bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of caffeine and its metabolites in urine by capillary electrophoresis‐mass spectrometry
Authors: Peri‐Okonny Unita L. , Wang Shao Xiong , Stubbs R. John , Guzman Norberto A. 
Published: June 2005

AbstractThe caffeine content of foods and beverages varies considerably, interfering with our ability to obtain valid interpretations in many human studies with regard to the mechanism of action(s) of caffeine and/or its metabolites. The rate of metabolism of caffeine and other xanthine drugs also varies greatly from one individual to another. Therefore, it is extremely important to develop accurate, reliable analytical methods to quantify caffeine and its metabolites in simple and complex matrixes. A simple method is described for the separation and characterization of caffeine and its major metabolites employing capillary electrophoresis (CE) coupled to ultraviolet‐absorption and mass spectrometry (MS) detection. After optimization of the electrophoresis separation conditions, a reliable separation of caffeine and 11 of its major metabolites was achieved in 50 mM ammonium carbonate buffer, pH 11.0. The volatile aqueous electrolyte system used with a normal electroosmotic flow polarity also provided an optimal separation condition for the characterization of the analytes by MS. The CE method achieved baseline resolution for all 12 compounds in less than 30 min. The CE‐MS method is suitable for use as a routine procedure for the rapid separation and characterization of caffeine and its metabolites. The usefulness of this method was demonstrated by the extraction, separation, and identification of caffeine and its 11 metabolites from normal urine samples. The urine specimens were first acidified to obtain optimum binding efficiency to the sorbents of the off‐line, solid‐phase extraction procedure employed here, and an acidified eluent solvent was employed for the desorption step to maximize the recovery of the bound analytes.
The role of time and timing in hominid dental evolution
Authors: Macho Gabriele A. , Wood Bernard A. 
Published: June 2005

AbstractExactly when during evolution hominids acquired their extended extra‐uterine growth period is a contentious issue. In order to shed light on the tempo and mode of ontogenetic changes during hominid evolution, research has focused on the pattern and, to a lesser extent, the rate of growth observed in the developing dentition of extant and extinct hominoid taxa. From these data, the absolute timing of events has often been inferred, either implicitly or explicitly. Differences in patterns of growth, especially of the eruption of teeth, are reasonably well documented among hominoids. However, data on the absolute timing of dental developmental events are much more scarce, rendering tentative all inferences about timing from patterns alone. Such inferences are even more tentative when they involve interpreting ontogenetic trajectories in extinct species such as Plio‐Pleistocene hominids, which almost certainly had unique patterns of maturation. In order to contribute to the debate about possible relations between pattern and timing in the developing dentition, we have collated information that specifically relates to the absolute timing of developmental events in extant and extinct hominoids and, hence, also to the rate at which processes occur. In doing so, we have attempted to identify both developmental constraints and possible heterochronic processes that may have led to the extended growth period characteristic of humans. There appears to be growing evidence that evolution toward an extended hominid ontogeny did not follow a path that can be described as a simple heterochronic event.
Evaluation of path analysis through computer simulation: Effect of incorrectly assuming independent distribution of familial correlations
Authors: McGue M. , Wette R. , Rao D. C. , MacCluer J. W. 
Published: June 2005

AbstractPath analysis of family data has been widely applied to resolve genetic and environmental patterns of familial resemblance. A prevalent statistical approach in path analysis has been, first, to estimate the familial correlations and, second, by assuming these estimates to be independently distributed, define a likelihood function from which maximum likelihood estimates of model parameters can be obtained and likelihood ratio tests of hypotheses performed. Although it is generally known that the independence assumption does not hold when multiple familial correlations are estimated from the same family data, this statistical method has still been used in these situations owing, in part, to the lack of any viable alternatives and, in part, to the lack of any knowledge about the specific quantitative effects of not meeting the assumption of independence. Here, using computer‐simulation methods, we evaluate the robustness of this statistical method to deviations from the assumption of independence. In general, we found that the failure to meet the assumption of independence leads to a conservative test of the goodness‐of‐fit of the path model, although likelihood ratio tests of specific null hypotheses were at times liberal, at times conservative, and at times nearly exact. Although the test statistics were found to be distorted, the parameter estimates using this method were nearly unbiased.
Complete hydatidiform mole in Hawaii: An epidemiological study
Authors: Matsuura Janice , Chiu Darryl , Jacobs Patricia A. , Szulman A. E. , Rao D. C. 
Published: June 2005

