Sanghyeon Kim

The Stanley Neuropathology Consortium Integrative Database: a Novel, Web-Based Tool for Exploring Neuropathological Markers in Psychiatric Disorders and the Biological Processes Associated with Abnormalities of Those Markers

An integrative database, Stanley Neuropathology Consortium Integrative Database (SNCID) (http://sncid.stanleyresearch.org), has been developed to facilitate psychiatric research. The SNCID includes 1749 neuropathological markers measured in 12 different brain regions in 60 human subjects (15 each schizophrenia, bipolar disorder, depression, and unaffected controls). Genome-wide expression microarray datasets from three independent studies are also included. Statistical analysis tools such as variance analysis, correlation analysis, and functional annotation tools have been integrated into the database. In this report, we first replicate an earlier correlation analysis between genome-wide expression profiles and an abnormal cytoarchitectural marker using the SNCID. We then show the potential for identifying neuropathological markers that are abnormal in subjects with psychiatric disorders. We also identify biological pathways associated with several abnormal neuropathological markers, including those in the dopamine, glutamate, Reelin, and γ-aminobutyric acid (GABA)ergic systems. Data exploration using the SNCID may provide insights into the biological pathways associated with the neurotransmitter abnormalities identified in subjects with major psychiatric disorders.

Putative psychosis genes in the prefrontal cortex: combined analysis of gene expression microarrays

BackgroundRecent studies have shown similarities between schizophrenia and bipolar disorder in phenotypes and in genotypes, and those studies have contributed to an ongoing re-evaluation of the traditional dichotomy between schizophrenia and bipolar disorder. Bipolar disorder with psychotic features may be closely related to schizophrenia and therefore, psychosis may be an alternative phenotype compared to the traditional diagnosis categories.MethodsWe performed a cross-study analysis of 7 gene expression microarrays that include both psychosis and non-psychosis subjects. These studies include over 400 microarray samples (163 individual subjects) on 3 different Affymetrix microarray platforms.ResultsWe found that 110 transcripts are differentially regulated (p < 0.001) in psychosis after adjusting for confounding variables with a multiple regression model. Using a quantitative PCR, we validated a set of genes such as up-regulated metallothioneins (MT1E, MT1F, MT1H, MT1K, MT1X, MT2A and MT3) and down-regulated neuropeptides (SST, TAC1 and NPY) in the dorsolateral prefrontal cortex of psychosis patients.ConclusionThis study demonstrates the advantages of cross-study analysis in detecting consensus changes in gene expression across multiple microarray studies. Differential gene expression between individuals with and without psychosis suggests that psychosis may be a useful phenotypic variable to complement the traditional diagnosis categories.

A ferroelectric photocatalyst for enhancing hydrogen evolution: polarized particulate suspension

A particle-based photocatalyst with a permanent internal field prepared by a corona poling method is presented as a novel approach to enhance the hydrogen evolution reaction in a particulate-suspension system. Photocatalytic activity of K0.5Na0.5NbO3 was significantly improved by 7.4 times after the polarization.

Association between SNPs and gene expression in multiple regions of the human brain

Identifying the genetic cis associations between DNA variants (single-nucleotide polymorphisms (SNPs)) and gene expression in brain tissue may be a promising approach to find functionally relevant pathways that contribute to the etiology of psychiatric disorders. In this study, we examined the association between genetic variations and gene expression in prefrontal cortex, hippocampus, temporal cortex, thalamus and cerebellum in subjects with psychiatric disorders and in normal controls. We identified cis associations between 648 transcripts and 6725 SNPs in the various brain regions. Several SNPs showed brain regional-specific associations. The expression level of only one gene, PDE4DIP, was associated with a SNP, rs12124527, in all the brain regions tested here. From our data, we generated a list of brain cis expression quantitative trait loci (eQTL) genes that we compared with a list of schizophrenia candidate genes downloaded from the Schizophrenia Forum (SZgene) database (http://www.szgene.org/). Of the SZgene candidate genes, we found that the expression levels of four genes, HTR2A, PLXNA2, SRR and TCF4, were significantly associated with cis SNPs in at least one brain region tested. One gene, SRR, was also involved in a coexpression module that we found to be associated with disease status. In addition, a substantial number of cis eQTL genes were also involved in the module, suggesting eQTL analysis of brain tissue may identify more reliable susceptibility genes for schizophrenia than case–control genetic association analyses. In an attempt to facilitate the identification of genetic variations that may underlie the etiology of major psychiatric disorders, we have integrated the brain eQTL results into a public and online database, Stanley Neuropathology Consortium Integrative Database (SNCID; http://sncid.stanleyresearch.org).

Ultra-high-throughput Production of III-V/Si Wafer for Electronic and Photonic Applications

Si-based integrated circuits have been intensively developed over the past several decades through ultimate device scaling. However, the Si technology has reached the physical limitations of the scaling. These limitations have fuelled the search for alternative active materials (for transistors) and the introduction of optical interconnects (called “Si photonics”). A series of attempts to circumvent the Si technology limits are based on the use of III-V compound semiconductor due to their superior benefits, such as high electron mobility and direct bandgap. To use their physical properties on a Si platform, the formation of high-quality III-V films on the Si (III-V/Si) is the basic technology ; however, implementing this technology using a high-throughput process is not easy. Here, we report new concepts for an ultra-high-throughput heterogeneous integration of high-quality III-V films on the Si using the wafer bonding and epitaxial lift off (ELO) technique. We describe the ultra-fast ELO and also the re-use of the III-V donor wafer after III-V/Si formation. These approaches provide an ultra-high-throughput fabrication of III-V/Si substrates with a high-quality film, which leads to a dramatic cost reduction. As proof-of-concept devices, this paper demonstrates GaAs-based high electron mobility transistors (HEMTs), solar cells, and hetero-junction phototransistors on Si substrates.

