Quasi-Newton Methods for Markov Chain Monte Carlo

The performance of Markov chain Monte Carlo methods is often sensitive to the scaling and correlations between the random variables of interest. An important source of information about the local correlation and scale is given by the Hessian matrix of the target distribution, but this is often either computationally expensive or infeasible. In this paper we propose MCMC samplers that make use of quasi-Newton approximations, which approximate the Hessian of the target distribution from previous samples and gradients generated by the sampler. A key issue is that MCMC samplers that depend on the history of previous states are in general not valid. We address this problem by using limited memory quasi-Newton methods, which depend only on a fixed window of previous samples. On several real world datasets, we show that the quasi-Newton sampler is more effective than standard Hamiltonian Monte Carlo at a fraction of the cost of MCMC methods that require higher-order derivatives.

Development assessment of leisure agriculture in Henan province of China based on SWOT-AHP method

Purpose: The development of leisure agriculture is an important means of agricultural industry structure adjustment of Henan province, China, to realize the transition from traditional agriculture to modern agriculture. Design/methodology/approach: The SWOT (Strength, Weakness, Opportunity, Threat) analysis of Henan leisure agriculture will contribute to the sustainable development of Henan leisure agriculture. The strength, weakness, opportunity and threat of developing leisure agriculture in Henan province were systematically analyzed using SWOT method in our study. The aspects including location, resources, traffic, population, economy, urbanization, industrialization, market, policy, capital, product, technology, management, marketing and environment were involved. The strength, weakness, opportunity and threat were quantified in this study using AHP (Analytic Hierarchy Process) method. Findings and Originality/value: The result showed that the total strength and total opportunity of Henan leisure agriculture are much greater than that of total weakness and total threat, which suggests that the opportunities outweigh threats, and advantage outweigh disadvantage. The growth-oriented strategy combining the external opportunities and its own advantages shall be employed in development of Henan leisure agriculture as indicated by the strategy strength coefficient in strategy quadrangle we have constructed. The barriers to the development need to be overcome while strengthening competitive advantages. Originality/value: New ideas for working out the developmental strategy for Henan leisure agriculture is provided by SWOT-AHP method.Peer Reviewe

Polymers, proteins and cells

Biopolymers such as proteins, nucleic acids and polysaccharides are essential components in living systems and enabling the modification and modulation of various cellular functions and cellular behaviour. Many synthetic polymers have been used in a cellular context mimicking these natural polymers. However, few studies have focused on polymerisation chemistry within the complicated biological environment inside cells. In the first part of this thesis, a new method of synthesising synthetic polymers in cells was developed, enabling the introduction of artificial components to tune cellular behaviour. Several biocompatible acrylic and styrene monomers were polymerised intracellularly and shown to control the cell cycle, alter the cytoskeleton and influence cell motility. Moreover, the introduction of specific functional monomers enabled the in situ formation of fluorescent polymers and nanoparticles which may contribute to further applications such as fluorescent imaging and cargo delivery. Chemical modifications of native biomacromolecules provides access to novel functions such as macromolecule based cargo delivery and imaging probes. In the second part of this thesis, linear acrylamide polymer scaffolds, bearing norbornene reactive centres for tetrazine ligation and a hexahistidine tag for ease of purification, were synthesised and conjugated to a clinical antibody. This enabled the selective labelling of cancer cells with amplified fluorescent signal. Simultaneously “switching on” and amplification of a fluorescent signal “in situ” were achieved by utilising a tetrazine quenched fluorophore, reacting with norbornenes on the polymer–antibody conjugate. This fluorescence signal amplification method has the potential to improve real-time tumour detection and fluorescence-guided surgeries while the amplification strategy can be expanded to enhance radio-therapy performances

