)ethane, 1,2,3,4-tetramethylcyclopentadienyllithium, and [TiCl3(thf)3] by a common procedure. Crystal structures of 2, 3, and 4 were determined by X-ray diffraction analysis.
Physicochemical Properties of 9-(Alkylsulfanyl)- and 9-(Arylsulfanyl)acridine Derivatives and Their Interaction with (2-Hydroxypropyl)cyclodextrins
Authors: Němcová Irena , Nesměrák Karel , Kafková Božena , Sejbal Jan
Published: March 2006

Acid-base properties and aggregations of 9-(alkylsulfanyl)- and 9-(arylsulfanyl)acridine derivatives were studied as a part of systematic study of physicochemical properties of these compounds synthesized as potential drugs. The effect of the (2-hydroxypropyl)cyclodextrins on these properties and their association with the acridines was also followed.
The Warwick system of prospective workload allocation in cellular pathology—an aid to subspecialisation: a comparison with the Royal College of Pathologists’ system
Authors: Carr R A , Sanders D S A , Stores O P , Smew F A , Parkes M E , Ross-Gilbertson V , Chachlani N , Simon J
Published: March 2006

Background:Guidelines on staffing and workload for histopathology and cytopathology departmentswas published by the Royal College of Pathologists (RCPath) in July 2003. In this document, a system is provided whereby the workload of a cellular pathology department and individual pathologists can be assessed with a scoring system based on specialty and complexity of the specimens. A similar, but simplified, system of scoring specimens by specialty was developed in the Warwick District General Hospital. The system was based on the specimen type and suggested clinical diagnosis, so that specimens could be allocated prospectively by the laboratory technical staff to even out workload and support subspecialisation in a department staffed by 4.6 whole-time equivalent consultant pathologists.

Methods:The pathologists were asked to indicate their reporting preferences to determine specialist reporting teams. The workload was allocated according to the “prospective” Warwick system (based on specimen type and suggested clinical diagnosis, not affected by final diagnosis or individual pathologist variation in reference to numbers of blocks, sections and special stains examined) for October 2003. The cumulative Warwick score was compared with the “retrospective” RCPath scoring system for each pathologist and between specialties. Four pathologists recorded their time for cut-up and reporting for the month audited.

Results:The equitable distribution of work between pathologists was ensured by the Warwick allocation and workload system, hence facilitating specialist reporting. Less variation was observed in points reported per hour by the Warwick system (6.3 (range 5.5–6.9)) than by the RCPath system (11.5 (range 9.3–15)).

Conclusions:The RCPath system of scoring is inherently complex, is applied retrospectively and is not consistent across subspecialities. The Warwick system is simpler, prospective and can be run by technical staff; it facilitates even workload distribution throughout the day. Subspecialisation within a small-sized or medium-sized department with fair distribution of work between pathologists is also allowed for by this system. Reporting times among pathologists were shown by time and motion studies to be more consistent with Warwick points per hour than with RCPath points per hour.
Fascin is a potential biomarker for early-stage oesophageal squamous cell carcinoma
Authors: Zhang H , Xu L , Xiao D , Xie J , Zeng H , Cai W , Niu Y , Yang Z , Shen Z , Li E
Published: March 2006

Background:Fascin, an actin-binding protein, is usually expressed at a low level in normal epithelium, but is markedly up regulated in several types of carcinomas. Reports on fascin expression in oesophageal squamous cell carcinoma (ESCC) and precancerous lesions remain rare.

Aim:To show the roles of fascin in the progression from normal epithelium to invasive ESCC.

Methods:Fascin expression in 102 sections embedded in paraffin wax, including samples of normal mucosa (n = 20), dysplasia (n = 10), ESCC (n = 62) and special sections (n = 10) of a full-length mucosa layer from the distant margin to the cancer focus of the excised oesophagus, and 49 fresh specimens of ESCC was analysed by immunohistochemistry, western blot and real-time reverse transcription-polymerase chain reaction. Fascin expression in ESCC cell lines was also investigated.

Results:In the immunohistochemical study, the positive rate of fascin was significantly higher in the tumour tissue than in the normal epithelium (p = 0.020), but no significant difference was shown between ESCC and dysplasia (p = 1.000). Immunostaining for fascin was only apparent in the basal layer of the normal epithelium. However, in the dysplasia, positive staining was observed in most of the heterogeneous cells from the basal layer to the granular layer of the epithelium. Fascin expression was seen to increase progressively from the normal epithelium to invasive ESCC. Up regulation of fascin was observed in 87.76% (43/49) and 77.55% (38/49) of the specimens, respectively, using western blot and real-time reverse transcription-polymerase chain reaction assays; 80% (4/5) of ESCC cell lines also expressed fascin at a high level. Furthermore, overexpression of fascin was markedly correlated with cell proliferation and lymph node metastasis.

