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NSFC/RGC Joint Research Scheme 2010/2011 Supported Applications - Layman Summaries of Projects Funded in 2010/2011 Exercise

Study on Magnetorheological Fluid Jet Polishing of Optical Freeform Surfaces (OFS) Using Computer-Controlled Polishing (CCP) Combined with Non-symmetrical Tool Functions
Hong Kong Principal Investigator : Prof Yeung Yam (The Chinese University of Hong Kong)
Mainland Principal Investigator : Prof Haobo Cheng (Beijing Institute of Technology)

This project is aimed at a comprehensive study of computer-aided polishing technology for freeform surfaces with non-uniform curvatures using magnetorheological fluid as medium. Building upon our extensive experience in magnetorheological and electrorheological processes as well as previous collaboration in computer-based optical polishing, the project serves to explore the relations between magnetorheological fluid jet formation and the ensuing polishing performance. Simulation will be performed to evaluate the effects of jet speed, pressure, diameter, nozzle angle and various geometric parameters of the nozzle on the resulting polishing characteristics and removal function. The project will aim at a feasible design and construction of a polishing platform with built-in functions of task planning, process simulation and performance predication. Given the amount of budget possible, experiments will be carried out supported by a combination of existing equipment in our laboratory and new ones from other resources. The project will focus on understanding and tackling the technical challenges on the controllability of Magnetorheological fluid-based polishing, the formation of surface micro-defects, and the edging effects of complex surfaces in order to facilitate a reliable and quality fabrication of freeform optical components of diameter 30 mm or above and surface gradient of no less than 10λ/mm.

Hybrid InGaAsP-silicon unidirectional-emission microcavity lasers for on-chip optical interconnects
Hong Kong Principal Investigator : Prof Andrew Wing On Poon (The Hong Kong University of Science and Technology)
Mainland Principal Investigator : Prof Yong-Zhen Huang (The Chinese Academy of Sciences)

This project aims to develop hybrid indium-gallium-arsenide-phosphide (InGaAsP) on silicon (Si) uni-port directional-emission microcavity laser sources for next-generation high-bandwidth energy-efficient on-chip optical interconnect applications.

For high-bandwidth energy-efficient on-chip interconnection, the conventional copper electrical interconnects become bandwidth-limiting and cause excessive electrical power consumption. One potential solution is on-chip optical interconnects, in which high-bandwidth optical signals are routed through submicrometer-sized low-loss integrated optical waveguides. In contrast with copper interconnects, optical interconnects feature many key advantages including wide bandwidth and potentially low-power consumption. Furthermore, wavelength-division multiplexing (WDM) technology potentially enables further increase of the data capacity.

Silicon photonics offers a promising technology platform for on-chip optical interconnects. However, silicon due to its indirect bandgap does not efficiently emit light. In order to enable on-chip laser sources, hybrid InGaAsP-Si lasers have been recently demonstrated and attracting significant research interests. Nonetheless, one shortcoming of the demonstrated hybrid silicon lasers using conventional optical microresonators such as racetrack microrings and circular-shaped microdisks output-coupled to a bus-waveguide is the bi-directional lasing emission, which results in significant optical power loss and imposes additional structures such as grating-based reflectors or waveguide couplers in order to re-route or combine the laser emissions. For optical interconnect applications, it is desirable to develop on-chip uni-port directional-emission microcavity laser sources that enable direct coupling to waveguides without imposing additional structures or excess footprint.

This project aims to leverage from the complementary expertise of HKUST team on silicon photonic microresonator devices and Institute of Semiconductors, Chinese Academy of Sciences (ISCAS) team on InGaAsP microcavity lasers and InGaAsP-on-silicon wafer bonding techniques. Based on our on-going work on passive silicon microspiral disk resonators, which feature a spiral notch for direct gapless coupling to a silicon waveguide, here we propose to develop hybrid InGaAsP-silicon uni-port directional-emission microspiral disk laser sources. We will investigate two hybrid integration schemes, namely, (A) bonding an InGaAsP gain medium on top of an evanescently coupled silicon microspiral disk resonator, and (B) fabricating an InGaAsP microspiral disk laser with a gaplessly coupled active waveguide on top of an evanescently coupled silicon waveguide. For each scheme, we will adopt and evaluate two die-to-wafer bonding techniques, namely, silica (SiO2) molecular bonding and benzocyclobutene (BCB) adhesive bonding. We will design the microcavities/waveguides on commercial silicon-on-insulator (SOI) and InGaAsP multiple quantum well (MQW)-on-InP substrates for uni-port directional emission and vertical p-i-n diodes in InGaAsP for current injection to the active region. We will characterize the hybrid-silicon laser performance in terms of the uni-port directional-emission output power, the threshold current, the power consumption, the laser spectrum and linewidth, etc. We will investigate the microspiral lasing mechanism and output-coupling properties.

Noise and Transient Dynamics in Intracellular Biochemical Networks
Hong Kong Principal Investigator : Prof Leihan Tang (Hong Kong Baptist University)
Mainland Principal Investigator : Prof Yuqiang Ma (Nanjing University)

How can genetically identical cells exhibit a broad range of phenotypes and responses? The search for answers to this question, which appears to violate some of the long-held believes in textbook biology, prompted active experimental and theoretical investigation of noise in molecular networks in recent years. The research is aided by recent advances in GFP fluorescent microscopy that tracks the copy number of selected proteins in a single cell, and in flow cytometry that enables collection of large number of single-cell data for detailed statistical analysis. In the proposed project, we aim at developing effective and robust methodologies to analyze the rapidly accumulating experimental data to extract underlying molecular mechanisms of noise generation and propagation. Through close collaboration between the participating theoretical and experimental groups, we will work on both the theory development to integrate molecular level knowledge and data for systems level modeling and analysis, and on testing the general framework in specific cases of interest, in particular the osmo-stress response pathway in yeast. Although the focus of the current project is on quantitative description of basic biological processes in a network setting, the capabilities developed will enable us to tackle problems related to complex dynamics in human disease such as cancer, thus gaining a broader impact. The project will also benefit the collaborating institutions in their respective research developments in this burgeoning interdisciplinary field.

