Prevalence and risk factors for refractive errors and their associations with major age-related eye diseases in adult Singapore Indians

Ph.DDOCTOR OF PHILOSOPH

A Mid-infrared Flare in the Active Galaxy MCG-02-04-026: Dust Echo of a Nuclear Transient Event

We report the discovery of a mid-infrared (MIR) flare using Wide field Infrared Survey Explorer data in the center of the nearby Seyfert 1.9 galaxy MCG-02-04-026. The MIR flare began in the first half of 2014, peaked around the end of 2015, and faded in 2017. During these years, energy of more than 7 × 10⁵⁰ erg was released in the infrared, and the flare's MIR color was generally turning red. We detected neither optical nor ultraviolet (UV) variation corresponding to the MIR flare based on available data. We explained the MIR flare using a dust echo model in which the radiative transfer is involved. The MIR flare can be well explained as thermal reradiation from dust heated by UV–optical photons of a primary nuclear transient event. Although the transient event was not seen directly owing to dust obscuration, we can infer that it may produce a total energy of at least ~10⁵¹ erg, most of which was released in less than ~3 yr. The nature of the transient event could be a stellar tidal disruption event by the central supermassive black hole (SMBH), or a sudden enhancement of the existing accretion flow onto the SMBH, or a supernova that was particularly bright

A Mid-infrared Flare in the Active Galaxy MCG-02-04-026: Dust Echo of a Nuclear Transient Event

We report the discovery of a mid-infrared (MIR) flare using WISE data in the center of the nearby Seyfert 1.9 galaxy MCG-02-04-026. The MIR flare began in the first half of 2014, peaked around the end of 2015, and faded in 2017. During these years, energy more than $7\times10^{50}$ erg was released in the infrared, and the flare's MIR color was generally turning red. We detected neither optical nor ultraviolet (UV) variation corresponding to the MIR flare based on available data. We explained the MIR flare using a dust echo model in which the radiative transfer is involved. The MIR flare can be well explained as thermal reradiation from dust heated by UV-optical photons of a primary nuclear transient event. Although the transient event was not seen directly due to dust obscuration, we can infer that it may produce a total energy of at least $\sim10^{51}$ erg, most of which was released in less than $\sim$3 years. The nature of the transient event could be a stellar tidal disruption event by the central supermassive black hole (SMBH), or a sudden enhancement of the existing accretion flow onto the SMBH, or a supernova which was particularly bright.Comment: 44 pages, 13 figures; Accepted to be published in Ap

Gene Regulation and Epigenetic Remodeling in Murine Embryonic Stem Cells by c-Myc

BACKGROUND:The Myc oncoprotein, a transcriptional regulator involved in the etiology of many different tumor types, has been demonstrated to play an important role in the functions of embryonic stem (ES) cells. Nonetheless, it is still unclear as to whether Myc has unique target and functions in ES cells. METHODOLOGY/PRINCIPAL FINDINGS:To elucidate the role of c-Myc in murine ES cells, we mapped its genomic binding sites by chromatin-immunoprecipitation combined with DNA microarrays (ChIP-chip). In addition to previously identified targets we identified genes involved in pluripotency, early development, and chromatin modification/structure that are bound and regulated by c-Myc in murine ES cells. Myc also binds and regulates loci previously identified as Polycomb (PcG) targets, including genes that contain bivalent chromatin domains. To determine whether c-Myc influences the epigenetic state of Myc-bound genes, we assessed the patterns of trimethylation of histone H3-K4 and H3-K27 in mES cells containing normal, increased, and reduced levels of c-Myc. Our analysis reveals widespread and surprisingly diverse changes in repressive and activating histone methylation marks both proximal and distal to Myc binding sites. Furthermore, analysis of bulk chromatin from phenotypically normal c-myc null E7 embryos demonstrates a 70-80% decrease in H3-K4me3, with little change in H3-K27me3, compared to wild-type embryos indicating that Myc is required to maintain normal levels of histone methylation. CONCLUSIONS/SIGNIFICANCE:We show that Myc induces widespread and diverse changes in histone methylation in ES cells. We postulate that these changes are indirect effects of Myc mediated by its regulation of target genes involved in chromatin remodeling. We further show that a subset of PcG-bound genes with bivalent histone methylation patterns are bound and regulated in response to altered c-Myc levels. Our data indicate that in mES cells c-Myc binds, regulates, and influences the histone modification patterns of genes involved in chromatin remodeling, pluripotency, and differentiation

Enhancement of Diffusion Assisted Bonding of the Bimetal Composite of Austenitic/Ferric Steels via Intrinsic Interlayers

We investigate the effect of the intrinsic interlayers on the diffusion assisted bonding properties of the austenitic steel (stainless steel 316L) and ferric steels (Low-carbon steel Q345R) in a hot rolling process by molecular dynamics simulations and experiment. The introduction of an intrinsic interlayer (Cr or Ni) widens the diffusion region, leading to enhancement of bonding. The thickness of the diffusion region enlarges with an increase of temperature, with an enhancement factor of 195% and 108%, for Cr and Ni interlayer, respectively, at the temperature of 1800 K. Further diffusion analysis reveals the unsymmetrical diffusion near the interface. Our experimental investigation evidenced our computation discovery

