bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Active Antimicrobial Fiber‐Based Chitosan Polysaccharide Nanostructures using Electrospinning
Authors: Torres‐Giner S. , Ocio M. J. , Lagaron J. M.
Published: July 2008

The electrospinning technology opens up enormous possibilities for the implementation of bio‐based materials and food hydrocolloids in numerous applications. In this context, chitosan is a sustainable, biocompatible, biodegradable, antimicrobial and non‐toxic polysaccharide of great relevance in many fields of application. Because of its abundance in nature and excellent biocompatibility, the cationic polysaccharide chitosan is a very promising polymer for producing functional nanofibers. Although the material has good physicochemical properties, the electrospinning of the polymer is far from easy. In the current study, the effect of an unprecedented number of parameters (including solvent nature, polymer origin, molecular weight and spinning conditions) on morphology is reported. The work also aims to ascertain the antimicrobial properties of the generated biofibers of chitosan and relate them to its chemical structure. Finally, a new route is provided to generate chitosan based nanoporous structures starting from blends of chitosan and polylactic acid.
Enzymatically‐Modified Melt‐Extruded Guides for Peripheral Nerve Repair
Authors: Chiono V. , Ciardelli G. , Vozzi G. , Cortez J. , Barbani N. , Gentile P. , Giusti P.
Published: July 2008

In this work, melt‐extruded guides for peripheral nerve repair were produced, based on blends between poly‐(ϵ‐caprolactone) and gelatin with a low gelatin amount (10 wt. %), with the aim of combining the good melt process ability of the synthetic polymer with the optimal biocompatibility of the natural polymer. In one case, a blend was produced between poly‐(ϵ‐caprolactone) and gelatin previously crosslinked by transglutaminase, using a solution mixing technique. The blend was then melt‐extruded obtaining nerve guidance channels. In another case, a blend between poly‐(ϵ‐caprolactone) and uncrosslinked gelatin was first produced, then melt‐extruded into tube‐shaped manufacts. Finally, poly‐L‐lysine was grafted on the gelatin domains exposed on the inner tube surface using transglutaminase catalysis, with the aim to confer to the channel guide a specific signaling for nerve cells attachment, proliferation and migration. Scanning electron microscopy (SEM) and Fourier transform infrared‐attenuated total reflectance spectroscopy (FTIR‐ATR) coupled with Chemical Imaging analysis showed that the obtained binary blends were poor compatible, however, appropriate mixing techniques might lead to an homogeneous distribution of gelatin domains within the poly‐(ϵ‐caprolactone) matrix. Confocal microscopy (CM) was applied as a powerful tool to study the accessibility of mTGase towards gelatin substrates, using suitable model lysine‐rich peptides (FITC‐labeled KKKKGY). Confocal microscopy also gave a confirmation of poly‐L‐lysine enzymatic grafting on the exposed gelatin domains on the inner blend tube surface. In vitro cell tests using S5Y5 neuroblastoma cells showed that the produced nerve guides were biocompatible, however, gelatin was confirmed to be a non‐specific protein for the attachment and proliferation of nerve cells. On the other hand, poly‐L‐lysine functionalization of the inner tube surface greatly improved the in‐vitro cell response.
A Novel Heme Peroxidase from Raphanus sativus Intrinsically Resistant to Hydrogen Peroxide
Authors: Gil‐Rodríguez P. , Ferreira‐Batista C. , Vázquez‐Duhalt R. , Valderrama B.
Published: July 2008

All known heme peroxidases are susceptible to self‐inflicted oxidative damage. Substrate oxidation in peroxidases is a naturally imperfect process and damage emerges from the utilization of protein elements as electron sources through the catalytic intermediate Compound III. Given their wide application potential, the search for more stable heme peroxidases has been actively pursued in the past, albeit with limited success. Here, the identification and biochemical characterization of a novel H2O2‐resistant isoenzyme is reported which was isolated from daikon radish (Raphanus sativus L. cv. daikon) and named Zo peroxidase (ZoPrx). Partial protein sequencing demonstrated that ZoPrx is more related to anionic isoenzyme 53 from Arabidopsis thaliana and to anionic isoenzyme 2 from Armoracia rusticana (HRPA2) than to any other protein known to date. The stability of ZoPrx was demonstrated by rigorous evaluation of resistance to H2O2 in the absence or presence of exogenous reductants which was consistent with porphyrin integrity. ZoPrx systematically outperformed the reference HRPA2 isoenzyme, a heme peroxidase known for its relative oxidative stability. The catalytic cycle of ZoPrx is conventional in the sense that the usual intermediate Compounds I and II were identified although reaction rates are significantly different compared to HRPA2. The distinctive characteristic of ZoPrx is that when Compound III is formed in the presence of excess H2O2, it is particularly more stable and, instead of engaging into the regular deactivation decay pathways, it commits to the ground state restoration decay pathway. ZoPrx is the only known case of a naturally occurring stable heme peroxidase based on intrinsic properties. Deeper study of the structural determinants underlying this property may eventually allow us to graft it into other peroxidases with established commercial potential.
Laccase‐Mediated Wood Surface Functionalization
Authors: Kudanga T. , Prasetyo E. N. , Sipilä J. , Nousiainen P. , Widsten P. , Kandelbauer A. , Nyanhongo G. S. , Guebitz G.
Published: July 2008

