bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous enhancement in strength and elongation of waterborne polyurethane and role of star‐like network with lignin core
Authors: Cui Guojuan , Fan Honglei , Xia Wenbing , Ai Fujin , Huang Jin
Published: March 2008

We have reported that a star‐like network structure with lignin as center in polyurethane resulted in the simultaneous enhancement in mechanical strength and elongation. In this study, we aimed to enhance the mechanical properties of waterborne polyurethane by adding nitro‐lignin (NL) to form analogical star‐like network. It was found that the resultant material has optimal mechanical performances when the NL content is 3.0 wt %, i.e., its apparent mechanical strength and elongation increased by about 80% at one time. Especially, its real mechanical strength reaches 71.3 MPa at this time, which is 3.6‐fold over that of neat waterborne polyurethane material. The simultaneous enhancements in strength and elongation are attributed to the forming of star‐like network in the composites. The stiffness of lignin improved the mechanical strength, while the entangling and crosslinking in polyurethane component increased the elongation. However, higher NL loading and lower grafting level induced the forming of supramolecular NL aggregates, and hence greatly inhibited star‐like network, resulting in lower mechanical strength and elongation. However, the Young's modulus of the material is enhanced with an increase of rigid supramolecular aggregates. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Electrostatic contribution to the energy of binding of aromatic ligands with DNA
Authors: Kostjukov V. V. , Khomytova N. M. , Davies D. B. , Evstigneev M. P.
Published: March 2008

The method of solution of the nonlinear Poisson–Boltzmann equation was used to calculate electrostatic energy of binding of various aromatic ligands with DNA oligomers of different length. Analysis of the electrostatic contribution was made in terms of a two‐step DNA binding process: formation of the intercalation cavity and insertion of the ligand. The total electrostatic energy was also partitioned into components: the energy of atom–atom coulombic interactions and the energy of interaction with surrounding water. The results indicate that electrostatic interactions are, as a whole, unfavorable to the intercalation process and that a correct analysis of structure‐energy interrelation for Ligand‐DNA interactions should only be accomplished at the level of the components rather than at the level of total electrostatic energy. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 680–690, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
The intracellular and nuclear‐targeted delivery of an antiandrogen drug by carrier peptides
Authors: Hodoniczky Jason , Sims Colette G. , Best Wayne M. , Bentel Jacqueline M. , Wilce Jacqueline A.
Published: March 2008

Cell permeable carrier peptides are currently of interest for their potential to improve the delivery of bioactive molecules into cells and to specific cellular compartments. We have investigated the activity of a derivative of the antiandrogen drug, bicalutamide, attached to the cell‐permeable carrier peptide penetratin®. We have used both disulfide (labile) and thioether (nonlabile) linkages to attach the bicalutamide derivative to the peptide in order to assess whether one type of chemistry has advantages over the other. In addition we have added a nuclear localization sequence (NLS) to the carrier peptide to investigate whether localization of the drug to the nucleus of the cell affects the activity of the drug. Biotin‐labeled peptides were used to demonstrate that the carrier peptide is rapidly accumulated inside cultured cells, and that the incorporation of an NLS in the sequence results in its nuclear targeting. The bicalutamide derivative linked to carrier peptides via a disulfide‐linkage exerted no greater antiproliferative effect in LNCaP cells, than the bicalutamide derivative alone. The bicalutamide derivative linked to the carrier peptide by a non‐labile thioether linkage showed a similar activity profile. When the construct includes a nuclear targeting sequence, however, a markedly increased antiproliferative effect was observed. This study has thus shown that the activity of bicalutamide may be enhanced by the nonlabile attachment of a cell‐permeable and nuclear‐targeted peptide, which has implications for the development of novel antiandrogens for the treatment of prostate cancer. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 595–603, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Intimate coupling of photocatalysis and biodegradation in a photocatalytic circulating‐bed biofilm reactor
Authors: Marsolek Michael D. , Torres César I. , Hausner Martina , Rittmann Bruce E.
Published: March 2008

Coupling advanced oxidative pretreatment with subsequent biodegradation demonstrates potential for treating wastewaters containing biorecalcitrant and inhibitory organic constituents. However, advanced oxidation is indiscriminate, producing a range of products that can be too oxidized, unavailable for biodegradation, or toxic themselves. This problem could be overcome if advanced oxidation and biodegradation occurred together, an orientation called intimate coupling; then, biodegradable organics are removed as they are formed, focusing the chemical oxidant on the non‐biodegradable fraction. Intimate coupling has seemed impossible because the conditions of advanced oxidation, for example, hydroxyl radicals and sometimes UV‐light, are severely toxic to microorganisms. Here, we demonstrate that a novel photocatalytic circulating‐bed biofilm reactor (PCBBR), which utilizes macro‐porous carriers to protect biofilm from toxic reactants and UV light, achieves intimate coupling. We demonstrate the viability of the PCBBR system first with UV only and acetate, where the carriers grew biofilm and sustained acetate biodegradation despite continuous UV irradiation. Images obtained by scanning electron microscopy and confocal laser scanning microscopy show bacteria living behind the exposed surface of the cubes. Second, we used slurry‐form Degussa P25 TiO2 to initiate photocatalysis of inhibitory 2,4,5‐trichlorophenol (TCP) and acetate. With no bacterial carriers, photocatalysis and physical processes removed TCP and COD to 32% and 26% of their influent levels, but addition of biofilm carriers decreased residuals to
2% and 4%, respectively. Biodegradation alone could not remove TCP. Photomicrographs clearly show that biomass originally on the exterior of the carriers was oxidized (charred), but biofilm a short distance within the carriers was protected. Finally, we coated TiO2 directly onto the carrier surface, producing a hybrid photocatalytic‐biological carrier. These carriers likewise demonstrated the concept of photocatalytic degradation of TCP coupled with biodegradation of acetate, but continued TCP degradation required augmentation with slurry‐form TiO2.Biotechnol. Biotechnol. Bioeng. 2008;101: 83–92. © 2008 Wiley Periodicals, Inc.
The roles of galactitol, galactose‐1‐phosphate, and phosphoglucomutase in galactose‐induced toxicity in Saccharomyces cerevisiae
Authors: de Jongh Willem A. , Bro Christoffer , Ostergaard Simon , Regenberg Birgitte , Olsson Lisbeth , Nielsen Jens
Published: March 2008

