bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and enhanced neuroprotective activity of C60-based ebselen derivatives
Authors: Liu Xu-Feng , Guan Wen-Chao , Ke Weng-Shan
Published: April 2007

A C60-based ebselen derivative 4 was synthesized through the cycloaddition of C60 with the azide (3) containing the ebselen component. It was obtained in a four-step synthesis starting from 2-(chloroseleno)benzoyl chloride and 2-(2-aminoethoxy)ethanol in 53% yield (based on consumed C60). Its structure was characterized by 1H NMR, 13C NMR, IR, UV, and FAB-MS. To verify that the C60-based ebselen derivative 4 had enhanced antioxidative and neuroprotective activity, the C60 derivative 5 and the ebselen derivative 6 were selected to treat cortical neuronal cells using the same procedures as with the C60-based ebselen derivative 4. The cellular viability of different derivative treatment groups was estimated by LDH leakage assay and MTT assay. At the same final concentration (30 µmol/L), the results showed that the antioxidative and protective potencies of the C60-based ebselen derivative 4 (MTT (OD) 0.340 ± 0.035, LDH release (UL–1) 4.80 ± 0.16) against H2O2-mediated neuronal injury have an advantage over those of C60 derivative 5 (MTT (OD) 0.297 ± 0.036, LDH release (UL–1) 5.37 ± 0.31) and ebselen derivative 6 (MTT (OD) 0.267 ± 0.027, LDH release (UL–1) 5.85 ± 0.26). Correspondingly, the GPX activity of 4 (1.62 U/µmol) was higher than that of 5 (0.77 U/µmol) and 6 (1.24 U/µmol). These findings demonstrate that the incorporation of two components with similar biological activity (C60 component and ebselen component) may be a desirable way of obtaining a new and more biologically effective C60-based compound.Key words: fullerene, ebselen derivative, azide, neuroprotective activity, cellular viability.
Acyl transfer from carboxylate, carbonate, and thiocarbonate esters to enzymatic and nonenzymatic thiolates
Authors: Gravel Christian , Lapierre Danielle , Labelle Judith , Keillor Jeffrey W
Published: April 2007

Transglutaminases (EC 2.3.2.13) (TGases) catalyze calcium-dependent acyl transfer reactions between peptide-bound glutamine residues as acyl donors and peptide-bound lysine residues as acyl acceptors, resulting in the formation of intermolecular ε-(γ-glutamyl)lysine crosslinks. The mechanistic details of its "ping-pong" transamidation reaction remain unknown. In particular, few studies have been published probing the nucleophilicity of TGase using acyl-donor substrates of varied electrophilicity. Herein we report the synthesis of activated esters of carbonates, carbamates, and thiocarbonates and their reactions with simple thiols, as a nonenzymatic point of reference, and with the catalytic cysteine residue of guinea pig liver TGase. Our kinetic results show that the simple substitution of a side chain methylene unit by oxygen or sulphur had a surprising effect on both substrate affinity and acylation reactivity. Furthermore, they provide unexpected insight into the importance of a side chain heteroatom for conferring affinity for tissue TGase as well as revealing an interesting class of irreversible inhibitors.Key words: enzyme kinetics, enzyme inhibition, transglutaminase, acyl-transfer reactions, carbamate, thiocarbonate, carbonate.
Zirconium(IV) chloride-catalyzed synthesis of 1,5-benzodiazepine derivatives
Authors: Reddy K Srinivasa , Reddy Ch. Venkateshwar , Mahesh M , Reddy K Rosi , Raju P VK , Narayana Reddy V V
Published: April 2007

Zirconium tetrachloride efficiently catalyzes the cyclocondensation reaction of o-phenylenediamine and a ketone in refluxing 1,2-dichloroethane to afford the corresponding 2,3-dihydro-1H-1,5-benzodiazepine in high yield. The formation of specific regioisomers and their structural elucidation are reported for the first time.Key words: zirconium tetrachloride, o-phenylenediamines, ketones, 1,5-benzodiazepines, 1H NMR, regioisomers.
YTTRIUM EFFECT ON LOCAL STRUCTURE OF BISMUTH-BORATE GLASSES
Authors: SIMON V. , ENIU D.
Published: April 2007

Glass samples with 3 B 2 O 3· Bi 2 O 3 and B 2 O 3· Bi 2 O 3 matrices containing up to 30 mol% Y 2 O 3 were prepared by melt fast quenching method. The effect of yttrium addition on the local order in glasses was investigated by infrared spectroscopic analysis. The results indicate that the local structure is more ordered in the glass system with higher bismuth content and the progressive addition of yttrium increases the local disorder in both bismuth-borate glass matrices.
ANDREEV SPECTRUM AND SUPERCURRENT IN A DOUBLE FERROMAGNET CLEAN JOSEPHSON JUNCTION
Authors: PALTOGLOU V. , MARGARIS I. , FLYTZANIS N.
Published: April 2007

