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Examining affinities of the Taung child by developmental simulation.

As a well-preserved juvenile and the type specimen of Australopithecus africanus, the Taung child figures prominently in taxonomic, ontogenetic, and phylogenetic analyses of fossil hominins. Despite general agreement about allocation of Sterkfontein and Makapansgat fossils to this species, limited morphological comparisons have been possible between these adult specimens and the juvenile Taung. Here, we used developmental simulation to estimate the adult form of the Taung child, and directly compare its morphology to that of other fossil hominins. Specimens were represented by 50 three-dimensional landmarks superimposed by generalized Procrustes analysis. The simulation process applied developmental trajectories from extant hominine species to the Taung fossil in order to generate its adult form. Despite differences found in the developmental patterns of these modern species, simulations tested on extant juveniles-transforming them into "adults" using trajectories from other species-revealed that these differences have negligible impact on adult morphology. This indicates that morphology already present by occlusion of the first permanent molar is the primary determinant of adult form, thereby supporting use of extant trajectories to estimate the morphology of an extinct species. The simulated Taung adult was then compared to other adult fossils. As these comparisons required assumptions about the pattern and magnitude of developmental change, additional analyses were performed to evaluate these two parameters separately. Results of all analyses overwhelmingly rejected the possibility that the Taung child was a juvenile robust australopith, but were consistent with the hypothesis that the Taung and Sterkfontein fossils are conspecific. Between Sts 5 and Sts 71, the latter is more likely to resemble the adult form of the Taung child.

Animals↗

Effect of pressure on the conformation of proteins. A molecular dynamics simulation of lysozyme.

The effect of pressure on the structure and mobility of lysozyme was studied by molecular dynamics computer simulation at 1 and 3 kbar (1 atm = 1.01325 bar = 101.325 kPa). The results have good agreement with the available experimental data, allowing the analysis of other features of the effect of pressure on the protein solution. The studies of mobility show that although the general mobility is restricted under pressure this is not true for some particular residues. From the analysis of secondary structure along the trajectories it is observed that the conformation under pressure is more stable, suggesting that pressure acts as a 'conformer selector' on the protein. The difference in solvent-accessed surface (SAS) with pressure shows a clear inversion of the hydrophilic/hydrophobic SAS ratio, which consequently shows that the hydrophobic interaction is considerably weaker under high hydrostatic pressure conditions.

Carbon↗

Quantifying in vivo MR spectra with circles.

Accurate and robust quantification of in vivo magnetic resonance spectroscopy (MRS) data is essential to its application in research and medicine. The performance of existing analysis methods is problematic for in vivo studies where low signal-to-noise ratio, overlapping peaks and intense artefacts are endemic. Here, a new frequency-domain technique for MRS data analysis is introduced wherein the circular trajectories which result when spectral peaks are projected onto the complex plane, are fitted with active circle models. The use of active contour strategies naturally allows incorporation of prior knowledge as constraint energy terms. The problem of phasing spectra is eliminated, and baseline artefacts are dealt with using active contours-snakes. The stability and accuracy of the new technique, CFIT, is compared with a standard time-domain fitting tool, using simulated 31P data with varying amounts of noise and 98 real human chest and heart 31P MRS data sets. The real data were also analyzed by our standard frequency-domain absorption-mode technique. On the real data, CFIT demonstrated the least fitting failures of all methods and an accuracy similar to the latter method, with both these techniques outperforming the time-domain approach. Contrasting results from simulations argue that performance relative to Cramer-Rao Bounds may not be a suitable indicator of fitting performance with typical in vivo data such as these. We conclude that CFIT is a stable, accurate alternative to the best existing methods of fitting in vivo data.

Artifacts↗

An improved technique for the extraction of stochastic parameters from stabilograms.

