Preview-Enabled Optimal Control of Wind Turbines

Wind turbine control systems have traditionally relied on feedback measurements for rotor-speed regulation. In the mid-2000s, the use of a lidar scanner to measure the wind upstream of the turbine was demonstrated, instigating research into the use of preview disturbance measurements within the turbine controller. Over the last fifteen years, many competing feedforward control laws have been proposed and demonstrated in simulation and field tests; today, lidars are being deployed on operational wind turbines, if still largely for research purposes. In this thesis, I present a series of optimal control methods for handling preview wind speed measurements in the wind turbine blade pitch controller. This begins with disturbance-accommodating control, which seeks to directly counteract the impact of the current disturbance on the system state and can be added directly to an already-designed feedback control law. Disturbance accommodating-control is presented mainly to establish the benefits of including lidar measurements in the turbine controller. The majority of the contributions of this thesis lie in extensions to the linear-quadratic regulator to handle preview disturbance information. Theoretical developments are presented first, followed by the demonstration of the disturbance-handling linear-quadratic regulator on an experimental scaled model wind turbine operating in a wind tunnel. Finally, constraints are included in the optimal control problem, resulting in a preview-enabled linear model predictive controller. This was also tested on the scaled model turbine using a range of gusty, turbulent, and transition wind conditions. Throughout this thesis, with the exception of a small demonstration of developed theory, I employ numerical linear models of wind turbines for controller design. For nonlinear simulation-based research in this thesis and adjacent studies, I use the NREL 5MW reference turbine. The physical wind tunnel experiments were carried out on the MoWiTO 1.8 turbine, which is itself based on the properties of the NREL 5MW turbine, operated by scientists at ForWind - Center for Wind Energy Research at the University of Oldenburg.</p

1997 Convocation

Prelude: Mr. Brad Friedman, 1996 IMSA Graduate Welcome: Dr. Stephanie Pace Marshall, President; Dr. Gregg Sinner, Principal; Ms. Jennifer Wang, Student Council President Musical Selection: Mr. Brad Friedman Keynote Speaker: Mr. Michael Peil, 1990 IMSA Graduat

Controllability of Formation Systems on Special Orthogonal Groups over Directed Graphs

Gradient flows provide a means for a networked formation system to reach and stabilize at a target configuration. However, the decentralization&nbsp; constraints and the geometry of the state space makes the appearance of stable but undesired configurations inevitable. The presence of these&nbsp; undesired stable configurations precludes global&nbsp; convergence to the target configuration. In this paper, we address the issue by considering a&nbsp; controlled formation system on special orthogonal&nbsp; groups over a directed graph. Agents of the system are tasked with stabilizing from others at target&nbsp; relative attitudes. The nominal dynamics of the agents are gradient flows of certain potential functions. These functions are parameter dependent, pretuned by the controller. To prevent the formation system from being trapped at an undesired configuration, we formulate and address the problem of whether the controller can steer the system from any configuration to any other configuration by retuning, on the fly, the parameters of the potential functions. We show that the answer is affirmative provided that the underlying graph is rooted with a single root node being fully actuated. We formulate the result as a main theorem and provide a complete proof of the result.</p

Therapies with CCL25 require controlled release via microparticles to avoid strong inflammatory reactions

Background: Chemokine therapy with C-C motif chemokine ligand 25 (CCL25) is currently under investigation as a promising approach to treat articular cartilage degeneration. We developed a delayed release mechanism based on Poly (lactic-co-glycolic acid) (PLGA) microparticle encapsulation for intraarticular injections to ensure prolonged release of therapeutic dosages. However, CCL25 plays an important role in immune cell regulation and inflammatory processes like T-cell homing and chronic tissue inflammation. Therefore, the potential of CCL25 to activate immune cells must be assessed more thoroughly before further translation into clinical practice. The aim of this study was to evaluate the reaction of different immune cell subsets upon stimulation with different dosages of CCL25 in comparison to CCL25 released from PLGA particles. Results: Immune cell subsets were treated for up to 5 days with CCL25 and subsequently analyzed regarding their cytokine secretion, surface marker expression, polarization, and migratory behavior. The CCL25 receptor C-C chemokine receptor type 9 (CCR9) was expressed to a different extent on all immune cell subsets. Direct stimulation of peripheral blood mononuclear cells (PBMCs) with high dosages of CCL25 resulted in strong increases in the secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), tumor-necrosis-factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), upregulation of human leukocyte antigen-DR (HLA-DR) on monocytes and CD4(+) T-cells, as well as immune cell migration along a CCL25 gradient. Immune cell stimulation with the supernatants from CCL25 loaded PLGA microparticles caused moderate increases in MCP-1, IL-8, and IL-1 beta levels, but no changes in surface marker expression or migration. Both CCL25-loaded and unloaded PLGA microparticles induced an increase in IL-8 and MCP-1 release in PBMCs and macrophages, and a slight shift of the surface marker profile towards the direction of M2-macrophage polarization. Conclusions: While supernatants of CCL25 loaded PLGA microparticles did not provoke strong inflammatory reactions, direct stimulation with CCL25 shows the critical potential to induce global inflammatory activation of human leukocytes at certain concentrations. These findings underline the importance of a safe and reliable release system in a therapeutic setup. Failure of the delivery system could result in strong local and systemic inflammatory reactions that could potentially negate the benefits of chemokine therapy

Experimental Testing of a Preview-enabled Model Predictive Controller for Blade Pitch Control of Wind Turbines

