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In this chapter, we consider the analysis and design of an output feedback controller for a perturbed nonlinear system in which the output is sampled and quantized. Using the attractive ellipsoid method, which is based on Lyapunov analysis techniques, together with the relaxation of a nonlinear optimization problem, sufficient conditions for the design of a robust control law are obtained. Since the original conditions result in nonlinear matrix inequalities, a numerical algorithm to obtain the solution is presented. The obtained control ensures that the trajectories of the closed-loop system will converge to a minimal (in a sense to be made specific) ellipsoidal region. Finally, numerical examples are presented to illustrate the applicability of the proposed design method.

In this chapter, we formulate our main problem and discuss some necessary mathematical concepts related to feedback control design for nonlinear systems under sample-data output measurements. Then we present a theoretical analysis of an extended version of the invariant ellipsoid method. Then two feedbacks are analyzed: a linear feedback proportional to the current state estimate obtained by a Luenberger-type estimator; and a full-order linear dynamic controller governed by a linear ordinary differential equation with available sample data as input.

In this chapter, a new sliding mode control design algorithm for a linear and a class of nonlinear quasi-Lipschitz disturbed systems is presented. It is based on the appropriate selection of a sliding surface via the invariant ellipsoid method. The designed control guarantees minimization of unmatched disturbance effects to system motions in a sliding mode. The theoretical results are verified by numerical simulations. Additionally, a methodology for the design of sliding mode controllers for linear systems subjected to matched and unmatched perturbations is proposed. It is considered that the control signal is applied through a first-order low-pass filter. The technique is based on the existence of an attracting (invariant) ellipsoid such that the convergence to a quasiminimal region of the origin using the suboptimal control signal is guaranteed. The design procedure is given in terms of the solution of a set of matrix inequalities. Benchmark examples illustrating the design are given.

In this chapter, we consider the class of uncertain time-delay affine-controlled systems in which a delay is admitted in state variables, and we show that the attractive ellipsoid method allows us to create a feedback that provides the convergence of any state trajectory of the controlled system from a given class to an ellipsoid whose “size” depends on the parameters of the applied feedback. Finally, we present a method for numerical calculation of these parameters that provides the “smallest” zone convergence for controlled trajectories.

This chapter deals with a new approach to robust control design for a class of nonlinearly affine control systems. The dynamic models under consideration are described by implicit differential equations in the presence of additive bounded uncertainties. The proposed robust feedback design procedure is based on an extended version of the classical invariant ellipsoid technique. In this book, this extension is called the attractive ellipsoid method. The stability/robustness analysis of the resulting closed-loop system involves a modified descriptor approach associated with the usual Lyapunov-type methodology. The theoretical schemes elaborated in our contribution are finally illustrated by a simple computational example.

In this chapter, a particular family of nonlinear affine control systems with a sufficiently general type of uncertainties is considered. Nonlinear uncertain systems, considered here, are governed by vector ordinary differential equations with so-called quasi-Lipschitz right-hand sides admitting a wide class of external and internal uncertainties (including discontinuous nonlinearities such as relay and hysteresis elements, time-delay blocks, and so on). Here, the simplest class of linear state-feedback controllers is analyzed. Sufficient conditions guaranteeing the boundedness of all possible trajectories of controlled systems are presented. Since bounded dynamics can always be imposed on an ellipsoid, it is suggested that the “robust-optimal” gain matrix of the designated linear feedback be selected in such a way that the “size” of this attractive ellipsoid will be minimal. Several numerical and experimental illustrative examples are considered.

This chapter deals with the development of a state estimator and adaptive controller based on the attractive ellipsoid method (AEM) for a class of uncertain nonlinear systems having “quasi-Lipschitz” nonlinearities as well as external perturbations. The set of stabilizing feedback matrices is given by a specific matrix inequality including the characteristic matrix of the attractive ellipsoid that contains all possible bounded trajectories around the origin. Here we present two modifications of the AEM that allow us to use online information obtained during the process and to adjust matrix parameters participating in constraints that characterize the class of adaptive stabilizing feedbacks. The proposed method guarantees that under a specific persistent excitation condition, the controlled system trajectories converge to an ellipsoid of “minimal size” having a minimal trace of the corresponding inverse ellipsoidal matrix.

This chapter deals with a bounded control design for a class of nonlinear systems whose mathematical model may not be explicitly given. This class of uncertain nonlinear systems is governed by a system of ordinary differential equations with quasi-Lipschitz right-hand sides and contains external perturbations as well. The attractive ellipsoid method (AEM) allows us to describe the class of nonlinear feedbacks (containing a nonlinear projection operator, a linear state estimator, and a feedback matrix gain) guaranteeing the boundedness of all possible trajectories around the origin. To satisfy this property, some modifications of the AEM are introduced: basically, some sort of sample-time corrections of the feedback parameters are required. The optimization of feedback within this class of controllers is associated with the selection of the feedback parameters such that the trajectory converges within an ellipsoid of “minimal size.” The effectiveness of the suggested approach is illustrated by its application to a flexible arm system.

