In the Footsteps of the Rugged Trail of Transcription

The nature of life is intrinsically simple and complex, with merely four basic nucleotides that ultimately make up countless lives with distinct appearances. Darwin’s theory of evolution reveals how time shapes the inhabitants of the planet, whereby it is the fundamental components that determine who we are. It is not until several decades ago, where we finally cracked the mystery of the DNA molecule with the swirling structure. Since then, waves of biology studies have entered an exponential phase. With the development of technologies, scientists have increased their understanding of the mechanisms behind biological questions in various organisms. As the initial step of all biological processes, transcription from DNA to RNA has been extensively characterized. We have acknowledged that this series of action is not at all effortless, but largely regulated. To name a few, the state of chromatin structure, level of transcription factor binding, initiation, and elongation of transcription, the post-transcriptional regulation of messenger RNA, and not to mention the influence of non-coding RNA. Moreover, the messenger RNA is stepwisely exported to the cytoplasm of the cells and translated into protein in mammalian cells. Despite being located in two spatially separate compartments, the crosstalk is never ignored. Hence, it is of great interest to investigate whether this crosstalk between transcription and translation has any consequences to cellular functions. Our study looks at the starting point of transcription – promoter, by performing an unbiased screen for candidate promoters that could potentially affect the translation process Interestingly, we discovered a set of promoters with TATA box, which boosts the translation of messenger RNA. Using CRISPR-Cas9 genome editing, genome-wide analysis, and in vitro experiments, we found that the effect is not limited to promoters with TATA box. Instead it is a rather general mechanism dictated by the rate of transcription, more specifically transcription elongation. More importantly, the performance requires cap-dependent translation. To examine the responsible factor, we assess the level of RNA modification - m6A on the messenger RNA and observe a reverse correlation between the status of translation and the level of m6A modification. Notably, although m6A are mostly found around stop codons, in our study m6A modification within the coding region of genes are crucial for the suppressive effect on translation. Finally, we propose a model that co-transcriptional deposition of m6A via retarded RNA Pol II elongation could lead to translational control. The study opens new doors to grasping the hidden regulators of gene expression. The advancement of CRISPR-Cas9 genome editing has led to a myriad of genome- wide studies in various organisms. While most studies focus on the coding regions of the genome, we have previously established a systemic approach to study the functions of non-coding genome by targeting transcription factor binding sites at enhancer elements. To broaden our understanding about how enhancer elements coordinate gene expression, we performed a genetic screen of enhancers with AP1 binding motif in oncogene-induced senescence. We successfully validated two sgRNAs targeting the same AP1 motif, showing it can affect the process of senescence. Mutations of the core AP1 binding site, in turn, abolished the enhancer function. Later, it was discovered that the FOXF1 gene was the interacting target, where disruption of FOXF1 lead to similar effects on senescence. Together, we suggest that AP1, a downstream target of mThis thesis explores multiple aspects of the transcription regulatory network with regards to human cells - From the initiation of transcription to the efficiency of translation. _Chapter 2_ attempts to establish a connection between the transcription and translation processes. By employing multiple in vitro experiments, a positive correlation between transcription and translation was first discovered, where it was solely controlled via transcription rate. The study leads to the identification of one of the first known functions of m6A at coding regions. While seemingly counterintuitive to the current recognition about m6A on translation, we augment the role of m6A on translation via the discovery of its co-transcriptional deposition. _Chapter 3_ reviews the connection between the transcription steps of splicing, export, decay, and translation of mRNA, reinforcing the hypothesis that transcription is not an independent event, and is instead linked to the entire life cycle of mRNA. _Chapter 4_ investigates the functional role of AP1 in enhancer regions during OIS. The study results in the identification of a novel enhancer with an AP1 binding motif regulating senescence through its target gene FOXF1. Although extensively characterized, AP1 and FOXF1 are not reported to act as regulators of senescence. A new trans-regulatory network of genes to counterbalance the effect of oncogene activation was uncovered. In _Chapter 5_, a general discussion about the current view of the field is conducted. Finally, some outlooks are raised to potentially generate a better understanding of transcriptional regulation

Deformable Generator Network: Unsupervised Disentanglement of Appearance and Geometry