Model predictive control (MPC) is a control method that involves determining the input to a dynamical system as the solution to an optimization problem that is solved online. In the wind turbine research literature, MPC has received considerable attention for its ability to handle both actuator constraints and preview disturbance information about the oncoming wind, which can be provided by a lidar scanner. However, while many studies simulate the wind turbine response under MPC, very few physical tests have been carried out, likely due in part to the difficulties associated with solving the MPC problem in real time. In this work, we implement MPC on an experimental, scaled wind turbine operating in a wind tunnel testbed, using an active grid to create reproducible wind sequences and a hot-wire anemometer to generate upstream wind measurements. To our knowledge, this work presents the first physical test of MPC for blade pitch control of a scaled wind turbine. We compare two MPC strategies: one including preview disturbance information and one without. Our results provide further evidence that feedforward control can improve wind turbine performance in transition and above-rated conditions without increasing actuation requirements, which we hope will encourage industry experimentation and uptake of feedforward control methods. We also provide a high-level analysis and interpretation of the computational performance of the chosen approach. This work builds upon the results of an earlier study, which considered unconstrained optimal blade pitch control. &nbsp;</p

Experimental Testing of a Preview-enabled Model Predictive Controller for Blade Pitch Control of Wind Turbines

Model predictive control (MPC) is a control method that involves determining the input to a dynamical system as the solution to an optimization problem that is solved online. In the wind turbine research literature, MPC has received considerable attention for its ability to handle both actuator constraints and preview disturbance information about the oncoming wind, which can be provided by a lidar scanner. However, while many studies simulate the wind turbine response under MPC, very few physical tests have been carried out, likely due in part to the difficulties associated with solving the MPC problem in real time. In this work, we implement MPC on an experimental, scaled wind turbine operating in a wind tunnel testbed, using an active grid to create reproducible wind sequences and a hot-wire anemometer to generate upstream wind measurements. To our knowledge, this work presents the first physical test of MPC for blade pitch control of a scaled wind turbine. We compare two MPC strategies: one including preview disturbance information and one without. Our results provide further evidence that feedforward control can improve wind turbine performance in transition and above-rated conditions without increasing actuation requirements, which we hope will encourage industry experimentation and uptake of feedforward control methods. We also provide a high-level analysis and interpretation of the computational performance of the chosen approach. This work builds upon the results of an earlier study, which considered unconstrained optimal blade pitch control. &nbsp;</p

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma

BACKGROUND & AIMS: We investigated the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with hepatocellular carcinoma (HCC) who received ICI-based therapies in a previous systemic line. METHODS: In this international, retrospective multicenter study, patients with HCC who received at least two lines of ICI-based therapies (ICI-1, ICI-2) at 14 institutions were eligible. The main outcomes included best overall response and treatment-related adverse events. RESULTS: Of 994 ICI-treated patients screened, a total of 58 patients (male, n = 41; 71%) with a mean age of 65.0±9.0 years were included. Median systemic treatment lines of ICI-1 and ICI-2 were 1 (range, 1-4) and 3 (range, 2-9), respectively. ICI-based therapies used at ICI-1 and ICI-2 included ICI alone (ICI-1, n = 26, 45%; ICI-2, n = 4, 7%), dual ICI regimens (n = 1, 2%; n = 12, 21%), or ICI combined with targeted therapies/anti-VEGF (n = 31, 53%; n = 42, 72%). Most patients discontinued ICI-1 due to progression (n = 52, 90%). Objective response rate was 22% at ICI-1 and 26% at ICI-2. Responses at ICI-2 were also seen in patients who had progressive disease as best overall response at ICI-1 (n = 11/21; 52%). Median time-to-progression at ICI-1 and ICI-2 was 5.4 (95% CI 3.0-7.7) months and 5.2 (95% CI 3.3-7.0) months, respectively. Treatment-related adverse events of grade 3-4 at ICI-1 and ICI-2 were observed in 9 (16%) and 10 (17%) patients, respectively. CONCLUSIONS: ICI rechallenge was safe and resulted in a treatment benefit in a meaningful proportion of patients with HCC. These data provide a rationale for investigating ICI-based regimens in patients who progressed on first-line immunotherapy in prospective trials. IMPACT AND IMPLICATIONS: Therapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy

Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma

BACKGROUND & AIMS: We investigated the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with hepatocellular carcinoma (HCC) who received ICI-based therapies in a previous systemic line. METHODS: In this international, retrospective multicenter study, patients with HCC who received at least two lines of ICI-based therapies (ICI-1, ICI-2) at 14 institutions were eligible. The main outcomes included best overall response and treatment-related adverse events. RESULTS: Of 994 ICI-treated patients screened, a total of 58 patients (male, n = 41; 71%) with a mean age of 65.0±9.0 years were included. Median systemic treatment lines of ICI-1 and ICI-2 were 1 (range, 1-4) and 3 (range, 2-9), respectively. ICI-based therapies used at ICI-1 and ICI-2 included ICI alone (ICI-1, n = 26, 45%; ICI-2, n = 4, 7%), dual ICI regimens (n = 1, 2%; n = 12, 21%), or ICI combined with targeted therapies/anti-VEGF (n = 31, 53%; n = 42, 72%). Most patients discontinued ICI-1 due to progression (n = 52, 90%). Objective response rate was 22% at ICI-1 and 26% at ICI-2. Responses at ICI-2 were also seen in patients who had progressive disease as best overall response at ICI-1 (n = 11/21; 52%). Median time-to-progression at ICI-1 and ICI-2 was 5.4 (95% CI 3.0-7.7) months and 5.2 (95% CI 3.3-7.0) months, respectively. Treatment-related adverse events of grade 3-4 at ICI-1 and ICI-2 were observed in 9 (16%) and 10 (17%) patients, respectively. CONCLUSIONS: ICI rechallenge was safe and resulted in a treatment benefit in a meaningful proportion of patients with HCC. These data provide a rationale for investigating ICI-based regimens in patients who progressed on first-line immunotherapy in prospective trials. IMPACT AND IMPLICATIONS: Therapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy