Shihua Li

Bio: Shihua Li is an academic researcher from Southeast University. The author has contributed to research in topics: Control theory & Huntingtin. The author has an hindex of 101, co-authored 616 publications receiving 35335 citations. Previous affiliations of Shihua Li include Johns Hopkins University School of Medicine & Central South University.

Disturbance-Observer-Based Control and Related Methods—An Overview

Abstract: Disturbance-observer-based control (DOBC) and related methods have been researched and applied in various industrial sectors in the last four decades. This survey, at first time, gives a systematic and comprehensive tutorial and summary on the existing disturbance/uncertainty estimation and attenuation techniques, most notably, DOBC, active disturbance rejection control, disturbance accommodation control, and composite hierarchical antidisturbance control. In all of these methods, disturbance and uncertainty are, in general, lumped together, and an observation mechanism is employed to estimate the total disturbance. This paper first reviews a number of widely used linear and nonlinear disturbance/uncertainty estimation techniques and then discusses and compares various compensation techniques and the procedures of integrating disturbance/uncertainty compensation with a (predesigned) linear/nonlinear controller. It also provides concise tutorials of the main methods in this area with clear descriptions of their features. The application of this group of methods in various industrial sections is reviewed, with emphasis on the commercialization of some algorithms. The survey is ended with the discussion of future directions.

Sliding-Mode Control for Systems With Mismatched Uncertainties via a Disturbance Observer

Abstract: This paper develops a sliding-mode control (SMC) approach for systems with mismatched uncertainties via a nonlinear disturbance observer (DOB). By designing a novel sliding surface based on the disturbance estimation, a DOB-based SMC method is developed in this paper to counteract the mismatched disturbance. The newly proposed method exhibits the following two attractive features. First, the switching gain is only required to be designed greater than the bound of the disturbance estimation error rather than that of the disturbance; thus, the chattering problem is substantially alleviated. Second, the proposed method retains its nominal performance, which means the proposed method acts the same as the baseline sliding-mode controller in the absence of uncertainties. Simulation results of both the numerical and application examples show that the proposed method exhibits much better control performance than the baseline SMC and the integral SMC (I-SMC) methods, such as reduced chattering and nominal performance recovery.

Nuclear and Neuropil Aggregates in Huntington’s Disease: Relationship to Neuropathology

Abstract: The data we report in this study concern the types, location, numbers, forms, and composition of microscopic huntingtin aggregates in brain tissues from humans with different grades of Huntington’s disease (HD). We have developed a fusion protein antibody against the first 256 amino acids that preferentially recognizes aggregated huntingtin and labels many more aggregates in neuronal nuclei, perikarya, and processes in human brain than have been described previously. Using this antibody and human brain tissue ranging from presymptomatic to grade 4, we have compared the numbers and locations of nuclear and neuropil aggregates with the known patterns of neuronal death in HD. We show that neuropil aggregates are much more common than nuclear aggregates and can be present in large numbers before the onset of clinical symptoms. There are also many more aggregates in cortex than in striatum, where they are actually uncommon. Although the striatum is the most affected region in HD, only 1–4% of striatal neurons in all grades of HD have nuclear aggregates. Neuropil aggregates, which we have identified by electron microscopy to occur in dendrites and dendritic spines, could play a role in the known dendritic pathology that occurs in HD. Aggregates increase in size in advanced grades, suggesting that they may persist in neurons that are more likely to survive. Ubiquitination is apparent in only a subset of aggregates, suggesting that ubiquitin-mediated proteolysis of aggregates may be late or variable.

A huntingtin-associated protein enriched in brain with implications for pathology

Abstract: HUNTINGTON's disease (HD) is an autosomal dominant neuro-degenerative disorder caused by an expanding polyglutamine repeat in the IT 15 or huntingtin gene1. Although this gene is widely expressed2–9 and is required for normal development10–12, the pathology of HD is restricted to the brain, for reasons that remain poorly understood. The huntingtin gene product is expressed at similar levels in patients and controls, and the genetics of the disorder13,14 suggest that the expansion of the polyglutamine repeat induces a toxic gain of function, perhaps through interactions with other cellular proteins15–18. Here we report the identification of a protein (huntingtin-associated protein (HAP)-l) that binds to huntingtin. This binding is enhanced by an expanded polyglutamine repeat, the length of which is also known to correlate with the age of disease onset19–21. The HAP-1 protein is enriched in the brain, suggesting a possible basis for the selective brain pathology of HD.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases

Abstract: Many lines of evidence suggest that mitochondria have a central role in ageing-related neurodegenerative diseases. Mitochondria are critical regulators of cell death, a key feature of neurodegeneration. Mutations in mitochondrial DNA and oxidative stress both contribute to ageing, which is the greatest risk factor for neurodegenerative diseases. In all major examples of these diseases there is strong evidence that mitochondrial dysfunction occurs early and acts causally in disease pathogenesis. Moreover, an impressive number of disease-specific proteins interact with mitochondria. Thus, therapies targeting basic mitochondrial processes, such as energy metabolism or free-radical generation, or specific interactions of disease-related proteins with mitochondria, hold great promise.

Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice

Abstract: Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.