In this chapter, we consider three types of possible linear feedbacks using only the current output information: static feedback proportional to the output measurable signal, observer-based feedback proportional to the state estimation vector, and full-order linear dynamic controllers. For each type of possible linear feedback, we suggest that one characterize the set of all stabilizing gain-feedback matrices by a system of the corresponding linear matrix inequalities, providing the boundedness of all possible trajectories of every controlled plant from the considered class of uncertain systems. We also suggest selecting the optimal feedback gain matrix from the described class of stabilizing feedbacks as the one that minimizes the “size” of the attractive ellipsoid containing all possible bounded dynamic trajectories. The corresponding numerical procedures for designing the best feedback gain matrices are introduced and discussed for each type of considered feedback. Several illustrative examples clearly show the effectiveness of the suggested technique.

This chapter deals with the problem of robust feedback design for a class of switched systems in the presence of bounded model uncertainties as well as external perturbations. Only the output of the system is supposed to be available for a designer. We consider nonlinear dynamic models under arbitrary switching mechanisms assuming that sample-switching times are known. Online state estimates are obtained by the use of a Luenberger-like observer using only current inputs and general information on the class of model uncertainties. The stabilization issue is solved in the sense of practical stability, and it is carried out by a linear (with respect to a current state estimate) feedback switching controller subject to an average dwell time scheme. We apply the newly elaborated (extended) version of the conventional attractive ellipsoid method for this purpose. Numerically implementable sufficient conditions for the practical stability of systems are derived using bilinear matrix inequalities. The effectiveness of the proposed method is illustrated by an example of a continuous stirred tank reactor in which only the temperature (not the concentration) is available during the process.

Sound lateralization can be induced by interaural intensity disparities (IIDs) or by interaural temporal disparities (ITDs). The purpose of this study was to indicate whether IIDs and ITDs are processed by the same central units that detect interaural disparity in timing of afferent activity. If sound lateralization to intensity and time cues was determined by the same afferent latency disparity detectors in the brainstem, lateralization would be the same, regardless of whether latency disparity was induced by IIDs or ITDs. Moreover, the disparity detectors, and thus their dipole equivalents, would be the same for equal lateralizations, whether induced by IIDs or ITDs. Auditory brainstem evoked potentials (ABEPs) were recorded in response to monaural and binaural clicks, with a variety of IIDs and ITDs. Peak II (proximal auditory nerve activity), peak III (input to the superior olivary complex), and binaural interaction components (BICs) BeI and BeII (binaurally activated upper pons) were identified and their latencies measured. The psychophysical lateralization of the clicks (in cm from vertex) was also measured in response to the same binaural stimuli. The correlations between interaural afferent latency disparities (difference in corresponding peak latencies originating in each ear) and psychophysical click lateralization were calculated. Similarly, the correlations with click lateralization of the BICs equivalent dipole latency as well as orientation change (relative to symmetrical clicks) were determined. A strong correlation with lateralization was found for peaks II and III latency disparities, with steeper slopes for IIDs than for ITDs. Moreover, binaural activity across the same lateralizations differed between IIDs and ITDs. These results, therefore, indicate that interaural time and intensity cues are processed by separate systems in the brainstem, both at the afferent convergence level and after interaural disparities are determined.

International audience; The problem of output control design for linear system with unknown and time-varying input delay, bounded exogenous disturbances and bounded deterministic measurement noises is considered. The prediction technique is combined with Luenberger-like observer design in order to provide the stabilizing output feedback. The scheme of parameters tuning for reduction of measurement noises effect and exogenous disturbances effects is developed basing on Attractive Ellipsoids Method. Under some restrictions it is formalized as semidefinite programming problem. The theoretical results are supported by numerical simulations.

International audience; The paper addresses the problem of exact average-consensus reaching in a prescribed time. The communication topology is assumed to be defined by a weighted undirected graph and the agents are represented by integrators. A nonlinear control protocol, which ensures a finite-time convergence, is proposed. With the designed protocol, any prescribed convergence time can be guaranteed regardless of the initial conditions.

International audience; The Implicit Lyapunov Function (ILF) method for finite-time stability analysis is introduced. The control algorithm for finite-time stabilization of a chain of integrators is developed. The scheme of control parameters selection is presented by a Linear Matrix Inequality (LMI). The robustness of the finite-time control algorithm with respect to system uncertainties and disturbances is studied. The new high order sliding mode (HOSM) control is derived as a particular case of the developed finite-time control algorithm. The settling time estimate is obtained using ILF method. The algorithm of practical implementation of the ILF control scheme is discussed. The theoretical results are supported by numerical simulations.