We consider a superconductor/double-ferromagnet/superconductor (S/I1/F/IC/F'/I2/S) ballistic junction with thin insulating layers in the interfaces. An extensive investigation is carried out for the possibility of 0- or π-junction and the important phaseshift. The average exchange field for the two ferromagnets has limited use, only for weak exchange fields. Several analytical formulas are obtained for the energy spectrum in simple cases with interface potential (a) absent, (b) between ferromagnets only, (c) double resonance barrier between S and F layers. They give reasonable agreement even outside their range of validity. For the case of strong S/F barriers we find a strong interplay of Andreev bound states and interbarrier resonances.
PHOTOLUMINESCENCE EMITTING PROPERTIES OF SINGLE ZnO NANOWIRE STUDIED BY SCANNING NEAR-FIELD OPTICAL MICROSCOPE
Authors: LIU DAN , ZHANG WEIHUA , ZHU XING , CAO LI , ZOU BINGSUO , ZHANG ZEBO
Published: April 2007

Scanning near-field optical microscope (SNOM) was employed to investigate the room temperature photoluminescence (PL) of single ZnO nanowires with different radii excited by 325 nm laser. Two-dimensional distribution of their PL intensity is provided for the analysis of intensity decay from emission source. It is found that the PL intensity at both ends of each ZnO nanowire (end emission) was much stronger than that at the sides of the wire (side emission). Further investigation indicates that the quality of end emission depends on the diameters of the wires. Some of the ZnO nanowires with special diameters emit stronger light, and the shape of the light is close to Gauss beam. In addition, the Gauss shape light can diffuse longer distance than what the side emission does, typically in the range of a few micrometers. It is a sign of the fact that special guided modes of the PL light are formed in the nanowires. The calculation results predicate that the special guiding mode strongly relies on the diameters of the ZnO nanowires. The good directional property and high intensity of the end emission have many potential applications, including optical switch and microanalysis. It has been shown that SNOM can provide direct evidence of light emission properties from single nanowires, and hence provide the clue of increasing light efficiency and the improvement of light-propagating mode.
q-DEFORMED SPIN NETWORKS, KNOT POLYNOMIALS AND ANYONIC TOPOLOGICAL QUANTUM COMPUTATION
Authors: KAUFFMAN LOUIS H. , LOMONACO SAMUEL J.
Published: April 2007

We review the q-deformed spin network approach to Topological Quantum Field Theory and apply these methods to produce unitary representations of the braid groups that are dense in the unitary groups. Our methods are rooted in the bracket state sum model for the Jones polynomial. We give our results for a large class of representations based on values for the bracket polynomial that are roots of unity. We make a separate and self-contained study of the quantum universal Fibonacci model in this framework. We apply our results to give quantum algorithms for the computation of the colored Jones polynomials for knots and links, and the Witten–Reshetikhin–Turaev invariant of three manifolds.
KHOVANOV HOMOLOGY FOR VIRTUAL KNOTS WITH ARBITRARY COEFFICIENTS
Authors: MANTUROV VASSILY OLEGOVICH
Published: April 2007

In the present paper, we construct Khovanov homology theory with arbitrary coefficients for arbitrary virtual knots. We give a definition of the complex, which is homotopy equivalent to the initial Khovanov complex in the classical case; our definition works in the virtual case as well. The method used in this work allows us to construct a Khovanov homology theory for "twisted virtual knots" in the sense of Bourgoin and Viro [4, 27] (in particular, for knots in RP3). We also generalize some results of the Khovanov homology for virtual knots with arbitrary atoms (Wehrli and Kofman–Champanerkar spanning tree, minimality problems, Frobenius extensions) and orientable ones (Rasmussen's invariant).
REGULARIZATION STRATEGIES FOR HYPERPLANE CLASSIFIERS: APPLICATION TO CANCER CLASSIFICATION WITH GENE EXPRESSION DATA
Authors: ANDRIES ERIK , HAGSTROM THOMAS , ATLAS SUSAN R. , WILLMAN CHERYL
Published: April 2007

Linear discrimination, from the point of view of numerical linear algebra, can be treated as solving an ill-posed system of linear equations. In order to generate a solution that is robust in the presence of noise, these problems require regularization. Here, we examine the ill-posedness involved in the linear discrimination of cancer gene expression data with respect to outcome and tumor subclasses. We show that a filter factor representation, based upon Singular Value Decomposition, yields insight into the numerical ill-posedness of the hyperplane-based separation when applied to gene expression data. We also show that this representation yields useful diagnostic tools for guiding the selection of classifier parameters, thus leading to improved performance.
PREDICTION OF TRANSCRIPTION FACTOR BINDING SITES USING ChIP-chip AND PHYLOGENETIC FOOTPRINTING DATA
Authors: FRIBERG MARKUS T.
Published: April 2007

We present an algorithm for predicting transcription factor binding sites based on ChIP-chip and phylogenetic footprinting data. Our algorithm is robust against low promoter sequence similarity and motif rearrangements, because it does not depend on multiple sequence alignments. This, in turn, allows us to incorporate information from more distant species. Representative random data sets are used to estimate the score significance. Our algorithm is fully automatic, and does not require human intervention. On a recent S. cerevisiae data set, it achieves higher accuracy than the previously best algorithms. Adaptive ChIP-chip threshold and the modular positional bias score are two general features of our algorithm that increase motif prediction accuracy and could be implemented in other algorithms as well. In addition, since our algorithm works partly orthogonally to other algorithms, combining several algorithms can increase prediction accuracy even further. Specifically, our method finds 6 motifs not found by the 2nd best algorithm.
MODELING CLASSIC ATTENUATION REGULATION OF GENE EXPRESSION IN BACTERIA
Authors: LYUBETSKY VASSILY A. , PIROGOV SERGEY A. , RUBANOV LEV I. , SELIVERSTOV ALEXANDER V.
Published: April 2007