Laccase‐catalyzed grafting of functional molecules on wood surface presents an eco‐friendly opportunity to improve wood properties. In a novel stepwise approach, functional molecules were bound to an enzymatically modified wood surface containing anchor groups. As anchor groups, phenolic amines were coupled to lignin moieties of wood using the 62 kDa Trametes hirsuta laccase. The coupling reaction to lignin was mimicked using the lignin model compounds 4‐O‐methyl guaiacylglycerol β‐guaiacyl ether A, guaiacylglycerol β‐guaiacyl ether E, dehydrodivanillyl alcohol type dibenzodioxocin D and syringylglycerol β‐guaiacylether G. Using this approach it was possible to increase binding of the fungicides propiconazole and thiabendazole by 42 % and 58 %, respectively, when compared to coupling onto wood pieces which were oxidized by laccase only.
Pharmacokinetics, dose‐range, and mutagenicity studies of methylphenidate hydrochloride in B6C3F1 mice
Authors: Manjanatha Mugimane G. , Shelton Sharon D. , Dobrovolsky Vasily N. , Shaddock Joseph G. , McGarrity Lynda G. , Doerge Daniel R. , Twaddle Nathan W. , Lin Chien‐Ju , Chen James J. , Mattison Donald R. , Morris Suzanne M.
Published: July 2008

Methylphenidate hydrochloride (MPH) is one of the most frequently prescribed pediatric drugs for the treatment of attention deficit hyperactivity disorder. In a recent study, increased hepatic adenomas were observed in B6C3F1 mice treated with MPH in their diet. To evaluate the reactive metabolite, ritalinic acid (RA) of MPH and its mode of action in mice, we conducted extensive investigations on the pharmacokinetics (PK) and genotoxicity of the drug in B6C3F1 mice. For the PK study, male B6C3F1 mice were gavaged once with 3 mg/kg body weight (BW) of MPH and groups of mice were sacrificed at various time points (0.25–24 hr) for serum analysis of MPH and RA concentrations. Groups of male B6C3F1 mice were fed diets containing 0, 250, 500, 1,000, 2,000, or 4,000 ppm of MPH for 28 days to determine the appropriate doses for 24‐week transgenic mutation studies. Also, the micronucleus frequencies (MN‐RETs and MN‐NCEs), and the lymphocyte Hprt mutants were determined in peripheral blood and splenic lymphocytes, respectively. Mice fed 4,000 ppm of MPH lost significant BW compared to control mice (P < 0.01). There was a significant increase in the average liver weights whereas kidneys, seminal vesicle, testes, thymus, and urinary bladder weights of mice fed higher doses of MPH were significantly lower than the control group (P ≤ 0.05). There was no significant increase in either the Hprt mutant frequency or the micronucleus frequency in the treated animals. These results indicated that although MPH induced liver hypertrophy in mice, no genotoxicity was observed. Environ. Mol. Mutagen., 2008. Published 2008 Wiley‐Liss, Inc.
Mutagenic potential of nitrenium ions of nitrobenzanthrones: Correlation between theory and experiment
Authors: Reynisson Jóhannes , Stiborová Marie , Martínek Václav , Gamboa da Costa Gonçalo , Phillips David H. , Arlt Volker M.
Published: July 2008

The mutagenic activity of nine substituted nitrobenzanthrone (NBA) derivatives was recently established in the Ames assay and ranged from near inactivity to extremely high mutagenic activity (Takamura‐Enya et al. 2006: Mutagenesis 21:399–404). Using thermochemical and molecular modeling techniques, the activation pathway of these NBA derivatives, namely 1‐nitro‐, 2‐nitro‐, 3‐nitro‐, 9‐nitro‐, 11‐nitro‐, 1,9‐dinitro‐, 3,9‐dinitro‐, 3,11‐dinitro‐, and 3,9,11‐trinitrobenzanthrone, and the formation of the corresponding aryl‐nitrenium ions, were investigated using density functional theory calculations. The calculated properties of the NBA derivatives were systematically compared with their bacterial mutagenic potency. Accommodation of the ligand substrates into the binding pocket of the bacterial nitroreductases was not sterically inhibited for the NBAs. Moreover, electron affinities, water elimination energies, esterification, and solvolysis energies did not reveal any possible links with the observed mutagenic potency of the NBAs. However, a strong negative linear correlation was found when the relative energies of the nitrenium ions of the mono and disubstituted NBAs were plotted against the logarithm of the mutagenic potency of the NBAs found in the different Salmonella typhimurium strains. Therefore, our data clearly indicate that the stability of the nitrenium ions is one critical determinant of the mutagenic potency of NBAs in Salmonella tester strains. Environ. Mol. Mutagen., 2008. © 2008 Wiley‐Liss, Inc.
Evaluation of putative hazard tests under background risk heterogeneity
Authors: Liu Yuan , Lawson Andrew B. , Ma Bo
Published: July 2008

In this paper, an evaluation of some tests for adverse health effects around fixed locations (putative hazard sites) is made. We address the situation where a heterogeneous background is included both in terms of correlated and uncorrelated heterogeneity (UH). In addition, we examine a set of tests for case event data (residential case addresses) including both distance and directional effects. The tests include distance and directional score tests (DIR), integrated intensity tests, the Besag & Newell (BES) test, and Kulldorff's focus clustering scan test. Monte Carlo power of the tests is evaluated and power curves are finally presented. Interesting results from this work include the lack of power found when correlated heterogeneity (CH) is present. This is not found with UH. The BES and Scan tests have lower power than the integrated intensity tests and score tests in general. The integrated intensity test demonstrates its omnibus ability to detect either distance or directional effects. Copyright © 2008 John Wiley & Sons, Ltd.
A hierarchical model for non‐stationary multivariate extremes: a case study of surface‐level ozone and NOxdata in the UK
Authors: Eastoe Emma F.
Published: July 2008

