bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of killer cell immunoglobulin‐like receptor genotypes with microscopic polyangiitis
Authors: Miyashita Risa , Tsuchiya Naoyuki , Yabe Toshio , Kobayashi Shigeto , Hashimoto Hiroshi , Ozaki Shoichi , Tokunaga Katsushi
Published: March 2006

Objective

Genetic background and infection have been implicated in the etiology of microscopic polyangiitis (MPA). Killer cell immunoglobulin‐like receptors (KIRs) are a diverse family of activating and inhibitory receptors expressed on natural killer (NK) cells and T cells, the genes of which show extreme polymorphism. Some KIRs bind to HLA class I subgroups, and genetic interactions between KIR genes and their ligand HLA have been shown to be associated with several autoimmune and viral diseases. In this study, we examined possible associations of the presence or absence of KIR loci with a genetic predisposition to MPA.

Methods

The presence or absence of 14 KIR loci was determined in 57 myeloperoxidase antineutrophil cytoplasmic antibody–positive Japanese subjects (43 patients with MPA and 239 healthy controls).

Results

The carrier frequency of activating KIR2DS3 was significantly decreased among patients with MPA compared with healthy controls (4.7% versus 16.7%; P = 0.038, odds ratio [OR] 0.24, 95% confidence interval [95% CI] 0.06–0.94). When KIRs were analyzed in combination with their HLA ligands, the proportion of individuals carrying inhibitory KIR3DL1 and HLA–Bw4 but not activating receptor KIR3DS1, a combination presumed to be the most inhibitory of all KIR3DS1/3DL1/HLA–B combinations, was significantly increased in the MPA group compared with the control group (46.5% versus 27.0%; P = 0.014, OR 2.35, 95% CI 1.18–4.70). Furthermore, when subjects were classified according to KIR3DL1/3DS1/HLA–B and KIR2DL1/ HLA–C combinations, an increasing trend toward susceptibility was observed as combinations became more inhibitory.

Conclusion

The decreased activation potential of NK and/or T cells associated with KIR/HLA genotypes may predispose to MPA, possibly through insufficient resistance against infections.
Neutrophils from patients with TNFRSF1A mutations display resistance to tumor necrosis factor–induced apoptosis: Pathogenetic and clinical implications
Authors: D'Osualdo Andrea , Ferlito Francesca , Prigione Ignazia , Obici Laura , Meini Antonella , Zulian Francesco , Pontillo Alessandra , Corona Fabrizia , Barcellona Roberto , Duca Marco Di , Santamaria Giuseppe , Traverso Francesco , Picco Paolo , Baldi Maurizia , Plebani Alessandro , Ravazzolo Roberto , Ceccherini Isabella , Martini Alberto , Gattorno Marco
Published: March 2006

Objective

To explore tumor necrosis factor (TNF)–induced apoptosis in neutrophils from patients with TNF receptor–associated periodic syndrome (TRAPS) and to correlate the results with the different kinds of TNFRSF1A mutations.

Methods

Two hundred sixty‐five patients with clinically suspected inherited autoinflammatory syndrome were screened for mutations of the TNFRSF1A gene. Neutrophils were isolated from heparinized blood by dextran sedimentation and incubated with and without cycloheximide (CHX) and TNFα. Cell apoptosis was assessed by human annexin V binding, and caspase 8 activation was assessed by flow cytometry.

Results

Twenty‐one patients were found to carry a variant of the TNFRSF1A gene: 13 patients had an R92Q substitution, and 8 patients presented other missense substitutions, 1 splicing mutation, and 1 in‐frame interstitial deletion. Neutrophil stimulation with TNF and CHX was associated with induction of apoptosis in 12 normal controls and in 10 subjects with the R92Q mutation. Conversely, neutrophils from 8 TRAPS patients with mutations of cysteine or threonine residues or interstitial deletion did not show any induction of apoptosis after stimulation. The incidence of the R92Q mutation among patients with recurrent autoinflammatory syndromes was similar to that observed in the normal population.

Conclusion

Resistance to TNF‐mediated apoptosis is a feature in TRAPS patients who have mutations of cysteine residues or interstitial deletion, and may play a pathogenic role. The R92Q mutation does not appear to be significantly associated with TRAPS.
Myo‐inositol enhances teratogenicity of valproic acid in the mouse
Authors: Massa Valentina , Wlodarczyk Bogdan , Giavini Erminio , Finnell Richard H.
Published: March 2006

BACKGROUND

Valproic acid (VPA) is an anticonvulsant drug that is widely used therapeutically for a variety of neurological conditions. VPA is also well known for its teratogenic potential in both humans and experimental animal models. The typical malformations observed following VPA exposure include neural tube defects (NTDs) and craniofacial and skeletal malformations. Nevertheless, the mechanisms underlying VPA's anticonvulsant efficacy or its teratogenicity remain to be elucidated. It was recently suggested that a relationship exists between VPA exposure and the cellular depletion of myo‐inositol (INO). Furthermore, INO has been shown to rescue NTDs in the curly tail mouse. The aim of this study was to investigate the interactions of VPA and INO in the developing embryo.

METHODS

For this purpose, 2 strains of mice were used: SWV/Fnn (known to be sensitive to VPA) and LM/Bc (known to be resistant to VPA‐induced NTDs). Pregnant females were randomly assigned to 4 experimental groups: control, VPA (600 mg/kg), INO (400 mg/kg), and VPA plus INO. VPA was injected IP at 8.5 days postcoitum (dpc). INO was administered PO twice a day from 6.5 to 10.5 dpc. At term the dams were killed, the uteri were removed, and all of the general toxicological parameters (number of implants, resorptions, dam weight, and fetus weight) were recorded and statistically analyzed.

RESULTS

Postimplantation loss in the SWV/Fnn strain and NTDs in the LM/Bc strain were significantly increased after the coadministration of VPA and INO.

