bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel enantioselective strong cation exchangers based on sulfodipeptide selectors: Evaluation for enantiomer separation of chiral bases by nonaqueous capillary electrochromatography
Authors: Hebenstreit Dieter , Bicker Wolfgang , Lämmerhofer Michael , Lindner Wolfgang
Published: January 2004

Strong cation exchange (SCX)‐type chiral stationary phases (CSPs) based on β‐amino sulfonic acid‐terminated dipeptide derivatives as chiral selectors, immobilized on thiol‐modified silica particles (3.5 μm), were synthesized and applied to enantiomer separations of chiral bases by nonaqueous capillary electrochromatography (CEC). The effect of structural variations of the sulfodipeptide selectors on the separation factors α was investigated. These studies included variation of the acid‐terminal amino sulfonic acid residue, variation of the configurations, i.e., comparison of the diastereomeric (S,S)‐ and (R,S)‐configurations of the sulfodipeptides, and finally comparison of sulfodipeptide selectors with corresponding β‐amino sulfonic acid analogs. In general, the capillary columns (100 μm ID) packed with the new SCX‐type CSPs showed enantioselectivity for an elaborated set of chiral basic drugs in CEC acting by an enantioselective cation‐exchange retention mechanism. N‐[N‐(4‐Allyloxy‐3,5‐dichlorobenzoyl)‐leucyl]‐2‐amino‐3,3‐dimethylbutane sulfonic acid, in particular with (R,S)‐configuration, turned out to be a more effective SCX‐type selector than a more rigid analog based on N‐[N‐(4‐Allyloxy‐3,5‐dichlorobenzoyl)‐leucyl]‐2‐pyrrolidinemethane sulfonic acid. Both of the former diastereomers were capable to baseline‐resolve the enantiomers of ca. 40% of the tested basic chiral solutes including sympathomimetics and β‐blockers, while for the latter SCX‐type CSPs only 10–20% of the selected solutes afforded resolutions > 1.5.
Ongoing development of two‐dimensional polyacrylamide gel electrophoresis data standards
Authors: Ravichandran Veerasamy , Lubell Joshua , Vásquez Gregory B. , Lemkin Peter , Sriram Ram D. , Gilliland Gary L.
Published: January 2004

We present an approach toward standardizing two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE) data in support of developing a globally relevant proteomics consensus in order to provide more efficient database querying and data comparisons through the establishment of the necessary definitions and interdisciplinary reference fields for both the 2‐D PAGE community, particularly in the proteomics area, and the clinical and experimental biological research communities, in general. This article covers the need for unifying the 2‐D PAGE data through a common data repository, and its usefulness in data standards and data interoperability.
Cyclic electrophoretic and chromatographic separation methods
Authors: Eijkel Jan C. T. , van den Berg Albert , Manz Andreas
Published: January 2004

A review is given of the application of cyclic analytical methods in capillary electroseparation (CE) and liquid chromatography (LC) systems. Cyclic methods have been used since the early sixties in chromatographic systems to overcome pressure limitations to resolution. From the early nineties on they have also been applied in capillary electroseparation systems to overcome voltage limitations. Some basic theory is given, outlining the temporal development of resolution in cyclic CE and LC systems and calculating the maximal resolution that can be obtained as a function of the operational parameters of pressure and electrical field. Simple equations are given for the temporal change in the peak capacity and the loss of peaks from the systems as it occurs in some cyclic systems. Finally, a circular open tubular chromatographic system is proposed using integrated pumping and continuous detection. The performance of such a system is discussed using magnetohydrodynamic and alternating current electroosmotic pumping as examples of integrated pumps and Shah Convolution Fourier transform detection as an example of a continuous detection method.
Determination of cationic mobilities and pKa values of 22 amino acids by capillary zone electrophoresis
Authors: Včeláková Kateřina , Zusková Iva , Kenndler Ernst , Gaš Bohuslav
Published: January 2004

The effective mobilities of the cationic forms of common amino acids – mostly proteinogenic – were determined by capillary zone electrophoresis in acidic background electrolytes at pH between 2.0 and 3.2. The underivatized amino acids were detected by the double contactless conductivity detector. Experimentally measured effective mobilities were fitted with the suitable regression functions in dependence on pH of the background electrolyte. The parameters of the given regression function corresponded to the values of the actual mobilities and the mixed dissociation constants (combining activities and concentrations) of the compound related to the actual ionic strength. McInnes approximation and Onsager theory were used to obtain thermodynamic dissociation constants (pKa) and limiting (absolute) ionic mobilities.
Preparative‐scale, recirculating, pH‐biased binary isoelectric trapping separations
Authors: Shave Evan , Vigh Gyula
Published: January 2004

In order to improve the production rates and lower the specific electrophoretic energy consumption values in preparative‐scale, recirculating, binary isoelectric trapping separations, we propose to add an auxiliary isoelectric agent to the solution in the anodic separation compartment and another to the solution in the cathodic separation compartment to implement pH‐biased isoelectric trapping. The auxiliary isoelectric agents are selected such that they are trapped in the respective anodic and cathodic separation compartments and also, have isoelectric point (pI) values that are different from the pI values of the analytes of interest. By proper selection of the auxiliary isoelectric agents and their concentrations, the analytes of interest can be kept in nonisoelectric, charged state during the entire course of the preparative‐scale, recirculating, binary isoelectric trapping separation. This results in higher electrophoretic mobilities and solubilities for the analytes than in their isoelectric or near‐isoelectric states, and leads to faster binary isoelectric trapping separations.
Preparative free‐flow electrofocusing in a vortex‐stabilized annulus
Authors: Ivory Cornelius F.
Published: January 2004