Conclusions:These findings suggested that fascin was associated with the transformation and development of ESCC and implicated the potential of fascin as a novel biomarker that would allow the tumour to be identified at an early stage in high-risk individuals.
External quality assessment slide schemes: pathologists’ experiences and perceptions
Authors: Parham D M
Published: March 2006

Background:External quality assessment schemes (EQAS) in pathology have been established in the United Kingdom for several years with the aim of raising standards.

Objective:To determine the experiences and perceptions of pathologists undertaking EQAS.

Methods:A questionnaire was distributed to histo/cytopathologists in the south and west of England.

Results:A large proportion of pathologists responding felt that the EQAS was educational, and 69% said participation had encouraged them to undertake additional educational activities. Some reservations were expressed about marking schemes. Asked if EQAS using digital images (CD-ROM or web based) rather that glass slides were valid alternatives two thirds responded no, despite 75% claiming to have appropriate IT skills.

Conclusions:EQAS play a valuable role in helping to maintain standards in histopathology and cytopathology. Some reservations were expressed about the marking schemes and further work is needed to establish a robust marking method. Significant barriers need to be overcome if digital EQAS are to be successfully implemented.
A LEVEL SET METHOD FOR FLUID-STRUCTURE INTERACTIONS WITH IMMERSED SURFACES
Authors: COTTET GEORGES-HENRI , MAITRE EMMANUEL
Published: March 2006

This paper is devoted to the derivation and the validation of a level set method for fluid-structure interaction problems with immersed surfaces. The test case of a pressurized membrane is used to compare our method to Peskin's Immersed Boundary methods in the two-dimensional case and to demonstrate its capabilities for three-dimensional flows. The method in particular exhibits appealing mass and energy conservation properties.
Loss of acidification of anterior prostate fluids in Atp12a-null mutant mice indicates that nongastric H-K-ATPase functions as proton pump in vivo
Authors: Pestov Nikolay B. , Korneenko Tatyana V. , Shakhparonov Mikhail I. , Shull Gary E. , Modyanov Nikolai N.
Published: March 2006

The physiological functions of nongastric (colonic) H-K-ATPase (gene symbol Atp12a), unlike those of Na-K-ATPase and gastric H-K-ATPase, are poorly understood. It has been suggested that it pumps Na+ more efficiently than H+; however, so far, there is no direct evidence that it pumps H+ in vivo. Previously, we found that the nongastric H-K-ATPase α-subunit is expressed in apical membranes of rodent anterior prostate epithelium, in a complex with the Na-K-ATPase β1-subunit. Here we report the effects of Atp12a gene ablation on polarization of the β1-subunit and secretory function of the anterior prostate. In nongastric H-K-ATPase-deficient prostate, the Na-K-ATPase α-subunit resided exclusively in basolateral membranes; however, the β1-subunit disappeared from apical membranes, demonstrating that β1 is an authentic subunit of nongastric H-K-ATPase in vivo and that apical localization of β1 in the prostate is completely dependent on its association with the nongastric H-K-ATPase α-subunit. A remarkable reduction in acidification of anterior prostate fluids was observed: pH 6.38 ± 0.14 for wild-type mice and 6.96 ± 0.10 for homozygous mutants. These results show that nongastric H-K-ATPase is required for acidification of luminal prostate fluids, thereby providing a strong in vivo correlate of previous functional expression studies demonstrating that it operates as a proton pump.
Urea and urine concentrating ability in mice lacking AQP1 and AQP3
Authors: Zhao Dan , Bankir Lise , Qian Liman , Yang Dayu , Yang Baoxue
Published: March 2006

