bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic etiology of stability of attention problems in young adulthood
Authors: van den Berg Stéphanie M. , Willemsen Gonneke , de Geus Eco J.C. , Boomsma Dorret I.
Published: November 2005

Variation in attention problems in children and adolescents from non‐clinical samples is highly heritable. It is unknown how attention problems develop later in life and whether the heritability in the general adult population is the same as in children and adolescents. We assessed the heritability and stability of individual differences in attention problems in the general young adult population and explored to what extent the stability can be attributed to genetic or environmental factors. On one or more occasions, young adult twins (age range, 18–30 years, N = 4,245) from the Netherlands Twin Registry filled out the attention problems (AP) subscale of the Young Adult Self‐Report [Achenbach, 1997]: in 1991, N = 1,755 (of which 842 complete pairs), in 1995, N = 2,428 (1156 complete pairs) and in 1997, N = 2,344 (958 pairs). There was only a slight decrease in the average level of attention problems during young adulthood. The heritability at each occasion was around 40%. The correlation of attention problems across a period of 6 years was 0.42, and 77% of this correlation could be ascribed to genetic influences. Thus, individual differences in attention problems in young adulthood are heritable, and stability in individual differences over time can largely be ascribed to genetic influences. Genetic correlations across time were high, suggesting that the genes that influence variability in attention problems in late adolescence are largely the same as those that influence variability in early adulthood. © 2005 Wiley‐Liss, Inc.
Recent progress towards a molecular understanding of Marfan syndrome
Authors: Dietz Harry C. , Loeys Bart , Carta Luca , Ramirez Francesco
Published: November 2005

Marfan syndrome (MFS) is a systemic disorder of the connective tissue that is inherited as an autosomal dominant trait and which displays variable manifestations in the ocular, skeletal, and cardiovascular systems. These pleiotropic manifestations are accounted for by mutations in fibrillin‐1, the building block of extracellular microfibrils. During the past 10 years, we have witnessed significant progress in delineating the pathological events responsible for the manifestations of MFS. Much of this progress has been based on the creation and analysis of fibrillin‐1 mutant mouse lines that faithfully recapitulate the spectrum of clinical severity of MFS. These studies have established the critical contribution of fibrillin‐1 deficiency to disease progression through altered cell–matrix interactions and dysregulated TGF‐β signaling. As a result, our definition of MFS as the prototypical structural disorder of the connective tissue has changed to that of a developmental abnormality with broad and complex effects on the morphogenesis and function of multiple organ systems. Importantly, new biological targets have emerged that may yield exciting new opportunities for the development of productive treatment strategies in MFS. © 2005 Wiley‐Liss, Inc.
Interleukin‐6 involvement in brain arteriovenous malformations
Authors: Chen Yongmei , Pawlikowska Ludmila , Yao Jianhua S. , Shen Fanxia , Zhai Wenwu , Achrol Achal S. , Lawton Michael T. , Kwok Pui‐Yan , Yang Guo‐Yuan , Young William L.
Published: November 2005

We recently reported that the GG genotype of the interleukin‐6 (IL‐6)–174G>C promoter polymorphism is associated with clinical presentation of intracranial hemorrhage in brain arteriovenous malformation (AVM) patients. In this study, we investigated whether tissue IL‐6 expression was associated with IL‐6–174G>C genotype, and whether IL‐6 was linked to downstream targets involved in angiogenesis and vascular instability. Our results showed that the highest IL‐6 protein levels in brain AVM tissue were associated with IL‐6–174GG genotype (GG: 57.7 ± 20.2; GC: 35.6 ± 26.6; CC: 13.9 ± 10.2pg/mg; p = 0.001). IL‐6 protein levels were increased in AVM tissue from patients with hemorrhagic presentation compared with patients without hemorrhage (55 ± 22 vs 40 ± 27pg/mg; p = 0.038). IL‐6 messenger RNA expression strongly correlated with messenger RNA levels of IL‐1β, tumor necrosis factor‐α, IL‐8, matrix metalloproteinase‐3 (MMP‐3), MMP‐9, and MMP‐12. We further investigated the plausibility of IL‐6 being an upstream cytokine responsible for initiating the angiogenic cascade by cell culture and animal experiments. IL‐6 induced MMP‐3 and MMP‐9 expression and activity in mouse brain and increased proliferation and migration of cerebral endothelial cells. Together, our results suggest that the IL‐6 genotype associated with intracranial hemorrhage modulates IL‐6 expression in brain AVM tissue, which is consistent with the hypothesis that inflammatory processes induce angiogenic activity possibly contributory to brain AVM intracranial hemorrhage. Ann Neurol 2005
Risk factors for variant Creutzfeldt–Jakob disease: A case–control study
Authors: Ward Hester J. T. , Everington Dawn , Cousens Simon N. , Smith‐Bathgate Blaire , Leitch Margaret , Cooper Sarah , Heath Craig , Knight Richard S. G. , Smith Peter G. , Will Robert G.
Published: November 2005

Objective

To investigate the potential risk factors for variant Creutzfeldt‐Jakob disease (VCJD) in the United Kingdom.

Methods

Definite and probable vCJD cases (n = 136) were residing in Great Britain at disease onset, and were referred between May 1995 and November 2003. Control subjects (n = 922) were recruited between 2002 and 2003, from 100 randomly selected geographical clusters sampled to represent the geographical distribution of vCJD.