An improved characterization of the dynamics of postural sway can provide a better understanding about the functional organization of the postural control system as well as a more robust tool for postural pattern recognition. To this aim, a novel parameterization was applied to the stabilogram diffusion analysis formerly proposed by Collins and De Luca [Collins JJ, De Luca CJ. Open-loop and closed-loop control of posture: a random-walk analysis of center-of-pressure trajectories. Exp Brain Res 1993;95:308-18] that considered the act of maintaining posture as a stochastic process. The main purpose of the present technique was to overcome some drawbacks of the model presented by Collins and De Luca that may restrain its potential application in clinical practice. The approach uses a unique non-linear model to describe the center of pressure (COP) dynamics that reduces the number of parameters and decreases their intra-subject variability; consequently, fewer trials are required to perform reliable estimates of stochastic parameters and this is of particular importance for subjects that cannot afford many repeated measurements because of age or pathology. Four new statistical mechanics parameters (NSMP) were computed on the log-log stabilogram diffusion plots and their estimates were compared in terms of reliability and sensitivity to the visual conditions with: (1) a minimal set of four summary statistic scores (SSS); and (2) the six statistical mechanics parameters (SMP) proposed by Collins and De Luca. All four NSMP showed at least a fair-to-good reliability (intraclass correlation coefficient, ICC>0.49) while SMP (ICC>0.20) showed some poor reliability. A better overall reliability was also observed with respect to SSS. Moreover, only NSMP had a similar score for eyes open and eyes closed conditions. Three out of four NSMP were also significantly sensitive to eyes open or closed conditions (P<0.001) while only three out of six SMP were sensitive to operating conditions (P<0.01).

Humans↗

Structure and dynamics of a DNA.RNA hybrid duplex with a chiral phosphorothioate moiety: NMR and molecular dynamics with conventional and time-averaged restraints.

The three-dimensional structure of two thiophosphate-modified DNA.RNA hybrid duplexes d(GCTATAApsTGG).r(CCAUUAUAGC), one with R-thiophosphate chirality and one with S-thiophosphate chirality, have been determined by restrained molecular dynamics simulations (rMD). As the two yielded almost identical results, a description of results can be presented in the singular. The conformational flexibility of this hybrid has been investigated by employing time-averaged constraints during the molecular dynamics simulations (MD-tar). A set of structural restraints, comprising 322 precise interproton distance constraints obtained by a complete relaxation matrix analysis of the 2D NOE intensities as well as J coupling constants obtained from quantitative simulations of DQF-COSY cross-peaks in deoxyriboses, was reported in our previous paper [González, C., Stec, W., Kobylanska, A., Hogrefe, R. I., Reynolds, M., & James, T. L. (1994) Biochemistry 33, 11062-11072]. Multiple conformations of the deoxyribose moieties were evident from the scalar coupling constant analysis. Accurate distance constraints, obtained from complete relaxation matrix analysis, yielded a time-averaged solution structure via conventional restrained molecular dynamics which is not compatible with the experimental J coupling constants (root-mean-square deviation in J value approximately 2 Hz). However, vicinal coupling constant information can be reproduced when time-averaged constraints are used during the molecular dynamics calculations instead of the conventional restraints (Jrms approximately 0.6 Hz). MD-tar simulations also improve the NMR R factors. This improvement is more evident in the DNA than in the RNA strand, where no indication of conformational flexibility had been obtained. Analysis of the MD-tar trajectories confirms that deoxyriboses undergo pucker transitions between the S and N domain, with the major conformer in the S domain. The ribose moieties in the RNA strand, however, remain in the N domain during the entire simulation. Conformations of deoxyriboses in the intermediate domain near O4'-endo are obtained when the average structure is calculated with conventional NMR restraints. Since these conformations cannot account for the experimental J coupling information, and they only appear in a very low population in the MD-tar ensemble, we conclude that intermediate E sugar puckers are artifacts produced by the attempt to fit all the structural constraints simultaneously when in reality more than one conformer is present. Most structural features of the duplex remain the same in the average structure and in the MD-tar ensemble, e.g., the minor groove width, exhibiting an intermediate value compared with those of canonical A- and B-like structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Structural fluctuation and dynamics of ribose puckering in aqueous solution from first principles.

Using the method of ab initio molecular dynamics, we examine the structural fluctuation and the low-frequency dynamics of beta-ribofuranose puckering in aqueous solution. Our analysis suggests that the distance between the anomeric and hydroxymethyl oxygens is a simple relevant geometrical parameter that dynamically correlates with the phase angle in the north region. The time-frequency analysis using the Hilbert-Huang transform also confirms the correlation, and most of the instantaneous frequencies for the phase angle and the above distance are found to be concentrated on the region below about 100 cm(-1). Our analysis of ab initio molecular dynamics trajectories suggests that the molecular origin of the hydration effects on the low-frequency dynamics of beta-ribofuranose puckering is closely related to this correlation and thus primarily attributed to the relatively local interactions among the anomeric and hydroxymethyl oxygens and the surrounding water molecules near them. Additionally, we discuss the difference in the low-frequency dynamics of beta-ribofuranose puckering between two hydroxymethyl rotamers.

