The nerve growth factor (NGF) is essential for the survival of both peripheral ganglion cells and central cholinergic neurons in the basal forebrain. The accelerated loss of central cholinergic neurons during Alzheimer’s disease may be a determinant cause of dementia, and this observation may suggest a possible therapeutic benefit from treatment with NGF. In recent years, convincing data have been published involving neurotrophic factors for the modulation of dopaminergic transmission within the brain and concerning the ability of NGF to prevent the degeneration of dopaminergic neurons. In this connection, the administration of NGF may slow down the progression of Parkinson’s disease. However, NGF, as well as other peptidic neurotrophic factors, does not significantly penetrate the blood–brain barrier (BBB) from the circulation. Therefore, any clinical usefulness of NGF as a potential CNS therapy will depend on the use of a suitable carrier system that enhances its transport through the BBB. The present study investigates brain delivery of NGF adsorbed on poly(butyl cyanoacrylate) (PBCA) nanoparticles coated with polysorbate 80 and the pharmacological efficacy of this delivery system in the model of acute scopolamine-induced amnesia in rats as well as in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonian syndrome. As shown by the passive avoidance reflex (PAR) test, the intravenous administration of the nanoparticle-bound NGF successfully reversed scopolamine-induced amnesia and improved recognition and memory. This formulation also demonstrated a significant reduction of the basic symptoms of Parkinsonism (oligokinesia, rigidity, tremor). In addition, the efficient transport of NGF across the BBB was confirmed by direct measurement of NGF concentrations in the murine brain. These results demonstrate that the PBCA nanoparticles coated with polysorbate 80 are an effective carrier system for the transport of NGF to the central nervous system across the BBB following intravenous injection. This approach may improve the NGF-based therapy of age-related neurodegenerative diseases.

Purpose. It has recently been suggested that the poly(butylcyanoacrylate) (PBCA) nanoparticle drug delivery system has a generalized toxic effect on the blood-brain barrier (BBB) (8) and that this effect forms the basis of an apparent enhanced drug delivery to the brain. The purpose of this study is to explore more fully the mechanism by which PBCA nanoparticles can deliver drugs to the brain.

Recent studies have shown that drugs that are normally unable to cross the blood-brain barrier (BBB) following intravenous injection can be transported across this barrier by binding to poly(butyl cyanoacrylate) nanoparticles and coating with polysorbate 80. However, the mechanism of this transport so far was not known. In the present paper, the possible involvement of apolipoproteins in the transport of nanoparticle-bound drugs into the brain is investigated. Poly(butyl cyanoacrylate) nanoparticles loaded with the hexapeptide dalargin were coated with the apolipoproteins AII, B, CII, E, or J without or after precoating with polysorbate 80. In addition, loperamide-loaded nanoparticles were coated with apolipoprotein E alone or again after precoating with polysorbate 80. After intravenous injection to ICR mice the antinociceptive threshold was measured by the tail flick test. Furthermore, the antinociceptive threshold of polysorbate 80-coated dalargin-loaded nanoparticles was determined in ApoEtm1Unc and C57BL/6J mice. The results show that only dalargin or loperamide-loaded nanoparticles coated with polysorbate 80 and/or with apolipoprotein B or E were able to achieve an antinociceptive effect. This effect was significantly higher after polysorbate-precoating and apolipoprotein B or E-overcoating. With the apolipoprotein E-deficient ApoEtm1Unc mice the antinociceptive effect was considerably reduced in comparison to the C57BL/6J mice. These results suggest that apolipoproteins B and E are involved in the mediation of the transport of drugs bound to poly(butyl cyanoacrylate) nanoparticles across the BBB. Polysorbate 80-coated nanoparticles adsorb these apolipoproteins from the blood after injection and thus seem to mimic lipoprotein particles that could be taken up by the brain capillary endothelial cells via receptor-mediated endocytosis. Bound drugs then may be further transported into the brain by diffusion following release within the endothelial cells or, alternatively, by transcytosis.