Within the last couple of decades much effort has been put into monitoring and analysing air pollution levels in an attempt to improve both our understanding of the scientific mechanisms involved and our ability to make predictions of future levels. In this paper we use extreme value methods to produce a statistical model for the joint distribution of surface‐level ozone (O3), nitric oxide (NO) and nitrogen dioxide (NO2) daily maxima, observed at a single urban location in the UK. Much recent work on the statistical analysis of extreme values has focused on methods for multivariate extremes, however, for all of the existing methods, it is unclear how to model non‐stationary data. By extending the pre‐processing method for the analysis of the extremes of non‐stationary univariate processes, we propose a hierarchical modelling approach for non‐stationary multivariate processes. This method allows prediction of the probabilities of any marginal or joint extreme events for non‐stationary multivariate data. We illustrate this by predicting marginal return levels for each of the pollutants of interest and then looking at the bivariate distribution of NO and NO2, conditional on ozone achieving a given marginal return level. Copyright © 2008 John Wiley & Sons, Ltd.
A buffered impact damper for multi‐degree‐of‐freedom structural control
Authors: Li Kuinian , Darby Antony P.
Published: July 2008

The results of an experimental investigation into the use of a buffered impact damper for controlling the dynamic response of an MDOF (multi‐degree‐of‐freedom) structure are presented in this paper. Free and forced vibration tests of a three‐DOF test structure equipped with a buffered impact damper are performed to evaluate the resulting damping effect and impact characteristics. The effect of damper parameters, such as clearance, and excitation type on the performance of the impact damper is also investigated. The performance of the buffered impact damper is compared with that of an equivalent conventional rigid impact damper. It is found that the buffered impact damper not only significantly reduces the peak contact force and the associated accelerations and noise generated by collisions but can also substantially enhance the damping effect over a wide range of frequencies, encompassing the natural frequencies of the test structure. Copyright © 2008 John Wiley & Sons, Ltd.
Dual high‐strength steel eccentrically braced frames with removable links
Authors: Dubina D. , Stratan A. , Dinu F.
Published: July 2008

Structural damage in buildings designed according to the dissipative design philosophy can be significant, even under moderate earthquakes. Repair of damaged members is an expensive operation and may affect building use, which in turn increases the overall economic loss. If damage can be isolated to certain dissipative members realized to be removable following an earthquake, the repair costs and time of interruption of building use can be reduced. Dual structural configurations, composed of a rigid subsystem with removable ductile elements and a flexible subsystem, are shown to be appropriate for the application of removable dissipative element concept. Eccentrically braced frames with removable links connected to the beams using flush end‐plate bolted connections are investigated as a practical way of implementing this design concept. High‐strength steel is used for members outside links in order to enhance global seismic performance of the structure by constraining plastic deformations to removable links and reducing permanent drifts of the structure. Copyright © 2008 John Wiley & Sons, Ltd.
On the use of the notion of suitable weak solutions in CFD
Authors: Guermond Jean‐Luc
Published: July 2008

The notion of suitable weak solutions for the three‐dimensional incompressible Navier–Stokes equations together with some standard regularization techniques for constructing these solutions is reviewed. The novel result presented in this paper is that Faedo–Galerkin weak solutions to the Navier–Stokes equations are suitable provided they are constructed using finite‐dimensional spaces having a discrete commutator property and satisfying a proper inf–sup condition. Low‐order mixed finite element spaces appear to be acceptable for this purpose. Connections between the notion of suitable solutions and LES modeling are investigated. A proposal for a large eddy scale model based on the notion of suitable solutions is made and numerically illustrated. Copyright © 2008 John Wiley & Sons, Ltd.
Onset of mixing layer instability in flow past a plate
Authors: Mittal Sanjay
Published: July 2008

A global stability analysis of the flow past a flat plate, normal to the flow, is carried out to determine the critical Re for the onset of convective instability of the mixing‐layer‐type modes. To suppress the primary wake mode, which leads to von Karman vortex shedding, flow past one half of the plate is studied and symmetry conditions are enforced along the wake centerline. The linearized perturbation equations for an incompressible flow are written in a moving frame of reference that travels with the perturbation and solved using a stabilized finite element method. The critical Re for the onset of convective instability is found to be 22, approximately, for H=5. Here, H is the distance of the lateral boundary from the plate centerline. Computations have also been carried out for H=10 and 20. The critical Re decreases with increase in H. Excellent agreement is observed between the results from global stability analysis and direct time integration of linearized disturbance equations. The results from the global analysis are compared with earlier reported results from local analysis of a Gaussian wake profile. Copyright © 2008 John Wiley & Sons, Ltd.
Wenn Maus und Tastatur ausgedient haben
Authors: Unterstell Rembert
Published: July 2008

Intelligente Lösungen für den digitalisierten Alltag: Der Münchner Medieninformatiker Andreas Butz erforscht die Zukunft des Computers
Eine Frage der Redlichkeit
Authors: Beisiegel Ulrike
Published: July 2008

Die DFG‐Empfehlungen zur Sicherung guter wissenschaftlicher Praxis sind auch nach zehn Jahren aktuell – und doch noch immer nicht im Alltag der Wissenschaft angekommen
Hilfe für den Zappelphilipp
Authors: Warnke Andreas , Renner Tobias , Romanos Marcel , Lesch Klaus‐Peter
Published: July 2008

