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Postural control in children with spastic diplegia: muscle activity during perturbations in sitting.

To clarify the neural mechanisms controlling equilibrium during sitting, and the implications for the optimal sitting position for children with CP, automatic postural adjustments after perturbations of the support surface during sitting were investigated in seven children with spastic diplegia and in seven age-matched controls. A sudden backward sway of the body evoked brisk responses in ¿ventral' muscles in both groups. However, the order of muscle recruitment, which in most non-disabled children was caudal, was reversed in the children with diplegia, whose first response was in the neck flexors. The children with diplegia also co-activated antagonistic neck and hip muscles. The authors concluded that although children with spastic diplegia may produce a basic muscle activation pattern (first level of the central pattern generator, CPG), they cannot adjust the pattern in response to external changes (second level of the CPG).

Cerebral Palsy↗

Kinetic characterization of [125I] iodo-prolactin in binding to primary monolayer cultures of rabbit mammary epithelium.

Monocellular suspensions of epithelial cells from mammary glands of rabbits at 20-22 days of pregnancy were prepared by sequential dissociation with collagenase-hyaluronidase followed by Pronase. Maintenance in D-valine-substituted minimum essential medium (D-valine-MEM) supplemented with 10% dialyzed calf serum yielded monolayers enriched for rabbit mammary epithelial cells (RMEC). RMEC specifically and reversibly bound bovine PRL with Ka = 1.41-1.85 x 10(9)M-1. Association of lactogen with RMEC receptor followed bimolecular reaction kinetics with rate of 5.17 (+/- 0.75) x 10(5)M-1 sec-1 at 24 C, and 1.03 (+/- 0.11) x 10(6)M-1 sec-1 at 37 C. Dissociation was first order (K-1 = 5.97 (+/- 0.70) x 10(-5) sec-1) and was unaffected by the presence of lactogen. Specific binding determined with an excess of unlabelled bPRL was 66-77% of the total binding, and was optimal at pH 7.4. The binding reaction reached equilibrium in 2 h at 37 C, in 3 h at 24 C, and after 24 h at 4 C. Studies of binding capacity revealed the presence of 4.6-6.3 x 10(3) sites per cell, competition for which was limited to hormones demonstrating lactogenic activity. Recovered lactogen was not degraded by incubation with or dissociation from RMEC. Approximately 25% of the radioactivity remained associated with the cells even upon prolonged incubation. These studies demonstrated several advantages of RMEC for the investigation of hormone-receptor interaction and receptor regulation.

Animals↗

The saturable high affinity association of factor X to ADP-stimulated monocytes defines a novel function of the Mac-1 receptor.

Initiation of the coagulation protease cascade as it assembles on cell surfaces requires limited proteolytic activation of the zymogen factor X. Not previously suspected to be the ligand of an organizing receptor on cell surfaces, we now describe that factor X specifically associates with cells of monocyte lineage and we identify the high affinity receptor for this zymogen. Following stimulation with ADP (10 microM), or with the ionophore ionomycin (1 microM), isolated human monocytes bind 125I-factor X in a saturable fashion with a dissociation constant (Kd) of 21.8-44.9 nM. Equilibrium binding analyses indicate that the reaction is optimal at room temperature, requires Ca2+ ions, and saturates at 128,500 +/- 21,300 molecules of 125I-factor X specifically associated with the cell surface. Molar excess of unlabeled factor X inhibits and reverses the binding, whereas the homologous gamma-carboxylated coagulation proteins factors II, VII, IX, IXa, and Xa are without effect. Similarly, chelation of divalent ions immediately dissociates bound 125I-factor X. The monoblast cell line U 937 and the monocytic cell line THP-1 when stimulated with ADP or ionomycin, bind 125I-factor X with characteristics similar to monocytes. Receptor identity was explored using antibodies to the leukocyte adhesive receptors Mac-1, LFA-1, and p150.95. Monoclonal antibodies specific for the alpha subunit of Mac-1 (M 1/70, LM 2/1) or for the common beta subunit (TS 1/18, 60.3) bound equally to resting and ADP- or ionomycin-stimulated cells and also completely blocked the binding of 125I-factor X to stimulated monocytes, U 937, or THP-1 cells. To distinguish between modulatory effects of the monoclonal antibodies and direct spatial hindrance binding of 125I-factor X to Mac-1 was analyzed directly. OKM10 anti-alpha subunit of Mac-1 monoclonal antibody immunoprecipitated 125I-factor X chemically cross-linked to its receptor on stimulated cells. In addition, the complement protein fragment C3bi, which is a recognized ligand for Mac-1, competitively inhibited the association of 125I-factor X. These findings indicate that human blood monocytes and less differentiated cells of this lineage possess an inducible receptor specific for factor X; and also support the conclusion that the heterodimeric leukocyte adhesive receptor Mac-1 functions as the specific receptor structure. We suggest that the novel properties of this receptor may be of importance in the organization and regulation of certain coagulation protease cascades on the monocyte surface.

