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Heterogeneity and probabilistic binding contributions to receptor-mediated cell detachment kinetics.

Biospecific cell adhesion is mediated by receptor-ligand bonds. Early theoretical work presented a deterministic analysis of receptor-mediated cell attachment and detachment for a homogeneous cell population. However, initial comparison of a deterministic framework to experimental detachment profiles of model "cells" (antibody-coated latex beads) did not show qualitative or quantitative agreement (Cozens-Roberts, C., D.A. Lauffenburger, and J.A. Quinn. 1990. Biophys. J. 58:857-872). Hence, we determine the contributions of population heterogeneity and probabilistic binding to the detachment behavior of this experimental system which was designed to minimize experimental and theoretical complications. This work also corrects an error in the numerical solution of the probabilistic model of receptor-mediated cell attachment and detachment developed previously (Cozens-Roberts, C., D.A. Lauffenburger, and J.A. Quinn. 1990. Biophys J. 58:841-856). Measurement of the population distribution of the number of receptors per bead has enabled us to explicitly consider the effect of receptor number heterogeneity within the cell-surface contact area. A deterministic framework that incorporates receptor number heterogeneity qualitatively and quantitatively accounts in large part for the model cell detachment data. Using measured and estimated parameter values for the model cell system, we estimate that about 90% of the observed kinetic detachment behavior originates from heterogeneity effects, while about 10% is due to probabilistic binding effects. In general, these relative contributions may differ for other systems.

Biophysical Phenomena↗

Dynamical chaos determines the variability of transcranial Doppler signals.

In order to estimate whether or not the variability of a timeseries of transcranial Doppler (TCD) waveforms is the result of a random or a deterministic process the following study was designed. From eight normal volunteers the middle cerebral artery blood flow velocities were measured for 50 sec and the maximum blood flow velocities (or waveforms) were analysed. From these waveforms socalled attractors were reconstructed and shown in a two dimensional phase portrait. The attractor of the TCD timeseries shows the entire range of states the cardiovascular system can display. The geometric structure of the attractor can be estimated by calculation of the correlation dimension D2. The correlation dimension D2 shows that the time evolution of the TCD timeseries is essentially nonperiodic and can be characterized by low dimensional chaos. It has been shown that the D2 value during hypocapnia has a significant higher value compared to the D2 values during normocapnia. The biological and clinical significance of these observations are outlined.

Adult↗

Physical causality and brain theories.

The history of deterministic theories in physics is reviewed, and four levels of determinism are found: 1) absolute, 2) asymptotic, 3) probabilistic, and 4) absolute indeterminism. Nagel's view that all causal laws are deterministic in the frame of the state descriptions to which they refer is acknowledged, but the inevitability of macroscopic measurement noise may hint that dynamical laws are innately noisy. Quantum mechanical effects are not the noise source. Symmetry and broken symmetry are introduced as physical concepts that can account both for lawfulness, and for the hierarchical nature of the universe. Physical ideas are chosen over those of formal systems with indirect self-reference as the basis of a global theory of brains. By exclusion it is concluded that only a statistical thermodynamics, combined with nonlinear mechanics, has the features needed for theorizing about brains in a physical sense. Quantum mechanics is judged not to be relevant. New statistical thermodynamic theories are briefly described, and their strengths and weaknesses noted. The question, "Why should neuroscience look to physics for its theories?" is raised and answered. Some concrete objectives for a program of theoretical research are stated.

Brain↗

A dynamic mechanical model for hand force in right angle nutrunner operation.

A deterministic mechanical model based on physical tool parameters was used for estimating static and dynamic hand forces from kinematic measurements. We investigated the effects of target torque (25, 40, and 55 Nm) and threaded fastener joint hardness (35-, 150-, 300-, 500-, and 900-ms torque buildup time) on hand force. Estimated hand force was affected by target torque and joint hardness. Peak and average dynamic hand force was least for the hard joint (35-ms buildup) and greatest for the medium hardness joint (150-ms buildup). Tool inertia played the major role in reducing hand reaction force. Estimated hand force decreased when the inertial force component increased. Inertial force decreased by 366% when buildup time increased from 35 to 300 ms. Static modeling overestimated hand force; the error ranged from 10% for a soft joint to 40% for a hard joint. Results from direct hand force measurements using a strain gauge dynamometer showed that the dynamic model overestimated peak hand force by 9%. However, average hand force and force impulse were not significantly overestimated.