The uptake and catabolism of galactose by the yeast Saccharomyces cerevisiae is much lower than for glucose and fructose, and in applications of this yeast for utilization of complex substrates that contain galactose, for example, lignocellulose and raffinose, this causes prolonged fermentations. Galactose is metabolized via the Leloir pathway, and besides the industrial interest in improving the flux through this pathway it is also of medical relevance to study the Leloir pathway. Thus, genetic disorders in the genes encoding galactose‐1‐phosphate uridylyltransferase or galactokinase result in galactose toxicity both in patients with galactosemia and in yeast. In order to elucidate galactose related toxicity, which may explain the low uptake and catabolic rates of S. cerevisiae, we have studied the physiological characteristics and intracellular metabolite profiles of recombinant S. cerevisiae strains with improved or impaired growth on galactose. Aerobic batch cultivations on galactose of strains with different combinations of overexpression of the genes GAL1, GAL2, GAL7, and GAL10, which encode proteins that together convert extracellular galactose into glucose‐1‐phosphate, revealed a decrease in the maximum specific growth rate when compared to the reference strain. The hypothesized toxic intermediate galactose‐1‐phosphate cannot be the sole cause of galactose related toxicity, but indications were found that galactose‐1‐phosphate might cause a negative effect through inhibition of phosphoglucomutase. Furthermore, we show that galactitol is formed in S. cerevisiae, and that the combination of elevated intracellular galactitol concentration, and the ratio between galactose‐1‐phosphate concentration and phosphoglucomutase activity seems to be important for galactose related toxicity causing decreased growth rates. Biotechnol. Bioeng. 2008;101: 317–326. © 2008 Wiley Periodicals, Inc.
Interrupting Vibrio cholerae infection of human epithelial cells with engineered commensal bacterial signaling
Authors: Duan Faping , March John C.
Published: March 2008

Vibrio cholerae El Tor serotypes are largely responsible for outbreaks of cholera in the developing world. The infection cycle for some strains of V. cholerae is coordinated, at least in part, through quorum sensing. That is, the expression of virulence genes depends on the concentration of V. cholerae autoinducers cholera autoinducer 1 (CAI‐1) and autoinducer 2 (AI‐2). High concentrations of CAI‐1 and AI‐2 have been shown previously to inhibit virulence gene expression. We have demonstrated here that a commensal bacterium, E. coli Nissle 1917 (Nissle), can be engineered to express CAI‐1 (Nissle expresses AI‐2 natively) and effectively interrupt V. cholerae virulence. We engineered Nissle to express CAI‐1 under control of the lac promoter, and demonstrated inhibition of V. cholerae expression of cholera toxin (CT, as indicated by presence of the CT subunit B (CTB)) and of the toxin co‐regulated pilus (TCP, as indicated by the relative transcript of TCP subunit A (TCPA)) in both monocultures of V. cholerae and co‐cultures with epithelial cells, Nissle, and V. cholerae. In the model system of Caco‐2 epithelia incubated with V. cholerae, we demonstrated that co‐cultures with Nissle expressing CAI‐1 activity reduced CTB binding to Caco‐2 cells by 63% over co‐cultures with wild‐type Nissle. Further, cultures with Nissle expressing CAI‐1 had significantly lower TCPA transcription than controls with wild‐type Nissle. These results represent a significant step towards a prophylactic method for combating enteric disease through engineered quorum signaling within a commensal bacterial strain. Biotechnol. Biotechnol. Bioeng. 2008;101: 128–134. © 2008 Wiley Periodicals, Inc.
Time‐lapse analysis and microdissection of living 3D melanoma cell cultures for genomics and proteomics
Authors: Demou Zoe N.
Published: March 2008

