Finite-temperature properties of quasi-2D Bose-Einstein condensates

Using the finite-temperature path integral Monte Carlo method, we investigate dilute, trapped Bose gases in a quasi-two dimensional geometry. The quantum particles have short-range, s-wave interactions described by a hard-sphere potential whose core radius equals its corresponding scattering length. The effect of both the temperature and the interparticle interaction on the equilibrium properties such as the total energy, the density profile, and the superfluid fraction is discussed. We compare our accurate results with both the semi-classical approximation and the exact results of an ideal Bose gas. Our results show that for repulsive interactions, (i) the minimum value of the aspect ratio, where the system starts to behave quasi-two dimensionally, increases as the two-body interaction strength increases, (ii) the superfluid fraction for a quasi-2D Bose gas is distinctly different from that for both a quasi-1D Bose gas and a true 3D system, i.e., the superfluid fraction for a quasi-2D Bose gas decreases faster than that for a quasi-1D system and a true 3D system with increasing temperature, and shows a stronger dependence on the interaction strength, (iii) the superfluid fraction for a quasi-2D Bose gas lies well below the values calculated from the semi-classical approximation, and (iv) the Kosterlitz-Thouless transition temperature decreases as the strength of the interaction increases.Comment: 6 pages, 5 figure

Human MicroRNA (miR-20b-5p) Modulates Alzheimer’s Disease Pathways and Neuronal Function, and a Specific Polymorphism Close to the \u3cem\u3eMIR20B\u3c/em\u3e Gene Influences Alzheimer’s Biomarkers

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with loss of cognitive, executive, and other mental functions, and is the most common form of age-related dementia. Amyloid-β peptide (Aβ) contributes to the etiology and progression of the disease. Aβ is derived from the amyloid-β precursor protein (APP). Multiple microRNA (miRNA) species are also implicated in AD. We report that human hsa-miR20b-5p (miR-20b), produced from the MIR20B gene on Chromosome X, may play complex roles in AD pathogenesis, including Aβ regulation. Specifically, miR-20b-5p miRNA levels were altered in association with disease progression in three regions of the human brain: temporal neocortex, cerebellum, and posterior cingulate cortex. In cultured human neuronal cells, miR-20b-5p treatment interfered with calcium homeostasis, neurite outgrowth, and branchpoints. A single-nucleotide polymorphism (SNP) upstream of the MIR20B gene (rs13897515) associated with differences in levels of cerebrospinal fluid (CSF) Aβ1-42 and thickness of the entorhinal cortex. We located a miR-20b-5p binding site in the APP mRNA 3′-untranslated region (UTR), and treatment with miR-20b-5p reduced APP mRNA and protein levels. Network analysis of protein-protein interactions and gene coexpression revealed other important potential miR-20b-5p targets among AD-related proteins/genes. MiR-20b-5p, a miRNA that downregulated APP, was paradoxically associated with an increased risk for AD. However, miR-20b-5p also reduced, and the blockade of APP by siRNA likewise reduced calcium influx. As APP plays vital roles in neuronal health and does not exist solely to be the source of “pathogenic” Aβ, the molecular etiology of AD is likely to not just be a disease of “excess” but a disruption of delicate homeostasi

Genome-wide association study of language performance in Alzheimer's disease

Language impairment is common in prodromal stages of Alzheimer's disease (AD) and progresses over time. However, the genetic architecture underlying language performance is poorly understood. To identify novel genetic variants associated with language performance, we analyzed brain MRI and performed a genome-wide association study (GWAS) using a composite measure of language performance from the Alzheimer's Disease Neuroimaging Initiative (ADNI; n=1560). The language composite score was associated with brain atrophy on MRI in language and semantic areas. GWAS identified GLI3 (GLI family zinc finger 3) as significantly associated with language performance (p<5×10-8). Enrichment of GWAS association was identified in pathways related to nervous system development and glutamate receptor function and trafficking. Our results, which warrant further investigation in independent and larger cohorts, implicate GLI3, a developmental transcription factor involved in patterning brain structures, as a putative gene associated with language dysfunction in AD

Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways

Adult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer's Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value < 0.05), of which 38 pathways were related to neurogenesis-related processes including neurogenesis, generation of new neurons, neuronal development, and neuronal migration and differentiation. For genes highly represented in the significantly enriched neurogenesis-related pathways, gene-based association analysis identified TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis

Codon bias among synonymous rare variants is associated with Alzheimer's disease imaging biomarker

Alzheimer's disease (AD) is a neurodegenerative disorder with few biomarkers even though it impacts a relatively large portion of the population and is predicted to affect significantly more individuals in the future. Neuroimaging has been used in concert with genetic information to improve our understanding in relation to how AD arises and how it can be potentially diagnosed. Additionally, evidence suggests synonymous variants can have a functional impact on gene regulatory mechanisms, including those related to AD. Some synonymous codons are preferred over others leading to a codon bias. The bias can arise with respect to codons that are more or less frequently used in the genome. A bias can also result from optimal and non-optimal codons, which have stronger and weaker codon anti-codon interactions, respectively. Although association tests have been utilized before to identify genes associated with AD, it remains unclear how codon bias plays a role and if it can improve rare variant analysis. In this work, rare variants from whole-genome sequencing from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were binned into genes using BioBin. An association analysis of the genes with AD-related neuroimaging biomarker was performed using SKAT-O. While using all synonymous variants we did not identify any genomewide significant associations, using only synonymous variants that affected codon frequency we identified several genes as significantly associated with the imaging phenotype. Additionally, significant associations were found using only rare variants that contains an optimal codon in among minor alleles and a non-optimal codon in the major allele. These results suggest that codon bias may play a role in AD and that it can be used to improve detection power in rare variant association analysis

Gene-based GWAS and -biological pathway analysis of the resilience of executive functioning

Resilience in executive functioning (EF) is characterized by high EF measured by neuropsychological test performance despite structural brain damage from neurodegenerative conditions. We previously reported single nucleotide polymorphism (SNP) genome-wide association study (GWAS) results for EF resilience. Here, we report gene- and pathway-based analyses of the same resilience phenotype, using an optimal SNP-set (Sequence) Kernel Association Test (SKAT) for gene-based analyses (conservative threshold for genome-wide significance = 0.05/18,123=2.8×10−6) and the gene-set enrichment package GSA-SNP for biological pathway analyses (False discovery rate (FDR) < 0.05). Gene-based analyses found a genome-wide significant association between RNASE13 and EF resilience (p=1.33×10−7). Genetic pathways involved with dendritic/neuron spine, presynaptic membrane, postsynaptic density etc. were enriched with association to EF resilience. Although replication of these results is necessary, our findings indicate the potential value of gene- and pathway-based analyses in research on determinants of cognitive resilience

Analysis of the Inverse Association between Cancer and Alzheimer’s Disease: Results from the Alzheimer’s Disease Neuroimaging Initiative Cohort

poster abstractAlthough a number of studies support a reciprocal inverse association between diagnoses of cancer and Alzheimer’s disease (AD), to date there has not been any systemic investigation of the neurobiological impact of or genetic risk factors underlying this effect. To facilitate this goal, this study aimed to replicate the inverse association of cancer and AD using data from the NIA Alzheimer’s Disease Neuroimaging Initiative, which includes age-matched cases and controls with information on cancer history, AD progression, neuroimaging, and genomic data. Subjects included individuals with AD (n=234), mild cognitive impairment (MCI, n=542), and healthy controls (HC, n=293). After controlling for sex, education, race/ethnicity, smoking, and apolipoprotein E (APOE) e2/3/4 allele groups, cancer history was protective against baseline AD diagnosis (p=0.042), and was associated with later age of AD onset (p=0.001). Cancer history appears to result in a cumulative protective effect; individuals with more than one cancer had a later age of AD onset compared to those with only one cancer (p=0.001). Finally, a protective effect of AD was also observed in individuals who developed incident cancer after enrolling (post-baseline visit); 20 individuals with MCI and 9 HC developed cancer, while no AD patients had subsequent cancer diagnoses (p=0.013). This supports previous research on the inverse association of cancer and AD, and importantly provides novel evidence that this effect appears to be independent of APOE, the major known genetic risk factor for AD. Future analyses will investigate the neurobiological and genetic basis of this effect