Results

Reported frequent consumption of beef and beef products thought likely to contain mechanically recovered or head meat, or both, including burgers and meat pies, was associated with increased risk for vCJD, as was reported frequent chicken consumption. Surgical operations were generally similarly reported for cases and control subjects, with the exception of a small group of minor operations, possibly attributable to underreporting in control subjects. Cases and control subjects had similar reported occupational histories and exposure to animals.

Interpretation

These findings are consistent with dietary exposure to contaminated beef products being the main route of infection of vCJD, but recall bias cannot be excluded. There was no convincing evidence of increased risk through medical, surgical, or occupational exposure or exposure to animals. Ann Neurol 2005
How do brain tumors alter functional connectivity? A magnetoencephalography study
Authors: Bartolomei Fabrice , Bosma Ingeborg , Klein Martin , Baayen Johannes C. , Reijneveld Jaap C. , Postma Tjeerd J. , Heimans Jan J. , van Dijk Bob W. , de Munck Jan C. , de Jongh Arent , Cover Keith S. , Stam Cornelis J.
Published: November 2005

Objective

This study was undertaken to test the hypothesis that brain tumors interfere with normal brain function by disrupting functional connectivity of brain networks.

Methods

Functional connectivity was assessed by computing the synchronization likelihood in a broad band (0.5–60Hz) or in the gamma band (30–60Hz) between all pairwise combinations of magnetoencephalography signals. Magnetoencephalography recordings were made at rest in 17 brain tumor patients and 15 healthy control subjects. For a given threshold of synchronization likelihood values, graphs of the suprathreshold connections between each magnetoencephalography channel and the others channels were built.

Results

In some regions, a variable number of channels without connectivity (missing connective points) at this threshold was found. The number of missing connective points was higher in patients with brain tumors than in control subjects (p < 0.0001, broad and gamma band) and was higher for left‐sided than right‐sided tumors (p = 0.008, broad band; p < 0.0001, gamma band). Individual results analysis indicates that the majority of brain tumor patients display several regions with missing connective point alterations in the affected and in the contralateral hemisphere.

Interpretation

Our findings suggest that brain tumors induce a loss of functional connectivity that affects multiple brain regions, and that left side brain tumors have the more severe consequences in this respect. Ann Neurol 2005
Organoschwefelverbindungen: elektrophile Reagentien für übergangsmetallkatalysierte C‐C‐Verknüpfungen
Authors: Dubbaka Srinivas Reddy , Vogel Pierre
Published: November 2005

Übergangsmetallkatalysierte Kohlenstoff‐Kohlenstoff‐Verknüpfungen zählen zu den leistungsfähigsten Verfahren der organischen Synthese und sind ferner von entscheidender Bedeutung für die moderne Materialwissenschaft und medizinische Chemie. Dank Fortschritten bei Liganden und Additiven gelingen inzwischen Kreuzkupplungen mit zahlreichen Ausgangsstoffen einschließlich der billigen und leicht verfügbaren Sulfonylchloride. Wir fassen hier den aktuellen Kenntnisstand bei Kohlenstoff‐Kohlenstoff‐Kreuzkupplungen unter Desulfurierung (Negishi‐, Stille‐, carbonylierenden Stille‐, Suzuki‐ Miyaura‐ und Sonogashira‐Hagihara‐artigen Kreuzkupplungen und Mizoroki‐Heck‐artigen Arylierungen) sowie bei Kohlenstoff‐Kohlenstoff‐Kreuzkupplungen mit anderen elektrophilen Organoschwefelverbindungen zusammen.
Organosulfur Compounds: Electrophilic Reagents in Transition‐Metal‐Catalyzed Carbon–Carbon Bond‐Forming Reactions
Authors: Dubbaka Srinivas Reddy , Vogel Pierre
Published: November 2005

Transition‐metal‐catalyzed carbon–carbon bond‐forming reactions are among the most powerful methods in organic synthesis and play a crucial role in modern materials science and medicinal chemistry. Recent developments in the area of ligands and additives permit the cross‐coupling of a large variety of reactants, including inexpensive and readily available sulfonyl chlorides. Their desulfitative carbon–carbon cross‐coupling reactions (Negishi, Stille, carbonylative Stille, Suzuki–Miyaura, and Sonogashira–Hagihara‐type cross‐couplings and Mizoroki–Heck‐type arylations) are reviewed together with carbon–carbon cross‐coupling reactions with other organosulfur compounds as electrophilic reagents.
Luminescence characteristics and X‐ray crystal structure of [Cd(bipy)3][PF6]2 (bipy = 2,2′‐bipyridine)
Authors: Kundu Nabanita , Mandal Debdas , Chaudhury Muktimoy , Tiekink Edward R. T.
Published: November 2005

The photoluminescence characteristics of the [Cd(bipy)3][PF6]2 complex are reported. A moderately large quantum yield (φ) of 1.07 × 10−2 is exhibited in acetonitrile solution at 298 K. Crystallography shows the dication to have a distorted octahedral geometry and the crystal structure to be stabilized by CH···π and CH···F interactions. Copyright © 2005 John Wiley & Sons, Ltd.
Microbial transformation of tributyltin chloride by Pseudomonas aeruginosa strain USS25 NCIM‐5224
Authors: Roy Upal , Bhosle Saroj
Published: November 2005

A bacterial isolate capable of utilizing tributyltin chloride (TBTC) as sole source of carbon was isolated from marine water samples. The isolate, producing a soluble green pigment, was identified as Pseudomonas aeruginosa strain USS25 NCIM‐5224. The isolate showed maximum growth with 2 mM of TBTC in mineral salt medium. Time course results showed complete elimination of TBTC after 75 days of incubation. During the growth on TBTC, a product (280 mg) was found to accumulate, which was extracted with chloroform and detected on thin‐layer chromatography. Based on the IR, NMR spectra and GC‐MS analysis, the isolated product was identified as monobutyltin dichloro hydride. Copyright © 2005 John Wiley & Sons, Ltd.
Polyacrylonitrile‐grafted Cassia pudibunda seed gum: A potential commercial gum from renewable source
Authors: Singh Vandana
Published: November 2005

