bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of statistical approaches to rare variant analysis for quantitative traits
Authors: Chen Han , Hendricks Audrey E , Cheng Yansong , Cupples Adrienne L , Dupuis Josée , Liu Ching-Ti 
Published: December 2011

Abstract
With recent advances in technology, deep sequencing data will be widely used to further the understanding of genetic influence on traits of interest. Therefore not only common variants but also rare variants need to be better used to exploit the new information provided by deep sequencing data. Recently, statistical approaches for analyzing rare variants in genetic association studies have been proposed, but many of them were designed only for dichotomous outcomes. We compare the type I error and power of several statistical approaches applicable to quantitative traits for collapsing and analyzing rare variant data within a defined gene region. In addition to comparing methods that consider only rare variants, such as indicator, count, and data-adaptive collapsing methods, we also compare methods that incorporate the analysis of common variants along with rare variants, such as CMC and LASSO regression. We find that the three methods used to collapse rare variants perform similarly in this simulation setting where all risk variants were simulated to have effects in the same direction. Further, we find that incorporating common variants is beneficial and using a LASSO regression to choose which common variants to include is most useful when there is are few common risk variants compared to the total number of risk variants.
Use of principal components to aggregate rare variants in case-control and family-based association studies in the presence of multiple covariates
Authors: Kazma Rémi , Hoffmann Thomas J , Witte John S 
Published: December 2011

Abstract
Rare variants may help to explain some of the missing heritability of complex diseases. Technological advances in next-generation sequencing give us the opportunity to test this hypothesis. We propose two new methods (one for case-control studies and one for family-based studies) that combine aggregated rare variants and common variants located within a region through principal components analysis and allow for covariate adjustment. We analyzed 200 replicates consisting of 209 case subjects and 488 control subjects and compared the results to weight-based and step-up aggregation methods. The principal components and collapsing method showed an association between the gene FLT1 and the quantitative trait Q1 (P<10−30) in a fraction of the computation time of the other methods. The proposed family-based test has inconclusive results. The two methods provide a fast way to analyze simultaneously rare and common variants at the gene level while adjusting for covariates. However, further evaluation of the statistical efficiency of this approach is warranted.
Use of Bayesian networks to dissect the complexity of genetic disease: application to the Genetic Analysis Workshop 17 simulated data
Authors: Kang Jia , Zheng Wei , Li Lun , Lee Joon Sang , Yan Xiting , Zhao Hongyu 
Published: December 2011

Abstract
Complex diseases are often the downstream event of a number of risk factors, including both environmental and genetic variables. To better understand the mechanism of disease onset, it is of great interest to systematically investigate the crosstalk among various risk factors. Bayesian networks provide an intuitive graphical interface that captures not only the association but also the conditional independence and dependence structures among the variables, resulting in sparser relationships between risk factors and the disease phenotype than traditional correlation-based methods. In this paper, we apply a Bayesian network to dissect the complex regulatory relationships among disease traits and various risk factors for the Genetic Analysis Workshop 17 simulated data. We use the Bayesian network as a tool for the risk prediction of disease outcome.
Large-scale risk prediction applied to Genetic Analysis Workshop 17 mini-exome sequence data
Authors: Li Gengxin , Ferguson John , Zheng Wei , Lee Joon Sang , Zhang Xianghua , Li Lun , Kang Jia , Yan Xiting , Zhao Hongyu 
Published: December 2011

Abstract
We consider the application of Efron’s empirical Bayes classification method to risk prediction in a genome-wide association study using the Genetic Analysis Workshop 17 (GAW17) data. A major advantage of using this method is that the effect size distribution for the set of possible features is empirically estimated and that all subsequent parameter estimation and risk prediction is guided by this distribution. Here, we generalize Efron’s method to allow for some of the peculiarities of the GAW17 data. In particular, we introduce two ways to extend Efron’s model: a weighted empirical Bayes model and a joint covariance model that allows the model to properly incorporate the annotation information of single-nucleotide polymorphisms (SNPs). In the course of our analysis, we examine several aspects of the possible simulation model, including the identity of the most important genes, the differing effects of synonymous and nonsynonymous SNPs, and the relative roles of covariates and genes in conferring disease risk. Finally, we compare the three methods to each other and to other classifiers (random forest and neural network).
Principal components ancestry adjustment for Genetic Analysis Workshop 17 data
Authors: Jin Jing , Cerise Jane E , Kang Sun Jung , Yoon Eun Jung , Yoon Seungtai , Mendell Nancy R , Finch Stephen J 
Published: December 2011