Aquaporin-1 (AQP1) and aquaporin-3 (AQP3) water channels expressed in the kidney play a critical role in the urine concentrating mechanism. Mice with AQP1 or AQP3 deletion have a urinary concentrating defect. To better characterize this defect, we studied the influence of an acute urea load (300 μmol ip) in conscious AQP1-null, AQP3-null, and wild-type mice. Urine was collected and assayed every 2 h, from 2 h before (baseline) to 8 h after the urea load. Mice of all genotypes excreted the urea load in ∼4 h with the same time course. Interestingly, despite their low baseline, the AQP3-null mice raised their urine osmolality and urea concentration progressively after the urea load to values almost equal to those in wild-type mice at 8 h. In contrast, urine non-urea solute concentration did not change. Urine volume fell in the last 4 h to about one-fourth of basal values. AQP1-null mice increased their urine flow rate much more than AQP3-null mice and showed no change in urine osmolality and urea concentration. The urea load strongly upregulated urea transporter UT-A3 expression in all three genotypes. These observations show that the lack of AQP3 does not interfere with the ability of the kidney to concentrate urea but impairs its ability to concentrate other solutes. This solute-selective response could result from the capacity of AQP3 to transport not only water but also urea. The results suggest a novel role for AQP3 in non-urea solute concentration in the urine.
Role of the JAK/STAT signaling pathway in diabetic nephropathy
Authors: Marrero Mario B. , Banes-Berceli Amy K. , Stern David M. , Eaton Douglas C.
Published: March 2006

Excessive cellular growth is a major contributor to pathological changes associated with diabetic nephropathy. In particular, high glucose-induced growth of glomerular mesangial cells is a characteristic feature of diabetes-induced renal complications. Glomerular mesangial cells respond to traditional growth factors, although in diabetes this occurs in the context of an environment enriched in both circulating vasoactive mediators and high glucose. For example, the vasoactive peptide ANG II has been implicated in the pathogenesis of diabetic renal disease, and recent findings suggest that high glucose and ANG II activate intracellular signaling processes, including the polyol pathway and generation of reactive oxygen species. These pathways activate the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling cascades in glomerular mesangial cells. Activation of the JAK/STAT signaling cascade can stimulate excessive proliferation and growth of glomerular mesangial cells, contributing to diabetic nephropathy. This review focuses on some of the key elements in the diabetic microenvironment, especially high glucose and the accumulation of advanced glycoxidation end products and considers their impact on ANG II and other vasoactive peptide-mediated signaling events in vitro and in vivo.
An emerging role for calcineurin Aα in the development and function of the kidney
Authors: Gooch Jennifer L.
Published: March 2006

For many years, calcineurin has been a familiar molecule as a target of the immunosuppressive agents cyclosporin A and FK-506. Calcineurin inhibition interferes with T cell signaling by preventing activation of the transcription factor NFATc. However, calcineurin is expressed in most tissues in the body, and calcineurin inhibition undoubtedly alters many other cellular processes. As a result, serious side effects of calcineurin inhibitors regularly occur, including hypertension and renal dysfunction. Because nephrotoxicity is often a barrier to continued clinical use of calcineurin inhibitors, understanding the role of calcineurin in the kidney is of particular importance. Recent work has demonstrated that the two main isoforms of the catalytic subunit of calcineurin, Aα and Aβ, may have distinct functions, particularly in the kidney. Calcineurin isoforms may be differentially expressed, and/or the activity of each may be differentially regulated, leading to tissue-specific functions. Differences between the action of the two isoforms are most evident in knockout mice lacking each isoform. Mice lacking the β-isoform are characterized principally by altered development and function of immune cells. α-Knockout mice, in contrast, can still be immune suppressed by cyclosporin A but display pervasive developmental defects, including renal dysfunction. Therefore, it is intriguing to consider that while the β-isoform may be responsible for calcineurin action in T cells, the α-isoform may be the predominant catalytic isoform in the kidney. This conclusion, if correct, may have substantial clinical implication for novel strategies to selectively target calcineurin action in T cells without associated nephrotoxicity.
Skeletal muscle dysfunction in chronic renal failure: effects of exercise
Authors: Adams Gregory R. , Vaziri Nosratola D.
Published: March 2006

A number of chronic illnesses such as renal failure (CRF), obstructive pulmonary disease, and congestive heart failure result in a significant decrease in exercise tolerance. There is an increasing awareness that prescribed exercise, designed to restore some level of physical performance and quality of life, can be beneficial in these conditions. In CRF patients, muscle function can be affected by a number of direct and indirect mechanisms caused by renal disease as well as various treatment modalities. The aims of this review are twofold: first, to briefly discuss the mechanisms by which CRF negatively impacts skeletal muscle and, therefore, exercise capacity, and, second, to discuss the available data on the effects of programmed exercise on muscle function, exercise capacity, and various other parameters in CRF.
Adaptive hyperfiltration in the aging kidney after contralateral nephrectomy
Authors: Saxena Anjali Bhatt , Myers Bryan D. , Derby Geraldine , Blouch Kristina L. , Yan Jieshi , Ho Bing , Tan Jane C.
Published: March 2006

