Internal models in sensorimotor integration: perspectives from adaptive control theory.
Internal models and adaptive controls are empirical and mathematical paradigms that have evolved separately to describe learning control processes in brain systems and engineering systems, respectively. This paper presents a comprehensive appraisal of the correlation between these paradigms with a view to forging a unified theoretical framework that may benefit both disciplines. It is suggested that the classic equilibrium-point theory of impedance control of arm movement is analogous to continuous gain-scheduling or high-gain adaptive control within or across movement trials, respectively, and that the recently proposed inverse internal model is akin to adaptive sliding control originally for robotic manipulator applications. Modular internal models' architecture for multiple motor tasks is a form of multi-model adaptive control. Stochastic methods, such as generalized predictive control, reinforcement learning, Bayesian learning and Hebbian feedback covariance learning, are reviewed and their possible relevance to motor control is discussed. Possible applicability of a Luenberger observer and an extended Kalman filter to state estimation problems-such as sensorimotor prediction or the resolution of vestibular sensory ambiguity-is also discussed. The important role played by vestibular system identification in postural control suggests an indirect adaptive control scheme whereby system states or parameters are explicitly estimated prior to the implementation of control. This interdisciplinary framework should facilitate the experimental elucidation of the mechanisms of internal models in sensorimotor systems and the reverse engineering of such neural mechanisms into novel brain-inspired adaptive control paradigms in future. (+info)
Tissue-engineered vessel strengthens quickly under physiological deformation: application of a new perfusion bioreactor with machine vision.
In order to develop a patent tissue-engineered blood vessel that grossly resembles native tissue, required culture times in most studies exceed 8 weeks. For the sake of shortening the maturation period of the constructs, we have used deformation as the basic index for mechanical environment control. A new bioreactor with a machine vision identifier was developed to accurately control the deformation of the construct during the perfusion process. Two groups of seeded constructs (n = 4 per group) were investigated in this study, with one group stimulated by a cyclic deformation of 10% and the other by a pulsatile pressure that gradually increased to 120 mm Hg (the control group). After 21 days of culture, the mechanical properties of the constructs were examined. The average burst strength and suture retention strength in the two groups were significantly different (t test, p < 0.05). For the experimental group, the average burst strength and suture retention strength were higher than those of the control group, by 31.6 and 23.4%, respectively. Specifically, the average burst strength of the constructs reached 1,402 mm Hg (close to that of the native vessel, i.e. 1,680 mm Hg) within a relatively short period of 21 days. In conclusion, deformation is an observable, controllable and very valuable index for mechanical environment control in vascular tissue engineering. It makes the control of mechanical stimuli more essential and experiments more comparable. (+info)
Structure, epitope mapping, and docking simulation of a gibberellin mimic peptide as a peptidyl mimotope for a hydrophobic ligand.
Using NMR spectroscopy and simulated annealing calculations, we determined the solution structure of the disulfide-linked cyclized decapeptide ACLPWSDGPC (SD), which is bound to an anti-(gibberellin A(4)) mAb 4-B8(8)/E9 and was found to be the first peptidyl mimotope for a hydrophobic ligand. The resulting structure of the peptide showed a beta-turn-like conformation in residues three to seven and the region converges well (average rmsd 0.54 A). The binding activity and the epitopes of the peptide to the antibody were assessed using saturation transfer difference (STD)-NMR experiments. We also conducted docking simulations between the peptide and the mAb to determine how the peptide is bound to the mAb. Resonances around the beta-turn-like conformation of peptide SD (residues 3-5) showed strong STD enhancement, which agreed well with results from docking simulation between peptide SD and the mAb. Together with the commonality of amino acid residues of the mAb involved in interactions with gibberellin A(4) (GA(4)) and peptide SD, we concluded that peptide SD is bound to the antigen-binding site of mAb 4-B8(8)/E9 as a GA(4) mimic, confirming evidence for the existence of peptide mimics even for hydrophobic ligands. (+info)
Functionalization of the cytochrome P450cam monooxygenase system in the cell-like aqueous compartments of water-in-oil emulsions.
The functionalization of the cytochrome P450cam monooxygenase system, which requires electron transfer among three different proteins, was investigated in the micro-scale aqueous compartments of stable water-in-oil (W/O) emulsions formed with the nonionic surfactant tetraethylene glycol dodecyl ether. Neither an organic-aqueous biphasic system nor a non-emulsified organic-aqueous solution containing the same amount of surfactant showed substantial hydroxylation of camphor, a natural substrate of P450cam, whereas substantial monooxygenation activity was detected when stable aqueous compartments were provided by the formation of W/O emulsions. Since the camphor hydroxylation in W/O emulsions was modest, we explored the integration of an enzymatic NADH regeneration system in order to effectively provide a reducing equivalent. Two different dehydrogenases, bacterial glycerol dehydrogenase (GLD) and yeast alcohol dehydrogenase (ADH), were selected, and each of these was coupled with the P450cam catalytic cycle in W/O emulsions. As a result, the camphor hydroxylation rate was successfully improved by approximately 5-fold when GLD was employed under optimized conditions. These results reveal the potential utility of the micro-scale cell-like aqueous compartments of W/O emulsions for multicomponent enzymatic reactions especially for substrates with low aqueous solubility. (+info)
Engineering a mimicry of bone marrow tissue ex vivo.
