SRFDP&RGC ERG Joint Research Scheme - Layman Summaries of Projects Funded in 2013/14 Exercise

Inference of Large Epidemic-like Information Spreading: Theories and Network Forensics

Hong Kong Principal Investigator: Dr Chee Wei Tan (City University of Hong Kong)
Mainland Principal Investigator: Prof Wenyi Zhang(University of Science and Technology of China)

Detection and identification of malicious information sources in a network, be it in the case of a computer virus spreading in Internet or a misinformation or rumor propagating in an online social network, allows timely quarantine of the epidemic-like spreading to limit the damage caused. For example, law enforcement agencies may be interested in identifying the perpetrators of false information used to manipulate the market prices of certain stocks. How to identify the source of the spreading given an observation of the infected nodes and the underlying network structure remains a rather unexplored and challenging problem. In an increasingly connected physical and cyber world, identification of information source nodes in social-technological networks is expected to play an ever more important role in many security applications to combat cyber-crimes. Reliable distributed network forensics protocols that can quickly isolate the sources to within a small subset of the entire infected population, expensive resources can be better deployed to build more robust social-technological networks and identify risks before hackers and fear-mongers do.

The source inference problem is a combinatorial problem that is complicated by the probabilistic spreading model and the size of the network that both lead to the computational barrier. We will develop mathematical theories and distributed algorithms to identify a single and multiple infection sources in a network, and quantify the detection performance in terms of the network structure. The novelty in our research is to utilize a novel link between Polya's urn model in probability theory and statistical inference on graph for the susceptible-infection model to quantify the exact detection performance in networks with large but finite number of infected nodes as well as asymptotically large networks. We will also develop network forensics algorithms using time-varying surveillance data in optimal sequential detection, and analyze the performance tradeoff between reliability and speed of detection. We will apply our research methodologies to large-scale online social networks such as Twitter and Weibo to evaluate the effectiveness of our algorithms to root out rumors.

Impact of Hypoxia-inducible Factor 1 Alpha on EpCAM+ Hepatic Cancer Stem Cells in Hepatocellular Carcinoma

Hong Kong Principal Investigator: Prof George Gong Chen (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Jia Fan (Fudan University)

Hepatocellular carcinoma (HCC), one of the most common cancers, is a highly aggressive and invasive tumor with a high rate of recurrence. This malignancy is often resistant to chemotherapy. The mechanisms underlying HCC resistance, aggression and invasion are not fully understood. Hepatic cancer stem cells (hCSC), identified by us and others, appear to play a key role in the aggression, invasion and resistance of HCC and thus effective anti-HCC treatments need to target and remove hCSC. However, the generation and maintenance of hCSC is largely unknown, which hampers the development of the anti-hCSC protocols. Accumulating evidence suggests that hypoxia-inducible factor 1 alpha (HIF1a) has a key role in the development of cancer stem cells (CSC) in solid tumors including breast cancer, glioma and prostate cancer. Studies including ours have demonstrated that the level of HIF1a is increased in HCC, and that it is involved the development of HCC and its resistance to anti-HCC treatments. However, the role of HIF1a in hCSC remains unknown. We therefore hypothesize that the increased expression of HIF1a in HCC has a key role in the generation and maintenance of hCSC. This proposal will employ HCC cells (cell lines and primary cells) as well as mice to test our hypothesis by determining the role of HIF1a in the development of hCSC, how HIF1a affects the main features of hCSC and the impact of changes in HIF1a levels on hCSC.