Hand Strength↗

Efficiency of multistage marker-assisted selection in the improvement of multiple quantitative traits.

The application of marker-assisted selection (MAS) to breeding programmes depends on its relative cost and the expected economic return compared to conventional phenotypic selection. The relative efficiency of MAS can be increased through a two-stage selection scheme or through marker-based, multiple-trait improvement. However, the effectiveness of these alternatives has not been quantified. In this study, we evaluate the efficiency of MAS relative to conventional phenotypic selection and marker-only selection in multistage selection for the improvement of multiple traits. We further incorporate the costs of obtaining measurements on phenotypic characters and marker loci into the objective function to evaluate the efficiency of MAS with respect to the gain per unit cost. Deterministic analyses indicate that excluding costs, multiple-trait MAS can be used to increase the aggregate breeding values in quantitative characters and is expected to be more effective than conventional selection or single-trait MAS. Two-stage MAS has a slightly reduced gain because of culling in the first stage. If the objective function is to maximize the gain per unit cost, multiple-trait MAS is inferior to phenotypic selection in most of the selection schemes investigated when the cost ratio (r) of obtaining measurements on phenotypic characters to scoring marker loci is less than unity (r < or = 1.0) and the heritability (h2) is greater than 0.3. The efficiency of MAS increases as r increases and h2 decreases. For MAS to be more effective, it is necessary to decrease further the cost associated with molecular marker assays.

Chromosome Mapping↗

Risk prevention and policy-making in automatic systems.

Accidents with automatic production systems are reported to be on the order of one in a hundred or thousand robot-years, while fatal accidents are found to occur one or two orders of magnitude less frequently. Traditions in occupational safety tend to seek for safety targets in terms of zero severe accidents for automatic systems. Decision-making requires a risk assessment balancing potential risk reduction measures and costs within the cultural environment of a production company. This paper presents a simplified procedure which acts as a decision tool. The procedure is based on a risk concept approaching prevention both in a deterministic and in a probabilistic manner. Eight accident scenarios are shown to represent the potential accident processes involving robot interactions with people. Seven prevention policies are shown to cover the accident scenarios in principle. An additional probabilistic approach may indicate which extra safety measures can be taken against what risk reduction and additional costs. The risk evaluation process aims at achieving a quantitative acceptable risk level. For that purpose, three risk evaluation methods are discussed with respect to reaching broad consensus on the safety targets.

Accidents, Occupational↗

Radiation protection recommendations as applied to the disposal of long-lived solid radioactive waste. ICRP Publication 81.

The present publication deals with the radiological protection of members of the public following the disposal of long-lived solid radioactive waste using the 'concentrate and retain' strategy. It covers options including shallow land burial and deep geological disposal. The recommendations made in this report apply to new disposal facilities.The main protection issue concerns exposure that may or may not occur in the far future, i.e. a situation of potential exposure. Constrained optimisation is the central approach to evaluating the radiological acceptability of a waste disposal system. In this context optimisation of protection is a judgmental process with social and economic factors being taken into account and should be conducted in a structured essentially qualitative way.Two broad categories of exposure situations have to be considered: natural processes and human intrusion. Application of the radiological protection criteria to these two categories of exposure situations is different.In the first case, assessed doses or risks arising from natural processes should be compared with a constraint of no more than about 0.3 mSv per year or its risk equivalent of around 10(-5) per year. With regard to human intrusion, understood here as inadvertent human intrusion, the consequences from one or more plausible stylised scenarios should be considered in order to evaluate the resilience of the repository to such events. The Commission considers that in circumstances where human intrusion could lead to doses to those living around the site sufficiently high that intervention on current criteria would almost always be justified, reasonable efforts should be made at the repository development stage to reduce the probability of human intrusion or to limit its consequences. In this respect, the Commission has previously advised that an existing(1) annual dose of around 10 mSv per year may be used as a generic reference level below which intervention is not likely to be justifiable. Conversely, an existing(1) annual dose of around 100 mSv per year may be used as a generic reference level above which intervention should be considered almost always justifiable. Similar considerations apply in situations where the thresholds for deterministic effects in relevant organs are exceeded.The conclusion of the report is that in the Commission's view, provided reasonable measures have been taken both to satisfy the constraint for natural processes and to reduce the probability or the consequences of inadvertent human intrusion, and technical and managerial principles have been followed, then radiological protection requirements can be considered to have been complied with.

