Toru Asai

Pressure Overload-Induced Cardiomyopathy in Heterozygous Carrier Mice of Carnitine Transporter Gene Mutation

Primary systemic carnitine deficiency is an autosomal recessive disorder caused by a decreased renal reabsorption of carnitine because of mutations of the carnitine transporter OCTN2 gene, and hypertrophic cardiomyopathy is a common clinical feature of homozygotes. Although heterozygotes for OCTN2 mutations are generally healthy with normal cardiac performance, heterozygotes may be at risk for cardiomyopathy in the presence of additional risk factors, such as hypertension. To test this hypothesis, we investigated the effects of surgically induced pressure overload on the hearts of heterozygous mutants of a murine model of OCTN2 mutation, juvenile visceral steatosis mouse (jvs/+). Eleven-week-old jvs/+ mice and age-matched wild-type mice were used. At baseline, there were no differences in physical characteristics between wild-type and jvs/+ mice. However, plasma and myocardial total carnitine levels in jvs/+ mice were lower than in wild-type mice. Both wild-type and jvs/+ mice were subjected to ascending aortic constriction with or without 1% l-carnitine supplementation for 4 weeks. At 4 weeks after ascending aortic constriction, jvs/+ mice showed an exaggeration of cardiac hypertrophy and pulmonary congestion, further increased gene expression of atrial natriuretic peptide in the left ventricles, further deterioration of left ventricular fractional shortening, reduced myocardial phosphocreatine:adenosine triphosphate ratio, and increased mortality compared with wild-type mice; l-carnitine supplementation prevented these changes in jvs/+ mice subjected to ascending aortic constriction. In conclusion, cardiomyopathy and heart failure with energy depletion may be induced by pressure overload in heterozygotes for OCTN2 mutations and could be prevented by l-carnitine supplementation.

A unified approach to LMI-based reduced order self-scheduling control synthesis

Abstract We consider a reduced order controller synthesis for a general class of control specifications for linear parameter-varying (LPV) systems, when some of state variables are exactly available. The class is defined in an abstract manner so that it uniformly deals with many significant specifications. A necessary and sufficient condition for the existence of a reduced order controller is given in terms of linear matrix inequalities (LMIs). We also show that the order of the controller can be reduced by the number of the state variables exactly available in the measurements. Moreover, in the case of linear time invariant (LTI) systems, a parameterization of all desirable reduced order LTI controllers is given by means of solutions of LMIs. The results in this paper generalize the class of control specifications in which a reduced order controller exists, making it possible to synthesize a reduced order controller based on LMIs for multi-objective control specifications. Furthermore, these results uniformly describe and generalize the existing results on synthesis of a constant state and a full order output feedback controller for LTI and LPV systems such that the specification is given by the existence of a constant positive definite matrix.

Simultaneous Modeling and Synthesis for Robust Control by LFT Scaling

Abstract We consider a problem of simultaneous controller synthesis and modeling for robust control against parametric perturbations. The tool we use to solve the problem is the LFT scaling, which gives a general framework for the robust stability test. We show the relationship between our generalized small gain condition based on the LFT scaling and the existing IQC condition. A method for simultaneously achieving the modeling of the poly topic uncertainties and the synthesis of the robustly stabilizing control is proposed in terms of some matrix inequalities. An application to AC linear servo motor shows the effectiveness of the proposed method with experimental validation.

Analysis of the worst-case bumpy responses based on LMIs

Proposes a mathematical formulation of bumpy responses and a method to analyze their magnitudes. Bumpy responses often appear when switching occurs in control systems. Since those responses are harmful, several methods have been proposed to attain bumpless transfer. However, most of the existing methods do not provide any guarantee for the resultant performance nor deal with uncertainty explicitly. This paper formulates the magnitude of bumpy responses as the worst-case /spl Lscr//sub 2/ gain from past disturbance to future outputs and proposes a method to analyze the worst-case gain based on linear matrix inequalities. Numerical examples clarify the effectiveness of the proposed method.

Constraints in Servo System Design for Non-Minimum Phase System

This paper is concerned with the analysis of constraints of poles and zeros for servo system design of plants which are non-minimum phase. It is a known fact that when a closed-loop system has a non-minimum phase zero, the output displays an inverse response before tracking the desired trajectory. This imposes limitations to the transient performance. In this paper, we consider a servo system for a SISO plant having only one non-minimum phase zero. We first characterize the achievable closed-loop system. Based on the characterization and the tracking condition, we show for some combinations of degree and relative degree of the closed-loop system that the admissible location of poles is restricted. For these cases, we provide a quantitative measure for the limitation of the constrained poles. Besides poles, we also show that zeros are constrained and that the number of NMP zeros must be increased in some cases. The latter suggests that it is necessary to worsen the transient performance by introducing additional non-minimum phase zeros into the system

Impact of α-tocopherol on cardiac hypertrophy due to energy metabolism disorder: the involvement of 1,2-diacylglycerol