CONCLUSIONS

This work clearly indicates that INO enhances VPA‐induced teratogenicity in the mouse. Birth Defects Research (Part A), 2006. © 2006 Wiley‐Liss, Inc.
Polyaza Crown Ethers as Non‐Nucleosidic Building Blocks in DNA Conjugates: Synthesis and Remarkable Stabilization of dsDNA
Authors: Rohr Katja , Vogel Stefan
Published: March 2006

The synthesis of amphiphilic polyaza crown ether monomers X (benzyl‐substituted), Y (palmityl‐substituted) and Z (cholesteryl‐substituted) and their incorporation into oligonucleotides are described. Their effects on thermal duplex stability were investigated by UV melting curve analysis in different alkaline metal buffer solutions. Thermal‐denaturation experiments showed remarkable stabilization of dsDNA by polyaza crown ether monomers when incorporated in opposite positions. The series of polyaza crown ether monomers (X, Y and Z) with different overall lipophilicities showed a trend of increased stability of the corresponding dsDNA with increasing lipophilicity of the polyaza crown ether monomer. Multiple incorporations of benzyl‐substituted polyaza crown ether monomer X as dangling ends on both sides of dsDNA resulted in strongly increased stability of the corresponding duplex.
Asymmetric Tandem Michael‐Aldol Reactions between 3‐Cinnamoyloxazolidine‐2‐thiones and Aldehydes
Authors: Kinoshita Hironori , Osamura Takashi , Mizuno Kazumi , Kinoshita Sayaka , Iwamura Tatsunori , Watanabe Shin‐ichi , Kataoka Tadashi , Muraoka Osamu , Tanabe Genzoh
Published: March 2006

Reactions between chiral 3‐cinnamoyl‐4‐methyl‐5‐phenyl‐1,3‐oxazolidine‐2‐thiones and aromatic aldehydes in the presence of BF3⋅Et2O diastereoselectively produced tricyclic compounds incorporating a bridgehead carbon bound to four heteroatoms in high yields. Four stereocenters were induced during the reaction. The tricyclic products were transformed into propane‐1,3‐diols bearing three consecutive stereocenters by acid hydrolysis, S‐methylation, and reductive removal of the chiral auxiliary.
Systembiotechnologische Ansätze zur Prozessentwicklung
Authors: Deckwer W.‐D. , Hempel D. C. , Zeng A.‐P. , Jahn D.
Published: March 2006

Mit Hilfe der Bioinformatik kann aus dem Genom eines Mikroorganismus das potenzielle metabolische Netzwerk rekonstruiert werden. Netzwerke stellen die eigentliche Basis der Systembiologie bzw. Systembiotechnologie dar. Für eine Systembiotechnologie, die auf Prozesse und Produkte fokussiert ist, müssen die potenziellen Netzwerke in geeigneter Weise funktionalisiert, d. h. der Phänotyp ermittelt werden, der optimale Prozesse bzw. Produkte und Produktivitäten liefert. Die Funktionalität der genregulatorischen und metabolischen Netzwerke wird durch die „Omics”︁‐Techniken abgefragt. Da die Funktionalität vom Environom abhängt, ist es erforderlich, diese Techniken in koordinierter Weise möglichst simultan anzuwenden. Das Fluxom (Flussverteilung der zentralen Stoffwechselwege) erfordert derzeit besonderes Interesse, das sowohl unter Variation genetischer Eigenschaften (Metabolic Engineering) als auch Änderungen des Environoms zu ermitteln ist. Im Rahmen einer im SFB 578 „Vom Gen zum Produkt”︁ angestrebten prozessorientierten Systembiotechnologie stellen sich für den Verfahrenstechniker vielfache Aufgaben, die nur in Kooperation mit Molekularbiologen und Bioinformatikern zu lösen sind. Dazu gehört neben der Bereitstellung definierter, reproduzierbarer Kultivierungsverfahren in hochinstrumentierten Bioreaktoren die Erfassung kinetischer Zusammenhänge in Abhängigkeit vom Environom sowie von Netzwerksimulationen. Die Erkennung des Effekts ingenieurtypischer Parameter auf die Funktionalität der Netzwerke steht jedoch erst am Anfang.
Integration gen‐ und verfahrenstechnischer Methoden zur Entwicklung biotechnologischer Prozesse Sonderforschungsbereich 578 – Vom Gen zum Produkt
Authors: Hempel D. C.
Published: March 2006

Verfahrenstechnische Prozesse erfordern sichere, robuste und modellgestützte Auslegungsmethoden, um optimale Betriebszustände in beliebig dimensionierten Anlagen vorausberechnen zu können. Biotechnologische Prozesse entbehren bisher weitgehend solcher hohen Anforderungen. Der Sonderforschungsbereich 578 stellt sich die Aufgabe, Arbeitsmethoden der Natur‐ und Ingenieurwissenschaften so zu bündeln, dass Prozesse zur Herstellung von Proteinen in rekombinanten Mikroorganismen systematisch bearbeitet werden können.
Bacillus megaterium als Produktionssystem für rekombinante Proteine
Authors: Hollmann R. , Malten M. , Biedendieck R. , Yang Y. , Wang W. , Jahn D. , Deckwer W.‐D.
Published: March 2006

Bei biotechnologischen Verfahren werden die eigentlichen wertschöpfenden chemischen Reaktionen durch Proteine durchgeführt. Diese Biokatalysatoren wandeln ihre Substrate direkt in Produkte um, die sich durch klassische chemische Synthese gar nicht oder nur unter großem Aufwand darstellen lassen. Die Produktion von Biokatalysatoren erfolgt im Allgemeinen in wenigen, gut charakterisierten Mikroorganismen. Es wird gezeigt, dass Bacillus megaterium als Produktionssystem für rekombinante Proteine eine gute Alternative zu bereits etablierten Systemen darstellt. Probleme mit der Gewinnung sekretierter Proteinmengen sind auf Schwierigkeiten der Adaption der Prozesse für Hochzelldichtekultivierungen zurückzuführen.
Scheinbare Sekretionsverzögerung durch Produktadsorption bei Aspergillus niger
Authors: Emmler M. , Jungebloud A. , Göcke Y. , Cordes C. , Horn H. , Hempel D. C.
Published: March 2006

