Singular perturbation techniques for real time aircraft trajectory optimization and control

The usefulness of singular perturbation methods for developing real time computer algorithms to control and optimize aircraft flight trajectories is examined. A minimum time intercept problem using F-8 aerodynamic and propulsion data is used as a baseline. This provides a framework within which issues relating to problem formulation, solution methodology and real time implementation are examined. Theoretical questions relating to separability of dynamics are addressed. With respect to implementation, situations leading to numerical singularities are identified, and procedures for dealing with them are outlined. Also, particular attention is given to identifying quantities that can be precomputed and stored, thus greatly reducing the on-board computational load. Numerical results are given to illustrate the minimum time algorithm, and the resulting flight paths. An estimate is given for execution time and storage requirements

Two time scale output feedback regulation for ill-conditioned systems

Issues pertaining to the well-posedness of a two time scale approach to the output feedback regulator design problem are examined. An approximate quadratic performance index which reflects a two time scale decomposition of the system dynamics is developed. It is shown that, under mild assumptions, minimization of this cost leads to feedback gains providing a second-order approximation of optimal full system performance. A simplified approach to two time scale feedback design is also developed, in which gains are separately calculated to stabilize the slow and fast subsystem models. By exploiting the notion of combined control and observation spillover suppression, conditions are derived assuring that these gains will stabilize the full-order system. A sequential numerical algorithm is described which obtains output feedback gains minimizing a broad class of performance indices, including the standard LQ case. It is shown that the algorithm converges to a local minimum under nonrestrictive assumptions. This procedure is adapted to and demonstrated for the two time scale design formulations

Research on output feedback control of systems with ill-conditioned dynamics

The accuracy of a two time scale approach to the output feedback regulator design problem is examined. An approximate quadratic performance index which reflects a two time scale decomposition of the system dynamics is developed. A sequential numerical algorithm is defined which obtains output feedback gains minimizing a broad class of performance indices, including the standard LQ case. A procedure for optimally zeroing selected gain elements in an output feedback gain matrix is developed and demonstrated. A summary of conference and journal publications from this research is also provided

Piloted simulation of an algorithm for onboard control of time-optimal intercept

A piloted simulation of algorithms for onboard computation of trajectories for time-optimal intercept of a moving target by an F-8 aircraft is described. The algorithms, use singular perturbation techniques, generate commands in the cockpit. By centering the horizontal and vertical needles, the pilot flies an approximation to a time-optimal intercept trajectory. Example simulations are shown and statistical data on the pilot's performance when presented with different display and computation modes are described

In vivo retroviral-mediated transfer of a marker-gene in ornithine transcarbamylase-deficient Spf(ash) mice.

Gene therapy is a new therapeutic approach for inherited metabolic hepatopathies. The authors studied the potential application of such a strategy to the correction of ornithine transcarbamylase (OTC) deficiency by in vivo protocol of retroviral-mediated gene transfer to the liver. A partial hepatectomy was followed (24 to 48 hours later) by asanguinous perfusion of the regenerating liver with beta-galactosidase (beta-gal) recombinant retrovirus. This protocol allowed beta-gal gene transfer in normal C57B6 mice liver with 60 +/- 52 positive cells per square centimeter. This proportion never exceeded 20 cells per square centimeter in OTC-deficient spf(ash) mice. The high mortality rate for spf(ash) mice was explained by an important sensitivity of those mice to the protein catabolism rather than by technical difficulties during intraportal perfusion. This first in vivo retroviral-mediated gene transfer study in animals with a life-threatening metabolic inherited hepatopathy showed that, despite efficiency of gene therapy in normal animal models, several experimental difficulties should be overcome before human application of this protocol is considered

Experimental test and numerical shape optimization of a point pivoted absorber for wave energy conversion

This paper presents a numerical study on an innovative system for converting energy from waves. It consists of a point pivoted body which oscillates in presence of waves. The system uses a linear electrical generator which converts floating movements of the buoyant body into electrical power. The buoyant body floats, describing an arc, by means of two hinges. A suitable Power Take-off Device (PTO) is placed between buoy support arms and the fixed structure and has the function to convert the mechanical power of the linear oscillating motion of the connecting piston into electrical power. A design assumption is made on the PTO control system: PTO reaction force is assumed to be linearly dependent on piston oscillation velocity with a given force-speed gain. This coefficient is strictly connected to electrical generator characteristics and its value has an effect on power conversion efficiency . A scaled model of this system has also been tested in the wave/towing tank facility of Department of industrial Engineering (DII) of University of Naples “Federico II”. A variety of numerical analyses, such as potential flow simulations and Unsteady Reynolds Averaged Navier-Stokes (URANS) simulations, have been performed to predict the system performances. Numerical and experimental analyses have included the performances of the baseline geometry, both in free response and under wave excitation, in order to characterize the response of the system, and results have been used to understand which parameters affect more the power production. Finally a numerical optimization procedure has been carried out to optimize the shape of the converter with the final objective of increasing the generated power, eventually imposing a constraint on the amount of immersed volume. In this way, a modified configuration has been predicted with higher power output and the same value of submerged volume, but with different shape

