bluuebunny/crossref_metadata_2025 huggingface dataset:
ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming
Authors: Segura Elodie , Nicco Carole , Lombard Bérangère , Véron Philippe , Raposo Graça , Batteux Frédéric , Amigorena Sebastian , Théry Clotilde
Published: March 2005

Exosomes are secreted vesicles formed in late endocytic compartments. Immature dendritic cells (DCs) secrete exosomes, which transfer functional major histocompatibility complex (MHC)–peptide complexes to other DCs. Since immature and mature DCs induce different functional T-cell responses (ie, tolerance versus priming), we asked whether DC maturation also influenced the priming abilities of their exosomes. We show that exosomes secreted by lipopolysaccharide (LPS)–treated mature DCs are 50- to 100-fold more potent to induce antigen-specific T-cell activation in vitro than exosomes from immature DCs. In vitro, exosomes from mature DCs transfer to B lymphocytes the ability to prime naive T cells. In vivo, only mature exosomes trigger effector T-cell responses, leading to fast skin graft rejection. Proteomic and biochemical analyses revealed that mature exosomes are enriched in MHC class II, B7.2, intercellular adhesion molecule 1 (ICAM-1), and bear little milk-fat globule–epidermal growth factor–factor VIII (MFG-E8) as compared with immature exosomes. Functional analysis using DC-derived exosomes from knock-out mice showed that MHC class II and ICAM-1 are required for mature exosomes to prime naive T cells, whereas B7.2 and MFG-E8 are dispensable. Therefore, changes in protein composition and priming abilities of exosomes reflect the maturation signals received by DCs.
Low dose docosahexaenoic acid protects normal colonic epithelial cells from araC toxicity
Authors: Cha Ming C , Lin Angela , Meckling Kelly A
Published: March 2005

Background

The nucleoside analogue arabinosylcytosine (araC) has been used for many years in the treatment of acute leukemia. Evidence in the literature suggests that araC may inhibit the growth of human colon carcinoma cell lines as well. Because araC action interferes with normal nucleoside metabolism, it is highly toxic to a number of normal cell types including bone marrow and intestinal mucosa cells. Here we investigate whether the omega-3 fatty acid docosahexaenoic acid (DHA) could selectively target araC toxicity toward colonic tumor cells while protecting the normal cells in vitro.

Results

Cultures of normal rat colonic epithelial cells (4D/WT) and those transformed by v-src (D/v-src) were supplemented with graded concentrations of DHA or arachidonic acid (AA) alone or in combination with araC. AraC was only 1.6 fold more toxic to D/v-src than 4D/WT in cultures without added fatty acids. Supplementing with as little as 3 μM of either AA or DHA increased araC toxicity by more than 30-fold in the tumorigenic cells. The toxic effect of araC on the normal cells was also increased by the fatty acid supplementation. IC50 values were decreased 1.7 fold by DHA in the 4D/WT cells but a more than 7-fold decrease was observed during AA supplementation. As a result, the therapeutic index of araC (IC50 normal/IC50 tumor) was more than 3-fold higher in the DHA than the AA supplemented cells. The expression of protein kinase C isoform epsilon was decreased in AA alone supplemented D/v-src cultures but in combination with araC decreased only in DHA supplemented 4D/WT cells.

Conclusion

Low dose DHA supplementation may enhance araC chemotherapy in colon cancer while protecting normal tissues, possibly through control of PKC signalling pathways.
Lumping or splitting: seeking the preferred areal unit for health geography studies
Authors: Gregorio David I , DeChello Laurie M , Samociuk Holly , Kulldorff Martin
Published: March 2005

Background

Findings are compared on geographic variation of incident and late-stage cancers across Connecticut using different areal units for analysis.

Results

Few differences in results were found for analyses across areal units. Global clustering of incident prostate and breast cancer cases was apparent regardless of the level of geography used. The test for local clustering found approximately the same locales, populations at risk and estimated effects. However, some discrepancies were uncovered.

Conclusion

In the absence of conditions calling for surveillance of small area cancer clusters ('hot spots'), the rationale for accepting the burdens of preparing data at levels of geography finer than the census tract may not be compelling.
Policymaking based on CERs: changes in costs are not the same as changes in benefits
Authors: Ament Andre JHA , Evers Silvia MAA
Published: March 2005

Background

Earlier cost-effectiveness studies showed the cost-effectiveness ratios for pneumococcal vaccination in preventing cases of Bacteremic Pneumococcal Disease (BPD) alone to vary between € 11,000 and € 33,000 per quality-adjusted life year. If vaccination is also assumed to be effective in preventing cases of Non Bacteremic Pneumococcal Disease (NBPD) (at the same level of effectiveness), vaccinating all elderly persons becomes highly cost-effective or even cost saving.

Methods

The present article examines the effect of partial preventive power of the vaccine against cases of NBPD additional to its preventive power against cases of BPD, and the consequences this has in terms of cost-effectiveness.

Results

The analysis shows that even a fairly small additional preventive power against cases of NBPD leads to a dramatic and unexpected decrease in the cost-effectiveness ratio.