Zur experimentellen Aufklärung der Produktbildung in Biopellets des Schimmelpilzes Aspergillus niger AB 1.13 bei der Gewinnung von Glucoamylase werden im Rahmen des Sonderforschungsbereiches 578 Methoden entwickelt. Zur Untersuchung des Produktweges wird die Enzymaktivität des Proteins im Biopellet des Schimmelpilzes sowie in der Bulkphase (extrapartikulär) herangezogen.
Mikro‐Bioverfahrenstechnik
Authors: Weuster‐Botz D.
Published: March 2006

Mikro‐Bioverfahrenstechnik gibt es bisher nicht als Fachdisziplin. Sie umfasst alle Aspekte der Bioprozesstechnik in kleinen Reaktionsvolumina. Einzelne Aspekte wurden bisher aus unterschiedlichen Fachrichtungen angestoßen: Biotechnologie, Biologie, Medizin, Bioverfahrenstechnik, aber auch Mikroreaktionstechnik. Ein Zusammenführen der unterschiedlichen Ansätze unter dem Dach einer neuen Mikro‐Bioverfahrenstechnik ist in Zukunft zwingend notwendig.
Produktintegrierter Umweltschutz am Beispiel der Rückführung bakterieller Biomasse
Authors: Blaesen M. , Flaschel E. , Friehs K.
Published: March 2006

Im Sinne eines produktintegrierten Umweltschutzes soll die Biomasse, die bei der Herstellung von biotechnischen Produkten auftreten kann, als wertvolle Nährstoffquelle zur Schonung energetischer und stofflicher Ressourcen wieder in den Produktionsprozess zurückgeführt werden. Beispielhaft wird ein Verfahren zur Rückführung der Biomasse des Gram‐negativen Bakteriums Klebsiella planticola in den Fermentationsprozess untersucht und entwickelt.
Bewertung biotechnologischer Prozesse in frühen Phasen der Entwicklung hinsichtlich Risiken bezüglich Ökologie, Sicherheit und Gesundheit
Authors: Heinzle Elmar , Biwer A. , Eissen M. , Abdul Kholiq M.
Published: March 2006

Vorgestellt wird eine Methode zur Charakterisierung von Risiken bezüglich Umwelt, Sicherheit und Gesundheit in sehr frühen Phasen der Entwicklung, insbesondere von biotechnologischen Prozessen. Auf der Basis von in der Regel gut verfügbaren Daten kann zusammen mit einer Stoffbilanz eine erste orientierende Bewertung vorgenommen werden. Dies ist besonders wegen der bekanntermaßen schon sehr früh stattfindenden Weichenstellung von großer praktischer Bedeutung bei der Identifizierung von Entwicklungschancen, aber auch von Schwachstellen.
Biotransformation: Von der Vision zur Technologie!
Authors: Kardinahl S. , Rabelt D. , Reschke M.
Published: March 2006

Die Fortschritte in der klassischen Mikrobiologie, insbesondere in den Kultivierungs‐ und Screening‐Techniken, aber auch eine zunehmende Interdisziplinarität der verschiedenen Naturwissenschaften haben die Biotransformation zu einem verlässlichen, unverzichtbaren Werkzeug gemacht, dessen Potenzial bei weitem noch nicht ausgeschöpft ist. Neue Entwicklungen in Kultivierungs‐ und Screeningtechniken, in der Verfahrenstechnik sowie neue Entwicklungen in der Klonierung und Expression von Genen in diversen Wirtszellen werden die Anzahl der enzymatischen Verfahren – Biotransformation wie auch Biokatalyse – in der Pharmazie, der Chemie und auch in der Nahrungsmittelindustrie weiter vorantreiben.
Enzymatische Technologien zur Synthese chiraler Alkohol‐Derivate
Authors: Daußmann T. , Hennemann H.‐G. , Rosen T. C. , Dünkelmann P.
Published: March 2006

Chirale Intermediate gehören zu den wichtigsten Synthesebausteinen sowohl für die chemische als auch für die pharmazeutische Industrie. Zur Herstellung dieser Verbindungen etablieren sich immer mehr biokatalytische Prozesse, bei denen neben ganzen Zellen auch Enzyme verwendet werden. So können Alkoholdehydrogenasen bei der Synthese von chiralen Alkoholen eingesetzt werden. Beschrieben werden zwei Alkoholdehydrogenasen aus Lactobacillus brevis bzw. Thermoanaerobacter species, die beide im industriellen Maßstab zur Generierung dieser Verbindungen genutzt werden. Eine weitere Enzymklasse, mit deren Hilfe sich verschiedenste Intermediate in enantiomerenreiner Form darstellen lassen und die ebenfalls in der industriellen Chemie angewendet werden, sind die Hydroxynitril‐Lyasen. Diese katalysieren die asymmetrische Addition von Blausäure an Carbonyl‐Funktionen.
Density results relative to the Dirichlet energy of mappings into a manifold
Authors: Giaquinta Mariano , Mucci Domenico
Published: March 2006

Let 𝒴 be a smooth, compact, oriented Riemannian manifold without boundary. Weak limits of graphs of smooth mapsuk:Bn→ 𝒴 with an equibounded Dirichlet integral give rise to elements of the space cart2,1(Bn× 𝒴). Assume that 𝒴 is 1‐connected and that its 2‐homology group has no torsion. In any dimensionnwe prove that every elementTin cart2,1(Bn× 𝒴) with no singular vertical part can be approximated weakly in the sense of currents by a sequence of graphs of smooth mapsuk:Bn→ 𝒴 with Dirichlet energies converging to the energy ofT. © 2006 Wiley Periodicals, Inc.
A cellular non‐linear network for image fusion based on data regularization
Authors: Anzalone Andrea , Bizzarri Federico , Storace Marco , Parodi Mauro
Published: March 2006