A model is proposed primarily for the classical RNA attenuation regulation of gene expression through premature transcription termination. The model is based on the concept of the RNA secondary structure macrostate within the regulatory region between the ribosome and RNA-polymerase, on hypothetical equation describing deceleration of RNA-polymerase by a macrostate and on views of transcription and translation initiation and elongation, under different values of the four basic model parameters which were varied. A special effort was made to select adequate model parameters. We first discuss kinetics of RNA folding and define the concept of the macrostate as a specific parentheses structure used to construct a conventional set of hairpins. The originally developed software that realizes the proposed model offers functionality to fully model RNA secondary folding kinetics. Its performance is compared to that of a public server described in Ref. 1. We then describe the delay in RNA-polymerase shifting to the next base or its premature termination caused by an RNA secondary structure or, herefrom, a macrostate. In this description, essential concepts are the basic and excited states of the polymerase first introduced in Ref. 2: the polymerase shifting to the next base can occur only in the basic state, and its detachment from DNA strand — only in excited state. As to the authors' knowledge, such a model incorporating the above-mentioned attenuation characteristics is not published elsewhere. The model was implemented in an application with command line interface for running in batch mode in Windows and Linux environments, as well as a public web server.3The model was tested with a conventional Monte Carlo procedure. In these simulations, the estimate of correlation between the premature transcription termination probability p and concentration c of charged amino acyl-tRNA was obtained as function p(c) for many regulatory regions in many bacterial genomes, as well as for local mutations in these regions.
MICROENTERPRISE DEVELOPMENT PROGRAM SUCCESS: A PATH ANALYSIS OF FACTORS THAT LEAD TO AND MEDIATE CLIENT SUCCESS
Authors: SCHMIDT MICHELE CRANWELL , KOLODINSKY JANE M.
Published: April 2007

Through a path regression analysis of data from the Vermont Micro Business Development Program, this study examines the relationships between client characteristics, program activities, interim outcomes, and impacts, to understand factors that lead to and mediate client success in microenterprise development programs and as entrepreneurs. Statistics demonstrated excellent model fit to the data. The interim outcome of improved personal well-being was related to more sources of capital, course completion, being partnered and younger. Starting a business was related to having more financial resources and mediated by improved well-being. Clients who experienced an increase in income had previous business experience and an increase in assets. Increased income was mediated by improved well-being and business start. Reduction in public assistance was related to course completion, more sources of capital, not being in poverty, and increased assets. Increased assets were related to more education, not being in poverty, and more sources of capital. Being older, more sources of capital, a larger family, and improved well-being led to job creation. Overall, access to more financial resources enabled clients to meet personal and business goals and work toward self-sufficiency. The results suggest implications for public policy regarding business training and loan financing.
BARRIERS TO ENTREPRENEURSHIP AND SME GROWTH IN TRANSITION: THE CASE OF KOSOVA
Authors: KRASNIQI BESNIK A.
Published: April 2007

This study investigates the barriers to growth of small- and medium-sized enterprises (SMEs) in Kosova. It is based on a SME survey conducted by Riinvest Institute at the end of 2002 which identified critical business environment barriers perceived by entrepreneurs such as legal environment, administrative burden, external financing, tax burden and unfair competition. First, based on this SME survey, the econometric model is constructed in order to test empirically the validity of Gibrat's Law. Then, in order to identify and measure the impact of current reported business environment barriers on SME growth, the Gibrat's Law is augmented with other business environment variables. The econometric results suggest that firms' growth is negatively linked to firms' size and age, suggesting that Gibrat's Law does not hold for growing SMEs in Kosova. Also, the growth of the SMEs is reduced by the presence of the business environmental barriers such as tax burden, unfair competition and inadequate financing. Econometric results raise important issues and policy implications for the development of the SME sector in Kosova.
ENTREPRENEURSHIP AND THE INFORMAL ECONOMY: A STUDY OF UKRAINE'S HIDDEN ENTERPRISE CULTURE
Authors: WILLIAMS COLIN C. , ROUND JOHN
Published: April 2007

How many entrepreneurs start-up their business ventures conducting some or all of their trade in the informal economy? The aim of this paper is to answer this key question that has been seldom addressed using data from 600 face-to-face structured interviews conducted in Ukraine in late 2005 and early 2006. Analyzing the 331 entrepreneurs identified (i.e., individuals starting-up an enterprise in the past three years), just 10 percent operate on a wholly legitimate basis, while 39 percent have a license to trade and/or have registered their business but conduct a portion of their trade in the informal economy, and 51 percent operate unregistered enterprises and conduct all of their trade on an off-the-books basis. Given that some 90 percent of all business start-ups operate partially or wholly in the informal economy, and that 40 percent of all respondents depend on the informal economy as either their principal or secondary contributor to their livelihoods, the paper concludes by considering the wider implications of these findings both for further research and public policy.
Finite Element Analysis and Understanding the Biomechanics and Evolution of Living and Fossil Organisms
Authors: Rayfield Emily J.
Published: April 2007