A novel technique is presented for the monitoring and morphological characterization of 3D cell cultures targeted for laser capture microdissection (LCM). A custom‐made chamber enables time‐lapse topography and pre‐selection of cell targets in order to minimize microdissection time, optimizing the quality of biomolecules for downstream analyses. The method complements the recently presented novel application of LCM in living 3D cultures, whose compatibility with standard genomics and proteomics assays such as microarrays, real‐time PCR, and 2D gel electrophoresis is further corroborated here. Specifically, the above techniques are employed in tandem to study, as a proof of principle, the dynamics of in vitro vasculogenic mimicry. It was shown previously that aggressive melanoma cells spontaneously differentiate on collagen gels into vascular‐like networks with strong endogenous angiogenic potential. Here the evolution of vasculogenic mimicry was quantified by three time‐dependent variables: the distribution of the vascular‐like network lengths, widths, and area coverage. Based on these morphological descriptors the networks were locally classified over time as “early” or “mature” stage. LCM of networks and randomly oriented cells followed by real‐time PCR for select genes revealed that differential expression was time‐dependent and increased with network maturity. The method is widely applicable for microgenomics and microproteomics analyses in phenotypically evolving 3D cultures (i.e., of stem cells), under spontaneous or directed differentiation. Therefore beyond enabling future rigorous analyses on the mechanistics of vasculogenic mimicry, it provides a practical discovery engine for a range of developmental studies and tissue regenerative engineering applications. Biotechnol. Bioeng. 2008;101: 307–316. © 2008 Wiley Periodicals, Inc.
Human bone derived cell culture on PLGA flat sheet membranes of different lactide:glycolide ratio
Authors: Ellis Marianne J. , Chaudhuri Julian B.
Published: March 2008

Providing a scaffold that can supply nutrients on a large scale (several cubic centimeters) is the key to successfully regenerating vascularized tissue: biodegradable membranes are a promising new scaffold suited to this purpose. Poly(lactic‐co‐glycolic‐acid) (PLGA) flat sheet membranes of different lactide:glycolide ratios, prepared by phase inversion using 1‐methyl‐2‐pyrrolidinone (NMP) as the solvent and water as the nonsolvent, were compared by assessing attachment, proliferation and osteogenic function of human bone derived cells (HBDC). Three different lactide:glycolide ratios, 50:50, 75:25, and 100:0, were compared to tissue culture polystyrene (TCPS). For attachment, 50:50 and 75:25 had similar numbers to TCPS but 100:0 had significantly fewer cells than TCPS. 50:50 and 75:25 had significantly lower HBDC numbers after 7 days but 100:0 had similar numbers compared to TCPS. For proliferation the cell number on the membranes were similar to each other. After 3 weeks, osteoblastic function of the HBDC, shown by mineralization and alkaline phosphatase activity, was present but was significantly lower compared to the TCPS control but similar when the membranes were compared. PLGA membranes fabricated from a range of ratios support HBDC culture so the optimum scaffold composition can be selected based on other factors, such as degradation rate. Biotechnol. Bioeng. 2008;101: 369–377. © 2008 Wiley Periodicals, Inc.
Structure–Catalytic Activity Relationship in Bridging Silacycloalkyl Ring Conformations of Constrained Geometry Titanium Complexes
Authors: Kang Eugene , Kim Sung‐Kwan , Kim Tae‐Jin , Chung Jae‐Ho , Hahn Jong Sok , Ko Jaejung , Ok Myung‐Ahn , Cheong Minserk , Kang Sang Ook
Published: March 2008

A series of cyclic silylene‐bridged (amidocyclopentadienyl)dichlorotitanium(IV) complexes [TiCl2{η5‐1‐(CySitBuN‐κN)‐2,3,4,5‐R4‐C5}] was prepared, where CySi = silacyclobutyl (a), silacyclopentenyl (b), silacyclopentyl (c), and silacyclohexyl (d); R = H (4), Me (5). The starting silane, dichlorosilacycloalkane CySiCl2 (1), was treated with NaCp (LiCp*), followed by LiNHtBu to yield the cyclic silylene‐bridged ligands (R4C5)CySi(NHtBu) [R = H (2); Me (3)]. Subsequent deprotonation with n‐butyllithium, followed by transmetalation with TiCl4 yielded the desired constrained geometry complexes (CGCs) (CpCySiNtBu)TiCl2 (4) and (Cp*CySiNtBu)TiCl2 (5). The structures of the resulting cyclopentadienyl‐ (4b and 4c) and tetramethylcyclopentadienyl(silacycloalkyl)amidotitanium(IV) dichloride (5a, 5c, and 5d) species were studied by using X‐ray crystallography to obtain geometrical information on cyclic silylene‐modified CGCs. The ethylene polymerization by the cyclic silylene‐bridged CGCs 4 and 5 was examined to verify the structure–catalytic activity relationship derived from variation of the size of a cyclic silylene ring. Indeed, the size of the cyclic silylene ring at the 1,1′‐position of 4 and 5 affected the catalytic activities through the ethylene polymerization. Systematic increase in the catalytic activities was observed as the cyclic silylene‐bridging unit was expanded from a four‐ to six‐membered ring. In the present study, we found that CGCs of TiIV with a six‐membered silylene‐bridged ligand (5d) produced active catalytic species for the formation of polyethylene with Mw = 42.7 × 10–4 g mol–1 and Mw/Mn = 2.1 with excellent catalytic activities (20.9 kg polymer per mmol of Ti). When titanium(IV) dimethyl complex (6d) was applied in continuous polymerization process, impressive high catalytic activity on copolymerization with 1‐octene was observed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Hybrid formulation of operator splitting (OS) and Newmark‐β methods for collaborative structural analysis (CSA)
Authors: Pan Peng , Tada Motohide
Published: March 2008