In this paper, a synthesis method developed in the last few years is applied to derive a cellular non‐linear network (CNN) able to find an approximate solution to a variational image‐fusion problem. The functional to be minimized is based on regularization theory and takes into account two complementary principles, namely, knowledge source corroboration and belief enhancement/withdrawal, both typical of data‐fusion approaches. The obtained CNN has been tested by simulations (i.e. by numerically integrating the circuit state equations) in some case studies. The quality of the results is good, as turns out from comparisons with some standard methods. Copyright © 2006 John Wiley & Sons, Ltd.
Expressed emotion and anorexia nervosa: The validation of the five‐minute speech sample in reference to the Camberwell family interview
Authors: Rein Zoé , Perdereau Fabienne , Curt Florence , Jeammet Philippe , Fermanian Jacques , Godart Nathalie
Published: March 2006

Objective:

The goal of the current study was to test whether the Five‐Minute Speech Sample (FMSS) assessments of expressed emotion (EE) in families with a daughter with anorexia nervosa (AN) are valid in comparison to the Camberwell Family Interview (CFI).

Method:

The sample included parents of hospitalized patients with AN. Assessments were conducted at the time of patients' discharge from the hospital. The participants (n = 40) were assessed individually with the FMSS and then the CFI. FMSS‐EE ratings were classified as high or low for Emotional Overinvolvement (EOI), Critical EE, and Final EE (overall rating). For the CFI, average EE scores were computed on the same subscales.

Results:

Comparisons of FMSS subgroups on the CFI mean scores revealed that parents rated high EE on the FMSS subscales (EOI and Final EE) had significantly greater mean scores on the CFI than parents rated low EE on the FMSS (EOI: p = .02; Final EE: p = .04). Furthermore, FMSS‐EE ratings were positively correlated to CFI‐EE ratings for EOI EE (r = .38, p = .01), Critical EE (r = .31, p = .05), and Final EE (r = .29, p = .07).

Conclusion:

The FMSS can reliably measure EE in reference to the CFI in terms of Final EE and EOI EE. For the Critical EE subgroup, further investigation is needed with a bigger sample size. © 2006 Wiley Periodicals, Inc., Int J Eat Disord, 2006
Peculiarities of the Synthesis of Lithium Ion Conducting Lanthanum Tantalate by Solid‐State Reaction and Precipitation from Solutions
Authors: Belous Anatolii , Gavrilenko Oksana , Pashkova Olena , Galven Cyrille , Bohnké Odile
Published: March 2006

Synthesis of lithium ion conducting tantalates has been carried out by conventional solid‐state reaction (SSR) techniques and by precipitation from solutions (PS). It is shown that the latter chemical route leads to the formation of a pure perovskite phase, made up of nanosized particles, and uses milder conditions when compared with the solid‐state reaction technique. Thermal analyses, X‐ray powder diffraction (XRD) and infrared (IR) spectroscopy are used to investigate the phase transformations that occur during the preparation of these tantalates from powder precursors. After sintering, the nanosized particles of the powder obtained by the (PS) route are preserved and pellets with good compactness (89 %) are obtained. The electrical properties of the sintered ceramics have been investigated by ac impedance spectroscopy. These experiments showed that the total ionic conductivity (bulk and grain boundaries) of the (PS) pellet is slightly lower than that of the (SSR) pellet. This decrease of conductivity is attributed to an enhancement of the blocking effect of the grain boundaries resulting from the microstructure of the fine‐grain ceramics. The bulk conductivity is not affected by the synthetic route. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
The First Example of a Dinuclear Platinum(III) Complex with Three Bridging Ligands
Authors: Pellicani Raffaella Z. , Intini Francesco P. , Maresca Luciana , Mesto Ernesto , Pacifico Concetta , Natile Giovanni
Published: March 2006

The first triply bridged dinuclear platinum(III) compound with acetamidate ligands, X[Pt2Cl4{N(H)C(CH3)O}3] (X = K+ or AsPh4+), has been isolated in the solid state and characterized by one‐ and two‐dimensional NMR spectroscopy and X‐ray crystallography. Owing to the asymmetry of the bridging acetamidate ligands, three isomers can be formed (HHH, HHT, and HTH), although only two are found in the crude reaction product: HHT and HTH. The HTH species is thermodynamically less stable and slowly (half life of around two days at room temperature) isomerizes into the HHT form. The more stable and less symmetric HHT isomer crystallizes from chloroform/pentane (AsPh4+ counter ion). The two [Pt2Cl4{N(H)C(CH3)O}3]– anions of the unit cell are linked by two strong N–H···O H‐bonds while contiguous anions of adjacent cells are linked together by two, slightly weaker N–H···Cl H‐bonds. The result is a chain of anions running along the a direction. The crystal packing allows for the formation of one‐dimensional pore channels, also running along the a direction, which are filled with disordered pentane molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Formation of Two 1D Polymeric Water Morphologies
Authors: Li Feng , Li Tao‐Hai , Su Wei , Gao Shui‐Ying , Cao Rong
Published: March 2006

Two complexes with double‐ or triple‐stranded chain structures, {[Cd(pg)(phen)]·3H2O}n (1) and {[Cd3(cpg)3(phen)2]·3H2O}n (2), have been hydrothermally synthesized [H2pg = 3‐phenylglutaric acid, H2cpg = 3‐(4‐chlorophenyl)glutaric acid, phen = 1,10‐phenanthroline]. In the crystal lattices of 1 and 2, two 1D polymeric water morphologies are observed (a treelike chain for 1 and a staircaselike tape for 2), both of which contain (H2O)6 subunits. The geometrical parameters of water chains and tapes are similar to those in ice, Ih, and liquid water, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis and Conformational Analysis of Saturated cis‐and trans‐1,3,2‐Benzodiazaphosphinine 2‐Oxides
Authors: Zalán Zita , Kivelä Henri , Lázár László , Fülöp Ferenc , Pihlaja Kalevi
Published: March 2006