Journal Article↗

Analysis of growth kinetics by division tracking.

Cell division tracking using fluorescent dyes, such as carboxyfluorescein diacetate succinimidyl ester, provides a unique opportunity for analysis of cell growth kinetics. The present review article presents new methods for enhancing resolution of division tracking data as well as derivation of quantities that characterize growth from time-series data. These include the average time between successive divisions, the proportion of cells that survive and the proliferation per division. The physical significance of these measured quantities is interpreted by formulation of a two-compartment model of cell cycle transit characterized by stochastic and deterministic cell residence times, respectively. The model confirmed that survival is directly related to the proportion of cells that enter the next cell generation. The proportion of time that cells reside in the stochastic compartment is directly related to the proliferation per generation. This form of analysis provides a starting point for more sophisticated physical and biochemical models of cell cycle regulation.

Cell Count↗

Nonlinear noise reduction using reference data.

We introduce a method to clean uncorrelated deterministic and stochastic noise components from time series. It combines recently developed techniques for nonlinear projection with properties of the wavelet transform to extract noise in state space. The method requires that time series are generated by a dynamical system which is at least approximately deterministic and that they are recorded together with a reference signal. Its efficiency was tested on both simulated signals and measured magnetic fields of the heart. Convincing results are obtained even at low signal-to-noise ratios.

Journal Article↗

Computer simulation of the effectiveness of male-linked translocations for the control of Anopheles albimanus Wiedemann.

A deterministic simulation model was used to establish the potential value of releasing male-linked translocation heterozygotes as a control measure for Anopheles albimanus Wiedemann. Theoretical population reductions exceeding 90% were obtained within 90 and 120 days after releases at initial ratios of 5 translocation males (TM): 1 normal male (NM) and 1 TM: 1 NM, respectively. Additional simulations emphasized the importance of the need for a method that would eliminate females from the release material. Releases containing 15% females were less effective than those with none. When a malaria subroutine was included in the model, the calculations showed that all the theoretical releases greatly reduced the number of malaria-infective females and therefore would have a profound effect on transmission of the disease. The number of malaria-infective females present was eliminated completely when only translocation males were released; however, a small number were present when the releases contained 15% females. Male-linked translocation males required longer periods of time to bring about population control than males that were completely sterile.

Animals↗

Linear birefringence of the central human cornea.

PURPOSE: To determine the polarization properties of the central cornea at perpendicular incidence in a normal human population on the assumption that the cornea behaves as a linear retarder. METHODS: A corneal polarimeter provided a view of the fourth Purkinje image of a yellow (585 nm) light-emitting diode through crossed polarizers and a variable retarder. The Purkinje image was extinguished by adjusting the fast axis and retardance of the retarder to match the slow axis and double-pass retardance of the cornea. Both eyes of 73 normal subjects (49 women, 24 men; ages, 21-71 years) were measured. Correlations were expressed as Pearson's r. RESULTS: In most corneas the slow axis pointed nasally downward, with the peak of the axis distribution falling between 10 degrees and 20 degrees nasally downward. Double-pass corneal retardance varied widely (range, 0-250 nm); 80% of retardance values were uniformly distributed from 40 to 140 nm. Retardance was moderately correlated with axis (r approximately 0.5), such that weaker retardance was associated with axes that were more nasally downward. Corneal birefringence was well correlated between the two eyes of a subject in both axis (r = 0.77) and retardance (r = 0.75). CONCLUSIONS: The variation of corneal birefringence among individuals is substantial enough to produce large, uncontrolled differences in the polarization state of a measuring beam, differences that can introduce variability in newer technologies for ophthalmic diagnosis. The interocular similarity of corneal birefringence suggests deterministic control of corneal development.