Abstract
Statistical tests on rare variant data may well have type I error rates that differ from their nominal levels. Here, we use the Genetic Analysis Workshop 17 data to estimate type I error rates and powers of three models for identifying rare variants associated with a phenotype: (1) by using the number of minor alleles, age, and smoking status as predictor variables; (2) by using the number of minor alleles, age, smoking status, and the identity of the population of the subject as predictor variables; and (3) by using the number of minor alleles, age, smoking status, and ancestry adjustment using 10 principal component scores. We studied both quantitative phenotype and a dichotomized phenotype. The model with principal component adjustment has type I error rates that are closer to the nominal level of significance of 0.05 for single-nucleotide polymorphisms (SNPs) in noncausal genes for the selected phenotype than the model directly adjusting for population. The principal component adjustment model type I error rates are also closer to the nominal level of 0.05 for noncausal SNPs located in causal genes for the phenotype. The power for causal SNPs with the principal component adjustment model is comparable to the power of the other methods. The power using the underlying quantitative phenotype is greater than the power using the dichotomized phenotype.
Evaluation of Sealed Joint Performance for the Selection of Sealants Suitable for Use in Autoclaved Lightweight Concrete Panels
Authors: Miyauchi Hiroyuki , Lacasse Michael A. , Murata Shigeki , Enomoto Noriyoshi , Tanaka Kyoji 
Published: December 2011

Abstract
The strength of autoclaved lightweight concrete (ALC) is evidently lower than that of normal concrete. Therefore, when movement occurs at a sealed joint between ALC panels, the sealant is required to deform and remain intact without damaging the ALC substrate. However, there is currently not sufficient information to permit evaluation of the expected performance of sealants applied to ALC substrates. In this study, static and dynamic tests were carried out in order to obtain an index that could be used to select the modulus of a sealant that can be expected to provide long-term performance when applied to an ALC substrate. To develop this index, an initial study was carried out in order to clarify actual joint movement between ALC panels of buildings; the expansion and contraction at the joint were measured, and shear joint movement was calculated based on the expected story-to-story drift of an external wall due to earthquake loads. Thereafter, in a subsequent stage of the study, five types of two-component polyurethane sealant products, of different elastic modulus, were subjected to tensile and shear tests from which the relationship between stress and the type of joint fracture was determined. The results from these tests revealed that when the stress is greater than 0.6 to 0.7 N/mm2, the ALC substrate is more easily fractured than the sealant. In a final stage of the study, the cyclic fatigue resistance of the same two-component sealants was evaluated using tensile and shear fatigue tests. Results from the fatigue tests indicated that the high modulus sealants lost adhesion from the ALC substrate at an early stage in the test. As well, the fatigue resistance of test specimens with joints having three-sided adhesion was lower than that of specimens having normally configured joints with adhesion on two sides of the sealant. Therefore, on the basis of results derived from all the studies, it was determined that a suitable sealant for use on ALC substrates is a sealant having a low modulus that is applied in the normal fashion as a two-sided joint.
Modellierung und Ausführung von multimodalen Anwendungen auf Basis von Zustandsdiagrammen
Authors: Feuerstack Sebastian , dos Santos Anjo Mauro , Pizzolato Ednaldo Brigante 
Published: December 2011

Zusammenfassung
Neuartige Interaktionsformen, wie die Verwendung von Gesten zur Steuerung von Benutzungsschnittstellen ermöglichen eine Anwendungsbedienung auch in Situationen wo hardwarebasierte Steuerungen nicht verwendbar sind oder können Personen mit körperlichen Beeinträchtigungen unterstützen. Das große Spektrum an denkbaren Gesten bietet zahlreiche Interaktionsmöglichkeiten, erfordert aber auch umfangreiche Nutzertests um eine intuitive, fehlertolerante, sowie zielgruppengerechte Steuerung zu entwickeln. Dieser Beitrag beschreibt wie mittels der modellbasierten Entwicklung basierend auf Interaktoren, die mit Zustandsdiagrammen beschrieben und Mappings verbunden werden, multimodale Benutzungsschnittstellen entworfen und direkt ausgeführt werden können. Dabei steht die schnelle Entwicklung von verschieden prototypischen Interaktionsvarianten im Vordergrund.
The Impact of Health Information Exchange on Health Outcomes
Authors: Warholak T. , Hincapie A. 
Published: December 2011