Characterizing Prevalent Clones of Multi-drug Resistant, Community-associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) in Mainland China and Hong Kong: Resistance Mechanisms and Virulence Factors Distribution
Hong Kong Principal Investigator : Prof Margaret Ip (The Chinese University of Hong Kong)
Mainland Principal Investigator : Prof Xuzhuang Shen (Capital Medical University)

Community-associated MRSA (CA-MRSA) is a major cause of bacterial infections and has emerged in the community in recent years and become epidemic in some countries. Studies indicate that CA-MRSA strains are more virulent and spread readily to cause disease, and MRSA is now a leading cause of death by any single infectious agent in the U.S., causing significant morbidity and mortality. These strains possess specific virulence factors that enhance survival and pathogenicity, including an arginine catabolic mobile element, alpha-type phenol-soluble modulins (PSMα 1-4), α-haemolysins and the presence of panton-valentine leukocidin (PVL) toxins, such that the latter, in particular, have been implicated in multiple recurrent skin abscesses to fatal necrotizing pneumonia. Initiatives have been introduced to control MRSA globally. However, the disease burden with MRSA remains significant, and it is a major concern that CA-MRSA becomes pandemic worldwide.

The major MRSA types in Hong Kong and mainland China belong to a few clonal types that are distinct and unique to the USA clones, in that they are often multidrug-resistant, thus significantly limiting the choice for treatment and increases clinical failure rates and mortality.

This study aims to (1) characterize the molecular types of prevalent multidrug-resistant CA-MRSA clones in mainland China and Hong Kong; (2) define the resistance mechanisms, the relationships of multiple resistance determinants within common mobile genetic element, inc. plasmids and transposons and their potential to spread; and (3) the presence of major virulence factors, including the arginine catabolic mobile element, alpha-type phenol-soluble modulins (PSMα 1-4), α-haemolysins and the presence of panton-valentine leukocidin toxins, and the pathogenic potential of CA-MRSA to cause severe disease in an animal infection model.

The study will contribute to the basis of future potential targets for treatment of staphylococcal disease and to public health importance in the formulation of programmes in the control of MRSA. An important endeavour will be to establish a platform to compare CA-MRSA strains locally, within mainland China and Hong Kong, in order to reveal major insights into transmission and micro-evolution of predominant clones.

Novel Strategies to Overcome ATP-binding Cassette Drug Efflux Transporters-mediated Multidrug Resistance in Cancer Cells
Hong Kong Principal Investigator : Prof Kin-wah To (The Chinese University of Hong Kong)
Mainland Principal Investigator : Prof Liwu Fu (Sun Yat-Sen University)

Inherent or acquired resistance of tumor cells to anticancer drugs represents a major limitation to the successful chemotherapeutic treatment of cancer. Over-expression of ATP-binding cassette (ABC) transporters is now known to be one of the most important mechanisms responsible for multidrug resistance (MDR), in which tumor cells exhibit simultaneous resistance to structurally unrelated anticancer drugs. Inhibitors against the ABC transporters, particularly P-glycoprotein (P-gp), have been designed and clinical trials conducted in the search for strategies to reverse the MDR phenotype. Tyrosine kinase inhibitors (TKIs) are an important new class of molecularly-targeted cancer chemotherapeutic agents for several cancer types. Several recent reports about the potent and specific inhibition of MDR transporters by various TKIs have renewed the research interest in developing drug transporter inhibitors for the circumvention of MDR The proposed study will systematically investigate selected TKIs, currently in clinical trials in China, for inhibition of ABC transporters and MDR reversal activity. Resistant cell line models with defined over-expression of the three major MDR transporters (P-gp, MRP1 and ABCG2) will be used. The potential mechanisms for MDR reversal will be studied in detail. Moreover, the MDR reversal activity observed in cancer cell lines will be confirmed in appropriate animal models. Cancer stem-like cells (CSCs), small population of cells within a tumor that drive tumor growth and metastasis, usually over-express MDR transporters including ABCG2 and P-gp. They are generally believed to be the ultimate cause of drug resistance and tumor recurrence. The potential targeting of CSCs by TKIs and the enhancement in the sensitivity of CSCs to other conventional chemotherapeutic drugs will be investigated. Unfavorable drug-drug interaction due to inhibition of drug metabolizing enzymes, especially cytochrome P450 (CYP) monooxygenases, is one of the obstacles hindering the further development of the 1st and 2nd generation of P-gp inhibitors and MDR reversing agents. Therefore, the TKIs will also be evaluated for their possible interaction with CYP isozymes and their potential interference with pharmacokinetics of some anticancer drugs. Last but not least, some TKIs are in fact substrates for the MDR transporters. Drug resistance to TKIs is fairly common and one of the mechanisms for the resistance is the over-expression of MDR transporters. Therefore, the efflux of TKIs by the MDR transporters will also be studied. Collectively, the obtained results will provide the basis for the rational use of TKIs in conjunction with conventional anticancer drugs for the reversal of multidrug resistance.

