The Role of PC4 in Oxidative Stress: A Dissertation

Oxidative stress is a cellular condition where cells are challenged by elevated levels of reactive oxygen species (ROS) that are produced endogenously or exogenously. ROS can damage vital cellular components, including lipid, protein, DNA and RNA. Oxidative damage to DNA often leads to cell death or mutagenesis, the underlying cause of various human disease states. Previously our laboratory discovered that human PC4 gene can prevent oxidative mutagenesis in the bacterium Escherichia coli and that the yeast homolog SUB1 has a conserved function in oxidation protection. In this thesis I examined the underlying mechanisms of PC4’s oxidation protection function. My initial efforts to examine the predicted role of SUB1 in transcription-coupled DNA repair essentially negated this hypothesis. Instead, results from our experiments suggest that PC4 and yeast SUB1 can directly protect genomic DNA from oxidative damage. While testing SUB1’s role in double strand DNA break (DSB) repair, I found the sub1Δ mutant resects DSB ends rapidly but still ligates chromosomal breaks effectively, suggesting that DSB resection is not inhibitory to nonhomologous end-joining, an important DSB repair pathway. Finally, in the course of studying transcription recovery after UV damage, I found UV induces a longer form of RPB2 mRNA and demonstrated that this is caused by alternative polyadenylation of the RPB2 mRNA and that alternative polyadenylation contributes to UV resistance. Based on results of preliminary experiments, I propose that UV activates an alternative RNA polymerase to transcribe RNA POL II mRNA, a novel mechanism to facilitate recovery from inhibition of transcription resulting from UV damage. The hypothetical polymerase switch may account for the UV-induced alternative polyadenylation of the RPB2 mRNA

UV damage regulates alternative polyadenylation of the RPB2 gene in yeast

Alternative polyadenylation (APA) is conserved in all eukaryotic cells. Selective use of polyadenylation sites appears to be a highly regulated process and contributes to human pathogenesis. In this article we report that the yeast RPB2 gene is alternatively polyadenylated, producing two mRNAs with different lengths of 3\u27UTR. In normally growing wild-type cells, polyadenylation preferentially uses the promoter-proximal poly(A) site. After UV damage transcription of RPB2 is initially inhibited. As transcription recovers, the promoter-distal poly(A) site is preferentially used instead, producing more of a longer form of RPB2 mRNA. We show that the relative increase in the long RPB2 mRNA is not caused by increased mRNA stability, supporting the preferential usage of the distal poly(A) site during transcription recovery. We demonstrate that the 3\u27UTR of RPB2 is sufficient for this UV-induced regulation of APA. We present evidence that while transcription initiation rates do not seem to influence selection of the poly(A) sites of RPB2, the rate of transcription elongation is an important determinant

RNA polymerase II depletion promotes transcription of alternative mRNA species

BACKGROUND: Cells respond to numerous internal and external stresses, such as heat, cold, oxidative stress, DNA damage, and osmotic pressure changes. In most cases, the primary response to stress is transcriptional induction of genes that assist the cells in tolerating the stress and facilitate the repair of the cellular damage. However, when the transcription machinery itself is stressed, responding by such standard mechanisms may not be possible. RESULTS: In this study, we demonstrate that depletion or inactivation of RNA polymerase II (RNAPII) changes the preferred polyadenylation site usage for several transcripts, and leads to increased transcription of a specific subset of genes. Surprisingly, depletion of RNA polymerase I (RNAPI) also promotes altered polyadenylation site usage, while depletion of RNA polymerase III (RNAPIII) does not appear to have an impact. CONCLUSIONS: Our results demonstrate that stressing the transcription machinery by depleting either RNAPI or RNAPII leads to a novel transcriptional response that results in induction of specific mRNAs and altered polyadenylation of many of the induced transcripts

Nonlinear Analytical Modelling for Surface-Mounted Permanent Magnet Motors with Magnet Defect Fault