We examined the magnitude of adaptive hyperfiltration in the remaining kidney of 16 aging (>57 yr) and 16 youthful (<55 yr) individuals who had undergone a contralateral nephrectomy. Healthy volunteers who were youthful ( n = 143) or aging ( n = 37) provided control values for the binephric condition. One-kidney glomerular filtration rate (GFR; +42%), renal plasma flow (+38%), plasma oncotic pressure (+2.8 mmHg), and mean arterial pressure (+7.0 mmHg) were all higher in youthful uninephric vs. binephric subjects. Corresponding excesses in aging uninephric vs. binephric subjects were by 38 and 36% and 1.4 and 14.0 mmHg, respectively. Modeling of these data revealed that an isolated increase in either the glomerular ultrafiltration coefficient ( Kf) by 110% or in the transcapillary hydraulic pressure gradient (ΔP) by 7 mmHg, could account for the observed level of hyperfiltration in youthful uninephric subjects. Corresponding increases for aging uninephric subjects were 61% for Kfand 5 mmHg for ΔP. We conclude that the magnitude of adaptive hyperfiltration is similar in aging to that in youthful uninephric subjects, albeit at a lower absolute GFR level. Isolated increases in either Kfor ΔP or a combination of smaller increases in both can account for the hyperfiltration. Greater adaptive arterial hypertension in aging than youthful uninephric subjects raises the possibility of a disproportionate role for glomerular hypertension and ΔP elevation in aging compared with youthful uninephric subjects. Glomerular hypertension could exacerbate the sclerosing glomerulopathy of senescence and lead to renal insufficiency. We recommend that living donors of a kidney transplantation in or beyond the seventh decade be used with caution.
Inhibition of the renal betaine transporter by calcium ions
Authors: Kempson Stephen A. , Edwards Jason M. , Sturek Michael
Published: March 2006

Chronic upregulation of the renal betaine/GABA transporter (BGT1) by hypertonic stress has been well documented, but it is not known whether BGT1 can be regulated acutely after insertion in the basolateral plasma membrane. Related transporters, such as the rat brain GABA transporter, can be rapidly removed from the plasma membrane through activation of G protein-coupled receptors. The goal of the present study was to determine whether acute changes in extracellular and/or intracellular Ca2+will regulate BGT1 transport activity at the plasma membrane level in Madin-Darby canine kidney cells subjected to 24-h hypertonic stress. After brief pretreatment with a Ca2+-free solution, the addition of extracellular Ca2+in the transport assay produced dose-dependent inhibition of Na+-GABA cotransport. Maximum inhibition was 49% at 2 mM Ca2+( P < 0.05). Fura 2 imaging confirmed that addition of 2 mM Ca2+produced a transient increase in intracellular Ca2+that preceded transport inhibition. Acute inhibition of Na+-GABA cotransport was reproduced by addition of thapsigargin (5 μM) and ionomycin (10 μM). Amino acid transport system A, assayed as a control, was not inhibited. Brief treatment with phorbol esters reproduced the specific inhibition of Na+-GABA cotransport, and the inhibition was blocked by staurosporine. Surface biotinylation confirmed that the response to phorbol esters was accompanied by loss of BGT1 protein from the plasma membrane, and immunohistochemistry showed a shift to an intracellular distribution. We conclude that BGT1 can be inhibited acutely by extracellular Ca2+through a mechanism involving BGT1 protein internalization, and protein kinase C may play a role.
VEGF-C promotes survival in podocytes
Authors: Foster R. R. , Satchell S. C. , Seckley J. , Emmett M. S. , Joory K. , Xing C. Y. , Saleem M. A. , Mathieson P. W. , Bates D. O. , Harper S. J.
Published: March 2006

