bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectopic expression of Hoxd10 in thoracic spinal segments induces motoneurons with a lumbosacral molecular profile and axon projections to the limb
Authors: Shah Veeral , Drill Emily , Lance‐Jones Cynthia
Published: June 2004

Hox genes encode anterior–posterior identity during central nervous system development. Few studies have examined Hox gene function at lumbosacral (LS) levels of the spinal cord, where there is extensive information on normal development. Hoxd10 is expressed at high levels in the embryonic LS cord but not the thoracic cord. To test the hypothesis that restricted expression of Hoxd10 contributes to the attainment of an LS identity, and specifically an LS motoneuron identity, Hoxd10 was ectopically expressed in thoracic segments in chick embryos by means of in ovo electroporation. Regional motoneuron identity was assessed after the normal period of motoneuron differentiation. Subsets of motoneurons in transfected thoracic segments developed a molecular profile normally shown by LS motoneurons, including Lim 1 and RALDH2 expression. In addition, motoneurons in posterior thoracic segments showed novel axon projections to two muscles in the anterodorsal limb, the sartorius and anterior iliotibialis muscles. At thoracic levels, we also found a decrease in motoneuron numbers and a reduction in gonad size. These last findings suggest that early and high levels of Hox expression impeded motoneuron development and neural–mesodermal interactions. Despite these adverse effects, our data indicate that Hoxd10 expression is sufficient to induce LS motoneuron identity and axon trajectories characteristic of motoneurons in the LS region. Developmental Dynamics 231:43–56, 2004. © 2004 Wiley‐Liss, Inc.
Embryonic development of folate binding protein‐1 (Folbp1) knockout mice: Effects of the chemical form, dose, and timing of maternal folate supplementation
Authors: Spiegelstein Ofer , Mitchell Laura E. , Merriweather Michelle Y. , Wicker Ned J. , Zhang Qiang , Lammer Edward J. , Finnell Richard H.
Published: June 2004

Inactivation of folate binding protein‐1 (Folbp1) adversely impacts murine embryonic development, as nullizygous embryos (Folbp1‐/‐) die in utero. Administration of folinic acid (N5‐formyl‐tetrahydrofolate) to Folbp1‐deficient dams before and throughout gestation rescues the majority of embryos from premature death; however, a portion of surviving embryos develop structural malformations, including neural tube defects. We examined whether maternal supplementation with L‐N5‐methyl‐tetrahydrofolate (L‐5M‐THF) has superior protective effects on embryonic development of Folbp1‐/‐ fetuses compared with L‐N5‐formyl‐tetrahydrofolate (L‐5F‐THF). We also examined the critical period during gestation when folate supplementation is most beneficial to the developing Folbp1‐/‐ embryos. Folbp1‐/‐ pups presented with a range of malformations involving the neural tube, craniofacies, eyes, and abdominal wall. The frequencies of these malformations decreased with increasing folate dose, regardless of the form used. There was no additional benefit provided by L‐5M‐THF compared with L‐5F‐THF. Despite rescuing the phenotype in Folbp1‐/‐ embryos, no significant elevation of Folbp1‐/‐ maternal folate levels was observed with supplementation. Developmental Dynamics 231:221–231, 2004. © 2004 Wiley‐Liss, Inc.
Expression and roles of connective tissue growth factor in Meckel's cartilage development
Authors: Shimo Tsuyoshi , Kanyama Manabu , Wu Changshan , Sugito Hiroki , Billings Paul C. , Abrams William R. , Rosenbloom Joel , Iwamoto Masahiro , Pacifici Maurizio , Koyama Eiki
Published: June 2004

Meckel's cartilage is a prominent feature of the developing mandible, but its formation and roles remain unclear. Because connective tissue growth factor (CTGF, CCN2) regulates formation of other cartilages, we asked whether it is expressed and what roles it may have in developing mouse Meckel's cartilage. Indeed, CTGF was strongly expressed in anterior, central, and posterior regions of embryonic day (E) 12 condensing Meckel's mesenchyme. Expression decreased in E15 newly differentiated chondrocytes but surged again in E18 hypertrophic chondrocytes located in anterior region and most‐rostral half of central region. These cells were part of growth plate‐like structures with zones of maturation resembling those in a developing long bone and expressed such characteristic genes as Indian hedgehog (Ihh), collagen X, MMP‐9, and vascular endothelial growth factor. At each stage examined perichondrial tissues also expressed CTGF. To analyze CTGF roles, mesenchymal cells isolated from E10 first branchial arches were tested for interaction and responses to recombinant CTGF (rCTGF). The cells readily formed aggregates in suspension culture and interacted with substrate‐bound rCTGF, but neither event occurred in the presence of CTGF neutralizing antibodies. In good agreement, rCTGF treatment of micromass cultures stimulated both expression of condensation‐associated macromolecules (fibronectin and tenascin‐C) and chondrocyte differentiation. Expression of these molecules and CTGF itself was markedly up‐regulated by treatment with transforming growth factor‐β1, a chondrogenic factor. In conclusion, CTGF is expressed in highly dynamic manners in developing Meckel's cartilage where it may influence multiple events, including chondrogenic cell differentiation and chondrocyte maturation. CTGF may aid chondrogenesis by acting down‐stream of transforming growth factor‐β and stimulating cell–cell interactions and expression of condensation‐associated genes. Developmental Dynamics 231:136–147, 2004. © 2004 Wiley‐Liss, Inc.
TRAF6‐dependent NF‐kB transcriptional activity during mouse development
Authors: Dickson Kathleen M. , Bhakar Asha L. , Barker Philip A.
Published: June 2004