Finite element analysis (FEA) is a technique that reconstructs stress, strain, and deformation in a digital structure. Although commonplace in engineering and orthopedic science for more than 30 years, only recently has it begun to be adopted in the zoological and paleontological sciences to address questions of organismal morphology, function, and evolution. Current research tends to focus on either deductive studies that assume a close relationship between form and function or inductive studies that aim to test this relationship, although explicit hypothesis-testing bridges these two standpoints. Validation studies have shown congruence between in vivo or in vitro strain and FE-inferred strain. Future validation work on a broad range of taxa will assist in phylogenetically bracketing our extinct animal FE-models to increase confidence in our input parameters, although currently, FEA has much potential in addressing questions of form-function relationships, providing appropriate questions are asked of the existing data.
The Early Origins of Terrestrial C4 Photosynthesis
Authors: Tipple Brett J. , Pagani Mark
Published: April 2007

The C4 photosynthetic pathway is a series of structural and biochemical modifications around the more primitive C3 pathway that improve the photosynthetic efficiency under specific climatic conditions. Hence, the origin and subsequent geographical expansion of the C4 plants likely reflects a record of climate change. Multiple paleoatmospheric pCO2 proxies indicate a critical CO2 threshold was breached ∼30 Ma, that potentially selected for CO2-concentrating mechanisms to overcome photorespiratory stresses imposed on the basic C3 pathway. Details of the C4 pathway's earliest origins remain enigmatic given the paucity of the geologic record. Nonetheless, δ13C proxy records from paleosol carbonates, ungulate teeth, and plant-derived compounds indicate C4 plants likely represented an important component of plant biomass by the Early Miocene. Low CO2 levels appear to be a precondition for the development of the C4 photosynthetic pathway; however, comparisons of δ13C proxy records indicate that the timing of C4 geographical expansion was not globally synchronous, and thus point toward more regional controls on the development of C4-dominated ecosystems. Terrestrial and marine records indicate that continental aridity and wind strength increased during the Late Miocene. These conditions would have likely increased fire occurrence and fire intensity leading to the clearing of large tree stands and the expansion of C4 grasses in warm-season precipitation regimes.
Stable Isotope-Based Paleoaltimetry
Authors: Rowley David B. , Garzione Carmala N.
Published: April 2007

The quantitative estimation of paleoaltitude has become an increasing focus of Earth scientists because surface elevation provides constraints on the geodynamic mechanisms operating in mountain belts, as well as the influence of mountain belt growth on regional and global climate. The general observation of decreasing δ18O and δ2H values in rainfall as elevation increases has been used in both empirical and theoretical approaches to estimate paleoelevation. These studies rely on the preservation of ancient surface water compositions in authigenic minerals to reconstruct the elevation at the time the minerals were forming. In this review we provide a theory behind the application of stable isotope-based approaches to paleoaltimetry. We apply this theory to test cases using modern precipitation and surface water isotopic compositions to demonstrate that it generally accords well with observations. Examples of the application of paleoaltimetry techniques to Himalaya-Tibet and the Andes are discussed with implications for processes that cause surface uplift.
Tectonics and Climate of the Southern Central Andes
Authors: Strecker M.R. , Alonso R.N. , Bookhagen B. , Carrapa B. , Hilley G.E. , Sobel E.R. , Trauth M.H.
Published: April 2007

The history of the southern central Andes, including the world's second largest plateau and adjacent intermontane basins and ranges of the Eastern Cordillera and the northern Sierras Pampeanas of Argentina and Bolivia, impressively documents the effects of tectonics and topography on atmospheric circulation patterns, the development of orographic barriers, and their influence on erosion and landscape evolution at various timescales. Protracted aridity in the orogen interior has facilitated the creation and maintenance of the Puna-Altiplano plateau. Contraction and range uplift, filling of basins, and possibly wholesale uplift of the plateau increased gravitational stresses in the orogen interior, which caused the eastward migration of deformation into the foreland and successive aridification. The uplift of the Andean orogen has also had a far-reaching influence on atmospheric and moisture-transport patterns in South America. This is documented by the onset of humid climate conditions on the eastern side of the Andes in late Miocene time, which was coupled with the establishment of dramatic precipitation gradients perpendicular to the orogen, and changes in tectonic processes in the Andean orogenic wedge.
Hemispheres Apart: The Crustal Dichotomy on Mars
Authors: Watters Thomas R. , McGovern Patrick J. , Irwin III Rossman P.
Published: April 2007

The hemispheric dichotomy is a fundamental feature of Mars, expressed by a physiographic and geologic divide between the heavily cratered southern highlands and the relatively smooth plains of the northern lowlands. The origin of the dichotomy, which may have set the course for most of the subsequent geologic evolution of Mars, remains unclear. Internally driven models for the dichotomy form the lowlands by mantle convection, plate tectonics, or early mantle overturn. Externally driven models invoke one giant impact or multiple impacts. Areal densities of buried basins, expressed by quasi-circular depressions and subsurface echoes in radar sounding data, suggest that the dichotomy formed early in the geologic evolution of Mars. Tectonic features along the dichotomy boundary suggest late-stage modification by flexure or relaxation of the highlands after volcanic resurfacing of the northern lowlands. Subsequent deposition and erosion by fluvial, aeolian, and glacial processes shaped the present-day dichotomy boundary.
Wally Was Right: Predictive Ability of the North Atlantic “Conveyor Belt” Hypothesis for Abrupt Climate Change
Authors: Alley Richard B.
Published: April 2007