This paper describes the development of an annular chamber designed for preparative free‐flow electrophoresis which can operate at voltages up to 20 kV, electric fields up to 65 kV/m, and power densities as high as 10 MW/m3. This apparatus uses counter‐rotating fluid vortices to stabilize the aqueous medium in the annulus against natural convection while improving heat and mass transfer over vortex‐free Couette flow. The vortices are generated by rotating the inner surface of the annulus and, if the rotor and stator have complementary shapes, dispersion induced by electrokinetic and electrohydrodynamic flows can be mitigated even at the highest operating voltages. Following a brief overview of contemporary annular free‐flow instrumentation, the theoretical principles for momentum and heat transport in the vortices are discussed in some detail and then the results of several electrofocusing experiments are provided to illustrate the resolving power of this instrument.
Zeta potential of microfluidic substrates: 2. Data for polymers
Authors: Kirby Brian J. , Hasselbrink Ernest F.
Published: January 2004

Zeta potential data are reviewed for a variety of polymeric microfluidic substrate materials. Many of these materials currently used for microchip fabrication have only recently been employed for generation of electroosmotic flow. Despite their recent history, polymeric microfluidic substrates are currently used extensively for microchip separations and other techniques, and understanding of the surface ζ potential is crucial for experimental design. This paper proposes the use of pC (the negative logarithm of the counterion concentration) as a useful normalization for the ζ potential on polymer substrates in contact with indifferent univalent counterions. Normalizing ζ by pC facilitates comparison of results from many investigators. The sparseness of available data for polymeric substrates prevents complete and rigorous justification for this normalization; however, it is consistent with double layer and adsorption theory. For buffers with indifferent univalent cations, normalization with the logarithm of the counterion concentration in general collapses data onto a single ζ/pC vs. pH curve, and (with the exception of PMMA) the repeatability of the data is quite encouraging. Normalization techniques should allow improved ability to predict ζ potential performance on microfluidic substrates and compare results observed with different parameters.
Mutation induction in haploid yeast after split‐dose radiation exposure. II. Combination of UV‐irradiation and X‐rays
Authors: Keller B. , Zölzer F. , Kiefer J.
Published: January 2004

Split‐dose protocols can be used to investigate the kinetics of recovery from radiation damage and to elucidate the mechanisms of cell inactivation and mutation induction. In this study, a haploid strain of the yeast, Saccharomyces cerevisiae, wild‐type with regard to radiation sensitivity, was irradiated with 254‐nm ultraviolet (UV) light and then exposed to X‐rays after incubation for 0–6 hr. The cells were incubated either on nutrient medium or salt agar between the treatments. Loss of reproductive ability and mutation to canavanine resistance were measured. When the X‐ray exposure immediately followed UV‐irradiation, the X‐ray survival curves had the same slope irrespective of the pretreatment, while the X‐ray mutation induction curves were changed from linear to linear quadratic with increasing UV fluence. Incubations up to about 3 hr on nutrient medium between the treatments led to synergism with respect to cell inactivation and antagonism with respect to mutation, but after 4–6 hr the two treatments acted independently. Incubation on salt agar did not cause any change in the survival curves, but there was a strong suppression of X‐ray‐induced mutation with increasing UV fluence. On the basis of these results, we suggest that mutation after combined UV and X‐ray exposure is affected not only by the induction and suppression of DNA repair processes, but also by radiation‐induced modifications of cell‐cycle progression and changes in the expression of the mutant phenotype. Environ. Mol. Mutagen. 43:28–35, 2004. © 2004 Wiley‐Liss, Inc.
Population doubling: A simple and more accurate estimation of cell growth suppression in the in vitro assay for chromosomal aberrations that reduces irrelevant positive results
Authors: Greenwood Susan K. , Hill Rosina B. , Sun Joan T. , Armstrong Michael J. , Johnson Timothy E. , Gara Jennifer P. , Galloway Sheila M.
Published: January 2004

International guidelines for cytotoxicity limits for the in vitro chromosomal aberration assay require reductions in cell growth of greater than 50%. This sets no upper limit on toxicity and there is concern about the number of false or irrelevant results obtained in the aberration assay, i.e., positive results at toxic dose levels only, with no evidence for primary DNA damaging ability and with negative results in the other genotoxicity tests. We have previously proposed that no truly genotoxic compound would be missed if the toxicity of the highest dose did not exceed 50%. Cell growth measured by cell counts as a percentage of controls can underestimate toxicity. For example, if we seed half a million cells per culture, and the controls double to 1 million during the experiment, a culture that truly has no growth will still have a cell count 50% of the control. Measurement of population doublings (PDs) more accurately assesses cell growth. To assess the use of PD in dose selection, we examined previous data from this lab and data from new experiments with “true,” primary DNA damaging clastogens, and with clastogens, including drugs, thought to act indirectly, through cytotoxicity‐associated mechanisms. We compared aberration results where the highest doses scored were based on 50% reductions in final cell counts with results obtained when the highest doses were based on PD. The PD method allows detection of true clastogens, including those that are active in a range with some toxicity, and reduces the number of toxicity‐related “false”‐positive results. Environ. Mol. Mutagen. 43:36–44, 2004. © 2004 Wiley‐Liss, Inc.
Use of a high‐throughput umu‐microplate test system for rapid detection of genotoxicity produced by mutagenic carcinogens and airborne particulate matter
Authors: Oda Yoshimitsu , Funasaka Kunihiro , Kitano Masaaki , Nakama Akihiko , Yoshikura Taro
Published: January 2004