Hyperaktiv und abgelenkt: Mehr als 650 000 Kinder und Jugendliche in Deutschland leiden unter ADHS. Forscher sind den Ursachen auf der Spur – und neuen Therapien
„Achtung, Zigeuner!”︁
Authors: Uerlings Herbert , Patrut Iulia‐Karin
Published: July 2008

Zwischen Verklärung und Vernichtung: Der gesellschaftliche Umgang mit dem „fahrenden Volk”︁ wandelte sich über Jahrhunderte immer wieder. Bis heute prägen Stereotype die Wahrnehmung der Sinti und Roma
NMR Studies of Proton Transport in Anhydrous Polymer Electrolytes for High Temperature Fuel Cells
Authors: Every H. A. , Ionescu L. D. , de Heer M. P. , Álvarez‐Gallego Y. , Janssen G. J. M.
Published: July 2008

This paper presents an NMR study of the dynamic processes related to proton transport in a new polymer consisting of two blocks – poly(2,6‐diphenylphenol) (P3O) and an imidazole functionalised poly(2,6‐dimethylphenol) (imi‐PPE) – and subsequently doped with polyphosphoric acid (PPA). From 1H and 31P NMR relaxation and diffusion measurements of the individual homopolymers and block copolymer, it was observed that addition of PPA significantly enhanced the mobility of imi‐PPE and the imi‐block copolymer, but not of P3O. The similarity in 1H T2 values between imi‐PPE and the imi‐block copolymer suggests that the relaxation behaviour in the block copolymer is dominated by the imi‐PPE phase. 1H diffusion in P3O and the imi‐block copolymer were comparable to pure PPA, suggesting that the proton diffusion is similar in each case. For imi‐PPE, the diffusion coefficients were several orders of magnitude lower, reflecting a restricted diffusion process that is not indicative of the proton mobility. For all three polymers, the 31P T2 relaxation behaviour and inability to measure 31P diffusion coefficients imply hindered translational motion of the phosphonate groups. From these results, it can be concluded that hydrogen bonds between the phosphoric acid and the polymer form a network that facilitates proton transport via a hopping mechanism.
Proton Conducting Membranes Based on Benzimidazole Sulfonic Acid Doped Sulfonated Poly(Oxadiazole–Triazole) Copolymer for Low Humidity Operation
Authors: Ponce M. L. , Boaventura M. , Gomes D. , Mendes A. , Madeira L. M. , Nunes S. P.
Published: July 2008

This work reports for the first time the preparation of sulphonated poly(oxadiazole–triazole) copolymer membranes doped with amphoteric molecule, 1H‐benzimidazole‐2‐sulphonic acid and their characterisation as proton conductors at 120 °C and low humidity. The membranes had not only high proton conductivities, up to 4 × 10–3 S cm–1 at 120 °C and low relative humidity (5 and 10%), but also had good mechanical properties with a storage modulus of about 3 GPa at 300 °C and high thermal stability with Tg up to around 420 °C. Because of their superior ion conducting and mechanical properties they have potential as a proton conducting membrane for fuel cell applications, in particular at high temperature and extremely low‐humidity conditions.
Novel K2NiF4‐Type Materials for Solid Oxide Fuel Cells: Compatibility with Electrolytes in the Intermediate Temperature Range
Authors: Sayers R. , Liu J. , Rustumji B. , Skinner S. J.
Published: July 2008

Many new materials have been identified as being of potential interest to solid oxide fuel cell developers. Recent work has suggested that materials of the La2NiO4 composition possess sufficient activity to act as an effective cathode. Whilst there have been many studies of the transport properties of materials of this family the reactivity with electrolyte compositions has received relatively little attention. In this work we have investigated the compatibility of La2NiO4 + d (LNO) with LSGM and ceria gadolinium oxide (CGO) electrolytes. It is clear that under an air atmosphere LNO reacts readily with CGO electrodes with the formation of a higher order Ruddlesden–Popper (Lan + 1NinO3n + 1) phase as one of the reaction products. In contrast, there is no evidence of secondary phase formation with LSGM electrolytes from the obtained diffraction data over a period of 72 h at temperatures up to 1,273 K.
Effect of Ionomer Content in Anode and Cathode Catalyst Layers on Direct Methanol Fuel Cell Performance
Authors: Krishnamurthy B. , Deepalochani S. , Dhathathreyan K. S.
Published: July 2008

The influence of ionomer content on the performance of direct methanol fuel cells (DMFC) is studied. The performance is studied as a function of the (nafion/carbon, N/C) ratio on the anode and cathode. The performance of the DMFC has been found to increase as a function of the N/C ratio. The ionomer content seems to influence the catalyst layer resistance in the anode and cathode and also the methanol oxidation potential on the anode. On the cathode, catalyst utilisation is seen to be affected by the ionomer content. Cyclic voltammetry (CV) is used to study the effect of ionomer content on Platinum (Pt) utilisation on the cathode. Theoretical calculations are used to study the catalyst layer resistance on the anode and cathode as a function of ionomer content. Findings indicate that ionomer content plays only a partial role in characterising the performance of a DMFC.
Novel SSBP2‐JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre‐B acute lymphocytic leukemia
Authors: Poitras Jennifer L. , Cin Paola Dal , Aster Jon C. , DeAngelo Daniel J. , Morton Cynthia C.
Published: July 2008