Conclusion

Because a Cost-Effectiveness Ratio (CER) is a ratio, changes in costs and changes in effects have rather different influences on its value. There is a linear relation between a change in costs and a change in CER if the effects are kept constant. This linear relation is not found on the effect side. Assuming that costs are constant, a change in effect will be different for low levels of effect than for high levels.
Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes
Authors: West Heloise , Richardson William D. , Fruttiger Marcus
Published: March 2005

Development of the retinal vasculature is controlled by a hierarchy of interactions among retinal neurons, astrocytes and blood vessels. Retinal neurons release platelet-derived growth factor (PDGFA) to stimulate proliferation of astrocytes, which in turn stimulate blood vessel growth by secreting vascular endothelial cell growth factor (VEGF). Presumably, there must be counteractive mechanisms for limiting astrocyte proliferation and VEGF production to prevent runaway angiogenesis. Here, we present evidence that the developing vessels provide feedback signals that trigger astrocyte differentiation – marked by cessation of cell division, upregulation of glial fibrillary acidic protein (GFAP) and downregulation of VEGF. We prevented retinal vessel development by raising newborn mice in a high-oxygen atmosphere, which leads, paradoxically, to retinal hypoxia (confirmed by using the oxygen-sensing reagent EF5). The forced absence of vessels caused prolonged astrocyte proliferation and inhibited astrocyte differentiation in vivo. We could reproduce these effects by culturing retinal astrocytes in a low oxygen atmosphere, raising the possibility that blood-borne oxygen itself might induce astrocyte differentiation and indirectly prevent further elaboration of the vascular network.
The Abelson tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor Frazzled in Drosophila
Authors: Forsthoefel David J. , Liebl Eric C. , Kolodziej Peter A. , Seeger Mark A.
Published: March 2005

The attractive Netrin receptor Frazzled (Fra), and the signaling molecules Abelson tyrosine kinase (Abl), the guanine nucleotide-exchange factor Trio,and the Abl substrate Enabled (Ena), all regulate axon pathfinding at the Drosophila embryonic CNS midline. We detect genetic and/or physical interactions between Fra and these effector molecules that suggest that they act in concert to guide axons across the midline. Mutations in Abland trio dominantly enhance fra and Netrin mutant CNS phenotypes, and fra;Abl and fra;trio double mutants display a dramatic loss of axons in a majority of commissures. Conversely,heterozygosity for ena reduces the severity of the CNS phenotype in fra, Netrin and trio,Abl mutants. Consistent with an in vivo role for these molecules as effectors of Fra signaling, heterozygosity for Abl, trio or ena reduces the number of axons that inappropriately cross the midline in embryos expressing the chimeric Robo-Fra receptor. Fra interacts physically with Abl and Trio in GST-pulldown assays and in co-immunoprecipitation experiments. In addition, tyrosine phosphorylation of Trio and Fra is elevated in S2 cells when Abl levels are increased. Together, these data suggest that Abl, Trio, Ena and Fra are integrated into a complex signaling network that regulates axon guidance at the CNS midline.
Functional analysis of the chickenδ1-crystallinenhancer activity inDrosophilareveals remarkable evolutionary conservation between chicken and fly
Authors: Blanco Jorge , Girard Franck , Kamachi Yusuke , Kondoh Hisato , Gehring Walter J.
Published: March 2005

Functional conservation of enhancers among evolutionarily diverged organisms is a powerful way to identify basic regulatory circuits and key developmental regulators. This is especially applicable to Crystallin genes. Despite unexpected heterogeneity and diversity in their DNA sequences, many studies have revealed that most of the Crystallin genes are regulated by a relatively small set of developmentally important transcription factors. The chicken δ1-crystallin is one of the best-characterized Crystallin genes. Its lens-specific regulation is governed by a 30 bp long DC5 fragment present in the third intron of the gene. DC5 contains PAX6 and SOX2 binding sites, and its activity depends on the cooperative binding of these two transcription factors. To test the idea that Pax6 and Sox2, together with the DC5 enhancer, could form a basic regulatory circuit functional in distantly related animals, we introduced the DC5 fragment into Drosophila and studied its activation pattern and regulation. The results show that the DC5 enhancer is not only active in the compound eye but, remarkably, is specifically active in those cells responsible for Crystallin secretion in Drosophila, i.e. the cone cells. However, regulation of the DC5 enhancer is carried out not by Pax6, but by Pax2 (D-Pax2; shaven –FlyBase) in combination with the Sox2 homologue SoxN. Both proteins (D-PAX2 and SOXN) bind cooperatively to the DC5 fragment and activate the enhancer synergistically. As PAX6 and PAX2 proteins derive from the same ancestor, we propose that during evolution Pax6 function in vertebrate lens development was retained by Pax2 in Drosophila.
IrreC/rst-mediated cell sorting duringDrosophilapupal eye development depends on proper localisation of DE-cadherin
Authors: Grzeschik Nicola A. , Knust Elisabeth
Published: March 2005

Remodelling of tissues depends on the coordinated regulation of multiple cellular processes, such as cell-cell communication, differential cell adhesion and programmed cell death. During pupal development, interommatidial cells (IOCs) of the Drosophila eye initially form two or three cell rows between individual ommatidia, but then rearrange into a single row of cells. The surplus cells are eliminated by programmed cell death, and the definitive hexagonal array of cells is formed, which is the basis for the regular pattern of ommatidia visible in the adult eye. Here, we show that this cell-sorting process depends on the presence of a continuous belt of the homophilic cell adhesion protein DE-cadherin at the apical end of the IOCs. Elimination of this adhesion belt by mutations in shotgun, which encodes DE-cadherin, or its disruption by overexpression of DE-cadherin, the intracellular domain of Crumbs, or by a dominant version of the monomeric GTPase Rho1 prevents localisation of the transmembrane protein IrreC-rst to the border between primary pigment cells and IOCs. As a consequence, the IOCs are not properly sorted and supernumerary cells survive. During the sorting process, Notch-mediated signalling in IOCs acts downstream of DE-cadherin to restrict IrreC-rst to this border. The data are discussed in relation to the roles of selective cell adhesion and cell signalling during tissue reorganisation.
even-skippedis not a pair-rule gene but has segmental and gap-like functions inOncopeltus fasciatus, an intermediate germband insect
Authors: Liu Paul Z. , Kaufman Thomas C.
Published: March 2005