In the present study, we developed a rapid umu‐microplate test system that uses the nitroreductase‐ and O‐acetyltransferase‐overproducing Salmonella typhimurium strain NM3009 and the O‐acetyltransferase‐overproducing S. typhimurium strain NM2009 to detect genotoxic activity in small volume samples. The assay was used to test the genotoxicity of several standard mutagens and environmental samples. Exponentially growing cultures of NM3009, NM2009, and the parental strain TA1535/pSK1002 were incubated in 96‐well microplates with test chemicals both in the presence and in the absence of rat liver S9. The relative β‐galactosidase activities were then determined colorimetrically using either chlorophenol red‐β‐D‐galactopyranoside (CPRG) or O‐nitrophenyl‐β‐D‐galactopyranoside (ONPG) as a measure of umuC gene induction activity. The sensitivities of NM3009 without S9 mix and NM2009 with S9 mix to nitroarenes and aromatic amines were up to 24‐ to 75‐fold higher than those of the parent strain. Induction of umuC gene expression was detected more readily with CPRG than ONPG. The umu‐microplate assay also detected genotoxicity in organic extracts of particulate matter from air samples collected in Osaka City, Japan. The pattern of the responses suggested that the genotoxic activity of the particulate extract was due primarily to nitrated polycyclic aromatic hydrocarbons. Our results indicate that the umu‐microplate assay may be a useful way of carrying out rapid screens for genotoxicity in small‐volume environmental samples. Environ. Mol. Mutagen. 43:10–19, 2004. © 2004 Wiley‐Liss, Inc.
Genetic damage detected in CD‐1 mouse pups exposed perinatally to 3′‐azido‐3′‐deoxythymidine and dideoxyinosine via maternal dosing, nursing, and direct gavage
Authors: Bishop Jack B. , Witt Kristine L. , Tice Raymond R. , Wolfe Gary W.
Published: January 2004

Human immunodeficiency virus (HIV)‐infected pregnant women are administered nucleoside‐analogue antiretrovirals to reduce maternal‐infant viral transmission. The current protocol recommends treating newborns for 6 additional weeks postpartum. The treatment is effective, but the risk of drug‐induced chromosomal damage in neonates remains undefined. We used a mouse model to investigate this concern. In a multigeneration reproductive toxicity study, female CD‐1 mice received 3′‐azido‐3′‐deoxythymidine (AZT) and dideoxyinosine (ddI) (50/250, 75/375, 150/750 mg/kg/day AZT/ddI) by gavage twice daily in equal fractions beginning prior to mating and continuing throughout gestation and lactation. Direct pup dosing (same regimen) began on postnatal day (PND) 4. Peripheral blood erythrocytes of male pups were screened for micronuclei, markers of chromosomal damage, on PNDs 1, 4, 8, and 21. Extraordinary increases in micronucleated cells were noted in pups for each treatment group at each sampling time; treated dams exhibited smaller yet significant increases in micronucleated erythrocytes. The frequencies of micronucleated cells in untreated pups were higher than in the untreated dams, and all pups had markedly elevated levels of circulating reticulocytes compared to dams. These observations suggest that fetal and neonatal mouse hematopoietic precursor cells have heightened sensitivity to genotoxic agents, perhaps due to rapid cell proliferation during the perinatal period of development. The amount of genetic damage observed in treated pups raises concern for the potential of similar damage in humans. Investigations of chromosomal integrity in exposed newborns and children are recommended. Environ. Mol. Mutagen. 43:3–9, 2004. © 2004 Wiley‐Liss, Inc.
Comparative genomic hybridization analysis of N‐methyl‐N′‐nitrosoguanidine‐induced rat gastrointestinal tumors discloses a cytogenetic fingerprint
Authors: Corso Chiara , Parry James M.
Published: January 2004