AbstractAn analysis of hydatidiform moles occurring in Hawaii over a 14‐year period (1968–1981) was undertaken. The pathology of all 278 reported molar pregnancies was reviewed and showed 69.4% to be complete, 24.5% to be partial, and 6.1% to be nonmolar.A case‐control epidemiological investigation of the complete moles showed maternal age and race to be important, moles being significantly more prevalent in women under 20 and over 40 yr of age and also in women of Japanese, Filipino, and other Oriental ancestry. However no difference was seen in the prevalence of moles between Oriental women born in the Orient and those born and raised in Hawaii. No significant difference was found in paternal age, paternal race, socioeconomic status, or reproductive history, suggesting that these factors do not play an important role in the etiology of complete hydatidiform mole.Incidence rates for complete moles were calculated taking age and race into consideration and ranged from a high of 1 in 150 to a low of 1 in 2,000 naturally terminating pregnancies.
Phenotypic effects of apolipoprotein structural variation on lipid profiles. I. APO H and quantitative lipid measures in the healthy women study
Authors: Eichner J. E. , Kuller L. H. , Kamboh M. I. , Ferrell R. E. , Vogler G. P. , Rao D. C. 
Published: June 2005

AbstractApolipoprotein H (APO H), also known as β2‐glycoprotein I, has been identified as a protein component of the major lipoprotein density fractions in human plasma. Recently, genetically determined structural polymorphism in white and black populations has been documented for this apolipoprotein. There are three common alleles in whites and blacks and a fourth allele found mainly in blacks. Family data confirm the autosomal codominant pattern of inheritance for the APO H structural gene. Little is known about the function of APO H, but it has demonstrated both lipid and platelet involvement. In this study we investigate the effect of APO H phenotypes on quantitative lipid measures in a group of 443 white women being followed through menopause for changes in cardiovascular risk. At baseline all women were premenopausal. None of the APO H phenotypes showed a statistically significant effect on lipid measures in this population.
Using survival methods to estimate age‐at‐onset distributions for genetic diseases with an application to Huntington disease
Authors: Cupples L. Adrienne , Terrin Norma C. , Myers Richard H. , D'Agostino Ralph B. , Rao D. C. 
Published: June 2005

AbstractTwo important considerations in genetic disease are the risk of inheriting the gene for a disease and the age‐at‐onset distribution among those inheriting it. This paper describes the use of survival data analytic methods to estimate these entities. When a sample consists of children and/or siblings of affected individuals, standard lifetable methods such as Kaplan‐Meier techniques can be applied. The desired estimators are functions of the Kaplan‐Meier estimator and their properties are derived using the invariance principle and delta methods. A discussion of the underlying assumptions and estimators of standard errors and mean onset age are given. In an application to Huntington disease, the risk (± SE) of inheriting the gene for disease among children of a singly affected parent is estimated to be 0.499 ± 0.020 and the estimated mean onset age (± SE) is 45.6 ± 0.7.
Can dietary intake patterns account for the familial aggregation of disease? Evidence from adult siblings living apart
Authors: Sellers Thomas A. , Kushi Lawrence H. , Potter John D. 
Published: June 2005

AbstractThe familial aggregation of certain chronic diseases is well documented [Perkins, 1986; King et al., 1984; Anderson, 1982]. Dietary data on adult brothers living apart were used to examine whether familial clustering of disease could be explained by nature or nutriture. Intakes of nutrients were strikingly more similar among siblings than expected: when correlations were adjusted for country of residence, 21 of 25 (84%) were statistically significant. Thus, dietary patterns among adult siblings are more alike than could be predicted by their sharing a common culture, as alike as has been described for monozygotic twins, and as alike as described for familial correlations of serum cholesterol. Incorporation of dietary measures in cotwin studies or studies of siblings can improve the estimates of the true genetic effect on disease pathogenesis.
Elementary methods for the analysis of dichotomous outcomes in unselected samples of Twins
Authors: Ramakrishnan Viswanathan , Goldberg Jack , Henderson William G. , Eisen Seth A. , True William , Lyons Michael J. , Tsuang Ming T. , Chakravarti Aravinda 
Published: June 2005

