- Browse by Author
Browsing by Author "Zhang, Jian"
Now showing 1 - 10 of 27
Results Per Page
Sort Options
Item Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood(MDPI, 2019-10-17) Meyers, Jacquelyn L.; Chorlian, David B.; Johnson, Emma C.; Pandey, Ashwini K.; Kamarajan, Chella; Salvatore, Jessica E.; Aliev, Fazil; Subbie-Saenz de Viteri, Stacey; Zhang, Jian; Chao, Michael; Kapoor, Manav; Hesselbrock, Victor; Kramer, John; Kuperman, Samuel; Nurnberger, John; Tischfield, Jay; Goate, Alison; Foroud, Tatiana; Dick, Danielle M.; Edenberg, Howard J.; Agrawal, Arpana; Porjesz, Bernice; Medical and Molecular Genetics, School of MedicineDifferences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18-31 (beta coefficients ranged from 0.02-0.06, p-values ranged from 10-6-10-12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective.Item Atomistic Modeling of Anisotropic Mechanical Properties of Lanthanum Zirconate Nanocystal(Elsevier, 2021-02) Guo, Xingye; Zhang, Jian; Park, Hye-Yeong; Jung, Yeon-Gil; Zhang, Jing; Mechanical and Energy Engineering, School of Engineering and TechnologyLanthanum zirconate (La2Zr2O7, or LZ) has been widely recognized as a promising candidate material for thermal barrier coating (TBC) applications since it has low thermal conductivity, high-temperature phase stability, and low sintering activity. However, the mechanical properties of LZ crystal have not been fully understood, which hinders it from future applications. In this work, atomistic simulations were performed to study the anisotropic mechanical properties of LZ crystal. Using both the first principles and molecular dynamics (MD) calculations, uniaxial tensile tests of LZ crystal in [001], [011], and [111] directions were simulated. The stress-strain curves of the tensile tests were calculated, and the ultimate tensile strength and toughness were derived. The Young's moduli in [001], [011], and [111] directions were calculated using both the stress-strain curves and an analytical method for small deformation. Additionally, shear stress-strain curves in {111}<110> and {111}<112> directions were investigated using both the first principles calculations and the MD method. Results show that Young's modulus of LZ crystal is highly anisotropic. The crystal has the highest Young's modulus in [111] direction, and {111}<112> direction is the favorable slip system during shear deformations.Item Clinical, genomic, and neurophysiological correlates of lifetime suicide attempts among individuals with alcohol dependence(medRxiv, 2023-04-29) Barr, Peter B.; Neale, Zoe; Schulman, Jessica; Mullins, Niamh; Zhang, Jian; Chorlian, David B.; Kamarajan, Chella; Kinreich, Sivan; Pandey, Ashwini K.; Pandey, Gayathri; Saenz de Viteri, Stacey; Acion, Laura; Bauer, Lance; Bucholz, Kathleen K.; Chan, Grace; Chao, Michael; Dick, Danielle M.; Edenberg, Howard J.; Foroud, Tatiana; Goate, Alison; Hesselbrock, Victor; Johnson, Emma C.; Kramer, John; Lai, Dongbing; Plawecki, Martin H.; Salvatore, Jessica E.; Wetherill, Leah; Agrawal, Arpana; Porjesz, Bernice; Meyers, Jacquelyn L.; Medical and Molecular Genetics, School of MedicineResearch has identified clinical, genomic, and neurophysiological markers associated with suicide attempts (SA) among individuals with psychiatric illness. However, there is limited research among those with an alcohol use disorder, despite their disproportionately higher rates of SA. We examined lifetime SA in 4,068 individuals with DSM-IV alcohol dependence from the Collaborative Study on the Genetics of Alcoholism (23% lifetime suicide attempt; 53% female; 17% Admixed African American ancestries; mean age: 38). We 1) explored clinical risk factors associated with SA, 2) conducted a genome-wide association study of SA, 3) examined whether individuals with a SA had elevated polygenic scores for comorbid psychiatric conditions (e.g., alcohol use disorders, lifetime suicide attempt, and depression), and 4) explored differences in electroencephalogram neural functional connectivity between those with and without a SA. One gene-based finding emerged, RFX3 (Regulatory Factor X, located on 9p24.2) which had supporting evidence in prior research of SA among individuals with major depression. Only the polygenic score for suicide attempts was associated with reporting a suicide attempt (OR = 1.20, 95% CI = 1.06, 1.37). Lastly, we observed decreased right hemispheric frontal-parietal theta and decreased interhemispheric temporal-parietal alpha electroencephalogram resting-state coherences among those participants who reported a SA relative to those who did not, but differences were small. Overall, individuals with alcohol dependence who report SA appear to experience a variety of severe comorbidities and elevated polygenic risk for SA. Our results demonstrate the need to further investigate suicide attempts in the presence of substance use disorders.Item Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder.(NPG, 2015-11-05) Mertens, Jerome; Wang, Qiu-Wen; Kim, Yongsung; Yu, Diana X.; Pham, Son; Yang, Bo; Zheng, Yi; Diffenderfer, Kenneth E.; Zhang, Jian; Soltani, Sheila; Eames, Tameji; Schafer, Simon T.; Boyer, Leah; Marchetto, Maria C.; Nurnberger, John I.; Calabrese, Joseph R.; Oedegaard, Ketil J.; McCarthy, Michael J.; Zandi, Peter P.; Alda, Martin; Nievergelt, Caroline M.; Mi, Shuangli; Brennand, Kristen J.; Kelsoe, John R.; Gage, Fred H.; Yao, Jun; Department of Psychiatry, IU School of MedicineBipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide. Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity. Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models, such as reduced glial cell number in the prefrontal cortex of patients, upregulated activities of the protein kinase A and C pathways and changes in neurotransmission. However, the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease. Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge. The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach. Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder. Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca2+ imaging, we have observed hyperactive action-potential firing. This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment. Therefore, hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.Item Direct observation of the magnetic anisotropy of an Fe(II) spin crossover molecular thin film(IOPP, 2023-07) Dale, Ashley S.; Yazdani, Saeed; Ekanayaka, Thinlini K.; Mishra, Esha; Hu, Yuchen; Dowben, Peter A.; Freeland, John W.; Zhang, Jian; Cheng, Ruihua; Physics, School of ScienceIn this work, we provide clear evidence of magnetic anisotropy in the local orbital moment of a molecular thin film based on the SCO complex [Fe(H2B(pz)2)2(bipy)] (pz = pyrazol−1−yl, bipy = 2,2'−bipyridine). Field dependent x-ray magnetic circular dichroism measurements indicate that the magnetic easy axis for the orbital moment is along the surface normal direction. Along with the presence of a critical field, our observation points to the existence of an anisotropic energy barrier in the high-spin state. The estimated nonzero coupling constant of ∼2.47 × 10−5 eV molecule−1 indicates that the observed magnetocrystalline anisotropy is mostly due to spin–orbit coupling. The spin- and orbital-component anisotropies are determined to be 30.9 and 5.04 meV molecule−1, respectively. Furthermore, the estimated g factor in the range of 2.2–2.45 is consistent with the expected values. This work has paved the way for an understanding of the spin-state-switching mechanism in the presence of magnetic perturbations.Item Finite Element Modeling of Coating Thickness Using Heat Transfer Method(Elsevier, 2021-01) Li, Yafeng; Dhulipalla, Anvesh; Zhang, Jian; Park, Hye-Yeong; Jung, Yeon-Gil; Koo, Dan Daehyun; Zhang, Jing; Mechanical and Energy Engineering, School of Engineering and TechnologyA new heat transfer based finite element model is proposed to simulate coating thickness in the electron-beam physical vapor deposition (EB-PVD) process. The major advantage of the proposed model is that it is much computationally efficient than the traditional ray-tracing based model by about two orders of magnitude. This is because the Gaussian distribution heating source has the same profile as the cosine relation used in the ray-tracing method. Firstly, the model simulates the temperature profile of a metal substrate heated by a heating source with a Gaussian distribution. Then using a calibrated conversion process, the temperature profile is converted to corresponding coating thickness. The model is successfully demonstrated by three validation cases, including a stationary disk, a stationary cylinder, and a rotary three-pin component. The predicted coating thicknesses in the validation cases are in good agreement with either the ray-tracing based analytical solution or experimental data. After its validation, the model is applied to a rotary turbine blade to predict its coating thickness distribution. In summary, the model is capable to simulate coating thickness in complex shaped parts.Item Gaussian