1. Research
                                    • Big data is revolutionizing our life, work and thinking. An important and imperative research project is how to mine and use the information in big data efficiently. Our research about big data and design of experiments will focus on the following four sub-projects: 1) big data mining and algorithm; 2) the statistical inference of high dimensional convariance matrix; 3) the monitoring and diagnostics for the on-line big data; 4) the design theory and modelling for complex experiments. The detailed research contents will include: 1) in the view of computer science: data fusion algorithms, data mining and recommendation algorithms, privacy preserving data mining algorithms and parallel algorithms; 2) in the view of statistics: the robust estimation of high dimensional and sparse covariance matrix, the robust two-sample t test for high dimensional data, on-line monitoring and diagnostics for high dimensional data stream, how to define and monitor the quality of big data, the on-line monitoring for multivariate functional data, the optimality theory and construction of supersaturated designs with high and mixed levels, the construction and modelling of various Latin hypercube designs, etc. Our research results will include patents or software copyrights, papers and the cultivation of PhD and Master students.

                                    • Emerging and re-emerging infectious diseases are one of the major threats to human health and economic loss. This project focuses on the molecular mechanism of the complete biology of emerging and re-emerging pathogens, including EV71/CAV, tubercolosis, heptatitis A virus, coronavirus, influenza virus and bunyavirus. We will dissect the molecular mechanisms underlying pathogens infection/entry, replication and transcription, as well as maturation/releasing, and provide new strategies for anti-infection drug discovery based on the structural information acquired.

                                    • Spider silk and silkworm silk are the most attractive biomaterials with extraordinary mechanical properties created by nature. Besides, chitin, cellulose and polysaccharides are the most abundant natural biomaterials and have been widely used by humans. Elucidating the precise control of the multi-scale structure and dynamics in biomacromolecules, and furthermore, developing biopolymer materials with high performance through multi-scale biomimetic methods, and achieving the high-performance for traditional synthetic polymers are important research topics in polymer science. In this project, multi-scale solid-state NMR in combination with other characterization techniques will be adopted to reveal the micro-phase separation structure and interface in high-performance natural biomaterials, such as the hydrogen bond interaction between water and biomacromolecules, the complex chain motion of the biomacromolecules, evolution of multi-scale structure and dynamics during the stretching process as well as its influence on the mechanical properties in different length and time scales, thus to establish an in-depth understanding of the structure-property relationships of high-performance biomaterials. On the basis of the above work and through multi-scale biomimetic molecular design, we will prepare a series of high-performance biomimetic polymer materials based on biopolymers and synthetic polymer with high density of hydrogen bonds, such as chitosan and multi-block polyurethanes. Our work will promote the fundamental research and industrial applications of high-performance biopolymer and polymer materials of our country.

                                    • In recent years, metal-organic frameworks (MOFs) have become one of the active and cutting-edge fields of chemistry and material science. During the past decades, the investigation in this field has primarily focused on the rigid MOFs, while the study of flexible MOFs is still rare, leaving many scientific issues to be resolved, such as the function-oriented construction of flexible MOFs; the dynamic structure of flexible frameworks as well as the characterization of their dynamic behaviors; and the intrinsic relationship between the dynamic structures and resulting properties of this class of materials. Focusing on these scientific issues and oriented by the aim of achieving effective material storage and dynamic separation, this project will proceed with the reasonable design and construction of flexible MOFs, along with the exploration of their fundamental assembly rules. Through establishing and improving the characterization methods for the dynamic structures and behaviors of such flexible MOFs, this project will then discover the mechanism of their dynamic behaviors and unravel the nature of the resulting unique properties as well as the implicit regularity, followed by further investigation of their material storage and separation functions to reveal the intrinsic structure-property relationship. On this basis, this project eventually aims to explore the functional optimization and practicalization of this class of flexible MOF materials. Finally, we hope to promote and lead the development of this field through the execution of this project together with the resolution of related scientific problems.

                                    • Development of precise and efficient methods and technologies for creating new materials is at the forefront of chemical science and the focus of technology innovation. In this project, we will combine traditional synthesis and asymmetric catalysis to develop new asymmetric catalytic kinetic resolution reactions, methods and strategies. We will study the kinetic resolutions and dynamic kinetic resolutions in the catalytic asymmetric hydrogenation of esters, ketones and enones, aiming for efficient, green, and atomic economic synthesis of chiral alcohols, especially the chiral alcohols with multiple chiral centers. We will also study the applications of asymmetric catalytic kinetic resolution in the total syntheses of chiral drugs and bioactive natural products. Hopefully, this project will develop new processes for creating chiral materials, and promote the pharmaceutical industry.