The pair-rule gene even-skipped is required for the initiation of metameric pattern in Drosophila. But Drosophila segmentation is evolutionarily derived and is not representative of most insects. Therefore, in order to shed light on the evolution of insect segmentation,homologs of the pair-rule gene even-skipped have been studied in several insect taxa. However, most of these studies have reported the expression eve but not its function. We report the isolation,expression and function of the homolog of Drosophila even-skippedfrom the intermediate germband insect Oncopeltus fasciatus. We find that in Oncopeltus, even-skipped striped expression initiates in a segmental and not pair-rule pattern. Weak RNAi suppression of Oncopeltus even-skipped shows no apparent pair-rule like phenotype, while stronger RNAi suppression shows deletion of nearly the entire body. These results suggest that in Oncopeltus, even-skipped is not acting as a pair-rule gene. In almost all insects, prior to its striped expression, even-skipped is expressed in a conserved broad gap-like domain but its function has been largely ignored. We find that this early broad domain is required for activation of the gap genes hunchback and Krüppel. Given the large RNAi deletion phenotype and its regulation of hunchback and Krüppel, even-skipped seems to act as an über-gap gene in Oncopeltus, indicating that it may have both upstream and downstream roles in segmentation.
Direct drive electrical power take-off for offshore marine energy converters
Authors: Mueller M A , Baker N J
Published: March 2005

This paper investigates the issues associated with converting the energy produced by marine renewable energy converters, namely wave and tidal stream devices, into electricity using direct drive electrical power take-off, without use of complex pneumatic, hydraulic or other mechanical linkages. In order to demonstrate the issues, two alternative topologies of linear electrical machines are investigated: the linear vernier hybrid permanent magnet machine and the air-cored tubular permanent magnet machine. The electrical characteristics of these machines are described and compared in the context of mechanical integration. Potential solutions to the issues of sealing, corrosion and lubrication are discussed taking into account the electrical properties of the two topologies.
Overexpression of Telomerase Confers Growth Advantage, Stress Resistance, and Enhanced Differentiation of ESCs Toward the Hematopoietic Lineage
Authors: Armstrong L. , Saretzki G. , Peters H. , Wappler I. , Evans J. , Hole N. , von Zglinicki T. , Lako M.
Published: March 2005

Embryonic stem cells (ESCs) are capable of extended self-renewal and maintenance of pluripotency even after many population doublings. This is supported by high levels of telomerase activity and enhanced antioxidant protection in ESCs, both of which are downregulated during differentiation. To examine the role of telomerase for ESC self-renewal and differentiation, we overexpressed the reverse transcriptase subunit (Tert) of murine telomerase in ESCs. Increased telomerase activity enhances the self-renewal ability of the Tert-overexpressing ESCs, improves their resistance to apoptosis, and increases their proliferation. The differentiated progeny of wild-type ESCs express little Tert and show shortening of telomeric overhangs. In contrast, the progeny of Tert-overexpressing ESCs maintain high telomerase activity, as well as the length of G-rich overhangs. In addition, these cells accumulate lower concentrations of peroxides than wild-type cells, implying greater resistance to oxidative stress. Finally, differentiation toward hematopoietic lineages is more efficient as a result of the continued expression of Tert. Microarray analysis revealed that overexpression of Tert altered expression of a variety of genes required for extended self-renewal and lifespan. Our results suggest that telomerase functions as a “survival enzyme” in ESCs and its differentiated progeny by protecting the telomere cap and by influencing the expression patterns of stress response and defense genes. This results in improved proliferation of ESCs and more efficient differentiation, and these results might have profound consequences for stem cell–replacement therapies.
Immobilization of pepsin on an acrylamide/2‐hydroxyethyl methacrylate copolymer and its use in casein hydrolysis
Authors: Shukla Sachin P. , Devi Surekha
Published: March 2005

Pepsin was immobilized through covalent bonding on a copolymer of acrylamide and 2‐hydroxyethyl methacrylate via the individual and simultaneous activation of both groups. The extent of enzyme coupling upon the activation of both the amino and hydroxyl groups of the copolymer resulted in a synergistic effect. However, the order of activation of the support was critical. The covalently bound enzyme retained more than 50% of its activity even after six cycles. The storage stability of the covalently bound enzyme was 60% after storage for 1 month, whereas the free enzyme lost all of its activity within 10 days of storage at 35°C. The Michaelis constant (Km) and maximum reaction velocity (Vmax) were 1.1 × 10−6 and 0.87 for the free enzyme and 1.2 × 10−6 and 0.98 for the covalently bound enzyme when the enzyme concentration was kept constant and the substrate concentration was varied. Similarly, Km and Vmax were 6.73 × 10−11 and 0.47 for the free enzyme and 7.59 × 10−11 and 0.545 for the covalently bound enzyme when the substrate concentration was kept constant and the enzyme concentration was varied; this indicated no conformational change during coupling, but the reaction was concentration‐dependent. The hydrolysis of casein was carried out with a fixed‐bed reactor (17 cm × 1 cm). Maximum hydrolysis (90%) was obtained at a 2 cm3/min flow rate at 35°C with a 1 mM casein solution. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1544–1549, 2005
Electron holography and AFM studies on styrenic block copolymers and a high impact polystyrene
Authors: Simon Paul , Adhikari Rameshwar , Lichte Hannes , Michler Goerg H. , Langela Marc
Published: March 2005