Electronic speckle pattern interferometry (ESPI) suits very well for nondestructive optical testing of products and components. Most of the currently existing methods and devices for out-of-plane sensitive ESPI require a big number of optical elements which are difficult to align. A novel method of ESPI for out-of-plane deformation and vibration measurements is introduced. In the proposed method a microstructured refractive optical element (MROE) is used which serves as beam combiner of object wave and reference wave guiding them inline, along the optical axis of the camera objective to the camera sensor. This MROE contains two groups of microstructures which deflect each ESPI wave (ESPI object and reference one) exactly on-axis tin one variant of the method only one group is sufficient). The reference wave is generated by reflective scattering of the laser radiation on an arbitrary surface. Different surfaces were tested in our experiments and in every case high quality ESPI evaluations were obtained. For example a simple sheet of white paper or a colour photograph serving as a reference surface suit very well. We present an innovative ESPI device utilizing a MROE and experimental results obtained by means of this device. The method and the device based on this method can be used among others in microelectronic industries in development and quality testing of components, integrated circuits acid printed circuit hoards.

When an oscillatory nonlinear system is driven by a periodic external stimulus, the system can lock at rational multiples p : q of the driving frequency. The frequency range of this resonant locking at a given p : q depends on the amplitude of the stimulus; the frequency width of locking increases from zero as the stimulus amplitude increases from zero, generating an “Arnol’d tongue” in a graph of stimulus amplitude vs stimulus frequency. Physical systems that exhibit frequency locking include electronic circuits [1, 2], Josephson junctions [3], chemical reactions [4], fields of fireflies [5, 6], and forced cardiac systems [7, 8]. Most studies of frequency locking have concerned either maps or systems of a few coupled ODEs. The Arnol’d tongue structure of the sine circle map has been extensively studied, and the theory of periodically driven ODE systems has been well developed [9], but there has been very little analysis of frequency locking phenomena in PDEs, except for a few studies of the parametrically excited Mathieu equation with diffusion and damping [10, 11, 12] and the parametrically excited complex Ginzburg-Landau equation [13, 14]. Our interest here is in the effect of periodic forcing on pattern forming systems such as convecting fluids, liquid crystals, granular media, and reaction-diffusion systems. Such systems are often subject to periodic forcing (e.g., circadian forcing of biological systems), but the effect of forcing on the bifurcations to patterns has not been examined in experiments or analyzed in PDE models of these systems.

We present a control method for high-dimensional nonlinear dynamical systems that car,target remote unstable states.without a priori knowledge of the underlying dynamical equations. The algorithm constructs a high-dimensional look-up table based on the system's responses to a sequence of random perturbations. The method is demonstrated by stabilizing unstable flow of a liquid bridge surface-tension-driven convection experiment that models the float zone refining process. Control of the dynamics is achieved by heating or cooling mio thermoelectric Peltier devices placed in the vicinity of the liquid bridge surface. The algorithm routines along with several example programs written in the MATLAB language can be found at ftp://ftp.mathworks.com/pub/contrib/v5/control/nlcontrol.

A new method of electronic speckle pattern interferometry (ESPI) for in-plane deformation measurements is presented. Unlike usual ESPI methods used for in-plane deformation measurements with two symmetrical smooth illuminating waves, we introduce miniature speckling elements and thin laser beam illumination of them. The minia- ture elements serve for generating two symmetrical speckled waves. These miniature speckling elements are produced as reflection or trans- mission holograms. Nonholographic speckling elements were also tested. We present a family of flexible electronic speckle pattern interfer- ometers for in-plane deformation analysis based on our method. Due to their simplicity, compactness, and low cost, the devices are ideally suited for industrial automated inspection. Experimental results obtained with the novel ESPI devices are given. © 1998 Society of Photo-Optical Instrumenta- tion Engineers. (S0091-3286(98)01508-6)

Prediction, filtering and control of nonlinear systems is formulated in terms of corresponding nonlinear surfaces in the phase space of delayed system readings and control parameters. The construction of these surfaces from time series and their use is demonstrated with a simple chemical model in the chaotic regime. (c) 1997 American Institute of Physics.

A periodic force applied to a nonlinear pendulum can cause the pendulum to become entrained at a frequency that is rationally related to the applied frequency, a phenomenon known as frequency-locking1. A recent theoretical analysis showed that anarray of coupled nonlinear oscillators can exhibit spatial reorganization when subjected to external periodic forcing2. We present here experimental evidence that reaction–diffusion processes, which govern pattern evolution and selection in many chemical and biological systems3, can also exhibit frequency-locking phenomena. For example, periodic optical forcing of the light-sensitive Belousov–Zhabotinsky (BZ) reaction transforms a rotating spiral wave4 to a labyrinthine standing-wave pattern (Fig. 1). As the forcing frequency is varied, we observe a sequence of frequency-locked regimes, analogous to the frequency-locked ‘tongues’ of a driven nonlinear pendulum, except that in the reactor different frequencies correspond to different spatial patterns. Resonant interactions leading to standing-wave patternshave not been observed previously in chemical or biological media, but periodic forcing (such as circadian rhythm) is abundant in nature and may lead to similar pattern-forming phenomena.