Molecular and Cellular Mechanisms of Hypoxia/HIFα Pathway in Regulating Biological Behavior of Mesenchymal Stem Cells
Hong Kong Principal Investigator : Prof Chao Wan (The Chinese University of Hong Kong)
Mainland Principal Investigator : Prof Lianfu Deng (Shanghai Jiao Tong University)

In clinic Orthopaedics, large bone defects or fracture non-union are difficult skeletal disorders that cause tremendous suffer and cost to the patients and society. The pathology of the impaired healing is characterized by less capacity of bone formation associated with decreased vascular supply and lacking of reparative stem cells. Skeletal development is initiated when mesenchymal cells aggregate at the location of and condense in the shape of future skeletal elements. The development of the cranium occurs though a process termed intramembranous ossification, whereas the long bones form by endochondral ossification mediated by a cartilage template. Following injury, mesenchymal stem cells (MSCs) together with other reparative cells are recruited and involved in the initiation of fibrous callus formation of the healing bone. Hypoxia is known to be an important developmental and reparative signal that controls the coupling of angiogenesis and osteogenesis, regulates differentiation and proliferation of stem/progenitor cells. Hypoxia-inducible factors (HIFs) have been identified as the major mediators of the hypoxia response. Our previous data shows that mice overexpressing HIF-1α (by deletion of VHL) in osteoblasts have dramatic bone phenotypes with increased vascularity, whereas mice lacking HIF-1α have narrow and less vascularized bones. In addition, manipulation of HIF-1α at an earlier condensing mesenchyme affects cranial bone development. However, the role of the HIF pathway in regulating MSC biological behavior remains unclear. In this proposal, we will investigate the essential function of HIFα in regulating MSC biological behavior using genetic mouse models, and explore the potential therapeutic effect of a chemically modified bone-seeking complex of HIF activators on bone defect reconstruction. We expect that the proposed studies will further our knowledge on the molecular and cellular mechanisms of the HIF pathway in regulating MSC function and lead to discovery of novel therapeutic agents or MSC based therapy for patients with impaired bone healing or acquisition.

Novel Strategy for Prevention of Disuse Bone Loss by Using Implantable Micro-Electrical Stimulators
Hong Kong Principal Investigator : Dr Xia Guo (The Hong Kong Polytechnic University)
Mainland Principal Investigator : Prof Lu-Ming Li (Tsinghua University)

It has been well known that mechanical force is an important factor influencing bone health. Disuse of limbs associated with immobilization or spinal cord injury can result in bone loss. Mechanical stimulation has been demonstrated to be effective in prevention of bone loss. But it remains largely unexplained how the physical force to be converted to biological signals triggering subsequent cellular reactions. Findings of our previous studies have demonstrated that sensory nerves in bone can perceive mechanical strain or stress and convert mechanical stimulation to biochemical or biological reactions of sensory neurons and bone cells. We hypothesized that electrical stimulation direct to the cell bodies of sensory neurons at dorsal root ganglia (DRG) may prevent bone loss as effective as external forces. Tsinghua team has successfully developed implantable micro-electrical stimulators (IMES) for treatment of diseases of nervous system since 2002. We would like to study further the feasibility of using IMES simulating DRG to prevent disuse bone loss.

Understanding genetic and epigenetic features of active promoters in human/mouse embryonic stem cells
Hong Kong Principal Investigator : Dr John Junwen Wang (The University of Hong Kong)
Mainland Principal Investigator : Prof Michael Qiwei Zhang (Tsinghua University)

Recent high throughput experiments discovered that mammalian transcriptomes are much more complex than we previously thought. First, even though only 2% of human DNA is coded for protein products, the majority of human DNA (~90%) is transcribed. Most of these transcripts, including microRNAs and long non-coding RNAs (lncRNAs), are also transcribed by PolII. Second, about 70-80% of promoters of known genes initiate transcripts in both sense and anti-sense directions (divergent transcription). Among them, 10% can produce long full length transcripts in both directions (bidirectional promoters). Third, mammalian embryonic stem cells (ESCs) have more active promoters, but as the cells differentiate and specialize, promoters become less active.

For the different types of transcripts produced by PolII, we hypothesize that the genetic and epigenetic features in their promoter regions are similar. Genetically, we will compare features such as CpG island association, molecular evolution, transcription factor binding modules, and chromatin interaction. Epigenetically, we will compare features such as histone modifications (methylation, acetylation), and DNA methylations. Specifically, we will compare these features of different subclasses of active promoters in human and mouse embryonic stem cells, based on the following classifications: 1) protein coding, microRNA, and long noncoding RNA genes; 2) unidirectional, bidirectional, and divergent transcribed genes; and 3) genes expressed in embryonic stem cells and in differentiated cells. With a better understanding of the different subclasses of promoters, we will incorporate these features to 4) develop novel algorithms for effective identification of active promoters for a specific cell type.

This research will provide us with novel insights into the causes of mammalian PolII's transcription divergence. It will tell us how these genetic and epigenetic features influence PolII's decision on which type of transcripts to produce, and when and where to produce them. With these deeper understandings, we will be able to design drugs to act on the relevant features, and thus pave the ways for therapeutic treatments for cancers.

p38 MAPK in human lung cancers and its potential involvement in treatment resistance to tyrosine kinase inhibitors
Hong Kong Principal Investigator : Dr Maria Pik Wong (The University of Hong Kong)
Mainland Principal Investigator : Prof Jiahuai Han (Xiamen University)