Many of the artifacts of conventional electron microscopy can be avoided if the unstained polymers are studied by electron holography and atomic force microscopy (AFM). Holograms of thin sections (50–70 nm) of organic block copolymers were recorded, and the corresponding phase images were reconstructed. In this way, typical structures such as lamellae and cylinders could be imaged without any staining. In addition, we successfully recorded holograms and performed Lorentz microscopy of an impact‐modified polystyrene (high‐impact polystyrene). The results were compared with the tapping mode AFM phase images. Electron holography and AFM have been demonstrated as suitable tools to image unstained heterogeneous polymers, leading to the understanding of their structure. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1573–1583, 2005
Polyaniline‐supported acid catalyst: Esterification of cinnamic acid with alcohols
Authors: Palaniappan Srinivasan , Sairam Malladi
Published: March 2005

Polyaniline‐supported acid salts such as polyaniline‐hydrochloride, polyaniline‐sulfate, and polyaniline‐nitrate were prepared by oxidation of aniline using benzoyl peroxide and ammonium persulfate as oxidizing agents. Polyaniline salts were used as catalysts in the esterification of cinnamic acid with alcohols. Polyaniline‐sulfate salt was found to be the best catalyst for the esterification of cinnamic acid. The reusability, handling, and recovery of the catalyst were found to be good. The yield of the ester depended on the type of the polyaniline salt, amount of the catalyst, amount of alcohol, and both the time and the temperature of the reaction. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1584–1590, 2005
Non‐parametric regression with wavelet kernels
Authors: Rakotomamonjy Alain , Mary Xavier , Canu Stéphane
Published: March 2005

This paper introduces a method to construct a reproducing wavelet kernel Hilbert spaces for non‐parametric regression estimation when the sampling points are not equally spaced. Another objective is to make high‐dimensional wavelet estimation problems tractable. It then provides a theoretical foundation to build reproducing kernel from operators and a practical technique to obtain reproducing kernel Hilbert spaces spanned by a set of wavelets. A multiscale approximation technique that aims at taking advantage of the multiresolution structure of wavelets is also described. Examples on toy regression and a real‐world problem illustrate the effectiveness of these wavelet kernels. Copyright © 2005 John Wiley & Sons, Ltd.
Protein‐Detecting Microarrays: Current Accomplishments and Requirements
Authors: Tomizaki Kin‐ya , Usui Kenji , Mihara Hisakazu
Published: March 2005

The sequencing of the human genome has been successfully completed and offers the chance of obtaining a large amount of valuable information for understanding complex cellular events simply and rapidly in a single experiment. Interestingly, in addressing these proteomic studies, the importance of proteindetecting microarray technology is increasing. In the coming few years, microarray technology will become a significantly promising and indispensable research/diagnostic tool from just a speculative technology. It is clear that the protein‐detecting microarray is supported by three independent but strongly related technologies (surface chemistry, detection methods, and capture agents). Firstly, a variety of surface‐modification methodologies are now widely available and offer site‐specific immobilization of capture agents onto surfaces in such a way as to keep the native conformation and activity. Secondly, sensitive and parallel detection apparatuses are being developed to provide highly engineered microarray platforms for simultaneous data acquisition. Lastly, in the development of capture agents, antibodies are now probably the most prominent capture agents for analyzing protein abundances. Alternative scaffolds, such as phage‐displayed antibody and protein fragments, which provide the advantage of increasing diversity of proteinic capture agents, however, are under development. An approach involving recombinant proteins fused with affinity tag(s) and coupled with a highly engineered surface chemistry will provide simple production protocols and specific orientations of capture agents on the microarray formats. Peptides and other small molecules can be employed in screening highly potent ligands as well as in measuring enzymatic activities. Protein‐detecting microarrays supported by the three key technologies should contribute in accelerating diagnostic/biological research and drug discovery.
Stenting vs. balloon angioplasty for discrete unoperated coarctation of the aorta in adolescents and adults
Authors: Pedra Carlos A.C. , Fontes Valmir F. , Esteves Cesar A. , Pilla Carlo B. , Braga Sérgio L.N. , Pedra Simone R.F. , Santana M. Virginia T. , Silva M. Aparecida P. , Almeida Tarcisio , Sousa J. Eduardo M.R.
Published: March 2005