Cassia pudibunda (CP) seed gum was grafted with poly(acrylonitrile) using persulphate/ascorbic acid redox initiator. Optimal grafting Conditions were determined and maximum % grafting and % efficiency observed were 294 and 85.3%, respectively. Grafted CP gum (gum‐g‐polyacrylonitrile; CP‐g‐PAN) was characterized using FTIR, XRD, and TGA analysis. The CP‐g‐PAN sample with maximum %G was observed to be water insoluble, however, 1% solution of the base‐hydrolyzed CP‐g‐PAN had a viscosity of 114.7 centipoises, which was observed to increase continuously for first 5 days and there upon became fixed and was shown to be stable even after 20 days when left at room temperature. Water and saline retention for CP‐g‐PAN after 10 min soaking were observed to be 47 and 30.15 g/g, respectively. Thus, base‐hydrolyzed CP‐g‐PAN samples may find use as water sorbents and their aqueous solutions may be used commercially where medium to low viscosity solutions with high shelf life is the requirement. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 619–627, 2006
Synthesis of telechelic C60 end‐capped polymers under microwave irradiation
Authors: Wu Huixia , Li Feng , Lin Yanghui , Yang Ming , Chen Wei , Cai Ruifang
Published: November 2005

Bromo‐Double‐Terminated polystyrene (Br‐PSt‐Br) and poly(methyl methacrylate) (Br‐PMMA‐Br) with predesigned molecular weight and narrow polydispersity were prepared by atom transfer radical polymerization (ATRP) using the initiating system aa′‐dibromo‐p‐xylene(DBX) / CuBr/2,2′‐bipyridine(bipy). The precursor bromo‐terminated polymers were subsequently functionalized with fullerene C60 using CuBr/bipy as the catalyst system under microwave irradiation (MI). The telechelic C60 end‐capped products were characterized by gel permeation chromatography (GPC), UV‐vis, FT‐IR, TGA, DSC, 1H NMR, and 13C NMR. The results showed that microwave irradiation could significantly increase the rate of fullerenation reaction, and the physical properties and structure of the C60 end‐capped polymers are not modified by the use of the microwave. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 828–834, 2006
A novel polyurethane sealant based on hydroxy‐terminated polybutadiene
Authors: Patri M. , Rath S. K. , Suryavansi U. G.
Published: November 2005

A novel two component polyurethane sealant has been prepared. Component A, known as prepolymer, is synthesized by capping hydroxy‐terminated polybutadiene (HTPB) with toluene diisocyanate. Component B, known as hardener, comprises of a polyol (polyoxypropylene triol) as crosslinker and 4,4′‐diamino‐3,3′‐dichlorodiphenylmethane (DADCDPM) and 4,4′‐diamino‐3,3′‐dichlorotriphenylmethane (DADCTPM) as chain extenders and fillers. Evaluation of mechanical properties and aging studies indicate that the sealant has excellent mechanical properties and stability in different environment. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 884–890, 2006
Preparation and properties of a siloxane‐containing 2‐vinylpyridine–styrene–butadiene copolymer with water glass
Authors: Inoue Shin‐Ichi , Nakakita Satoshi , Zhang Ming , Imoto Yoji , Sakaki Toshiaki , Muraoka Kiyoshige , Mizoguti Tetsuo , Okamoto Hiroshi
Published: November 2005

A siloxane‐containing 2‐vinylpyridine–styrene–butadiene copolymer (PSBR/WG) was prepared from a 2‐vinylpyridine–styrene–butadiene copolymer (PSBR) latex and water glass. The water glass was added slowly, with stirring, to the PSBR latex. The latex mixture was stirred for 3 h at room temperature, and then, it was coagulated with 1N sulfuric acid producing a sulfate of PSBR with siloxane. The physical properties, such as the filling and stiffening effects of the hybrid polymer, and the vulcanizates were improved. An important advantage of this system is that it is possible to prepare the hybrid polymer simply, and the sodium ions formed in the reaction can also be easily removed. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 891–899, 2006
Synthesis by Microwave Irradiation and Antidiarrhoeal Activity of Benzotriazinone and Saccharine Derivatives
Authors: Fiorino Ferdinando , Caliendo Giuseppe , Perissutti Elisa , Severino Beatrice , Frecentese Francesco , Preziosi Barbara , Izzo Angelo A. , Capasso Raffaele , Santagada Vincenzo
Published: November 2005

The synthesis by microwave irradiation and the biological results of novel benzotriazinone and saccharine derivatives with potential antidiarrhoeal activity is described. Conventional and microwave heatings were compared for the reactions. Good yields and short reaction times are the main advantages of our synthetic route. Among the tested compounds, compound 12 inhibited motility both in in‐vitro and in‐vivo tests.
An example of information management in biology: Qualitative data economizing theory applied to the Human Genome Project databases
Authors: Daizadeh Iraj
Published: November 2005