A collaborative structural analysis (CSA) system is developed, which is capable of performing highly sophisticated structural analyses utilizing beneficial features of existing individual structural analysis programs. In the system, the global equations of motion for the overall structural system are formulated in the host program. Some substructures, whose behaviors are relatively simple, are directly solved in the host program, whereas those having complex behavior are analyzed by the station programs. A time‐consuming static condensation procedure is needed for the substructures analyzed by the station programs if adopting an implicit integration scheme. The operator splitting (OS) method, which does not require tangential stiffness, can be used to improve the system efficiency. To this end, a hybrid formulation of the Newmark‐β and OS methods is proposed, and a CSA scheme based on the hybrid formulation is developed. In the CSA system adopting the hybrid formulation, the degrees of freedom whose tangential stiffness are unavailable are formulated by the OS method, whereas the rest are still formulated by the commonly used Newmark‐β method. Using the system, analyses of a three‐story‐braced steel moment‐resisting frame are conducted. In the analyses, the column bases are analyzed using the commercial finite element method software ABAQUS, and the remaining structural elements are analyzed using a frame analysis program called NETLYS. Results suggest that the hybrid formulation is very effective for the CSA system. Copyright © 2008 John Wiley & Sons, Ltd.
Glacial geomorphology of the Central Arctic Ocean: the Chukchi Borderland and the Lomonosov Ridge
Authors: Jakobsson Martin , Polyak Leonid , Edwards Margo , Kleman Johan , Coakley Bernard
Published: March 2008

The last decade of geophysical seafloor mapping in the Arctic Ocean from nuclear submarines and icebreakers reveals a wide variety of glaciogenic geomorphic features at water depths reaching 1000 m. These findings provide new and intriguing insights into the Quaternary glacial history of the Northern Hemisphere. Here we integrate multi‐ and single beam bathymetric data, chirp sonar profiles and sidescan images from the Chukchi Borderland and Lomonosov Ridge to perform a comparative morphological seafloor study. This investigation aims to elucidate the nature and provenance of ice masses that impacted the Arctic Ocean sea floor during the Quaternary. Mapped glaciogenic bedforms include iceberg keel scours, most abundant at water depths shallower than ∼350–400 m, flutes and megascale glacial lineations extending as deep as ∼1000 m below the present sea level, small drumlin‐like features and morainic ridges and grounding‐zone wedges. The combination of these features indicates that very large glacial ice masses extended into the central Arctic Ocean from surrounding North American and Eurasian ice sheets several times during the Quaternary. Ice shelves occupied large parts of the Arctic Ocean during glacial maxima and ice rises were formed over the Chukchi Borderland and portions of the Lomonosov Ridge. More geophysical and sediment core data combined with modeling experiments are needed to reconstruct the timing and patterns of these events. Copyright © 2008 John Wiley & Sons, Ltd.
Geological constraints on Antarctic palaeo‐ice‐stream retreat
Authors: Cofaigh Colm Ó , Dowdeswell Julian A. , Evans Jeffrey , Larter Rob D.
Published: March 2008

Submarine landforms preserved in bathymetric troughs on the Antarctic continental shelf show that the style of ice stream retreat across the shelf following the last glacial maximum varied between different troughs. Three styles of retreat are inferred from the geological evidence: rapid, episodic and slow. Rapid retreat by ice stream floatation and calving is recorded by the preservation of a landform assemblage of unmodified streamlined subglacial bedforms including mega‐scale glacial lineations (MSGLs) that record streaming flow along these troughs. These elongate bedforms are not overprinted by recessional glacial landforms formed transverse to ice flow such as moraines or grounding‐zone wedges, and overlying deglacial sediments are thin. A second type of landform assemblage consists of MSGLs overprinted or interrupted by transverse grounding‐zone wedges. This assemblage implies episodic retreat between successive grounding‐zone positions. The third type of landform assemblage is that of numerous, closely spaced, recessional moraines and intermittent grounding‐zone wedges that overlie and interrupt MSGLs. This assemblage records the slow retreat of grounded ice across the shelf. Variation in the style of ice stream retreat between the different bathymetric troughs indicates that Antarctic palaeo‐ice‐streams did not respond uniformly to external forcing at the end of the last glacial cycle. Rather, their diachronous retreat reflects the dominance of local controls in the form of bathymetry and drainage basin size. More broadly, these data show that retreat of marine‐based ice sheets in areas of reverse bed slope is not necessarily catastrophic, and they provide important constraints for numerical models that attempt to predict the dynamics of large polar ice sheets. Copyright © 2008 John Wiley & Sons, Ltd.
Antarctic subglacial topography and ice‐sheet evolution
Authors: Siegert Martin J.
Published: March 2008

Although ice‐sheet flow and form in Antarctica is controlled to a large degree by topography, the continent's landscape evolution and therefore its influence on ice‐sheet development is poorly understood. The oscillation of ice sheets throughout the last 34 million years will have affected topography through glacial erosion and deposition. Consequently, the macro bedforms on which the modern ice sheet flows originate from previous, and probably dissimilar, ice sheets. This problem is both obvious and difficult to resolve given the lack of bed exposure and paucity of data concerning sedimentary deposits. Nonetheless, several attempts have been made, using numerical modelling, to comprehend the interrelation between topography and ice sheets in Antarctica. In this review, the subglacial topography of Antarctica is inspected with reference to both contemporary ice‐flow processes and ice‐sheet history. Examples of how landscape evolution have been estimated are discussed, which provides a means by which the continental scale link between topography and ice‐sheet development can be investigated in future. Copyright © 2008 John Wiley & Sons, Ltd.
Superimposition of ribbed moraines on a palaeo‐ice‐stream bed: implications for ice stream dynamics and shutdown
Authors: Stokes Chris R. , Lian Olav B. , Tulaczyk Slawek , Clark Chris D.
Published: March 2008

