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Biomedical subjects

J L Hudson

Publications and source records attributed to J L Hudson.

At least 19 recordsLinked to original sources

Adaptive control of unknown unstable steady states of dynamical systems.

A simple adaptive controller based on a low-pass filter to stabilize unstable steady states of dynamical systems is considered. The controller is reference-free; it does not require knowledge of the location of the fixed point in the phase space. A topological limitation similar to that of the delayed feedback controller is discussed. We show that the saddle-type steady states cannot be stabilized by using the conventional low-pass filter. The limitation can be overcome by using an unstable low-pass filter. The use of the controller is demonstrated for several physical models, including the pendulum driven by a constant torque, the Lorenz system, and an electrochemical oscillator. Linear and nonlinear analyses of the models are performed and the problem of the basins of attraction of the stabilized steady states is discussed. The robustness of the controller is demonstrated in experiments and numerical simulations with an electrochemical oscillator, the dissolution of nickel in sulfuric acid; a comparison of the effect of using direct and indirect variables in the control is made. With the use of the controller, all unstable phase-space objects are successfully reconstructed experimentally.

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Sudden onset of pitting corrosion on stainless steel as a critical phenomenon.

Stainless steels undergo a sharp rise in pitting corrosion rate as the potential, solution concentration, or temperature is changed only slightly. We report experiments using real-time microscopic in situ visualizations that resolve the nucleation and evolution of individual pits during the transition. They suggest that the sudden onset of corrosion is explained by an explosive autocatalytic growth in the number of metastable pits and that stabilization of individual pits takes place only later. This finding agrees with a theoretical approach treating the onset of pitting corrosion as a cooperative critical phenomenon resulting from interactions among metastable pits, and it extends perspectives on the control and prevention of corrosion onset.

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Cooperative action of coherent groups in broadly heterogeneous populations of interacting chemical oscillators.

We present laboratory experiments on the effects of global coupling in a population of electrochemical oscillators with a multimodal frequency distribution. The experiments show that complex collective signals are generated by this system through spontaneous emergence and joint operation of coherently acting groups representing hierarchically organized resonant clusters. Numerical simulations support these experimental findings. Our results suggest that some forms of internal self-organization, characteristic for complex multiagent systems, are already possible in simple chemical systems.

Animals↗

Spatial learning deficits induced by muscimol and CL218,872: lack of effect of prenatal malnutrition.

The sensitivity of prenatal protein malnourished rats to the amnestic properties of the direct GABAA receptor agonist muscimol and the selective benzodiazepine (BZ) receptor agonist, CL218,872, was studied in the male offspring of rats provided with a protein deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy. At postnatal day 90, rats were tested during acquisition of the submerged platform version of the Morris water maze task using four systemic doses of muscimol (0.1, 0.3, 1.0 and 1.8 mg/kg i.p.) or three systemic doses of CL218,872 (1.0, 3.2, and 5.6 mg/kg i.p.). In a dose dependent manner both drugs impaired acquisition of the task and impaired accuracy of the search pattern on the probe trial (platform removed). However, neither drug dissociated the performance of the two nutritional groups. These data are important in light of previous findings of differential behavioral effects of the non-specific BZ agonist, chlordiazepoxide (CDP), on spatial learning and on drug discrimination in prenatally malnourished rats and in the context of previous findings of reduced sensitivity to the anxiolytic effects of non-specific BZ receptor agonists across a wide variety of models of malnutrition. The present findings also support the concept that prenatal malnutrition does not affect the global functioning of the GABAA receptor, but fundamentally alters the way in which a subset of GABAA receptors (i.e. those containing the alpha2, alpha3 and/or the alpha5 but not the alpha1 subunit) is modulated by BZs.

Animals↗

Stabilizing and tracking unknown steady States of dynamical systems.

An adaptive dynamic state feedback controller for stabilizing and tracking unknown steady states of dynamical systems is proposed. We prove that the steady state can never be stabilized if the system and controller in sum have an odd number of real positive eigenvalues. For two-dimensional systems, this topological limitation states that only an unstable focus or node can be stabilized with a stable controller, and stabilization of a saddle requires the presence of an unstable degree of freedom in a feedback loop. The use of the controller to stabilize and track saddle points (as well as unstable foci) is demonstrated both numerically and experimentally with an electrochemical Ni dissolution system.