Linked, abrupt changes of North Atlantic deep water formation, North Atlantic sea ice extent, and widespread climate occurred repeatedly during the last ice age cycle and beyond in response to changing freshwater fluxes and perhaps other causes. This paradigm, developed and championed especially by W.S. Broecker, has repeatedly proven to be successfully predictive as well as explanatory with high confidence. Much work remains to fully understand what happened and to assess possible implications for the future, but the foundations for this work are remarkably solid.
Advanced Noninvasive Geophysical Monitoring Techniques
Authors: Snieder Roel , Hubbard Susan , Haney Matthew , Bawden Gerald , Hatchell Paul , Revil André , Geophysical Monitoring Working Group DOE
Published: April 2007

Geophysical methods can be used to create images of the Earth's interior that constitute snapshots at the moment of data acquisition. In many applications, it is important to measure the temporal change in the subsurface, because the change is associated with deformation, fluid flow, temperature changes, or changes in material properties. We present an overview of how noninvasive geophysical methods can be used for this purpose. We focus on monitoring mechanical properties, fluid transport, and biogeochemical processes, and present case studies that illustrate the use of geophysical methods for detecting time-lapse changes in associated properties.
Using the Paleorecord to Evaluate Climate and Fire Interactions in Australia
Authors: Lynch Amanda H. , Beringer Jason , Kershaw Peter , Marshall Andrew , Mooney Scott , Tapper Nigel , Turney Chris , Van Der Kaars Sander
Published: April 2007

Burning has been a near-continuous feature of the Australian environment but has become progressively more important since the mid-Tertiary, associated with the development of the characteristic sclerophyll vegetation. In the Quaternary, the extent of burning has varied temporally and regionally with glacial-interglacial cyclicity. Burning during glacial periods was reduced in drier areas, presumably because of a critical reduction in fuel availability, but increased in relatively wetter areas where fuel levels were high. On both glacial and Holocene timescales, peaks in charcoal often accompany transitions between fire-insensitive vegetation types, suggesting that burning is facilitated during periods of climate change and environmental instability. This suggestion has been supported by the demonstration of close relationships between fire and El Niño activity. Burning has also increased progressively over the past few hundred thousand years with major accelerations around the time of first human settlement of the continent and with the arrival of Europeans. To provide a firmer base for application of paleofire records to environmental management, there is an urgent need for a spatially more-substantial coverage of high-resolution fire records with good chronological control.
Statistical Models for Haplotype Sharing in Case-Parent Trio Data
Authors: Allen Andrew S. , Satten Glen A.
Published: April 2007

Background: Haplotype sharing statistics have been introduced in an ad-hoc way, often relying heavily on permutation testing. As a result, applying these approaches to whole genome association studies or to evaluate their properties in extensive simulation experiments is problematic. Further, permutation testing may be inappropriate in the presence of phase ambiguity and population stratification. Aims: To present a simple framework for a class of haplotype sharing statistics useful for association mapping in case-parent trio data. This framework allows derivation of novel haplotype sharing tests as well as simple variance estimators and asymptotic distributions for haplotype sharing tests. Results and Conclusions: We validated that our approach is appropriately sized using simulated data, and illustrate the methodology by analyzing a Crohn’s disease dataset. We find that haplotype-based analyses are much more powerful than single-locus analyses for these data.
An R Package for Analysis of Whole-Genome Association Studies
Authors: Clayton David , Leung Hin-Tak
Published: April 2007

Objective: To provide data classes and methods to facilitate the analysis of whole genome association studies in the R language for statistical computing. Methods: We have implemented data classes in which each genotype call is stored as a single byte. At this density, data for single chromosomes derived from large studies and new high-throughput gene chip platforms can be handled in memory. We use the object-oriented programming model introduced with version 4 of the S-plus package, usually termed ‘S4 methods’. Results: At the current state of development the package only supports population-based studies, although we would hope to provide support for family-based studies soon. Both quantitative and qualitative phenotypes may be analysed. Flexible association testing functions are provided which can carry out single SNP tests which control for potential confounding by quantitative and qualitative covariates. Tests involving several SNPs taken together as ‘tags’ are also supported. Efficient calculation of pair-wise linkage disequilibrium measures is implemented and data input functions include a function which can download data directly from the international HapMap project website.
Relative Efficiency of Haplotype Frequency Estimation in Sibships and Nuclear Families Compared to Unrelated Individuals
Authors: Putter H. , Meulenbelt I. , van Houwelingen J.C.
Published: April 2007

