Takagi-Sugeno Fuzzy Model Based Discrete Time Model Predictive Control for a Hypersonic Re-Entry Vehicle

In this thesis, we present a control algorithm for a hypersonic re-entry vehicle during a Martian aerocapture maneuver. The proposed algorithm utilizes a discrete-time model predictive control technique with a Takagi-Sugeno fuzzy model of the vehicle to control the re-entry vehicle along an arbitrary trajectory using bank angle modulation. Simulations using model parameters and initial conditions from a Martian aerocapture mission demonstrate the stability, performance, and robustness of the proposed controller

PATJ regulates tight junction formation and polarity in mammalian epithelial cells

Recent studies have revealed an important role for tight junction protein complexes in epithelial cell polarity. One of these complexes contains the apical transmembrane protein, Crumbs, and two PSD95/discs large/zonula occludens domain proteins, protein associated with Lin seven 1 (PALS1)/Stardust and PALS1-associated tight junction protein (PATJ). Although Crumbs and PALS1/Stardust are known to be important for cell polarization, recent studies have suggested that Drosophila PATJ is not essential and its function is unclear. Here, we find that PATJ is targeted to the apical region and tight junctions once cell polarization is initiated. We show using RNAi techniques that reduction in PATJ expression leads to delayed tight junction formation as well as defects in cell polarization. These effects are reversed by reintroduction of PATJ into these RNAi cells. This study provides new functional information on PATJ as a polarity protein and increases our understanding of the Crumbs–PALS1–PATJ complex function in epithelial polarity

FIP 5 phosphorylation during mitosis regulates apical trafficking and lumenogenesis

Apical lumen formation is a key step during epithelial morphogenesis. The establishment of the apical lumen is a complex process that involves coordinated changes in plasma membrane composition, endocytic transport, and cytoskeleton organization. These changes are accomplished, at least in part, by the targeting and fusion of Rab11/ FIP 5‐containing apical endosomes with the apical membrane initiation site ( AMIS ). Although AMIS formation and polarized transport of Rab11/ FIP 5‐containing endosomes are crucial for the formation of a single apical lumen, the spatiotemporal regulation of this process remains poorly understood. Here, we demonstrate that the formation of the midbody during cytokinesis is a symmetry‐breaking event that establishes the location of the AMIS . The interaction of FIP 5 with SNX 18, which is required for the formation of apical endocytic carriers, is inhibited by GSK ‐3 phosphorylation at FIP 5‐T276. Importantly, we show that FIP 5‐T276 phosphorylation occurs specifically during metaphase and anaphase, to ensure the fidelity and timing of FIP 5‐endosome targeting to the AMIS during apical lumen formation. Synopsis This study shows that epithelial lumen formation is regulated by FIP 5 phosphorylation, which inhibits its interaction with SNX 18 during metaphase and anaphase, ensuring that the transport of apical endocytic carriers happens only after the formation of the AMIS . FIP 5‐endosomes travel along the central spindle to the apical membrane initiation site ( AMIS ). FIP 5‐T276 phosphorylation by GSK ‐3 regulates the timing of apical lumen formation. The midbody formation during cytokinesis is a symmetry‐breaking event leading to the establishment of a single apical lumen site. This study shows that epithelial lumen formation is regulated by FIP5 phosphorylation, which inhibits its interaction with SNX18 during metaphase and anaphase, ensuring that the transport of apical endocytic carriers happens only after the formation of the AMIS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/1/embr201338128-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/2/embr201338128-SourceData-Fig4G.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/3/embr201338128-sup-0003-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/4/embr201338128.reviewer_comments.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/5/embr201338128.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/6/embr201338128-sup-0004-FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/7/embr201338128-SourceData-Fig2B-C-D.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/8/embr201338128-sup-0005-FigS5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/9/embr201338128-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106968/10/embr201338128-sup-0006-Methods.pd

Structural basis for L27 domain‐mediated assembly of signaling and cell polarity complexes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102252/1/emboj7600294.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102252/2/emboj7600294-sup-0001.pd