The notion of geometric homogeneity is extended for differential inclusions. This kind of homogeneity provides the most advanced coordinate-free framework for analysis and synthesis of nonlinear discontinuous systems. Theorem of L. Rosier [1] on a homogeneous Lyapunov function existence for homogeneous differential inclusions is presented. An extension of the result of Bhat and Bernstein [2] about the global asymptotic stability of a system admitting a strictly positively invariant compact set is also proved.

The output stabilization problem for a linear system with an unknown time-varying bounded input delay is considered. The interval observer technique is applied in order to obtain guaranteed interval estimates of the system state. The procedure of the interval observer design, which is based on resolving of the Sylvester's equation, is discussed. Interval predictor is introduced and applied for a linear output stabilizing feedback design. The design procedure is based on Linear Matrix Inequalities (LMI). The theoretical results are supported by numerical simulations.

International audience; This paper is devoted to constructive approximations and an alternative theoretic characterization of some classes of sliding mode control processes. We construct the consistent approximations of the differential inclusions associated with the 1rst order variable structures dynamics and also propose a variational description of the sliding mode control in the framework of an auxiliary Hamiltonian based formalism. A trajectory of the closed-loop systems can be then constructively specifed as a result of a particular system optimization procedure applied to the original model. The presented approximations and variational description of the sliding mode-type control design can provide a new analytic basis for constructive numerical schemes and implementable control algorithms. The mathematical tool elaborated in our contribution constitutes a formal extension of the classic Fillipovs results.

The structure of E. coli core RNA polymerase (RNAP) has been determined to approximately 23 A resolution by three-dimensional reconstruction from electron micrographs of flattened helical crystals. The structure reveals extensive conformational changes when compared with the previously determined E. coli RNAP holoenzyme structure, but resembles the yeast RNAPII structure. While each of these structures contains a thumb-like projection surrounding a channel 25 A in diameter, the E. coli RNAP holoenzyme thumb defines a deep but open groove on the molecule, whereas the thumb of E. coli core and yeast RNAPII form part of a ring that surrounds the channel. This may define promoter-binding and elongation conformations of RNAP, as E. coli holoenzyme recognizes promoter sites on double-stranded DNA, while both E. coli core and yeast RNAPII are elongating forms of the polymerase and are incapable of promoter recognition.

Transcription elongation factors stimulate the activity of DNA-dependent RNA polymerases by increasing the overall elongation rate and the completion of RNA chains. One group of such factors, which includes Escherichia coli GreA, GreB and eukaryotic SII (TFIIS), acts by inducing hydrolytic cleavage of the transcript within the RNA polymerase, followed by release of the 3'-terminal fragment. Here we report the crystal structure of GreA at 2.2 A resolution. The structure contains an amino-terminal domain consisting of an antiparallel alpha-helical coiled-coil dimer which extends into solution, reminiscent of the coiled coil in seryl-tRNA synthetases. A site near the tip of the coiled-coil 'finger' plays a direct role in the transcript cleavage reaction by contacting the 3'-end of the transcript. The structure exhibits an unusual asymmetric charge distribution which indicates the manner in which GreA interacts with the RNA polymerase elongation complex.

Three-channel Lissajous' trajectories (3-CLTs) of the binaural interaction component (BI) of auditory middle latency evoked potentials (AMLEPs) were derived from 14 normally hearing adults by subtracting the response to binaural clicks from the algebraic sum of monaural responses. AMLEPs were recorded in response to 65 dB nHL, rarefraction clicks, presented at a rate of 3.3/s. A normative set of BI 3-CLT measures was calculated and compared with the corresponding measures of simultaneously recorded, single-channel vertex-left mastoid and vertex-neck derivations of BI and of AMLEP to binaural stimulation (B). 3-CLT measures included: apex latency, amplitude and orientation, as well as planar segment duration, orientation, size and shape. The results showed seven main apices and associated planar segments (‘Be’, ‘Bf’, ‘Bg’, ‘Bh’, ‘Bi1’, ‘Bi2’ and ‘Bj’) in the 3-CLT of BI. Apex latencies of the BI 3-CLT were comparable to peak latencies of the vertex-left mastoid and vertex-neck AMLEP and BI records, both in their absolute values and in intersubject variability. Durations of BI planar segments were approximately 5.0 ms. Apex amplitudes of BI 3-CLT were larger than the respective peak amplitudes of the vertex-mastoid and vertex-neck BI records, while their intersubject variabilities were comparable. The lateralization of BI components may indicate asymmetric processing of binaural auditory input, or may be connected with anatomical asymmetry such as skull thickness. Preliminary analyses did not reveal a clear correlation between the lateralization of the BI component ‘Bi2’ and the handedness of the subject. We suggest that BI components of AMLEP may be associated with the primary auditory cortex and subcortical ascending structures.