Adenosine Diphosphate↗

Coordination between equilibrium and hand trajectories during whole body pointing movements.

We examined the coordination between equilibrium and voluntary pointing movements executed from the standing position, using the whole body. It has previously been shown that trunk movement has little effect upon kinematic characteristics of hand pointing when movements are executed in the sitting position. The present study asked if elements of hand trajectory are modified by requirements of large trunk displacements and fine equilibrium control when pointing movements are executed from the standing position. To achieve this, center of pressure (CoP) and center of mass (CoM) displacements were analyzed along with the kinematics of the pointing hand. Results showed that the CoM was not stabilized (it displaced between 23% and 61+/-21% of the foot's length), confirming that instead of a compensation of mechanical perturbations due to arm and trunk movements, the present equilibrium strategy consisted of controlling CoM acceleration towards the target. Hand paths were curved and were not distance or speed invariant. Rather than simple inefficiencies in programming or execution, path curvature suggested that different hand movement strategies were chosen as a function of equilibrium constraints. In light of these results, we hypothesize that postural stability may play a role in the generation of hand trajectory for complex, whole-body pointing movements, in addition to constraints placed upon end-effector kinematics or the dynamic optimization of upper-limb movements. A dependent regulation of equilibrium and spatial components of the movement is proposed.

Acoustic Stimulation↗

A noisy self-organizing neural network with bifurcation dynamics for combinatorial optimization.

The self-organizing neural network (SONN) for solving general "0-1" combinatorial optimization problems (COPs) is studied in this paper, with the aim of overcoming existing limitations in convergence and solution quality. This is achieved by incorporating two main features: an efficient weight normalization process exhibiting bifurcation dynamics, and neurons with additive noise. The SONN is studied both theoretically and experimentally by using the N-queen problem as an example to demonstrate and explain the dependence of optimization performance on annealing schedules and other system parameters. An equilibrium model of the SONN with neuronal weight normalization is derived, which explains observed bands of high feasibility in the normalization parameter space in terms of bifurcation dynamics of the normalization process, and provides insights into the roles of different parameters in the optimization process. Under certain conditions, this dynamical systems view of the SONN reveals cascades of period-doubling bifurcations to chaos occurring in multidimensional space with the annealing temperature as the bifurcation parameter. A strange attractor in the two-dimensional (2-D) case is also presented. Furthermore, by adding random noise to the cost potentials of the network nodes, it is demonstrated that unwanted oscillations between symmetrical and "greedy" nodes can be sufficiently reduced, resulting in higher solution quality and feasibility.

Electricity↗

Desiccation tolerance of recalcitrant Theobroma cacao embryonic axes: the optimal drying rate and its physiological basis.

