Bias analysis in mode-based Kalman filters for stochastic hybrid systems

Doctor of PhilosophyDepartment of Electrical and Computer EngineeringBalasubramaniam NatarajanStochastic hybrid system (SHS) is a class of dynamical systems that experience interaction of both discrete mode and continuous dynamics with uncertainty. State estimation for SHS has attracted research interests for decades with Kalman filter based solutions dominating the area. Mode-based Kalman filter is an extended version of the traditional Kalman filter for SHS. In general, as Kalman filter is unbiased for non-hybrid system estimation, prior research efforts primarily focus on the behavior of error covariance. In SHS state estimate, mode mismatch errors could result in a bias in the mode-based Kalman filter and have impacts on the continuous state estimation quality. The relationship between mode mismatch errors and estimation stability is an open problem that this dissertation attempts to address. Specifically, the probabilistic model of mode mismatch errors can be independent and identically distributed (i.i.d.), correlated across different modes and correlated across time. The proposed approach builds on the idea of modeling the bias evolution as a transformed system. The statistical convergence of the bias dynamics is then mapped to the stability of the transformed system. For each specific model of the mode mismatch error, the system matrix of the transformed system varies which results in challenges for the stability analysis. For the first time, the dissertation derives convergence conditions that provide tolerance regions for the mode mismatch error for three mode mismatch situations. The convergence conditions are derived based on generalized spectral radius theorem, Lyapunov theorem, Schur stability of a matrix polytope and interval matrix method. This research is fundamental in nature and its application is widespread. For example, the spatially and timely correlated mode mismatch errors can effectively capture cyber-attacks and communication link impairments in a cyber-physical system. Therefore, the theory and techniques developed in this dissertation can be used to analyze topology errors in any networked system such as smart grid, smart home, transportation, flight management system etc. The main results provide new insights on the fidelity in discrete state knowledge needed to maintain the performance of a mode-based Kalman filter and provide guidance on design of estimation strategies for SHS

Iron Ion and Iron Hydroxide Adsorption to Charge-Neutral Phosphatidylcholine Templates

Surface-sensitive X-ray scattering and spectroscopy techniques reveal significant adsorption of iron ions and iron-hydroxide (Fe(III)) complexes to a charge-neutral zwitterionic template of phosphatidylcholine (PC). The PC template is formed by a Langmuir monolayer of dipalmitoyl-PC (DPPC) that is spread on the surface of 2 to 40 μM FeCl3 solutions at physiological levels of KCl (100 mM). At 40 μM of Fe(III) as many as ∼3 iron atoms are associated with each PC group. Grazing incidence X-ray diffraction measurements indicate a significant disruption in the in-plane ordering of DPPC molecules upon iron adsorption. The binding of iron-hydroxide complexes to a neutral PC surface is yet another example of nonelectrostatic, presumably covalent bonding to a charge-neutral organic template. The strong binding and the disruption of in-plane lipid structure has biological implications on the integrity of PC-derived lipid membranes, including those based on sphingomyelin

Single-nucleotide polymorphisms in a short basic motif in the ABC transporter ABCG2 disable its trafficking out of endoplasmic reticulum and reduce cell resistance to anticancer drugs

ATP-binding cassette (ABC) subfamily G member 2 (ABCG2) belongs to the ABC transporter superfamily and has been implicated in multidrug resistance of cancers. Although the structure and function of ABCG2 have been extensively studied, little is known about its biogenesis and the regulation thereof. In this study, using mutagenesis and several biochemical analyses, we show that the positive charges in the vicinity of the RKR motif downstream of the ABC signature drive trafficking of nascent ABCG2 out of the endoplasmic reticulum (ER) onto plasma membranes. Substitutions of and naturally occurring single-nucleotide polymorphisms within these positively charged residues disabled the trafficking of ABCG2 out of the ER. A representative ABCG2 variant in which the RKR motif had been altered underwent increased ER stress-associated degradation. We also found that unlike WT ABCG2, genetic ABCG2 RKR variants have disrupted normal maturation and do not reduce accumulation of the anticancer drug mitoxantrone and no longer confer resistance to the drug. We conclude that the positive charges downstream of the ABC signature motif critically regulate ABCG2 trafficking and maturation. We propose that single-nucleotide polymorphisms of these residues reduce ABCG2 expression via ER stress-associated degradation pathway and may contribute to reduced cancer drug resistance, improving the success of cancer chemotherapy