The paper addresses the problem of row straightening of agents via local interactions. A nonlinear control protocol that ensures finite-time equidistant allocation on a segment is proposed. With the designed protocol, any settling time can be guaranteed regardless of the initial conditions. A robust modification of the control algorithm based on sliding mode control technique is presented. The case of multidimensional agents is also considered. The theoretical results are illustrated via numerical simulations.

In this paper we study a class of continues nonlinear control systems associated with the specific sampled outputs. The dynamical model under consideration is described by ordinary differential equations in the presence of additive bounded uncertainties. We propose a linear-type control design procedure that guarantee robustness property of the closed-loop realization. The proposed design method incorporates a concept of the dynamic feedback controller and a newly elaborated extended version of the classic invariant ellipsoid method. The applicability of the proposed control design scheme is illustrated by a computational example. A brief discussion on the numerical issues is also included.

Background Prolonged neutrophil survival is evident in various cardiovascular and respiratory morbidities, in hypoxic conditions in-vitro and in patients with obstructive sleep apnea (OSA) characterized by nightly intermittent hypoxia (IH). This may lead to persistent inflammation, tissue injury and dysfunction. We therefore investigated by a translational approach the potential contribution of the intrinsic stress-induced mitochondrial pathway in extending neutrophil survival under IH conditions. Thus, neutrophils of healthy individuals treated with IH in-vitro and neutrophils of OSA patients undergoing nightly IH episodes in-vivo were investigated. Specifically, the balance between pro-apoptotic Bax and anti-apoptotic Mcl-1 protein expression, and the potential involvement of p38MAPK and ERK1/2 signaling pathways in the control of Mcl-1 expression were investigated. Methods Purified neutrophils were exposed to IH and compared to normoxia and to sustained hypoxia (SH) using a BioSpherix-OxyCycler C42 system. Bax and Mcl-1 levels, and p38MAPK and ERK1/2 phosphorylation were determined by western blotting. Also, Bax/Mcl-1 expression and Bax translocation to the mitochondria were assessed by confocal microscopy in pre-apoptotic neutrophils, before the appearance of apoptotic morphology. Co-localization of Bax and mitochondria was quantified by LSM 510 CarlZeiss MicroImaging using Manders Overlap Coefficient. A paired two-tailed t test, with Bonferroni correction for multiple comparisons, was used for statistical analysis. Results Compared to normoxia, IH and SH up-regulated the anti-apoptotic Mcl-1 by about 2-fold, down-regulated the pro-apoptotic Bax by 41% and 27%, respectively, and inhibited Bax co-localization with mitochondria before visible morphological signs of apoptosis were noted. IH induced ERK1/2 and p38MAPKs phosphorylation, whereas SH induced only p38MAPK phosphorylation. Accordingly, both ERK and p38MAPK inhibitors attenuated the IH-induced Mcl-1 increase. In SH, only p38MAPK inhibition decreased Mcl-1 expression. Similar to neutrophils of healthy subjects exposed to IH (0.97± 0.2), in OSA neutrophils, Bax/Mcl-1 ratio was significantly lower compared to normoxic controls (1.0±0.5 vs.1.99±0.3, p=0.015), and Bax did not co-localize with mitochondria. Conclusions These findings suggest that decreased Bax/Mcl-1 balance promotes neutrophil survival in IH in-vitro as well as in OSA patients. Moreover, Bax/Mcl-1 protein function in IH and SH might be regulated by different signal transduction pathways, highlighting a novel regulatory function through ERK1/2 signaling in IH.

The paper presents some new sliding mode control algorithms for uncertain linear plants. The first class of controllers provide global asymptotic stability of the closed-loop system and allow to adjust a guaranteed convergence time of system trajectories into selected neighborhood of the origin independently on domain of initial system states. The design procedure essentially uses block reduction principles and finite-time attractivity properties for polynomial switching surface. The second class of controllers is meant to guarantee global finite-time stability of the closed-loop system with globally bounded settling-time function. The control design algorithms are presented for both single-input and multi-input systems. Theoretical results are supported by numerical simulations.

The paper addresses the problem of discovering the necessary and sufficient stability conditions of vector relay systems and studying the settling time function of this system. It shows that this function is piecewise linear in some cases and the linearity domains of this function are some convex cones. This fact helps to prove that the existence of the piecewise linear Lyapunov function for such vector relay system is a criterion of its stability. Some theoretical results are supported by numerical example.

Spatial organization of the binding sites for the priming substrate, the template DNA, and the transcription inhibitor rifampicin (Rif) in Escherichia coli RNA polymerase (EC 2.7.7.6) was probed with chimeric compounds in which Rif is covalently attached to a ribonucleotide. The compounds bind to RNA polymerase in bifunctional manner and serve as substrates for RNA chain extension, yielding chains up to 8 nucleotides in length, with Rif linked to their 5' termini. These products act as potent inhibitors of normal transcription. Using the linker between the two ligands as ruler, we determined the distance between the sites for Rif and the priming nucleotide to be approximately 15 A. A reactive side group placed in the linker next to Rif crosslinks to the template strand of DNA at the -2 or -3 position of the promoter. Thus, bound Rif is juxtaposed to DNA immediately upstream of the start site, suggesting that Rif plugs the channel leading RNA out of the active center.

