Adaptive Mantel Test for AssociationTesting in Imaging Genetics Data

Mantel's test (MT) for association is conducted by testing the linear relationship of similarity of all pairs of subjects between two observational domains. Motivated by applications to neuroimaging and genetics data, and following the succes of shrinkage and kernel methods for prediction with high-dimensional data, we here introduce the adaptive Mantel test as an extension of the MT. By utilizing kernels and penalized similarity measures, the adaptive Mantel test is able to achieve higher statistical power relative to the classical MT in many settings. Furthermore, the adaptive Mantel test is designed to simultaneously test over multiple similarity measures such that the correct type I error rate under the null hypothesis is maintained without the need to directly adjust the significance threshold for multiple testing. The performance of the adaptive Mantel test is evaluated on simulated data, and is used to investigate associations between genetics markers related to Alzheimer's Disease and heatlhy brain physiology with data from a working memory study of 350 college students from Beijing Normal University

Program Comments

I just want to give you a little history because I think we tend to forget where we started from, not that many years ago, in this technology and what led up to the approach which is described in the film. I think this program really had its origins in the Air Force. 1970 to 1972 was a good period, particularly 1970, when you had the crash of the F111 and a major increase in concern about the safety of aircraft structures. A lot of things changed and, basically, what happened was that there was the recognition that nondestructive evaluation or nondestructive inspection had to change from simply the problem of detection to the problem of measurement in order to incorporate fracture mechanics into life prediction. It changed from a zero-defects philosophY to a damage-tolerant philosophy

2: The Mapping of Chromosome 16

Human chromosome 16 is the main focus of the mapping efforts at Los Alamos. The large photomicrograph on these opening pages illustrates the starting point for those mapping efforts, the evaluation of our chromosome-16-specific library of cloned fragments. Among the 23 pairs of human chromosomes, one pair, chromosome 16, is identified by fluorescence in-situ hybridization. Thousands of yellow fluorescent probes derived from the clone library have hybridized to both copies of chromosome 16. The high density and uniform coverage of the fluorescent signals were a strong indication that we could use the library to construct a map of overlapping cloned fragments spanning the entire length of the chromosome

Characterization of two marker chromosomes in a patient with acute nonlymphocytic leukemia by two-color fluorescence in situ hybridization

A patient with acute nonlymphocytic leukemia (ANLL), M5b according to French-American-British (FAB) classification, showed monosomy 16, an extra 1p−, and a 21q+. These derivative chromosomes could not be defined by GTG-banding. For better characterization, we performed two-color fluorescence in situ hybridization (FISH) experiments applying DNA libraries from sorted human chromosomes, chromosome-specific repetitive probes, and a band-specific YAC-clone. With these FISH studies the karyotype could be characterized as 46,XY,+der(1)t(1;21)(p11;?),−16,der(21)t(16;21)(p11.1;q22)

