Chemical dynamics using wavepacket methods

This thesis is concerned with studying chemical dynamics using time-dependent quantum mechanics and in particular using the Fourier method. Various ways of implementing the Fourier method are described, both for calculations in one dimension and for those in many dimensions. The Fourier method is then used to simulate time-resolved femtosecond and picosecond pump-probe experiments, which investigate the B state of the sodium trimer. The simulation is divided into three stages: the initial wavefunction is generated by modelling the effect of the pump laser pulse on the ground state wavefunction of the X state of the sodium trimer; the wavepacket now on the B state is propagated in time; the observables are extracted from the time-dependent wavefunction. The calculations are carried out initially in two dimensions, corresponding to the bending and asymmetric stretch normal modes, and then in three dimensions, i.e. including the symmetric stretch normal mode. The simulation of the time-resolved experiments produced physically plausible results. The correspondence with the experimental results was only fair, but this could be mostly accounted for by the poor quality of the potential energy surfaces used. Thus, even the relatively simple model used to simulate the time-resolved experiments is useful to gain both a qualitative explanation of the results of these experiments and an insight into the dynamics of systems which are in non-stationary states

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes(1). This recent study-and most other large-scale human genetics studies-was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 x 10(-6)). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.Peer reviewe