By cyclization of N‐unsubstituted, and N1‐ or N3‐methyl‐substituted cis‐ and trans‐2‐(aminomethyl)cyclohexylamines with phenylphosphonic dichloride, phenyl dichlorophosphate and bis(2‐chloroethyl)phosphoramidic dichloride, P epimeric diastereomers a and b of the corresponding 1,3‐unsubstituted and 1‐ or 3‐methyl‐substituted 2‐phenyl‐, 2‐phenoxy‐ and 2‐[bis(2‐chloroethyl)amino]decahydro‐1,3,2‐benzodiazaphosphinine 2‐oxides have been synthesized. The stereochemistry and conformations of the prepared saturated 1,3,2‐benzodiazaphosphinine 2‐oxides were determined by 1H, 13C and 31P NMR spectroscopy aided by DFT geometry optimizations and J‐coupling‐constant calculations for selected structures. The 2‐phenoxy‐substituted trans‐fused derivatives with an equatorial phenoxy group in a hypothetical double‐chair conformation (14a, 16a, 18a) were observed to adopt nonchair heteroring conformations with a pseudoaxial P–OPh bond instead. The corresponding b epimers, as well as the trans‐fused 2‐phenyl and 2‐[bis(2‐chloroethyl)amino] derivatives (both P epimers) were found to retain double‐chair conformations. In the cis‐fused series, the position of the N‐in/N‐out equilibrium was dependent on the steric and stereoelectronic requirements of the phosphorus substituents (and thus on the phosphorus configuration) as well as on the substituents at the ring nitrogen atoms. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Dendritic Encapsulation – “Postsynthetic” Functionalizations of a Single Benzophenone Shielded by Shape‐Persistent Polyphenylene Dendrons
Authors: Bernhardt Stefan , Baumgarten Martin , Müllen Klaus
Published: March 2006

First‐ and second‐generation polyphenylene dendrimers were synthesized starting from benzophenone as core. Variation of the size and the density of the dendrimer shell resulted in different isolation of the cores. To investigate the effect of shielding upon the reactivity of the core, chemical functionalizations as well as the alkali‐metal reduction of the encapsulated benzophenone core were performed. The herein presented synthetic concept opens the way to spatially well‐defined spherical nanoparticles bearing a single isolated function in the center. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis of 5a‐α‐Tocopheryl Azide and Its Reaction to 1‐(5a‐α‐Tocopheryl)‐1,2,3‐triazols by [2+3]‐Cycloaddition
Authors: Adelwöhrer Christian , Rosenau Thomas , Kloser Elisabeth , Mereiter Kurt , Netscher Thomas
Published: March 2006

1,2,3‐Triazoles with 1‐position substituents, derived from α‐tocopherol (vitamin E), were synthesized by 1,3‐dipolar cycloaddition reactions of 5a‐azido‐α‐tocopheryl acetate with alkynes, and were fully analytically characterized. NMR spectra of the compounds and crystal structures of derivatives with a truncated isoprenoid side chain are presented. The tocopheryl moiety is readily cleaved in basic media, as a prerequisite for the use in delivery systems showing pH‐dependent drug release. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Synthesis of Aromatic Analogs of 8(S)‐HETE and Their Biological Evaluation as Activators of the PPAR Nuclear Receptors
Authors: Caijo Frédéric , Mosset Paul , Grée René , Audinot‐Bouchez Valérie , Boutin Jean , Renard Pierre , Caignard Daniel‐Henri , Dacquet Catherine
Published: March 2006

A new family of 8‐HETE analogs has been synthesized as dual PPAR α and γ agonists. A versatile strategy has been developed to allow modulations not only around the aromatic core but also on the side chains of these analogs. The affinity of these compounds towards the PPARα and PPARγ receptors is reported, together with their transactivation percentage. The derivatives having a propargylic type side chain gave the most promising results as dual agonists. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Photoinduced Nucleophilic Substitution of Aryl Halides with Potassium Thioacetate – A One‐Pot Approach to Aryl Methyl and Diaryl Sulfides
Authors: Schmidt Luciana C. , Rey Valentina , Peñéñory Alicia B.
Published: March 2006

Aryl methyl sulfides and diaryl sulfides were prepared by photoinduced reactions of potassium thioacetate with aryl halides under entrainment conditions. Without isolation, the arene thiolates obtained by the aromatic substitution were quenched with methyl iodide to afford the aryl methyl sulfides in 26–59 % yields in a “one‐pot” procedure together with the diaryl sulfides in variable yields (3–31 %). By optimization of the reaction conditions it was possible to improve the formation of the Ar2S, going from moderate to good yields (64–83 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Calculating the optimal number of contaminant samples by means of data worth analysis
Authors: Norberg Tommy , Rosén Lars
Published: March 2006

This is a study of Bayesian data worth analysis in environmental clean‐up applications. Its focus is on calculating the worth of simultaneously taking several (soil) samples in a small homogeneous area and on finding the optimal number of samples to take, by relating the reduction in risk cost from sampling, that is, data worth, to the cost of the samples. Even though the cost of one sample may be higher than the risk cost reduction it provides, this study shows that several samples may be cost‐efficient. This is mainly due to two factors: one is that the unit sample cost often decreases as the number of samples increase; another, more important, factor is that the data worth of several samples typically is higher than the worth of fewer samples. Copyright © 2006 John Wiley & Sons, Ltd.
A systematic review and quantitative appraisal of fMRI studies of verbal fluency: Role of the left inferior frontal gyrus
Authors: Costafreda Sergi G. , Fu Cynthia H.Y. , Lee Lucy , Everitt Brian , Brammer Michael J. , David Anthony S.
Published: March 2006