Exposure to N‐nitroso compounds is thought to play a key role in the development of gastric cancer in humans. The alkylating agent N‐methyl‐N′‐nitrosoguanidine (MNNG) is carcinogenic in a number of animal models and its preferential target tissue is the gastrointestinal (GI) tract. The genetic synteny among rats and humans makes the rat a useful model for induced tumorigenesis. However, because of the limited availability of genetic information, cytogenetic and molecular studies are rarely performed in the rat. We report an investigation of eight MNNG‐induced rat gastric tumors by comparative genomic hybridization (CGH). The tumors were from forestomach (induced by a single dose of MNNG) and from pylorus (induced by chronic exposure). CGH identified a genetic fingerprint of chromosomal imbalances common to the two types of the tumors. Frequent gains were observed at 9q11–q12, 15q22–25, and Xq11–q12. Forestomach carcinomas were also characterized by gains in 7q11–q12, 20q13, and Yq12. Homology studies between the rat and human genomes indicate the presence of genes within these regions with potential relevance to tumorigenesis in the GI tract. Our findings provide new insights into the location of genes involved in MNNG‐induced gastric cancer initiation and/or progression in the rat. Environ. Mol. Mutagen. 43:20–27, 2004. © 2004 Wiley‐Liss, Inc.
Effect of cyanidin 3‐O‐β‐glucopyranoside on micronucleus induction in cultured human lymphocytes by four different mutagens
Authors: Fimognari Carmela , Berti Fausto , Cantelli‐Forti Giorgio , Hrelia Patrizia
Published: January 2004

The anthocyanin cyanidin 3‐O‐β‐glucopyranoside (Cy‐g) is reported to be one of the most effective antioxidants, but little is currently known regarding its potential chemopreventive properties. In this study, we evaluated the ability of Cy‐g to protect cultured human lymphocytes from micronucleus (MN) induction by four different mutagens: ethyl methanesulfonate (EMS), colchicine (COL), H2O2, and mitomycin C (MMC). To gain insight into the mechanisms of action of Cy‐g, the cultures were treated with the compound before, during, and after treatment with the mutagens; in addition, the cultures were evaluated for the induction of apoptosis. When used by itself, up to 100 μg/ml of Cy‐g was nongenotoxic, while 100 μg/ml Cy‐g reduced the replicative index of the cells by nearly 50%. In addition, Cy‐g was able to reduce the frequency of micronuclei induced by EMS, COL, and H2O2 using all three treatment protocols, but it had no significant effect on MN induction by MMC in any of the protocols. Apoptosis was produced in the cultures treated with Cy‐g alone and was increased under conditions in which Cy‐g produced anti‐genotoxic effects, suggesting that Cy‐g mediated‐apoptosis may remove highly damaged cells. However, increases in apoptosis were found under conditions in which Cy‐g was not significantly anti‐genotoxic, indicating that the increases in apoptosis were not sufficient to account for the anti‐genotoxicity of Cy‐g. Taken together, our findings indicate that Cy‐g possesses anti‐genotoxic activity in vitro, which suggests its potential use as a chemopreventive agent. Environ. Mol. Mutagen. 43:45–52, 2004. © 2004 Wiley‐Liss, Inc.
Barchan‐shaped ripple marks in a wave flume
Authors: Endo Noritaka , Kubo Hidehito , Sunamura Tsuguo
Published: January 2004

Barchans, isolated crescent‐shaped bedforms, are believed to be formed under almost unidirectional wind or water ﬂows and limited sand supply. The formation of barchan morphologies under the action of purely oscillatory wave motion has not yet been fully investigated. The present study attempted to form barchan topography in a wave ﬂume and to compare this with barchans in the ﬁeld. Barchan morphologies of ripple size, called the barchan ripples, were generated from a ﬂat bed by the action of waves. The horn width, the distance between horn tips, of the barchan ripples increased linearly with an increase in the total length, the overall length projected on the centre line of the barchan, with a coefﬁcient common to barchan dunes in deserts. The ratio of horn length to horn width of the barchan ripples was smaller than that of barchan dunes, but similar to that of subaqueous barchans in the ﬁeld. The longer the wave period was, the larger the ratio of the body length to horn width became. Most subaqueous barchans formed under waves (in the laboratory) and unidirectional ﬂows (in the ﬁeld) had blunter horns than subaerial barchans. The shape of the barchan ripples changed with wave period. The outer rim became rounder with increasing wave period. The relationship between the base area and the height of barchan morphologies seems to be linear, with a constant coefﬁcient for the scale from ripples to dunes. The barchan ripples showed a linear relationship between the height and the horn width, similar to that for barchan dunes. The migration speed of the barchan ripples was proportional to the cube of the ﬂow velocity and was inversely proportional to height. The same relation with a different value of the coefﬁcient was obtained for barchan dunes. Copyright © 2004 John Wiley & Sons, Ltd.
Sediment movement rates and processes on cinder cones in the maritime Subantarctic (Marion Island)
Authors: Holness Stephen Dale
Published: January 2004

Sediment transport in the scoria areas of Marion Island is primarily the result of needle‐ice‐induced frost creep associated with diurnal soil frost cycles. Clasts move most rapidly in ﬁne textured areas (532 mm a−1; SD 382), more slowly in stony areas (161 mm a−1; SD 179), and most slowly in blocky areas (26 mm a−1; SD 23). Movement rates increase with increasing frost susceptibility of sediments, slope angle and altitude. The heave of dowels indicates that frost heave is active in all the scoria areas examined. The depth of effective frost heave increases with increasing altitude, with frost heave being restricted to the upper 100 mm of the soil in low altitude areas (<200 m). The heave of 150 mm dowels at the higher altitude sites provides evidence for segregation ice formation at depths greater than those associated with needle ice and diurnal soil frost cycles. Vertical movement proﬁles show a concave downslope proﬁle, with sediment movement rates being most rapid at the soil surface and decreasing rapidly with depth. This proﬁle shape is typical of areas dominated by diurnal freeze–thaw cycles and needle ice. The capture of sediments moving downslope in troughs and the sampling of material lifted by needle ice, suggest that sediment transport by needle ice under present conditions is extremely effective. Observations suggest that although both ﬁne material and clasts are transported downslope, some preferential transport of clasts occurs.

