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At least 19 recordsLinked to original sources

A worst-case optimal parameter selection model of cancer chemotherapy.

An optimal parameter selection model of cancer chemotherapy in which two system parameters are unknown is formulated as a worst-case optimal parameter selection model. The model assumes that the unknown parameters lie within a known set. The system constraints must be satisfied over this entire set, and the objective function minimized in the worst case. The continuous dependence of the objective function and the system constraints upon the unknown parameters can be removed, making a numerical solution tractable. For the data considered it is proven that a cure is impossible no matter what the values of the unknown parameters in the parameter set. The optimal policy is shown to be relatively low dose intensity for the majority of the treatment, with the remaining drug delivered towards the end of the treatment interval.

Humans

A parameter optimization approach for the optimal control of large-scale musculoskeletal systems.

This paper describes a computational method for solving optimal control problems involving large-scale, nonlinear, dynamical systems. Central to the approach is the idea that any optimal control problem can be converted into a standard nonlinear programming problem by parameterizing each control history using a set of nodal points, which then become the variables in the resulting parameter optimization problem. A key feature of the method is that it dispenses with the need to solve the two-point, boundary-value problem derived from the necessary conditions of optimal control theory. Gradient-based methods for solving such problems do not always converge due to computational errors introduced by the highly nonlinear characteristics of the costate variables. Instead, by converting the optimal control problem into a parameter optimization problem, any number of well-developed and proven nonlinear programming algorithms can be used to compute the near-optimal control trajectories. The utility of the parameter optimization approach for solving general optimal control problems for human movement is demonstrated by applying it to a detailed optimal control model for maximum-height human jumping. The validity of the near-optimal control solution is established by comparing it to a solution of the two-point, boundary-value problem derived on the basis of a bang-bang optimal control algorithm. Quantitative comparisons between model and experiment further show that the parameter optimization solution reproduces the major features of a maximum-height, countermovement jump (i.e., trajectories of body-segmental displacements, vertical and fore-aft ground reaction forces, displacement, velocity, and acceleration of the whole-body center of mass, pattern of lower-extremity muscular activity, jump height, and total ground contact time).

Adult

MRDagent: iterative and adaptive parameter optimization for stable ctDNA-based MRD detection in heterogeneous samples.

MOTIVATION: Minimal residual disease (MRD) as critical biomarker for cancer prognosis and management plays a crucial role in improving patient outcomes. However, detecting MRD via next-generation sequencing-based circulating tumor DNA variant calling remains unstable due to the extremely low variant allele frequency and significant inter- and intra-sample heterogeneity. Although parameter optimization can theoretically enhance the detection performance of variants, achieving stable MRD detection remains challenging due to three key factors: (i) the necessity for individualized parameter tuning across numerous heterogeneous genomic intervals within each sample, (ii) the tightly interdependent parameter requirements across different stages of variant detection workflows, and (iii) the limitations of current automated parameter optimization methods. RESULTS: In this study, we propose MRDagent, a novel variant detection tool designed specifically for MRD detection. MRDagent incorporates an iterative and self-adaptive optimization framework capable of handling unknown objectives, varying constraints, and highly coupled parameters across stages. A key innovation of MRDagent is the integration of a convolutional neural network-based meta-model, trained on historical data to enable rapid parameter prediction. This significantly enhances computational efficiency and generalization performance. Extensive evaluations on simulated and real-world datasets demonstrate MRDagent's superior and stable performance, providing an efficient, reliable solution for MRD detection in clinical and high-throughput research applications. AVAILABILITY AND IMPLEMENTATION: MRDagent is freely available at https://github.com/aAT0047/MRDagent.git. The corresponding dataset and software archive are available at Zenodo: https://doi.org/10.5281/zenodo.15458496.

Circulating Tumor DNA

Parameter optimization model of learning in stepping motion.