Hematopoietic stem cells reside in specific niches in the bone marrow and give rise to either more stem cells or maturing hematopoietic progeny depending on the signals provided in the bone marrow microenvironment. This microenvironment is comprised of cellular components as well as soluble constituents called cytokines. The use of cytokines alone for the ex vivo expansion of stem cells in flat, two-dimensional culture flasks, dishes or bags is inadequate and, given the three-dimensionality of the in vivo bone marrow microenvironment, inappropriate. Three-dimensional culture conditions can therefore provide an ex vivo mimicry of bone marrow, recapitulate the desired niche, and provide a suitable environment for stem cell expansion and differentiation. Choice of scaffold, manipulation and reproducibility of the scaffold properties and directed structuring of the niche, by choosing pore size and porosity may inform the resident stem cells of their fate in a directed fashion. The use of bioreactors for cultivation of hematopoietic cells will allow for culture control, optimization, standardization, scale-up, and a "hands-off" operation making the end-product dependable, predictable and free of contaminants, and therefore suitable for human use and therapeutic applications. (+info)
A method for generating precise temporal patterns of retinal spiking using prosthetic stimulation.
The goal of retinal prosthetic devices is to generate meaningful visual information in patients that have lost outer retinal function. To accomplish this, these devices should generate patterns of ganglion cell activity that closely resemble the spatial and temporal components of those patterns that are normally elicited by light. Here, we developed a stimulus paradigm that generates precise temporal patterns of activity in retinal ganglion cells, including those patterns normally generated by light. Electrical stimulus pulses (> or =1-ms duration) elicited activity in neurons distal to the ganglion cells; this resulted in ganglion cell spiking that could last as long as 100 ms. However, short pulses, <0.15 ms, elicited only a single spike within 0.7 ms of the leading edge of the pulse. Trains of these short pulses elicited one spike per pulse at frequencies < or =250 Hz. Patterns of short electrical pulses (derived from normal light elicited spike patterns) were delivered to ganglion cells and generated spike patterns that replicated the normal light patterns. Finally, we found that one spike per pulse was elicited over almost a 2.5:1 range of stimulus amplitudes. Thus a common stimulus amplitude could accommodate a 2.5:1 range of activation thresholds, e.g., caused by differences arising from cell biophysical properties or from variations in electrode-to-cell distance arising when a multielectrode array is placed on the retina. This stimulus paradigm can generate the temporal resolution required for a prosthetic device. (+info)
Texture signals in whisker vibrations.
Rodents excel in making texture judgments by sweeping their whiskers across a surface. Here we aimed to identify the signals present in whisker vibrations that give rise to such fine sensory discriminations. First, we used sensors to capture vibration signals in metal whiskers during active whisking of an artificial system and in natural whiskers during whisking of rats in vivo. Then we developed a classification algorithm that successfully matched the vibration frequency spectra of single trials to the texture that induced it. For artificial whiskers, the algorithm correctly identified one texture of eight alternatives on 40% of trials; for in vivo natural whiskers, the algorithm correctly identified one texture of five alternatives on 80% of trials. Finally, we asked which were the key discriminative features of the vibration spectra. Under both artificial and natural conditions, the combination of two features accounted for most of the information: The modulation power-the power of the part of the whisker movement representing the modulation due to the texture surface-increased with the coarseness of the texture; the modulation centroid-a measure related to the center of gravity within the power spectrum-decreased with the coarseness of the texture. Indeed, restricting the signal to these two parameters led to performance three-fourths as high as the full spectra. Because earlier work showed that modulation power and centroid are directly related to neuronal responses in the whisker pathway, we conclude that the biological system optimally extracts vibration features to permit texture classification. (+info)
SuperMimic--fitting peptide mimetics into protein structures.
BACKGROUND: Various experimental techniques yield peptides that are biologically active but have unfavourable pharmacological properties. The design of structurally similar organic compounds, i.e. peptide mimetics, is a challenging field in medicinal chemistry. RESULTS: SuperMimic identifies compounds that mimic parts of a protein, or positions in proteins that are suitable for inserting mimetics. The application provides libraries that contain peptidomimetic building blocks on the one hand and protein structures on the other. The search for promising peptidomimetic linkers for a given peptide is based on the superposition of the peptide with several conformers of the mimetic. New synthetic elements or proteins can be imported and used for searching. CONCLUSION: We present a graphical user interface for finding peptide mimetics that can be inserted into a protein or for fitting small molecules into a protein. Using SuperMimic, promising locations in proteins for the insertion of mimetics can be found quickly and conveniently. (+info)