PURPOSE:The possibility of using polysorbate 80-coated nanoparticles for the delivery of the water insoluble opioid agonist loperamide across the blood-brain barrier was investigated. The analgesic effect after i.v. injection of the preparations was used to indicate drug transport through this barrier.METHODS:Loperamide was incorporated into PBCA nanoparticles. Drug-containing nanoparticles were coated with polysorbate 80 and injected intravenously into mice. Analgesia was then measured by the tail-flick test.RESULTS:Intravenous injection of the particulate formulation resulted in a long and significant analgesic effect. A polysorbate 80 loperamide solution induced a much less pronounced and very short analgesia. Uncoated nanoparticles loaded with loperamide were unable to produce analgesia.CONCLUSIONS:Polysorbate 80-coated PBCA nanoparticles loaded with loperamide enabled the transport of loperamide to the brain.

We use infrared imaging to visualize time-dependent flow in a liquid bridge (Prandtl number 35 and aspect ratio 1) with an imposed vertical temperature gradient. The primary instability leads from an axisymmetric time-independent state to helical traveling waves with an azimuthal wavenumber m=1. A secondary instability introduces an additional traveling wave with m=2. The structure and phase of the modes is determined from the infrared images.

A new method of electronic speckle pattern interferometry (ESPI) is introduced. It is a two-stage process. In the first stage a holographic optical element (HOE) is recorded in a usual holographic arrangement. This HOE illuminated later reconstructs an object wave that serves as an ESPI reference wave. Well suited HOEs are produced on photothermoplastic or silver halide media. In the case of silver halide media, both recording and momental monobath photoprocessing of the HOE are performed in presence of an intense polychromatic illumination to meet industrial requirements. Due to the introduction of HOE the second stage, ESPI implementation can be performed with an extremely simple optical setup. The number of optical elements, apart from the video camera, can be drastically reduced to only two elements: a plane mirror and the HOE. High accuracy alignment of the optical elements is not necessary. Our method also enables HOE recording in the ESPI setup practically without modifications. Both experimental results and the ready device are presented. Our optical setup is compact and needs no sophisticated vibration insulation and no dark room, thus it is ideally suited for industrial applications.

Spatiotemporal chaos in a two-variable, cubic autocatalator model with equal diffusivities of thespecies is described. The interplay between an unstable homogeneous state and propagating frontswhich return the system to that state gives rise to a reinjection mechanism for chaotic behavior. Extremesensitivity to initial conditions in both space and time and a rapid falloff of the spatial correlationfunction are exhibited in the chaotic regime.

We demonstrate the stabilization of unstable periodic orbits whose trajectories in phase space are distant from the unperturbed dynamics in a convective flow experiment. A model independent, nonlinear control algorithm uses temperature measurements near the free surface of a convecting liquid bridge to compute control perturbations which are applied by a thermoelectric element. The algorithm employs a time series reconstruction of a nonlinear control surface to alter the system dynamics.

Feedback control of multidimensional, nonlinear single-input single-output systems is formulated in terms of an invariant hypersurface in the delayed state space of a system observable and a control parameter. The surface is created directly from the response of the system to random perturbations, providing a model-independent nonlinear control algorithm. The algorithm can be used to stabilize unstable states or to drive a system to any particular objective state in a minimum number of steps.

Illumination of ruthenium-catalyzed Belousov−Zhabotinsky reaction decreases the rotational frequency of spirals at low bromate concentrations but increases the frequency at high bromate concentrations. The effective diffusion coefficient D deduced from the Keener−Tyson relation for the spirals, D ≈ ω/3k2, is independent of light intensity (D = 2.5 × 10-6 cm2/s).

Experiments on the Belousov-Zhabotinksy reaction unfold the bifurcation from simple (temporally periodic) rotating spirals to meandering (quasiperiodic) spirals in the neighborhood of a codimension-2 point. There are two types of meandering spirals, inward-petal (epicycloid) spirals and outward-petal (hypocycloid) spirals. These two types of meandering regimes are separated in the phase diagram by a line of traveling spirals that terminates at the codimension-2 point. The observations are in good accord with theory.