Feedback↗

Suppressing spatiotemporal disorder via local perturbations in an electrochemical cell.

We report experimental results depicting suppression of complex spatiotemporal dynamics under the influence of local periodic stimulations. In an experimental electrochemical system, applying a continuous forcing signal to one of the sites in an array of eight coupled oscillators, the naturally complex behavior of the remaining seven electrodes can be converted to periodic responses. The oscillations remain periodic as long as the forcing is active and revert back to exhibiting chaotic dynamics after the control is switched off. These results can also be interpreted as experimental realization of "phase-synchronization" induced via local driving in an extended system. A possible relevance to the experimentally observed calcium wave patterns is pointed out.

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Phase synchronization and suppression of chaos through intermittency in forcing of an electrochemical oscillator.

External periodic forcing was applied to a chaotic chemical oscillator in experiments on the electrodissolution of Ni in sulfuric acid solution. The amplitude and the frequency (Omega) of the forcing signal were varied in a region around Omega=omega(0), where omega(0) is the frequency of the unforced signal. Phase synchronization occurred with increase in the amplitude of the forcing. For Omega/omega(0) near 1 the signal remained chaotic after the transition to the phase-locked state; for Omega/omega(0) somewhat farther from 1 the transition was to a periodic state via intermittency. The experimental results are supported by numerical simulations using a general model for electrochemical oscillations.

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Controlling spatiotemporal chemical chaos using delayed feedback.

Control of chemical chaos in a spatially extended system mimicking CO oxidation on a Pt(110) single-crystal surface is achieved using delayed feedback techniques. For appropriate parameter values the uncontrolled model system exhibits both amplitude and phase turbulence. Superimposing a delayed feedback on the natural dynamics, suppression of spatiotemporal complexity is attained via stabilization of ordered states consisting of stable patterns.

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Clustering of arrays of chaotic chemical oscillators by feedback and forcing.

Feedback and external forcing are applied to an array of chaotic electrochemical oscillators through variations in the applied potential. We see transitions from intermittent clusters to stable chaotic clusters to stable periodic clusters to synchronized states as the feedback gain and forcing amplitude, respectively, are varied. With forcing up to four clusters are observed in stable states. The transition to synchronization with feedback occurs by the increase in the size of one cluster at the expense of the others.

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Spatiotemporal patterns and symmetry breaking on a ring electrode.

A series of experiments on a ring electrode with changes in a parameter, the applied potential, are described. Spatiotemporal patterns are investigated in a region of parameter space in which relaxation oscillations occur. The simplest state is a period 2Pi oscillation that has full O(2) symmetry so that at each instant the pattern is unchanged by rotations or reflections of the ring. With change in parameter a spatiotemporal period doubling occurs to period 4Pi. This is followed by a symmetry breaking to another state with period 4Pi and subsequently by a second period doubling to period 8Pi. Proper orthogonal decomposition is used as an aid in elucidating the nature of the transitions.

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Parent-child interactions and anxiety disorders: an observational study.

Past research has indicated a potential link between anxiety and parenting styles that are characterised by control and rejection. However, few studies have utilised observational methods to support these findings. In the current study, mother-child interactions were observed while the child completed two difficult cognitive tasks. The sample consisted of clinically anxious children (n=43), oppositional defiant children (n=20) and non-clinical children (n=32). After adjusting for the age and sex of the child, mothers of anxious children and mothers of oppositional children displayed greater and more intrusive involvement than mothers of non-clinical children. Mothers of anxious children were also more negative during the interactions than mothers of non-clinical children. The differences between anxious and non-clinical interactions were equivalent across three separate age groups. The results support the relationship between an overinvolved parenting style and anxiety but question the specificity of this relationship.

Adolescent↗

Issues in the diagnosis and assessment of anxiety disorders in children and adolescents.