Recalcitrant seed axes were reported to survive to lower water contents under fast-drying conditions. The present study was to examine the hypothesis that drying rate and dehydration duration could interact to determine desiccation tolerance through different physico-chemical mechanisms. The effect of drying rate on desiccation tolerance of Theobroma cacao seed axes at 16 degrees C was examined. Rapid-drying at low relative humidity (RH) and slow-drying at high RH were more harmful to cocoa axes, because electrolyte leakage began to increase and axis viability began to decrease at high water contents. Maximum desiccation tolerance was observed with intermediate drying rates at RH between 88% and 91%, indicating the existence of an optimal drying rate or optimal desiccation duration. This maximum level of desiccation tolerance for cocoa axes (corresponding to a critical water potential of -9 MPa) was also detected using the equilibration method, in which axes were dehydrated over a series of salt solutions or glycerol solutions until the equilibrium. These data confirmed that the physiological basis of the optimal drying rate is related to both mechanical stress during desiccation and the length of desiccation duration during which deleterious reactions may occur. The optimal drying rate represents a situation where combined damages from mechanical and metabolic stresses become minimal.

Adaptation, Physiological↗

Perfection of a synaptic receptor: kinetics and energetics of the acetylcholine receptor.

The energetics and kinetics of activation of the acetylcholine receptor are evaluated in the context of optimizing rapid synaptic transmission. Physiological needs are used as the basis for estimating optimal values for the closed-to-open channel equilibrium constants of the liganded and unliganded receptor. An estimate is made of the maximum energy that can be derived from the binding of acetylcholine to a perfectly designed receptor binding site. Application of the principle of detailed balance shows that with only one ligand binding site the receptor will not be able to derive enough energy from acetylcholine binding to drive a sufficiently large change in the channel conformational equilibrium. This then provides a rationale for the existence of a second binding site, rather than the often invoked advantage of cooperativity. With two binding sites there is a considerable excess of binding energy and consequently considerable flexibility in how binding energy can be utilized. It is shown that the receptor must have at least one binding site that binds acetylcholine weakly when the channel is closed. This is essential to rapid response termination. However, making the other binding site bind more tightly can enhance and accelerate the activation of the receptor. To optimize both response activation and termination the best solution is to make the two binding sites different in their binding affinities. This qualitatively reproduces an experimental observation.

Calorimetry↗

Context-dependent reflex control: some insights into the role of balance.

Recent research suggests that the balance requirements of a task dictate the reflexive response. However, these observations were inferred indirectly from either different tasks or different phases of the same task. This study directly tested the hypothesis of balance-dependent control during recovery from an unexpected trip. The subjects were tripped in two different support conditions: unilimb support (provided by the stance limb) or trilimb support (provided by the stance limb and both arms placed on adjacent parallel bars). The subjects exhibited anticipatory changes: they biased the body center of mass toward the support limb in the mediolateral direction and elevated the swing limb higher when there was a possibility of being tripped. The electromyographic (EMG) latencies were not influenced by the threat to equilibrium. The magnitudes of the EMG reflexive response to the trip were clearly modulated as a function of the threat to stability, not in a simple manner, but rather in a complex manner, which optimized the recovery strategy. It is evident that the overriding concern, equilibrium control during locomotion, has a dominant influence on reflex modulation.

Adaptation, Physiological↗

Inverse analyses of transport of chlorinated hydrocarbons subject to sequential transformation reactions.

Chemical and biological transformations can significantly affect contaminant transport in the subsurface. To better understand such transformation reactions, an equilibrium-nonequilibrium sorption transport model, HYDRUS-1D, was modified by including inverse solutions for multiple breakthrough curves resulting from the transport of solutes undergoing sequential transformations. The inverse solutions were applied to miscible-displacement experiments involving dissolved concentrations of trichloroethylene (TCE) undergoing reduction and/or transformations in the presence of zero-valent metal porous media (i.e., iron or copper-coated iron filings) to produce ethylene. The inverse model solutions provided a reasonable description of the transport and transformation processes. Simultaneous fitting of multiple breakthrough curves of TCE and ethylene placed additional constraints on the inverse solution and improved the reliability of parameter estimates. Confidence intervals of optimized parameters were reduced significantly in comparison with those obtained by fitting TCE breakthrough curves independently. Further evidence for accurate parameter estimates was given when the parameter values agreed with previously reported values from independent batch and degradation experiments. Optimized values of the normalized degradation rates for the equilibrium (1.4 x 10(-4) to 7.2 x 10(-5) L h(-1)m(-2)) and nonequilibrium (1.2 x 10(-4) to 5.5 x 10(-5)L h(-1)m(-2)) models compared well with values (0.03 to 6.5 x 10(-5) L h(-1) m(-2)) obtained from previous studies. The estimated TCE-iron sorption coefficients (0.52 to 2.85 L kg(-1)) were also consistent with a previously reported value (1.47 L kg(-1)).