The problem of estimating haplotype frequencies from unphased single nucleotide polymorphism (SNP) genotype data in sibships with and without parents is considered. We focus on the Fisher information of the haplotype frequencies of the parents in order to correctly deal with the dependence of haplotypes within sibships. We compare these Fisher information matrices with those obtained for unrelated individuals and study the relative efficiency of sibships with and without parents compared to unrelated individuals in estimating haplotype frequencies. Crudely summarizing, the second sib contributes half the information of the first, except for rare haplotypes, when the second sib counts almost as one. We argue that the relative efficiencies can also be used to correct for dependence in the calculation of standard errors after initially ignoring the dependence in the estimation phase.
Data Acquisition for Meta-Analysis of Genome-Wide Linkage Studies Using the Genome Search Meta-Analysis Method
Authors: Forabosco Paola , Ng Mandy Y.M. , Bouzigon Emmanuelle , Fisher Sheila A. , Levinson Douglas F. , Lewis Cathryn M.
Published: April 2007

Background: The Genome Search Meta-Analysis (GSMA) method enables researchers to pool results across genome-wide linkage studies, to increase the power to detect linkage. Results from individual studies must be extracted, with the maximum evidence for linkage placed into bins, usually of 30 cM width, and ranked within the study. Ranks are then summed across studies, with high summed ranks potentially showing evidence for linkage in the meta-analysis. Objectives: In this paper we study the properties of the GSMA method considering two different issues: (1) data binning from genome-wide results when indexed markers or graphs are available, based on either predefined boundary markers, or equal-length bins; (2) the use of selected instead of genome-wide results, using simulation to estimate power and type I error rates of GSMA. This is relevant when published papers show only summary results (e.g. with NPL score >1). Results: Using digitizing software to extract linkage statistics from graphs and assigning equal bin length is accurate, with the resulting ranking of bins similar to those defined through boundary markers. Simulation results show that power can fall substantially when genome-wide results are not available, particularly when only results from a single marker are available in a linked region. However there is no increase in false positive findings. Conclusions: The GSMA method is robust across different bin definitions and methods of data presentation and extraction. Using studies based on only the top ranked bins does not produce false positive results, but lacks power to detect genes conferring a modest increase in risk. Therefore, we advise that effort should be made to obtain genome-wide results from investigators or from published papers to avoid limiting the utility of the GSMA.
A Simple and Robust TDT-Type Test against Genotyping Error with Error Rates Varying across Families
Authors: Cheng K.F. , Chen J.H.
Published: April 2007

The transmission/disequilibrium test (TDT), a family based test of linkage and association, is a popular test for studies of complex inheritance, as it is nonparametric and robust against spurious conclusions induced by hidden genetic structure, such as stratification or admixture. However, the TDT may be biased by genotyping errors. Undetected genotyping errors may be contributing to an inflated type I error rate among reported TDT-derived associations. To adjust for bias, a popular approach is to assume a genotype error model for describing the pattern of errors and propose association tests using likelihood method. However, all model-based approaches tend to perform unsatisfactorily if the related genotyping error rates are not identical across all families. In this paper, we propose a TDT-type association test which is not only simple, robust against population stratification (and hence the assumption of Hardy-Weinberg equilibrium is not required), but also robust against genotyping error with error rates varying across families. Simulation studies confirm that the new test has very reasonable performance.
Campora: A Young Genetic Isolate in South Italy
Authors: Colonna Vincenza , Nutile Teresa , Astore Maria , Guardiola Ombretta , Antoniol Giuliano , Ciullo Marina , Persico M.Graziella
Published: April 2007

Genetic isolates have been successfully used in the study of complex traits, mainly because due to their features, they allow a reduction in the complexity of the genetic models underlying the trait. The aim of the present study is to describe the population of Campora, a village in the South of Italy, highlighting its properties of a genetic isolate. Both historical evidence and multi-locus genetic data (genomic and mitochondrial DNA polymorphisms) have been taken into account in the analyses. The extension of linkage disequilibrium (LD) regions has been evaluated on autosomes and on a region of the X chromosome. We defined a study sample population on the basis of the genealogy and exogamy data. We found in this population a few different mitochondrial and Y chromosome haplotypes and we ascertained that, similarly to other isolated populations, in Campora LD extends over wider region compared to large and genetically heterogeneous populations. These findings indicate a conspicuous genetic homogeneity in the genome. Finally, we found evidence for a recent population bottleneck that we propose to interpret as a demographic crisis determined by the plague of the 17th century. Overall our findings demonstrate that Campora displays the genetic characteristics of a young isolate.
Prospective Volumetric Analysis of Gallbladders in Critically Ill Newborns: The Impact of Nutrition
Authors: Schmidt Beate , Roth Bernhard , Stützer Hartmut , Benz-Bohm Gabriele
Published: April 2007