                                    • The microscopic analysis of stained tissue slides is the gold standard of cancer diagnosis in pathology. A new visualization concept, namely digital pathology medical, is being widely accepted. Meanwhile, a new application area, namely virtual microscopy, has formed. However, there is still a gap between the user needs and the performance of the digital pathology scanner products available on the market. So it is difficult for these products to replace the existing technology on a large scale. Here we propose a novel instrument research project based on a new principle called Fourier ptychographic microscopy (FPM), together with many key technologies, such as aperture optimization and parallel algorithms. It is worth noting that our new project breaks the resolution limitation of the traditional imaging theory and the resolution of the same lens can be increased several times to more than ten times. In addition, high throughput and high efficiency will be achieved through simultaneously sampling in spatial and frequency domain. With the contradiction between wide field and high resolution solved, the instrument performance could be comprehensively improved. Compared with the products on the current market, the overall performance of the new instrument will be improved by more than 5 times. Through the research project, we expect to get new high-end microscopy imaging technology and product with independent intellectual property rights and the ability to occupy the domestic and foreign markets.

                                    • In the NSFC key program finished and the 973 program to be finished, the study on vector optical fields focuses on: principles of manipulating polarization, spatiotemporal evolution, and novel effects and potential applications of linear and nonlinear interaction with the matter. We have resolved the issues on the principles and experimental realization of the local linearly-polarized vector fields with arbitrarily spatial distribution and arbitrarily orientated polarization, and of some hybridly polarized vector fields with special spatial distributions. However, we still cannot resolve the issue on principles and experimental realization of vector fields with arbitrarily spatial distribution and arbitrary polarization states (including linear polarization with arbitrary orientation, elliptic polarization with arbitrary orientation, ellipticity and sense, and circular polarization with arbitrary sense). In fact, such an unresolved issue as mentioned above is one of the key issues focused on in this project. After the above issue has been resolved, the second set of issues focused in this project is, through introducing the concept of fractal and based on the self-similarity and iteration rules, to realize the design and control of spatial fractal structures and the generation of spatial fractal vector fields. Furthermore, we will study the unique novel linear and nonlinear effects, peculiar properties and potential applications, which are originated from the fractal structure. We will also reveal the regularities and mechanisms of influences of structure and dimension and level of the spatial fractals. We will explore the principles, schemes and feasible approaches in realizing the far-field focusing beyond the diffraction and the far-field imaging beyond the resolution by using the spatial fractal structure.

                                    • The high restenosis rate of small-diameter vascular grafts has restrained its clinical application. The main bottle-neck in this research is that the regeneration mechanism of small-diameter vascular grafts is not clear yet. The challenge is to achieve rapid endothelialization, regeneration of tunicae media and adventitia and prevention of late stage restenosis. Under the old and sick conditions, the regeneration of vascular grafts is more difficult. The function of endothelium often declines in late stage, which causes vascular wall calcification, neointimal formation and complete occlusion of the implants. In this project, we will use transgenic mice and bone marrow transplantation mice to investigate the regeneration mechanism of vascular grafts, the source of vascular cells and their migration route. We will also investigate the regulatory role of macrophages and explore the key active substances that play critical roles in vascular regeneration. Following the mechanism study, we will fabricate vascular grafts with aligned pores and fibers that can well facilitate the regeneration of the three vessel layers. We will further modify these grafts with VEGF, NO, protein XBP1 and DDK3 peptide in suitable composition, dosage, immobilization manner, spatial distribution and release profile. We will perform a certain amount of rat and rabbit experiments to verify the regeneration mechanism found in the mouse study and systemically evaluate the regeneration capacity of the small diameter vascular grafts which we prepared with the optimized techniques. In the end, we will carry out large animal tests and evaluation in diseased rats and rabbits to further investigate the effect of structure and bioactive modification on vascular regeneration. These animal experiments will help to further optimize the preparation of vascular grafts which may lead to potential vascular graft products for clinical treatment.

                                    • Infection diseases caused by high pathogenic viruses are some of the major threats to public health and economic development. In recent years, numbers of high pathogenic viruses have led to worldwide pandemics and caused severe infection diseases. Infections with these viruses often are associated with deadly hemorrhagic fevers with extremely high mortality rates, and currently there is no effective therapeutics or vaccines for any of these agents. Some of them are classified as Biosafety Level 4 (BSL-4) pathogens, and also represent potential bioterrorism threats. Therefore, the demand for the understanding of these high pathogenic viruses and inhibition mechanisms to their infection is emerging. The applicant (Dr. Zihe Rao, MCAS, Tsinghua University) and the co-applicant (Dr. David Stuart, FRS, University of Oxford) are both interested in the structure and function of the key protein complexes which are essential for high pathogenic viruses’ infection and replication. In the past several years, both have published a series of high impact works on the structures of hand-foot-and-mouth disease virus (HFMDV), hepatitis A virus (HAV) and other high pathogenic viruses, through X-ray crystallography, EM and other integrated methods. According to our common interests and expertise, we plan to further investigate the structure and function of the protein complexes encoded by high pathogenic viruses, including Ebola/Marburg viruses, HFMDV, SARS-CoV/MERS-CoV, HAV, etc. We will also discover leading compounds to inhibit the infection and replication of high pathogenic viruses based on the structural information.



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