STATISTICAL METHODS FOR GENETIC AND EPIGENETIC ASSOCIATION STUDIES

First, in genome-wide association studies, few methods have been developed for rare variants which are one of the natural places to explain some missing heritability left over from common variants. Therefore, we propose EM-LRT that incorporates imputation uncertainty for downstream association analysis, with improved power and/or computational efficiency. We consider two scenarios: I) when posterior probabilities of all possible genotypes are estimated; and II) when only the one-dimensional summary statistic, imputed dosage, is available. Our methods show enhanced statistical power over existing methods and are computationally more efficient than the best existing method for association analysis of variants with low frequency or imputation quality. Second, although genome-wide association studies have identified a large number of loci associated with complex traits, a substantial proportion of the heritability remains unexplained. Thanks to advanced technology, we may now conduct large-scale epigenome-wide association studies. DNA methylation is of particular interest because it is highly dynamic and has been shown to be associated with many complex human traits, including immune dysfunctions, cardiovascular diseases, multiple cancer, and aging. We propose FunMethyl, a penalized functional regression framework to perform association testing between multiple DNA methylation sites in a region and a quantitative outcome. Our results from both real data based simulations and real data clearly show that FunMethyl outperforms single-site analysis across a wide spectrum of realistic scenarios. Finally, large studies may have a mixture of old and new arrays, or a mixture of old and new technologies, on the large number of samples they investigate. These different arrays or technologies usually measure different sets of methylation sites, making data analysis challenging. We propose a method to predict site-specific DNA methylation level from one array to another - a penalized functional regression model that uses functional predictors to capture non-local correlation from non-neighboring sites and covariates to capture local correlation. Application to real data shows promising results: the proposed model can predict methylation level at sites on a new array reasonably well from those on an old array.Doctor of Philosoph

Nanographite/polyaniline composite films as the counter electrodes for dye-sensitized solar cells

100學年度研究獎補助論文[[abstract]]Nanographite/polyaniline (NG/PANI) composite films were developed and characterized, and the performances of the dye-sensitized solar cells (DSSCs) employing these composite films as the counter electrode (CE) were evaluated in this study. The nanographite/aniline (NG/ANI) particle was firstly synthesized by a reflux method and served as the monomer for the electro-polymerization of the NG/PANI composite films. The surface modification of NG by ANI was confirmed by EDX mapping, TEM image, zeta-potential, and UV-Vis absorption measurements. The electro-polymerized NG/PANI composite films were characterized by Raman spectroscopy, XPS, and conducting-AFM, which verified the successful incorporation of NGs in the PANI films. The electro-catalytic activity of the NG/PANI composite film was evaluated using the positive-feedback mode of scanning electrochemical microscopy (SECM), by which a comparable heterogeneous rate constant (ks0) for the ferrocene/ferrocenium (Fc/Fc+) redox pair was obtained and compared with that of a sputtered Pt. The DSSC employing the NG/PANI (20 mC cm−2) CE exhibited a higher short-circuit current density (JSC) but lower fill factor (FF), and gave a comparable power-conversion efficiency (η) of 7.07%, as compared to that of a DSSC containing a sputtered Pt CE (η = 7.19%).[[incitationindex]]SCI[[booktype]]紙

Strong Gravitational Lensing Parameter Estimation with Vision Transformer

Quantifying the parameters and corresponding uncertainties of hundreds of strongly lensed quasar systems holds the key to resolving one of the most important scientific questions: the Hubble constant ($H_{0}$) tension. The commonly used Markov chain Monte Carlo (MCMC) method has been too time-consuming to achieve this goal, yet recent work has shown that convolution neural networks (CNNs) can be an alternative with seven orders of magnitude improvement in speed. With 31,200 simulated strongly lensed quasar images, we explore the usage of Vision Transformer (ViT) for simulated strong gravitational lensing for the first time. We show that ViT could reach competitive results compared with CNNs, and is specifically good at some lensing parameters, including the most important mass-related parameters such as the center of lens $\theta_{1}$ and $\theta_{2}$, the ellipticities $e_1$ and $e_2$, and the radial power-law slope $\gamma'$. With this promising preliminary result, we believe the ViT (or attention-based) network architecture can be an important tool for strong lensing science for the next generation of surveys. The open source of our code and data is in \url{https://github.com/kuanweih/strong_lensing_vit_resnet}.Comment: Accepted by ECCV 2022 AI for Space Worksho