The left inferior frontal gyrus (LIFG) has consistently been associated with both phonologic and semantic operations in functional neuroimaging studies. Two main theories have proposed a different functional organization in the LIFG for these processes. One theory suggests an anatomic parcellation of phonologic and semantic operations within the LIFG. An alternative theory proposes that both processes are encompassed within a supramodal executive function in a single region in the LIFG. To test these theories, we carried out a systematic review of functional magnetic resonance imaging studies employing phonologic and semantic verbal fluency tasks. Seventeen articles meeting our pre‐established criteria were found, consisting of 22 relevant experiments with 197 healthy subjects and a total of 41 peak activations in the LIFG. We determined 95% confidence intervals of the mean location (x,y, andzcoordinates) of peaks of blood oxygenation level‐dependent (BOLD) responses from published phonologic and semantic verbal fluency studies using the nonparametric technique of bootstrap analysis. Significant differences were revealed in dorsal–ventral (z‐coordinate) localizations of the peak BOLD response: phonologic verbal fluency peak BOLD response was significantly more dorsal to the peak associated with semantic verbal fluency (confidence interval of difference: 1.9–17.4 mm). No significant differences were evident in antero–posterior (x‐coordinate) or medial–lateral (y‐coordinate) positions. The results support distinct dorsal–ventral locations for phonologic and semantic processes within the LIFG. Current limitations to meta‐analytic integration of published functional neuroimaging studies are discussed. Hum Brain Mapp, 2006. © 2006 Wiley‐Liss, Inc.
Regional brain variations of cytochrome oxidase activity in Relnrl‐orl mutant mice
Authors: Strazielle C. , Hayzoun K. , Derer M. , Mariani J. , Lalonde R.
Published: March 2006

Cell malpositioning has been described in laminated structures of the spontaneous mutation, reeler, including the cerebellum, the hippocampus, and the neocortex. Despite the ectopic positions of different neuronal populations, the specificity of synaptic connections is maintained. The metabolic consequences of this form of neuropathology were examined in Relnrl mutant mice by quantitative measures of cytochrome oxidase (CO) activity, a mitochondrial enzyme essential for oxidative metabolism in neurons. Despite severe tissue disorganization but in line with the intact synaptic organization, the reeler mutation did not affect global metabolic activity of the laminated structures of the brain. CO activity, however, was altered in specific subregions of the cerebellum, hippocampus, and neocortex, as well as in septum and various brainstem (medial pontine, paramedial reticular, paragigantocellular reticular) regions anatomically related to these structures, attesting to large functional alterations in Relnrl‐orl brain. Metabolic activity variations were also detected in the ventral tegmental area and ventral neostriatum of the mesolimbic dopaminergic pathway. The results are discussed and compared to the regional CO variations found in other ataxic mice, in regard to the structural defects, the integrity of the connections, and the mutation‐specific effects. © 2006 Wiley‐Liss, Inc.
Characterization and location of secretory phospholipase A2 groups IIE, V, and X in the rat brain
Authors: Kolko Miriam , Christoffersen Nanna R. , Barreiro Sebastian G. , Miller Martin L. , Pizza Andrew J. , Bazan Nicolas G.
Published: March 2006

Secretory phospholipases A2 (sPLA2) form a diverse family of enzymes involved in a variety of physiologic and pathologic processes. Common among all sPLA2 is the ability to cleave the second position of phospholipids, thereby releasing fatty acid and a lysophospholipid. Several sPLA2 have been cloned and characterized in various tissues and receptors have been identified. In the nervous system, sPLA2 groups IB, IIA, IIE, IIF, V, and XII have been identified, and binding sites for sPLA2 have been found. Here, we report sPLA2‐IIE and sPLA2‐X in rat brain as well as in neurons in primary culture. We furthermore confirm the presence of sPLA2‐V in rat brain and demonstrate the presence of sPLA2‐V in primary neuronal cultures. The distribution of sPLA2‐IIE, V, and ‐X seems to be mainly neuronal, with the highest abundance occurring in the cerebral cortex and hippocampus. We also find that sPLA2‐IIE, ‐V, and ‐X are differentially induced by kainic acid. This study supports the concept that sPLA2 heterogeneity in brain is functionally relevant and responsive to seizures. © 2006 Wiley‐Liss, Inc.
Role of Purα in targeting mRNA to sites of translation in hippocampal neuronal dendrites
Authors: Johnson Edward M. , Kinoshita Yayoi , Weinreb David B. , Wortman Margaret J. , Simon Ruth , Khalili Kamel , Winckler Bettina , Gordon Jennifer
Published: March 2006

Using genetic inactivation in the mouse, PURA, encoding Purα, is demonstrated to be essential for developmentally‐timed dendrite formation in the cerebellum and hippocampus. Comparison of RNA species bound by Purα prompts the hypothesis that Purα functions with non‐coding RNA in transport of certain mRNA molecules to sites of translation in dendrites. Purα binds to human BC200 RNA, implicated in dendritic targeting, and this has homologies to 7SL RNA, implicated in compartmentalized translation. Results using hippocampal rat neurons in situ show that Purα binds to BC1 RNA, implicated in dendritic targeting as a mouse counterpart of BC200, and to mRNA molecules translated in dendrites; Purα is specifically located in dendrites, where it is colocalized with Map2, but not in axons, where it fails to colocalize with Ankyrin G. Purα and Staufen are colocalized at dendritic sites of mRNA translation. Microtubule disruptors inhibit Purα dendritic targeting and allow its mislocalization to axons. Using mouse brain, double‐RNA immunoprecipitation places Purα together with Staufen or FMRP on BC1 RNA and specific mRNA species in vivo. These results help define a mechanism by which Purα targets specific mRNA molecules to sites of dendritic translation. © 2006 Wiley‐Liss, Inc.
Phosphorylated cAMP response element‐binding protein levels in guinea pig brainstem auditory nuclei after unilateral cochlear ablation
Authors: Mo Zhicheng , Suneja Sanoj K. , Potashner Steven J.
Published: March 2006