Computer Simulation↗

Combinatorial explosion in model gene networks.

The explosive growth in knowledge of the genome of humans and other organisms leaves open the question of how the functioning of genes in interacting networks is coordinated for orderly activity. One approach to this problem is to study mathematical properties of abstract network models that capture the logical structures of gene networks. The principal issue is to understand how particular patterns of activity can result from particular network structures, and what types of behavior are possible. We study idealized models in which the logical structure of the network is explicitly represented by Boolean functions that can be represented by directed graphs on n-cubes, but which are continuous in time and described by differential equations, rather than being updated synchronously via a discrete clock. The equations are piecewise linear, which allows significant analysis and facilitates rapid integration along trajectories. We first give a combinatorial solution to the question of how many distinct logical structures exist for n-dimensional networks, showing that the number increases very rapidly with n. We then outline analytic methods that can be used to establish the existence, stability and periods of periodic orbits corresponding to particular cycles on the n-cube. We use these methods to confirm the existence of limit cycles discovered in a sample of a million randomly generated structures of networks of 4 genes. Even with only 4 genes, at least several hundred different patterns of stable periodic behavior are possible, many of them surprisingly complex. We discuss ways of further classifying these periodic behaviors, showing that small mutations (reversal of one or a few edges on the n-cube) need not destroy the stability of a limit cycle. Although these networks are very simple as models of gene networks, their mathematical transparency reveals relationships between structure and behavior, they suggest that the possibilities for orderly dynamics in such networks are extremely rich and they offer novel ways to think about how mutations can alter dynamics. (c) 2000 American Institute of Physics.

Journal Article↗

A consensus view of protein dynamics.

The dynamics of proteins in aqueous solution has been investigated through a massive approach based on "state of the art" molecular dynamics simulations performed for all protein metafolds using the four most popular force fields (OPLS, CHARMM, AMBER, and GROMOS). A detailed analysis of the massive database of trajectories (>1.5 terabytes of data obtained using approximately 50 years of CPU) allowed us to obtain a robust-consensus picture of protein dynamics in aqueous solution.

Computational Biology↗

Predictors of transitions in vitality: the italian longitudinal study on aging.

It is widely acknowledged that there is a strong need to identify which modifiable risk factors predict healthy aging to use this information as the scientific basis for systematic interventions. Data from a 4-year longitudinal study on aging among 5632 older Italians were used. The definition of vitality was based on both cognitive and physical status, and the envisaged transitions were: positive or nonpositive stable, positive or negative transition, lost, and deceased. Predictors associated with different vitality trajectories were investigated by multinomial logistic analysis with a six-level outcome. Age and educational level were predictors of being "positive stable," whereas the other factors behaved differently according to comparison group. For example, being overweight is a common predictor except when compared to the deceased group, as is depressive symptomatology except when compared to the "positive transition" group. Interventions are warranted to reduce social inequalities, promote adequate body weight, and prevent and treat depressive symptoms.

Aged↗

Nonlinear analysis of autonomic responses in a therapist during psychotherapy.

An experienced, analytically trained psychotherapist was physiologically monitored while conducting a 28-session exploratory psychotherapy with a patient suffering a pathological grief reaction. The therapist's autonomic responses, as manifested by perturbations in heart rate, were subjected to nonlinear dynamical analysis, yielding a series of characteristic "trajectories" representing the flow of these responses in time. We report interrater reliability and present descriptive statistics resulting from classifying these trajectories into four types. Interesting but preliminary clinical correlates of these autonomic trajectories were obtained by having the therapist review videotaped excerpts of the sessions and complete a self-report questionnaire. In conjunction with a previous report focusing on autonomic responses in the patient, this study further demonstrates the application of nonlinear dynamical methods to investigations of psychophysiology in the setting of psychotherapy, and perhaps in dyadic interactions more generally.

Adult↗

Entropic analysis of biological growth models.

