Dynamics of higher order chromatin structures

During the last few decades, the intensive focus on microscopy observations and genome sequencing analyses has proved that the genomic DNA is packaged in the non-random manner in the nucleus of interphase cells. Accumulated evidence have thus documented that the chromatin organization in 3D plays key roles in central biological processes, such as transcription, replication and DNA repair. In the interphase nucleus, each chromosome is expanded and organized in a manner depending on structural hallmarks of the nucleus. Thus, repressed domains localize to the nuclear periphery to form lamina associated domains (LADs) or large organized chromatin K9 modifications (LOCKs). In addition, prevalent chromatin interactions can be formed from same chromosome (in cis) or different chromosome (in trans). It is still not clear how such dynamic interactions between chromatin fibers control the expressivity of the genome and to what extent these depend on epigenetic chromatin states. The study in this thesis had focused on the dynamics of higher order chromatin structures, particularly on the relationship between the dynamics of chromatin structure and chromatin states. Since the resolution of current single cell techniques in the chromatin organization research, such as DNA FISH and immuno-staining, are limited by the resolution of the microscopy, we invented a new in situ single cell technique termed ChrISP (paper I). Using this technique we could detect chromatin proximities with a resolution less than 17nm even though the analysis was implemented using the low resolution confocal microscope. In paper II, the scope of the ChrISP technique was extended to include an analysis of chromatin states within a single chromosome in a single cell to document that compacted chromatin at the nuclear periphery depends on the H3K9me2 mark that impinges on the nuclear periphery in finger-like structures. Moreover, upon the removal of these marks the rest of the chromosome showed signs of compaction, potentially related to chromosome condensation. These results are consistent with the interpretation that the H3K9me2 mark regulates pleiotropic features of higher order chromatin structure. In paper III, we had used the view point of a single locus to explore the dynamics of chromatin interactions in developmental window using the circular chromatin conformation capture (4C) technique. The resulting inter-chromosomal network connected, surprisingly, both active and repressive chromatin domains involving LADs. Moreover, this network depended on the circadian recruitment of active chromatin hubs to the repressed chromatin structures at the nuclear periphery mediated by the physical proximities between CTCF and PARP1. This circadian pattern was required to attenuate transcription of the active chromatin hubs in a rhythmic manner. In summary, a new high-resolution technique termed ChrISP was invented in this thesis to enable quantitative analyses of dynamic of higher order chromatin structures. This technique could, moreover, be used to visualize specific chromatin marks, notably H3K9me2, within a specific chromosome in relation to structural hallmarks of the nucleus within a single cell. The compact chromatin structure thus identified was discovered to transiently harbor active chromatin hubs, which was recruited to the nuclear periphery in oscillating manner. We show that this feature likely underlies the attenuation of genes under circadian control. These findings open new perspectives to understand the function of dynamics of higher order chromatin structure

An analytical model for dynamic simulation of the composite rotor with internal damping

A theoretical model for the dynamics of composite rotor is presented. The composite shaft that includes rigid disks and is supported on rigid bearings is considered as a thin-walled Euler-Bernoulli beam. Internal damping of the composite shaft is taken into account. The equations of motion are derived using the thin-walled composite beam theory based on variational asymptotic method and Hamilton’s principle. The internal damping of shaft is introduced by adopting the multi-scale damping analysis method. Galerkin’s method is used to discretize and solve the governing equations. To demonstrate the validity of the present model, the convergence of the method is examined and the results are compared with those available in the literature. Numerical study shows the effect of design parameters on the natural frequencies, critical rotating speeds and instability thresholds of composite shaft. In addition, the free vibration responses due to the initial perturbations and the forced responses to unbalance for composite shaft are also presented