Summary
Background and Objective: Healthcare professionals, industry and policy makers have identified Health Information Exchange (HIE) as a solution to improve patient safety and overall quality of care. The potential benefits of HIE on healthcare have fostered its implementation and adoption in the United States. However,there is a dearth of publications that demonstrate HIE effectiveness. The purpose of this review was to identify and describe evidence of HIE impact on healthcare outcomes.
Methods: A database search was conducted. The inclusion criteria included original investigations in English that focused on a HIE outcome evaluation. Two independent investigators reviewed the articles. A qualitative coding approach was used to analyze the data.
Results: Out of 207 abstracts retrieved, five articles met the inclusion criteria. Of these, 3 were randomized controlled trials, 1 involved retrospective review of data, and 1 was a prospective study. We found that HIE benefits on healthcare outcomes are still sparsely evaluated, and that among the measurements used to evaluate HIE healthcare utilization is the most widely used.
Conclusions: Outcomes evaluation is required to give healthcare providers and policy-makers evidence to incorporate in decision-making processes. This review showed a dearth of HIE outcomes data in the published peer reviewed literature so more research in this area is needed. Future HIE evaluations with different levels of interoperability should incorporate a framework that allows a detailed examination of HIE outcomes that are likely to positively affect care.
Auf dem Weg zur automatisierten Oligosaccharid‐ Synthese
Authors: Hsu Che‐Hsiung , Hung Shang‐Cheng , Wu Chung‐Yi , Wong Chi‐Huey 
Published: December 2011

AbstractKohlenhydrate spielen eine wichtige Rolle bei biologischen Vorgängen. Das Fortschrittstempo der Kohlenhydratforschung ist jedoch relativ langsam, was unter anderem mit der Komplexität der Kohlenhydratstrukturen und dem Fehlen allgemein anwendbarer Synthesemethoden und Verfahren zur Untersuchung dieser Klasse von Biomolekülen zusammenhängt. Jüngste Fortschritte in der Synthese haben ergeben, dass viele dieser Probleme umgangen werden können. In diesem Aufsatz beschreiben wir die Methoden, die entwickelt wurden, um mit den Herausforderungen kohlenhydratvermittelter biologischer Vorgänge umzugehen. Besonderes Augenmerk wird dabei auf die Entwicklung der automatisierten Synthese von Oligosacchariden gerichtet. Darüber hinaus werden auch Kohlenhydrat‐Mikroarrays und Impfstoffe auf Kohlenhydratbasis behandelt.
Preparation and characterization of high‐molecular‐weight poly(l‐lactic acid) by chain‐extending reaction with phosphites
Authors: Xie Ji‐Xing , Yang Rong‐Jie 
Published: December 2011

AbstractPoly(l‐lactic acid) (PLLA) of high molecular weight was prepared by a chain‐extending reaction in a microcompounder. Phosphites were used as chain extenders to increase the molecular weight of the PLLA prepolymer, which was prepared by the bulk polycondensation of l‐lactic acid. The effects of the amount of phosphite, the temperature, and the screw speed on the torque of the PLLA melt were studied. Under the optimal conditions, the molecular weight of PLLA increased from 62,100 to 126,000 g/mol. The chemical structure and crystallinity of PLLA were characterized by Fourier transform infrared spectroscopy, 1H‐NMR and 13C‐NMR, differential scanning calorimetry, and X‐ray diffraction. The mechanical properties of PLLA were measured. The results indicate that triphenyl phosphite (TPPi) was an effective chain extender for PLLA. The role of the TPPi in chain extending is suggested to be an esterification‐promotion agent. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Kinetics and mechanism of the charge‐transfer polymerization of methyl methacrylate initiated with n‐butyl amine and carbon tetrachloride catalyzed by palladium dichloride
Authors: Tiwari Rajesh , Spivak David A. 
Published: December 2011

AbstractWe studied the kinetics and mechanism of the charge‐transfer polymerization of methyl methacrylate (MMA) initiated with n‐butyl amine (BA) and carbon tetrachloride (CCl4) catalyzed by palladium dichloride (PdCl2 or PdII) in a dimethyl sulfoxide medium by using a dilatometric technique at 60°C. The rate of polymerization (Rp) was a function of [MMA], [BA], [CCl4], and [PdII]. The kinetic data indicated a mechanism involving the possible participation of the charge‐transfer complex formed between the {BA–PdII} complex and CCl4 or monomer in the polymerization of MMA. In the absence of either CCl4 or BA, no polymerization of MMA was observed under these experimental conditions. Rp was inhibited by hydroquinone; this suggested a free‐radical initiation. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Morphological, infrared, and ionic conductivity studies of poly(ethylene oxide)–49% poly(methyl methacrylate) grafted natural rubber–lithium perchlorate salt based solid polymer electrolytes
Authors: Ahmad A. , Rahman M. Y. A. , Su′ait M. S. 
Published: December 2011