The p38 MAPK pathway regulates the body response to a wide range of stress stimuli in a context-dependent and tissue-specific manner. The isoform p38 (p38) mediates multiple tumour suppressive functions such as oncogene-induced senescence, enhanced differentiation, apoptosis and DNA repair. Genetically altered adult mice with no p38 expresssion show predisposition to mutant RAS-induced lung carcinogenesis, indicating that p38 could serve as a tumour suppressor gene of the lungs. However, some of the functions mediated by p38 in reactive conditions, e.g. enhancement of cell survival and migration, can positively affect tumour development in established cancers. Inhibition of p38 has been reported to result in tumour suppressor effects in some cancers; however, data regarding lung cancer is limited. Non-smoking women in Hong Kong, China and Asian countries have unusually high risks of lung cancers with frequent somatic activating mutations of EGFR. Tumours with mutant but not wild type EGFR show initial good response to anti-EGFR targeted therapy by tyrosine kinase inhibitors (TKI) but drug resistance develops within 1 year and the mechanism is not fully understood. p38 is a downstream target of EGFR through activation by the MAPKinase cascade. It is also involved in multiple crosstalks with other signaling pathways. Limited information on the interaction between mutant EGFR and p38, and the effects of TKI treatment are available. We hypothesize that in lung cancers, p38 could play a tumour-supportive role by augmenting pro-survival pathways and epithelial to mesenchymal transition (EMT). Modulation of p38 activities could influence tumour sensitivity to TKI treatment. Since p38 activities are regulated in a context-dependent manner, p38 activities could be influenced by different micro-environmental conditions such as the degree of hypoxia, inflammation, necrosis, etc. in the cancer. To test these hypotheses, we propose: 1). To study the functional role and effects of p38 modulation, as well as relation with TKI response with regard to cell survival and EMT in lung cancer using cell-based models. 2). To study the in vivo p38 gene expression/activation status and their correlation with signaling markers and clinicopathological parameters including patient survival in a panel of clinical lung cancers. The results would lead to a better understanding of the role of p38 in lung cancers, and help to determine whether p38 could be a useful molecular target for lung cancer treatment especially in relation to EGFR mutations and TKI resistance.

Mechanism and Novel Therapy for Aristolochic Acid Nephropathy: Role of Smad7
Hong Kong Principal Investigator : Prof Hui-yao Lan (The Chinese University of Hong Kong)
Mainland Principal Investigator : Prof Ping Fu (Sichuan University)

Aristolochic acid nephropathy (AAN) is the most severe complications related to the use of Traditional Chinese Medicine (TCM) and has become a world-wide disease. However, the mechanisms of AAN remain largely unclear, no prevention and treatment to AAN are yet available. Therefore, it is timely and urgently to define the molecular mechanisms and develop effective therapy for AAN.

Recently, we found that AA caused chronic AAN via the scarring pathway called TGF-β/Smad3. Our preliminary studies also found that development of chronic AAN is associated with activation of the inflammatory pathway called NF-κB and that over-activation of both fibrosis (TGF-β/Smad3) and inflammatory (NF-κB) pathways in chronic AAN was associated with a loss of Smad7, an inhibitor to both pathways. In contrast, in vitro over-expression of Smad7 was capable of blocking AA-induced TGF-β/Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation. All these preliminary findings strongly suggest that loss of Smad7 may be a key mechanism in the development of chronic AAN. Therefore, we hypothesized that Smad7 may have protective role and therapeutic potential for chronic AAN. We plan to examine this hypothesis in 3 specific aims: 1) To determine the mechanisms of AA-induced loss of renal Smad7 and the importance of Smad7 in protection against AA-induced renal fibrosis and inflammation in vitro in tubular epithelial cells that lack or over-express Smurf2 or Smad7; 2) to investigate the mechanisms and protective role of Smad7 in a mouse model of chronic AAN induced in Smad7 gene knockout (KO) mice; 3) to develop a therapeutic strategy for prevention and treatment of chronic AAN by a novel Smad7 gene therapy using an established ultrasound-microbubble-Smad7 gene therapy approach.

Ultimately, the significance of this study is to determine the mechanisms and protective role of Smad7 in chronic AAN, which is the first step towards designing a novel and specific therapy for this severe complication of TCM by gene transfer of Smad7. We predict that AA induces a loss of renal Smad7 to promote TGF-β/Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation in chronic AAN. We also expect that progressive renal injury in chronic AAN will be enhanced in mice deficient for Smad7, but prevented or reversed by treatment with Smad7. The outcomes from this study will provide a novel and specific therapy for chronic AAN using Smad7. Thus, the proposed study is highly significant both scientifically and clinically.

Novel Highly Ordered Micro-nano-tube Electrode Materials: Preparation, Characterization and Application in Photoelectrochemical Degradation of Priority PTS Pollutants
Hong Kong Principal Investigator : Prof Guohua Chen (The Hong Kong University of Science and Technology)
Mainland Principal Investigator : Prof Xinyong Li (Dalian University of Technology)

The removal of persistent toxic substances (PTS) from water is a challenging research topic globally. The halogen-containing PTS, such as polychlorinated biphenyls and chloro-phenols that are widely used as preservative agents, disinfectants and industrial chemicals, have been discharged into the environment in the past century. The conventional biological processes generally find it difficult to deal with those recalcitrant and toxic organic species. Physical separation normally ends up with a concentrate stream that needs further treatment. The advanced oxidation employing photocatalysts with solar light is considered to be one of the most economic and effective technologies in the degradation of these PTS. The development of proper photocatalysts is the focal point of this type of research.

Since the report of hydrogen generation from the surface of TiO2 upon photo illumination in 1972, scientists worldwide have been working on this material and have accumulated plenty amount of knowledge. In spite of its excellent stability and abundance, pure TiO2 is not practically applicable for its low spectral utilization of solar light, because of its wide band-gap (3.2 eV for anatase form). Recent success in the production of TiO2 nanotube arrays and their enhanced photochemical properties have opened up a new field of research. In particular, quantum dot modified TiO2 nanotube arrays have been shown effective in enhancing energy conversion and removing typical PTS. At present, the nanotubes are generally employed as photoanodes only to produce holes, whereas the photo-induced electrons are not utilized efficiently. There are also many toxic intermediates produced during the oxidative degradation of PTS at the anodes.

