Overcoming Mass Transfer Barriers in Sandwich Configuration for Primary Hepatocytes Culture

Master'sMASTER OF SCIENC

Improvements to a Transport Model of Asphalt Binder Oxidation in Pavements: Pavement Temperature Modeling, Oxygen Diffusivity in Asphalt Binders and Mastics, and Pavement Air Void Characterization

Although evidence is mounting that asphalt binder oxidizes in pavements, and that oxidation and subsequent hardening of asphalt binder has a profound effect on pavement durability, important implementation issues remain to be better understood. Quantitative assessment of asphalt binder oxidation for a given pavement is a very important, but complex issue. In this dissertation, a fundamentals-based oxygen transport and reaction model was developed to assess quantitative asphalt binder oxidation in pavements. In this model, oxygen transport and reaction were described mathematically as two interlinked steps: 1) diffusion and/or flow of oxygen from the atmosphere above the pavement into the interconnected air voids in the pavement; and 2) diffusion of oxygen from those air voids into the adjoining asphalt-aggregate matrix where it reacts with the asphalt binder. Because such a model calculation depends extensively on accurately representing pavement temperature, understanding oxygen diffusivity in asphalt binders and mastics, and characterizing air voids in pavements, these key model elements were studied in turn. Hourly pavement temperatures were calculated with an improved one-dimensional heat transfer model, coupled with methods to obtain model-required climate data from available databases and optimization of site-specific pavement parameters nationwide; oxygen diffusivity in binders was determined based on laboratory oxidation experiments in binder films of known reaction kinetics by comparing the oxidation rates at the binder surface and at a solid-binder interface at the film depth. The effect of aggregate filler on oxygen diffusivity also was quantified, and air voids in pavements were characterized using X-ray computed tomography (X-ray CT) and image processing techniques. From these imaging techniques, three pavement air void properties, radius of each air void (r), number of air voids (N), and average shell distance between two air voids (rNFB) were obtained to use as model inputs in the asphalt binder oxidation model. Then, by incorporating these model element improvements into the oxygen transport and reaction model, asphalt binder oxidation rates for a number of Texas and Minnesota pavements were calculated. In parallel, field oxidation rates were measured for these corresponding pavement sites and compared to the model calculations. In general, there was a close match between the model calculations and field measurements, suggesting that the model captures the most critical elements that affect asphalt binder oxidation in pavements. This model will be used to estimate the rate of asphalt binder oxidation in pavements as a first step to predicting pavement performance, and ultimately, to improve pavement design protocols and pavement maintenance scheduling

Promoting Cardiac Repair through Simple Engineering of Nanoparticles with Exclusive Targeting Capability toward Myocardial Reperfusion Injury by Thermal Resistant Microfluidic Platform

Nanoparticle (NP)-based intravenous administration represents the most convenient cardiac targeting delivery routine, yet, there are still therapeutic issues due to the lack of targeting efficiency and specificity. Active targeting methods using functionalization of ligands onto the NPs' surface may be limited by trivial modification procedures and reduced targeting yield in vivo. Here, a microfluidics assisted single step, green synthesis method is introduced for producing targeting ligands free heart homing NPs in a tailored manner. The generated beta-glucan-based NPs exhibit precise and efficient targeting capability toward Dectin-1(+) monocytes/macrophages, which are confirmed as main pathogenesis mediators for cardiac ischemic/reperfusion (I/R) injury, with a sequentially enhanced cardiac NP accumulation, and this targeting strategy is exclusively suitable for cardiac I/R but not for other cardiovascular diseases, as confirmed both in murine and human model. Comparing to FDA-approved nano-micelles formulation, beta-glucan NPs loaded with NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome inhibitor (CY-09) exhibit better efficiency in ameliorating myocardial injury and heart failure induced by surgically induced I/R. These findings indicate a simple production of targeting-ligand free NPs, and demonstrate their potential therapeutic applications for preclinical I/R-induced cardiac injury amelioration.Peer reviewe

Promoting Cardiac Repair through Simple Engineering of Nanoparticles with Exclusive Targeting Capability toward Myocardial Reperfusion Injury by Thermal Resistant Microfluidic Platform