AbstractThe potential of poly(ethylene oxide) (PEO) and 49% poly(methyl methacrylate) grafted natural rubber (MG49) as a polymer host in solid polymer electrolytes (SPE) was explored for electrochemical applications. PEO–MG49 SPEs with various weight percentages of lithium perchlorate salt (LiClO4) was prepared with the solution casting technique. Characterization by scanning electron microscopy, Fourier transform infrared spectroscopy, and impedance spectroscopy was done to investigate the effect of LiClO4 on the morphological properties, chemical interaction, and ionic conductivity behavior of PEO–MG49. Scanning electron microscopy analysis showed that the surface morphology of the sample underwent a change from rough to smooth with the addition of lithium salts. Infrared analysis showed that the interaction occurred in the polymer host between the oxygen atom from the ether group (COC) and the Li+ cation from doping salts. The ionic conductivity value increased with the addition of salts because of the increase in charge carrier up to the optimum value. The highest ionic conductivity obtained was 8.0 × 10−6 S/cm at 15 wt % LiClO4. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Biodegradable poly(butylene succinate‐co‐butylene adipate)/multiwalled carbon nanotube nanocomposites: Preparation, morphology, and crystallization behavior
Authors: Zhu Siyu , Zhao Yuanyuan , Qiu Zhaobin 
Published: December 2011

AbstractBiodegradable poly(butylene succinate‐co‐butylene adipate) (PBSA)/multiwalled carbon nanotubes (MWCNTs) nanocomposites were prepared via a simple melt‐compounding method at low MWCNTs contents. Scanning and transmission electron microscopy observations revealed a relatively nice dispersion of MWCNTs throughout the PBSA matrix. Both the nonisothermal and isothermal melt crystallizations of PBSA were enhanced significantly in the nanocomposites relative to neat PBSA because of the presence of MWCNTs; however, the crystal structure of PBSA remained unchanged. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
A Diverted Total Synthesis of Mycolactone Analogues: An Insight into Buruli Ulcer Toxins
Authors: Chany Anne‐Caroline , Casarotto Virginie , Schmitt Marjorie , Tarnus Céline , Guenin‐Macé Laure , Demangel Caroline , Mirguet Olivier , Eustache Jacques , Blanchard Nicolas 
Published: December 2011

AbstractMycolactones are complex macrolides responsible for a severe necrotizing skin disease called Buruli ulcer. Deciphering their functional interactions is of fundamental importance for the understanding, and ultimately, the control of this devastating mycobacterial infection. We report herein a diverted total synthesis approach of mycolactones analogues and provide the first insights into their structure–activity relationship based on cytopathic assays on L929 fibroblasts. The lowest concentration inducing a cytopathic effect was determined for selected analogues, allowing a clear picture to emerge by comparison with the natural toxins.
Covalent and Noncovalent Immobilization of Arylid‐BOX Ligands and Their Derivatives: Evaluation in the Catalytic Asymmetric Cyclopropanation of Styrenes
Authors: Carreiro Elisabete P. , Moura Nuno M. M. , Burke Anthony J. 
Published: December 2011