More information is needed to clarify whether stenting is superior to balloon angioplasty (BA) for unoperated coarctation of the aorta (CoA). From September 1997, 21 consecutive adolescents and adults (24 ± 11 years) with discrete CoA underwent stenting (G1). The results were compared to those achieved by BA performed in historical group of 15 patients (18 ± 10 years; P = 0.103; G2). After the procedure, systolic gradient reduction was higher (99% ± 2% vs. 87% ± 17%; P = 0.015), residual gradients lower (0.4 ± 1.4 vs. 5.9 ± 7.9 mm Hg; P = 0.019), gain at the CoA site higher (333% ± 172% vs. 190% ± 104%; P = 0.007), and CoA diameter larger (16.9 ± 2.9 vs. 12.9 ± 3.2 mm; P < 0.001) in G1. Aortic wall abnormalities were found in eight patients in G2 (53%) and in one in G1 (7%; P < 0.001). There was no major complication. Repeat catheterization (n = 33) and/or MRI (n = 2) was performed at a median follow‐up of 1.0 year for G1 and 1.5 for G2 (P = 0.005). Gradient reduction persisted in both groups, although higher late gradients were seen in G2 (median of 0 mm Hg for G1 vs. 3 for G2; P = 0.014). CoA diameter showed no late loss in G1 and a late gain in G2 with a trend to being larger in G1 (16.7 ± 2.9 vs. 14.6 ± 3.9 mm; P = 0.075). Two patients required late stenting due to aneurysm formation or stent fracture in G1. Aortic wall abnormalities did not progress and one patient required redilation in G2. Blood pressure was similar in both groups at follow‐up (126 ± 12/81 ± 11 for G1 vs. 120 ± 15/80 ± 10 mm Hg for G2; P = 0.149 and 0.975, respectively). Although satisfactory and similar clinical outcomes were observed with both techniques, stenting was a better means to relieve the stenosis and minimize the risk of developing immediate aortic wall abnormalities. Catheter Cardiovasc Interv 2005;64:495–506. © 2005 Wiley‐Liss, Inc.
A Bicyclic P–P‐Bridged 1,3,2,4‐Diphosphadiboretane Cation and an Imino(phosphinidene)borane–AlBr3 Adduct
Authors: Knabel Klaus , Klapötke Thomas M. , Nöth Heinrich , Paine Robert T. , Schwab Ingo
Published: March 2005

Depending on reaction conditions the 1,3,2,4‐diphosphadiboretane 1 reacts with AlBr3 to give the unstable adduct tmp=B=P(tBu)AlBr3, 3, and/or the somewhat more stable salt [(tmpB)2(PtBu)P]+[AlBr4], 2. The X‐ray structure determination of 3 shows an almost linear NBP array with BN and BP double bonds resembling an allene type structure. NBO analysis shows the presence of BN‐ and BP‐π‐bonds. On the other hand, the cation of compound 2 has a bicyclic structure with a long P–P bond [2.349(2) Å]. The B–P bonds to the phosphonium type P2 atom [av. 1.939(5) Å] are longer than those to the tri‐coordinated P1 atom [1.889(6) Å]. NBO analysis of the model compound (H2NB)2(PMe)P+, 9, show that the P–P bond in 2 is formed from p‐orbitals.

(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A Surprisingly Stable 1‐(Chlorosilyl)‐2‐phosphaethenyllithium Compound, RCl2SiC(Li)=PMes*
Authors: Cretiu Nemes Gabriela , Ranaivonjatovo Henri , Escudié Jean , Silaghi‐Dumitrescu Ioan , Silaghi‐Dumitrescu Luminita , Gornitzka Heinz
Published: March 2005

RCl2Si–C(Li)=PMes* (1) (R = 9‐methylfluoren‐9‐yl, Mes* = 2,4,6‐tri‐tert‐butylphenyl), considered as a key intermediate in the synthesis of the heteroallene RClSi=C=PMes*, was obtained from RCl2Si–C(Cl)=PMes* by lithium/chlorine exchange with nBuLi and evidence for its identity was obtained by hydrolysis. Remarkably, however, it failed to undergo a lithium salt elimination to form the corresponding chlorophosphasilaallene, RClSi=C=PMes*, even under prolonged heating in toluene. As shown by theoretical studies (RHF/3‐21G* and RHF/6‐31G**//RHF/3‐21G* level), interactions between the lithium ion and the π‐systems of the substituents at the phosphorus and silicon atoms could partly account for this stability. The lithium compound 1 reacts with methanol or chlorotrimethylsilane leading to new silylphosphaalkenes. The reaction of the lithium derivative 1 with benzaldehyde gave a four‐membered heterocycle with an exocyclic P=C bond which virtually corresponds to the product of a [2+2] cycloaddition between the Si=C and C=O double bonds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis and Physicochemical Characterization of Bis(macrocycles) Involving a Porphyrin and a meso‐Substituted Corrole – X‐ray Crystal Structure of a [(Free‐base porphyrin)–corrole]bis(pyridine)cobalt Complex
Authors: Barbe Jean‐Michel , Burdet Fabien , Espinosa Enrique , Guilard Roger
Published: March 2005

A very efficient, simple synthesis of face‐to‐face porphyrin–corrole free‐bases bearing substituents at the meso positions of the corrole ring is reported. Starting from the (porphyrin–aldehyde)zinc species 1Zn, porphyrin–corrole free‐bases (3M, 3C) are obtained in two steps, in fairly good yields (40–43 %), compared to 11 steps for their corrole β‐pyrrole‐substituted counterparts. Moreover, the possibility to directly synthesize the free‐base (porphyrin–corrole)cobalt complex (5M or 5C) allows for the further preparation of heterodimetallic derivatives. Crystals of the bis(pyridine) adduct of 5M have been grown; the molecular structure clearly shows that the two pyridine molecules are coordinated to the cobalt ion in endo and exo positions, leading to an open‐mouth geometry of the bis(macrocycle). The structure of 5M(py)2also shows intermolecular π–π interactions along the [1 0 0] direction, leading to stacking of the complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Shape optimization of a body located in low Reynolds number flow
Authors: Yagi Hiroko , Kawahara Mutsuto
Published: March 2005

The purpose of this study is to perform a numerical application of the shape optimization formulation of a body located in an incompressible viscous flow field. The formulation is based on an optimal control theory in which a performance function of the fluid force is introduced. The performance function should be minimized satisfying the state equation. This problem can be transformed into the minimization problem without constraint condition by the Lagrange multiplier method and the adjoint equations using adjoint variables corresponding to the state equations. As a numerical study, the drag force minimization problem in the steady Stokes flow, which means approximated equation of the low Reynolds number Navier–Stokes equation is carried out. After that, the unsteady Navier–Stokes flow is analysed. As the minimization algorithm, the steepest descent method is successfully applied. Copyright © 2005 John Wiley & Sons, Ltd.
Bayesian modelling of multivariate quantitative traits using seemingly unrelated regressions
Authors: Verzilli Claudio J. , Stallard Nigel , Whittaker John C.
Published: March 2005