Elucidating the Therapeutic Mechanisms of Deep Brain Stimulation in Parkinson's Disease by Selective in vivo Optogenetic Manipulation Strategy

Hong Kong Principal Investigator: Prof Wing-ho Yung (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Jian-jun Wang (Nanjing University)

Parkinson's disease (PD) is the second most common neurodegenerative and motor disease in the world, estimated to affect up to 5 million people globally - a figure that is expected to rise significantly as human life expectancy increases in the coming decades. The disease has no known cure, and current treatments aim to alleviate debilitating motor symptoms that progressively worsen over time. A surgical treatment known as deep brain stimulation (DBS) has been shown to reduce motor symptoms and restore some degree of quality of life to patients. Over 70,000 patients have received DBS surgical treatment. DBS involves implantation of a stimulation electrode into the deep structures of the brain, such as the subthalamic nucleus, through which continuous high frequency pulses (~125Hz) of electric current are delivered. Despite its successes, both the genesis of pathological motor symptoms and the underlying mechanism by which therapeutic effects of DBS occur are still not clear. This limits the ability to improve upon DBS procedures and minimize risks associated with major invasive surgery and device malfunction. Using in vivo multi-unit recording techniques in a dopamine-depleted rat PD model, our laboratory had recently discovered that DBS of the subthalamic nucleus could directly affect the excitability of primary motor cortex neurons via antidromic activation of layer V projection neurons, bypassing the complex relays of the basal ganglia system. Based on our observations, we hypothesize that the projection neurons and inhibitory interneurons of the layer V cortex laterally propagate the therapeutic DBS signals and mitigates the pathological neuronal synchrony that leads to motor symptoms. To test this hypothesis, it is necessary to selectively manipulate a set of neurons and observe the responses of the neuronal population. We designed a novel optical system that can modify the spatial pattern of laser light and project it into the deeper tissues through a very thin implantable lens. The light is used to excite or inhibit individual neurons, in a technique known as optogenetics. With appropriate strategies of stimulation and careful interpretation of the neuronal responses, we aim to uncover the mystery behind PD motor symptoms and therapeutic DBS. This work aims to train at least two full time PhD candidates in Hong Kong and mainland and publication in high impact journals.

Ethylene-induced Subcellular Re-distribution of EIN2 and Its Functional Implications

Hong Kong Principal Investigator: Prof Li-wen Jiang (The Chinese University of Hong Kong)
Mainland Principal Investigator: Prof Hong-wei Guo (Peking University)

The gaseous phytohormone ethylene plays vital roles in both plant developmental process and plant responses to abiotic or biotic stresses. Studies have identified key components of ethylene signaling pathway in Arabidopsis. ETHYLENE INSENTITIVE2 (EIN2), an NRAMP-like membrane protein, mediates all ethylene responses as the central component. Studies about ethylene growth kinetics found that ethylene responses are composed of an early quick transcription-independent response phase (phase I) and a late transcription-dependent phase (phase II), and EIN2 is essential for both phases. EIN2 locates at the endoplasmic reticulum (ER) membrane. Recent research found that ethylene triggers the cleavage of EIN2 carboxyl-terminal (EIN2C) and its subsequent translocation into nucleus, thus linking ethylene perception with nuclear transcriptional regulation. However, the molecular mechanism of ethylene signaling mediating the quick transcription-independent response by EIN2 remains unknown. Our preliminary study using transgenic EIN2-GFP cell lines found that in a short time period, ethylene specifically induced the redistribution of EIN2 from an ER pattern into a punctate speckle pattern distinct from known organelle markers representative of Golgi, TGN and PVC. Both the translational inhibitor CHX and the ethylene perception inhibitor Ag+ fully blocked the ethylene-induced EIN2 speckle formation. Transient co-localization study found that EIN2 speckle partially co-localized with processing body (P-body) components DCP1 and XRN4 (EIN5). We thus hypothesize that such ethylene-induced EIN2 re-distribution may function in mediating the quick ethylene response (phase I), and the new EIN2-containing compartment may correlate with the translational process within the P-body. Therefore, the goal of this proposal is to study the molecular mechanism of ethylene-induced redistribution of EIN2 as well as the nature and function of the EIN2-containing compartment in plants using a combination of molecular, cellular, biochemical and genetic approaches, which can be achieved by bringing together the expertise of two internationally renowned laboratories with excellent track records in plant genetics and hormone signaling transduction (PKU) and plant cell biology (CUHK), respectively.