Experiment results and observations of soil frost processes suggest that frost creep associated with needle ice activity is the dominant slope process in the scoria areas of Marion Island. Other slope processes such as slopewash and debris ﬂows appear to play a relatively minor and localized role in sediment transport. It is suggested that needle ice activity is likely to be the dominant geomorphic agent in other areas of the Subantarctic with similar climatic characteristics to Marion Island. Copyright © 2004 John Wiley & Sons, Ltd.
Multipath parameters estimation with a reduced complexity unitary‐SAGE algorithm
Authors: Min Tan Chor , Beach Mark A. , Nix Andrew
Published: January 2004

Estimating multipath parameters from multi‐dimensional measurement data using maximum‐likelihood methods can be a very time‐consuming process due to the iterative nature of these algorithms. Although the Space‐Alternating Generalized Expectation‐maximization (SAGE) algorithm has a higher convergence speed compared to the classical Expectation‐Maximization (EM) algorithm, it can still be computational‐intensive. Since most of the computations of the SAGE algorithm are concentrated in the maximization step (M‐step), we propose a new implementation of this algorithm, namely the Unitary‐SAGE (U‐SAGE) algorithm, where the entire M‐step in every iteration is evaluated in the real‐valued domain. This helps to reduce the processing time and memory requirements of the classical SAGE algorithm since all computations of the M‐step are performed using efficient matrix manipulation. Here, we present the general implementation of the U‐SAGE algorithm in the frequency domain when applied in both the element‐space (ES) and the newly developed beamspace (BS) domains. We show that the convergence characteristics and accuracy of the newly proposed U‐SAGE algorithm is similar to the classical SAGE algorithm, but with a significant reduction in overall computation time and memory usage. Copyright © 2004 AEI
Numerical simulation of turbulent free surface flow with two‐equation k–ε eddy‐viscosity models
Authors: Ferreira V. G. , Mangiavacchi N. , Tomé M. F. , Castelo A. , Cuminato J. A. , McKee S.
Published: January 2004

This paper presents a finite difference technique for solving incompressible turbulent free surface fluid flow problems. The closure of the time‐averaged Navier–Stokes equations is achieved by using the two‐equation eddy‐viscosity model: the high‐Reynolds k–ε (standard) model, with a time scale proposed by Durbin; and a low‐Reynolds number form of the standard k–ε model, similar to that proposed by Yang and Shih. In order to achieve an accurate discretization of the non‐linear terms, a second/third‐order upwinding technique is adopted. The computational method is validated by applying it to the flat plate boundary layer problem and to impinging jet flows. The method is then applied to a turbulent planar jet flow beneath and parallel to a free surface. Computations show that the high‐Reynolds k–ε model yields favourable predictions both of the zero‐pressure‐gradient turbulent boundary layer on a flat plate and jet impingement flows. However, the results using the low‐Reynolds number form of the k–ε model are somewhat unsatisfactory. Copyright © 2004 John Wiley & Sons, Ltd.
A stabilized finite element predictor–corrector scheme for the incompressible Navier–Stokes equations using a nodal‐based implementation
Authors: Codina R. , Folch A.
Published: January 2004

A finite element model to solve the incompressible Navier–Stokes equations based on the stabilization with orthogonal subscales, a predictor–corrector scheme to segregate the pressure and a nodal based implementation is presented in this paper. The stabilization consists of adding a least‐squares form of the component orthogonal to the finite element space of the convective and pressure gradient terms, which allows to deal with convection‐dominated flows and to use equal velocity–pressure interpolation. The pressure segregation is inspired in fractional step schemes, although the converged solution corresponds to that of a monolithic time integration. Finally, the nodal‐based implementation is based on an a priori calculation of the integrals appearing in the formulation and then the construction of the matrix and right‐hand side vector of the final algebraic system to be solved. After appropriate approximations, this matrix and this vector can be constructed directly for each nodal point, without the need to loop over the elements and thus making the calculations much faster. Some issues related to this implementation for fractional step and our predictor–corrector scheme, which is the main contribution of this paper, are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Level‐set based numerical simulation of a migrating and dissolving liquid drop in a cylindrical cavity
Authors: Bassano Edmondo
Published: January 2004

In the present paper the dissolution of a binary liquid drop having a miscibility gap and migrating due to thermo‐solutal capillary convection in a cylindrical cavity is studied numerically. The interest in studying this problem is twofold. From a side, in the absence of gravity, capillary migration is one of the main physical mechanisms to set into motion dispersed liquid phases and from the other side, phase equilibria of multi‐component liquid systems, ubiquitous in applications, often exhibit a miscibility gap. The drop capillary migration is due to an imposed temperature gradient between the cavity top and bottom walls. The drop dissolution is due to the fact that initial composition and volume values, and thermal boundary conditions are only compatible with a final single phase equilibrium state. In order to study the drop migration along the cavity and the coupling with dissolution, a previously developed planar two‐dimensional code is extended to treat axis‐symmetric geometries. The code is based on a finite volume formulation. A level‐set technique is used for describing the dynamics of the interface separating the different phases and for mollifying the interface discontinuities between them. The level‐set related tools of redistancing and off‐interface extension are used to enhance code resolution in the critical interface region. Migration speeds and volume variations are determined for different drop radii. Copyright © 2004 John Wiley & Sons, Ltd.
Higher‐order upwind leapfrog methods for multi‐dimensional acoustic equations
Authors: Kim Cheolwan
Published: January 2004

A non‐dissipative and very accurate one‐dimensional upwind leapfrog method was successfully extended to higher‐order and multi‐dimensional acoustic equations. The governing equations in characteristic form and staggered grid were utilized to preserve the accuracy. Fourier analysis was performed to find the accurate scheme for acoustics and the resultant two‐dimensional methods were successfully applied to several classical test cases. Copyright © 2004 John Wiley & Sons, Ltd.
Space–time integrated least squares: a time‐marching approach
Authors: Besson Olivier , de Montmollin Gautier
Published: January 2004

A time‐marching formulation is derived from the space–time integrated least squares (STILS) method for solving a pure hyperbolic convection equation and is numerically compared to various known methods. Copyright © 2004 John Wiley & Sons, Ltd.
An improved numerical simulator for multiphase flow in porous media
Authors: Garrido I. , Fladmark G. E. , Espedal M.
Published: January 2004

In basin modelling the thermodynamics of a multicomponent multiphase fluid flux are computationally too expensive when derived from an equation of state and the Gibbs equality constraints. In this article we present a novel implicit molar mass formulation technique using binary mixture thermodynamics. The two proposed solution methods, with and without cross derivative terms between components, are based on a preconditionedNewton‐GMRESscheme for each time‐step with analytical computation of the derivatives. These new algorithms reduce significantly the numerical effort for the computation of the molar masses, and we illustrate the behavior of these methods with numerical computations. Copyright © 2004 John Wiley & Sons Ltd.
A ‘poor man's Navier–Stokes equation’: derivation and numerical experiments—the 2‐D case
Authors: McDonough J. M. , Huang M. T.
Published: January 2004

We present a systematic derivation of a discrete dynamical system directly from the two‐dimensional incompressible Navier–Stokes equations via a Galerkin procedure and provide a detailed numerical investigation (covering more than 107 cases) of the characteristic behaviours exhibited by the discrete mapping for specified combinations of the four bifurcation parameters. We show that this simple 2‐D algebraic map, which consists of a bilinearly coupled pair of logistic maps, can produce essentially any (temporal) behaviour observed either experimentally or computationally in incompressible Navier–Stokes flows as the bifurcation parameters are varied in pairs over their ranges of stable behaviours. We conclude from this that such discrete dynamical systems deserve consideration as sources of temporal fluctuations in synthetic‐velocity forms of subgrid‐scale models for large‐eddy simulation. Copyright © 2004 John Wiley & Sons, Ltd.
From the other side of the academy to academic leadership roles: Crossing the great divide
Authors: Land Patricia C.
Published: January 2004

Evolutionary paths for faculty are no longer sacred routes to chief academic officer roles.
The role of doctoral programs in preparing faculty for multiple roles in the academy
Authors: Speck Bruce W.
Published: January 2004

The transition from faculty to administration roles, as well as full‐orbed faculty positions, would be smoother if doctoral programs were expanded to include a focus on collegiality and service.
Faculty governance and effective academic administrative leadership
Authors: Johnston Susan Whealler
Published: January 2004

Faculty members desiring administrative roles can find the structure and function of shared governance a fertile ground for growth through practical experience in institutional decision making.
Promoting diversity in academic leadership
Authors: Page Oscar C.
Published: January 2004

Five key features of community undergird commitment to diversity in a university or college based on the principles of servant leadership.
Bedside manner and effective academic administrative leadership
Authors: Gilley Daryl
Published: January 2004

Bedside manner is about relationships, and tailoring attitudes, approaches, and demeanor to accommodate individuals results in improved collegiality.
Microarray proﬁle analysis of toxic cocaine‐induced alterations in the expression of mouse brain gene sequences: a possible ‘protective’ effect of buprenorphine
Authors: Hayase Tamaki , Yamamoto Yoshiko , Yamamoto Keiichi , Muso Eri , Shiota Kohei
Published: January 2004