Using the concept of isomorphism, we provide a quantitative description of the thermodynamic characteristics of the Logistic, Bertalanffy, and Gompertz biological growth models. With the help of the entropy expressions derived from the isomorphic probabilistic models, we show that the Logistic, Bertalanffy, and Gompertz growth models have distinct thermodynamic characteristics, though they have similar sigmoid trajectories in the time domain. The entropic analysis further reveals that the Gompertz model corresponds to a completely open system, in which cells receive adequate nutrition and competition among cells can be neglected. We have also applied the present entropic analysis to the modeling of tumor growth. Our results suggest that the entropic expression provides a theoretical justification for using the Gompertz model for describing the development of tumor cell populations. The entropic analysis may play an important role in studying the mechanisms of different biological growth processes.

Animals↗

Functional electrical stimulation using microstimulators to correct foot drop: a case study.

This paper presents a case study that tested the feasibility and efficacy of using injectable microstimulators (BIONs) in a functional electrical stimulation (FES) device to correct foot drop. Compared with surface stimulation of the common peroneal nerve, stimulation with BIONs provides more selective activation of specific muscles. For example, stimulation of the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles with BIONs produces ankle flexion without excessive inversion or eversion of the foot (i.e., balanced flexion). Efficacy was assessed using a 3-dimensional motion analysis of the ankle and foot trajectories during walking with and without stimulation. Without stimulation, the toe on the affected leg drags across the ground. BION stimulation of the TA muscle and deep peroneal nerve (which innervates TA and EDL) elevates the foot such that the toe clears the ground by 3 cm, which is equivalent to the toe clearance in the less affected leg. The physiological cost index (PCI) measured effort during walking. The PCI equals the change in heart rate (from rest to activity) divided by the walking speed; units are beats per metre. The PCI is high without stimulation (2.29 +/- 0.37, mean +/- SD) and greatly reduced with surface (1.29 +/- 0.10) and BIONic stimulation (1.46 +/- 0.24). Also, walking speed increased from 9.4 +/- 0.4 m/min without stimulation to 19.6 +/- 2.0 m/min with surface and 17.8 +/- 0.7 m/min with BIONic stimulation. These results suggest that FES delivered by a BION is an alternative to surface stimulation and provides selective control of muscle activation.

Adult↗

Distributed population mechanism for the 3-D oculomotor reference frame transformation.

Human saccades require a nonlinear, eye orientation-dependent reference frame transformation to transform visual codes to the motor commands for eye muscles. Primate neurophysiology suggests that this transformation is performed between the superior colliculus and brain stem burst neurons, but provides little clues as to how this is done. To understand how the brain might accomplish this, we trained a 3-layer neural net to generate accurate commands for kinematically correct 3-D saccades. The inputs to the network were a 2-D, eye-centered, topographic map of Gaussian visual receptive fields and an efference copy of eye position in 6-dimensional, push-pull "neural integrator" coordinates. The output was an eye orientation displacement command in similar coordinates appropriate to drive brain stem burst neurons. The network learned to generate accurate, kinematically correct saccades, including the eye orientation-dependent tilts in saccade motor error commands required to match saccade trajectories to their visual input. Our analysis showed that the hidden units developed complex, eye-centered visual receptive fields, widely distributed fixed-vector motor commands, and "gain field"-like eye position sensitivities. The latter evoked subtle adjustments in the relative motor contributions of each hidden unit, thereby rotating the population motor vector into the correct correspondence with the visual target input for each eye orientation: a distributed population mechanism for the visuomotor reference frame transformation. These findings were robust; there was little variation across networks with between 9 and 49 hidden units. Because essentially the same observations have been reported in the visuomotor transformations of the real oculomotor system, as well as other visuomotor systems (although interpreted elsewhere in terms of other models) we suggest that the mechanism for visuomotor reference frame transformations identified here is the same solution used in the real brain.

Feedback↗

Changes in flagellar bending during the course of hyperactivation in hamster spermatozoa.