High Performance Aqueous Rechargeable Battery Based on Anodic Compound Electrodes

Hong Kong Principal Investigator: Dr. Haitao Huang (The Hong Kong Polytechnic University)
Mainland Principal Investigator: Prof Bingqing Wei (Northwestern Polytechnical University)

Aqueous rechargeable lithium batteries, with high-safety, low-cost and high-rate capability, are attractive electrochemical energy storage devices. However, their energy density is limited by low voltage, low capacity and the electrode fabrication method. Based on our recent success in the fabrication of hierarchical Ni(OH)2 and TiO2 nanotube array as the electrode for electrochemical energy storage via the anodization method, we propose a novel aqueous rechargeable battery which uses anodic Ni(OH)2/Ti and anodic TiO2/Ti as the positive/negative electrodes and mixed LiOH/KOH solution as the aqueous electrolyte. Efforts will be devoted to the optimization of anodization technique on valve and non-valve metals, to the study of formation mechanism and to the development of new fabrication technique of flexible electrode with controllable structure and hence controllable performance. The relationship between the battery architecture and its electrochemical performances would be established and the multi-ion energy storage mechanism would also be clarified. The proposed project will shed light on the design and development of novel high-performance aqueous rechargeable lithium batteries.

Theoretical Chemical Kinetics for Pyrolysis and Oxidation of Large Biodiesel Molecules

Hong Kong Principal Investigator: Dr. Peng Zhang (The Hong Kong Polytechnic University)
Mainland Principal Investigator: Prof Chung K. Law (Tsinghua University)

Utilization of biofuels to supplement/replace the petroleum-based fuels has been proposed as a viable solution to the increasingly concerned problems such as energy sustainability, energy security and climate change. Biodiesel is one of the most widely used biofuels due to its numerous desirable fuel properties. Considerable effort is currently being devoted to the development of quantitatively predictive mechanisms for biodiesel combustion chemistry. The proposed program aims to study the key reactions in the pyrolysis and oxidation of large biodiesel molecules by using the theoretical chemical kinetics. In addition, efforts will be made to explore theoretical methodology for high-level quantum chemistry calculation of the kinetic and thermochemical data for large methyl ester molecules. The proposed program covers the two most important biodiesel components, namely, methyl oleate and methyl linoleate. It is believed that the proposed concepts and approaches are sufficiently solid and novel such that new and useful information on the chemical kinetics of biodiesel combustion will result.

Elucidating molecular mechanisms of the Maltose transporter (MalFGK2) using Markov State Models

Hong Kong Principal Investigator: Dr. Xuhui Huang (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Wenning Wang (Fudan University)

Maltose transporter MalFGK2 is a typical model system in the study of molecular mechanism of ABC transporters. This project aims to study the thermodynamics and kinetics of conformational change of MalFGk2 at atomic level using molecular simulation methods. We propose to develop a Metadynamics Guided Markov State Model (MG-MSM) method to calculate the free energy profiles of conformational transition among the three conformations of MalFGK2, obtaining the overall picture of conformational movement during translocation cycle of MalFGK2. In order to elucidate the regulation roles of MBP and nucleotides to MalFGK2 conformational transition, we will calculate the free energy change upon their association to the transporter. It is aimed to reveal the detailed working mechanism of MalFGK2 through analysing the relationship between protein conformational change and substrate translocation.

A Fundamental Investigation of PCC Energy Pile and Load Transfer Mechanism: Geotechnical Aspects

Hong Kong Principal Investigator: Prof Charles Wang-wai Ng (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Hanlong Liu (Hohai University)

By means of energy pile technology, which is combination of ground source heat pump technology and purposely designed piled foundation, the utilization of energy piles in the UK has shown to reduce the energy requirement and the carbon dioxide emission from heating and cooling by 60% and 50%, respectively (Patel & Bull (2011). However, the use of energy piles has one major drawback: the circulation of heat-exchange fluids subjects piles to temperature fluctuations, which in turn induce extra axial load and additional settlement. Our current understanding of the thermo-hydro-mechanical interactions and load transfer mechanisms of energy piles in various ground conditions is still far from satisfactory.