Activating mutations in JAK2 are found in virtually all patients with polycythemia vera, and about half of those with essential thrombocythemia and primary myelofibrosis. In addition, less common aberrations (particularly gene fusions) involving JAK2 have been described in acute leukemias. With the advent of JAK2 inhibitor trials in myeloproliferative disorders, tumors with JAK2 mutations or rearrangements have become candidates for targeted therapy. In this report, we identify SSBP2 as a new JAK2 fusion partner in a patient with pre‐B cell acute lymphocytic leukemia. This finding adds to the expanding compendium of JAK2 aberrations found in various hematopoietic malignancies, as well as the potential need for a diagnostic FISH analysis in the appropriate clinical setting. © 2008 Wiley‐Liss, Inc.
Redundant DNA methylation in colorectal cancers of Lynch‐syndrome patients
Authors: Alemayehu Aster , Sebova Katarina , Fridrichova Ivana
Published: July 2008

Lynch syndrome is an inherited disease resulting predominantly in colorectal cancer (CRC). The crucial cause is DNA mismatch repair (MMR) malfunction that is associated mostly with MLH1 or MSH2 germline mutations. A significant hallmark of repair defects is a high level of instability in microsatellites (MSI‐H). In many sporadic unstable CRCs, the MLH1 gene is inactivated by promoter hypermethylation in addition to extensive promoter methylation in many tumor‐suppressor genes known as CpG island methylation phenotype (CIMP). To investigate the possible role of epigenetic alterations in causing MMR deficiency and thereby Lynch syndrome, we evaluated the MLH1 specific and global hypermethylation in hereditary CRCs. Of 22 Lynch‐syndrome‐related CRCs, 18 (81.8%) demonstrated various levels of DNA methylation; of these, 14 (63.6%) and 4 (18.2%) were methylated in distal and both distal and proximal regions of the MLH1 promoter, respectively. However, only 7/18 (38.9%) of results were confirmed by bisulfite sequencing. Similar methylation patterns in tumors and frequently in matched normal DNA were found in twelve and four patients with MLH1 and MSH2 alterations documented by the absence of protein or presence of germline mutation, respectively. Moreover, the same results were observed in five stable CRCs. None of 22 Lynch‐syndrome‐related tumors presented CIMP in contrast to 3/10 (30%) stable carcinomas. The rather randomly distributed weak methylation patterns in hereditary CRCs indicate that epigenetic events are redundant in Lynch‐syndrome etiology, in contrast to the widespread DNA methylation in sporadic unstable CRCs. These methylation‐profile differences can lead to more effective molecular diagnosis of Lynch syndrome. © 2008 Wiley‐Liss, Inc.
Bayesian variable and model selection methods for genetic association studies
Authors: Fridley Brooke L.
Published: July 2008

Variable selection is growing in importance with the advent of high throughput genotyping methods requiring analysis of hundreds to thousands of single nucleotide polymorphisms (SNPs) and the increased interest in using these genetic studies to better understand common, complex diseases. Up to now, the standard approach has been to analyze the genotypes for each SNP individually to look for an association with a disease. Alternatively, combinations of SNPs or haplotypes are analyzed for association. Another added complication in studying complex diseases or phenotypes is that genetic risk for the disease is often due to multiple SNPs in various locations on the chromosome with small individual effects that may have a collectively large effect on the phenotype. Hence, multi‐locus SNP models, as opposed to single SNP models, may better capture the true underlying genotypic‐phenotypic relationship. Thus, innovative methods for determining which SNPs to include in the model are needed. The goal of this article is to describe several methods currently available for variable and model selection using Bayesian approaches and to illustrate their application for genetic association studies using both real and simulated candidate gene data for a complex disease. In particular, Bayesian model averaging (BMA), stochastic search variable selection (SSVS), and Bayesian variable selection (BVS) using a reversible jump Markov chain Monte Carlo (MCMC) for candidate gene association studies are illustrated using a study of age‐related macular degeneration (AMD) and simulated data.Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
A nonparametric method for penetrance function estimation
Authors: Alarcon F. , Bonaïti‐Pellié C. , Harari‐Kermadec H.
Published: July 2008

In diseases caused by a deleterious gene mutation, knowledge of age‐specific cumulative risks is necessary for medical management of mutation carriers. When pedigrees are ascertained through at least one affected individual, ascertainment bias can be corrected by using a parametric method such as the Proband's phenotype Exclusion Likelihood, or PEL, that uses a survival analysis approach based on the Weibull model. This paper proposes a nonparametric method for penetrance function estimation that corrects for ascertainment on at least one affected: the Index Discarding EuclideAn Likelihood or IDEAL. IDEAL is compared with PEL, using family samples simulated from a Weibull distribution and under alternative models. We show that, under Weibull assumption and asymptotic conditions, IDEAL and PEL both provide unbiased risk estimates. However, when the true risk function deviates from a Weibull distribution, we show that the PEL might provide biased estimates while IDEAL remains unbiased. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
Impaired performance of FDR‐based strategies in whole‐genome association studies when SNPs are excluded prior to the analysis
Authors: Marenne Gaëlle , Dalmasso Cyril , Perdry Hervé , Génin Emmanuelle , Broët Philippe
Published: July 2008