Spin-dynamics simulations of the triangular antiferromagnetic XY model

Using Monte Carlo and spin-dynamics methods, we have investigated the dynamic behavior of the classical, antiferromagnetic XY model on a triangular lattice with linear sizes $L \leq 300$. The temporal evolutions of spin configurations were obtained by solving numerically the coupled equations of motion for each spin using fourth-order Suzuki-Trotter decompositions of exponential operators. From space- and time-displaced spin-spin correlation functions and their space-time Fourier transforms we obtained the dynamic structure factor $S({\bf q},w)$ for momentum ${\bf q}$ and frequency $\omega$. Below $T_{KT}$(Kosterlitz-Thouless transition), both the in-plane ($S^{xx}$) and the out-of-plane ($S^{zz}$) components of $S({\bf q},\omega)$ exhibit very strong and sharp spin-wave peaks. Well above $T_{KT}$, $S^{xx}$ and $S^{zz}$ apparently display a central peak, and spin-wave signatures are still seen in $S^{zz}$. In addition, we also observed an almost dispersionless domain-wall peak at high $\omega$ below $T_{c}$(Ising transition), where long-range order appears in the staggered chirality. Above $T_{c}$, the domain-wall peak disappears for all $q$. The lineshape of these peaks is captured reasonably well by a Lorentzian form. Using a dynamic finite-size scaling theory, we determined the dynamic critical exponent $z$ = 1.002(3). We found that our results demonstrate the consistency of the dynamic finite-size scaling theory for the characteristic frequeny $\omega_{m}$ and the dynamic structure factor $S({\bf q},\omega)$ itself.Comment: 8 pages, RevTex, 10 figures, submitted to PR

Critical behavior of the planar magnet model in three dimensions

We use a hybrid Monte Carlo algorithm in which a single-cluster update is combined with the over-relaxation and Metropolis spin re-orientation algorithm. Periodic boundary conditions were applied in all directions. We have calculated the fourth-order cumulant in finite size lattices using the single-histogram re-weighting method. Using finite-size scaling theory, we obtained the critical temperature which is very different from that of the usual XY model. At the critical temperature, we calculated the susceptibility and the magnetization on lattices of size up to $42^3$. Using finite-size scaling theory we accurately determine the critical exponents of the model and find that $\nu$=0.670(7), $\gamma/\nu$=1.9696(37), and $\beta/\nu$=0.515(2). Thus, we conclude that the model belongs to the same universality class with the XY model, as expected.Comment: 11 pages, 5 figure

Initiation of antidepressant medication and risk of incident stroke: using the Adult Changes in Thought cohort to address time-varying confounding

Purpose Depression strongly predicts stroke incidence, suggesting that treating depression may reduce stroke risk. Antidepressant medications, however, may increase stroke risk via direct pathways. Previous evidence on antidepressant medication and stroke incidence is mixed. We evaluated associations between antidepressant use and incident stroke. Methods For 2302 Adult Changes in Thought cohort participants with no stroke at study entry, we characterized antidepressant use from pharmacy records, biennial depressive symptoms with a 10-item Centers for Epidemiologic Study–Depression scale, and incident strokes from ICD codes. We used discrete-time survival models with inverse probability weighting to compare stroke risk associated with filling antidepressant prescriptions and by medication category: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors, or other. Results Over an average 8.4-year follow-up, 441 incident strokes occurred. Filling antidepressant medications 3+ times versus 0–2 times predicted 35% increased odds of stroke (OR = 1.35; 95% CI: 0.98, 1.66). Use of TCAs was associated with stroke onset (OR per 10 fills = 1.28; CI: 1.04, 1.57), but use of selective serotonin reuptake inhibitors (OR = 0.98; CI: 0.80, 1.20) or other antidepressants (OR = 0.99; CI: 0.67, 1.45) was not. Conclusions Although patients who received antidepressant medication were at higher risk of stroke, this association appeared specific to TCA prescriptions