In this proposed project, systematic centrifuge and large-scale model tests will be carried out respectively at HKUST and Hohai University to explore the complex thermo-hydro-mechanical interactions and load transfer mechanisms of large-diameter Cast-in place Concrete Pipe (PCC) energy piles. Possible governing factors which control the performance and capacity of PCC energy piles will be simulated and investigated. These factors include soil types, soil density for sand and silt and over-consolidation ratio for clay, degrees of saturation (i.e., different hydro conditions), and thermal load and cycles. To interpret and back-analyze pile load test results, the state-dependent constitutive model originally developed by the PI at HKUST will be extended to capture the thermally-induced plasticity and dilatancy of soils. By carrying out the proposed centrifuge and large-scale model tests and numerical simulations, it is anticipated that a novel and more effective large-diameter PCC energy pile will be developed and new design guidelines for constructing energy piles will be produced. The outcomes of this joint project will thus result in more efficient and energy saving environments and also lead to lower CO2 emissions worldwide.

Quality control and mechanism study of Guizhi-Fuling-Capsule, An ancient herbal formulation for primary dysmenorrhea, by a systemic biology approach

Hong Kong Principal Investigator: Prof Karl W K Tsim (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Ping Li (China Pharmaceutical Unive

Dysmenorrhea is the medical term for pain during menstruation. The disorder can be due to either contractions of the uterus (primary dysmenorrhea) or caused by a disease in the uterus, fallopian tubes, or ovaries (secondary dysmenorrhea). Currently, no treatment is available, except that herbal remedy is commonly applied for women in Asia and Europe.

Guizhi-Fuling pill is a traditional Chinese herbal medicine consisting of five herbs: Cinnamomi Ramulus, Poria, Paeoniae Radix Alba, Moutan Cortex and Persicae Semen. This pill has been used to treat gynecological diseases for thousands of years in China. Studies also revealed its protective effect in treating primary dysmenorrhea. In 2007, the US FDA approved the phase II clinical trial of this formula against primary dysmenorrhea.

The current project aims to better promote the modernization of Guizhi-Fuling pill through 1) seting up the quality control of Guizhi-Fuling pill by chemical analysis and 2) investigating the action mechanisms of this formular against primary dysmenorrhea by different biological analyses.

Control of the fabrication process and properties of multifunctional magnetoelectric oxide films

Hong Kong Principal Investigator: Prof Jiannong Wang (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Hong Wang (Xian Jiaotong University)

With the rapid advances in information and wireless technologies, materials for fabricating electronic components with shrinking dimensions and high levels of passive integration are becoming increasingly sought after. Such materials should be magnetoelectric, magnetic-optical, and flexible. Among them, magnetoelectric materials which simultaneously exhibit ferroelectricity and ferromagnetism have attracted a lot of attention because of their scientific value and potential application in novel multifunctional devices. Natural magnetoelectric single-phase compounds are rare, so most of the research is focused on magnetoelectric composites which incorporate ferroelectric and ferri-/ferromagnetic phases artificially. In this project, we will develop novel multifunctional composite oxides exhibiting low loss and high frequency magnetoelectric properties. We will focus on developing controlled processes for producing multifunctional oxides in the form of textured films and multilayer films, and investigating the influence of ion substitution, defect, and interfacial structure to enhance their magnetoelectric properties.

Revenue Maximization for Wireless Operators in Hybrid Macrocell-Femtocell Networks

Hong Kong Principal Investigator: Prof Qian Zhang (The Hong Kong University of Science and Technology)
Mainland Principal Investigator: Prof Tao Jiang (Huazhong University of Science and Technology)

Femtocell, which is a low-power small access point designed for indoor usage, is recognized as a promising approach to cost-effective solutions to achieve good indoor coverage with high capacity. However, to exploit the merits of femtocell technology, several fundamental technical and commercial challenges must first be thoroughly addressed. To maximize their revenue, the operators need to incentivize users to adopt proper access mode so as to fully utilize femto facilities and spectrum resources. While at the same time the cost of maintaining femtocells should be kept low. To improve user experience, the cross-tier interference between femtocells and macrocells must be properly controlled.