With recent advances in genomewide microarray technologies, whole‐genome association (WGA) studies have aimed at identifying susceptibility genes for complex human diseases using hundreds of thousands of single nucleotide polymorphisms (SNPs) genotyped at the same time. In this context and to take into account multiple testing, false discovery rate (FDR)‐based strategies are now used frequently. However, a critical aspect of these strategies is that they are applied to a collection or a family of hypotheses and, thus, critically depend on these precise hypotheses. We investigated how modifying the family of hypotheses to be tested affected the performance of FDR‐based procedures in WGA studies. We showed that FDR‐based procedures performed more poorly when excluding SNPs with high prior probability of being associated. Results of simulation studies mimicking WGA studies according to three scenarios are reported, and show the extent to which SNPs elimination (family contraction) prior to the analysis impairs the performance of FDR‐based procedures. To illustrate this situation, we used the data from a recent WGA study on type‐1 diabetes (Clayton et al. [2005] Nat. Genet. 37:1243–1246). and report the results obtained when excluding or not SNPs located inside the human leukocyte antigen region. Based on our findings, excluding markers with high prior probability of being associated cannot be recommended for the analysis of WGA data with FDR‐based strategies. Genet. Epidemiol. 2008. © 2008 Wiley‐Liss, Inc.
Generation of brachiopod‐dominated shell beds in the Miocene rocks of Carriacou, Lesser Antilles
Authors: Harper David A. T. , Pickerill Ron K.
Published: July 2008

Brachiopod‐dominated shell concentrations occur within the turbiditic rocks of the Miocene Grand Bay Formation on the Antillean island of Carriacou. The shells, mainly Tichosina, form dispersed and loose accumulations. Exceptional conditions on the deep‐water flanks of submarine volcanic edifices encouraged the recruitment of large populations of Tichosina and the subsequent entrainment of the shells in gravity‐driven deposits. The shells are a rare example, in the Caribbean Basin, of transported Archaic‐type shell beds constructed by a taxonomic group more typical of the Palaeozoic fauna. Copyright © 2008 John Wiley & Sons, Ltd.
Methylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytes
Authors: Liu Wei‐Lin , Lee Yi‐Hsuan , Tsai Shih‐Ying , Hsu Chung Yi , Sun Yu‐Yo , Yang Liang‐Yo , Tsai Shing‐Han , Yang Wei‐Chung Vivian
Published: July 2008

Reactive gliosis caused by post‐traumatic injury often results in marked expression of chondroitin sulfate proteoglycan (CSPG), which inhibits neurite outgrowth and regeneration. Methylprednisolone (MP), a synthetic glucocorticoid, has been shown to have neuroprotective and anti‐inflammatory effects for the treatment of acute spinal cord injury (SCI). However, the effect of MP on CSPG expression in reactive glial cells remains unclear. In our study, we induced astrocyte reactivation using α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) and cyclothiazide to mimic the excitotoxic stimuli of SCI. The expression of glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivation, and CSPG neurocan and phosphacan were significantly elevated by AMPA treatment. The conditioned media from AMPA‐treated astrocytes strongly inhibited neurite outgrowth of rat dorsal root ganglion neurons, and this effect was reversed by pretreatment with MP. Furthermore, MP downregulated GFAP and CSPG expression in adult rats with SCI. Additionally, both the glucocorticoid receptor (GR) antagonist RU486 and GR siRNA reversed the inhibitory effects of MP on GFAP and neurocan expression. Taken together, these results suggest that MP may improve neuronal repair and promote neurite outgrowth after excitotoxic insult via GR‐mediated downregulation of astrocyte reactivation and inhibition of CSPG expression. © 2008 Wiley‐Liss, Inc.
Differential NMDA‐dependent activation of glial cells in mouse hippocampus
Authors: Serrano Alexandre , Robitaille Richard , Lacaille Jean‐Claude
Published: July 2008

In the hippocampus, the NMDA receptor is thought to be an important glutamate receptor involved in synaptic plasticity and in memory processes. Until recently, NMDA receptors have been considered solely as neuronal components, but some evidence suggests that glial cells in the hippocampus, and in particular astrocytes, also could be activated by NMDA applications. On the basis of their shape and electrophysiological properties (linear and rectified I/V curve), we describe two different populations of glial cells from GFAP‐GFP transgenic mice that are activated differentially by NMDA. We found that linear glial cells were depolarized by NMDA that was not dependent on Ca2+ rise but partially involved a Ca2+ entry. Additionally, NMDA‐induced depolarization of linear glial cells involved both a TTX‐independent pathway likely through a direct activation, and a TTX‐dependent pathway that required neuronal activity. The NMDA‐induced depolarization in these cells was in part due to the activation of glutamate transporters and GABAB receptors. Furthermore, TTX‐dependent NMDA‐induced activation regulates the level of gap junction coupling between linear glial cells. In contrast, NMDA‐induced depolarization in outward rectifying cells do not require a Ca2+ rise but are mediated directly by Ca2+ entry and are independent of glutamate transporters, GABAB and GABAA receptors. Our findings reveal that NMDA differentially activates hippocampal glial cells and the glial network through heterogeneous mechanisms in a cell‐type specific manner. © 2008 Wiley‐Liss, Inc.
Modality of physical exercise and cognitive function in Hong Kong older Chinese community
Authors: Lam Linda C. W. , Tam Cindy W. C. , Lui Victor W. C. , Chan W. C. , Chan Sandra S. M. , Chiu Helen F. K. , Wong Ada , Tham M. K. , Ho K. S. , Chan W. M.
Published: July 2008

Objective

We reported the association between modality of Physical Exercise and cognitive function in 782 older Chinese adults assessed in the second phase of a population survey for dementia in Hong Kong.

Methods

Profiles of physical exercise was measured by a questionnaire (no exercise, stretching, aerobic and mind‐body exercise). Cognitive Assessments included the CMMSE, ADAS‐Cog, and Category Verbal Fluency Test (CVFT).

Results

The aerobic and mind body exercise groups with longer exercise habits (>5 years) had higher scores in most cognitive tests (Kruskal Wallis tests, p < 0.01). Beneficial effects were more significant in the young old group from 65– 75 years.