The sediments and landforms preserved on palaeo‐ice‐stream beds can provide important information about their subglacial conditions and flow mechanisms, and the processes accompanying their shutdown. In this paper, detailed observations of an intriguing subglacial landform assemblage of ribbed moraines superimposed on glacial lineations on the Dubawnt Lake Ice Stream bed (north‐west Canadian Shield) are presented, including their morphometry, internal structure (from ground penetrating radar (GPR) surveys and from glaciogeological analysis) and sedimentological characteristics (from sediment architecture and lithofacies analysis). The observations suggest an abrupt change in ice dynamics that correlates with two phases of glacial landform development. This hypothesis is based on evidence from a deformed lodgement till, which subsequently underwent brittle deformation and developed prominent thrust (shear) structures and tension fractures. Tension fractures are observed in a sediment exposure and thrust structures are observed in GPR surveys, where they occur most prominently in the ribbed moraine ridge crests. The presence of the fractures, and their association with a population of clasts in the till that are orientated with their a‐axes transverse to the inferred ice flow direction, suggests a compressional flow regime. It is therefore inferred that the glacial lineations were formed under an extensional flow regime during ice stream activity, but that at some point patches of till under the ice stream stiffened through dewatering. The subsequent increase in basal shear stress resulted in compressional flow and the development of subglacial thrusting and the building of ribbed moraines. We therefore suggest that ribbed moraines may form in areas of compressional flow under ice streams, i.e. sticky spots, and/or at the transition between slow and fast ice flow along parts of an ice stream. The general absence of ribbed moraines on most other palaeo‐ice‐stream beds suggests that either these ice streams continued operating during deglaciation or processes other than the development of localized compressional flow (sticky spots) led to their shutdown (e.g. ice depletion). Copyright © 2008 John Wiley & Sons, Ltd.
A two‐dimensional prototype multi‐physics model of the right ventricle of the heart
Authors: Croft T. N. , Williams A. J. , Slone A. K. , Cross M.
Published: March 2008

The heart operates as a delicate function of the interactions among its electro‐chemical, structural and fluid components. The objective of this paper is to describe the computational modelling of the interaction between simplified forms of the electro‐chemical, structural and fluid behaviour. It is because the objective here is to evaluate the interactions among the phenomena that the specific models of the electro‐chemical, fluid and structural behaviour are kept as simple as possible. The electro‐chemical model is drawn from that of Clayton and Holden, while the blood is assumed to be a conventional slightly compressible Navier–Stokes fluid and the heart wall is a simple elastic structure modelled via the static equations. The model is implemented within a multi‐physics finite volume solver environment using an unstructured mesh approach, which enables the implementation of models for each of the specific phenomenon and their interactions. The model is two dimensional, but shows how the electric field drives a cross section of the wall so that it pumps the blood in and out of the right ventricle geometry. Copyright © 2008 John Wiley & Sons, Ltd.
Multiphase modelling of pouring glass over the spout lip of an industrial float in the flat glass forming process
Authors: Fernández Oro J. M. , Argüelles Díaz K. M. , Santolaria Morros C. , Cobo Hedilla A. F. , Lemaille M.
Published: March 2008

This paper describes the numerical modelling of the three‐phase flow that is established when pouring molten glass onto a tin bath (float) under a non‐reactive atmosphere. Discharged from the furnace, the glass is spouted over a lip onto the bath, where it floats and spreads out in the form of a long ribbon, leading to the flat glass forming process. Numerically, the physical modelling must consider a multiphase problem with three immiscible phases: glass, tin and air. The simulation of this complex free‐surface flow involves the solution of the Navier–Stokes set of equations for all the phases simultaneously, using a volume‐of‐fluid formulation that introduces a marker function convected by the flow to identify each phase. The evolution of the interphases is tracked over time with the implementation of a continuous surface force algorithm. A general purpose, well‐tested commercial code, FLUENT, is employed for the computations. Firstly, a two‐dimensional model considering the symmetry plane of the float is developed to fit accurate physical and numerical parameters. The high complexity of the interphases in addition to great differences between the physical properties of the phases has required extensive tests to ensure the consistency and accuracy of the solutions. Afterwards, a complete three‐dimensional model is built to simulate the pouring process in a real geometry and predict the behaviour of the industrial facility when the operating conditions are modified. Typical flow phenomena inside the tin bath, such as tin currents, wet back flow or even the equilibrium thickness, are also obtained as a promising result of the numerical modelling. Copyright © 2008 John Wiley & Sons, Ltd.
Identification of midbrain floor plate radial glia‐like cells as dopaminergic progenitors
Authors: Bonilla Sonia , Hall Anita C. , Pinto Luisa , Attardo Alessio , Götz Magdalena , Huttner Wieland B. , Arenas Ernest
Published: March 2008