We present a deformable generator model to disentangle the appearance and geometric information for both image and video data in a purely unsupervised manner. The appearance generator network models the information related to appearance, including color, illumination, identity or category, while the geometric generator performs geometric warping, such as rotation and stretching, through generating deformation field which is used to warp the generated appearance to obtain the final image or video sequences. Two generators take independent latent vectors as input to disentangle the appearance and geometric information from image or video sequences. For video data, a nonlinear transition model is introduced to both the appearance and geometric generators to capture the dynamics over time. The proposed scheme is general and can be easily integrated into different generative models. An extensive set of qualitative and quantitative experiments shows that the appearance and geometric information can be well disentangled, and the learned geometric generator can be conveniently transferred to other image datasets to facilitate knowledge transfer tasks.Comment: version

Can command-and-control policy drive low-carbon transition in energy-intensive enterprises? -a study based on evolutionary game theory

There are two views on whether command-and-control policy can promote carbon emission reduction: the “compliance cost” theory and the “innovation compensation” theory. In this paper, we construct an evolutionary game model among energy-intensive enterprises, verification agencies, and local governments from the game theory perspective to explore the impact of command-and-control policy on the low-carbon transition of energy-intensive enterprises. The interaction mechanism of the three actors and the main factors affecting the low-carbon transition of the enterprises are further analyzed with the help of the MATLAB simulation method. The study results show that command-and-control policies can promote the low-carbon transition of enterprises and have a suppressive effect on bribery behavior. In the actual game process, enterprises will compare the cost of low-carbon transition with that of no low-carbon transition. The cost of low-carbon transition is higher when the government’s incentives and penalties are small, so there is a “compliance cost” effect, and the government cannot promote low-carbon transition by increasing the intensity of regulation. On the contrary, when the government’s incentives and penalties are strong enough, enterprises will make a low-carbon transition spontaneously in the face of continuously increasing environmental regulation intensity, which supports the theory of “innovation compensation.” In addition, increasing the profitability of product sales and increasing the cost of bribes are also effective ways to promote low-carbon transition. Finally, relevant policy recommendations were proposed based on the main conclusions. This work opens up a new perspective for environmental regulation theory and provides a theoretical reference and practical basis for developing low-carbon transition

Automated Mapping of Adaptive App GUIs from Phones to TVs

With the increasing interconnection of smart devices, users often desire to adopt the same app on quite different devices for identical tasks, such as watching the same movies on both their smartphones and TV. However, the significant differences in screen size, aspect ratio, and interaction styles make it challenging to adapt Graphical User Interfaces (GUIs) across these devices. Although there are millions of apps available on Google Play, only a few thousand are designed to support smart TV displays. Existing techniques to map a mobile app GUI to a TV either adopt a responsive design, which struggles to bridge the substantial gap between phone and TV or use mirror apps for improved video display, which requires hardware support and extra engineering efforts. Instead of developing another app for supporting TVs, we propose a semi-automated approach to generate corresponding adaptive TV GUIs, given the phone GUIs as the input. Based on our empirical study of GUI pairs for TV and phone in existing apps, we synthesize a list of rules for grouping and classifying phone GUIs, converting them to TV GUIs, and generating dynamic TV layouts and source code for the TV display. Our tool is not only beneficial to developers but also to GUI designers, who can further customize the generated GUIs for their TV app development. An evaluation and user study demonstrate the accuracy of our generated GUIs and the usefulness of our tool.Comment: 30 pages, 15 figure

Doing housework and having regular daily routine standing out as factors associate with physical function in the older people

Background and objectivesNationwide data were used to explore factors associated with physical function in order to identify interventions that could improve and maintain physical function in the older people.MethodsThe physical function was assessed by gait speed (GS). We selected 2,677 male and 2,668 female older adults (aged ≥60) who could perform the GS test as study subjects. GS was measured by having subjects walk across and back a 10-m course. A gait speed less than 20% that of a reference population (<0.7 m/s) was used as the definition of slow gait speed (SGS). Co-morbidity, polypharmacy, medical expenses, need for care, and hospitalization were used to evaluate health status. A stepwise logistic regression model was used to determine factors associated with SGS.ResultsSGS was associated with poorer health status, higher medical cost, lower ranking on the Geriatric Depression Scale (GDS) and decreased Mini-mental State Examination (MMSE). Co-morbidity (OR = 1.81, 1.58–2.07), polypharmacy (OR = 1.47, 1.25–1.74), MMSE <24 (OR = 1.85, 1.54–2.22), and GDS ≥ 11 (OR = 1.40, 1.18–1.65) were associated with SGS. In contrast, doing housework (DHW, OR = 0.43, 0.38–0.49), having a regular daily routine (RDR, OR = 0.64, 0.45–0.91), and current alcohol consumption (OR = 0.74, 0.62–0.90) were inversely associated with SGS. DHW plus having RDR could greatly reduce the risk of SGS (OR = 0.29, 0.19–0.43).ConclusionPoor physical function is associated with poorer health status in Chinese older people. Maintaining a regular daily routine and doing some housework may be important factors that can help older people preserve their physical function