AbCD: arbitrary coverage design for sequencing-based genetic studies

Summary: Recent advances in sequencing technologies have revolutionized genetic studies. Although high-coverage sequencing can uncover most variants present in the sequenced sample, low-coverage sequencing is appealing for its cost effectiveness. Here, we present AbCD (arbitrary coverage design) to aid the design of sequencing-based studies. AbCD is a user-friendly interface providing pre-estimated effective sample sizes, specific to each minor allele frequency category, for designs with arbitrary coverage (0.5–30×) and sample size (20–10 000), and for four major ethnic groups (Europeans, Africans, Asians and African Americans). In addition, we also present two software tools: ShotGun and DesignPlanner, which were used to generate the estimates behind AbCD. ShotGun is a flexible short-read simulator for arbitrary user-specified read length and average depth, allowing cycle-specific sequencing error rates and realistic read depth distributions. DesignPlanner is a full pipeline that uses ShotGun to generate sequence data and performs initial SNP discovery, uses our previously presented linkage disequilibrium-aware method to call genotypes, and, finally, provides minor allele frequency-specific effective sample sizes. ShotGun plus DesignPlanner can accommodate effective sample size estimate for any combination of high-depth and low-depth data (for example, whole-genome low-depth plus exonic high-depth) or combination of sequence and genotype data [for example, whole-exome sequencing plus genotyping from existing Genomewide Association Study (GWAS)]

Analysis and Monitoring Results of a Building Integrated Photovoltaic Façade Using PV Ceramic Tiles in Taiwan

Single-crystal silicon-based solar cells laminated with tempered-glass and ceramic tiles for use in a building’s façade have been developed. The optical, thermal, and electrical properties of the proposed PV module are first evaluated, and then a wind-resistance test is carried out to evaluate the feasibility of installing it in Taiwan. The electrical and deflection characteristics of the proposed PV module did not change significantly after a 50 thermal cycling test and a 200-hour humidity-freeze test, based on IEC 61215 and a wind-resistance test. Finally, the electrical power generation ability of the proposed BIPV system with 1 kWp electrical power capacity was examined. Building information modeling software tools were used to simulate the BIPV system and carry out the energy analysis. The simulation results show a very consistent trend with regard to the actual monthly electricity production of the BIPV system designed in this work. The BIPV system was able to produce an accumulative electrical power of 185 kWh during the 6-month experimental period. In addition, the exterior temperature of the demonstration house was about 10°C lower than the surface of the BIPV system, which could reduce indoor temperature

Comparison of Skull Motions in Six Degrees of Freedom Between Two Head Supports During Frameless Radiosurgery by CyberKnife