The floor plate (FP), a signaling center and a structure rich in radial glia‐like cells, has been traditionally thought to be devoid of neurons and neuronal progenitors. However, in the midbrain, the FP contains neurons of the dopaminergic (DA) lineage that require contact with radial glia‐like cells for their induction. We, therefore, decided to explore the interaction relationship between radial glia and neurons during DA neurogenesis. Taking advantage of a novel FP radial glia‐like cell culture system and retroviruses, DA neurons were lineage traced in vitro. In utero BrdU pulse‐chases extensively labeled the midbrain FP and traced DA neurons both in vivo and in FP cultures. Moreover, from E9.5 to E13.5 the midbrain FP contained dividing cells only in the most apical part of the neuroepithelium, in cells identified as radial glia‐like cells. We, therefore, hypothesized that midbrain FP radial glia‐like cells could be DA progenitors and tested our hypothesis in vivo. Lineage tracing of DA progenitors with EGFP in Tis21‐EGFP knock‐in mice, and genetic fate mapping in GLAST::CreERT2/ZEG mice identified the neuroepithelium of the midbrain FP, and specifically, GLAST+ radial glia‐like cells as DA progenitors. Combined, our experiments support the concept that the midbrain FP differs from other FP regions and demonstrate that FP radial glia‐like cells in the midbrain are neurogenic and give rise to midbrain DA neurons. © 2008 Wiley‐Liss, Inc.
The duration effect: a link between TTO and VAS values
Authors: Craig Benjamin M.
Published: March 2008

The value of a health state may depend on how long an individual has had to endure the health state (i.e. hedonic load). In this paper, we test the constant proportionality (CP) assumption and determine the sign of relationship between duration and health state value for 42 health states using the nationally representative data from the United Kingdom Measurement and Valuation of Health study. The results reject the CP assumption and suggest that the relationship is negative for optimal health (i.e. fair innings argument) and that the relationship is positive for poorer health states (i.e. adaptation). We find no evidence of the maximum endurable time hypothesis using these data. This evidence on the duration effect has important implications for outcomes research and the economic evaluation of interventions. Copyright © 2008 John Wiley & Sons, Ltd.
Older siblings influence younger siblings' motor development
Authors: Berger Sarah E. , Nuzzo Katie
Published: March 2008

Evidence exists for two competing theories about the effects of having an older sibling on development. Previous research has found that having an older sibling has both advantages and disadvantages for younger siblings' development. This study examined whether and how older siblings influenced the onset of their own younger siblings' motor milestones, a heretofore unstudied developmental domain in the sibling literature. Parents of 51 sibling pairs reported their children's crawling and walking onset dates. In keeping with imitation theories, in families where younger siblings crawled or walked earlier than their own older sibling, they did so significantly earlier. Moreover, in keeping with limited parental resource theories, in families where older siblings crawled or walked earlier than their own younger sibling, they did so significantly earlier. Older siblings did influence younger siblings' motor development, but how they did so may have depended on unique family characteristics. Copyright © 2008 John Wiley & Sons, Ltd.
Aerobic glycolysis in cancers: Implications for the usability of oxygen‐responsive genes and fluorodeoxyglucose‐PET as markers of tissue hypoxia
Authors: Busk Morten , Horsman Michael R. , Kristjansen Paul E.G. , van der Kogel Albert J. , Bussink Johan , Overgaard Jens
Published: March 2008

The hypoxia‐responsiveness of the glycolytic machinery may allow pretreatment identification of hypoxic tumors from HIF‐1 targets (e.g., Glut‐1) or [18F]‐fluorodeoxyglucose positron emission tomography but results have been mixed. We hypothesized that this discrepancy is an inevitable consequence of elevated aerobic glycolysis in tumors (Warburg effect) as energetics in predominantly glycolytic cells is little affected by hypoxia. Accordingly, we characterized glycolytic and mitochondrial ATP generation in normoxic and anoxic cell lines. Measurements demonstrated that most cancer cells rely largely on aerobic glycolysis as it accounts for 56–63% of their ATP budget, but in the cervical carcinoma SiHa, ATP synthesis was mainly mitochondrial. Moreover, the stimulatory effect of anoxia on glycolytic flux was inversely correlated to the relative reliance on aerobic glycolysis. Next, tumor cells representing a Warburg or a nonglycolytic phenotype were grown in mice and spatial patterns of hypoxia (pimonidazole‐stained), Glut‐1 expression and 18F‐FDG uptake were analysed on sectioned tumors. Only in SiHa tumors did foci of elevated glucose metabolism consistently colocalize with regions of hypoxia and elevated Glut‐1 expression. In contrast, spatial patterns of Glut‐1 and pimonidazole staining correlated reasonably well in all tumors. In conclusion, Glut‐1's value as a hypoxia marker is not severely restricted by aerobic glycolysis. In contrast, the specificity of 18F‐FDG uptake and Glut‐1 expression as markers of regional hypoxia and glucose metabolism, respectively, scales inversely with the intensity of the Warburg effect. This linkage suggests that multi‐tracer imaging combining FDG and hypoxia‐specific markers may provide therapeutically relevant information on tumor energetic phenotypes. © 2008 Wiley‐Liss, Inc.
Gain of 1q21 and distinct adverse cytogenetic abnormalities correlate with increased microcirculation in multiple myeloma
Authors: Hillengass Jens , Zechmann Christian M. , Nadler Andreas , Hose Dirk , Cremer Friedrich W. , Jauch Anna , Heiss Christiane , Benner Axel , Ho Anthony D. , Bartram Claus R. , Kauczor Hans‐Ulrich , Delorme Stefan , Goldschmidt Hartmut , Moehler Thomas M.
Published: March 2008