This paper analyzes magnet defect fault signature in the surface-mounted permanent magnet motor (SPMM) using nonlinear analytical model considering the influence of magnet shape and magnetization direction. Based on the surface current method and conformal mapping technique, the magnet defect equivalent current and equivalent nonlinearity current are proposed to represent the magnet defect. Accordingly, the performance of SPMM can be obtained. The proposed model has great potential to investigate SPMM with non-uniform magnet defect and gives theoretical basis for fault diagnosis. The extra sensing coil is added to measure the voltage waveforms, which can also be predicted using the nonlinear analytical model and shows the influence of magnet defect fault. Finally, the finite element analysis and experimental results verify the high accuracy of nonlinear analytical model

Analytical Calculation of Eccentric Surface-Mounted Permanent-Magnet Motor Accounting for Iron Saturation

This article presents an analytical model to predict the performance of eccentric surface-mounted permanent-magnet (ESPM) motor based on the nonlinear conformal mapping and reluctance network hybrid model (NCRHM). The proposed model can reveal the mutual influence of rotor eccentricity on the stator slotting and iron saturation accounting for the distortion of the equivalent current positions and air-gap path among the conformal mappings. The transformation between magnetic voltage drop of iron and equivalent current in the air region (including air-gap and slot region) is employed to consider the increased iron saturation due to the reduced air-gap length. Based on the proposed model, the electromagnetic performance including flux linkage, back electromotive force (EMF), torque, and unbalanced magnetic force (UMF) can be accurately predicted for any kind of rotor eccentricity. In addition, the NCRHM is compared with the complex permeance model (CPM) neglecting both iron saturation and the field distortion in conformal mappings, which exhibits the great advantage of NCRHM for ESPM motor. The excellent accuracy and great efficiency of the proposed model are validated by both finite-element analysis and test results

GPAvatar: Generalizable and Precise Head Avatar from Image(s)

Head avatar reconstruction, crucial for applications in virtual reality, online meetings, gaming, and film industries, has garnered substantial attention within the computer vision community. The fundamental objective of this field is to faithfully recreate the head avatar and precisely control expressions and postures. Existing methods, categorized into 2D-based warping, mesh-based, and neural rendering approaches, present challenges in maintaining multi-view consistency, incorporating non-facial information, and generalizing to new identities. In this paper, we propose a framework named GPAvatar that reconstructs 3D head avatars from one or several images in a single forward pass. The key idea of this work is to introduce a dynamic point-based expression field driven by a point cloud to precisely and effectively capture expressions. Furthermore, we use a Multi Tri-planes Attention (MTA) fusion module in the tri-planes canonical field to leverage information from multiple input images. The proposed method achieves faithful identity reconstruction, precise expression control, and multi-view consistency, demonstrating promising results for free-viewpoint rendering and novel view synthesis.Comment: ICLR 2024, code is available at https://github.com/xg-chu/GPAvata

Voxel2Hemodynamics: An End-to-end Deep Learning Method for Predicting Coronary Artery Hemodynamics

Local hemodynamic forces play an important role in determining the functional significance of coronary arterial stenosis and understanding the mechanism of coronary disease progression. Computational fluid dynamics (CFD) have been widely performed to simulate hemodynamics non-invasively from coronary computed tomography angiography (CCTA) images. However, accurate computational analysis is still limited by the complex construction of patient-specific modeling and time-consuming computation. In this work, we proposed an end-to-end deep learning framework, which could predict the coronary artery hemodynamics from CCTA images. The model was trained on the hemodynamic data obtained from 3D simulations of synthetic and real datasets. Extensive experiments demonstrated that the predicted hemdynamic distributions by our method agreed well with the CFD-derived results. Quantitatively, the proposed method has the capability of predicting the fractional flow reserve with an average error of 0.5\% and 2.5\% for the synthetic dataset and real dataset, respectively. Particularly, our method achieved much better accuracy for the real dataset compared to PointNet++ with the point cloud input. This study demonstrates the feasibility and great potential of our end-to-end deep learning method as a fast and accurate approach for hemodynamic analysis.Comment: 8page

Multi-frame image restoration method for novel rotating synthetic aperture imaging system