The 3-channel Lissajous' trajectory (3-CLT) of the binaural interaction components (BI) in auditory brain-stem evoked potentials (ABEPs) was derived from 17 normally hearing adults by subtracting the response to binaural clicks (B) from the algebraic sum of monaural responses (L + R). ABEPs were recorded in response to 65 dB nHL, alternating polarity clicks, presented at a rate of 11/sec. A normative set of BI 3-CLT measures was calculated and compared with the corresponding measures of simultaneously recorded, single-channel vertex-left mastoid and vertex-neck derivations of BI and of ABEP L + R and B. 3-CLT measures included: apex latency, amplitude and orientation, as well as planar segment duration and orientation. The results showed 3 apices and associated planar segments ("BdII," "Be" and "Bf") in the 3-CLT of BI which corresponded in latency to the vertex-mastoid and vertex-neck peaks IIIn, V and VI of ABEP L + R and B. These apices corresponded in latency and orientation to apices of the 3-CLT of ABEP L + R and ABEP B. This correspondence suggests generators of the BI components between the trapezoid body and the inferior colliculus output. Durations of BI planar segments were approximately 1.0 msec. Apex amplitudes of BI 3-CLT were larger than the respective peak amplitudes of the vertex-mastoid and vertex-neck recorded BI, while their intersubject variabilities were comparable.

Three-channel Lissajous trajectories (3-CLTs) of the binaural interaction components of the auditory brainstem-evoked potentials were recorded from 17 adult subjects in response to rarefaction, condensation and alternating polarity clicks. All 3-CLTs included 3 planar segments (named Bd, Be and Bf) whose latencies, amplitudes, orientations, sizes and shapes were not affected by click polarity. A significant increase was found in the duration of planar segment Be to alternating polarity clicks. This effect may be explained by limitations of spatiotemporal resolution of the method, which did not allow distinction of contributions from temporally overlapping generators participating in binaural processing.

Fibronectin (FN) is an extracellular matrix protein promoting cell proliferation, adhesion, and survival and is localized in the intimal layer of normal and atherosclerotic blood vessels. Dendritic cells (DCs) are potent antigen-presenting cells located in healthy and diseased intima, and thus may predispose arteries to atherosclerosis. Besides their pro-atherogenic activities DCs can promote neovascularization, by releasing pro-angiogenic mediators and/or by trans-differentiating into endothelial-like cells. Here, we investigated changes in morphology, function and angiogenic properties of monocyte-derived immature DCs (Mo-iDCs) after a short-term FN treatment and some of the signaling pathways involved in these processes. The cells were analyzed by time-lapse, confocal microscopy and flow cytometry. Within 90 min of re-plating, FN induced a swift morphologic transformation of most round iDCs into spindle-shaped iDCs (sp-iDCs). This was characterized by redistribution of mitochondria into dendritic spindles, decreased CD1c, and increased thrombomodulin (CD141) expression. Functionally, sp-iDCs acquired Ulex-europaeus-agglutinin-1 lectin binding, phagocytosis was decreased and intracellular (nuclear and cytosolic) vascular endothelial growth factor (VEGF) was increased. FN also induced ERK1/2 phosphorylation in round-iDCs, and p38MAPK phosphorylation in sp-iDCs. Inhibiting p38MAPK, but not ERK1/2, restrained the FN-induced transformation into sp-iDCs. Furthermore, FN-treatment of Mo-iDCs induced a paracrine angiogenic effect on endothelial tube formation, which was abolished by inhibiting ERK1/2 or VEGF. Inhibiting p38MAPK had no effect on endothelial tube formation. By contrast, in laminin-treated Mo-iDCs, which had round-shaped morphology, CD1c and CD141 expression was similar to control untreated cells, but intracellular VEGF levels were higher, and endothelial tube formation was an individual trait. We conclude that a short-term FN treatment induced angiogenic intracrine and paracrine properties in Mo-iDCs. This may act as an immediate protective mechanism to maintain vascular homeostasis. Moreover, inducing sp-iDCs by short term FN-treatment or ERK1/2 modulation might be considered as new approaches for regulating angiogenesis through the production/inhibition of pro-angiogenic mediators. Collectively, these findings may support a role for FN and Mo-iDCs in vascular function and angiogenesis.

This paper considers the finite-time stabilization problem for an integrator chain in the context of uncertain measurement nonlinearities, such that the signs of the state variables are the only available information for feedback. The solutions of this problem are known for single, double, and triple integrators. The main result of the present paper is a higher-order sliding mode (HOSM) controller that stabilizes an integrator chain of arbitrary length. Computer simulations are provided to validate theoretical results.