To identify genetic mechanisms controlling bone marrow microcirculation and angiogenesis in patients with plasma cell disease we simultaneously performed bone marrow dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) and cytogenetics (iFISH) on CD138 purified plasma cells of MGUS (n=31) and untreated multiple myeloma (MM) (n = 87) patients. The adverse cytogenetic abnormalities gain of 1q21, deletion 17p13 and deletion 13q14 significantly correlated with at least one DCE‐MRI finding (aberrant “focal” microcirculation pattern, increase in median microcirculation parameter Amplitude A or exchange rate constant kep). We conclude that gain of 1q21, deletion 13q14 and deletion 17p13 trigger the angiogenic cascade in MM. Our findings will have important implications for the design, analysis and stratification for clinical studies of patients with MM in particular if compounds with antiangiogenic activity are used. © 2008 Wiley‐Liss, Inc.
Selected class I and class II HLA alleles and haplotypes and risk of high‐grade cervical intraepithelial neoplasia
Authors: Ades Steven , Koushik Anita , Duarte‐Franco Eliane , Mansour Nabil , Arseneau Jocelyne , Provencher Diane , Gilbert Lucy , Gotlieb Walter , Ferenczy Alex , Coutlée François , Roger Michel , Franco Eduardo L. ,   for the Biomarkers of Cervical Cancer Risk (BCCR) Study Team
Published: March 2008

Human leukocyte antigens (HLAs) present foreign antigens to the immune system and may be important determinants of cervical neoplasia. Previously published associations between HLA and cervical neoplasia exhibit considerable variation in findings. The biomarkers of cervical cancer risk (BCCR) case‐control study addressed the role of specific HLA alleles as cofactors in the development of high‐grade cervical intraepithelial neoplasia (HG‐CIN) based on the most consistent evidence from published literature. Cases (N = 381) were women with histologically‐confirmed HG‐CIN attending colposcopy clinics and controls (N = 884) were women from outpatient clinics with normal cytological screening smears. Subjects were mainly of French‐Canadian descent. Cervical specimens were tested for human papillomavirus (HPV) DNA and HLA genotypes by PGMY L1 consensus primer PCR and a PCR sequence‐specific primer method, respectively. Unlike other studies, the DQB1*03 and DRB1*13 allele groups were not associated with risk of HG‐CIN. The B7‐DRB1*1501‐DQB1*0602 haplotype was associated with a 41% overall reduction in HG‐CIN risk (odds ratio [OR] = 0.59; 95% confidence interval [CI]: 0.36–0.96), and an 83% reduction in risk of HG‐CIN among HPV 16 or HPV 18‐positive subjects (OR = 0.17; 95%CI: 0.05–0.54). Paradoxically, however, the same haplotype was associated with HPV 16/18 infection risk among controls (OR = 8.44, 95%CI: 1.12–63.73). In conclusion, the B7‐DRB1*1501‐DQB1*0602 haplotype was protective against HG‐CIN, especially in individuals infected with oncogenic HPV, but the mechanism of the association seems to involve multiple steps in the natural history of HPV and CIN. © 2008 Wiley‐Liss, Inc.
Two‐dimensional differential gel electrophoresis/analysis of diethylnitrosamine induced rat hepatocellular carcinoma
Authors: Qi Yanting , Chen Xiaona , Chan Chu‐yan , Li Dan , Yuan Chonggang , Yu Fei , Lin Marie C. , Yew David T. , Kung Hsiang‐Fu , Lai Lihui
Published: March 2008

Diethylnitrosamine (DEN) is a known carcinogen that can alkylate DNA molecules. In rats, DEN‐induced hepatocellular carcinoma (HCC) model is well established. In this study, we used a two‐dimensional differential gel electrophoresis (2D‐DIGE) system and liquid chromatography/mass spectrometry/mass spectrometry to identify the differential expression protein profiles between the DEN‐induced HCC and healthy liver cells. Western blotting and semiquantitative RT‐PCR were used to further confirm the results. Seventeen differentially expressed spots were identified in DEN‐induced HCC cells. Among all, the most prominent upregulated proteins include the members of the glutathione S‐transferase super family, aldo‐keto reductase superfamily and proteins involved in the response to oxidative stress. Downregulation was observed in 2 proteins that were known to contribute to hepatic dysfunction. This study provides the first comprehensive protein profiling of the DEN‐induced HCC in rats. This model simulates the differential protein expression of human HCC and may be useful for further understanding the mechanism of HCC tumorigenesis. © 2008 Wiley‐Liss, Inc.
Nonadditive effects in ternary H2–cation–PAH systems
Authors: Donchev Alexander G.
Published: March 2008