Nuclear factor‐kappa B (NF‐kB) transcriptional activity is induced by numerous stimuli. To identify tissues exhibiting NF‐kB transcriptional activity during development, we analyzed transgenic reporter mice that express β‐galactosidase from an NF‐kB–responsive element. We report that NF‐kB activation is widespread and present in numerous epithelial structures and within vasculature. Several regions of the developing central nervous system, including the roof plate and floor plate of the midbrain, show prominent NF‐kB activation. To assess the role of the TRAF6 adaptor protein in developmental NF‐kB activity, we analyzed NF‐kB activation in reporter mice rendered null for TRAF6. Deletion of TRAF6 resulted in the loss of NF‐kB activity in epithelia, in vasculature, and in roof and floor plate but had no effect on NF‐kB activity developing telencephalon, choroid plexus, cochlear canal, and thymus. These data indicate that NF‐kB transcriptional activity is present in a broad range of structures during development and that TRAF6 plays a critical role mediating developmental NF‐kB activation in many but not all tissues. Developmental Dynamics 231:122–127, 2004. © 2004 Wiley‐Liss, Inc.
Bidirectional inhibitory interactions between the embryonic chicken metanephros and lumbosacral nerves in vitro
Authors: Silver Lee , Qiang Liang , Loudon Robert , Gallo Gianluca
Published: June 2004

During chicken embryonic development the metanephros forms from the uretic duct at embryonic day (E) 7. As the metanephric tissue develops between E7 and E10, it comes into close apposition with lumbosacral nerves. Coculturing of metanephric and nerve explants demonstrated that the Schwann cells of the sciatic nerve inhibit the migration of metanephric cells in a contact‐dependent manner. Conversely, metanephric cells inhibit dorsal root ganglion axon extension in a contact‐dependent manner. However, metanephric cells are not inhibited by contact with growth cones or axons. Dorsal root ganglion growth cones become sensitive to the inhibitory signals on the surfaces of metanephric cells around E8, a time when the metanephros is expanding into the territory occupied by nerves in vivo. These observations demonstrate inhibitory bidirectional tissue–tissue interactions in vitro and provide a novel model system for the study of contact‐based guidance of both neuronal and non‐neuronal cell migration. Developmental Dynamics 231:190–198, 2004. © 2004 Wiley‐Liss, Inc.
Entire mitogen activated protein kinase (MAPK) pathway is present in preimplantation mouse embryos
Authors: Wang Yingchun , Wang Fangfei , Sun Tong , Trostinskaia Anna , Wygle Dana , Puscheck Elizabeth , Rappolee Daniel A.
Published: June 2004

To understand how mitogenic signals are transduced into the trophoblasts in preimplantation embryos, the expression of mitogen‐activated protein kinase (MAPK) pathway molecules was tested. We used immunocytochemical means and reverse transcriptase‐polymerase chain reaction to test whether MAPK pathway molecule gene products exist at the protein and phosphoprotein level in the zygote and the RNA level in the egg and zygote. In addition, all antibodies detected the correct‐sized major band in Westerns of placental cell lines representing the most prevalent cell type in preimplantation embryos. A majority of mRNA transcripts of MAPK pathway genes were detected in unfertilized eggs, and all were expressed in the zygote. We found that the MAPK pathway protein set consisting of the following gene products was present: FRS2α, GRB2, GAB1, SOS1, Ha‐ras, Raf1/RafB, MEK1,2,5, MAPK/ERK1,2, MAPK/ERK5, and RSK1,2,3 (see abbreviations). These proteins were detected in trophoblasts in embryonic day (E) 3.5 embryos when they could mediate mitogenic fibroblast growth factor signals from the embryo or colony stimulating factor‐1 signals from the uterus. The phosphorylation state and position of the phosphoproteins in the cells suggested that they might function in mediating mitogenic signals. Interestingly, a subtle transition from maternal MAPK function to zygotic function was suggested by the localization for three MAPK pathway enzymes between E2.5 and E3.5, Raf1 phospho is largely cell membrane‐localized at E2.5 and E3.5, and MEK1,2 phospho accumulates in the nucleus on E2.5 and E3.5. However, MAPK phospho shifts from nuclear accumulation at E2.5 to cytoplasmic accumulation at E3.5. This finding is similar to the cytoplasmic MAPK phospho localization reported in fibroblast growth factor signaling fields in postimplantation embryos (Corson et al. [2003] Development 130:4527–4537). This spatial and temporal expression study lays a foundation to plan and analyze perturbation studies aimed at understanding the role of the major mitogenic pathway in preimplantation mouse embryos. Developmental Dynamics 231:72–87, 2004. © 2004 Wiley‐Liss, Inc.
Nogo and Nogo‐66 receptor in human and chick: Implications for development and regeneration
Authors: O'Neill Paul , Whalley Katherine , Ferretti Patrizia
Published: June 2004

Antibodies to the myelin protein Nogo increase axonal regrowth after central nervous system injury. We have investigated whether Nogo expression contributes to loss of regenerative potential during development by using chick embryos, which regenerate their spinal cord until embryonic day (E) 13, when myelination begins. We show that Nogo‐A and the Nogo receptor (NgR) are developmentally regulated both in chick and human embryos, are first detected at developmental stages when the chick spinal cord regenerates, and are not down‐regulated after injury at permissive stages for regeneration. Therefore, expression of Nogo‐A and NgR in pre‐E13 chick spinal cords is not sufficient to inhibit regeneration. Nogo‐A expression in the chick early embryo is primarily observed in axons, whereas NgR is mainly located on neuronal cell bodies, both in spinal cord and eye, and in striated muscle including the heart. With the onset of myelination, there is down‐regulation of Nogo‐A expression in neurons. Therefore, loss of regenerative potential might be linked to changes in its cellular localization. The possibility that only Nogo expressed in mature oligodendrocytes can exercise inhibitory effects would reconcile the lack of inhibition we observe in developing chick spinal cords before the onset of myelination with evidence from other laboratories on the inhibitory effects of Nogo in mature central nervous system. The distinctive and complementary patterns of Nogo‐A and NgR expression and their conservation throughout evolution support the view that Nogo signaling represents a key pathway in nervous system and striated muscle development. Its putative role in target innervation and establishment of neural circuitry is discussed. Developmental Dynamics 231:109–121, 2004. © 2004 Wiley‐Liss, Inc.
Identification and embryonic expression of a new AP‐2 transcription factor, AP‐2ϵ
Authors: Wang Hao‐Ven , Vaupel Kristina , Buettner Reinhard , Bosserhoff Anja‐Katrin , Moser Markus
Published: June 2004