Anti-Rods/Rings: A Human Model of Drug-Induced Autoantibody Generation

In recent years, autoantibodies targeting subcellular structures described as the rods and rings pattern in HEp-2 ANA have been presented as a unique case of autoantibody generation. These rod and ring structures (RR) are at least partially composed of inosine monophosphate dehydrogenase type 2 (IMPDH2), and their formation can be induced in vitro by several small-molecule inhibitors, including some IMPDH2 inhibitors. Autoantibodies targeting these relatively unknown structures have been almost exclusively observed in hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferon-alpha/ribavirin (IFN/RBV) combination therapy. To date, anti-RR antibodies have not been found in treatment-naive HCV patients or in patients from any other disease groups, with few reported exceptions. Here, we describe recent advances in characterizing the RR structure and the strong association between anti-RR antibody response and HCV patients treated with IFN/RBV, detailing why anti-RR can be considered a human model of drug-induced autoantibody generation

Surgical Approach for Long-term Survival of Patients With Intrahepatic Cholangiocarcinoma: A Multi-institutional Analysis of 434 Patients.

OBJECTIVES To examine the outcomes of a hepatectomy for intrahepatic cholangiocarcinoma (IHC) and to clarify the prognostic impact of a lymphadenectomy and the surgical margin. Large series of patients who were surgically treated for IHC are scarce. Thus, prognostic factors and long-term survival after resection of IHC remain uncertain. DESIGN Prospective study of patients who were surgically treated for IHC. Clinicopathologic, operative, and long-term survival data were analyzed. SETTING Prospectively collected data of all consecutive patients with pathologically confirmed IHC who had undergone liver resection with a curative intent at 1 of 16 tertiary referral centers were entered into a multi-institutional registry. PATIENTS All consecutive patients who underwent a hepatectomy with a curative intent for IHC (1990-2008) were identified from a multi-institutional registry. RESULTS A total of 434 patients were included in the analysis. Most patients underwent a major or extended hepatectomy (70.0%) and a systematic lymphadenectomy (62.2%). The incidence of lymph node metastases (overall, 36.9%) increased with increased tumor size, with 24.4% of patients with a small IHC (diameter 643 cm) having N1 disease. Almost one-third of patients required an additional major procedure to obtain a R0 resection in 84.6% of the cases. In these patients, the median time of survival was 39 months, and the 5-year survival rate was 39.8%. Lymph node metastases (hazard ratio, 2.21; P < .001), multiple tumors (hazard ratio, 1.50; P = .009), and an elevated preoperative cancer antigen 19.9 level (hazard ratio, 1.62; P = .006) independently predicted an adverse prognosis. Conversely, survival was not influenced by the width of a negative resection margin (P = .61). The potential survival benefit of a lymphadenectomy was assessed with the therapeutic value index, which was calculated to be 5.9 points. CONCLUSIONS Survival rates after a hepatectomy with a curative intent for IHC at tertiary referral centers exceed the survival rates reported in most study series in single institutions, which strengthens the value of an aggressive approach to radical resection. Lymph node metastases and multiple tumors are associated with decreased survival rates, but they should not be considered selection criteria that prevent other patients from undergoing a potentially curative resection. Lymphadenectomy should be considered for all patients

Hydrogel Cross-Linking via Thiol-Reactive Pyridazinediones

Thiol-reactive Michael acceptors are commonly used for the formation of chemically cross-linked hydrogels. In this paper, we address the drawbacks of many Michael acceptors by introducing pyridazinediones as new cross-linking agents. Through the use of pyridazinediones and their mono- or dibrominated analogues, we show that the mechanical strength, swelling ratio, and rate of gelation can all be controlled in a pH-sensitive manner. Moreover, we demonstrate that the degradation of pyridazinedione-gels can be induced by the addition of thiols, thus providing a route to responsive or dynamic gels, and that monobromo-pyridazinedione gels are able to support the proliferation of human cells. We anticipate that our results will provide a valuable and complementary addition to the existing toolkit of cross-linking agents, allowing researchers to tune and rationally design the properties of biomedical hydrogels