This article reports state‐of‐the‐art ab initio calculations at the second order of Møller‐Plesset perturbation theory of molecular hydrogen binding in its ternary complexes with lightweight alkali cations (M = Li or Na) and polycyclic aromatic hydrocarbons (PAHs) up to coronene. The study revealed a substantial nonadditive contribution to the H2 stabilization energy. In the most stable conformation, the nonadditive contribution weakens the H2 binding by a factor of nearly 1.5 and 1.3 for Li and Na cations, respectively, as compared with the pairwise sum of direct H2–M+ and H2–PAH contributions. In the Li case, the presence of PAH not only does not promote H2 binding but has a large (∼20%) weakening effect in comparison with the initial H2–Li+ interaction. In the Na case, the presence of PAH has the usual stabilizing influence on the hydrogen binding. A careful analysis of the physical components of the nonadditive effect on the example of H2–M+–benzene complexes revealed the dominating role of the induction nonadditivity. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Combining a polarizable force‐field and a coarse‐grained polarizable solvent model: Application to long dynamics simulations of bovine pancreatic trypsin inhibitor
Authors: Masella Michel , Borgis Daniel , Cuniasse Philippe
Published: March 2008

The dynamic coupling between a polarizable protein force field and a particle‐based implicit solvent model is described. The polarizable force field, TCPEp, developed recently to simulate protein systems, is characterized by a reduced number of polarizable sites, with a substantial gain in efficiency for an equal chemical accuracy. The Polarizable Pseudo‐Particle (PPP) solvent model represents the macroscopic solvent polarization by induced dipoles placed on mobile Lennard‐Jones pseudo‐particles. The solvent‐induced dipoles are sensitive to the solute electric field, but not to each other, so that the computational cost of solvent–solvent interactions is basically negligible. The solute and solvent induced dipoles are determined self‐consistently and the equations of motion are solved using an efficient iterative multiple time step procedure. The solvation cost with respect to vacuum simulations is shown to decrease with solute size: the estimated multiplicative factor is 2.5 for a protein containing about 1000 atoms, and as low as 1.15 for 8000 atoms. The model is tested for six 20 ns molecular dynamics trajectories of a traditional benchmark system: the hydrated Bovine Pancreatic Trypsin Inhibitor (BPTI). Even though the TCPEp parameters have not been refined to be used with the solvent PPP model, we observe a good conservation of the BPTI structure along the trajectories. Moreover, our approach is able to provide a description of the protein solvation thermodynamic at the same accuracy as the standard Poisson‐Boltzman continuum methods. It provides in addition a good description of the microscopic structural aspects concerning the solute/solvent interaction. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Empirical entropic contributions in computational docking: Evaluation in APS reductase complexes
Authors: Chang Max W. , Belew Richard K. , Carroll Kate S. , Olson Arthur J. , Goodsell David S.
Published: March 2008

The results from reiterated docking experiments may be used to evaluate an empirical vibrational entropy of binding in ligand–protein complexes. We have tested several methods for evaluating the vibrational contribution to binding of 22 nucleotide analogues to the enzyme APS reductase. These include two cluster size methods that measure the probability of finding a particular conformation, a method that estimates the extent of the local energetic well by looking at the scatter of conformations within clustered results, and an RMSD‐based method that uses the overall scatter and clustering of all conformations. We have also directly characterized the local energy landscape by randomly sampling around docked conformations. The simple cluster size method shows the best performance, improving the identification of correct conformations in multiple docking experiments. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Systematic investigation on the geometric dependence of the calculated nuclear magnetic shielding constants
Authors: Zhang Ying , Xu Xin , Yan Yijing
Published: March 2008

We perform a systematic examination on the dependence of the calculated nuclear magnetic shielding constants on the chosen geometry for a selective set of density functional methods of B3LYP, PBE0, and OPBE. We find that the OPBE exchange‐correlation functional performs remarkably well when either the optimized geometries or the experimental geometries are used. The popular B3LYP and PBE0 functionals have a clear tendency of deshielding, giving shieldings that are usually too low and shifts that are usually too high, at the experimental geometries. Combined with the Hartree‐Fock geometries, however, much improved magnetic constants are obtained for B3LYP and PBE0, due to the compensation effect from the systematic underestimation of bond lengths by the Hartree‐Fock method. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Novel H‐bonded base dimers as repeat units for information‐bearing self‐associative duplexes: A B3LYP/6‐31G* search
Authors: Neihsial Siamkhanthang , Lyngdoh Richard H. Duncan
Published: March 2008

Density functional theory at the B3LYP/6‐31G* level with counterpoise correction has been employed to study six sets of nitrogenous bases for the capacity of each to form H‐bonded dimers restricted to a chosen pairing configuration. These results are augmented by MP2/6‐311++G(d,p) single point calculations on the B3LYP/6‐31G* optimized geometries. Each set has two bases, including substituted azoles, imidazoles, pyrimidines, and fused ring systems. This study aims to determine the suitability of each set to furnish H‐bonded base pairs which may serve as repeat units for self‐associative H‐bonded macromolecular duplexes with the capacity to store and replicate information at the molecular level. Out of the various possibilities tested here, a set of two substituted pyrimidines best satisfies the prescribed criteria and may be put forward as a good candidate to yield isomorphic repeat units for designing such synthetic information‐bearing macromolecular duplexes. The optimized configurations of these chosen base pairs as calculated at the B3LYP/6‐31G* level compare well with those calculated at the B3LYP/6‐31++G(d,p) and MP2/6‐31G(d,p) levels, and indicate that isomorphism of the two base pairs is independent of method used. Assuming a one‐to‐one correspondence for encoding information in the macromolecule, such a set of two bases can allow the macromolecule to encode up to 8 types of encrypted species. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008