Conclusions

Possible age related specific effects of aerobic and mind body exercise on cognitive reserve are worthy of further exploration. Copyright © 2008 John Wiley & Sons, Ltd.
Understanding care of people with dementia in Spain: Cohabitation arrangements, rotation and rejection to long term care institution
Authors: Rivera Jesús , Bermejo Felix , Franco Manuel , Morales‐González José Manuel , Benito‐León Julian
Published: July 2008

Background

Most people with dementia in Spain live at home with their families. Current changes in the family structure are transforming the care of people with dementia through new cohabitation arrangenments and rotation practices.

Objective

To describe the cohabitation arrangements of families of people with dementia in Spain and to understand the caregivers' characteristics related to rotation and the rejection of long term care institutions.

Methods

A cross sectional study ‐NEDICES study‐ was conducted using both quantitative and qualitative methodologies.150 caregivers of people with dementia from two communities from Madrid, Spain, were surveyed using a questionnaire designed to describe cohabitation arrangements and care. Qualitative methods included: 13 caregivers participating in focus groups, and 3 caregivers in Semi Structured Interviews aimed to understand rotation practices and rejection to long term care institution.

Results

Characteristics related with rotation were: sex of persons with dementia, widowhood, socio‐economic status, caregiver relationship and burden of the caregiver. The qualitative study showed that the use of the rotation was related to normative behaviors and with obligation feelings, along with a change in the role of women in the current Spanish family. The use of long term care institutions was related to geographical distance of the family.

Conclusions

The results of this study suggest that rotation has appeared in Spain as a new mechanism of care for people with dementia, and its related to the rejection of long term care institutions. Copyright © 2008 John Wiley & Sons, Ltd.
Validity and reliability of the Simpson‐Angus Scale (SAS) in drug induced parkinsonism in the elderly
Authors: Knol Wilma , Keijsers Carolina J. P. W. , Jansen Paul A. F. , Belitser Svetlana V. , Schobben Alfred F. A. M. , Egberts Antoine C. G. , van Marum Rob J.
Published: July 2008

Background

Quantification of drug induced parkinsonism (DIP) for study purposes is difficult. The most often used Simpson Angus Scale (SAS) lacks proper clinimetric evaluation. The newer Schedule for Assessment of Drug‐Induced Movement Disorders (SADIMoD) shows good clinimetric characteristics, but has not been used in published clinical studies, probably due to the complexity of the scale.

Objectives

To evaluate internal consistency and inter‐rater reliability of the SAS and the correlation ot f the SAS with the parkinsonism subscale of the SADIMoD in elderly.

Method

Fifteen elderly diagnosed with DIP were recruited. The patients were assessed three times with the SAS by three independent investigators. The resident also performed the SADIMoD. Internal consistency was measured by Cronbach's α‐coefficient, inter‐rater variability was examined with weighted kappa values and percentage of agreement and correlation to SADIMoD by Spearman's correlation coefficient.

Results

SAS demonstrated good internal consistency reliability (Cronbach's α coefficients 0.83). Inter‐rater reliability for sum score was good. For individual items slight agreement on the item salivation and moderate to very good agreement on remaining items calculated by weighted kappa values was reached. We found 87–100% agreement on the individual items with acceptance of 1 point difference between raters. The SAS demonstrated acceptable correlation with the SADIMoD parkinsonism subscale scores (Spearman's rho = 0.66; p < 0.01).

Conclusion

The SAS appears to be a valid and by different instructed health care professionals easy to perform research tool to evaluate DIP. Copyright © 2008 John Wiley & Sons, Ltd.
Effects of Alzheimer's disease and mild cognitive impairment on driving ability: a controlled clinical study by simulated driving test
Authors: Frittelli Cristina , Borghetti Davide , Iudice Giovanni , Bonanni Enrica , Maestri Michelangelo , Tognoni Gloria , Pasquali Livia , Iudice Alfonso
Published: July 2008

Objective

To assess the effects of Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) on simulated car driving ability.

Methods

Twenty patients with a probable AD of mild severity (Clinical Dementia Rating, CDR = 1) were compared with 20 subjects with MCI (CD = 0.5), and a group of age‐matched neurologically normal controls on a driving simulation task. Measures of driving competence included the length of run, the number of infractions (omission of stop at pedestrian crossings, speed limits violation), the number of stops at traffic lights, the mean time to collision, and the number of off‐road events. Results in the driving competence measures were correlated with scores obtained from simple visual reaction times and mini‐mental state examination (MMSE).

Results

The patients with mild AD performed significantly worse than MCI subjects and controls on three simulated driving measures, length of run and mean time to collision (p < 0.001), and number of off‐road events (p < 0.01). MCI subjects had only a significantly shorter time‐to‐collision than healthy controls (p < 0.001). Simple visual reaction times were significantly longer (p < 0.001) in patients with AD, compared to MCI and healthy controls, and showed a borderline significant relation (p = 0.05) with simulated driving scores. Driving performance in the three groups did not significantly correlate with MMSE score as measure of overall cognitive function.