Ironically, although much work has been done on elucidating algorithms for enabling scientists to efficiently retrieve relevant information from the glut of data derived from the efforts of the Human Genome Project and other similar projects, little has been performed on optimizing the levels of data economy across databases. One technique to qualify the degree of data economization is that constructed by Boisot. Boisot's Information Space (I‐Space) takes into account the degree to which data are written (codification), the degree to which the data can be understood (abstraction), and the degree to which the data are effectively communicated to an audience (diffusion). A data system is said to be more data economical if it is relatively high in these dimensions. Application of the approach to entries in two popular, publicly available biological data repositories, the Protein DataBank (PDB) and GenBank, leads to the recommendation that PDB increases its level of abstraction through establishing a larger set of detailed keywords, diffusion through constructing hyperlinks to other databases, and codification through constructing additional subsections. With these recommendations in place, PDB would achieve the greater data economies currently enjoyed by GenBank. A discussion of the limitations of the approach is presented.
“Irrational” searchers and IR‐rational researchers
Authors: Pharo Nils , Järvelin Kalervo
Published: November 2005

In this article the authors look at the prescriptions advocated by Web search textbooks in the light of a selection of empirical data of real Web information search processes. They use the strategy of disjointed incrementalism, which is a theoretical foundation from decision making, to focus on how people face complex problems, and claim that such problem solving can be compared to the tasks searchers perform when interacting with the Web. The findings suggest that textbooks on Web searching should take into account that searchers only tend to take a certain number of sources into consideration, that the searchers adjust their goals and objectives during searching, and that searchers reconsider the usefulness of sources at different stages of their work tasks as well as their search tasks.
Zum Einfluß der Temperatur auf die Bemessung von Kühlturmschalen aus Stahlbeton
Authors: Bender Michél , Bockhold Jörg , Meyer Joachim , Mark Peter
Published: November 2005

Zwangsmomente aus Temperaturgradienten haben erheblichen Einfluß auf die Bewehrungsmengen in Kühlturmschalen aus Stahlbeton. Dabei spielen nicht nur charakteristische Temperaturrandwerte und deren Kombination mit weiteren Einwirkungen eine Rolle, sondern auch die bei linearen Schnittgrößenberechnungen angenommenen Steifigkeitsreduktionen zur pauschalen Berücksichtung zwangsabbauender Rißbildung. Im Rahmen einer Sensitivitätsanalyse wird der Einfluß von Temperatureinwirkungen auf die Bemessung der Kühlturmschale vorgestellt. Basis der Parametervariation sind die spezifischen Berechnungsvorschriften der Bautechnischen Richtlinie BTR für Kühltürme (2005). Die maßgebenden rechnerischen Bemessungsszenarien werden anschließend in materiell und geometrisch nichtlinearen Analysen der Schale nachvollzogen, um die zwangsabbauende Rißbildung, den Einfluß der Temperatur auf Grenzzustände sowie Stahl‐ und Betonspannungswerte realistisch abzuschätzen und rechnerischen Werten gegenüberzustellen.
Gründungstechnische Aspekte beim Wiederaufbau der Frauenkirche zu Dresden
Authors: Schulz Eckart , von Wolffersdorff Peter‐Andreas
Published: November 2005

Die Frauenkirche in Dresden wies bis zu ihrer Zerstörung ständig Schäden auf, deren Ursachen auch in der Gründung bzw. im Baugrund vermutet wurden. Es wird das im Rahmen des Wiederaufbaus realisierte Gründungskonzept für die Kirche vorgestellt. Dieses Konzept basiert auf einer optimierten Lastabtragung auf die vorhandenen historischen Mauerwerksfundamente durch ein statisch verbessertes Tragwerk der wiederaufgebauten Kirche. Die wichtigsten Ergebnisse der vorausgegangenen Schadensanalyse werden dabei vorgestellt. Außerdem werden die hierfür notwendigen, umfangreichen geotechnischen Untersuchungen der Baugrundverhältnisse und der historischen Gründungselemente beschrieben. Schließlich werden die beobachteten Hebungen und Setzungen während der Enttrümmerung und des Wiederaufbaus ausgewertet und mit den prognostizierten Werten verglichen. Die im Gründungsbereich beim Wiederaufbau gemessenen, weitgehend gleichmäßigen Verformungen bestätigen das Tragwerks‐ und Gründungskonzept und die daraus resultierende hohe Standsicherheit dieses Teil s der Kirche.
Die Bogenbrücken der A 17 – Entwurf und Ausführung
Authors: Reintjes Karl‐Heinz
Published: November 2005

Im Zuge der neu gebauten A 17 wurden drei Bogenbrücken mit obenliegender Fahrbahn entworfen, die die mögliche Bandbreite und die besonderen Eigenschaften dieser Bauweise aufzeigen.

Die Brücke über das Seidewitztal mit einer Gesamtlänge von 568 m und einer Bogenstützweite von 154 m ist von der Aufgabenstellung her der klassische Anwendungsfall für eine im freien Vorbau erstellte Bogenbrücke über ein tiefer eingeschnittenes Tal.

Die Brücke Wölkau ist mit einer Gesamtlänge von 57 m und einer Bogenstützweite von 47 m ein Beispiel für eine Überführung über die Autobahn.