We investigate a Bayesian approach to modelling the statistical association between markers at multiple loci and multivariate quantitative traits. In particular, we describe the use of Bayesian Seemingly Unrelated Regressions (SUR) whereby genotypes at the different loci are allowed to have non‐simultaneous effects on the phenotypes considered with residuals from each regression assumed correlated. We present results from simulations showing that, under rather general conditions that are likely to hold in real situations, the Bayesian SUR approach has increased probability of selecting the true model compared to univariate analyses. Finally, we apply our methods to data from subjects genotyped for 12 SNPs in the apolipoprotein E (APOE) gene. Phenotypes relate to response to treatment with atorvastatin and include changes in total cholesterol, low‐density lipoprotein cholesterol, and triglycerides. Missing genotype data are naturally accommodated in our Bayesian framework by imputing them using a nested haplotype phasing algorithm. Genet. Epidemiol. © 2005 Wiley‐Liss, Inc.
Thrombin‐activated microglia contribute to death of dopaminergic neurons in rat mesencephalic cultures: Dual roles of mitogen‐activated protein kinase signaling pathways
Authors: Lee Da Yong , Oh Young J. , Jin Byung Kwan
Published: March 2005

This study evaluated the role of thrombin‐activated microglia in the neurodegeneration of mesencephalic cultures. Immunocytochemical and biochemical evidence indicated that in co‐cultures consisting of rat cortical microglia and mesencephalic neurons, thrombin led to nonselective loss of mesencephalic neurons. Accompanying neurodegeneration, microglial activation was obvious, evidenced by expression of tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, IL‐1β, inducible nitric oxide synthase (iNOS), and cyclooxygenase‐2 (COX‐2) and by increasing production of TNF‐α and nitric oxide (NO). In mesencephalic neurons treated with conditioned media (CM) taken from thrombin‐activated microglia, the number of dopaminergic neurons was significantly attenuated. The neurotoxicity of the CM was diminished when it was derived from microglia co‐treated with thrombin and either an extracellular signal‐regulated kinase 1/2 (ERK1/2) pathway inhibitor (PD98059) or a p38‐mitogen‐activated protein kinase (p38‐MAPK) inhibitor (SB203580). Moreover, jun N‐terminal kinase (JNK) and p38‐MAPK were activated in mesencephalic neurons treated with CM of thrombin‐activated microglia. Inhibition of JNK and p38‐MAPK rescued the dopaminergic neurons. Collectively, these results indicate that thrombin‐activated microglia induce neurodegeneration in cultured mesencephalic neurons and that the MAPKs actively participate in both microglial activation and neurodegeneration. The present data carefully suggest that microglial activation triggered by thrombin may be involved in the neuropathological processes of dopaminergic neuronal cell death that occur in Parkinson's disease. © 2005 Wiley‐Liss, Inc.
AIDS education, condom demand, and the sexual activity of American youth
Authors: Tremblay Carol Horton , Ling Davina C.
Published: March 2005

This paper examines the effects of AIDS education at school and at home on the sexual behavior of American youth. Multinomial logit equations of the probabilities of abstinence, sexual intercourse with a condom, and intercourse without a condom are estimated using data from the Youth Risk Behavior Supplement of the 1992 National Health Interview Survey. We find no significant effects of AIDS education on the probability of abstinence, but we do find that AIDS education significantly raises the likelihood of condom‐protected relative to unprotected intercourse. These results indicate that risk‐altering and risk‐revealing AIDS education dominate any utility‐altering effects favoring intercourse over abstinence. We also find that young women are influenced by AIDS education to a greater extent than young men. Overall, our results suggest that educating young people about AIDS does not promote sex and encourages safer sex, reducing the likelihood of HIV transmission and lowering the subsequent social costs. Copyright © 2005 John Wiley & Sons, Ltd.
Gas/liquid mass transfer processes in a carbon dioxide/alkane system
Authors: Gómez‐Díaz D , Navaza JM
Published: March 2005

A gas/liquid mass transfer process has been studied using carbon dioxide/alkane systems in a stirred vessel. Four linear alkanes (n‐heptane, n‐octane, n‐decane and n‐dodecane) have been used as the liquid phase in the present paper, and they have been employed to study the influence of the carbon length upon the mass transfer velocity. The mass transfer along the liquid phase has been studied using the mass transfer coefficient of the liquid phase, kL. Pure carbon dioxide has been employed as the phase in all cases for this reason. The effects of the power supplied to the liquid phase and the gas flow rate upon the absorption process have also been analysed. Finally, the equations that allow calculation of the mass transfer coefficients have been applied for these systems, with acceptable results. Copyright © 2005 Society of Chemical Industry
Immune responses following salivary gland administration of recombinant adeno‐associated virus serotype 2 vectors
Authors: Kok Marc R. , Voutetakis Antonis , Yamano Seiichi , Wang Jianghua , Cotrim Ana , Katano Hisako , Bossis Ioannis , Chiorini John A. , Tran Simon D. , Tak Paul P. , Baum Bruce J.
Published: March 2005

Background

Gene transfer to salivary glands (SGs) can be accomplished in a minimally invasive manner, resulting in stable, long‐term secretion of the transgene product. Therefore, SGs provide a novel target site for several potentially useful clinical gene therapeutics applications. Previous studies have indicated that intravenous, intramuscular and intranasal administration of recombinant adeno‐associated virus serotype 2 (rAAV2) vectors induce host immune responses. There are no reported studies on immune responsiveness of rAAV2 vector administration to SGs.