MIXED-FLOW PUMP OPTIMISATION AND FLOW CHARACTERISTICS BASED ON THE ‘DUAL CARBON’ GOALS

Urban water supply and drainage, the shipbuilding industry, the petrochemical industry and other professional fields rely heavily on mixed-flow pumps. Enhancing the efficiency of mixed-flow pumps is crucial for achieving the ‘dual carbon’ goals and promote energy saving and emission reduction. In this study, the guide vane and impeller of the mixed-flow pump were optimised, focusing on its low head and effectiveness in power plants. The performance of the original and optimised pumps was then evaluated under various flow rate conditions, and their hydraulic performance was compared. Results showed that the efficiency of the optimised mixed-flow pump was improved, resulting in effective enhancement of energy loss in the pump passage. The optimised guide vane facilitated smoother water flow into the outlet pipeline, achieving energy savings, emission reduction and contributing to the realisation of the ‘dual carbon’ goals

Semi-WTC: A Practical Semi-supervised Framework for Attack Categorization through Weight-Task Consistency

Supervised learning has been widely used for attack categorization, requiring high-quality data and labels. However, the data is often imbalanced and it is difficult to obtain sufficient annotations. Moreover, supervised models are subject to real-world deployment issues, such as defending against unseen artificial attacks. To tackle the challenges, we propose a semi-supervised fine-grained attack categorization framework consisting of an encoder and a two-branch structure and this framework can be generalized to different supervised models. The multilayer perceptron with residual connection is used as the encoder to extract features and reduce the complexity. The Recurrent Prototype Module (RPM) is proposed to train the encoder effectively in a semi-supervised manner. To alleviate the data imbalance problem, we introduce the Weight-Task Consistency (WTC) into the iterative process of RPM by assigning larger weights to classes with fewer samples in the loss function. In addition, to cope with new attacks in real-world deployment, we propose an Active Adaption Resampling (AAR) method, which can better discover the distribution of unseen sample data and adapt the parameters of encoder. Experimental results show that our model outperforms the state-of-the-art semi-supervised attack detection methods with a 3% improvement in classification accuracy and a 90% reduction in training time.Comment: Tech repor

Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity.

Here we introduce Protein-indexed Assay of Transposase Accessible Chromatin with sequencing (Pi-ATAC) that combines single-cell chromatin and proteomic profiling. In conjunction with DNA transposition, the levels of multiple cell surface or intracellular protein epitopes are recorded by index flow cytometry and positions in arrayed microwells, and then subject to molecular barcoding for subsequent pooled analysis. Pi-ATAC simultaneously identifies the epigenomic and proteomic heterogeneity in individual cells. Pi-ATAC reveals a casual link between transcription factor abundance and DNA motif access, and deconvolute cell types and states in the tumor microenvironment in vivo. We identify a dominant role for hypoxia, marked by HIF1α protein, in the tumor microvenvironment for shaping the regulome in a subset of epithelial tumor cells

A novel surface-cluster approach towards transient modeling of hydro-turbine governing systems in the start-up process

Transient process, an essential condition for the operation of the hydro-turbine governing system, is critical for the safety and stability of a hydropower station. This research focuses on the transient modeling and dynamic analysis of the hydro-turbine governing system in the start-up process. A novel approach is developed to establish the dynamic model of the hydro-turbine governing system in transient process. The flow equation and torque equation were improved to reflect the dramatic changes of system parameters during the start-up process. As a pioneering work, the effect of guide vane opening law on the dynamic characteristics of the hydro-turbine governing system in the start-up process was investigated by numerical simulations. The results of this research can promote the development of transient modeling and performance improvement of hydro-turbine governing systems in transient process