The new sliding mode control design algorithm for a linear disturbed system is presented. It is based on the appropriate selection of the sliding surface via invariant ellipsoid method. The designed control guarantees minimization of the effects of unmatched disturbances to the system motion in the sliding mode. All theoretical results are approved by numerical simulations.

Genetic diversity between of the Novosibirsk and Tomsk chromosome races of the common shrew (Sorex araneus) was analyzed using 39 polymorphic AFLP (amplified fragments length polymorphism) markers. Exact and F-statistics tests for population differentiation demonstrated significant interracial difference in allele frequencies and significant subdivision between the races. The value of the genetic distance between the chromosome races observed in this study corresponds to that found between subspecies of mammals studied so far.

This paper deals with the problem of robust stabilization of an uncertain nonlinear system with output measurements using the invariant ellipsoid method. The non-linear system is uncertain but bounded according to a ‘quasi-lipschitz’ condition and the output measurements are subjected to perturbations bounded by ellipsoids.The invariant ellipsoid method allows to obtain the robust linear feedback as a solution of the special linear optimization problem with bilinear constraints. The methods for solving this optimization problem involves the LMI technique. The stabilization of the double mass-spring system is considered as an illustrative example.

The active center of DNA-dependent RNA polymerase performs the principal biochemical reaction of gene expression. Using cross-linkable substrate analogs and site-directed mutations, two evolutionarily invariant amino acids in the beta subunit of the Escherichia coli enzyme (Lys1065 and His1237) were mapped close to the binding site of the priming substrate of the reaction. Surprisingly, the mutational substitution of these residues (Lys1065----Arg and His1237----Ala) did not inactivate the catalytic function, but inhibited transition from the initiation to the elongation stage of transcription.

The robust output stabilization problem for a class of uncertain nonlinear systems with disturbances is considered. The suggested control scheme as well as the observation algorithm are based on the invariant ellipsoid method, which allows to obtain the robust linear feedback as a solution of the special linear optimization problem with bilinear constraints. The methods for solving this optimization problem involves the LMI technique. The stabilization of a single link flexible joint manipulator is considered as an illustrative example.

A new method of a Lyapunov functions design is presented. It is based on the characteristic method application and related to resolving of the first-order partial differential equation of a special type. A successful resolution of this equation guaranties of finite-time convergence for the corresponding dynamics given by an ordinary differential equation with a discontinuous right-hand side and allows to estimate convergence time. The suggested method is illustrated by its application to the ldquotwistingrdquo and ldquosuper-twistingrdquo controllers stability analysis. The constructed Lyapunov function as well its level lines sections is graphically illustrated.

Two problems of practical stabilization (local and semiglobal) via relay delayed control are considered. Control design algorithms for linear plants operating under uncertainty conditions are proposed. The necessary and sufficient existence conditions are stabilizing relay delayed controls are given. The stabilization problem of an inverted pendulum controlled by flywheel is considered as numerical example.

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia/reoxygenation (IHR), is associated with atherosclerosis. Polymorphonuclear leukocytes (PMNs) are implicated in atherogenesis by producing oxidizing radicals and proteolytic enzymes during PMN-endothelium interactions. PMN apoptosis is a fundamental, injury-limiting mechanism, which prevents their destructive potential.To determine whether PMN apoptosis and expression of adhesion molecules are affected by OSA and IHR in vitro.Apoptosis and expression of adhesion molecules were assessed in whole blood PMNs by flow cytometry, verified by various culture conditions, and morphology. These were complemented by exposing whole blood and purified PMNs to IHR and to sustained hypoxia in vitro.This study demonstrates for the first time that, in patients with moderate to severe OSA, PMN apoptosis is delayed. Apoptosis was attenuated in patients with an apnea-hypopnea index (AHI) of more than 15, determined by decreased expression of low-CD16/annexin-V-positive PMNs, by lowered caspase-3 activity and nuclear condensation. Concomitantly, selectin-CD15 expression was increased in a severity-dependent manner in patients with moderate to severe OSA having an AHI greater than 15. The percentage of apoptotic PMNs was negatively correlated with OSA severity, determined by AHI, and positively with CD15 expression. In nasal continuous positive airway pressure-treated patients, CD15 expression was attenuated and low CD16 was increased, whereas omitting nasal continuous positive airway pressure for a single night increased CD15 expression and decreased the percentage of low CD16. IHR in vitro delayed PMN apoptosis as well.Decreased apoptosis and increased expression of adhesion molecules were noted in OSA PMNs. Although adhesion molecules may facilitate increased PMN-endothelium interactions, decreased apoptosis may further augment these interactions and facilitate free radical and proteolytic enzyme release.