AbstractThe aim of this work was to immobilize an Arylid‐BOX ligand on solid supports either by covalent attachment (to Wang resin) or by noncovalent attachment (on MK10 and SiO2) and to evaluate the products in the catalytic asymmetric cyclopropanation (CACP) of styrene in the presence of CuI and CuII. The synthetic strategy used to obtain the target functionalized Arylid‐BOX furnished a new, partially hydrogenated, Arylid‐BOX derivative. Evaluation of this ligand in the catalytic asymmetric cyclopropanation of styrene in the presence of CuI gave a highest ee of 68 %, a result better than that obtained for the nonhydrogenated Arylid‐BOX ligand. The new ligand was grafted to Wang resin; a loading of 0.321 mmol of ligand per gram of polymer could be obtained. [Cu(CH3CN)4]PF6 or Cu(OTf)2 were used in the CACP of styrene with CH2Cl2 or toluene as solvents. A highest ee of 71 % was obtained and the catalyst could be recycled and reused up to four times. In the case of the heterogeneous CACP in the presence of [Cu(CH3CN)4]PF6 and toluene, the yields, ees, des, and selectivities were maintained over the four cycles. This heterogeneous catalyst was shown to be very similar to the homogeneous catalyst with regard to selectivity and activity. In the case of noncovalent immobilization, both CuI and CuII Arylid‐BOX complexes were immobilized on Montmorillonite K10 (MK10) and silica gel through noncovalent interactions. The obtained results depended on the natures both of the chiral ligand and of the support. In the case of MK10, enantioselectivities of 62 % ee (trans‐cyclopropane) and 65 % ee (cis‐cyclopropane) could be achieved, whereas in the case of the silica‐gel‐supported catalyst, enantioselectivities of 50 % ee (trans‐cyclopropane) and 43 % ee (cis‐cyclopropane) were obtained.
Dealing with high dimensionality for the identification of common and rare variants as main effects and for gene‐environment interaction
Authors: Bickeböller Heike , Houwing‐Duistermaat Jeanine J. , Wang Xuefeng , Yan Xiting 
Published: December 2011

AbstractIn addition to genome‐wide association studies, sequence data are now up and coming, increasing the need for even more effective methods of dealing with high dimensionality and the identification of variants beyond common variant main effects. The contributors to Genetic Analysis Workshop 17 Group 4 applied novel and recently proposed methods for handling population structure, high dimensionality, and gene‐environment interactions in the context of mini‐exome sequence data. For the collapsing of rare variants into gene summaries, some of the contributions considered the computationally fast, straightforward summing of all or particular subsets of rare variants. Other methods were comparatively time‐consuming and complex but offered a data‐driven approach, such as reduction in the subset of rare variants to be considered using a U statistic and semiparametric modeling of single‐nucleotide polymorphism effects implementing kernel machines. Several approaches were applied using regression models, regularized regression, and kernels. Testing for gene‐specific main effects and gene‐environment interaction using least‐squares kernel machines showed more flexibility and was supervised compared with a two‐step approach that used a random effects model that incorporated an empirical Bayes estimate. However, the random effects model was the only method capable of treating family data, at least in their present form. Genet. Epidemiol. 35:S35–S40, 2011. © 2011 Wiley Periodicals, Inc.
Peripheral low intensity sign in hepatic hemangioma: Diagnostic pitfall in hepatobiliary phase of Gd‐EOB‐DTPA‐enhanced MRI of the liver
Authors: Tamada Tsutomu , Ito Katsuyoshi , Ueki Ai , Kanki Akihiko , Higaki Atsushi , Higashi Hiroki , Yamamoto Akira 
Published: December 2011

AbstractPurpose:To describe the presence of “peripheral low intensity sign” in hepatic hemangioma in the hepatobiliary phase (HP) of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) and to compare the frequency of this sign between hepatic hemangiomas and hepatic metastases.Materials and Methods:The Institutional Review Board approved this study and waived the requirement for informed consent. Sixty‐four patients with 51 hepatic hemangiomas (n = 31 patients) and with 58 hepatic metastases (n = 33 patients) underwent Gd‐EOB‐DTPA‐enhanced MRI. In all hepatic hemangiomas, 41 lesions were the typical type and 10 were the high flow type. HP images were qualitatively evaluated for the frequency of peripheral low intensity sign in hepatic hemangiomas and hepatic metastases using a four‐point scale. Statistical evaluations were performed with a Mann–Whitney U‐test.Results:Peripheral low intensity signs were demonstrated in 24 (47%) of 51 hepatic hemangiomas, while they were seen in 27 (47%) of 58 hepatic metastases. There was no significant difference in the mean visual score of peripheral low intensity sign between all hepatic hemangiomas (0.84 ± 1.03) and hepatic metastases (0.76 ± 0.92). The mean visual score of peripheral low intensity sign in typical hemangiomas (1.02 ± 1.06) was significantly higher than that in high flow hemangiomas (0.10 ± 0.32) (P = 0.008).Conclusion:Peripheral low intensity sign is not specific for malignant tumors, and can be seen even in hepatic hemangiomas on HP of Gd‐EOB‐DTPA‐enhanced MRI. J. Magn. Reson. Imaging 2012;35:852–858. © 2011 Wiley Periodicals, Inc.