AP‐2 proteins comprise a family of highly related transcription factors, which are expressed during mouse embryogenesis in a variety of ectodermal, neuroectodermal, and mesenchymal tissues. AP‐2 transcription factors were shown to be involved in morphogenesis of craniofacial, urogenital, neural crest‐derived, and placental tissues. By means of a partial cDNA fragment identified during an expressed sequence tag search for AP‐2 genes, we identified a fifth, previously unknown AP‐2–related gene, AP‐2ϵ. AP‐2ϵ encodes an open reading frame of 434 amino acids, which reveals the typical modular structure of AP‐2 transcription factors with highly conserved C‐terminal DNA binding and dimerization domains. Although the N‐terminally localized activation domain is less homologous, position and identity of amino acids essential for transcriptional transactivation are conserved. Reverse transcriptase‐polymerase chain reaction analyses of murine embryos revealed AP‐2ϵ expression from gestational stage embryonic day 7.5 throughout all later embryonic stages until birth. Whole‐mount in situ hybridization using a specific AP‐2ϵ cDNA fragment demonstrated that during embryogenesis, expression of AP‐2ϵ is mainly restricted to neural tissue, especially the midbrain, hindbrain, and olfactory bulb. This expression pattern was confirmed by immunohistochemistry with an AP‐2ϵ–specific antiserum. By using this antiserum, we could further localize AP‐2ϵ expression in a hypothalamic nucleus and the neuroepithelium of the vomeronasal organ, suggesting an important function of AP‐2ϵ for the development of the olfactory system. Developmental Dynamics 231:128–135, 2004. © 2004 Wiley‐Liss, Inc.
Levels of Gli3 repressor correlate withBmp4expression and apoptosis during limb development
Authors: Bastida Maria Félix , Delgado M. Dolores , Wang Baolin , Fallon John F. , Fernandez‐Teran Marian , Ros Maria A.
Published: June 2004

Removal of the posterior wing bud leads to massive apoptosis of the remaining anterior wing bud mesoderm. We show here that this finding correlates with an increase in the level of the repressor form of the Gli3 protein, due to the absence of the Sonic hedgehog (Shh) protein signaling. Therefore, we used the anterior wing bud mesoderm as a model system to analyze the relationship between the repressor form of Gli3 and apoptosis in the developing limb. With increased Gli3R levels, we demonstrate a concomitant increase in Bmp4 expression and signaling in the anterior mesoderm deprived of Shh signaling. Several experimental approaches show that the apoptosis can be prevented by exogenous Noggin, indicating that Bmp signaling mediates it. The analysis ofBmp4expression in several mouse and chick mutations with defects in either expression or processing of Gli3 indicates a correlation between the level of the repressor form of Gli3 andBmp4expression in the distal mesoderm. Our analysis adds new insights into the way Shh differentially controls the processing of Gli3 and how, subsequently, BMP4 expression may mediate cell survival or cell death in the developing limb bud in a position‐dependent manner. Developmental Dynamics 231:148–160, 2004. © 2004 Wiley‐Liss, Inc.
Elucidation of the Solution Structures of Transition Metal Complex Ion Pairs by NOE NMR Experiments
Authors: Macchioni Alceo
Published: June 2004

Our results from structural investigations of transition metal complex ion pairs in solution by homonuclear and heteronuclear 1D‐ and 2D‐NOE NMR spectroscopy are reviewed. Both model (A) and catalytically active (B) complexes have been taken into account; their general formulas are: trans‐[ML2(N,X)(Y)(Z)]+A− (A) {M = FeII, RuII and OsII, L = PMe3, Y = CO, Z = COMe, A− = BPh3R−, CF3SO3−, BF4−, PF6− and B[3,5‐(CF3)2C6H3]4−; M = IrIII, L = PR3, Y = Z = H and A− = BPh4−, CF3SO3−, BF4−, PF6−} and [M′(N,X)(R,olefin)]+A− (B) {M′ = Pt, R = Me, olefin = ethene, propene and CH2=CHCOOMe, A− = BF4−; M′ = Pd, (R,olefin) = η1,η2‐5‐methoxycyclooctenyl, A− = BPh4−, CF3SO3−, BF4−, PF6−, SbF6− and B[3,5‐(CF3)2C6H3]4−}, where N,X = bis(pyrazolyl)methane, bipyridine, α‐diimines, α‐diamines or α‐oxo imines. The detection of dipolar interionic interactions in 1H‐NOESY and 19F,1H‐HOESY NMR spectra allowed relative anion‐cation orientations to be determined, these being well defined in most cases, with one orientation predominating in solution. We often found that the anion approaches the complexes from the side of the N,X‐ligands, due to an accumulation of positive charge at the junction of the moieties containing the N‐ and X‐donor atoms. In square‐planar complexes B, the apparently favoured apical positions were often protected either by electronic factors [N,X = bis(2‐pyridyl)amine or bis(pyrazolyl)methane] or by a combination of electronic and steric factors (N,X = α‐diimines). For M′ complexes, bearing Ar−N=C(Me)−C(Me)=N−Ar ligands, the position of the counter‐anion is finely modulated by the steric hindrance of the ortho‐aryl substituents. The accessibility of the metal centre, which is directly associated with the catalytic performances of the complexes, was determined by using the counteranion as a probe. Finally, average interionic distances were estimated for model complexes A, bearing unsymmetrical BPh3R− counter‐anions, based on the quantification of interionic NOEs. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2003)
Rhodium Clusters Substituted by Cycloheptatrienyl Ligands: Synthesis and Solid‐State Structure of [Rh11(CO)14(μ3‐η2:η3:η2‐C7H7)3]
Authors: Della Pergola Roberto , Comensoli Emanuela , Garlaschelli Luigi , Manassero Mario , Sansoni Mirella , Strumolo Donatella
Published: June 2004