Conclusions

Mild AD significantly impaired simulated driving fitness, while MCI limitedly affected driving performance. Unsafe driving behaviour in AD patients was not predicted by MMSE scores. Copyright © 2008 John Wiley & Sons, Ltd.
Synthesis of new organophosphorus‐substituted derivatives of ethanesulfonic acid
Authors: Prishchenko Andrey A. , Livantsov Mikhail V. , Novikova Olga P. , Livantsova Ludmila I. , Petrosyan Valery S.
Published: July 2008

Nucleophilic addition of trimethylsilyl esters of hypophosphorus acid to trimethylsilyl ester and diethylamide of vinylsulfonic acid is proposed as convenient methods for the synthesis of new 2‐sulfonylethylphosphonites and their derivatives under mild conditions. Also the new functionalized derivatives of these phosphonites, including aminomethyl fragments as well as certain properties of these compounds as important precursors of new organophosphorus‐substituted derivatives of ethanesulfonic acid, are presented. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:470–473, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20448
Chalcogenation reactions of a stable ferrocenyldiphosphene: Formation of thia‐, selena‐, and telluradiphosphiranes
Authors: Nagahora Noriyoshi , Sasamori Takahiro , Tokitoh Norihiro
Published: July 2008

The reactions of TbtPPTbt (Tbt = 2,4,6‐tris[bis(trimethylsilyl)methyl]phenyl) with elemental sulfur and selenium in the presence of triethylamine resulted in the formation of the corresponding thia‐ and selenadiphosphiranes in 71% and 65%, respectively, whereas the tellurization reaction was unsuccessful probably due to the steric reason. On the other hand, treatment of TbtPPFc (Fc = ferrocenyl) with elemental sulfur, selenium, and tributylphosphine telluride afforded the corresponding thia‐, selena‐, and telluradiphosphiranes in 84%, 88%, and 66% yields, respectively. The molecular structures of these three‐membered heterocyclic compounds were confirmed by spectroscopic analysis. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:443–449, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20449
Synthesis of functionalized 2‐trimethylsiloxy‐substituted O‐trimethylsilyl alkylphosphonites, their analogues, and derivatives
Authors: Prishchenko Andrey A. , Livantsov Mikhail V. , Novikova Olga P. , Livantsova Ludmila I. , Petrosyan Valery S.
Published: July 2008

Nucleophilic addition of trimethylsilyl esters of tricoordinate organophosphorus acids to several functionalized alkylene oxides is proposed as convenient methods for the synthesis of new 2‐trimethylsiloxysubstituted alkylphosphonites, their analogues, and derivatives. Also the new functionalized derivatives of these phosphonites, including amino, carboxy, or sulfo groups as well as certain properties of these compounds, which may be the important precursors of new functionalized 2‐hydroxyalkylorganophosphorus acids, are presented. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:450–454, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20453
The unexpected chemistry of a bis(phospholyl)acetylene
Authors: Duffy Matthew P. , Donnadieu Bruno , Mathey François
Published: July 2008

The reaction of lithium 3,4‐dimethyl‐phospholide with tetrachloroethylene gives the corresponding 1,2‐bis(phospholyl)acetylene that has been characterized by X‐ray crystal structure analysis of its bis(pentacarbonylmolybdenum) complex. The reaction with sulfur leads to the corresponding disulfide that spontaneously undergoes a self‐condensation via a Diels‐‐Alder cycloaddition between the CC triple bond and the phosphole dienic system giving, after aromatization by loss of the phosphorus bridge, the corresponding 1,2‐bis(phospholyl)benzene. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:537–541, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20457
A facile synthesis of new 1,2‐dihydro‐2λ5‐[1,3]oxazolo[5,4‐d][1,3,2]diazaphosphinine derivatives starting from 2‐benzoylamino‐3, 3‐dichloroacrylonitrile
Authors: Shablykin Oleg V. , Gakh Andrei A. , Brovarets Vladimir S. , Rusanov Eduard B. , Drach Boris S.
Published: July 2008

Easily accessible 2‐benzoylamino‐3,3‐dichloroacrylonitrile, when treated successively with primary amines, phosphorus pentachloride, sulfur dioxide, and various N‐ or S‐nucleophiles, furnishes the corresponding derivatives of 1,2‐dihydro‐2λ5‐[1,3]oxazolo[5,4‐d][1,3,2]diazaphosphinine, a novel fused heterocycle. The structure of the compounds obtained is unequivocally confirmed by spectroscopic methods and X‐ray diffraction analysis. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:506–511, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20470
Synthesis and antitumor activity of novel α‐aminophosphonates from diterpenic dehydroabietylamine
Authors: Rao Xiaoping , Song Zhanqian , He Ling
Published: July 2008

A series of novel α‐aminophosphonates were synthesized from diterpenic dehydroabietylamine, and their structures were characterized by IR, 1H NMR, and 31P NMR spectroscopy. Their antitumor activities against SMMC7721 liver cancer cells were evaluated by the MTT method. Compounds 4 and 6 exhibited higher activities even at very low concentrations, and the inhibition ratios reached 75% and 79% at 0.1 µM, respectively. The inhibition ratio of compound 9 reached 99% after 72‐h incubation. α‐Aminophosphonates with a fluorine atom and a nitro group fused to the benzene ring exhibited higher activities. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:512–516, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20471
Synthesis of phosphorous acid and its derivatives based on the reaction of elemental phosphorus (P4) and aqueous solution of choline in the presence of the hydroxides of earth alkali metals
Authors: Platova Elena V. , Batyeva Elvira S. , Kursheva Lidiya I. , Sinyashin Oleg G.
Published: July 2008

A nonchloric method for the synthesis of phosphorous acid and barium and calcium phosphites is proposed, involving the reaction of elemental phosphorus (P4) with aqueous barium and calcium hydroxides in the presence of quaternary ammonium base (choline). Conditions for the preparation of high‐purity phosphorous acid based on the oxidation of the hypophosphite ion to the phosphite ion in a strong alkali medium were studied. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:517–519, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20472