Process-Based Model to Optimize Additively Manufactured Powder Microstructures From Phase Field Modeling(ASME, 2022-03) Batabyal, Arunabha; Sagar, Sugrim; Zhang, Jian; Dube, Tejesh; Yang, Xuehui; Zhang, Jing; Mechanical Engineering, School of Engineering and TechnologyA persistent problem in the selective laser sintering process is to maintain the quality of additively manufactured parts, which can be attributed to the various sources of uncertainty. In this work, a two-particle phase-field microstructure model has been analyzed using a Gaussian process-based model. The sources of uncertainty as the two input parameters were surface diffusivity and interparticle distance. The response quantity of interest (QOI) was selected as the size of the neck region that develops between the two particles. Two different cases with equal and unequal-sized particles were studied. It was observed that the neck size increased with increasing surface diffusivity and decreased with increasing interparticle distance irrespective of particle size. Sensitivity analysis found that the interparticle distance has more influence on variation in neck size than that of surface diffusivity. The machine learning algorithm Gaussian process regression was used to create the surrogate model of the QOI. Bayesian optimization method was used to find optimal values of the input parameters. For equal-sized particles, optimization using Probability of Improvement provided optimal values of surface diffusivity and interparticle distance as 23.8268 and 40.0001, respectively. The Expected Improvement as an acquisition function gave optimal values of 23.9874 and 40.7428, respectively. For unequal-sized particles, optimal design values from Probability of Improvement were 23.9700 and 33.3005, respectively, while those from Expected Improvement were 23.9893 and 33.962, respectively. The optimization results from the two different acquisition functions seemed to be in good agreement.Item A genome wide association study of fast beta EEG in families of European ancestry(Elsevier, 2017-05) Meyers, Jacquelyn L.; Zhang, Jian; Manz, Niklas; Rangaswamy, Madhavi; Kamarajan, Chella; Wetherill, Leah; Chorlian, David B.; Kang, Sun J.; Bauer, Lance; Hesselbrock, Victor; Kramer, John; Kuperman, Samuel; Nurnberger, John I., Jr.; Tischfield, Jay; Wang, Jen Chyong; Edenberg, Howard J.; Goate, Alison; Foroud, Tatiana; Porjesz, Bernice; Medical and Molecular Genetics, School of MedicineBACKGROUND: Differences in fast beta (20-28Hz) electroencephalogram (EEG) oscillatory activity distinguish some individuals with psychiatric and substance use disorders, suggesting that it may be a useful endophenotype for studying the genetics of disorders characterized by neural hyper-excitability. Despite the high heritability estimates provided by twin and family studies, there have been relatively few genetic studies of beta EEG, and to date only one genetic association finding has replicated (i.e., GABRA2). METHOD: In a sample of 1564 individuals from 117 families of European Ancestry (EA) drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Genome-Wide Association Study (GWAS) on resting-state fronto-central fast beta EEG power, adjusting regression models for family relatedness, age, sex, and ancestry. To further characterize genetic findings, we examined the functional and behavioral significance of GWAS findings. RESULTS: Three intronic variants located within DSE (dermatan sulfate epimerase) on 6q22 were associated with fast beta EEG at a genome wide significant level (p<5×10-8). The most significant SNP was rs2252790 (p<2.6×10-8; MAF=0.36; β=0.135). rs2252790 is an eQTL for ROS1 expressed most robustly in the temporal cortex (p=1.2×10-6) and for DSE/TSPYL4 expressed most robustly in the hippocampus (p=7.3×10-4; β=0.29). Previous studies have indicated that DSE is involved in a network of genes integral to membrane organization; gene-based tests indicated that several variants within this network (i.e., DSE, ZEB2, RND3, MCTP1, and CTBP2) were also associated with beta EEG (empirical p<0.05), and of these genes, ZEB2 and CTBP2 were associated with DSM-V Alcohol Use Disorder (AUD; empirical p<0.05).' DISCUSSION: In this sample of EA families enriched for AUDs, fast beta EEG is associated with variants within DSE on 6q22; the most significant SNP influences the mRNA expression of DSE and ROS1 in hippocampus and temporal cortex, brain regions important for beta EEG activity. Gene-based tests suggest evidence of association with related