The cluster [Rh11(CO)14(C7H7)3] (1) was obtained from the reaction of [Rh6(CO)16] and an excess of cycloheptatriene in refluxing toluene. Initially, the substituted cluster [Rh6(CO)13(C7H8)] (2) could be identified spectroscopically, which is transformed into 1 after prolonged refluxing. In the solid state, the eleven rhodium atoms define a trioctahedral metal cage, condensed through a common edge. The three planar, equivalent C7 rings sit on the top of triangular faces. The spectroscopic characterisation of the product is hampered by its low solubility. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis and Characterization of a Carbene·SO2 Adduct − New Insights into the Structure and Bonding of Thiourea S,S‐Dioxides
Authors: Denk Michael K. , Hatano Ken , Lough Alan J.
Published: June 2004

The title compound 1,3‐di‐tert‐butylimidazol‐2‐ylidene·SO2 (2) was obtained from the respective stable carbene 1 and SO2 in quantitative yield and investigated by single crystal X‐ray crystallography and NMR spectroscopy. Quantum chemical calculations show that thiourea‐S,S‐dioxides like 2 are Lewis acid‐base adducts of the respective diamino carbenes with SO2 (CS bond energies < 20 kcal·mol−1). They possess long CS bonds and a pyramidal sulfur atom and are thus structurally distinct from sulfur ylides or sulfenes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Use of Molecular Scaffolding for the Stabilization of an Intramolecular Dative PIII‐PV System
Authors: Kilian Petr , Philp Douglas , Slawin Alexandra M. Z. , Woollins J. Derek
Published: June 2004

The reaction of NapP2S4 (1; Nap = naphthalene‐1,8‐diyl) with chlorine gas gave [Nap(PCl2)(PCl4)] (2), displaying a rare σ4P‐σ6P bonding interaction. An X‐ray structure analysis confirmed the PCl5‐like, P−P bond containing phosphonium‐phosphoride structure of 2 in the crystal, which was also found in solution at low temperature. At ambient and higher temperatures, dynamic behaviour on the NMR time‐scale was observed, which was assigned to interchange of the ionic phosphonium‐phosphoride form 2 and the molecular bis(phosphorane) Nap(PCl3)2 form 3, rather than to the ionic phosphonium salt‐phosphorane form [Nap(PCl3)(PCl2)][Cl] 4. Electronic structure calculations were performed at the B3LYP/6−31G(d,p) level of theory on structures 2 and 3; structure 3 was located as a local minimum on the potential energy surface, 15 kcal·mol−1 higher in energy than structure 2. The crystal structure and calculated P−P distances are 2.34 and 2.31 Å for 2 and 3, respectively. An activation energy of 19.7 kcal·mol−1 was found for the transition state structure by coordinate driving calculations; the line‐shape analysis of variable temperature 31P{1H} NMR spectra gave an activation energy of 14.4 kcal·mol−1. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Facile Metal‐Mediated Synthesis of Macrocyclic Diselenoethers
Authors: Yeo Jeremy S. L. , Vittal Jagadese J. , Hor T. S. Andy
Published: June 2004

Nucleophilic attack of [Pt2(μ‐Se)2(PPh3)4] on dihaloalkanes gives stable diselenolato complexes, which release macrocyclic diselenoethers upon treatment with dihaloalkanes. The overhead‐bridged diplatinum intermediates have been isolated and structurally characterized by single‐crystal X‐ray crystallography. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2003)
A CuII Chain Compound Showing a Ferromagnetic Coupling through Triple N1,N2‐1,2,4‐Triazole Bridges
Authors: Garcia Yann , van Koningsbruggen Petra J. , Bravic Georges , Chasseau Daniel , Kahn Olivier
Published: June 2004

[Cu(hyetrz)3](CF3SO3)2·H2O [hyetrz = 4‐(2′‐hydroxyethyl)‐1,2,4‐triazole] represents the first structurally characterised ferromagnetically coupled CuII chain compound containing triple N1,N2‐1,2,4‐triazole bridges. catena‐[μ‐Tris{4‐(2′‐hydroxyethyl)‐1,2,4‐triazole‐N1,N2}copper(II)] bis(trifluoromethanesulfonate) hydrate (C14H23F6S2O10CuN9) crystallises in the triclinic space group P$\bar 1$
, a = 13.54(3), b = 14.37(3), c = 15.61(4) Å, α = 95.9(1), β = 104.9(1), γ = 106.5(1)°, V = 2763(11) Å3, Z = 4 (CuII units). The CuII ions are linked by triple N1,N2‐1,2,4‐triazole bridges yielding an alternating chain with Cu1−Cu2 = 3.8842(4) Å and Cu2−Cu3 = 3.9354(4) Å. Analysis of the magnetic data according to a high‐temperature series expansion gives a J value of +1.45(3) cm−1. The nature and the magnitude of the ferromagnetic exchange have been discussed on the basis of the structural features. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Convenient Controllable Synthesis of Inorganic 1D Nanocrystals and 3D High‐Ordered Microtubes
Authors: Kang Zhenhui , Wang Enbo , Jiang Min , Lian Suoyuan , Li Yangguang , Hu Changwen
Published: June 2004