Material and methods

Vectors were administered by retrograde infusion to the SGs of Balb/c mice in various combinations. Thereafter, transgene expression was determined, and evaluations of host innate and adaptive immune responsiveness performed over a 56‐day period.

Results

Histological examination of SGs from vector‐treated mice showed no significant changes in appearance from controls, including the frequency of activated macrophage detection. There were also no differences in salivary flow rates among experimental groups. In vitro stimulation of splenocytes from mice administered rAAV2 showed elevated interferon‐γ levels in culture media. Significant titers of neutralizing antibodies to rAAV2 were detected in serum of mice following rAAV2 vector administration. While SGs could be transduced with low doses of vector it was not possible to repeat the administration and detect transduction with the same serotype at low doses. However, repeat administration was possible with an alternative serotype (rAAV4).

Conclusions

Following a single administration of rAAV2 vectors to SGs there is no significant innate immune response. However, rAAV2 vector administration to SGs results in both cellular and humoral immune responses. The latter may interfere with the efficacy of repeated rAAV2 vector administration. Copyright © 2004 John Wiley & Sons, Ltd.
Contractile properties of the developing fetal sheep bladder
Authors: Nyirády Peter , Thiruchelvam Nikesh , Godley Margaret L. , David Anna , Cuckow Peter M. , Fry Christopher H.
Published: March 2005

Aim

To characterise the developmental changes to the normal bladder by examining the in vitro contractile properties of the fetal sheep detrusor smooth muscle bladder at different gestational ages.

Methods

Three groups of normally developing fetal sheep bladders were investigated: (1) 65–70 days gestation (2nd trimester); (2) 105–110days (3rd trimester); (3) 135–140 days (term). Isometric contractions in isolated detrusor strips were measured during either electrical field stimulation (EFS) or exposure to agonists: carbachol, α‐β methylene‐ATP (ABMA) and KCl.

Results

There was a significant increase of absolute force elicited by EFS with fetal age. Contractures elicited by carbachol, ABMA and KCl increased between Groups 1 and 2, but not thereafter. The proportional increase of contractions elicited by carbachol and ABMA was also greater between Groups 1 and 2, than for EFS and KCl.

Conclusions

Fetal development between 65 and 140 days in the sheep is associated with increased contractile activation. The data are consistent with an increase of muscle development in the earlier stages (65–110 days). In the later stage (110–140 days) muscle development is complete but functional innervation of the tissue continues. © 2005 Wiley‐Liss, Inc.
On advanced solution strategies to overcome locking effects in strong discontinuity approaches
Authors: Mosler J.
Published: March 2005

This paper is concerned with the analysis of locking effects resulting from different orientations of micro‐defects and those of the corresponding macro‐defects. Based on a mixed‐mode material model embedded within the framework of the strong discontinuity approach (SDA), the described locking effect is illustrated by means of a crack analysis of a notched concrete beam. To overcome the deficiency of the proposed finite element model, the original SDA is modified and extended. For that purpose, two different advanced numerical formulations are developed: a rotating crack approach and a multiple crack approach. Restricting the governing equations to the material point level, a standard return‐mapping procedure is applied to the algorithmic formulations of both models. The applicability and the performance of the proposed numerical implementations are investigated by means of a re‐analysis of the two‐dimensional notched concrete beam. Copyright © 2005 John Wiley & Sons, Ltd.
Prenatal diagnosis of trisomy 4p: a new locus for holoprosencephaly?
Authors: Karmous‐Benailly Houda , Tabet Anne‐Claude , Thaly Adeline , Dupuy Olivier , Huten Yolène , Luton Dominique , Baumann Clarisse , Delezoide Anne‐Lise
Published: March 2005

Trisomy of the short arm of chromosome 4 is a well‐known syndrome, and several observations have been made in the last 30 years. Herein, we report a new observation of trisomy 4p in a fetus with a semi‐lobar holoprosencephaly (HPE), dysmorphic features and multiple malformations.

The diagnosis of HPE was made, at 33 weeks' gestation, on the fetus of a healthy G1P0 woman. Amniocentesis was performed for chromosome analysis and additional material was found on a chromosome 22. The couple elected to terminate the pregnancy and fetal examination was realized. Conventional and molecular cytogenetic studies were performed on the fetus and the parents, which showed that the additional material found on one chromosome 22 corresponded to the short arm of chromosome 4 and therefore led us to establish a diagnosis of trisomy 4p inherited from the malsegregation of a paternal translocation t(4;22)(q12;q11.1).

The etiology of HPE is very heterogeneous; it includes non‐genetic factors such as maternal diabetes and genetic causes. HPE cases have been described in association with many chromosomal anomalies, trisomy 13 being the most frequent. However, to our knowledge, HPE has never been previously reported in association with a trisomy involving solely the short arm of chromosome 4. Copyright © 2005 John Wiley & Sons, Ltd.
Cysteinylation of maternal plasma albumin and its association with intrauterine growth restriction
Authors: Bar‐Or David , Heyborne Kent D. , Bar‐Or Raphael , Rael Leonard T. , Winkler James V. , Navot Daniel
Published: March 2005

Objectives

We investigated cysteinylation of maternal plasma albumin in an observational study of intrauterine growth restriction (IUGR). High‐risk pregnancies and uteroplacental insufficiency (UPI) have been associated with elevated levels of homocysteine, and, in oxidizing environments, homocysteine is converted to cysteine, resulting in cysteinylation of proteins.