AbstractThis paper presents an elementary statistical method for analyzing dichotomous outcomes in unselected samples of twin pairs using stratified estimators of the odds ratio. The methodology begins by first randomly designating one member of each twin pair as an ‘index’ twin and the other member as the ‘co‐twin.’ Stratifying on zygosity, odds ratios are used to measure the association between disease in the index twin and disease in the co‐twin. From these zygosity‐specific tables we cal‐culate the Woolf‐Haldane estimator of the common odds ratio (ψF, the weighted average of the zygosity‐specific odds ratios), the Mantel‐Haenszel test statistic (χ) for the common odds ratio, and a test (χ) for the difference in the zy‐gosity‐specific odds ratios. In this application, ψF provides an estimate of the familial association for disease and the accompanying χ provides a test of the null hypothesis, ψF = 1 (i.e., there is no evidence for a familial influence on disease). The χ is a test of the null hypothesis that ψMZ = ψDZ; a significant value for χ suggests a genetic influence on disease (assuming that the observed odds ratios follow a pattern where ψMZ>ψDZ). A new test statistic (χ) is proposed that incor‐porates the expectation that ψMZ = ψ under a purely additive genetic model with no common environmental effects. A significant value of χ indicates that the different odds ratios across zygosity are partly due to common environmental influences. Conversely, a nonsignificant value of χ is an indication that the zygosity‐specific odds ratios are due solely to additive genetic effects and not to common environment. This basic approach is extended to examine the effects of measured indicators of the specific environment and the assessment of certain forms of gene by environment interaction. All of the methods are easily understood, highly flexible, readily computed using a hand calculator, and incorporate the inherent genetic information contained within twin samples. © 1992 Wiley‐Liss, Inc.
Segregation analysis of 159 soft tissue sarcoma kindreds: Comparison of fixed and sequential sampling schemes
Authors: Bondy Melissa L. , Lustbader Edward D. , Strom Sara S. , Strong Louise C. , Chakravarti Aravinda 
Published: June 2005

AbstractIn this study we compared parameter estimates and model hypotheses in pedigree data collected by fixed sampling with estimates and hypotheses derived by sequential sampling. Employing a fixed sampling scheme, we previously analyzed data on relatives of 159 childhood sarcoma patients. We have now extracted from that data set individuals who would have been included in a sequentially sampled study. We applied segregation analysis to the truncated data, to determine the mode of inheritance and major locus parameter estimates. With data from both sampling schemes we made a family‐by‐family comparison to determine each family's contribution to a major gene model. The two sampling schemes yielded similar results: we detected segregation of a dominant major gene and obtained similar major locus parameter estimates. However, the sequential sampling scheme derived these conclusions from data on 982 relatives rather than the 2,451 ascertained in the fixed sampling scheme. The sequential sampling scheme failed to identify only one of the kindreds likely to be segregating the gene. For this data set, the sequential sampling scheme would have provided an efficient mechanism to discriminate genetic hypotheses and would have permitted focus of resources on the specific kindreds likely to segregate a major gene. © 1992 Wiley‐Liss, Inc.
A generalized estimating equations approach to fitting major gene models in segregation analysis of continuous phenotypes
Authors: Lee Hang , Stram Daniel O. , Thomas Duncan C. 
Published: June 2005

AbstractThis paper discusses the application of estimating equations methods based on a quadratic exponential model [Prentice and Zhao, 1991] as a potential competitor with full likelihood approaches to estimating the effect of major genes in a segregation analysis [Elston, 1981] of continuous phenotypes, in the single allele problem. We show that while the estimating equations methods based on the quadratic exponential family cannot be used by themselves to estimate all parameters of interest, an iterative two‐stage approach can be used, in which the population allele frequency is first considered to be a known parameter, which permits the estimating equations method to estimate the remaining parameters. At the second stage a “pseudo‐profile” loglikelihood based only on the founders is used to estimate the allele frequency. After each maximization of the pseudo‐profile loglikelihood at the second stage, the parameters in the first stage are reestimated using a new value of the allele frequency, and a new value of the second stage pseudo‐profile loglikelihood is obtained. We used simulated pedigree data for illustrations. © 1993 Wiley‐Liss. Inc.
Path analysis and sib‐pair linkage
Authors: Carey Gregory , Williamson John A. 
Published: June 2005