In this study we combine the representation of motion by a finite number of hardwired functions with parameter optimization to model learning during a stepping motion. Representation of experimental kinematic data by a finite number of predetermined functions and undetermined coefficients was analyzed. Least squares approximation was used to represent experimental data of stepping motions over obstacles of different heights. Functional relationships between coefficients and obstacles heights were also obtained. Learning of stepping over an obstacle was then formulated as a finite dimensional optimization problem. The pattern of foot path, and joint angles trajectories obtained by this learning model, were then compared to the experimental data. The results of the data fitting analysis and of the optimization process as a model for motion learning, indicate that motion can be adequately represented by a set of hardwired functions, and a finite number of task dependent coefficients.

Humans

Blood pressure levels and variance assessed by ambulatory monitoring: optimal parameters.

We obtained multiple ambulatory blood pressure monitoring (ABPM) records over five years from two trained, normotensive subjects experienced in wearing the apparatus. The resulting time series data on systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were used to suggest optimal parameters for monitoring by two instruments (Colin Medical Instruments ABPM-630 and Del Mar Avionics Pressurometer) and to compare two indirect methods (auscultatory and oscillometric). A 10-min sampling interval day and night provided sufficient density of data to support spectral analysis for ultradian rhythms in the frequency range of one cycle per hour to one cycle per 9 h on a 24-h record. Rhythms with major periods of approximately 3, 6, and 9 h were variously found in 94 normotensive subjects, aged 20 to 95 years, including the two trained subjects. When the monitoring period was extended to 72 h, the circadian (approximately 24 h) rhythm could be more sharply defined, as well as a 12-h harmonic. In some studies the two trained subjects wore two monitors, one on each arm, set to read simultaneously. From the simultaneous measurements on both arms, it was shown that averaging across three points (30 min of record) reduced the coefficient of variation between the two simultaneous records to 6% or less. Auscultatory and oscillometric methods were equally reliable. Echocardiographic data were obtained in five normotensive subjects and compared to their ABPM data. The ABPM records provided additional information about cardiovascular function not merely duplicating that obtained by acute stress tests, such as exercise or cold pressor responses, or echocardiography. Standards for ABPM are suggested.

Adult

Optimal parameters for eliciting cardio-acceleration by electrical stimulation of the ventromedial hypothalamus.

The ventromedial hypothalamus of the unrestrained cat was stimulated electrically through permanent electrodes. The stimulation parameters, amplitude, duration and frequency of the square wave pulses were combined to produce a 20% increase of the resting heart rate value. The total electric charge for each parametric combination was calculated. The charge per stimulation (10 s) varied from about 1 to 100 micro-coulombs, depending on the parametric combination used. The response could therefore not be expressed as a function of the charge but depended on the individual parametric combinations. The relation among the stimulation parameters and the total amount of electric charge of the pulses was estimated by the correlation technique. The results suggested that about 60% of the variation in the electric charge resulting in the constant response was due to the variation of the pulse repetition frequency. The optimal parameters for eliciting cardio-acceleration in the cat by stimulation of the ventromedial hypothalamus seem to be pulse durations between 0.1 and 0.5 ms and pulse repetition frequencies below 100 P/s, with pulse amplitude as the dependent variable.

Animals

Optimal parameters for CO2 laser reconstruction of urethral tissue using a protein solder.

This study was designed to determine the optimal laser parameters for welding urethral tissue and to develop further understanding of the welding process. A partial transection of the pendulous rat urethra was repaired using laser powers of 80, 120, and 160 milliwatts with shutter speeds of 50 milliseconds, 100 milliseconds, and in a continuous wave mode. Repairs were made using the laser alone and the laser plus a protein solder. Measurements of intraluminal bursting strength, percentage stricture and histology were performed. The highest bursting strength with the least amount of tissue damage was achieved using a power of 120 milliwatts with 100 milliseconds pulses and the addition of a protein solder. The average percentage stricture was lowest with the laser plus solder repair (4.2%) when compared to laser only repair (14%). Intraluminal bursting strength was similar in both types of repairs. Histology demonstrated marked changes in collagen organization after laser application in all models.