Research on energy dissipation characteristics and coal burst tendency of fissured coal mass

Coal burst tendency is the natural property of whether coal rock mass can have coal burst, and the distribution of fissures has an important influence on it. In order to study the influence mechanism of the original coal fissures on the energy dissipation characteristics and coal burst tendency, the PFC2D numerical simulation method was used to conduct uniaxial compression tests on coal specimens with different fracture types. The results show that: ①With the increase of the inclination angle of the fissure, the compressive strength and elastic modulus of the macroscopic mechanical parameters show a trend of decreasing first and then increasing; when the inclination angle of the fissure is 30, both of them reach the minimum value. The relationship between the macro-mechanical parameters of different fracture types is: non-coplanar parallel double-fissure specimen < single-fissure specimen < co-planar discontinuous double-fissure specimen.②The variation law of elastic strain energy and total strain energy is similar to that of macroscopic mechanical parameters. The parallel and non-coplanar fracture specimens form an energy dissipation structure between the fissures, and the coplanar discontinuous double-fissure specimen forms an energy concentration area between the fissures, revealing the intrinsic reason for the relationship between the elastic energy of different fracture types. ③The coal burst tendency is analyzed from the two perspectives of the ability of coal and rock to store elastic energy and the ability to release elastic energy after failure, and two coal burst tendency indicators, elastic energy storage rate and elastic energy release rate, are proposed. ④With the increase of the fissure inclination angle, both the elastic energy storage rate and the elastic energy release rate showed a trend of first decreasing and then increasing; when the fissure inclination angle was 30, the two coal burst propensity indexes both achieved the minimum value. The relationship between the coal burst tendency of different fracture types is: non-coplanar parallel double-fissure specimen < single-fissure specimen < co-planar discontinuous double-fissure specimen. The distribution of fissures has a significant coal burst on the coal burst tendency of coal mass, and the factor of fissures should be considered in the evaluation of the coal burst tendency of coal and rock mass and the prevention and control of rock burst

Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation

Transcription and translation are two main pillars of gene expression. Due to the different timings, spots of action, and mechanisms of regulation, these processes are mainly regarded as distinct and generally uncoupled, despite serving a common purpose. Here, we sought for a possible connection between transcription and translation. Employing an unbiased screen of multiple human promoters, we identified a positive effect of TATA box on translation and a general coupling between mRNA expression and translational efficiency. Using a CRISPR-Cas9-mediated approach, genome-wide analyses, and in vitro experiments, we show that the rate of transcription regulates the efficiency of translation. Furthermore, we demonstrate that m6A modification of mRNAs is co-transcriptional and depends upon the dynamics of the transcribing RNAPII. Suboptimal transcription rates lead to elevated m6A content, which may result in reduced translation. This study uncovers a general and widespread link between transcription and translation that is governed by epigenetic modification of mRNAs

Do Credit Associations Compete with Each Other in Japanese Regional Lending Markets?

This paper examines whether credit associations in Japanese regional lending markets compete on price now that Japanese financial authorities have replaced the convoy system of financial regulation with the principle of competition. Specifically, the effects of the market share of credit associations in regional markets on their lending rates are empirically investigated. Accordingly, we determined that credit associations compete with each other in regional lending markets by using two different proxies for the market share held by credit associations in a region. The first proxy was the credit associations’ share of all deposits in a region and the second was the credit associations’ share of all branch offices in a region. In addition, credit associations that face more intense competition from regional banks in regional markets were found to face more intense competition from other credit associations