AbstractWhen the distance between linked loci is expressed in terms of the correlation between the identity‐by‐descent (idb) values of the loci, then a path model may be used to order loci with data on sib‐pairs and their parents. The relationship between the recombination fraction and the correlation coefficient is developed and a method for fitting a covariance matrix predicted by a specific ordering of loci to an observed covariance matrix is proposed. © 1993 Wiley‐Liss. Inc.
Analysis of discrete phenotypes using a multipoint identity‐by‐descent method: Application to Alzheimer's disease
Authors: Goldgar David E. , Lewis Cathryn M. , Gholami Khosrow 
Published: June 2005

AbstractThe multipoint identity‐by‐descent method was developed to detect linkage to a specific chromosomal region through partitioning the genetic variance. This method has previously been applied to quantitative traits, and here is extended to a qualitative trait, where a dichotomous affected/unaffected status variable is transformed to a quantitative variable by incorporating covariates. This method is applied to the Alzheimer's disease data sets from Genetic Analysis Workshop 8, to investigate putative linkage to chromosomes 19 and 21. The multipoint identity‐by‐descent method is used to test for linkage through the qualitative trait, and for excess sharing of the chromosomal region among affected sibs. Results are compared to those of the affected‐pedigree‐member method and classical linkage analysis. None of these methods gave results showing clear linkage, with the only marginally significant results occurring for the Boston data set on chromosome 19 and the Duke data set for chromosome 21 using the multipoint identity‐by‐descent method. © 1993 Wiley‐Liss, Inc.
The application of jackknife statistics to estimates of the recombination fraction
Authors: Berger B. D. , Greenberg D. A. , Hodge S. E. , Mendell N. R. 
Published: June 2005

AbstractWe develop and evaluate the jackknife statistics [Efron, 1982] for obtaining confidence intervals for the recombination fraction. We consider two cases: (1) a single sibship of size S with phase known parents (one doubly heterozygous and one doubly homozygous) and (2) a sample of 20 nuclear families. We compare the jackknife confidence interval to the −1.00 lod and −0.83 lod intervals. For the first case we compare our intervals with a confidence interval which we develop that has coverage of exactly 95%. For the second case, we do a simulation study and compare the coverage of the intervals and the endpoints of the intervals with the actual 2.5th and 97.5th percentiles. Our results indicate that in case (1) the lod intervals provide closer estimates to the 95% exact interval than does the jackknife approach. However, in case (2), although the lod intervals have better coverage probabilities, the jackknife interval endpoints are closer to the actual percentile points than either of the lod interval endpoints. © 1993 Wiley‐Liss, Inc.
The NHLBI male veteran twin study data
Authors: Reed Terry , Carmelli Dorit , Christian Joe C. , Selby Joseph V. , Fabsitz Richard R. 
Published: June 2005

AbstractThe National Heart, Lung and Blood Institute (NHLBI) twin study is a collaborative, longitudinal study of the role of genetic risk factors on subsequent cardiovascular disease processes in 514 pairs of white, male World War II and Korean veteran twins born between 1917 and 1927. This paper describes the sampling procedures and zygosity determination at the initial examination, participation by the cohort members at later examinations, and a summary of the variables provided for Genetic Analysis Workshop 8 (GAW8). © 1993 Wiley‐Liss, Inc.
Statistical validity of the Haseman‐Elston sib‐pair test in small samples
Authors: Wilson Alexander F. , Elston Robert C. 
Published: June 2005