Abstract The novel rotating synthetic aperture (RSA) optical imaging system is an important development direction for future high-resolution optical remote sensing satellites in geostationary orbit. However, owing to the rotating rectangular pupil, the point spread function of the RSA system has an asymmetric spatial distribution, and the images obtained using the primary mirror from different rotation angles have nonuniform blur degradation. Moreover, platform vibration and pupil rotation have coupling effects on the RSA imaging, resulting in further radiometric and geometric quality degradation. To address these problems, the image degradation characteristics are first analyzed according to the imaging mechanism. Then, combined with the theory of mutual information, an image registration method is suggested by introducing the orientation gradient information. From this, a multi-frame image restoration model is proposed based on the directional gradient prior of the RSA system image. From the perspective of interpretation and application, when the aspect ratio is less than 3, the proposed inversion restoration method can achieve a satisfactory processing performance. This work can provide engineering application reference for the future space application of RSA imaging technology

Novel Quasi‐Liquid K‐Na Alloy as a Promising Dendrite‐Free Anode for Rechargeable Potassium Metal Batteries

Rechargeable potassium metal batteries are promising energy storage devices with potentially high energy density and markedly low cost. However, eliminating dendrite growth and achieving a stable electrode/electrolyte interface are the key challenges to tackle. Herein, a novel "quasi-liquid" potassium-sodium alloy (KNA) anode comprising only 3.5 wt% sodium (KNA-3.5) is reported, which exhibits outstanding electrochemical performance able to be reversibly cycled at 4 mA cm-2 for 2000 h. Moreover, it is demonstrated that adding a small amount of sodium hexafluorophosphate (NaPF6 ) into the potassium bis(fluorosulfonyl)imide electrolyte allows for the formation of the "quasi-liquid" KNA on electrode surface. Comprehensive experimental studies reveal the formation of an unusual metastable KNa2 phase during plating, which is believed to facilitate simultaneous nucleation and suppress the growth of dendrites, thereby improving the electrode's cycle lifetime. The "quasi-liquid" KNA-3.5 anode demonstrates markedly enhanced electrochemical performance in a full cell when pairing with Prussian blue analogs or sodium rhodizonate dibasic as the cathode material, compared to the pristine potassium anode. Importantly, unlike the liquid KNA reported before, the "quasi-liquid" KNA-3.5 exhibits good processability and can be readily shaped into sheet electrodes, showing substantial promise as a dendrite-free anode in rechargeable potassium metal batteries.Z.T. acknowledges the financial support of Maria Curie COFUND fellowship (Grant No. 713640). Z.L. thanks the financial support of China Scholarship Council (Grant No. 201 806 400 066). This project was partly funded by the “Baterias 2030” project through the Mobilizadore Programme by the National Innovation Agency of Portugal (Grant No. POCI-01-0247- FEDER-046109). G.Y. acknowledges the financial support from the Welch Foundation Award F-1861. The authors thank Dr. Artur Martins for his assistance in mechanical property measurement.info:eu-repo/semantics/publishedVersio

Unlocking opportunities for migrant workers in China: Analyzing the impact of health insurance on hukou switching intentions

The Chinese urban–rural binary health insurance structure has contributed to a significant urban–rural segmentation and regional fragmentation, which will affect labor mobilization and urbanization. The purpose of this research is to study whether and how urban–rural binary health insurance impacts the intentions of migrant workers to switch between rural and urban hukou. Pooled data were drawn from China Migrants Dynamic Survey, collected by the National Health Commission of China. The study applied the instrument variable model due to the existence of the endogeneity; and the IVprobit model to conduct the empirical analysis. Our findings are as follows: (1) the urban–rural binary health insurance affects migrant workers’ intentions to switch to urban hukou significantly. (2) The negative impact of originally rural health insurance on migrant workers’ intention of switching to urban hukou is relatively large for low-education-level migrant workers. (3) Compared with new generation of migrant workers, old migrant workers have higher health insurance dependency levels. Finally, our research suggested several policy implications, such as accelerating the establishment of a unified urban–rural health insurance system, increasing the urban health insurance participation rate of migrant workers in their working cities, and including migrant workers in the scope of equal access to urban public services, etc. All the policy suggestions are essential in order to accelerate the citizenization of migrant workers, improve the quality of urbanization, and promote the construction of a unified national labor market.Web of Science158art. no. 699