OBJECTIVE The juvenile visceral steatosis (JVS) mouse, a murine model of systemic carnitine deficiency, shows a disorder of fatty acid oxidation and develops cardiac hypertrophy associated with lipid accumulation. Recently, alpha-tocopherol was shown to decrease 1,2-diacylglycerol (DAG) levels. We investigated the involvement of DAG in cardiac hypertrophy due to energy metabolism disorder by evaluating the effects of alpha-tocopherol administration on the hearts of JVS mice. METHODS Both JVS and control mice were fed a high alpha-tocopherol diet or a standard diet from 4 to 8 weeks of age. Myocardial DAG levels and fatty acid composition were assessed at 8 weeks of age. RESULTS The ventricular to body weight ratio in the JVS mice was significantly higher than that in the control mice [11.2+/-0.1 (mean+/-S.E.M.) versus 3.8+/-0.1 mg/g, P<0.01], and was reduced by alpha-tocopherol treatment (9.7+/-0.2 mg/g, P<0.01 versus JVS mice). However, echocardiographic analysis showed the exaggeration of left ventricular dilatation in the alpha-tocopherol treated JVS mice (P<0.01 versus JVS mice). The myocardial thiobarbituric-acid-reactive substance level was not affected by alpha-tocopherol treatment. The myocardial DAG level was 2.5-fold higher in the JVS mice compared with that in the control mice (2004+/-136 versus 806+/-36 ng/mg dry weight, P<0.01) with a significant increase in 18:1 and 18:2 fatty acids. alpha-Tocopherol treatment reduced myocardial DAG levels in the JVS mice (1443+/-49 ng/mg dry weight, P<0.01 versus JVS mice) without any alteration of the fatty acid composition. CONCLUSIONS alpha-Tocopherol treatment may partially reduce cardiac hypertrophy but it may also depress cardiac function in the JVS mice by decreasing the myocardial DAG level. An increase in DAG might be involved in the development of cardiac hypertrophy and in the maintenance of cardiac function in energy metabolism disorder of the heart.

Inverse correlation between soluble CD40 ligand and soluble CD40 is absent in patients with unstable angina

The CD40/CD40 ligand (CD40L) system mediates inflammatory processes important in atherogenesis and plaque instability. The expression of CD40L on activated T cells was suppressed by soluble CD40 (sCD40) in vitro. However, the relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is still unknown. Thirty-seven consecutive patients with recent chest pain or discomfort were recruited. Patients with both Braunwalds class IB–IIIB and with coronary stenosis (or stenoses) of >75% were assigned to the UA group (n = 19, aged 67.2 ± 8.2 years), and the rest to the control group (n = 18, aged 63.4 ± 8.7 years). The serum levels of sCD40L and sCD40, and the plasma levels of matrix metalloproteinase (MMP)-9, were measured by enzyme-linked immunosorbent assays. A significantly inverse correlation between sCD40L and sCD40 was shown in the controls (r = −0.72, P = 0.0007), but was absent in the UA group (r = −0.16, P not significant), although there was no statistical significance between these groups in terms of serum levels of sCD40L or sCD40. The difference of the regression slopes of these regression lines was statistically significant (P < 0.01). Additionally, there was a significant correlation between sCD40 and plasma levels of MMP-9 in the patients with and without UA (r = 0.58, P = 0.0096), but no significant correlation between sCD40L and MMP-9 levels (r = 0.00, P not significant). The balance between CD40 and CD40L may be lost in patients with UA. Soluble CD40 expression may also be related to MMP-9 expression in atherosclerotic tissues.

Multiagent Consensus With Noisy Communication: Stopping Rules Based on Network Graphs

A stopping rule is presented for a multiagent consensus algorithm with noisy communication. A stochastic approximation method is employed and the relation between the closeness of the agreement and the number of iterations is established. A bound of the variation of the agents at the specific number of iterations is then derived with a probabilistic guarantee, which gives a rigorous stopping rule of the consensus algorithm with noisy communication. This stopping rule is given in terms of characteristic values of communication network graphs, which suggests a difference in transient behaviors by undirected and directed graphs. These theoretical results are demonstrated through numerical examples.

Performance limitation of tracking control problem for a class of references

This technical note deals with analysis of fundamental limitations for SISO systems in tracking control problems. In the existing results, the fundamental limitations are analyzed based on detailed assumptions of reference signals such as the step, the trigonometrical signals and so on. On the other hand, we define a class of reference signals in an abstract but general manner. For the general class of reference inputs, we give the analysis of the tracking performance limitations based on the achievable set of the outputs. The analysis results can separate the contributions of the plant and the reference signal clearly.

Optimal velocity control method in path following control problem

Abstract Path following control problem is treated in recent years. In many past results of path following control, it is assumed the plant has single-input and the velocity of the plant is considered as constant value. However, when we have to reduce traveling time, we must control velocity of the plant in tracking problem. In this paper, velocity control and path following task are achieved at the same time by optimal control. To achieve these tasks, we assume multi-input plants are given. Since sum of reaching time and input costs is used as a cost, we can obtain good acceleration and deceleration input. By a constraint for the cost function, the error from the plant to a given reference path goes to zero when time goes to infinity. The effectiveness of the proposed method is examined by numerical examples of an automobile model.