genes, ZEB2, RND3, MCTP1, CTBP2, and beta EEG. Converging data from GWAS, gene expression, and gene-networks presented in this study provide support for the role of genetic variants within DSE and related genes in neural hyperexcitability, and has highlighted two potential candidate genes for AUD and/or related neurological conditions: ZEB2 and CTBP2. However, results must be replicated in large, independent samples.Item A Genome Wide Association Study of Interhemispheric Theta EEG Coherence: Implications for Neural Connectivity and Alcohol Use Behavior(Springer Nature, 2021) Meyers, Jacquelyn L.; Zhang, Jian; Chorlian, David B.; Pandey, Ashwini K.; Kamarajan, Chella; Wang, Jen-Chyong; Wetherill, Leah; Lai, Dongbing; Chao, Michael; Chan, Grace; Kinreich, Sivan; Kapoor, Manav; Bertelsen, Sarah; McClintick, Jeanette; Bauer, Lance; Hesselbrock, Victor; Kuperman, Samuel; Kramer, John; Salvatore, Jessica E.; Dick, Danielle M.; Agrawal, Arpana; Foroud, Tatiana; Edenberg, Howard J.; Goate, Alison; Porjesz, Bernice; Medical and Molecular Genetics, School of MedicineAberrant connectivity of large-scale brain networks has been observed among individuals with alcohol use disorders (AUDs) as well as in those at risk, suggesting deficits in neural communication between brain regions in the liability to develop AUD. Electroencephalographical (EEG) coherence, which measures the degree of synchrony between brain regions, may be a useful measure of connectivity patterns in neural networks for studying the genetics of AUD. In 8810 individuals (6644 of European and 2166 of African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Multi-Trait Analyses of genome-wide association studies (MTAG) on parietal resting-state theta (3-7 Hz) EEG coherence, which previously have been associated with AUD. We also examined developmental effects of GWAS findings on trajectories of neural connectivity in a longitudinal subsample of 2316 adolescent/young adult offspring from COGA families (ages 12-30) and examined the functional and clinical significance of GWAS variants. Six correlated single nucleotide polymorphisms located in a brain-expressed lincRNA (ENSG00000266213) on chromosome 18q23 were associated with posterior interhemispheric low theta EEG coherence (3-5 Hz). These same variants were also associated with alcohol use behavior and posterior corpus callosum volume, both in a subset of COGA and in the UK Biobank. Analyses in the subsample of COGA offspring indicated that the association of rs12954372 with low theta EEG coherence occurred only in females, most prominently between ages 25 and 30 (p < 2 × 10-9). Converging data provide support for the role of genetic variants on chromosome 18q23 in regulating neural connectivity and alcohol use behavior, potentially via dysregulated myelination. While findings were less robust, genome-wide associations were also observed with rs151174000 and parieto-frontal low theta coherence, rs14429078 and parieto-occipital interhemispheric high theta coherence, and rs116445911 with centro-parietal low theta coherence. These novel genetic findings highlight the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.Item IL-33 promotes the egress of group 2 innate lymphoid cells from the bone marrow(Rockefeller University Press, 2018-01-02) Stier, Matthew T.; Zhang, Jian; Goleniewska, Kasia; Cephus, Jacqueline Y.; Rusznak, Mark; Wu, Lan; Kaer, Luc Van; Zhou, Baohua; Newcomb, Dawn C.; Peebles, R. Stokes, Jr.; Pediatrics, School of MedicineGroup 2 innate lymphoid cells (ILC2s) are effector cells within the mucosa and key participants in type 2 immune responses in the context of allergic inflammation and infection. ILC2s develop in the bone marrow from common lymphoid progenitor cells, but little is known about how ILC2s egress from the bone marrow for hematogenous trafficking. In this study, we identified a critical role for IL-33, a hallmark peripheral ILC2-activating cytokine, in promoting the egress of ILC2 lineage cells from the bone marrow. Mice lacking IL-33 signaling had normal development of ILC2s but retained significantly more ILC2 progenitors in the bone marrow via augmented expression of CXCR4. Intravenous injection of IL-33 or pulmonary fungal allergen challenge mobilized ILC2 progenitors to exit the bone marrow. Finally, IL-33 enhanced ILC2 trafficking to the lungs in a parabiosis mouse model of tissue disruption and repopulation. Collectively, these data demonstrate that IL-33 plays a critical role in promoting ILC2 egress from the bone marrow.
- «
- 1 (current)
- 2
- 3
- »