Biotransformation↗

Optimal harvesting and stability for a two-species competitive system with stage structure.

In this paper, we consider a stage-structured competitive population model with two life stages, immature and mature, with a mature population of harvesting. We obtain conditions for the existence of a globally asymptotically stable positive equilibrium and a threshold of harvesting for the mature population. The optimal harvesting of the mature population is also considered.

Animals↗

The role of packaging film permselectivity in modified atmosphere packaging.

Modified atmosphere packaging (MAP) is commercially used to increase the shelf life of packaged produce by reducing the produce respiration rate, delaying senescence, and inhibiting the growth of many spoilage organisms, ultimately increasing product shelf life. MAP systems typically optimize O(2) levels to achieve these effects while preventing anaerobic fermentation but fail to optimize CO(2) concentrations. Altering film permselectivity (i.e., beta, which is the ratio of CO(2)/O(2) permeation coefficients) could be utilized to concurrently optimize levels of both CO(2) and O(2) in MAP systems. We investigated the effect of modifying film permselectivity on the equilibrium gas composition of a model MAP produce system packaged in containers incorporating modified poly(ethylene) ionomer films with CO(2)/O(2) permselectivites between 4-5 and 0.8-1.3. To compare empirical to calculated data of the effect of permselectivity on the equilibrium gas composition of the MAP produce system, a mathematical model commonly used to optimize MAP of respiring produce was applied. The calculated gas composition agreed with observed values, using empirical respiration data from fresh cut apples as a test system and permeability data from tested and theoretical films. The results suggest that packaging films with CO(2)/O(2) permselectivities lower than those commercially available (<3) would further optimize O(2) and CO(2) concentration in MAP of respiring produce, particularly highly respiring and minimally processed produce.

Carbon Dioxide↗

Natural selection on multivariate traits in age-structured populations.

The theory of selection on multivariate traits in age-structured populations has important implications for empirical and theoretical studies of life-history evolution. A model of natural selection on a set of correlated quantitative traits with age structure is derived here, using an extension of previous work on selection at a single locus. This formulation provides an equation for the change of the mean of a vector of traits that is accurate is selection is weak, and does not require the population always to be in demographic equilibrium as selection proceeds. The treatment is extended to density-dependent populations, and to equilibrium populations under frequency-dependent selection. In addition, further approximations are derived that produce evolutionary equilibria equivalent to those predicted by optimization and evolutionarily stable strategy (ESS) theory. It is shown that the conditions for equilibrium are valid even if selection is strong.

Aging↗

First-pass myocardial perfusion imaging and equilibrium signal changes using the intravascular contrast agent NC100150 injection.

In this phase I clinical study, the new ultrasmall superparamagnetic iron oxide contrast agent, NC100150 Injection (Nycomed AS, Oslo, Norway, a part of Nycomed Amersham), was assessed for first-pass magnetic resonance myocardial perfusion studies and its ability to produce equilibrium signal changes, as a possible indicator of myocardial blood volume. Data were acquired in 18 healthy male volunteers at 0.5 T and 1.5 T. At both field strengths, first-pass studies using T1-weighted sequences were acquired. Long TE spin-echo echoplanar imaging (EPI) was used at 0.5 T and short TE fast low-angle shot (FLASH) imaging at 1.5 T. With both sequences, T1 effects dominated the images for low doses, and time intensity curves potentially suitable for perfusion analysis were generated. At higher doses, T2 and T2* effects were observed. At 1.5 T, these predominantly affected the blood pool signal; however, at 0.5 T the myocardial signal was also involved, reflecting the relative T2 and T2* sensitivity of the spin-echo EPI sequence as a result of the long TE and long readout window, respectively. Equilibrium changes were assessed at both field strengths using T1-weighted FLASH sequences and in addition at 1.5 T using T2*-weighted gradient-echo EPI. With the T1-weighted images at both field strengths, signal changes were observed in all subjects; however, no dose-response relationship could be shown. With the T2*-weighted EPI there was significantly lower signal (P < 0.05) with the 3 and 4 mg/kg doses than with the 2 mg/kg dose. In conclusion, NC100150 Injection is useful for first-pass myocardial perfusion using T1-weighted sequences; however, low doses in combination with short TE sequences are required to minimize sensitivity to T2* effects. Equilibrium signal changes can also be induced in the myocardium. More work is required to optimize the imaging sequences and dose of NC100150 Injection for first-pass studies and also to determine whether the equilibrium signal changes can be used to measure myocardial blood volume changes in ischemic heart disease.