Methods

The study population included pregnancies with IUGR (n = 12) and uncomplicated pregnancies as controls (n = 8). In all cases, cysteinylation of maternal plasma albumin was measured in a blinded fashion using liquid chromatography coupled with electrospray ionization mass spectrometry.

Results

Markedly elevated maternal plasma levels of cysteinylated albumin were detected in pregnancies with IUGR (44.7 ± 14.8% of total albumin) compared to those in normal pregnancies (20.9 ± 6.1%). As a result, native albumin decreased from 52.5 ± 6.5% of total albumin in normal pregnancies to 30.1 ± 13.3% in IUGR pregnancies.

Conclusions

We hypothesize that sustained oxidative stress present in UPI is reflected by high levels of maternal cysteinylated albumin and may be a factor in the etiology of IUGR. Results of this preliminary study suggest that measurement of maternal plasma cysteinylated albumin may be useful for monitoring pregnancies associated with UPI and for detection of IUGR. Copyright © 2005 John Wiley & Sons, Ltd.
Magnetic resonance image findings of placental lake: report of two cases
Authors: Morikawa Mamoru , Cho Kazutoshi , Kataoka Soromon , Kato Emi H. , Yamada Takashi , Yamada Hideto , Minakami Hisanori
Published: March 2005

Two cases with a large cystic mass within the placenta are reported. By ultrasonography, it was found that both women had a subchorionic hypoechoic lesion (11.0 × 4.8 × 4.0 cm and 6.6 × 3.7 × 2.2 cm, respectively) at 24 and 35 weeks of gestation, respectively. In both cases, turbulent blood flow generated by a pulsatile jet flow (pulse rate; 40 to 60 beats per minute) into the cystic lesion seen on real‐time imaging and lesions being low intensity on T1‐weighted and isointensity on T2‐weighted magnetic resonance image suggested that they contained fresh maternal blood. In both cases, the sonolucency of the lesions did not change until cesarean deliveries of females, both of whom were small‐for‐gestational‐age infants (1940 g at 37 weeks and 2195 g at 37 weeks, respectively). Biochemical analysis of the fluid in the cystic lesion sampled during the cesarean section in the latter case confirmed that the fluid had originated from the maternal blood. These lesions histologically corresponded to large avillous areas surrounded by normal villi. Thus, a huge placental lake was diagnosed in both cases. Copyright © 2005 John Wiley & Sons, Ltd.
Variation of Ozone Reflection Coefficient at a Metal Surface with its Gradual Oxidation
Authors: Itoh Haruo , Rusinov Ilko M. , Suzuki Susumu , Suzuki Tooru
Published: March 2005

Summary: Investigation of ozone loss rate in a metallic chamber has been performed paying attention to the wall materials effect. Stainless steel, copper, and aluminum are used in the experiments. Ozone is produced by corona discharge electrode, which was mounted on the secondary electrode of a piezoelectric transformer. The decaying ozone density, which was observed after the corona discharge interruption, was measured using the HgI 254 nm photo absorption method. The temporal decrease of ozone density shows a single‐exponential and the loss rates of ozone, that is, the inverse of ozone lifetimes are determined. During the experiment with repetition using the same surface material, we found a gradual increase of the ozone reflection coefficient in the low‐pressure region. We adopted surface inspection of specimens using electron probe micro analysis (EPMA), Auger electron spectroscopy (Auger), and X‐ray photo‐electron spectroscopy (XPS). The results indicate that some amount of oxygen atoms is detected in the surface layer of the specimen. We consider that the increase of ozone reflection coefficient with the repeated measurement corresponds to gradual oxidation of the surface wall material.

Variation of effective lifetime over repeated measurements using same material.

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Variation of effective lifetime over repeated measurements using same material.
DC Glow Discharge in Atmospheric Air as a Source for Volatile Organic Compounds Abatement
Authors: Machala Zdenko , Marode Emmanuel , Morvová Marcela , Lukáč Peter
Published: March 2005

Summary: In this article, a direct current (DC) discharge in atmospheric pressure air as a source for pollution control is presented. The investigated continuous discharge occurring between two metal electrodes was of the glow type. The discharge generated a highly ionized, non‐equilibrium air plasma with gas temperatures of 1 500–2 500 K. Single and multiple discharges of this type were successfully tested in glass and copper tube reactors for the abatement of selected VOCs (cyclohexanone and toluene). Depending on the reactor type, discharge parameters and the energy density, abatement efficiencies of 30–95% were obtained, with energy costs of 200–1 000 eV/molecule. The thermal VOC decomposition in the discharge was coupled with radical‐induced volume reactions. It was found that extending the radical‐dominated decomposition phase yielded a better performance. The VOCs tested were converted to some gaseous and some condensed products. Copper electrode surfaces influenced the character of the condensed products and seemed to have a certain catalytic effect on the process.

Removal efficiency, η, as a function of the energy density w. Both polarities of HPGD in dry and humid air, 5‐point glass tube reactor, cyclohexanone 2 000 ppm. Toluene 2 000 ppm in negative HPGD has been added for comparison.

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Removal efficiency, η, as a function of the energy density w. Both polarities of HPGD in dry and humid air, 5‐point glass tube reactor, cyclohexanone 2 000 ppm. Toluene 2 000 ppm in negative HPGD has been added for comparison.