Analysis of aircraft pitch axis stability augmentation system using sum of squares optimization

In this paper, we use SOS (sum of squares) programming approaches to analyze the stability and robustness properties of the controlled pitch axis (6 state system) of a nonlinear model of an aircraft. The controller is a LTI dynamic inversion based control law designed for the short period dynamics of the aircraft. The closed loop system is tested for its robustness to uncertainty in the location of center of gravity along the body x-axis. Results in the form of stability regions about a trim point are computed and verified using simulations

Gender Related Differences in the Clinical Presentation of Hypertrophic Cardiomyopathy-An Analysis from the SILICOFCM Database

Background and Objectives: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease that affects approximately 1 in 500 people. Due to an incomplete disease penetrance associated with numerous factors, HCM is not manifested in all carriers of genetic mutation. Although about two-thirds of patients are male, it seems that female gender is associated with more severe disease phenotype and worse prognosis. The objective of this study was to evaluate the gender related differences in HCM presentation. Materials and Methods: This study was conducted as a part of the international multidisciplinary SILICOFCM project. Clinical information, laboratory analyses, electrocardiography, echocardiography, and genetic testing data were collected for 362 HCM patients from four clinical centers (Florence, Newcastle, Novi Sad, and Regensburg). There were 33% female patients, and 67% male patients. Results: Female patients were older than males (64.5 vs. 53.5 years, p < 0.0005). The male predominance was present across all age groups until the age of 70, when gender distribution became comparable. Females had higher number of symptomatic individuals then males (69% vs. 52%, p = 0.003), most frequently complaining of dyspnea (50% vs. 30%), followed by chest pain (30% vs. 17%), fatigue (26% vs. 13%), palpitations (22% vs. 13%), and syncope (13% vs. 8%). The most common rhythm disorder was atrial fibrillation which was present in a similar number of females and males (19% vs. 13%, p = 0.218). Levels of N-terminal pro-brain natriuretic peptide were comparable between the genders (571 vs. 794 ng/L, p = 0.244). Echocardiography showed similar thickness of interventricular septum (18 vs. 16 mm, p = 0.121) and posterolateral wall (13 vs. 12 mm, p = 0.656), however, females had a lower number of systolic anterior motion (8% vs. 16%, p = 0.020) and other mitral valve abnormalities. Conclusions: Female patients are underrepresented but seem to have a more pronounced clinical presentation of HCM. Therefore, establishing gender specific diagnostic criteria for HCM should be considered

Safety Verification of Controlled Advanced Life Support System Using Barrier Certificates.

In this paper we demonstrate how to construct barrier certificates for safety verification of nonlinear hybrid systems using sum of squares methodologies, with particular emphasis on the computational challenges of the technique when applied to an Advanced Life Support System. The controlled system aims to ensure that the carbon dioxide and oxygen concentrations in a Variable Configuration CO2 Removal (VCCR) subsystem never reach unacceptable values. The model we use is in the form of a hybrid automaton consisting of six modes each with nonlinear continuous dynamics of state dimension 10. The sheer size of the system makes the task of safety verification difficult to tackle with any other methodology. This is the first application of the sum of squares techniques to the safety verification of an intrinsically hybrid system with such high dimensional continuous dynamics. © Springer-Verlag Berlin Heidelberg 2005

Controlled hybrid system safety verification: Advanced life support system testbed

In this paper we demonstrate the use of Barrier Certificates as a method to verify safe performance of a hybrid Variable Configuration CO 2 Removal (VCCR) system. We designed a simple nonlinear feedback controller that tracks a desired CO 2 profile, while ensuring that the CO 2 and O 2 concentrations stay within acceptable limits. Though the controller and its switching rules are simple, we do not have a closed form expression for the equilibrium sets of the closed loop hybrid system, and hence Lyapunov stability analysis and computation of region of attraction are impossible. We used Sum-Of-Squares programming approach to construct and verify that our control law provides safe functionality of VCCR system. ©2005 AACC

A Nonlinear Hybrid Life Support System: Dynamic Modeling, Control Design, and Safety Verification.