AbstractSimulation experiments were used to determine the empiric type I error rate of the Haseman‐Elston sib‐pair test for linkage between a quantitative trait and a marker locus in samples with 60 or fewer sib pairs. The effect of different levels of marker‐locus heterozygosity on statistical validity was also considered. The test was performed on the trait and each of five unlinked markers, and evaluated using two different degrees of freedom for the t‐distribution. The number of degrees of freedom in the first evaluation was based on the number of sib pairs in each sibship, ∑ sI(sI ‐ 1)/2 ‐ 2. In the second evaluation, the number of degrees of freedom was based on the number of sibs minus 1 in each sibship, ∑ (si ‐ 1) ‐ 2. Empirically determined type I error rates using C sI(sI ‐ 1)/2 ‐ 2 degrees of freedom were slightly liberal. For ∑ (si ‐ 1) ‐ 2 degrees of freedom, the estimated empiric p‐values were nearly identical to their respective nominal p‐values. Decreasing levels of heterozygosity did not increase the empiric type I error rate when the sample size was small. © 1993 Wiley‐Liss, Inc.
Genotype by sex interaction in measures of lipids, lipoproteins, and apolipoproteins
Authors: Towne Bradford , Blangero John , Siervogel Roger M. 
Published: June 2005

AbstractGenotype by sex (GxS) interaction in a quantitative trait indicates that the sexual dimorphism exhibited in that trait is heritable. GxS interaction has implications for the modeling of traits in segregation analyses and for the assessment of disease risk in males and females. Thirteen quantitative measures of lipids, lipoproteins, and apolipoproteins from 203 to 301 individuals in 25 to 27 kindreds were examined for evidence of GxS interaction. These measures included serum concentrations of total cholesterol, triglycerides, LDL‐C, HDL‐C, apo B, and apo AI, and peak LDL particle diameter, small LDL mass, large LDL mass, IDL mass, VLDL mass, HDL, mass, and HDL, mass. GxS interaction was indicated for transformed values of LDL‐C and small LDL mass by an additive genetic correlation between males and females significantly less than 1.0, and GxS interaction was indicated for transformed values of HDL, mass and HDL, mass by males and females having significantly different additive genetic variances. © 1993 Wiley‐Liss, Inc.
Evaluation of the sampling plan used in collecting data for a study of LDL subclass pattern
Authors: Zhao Lue Ping , Grove John S. , Quiaoit Filemon 
Published: June 2005

AbstractThe genetic epidemiologic study of coronary heart disease conducted by a group in the Donner Laboratory used survey and ad hoc sampling plans, resulting in a random and an ad hoc sample of families, respectively. These two samples were used to evaluate the ad hoc sampling plan used in that study. Following the description of data collection, we adjusted for ascertainment, but still found that the aggregation patterns of many lipoproteins in the ad hoc sample were different from those in the random sample. © 1993 Wiley‐Liss, Inc.
Exploring the HDL likelihood surface
Authors: Atwood Larry D. , Kammerer Candace M. , Mitchell Braxton D. 
Published: June 2005

AbstractUsing random initial parameter estimates, three segregation analysis models of the inheritance of HDL, in the Berkeley GAW8 data set were maximized 5000 times each. Initial parameter estimates were assumed to be uniformly distributed on intervals formed by parameter boundaries. The three models were unrestricted, environmental, and Mendelian regressive type A models. Likelihood ratio tests of the global maxima rejected the Mendelian model and accepted the environmental model. However, tests using local maxima accepted the Mendelian model and both rejected and accepted the environmental model. Patterns among the initial parameter estimates of convergent runs were examined to develop empirical rules to increase the frequency of convergence. These rules were tested using data on apo AI in the Berkeley GAWS data set. © 1993 Wiley‐Liss, Inc.
Structure and stability of β‐pleated sheets*
Authors: Perczel András , Gáspári Zoltán , Csizmadia Imre G. 
Published: June 2005

AbstractBeside α‐helices, β‐sheets are the most common secondary structure elements of proteins. In this article, the question of structure and stability of parallel and antiparallel sheets of various lengths is addressed. All data obtained are compared to a selected set of protein structures. In antiparallel β‐sheets, one of the two possible H‐bonded structures (containing 14 atoms in the H‐bonded pseudoring) is energetically more favored and also more abundant in proteins than the other one (with 10 atoms involved in the pseudoring). Parallel β‐sheets and their subunits are energetically less stable and indeed found to occur more rarely in proteins. Antiparallel hairpins are disfavored compared to β‐sheets formed by sequentially separated strands. Agreement between theory and experimental data indicates that characterization of structural building blocks at an appropriately accurate level of theory is a useful tool to get insight into fundamentals of protein structure. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1155–1168, 2005