Association of hysterectomy with nonalcoholic fatty liver disease among US women

Abstract Background A postmenopausal rise in the rates of nonalcoholic fatty liver disease (NAFLD) has been reported in women. This study thus sought to further probe the association of hysterectomy with NAFLD. Methods The data utilized in this investigation were attained from the 2017-March 2020 cycle of the National Health and Nutrition Examination Survey (NHANES), reflecting a strategic utilization of comprehensive health and nutrition information in the US population, to conduct a cross-sectional examination of the relationship between self-reported hysterectomy and NAFLD. Subjects included in this study were women aged 20 years or older. The multivariable logistic regression methodologies were utilized to determine the pertinent odds ratios (ORs) and their associated 95% confidence intervals (CIs). Results Of the 2,868 subjects enrolled in this study (mean age: 51.3 years, 95%CI: 50.0-52.6 years), 22.1% (95%CI: 19.7–24.7%) reported having undergone a hysterectomy, while 31.1% (95%CI: 28.1–34.1%) exhibited elastographic evidence of NAFLD, and 3.8% (95%CI: 2.6–5.6%) exhibited clinically significant fibrosis (CSF). Relative to women with no history of hysterectomy, those that had undergone hysterectomy exhibited a higher odd of NAFLD (OR:1.66, 95%CI: 1.24–2.21) in a multivariable model fully adjusted for age, ethnicity, body mass index, female hormone use, oophorectomy, diabetes, hyperlipidemia, and smoking status. Subgroup analyses revealed a stronger association among women who were not obese (OR:2.23, 95%CI:1.61–3.11), women who were not affected by diabetes (OR:1.76, 95%CI: 1.25–2.46), and without hyperlipidemia (OR: 1.87, 95%CI: 1.10–3.16). No significant association of hysterectomy with NAFLD encompassing CSF was identified. Conclusions The results of the present nationally representative analysis suggested an association between hysterectomy and increased NAFLD prevalence among US women. Knowledge of this relationship may better aid clinical efforts to screen for and manage NAFLD

Enhanced expression of cystathionine β-synthase and cystathionine γ-lyase during acute cholecystitis-induced gallbladder inflammation.

BACKGROUND: Hydrogen sulfide (H2S) has recently been shown to play an important role in the digestive system, but the role of endogenous H2S produced locally in the gallbladder is unknown. The aim of this study was to investigate whether gallbladder possesses the enzymatic machinery to synthesize H2S, and whether H2S synthesis is changed in gallbladder inflammation during acute acalculous cholecystitis (AC). METHODS: Adult male guinea pigs underwent either a sham operation or common bile duct ligation (CBDL). One, two, or three days after CBDL, the animals were sacrificed separately. Hematoxylin and eosin-stained slides of gallbladder samples were scored for inflammation. H2S production rate in gallbladder tissue from each group was determined; immunohistochemistry and western blotting were used to determine expression levels of the H2S-producing enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in gallbladder. RESULTS: There was a progressive inflammatory response after CBDL. Immunohistochemistry analysis showed that CBS and CSE were expressed in the gallbladder epithelium, muscular layer, and blood vessels and that the expression increased progressively with increasing inflammation following CBDL. The expression of CBS protein as well as the H2S-production rate was significantly increased in the animals that underwent CBDL, compared to those that underwent the sham operation. CONCLUSIONS: Both CBS and CSE are expressed in gallbladder tissues. The expression of these enzymes, as well as H2S synthesis, was up-regulated in the context of inflammation during AC

Active Immunization against Transforming Growth Factor-beta1 Prevents Hepatic Fibrosis in a Rat Model of Liver Disease

Transforming growth factor-beta1 (TGF-β1) plays an important role in hepatic fibrogenesis. To document the effects of active immunization against TGF-β1 on hepatic fibrosis in an animal model of chronic liver disease. BALB/c mice were immunized against three different peptides of TGF-β1 ligated into hepatitis B virus core protein (HBVc). Titers of TGF-β1 antibodies were documented by enzyme linked immunoassays and antibody activity by cell membrane receptor binding and proliferation assays. The most immunogenic recombinant HBVc+TGF-β1 peptide (HBVc+C) then served as a vaccine in Sprague-Dawley rats with dimethylnitrosamine-induced chronic liver disease. Hepatic fibrosis was documented by serum hyaluronic acid levels, liver histology and real time polymerase chain reaction for hepatic collagen 1(α1) and alpha-smooth muscle actin mRNA expression. Relative to control rats vaccinated with HBVc alone, recombinant HBVc+C vaccinated animals had significantly lower serum hyaluronic acid levels, less histologic evidence of hepatic fibrosis and reduced expression of collagen type 1(α1) and alpha-smooth muscle actin mRNA in the liver. The results of this proof-of-concept study suggest that active immunization against TGF-β1 is a worthwhile strategy to pursue in efforts to prevent hepatic fibrosis associated with chronic liver disease.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author