Adult↗

Glucocorticoid receptors: evidence for a second, non-glucocorticoid binding site.

Previous studies on cytoplasmic glucocorticoid receptors and enzyme induction led to the classification of steroids as inducers (optimal or sub-optimal), antagonists, or inactive steroids, with respect to their activity as glucocorticoids. The receptor was postulated to exist in allosteric equilibrium between two conformational states, one "active" and the other "inactive". Steroids behaved as inducers (optimal or sub-optimal), antagonists, or inactive steroids depending on their relative affinity for the active and inactive conformational state of the receptor. Another possible model would invoke multiple binding sites on a single receptor with interactions between the binding sites depending upon the particular steroid bound. To test this latter possibility, an experimental technique was developed to measure the rate of dissociation of tritiated dexamethasone ([3H]DM) or tritiated aldosterone ([3H]A) from the glucocorticoid receptor of rat liver or kidney cytosol. The dissociation of the [3H]DM-receptor at 25 C was not due to irreversible denaturation, and minimal recombination of the receptor with [3H]DM occurred. Progesterone and a number of other steroids consistently and significantly increased the dissociation rate of [3H]DM-receptor complexes in both liver and kidney cytosol. An identical effect was seen with hepatic glucocorticoid receptors labelled with [3H]A, like dexamethasone an optimal inducer. All steroids which enhanced glucocorticoid-receptor dissociation were either antagonists or sub-optimal inducers. Thus, it is postulated that glucocorticoid receptors have at least two classes of binding sites, and that occupation of the second site increases the dissociation rate of agonists from glucocorticoid receptors.

Aldosterone↗

Metabolic control of respiratory neuronal activity and the accompanying changes in breathing movements of the rabbit. III. Phase shifts in respiratory neurons induced by inflation and collapse of the lung, hyperventilation, or metabolic modifiers.

Phase shifts between inspiratory-related and expiratory-related discharge patterns can be reversibly induced in respiratory neurons following volume changes of the lung, hypocapnic apnea as a result of hyperventilation, or superfusion with certain metabolic modifiers. Phase-spanning expiratory-inspiratory or inspiratory-expiratory discharges are frequently induced in those neurons which are activated either by pulmonary stretch receptors or collapse afferents. The same is true for regulatory effectors which activate key steps of the neuronal metabolism such as ADP, 3-phosphoglycerate, L-glutamine, fructose-6-phosphate and fructose-1,6-diphosphate. In contrast, inhibitory vagal inputs or superfusion with citrate, an inhibitory metabolic modifier, revert preexisting expiratory-inspiratory discharges into a phase-coupled inspiratory pattern. It is postulated that the respiratory neuronal networks represents a time-optimal control system which strives to adjust to a new equilibrium value in a minimum of time, following a given mechanical or chemical perturbation. Following the hypothesis advanced by Cohen (1974) that the phase-spanning units modulate the activity of the in-phase neurons, it is suggested that the additional recruitment of expiratory-inspiratory and inspiratory-expiratory units provides a measure of the quality of time-optimal control and hence a performance index of the system.

Animals↗

Thyrotropin binding to porcine thyroid plasma membranes: kinetic and thermodynamic analyses.

