Autonomous Flight, Fault, and Energy Management of the Flying Fish Solar-Powered Seaplane.

The Flying Fish autonomous unmanned seaplane is designed and built for persistent ocean surveillance. Solar energy harvesting and always-on autonomous control and guidance are required to achieve unattended long-term operation. This thesis describes the Flying Fish avionics and software systems that enable the system to plan, self-initiate, and autonomously execute drift-flight cycles necessary to maintain a designated watch circle subject to environmentally influenced drift. We first present the avionics and flight software architecture developed for the unique challenges of an autonomous energy-harvesting seaplane requiring the system to be: waterproof, robust over a variety of sea states, and lightweight for flight. Seaplane kinematics and dynamics are developed based on conventional aircraft and watercraft and upon empirical flight test data. These models serve as the basis for development of flight control and guidance strategies which take the form of a cyclic multi-mode guidance protocol that smoothly transitions between nested gain-scheduled proportional-derivative feedback control laws tuned for the trim conditions of each flight mode. A fault-tolerant airspeed sensing system is developed in response to elevated failure rates arising from pitot probe water ingestion in the test environment. The fault-tolerance strategy utilizes sensor characteristics and signal energy to combine redundant sensor measurements in a weighted voting strategy, handling repeated failures, sensor recovery, non-homogenous sensors, and periods of complete sensing failure. Finally, a graph-based mission planner combines models of global solar energy, local ocean-currents, and wind with flight-verified/derived aircraft models to provide an energy-aware flight planning tool. An NP-hard asymmetric multi-visit traveling salesman planning problem is posed that integrates vehicle performance and environment models using energy as the primary cost metric. A novel A* search heuristic is presented to improve search efficiency relative to uniform cost search. A series of cases studies are conducted with surface and airborne goals for various times of day and for multi-day scenarios. Energy-optimal solutions are identified except in cases where energy harvesting produces multiple comparable-cost plans via negative-cost cycles. The always-on cyclic guidance/control system, airspeed sensor fault management algorithm, and the nested-TSP heuristic for A* are all critical innovation required to solve the posed research challenges.Ph.D.Aerospace EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91453/1/eubankrd_1.pd

Energy-Aware Multiflight Planning for an Unattended Seaplane: Flying Fish

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/143017/4/1.i010484.pd

The Flying Fish Persistent Ocean Surveillance Platform

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77030/1/AIAA-2009-1902-584.pd

M-CSF Signals through the MAPK/ERK Pathway via Sp1 to Induce VEGF Production and Induces Angiogenesis In Vivo

BACKGROUND: M-CSF recruits mononuclear phagocytes which regulate processes such as angiogenesis and metastases in tumors. VEGF is a potent activator of angiogenesis as it promotes endothelial cell proliferation and new blood vessel formation. Previously, we reported that in vitro M-CSF induces the expression of biologically-active VEGF from human monocytes. METHODOLOGY AND RESULTS: In this study, we demonstrate the molecular mechanism of M-CSF-induced VEGF production. Using a construct containing the VEGF promoter linked to a luciferase reporter, we found that a mutation reducing HIF binding to the VEGF promoter had no significant effect on luciferase production induced by M-CSF stimulation. Further analysis revealed that M-CSF induced VEGF through the MAPK/ERK signaling pathway via the transcription factor, Sp1. Thus, inhibition of either ERK or Sp1 suppressed M-CSF-induced VEGF at the mRNA and protein level. M-CSF also induced the nuclear localization of Sp1, which was blocked by ERK inhibition. Finally, mutating the Sp1 binding sites within the VEGF promoter or inhibiting ERK decreased VEGF promoter activity in M-CSF-treated human monocytes. To evaluate the biological significance of M-CSF induced VEGF production, we used an in vivo angiogenesis model to illustrate the ability of M-CSF to recruit mononuclear phagocytes, increase VEGF levels, and enhance angiogenesis. Importantly, the addition of a neutralizing VEGF antibody abolished M-CSF-induced blood vessel formation. CONCLUSION: These data delineate an ERK- and Sp1-dependent mechanism of M-CSF induced VEGF production and demonstrate for the first time the ability of M-CSF to induce angiogenesis via VEGF in vivo