This project therefore aims at first developing a series of novel materials with multiple heterojunctions based on modified TiO2 nanotube arrays or TiO2 microtubes. TiO2 nanotube arrays will be produced by anodization of titanium foil. TiO2 microtubes will be prepared with a sol-gel method. The quantum dots of coupling species potentially implanted into TiO2 tubes include boron-doped diamond (BDD), spinels (AB2O4) (as hole collectors), Ni, Ag, Pd, and Pt (as electron collectors), etc. The novel materials will be characterized for their physical, chemical, photo, photoelectrochemical properties. The promising composite materials will be employed as anodes and cathodes, respectively, and assembled in photoelectrochemical cells to mineralize chlorine-containing priority persistent and toxic substances. Besides the efficient harnessing of visible solar energy, the arrangement merits cathodic reduction of the recalcitrant intermediates produced by anodic oxidation, maximizing the energy efficiency by utilizing the photo-induced electrons in addition to the holes. The intermediate and the final products will be monitored so that the degradation mechanism can be studied. The photovoltaic behaviors of the novel materials will also be examined.

Eutrophication and Associated Hypoxia in Lingding Bay and Adjacent Coastal Waters: Biogeochemical Processes and Sedimentary Records
Hong Kong Principal Investigator : Dr Zhonghui Liu (The University of Hong Kong)
Mainland Principal Investigator : Dr Guodong Jia (The Chinese Academy of Sciences)

Eutrophication and its induced hypoxia in estuaries and coastal waters can cause a series of environmental issues. Although the current occurrence of hypoxia in Lingding Bay and adjacent coastal waters is less severe as compared to some severe regions, the likelihood of future development of such conditions due to increased human activities in this region requires our great awareness. In order to further understand the occurrence of eutrophication and hypoxia in this region, we propose to conduct systematic studies of modern biogeochemical processes and historical (sedimentary) records. We plan to choose geochemical indicators which are present in both waters and sediments and can address specific scientific problems. These geochemical indicators, including elemental (Re, V, U, Mo and sulfur compounds), isotopic (δ15N and δD), and organic geochemical analyses (TEX86, MBT/CBT), will be assessed with modern processes and then applied to reconstruction of sediment records.

We aim to better understand temporal and spatial patterns of (1) nitrogen cycling process, (2) phytoplankton community structure, and (3) bottom water redox conditions within the coastal waters near Hong Kong, through investigations of water and sediment samples using multiple geochemical tools, to reconstruct the history (last hundreds of years) of coastal eutrophication and hypoxia in this region and their potential relations with past climatic and environmental changes, and to assess current state and possible future trend of coastal eutrophication and hypoxia. We hope this study could provide scientific bases to policy-makers for coastal environment management.

The effects of social capital on organizational performance in the context of e-business: A longitudinal research
Hong Kong Principal Investigator : Prof Wei Kwok Kee (City University of Hong Komg)
Mainland Principal Investigator : Dr Lu Yao Bin (Huazhong University of Science and Technology)

Social capital increasingly becomes a mechanism that engenders access to resources through social networks and thus, it is regarded as an enduring source of competitive advantage. Understanding the performance outcomes of social capital is of great significance and attracts attention from researchers and practitioners. However, the previous findings on the outcomes of social capital have been mixed and even controversial. Furthermore, more and more organizations are developing and managing their social networks via the Internet. The prevalence of the Internet thus is challenging our current understanding of social capital as the Internet affords open connection and low switching cost, and therefore reconstructs social networks. Yet, there is a dearth of research empirically exploring the outcomes of social capital and how dimensions of social capital (i.e. structural, relational, and cognitive capital) interact with each other in the context of e-business. As such, the true value of social capital remains unclear, and practitioners are left with little guidance on whether the purported benefits of social capital can be materialized in the Internet era.

To address these pending research questions, our study aims to reveal (1) Salient factors rooted in social capital that are critical for performance in the context of e-business, (2) How dimensions of social capital are related differently with substantive and symbolic performance, respectively, (3) How structural, relational, and cognitive capital impact performance interactively. Drawing upon social capital and institutional theory, we develop a research framework on the relationship between social capital and organizational performance in the context of e-business. Specifically, we argue that social capital does not only impact substantive performance, but also influences symbolic performance. We further propose that structural, relational, and cognitive capital would improve organizational performance interactively, and their influences on substantive and symbolic performance would vary.

To examine the proposed conceptual framework, we will conduct a longitudinal survey study in China. The results obtained will have significant theoretical and practical implications. It will contribute to the social capital and value creation literature by offering a more complex picture of how social capital influences organizational performance in the context of e-business in China. It will extend our understanding of the different effects of structural, relational, and cognitive capital on substantive and symbolic performance. Furthermore, this study may be among the first to investigate how structural, relational, and cognitive capital affect organizational performance interactively. The findings of this proposal research will contribute to the practice by offering guidelines regarding tactics for promoting the right social capital dimensions to enhance right organizational performance.

Combining Simulation and Optimization with Applications in Financial Risk Management
Hong Kong Principal Investigator : Prof Jeff Hong (The Hong Kong University of Science and Technology)
Mainland Principal Investigator : Prof Jianqiang Hu (Fudan University)

Since Markowitz's classical work on mean-variance framework in 1950s, portfolio selection has become one of the pillars of today's finance research and practice. The basic intuition is that an investor needs to balance the expected return and the risk of possible loss. However, variance being a measure of risk is fundamentally problematic as it penalizes not only the excessive losses but also the excessive returns. Value-at-risk (VaR), which measures only excessive losses, is a more appropriate risk measure. It has been used widely in financial industries to control portfolio risk and to regulate bank capital requirements. In this project, we will study several problems related to VaR constrained stochastic optimization problems, including VaR constrained mean-variance portfolio selection problems, portfolio selection problems with marginal risk controls, and a two-level loan portfolio management problem. These problems are all from financial industries and are important to investors, fund managers and bankers, as well as academics.