Nanoparticle (NP)-based intravenous administration represents the most convenient cardiac targeting delivery routine, yet, there are still therapeutic issues due to the lack of targeting efficiency and specificity. Active targeting methods using functionalization of ligands onto the NPs' surface may be limited by trivial modification procedures and reduced targeting yield in vivo. Here, a microfluidics assisted single step, green synthesis method is introduced for producing targeting ligands free heart homing NPs in a tailored manner. The generated beta-glucan-based NPs exhibit precise and efficient targeting capability toward Dectin-1(+) monocytes/macrophages, which are confirmed as main pathogenesis mediators for cardiac ischemic/reperfusion (I/R) injury, with a sequentially enhanced cardiac NP accumulation, and this targeting strategy is exclusively suitable for cardiac I/R but not for other cardiovascular diseases, as confirmed both in murine and human model. Comparing to FDA-approved nano-micelles formulation, beta-glucan NPs loaded with NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome inhibitor (CY-09) exhibit better efficiency in ameliorating myocardial injury and heart failure induced by surgically induced I/R. These findings indicate a simple production of targeting-ligand free NPs, and demonstrate their potential therapeutic applications for preclinical I/R-induced cardiac injury amelioration.Peer reviewe

Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity

该研究成果揭示了吞噬性细胞内Hippo信号通路关键激酶Mst1和Mst2通过活化Rac家族蛋白来调节线粒体向吞噬小泡募集并释放ROS来清除病原体，这个生物学过程在天然免疫和宿主防御中发挥着重要作用。该成果解析了人的Mst1基因缺失或Rac2基因突变引发免疫缺陷综合症的致病机理，为研究人类感染性疾病提供了全新的视角。 该论文的主要工作由2012级博士生耿晶、2013级博士生孙秀峰以及王平、张世浩和王晓珍等学生共同承担，并与厦门市第一医院、台湾长庚大学、中国科学技术大学等单位合作完成，通讯作者为周大旺教授和陈兰芬教授。该研究工作获得了“青年千人计划”、国家自然科学基金委和科技部的资助。Mitochondria need to be juxtaposed to phagosomes for the synergistic production of ample reactive oxygen species (ROS) in phagocytes to kill pathogens. However, how phagosomes transmit signals to recruit mitochondria has remained unclear. Here we found that the kinases Mst1 and Mst2 functioned to control ROS production by regulating mitochondrial trafficking and mitochondrion-phagosome juxtaposition. Mst1 and Mst2 activated the GTPase Rac to promote Toll-like receptor (TLR)-triggered assembly of the TRAF6-ECSIT complex that is required for the recruitment of mitochondria to phagosomes. Inactive forms of Rac, including the human Rac2D57N mutant, disrupted the TRAF6-ECSIT complex by sequestering TRAF6 and substantially diminished ROS production and enhanced susceptibility to bacterial infection. Our findings demonstrate that the TLR-Mst1-Mst2-Rac signaling axis is critical for effective phagosome-mitochondrion function and bactericidal activity.Supported by the National Basic Research Program (973) of China (2015CB910502 to L.C.), China's 1000 Young Talents Program (D.Z. and L.C.), the 111 Projects (B12001 and B06016), the Fundamental Research Funds for the Central Universities of China-Xiamen University (CXB2014004 to J.Z.; 20720140551 to L.C.; and 2013121034 and 20720140537 to D.Z.), the National Natural Science Foundation of China (31270918, 81222030 and J1310027 to D.Z.; 81372617, 81422018 and U1405225 to L.C.; 81472229 to L.H.; and 81302529 to X.L.), the Natural Science Foundation of Fujian (2013J06011 to D.Z. and 2014D007 to X.L.), the US National Institutes of Health (RO1 CA136567 for J.A.) and institutional funds from Massachusetts General Hospital (for J.A.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Prevalence and trend of hepatitis C virus infection among blood donors in Chinese mainland: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Blood transfusion is one of the most common transmission pathways of hepatitis C virus (HCV). This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection among blood donors in Chinese mainland, so as to help make prevention strategies and guide further research.</p> <p>Methods</p> <p>A systematic review was constructed based on the computerized literature database. Infection rates and 95% confidence intervals (95% CI) were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Data manipulation and statistical analyses were performed using STATA 10.0 and ArcGIS 9.3 was used for map construction.</p> <p>Results</p> <p>Two hundred and sixty-five studies met our inclusion criteria. The pooled prevalence of HCV infection among blood donors in Chinese mainland was 8.68% (95% CI: 8.01%-9.39%), and the epidemic was severer in North and Central China, especially in Henan and Hebei. While a significant lower rate was found in Yunnan. Notably, before 1998 the pooled prevalence of HCV infection was 12.87% (95%CI: 11.25%-14.56%) among blood donors, but decreased to 1.71% (95%CI: 1.43%-1.99%) after 1998. No significant difference was found in HCV infection rates between male and female blood donors, or among different blood type donors. The prevalence of HCV infection was found to increase with age. During 1994-1995, the prevalence rate reached the highest with a percentage of 15.78% (95%CI: 12.21%-19.75%), and showed a decreasing trend in the following years. A significant difference was found among groups with different blood donation types, Plasma donors had a relatively higher prevalence than whole blood donors of HCV infection (33.95% <it>vs </it>7.9%).</p> <p>Conclusions</p> <p>The prevalence of HCV infection has rapidly decreased since 1998 and kept a low level in recent years, but some provinces showed relatively higher prevalence than the general population. It is urgent to make efficient measures to prevent HCV secondary transmission and control chronic progress, and the key to reduce the HCV incidence among blood donors is to encourage true voluntary blood donors, strictly implement blood donation law, and avoid cross-infection.</p

