Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI:C caused significant global DNA hypomethylation (t=2.44, P=0.019, PolyI:C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t=3.32, P=0.002; PolyI:C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment.

Extended abstract of a paper presented at Microscopy and Microanalysis 2006 in Chicago, Illinois, USA, July 30 – August 3, 2006

We have prepared FeSi2 precipitates of nanometer size in Si by ion implantation using a metal vapor vacuum arc (MEVVA) ion source and studied their photoluminescence properties. Broad photoluminescence (PL) spectra at around 1550 nm were observed for all samples attributed to emission from the FeSi2 precipitates. It was found that all the PL spectra can be decomposed into two peaks, a main peak at near 1530 nm and a satellite peak at 1607 nm. Samples with a furnace annealing (FA) step at a lower temperature of 850°C are found to have a main peak position at a longer wavelength close to 1540 nm. For samples with a FA step at higher temperatures, the main peak position shifts to shorter wavelengths of near 1525 nm. In addition, we have also prepared MOS structures with implanted FeSi2 precipitates incorporated in the structures and measured their EL properties. The EL properties from these FeSi2-Si MOS structures after various thermal treatments were measured as a function of temperature from 80 to 300 K. Our preliminary results show that clear EL signals are obtained even at room temperature under appropriate processing conditions.

Composite films consisting of Si nanoclusters embedded in silicon oxide (also known as silicon rich oxide (SRO)) have attracted much attention due to their potential technological importance in the Si-based optoelectronic industry. The annealing process significantly affects the luminescence of the SRO films, causing major changes in the integrated luminescence intensity and the peak wavelength. The effect of annealing has been generally summarized as the generation of Si nanocrystals hosted in the SiO 2 matrix, followed by a nanocrystal growth process as the annealing temperature increases [1]. The luminescence has always been ascribed to the radiative recombination process in the Si nanocrystals or at the interface [2]. However, it has been found that even the low temperature (well below what would be expected to generate the Si nanocrystals) annealed SRO films give luminescence peak(s) in the visible range [3]. As the optical properties of the films are determined by the microstructure/electronic structure of the material, it is important to understand the films' structure change as a function of the annealing temperature.In the present work [4], we have carried out a systematic study on the microstructure and electronic structure evolution of the as-deposited SRO film and the films annealed at temperatures ranging from 300-1100 o C, using combined transmission electron microscopy and electron energy loss (EEL) spectroscopy related techniques. We have found that the asdeposited SRO film is basically a single phase SiO 1.0 , as suggested by its electronic structure characteristics disclosed by valence electron energy loss spectrum. Such single phase undergoes a continuous but incomplete phase decomposition to Si and SiO 2 , indicating that the matrix of the Si clusters is not phase pure SiO 2 , but a mixture of SiO 2 and SiO (i.e., SiO x ). The resulted Si phase first appears as small amorphous clusters, which continue to grow to larger sizes at higher annealing temperatures, but only crystallize at a critical temperature of ~800-900 o C. Such cluster/matrix configuration of the annealed SiO films is also consistent with the appearance of the interfacial plasmon in the EEL spectrum and its oscillation strength change with the annealing temperature. An interesting correlation between the films' phase/electronic structure evolution and the trend of their photoluminescence property change is identified.

Funding Acknowledgements CUHK Direct Grant, CUHK Lui Che Woo Institute of Innovative Medicine, Food and Health Bureau of HKSAR (EF); Hong Kong Jockey Club Charities Trust (JW) Background/Introduction 6-min walk distance (6MWD) can indicate frailty extent, cardiac dysfunction, and heart failure (HF) trajectory. Association of 6MWD with diastolic dysfunction (DD) or cardiac biomarker in community-living elderly without a history of HF remains underexplored. Purpose This study aims to determine the association between 6MWD, serum N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and DD in a community-living elderly population without known HF. Methods Between Nov 2017 and Aug 2018, 302 Hong Kong Chinese aged ≥60 y and without known HF were recruited into the Undiagnosed heart Failure in Older individuals (UFO) study consisting of robust, pre-frail and frail older adults stratified by FRAIL scale in a ratio of 1:1:1. 6MWD was divided into tertiles. Transthoracic echocardiography and serum NT-proBNP were used to assess cardiac dysfunction. Diastolic function was classified according to international guidelines and NT-proBNP >300 pg/ml was considered elevated. Results The ages of participants in the bottom, middle and top tertiles were 80.3 ± 7.4, 73.9 ± 6.3 and 70.0 ± 5.7 years (P < 0.01), respectively, corresponding to a female preponderance of 85.0%, 75.2%, 46.5% (P < 0.01). The highest prevalence rates of hypertension (HT, 76.0% vs 68.3% vs 51.5%, P < 0.01), diabetes mellitus (DM, 41.0% vs 30.7% vs 12.9%, P < 0.01), and ischaemic heart disease (IHD, 14.0% vs 4.0% vs 2.0%, P < 0.01) were observed in the bottom tertile of 6MWD. However, the prevalence of atrial fibrillation (AF) was distributed equally across tertiles (2.0% vs 2.0% vs 2.0%). Frail (63.0% vs 25.7% vs 3.0%, P < 0.01) and pre-frail (36.5% vs 44.6% vs 24.8%, P < 0.01) individuals were most frequently seen in the bottom and middle tertiles of 6MWD. Using multiple linear regression analysis, S’ velocity, E:E’ ratio and E’ velocity were associated with 6MWD independent of age and sex. Associations between 6MWD and S’, left atrial volume index, E’ and E:E’ remained statistically significant even after adjusting for HT, DM, IHD, AF, stroke, chronic pulmonary disease and arthritis. No correlation was observed between 6MWD and left ventricular ejection fraction.  Compared with the top tertile of 6MWD, the bottom tertile was associated with increased risks for grade II–IV DD (odds ratio (OR) 3.47, 95% confidence interval (CI) 1.52–7.96, P < 0.01) and NT-proBNP >300pg/ml (OR 10.20, CI 3.74–27.85, P < 0.01, respectively, after adjusting for co-morbidities. The association between reduced 6MWD and elevated NT-proBNP, but not between 6MWD and DD, remained significant (OR 6.00, CI 2.06–17.46) after adjusting for age and sex. The middle tertile was not significantly associated with an increased risk for grade II–IV DD or elevated NT-proBNP. Conclusion(s) In this cohort of community-living Hong Kong Chinese elderly recruited equally by frailty status, performance of 6MWD in the bottom and top tertiles was inversely associated with NT-proBNP levels but not with DD.