Objective: To study effects of forward masking and rapid stimulation on human monaurally- and binaurally-evoked brainstem potentials and suggest their relation to synaptic fatigue and recovery and to neuronal action potential refractoriness. Methods: Auditory brainstem evoked potentials (ABEPs) were recorded from 12 normally- and symmetrically hearing adults, in response to each click (50 dB nHL, condensation and rarefaction) in a train of nine, with an inter-click interval of 11 ms, that followed a white noise burst of 100 ms duration (50 dB nHL). Sequences of white noise and click train were repeated at a rate of 2.89 s−1. The interval between noise and first click in the train was 2, 11, 22, 44, 66 or 88 ms in different runs. ABEPs were averaged (8000 repetitions) using a dwell time of 25 μs/address/channel. The binaural interaction components (BICs) of ABEPs were derived and the single, centrally located equivalent dipoles of ABEP waves I and V and of the BIC major wave were estimated. Results: The latencies of dipoles I and V of ABEP, their inter-dipole interval and the dipole magnitude of component V were significantly affected by the interval between noise and clicks and by the serial position of the click in the train. The latency and dipole magnitude of the major BIC component were significantly affected by the interval between noise and clicks. Interval from noise and the click's serial position in the train interacted to affect dipole V latency, dipole V magnitude, BIC latencies and the V–I inter-dipole latency difference. Most of the effects were fully apparent by the first few clicks in the train, and the trend (increase or decrease) was affected by the interval between noise and clicks. Conclusions: The changes in latency and magnitude of ABEP and BIC components with advancing position in the click train and the interactions of click position in the train with the intervals from noise indicate an interaction of fatigue and recovery, compatible with synaptic depletion and replenishing, respectively. With the 2 ms interval between noise and the first click in the train, neuronal action potential refractoriness may also be involved.

Time delay does not allow realization of an ideal sliding mode, but implies oscillations in the space of state variables. The delayed relay control algorithms for stabilization of oscillation amplitudes are suggested.

Our objective was to study the effects of sound source direction and elevation on human brainstem electrical activity associated with sound localization. The subjects comprised 15 normal-hearing and symmetrically hearing adults Auditory brainstem evoked potentials (ABEPs) were recorded from three channels, in response to alternating-polarity clicks, presented at a rate of 21.1/s, at nine virtual spatial locations with different direction and elevation attributes Equivalent dipoles of the binaural interaction components (BICs) of ABEPs were derived by subtracting the response to binaural clicks at each spatial location from the algebraic sum of monaural responses to stimulation of each ear in turn. The BICs included two major components corresponding in latency to the vertex-neck-recorded components V and VI of ABEP. A significant decrease of the first BIC's equivalent dipole magnitude was observed for clicks in the horizontal-frontal position (no elevation) in the midsagittal plane, and for clicks in the left-horizontal (no elevation) and right diagonally above the head (medium elevation) positions in the coronal plane, compared to clicks positioned directly above the head. Significant effects on equivalent dipole latencies of this component were found for front-back positions in the midsagittal plane and left-right positions in the coronal plane, compared to clicks positioned directly above the head. The most remarkable finding was a significant change in equivalent dipole orientations across stimulus conditions. We conclude that the changes in BIC equivalent dipole latency, amplitude and orientation across stimulus conditions reflect differences in the distribution of binaural pontine activity evoked by sounds in different spatial locations.

Objective : The objective of the present study was to compare the effects of high stimulus rate and click position in the train on monaurally and binaurally evoked activities in the human auditory brainstem and suggest their possible physiological mechanism. Methods : Auditory brainstem evoked potentials (ABEPs) were recorded from 15 normally and symmetrically hearing adults from 3 channels, in response to 50 dB nHL, alternating polarity clicks, presented at a rate of 21/s as well as separately to each click in a train of 10 with an interstimulus interval of 11 ms. Click trains were presented at a rate of 5.13/s. The binaural interaction components (BICs) of ABEPs were derived by subtracting the response to binaural clicks from the algebraic sum of monaural responses. Single, centrally located equivalent dipoles were estimated as concise measures of the surface-summated activity of ABEPs and BICs generators. Results : A significant effect of click position in the train on equivalent dipole latency of ABEP component V and on equivalent dipole magnitude of III were found. Latency was prolonged and amplitude was increased the later the click's position in the train. A significant effect of click position in the train on equivalent dipole latencies of all components of BICs was found. Latencies were prolonged if the click's position occurred later in the train, with most of the latency shift achieved by the third click in the train for the first major BIC and by the seventh click for other BIC components. No significant effects on equivalent dipole magnitudes of BICs were found. No significant effect of click position in the train on orientation of any of the equivalent dipoles of ABEP or BIC was found. Conclusions : The progressive prolongation of latency of ABEP and BIC components with advancing position in the train may be attributed to cumulatively decreased synaptic efficacy at high stimulus rates, resulting in prolonged synaptic delays along the auditory pathway. The paradoxic enhancement of ABEP dipole III magnitude with advancing click position in the train may reflect higher sensitivity of inhibitory brainstem neurons to increased stimulus rate, resulting in disinhibition. The absence of significant effects on BIC dipole magnitudes may reflect the amplifying effect of divergence in the ascending auditory pathway, as has been observed for the monaurally evoked ABEP components from the upper pons.

