OCS in small para-hydrogen clusters: energetics and structure with N=1-8 complexed hydrogen molecules

We determine the structure and energetics of complexes of the linear OCS molecule with small numbers of para-hydrogen molecules, N=1-8, using zero temperature quantum Monte Carlo methods. Ground state calculations are carried out with importance-sampled rigid body diffusion Monte Carlo (IS-RBDMC) and excited state calculations with the projection operator imaginary time spectral evolution (POITSE) methodology. The ground states are found to be highly structured, with a gradual build up of two axial rings as N increases to 8. Analysis of the azimuthal density correlations around the OCS molecule shows that these rings are quite delocalized for small N values, but become strongly localized for N \geq 5 . Excited state calculations are made for a range of total cluster angular momentum values and the rotational energy levels fitted to obtain effective rotational and distortion constants of the complexed OCS molecule as a function of cluster size N. Detailed analysis of these spectroscopic constants indicates that the complexes of OCS with para-hydrogen have an unusually rich variation in dynamical behavior, with sizes N=1-2 showing near rigid behavior, sizes N=3-4 showing extremely floppy behavior, and the larger sizes N=5-8 showing more rigid behavior again. The large values of the distortion constant D obtained for N=3-4 are rationalized in terms of the coupling between the OCS rotations and the "breathing" mode of the first, partially filled ring of para-hydrogen molecules.Comment: 26 pages, 11 figures. accepted for publication in the Journal of Chemical Physic

Multi-Omics Analysis of Alcohol Use Disorder in Postmortem Human Brain Tissue

Alcohol use disorder is characterized by a loss of control over alcohol intake and contributes to a large number of premature deaths worldwide by representing a strong risk factor for numerous diseases. Despite decade-long research on alcohol use disorder, treatment options are limited and relapse rates following withdrawal treatment are high. Currently, alcohol use disorder is understood as a brain disorder as neuroimaging studies have shown substantial alcohol use disorder-associated connectivity and activity alterations in the human brain. This led to the hypothesis of a neurocircuitry of addiction involving multiple brain regions such as the ventral and dorsal striatum, but also cortical regions that display aberrant functional connectivity patterns in alcohol use disorder. These profound brain changes in alcohol use disorder are assumed to be established by molecular processes such as aberrant DNA methylation and gene expression patterns. To investigate these processes in the human brain, postmortem brain tissue depicts a valuable resource. Previous studies have been published reporting on alcohol use disorder-associated differential methylation or differentially expressed genes mainly in the prefrontal cortex. So far, no analysis has integrated DNA methylation and gene expression data in a multi-Omics approach. Further, it remains unclear how alterations in DNA methylation and gene expression are related to each other in the alcohol use disorder brain. The overall aim of the presented studies was to identify functionally relevant molecular mechanisms of alcohol use disorder in the neurocircuitry of addiction. To address these points, the first paper aimed to expand the epigenetic characterization of alcohol use disorder to the neurocircuitry of addiction by performing an epigenome-wide association study of DNA methylation in alcohol use disorder in five brain regions: the cortical regions anterior cingulate cortex and Brodmann Area 9, and the striatal regions caudate nucleus, putamen, and ventral striatum. In the second study, the gene expression profile of the striatal brain regions was investigated using RNA-Sequencing enabling the integration of DNA methylation and gene expression data in a multi-omics approach. The biological implication of alcohol use disorder-associated DNA methylation and expression signatures was investigated in both studies using a comprehensive set of bioinformatic tools including Gene Ontology- and gene-set enrichment analyses, weighted correlation network analyses, enrichment analyses of results from genome-wide association studies of substance use disorder phenotypes, and protein-protein interaction networks. In the epigenome-wide association study of alcohol use disorder in five brain regions, 20 differentially methylated CpG sites were detected, two in caudate nucleus and 18 in the ventral striatum, that were associated with alcohol use disorder at epigenome-wide significance. Alcohol use disorder-associated DNA methylation signatures were strongest in the caudate nucleus, putamen, and ventral striatum and were enriched within immune-related cellular pathways. Gene expression analysis in the second study suggested converging evidence for inflammatory and immunological signaling in alcohol use disorder. While the overlap of differential methylation and differential expression at the gene level was limited, it was evident on the network level. Consistent differential expression of the ARHGEF15 gene was found in the caudate nucleus, putamen, and ventral striatum in alcohol use disorder. Further, the STAT3 gene was identified as a conserved hub node in alcohol use disorder-associated gene networks and might be a promising candidate for further evaluation. In conclusion, this is the first study that integrated DNA methylation and gene expression data from the same individuals in multiple brain regions in the context of alcohol use disorder. Converging evidence from this study supports the role of (neuro) inflammation in the pathophysiology of alcohol use disorder. Methods for multi-omics integration are rapidly emerging and the integration of multiple omics including epigenome-wide DNA Methylation, transcriptomics, proteomics, and non-coding RNAs enables the complementation, but also the prioritization of findings from single omics layers. In follow-up studies, functional validation of multi-omics-derived candidate genes and pathways should be performed using animal models and patient-derived brain organoids. Conducting such precision medicine approaches might lead to the discovery of novel therapeutic strategies in alcohol use disorder, which are urgently required

Gapped spectrum in pair-superfluid bosons

We study the ground state of a bilayer system of dipolar bosons with dipoles oriented by an external field perpendicularly to the two parallel planes. By decreasing the interlayer distance, for a fixed value of the strength of the dipolar interaction, the system undergoes a quantum phase transition from an atomic to a pair superfluid. We investigate the excitation spectrum on both sides of this transition by using two microscopic approaches. Quantum Monte Carlo methods are employed to obtain the static structure factors and intermediate scattering functions in imaginary time. The dynamic response is calculated using both the correlated basis functions (CBF) method and the approximate inversion of the Laplace transform of the quantum Monte Carlo imaginary time data. In the atomic phase, both the density and spin excitations are gapless. However, in the pair-superfluid phase a gap opens in the excitation energy of the spin mode. For small separation between layers, the minimal spin excitation energy equals the binding energy of a dimer and is twice the gap value.Postprint (author's final draft

Extrapolated High-Order Propagators for Path Integral Monte Carlo Simulations

We present a new class of high-order imaginary time propagators for path-integral Monte Carlo simulations by subtracting lower order propagators. By requiring all terms of the extrapolated propagator be sampled uniformly, the subtraction only affects the potential part of the path integral. The negligible violation of positivity of the resulting path integral at small time steps has no discernable affect on the accuracy of our method. Thus in principle arbitrarily high order algorithms can be devised for path-integral Monte Carlo simulations. We verify this claim is by showing that fourth, sixth, and eighth order convergence can indeed be achieved in solving for the ground state of strongly interacting quantum many-body systems such as bulk liquid $^4$He.Comment: 9 pages and 3 figures. Submitted to J. Chem. Phy

Root curvature localizations as indicators of post length in various tooth groups

— The straight line length available for post preparations in pulps of 957 human teeth was evaluated. Analysis of radiographs in both buccolingual and mesiodistal directions showed that only 2.7% of the teeth studied were straight to the apex in both views. Average straight line lengths were calculated for the different types of teeth and used to offer guidelines for the length of post preparation. Buccal roots of maxillary molars and the mesial roots of the mandibular molars frequently showed straight line lengths insufficient for post preparations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72918/1/j.1600-9657.1986.tb00125.x.pd