Polyoxometalates (POMs) nanorods, hollow particles, microtubes, and 3D‐ordered tube systems were prepared using a novel and simple PEG/H2O liquid system. POM nanorods with various diameters (30−400 nm) and lengths (500 nm to 2 μm) were produced in a well‐controlled manner. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A New Highly Active Diphosphane‐Palladium(II) Complex as a Catalyst Precursor for the Heck Reaction
Authors: Sjövall Sven , Johansson Maria H. , Andersson Carlaxel
Published: June 2004

The new diphosphane ligand cis‐1,3‐bis[(diphenylphosphanyl)methyl]cyclohexane (4) has been prepared and has allowed the synthesis of the palladium complex cis‐[Pd(4)(CO2CF3)2] (6). To obtain cis complexation of the diphosphane in 6 the cyclohexane skeleton adopts a chair conformation with a diaxial orientation of the substituents, a structure that has been verified by an X‐ray structure determination. This complex efficiently catalyses the vinylation of iodo‐ and bromobenzenes in high yields. For the best reaction, with methyl acrylate and iodobenzene, a yield of >98% was obtained with an average turnover frequency of 11 760 h−1 and a turnover number of 1 176 000.
2,6‐Di‐tert‐butyl‐4‐(3,3‐diarylpropadienylidene)‐2,5‐cyclohexadien‐1‐ones, the First Stable p‐Quinopropadienes
Authors: Kawase Takeshi , Nishigaki Naoki , Kurata Hiroyuki , Oda Masaji
Published: June 2004

Treatment of 2,6‐di‐tert‐butyl‐4‐ethynylphenol with 2 equivalents of nBuLi, followed by addition of diaryl ketones, afforded the corresponding p‐quinopropadienes 2a−f upon appropriate dehydrative treatments. These compounds are fairly stable, orange to purple, crystalline substances, exhibiting intense absorptions at longer wavelengths. In particular, the bis(dimethylamino) derivative 2a absorbs across the whole of the visible spectrum and into the near infrared. Unlike the quinone methides 1, compounds 2 exhibited irreversible oxidation waves together with irreversible reduction waves on cyclic voltammetry. The very small E1sum value of 2a also indicates the highly amphoteric redox properties of 2a; however, both the anion and cation radicals of 2 are highly reactive. The molecular structures of 2a and 2e exhibit relatively small dihedral angles between two aromatic ring planes (2a for 47° and 2e for 52°), and each has a short central double bond and long side double bonds. The short central double bond (2a for 1.228 Å and 2e for 1.235 Å) indicates the importance of the resonance contribution of the dipolar structure with an acetylenic bond. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Two New Haliclamines from the Arctic Sponge Haliclona viscosa
Authors: Volk Christian A. , Lippert Heike , Lichte Ellen , Köck Matthias
Published: June 2004

There are a large number of studies on sponges from warm or tropical waters, whereas little is known about the chemistry of sponges from Arctic waters. Here, we describe the isolation and structure elucidation of two new 3‐alkyltetrahydropyridine alkaloids (haliclamines C and D) from the Arctic sponge Haliclona viscosa. MS and 2D NMR spectroscopy were used to analyse the structure of the two new compounds. Since the haliclamines consist of long alkyl chains, MS/MS methods were necessary for the unambiguous assignment of the constitution of the new alkaloids. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Concave 1,10‐Phenanthrolines by a Combination of Suzuki Coupling, Ring Closing Metathesis and Hydrogenation
Authors: Lüning Ulrich , Fahrenkrug Frank
Published: June 2004

A wide variety of saturated and unsaturated concave 1,10‐phenanthrolines 2 and 4 have been synthesized in good yields starting from dichloro‐1,10‐phenanthroline 14. In the three step synthesis, Suzuki couplings of bis‐ortho‐substituted boronic acids were used to introduce two different or two identical aryl bridgeheads into the 2‐ and 9‐positions of the 1,10‐phenanthroline (yields ⩾70%). The resulting diaryl‐1,10‐phenanthrolines 3, substituted with alkenyloxy groups of different lengths, underwent ring closing metathesis reactions giving (bi)macrocyclic 1,10‐phenanthrolines 4 in yields between 73 and 96%. The alkene chains of 4 were saturated using hydrogen and Pd/C giving the concave 1,10‐phenanthrolines 2 in yields between 75 and 99%. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Hydrogen Evolution from Peroxides − a Concerted Reaction
Authors: Thiel Werner R.
Published: June 2004

DFT calculations provide strong evidence that the evolution of hydrogen from mixtures of aldehydes and hydrogen peroxide proceeds by a concerted mechanism. The electronic influence of a series of substituents is correlated with the enthalpies of activation and reaction, and the calculated isotope effect of the reaction is compared with experimentally obtained data. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Charge‐Transfer Interactions in 4‐Donor 4′‐Acceptor Substituted 1,1‐Diphenylethenes
Authors: van Walree Cornelis A. , Kaats‐Richters Veronica E. M. , Veen Sandra J. , Wieczorek Birgit , van der Wiel Johanna H. , van der Wiel Bas C.
Published: June 2004