Time delay does not allow to realize an ideal sliding mode, but implies oscillations in the space of state variables. Algorithm of delayed relay control gain adaptation is suggested for nonlocal stabilization using delayed information about oscillation's amplitudes.

Objectives and methods: Auditory brain-stem evoked potentials (ABEPs) were recorded from 10 normal hearing subjects in response to rarefaction clicks, presented at a rate of 11/s. Stimuli were binaurally symmetrical and isochronic at 75 dB peSPL or with interaural time disparities (ITDs) of ±0.4 ms, or intensity disparities (IIDs) of ±10 dB. Potentials were recorded from vertex-neck, as well as from 3 orthonormally positioned differential derivations. The amplified potentials were averaged over 8000 repetitions using a dwell time of 20 μ s/address/channel. The effects of contralateral stimulation on neural responses of the peripheral auditory system were obtained by subtracting the binaural response from the algebraic sum of responses to left and right monaural stimuli. From the 3 orthonormal derivations, 3-channel Lissajous' trajectories (3-CLTs) to the various stimulus conditions and difference waveforms were derived. Results: The results corroborated earlier studies on binaural interaction components (BICs), which include 3 major components corresponding in latency to the vertex-mastoid peaks IV–VI of ABEP. In addition, the binaural difference waveforms included 3 earlier, low-amplitude components. Latency correspondence and comparison of difference waveform and ABEP 3-CLTs indicated that the first and third early difference waveform components corresponded to the negative peaks following I and III, respectively, of the vertex-neck ABEP to binaural clicks. Conclusions: These results indicate that early ABEP peaks, generated peripheral to binaural convergence, may be affected by contralateral stimulation. These contralateral effects were in a pattern compatible with suppression. most probably by efferents of the olivo-cochlear bundle.

Objectives and mehtods : Four sets of measurements were obtained from 11 patients (44–80 years old) with small, localized pontine lesions due to vascular disease: (1) Monaural auditory brain-stem evoked potentials (ABEPs; peaks I to VI); (2) Binaural ABEPs processed for their binaural interaction components (BICs) in the latency range of peaks IV to VI; (3) magnetic resonance imaging (MRI) of the brain-stem; and (4) psychoacoustics of interaural time disparity measures of binaural localization. ABEPs and BICs were analyzed for peak latencies and interpeak latency differences. Three-channel Lissajous' trajectories (3-CLTs) were derived for ABEPs and BICs and the latencies and orientations of the equivalent dipoles of ABEP and BICs were inferred from them. Results : Intercomponent latency measures of monaurally evoked ABEPs were abnormal in only 3 of the 11 patients. Consistent correlations between sites of lesion and neurophysiological abnormality were obtained in 9 of the 11 patients using 3-CLT measures of BICs. Six of the 11 patients had absence of one or more BIC components. Seven of the 11 had BICs orientation abnormality and 3 had latency abnormalities. Trapezoid body (TB) lesions (6 patients) were associated with an absent (two patients with ventral-caudal lesions) or abnormal (one patient with ventral-rostral lesions) dipole orientation of the first component (at the time of ABEPs IV), and sparing of this component with midline ventral TB lesions (two patients). A deviant orientation of the second BICs component (at the time of ABEPs V) was observed with ventral TB lesions. Psychoacoustic lateralization in these patients was biased toward the center. Rostral lateral lemniscus (LL) lesions (3 patients) were associated with absent (one patient) or abnormal (two patients) orientation of the third BICs component (at the time of ABEPs VI); and a side-biased lateralization with behavioral testing. Conclusions : These results indicate that: (1) the BICs component occurring at the time of ABEPs peak IV is dependent on ventral-caudal TB integrity; (2) the ventral TB contributes to the BICs component at the time of ABEPs peak V; and (3) the rostral LL is a contributing generator of the BICs component occurring at the time of ABEP peak VI.

The structure of Escherichia coli core RNA polymerase (RNAP) complexed with the transcript cleavage factor GreB was determined from electron micrographs of negatively stained, flattened helical crystals. A binding assay was developed to establish that GreB was incorporated into the RNA polymerase crystals with high occupancy through interactions between the globular C-terminal domain and the RNA polymerase. Comparison of the core RNAP:GreB structure with the previously determined structure of core RNAP located the GreB binding site on one face of the RNA polymerase, next to but not in the 25 A-diameter channel of RNA polymerase.