Although these problems are very important, there are lack of efficient algorithms to solve them due to the difficulty in evaluating VaR and non-convexity of VaR functions. In this project, we propose to use Monte Carlo methods, which estimate VaR functions using Monte Carlo samples, to solve these difficult portfolio selection and risk management problems. We will focus mainly on developing efficient algorithms that can be used to solve these problems of practical sizes. In particular, we will analyze a semi-definite relaxation method for VaR constrained mean-variance portfolio selection problem, investigate a difference-of-convex (DC) reformulations for portfolio selection problems with marginal risk controls, and look into a gradient-based approach for the two-level loan portfolio management problem. We will also study the conditional VaR (CVaR) approximation to VaR constrained problems, and develop iterative algorithms that repeatedly use CVaR approximations to find better solutions.

We will test our approaches on problems of realistic sizes, and will work with financial industry, in particular Shanghai Pudong Development Bank, to apply our algorithms and results to improve their portfolio selection and risk management practices.

Workplace ostracism: A longitudinal examination of its antecedents and work and family outcomes
Hong Kong Principal Investigator : Prof Chun Hui (The University of Hong Kong)
Mainland Principal Investigator : Dr Jun Liu (Renmin University of China)

The present proposal is an attempt to examine the antecedents and consequences of workplace ostracism. Workplace ostracism refers to the extent to which individuals perceive that they are ignored or excluded by other employees in the workplace (Ferris, Brown, Berry, & Lian, 2008). Workplace ostracism frequently occurs and is observed in both the academia and the business world.

Research on workplace ostracism, however, can benefit from more systematic analyses of the predictors and outcomes of this important construct. First, we propose to study the effects of target characteristics (extroversion, agreeableness, neuroticism) and situation characteristics (team affective climate) on workplace ostracism by integrating the victim precipitation and social control theoretical perspectives. We expect that workplace ostracism is negatively influenced by extroversion, agreeableness, and team affective climate, and is positively influenced by neuroticism.

Second, the present proposal suggests examining whether organization identification can explain the negative relationships of workplace ostracism with task performance and organizational citizenship behavior, which are two important and widely studied employee outcomes (Motowidlo, 2003). Drawing on social identity theory (Ashforth & Mael, 1989), we expect that workplace ostracism leads to decreased organization identification, which causes reduced task performance and organizational citizenship behavior.

Third, by integrating stress (Hobfoll, 1989) and boundary theories (Ashforth et al., 2000), our proposal suggests examining whether work-family conflict can explain the positive relationship between workplace ostracism and family undermining. We expect that workplace ostracism leads to increased work-family conflict, which facilitates family undermining.

Finally, our proposal provides boundary considerations of collectivism on the relationship of workplace ostracism with organization identification, and those of work-family segmentation preference on the relationship of workplace ostracism with work-family conflict. We expect that collectivism strengthens the relationship of workplace ostracism with organization identification, whereas work-family segmentation preference weakens the relationship of workplace ostracism with work-family conflict.

The present proposal, by integrating the theoretical perspectives outlined earlier, contributes theoretically to understandings of relationships of workplace ostracism with personality traits, organization climate, organization identity, job performance, work-family conflict, family undermining, individual's cultural value orientation, and individual preferences. The present proposal also contributes to the management of workplace ostracism by highlighting how workplace ostracism can be functional.

Synthesis and Design of New Photocatalysts for Degradation of Toxic Organic Compounds
Hong Kong Principal Investigator : Prof Jimmy Chai-mei Yu (The Chinese University of Hong Kong)
Mainland Principal Investigator : Prof Shuhong Yu (University of Science & Technology of China)

Environmental issues are the biggest challenges for developing countries such as China. Ironically, the solution to these large problems may lie in something very small. Nanomaterials, with attractive chemical and physical properties, are being explored for their potential in environmental applications. During the past decade, rapid advances in materials science have led to significant progress in environmental remediation technologies such as photocatalysis. Photocatalysis has attracted much attention because it allows the utilization of clean, safe, and renewable solar energy to solve environmental problems. Titanium dioxide has been widely studied as an efficient photocatalyst for its chemical properties and long-term stability. However, TiO2 has a relatively large band gap that requires UV light for activation. This proposal describes a new approach to extend the response of photocatalysts into the visible-light and near-infrared (NIR) regions.

The two principal investigators have had strong track records in nanomaterial research. The Mainland team is particularly strong in the fabrication of novel functional nanomaterials, while the Hong Kong team is known for the modification and enhancement of photocatalytic nanostructures. Working together, we will design and fabricate new bimetal oxide nanostructures that are active under sunlight. These nanostructures will be further enhanced by combining with an upconversion material. When capturing NIR photons, the upconversion material emits relatively strong visible-light. Coupling the bimetal oxide nanostructures with upconversion particles will make the final composite materials responsive to both visible-light and near-infrared radiation. This would be a much more efficient utilization of solar energy than the UV-responsive TiO2-based photocatalytic systems because energy from the sun is mostly in the visible and infrared regions. Degradation of toxic organic compounds such as azo dyes on the broad-spectrum photocatalysts will be investigated. Findings from this collaborative research may revolutionize the design of future energy-saving environmental remediation systems.

Development of Functional Transition Metal Supramolecules for the Fabrication of Dye-Sensitized Photovoltaic Cells by Self-Assembly Method
Hong Kong Principal Investigator : Prof Wai Kin Chan (The University of Hong Kong)
Mainland Principal Investigator : Prof Yuping Dong (Beijing Institute of Technology)

In this proposal, the Beijing and Hong Kong teams propose to investigate the physical properties and applications of some organic-inorganic hybrid materials fabricated from organic functional molecules and aligned inorganic nanostructures. The surface of various inorganic semiconductors nanostructures will be modified by chemical methods. Multilayer thin films will then be introduced to the surface of these nanostructures. It is envisaged that the properties of the resulting materials exhibit interesting optical and electronic properties. The results will be important in the design and fabrication of more efficient dye-sensitized photovoltaic cells.