Accurate diagnosis and assessment of anxiety disorders in children and adolescents is important for both treatment and research. In this paper, we review research related to the discriminant validity of the childhood anxiety disorders, and outline methods of assessment for children, including diagnostic interviews, self-report instruments, and behavioural, cognitive, and psychophysiological measures. Particular attention is given to psychometric and developmental issues, and their influence on assessment. The evidence provides support for the validity of the anxiety disorders as a whole, but only partial support for differentiation between specific anxiety disorders in children. Similarly, assessment methods used with anxious children provide reasonably accurate information on anxious symptoms, however are limited by poor discriminant validity and lack of sensitivity to developmental levels.

Adolescent↗

The origins of social phobia.

A greater understanding of the origins of social phobia is much needed. The research to date is limited by the relatively small number of studies that sample clinical populations of individuals with social phobia. There is, however, research derived from related areas such as shyness, social anxiety, self-consciousness, peer neglect, and social withdrawal that contributes to a richer understanding of the etiology of social fears. Combining these areas of research, this review addresses four main factors that may be important to the origins of social phobia: (a) genetic factors; (b) family factors; (c) other environmental factors; and (d) developmental factors.

Adult↗

Impact of mitochondrial Ca2+ cycling on pattern formation and stability.

Energization of mitochondria significantly alters the pattern of Ca2+ wave activity mediated by activation of the inositol (1,4,5) trisphosphate (IP3) receptor (IP3R) in Xenopus oocytes. The number of pulsatile foci is reduced and spiral Ca2+ waves are no longer observed. Rather, target patterns of Ca2+ release predominate, and when fragmented, fail to form spirals. Ca2+ wave velocity, amplitude, decay time, and periodicity are also increased. We have simulated these experimental findings by supplementing an existing mathematical model with a differential equation for mitochondrial Ca2+ uptake and release. Our calculations show that mitochondrial Ca2+ efflux plays a critical role in pattern formation by prolonging the recovery time of IP3Rs from a refractory state. We also show that under conditions of high energization of mitochondria, the Ca2+ dynamics can become bistable with a second stable stationary state of high resting Ca2+ concentration.

Animals↗

Microglial cell responses to fetal ventral mesencephalic tissue grafting and to active and adoptive immunizations.

Microglia express cytokines, major histocompatibility (MHC) loci, and several other immunologically important constituents. The aim of this study was to detect immunological responses of microglial cells following allogeneic dopaminergic transplantation using active and adoptive immunizations. Adult inbred Fisher 344 (F344 RT1) rats were unilaterally dopamine (DA) depleted in striatum by injection of 6-hydroxydopamine. The degree of degeneration was assessed by recording the rotational response to apomorphine. Fetal ventral mesencephalic tissue containing DA neuroblasts from Wistar-Furth (WF, RT1u) rat donors (9-12 mm CRL) were later implanted in striatum on the lesioned side. Lymph nodes and spleen cells were collected aseptically, resuspended, and diluted for isovolumetric injections. Animals selected for active immunization were injected intraperitoneally with varying amounts of WF lymphocytes. Animals selected for adoptive immunization (transferred immunity) were intraperitoneally injected with 10(8) F344 lymphocytes prepared from animals actively immunized 3 weeks previously. Monoclonal antibodies against CD4 (OX38), CD8 (OX8), CD11b (OX42), MHC class I (OX18), monomorphic MHC class II (OX-6), and ED1 and polyclonal antibodies against tyrosine hydroxylase (TH) were used for immunohistochemistry. We found that the degree of ED1-positive cell proliferation was well correlated to the immunization patterns. Groups that were actively immunized with or without prior adoptive immunization had a larger amount of reactive microglial proliferation. ED1 immunohistochemistry revealed patterns of immunolabeling of engrafted areas: 8-12 weeks after grafting in nonimmunized and adoptively immunized groups reactive microglial proliferation occurred only at the graft periphery. Active and adoptive + active immunization led to ED1-IR within the grafts themselves. At early stages nonimmunized groups had an ED1 pattern which was partially inside the grafts. At early time points nonimmunized groups contained ameboid microglial cells within the grafts which disappeared at later stages and were absent in the immunized groups. ED1-positive ameboid microglial cells within the grafts may be of graft origin and constitute a part of a continued normal development of the fetal tissue.