DRD4 genotype predicts longevity in mouse and human

Longevity is influenced by genetic and environmental factors. The brain's dopamine system may be particularly relevant, since it modulates traits (e.g., sensitivity to reward, incentive motivation, sustained effort) that impact behavioral responses to the environment. In particular, the dopamine D4 receptor (DRD4) has been shown to moderate the impact of environments on behavior and health. We tested the hypothesis that the DRD4 gene influences longevity and that its impact is mediated through environmental effects. Surviving participants of a 30-year-old population-based health survey (N = 310; age range, 90-109 years; the 90+ Study) were genotyped/resequenced at the DRD4 gene and compared with a European ancestry-matched younger population (N = 2902; age range, 7-45 years). We found that the oldest-old population had a 66% increase in individuals carrying the DRD4 7R allele relative to the younger sample (p = 3.5 × 10(-9)), and that this genotype was strongly correlated with increased levels of physical activity. Consistent with these results, DRD4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7-9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment. These results support the hypothesis that DRD4 gene variants contribute to longevity in humans and in mice, and suggest that this effect is mediated by shaping behavioral responses to the environment.Fil: Grady, Deborah L.. University of California. College of Medicine. Department of Biological Chemistry; Estados UnidosFil: Thanos, Panayotis K.. National Institute on Alcohol Abuse and Alcoholism. Laboratory of Neuroimaging; Estados Unidos. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos. Stony Brook University. Department of Psychology; Estados UnidosFil: Corrada, Maria M.. University of California. Department of Neurology; Estados UnidosFil: Barnett Jr., Jeffrey C.. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Ciobanu, Valentina. University of California. College of Medicine. Department of Biological Chemistry; Estados UnidosFil: Shustarovich, Diana. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Napoli, Anthony. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Moyzis, Alexandra G.. University of California. College of Medicine. Department of Biological Chemistry; Estados UnidosFil: Grandy, David. Oregon Health Sciences University. Physiology and Pharmacology; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Wang, Gene-Jack. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Kawas, Claudia H.. University of California. Department of Neurology; Estados UnidosFil: Chen, Chuansheng. University of California. Department of Psychology and Social Behavior; Estados UnidosFil: Dong, Qi. Beijing Normal University. National Key Laboratory of Cognitive Neuroscience and Learning; ChinaFil: Wang, Eric. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos. Aria Diagnostics Inc.; Estados Unidos. University of California. Institute of Genomics and Bioinformatics; Estados UnidosFil: Volkow, Nora D.. National Institute on Alcohol Abuse and Alcoholism. Laboratory of Neuroimaging; Estados Unidos. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos. National Institute on Drug Abuse; Estados UnidosFil: Moyzis, Robert K.. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos. Beijing Normal University. National Key Laboratory of Cognitive Neuroscience and Learning; China. University of California. Institute of Genomics and Bioinformatics; Estados Unido

Influence of Yb:YAG laser beam parameters on Haynes 188 weld fusion zone microstructure and mechanical properties

The weldability of 1.2 mm thick Haynes 188 alloy sheets by a disk Yb:YAG laser welding was examined. Butt joints were made, and the influence of parameters such as power, size, and shape of the spot, welding speed, and gas flow has been investigated. Based on an iconographic correlation approach, optimum process parameters were determined. Depending on the distribution of the power density (circular or annular), acceptable welds were obtained. Powers greater than 1700 W, welding speeds higher than 3.8 m mm1, and spot sizes between 160 and 320 lm were needed in the circular (small fiber) configuration. By comparison, the annular (large fiber) configuration required a power as high as 2500 W, and a welding speed less than 3.8 m min�1. The mechanical properties of the welds depended on their shape and microstructure, which in turn depended on the welding conditions. The content of carbides, the proportion of areas consisting of cellular and dendritic substructures, and the size of these substructures were used to explain the welded joint mechanical properties

Molecular genetic contribution to the developmental course of attention-deficit hyperactivity disorder

Objective: The developmental trajectory of attention-deficit hyperactivity disorder (ADHD) is variable. Utilizing a longitudinally assessed sample, we investigated the contribution of susceptibility gene variants, previously implicated through pooled or meta-analyses, to the developmental course of Attention-Deficit Hyperactivity Disorder over time. Methods: 151 children (aged 6–12) who met diagnostic criteria for ADHD were assessed using research diagnostic interviews during childhood and 5 years later in adolescence. Severity was defined as total number of ADHD symptoms at baseline and reassessment. Association with variants at DRD4, DRD5, and the dopamine transporter gene, DAT was analyzed using linear regression. Results: As expected, affected individuals showed a decline in ADHD severity over time. The DRD4 48 bp VNTR 7-repeat and DRD5 CA(n) microsatellite marker 148 bp risk alleles were associated with persistent ADHD. Those possessing the DRD4 7 repeat risk allele showed less of a decline in severity at reassessment than those without the risk allele. Conclusions: Those carrying the DRD4 7 risk allele showed greater symptom severity at follow-up and less ADHD reduction over time. These findings support the hypothesis that some susceptibility genes for ADHD also influence its developmental course