We present control design for a variable configuration CO2 removal (VCCR) system, which exhibits a hybrid dynamical character due to the various modes in which one needs to operate the system. The VCCR is part of an overall NASA Air Recovery System of an intended human life support system for space exploration. The objective of the control system is to maintain CO2 and O2 concentrations in the crew cabin within safe bounds. We present a novel adaptation of the model predictive control technique to a nonlinear hybrid dynamic system. We exploit the problem structure and map the hybrid optimization problem into a continuous nonlinear program (NLP) with the aid of an appropriate representation of time and set definitions. We present a systematic approach for designing the objective function for the nonlinear model predictive control (NMPC) regulation problem that achieves a long-term, cyclic steady state. We also present a simple switching feedback controller and compare the performance of the two controllers during off-nominal and failure conditions to highlight the benefits of a systematically designed NMP controller. We then perform safety verification of both control designs-the model predictive control with techniques from statistical learning theory and the switching feedback controller with Barrier certificates computed using sum of squares programming. The two approaches yield consistent results. © 2007 IEEE

Acute death of astrocytes in blast-exposed rat organotypic hippocampal slice cultures.

Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast exposure did not evoke significant changes in glutamate transporter 1 (GLT-1) expression, loss of GLT-1-expressing astrocytes suggests dysregulation of glutamate uptake following injury. Our data illustrate the profound effect of blast overpressure on astrocytes in OHCs at 2 h following injury and suggest increased calpain activity and membrane disruption as potential underlying mechanisms

Limited early apoptotic death of astrocytes following blast exposure.

<p>At 2 h following injury, Annexin V conjugated to Alexa 488 (green; A, E, I) was used to identify apoptotic cells in sham control (A-D), low-blast (E-H), and high-blast (I-L) groups. Samples were additionally labeled with the cell death marker PI (red; B, F, J), an antibody against GFAP (gray; C, G, K), and DAPI (blue). Overlay of Annexin V, PI, GFAP, and DAPI staining (D, H, L). Annexin V positive cells (arrow) were infrequent in all three experimental groups. Almost none of the observed Annexin V positive cells were co-labeled with GFAP. Scale bars 20 μm.</p

Blast-induced loss of GLT-1-expressing astrocytes.

<p>At 2 h following injury, sham control (A), low-blast (B), and high-blast (C) OHCs were stained using antibodies against GLT-1 (green), GFAP (gray), PI (red), and DAPI (blue). Dead astrocytes, identified by co-labeling of GFAP and PI (arrows) were also positive for GLT-1. (D) Representative immunoblot analyses of GLT-1 protein expression in sham control (Sham) and OHCs exposed to blast overpressure (L-Blast and H-Blast). (E) Densitometry analysis of GLT-1/GAPDH ratio for 3 independent experiments revealed no significant (ns) differences between sham control, low-blast, and high blast groups. Scale bars 20 μm.</p

Acute morphological changes and demise of astrocytes following blast exposure.

<p>Representative confocal images acquired in the CA1 hippocampal region from sham controls (A, D), low-blast (B, E), and high-blast (C, F) OHCs that were fixed at 2 h following injury and stained with an anti-GFAP antibody (green), PI (red), and DAPI (blue). Shearing of the astrocytes (thin arrows) was detected in OHCs exposed to blast overpressure (B, C) while it was absent in the sham controls (A). Clasmatodendrosis (arrowheads) was also observed in the low- (E) and high-blast (F) groups, but it was very infrequent in the sham control group (D). At the same time point, only a few dead astrocytes were present in sham control OHCs (D) while significant number of dead astrocytes (thick arrows) was revealed in the low- (E) and high-blast (F) groups. (G) Schematic diagram of OHC, indicating approximate locations in the CA1 region (boxes) where images for quantification of dead astrocytes were taken. (H) Number of dead astrocytes per counting area in the CA1 hippocampal region at 2 h following injury was significantly higher in both the low- (*; P< 0.05; n = 5) and high-blast groups (*; P < 0.05; n = 5) compared to the sham control group (n = 5). Scale bars (A-C) 50 μm (D-F) 20 μm.</p