Die Brücke über das Lockwitztal überquert in einer Höhe von 64 m und mit einer Gesamtlänge von 723 m ein lang gezogenes Tal. Die Stützweiten in den zwei Hauptfeldern betragen jeweils 125 m. In vier Feldern der Brücke sind Betonhalbbögen angeordnet, die mit dem vorgespannten Stahlverbundüberbau und den Stützen zusammen ein einheitlich wirkendes System bilden. Die Brücke zeigt einen neuen Weg, die gestalterische Wirkung von Bogentragwerken auch bei Talüberquerungen einzusetzen, die von der Topographie und der Straßentrassierung bisher als nicht dafür geeignet erschienen.
Nichtlineare Querschnittsanalyse als Optimierungsproblem
Authors: Raue Erich
Published: November 2005

Bei nichtlinearem Materialverhalten lassen sich die Dehnungen und Normalspannungen in Stabquerschnitten meist nicht mehr mit den Ansätzen der elementaren Festigkeitslehre bestimmen. Vielfach werden numerische Lösungen mit Hilfe der Methode der finiten Elemente u. ä. ermittelt. Im allgemeinen sind dabei nichtlineare Gleichungssysteme zu lösen. Im vorliegenden Beitrag wird eine alternative Problemformulierung und Problemlösung auf der Grundlage des Prinzips vom Minimum des Gesamtpotentials und der nichtlinearen Optimierung verwendet. Die Formänderungsenergie geht direkt in das Berechnungsmodell ein. Dadurch lassen sich Besonderheiten des Materialverhaltens ohne prinzipielle Modifikationen des Berechnungsmodells erfassen. Ein weiterer wesentlicher Vorteil besteht darin, daß allgemein verfügbare mathematische Standardsoftware eingesetzt werden kann.
Berichtigung: Zur Neufassung der DIN 4178 “Glockentürme”
Authors: Haupt Wolfgang
Published: November 2005

See original .
Comparative bioavailability of two oral formulations of ranitidine
Authors: Flores‐Murrieta Francisco J. , Toledo Alejandra , Carrasco‐Portugal Miriam del Carmen , Reyes‐García Gerardo , Rodríguez‐Silverio Juan , Medina‐Santillán Roberto , Herrera Jorge E.
Published: November 2005

The current requirement of the Mexican Authorities to demonstrate the interchangeability of ranitidine formulations is to establish that the dissolution profile of the drug shows similarity. In order to establish if this requirement is adequate, the bioavailability of two formulations that did not meet this similarity were compared. Twenty‐five female volunteers received 150 mg ranitidine (Azantac® or Midaven®) under fasting conditions in two separate sessions using a cross‐over design. Plasma samples were obtained at selected times for a period of 12 h and stored frozen at −80°C until analysed. Ranitidine plasma levels were determined and pharmacokinetic parameters were obtained. Values (mean ± SEM) were: Cmax 528.85 ± 25.34 and 563.03 ± 33.25 ng/ml, tmax 2.76 ± 0.19 and 2.79 ± 0.18 h, and AUC12 h 2694.94 ± 99.50 and 2648.51 ± 133.38 ng.h/ml, for Azantac® or Midaven®, respectively. No statistically significant difference was obtained in the parameters evaluated. Moreover, 90% confidence limits were 96.6%–116.2% and 90.7%–105.1% for Cmax and AUC12 h ratios, respectively, indicating that the formulations tested are bioequivalent, despite the dissimilarity in the dissolution profile of the formulations. These results suggest that the comparative dissolution profile is not an adequate test to demonstrate the interchangeability of ranitidine formulations. Copyright © 2005 John Wiley & Sons, Ltd.
Molecular dynamics simulation studies of a protein–RNA complex with a selectively modified binding interface
Authors: Zhao Ying , Kormos Bethany L. , Beveridge David L. , Baranger Anne M.
Published: November 2005

The RNA recognition motif (RRM) is one of the most common RNA binding domains. We have investigated the contribution of three highly conserved aromatic amino acids to RNA binding by the N‐terminal RRM of the U1A protein. Recently, we synthesized a modified base (A‐4CPh) in which a phenyl group is tethered to adenine using a linker of 4 methylene groups. The substitution of this base for adenine in the target RNA selectively stabilizes the complex formed with a U1A protein in which one of the conserved aromatic amino acids is replaced with Ala (Phe56Ala). In this article, we report molecular dynamics (MD) simulations that probe the structural consequences of the substitution of A‐4CPh for adenine in the wild type and Phe56Ala U1A–RNA complexes and in the free RNA. The simulations suggest that A‐4CPh stabilizes the complex formed with Phe56Ala by adopting a folded conformation in which the tethered phenyl group fills the site occupied by the phenyl group of Phe56 in the wild‐type complex. In contrast, an extended conformation of A‐4CPh is predicted to be most stable in the complex formed with the wild‐type protein. The calculations indicate A‐4CPh is in an extended conformation in the free RNA. Therefore, preorganizing the structure of the phenyl‐tethered base for binding may improve both the affinity and specificity of the RNA containing A‐4CPh for the Phe56Ala U1A protein. Taken together, the previous experimental work and the calculations reported here suggest a general design strategy for altering RRM–RNA complex stability. © 2005 Wiley Periodicals, Inc. Biopolymers 81: 256–269, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Electrostatic properties of cowpea chlorotic mottle virus and cucumber mosaic virus capsids
Authors: Konecny Robert , Trylska Joanna , Tama Florence , Zhang Deqiang , Baker Nathan A. , Brooks Charles L. , McCammon J. A.
Published: November 2005

Electrostatic properties of cowpea chlorotic mottle virus (CCMV) and cucumber mosaic virus (CMV) were investigated using numerical solutions to the Poisson–Boltzmann equation. Experimentally, it has been shown that CCMV particles swell in the absence of divalent cations when the pH is raised from 5 to 7. CMV, although structurally homologous, does not undergo this transition. An analysis of the calculated electrostatic potential confirms that a strong electrostatic repulsion at the calcium‐binding sites in the CCMV capsid is most likely the driving force for the capsid swelling process during the release of calcium. The binding interaction between the encapsulated genome material (RNA) inside of the capsid and the inner capsid shell is weakened during the swelling transition. This probably aids in the RNA release process, but it is unlikely that the RNA is released through capsid openings due to unfavorable electrostatic interaction between the RNA and capsid inner shell residues at these openings. Calculations of the calcium binding energies show that Ca2+ can bind both to the native and swollen forms of the CCMV virion. Favorable binding to the swollen form suggests that Ca2+ ions can induce the capsid contraction and stabilize the native form. © 2005 Wiley Periodicals, Inc. Biopolymers 82: 106–120, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Electrostatic calculations for assignment of infrared difference bands to carboxyl groups getting protonated during protein reactions
Authors: Hauser Karin
Published: November 2005

Fourier transform infrared (FTIR) difference spectroscopy is predestinated to monitor the protonation of carboxyl groups during protein reactions, making glutamic and aspartic amino acids unique to follow proton pathways. The absorption of the corresponding vibrations are clearly distinguishable from the absorption of other amino acids. However, the assignment to specific groups within the protein needs additional information, e.g., from induced spectral changes due to isotopic labeling or mutation. Here, the capability of electrostatic calculations to assign IR difference bands to specific carboxyl groups getting protonated is demonstrated by the ion pump mechanism of the sarcoplasmic reticulum Ca2+‐ATPase. Active Ca2+ transport is coupled to the hydrolysis of ATP. Two Ca2+ ions are transported per ATP hydrolysed and two or three H+ ions are countertransported. FTIR difference spectra show that during the Ca2+ release step, carboxyl groups become protonated. Multiconformation continuum electrostatic calculations (MCCE) have been carried out to determine the equilibrium distribution of residue ionization and side chain conformation in dependence of pH. Available structural X‐ray data from the calcium‐bound and the calcium‐free state allows us to simulate the transition between the two states monitored in the IR difference spectra. Exemplarily for Asp 800, ligand of both calcium ions, it is shown that MCCE calculations can identify this specific Asp to contribute to the IR bands and therefore to take part in the proton countertransport of the Ca2+‐ATPase. In addition, an energy analysis can be performed to understand what interactions shift the pKa. © 2005 Wiley Periodicals, Inc. Biopolymers 82: 430–434, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Fast and versatile microwave‐assisted intramolecular Heck reaction in peptide macrocyclization using microwave energy
Authors: Byk Gerardo , Cohen‐Ohana Mirit , Raichman Daniel
Published: November 2005

We have revisited the intramolecular Heck reaction and investigated the microwave‐assisted macrocyclization on preformed peptides using a model series of ring‐varying peptides acryloyl‐Gly‐[Gly]n‐Phe(4‐I)NHR; n  0–4. The method was applied to both solution and solid supported cyclizations. We demonstrate that the intramolecular Heck reaction can be performed in peptides both in solution and solid support using a modified domestic microwave within 1 to 30 minutes in DMF under reflux with moderate yields ranging from 15 to 25% for a scale between 2–45 mg of linear precursors. The approach was applied to the synthesis of a constrained biologically relevant peptidomimetic bearing an Arg‐Gly‐Asp (RGD) sequence. These results make the microwave‐assisted Heck reaction an attractive renovated approach for peptidomimetics. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 274–282, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Interfacial behavior of cytoplasmic and mitochondrial creatine kinase oligomeric states
Authors: Vernoux Nathalie , Granjon Thierry , Marcillat Olivier , Besson Françoise , Vial Christian
Published: November 2005

Adsorption to the air/water interface of isoenzymes of creatine kinase was investigated using surface pressure–area isotherms and Brewster angle microscopy (BAM) observations. Octameric mitochondrial creatine kinase (mtCK) exhibits a significant affinity for the air/water interface. Whatever the mode of formation of the interfacial film, i.e., injection of the protein in the subphase or spreading onto the buffer surface, the final arrangement and conformation adopted by mtCK molecules lead to a similar result. In contrast, the dimeric isoenzymes mtCK and cytosolic MMCK do not induce any surface pressure variation. However, when the subphase contains 0.3M NaCl, both isoenzymes adsorb to the interface. When treated with 0.8 or 3M GdnHCl, muscle creatine kinase (MMCK) becomes surface active and occupies a greater surface than mtCK. This result contrasts with previous observations, often derived from monomeric proteins, that their surface activity is increased upon unfolding. It underlines the possible influence exerted by the protein oligomeric state on its interfacial activity. At a subphase pH of 8.8, which corresponds to the pI of octameric mtCK, the profiles of the isotherms obtained with dimeric and octameric states and the resistance to compression of the protein monolayers are significantly affected when compared to those recorded at pH 7.4. These data suggest that the octamer is more hydrophobic than the dimer and may contribute to explaining why octamers bind to the inner mitochondrial membrane while dimers do not. © 2005 Wiley Periodicals, Inc. Biopolymers 81: 270–281, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Prevention of thermal induced aggregation of cytochrome c at isoelectric pH values by polyanions
Authors: Fedunová Diana , Antalík Marián
Published: November 2005

Differential scanning calorimetry, viscometry, optical and CD spectroscopy were used to characterize the influence of two polyanions, poly(vinylsulfate) (PVS), and poly(4‐styrene‐sulfonate) (PSS) on thermal transition reversibility of ferricytochrome c at or near isoelectric pH. In these conditions, both PVS and PSS enhance the thermal transition reversibility of cytochrome c by preventing the aggregation of denatured protein molecules. Data indicate that the polyanions are in complex with cytochrome c that is stabilized by synergistic effect of Coulombic and non‐Coulombic interactions. © 2005 Wiley Periodicals, Inc.
Causes and outcomes of pouch excision after restorative proctocolectomy
Authors: Prudhomme M , Dehni N , Dozois R R , Tiret E , Parc R
Published: November 2005

Background

Pouch failure occurs in up to 10 per cent of patients after ileal pouch–anal anastomosis (IPAA). The aims of this study were to determine the reasons for pouch excision and to evaluate the outcome of the perineal wound after pouch excision.