Evaluation of TSH binding to plasma membranes of porcine thyroid revealed unique sensitivity to pH and temperature. Analysis of apparent equilibrium binding yielded a linear Scatchard plot at the optimal pH of 6.0, indicating one class of binding sites. At physiological pH 7.4 a curvilinear Scatchard plot was obtained, resolved by computer analysis into two classes of binding sites of different affinities and capacities. Treatment of membranes with phospholipase C resulted in a 20% decrease in the number of high affinity sites, but no change occurred in binding affinity. In contrast, low affinity sites were not altered. To evaluate the significance of the curvilinear Scatchard plot, the kinetics of association were examined. The intrinsic Kd (kd/ka) was 0.20 nM, a value essentially equivalent to that of the high affinity binding component. The 'negative cooperativity' model of hormone binding was evaluated by examining the effect of excess unlabeled TSH on dissociation rate. Dissociation of bound 125I-labeled TSH was biphasic, and was enhanced by unlabeled hormone, regardless of whether the membranes were prelabeled at pH 6.0 or 7.4. This effect was not correlated with curvilinear Scatchard plots, and therefore not proof of negative cooperativity. Binding sites for TSH were further distinguished by their sensitivity to temperature. A van't Hoff plot of temperature dependence of the apparent Kd of the high affinity site was linear from 4 to 37 degrees C. In contrast, the apparent Kd of low affinity binding did not vary with respect to temperature. These results demonstrate that there are at least two independent binding sites for TSH on porcine thyroid plasma membranes, distinguishable by their equilibrium binding properties.

Animals↗

Dynamic contrast-enhanced CT of the liver: comparison of contrast medium injection rates and uniphasic and biphasic injection protocols.

To determine the effect of contrast medium injection rate and biphasic versus uniphasic bolus on hepatic parenchymal enhancement at computed tomography (CT), 105 patients were randomized into four protocols. Hepatic and aortic enhancement curves were measured for each protocol. The optimal scanning interval (the duration between onset of a desired hepatic enhancement threshold and decline of enhancement below the threshold or onset of the equilibrium phase) and contrast enhancement index (CEI) (area under the hepatic enhancement curve above a desired threshold during the nonequilibrium phase) were the primary determinants of merit. Measurements were performed at hepatic enhancement thresholds between 10 and 60 HU. At most thresholds of hepatic enhancement, optimal scanning intervals were significantly longer and CEIs were significantly higher for the biphasic protocols than for the uniphasic protocols (P < .03). A biphasic injection with a high initial flow rate produces high peak contrast enhancement but delayed onset of equilibrium and thus provides a longer optimal scanning interval.

Adult↗

Biodegradable dextran-based microspheres for delivery of anticancer drug mitomycin C.

The purpose of this work was to develop a biodegradable microsphere (MS) system for delivering mitomycin C (MMC). Various dextran-based MS systems were investigated for their loading and release characteristics, including nonionic MS, sulfopropyl dextran microspheres (SP-MS) with low or high cross-linking density, oxidized SP-MS (Ox-MS), and hydrophobically modified SP-MS. SP-MS were chemically modified by oxidation with sodium periodate or by reaction with anhydride. The chemical structure of modified SP-MS and MMC-loaded MS (MMC-MS) were examined using Fourier transform infrared (FTIR) and solid-state nuclear magnetic resonance (NMR) spectrophotometry. Drug release was conducted at 37 degrees C in aqueous solutions of 0.15 m phosphate buffer solution. The kinetics of drug absorption and release and the stability of MMC after loading and release were determined by spectrophotometry and high-performance liquid chromatography. Ionic SP-MS exhibited a higher drug-loading rate and capacity when compared to nonionic MS, while hydrophobically modified SP-MS showed an even greater loading capacity than SP-MS. These results suggest that both ionic complexation and hydrophobic interaction were important factors in MMC loading. The Ox-MS system demonstrated higher drug-loading capacity, more fractional drug release and a longer time to reach release equilibrium as compared to other investigated MS systems. Under optimized reaction and loading conditions, MMC released from Ox-MS was found to be unaltered. This work demonstrates that the Ox-MS system is a potentially useful system for the delivery of MMC.

Absorbable Implants↗