Background:Neonatal reference values of gallbladder size have been assessed in healthy newborns with enteral feeding regimen. Their applicability to critically ill patients under total parenteral nutrition (TPN) remains to be questioned. Objective: Our aim was to evaluate the impact of short-term TPN versus enteral nutrition (EN), gender and birth weight on neonatal gallbladder volume. Method: A prospective pilot study was initiated with a single sonographic investigator blinded towards feeding regimen. In total, 61 neonates (33 males, 28 females) were consecutively enrolled on the intensive care unit; 31 newborns were examined both under TPN and bolus EN (breast milk/formula). Patients with malformations of the biliary tract were excluded. Prior to ultrasound examinations, a minimum fasting period of 2 h was maintained. Sonographic measurements of gallbladder length, depth and width were performed to calculate gallbladder volume using the ellipsoid formula. Results: Neonatal gallbladder volume differed significantly between TPN and EN (p < 0.001). Using TPN, range of gallbladder length, width and volume exceeded reference values. Birth weight was weakly correlated with gallbladder volume (correlation index 0.3776, p = 0.01). We found no gender-related differences. Conclusions: Neonatal gallbladder volume under TPN was significantly larger compared to EN. Using TPN, gallbladder dimensions exceeded reference values without causing clinical complications. The benign course of gallbladder enlargement required no specific medication or surgical treatment.
GBR12909 Possesses Anticonvulsant Activity in Zebrafish and Rodent Models of Generalized Epilepsy but Cardiac Ion Channel Effects Limit Its Clinical Utility
Authors: Goldsmith Paul , Golder Zoe , Hunt Julia , Berghmans Stephane , Jones Derek , Stables James P. , Murphree Lauren , Howden Diane , Newton Paul E. , Richards Frances M.
Published: April 2007

Background/Aims: GBR12909 has been reported to possess anticonvulsant activity with focal brain perfusion to the hippocampus of pilocarpine, although an earlier publication suggested any anticonvulsant effects were only mild. Here we further explored the anticonvulsant potential of GBR12909 with a suite of anticonvulsant assays in both zebrafish and mammals and then explored whether it possessed any QT effects which might limit clinical utility. Methods: We assessed the anticonvulsant effects of GBR12909 in zebrafish pentylenetetrazole (PTZ), mammalian maximal electroshock and PTZ models of generalized epilepsy and a rodent hippocampal kindling model. Cardiac effects were assessed in zebrafish and man. Results: GBR12909 possesses anticonvulsant activity in zebrafish and rodent models of generalized epilepsy. However, phase 1 human data indicated potential QT effects. Subsequent testing in a zebrafish QT assay confirmed marked arrhythmogenic potential. Conclusion: Further clinical development of GBR12909 in epilepsy was considered inappropriate because of insufficient window between the therapeutic effects and the cardiac arrhythmia problems identified in zebrafish assays. Any further development based on this mechanism of action should avoid the GBR12909 chemical scaffold, or involve structure-activity dissociation of its neurological and cardiac effects.
Nucleated Red Blood Cells in Term Fetuses: Reference Values Using an Automated Analyzer
Authors: Rolfo Alessandro , Maconi Mariacaterina , Cardaropoli Simona , Biolcati Marilisa , Danise Paolo , Todros Tullia
Published: April 2007

Background: Nucleated red blood cells (NRBCs) are present in small numbers in the cord blood of healthy fetuses at birth. Acute and chronic stimuli, such as fetal hypoxia, cause increased circulating levels of NRBCs. Manual counting is presently the only way to quantify NRBCs, but it is time-consuming and inaccurate. Recently, automated approaches have been developed in order to quantify NRBCs. Objectives: Our aim was to compare manual vs. automated NRBC counting and derive reference values in umbilical cord blood samples from healthy term fetuses. Methods: We analyzed blood samples from 131 healthy term fetuses by the automated approach and calculated reference values of NRBC counts as percentiles. To compare automated NRBC count with manual count we obtained umbilical cord blood samples from 50 further fetuses. Results: Significant positive correlation was obtained between the two methods (r2 = 0.988, Bland-Altman plot mean difference NRBCs/100 WBC: –0.590). The median for NRBCs/100 WBC was 3.05 (range 0–11.6) and the median for absolute NRBC counts ×109/l was 0.39 (range 0–1.8). Conclusions: We demonstrate that values obtained with the automated NRBC counting method are comparable to those obtained with the microscopic manual evaluation and give reference values for umbilical cord NRBCs at term that can be used in clinical practice.
Nutritional Proteomics: Methods and Concepts for Research in Nutritional Science
Authors: Schweigert Florian J.
Published: April 2007

Nutritional proteomics or nutriproteomics is the application of proteomics methodology to nutrition-related research but also represents the interaction of bioactive food ingredients with proteins, whereby the interaction with proteins occurs in two basically specific ways. Firstly, the effect of nutrients on protein expression, which can be monitored by protein mapping, and secondly, the interaction of nutrients with proteins by post-translational modifications or small-molecule protein interactions. These interactions result in changes to the three-dimensional structure of such effected proteins. As a consequence, their original functions are modulated, resulting for example in reduced activity in the case of enzymes or changes in ability of recognition between molecules such as protein-protein interactions and ligand-receptor interactions. The characterization of such modifications together with functional data from established biochemical and physiological methods will result in a better understanding of the interplay between bioactive dietary components and diet-related diseases such as cancer, diabetes or neurodegenerative diseases. The occurrence of such modifications can possibly be additionally used as biomarkers in the diagnosis and therapy of these diseases as well as biomarkers for the efficacy or safety of selected nutrients.
Validity of Stroke Diagnoses in a National Register of Patients
Authors: Krarup Lars-Henrik , Boysen Gudrun , Janjua Huma , Prescott Eva , Truelsen Thomas
Published: April 2007