Two 1,1‐diphenylethenes bearing either a 4‐dimethylamino or 4‐methoxy group as electron donor and a 4′‐cyano group as electron acceptor, as well as compounds containing only a donor or acceptor functionality, were synthesized. The observation of strong fluorescence solvatochromism (originating from a biradicaloid twisted intramolecular charge‐transfer state) of the donor‐acceptor compounds reveals that photoinduced charge separation through the cross‐conjugated 1,1‐diphenylethene spacer occurs. The presence of weak charge‐transfer absorption bands in the UV spectra reflects modest ground state donor‐acceptor coupling. These results show that charge transport through a branched conjugation path is possible. 1‐[4‐(Dimethylamino)phenyl]‐1‐phenylethene was found to fluoresce from two different states. In nonpolar solvents the source is a local aniline‐like state, whereas in polar solvents the fluorescence originates from a twisted intramolecular charge‐transfer state. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Foam Fractionation of Rinsing Waters Containing Surfactants
Authors: Morgan G. , Wiesmann U.
Published: June 2004

Foam fractionation (FF) can be utilized to separate the surfactants from rinsing waters of surfactant production plants and recover a concentrated surfactant solution. By bubbling air through the solution the surfactants are removed with the foam, which has a high surface to liquid volume ratio. The foam, once destroyed, has a high concentration of surfactants and represents a usable product. At concentrations above 1 g/L a multi‐stage treatment of the effluent leads to an increase both in the removal degree and enrichment when the operating parameters are correctly chosen for each stage. Countercurrent operation with foamate recycle makes it possible to increase the enrichment significantly.
Fuzzy State Controller for the Soft Process Drying of Natural Material Foil
Authors: Ewald T. , Delgado A. , Becker T.
Published: June 2004

This contribution describes the development of a fuzzy‐based process control system for the soft process drying of natural material foils. The system should maintain constant product moisture to facilitate automatic treatment of the foils in subsequent processing steps. A pilot plant was constructed to support the development of the control system. The core of the experimental setup is an optical measuring device, that provides for the simultaneous in‐line determination of drying foil water content and thickness at different places in the drying plant. The sensor possesses a measuring range of 10 %–80 % for water content (X*) and 50 μm–500 μm for thickness. Compared to a reference method, the system shows an accuracy of ± 3 % for the water concentration and 3.5 % for the foil thickness. No significant drift in the output signal could be detected for 5 weeks. These quantities, together with other process information, were used as inputs for a multistage fuzzy control system, which adjusts the outputs temperature and velocity of drying air and belt velocity for optimal soft process drying. In normal operation without the controller, foil moisture variations of 7 % over a period of 2 hours were obtained, while applying the fuzzy logic controller decreased the variations to 4 %. After disturbances of up to 17.5 % in initial viscosity, 6.8 % in concentration and 20 % in foil thickness variations, outlet moisture content variations of only 6.2 % were attained.
Hydrodynamics and Gas Dispersion Characterization in a System Equipped with a New Gas‐Inducing Impeller
Authors: Sardeing R. , Ferrand F. , Poux M. , Avrillier P. , Xuereb C.
Published: June 2004

A new agitation system, called Turboxal, used for the oxygenation and the mixing of wastewater biological treatment tanks has been studied. The interactions between the shell and the three impellers which compose the Turboxal have been analyzed by single‐phase flow patterns. The pumping capacity and the power consumption have also been measured. In addition, the gas dispersion regimes have been analyzed in the tank and in the shell. Finally, the effect of the interaction and the effect of the position of the different agitators on the limit of the flooding regime have been determined.
A Screening Analysis of the High‐Pressure Extraction of Anthocyanins from Red Grape Pomace with Carbon Dioxide and Cosolvent
Authors: Mantell C. , Rodríguez M. , Martínez de la Ossa E.
Published: June 2004

In the work described here, a set of screening factorial design experiments was carried out in order to study the extraction process of anthocyanins from red grape pomace with carbon dioxide, along with either methanol or water as cosolvent, at high pressure. The variables studied were pressure, temperature, solvent flow‐rate, cosolvent percentage, cosolvent type (methanol or water) and extraction time. The quantification of the total amount of anthocyanins was performed by a colorimetric method. The results of the ANOVA study show a strong influence of the type and percentage of cosolvent. The best results were obtained with 20 mol‐% of methanol, 100 bar, 60 °C and a flow‐rate of 22 mmol/min after two hours of extraction.
Improved design of sliding mode control for civil structures with saturation problem
Authors: Lee Sang‐Hyun , Min Kyung‐Won , Lee Young‐Cheol , Chung Lan
Published: June 2004

A systematic and improved design procedure for sliding mode control (SMC) of seismically excited civil structures with saturation problem is provided in this paper. In order to restrict the control force to a certain level, a procedure for determining the upper limits of the control forces for single or multiple control units is proposed based on the design response spectrum of external loads. Further, an efficient procedure using the LQR method for determining sliding surfaces appropriate for different controller types is provided through the parametric evaluation of the dynamic characteristics of sliding surfaces in terms of SMC controller performance. Finally, a systematic design procedure for SMC required to achieve a given performance level is provided and its effectiveness is verified by applying it to multi‐degree‐of‐freedom (MDOF) systems. Copyright © 2004 John Wiley & Sons, Ltd.
Cultural competence in evaluation: An overview
Authors: SenGupta Saumitra , Hopson Rodney , Thompson‐Robinson Melva
Published: June 2004

This chapter is an overview of the understanding of cultural competence and context in evaluation, highlighting how other disciplines have addressed the importance of culture and suggesting the value‐addedness of culture to program evaluation and design.
A journey to understand the role of culture in program evaluation: Snapshots and personal reflections of one African American evaluator
Authors: Hood Stafford
Published: June 2004