Role of Stronitum-calcium Silicate - A Novel Biomaterial in the Regeneration of Osteoporotic Bone - An In-vivo/vitro study
Hong Kong Principal Investigator : Prof William W Lu (The University of Hong Kong)
Mainland Principal Investigator : Prof Jiang Chang (Shanghai Institute of Ceramics)

Osteoporosis, a primarily age-related disease, results in progressive bone loss and concurrent changes in bony micro-architecture, leading to a consequent increase in bone fragility and susceptibility to fracture. Unfortunately, to date, there are no effective ways to clinically treat osteoporotic bone fractures. Conventional metallic reinforcement methods for fixing fractured bones are not applicable for osteoporotic cases owing to fragility of the bone. Our previous studies indicate that strontium, a trace element in the human body, plays an important role in the treatment of osteoporosis by its uncoupling effect on bone formation and resorption. Recently, we have found that the uncoupling effect can be improved by combining strontium with calcium silicate (CS), a novel biodegradable material, in an ideal alkaline environment. Thus, we postulate that the newly developed strontium-incorporated calcium silicate (Sr-CS) may yield a unique effect in stimulating osteoporotic bone regeneration.

A longstanding observation shows that pH of the tissue's microenvironment regulates the balance between bone resorption and formation/mineralization. In particular, the regulation of the function of alkaline phosphatase (ALP) depends on the pH of its microenvironment. Our recent study shows that an ideal alkaline environment at ~pH 8-8.5 can significantly increase the activity of osteoblasts. Therefore, we hypothesize that: with the degradation of Sr-CS, the localized pH will first increase, not only neutralizing the acidic by-products due to ageing, but also increasing the activity of osteoblasts. Ultimately, the released ions (Sr and Si) will serve as 'drugs' to stimulate new bone formation.

Aims
(1) Fabricate novel Sr-incorporated calcium silicate (Sr-CS) scaffolds;
(2) Identify the optimum alkaline pH level by adjusting the degradation of the scaffold (3) Evaluate whether the released Sr and Si ions can promote bone formation in osteoporotic OVX rat model in vitro and in vivo .

This study will render a new approach to stimulate osteoporotic bone regeneration, leading to better treatment of osteoporosis related fractures by emphasizing the importance of the environment for bone regeneration, ultimately enabling us to design and engineer better biomaterials for clinical application.

Novel quantum states of ultracold atoms in optical lattices
Hong Kong Principal Investigator : Prof Shunqing Shen (The University of Hong Kong)
Mainland Principal Investigator : Prof Wuming Liu (Chinese Academy of Sciences)

Optical lattice refers to an effective micro-confining potential of cold atoms formed by periodic laser beam intensity made of two counter-propagating laser waves. It has gradually become a controllable platform to simulate and study a lot of quantum phenomena in condensed matter physics because its parameters can be adjusted easily through experimental methods such as adjusting the depth of potential well by changing light intensity and the symmetry and size of lattice through changing the space distribution of laser beam. Recent development of experimental technology makes it possible to study optical super-lattice systems, and a variety of physics phenomena caused by the light-induced gauge field. On the other hand it is developed very rapidly in the direction to explore novel states of quantum matters, such as the theoretical prediction and experimental verification of topological insulators in several semiconductor materials, and novel quantum spin states in strongly correlated electron systems. Topological property of electron bands and its application to quantum transport attracted a lot of attentions in the community of condensed matter physics. The joint project will make use of the cold-atom system to simulate and to investigate quantum collective phenomena in many-body interacting system. Based the current technology and peculiar properties of cold-atom systems, we plan to explore novel quantum states in cold-atoms in optical lattices and semiconductors, coherent dynamics and quantum transport properties in interacting system, and various features arisen from electromagnetically induced gauge field in optical lattice.

Enamel microstructure regeneration in macroscale by molecular mimetic method
Hong Kong Principal Investigator: Dr Chun Hung Chu (The University of Hong Kong)
Mainland Principal Investigator: Dr Quanli Li (Anhui Medical University)

Enamel, the exterior layer of teeth, is the hardest and most highly mineralized human tissue. Ninety-six percent of enamel is hydroxyapatite, an inorganic mineral made of calcium phosphate crystals arranged in prisms. These prisms are tightly packed in an organized microstructure, thereby enabling enamel to be remarkably hard. However, the high mineral content makes enamel susceptible to acid attack by bacteria, which leads to dental decay. Enamel is also damaged by acids in food and drink, causing dental erosion. Human saliva can chemically remineralize enamel, but only very slowly, inefficiently, and incompletely. Until now, enamel treatment has focused on repair mainly by dental materials such as composite resin, but this approach has serious limitations. The natural structure of enamel has also been thought to be too complex for artificial regeneration. This study aims to induce enamel regeneration to treat enamel defects, by using a new technology to replicate the process of natural enamel formation during tooth development.

The oral micro-environment during initial enamel formation will be simulated in the laboratory by a molecular biomimetic technique. Molecular biomimetics is an emerging field in which hybrid technologies are developed with the tools of molecular biology and nanotechnology. Short chains of protein, or oligopeptides, are a promising biomimetic biomaterial because they can be engineered to specifically bind to selected inorganic compounds. In this study, an oligopeptide will be designed to self-assemble into a superstructure of nanospheres whose activities will resemble those of amelogenin, which is a major extracellular-matrix protein that is naturally found in enamel. In the developing tooth, amelogenin regulates the initiation and growth of hydroxyapatite crystals during enamel mineralization and plays a vital role in the formation of enamel's structure. The newly developed oligopeptide will be applied to the surface of defective enamel in a gel matrix, and calcium and phosphate ions, and other inorganic ions, will be added to regenerate enamel.