Animals↗

Allogeneic grafts of fetal dopamine neurons: immunological reactions following active and adoptive immunizations.

To define the importance of adoptive sensitization and duration of graft residence on transplant alloimmunization, behavioral and histochemical parameters were examined in unilaterally 6-OHDA-lesioned F344 rat hosts which received fetal ventral mesencephalic (VM) grafts from Wistar-Furth (WF) donors. In all animals which showed increased rotations after alloimmunization, increased numbers of T cell receptor (TcR) positive, CD8+ lymphocytes were detected in the grafts. In addition, an increased density of class I MHC antigens was seen in the graft and in the adjacent host brain. Lesser numbers of CD4+, CD11b+, and MHCII+ positive elements were also seen. Perivascular cuffing was often found in actively immunized animals. An increase in TcR+ and MHC class I+ elements was also seen in animals only adoptively immunized. The tyrosine hydroxylase positive graft area was also markedly reduced in actively immunized animals and the extent of reduction correlated with the number of cells used for immunization. These studies indicate that established allografts can evade rejection as long as host lymphocytes are not activated against graft alloantigens. In addition, increasing graft residence time in the host and adoptive immunization render the graft more susceptible to subsequent rejection.

Animals↗

Allogeneic grafts of fetal dopamine neurons: behavioral indices of immunological interactions.

Fetal central nervous system transplants to the adult brain have been utilized to understand brain connectivity and as replacement therapy in Parkinson's disease (PD). Here we use fetal brain allografting in the rat unilaterally depleted of dopamine, a unilateral model of PD, and apomorphine-induced rotations as an index of graft functional status while peripherally manipulating the host's alloimmune status. This system allows the investigator to examine, dynamically, host-allograft interactions in the brain under differing states of alloimmunoreactivity without the need to biopsy or sacrifice the animal. In addition to this novel application, we established that brain allografts are differentially susceptible to immunologic attack depending upon the graft's duration of residence in the host brain. Increasing residence time increases graft 'rejectability' to peripheral allosensitization. Passive immunization also sensitizes the host to subsequent graft rejection. Lastly, simple host alloimmunocompetence is necessary but not sufficient to cause fetal graft 'rejection', defined as a return of apomorphine-induced rotations.

Animals↗

Chronic treatment with levodopa and/or selegiline does not affect behavioral recovery induced by fetal ventral mesencephalic grafts in unilaterally 6-hydroxydopamine-lesioned rats.

It has been suggested that levodopa (L-dopa), a dopamine precursor used to treat Parkinson's disease, may be toxic to grafted fetal neuroblasts; if so, the use of the monoamine oxidase B inhibitor selegiline might prevent such toxicity. We randomly assigned 30 unilaterally 6-hydroxydopamine-lesioned male Sprague-Dawley rats, whose lesions were verified with low-dose apomorphine-induced rotations, to one of five treatment groups: (i) L-dopa methyl ester (125 mg/kg/day) with benserazide (a peripheral decarboxylase inhibitor; 25 mg/kg/day), (ii) L-dopa methyl ester with benserazide and selegiline (L-deprenyl; 0.5 mg/kg/day), (iii) selegiline only, (iv) and (v) vehicle (ascorbate in normal saline) only. After 2 weeks of twice-daily ip injections, the rats received fetal ventral mesencephalic grafts into the lesioned striatum; one vehicle group received sham grafts. Drug therapy was continued for 2 1/2 months post grafting. At 1 month after grafting, and every 2 weeks thereafter, the rats were tested using low-dose apomorphine-induced rotation. A 70% decrease in rotations among all grafted groups, relative to the shams, was found. No statistical differences among groups receiving various drug therapies were seen in behavior or in counts or dimensions of tyrosine hydroxylase-positive cells. We therefore conclude that, in the unilaterally lesioned rat model of Parkinson's disease, there is no adverse effect of L-dopa nor any significant effect of selegiline, either alone or coadministered with L-dopa, on behavioral recovery induced by fetal ventral mesencephalic grafts.

Animals↗