Background: Many registers containing routine medical information have been developed for research and surveillance purposes. In epidemiological research assessment of endpoints is often conducted via registers. In the present study we validated stroke and transient ischemic attack (TIA) diagnoses in the Danish National Register of Patients (DNRP). Methods: Subjects from a Danish cohort study, the Copenhagen City Heart Study (n = 19,698), were crosslinked with the DNRP. The following International Classification of Disease 10th revision codes were used to identify possible strokes and TIAs: I60–I69 and G45. Two independent raters reviewed all cases. Positive predictive values of stroke, TIA and stroke subtypes were estimated by dividing the confirmed cases by the total number of cases located in the DNRP. Interrater reliability was tested using ĸ statistics. Results: Of 236 possible cerebrovascular events, 1 in 6 stroke diagnoses did not meet study criteria. The majority of events in the DNRP were registered as unspecified stroke (I64), n = 105 (44%), of which two thirds were diagnosed as ischemic stroke events by the raters. Intracerebral hemorrhage and ischemic stroke had a positive predictive value from 74 to 97%, respectively. Conclusion: Our results show that the DNRP tends to overestimate the number of cerebrovascular events, while ischemic stroke is underestimated.
Extraction of Pins from the Airway with Flexible Bronchoscopy
Authors: Gencer Mehmet , Ceylan Erkan , Koksal Nurhan
Published: April 2007

Background: Tracheobronchial foreign body aspiration is a worldwide health problem which often results in life threatening complications. Standard flexible bronchoscopy (FB) is used increasingly in the treatment of tracheobronchial foreign body aspiration in adults and older children, especially in the removal of aspirated foreign bodies which have entered into the peripheral bronchi. Objectives: In the present study, we discuss how to minimize complications and increase the success rate of FB in the aspiration of pins, and recommend techniques to facilitate the application. Methods: The study was performed at a community hospital in Van, the Harran University Hospital in Sanliurfa and the Sutcuimam University Hospital in Kahramanmaras, Turkey. Between 2000 and 2005, 23 female patients between the ages of 12 and 23, who were admitted to the clinics and diagnosed as having tracheobronchial headscarf pin aspirations were included in our study to evaluate the efficiency of FB. Diagnosis of the patients was established by history, FB and radiological methods. All patients received transoral FB under local anesthesia. Results: FB was successfully applied in all cases. During removal, the pins in 2 patients dropped at the proximal trachea and subglottic zone, and were ingested into the gastrointestinal track. In both cases, the pins were spontaneously excreted from the body in the stool within one day. No other complication was detected in the other patients during or following bronchoscopy. Conclusions: Our study suggests that FB is a safe, easy and successful method used in the removal of foreign bodies, such as pins, from the tracheobronchial trees. By employing FB, indications of thoracotomy and other invasive methods can be reduced especially in the cases of pins localized in distal airways and in the evaluation of suspected foreign bodies.
Logo Logic: The Ups and Downs of Branded Political Communication
Authors: Bennett W. Lance , Lagos Taso
Published: April 2007

Activists often have difficulties getting messages to larger publics. This is particularly challenging in the U.S. press/politics system, where the mainstream media tend to open the news gates only after government institutions engage with issues. Yet there are signs in recent years that activists are finding creative ways of publicizing their causes by attaching political messages to familiar corporate brands. For example, complex messages about labor conditions in foreign factories making shoes and apparel may travel more easily when attached to a major brand, for example, Nike sweatshop. The first part of this analysis examines how branded political communication works and how it may be effective. The second part looks at possible downsides of getting consumer audiences to actually grasp the larger import of the politics behind the brands and getting targeted companies and industrial sectors (fashion, food, forest products, etc.) to change their offending behaviors.
Digital Renaissance: Young Consumer and Citizen?
Authors: de Vreese Claes H.
Published: April 2007

This article explores the relationship between Internet use among young people, their political consumption, and their political participation. The study widens the notion of online civic and political engagement and includes measures of active and passive forms of participation. To test a number of hypotheses developed on the basis of extant research, a survey was conducted in 2006 among 2,404 young Dutch respondents (aged sixteen to twenty-four). The results demonstrate the importance of the Internet for political activities for young people. They also show that most online activities (ranging from news use, peer communication, and consumption to online service use) are positively related to political participation. Contrary to common wisdom, this article shows that the young online consumer is also politically active.
Representing Citizens and Consumers in Media and Communications Regulation
Authors: Livingstone Sonia , Lunt Peter
Published: April 2007

What do citizens need from the media, and how should this be regulated? Western democracies are witnessing a changing regulatory regime, from “command-andcontrol” government to discursive, multistakeholder governance. In the United Kingdom, the Office of Communications (Ofcom) is required to further the interests of citizens and consumers, which it does in part by aligning them as the citizen-consumer. What is meant by this term, and whether it captures the needs of citizens or subordinates them to those of consumers, has been contested by civil society groups as well as occasioning some soul-searching within the regulator. By triangulating a discursive analysis of the Communications Act 2003, key actor interviews with the regulator and civil society bodies, and focus groups among the public, the authors seek to understand how these terms (“citizen,” “consumer,” and “citizen-consumer”) are used to promote stakeholder interests in the media and communications sector, not always to the benefit of citizens.