Analysis of Variance

[The evolutionarily optimal rates of body development. The age of onset of sexual maturity and species-specific longevity as the parameters optimized during evolution].

Dynamics of biological community of the "resource--consumer" type considering age structure of consumer population is described by a system of differential equations with special derivatives. On the basis of such a model, a competition model for non-crossing populations with different individual development rates is elaborated. It is shown that only a population with development rates maximizing the Malthusian function (reaching zero value at the equilibrium state of the system) is able to survive under competition for food resources. Equilibrium density of the resources is provided being minimal. Thus maximum energy influx into the population is gained. Search algorithm of evolutionary values of puberty, age and maximal longevity of individuals belonging to the consumer population is proposed. Analytic dependence of maximal longevity on environmental factors and some other parameters are found. Aging is considered to be mechanism leading to death while individual approaches evolutionary optimal longevity.

Animals

Learning-related patterns of CA1 spike trains parallel stimulation parameters optimal for inducing hippocampal long-term potentiation.

Recent studies have revealed 3 stimulation parameters that together comprise the temporal pattern of neuronal activation optimal for the induction of hippocampal LTP: high-frequency bursts, activity 100-200 ms prior to a burst, and burst delivery in phase with the ongoing hippocampal theta rhythm. The present paper reports that these 3 aspects of patterned neural activity, collectively referred to as "theta-bursting," are characteristic of the spike trains of CA1 pyramidal cells in rats during the sampling and analysis of learning cues in an odor discrimination task and during performances of a spatial memory task. In contrast, theta-bursting occurs relatively infrequently during behavioral events less directly related to task-relevant mnemonic processing. These findings suggest that the optimal conditions for the induction of LTP occur naturally in behaving animals, time-locked to behavioral events critical to learning.

Animals

Optimal parameters for the histochemical demonstration of acetylcholinesterase in plastic sections of rat brain.

A modified method for improved preservation and optical resolution of acetylcholinesterase (AChE)-containing structures in adult rat brain is described. Optimal tissue preparation included fixation in paraformaldehyde 4%, glutaraldehyde 0.1%, and sucrose 7% in 0.1M Sorensen's phosphate buffer, pH 7.4, rinsing in buffer 50 mM with respect to NH4Cl and 2% with respect to sucrose, acetone dehydration, vacuum infiltration with LKB Historesin, and polymerization at 4 C, overnight incubation of 10 microns sections at 37 C in the AChE histochemical reaction mixture and silver intensification according to Hedreen et al. Demonstration of AChE enzyme activity in the cholinergic projection from the rat basal forebrain to the ipsilateral hippocampus exemplifies the usefulness of the technique. The method provides an excellent demonstration of AChE-positive axonal processes and enables the pharmacohistochemical visualization of cholinergic neurons. This procedure offers a convenient method for analysis of cholinergic neurons that avoids potential artifacts inherent in other AChE histochemical procedures.

Acetylcholinesterase

Electroporation of rat pituitary (GH) cell lines: optimal parameters and effects on endogenous hormone production.

An efficient electroporation procedure was established for the genetic transformation of two clonal strains of hormone producing rat pituitary cells (GH12C1 and GH3). We used the bacterial chloramphenicol acetyltransferase (CAT) gene as reporter gene to determine optimal conditions for electroporation. The conditions found to be optimal, measured as expression of the highest CAT activity, were 240-300 V and a DNA concentration of 30-60 micrograms/ml in sucrose buffer. Cell viability was then about 50 per cent. Maximum CAT activity was seen 24 hours after electroporation. The electroporation procedure, in the presence or absence of DNA, caused a transient decrease in endogenous growth hormone (GH) and prolactin (PRL) production.

Animals

Optimizing parameters for correlative immunogold localization by video-enhanced light microscopy, high-voltage transmission electron microscopy, and field emission scanning electron microscopy.