The University of Hong Kong has been working in dental hard tissue remineralization research for the past 10 years. The Anhui Medical University has extensive experience in biomimetic biomaterials research. This collaborative study fully utilizes the expertise and facilities of the two universities to develop a novel method to regenerate tooth enamel. The long-term benefits of this study could be immense, as the technology developed would be useful in managing the very common problems of dental decay and dental erosion, and would improve people's dental health throughout the world.

Supramolecular Assembly of Novel Tribenzotriquinacene (TBTQ) Derivatives
Hong Kong Principal Investigator : Prof Hak-fun Chow (The Chinese University of Hong Kong)
Mainland Principal Investigator : Prof Xiao-ping Cao (Lanzhou University)

The rapid construction of molecular materials with defined size and shape of nanoscopic dimensions is of utmost importance in the realm of nanotechnology. This proposal seeks to utilize a chemical method, namely, self-assembly to achieve the above goals. Self-assembly is a process whereby simple molecular components with built-in machineries can interact in a predictable manner to generate the target system spontaneously in one operation. However, the initial geometry of the molecular components has a deciding role in the final shape of the assembled objects. While many interesting molecules have been chosen in self assembly investigation, the use of molecular modules that can give rise to cubic shape nano-objects is less studied. Here we propose to use a unique class of molecules called tribenzotriquinacenes (TBTQs) and investigate their self assembling properties on their own or in the presence of metal ions. Due to the unique geometry of TBTQs, they have the potential to assemble into cubic-shape objects that can further interact with other guest molecules to create other complex yet fascinating structures. It is envisaged that through this study, new synthetic methodologies to TBTQ derivatives can be developed, new materials with novel geometry will be created, and new principles of the self-assembly process will be revealed.

Group 4 Metal Complexes for Hydroamination Catalysis
Hong Kong Principal Investigator : Prof Zuowei Xie (The Chinese University of Hong Kong)
Mainland Principal Investigator : Prof Yong Tang (Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences)

Catalytic hydroamination is a highly atom-efficient method for the addition of amines to unsaturated bonds to give new C−N bonds, which has led to intensified research efforts over the last decade as the importance of nitrogen-containing compounds in biological systems and industrially relevant basic and fine chemicals. Various catalyst systems have been developed to achieve this goal. Among them, group 4 metal catalysts are very attractive for their low cost, low toxicity, and high reactivity. However, they are often restricted to certain types of substrates. The development of catalysts for efficient symmetric/asymmetric hydroamination/cyclization of a wide spectrum of substrates is still a great challenge. Inspired by our own work on the unique reactivity of the neutral group 4 metal monoamide [σ:η1:η5-(OCH2)(Me2NCH2)C2B9H9]Ti(NMe2) and cationic zirconium alkyl incorporating a tridentate [O-N-S] ligand as well as catalytic construction and reconstruction of guanidines, we plan in this proposal to combine the expertises of both Hong Kong and Mainland teams in organometallic chemistry and catalysis to develop a novel class of group 4 metal catalysts for both asymmetric and symmetric hydroamination catalysis through an elegant design of ligands. The results obtained from these joint efforts will certainly offer valuable information on the structure/reactivity relationships and new methodologies for the construction of a variety of N-containing compounds/N-heterocycles in a catalytic manner.

Corrosion and Fatigue Damage Monitoring in Large Scale Tubular Structures Using Guided Ultrasonic Waves
Hong Kong Principal Investigator : Prof. Limin Zhou (The Hong Kong Polytechnic University)
Mainland Principal Investigator : Prof. Guang Meng (Shanghai Jiao Tong University)

In Hong Kong and the Mainland China there are many large-scale engineering structures which are made of metallic tubular structures with joints, junctions, stiffeners and weld lines, e.g. building/bridge supports, train/rail components, chemical plant, and gas/oil pipelines. Corrosion and fatigue damages can considerably lower the integrity of critical sections of tubular structures and potentially lead to catastrophic failure of the entire structure, with disastrous consequences. In particular, many of these facilities function beyond their design service objectives, presenting new challenges for the structural safety and integrity. Keeping these assets under online or real-time surveillance is therefore of vital importance and has become a prime concern in communities. In this regard, embedding active sensor networks on critical sections of such structures is a promising solution, in which multi-functional sensors are capable of sensing and providing continuous and detailed information on structural integrity status, identifying defects at the earliest stage. This project will involve a multidisciplinary approach. Over the years, there have been substantial advances in materials science and signal processing/pattern recognition techniques, e.g. advanced sensors and sensor network, guided ultrasonic waves, artificial intelligence, associated with exponential development in informatics, computing and communication technologies. These developments have paved technical paths and presented a unique opportunity to address fundamental issues and breakthroughs in developing guided-wave-based damage identification algorithms for large-scale tubular structures. This project aims to develop a framework for activation, propagation and acquisition of guided waves in tubular structures and to improve fundamental knowledge of sensor network-based damage identification for applications of corrosion and fatigue damage monitoring. According to the conditions that there has been little systematic investigation of guided wave propagation in tubular structures with complex boundary conditions under real-world working conditions and an obvious lack in developing active sensor networks for tubular structures of irregular cross-section with a purpose of monitoring corrosion and fatigue damage, the key outcomes of the project will be new algorithmic understanding of the models, tools and methods necessary to design and construct practical active sensor networks for corrosion and fatigue damage identification in large-scale tubular structures. Successful applications of the sensor network techniques will enable online identification and assessment of corrosion and fatigue damages, driving down maintenance costs and extending the lifespan of engineering structures in Hong Kong and the Mainland China.