Methods

Between 1984 and 2002, 91 patients with severe ileal pouch dysfunction were treated. This was a retrospective analysis of data collected prospectively from 24 patients who underwent pouch excision.

Results

Patients were grouped according to the final histological diagnosis. Fourteen patients with Crohn's disease developed extensive fistulous disease and/or recurrent abscesses, of whom six had a persistent perineal sinus after pouch excision. Five patients had familial adenomatous polyposis, in three of whom desmoid tumours were the cause of failure. Three patients had chronic ulcerative colitis and developed recurrent pelvic sepsis. Finally, two patients with multiple colorectal adenocarcinoma developed recurrent cancer (one) or sepsis (one).

Conclusion

Sepsis was the principal reason for pouch excision and was usually associated with recrudescent Crohn's disease in the pouch. Perineal wound healing was problematic after pouch excision for Crohn's disease.
Evaluation of outcome of laparoscopic colorectal resection with POSSUM, Portsmouth POSSUM and colorectal POSSUM
Authors: Law W L , Lam C M , Lee Y M
Published: November 2005

Background

This study evaluated the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM), Portsmouth (P) POSSUM and colorectal (CR) POSSUM in laparoscopic colorectal resection.

Methods

Observed mortality and morbidity rates in 400 patients who underwent laparoscopic colorectal resection were compared with those predicted by POSSUM, P-POSSUM and CR-POSSUM.

Results

Observed mortality and morbidity rates were 0·5 and 19·0 per cent respectively. Mortality rates predicted by POSSUM, P-POSSUM and CR-POSSUM were 10·8, 4·0 and 5·6 per cent respectively, and the morbidity rate predicted by POSSUM was 43·0 per cent. The predicted and observed mortality and morbidity rates showed significant lack of fit. The conversion rate to open surgery was 11·5 per cent. The mortality rate for patients having conversion was 2 per cent and was not significantly different to that predicted by P-POSSUM (4 per cent; P = 0·493) or CR-POSSUM (5 per cent; P = 0·370). In this group, the observed and POSSUM-predicted morbidity rates were also similar (43 versus 48 per cent respectively; P = 0·104).

Conclusion

POSSUM, P-POSSUM and CR-POSSUM overestimated mortality and morbidity in patients who underwent laparoscopic colorectal resection. However, the mortality rate in patients who required conversion fitted the models of P-POSSUM and CR-POSSUM, and the morbidity rate was comparable to that predicted by POSSUM.
Synthesis and Two‐photon Photolysis of 6‐(ortho‐Nitroveratryl)‐Caged IP3 in Living Cells
Authors: Kantevari Srinivas , Hoang Caroline J. , Ogrodnik Jakob , Egger Marcel , Niggli Ernst , Ellis‐Davies Graham C. R.
Published: November 2005

The synthesis of a photolabile derivative of inositol‐1,4,5‐trisphosphate (IP3) is described. This new caged second messenger (6‐ortho‐nitroveratryl)‐IP3 (6‐NV‐IP3) has an extinction coefficient of 5000 M−1 cm−1 at 350 nm, and a quantum yield of photolysis of 0.12. Therefore, 6‐NV‐IP3 is photolyzed with UV light about three times more efficiently than the widely used P4(5)‐1‐(2‐nitrophenyl)ethyl‐caged IP3 (NPE‐IP3). 6‐NV‐IP3 has a two‐photon cross‐section of about 0.035 GM at 730 nm. This absorbance is sufficiently large for effective two‐photon excitation in living cells at modest power levels. Using near‐IR light (5 mW, 710 nm, 80 MHz, pulse‐width 70 fs), we produced focal bursts of IP3 in HeLa cells, as revealed by laser‐scanning confocal imaging of intracellular Ca2+ concentrations. Therefore, 6‐NV‐IP3 can be used for efficient, subcellular photorelease of IP3, not only in cultured cells but also, potentially, in vivo. It is in the latter situation that two‐photon photolysis should reveal its true forte.
Continuous Matrix‐assisted Refolding of Inclusion‐body Proteins: Effect of Recycling
Authors: Schlegl R. , Necina R. , Jungbauer A.
Published: November 2005

A recombinant therapeutic protein expressed inEscherichia coliin form of inclusion bodies was used as a model system for comparative studies on the refolding efficiencies obtained by continuous matrix‐assisted refolding or batch‐dilution in a stirred tank reactor. Due to the strong aggregation tendency the refolding yield after dilution into an appropriate renaturation buffer was only 10 % at a protein concentration of 0.1 mg/mL. To improve the yield of active protein matrix‐assisted refolding using size‐exclusion chromatography was tested. A preparative continuous annular chromatography system (PCAC) equipped with a size‐exclusion resin was used for continuous processing of the solubilized unfolded protein. As the protein passed through the column, it was separated from the chaotropic agent and started to regain its native structure. Tightly bound aggregates produced during the refolding reaction were continuously removed from the rotating bed by 6 M guanidine‐hydrochloride. The aggregate fraction was recycled to the feed stream after concentrating by ultradiafiltration to increase the amount of refolded protein. The refolding yield of 27 % without recycling was increased to 45 % at a recycling rate of 0.51 at a protein concentration of 1 mg/mL. The stability of the reactor under continuous operation was shown for 15 hours without any significant loss of refolding efficiency or chromatographic resolution. Interdependencies of operational parameters such as protein concentration, loading factor and recycling rate on throughput of refolded protein are shown.
High Throughput Screening of Chromatographic Phases for Rapid Process Development
Authors: Bensch M. , Schulze Wierling P. , von Lieres E. , Hubbuch J.
Published: November 2005