The motility pattern of mammalian spermatozoa changes during migration in the female genital tract and during incubation in vitro. This change in motility is termed hyperactivation. Hyperactivated spermatozoa swim vigorously in 'whiplash', 'figure-8' or 'small circle' trajectories. In this study, a quantitative analysis was carried out of the changes in the motility pattern of hamster spermatozoa during incubation to investigate the mechanism regulating hyperactivation. In the culture system used in this study, hyperactivation occurred 4 h after incubation. Several parameters in the analysis of sperm movement pattern were examined. Curvilinear velocity, average path velocity and straightness abruptly increased between 2 and 4 h. However, linearity, amplitude of lateral head displacement, beat cross frequency and average wavelength gradually changed with time. In the analysis of flagellar bending, the bend angles were measured after dividing images of the flagellum into short lengths. Flagellar bending changed in different manners in each region during incubation. The asymmetry in the direction of the curve of the head gradually increased with time in the first half of the flagellum. The flexibility, which was determined using the amplitude of bending and the rate of change in bend angles, abruptly decreased between 10 min and 1 h, and then increased between 2 and 4 h in the first half of flagellum. These results indicate that complex physiological changes occur before hyperactivation.

Animals↗

The excitator as a minimal model for the coordination dynamics of discrete and rhythmic movement generation.

The authors identify a class of excitable two-dimensional model systems, the excitators, that provide an entry point to the understanding of the mechanisms of discrete and rhythmic movement generation and a variety of related phenomena, such as false starts and the geometry of phase space trajectories. The starting point of their analysis is the topological properties of the phase flow. In particular, the phenomenon of false starts provides a characteristic structural condition for the phase flow, the separatrix, which partitions the phase space. Threshold phenomena, which are characteristic of excitable systems, as well as stable and unstable fixed points and periodic orbits, are discussed. Stable manifolds in the proximity of fixed points, resulting in an overshoot and a slow return phase after movement execution, are predicted in the analysis. To investigate coordination phenomena, the authors discuss the effects of two types of couplings, the sigmoidal coupling and a truncated version thereof, known as the Haken-Kelso-Bunz (HKB) coupling. They show analytically and numerically that the sigmoidal coupling leads to convergence phenomena in phase space, whereas the HKB coupling displays convergent as well as divergent behaviors. The authors suggest a specific representation of the excitator that allows the quantification of the predictions.

Humans↗

Human arm movements described by a low-dimensional superposition of principal components.

A new method for analyzing kinematic patterns during smooth movements is proposed. Subjects are asked to move the end of a two-joint manipulandum to copy a smooth initial target path. On subsequent trials the target path is the subject's actual movement from the preceding trial. Using Principal Components Analysis, it is shown that the trajectories have very low dimension and that they converge toward a linear superposition of the first few principal components. We show similar results for handwriting on an electronic pen tablet. We hypothesize that the low dimensionality and convergence are attributable to combined properties of the internal controller and the musculoskeletal system. The low dimensionality may allow for efficient descriptions of a large class of arm movements.

Arm↗

[Video technology of qualitative control of eyeball movements in nystagmus].

A method for controlling voluntary movements of the eye is suggested, based on video-image processing and computer analysis. The program can be used for analysis of eye movements by its trajectory and spectrum. Results of measurements of voluntary movements of the eye in patients with nystagmus are presented. The results of measurements, characterizing the changes in nystagmus before and after operation for strabismus correction are discussed.

Child↗

Kinematics of the wrist. I. An experimental study of radial-ulnar deviation and flexion-extension.

The kinematics of the wrist during radial-ulnar deviation and flexion-extension were studied in several ways. In six fresh cadaver wrists, the forearm was fixed in full pronation, each motion was constrained to one plane, and two metal markers were placed in each of the finger metacarpals, as well as in the radius and all of the carpal bones except the pisiform and greater multangular. Radial ulnar and flexion-extension movements in these wrists were studied roentgenographically. In the wrists of six normal volunteers, a similar roentgenographic analysis was carried out and the trajectories of wrist motions also were studied using light-emitting diodes. Finally, roentgenographic measurements were made on 100 wrists of normal subjects. From these studies, it was concluded that: (1) during each of these motions, rotation occurs about a fixed axis located within the head of the capitate, and the location of each axis is not changed by the position of the hand in either plane; (2) the distance from the base of the third metacarpal to the distal articular surface of the radius (the carpal height), measured along the proximally projected axis of the third metacarpal on posteroanterior roentgenograms, is constant throughout radial-ulnar deviation of the normal wrist and can be used as a measure of carpal collapse; and (3) the perpendicular distance of the fixed axis of rotation for radial-ulnar deviation from the distally projected longitudinal axis of the ulna can be used as a quantitative measurement of the amount of translation of the carpus in pathological conditions.

Biomechanical Phenomena↗