Introduction: Maintaining immobilization to minimize skull motion is important during frameless radiosurgery. This study aimed to compare the intrafractional skull motions between two head supports.Methods: With 6D skull tracking system, 4,075 image records from 45 patients receiving radiosurgery by CyberKnife were obtained. Twenty-three patients used TIMO head supports (CIVCO) (Group A) and twenty-two patients used Silverman head supports (CIVCO) with MoldCare cushions (ALCARE) (Group B). The skull motions in X (superior-inferior), Y (right-left), Z (anterior-posterior) axes, 3D (three-dimensional) vector, Roll, Pitch and Yaw between the two groups were compared and the margins of planning target volume were estimated.Results: The translational motions in Group A were similar in three axes at initial but became different after 10 min, and those in Group B were less prominent in the Y axis. The rotational errors in Group A were most obvious in Yaw, but those in Group B were stationary in three axes. The motions in the X axis, 3D vector, Pitch and Yaw in Group B were significantly smaller than those in Group A; conversely, the motions in the Z axis in Group B were larger. To cover the 95% confidence intervals, margins of 0.77, 0.79, and 0.40 mm in the X, Y, and Z axes, respectively, were needed in Group A, and 0.69, 0.50, and 0.51 mm were needed in Group B.Conclusions: Both head supports could provide good immobilization during the frameless radiosurgery. Silverman head support with MoldCare cushion was better than TIMO head support in the superior-inferior direction, 3D vector, Pitch and Yaw axes, but worse in the anterior-posterior direction

Catechin prevents ultraviolet B-induced human keratinocyte death via inhibition of JNK phosphorylation

Abstract High levels of (+)-catechin are found in the skin and seed of many fruits such as apples and grapes. Dietary supplementation with (+)-catechin has been demonstrated to protect epidermal cells against damage induced by ultraviolet B (UVB) radiation. However, the underlying mechanisms are not well understood yet. To determine whether (+)-catechin protects keratinocytes from UVB-induced damage, the viability of UVB-and H 2 O 2 -treated cells was determined by cell viability assay. Intracellular H 2 O 2 level was measured by flow cytometry. UVB-or H 2 O 2 -induced signaling pathways were detected by Western blotting. The results indicated that (+)-catechin inhibited UVB-and H 2 O 2 -induced keratinocyte death. In parallel, intracellular H 2 O 2 generation in keratinocytes irradiated by UVB was inhibited by (+)-catechin in a concentration-dependent manner. (+)-Catechin also inhibited UVB-and H 2 O 2 -induced JNK activation in keratinocytes. However, it had little inhibitory effect on UVB-and H 2 O 2 -induced ERK and p38 activation even at a higher concentration, suggesting indirectly that JNK activation is required for the induction of apoptosis in keratinocytes exposed to UVB. Finally, we compared the cytotoxicity of (+)-catechin and (−)-epigallocatechin-3-gallate (EGCG) on keratinocytes. Cell viability assay showed that (+)-catechin was relatively nontoxic at higher doses. Taken together, our results demonstrate that (+)-catechin inhibits UVB-and oxidative stress-induced H 2 O 2 production and JNK activation and enhances human keratinocyte survival. However, although it seems that (+)-catechin and EGCG are equally effective in preventing keratinocyte death, (+)-catechin is relatively nontoxic and thus is suitable for developing as an anti-ageing agent for skin care

Across-Platform Imputation of DNA Methylation Levels Incorporating Nonlocal Information Using Penalized Functional Regression: Cross-Platform Imputation of Methylation Profile

DNA methylation is a key epigenetic mark involved in both normal development and disease progression. Recent advances in high-throughput technologies have enabled genome-wide profiling of DNA methylation. However, DNA methylation profiling often employs different designs and platforms with varying resolution, which hinders joint analysis of methylation data from multiple platforms. In this study, we propose a penalized functional regression model to impute missing methylation data. By incorporating functional predictors, our model utilizes information from nonlocal probes to improve imputation quality. Here, we compared the performance of our functional model to linear regression and the best single probe surrogate in real data and via simulations. Specifically, we applied different imputation approaches to an acute myeloid leukemia dataset consisting of 194 samples and our method showed higher imputation accuracy, manifested, for example, by a 94% relative increase in information content and up to 86% more CpG sites passing post-imputation filtering. Our simulated association study further demonstrated that our method substantially improves the statistical power to identify trait-associated methylation loci. These findings indicate that the penalized functional regression model is a convenient and valuable imputation tool for methylation data, and it can boost statistical power in downstream epigenome-wide association study (EWAS)