The necessity of being “first on the market” paired with the need to cut production costs highlights the need for strategies and techniques allowing a fast process development while at the same time covering a high number of potential process parameters in order to reach an optimal process sequence. This can only be met by the use of high throughput screening (HTS) techniques. In this paper HTS applications presently applied in bioprocess development are reviewed, their use in chromatographic process parameter evaluation is discussed and concepts for the rational design of HTS experiments are presented. A rational approach for chromatographic parameter screening comprehends an initial screening procedure for ligand selection followed by the incorporation of specific adsorbent features using HTS pipetting systems finalized by a fine tuning step using packed mini‐columns. The analytical part of these screening techniques clearly sets the bottleneck of these procedures with a trade off between analytical information and analysis time. Finally, intelligent HTS strategies should in addition include efficient data processing paired with modern tools for design of experiments or model based process design.
Electrostatic Interaction Chromatography Process for Protein Separations: Impact of Engineering Analysis of Biorecognition Mechanism on Process Optimization
Authors: Yamamoto S.
Published: November 2005

A simple model for obtaining important information on the retention and the resolution of proteins by electrostatic interaction chromatography is described. The relationships among different definitions of distribution coefficients are explained in detail. The method employs a linear gradient elution experiment, in which a salt concentration is increased linearly with time at a fixed pH. The experimental data for electrostatic interaction chromatography and hydroxyapatite chromatography of proteins have shown that the number of binding sites values (B) determined from the experimental data as a function of pH can provide instructive information on the retention and the optimization of protein separations.
Multiple factor analysis with confidence ellipses: a methodology to study the relationships between sensory and instrumental data
Authors: Pagés Jérôme , Husson François
Published: November 2005

This paper describes a methodology to simultaneously analyse instrumental and sensory variables. The methodology is based on multiple factor analysis (MFA) which provides dimensions of variability of the products, connected to the two types of variables. The MFA graphics are constructed with confidence ellipses around the products in order to visualize the uncertainty in their position. These ellipses are drawn using a bootstrap procedure on the basis of both the instrumental and the sensory data or on the basis of the sensory data only. Copyright © 2005 John Wiley & Sons, Ltd.
PLS regression, PLS path modeling and generalized Procrustean analysis: a combined approach for multiblock analysis
Authors: Tenenhaus Michel , Vinzi Vincenzo Esposito
Published: November 2005

A situation where J blocks of variables are observed on the same set of individuals is considered in this paper. A factor analysis logic is applied to tables instead of variables. The latent variables of each block should well explain their own block and, at the same time, the latent variables of same order should be as positively correlated as possible to improve interpretation. The paper first (1) reviews the main methods for multiblock analysis based on a criterion to be optimized, (2) describes the hierarchical PLS path modeling algorithm and (3) recalls that it allows one to recover some usual multiblock analysis methods. It is then supposed that the number of latent variables can be different from one block to another and that these latent variables are orthogonal. PLS regression and PLS path modeling are used for this situation. The relation between Horst's generalized canonical correlation analysis and generalized Procrustean analysis for this specific application is also studied. The approach is illustrated by an example from sensory analysis. Copyright © 2005 John Wiley & Sons, Ltd.
Comparing and predicting sensory profiles from NIRS data: use of the GOMCIA and GOMCIA‐PLS multiblock methods
Authors: Vivien Myrtille , Verron Thomas , Sabatier Robert
Published: November 2005

Sequential multiblock component and regression methods are used to analyse pea sensory data. First the repeatability of sensory profiles is studied with the generalized orthogonal multiple co‐inertia analyis (GOMCIA) method. Then a calibration model is built to predict the averaged sensory profiles from near‐infrared spectroscopy (NIRS) data by means of the GOMCIA partial least squares (GOMCIA‐PLS) method. It is proposed to split the NIRS data into blocks and search the most influential block in the calibration model in order to select spectral wavelengths. This approach is compared with a PLS regression model. It is shown that a PLS regression model can be less efficient than a multiblock regression model in terms of prediction. Copyright © 2005 John Wiley & Sons, Ltd.
Independent component analysis and regression applied on sensory data
Authors: Westad Frank
Published: November 2005

In this paper, independent component analysis (ICA) and a partial least squares implementation of independent component regression (ICR) were applied on two sensory data sets. A brief introduction to the theory of ICA is presented, and how to find the optimal model rank is discussed. The effect of the number of independent components extracted is illustrated by comparison of ICA loadings from models with different numbers of components. Principal component analysis (PCA) and ICA were employed on the sensory data, and these methods are interpreted based on explained variance for the components and groupings of the sensory attributes. Significance testing on each sensory attribute for the components gave valuable information about the relevance in interpreting the individual attributes and components. ICA was also applied for regression purposes similarly to principal component regression (PCR) and partial least squares regression (PLSR). An algorithm which combines ICA and PLSR (IC‐PLSR) is presented. Single‐response IC‐PLSR seemed to be a promising complementary method to PLSR in extracting informative and valid components. Copyright © 2005 John Wiley & Sons, Ltd.