Taking a historical view of selected program evaluation approaches, this chapter articulates a personal lens and journey of understanding how culturally responsive evaluation is geared toward effectiveness, benefits, and outcomes of programs designed to serve the less powerful.
Culturally competent evaluation in Indian Country
Authors: LaFrance Joan
Published: June 2004

Culturally competent evaluation in Indian Country requires an understanding of the rich diversity of tribal peoples and the importance of self‐determination and sovereignty. If an evaluation can be embedded within an indigenous framework, it is more responsive to tribal ethics and values. An indigenous orientation to evaluation suggests methodological approaches, a partnership between the evaluator and the program, and reciprocity.
Developing and implementing culturally competent evaluation: A discussion of multicultural validity in two HIV prevention programs for Latinos
Authors: Conner Ross F.
Published: June 2004

This chapter describes two projects and develops from them a set of five factors that facilitate multicultural validity. The chapter also includes a discussion of some limitations of these case examples and suggestions for further testing and refinement of multicultural validity in the more general context of validity within the evaluation field.
Lessons for culturally competent evaluation from the study of a multicultural initiative
Authors: King Jean A. , Nielsen Julie E. , Colby Jeanette
Published: June 2004

Bringing together individuals from cultural backgrounds with varied values and norms for expressing conflicting ideals can elevate the tensions inherent in participatory evaluation. As the authors of this chapter found out, even the most deliberate attention to cultural issues does not guarantee a smooth ride.
A high‐resolution scheme for low Mach number flows
Authors: Chakravorty Saugata , Mathew Joseph
Published: June 2004

A method for computing low Mach number flows using high‐resolution interpolation and difference formulas, within the framework of the Marker and Cell (MAC) scheme, is presented. This increases the range of wavenumbers that are properly resolved on a given grid so that a sufficiently accurate solution can be obtained without extensive grid refinement. Results using this scheme are presented for three problems. The first is the two‐dimensional Taylor–Green flow which has a closed form solution. The second is the evolution of perturbations to constant‐density, plane channel flow for which linear stability solutions are known. The third is the oscillatory instability of a variable density plane jet. In this case, unless the sharp density gradients are resolved, the calculations would breakdown. Under‐resolved calculations gave solutions containing vortices which grew in place rather than being convected out. With the present scheme, regular oscillations of this instability were obtained and vortices were convected out regularly. Stable computations were possible over a wider range of sensitive parameters such as density ratio and co‐flow velocity ratio. Copyright © 2004 John Wiley Sons, Ltd.
Psychosocial correlates of late‐onset psychosis: life experiences, cognitive schemas, and attitudes to ageing
Authors: Giblin Sharon , Clare Linda , Livingston Gill , Howard Rob
Published: June 2004

Background

Psychosis with first onset after the age of 60, and arising in the absence of dementia or primary affective disorder, is thought to affect 2–4% of older people, and as many as half will not respond fully to medication.

Aims

This study represents a preliminary attempt to explore a number of possible psychosocial correlates of late‐onset psychosis with potential relevance for a cognitive‐behavioural formulation and for the development of psychosocial interventions for this group.

Methods

The nature and extent of adverse early life experiences, presence of maladaptive cognitive schemas, and morale in relation to ageing were compared for older people with a diagnosis of late‐onset psychosis (LOP; n = 14) or late‐onset depression (DEP; n = 13) and healthy older volunteers (HEV; n = 18) in a cross‐sectional design.

Results

Both LOP and DEP groups reported significantly higher levels of adverse life experiences than the HEV group, with between‐group differences in the types of experiences described. The LOP group scored significantly higher than the HEV group on four out of five schema domains, and significantly higher than the DEP group on two domains, other‐directedness and over‐vigilance/inhibition. The LOP group had significantly lower overall morale in relation to ageing than the HEV group, reflecting significantly higher levels of lonely‐dissatisfaction.

Conclusions

Life experiences, cognitive schemas and attitudes to ageing are important psychosocial correlates of LOP. These findings contribute to an understanding of the emotional world of individuals who develop psychosis in later life and may have implications for developing more effective intervention approaches. Copyright © 2004 John Wiley & Sons, Ltd.
Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer's disease: a meta‐analysis of individual patient data from randomised controlled trials
Authors: Whitehead Anne , Perdomo Carlos , Pratt Raymond D. , Birks Jacqueline , Wilcock Gordon K. , Evans John Grimley
Published: June 2004

Background

The objective was to evaluate the efficacy and tolerability of donepezil (5 and 10 mg/day) compared with placebo in alleviating manifestations of mild to moderate Alzheimer's disease (AD).

Method

A systematic review of individual patient data from Phase II and III double‐blind, randomised, placebo‐controlled studies of up to 24 weeks and completed by 20 December 1999. The main outcome measures were the ADAS‐cog, the CIBIC‐plus, and reports of adverse events.

Results

A total of 2376 patients from ten trials were randomised to either donepezil 5 mg/day (n = 821), 10 mg/day (n = 662) or placebo (n = 893). Cognitive performance was better in patients receiving donepezil than in patients receiving placebo. At 12 weeks the differences in ADAS‐cog scores were 5 mg/day–placebo:  − 2.1 [95% confidence interval (CI),  − 2.6 to  − 1.6;p < 0.001], 10 mg/day–placebo:  − 2.5 ( − 3.1 to  − 2.0;p < 0.001). The corresponding results at 24 weeks were  − 2.0 ( − 2.7 to  − 1.3;p < 0.001) and  − 3.1 ( − 3.9 to  − 2.4;p < 0.001). The difference between the 5 and 10 mg/day doses was significant at 24 weeks (p = 0.005). The odds ratios (OR) of improvement on the CIBIC‐plus at 12 weeks were: 5 mg/day–placebo 1.8 (1.5 to 2.1;p < 0.001), 10 mg/day–placebo 1.9 (1.5 to 2.4;p < 0.001). The corresponding values at 24 weeks were 1.9 (1.5 to 2.4;p = 0.001) and 2.1 (1.6 to 2.8;p < 0.001). Donepezil was well tolerated; adverse events were cholinergic in nature and generally of mild severity and brief in duration.