Adult↗

Absorbed dose and deterministic effects to patients from interventional neuroradiology.

Following the presentation of radiation-induced skin effects by three patients who had undergone glue embolisation of intracranial arteriovenous malformation (AVM), measurements were made of absorbed dose to the skin of patients undergoing other interventional neuroradiological procedures that involve long fluoroscopy times. The maximum absorbed dose to the skin measured by thermoluminescent dosemeters during these procedures was 4 Gy. From these measurements and from records of fluoroscopy time and the number of digital runs acquired, estimates of the maximum absorbed skin dose were made for the AVM patients. The best estimate of maximum absorbed dose to the skin received by any of the AVM patients during a procedure was 5 Gy, which is consistent with the skin effects presented by the AVM patients, that is temporary epilation and main erythema. Maximum absorbed dose to the skull was estimated to be 45 Gy and to the outer table of the skull 55 Gy. Although it is unlikely that the AVM patients will suffer serious effects from these skin doses, there remains some uncertainty over the risk of long-term effects to the skull. Examination of the fluoroscopy unit showed that the image intensifier was not performing optimally in terms of entrance dose rate and resolution. Replacement of the unit with modern X-ray equipment designed for interventional radiology was prioritized. Operators should be aware of the potential risks to patients from complex interventional neuroradiology procedures and should optimize their procedures to minimize such risks. Patients undergoing prolonged and complex procedures should be counselled regarding the symptoms and risks of large doses of radiation.

Alopecia↗

Nonlinear deterministic analysis of tissue texture: a stereological study on mastopathic and mammary cancer tissue using chaos theory.

Signals from some dynamical systems look like stochastic processes although their latent mechanism is deterministic. When such systems show sensitive dependence on small changes of initial conditions, they are denoted as deterministic chaos. Motivated by recent advances in statistical inference methods for chaotic systems and by the concept of spatial chaos, we present a deterministic approach to the study of epithelial tissue texture. Methods for estimation of the autocorrelation function, for evaluation of the power spectrum, for attractor reconstruction, for estimation of the Lyapunov exponent and of the correlation dimension, and for the generation of surrogate data sets are outlined. In our biological example, these methods are applied to 20 cases of mastopathy as compared to 20 cases of mammary cancer. The input signals for the analysis were estimates of epithelial fraction measured at low magnification within 5100 equally spaced line segments per case perpendicular to an arbitrarily directed axis. The results suggest the existence of a low-dimensional deterministic attractor in mastopathic tissue texture, which is replaced by coloured noise in the majority of mammary carcinomas. Biological mechanisms for this finding and scale effects are discussed, and some methodological aspects and possible extensions of our approach are outlined.

Breast Neoplasms↗

Nonlinear noise reduction for electrocardiograms.

The electrical activity of the heart usually shows dynamical behavior which is neither periodic nor deterministically chaotic: The interbeat intervals seem to contain a random component. Although long term predictions are thus impossible, good predictions can be made for times smaller than one heart cycle. This fact is used in order to suppress measurement errors by a local geometric projection method which was originally developed for chaotic signals. The result constitutes evidence that techniques of time series analysis based on chaos theory can be useful despite the fact that very few natural phenomena have been actually established to be deterministically chaotic. (c) 1996 American Institute of Physics.

Journal Article↗

Application of the new MultiTrans SP3 radiation transport code in BNCT dose planning.