In this project, we address the above challenges in the following three aspects. First, we will propose a utility-aware refunding framework to promote the adoption of hybrid access, where an operator will provide a certain amount of refund to the hybrid access femto holders (FHs) for making any redundant femto facilities and spectrum resources available to macro users. Second, to provide femto users with stable service, we will propose an outage detection architecture to detect femtocells with decreased capacity and coverage gap. In particular, we will solve the challenges associated with the two-tier macro-femto network architecture and the small coverage nature of femtocells. Moreover, we will propose several interference management schemes to handle the interference problem in the femtocell network by considering base station deployment, spectrum allocation, and power control.

Few studies have systematically investigated the maximization of operator revenue through access control, outage detection and interference management. In light of the rapid development of next-generation wireless technologies and the wide deployment of new wireless services in Hong Kong and mainland China, the timely research proposed in this project not only bears tremendous academic significance, but also holds great potential in practical system implementation.

In search for critical Inflammatory modulator regulated by MT1-MMP

Hong Kong Principal Investigator: Dr Zhongjun Zhou (The University of Hong Kong)
Mainland Principal Investigator: Prof Pengyuan Yang (Fudan University)

Lymphatic vessel growth is critical for development, growth and various diseases. Inflammatory-associated lymphatic vessel growth is the primary mechanism of metastasis for many cancers. Despite its important roles in physiological and pathological conditions, at the present no drug that specifically targets lymphatic growth or function is identified. A significant difficulty in therapeutic manipulation of lymphatic vessel growth is the lack of specific molecular regulators. Understanding the signals that direct lymphatic growth and the biological roles of lymphatic vessels has been challenging because blood and lymphatic vessels utilize common signaling and transcriptional pathways and participate in linked physiological functions. Identification of lymphatic-specific molecular pathways is necessary to design innovative therapeutic strategies that specifically block lymphatic vessel growth. VEGF-C, a ligand for the VEGFR3 receptor that is expressed on lymphatic endothelial cells (LECs) but not blood endothelial cells (BECs) after mid-gestation, is lymphatic-specific growth factor (6, 7). However, how inflammatory-associated lymphatic vessel growth is specifically regulated at both the cellular and molecular level remains largely unknown. This proposal will address these questions within the context of MT1-MMP itself and the functional crosstalk between MT1-MMP and VEGF-C/VEGFR3 signaling axis.

MT1-MMP, a membrane bound metalloproteinase, is essential for various physiological and pathological processes through extracellular matrix remodeling and pericellular proteolysis. Our current studies on MT1-MMP deficient mice revealed unexpected evidence that MT1-MMP is a non-dispensable endogenous negative modulator for inflammatory-associated lymphatic vessel growth. This proposal will utilize molecular and proteomic approaches to determine how MT1-MMP regulates inflammatory associated macrophages and remodels extracellular matrix in order to modulate lymphatic vessel growth. These studies are expected to provide to a new paradigm and will serve as a foundation for innovative approaches to treat lymphatic diseases. The innovation of this proposal is to identify a novel mechanism of regulating lymphatic vascular growth in pathological conditions.

Magmatic conduit system of the Jinchuan Cu-Ni-(PGE) sulfide deposit (NW China) with implication for exploration

Hong Kong Principal Investigator: Professor Mei Fu Zhou (The University of Hong Kong)
Mainland Principal Investigator: Professor Shangguo Su (China University of Geosciences Beijing)

The Jinchuan Cu-Ni-(PGE) sulfide deposit is the third largest magmatic sulfide deposit in the world, and provides an excellent opportunity to examine the origin of magmatic sulfide deposits. Based on detailed mineralogical, petrological, geochemical and isotopic studies, this project aims to understand the processes that led to the enrichment of sulphide ores. Such a study will have general implication for the origin of world class magmatic sulfide deposits. Origin and emplacement processes of sulfide-bearing magmas are keys to ore prospecting for magmatic sulfide deposits. Therefore, this project examines the possible "magmatic conduit system" of the Jinchuan deposit and to explore the possibility to use a three dimensional ore exploration model to guide mineral resource prospecting of magmatic sulfide deposits.