Manufacturing consent in cyberspace: China's "Fifty-Cent Army"

Studies on public expression in China tend to focus on how the state and internet users (netizens) struggle over the limits of online expression. Few have systematically traced discourse competition within state-imposed boundaries, particularly how the authoritarian state has adapted to manage, rather than censor, online expression. This paper explores and evaluates the state's attempts to manipulate online expression without resorting to censorship and coercion by examining the role of internet commentators, known as the "fifty-cent army", in Chinese cyberspace. To cope with the challenge of online expression, the authoritarian state has mobilized its agents to engage anonymously in online discussions and produce apparently spontaneous pro-regime commentary. However, due to a lack of proper motivation and the persistence of old propaganda logic, this seemingly smart adaptation has proven ineffective or even counter-productive: It not only decreases netizens' trust in the state but also, ironically, suppresses the voices of regime supporters. (author's abstract

A final resolution to the peasant burden problem? The politics of fee-to-tax reform in rural China

Master'sMASTER OF SOCIAL SCIENCE

Challenging the Regime, Defending the Regime: Contesting Cyberspace in China

Drawing on twelve months of fieldwork and over two years of in-depth online ethnographic work, the dissertation examines state management and popular activism on Chinese internet forums as a window onto China's authoritarian state. Through examination of state management and popular activism on Chinese internet forums, I find not only a conventional cat-and-mouse censorship game in which the party-state, intermediary actors and forum users struggle over the limits of online expression, but also discourse competition in which the regime, its critics and netizens engineer popular opinion to their advantage.I find that censorship is more complicated than the usual picture of state-society confrontation. It involves the fragmented state, many intermediary actors and netizens with diverse purposes and motivations. To understand the mechanism of the censorship, I trace the evolution of the state censorship system, and explore its external challenges and internal fragmentation (Chapter 2). I also examine forum managers' censorship responsibilities and their "discontented compliance" as a response to state control and netizens' demands (Chapter 3). My examination of netizen activism shows that forum users engage in "pop activism" that blurs the boundary of political participation and popular entertainment (Chapter 4). In the censorship game, though state coercive power establishes the basic logic of censorship, technological know-how and expressive creativity enable forum managers and netizens to counterbalance state control.In discourse competition, both the regime and its critics have attempted to engineer popular opinion through anonymous public relations strategies. The state's attempts to turn propaganda into public relations through mobilization of paid internet commentators - popularly known as the "fifty cents army" -frequently backfire and chip away at its legitimacy (Chapter 5). However, regime critics' efforts in discourse competition have produced the political framing of regime challengers as saboteurs of the nation rather than freedom fighters (Chapter 6), leading to the rise of pro-regime netizen communities that voluntarily defend the authoritarian regime. By examining how these regime-defending netizens adopt their identity, construct a community and sustain pro-regime discourse, I challenge assumptions about the internet's democratizing power (Chapter 7).My dissertation presents a nuanced picture of internet politics and a complex pattern of state-society interaction in a reforming authoritarian regime. Unlike earlier work which assumes a control-liberalization relationship between the state and the netizens, both of which are implicitly treated as single entities, my dissertation highlights the internal fragmentation of Chinese state and challenges the assumption of a monolithic internet that is inherently liberalizing and democratizing. These findings also speak to both the literature on authoritarian resilience as well as recent work on technological empowerment. As scholars devote more attention to understanding varieties of authoritarianism and authoritarian resilience, my work suggests that the "authoritarian resilience" literature focuses too heavily on the regime's adaptability without sufficient attention to the nature and impact of challenges towards the regime. My findings also propose that work on "technological empowerment" overemphasizes the emancipatory character of the internet while neglecting the limitations of internet mobilization