Dose planning in boron neutron capture therapy (BNCT) is a complex problem and requires sophisticated numerical methods. In the framework of the Finnish BNCT project, new deterministic three-dimensional radiation transport code MultiTrans SP3 has been developed at VTT Chemical Technology, based on a novel application of the tree multigrid technique. To test the applicability of this new code in a realistic BNCT dose planning problem, cylindrical PMMA (polymethyl-methacrylate) phantom was chosen as a benchmark case. It is a convenient benchmark, as it has been modeled by several different codes, including well-known DORT and MCNP. Extensive measured data also exist. In this paper, a comparison of the new MultiTrans SP3 code with other methods is presented for the PMMA phantom case. Results show that the total neutron dose rate to ICRU adult brain calculated by the MultiTrans SP3 code differs less than 4% in 2 cm depth in phantom (in thermal maximum) from the DORT calculation. Results also show that the calculated 197Au(n,gamma) and 55Mn(n,gamma) reaction rates in 2 cm depth in phantom differ less than 4% and 1% from the measured values, respectively. However, the photon dose calculated by the MultiTrans SP3 code seems to be incorrect in this PMMA phantom case, which requires further studying. As expected, the deterministic MultiTrans SP3 code is over an order of magnitude faster than stochastic Monte Carlo codes (with similar resolution), thus providing a very efficient tool for BNCT dose planning.

Adult↗

Orderliness of hormone release.

ApEn, approximate entropy, is a recently formulated family of parameters and statistics quantifying regularity (orderliness) in serial data, with developments both within theoretical mathematics, as well as numerous applications to multiple biological contexts. ApEn appears to have broad application to hormone pulsatility analysis within endocrinology, bringing a new perspective to the assessment of secretory patterns. ApEn is complementary to pulse detection algorithms widely employed to evaluate hormone secretion time-series--it is scale-invariant and model-independent, evaluates both dominant and subordinant patterns in data, discriminates series for which clear pulse recognition is difficult, and often provides a direct barometer of feedback between subsystems. ApEn is applicable to systems with at least 50 data points and to broad classes of models: it can be applied to discriminate both general classes of correlated stochastic processes, as well as noisy deterministic systems. Moreover, ApEn is complementary to spectral and autocorrelation analyses, providing effective discriminatory capability in instances in which the aforementioned measures exhibit minimal distinctions. We present some basic background on the above, and illustrate various facets of ApEn utility via several representative endocrinological studies.

Animals↗

A stochastic model for the development of an AIDS epidemic in a heterosexual population.

A non-age-dependent model, describing the evolution of a bisexual population, is developed in this paper and applied to projecting an AIDS epidemic in a heterosexual population. Included in the formulation are frequency- and non-frequency-dependent rules of partnership formation as well as five states of HIV disease, affecting the probability of infection per sexual contact. Results from computer experiments, designed to study the development of an AIDS epidemic in a heterosexual population fed by single males with a 50% prevalence of HIV infection prior to becoming active in heterosexual partnerships, are reported. In these experiments, the only source of HIV infection for females was sexual contacts with infected males within partnerships. Data on the probability of infection per sexual contact with an infected partner and the number of sexual contacts per month were incorporated into the model. However, the numbers used for the initial population of singles, couples, and those becoming sexually active per month were hypothetical. Even though the prevalence of HIV infection among males entering heterosexual partnerships was high, after 30 years the projected prevalence of HIV infection among females ranged from about 10 to 15% depending in part on the expected duration of partnerships and on whether the frequency- or non-frequency-dependent model was used. In these experiments, solutions of the embedded, nonlinear, deterministic equations for the incidence of HIV infection and the cumulative number of deaths due to AIDS proved to be good measures of central tendency for the sample functions of the stochastic population process.

Acquired Immunodeficiency Syndrome↗

A Powerful Algorithm to aid Cardiac Arrhythmia Diagnosis.

The Electrocardiogram (ECG), represents the electrical activity of the heart. It is characterised by a number of waves P, QRS, T which are correlated to the status of the heart activity. In this paper, the aim is to present a powerful algorithm to aid cardiac diagnosis. The approach used is based on a determinist method, that of the tree decision. However, the different waves of the ECG signal need to be identified and then measured following a signal to noise enhancement. Signal to noise enhancement is performed by a combiner linear adaptive filter whereas P, QRS, T wave identification and measurement are performed by a derivative approach. Results obtained on simulated and real ECG signals are shown to be highly, satisfactory in the aid of cardiac arrhythmia diagnosis, such as junctionnal escapes, blocks, etc.

Journal Article↗