1,912 research outputs found

    DNA G-quadruplex structures in the mammalian genome : dissecting genome-wide mechanisms of formation and turnover of DNA G-quadruplexes

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    Since the beginning of 20th century, when the G-tetrad was first discovered, scientists have been seeking to understand the role of G4 quadruplex structures (G4s) in replication, DNA damage, telomere integrity and the regulation of gene expression. However, it is likely that the field has just scratched the tip of the iceberg when it comes to assessing and interpreting the function of individual G4s, forming in a specific locus, in the complex context of chromatin. This is partially due to the limitations of available genome-wide G4 mapping methods, for example in terms of sensitivity and signal-to-noise ratio. Therefore, to further investigate G4 dynamics in mammalian cells, it is critical to develop robust, sensitive and quantitative methods to map endogenous G4s genome-wide. To achieve this, in paper I, we developed a quantitative method for genome-wide G4 mapping, termed G4 qCUT&Tag, by combining a G4-specific antibody with a modified CUT&Tag. We showed that G4 qCUT&Tag accurately and reproducibly generates genome-wide G4 maps, allowing us to study: 1) G4 landscapes in mESCs; 2) relation of G4s with other chromatin features in mESCs; 3) G4 dynamics during transcription and mESCs differentiation; (4) correlation of G4s and R-loops. G4s largely correlate with open chromatin, and since nucleosomes and G4s are mutually exclusive on a given stretch of DNA, it is believed that nucleosome dynamics affect G4 dynamics and vice versa. Thus, in paper II, we elucidated the mechanism of histone turnover and histone variant H3.3 incorporation in mESC-specific interstitial heterochromatin. We discovered that in the H3K9me3-featured heterochromatin the chromatin remodeler Smarcad1 evicts nucleosome and create accessible DNA, allowing H3.3 incorporation. The proposed model in paper II provided the basis for understanding the causal relationship between G4s and H3.3 incorporation in the heterochromatin

    VR Interactive Prototype: The Future Wardrobe. Explore VR interaction design for the sense of presence enhancement through an immersive VR installation

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    Virtual Reality (VR) is a new platform that provides the public with an immersive experience in a virtual space. With the development and promotion of VR hardware devices, virtual reality technology is applied in various industries such as the advertising of products, traveling, game, art, therapy, education and many others. Unlike media such as videos and pictures, VR applications allow users to interact with content instead of only watching. Beyond the novelty of the technology, for a meaningful immersive experience, VR interaction design and visual design must work together to place the user in a natural and comfortable state. The immersive VR interaction design is the key to improve the sense of presence in VR. However, most VR applications are still using traditional two-dimensional interactions. The most common is that information is displayed on a two-dimensional plane or a three-dimension space only has few interactions available. It is hard for users to keep having the presence through those traditional interactive ways. This project is a VR interactive prototype exploring VR interaction design to enhance the sense of presence through the showcase of the future wardrobe. It creates an immersive experience of integrating the futuristic user interface design, responsive gesture-based interactions, and VR environment design

    Effect of thermal cycling frequency on the durability of Yb-Gd-Y-based thermal barrier coatings

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    The effects of thermal cycling frequency and buffer layer on the crack generation and thermal fatigue behaviors of Yb–Gd–Y-stabilized zirconia (YGYZ)-based thermal barrier coatings (TBCs) were investigated through thermally graded mechanical fatigue (TGMF) test. TGMF tests with low- (period of 10 min) and high-frequency (period of 2 min) cycling were performed at 1100 °C with a 60 MPa tensile load. Different cycling frequencies in TGMF test generate two kinds of crack propagation modes. The sample with low-frequency cycling condition shows penetration cracks in the YGYZ top coat, and multiple narrow vertical cracks are generated in high-frequency cycling. To enhance the thermomechanical properties, different buffer layers were introduced into the TBC systems, which were deposited with the regular (RP) or high-purity 8 wt% yttria stabilized zirconia (HP-YSZ) feedstock. The purity of the feedstock powder used for preparing the buffer layer affected the fracture behavior, showing a better thermal durability for the TBCs with the HP-YSZ in both frequency test conditions. A finite element model is developed, which takes creep effect into account due to thermal cycling. The model shows the high stresses at the interfaces between different layers due to differential thermal expansion. The failure mechanisms of YGYZ-based TBCs in TGMF test are also proposed. The vertical cracks are preferentially created, and then the vertical and horizontal cracks will be propagated when the vertical cracks are impeded by pores and micro-cracks
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