After left unilateral cochlear ablation (UCA) in young adult guinea pigs, the appearance of plasticities in auditory pathways suggested altered gene expression and modified phenotypic behaviors of auditory neurons. Because phosphorylated cyclic‐AMP response element‐binding protein (CREB‐P) is a transcription factor that binds to certain genes to facilitate their expression, CREB‐P levels were measured after UCA and correlated with postablation plasticities. After UCA, Western blotting was employed to quantify CREB‐P levels and illustrate CREB levels in the anteroventral (AVCN), posteroventral (PVCN), and dorsal (DCN) cochlear nucleus; the lateral (LSO) and medial superior olive (MSO); the medial nucleus of the trapezoid body (MNTB); and the central nucleus of the inferior colliculus (ICc) for up to 145 days. We also quantified the levels of several protein synthesis regulators and synaptic markers in the AVCN at 60 days. Sucrose‐based extraction buffer improved CREB‐P recovery. CREB‐P levels became depressed at 3 and 7 postablation days, except in the PVCN, where they were elevated at 7 days, and in the ICc, where they were elevated at both times. At 60 days, CREB‐P levels in all the nuclei were elevated. In the AVCN, levels of the protein synthesis regulators and synaptic markers were also elevated at 60 days. By 145 days, CREB‐P levels again declined, except in the AVCN, where elevations persisted and increased on the ablated side, and in the ICc, where CREB‐P elevations remained. The changes in CREB‐P levels coincided with several plasticities in glutamatergic and glycinergic transmitter release and receptor activities, and alterations in neurotrophic support, that developed after UCA. These findings suggest that UCA altered CREB‐P levels, which in turn might have contributed to plasticities that appear after UCA. © 2006 Wiley‐Liss, Inc.
Characterization of chronic constriction of the saphenous nerve, a model of neuropathic pain in mice showing rapid molecular and electrophysiological changes
Authors: Walczak Jean‐Sébastien , Pichette Vincent , Leblond François , Desbiens Karine , Beaulieu Pierre
Published: March 2006

Neuropathic pain is one of the most inextricable problems encountered in clinics, because few facts are known about its etiology. Nerve injury often leads to allodynia and hyperalgesia, which are symptoms of neuropathic pain. The aim of this study was to understand some molecular and electrophysiological mechanisms of neuropathic pain after chronic constriction of the saphenous nerve (CCS) in mice. After surgery, CCS mice displayed significant allodynia and hyperalgesia, which were sensitive to acute systemic injection of morphine (4 mg/kg), gabapentin (50 mg/kg), amitriptyline (10 mg/kg), and the cannabinoid agonist WIN 55,212‐2 (5 mg/kg). These behavioral changes were accompanied after surgery by an increase of c‐Fos expression and by an overexpression of μ‐opioid and cannabinoid CB1and CB2receptors in the spinal cord and the dorsal hind paw skin. In combination with the skin‐nerve preparation, this model showed a decrease in functional receptive fields downstream to the injury and the apparition of A‐fiber ectopic discharges. In conclusion, CCS injury induced behavioral, molecular, and electrophysiological rearrangements that might help us in better understanding the peripheral mechanisms of neuropathic pain. This model takes advantage of the possible use in the future of genetically modified mice and of an exclusively sensory nerve for a comprehensive study of peripheral mechanisms of neuropathic pain. © 2006 Wiley‐Liss, Inc.
Multidimensional liquid chromatography for sample characterisation
Authors: Toups E. Peter , Gray Michael J. , Dennis Gary R. , Reddy Narsimha , Wilson Michael A. , Shalliker R. Andrew
Published: March 2006

While LC finds enormously widespread use in almost all areas of chemical science, the technique is limited as a means of identification because compounds do not elute with unique retention times. This limitation spurred the growth of hyphenated instrumental methods of analysis, such as LC–MS/MS, which because of the MS/MS detection became a method of identification. However, techniques like LC–MS/MS are specialised and require high initial purchase and running costs, inhibiting the more widespread growth of the technique. In an attempt to increase the separation power of LC, multi‐dimensional LC was developed. This expanded the separation space and subsequently has allowed the development of methods with fingerprinting ability due to the lower probability of component overlap. The work in this study illustrates the application of 2‐D LC as a means of chemical fingerprinting. We employed a sample base of various low molecular weight oligostyrenes and their diastereomers that represent a population of compounds whose selectivities in a one‐dimensional separation are almost unity and hence essentially impossible to separate. Yet in a 2‐D domain almost all individual components occupy unique 2‐D retention times.
Controlling LC–SPE–NMR systems
Authors: Wilson Steven Ray , Malerød Helle , Petersen Dirk , Simic Nebojsa , Bobu Maria‐Magdalena , Rise Frode , Lundanes Elsa , Greibrokk Tyge
Published: March 2006

There are several stages of the LC–SPE–NMR process that should be monitored closely to ensure an efficient isolation and concentration of the target analyte, for instance analyte break‐through and compound transfer from the LC–SPE to the NMR probe. In this study, analyte break‐through monitoring was performed with a UV detector and a mass spectrometer placed after the SPE unit. Easy break‐through was a problem when attempting multiple trapping of various compounds using C18 SPE cartridges with the original commercial system. However, on lowering the flow rate over the SPE system and using SPE cartridges packed with porous carbon, the number of trappings possible increased five‐fold. To increase control over the on‐line SPE–NMR transfer, a gradient pump‐UV system was used to elute compounds trapped on an SPE to an NMR probe. The analyte band was placed in the active volume of the probe by a stop‐flow mechanism. The modified LC–SPE system was also coupled with off‐line NMR analysis for determination of a degradation product of the insecticide monuron, present in the low ppm range.
Direct sensitive quantitative LC/MS analysis of C‐peptide from human urine by two dimensional reverse phase/reverse phase high‐performance liquid chromatography
Authors: Rogatsky Eduard , Tomuta Vlad , Cruikshank Greg , Vele Louis , Jayatillake Harsha , Stein Daniel
Published: March 2006