Conclusion

Donepezil (5 and 10 mg/day) provides meaningful benefits in alleviating deficits in cognitive and clinician‐rated global function in AD patients relative to placebo. Increased improvements in cognition were indicated for the higher dose. Copyright © 2004 John Wiley & Sons, Ltd.
Depression in frail elders: impact on family caregivers
Authors: Sewitch Maida J. , McCusker Jane , Dendukuri Nandini , Yaffe Mark J.
Published: June 2004

Objectives

To examine the relationship between depression among medically ill, frail elders and family caregivers' hours of care, health status, and quality of life.

Design and Methods

A cross‐sectional study of 193 family caregivers of seniors treated in the emergency department (ED) was conducted. Measures included patient depression (Geriatric Depression Scale—15), and caregivers' hours of care, mental health and physical functioning (SF‐36), and quality of life (EQ‐5D).

Results

Mean caregiver age was 60.0 ± 16.1 years and 70.5% were female. More caregivers of depressed seniors provided more care in the previous month (37.3% vs 22.4%, p = 0.03), had poor mental health (63.5% vs 47.0%, p = 0.03), and poor perceived quality of life (63.5% vs 50.4%, p = 0.04) compared to caregivers of non‐depressed seniors. Multiple logistic regression analyses indicated that patient depression was associated with poor caregiver quality of life (OR = 3.15, 95% CI 1.48, 6.73), and poor mental health in spousal and adult child caregivers (OR = 2.72, 95% CI = 0.88, 8.39, and OR = 3.29, 95% CI = 1.10, 9.86, respectively).

Conclusions

Psychosocial support may be needed for caregivers of depressed seniors. Copyright © 2004 John Wiley & Sons, Ltd.
Risk indicators of depression in residential homes
Authors: Eisses A. M. H. , Kluiter H. , Jongenelis K. , Pot A. M. , Beekman A. T. F. , Ormel J.
Published: June 2004

Objectives

To assess risk indicators of depressive symptoms in social and personal domains of residents of residential homes.

Methods

In a cross‐sectional study risk indicators for depressive symptoms (Geriatric Depression Scale) were examined in bivariate and multivariate analyses, four hundred and seventy‐nine elderly subjects from 11 residential homes took part in the study.

Results

Functional impairment, loneliness, higher education levels, a family history of depression and neuroticism are associated with depressive symptom.

Conclusion

The risk indicators of depression found in residential homes are similar to those in the community. Copyright © 2004 John Wiley & Sons, Ltd.
Plasma homocysteine concentration relates to the severity but not to the duration of Alzheimer's disease
Authors: Nilsson Karin , Gustafson Lars , Hultberg Björn
Published: June 2004

Background

It has been reported that plasma tHcy concentration is elevated in patients with Alzheimer's disease (AD) and relates to the progress or the development of AD. In the present study we have compared plasma tHcy concentrations at different times during the course of AD and with measures corresponding to the severity and the progress rate of AD.

Methods

The study population consisted of 159 patients with AD. Three measures corresponding to the progress rate of AD were created by dividing the actual scores of the severity of the dementia, the Berger scale and the Katz index by the estimated duration.

Results

AD patients without a history of cardiovascular disease did not show a significant increase of plasma tHcy concentration compared to the control subjects, whereas AD patients with cardiovascular disease exhibited a significant increase of plasma tHcy concentration compared to both control subjects and patients without cardiovascular disease. However, after creatinine adjustment of plasma tHcy in control subjects and AD patients a significant increase of plasma tHcy was observed also in AD patients without cardiovascular disease compared to controls. The concentration of plasma tHcy in AD patients with and without cardiovascular history did not increase with time after disease onset. Plasma tHcy concentration correlated with the severity of the disease. The correlations between plasma tHcy and measures of rate progression of AD did not improve compared with the correlations between plasma tHcy and the severity of dementia.

Conclusion

An interpretation of these findings may be that plasma tHcy is additionally increased in AD patients when a complication occurs, such as folate/cobalamin deficiency or a cardiovascular disease. Copyright © 2004 John Wiley & Sons, Ltd.
The effect of private insurance access on the choice of GP/specialist and public/private provider in Spain
Authors: Rodríguez Marisol , Stoyanova Alexandrina
Published: June 2004

This paper sheds light into the investigation of differential patterns of utilisation of physician services by populations subgroups that is emerging in a number of studies. Using Spanish data from the National Health Survey of 1997 we try to explain the distinct role of the type of insurance on the choice between specialists and GPs and its intertwining with the choice between private and public providers. We estimate a two‐stages probit to conclude that differences in insurance access is the main determinant of both, the choice of sector and the kind of physician contacted, giving rise to very different patterns of consumption of GP and specialist visits. People with only public insurance go 2.8 times to the GP per one time that they visit a specialist; individuals with duplicate coverage have a ratio of GP/specialist visits equal to 1.4 (the combination being public GP and private specialist) and people with only private insurance access actually have an ‘inverted’ pattern of visits: they contact specialists more often than GPs. Age, sex and health and public supply characteristics also have a distinct and interesting impact on these choices. Finally, equity concerns based on the implied assumption that specialists care is superior to general practitioner care are discussed. Copyright © 2003 John Wiley & Sons, Ltd.