Using a mouse brain cDNA microarray consisting of 2688 gene sequences, which include unknown sequences with the empirical possibility of expression in the brain, the effects of repeated toxic doses of intraperitoneal (i.p.) cocaine (40 mg kg−1, 4 days) on the expression proﬁle of the cerebral genes were investigated. The modiﬁcations in this proﬁle caused by buprenorphine (BUP) (0.25 mg kg−1 i.p., 4 days), a protective drug against cocaine, were also examined. In the cocaine group, the expression levels reached the recommended increased levels (≥2 times the control value in the saline‐treated control group) in 24.0% of the genes but were equal to or less than the recommended attenuation levels (≤0.5 times the control value) in 14.0% of the genes. In the cocaine–BUP group, the expression levels of the other 15.4% of the total genes were increased and those of the other 18.2% of the total genes were attenuated. However, corresponding to the BUP‐attenuated mortality rate and severity of seizures, the expression levels of 80.1% of the cocaine‐modiﬁed genes with above‐background levels recovered to the recommended normal levels (>0.5 and <2 times the control value). Although statistically signiﬁcant modiﬁcations in the expression of cocaine‐ or BUP‐related brain‐region‐speciﬁc genes were not proved using whole cerebrums, including many unknown genes, our results suggest that the expression of genes related to neuronal cell damage, including non‐peculiar genes related to the damage accompanying convulsive seizures and malignant tumors, were normalized and the genes related to the protection of neural cells were induced by BUP. Copyright © 2004 John Wiley & Sons, Ltd.
Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin‐induced nephrotoxicity in rats
Authors: Özen Süleyman , Akyol Ömer , Iraz Mustafa , Söğüt Sadık , Özuğurlu Fikret , Özyurt Hüseyin , Odacı Ersan , Yıldırım Zeki
Published: January 2004

We have investigated the effect of caffeic acid phenethyl ester (CAPE) on cisplatin‐induced nephrotoxicity in rats. Administration of a single dose of cisplatin resulted in the elevation of blood urea nitrogen and creatinine in serum, as well as nitric oxide in kidney tissue of rats. Cisplatin also caused reduction of catalase (P < 0.0001), superoxide dismutase (P = 0.149) and glutathrone peroxidase (P < 0.0001) activities in kidney tissue. Although cisplatin caused elevation in malondialdehyde levels and myeloperoxidase activities in kidney tissue, they were not statistically signiﬁcant. Caffeic acid phenethyl ester was found to be protective against cisplatin‐induced antioxidant enzyme reductions. Treatment with free‐radical scavenger CAPE attenuated the increase in plasma blood urea nitrogen and kidney nitric oxide levels, and showed histopathological protection against cisplatin‐induced acute renal failure. Extensive epithelial cell vacuolization, swelling, desquamation and necrosis were observed in the kidney of the cisplatin‐treated rat. There were also larger tubular lumens in cisplatin‐treated rats than those of the control and the CAPE groups. Caffeic acid phenethyl ester caused a marked reduction in the extent of tubular damage. It is concluded that administration of cisplatin imposes an oxidative stress to renal tissue and CAPE confers protection against the oxidative damage associated with cisplatin. This mechanism may be attributed to its free‐oxygen‐radical scavenging activity. Copyright © 2004 John Wiley & Sons, Ltd.
Examination of changes in connective tissue macromolecular components of large white pig skin following application of lewisite vapour
Authors: Lindsay Christopher D. , Hambrook Joy L. , Brown Roger F. R. , Platt Jan C. , Knight Robert , Rice Paul
Published: January 2004

The aim of this study was to provide information about the degradative processes that occur in major connective tissue components in skin following exposure of large white pigs to Lewisite vapour. Of particular interest were alterations in glycoproteins, which are known to mediate dermo‐epidermal attachment (laminin and type IV collagen) and the main collagen found in the dermis (type III collagen). The immunostaining of transfer blots from skin extracts run on sodium dodecyl sulphate polyacrylamide gel electrophoresis gels revealed no evidence of cross‐linking of laminin or of type III or IV collagen. However, there was evidence of a very considerable degradation of laminin and, to a lesser extent, of type IV collagen. Type III collagen did not appear to be degraded in skin exposed to Lewisite. These degradative processes appeared to be more severe than found in previous studies in Yucatan mini‐pigs percutaneously exposed to sulphur mustard, in which only laminin was found to undergo partial cleavage rather than wholesale degradation.

The results suggest that damage to macromolecular components in the sub‐epidermal basement membrane in skin which mediate dermo‐epidermal separation processes may be a common feature in the mechanism of action of vesicating agents such as Lewisite and sulphur mustard. It is of interest that the damage to laminin in this study appeared to be more severe than that previously found for sulphur mustard. This suggests that skin can suffer substantial damage yet, in the case of Lewisite exposure, recover relatively quickly. However, Lewisite is not an alkylating agent. Sulphur mustard, in contrast, generates characteristically slow healing lesions, most probably because of its ability to alkylate cell types that normally would be involved in skin regenerative processes. © Crown copyright 2004. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
Low‐level exposure of guinea pigs and marmosets to sarin vapour in air: lowest‐observable‐adverse‐effect level (LOAEL) for miosis
Authors: Helden Herman P. M. van , Trap Henk C. , Kuijpers Willem C. , Oostdijk John P. , Benschop Hendrik P. , Langenberg Jan P.
Published: January 2004

The purpose of this pilot study was to indicate, for low‐level exposure of conscious guinea pigs and marmoset monkeys to sarin vapour in air, the lowest‐observable‐adverse‐effect level (LOAEL) of sarin for miosis. This is the concentration × time (C·t) value (t = 5 h) of exposure at which miosis becomes signiﬁcant.

The ratio of pupil and iris diameters, measured on digital photographs taken on‐line during exposure, was calculated as a measure for miosis. The exposure concentrations were in the range 7–150 µg m−3 and the exposure times needed to achieve signiﬁcant miosis were in the range 10–300 min. Both vehicle‐ and pyridostigmine‐pretreated animals were used in the experiments. The latter pretreatment resulted in ca. 30% inhibition of erythrocyte acetylcholinesterase in both species.