Prognostic Roles of ceRNA Network-Based Signatures in Gastrointestinal Cancers

Gastrointestinal cancers (GICs) are high-incidence malignant tumors that seriously threaten human health around the world. Their complexity and heterogeneity make the classic staging system insufficient to guide patient management. Recently, competing endogenous RNA (ceRNA) interactions that closely link the function of protein-coding RNAs with that of non-coding RNAs, such as long non-coding RNA (lncRNA) and circular RNA (circRNA), has emerged as a novel molecular mechanism influencing miRNA-mediated gene regulation. Especially, ceRNA networks have proven to be powerful tools for deciphering cancer mechanisms and predicting therapeutic responses at the system level. Moreover, abnormal gene expression is one of the critical breaking events that disturb the stability of ceRNA network, highlighting the role of molecular biomarkers in optimizing cancer management and treatment. Therefore, developing prognostic signatures based on cancer-specific ceRNA network is of great significance for predicting clinical outcome or chemotherapy benefits of GIC patients. We herein introduce the current frontiers of ceRNA crosstalk in relation to their pathological implications and translational potentials in GICs, review the current researches on the prognostic signatures based on lncRNA or circRNA-mediated ceRNA networks in GICs, and highlight the translational implications of ceRNA signatures for GICs management. Furthermore, we summarize the computational approaches for establishing ceRNA network-based prognostic signatures, providing important clues for deciphering GIC biomarkers

Inverse association between type 2 diabetes and hepatocellular carcinoma in East Asian populations

AimsTo investigate the potential association between type 2 diabetes (T2D) and hepatocellular carcinoma (HCC) in East Asian populations using Mendelian randomization (MR) analyses.MethodsBidirectional Mendelian randomization (MR) studies were conducted using summary statistics from genome-wide association studies (GWAS) related to T2D and HCC. The potential effects of confounders such as chronic hepatitis B, chronic hepatitis C, body mass index, and alcohol intake frequency were corrected using a multivariate MR study. Various MR methods, including the inverse variance weighted (IVW) approach, were used to estimate the associations between T2D and HCC. Sensitivity analysis and assessment of heterogeneity were performed to ensure the robustness of the results.ResultsIn the forward MR study, the IVW approach of MR analysis suggested an inverse association between T2D and HCC, with a risk odds ratio of 0.8628 (95% confidence interval [CI], 0.7888–0.9438). Furthermore, even after adjusting for BMI, chronic hepatitis B, and alcohol intake frequency, this study still supports the inverse association between T2D and HCC. Additional MR methods provided further support for this relationship. Sensitivity analysis and assessment of heterogeneity confirmed the robustness of the results. The reverse MR analysis did not show a clear impact of genetic liability to HCC on reduced risk of T2D(OR=0.9788; 95% CI, 0.9061-1.0574).ConclusionThis study provides evidence of an inverse association between T2D and HCC in East Asian populations using MR analysis. Further studies are warranted to validate these findings

Signals of Hotel Effort on Enhancing IAQ and Booking Intention: Effect of Customer's Body Mass Index Associated with Sustainable Marketing in Tourism

Since outdoor air pollutants may penetrate into hotels, indoor air quality (IAQ) has recently developed as an important criterion for tourists' decision to choose traveling destinations and for business travelers to select accommodation. Thus, some hoteliers have raised concern about the negative effects of emerging air quality issues on guests' experience and are willing to invest in improving the IAQ. Unlike hotel's currently offered services and products which are observable, the improved IAQ is almost invisible and the mitigation technology of air pollutants is new to hoteliers, consumers and researchers in the tourism. Hence, the search and understanding of the relationship of signals communicating hotel's effort on air quality enhancement and booking intention plus the mediating and moderating factors becomes the main objective of the research and can fill the knowledge gap plus meet the practical need. The study found that the more reinforced IAQ effort included in the website presentation, the higher the travelers' booking intention. The travelers' trust belief on hotel partially mediated the relationship between travelers' perception of reinforced IAQ effort input by hoteliers and their booking intention. Further, the study finds that enhancement of online booking intention do exist in segment of travelers who are high health-conscious. Also, the influence of health-conscious traveler's perception of hotel IAQ enhancement effort via portal on dependent variable-hotel booking was statistically significant. The findings enable hotel managers to have a deeper understanding of the relationship between the potential customers' booking intention on hotel rooms and the online marketing communication signals mediated by their trust on hotel's cleaning air effort. The results can serve as a reference for designing more effective 2 marketing communication programs and channels for hotels' endeavor to improve indoor air quality, especially sustaining the tourism development in the post epidemic era. Also, the study unveils some applied measures in improving hotel air quality not being documented in hospitality and tourism journals