FUNCTIONAL CHARACTERIZATION OF HUMAN METHYLTRANSFERASE LIKE PROTEIN 8 IN DNA DAMAGE RESPONSE

Ph.DDOCTOR OF PHILOSOPH

Cryptanalysis of optical ciphers integrating double random phase encoding with permutation

This paper presents the cryptanalysis of optical ciphers combining double random phase encoding with permutation techniques, and shows its vulnerability against plaintext attack regardless of the implementation order of the two procedures. The equivalent secret keys of both the combination fashions can be retrieved, instead of the recovery of random phase masks and permutation matrix. Numerical simulations are also given for validation

Revealing the Impact of Urban Form on COVID-19 Based on Machine Learning: Taking Macau as an Example

The COVID-19 pandemic has led to a re-examination of the urban space, and the field of planning and architecture is no exception. In this study, a conditional generative adversarial network (CGAN) is used to construct a method for deriving the distribution of urban texture through the distribution hotspots of the COVID-19 epidemic. At the same time, the relationship between urban form and the COVID-19 epidemic is established, so that the machine can automatically deduce and calculate the appearance of urban forms that are prone to epidemics and may have high risks, which has application value and potential in the field of planning and design. In this study, taking Macau as an example, this method was used to conduct model training, image generation, and comparison of the derivation results of different assumed epidemic distribution degrees. The implications of this study for urban planning are as follows: (1) there is a correlation between different urban forms and the distribution of epidemics, and CGAN can be used to predict urban forms with high epidemic risk; (2) large-scale buildings and high-density buildings can promote the distribution of the COVID-19 epidemic; (3) green public open spaces and squares have an inhibitory effect on the distribution of the COVID-19 epidemic; and (4) reducing the volume and density of buildings and increasing the area of green public open spaces and squares can help reduce the distribution of the COVID-19 epidemic

Obstructive Sleep Apnea and Obesity Are Associated with Hypertension in a Particular Pattern: A Retrospective Study

Obstructive sleep apnea (OSA) and obesity can increase the risk of hypertension, but the combined effects of these two conditions on hypertension are not yet known. We collected the basic characteristics, sleep parameters, and glucose levels of subjects with a polysomnography test and divided them into four groups, according to whether they had severe OSA and obesity or not. The main effects of severe OSA and obesity and the interactions of the two on systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels were detected using analysis of covariance. The association between obesity and severe OSA and abnormal blood pressure and their combined effects were detected with logistic regression. In total, 686 subjects were included. After adjusting for multiple confounding factors, the strong main effects of obesity and severe OSA were detected in the SBP and DBP levels, with no combined effects from the two conditions on SBP or DBP. Obesity was independently associated with the presence of hyper-systolic blood pressure (hyper-SBP) and hypertension, and severe OSA was independently associated with the presence of hyper diastolic blood pressure (hyper-DBP) and hypertension. No effects of the interaction between severe OSA and obesity on the presence of abnormal blood pressure were observed. Both severe OSA and obesity were associated with hypertension, while obesity was closely associated with hyper-SBP, and severe OSA was associated with hyper-DBP. No effects of the interaction between these two on hypertension were observed

Alteration effects of karstification and hydrothermalism on middle Permian Qixia formation at the Wulong section, South China

Abstract Middle Permian Qixia Formation in the southwestern region of Sichuan (SW China) has experienced multiphase fluidisation, resulting in an unclear understanding of the reservoir reconstruction effect. In this study, a systematic analysis of the Qi2 member in Wulong Town was carried out by combining field outcrop petrology and geochemistry. The results demonstrated that multiple sets of crystalline dolomite-bioclastic limestone cycles were stacked vertically in the Qi2 member, accompanied by the development of fractures and karst channels. The dolomite was mainly composed of silty-fine dolomite (D1) and recrystallised dolomite (D2). Furthermore, obvious multiphase dolomitic cements (Cd1-Cd2) were present in the fractures and pores. Early karst is known to have lithologic mutation surface development and karst channel development at the top of several secondary cycles. The vadose silt dolomites (Cd1) having karst channels developed dull luminescence under cathode luminescence (CL). Both the geochemical indicators of elements and rare earth element (REE) content indicated dysoxic-oxic environmental conditions. The hydrothermal solution displayed tectonic carniole characteristics in the strata burial stage. Fractures and pores were filled with hydrothermal minerals such as coarse dolomites-saddle dolomites (Cd2, with some caused by recrystallisation of the Cd1 hydrothermal solution) and fluorites. Coarse dolomites-saddle dolomites developed dull-red luminescence with a bright-red rim under CL and their δ18OVPDB values were more negative than those of middle Permian limestone samples. Both the geochemical indicators of elements and REE content indicated the suboxic-anoxic environmental conditions. Karstification had minor constructive impact on the reservoir of the Qi2 member in Baoxing in southwestern Sichuan. Most products of karstification were distributed as fillings in channels. Aside from creating certain networked fractures, the hydrothermal solution was mainly filled with hydrothermal minerals along the fractures, pores and early karst channels. Karst and the hydrothermal solution mainly damaged the middle and upper parts of the middle Permian Qixia Formation in Southwest Sichuan. The impact of episodic fluid on the restoration of the carbonate reservoir was mainly restricted by channels for fluid migration and thickness differences among the reservoir. However, certain thick-layered and massive crystalline dolomite may hold promise for exploration