LIPID NANOPARTICLE-MEDIATED DELIVERY OF ENHANCED COSTIMULATION BLOCKADE TO PREVENT TYPE 1 DIABETES

Type 1 diabetes (T1D) remains an untreatable autoimmune disease caused by the destruction of pancreatic beta cells by autoreactive T cells. Because of its complex etiology, many immunotherapy strategies have been investigated, but with disappointing results. Costimulation blockade, blocking the CD28 pathway via administration of CTLA4-Ig is a promising approach, but recent observations suggest its efficacy is antagonized by inflammatory factors. As antigen presenting cells malfunctions and aberrant accumulation of type 1 interferons are associated with T1D, we pose that inhibiting the signaling of inflammatory cytokines via Tofacitinib (Tofa), a JAK inhibitor, would enhance the efficacy of CTLA4-Ig to prevent T1D development. The objective of this study was to design the controlled and localized delivery of Tofa via implementation of biocompatible lipid nanoparticles, Nanostructured Lipid Carrier (NLC), and assess the immunomodulatory impact of this strategy. We identified a specific composition of NLC that had negligible toxicity, could be readily taken up intracellularly by multiple immune cells, and had a favorable Tofa encapsulation efficiency. Live animal imaging using fluorescently-labeled NLC confirmed that these particles have the unique property of accumulating in lymphoid tissues. Moreover, when administrated via oral gavage, they bypassed first-pass metabolism and accumulated in spleen, pancreatic and mesenteric lymph nodes. Ex-vivo, Tofa is rapidly delivered by Tofa-NLC to mouse antigen presenting cells preventing their maturation. Short-term administration of Tofa-NLC via oral gavage at early or later stage in NOD mouse can promote a significant reduction of T1D onset and delay the development of the disease. The use of CTLA4-Ig at different dosage yet did not give any protective effect. Current works demonstrate a promising delivery vehicle in local delivery of anti-inflammatory agent, which provide therapeutic effect on T1D, and the mechanism(s) behind is still underway

Efficient Algorithm for Solving Hyperbolic Programs

Hyperbolic polynomials is a class of real-roots polynomials that has wide range of applications in theoretical computer science. Each hyperbolic polynomial also induces a hyperbolic cone that is of particular interest in optimization due to its generality, as by choosing the polynomial properly, one can easily recover the classic optimization problems such as linear programming and semidefinite programming. In this work, we develop efficient algorithms for hyperbolic programming, the problem in each one wants to minimize a linear objective, under a system of linear constraints and the solution must be in the hyperbolic cone induced by the hyperbolic polynomial. Our algorithm is an instance of interior point method (IPM) that, instead of following the central path, it follows the central Swath, which is a generalization of central path. To implement the IPM efficiently, we utilize a relaxation of the hyperbolic program to a quadratic program, coupled with the first four moments of the hyperbolic eigenvalues that are crucial to update the optimization direction. We further show that, given an evaluation oracle of the polynomial, our algorithm only requires $O(n^2d^{2.5})$ oracle calls, where $n$ is the number of variables and $d$ is the degree of the polynomial, with extra $O((n+m)^3 d^{0.5})$ arithmetic operations, where $m$ is the number of constraints

Quantitative Evaluation of the Environmental Quality of New Rural Communities-a Case Study of Henan Province, China

Abstract: The construction of new rural communities is an important measure to promote the integration of urban and rural areas. The environmental quality of new rural communities represents the residential suitability of the communities. The evaluation of the environmental quality can help promote the healthy development of new rural communities. The present study combines AHP (Analytic Hierarchy Process) and TOPSIS (Technique for Order Preference by Similarity to an Lead Solution) for the evaluation and ordering of the environmental quality of 28 new rural communities in Henan Province, China. The AHP model containing four hierarchies is constructed: objective hierarchy, principle hierarchy, index hierarchy and factor hierarchy. The principle hierarchy is composed of 3 factors: social environment, material environment and ecological environment; the index hierarchy consists of 7 factors: service environment, civilized environment, planning environment, architectural environment, facility environment, greening environment, sanitation environment; the factor hierarchy consists of 14 factors: life service, health service, education degree, neighborhood relationship, spatial layout, functional layout, architectural style, architectural functions, infrastructure, public facilities, percentage of green open space, leisure and entertainment facilities, garbage treatment rate and wastewater treatment rate. By AHP model, the weight of the factors in every hierarchy is obtained and TOPSIS is employed for the ordering of the environmental quality of the 28 new rural communities. The results show: in the environmental evaluation, spatial layout, functional layout, architectural functions, infrastructure and neighborhood relationship have a relatively higher weight and more importance should be attached to these respects. The ordering of environmental quality of new rural communities has a high discrimination. The five communities with the highest environmental quality (representing 17.8% of the total communities) are R 13 , R 6 , R 24 , R 23 and R 28 . The result can effectively reflect the environmental quality of new rural communities. On the one hand, this result can provide the basis for the transform and restructuring of the existing communities; on the other hand, it can be used as the reference for the quality control of newly-built communities, so that the objectives of new rural community construction will be met

Workload patterns for quality-driven dynamic cloud service configuration and auto-scaling

Cloud service providers negotiate SLAs for customer services they offer based on the reliability of performance and availability of their lower-level platform infrastructure. While availability management is more mature, performance management is less reliable. In order to support an iterative approach that supports the initial static infrastructure configuration as well as dynamic reconfiguration and auto-scaling, an accurate and efficient solution is required. We propose a prediction-based technique that combines a pattern matching approach with a traditional collaborative filtering solution to meet the accuracy and efficiency requirements. Service workload patterns abstract common infrastructure workloads from monitoring logs and act as a part of a first-stage high-performant configuration mechanism before more complex traditional methods are considered. This enhances current reactive rule-based scalability approaches and basic prediction techniques based on for example exponential smoothing