Hierarchical assembly of TiO2-SrTiO3 heterostructures on conductive SnO2 backbone nanobelts for enhanced photoelectrochemical and photocatalytic performance.

Heterostructures can play a role in enhanced photoinduced electrochemical and catalytic reactions due to the advantageous combination of two compounds. Herein, we demonstrate the fabrication of Sb:SnO2@TiO2-SrTiO3 3D heterostructures via a simple hydrothermal method using a conductive Sb:SnO2@TiO2 nanobelt electrode as a template. XRD, FESEM, and TEM analyses confirm that a well-dispersed and crystalized SrTiO3 layer is formed on the surface of TiO2 nanorods. The photoelectrochemical (PEC) performance of the heterostructure is optimized by controlling the reaction time. Details about the effect of the hydrothermal reaction time on the PEC performance are discussed. The optimized Sb:SnO2@TiO2-SrTiO3 heterostructure exhibited a higher onset potential and a saturated photocurrent in comparison to the Sb:SnO2@TiO2 nanostructure. The result is attributed to a Fermi level shift and a blocking layer effect caused by the SrTiO3. Furthermore, the photocatalytic degradation of methylene blue was significantly enhanced on the optimized Sb:SnO2@TiO2-SrTiO3. This work demonstrates that a synergetic effect between three-dimensional nanoarchitecturing and a heterojunction structure is responsible for enhanced PEC as well as improved photocatalytic performance levels, both of which can be extended to other metal-oxide and/or ternary compounds.

Neuropathology markers and pathways associated with molecular targets for antipsychotic drugs in postmortem brain tissues: Exploration of drug targets through the Stanley Neuropathology Integrative Database

The atypical antipsychotics bind multiple receptor targets, including dopamine D₂ receptors (DRD2), 5-HT₂ receptors (HTR2A), α-2 adrenergic receptors (ADRA2A), and muscarinic receptors (CHRM1/4). Deficits in antipsychotic targets, their associated pathways, and the causal relationships between the various targets were explored using the Stanley Neuropathology Consortium Integrative Database (SNCID; http://sncid.stanleyresearch.org) and the Network Edge Orienting (NEO) software. There were brain region-specific deficits in the level of the antipsychotic targets, and the level of each target correlated with the mRNA level of the neurotrophic factor BDNF. While myelination was a common process correlated with both DRD2 mRNA levels and ADRA2A activity in the frontal cortex, metabolic processes were specifically correlated with DRD2 mRNA. Immune and inflammatory responses and apoptosis pathways were correlated with group II metabotropic glutamate receptors (GRM2), which are a target for the development of the next-generation antipsychotics. The NEO analysis revealed that HTR2A and GRM2 are likely to regulate BDNF levels in the hippocampus and frontal cortex, respectively, whereas DRD2 and ADRA2A activity are likely to be regulated by BDNF in the frontal cortex. BDNF may play an important role in mechanisms of action of the current antipsychotics and the next-generation antipsychotics that target GRM2. However, this data-mining approach indicates that the next-generation antipsychotics are likely to work through pathways that are distinct from those through which the current antipsychotics work. Exploratory analyses such as these may initiate future hypothesis-driven studies to reveal the mechanisms of action underlying the efficacy and side-effects of the antipsychotics.

Carrier lifetimes in dielectric cap disordered GaAs/AlGaAs multiple quantum well with SiN capping layers

Time resolved photoluminescence (PL) characteristics of a SiN cap disordered GaAs/AlGaAs multiple quantum well (MQW) structure exhibit a decrease in carrier lifetime in conjunction with an increase in quantum well disordering (QWD) as the SiN capping layer thickness is increased. The decrease in carrier lifetime is attributed to enhanced carrier trapping due to the defects introduced during dielectric cap quantum well disordering and the relaxation of the momentum conservation during radiative recombination by QWD. Potential applications of these effects on high speed optical devices such as laser diodes (LD’s) and optical modulators are discussed.

Somatic deletions implicated in functional diversity of brain cells of individuals with schizophrenia and unaffected controls

While somatic DNA copy number variations (CNVs) have been identified in multiple tissues from normal people, they have not been well studied in brain tissues from individuals with psychiatric disorders. With ultrahigh depth sequencing data, we developed an integrated pipeline for calling somatic deletions using data from multiple tissues of the same individual or a single tissue type taken from multiple individuals. Using the pipelines, we identified 106 somatic deletions in DNA from prefrontal cortex (PFC) and/or cerebellum of two normal controls subjects and/or three individuals with schizophrenia. We then validated somatic deletions in 18 genic and in 1 intergenic region. Somatic deletions in BOD1 and CBX3 were reconfirmed using DNA isolated from non-pyramidal neurons and from cells in white matter using laser capture microdissection (LCM). Our results suggest that somatic deletions may affect metabolic processes and brain development in a region specific manner.

Postmortem Brain Tissue for Drug Discovery in Psychiatric Research

Schizophrenia, bipolar disorder, and severe depression are common and extremely disabling diseases thought to be caused by an interaction of genetic and environmental factors. Medications currently available to treat these diseases produce varying degrees of symptom amelioration in most patients but often cause unwanted side effects. The need for more effective medications with fewer side effects is universally acknowledged.