Episodic hydrothermal alteration on Middle Permian carbonate reservoirs and its geological significance in southwestern Sichuan Basin, SW China

To analyze the episodic alteration of Middle Permian carbonate reservoirs by complex hydrothermal fluid in southwestern Sichuan Basin, petrology, geochemistry, fluid inclusion and U-Pb dating researches are conducted. The fractures and vugs of Middle Permian Qixia–Maokou formations are filled with multi-stage medium−coarse saddle dolomites and associated hydrothermal minerals, which indicates that the early limestone/dolomite episodic alteration was caused by the large-scale, high-temperature, deep magnesium-rich brine along flowing channels such as basement faults or associated fractures under the tectonic compression and napping during the Indosinian. The time of magnesium-rich hydrothermal activity was from the Middle Triassic to the Late Triassic. The siliceous and calcite fillings were triggered by hydrothermal alteration in the Middle and Late Yanshanian Movement and Himalayan Movement. Hydrothermal dolomitization is controlled by fault, hydrothermal property, flowing channel and surrounding rock lithology, which occur as equilibrium effect of porosity and permeability. The thick massive grainstone/dolomites were mainly altered by modification such as hydrothermal dolomitization/recrystallization, brecciation and fracture-vugs filling. Early thin–medium packstones were mainly altered by dissolution and infilling of fracturing, bedding dolomitization, dissolution and associated mineral fillings. The dissolved vugs and fractures are the main reservoir space under hydrothermal conditions, and the connection of dissolved vugs and network fractures is favorable for forming high-quality dolomite reservoir. Hydrothermal dolomite reservoirs are developed within a range of 1 km near faults, with a thickness of 30–60 m. Hydrothermal dolomite reservoirs with local connected pore/vugs and fractures have exploration potential

Functional titanium dioxide nanoparticle conjugated with phthalocyanine and folic acid as a promising photosensitizer for targeted photodynamic therapy in vitro and in vivo

Photodynamic therapy (PDT) is a promising cancer treatment that can be implemented using various agents. The conventional photosensitizer Al (III) phthalocyanine chloride tetrasulfonic acid (Pc) has limitations of selectivity in tumor targeting, low affinity to cancer cells, and low two-photon absorption. This study presents a novel photosensitizer FA-TiO2-Pc, which has the TiO2 nanoparticle conjugated with a tumor targeting agent of folic acid (FA), and Pc. FA-TiO2-Pc possessed high targeted photodynamic therapeutic activity and excellent biocompatibility. This promising photosensitizer showed high therapeutic drug efficiency in vitro at a low concentration dose and short incubation time under one-photon excitation (OPE). In vivo, when treated with a low dose of FA-TiO2-Pc and low light irradiation, the tumor growth was depressed in mice bearing HeLa xenograft tumors with minimal side effects. In addition, the two-photon absorption of FA-TiO2-Pc was also enhanced compared to Pc, proving that FA-TiO2-Pc system has a great potential to be used for the therapy of the folate receptor positive cancer cells in both OPE-PDT and two-photon excitation (TPE)-PDT agents. © 2020 Elsevier B.V.Fig. 1B and C was modified from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Common Attribution 3.0 Generic License. (https://creativecommons.org/licenses/by/3.0/)

Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and mRNA in mice and humans

Chemical RNA modifications are central features of epitranscriptomics, highlighted by the discovery of modified ribonucleosides in mRNA and exemplified by the critical roles of RNA modifications in normal physiology and disease. Despite a resurgent interest in these modifications, the biochemistry of 3-methylcytidine (m3C) formation in mammalian RNAs is still poorly understood. However, the recent discovery of trm141 as the second gene responsible for m3C presence in RNA in fission yeast raises the possibility that multiple enzymes are involved in m3C formation in mammals as well. Here, we report the discovery and characterization of three distinct m3C-contributing enzymes in mice and humans. We found that methyltransferase-like (METTL) 2 and 6 contribute m3C in specific tRNAs and that METTL8 only contributes m3C to mRNA. MS analysis revealed that there is an ∼30–40% and ∼10–15% reduction, respectively, in METTL2 and -6 null-mutant cells, of m3C in total tRNA, and primer extension analysis located METTL2-modified m3C at position 32 of tRNAThr isoacceptors and tRNAArg(CCU). We also noted that METTL6 interacts with seryl-tRNA synthetase in an RNA-dependent manner, suggesting a role for METTL6 in modifying serine tRNA isoacceptors. METTL8, however, modified only mRNA, as determined by biochemical and genetic analyses in Mettl8 null-mutant mice and two human METTL8 mutant cell lines. Our findings provide the first evidence of the existence of m3C modification in mRNA, and the discovery of METTL8 as an mRNA m3C writer enzyme opens the door to future studies of other m3C epitranscriptomic reader and eraser functions.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)Published versio