Recent Progress in Psychiatric Genetics—Some Hope but No Hype

The reputation of the field of psychiatric genetics has recently become tarnished in the view of many human geneticists. Too many linked loci were claimed and withdrawn, too many association studies published and not confirmed, and, more recently, too many new and different chromosomal regions have been implicated for the same disorder. Here, we summarize recent trends, focusing on research that moves away from traditional linkage studies. Some promising strategies include psychopharmacogenetics and consideration of endophenotypes such as neurophysiological and behavioral markers in addition to the clinical diagnosis. Utilization of rapid and automated methods for scoring genetic variants in large-scale association studies followed by multivariate analyses, which include environmental as well as genetic data, will likely fare better than traditional linkage analysis in disentangling the complex genetics of psychiatric disorders. Some notable areas of recent progress include quantification of the genetic complexity of autism, identification of genetic variants protecting individuals from alcoholism, and the description of several polymorphisms likely to be relevant to behavior and psychiatry. The most notable example may be a common variant that affects the transcription rate in the promoter for the serotonin transporter gene that may be relevant for individual differences in the response to common antidepressants

Algebraic transformation of unary partial algebras II: Single-pushout approach

AbstractThe single-pushout approach to graph transformation is extended to the algebraic transformation of partial many-sorted unary algebras. Such a generalization has been motivated by the need to model the transformation of structures which are richer and more complex than graphs and hypergraphs.The main result presented in this article is an algebraic characterization of the single-pushout transformation in the categories of all conformisms, all closed quomorphisms, and all closed-domain closed quomorphisms of unary partial algebras over a given signature, together with a corresponding operational characterization that may serve as a basis for implementation.Moreover, all three categories are shown to satisfy all of the HLR (high-level replacement) conditions for parallelism, taking as occurrences the total morphisms in each category. Another important result presented in this article is the definition of HLR conditions for amalgamation, which are also satisfied by the categories of partial homomorphisms considered here, taking again the corresponding total morphisms as occurrences

High reflectivity grating waveguide coatings for 1064nm

We propose thin single-layer grating waveguide structures to be used as high-reflectivity, but low thermal noise, alternative to conventional coatings for gravitational wave detector test mass mirrors. Grating waveguide (GWG) coatings can show a reflectivity of up to 100% with an overall thickness of less than a wavelength. We theoretically investigate GWG coatings for 1064nm based on tantala (Ta2O5) on a Silica substrate focussing on broad spectral response and low thickness

Experimental demonstration of a suspended diffractively coupled optical cavity

All-reflective optical systems are under consideration for future gravitational wave detector topologies. One approach in proposed designs is to use diffraction gratings as input couplers for Fabry–Perot cavities. We present an experimental demonstration of a fully suspended diffractively coupled cavity and investigate the use of conventional Pound–Drever–Hall length sensing and control techniques to maintain the required operating condition

Fluctuations of the Atlantic North Equatorial Undercurrent and associated changes in oxygen transports

Although the core velocity of the Atlantic North Equatorial Undercurrent (NEUC) is low (0.1−0.3 m s−1), it has been suggested to act as an important oxygen supply route towards the oxygen minimum zone in the eastern tropical North Atlantic. For the first time, the intraseasonal to interannual NEUC variability and its impact on oxygen are investigated based on shipboard and moored velocity observations around 5°N, 23°W. In contrast to previous studies that were mainly based on models or hydrographic data, we find hardly any seasonal cycle of NEUC transports in the central Atlantic. The NEUC transport variability is instead dominated by sporadic intraseasonal events. Only some of these events are associated with high oxygen levels suggesting an occasional eastward oxygen supply by NEUC transport events. Nevertheless, they likely contribute to the local oxygen maximum in the mean shipboard section along 23°W at the NEUC core position

Chromosome mapping: radiation hybrid data and stochastic spin models

This work approaches human chromosome mapping by developing algorithms for ordering markers associated with radiation hybrid data. Motivated by recent work of Boehnke et al. [1], we formulate the ordering problem by developing stochastic spin models to search for minimum-break marker configurations. As a particular application, the methods developed are applied to 14 human chromosome-21 markers tested by Cox et al. [2]. The methods generate configurations consistent with the best found by others. Additionally, we find that the set of low-lying configurations is described by a Markov-like ordering probability distribution. The distribution displays cluster correlations reflecting closely linked loci.Comment: 26 Pages, uuencoded LaTex, Submitted to Phys. Rev. E, [email protected], [email protected]

Impulsiveness Mediates the Association between \u3ci\u3eGABRA2\u3c/i\u3e SNPs and Lifetime Alcohol Problems

Genetic variants in GABRA2 have previously been shown to be associated with alcohol measures, electroencephalography (EEG) β waves and impulsiveness-related traits. Impulsiveness is a behavioral risk factor for alcohol and other substance abuse. Here, we tested association between 11 variants in GABRA2 with NEO-impulsiveness and problem drinking. Our sample of 295 unrelated adult subjects was from a community of families with at least one male with DSM-IV alcohol use diagnosis, and from a socioeconomically comparable control group. Ten GABRA2 SNPs (single-nucleotide polymorphisms) were associated with the NEO-impulsiveness (P \u3c 0.03). The alleles associated with higher impulsiveness correspond to the minor alleles identified in previous alcohol dependence studies. All ten SNPs are in linkage disequilibrium (LD) with each other and represent one effect on impulsiveness. Four SNPs and the corresponding haplotype from intron 3 to intron 4 were also associated with Lifetime Alcohol Problems Score (LAPS, P \u3c 0.03) (not corrected for multiple testing). Impulsiveness partially mediates (22.6% average) this relation between GABRA2 and LAPS. Our results suggest that GABRA2 variation in the region between introns 3 and 4 is associated with impulsiveness and this effect partially influences the development of alcohol problems, but a direct effect of GABRA2 on problem drinking remains. A potential functional SNP rs279827, located next to a splice site, is located in the most significant region for both impulsiveness and LAPS. The high degree of LD among nine of these SNPs and the conditional analyses we have performed suggest that all variants represent one signal