Vascular endothelial growth factor (VEGF)-A is an autocrine survival factor for podocytes, which express two VEGF receptors, VEGF-R1 and VEGF-R3. As VEGF-A is not a known ligand for VEGF-R3, the aim of this investigation was to examine whether VEGF-C, a known ligand for VEGF-R3, served a function in podocyte biology and whether this was VEGF-R3 dependent. VEGF-C protein expression was localized to podocytes in contrast to VEGF-D, which was expressed in parietal epithelial cells. Intracellular calcium ([Ca2+]i) experiments demonstrated that VEGF-C induced a 0.74 ± 0.09-fold reduction in [Ca2+]icompared with baseline in human conditionally immortalized podocytes (hCIPs; P < 0.05, one sample t-test, n = 8). Cytotoxicity experiments revealed that in hCIPs VEGF-C reduced cytotoxicity to 81.4 ± 1.9% of serum-starved conditions ( P < 0.001, paired t-test, n = 16), similar to VEGF-A (82.8 ± 4.5% of serum-starved conditions, P < 0.05, paired t-test). MAZ51 (a VEGF-R3 kinase inhibitor) inhibited the VEGF-C-induced reduction in cytotoxicity (106.2 ± 2.1% of serum-starved conditions), whereas MAZ51 by itself had no cytotoxic effects on hCIPs. VEGF-C was also shown to induce a 0.5 ± 0.13-fold reduction in levels of MAPK phosphorylation compared with VEGF-A and VEGF-A-Mab treatment ( P < 0.05, ANOVA, n = 4), yet had no effect on Akt phosphorylation. Surprisingly, immunoprecipitation studies detected no VEGF-C-induced autophosphorylation of VEGF-R3 in hCIPs but did so in HMVECs. Moreover, SU-5416, a tyrosine kinase inhibitor, blocked the VEGF-C-induced reduction in cytotoxicity (106 ± 2.8% of serum-starved conditions) at concentrations specific for VEGF-R1. Together, these results suggest for the first time that VEGF-C acts in an autocrine manner in cultured podocytes to promote survival, although the receptor or receptor complex activated has yet to be elucidated.
Rho kinase regulates renal blood flow by modulating eNOS activity in ischemia-reperfusion of the rat kidney
Authors: Versteilen Amanda M. G. , Korstjens Iolente J. M. , Musters René J. P. , Groeneveld A. B. Johan , Sipkema Pieter
Published: March 2006

Renal ischemia-reperfusion (I/R) results in vascular dysfunction characterized by a reduced endothelium-dependent vasodilatation and subsequently impaired blood flow. In this study, we investigated the role of Rho kinase in endothelial nitric oxide synthase (eNOS)-mediated regulation of renal blood flow and vasomotor tone in renal I/R. Male Wistar rats were subjected to 60-min bilateral clamping of the renal arteries or sham procedure. One hour before the clamping, the Rho kinase inhibitor Y27632 (1 mg/kg) was intravenously infused. After I/R, renal blood flow was measured using fluorescent microspheres. I/R resulted in a 62% decrease in renal blood flow. In contrast, the blood flow decrease in the group treated with the Rho kinase inhibitor (YI/R) was prevented. Endothelium-dependent vasodilatation of renal arcuate arteries to ACh was measured ex vivo in a pressure myograph. These experiments demonstrated that the in vivo treatment with the Rho kinase inhibitor prevented the decrease in the nitric oxide (NO)-mediated vasodilator response. In addition, after I/R renal interlobar arteries showed a decrease in phosphorylated eNOS and vasodilator-stimulated phosphoprotein, a marker for bioactive NO, which was attenuated by in vivo Rho kinase inhibition. These findings indicate that in vivo inhibition of Rho kinase in renal I/R preserves renal blood flow by improving eNOS function.
Tissue oxygen and hemodynamics in renal medulla, cortex, and corticomedullary junction during hemorrhage-reperfusion
Authors: Whitehouse Tony , Stotz Martin , Taylor Valerie , Stidwill Ray , Singer Mervyn
Published: March 2006

Previous studies of intrarenal perfusion and tissue oxygenation have produced a wide range of results and have not matched tissue oxygen tension (tPo2) with concurrent changes in flow in three distinct regions. We thus used an anesthetized rat model of hemorrhage-reperfusion to address this question. Combined tpo2/laser-Doppler fiber-optic probes were simultaneously sited in cortical, corticomedullary (CMJ), and medullary regions of the left kidney. Total renal blood flow was measured in separate experiments. Recordings were made during exsanguination of 10 and 20% of estimated blood volume at 10-min intervals, followed by shed-blood resuscitation after a further 10 min. The decay in tpo2was then recorded following total cessation of blood flow, allowing estimation of local oxygen consumption. During exsanguination, tPo2was maintained in all intrarenal regions, despite significant falls in blood pressure and total renal blood flow. However, intrarenal flow was redistributed with reduced cortical, unchanged CMJ, and increased medullary blood flow. After resuscitation, significant rises above baseline were seen in blood pressure and in tpo2across all regions. Whereas cortical and medullary flows regained baseline values, CMJ flow fell. The ratio of tpo2to microvascular blood flow increased significantly in all regions during resuscitation, suggesting decreased oxygen consumption. On total cessation of blood flow, the cortex and CMJ showed significant increases in the oxygen decay half-life, consistent with decreased consumption. To our knowledge, this is the first quantitative demonstration of a markedly heterogeneous intrarenal cardiorespiratory response to a hemodynamic insult, with effects most marked at the corticomedullary junction.