A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin β interactions

The Crumbs family of apical transmembrane proteins regulates apicobasal polarity via protein interactions with a conserved C-terminal sequence, ERLI. However, one of the mammalian Crumbs proteins, Crumbs3 (CRB3) has an alternate splice form with a novel C-terminal sequence ending in CLPI (CRB3-CLPI). We report that CRB3-CLPI localizes to the cilia membrane and a membrane compartment at the mitotic spindle poles. Knockdown of CRB3-CLPI leads to both a loss of cilia and a multinuclear phenotype associated with centrosomal and spindle abnormalities. Using protein purification, we find that CRB3-CLPI interacts with importin β-1 in a Ran-regulated fashion. Importin β-1 colocalizes with CRB3-CLPI during mitosis, and a dominant-negative form of importin β-1 closely phenocopies CRB3-CLPI knockdown. Knockdown of importin β-1 blocks targeting of CRB3-CLPI to the spindle poles. Our data suggest an expanded role for Crumbs proteins in polarized membrane targeting and cell division via unique interactions with importin proteins

Depletion of CD4 T lymphocytes in human lymphoid tissue infected ex vivo with doxycycline-dependent HIV-1

AbstractWe investigated whether CD4+ T cells that do not produce HIV-1 are killed in HIV-infected human lymphoid tissue. Tissue blocks were inoculated with high amount of doxycycline-dependent HIV-rtTA. Doxycycline triggered productive infection and loss of CD4+ T cells in these tissues, whereas without doxycycline, neither productive infection nor CD4+ T cell depletion was detected in spite of the massive presence of virions in the tissue and of viral DNA in the cells. Thus, HIV-1 alone is sufficient to deplete productively infected CD4+ T cells but is not sufficient to cause the death of uninfected or latently infected CD4+ T cells

Control and Simulation of a Deployable Entry Vehicle with Aerodynamic Control Surfaces

In this paper, we investigate the static stability of a deployable entry vehicle called the Lifting Nano-ADEPT and design a control system to follow bank angle, angle-of-attack, and sideslip guidance commands. The control design, based on linear quadratic regulator optimal techniques, utilizes aerodynamic control surfaces to track angle-of-attack, sideslip angle, and bank angle commands. We demonstrate, using a nonlinear simulation environment, that the controller is able to accurately track step commands that may come from a guidance algorithm

Pterodactyl: Trade Study for an Integrated Control System Design of a Mechanically Deployable Entry Vehicle

This paper presents the trade study method used to evaluate and downselect from a set of guidance and control (G&C) system designs for a mechanically Deployable Entry Vehicle (DEV). The Pterodactyl project was prompted by the challenge to develop an effective G&C system for a vehicle without a backshell, which is the case for DEVs. For the DEV, the project assumed a specific aeroshell geometry pertaining to an Adaptable, Deployable Entry and Placement Technology (ADEPT) vehicle, which was successfully developed by NASAs Space Technology Mission Directorate (STMD) prior to this study. The Pterodactyl project designed three different entry G&C systems for precision targeting. This paper details the Figures of Merit (FOMs) and metrics used during the course of the projects G&C system assessment. The relative importance of the FOMs was determined from the Analytic Hierarchy Process (AHP), which was used to develop weights that were combined with quantitative design metrics and engineering judgement to rank the G&C systems against one another. This systematic method takes into consideration the projects input while simultaneously reducing unintentional judgement bias and ultimately was used to select a single G&C design for the project to pursue in the next design phase

The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost

Membrane-associated guanylate kinase (Maguk) proteins are scaffold proteins that contain PSD-95–Discs Large–zona occludens-1 (PDZ), Src homology 3, and guanylate kinase domains. A subset of Maguk proteins, such as mLin-2 and protein associated with Lin-7 (Pals)1, also contain two L27 domains: an L27C domain that binds mLin-7 and an L27N domain of unknown function. Here, we demonstrate that the L27N domain targets Pals1 to tight junctions by binding to a PDZ domain protein, Pals1-associated tight junction (PATJ) protein, via a unique Maguk recruitment domain. PATJ is a homologue of Drosophila Discs Lost, a protein that is crucial for epithelial polarity and that exists in a complex with the apical polarity determinant, Crumbs. PATJ and a human Crumbs homologue, CRB1, colocalize with Pals1 to tight junctions, and CRB1 interacts with PATJ albeit indirectly via binding the Pals1 PDZ domain. In agreement, we find that a Drosophila homologue of Pals1 participates in identical interactions with Drosophila Crumbs and Discs Lost. This Drosophila Pals1 homologue has been demonstrated recently to represent Stardust, a crucial polarity gene in Drosophila. Thus, our data identifies a new multiprotein complex that appears to be evolutionarily conserved and likely plays an important role in protein targeting and cell polarity