In vehicle‐pretreated guinea pigs and marmosets the pupil size was decreased signiﬁcantly (P < 0.05) at sarin doses of 1.8 ± 0.3 and 2.5 ± 0.8 mg min m−3, respectively. In pyridostigmine‐pretreated guinea pigs and marmosets the pupil size was affected signiﬁcantly (P < 0.05) at 1.8 ± 0.5 and 3.0 ± 0.8 mg min m−3, respectively. Evidently there is no signiﬁcant inﬂuence of pyridostigmine pretreatment on the LOAEL. These data were addressed in light of the recommended occupational and detection limits for sarin vapour in air. It was concluded that miosis will occur during low‐level sarin exposure at levels that are not detectable by the currently ﬁelded alarm systems, assuming that humans are as sensitive for sarin vapour in air as guinea pigs and marmosets. Copyright © 2004 John Wiley & Sons, Ltd.
Assessment of the skin sensitization potency of eugenol and its dimers using a non‐radioisotopic modiﬁcation of the local lymph node assay
Authors: Takeyoshi Masahiro , Noda Shuji , Yamazaki Shunsuke , Kakishima Hiroshi , Yamasaki Kanji , Kimber Ian
Published: January 2004

Allergic contact dermatitis is a serious health problem. There is a need to identify and characterize skin sensitization hazards, particularly with respect to relative potency, so that accurate risk assessments can be developed. For these purposes the murine local lymph node assay (LLNA) was developed. Here, we have investigated further a modiﬁcation of this assay, non‐radioisotopic LLNA, which in place of tritiated thymidine to measure lymph node cell proliferation employs incorporation of 5‐bromo‐2'‐deoxyuridine. Using this method we have examined the skin sensitizing activity of eugenol, a known human contact allergen, and its dimers 2,2'‐dihydroxyl‐3,3'‐dimethoxy‐5,5'‐diallyl‐biphenyl (DHEA) and 4,5'‐diallyl‐2'‐hydroxy‐2,3'‐dimethoxy phenyl ether (DHEB). Activity in the guinea pig maximization test (GPMT) also measured. On the basis of GPMT assays, eugenol was classiﬁed as a mild skin sensitizer, DHEA as a weak skin sensitizer and DHEB as an extreme skin sensitizer. In the non‐radioisotopic LLNA all chemicals were found to give positive responses insofar as each was able to provoke a stimulation index (SI) of ≥3 at one or more test concentrations. The relative skin sensitizing potency of these chemicals was evaluated in the non‐radioisotopic LLNA by derivation of an ec3 value (the concentration of chemical required to provoke an SI of 3). The ec3 values calculated were 25.1% for eugenol, >30% for DHEA and 2.3% for DHEB. Collectively these data suggest that assessments of relative potency deriving from non‐radioisotopic LLNA responses correlate well with evaluations based on GPMT results. These investigations provide support for the proposal that the non‐radioisotopic LLNA may serve as an effective alternative to the GPMT where there is a need to avoid the use of radioisotopes. Copyright © 2004 John Wiley & Sons, Ltd.
Concentrations of parabens in human breast tumours
Authors: Darbre P. D. , Aljarrah A. , Miller W. R. , Coldham N. G. , Sauer M. J. , Pope G. S.
Published: January 2004

Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long‐term, low‐dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin‐layer chromatography. More detailed studies enabled identiﬁcation and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high‐pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 ± 4.2 ng g−1 tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 ± 2.2 ng g−1 tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues. Copyright © 2004 John Wiley & Sons, Ltd.
Colon cancer specific nuclear matrix protein alterations in human colonic adenomatous polyps
Authors: Brünagel Gisela , Schoen Robert E. , Getzenberg Robert H.
Published: January 2004

Most colon cancers arise within preexisting adenomatous polyps or adenomas. The slow evolution from the non‐invasive premalignant lesion, the adenomatous polyp, to invasive cancer supports a strategy of early detection. Recently, we identified unique nuclear matrix proteins (NMPs) specific for colon cancer (CC2, CC3, CC4, CC5). Most of the NMPs identified are common to all cell types, but several identified NMPs are tissue and cell line specific. The objective of this study is to describe and characterize the NMP profile of premalignant adenomatous colon polyps. Specifically when in the adenoma‐carcinoma sequence four specific colon cancer NMPs, previously described, appear. Using two‐dimensional (2‐D) gel analysis 20 colon polyps (one juvenile polyp, six tubular adenoma (TA), seven tubulovillous adenoma (TVA), six TVA with focal high‐grade dysplasia (HGD), were analyzed for the presence of four (CC2, CC3, CC4, CC5) specific NMPs. CC2 was not seen in any of the premalignant polyps. CC5 was present in only two premalignant TVA with HGD and in one TA. CC3 and CC4 were present in most adenomas. None of the NMPs were seen in the juvenile polyp, which is not considered to be a precursor of colon cancer. CC2 and CC5 are NMPs expressed at the junction of an advanced adenoma and invasive colorectal cancer. CC3 and CC4 are expressed earlier in the evolution of adenomatous polyps. Development of an assay to these proteins may serve as a new method for early detection of colorectal cancer. © 2003 Wiley‐Liss, Inc.