Correlative video-enhanced light microscopy, high-voltage transmission electron microscopy, and low-voltage high resolution scanning electron microscopy were used to examine the binding of colloidal gold-labeled fibrinogen to platelet surfaces. Optimal conditions for the detection of large (18 nm) and small (3 nm) gold particles are described.

Blood Platelets

Global parameter optimization for cardiac potassium channel gating models.

Quantitative ion channel model evaluation requires the estimation of voltage dependent rate constants. We have tested whether a unique set of rate constants can be reliably extracted from nonstationary macroscopic voltage clamp potassium current data. For many models, the rate constants derived independently at different membrane potentials are not unique. Therefore, our approach has been to use the exponential voltage dependence predicted from reaction rate theory (Stevens, C. F. 1978. Biophys. J. 22:295-306; Eyring, H., S. H. Lin, and S. M. Lin. 1980. Basic Chemical Kinetics. Wiley and Sons, New York) to couple the rate constants derived at different membrane potentials. This constrained the solution set of rate constants to only those that also obeyed this additional set of equations, which was sufficient to obtain a unique solution. We have tested this approach with data obtained from macroscopic delayed rectifier potassium channel currents in voltage-clamped guinea pig ventricular myocyte membranes. This potassium channel has relatively simple kinetics without an inactivation process and provided a convenient system to determine a globally optimized set of voltage-dependent rate constants for a Markov kinetic model. The ability of the fitting algorithm to extract rate constants from the macroscopic current data was tested using "data" synthesized from known rate constants. The simulated data sets were analyzed with the global fitting procedure and the fitted rate constants were compared with the rate constants used to generate the data. Monte Carlo methods were used to examine the accuracy of the estimated kinetic parameters. This global fitting approach provided a useful and convenient method for reliably extracting Markov rate constants from macroscopic voltage clamp data over a broad range of membrane potentials. The limitations of the method and the dependence on initial guesses are described.

Analysis of Variance

Microinjection into Xenopus oocytes: a precise semi-automatic instrument and optimal parameters for injection of mRNAs.

A new apparatus for the injection of Xenopus oocytes is described which provides semi-automatic cell handling together with highly accurate and reproducible volume delivery. Using the system requires very little skill, yet it gives 6.3% average reproducibility in the 5 to 70 nl volume range. The instrument uses a fixed injector system driven by an Inchworm piezoelectric positioner or, in a low-cost version, by a Rainin EDP-2 battery-operated motorized pipette. A movable, vacuum-operated oocyte holder minimizes lateral movement of the oocyte during injection. Oocytes injected with the system show better survival and enhanced expression of mRNA compared with those injected with a widely used type of manual injector (Coleman, 1984).

Animals

Parameter optimization and calibration of 19F magnetic resonance imaging at 1.5 Tesla.

Fluorine-19 magnetic resonance imaging is limited by the fact that acquisition times are long and that high concentrations must be used in order to obtain good signal to noise. A significant improvement in signal to noise ratio may be brought about by the addition of Gd-DTPA, a paramagnetic agent which shortens T1. Images of phantoms containing trifluoroacetic acid (TFA) doped with Gd-DTPA were obtained using a standard spin echo sequence in a 1.5 T field. Interpulse times (TR and TE) and Gd-DTPA concentrations were optimized to yield maximum signal to noise ratios. The use of fast-field-echo scans to image fluorine is also demonstrated. Signal averaging successive FFE scans yields good signal to noise and resolution and may find clinical applicability in imaging areas subject to motion.

Calibration

[Optimal parameters of carbon dioxide laser irradiation in the prevention and treatment of suppurative-inflammatory surgical diseases in children].

An analysis of experience with using the CO2 laser radiation with power density of 15-60 Wt/cm2 and 100 Wt/cm2 with the purpose in mind to prevent acute inflammatory complications and treat pyo-inflammatory surgical diseases in children. Results of microbiological and histological researches of the laser radiation studied are presented.

Acute Disease