We describe for the first time the direct quantitative analysis of human C‐peptide from urine by isotope dilution assay. Implementation of 2‐D reverse phase‐reverse phase chromatography (2‐D RP‐RP) with SIM detection resulted in high assay sensitivity (LOQ = 5 pg on column), accuracy, and method ruggedness. Our experiments demonstrate the strong resolving capability of our proposed 2‐D RP‐RP platform which significantly reduces strong matrix effects and their resulting quantitation error over a wide range of urine concentrations. In contrast, single column methods (both SIM and multiple reaction monitoring) were found acceptable only for strongly diluted urine samples.
Two‐dimensional reverse phase‐reverse phase chromatography: A simple and robust platform for sensitive quantitative analysis of peptides by LC/MS. Hardware design
Authors: Rogatsky Eduard , Stein Daniel T.
Published: March 2006

We have revised current two‐dimensional RP‐RP approaches and developed a new robust 2‐D RP‐RP platform. This platform was implemented on an Agilent 1100 2‐D liquid chromatography system and is based on high pressure switching between two high‐resolution RP columns. An independent binary gradient was implemented for each dimension. The powerful combination of dual analytical columns with independent gradient elution achieves high analyte purity, effectively eliminates matrix effects, and maximizes MS sensitivity in Q1 SIM comparable to the sensitivity enhancements of MS/MS‐based methods. Implementation of dual simultaneous gradient profiles (overlapped gradients) reduces 2‐D method run‐time to the scale of 1‐D method run‐times. This robust and sensitive approach is particularly suitable for hydrophobic peptides and small proteins and can be used as a routine standard technique for enhanced on‐line peptide purification coupled with mass spectrometric detection.
Effect of Temperature on the Mobility of Core‐Shell‐Type Nanoparticles Composed of Poly(γ‐benzyl‐L‐glutamate) and Poly(N‐isopropylacrylamide)
Authors: Yoo Mi Kyong , Jang Mi Kyeong , Nah Jae Woon , Park Mi Ran , Cho Chong Su
Published: March 2006

Summary:Core‐shell‐type nanoparticles composed of PBLG and PNIPAAm were prepared in an attempt to study the effects of temperature on the dynamic behavior of temperature‐sensitive polymeric shell, PNIPAAm, in the nanoparticles by1H NMR spectroscopy. Spin‐lattice relaxation time (T1) and line halfwidth in D2O and CDCl3were measured to monitor the change of the chain mobility of PNIPAAm in the GN nanoparticles within the temperature range encompassing its LCST. The molecular motion of PBLG segment in GN nanoparticles in CDCl3was also examined and compared with that of the PNIPAAm. The morphology, size distribution, and effect of temperature on the sizes of the GN nanoparticles were also investigated. The temperature dependence ofT1and line halfwidth suggests that theN‐isopropyl group turns gradually into the solid‐like aggregates at temperatures higher than the LCST of PNIPAAm due to the collapsed coil‐globule transition.T1values ofN‐isopropyl groups decreased with increasing PBLG content in GN diblock copolymer, suggesting the mobility of PNIPAAm chain, as the shell, becomes more restricted at higher PBLG core content.

Changes in the mobility of PNIPAAm shell in the core‐shell‐type nanoparticles composed of PBLG and PNIPAAm.

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Changes in the mobility of PNIPAAm shell in the core‐shell‐type nanoparticles composed of PBLG and PNIPAAm.
Novel Random Low‐Band‐Gap Fluorene‐Based Copolymers for Deep Red/Near Infrared Light‐Emitting Diodes and Bulk Heterojunction Photovoltaic Cells
Authors: Xia Yangjun , Luo Jie , Deng Xianyu , Li Xianzhen , Li Dongyun , Zhu Xuhui , Yang Wei , Cao Yong
Published: March 2006

Summary: Novel readily soluble random low‐band‐gap conjugated copolymers (PFO–DTTP, Eg ≈ 1.77–2.00 eV) derived from 9,9‐dioctylfluorene (DOF) and 2,3‐dimethyl‐5,7‐dithien‐2‐yl‐thieno[3,4‐b]pyrazine (DTTP) were prepared. The solutions and the solid thin films of the copolymers absorbed light from 300–690 nm. Prototype photovoltaic cells from solid state composite films with the copolymer PFO–DTTP30 and [6,6]‐phenyl C61 butyric acid methyl ester (PCBM) showed power conversion efficiencies up to 0.83% under an AM1.5 solar simulator (100 mW · cm−2). For electroluminescent devices, the emission peaks were around 734–780 nm. This indicates that the low band gap copolymers are promising materials for polymeric solar cells and deep red/near infrared light‐emitting diodes.

Synthesis of novel low‐band‐gap fluorene‐based copolymer.

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Synthesis of novel low‐band‐gap fluorene‐based copolymer.
Synthesis, Sequential Crystallization and Morphological Evolution of Well‐Defined Star‐Shaped Poly(ε‐caprolactone)‐b‐poly(L‐lactide) Block Copolymer
Authors: Wang Jing‐Liang , Dong Chang‐Ming
Published: March 2006

Summary: Well‐defined star‐shaped poly(ε‐caprolactone)‐b‐poly(L‐lactide) copolymers (PCL‐b‐PLLA) were synthesized via sequential block copolymerization, and their molecular weights and arm length ratio could be accurately controlled. Both differential scanning calorimetry and wide angle X‐ray diffraction analysis indicated that the crystallization of both the PLLA and PCL blocks within the star‐shaped PCL‐b‐PLLA copolymer could be adjusted from the arm length of each block, and both blocks mutually influenced each other. The sequential isothermal crystallization process of both the PLLA and PCL blocks within the PCL‐b‐PLLA copolymers was directly observed with a polarized optical microscope, and the isothermal crystallization of the PCL segments was mainly templated by the existing spherulites of PLLA. Moreover, the PLLA blocks within the star‐shaped PCL‐b‐PLLA copolymer progressively changed from ordinary spherulites to banded spherulites when the arm length ratio of PCL to PLLA was increased while concentric spherulites were observed for the linear analog. Significantly, these novel spherulites with concentric or banded textures and the morphological evolution of the spherulites have been observed for the first time in the PCL‐b‐PLLA block copolymers.

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