Modeling the inhibition of breast cancer growth by GM-CSF

M-CSF is overexpressed in breast cancer and is known to stimulate macrophages to produce VEGF resulting in angiogenesis. It has recently been shown that the growth factor GM-CSF injected into murine breast tumors slowed tumor growth by secreting soluble VEGF receptor-1 (sVEGFR-1) that binds and inactivates VEGF. This study presents a mathematical model that includes all the components above, as well as MCP-1, tumor cells, and oxygen. The model simulations are representative of the in vivo data through predictions of tumor growth using different protocol strategies for GM-CSF for the purpose of predicting higher degrees of treatment success. For example, our model predicts that once a week dosing of GM-CSF would be less effective than daily, twice a week, or three times a week treatment because of the presence of essential factors required for the anti-tumor effect of GM-CSF. (C) 2012 Elsevier Ltd. All rights reserved

GM-CSF Induces Expression of Soluble VEGF Receptor-1 from Human Monocytes and Inhibits Angiogenesis in Mice

AbstractGM-CSF promotes homeostasis of myeloid cells. We report that GM-CSF upregulates mRNA and protein production of the soluble form of membrane bound VEGF receptor-1 (sVEGFR-1) in human monocytes. This sVEGFR-1 was biologically active, as cell-free supernatants from GM-CSF-stimulated monocytes blocked detection of endogenously expressed VEGF and inhibited endothelial cell migration and tube formation, even in the presence of exogenous rhVEGF. VEGF activity was recovered by neutralizing sVEGFR-1. To determine whether these events were important in vivo, Matrigel plugs were incubated with rhVEGF, rhGM-CSF, or rhGM-CSF/rhVEGF and injected into mice. Plugs containing GM-CSF or GM-CSF/VEGF had less endothelial cell invasion than plugs containing rhVEGF and were similar to plugs incubated with PBS alone. Neutralizing antibodies specific for sVEGFR-1 injected in these plugs reversed the effects of GM-CSF or GM-CSF/VEGF, while an isogenic antibody did not. Thus, GM-CSF and monocytes play a vital role in angiogenesis through the regulation of VEGF and sVEGFR-1

M-CSF induces mononuclear phagocyte recruitment <i>in vivo</i>.

<p>A) Matrigel™ was resuspended with PBS <i>(PBS)</i> or rmM-CSF (100 ng/ml) <i>(M-CSF)</i> at 4°C overnight and then injected subcutaneously into mice. Matrigel™ was left <i>in situ</i> for 10 days and then harvested. The plugs were stained for mononuclear phagocytes using an anti-mouse F4/80 antibody. Brown staining represents F4/80(+) cells within the plug. Pictures shown were taken using a dissecting microscope (1.5× objective lens) <i>(left)</i> to display overall mononuclear phagocyte influx between conditions as well as an inverted microscope (20× objective lens) <i>(right)</i> to show detailed staining of these cells. B) The percent of F4/80(+) cells (brown stain) per plug was evaluated from 15 digital images captured randomly in a blinded manner. Adobe Photoshop histogram pixel analysis of the brown stain was used for quantification. This data represents three plugs per group.</p

M-CSF induced VEGF production occurs through a HIF-independent mechanism.

<p>A) The 1.5 kb wild type VEGF promoter <i>(WT1.5 kb)</i> and the same promoter sequence containing a non-functional mutation of the hypoxia regulatory element (HRE) <i>(ΔHRE)</i> were inserted into the pGL3-basic vector to create constructs that produce luciferase upon VEGF promoter activation. Nucleotides changed from the original wild type sequence are designated in bold. Human monocytes were transfected with either the control empty construct (pGL3-Basic), or pGL3 containing 1 µg of each of the described VEGF promoter constructs above. B) Transfected monocytes containing <i>(WT1.5 kb)</i> or <i>(ΔHRE)</i> were allowed to adhere for 1 hour in RPMI/5% FBS followed by the addition of fresh media containing rhM-CSF (100 ng/ml) for 16 hours. The adherent cells were lysed and assayed for luciferase production using a luminometer. This data represents the mean+/−SEM of six individual blood donors. All data is represented as the fold change in luciferase over the pGL3 control construct.</p