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Fractal analysis of capacitating human spermatozoa.

While head centroid-derived kinematic values have been determined for the trajectories of hyperactivated human spermatozoa, the definitions are not robust with respect to image sampling frequency and track analysis methods. The determination of the fractal dimension of a trajectory has been suggested as an alternative descriptive parameter for hyperactivated motility. Here, we have investigated two methods for the determination of the fractal dimension of a trajectory. A simple but useful equation was found to be: D = log(n)/[log (n + log (d/L)], where the n is the number of intervals in the trajectory, d is the planar extent of the curve and L is the length of the trajectory. This equation was not influenced by scaling of the trajectory. A fractal dimension (D) >=1.30 was found to define hyperactivated trajectories, and D <= 1.20 defined non-hyperactivated trajetories, reconstructed at both 30 and 60 Hz. However, when circling tracks were studied, all had D > 1.30, even though they were classified as non-hyperactivated by curvilinear velocity and/or amplitude of lateral head displacement values. An analysis of a series of non-ideal track segments suggested a relationship between a track's linearity and its fractal dimension. It was determined by a linear regression analysis that the fractal dimension of a trajectory was inversely proportional to its linearity (r = -0.77, P < 0.001). Although the fractal dimension of a trajectory is a good indicator of its regularity (describing its space-filling properties), it should not be used as the sole criterion for the classification of a trajectory as hyperactivated.

Fractals↗

The influence of changes in marital status on developmental trajectories of alcohol use in young adults.

OBJECTIVE: Multiple group latent curve analysis was used to assess the impact of changes in marital status on alcohol use trajectories in young adults and to test if these effects varied across ethnicity and gender. METHOD: Four years of data were obtained from a sample of young adults (N = 4,052; 54% male) drawn from the National Longitudinal Survey of Youth. Alcohol use and marital status were assessed once per year and covariates included age, gender, education and ethnicity. RESULTS: Latent curve models indicated that there was an overall nonlinear negative alcohol use trajectory across the four time points and that becoming married was reliably associated with an added down-turn to this trajectory. Multiple group models indicated that there was an interaction between ethnicity and marital status in the prediction of alcohol growth trajectories, but there was no interaction with gender. CONCLUSIONS: Becoming married for the first time exerted a unique effect on the overall developmental trajectory of alcohol use over time. This effect held for both ethnic groups but was reliably stronger for white compared to black respondents. This interaction may be attributable to lower levels of alcohol use reported by black respondents, or may be related to individual differences in reactivity to social influences by blacks relative to whites.

Adult↗

Transitions between inherent structures in water.

The energy landscape approach has been useful to help understand the dynamic properties of supercooled liquids and the connection between these properties and thermodynamics. The analysis in numerical models of the inherent structure (IS) trajectories-the set of local minima visited by the liquid-offers the possibility of filtering out the vibrational component of the motion of the system on the potential energy surface and thereby resolving the slow structural component more efficiently. Here we report an analysis of an IS trajectory for a widely studied water model, focusing on the changes in hydrogen bond connectivity that give rise to many IS's separated by relatively small energy barriers. We find that while the system travels through these IS's, the structure of the bond network is continuously modified, exchanging linear bonds for bifurcated bonds and usually reversing the exchange to return to nearly the same initial configuration. For the 216-molecule system we investigate, the time scale of these transitions is as small as the simulation time scale ( approximately 1 fs). Hence, for water, the transition between each of these IS's is relatively small and eventual relaxation of the system occurs only by many of these transitions. We find that during IS changes the molecules with the greatest displacements move in small "clusters" of 1-10 molecules with displacements of approximately 0.02-0.2 nm, not unlike simpler liquids. However, for water these clusters appear to be somewhat more branched than the linear "stringlike" clusters formed in a supercooled Lennard-Jones system found by Glotzer and her collaborators.

Journal Article↗

Juvenile drug use and delinquency: youths' accounts of their trajectories.

This study focuses mainly on youths' opinions about their delinquency and drug use trajectories. A qualitative approach was taken for this phenomenological research. The life account method was used to conduct a total of 62 interviews: 36 boys and 26 girls recruited in youth detention and addiction treatment centers, youth centers, high schools, and on the streets of three cities in Quebec between 1996 and 2002. Thematic analysis was used, and the deviant trajectories of the youths are broken down into five stages. Our study provides an incomplete view of these youths' more or less deviant trajectories. It would be interesting to do a follow-up study.

Adolescent↗

Limb movement adaptations in horses with experimentally induced fore- or hindlimb lameness.

The kinematic patterns of all limbs of 11 clinically nonlame Dutch Warmblood horses were studied during induced supporting limb lameness to gain insight into the compensation mechanisms horses use to manage lameness and to test kinematic limb variables for their significance as lameness indicators. Using the locomotion analysis system CODA-3, the kinematics of the horses were recorded while walking (1.6 m/s) and trotting (3.5 m/s) on a treadmill. A transient lameness model, evoking pressure on the hoof sole, was used to induce 3 degrees of fore- and hindlimb lameness. Joint angle patterns and hoof movements were analysed using joint angle/time diagrams and the hoof trajectories in the sagittal plane. Quantitative analysis of 13 selected variables in each limb was done using a 2-way analysis of variance. Hyperextension of the fetlock joint and flexion of the coffin joint during the stance phase decreased significantly (P < 0.05) in the lame limb, both in fore- and hindlimb lameness, at both gaits. In the contralateral nonlame limbs both variables increased compensatorily. Flexion increased with increasing lameness in the proximal joints, i.e. the shoulder joint and even more the tarsal joint of the lame limb. The retraction of both forelimbs decreased during forelimb lameness at the walk, while in the lame hindlimb the protraction decreased. The hoof arcs were lower in the lame limb than in the nonlame limb, due to an increased hoof height in the nonlame limb during forelimb lameness and to a decreased height in the lame limb during hindlimb lameness. It was concluded that patterns of the distal joints reflect the different loadings of the limbs during lameness. Proximal joints acted as load dampers to reduce peak forces in the lame limb. Hyperextension of the fetlock and flexion of the coffin joint proved to be the most sensitive indicators for fore- and hindlimb lameness.

Adaptation, Physiological↗

Stability and control of a frontal four-link biped system.

A conceptual model for studying the involvement of the central nervous system (CNS) in the performance of lateral swaying movements is described. The model is based on a four-link planar biped that approximates gross human locomotion in the frontal plane. The viscoelastic function of the musculoskeletal system provides a linear controller for the system. Such an intrinsic controller can effectively duplicate simple well-learned tasks in the absence of higher level CNS feedback. This hypothesis is supported by comparing the proposed controller with two neurophysiologically involved linear decoupling schemes. Reference trajectories for swaying commands are recorded from experiments conducted in the Gait Analysis Laboratory of the Ohio State University Hospitals. These reference trajectories are inputs to all three controllers. The viability of intrinsic feedback scheme in the execution of swaying tasks is demonstrated via comparison of responses from the three controllers.

Central Nervous System↗

Factors influencing human sperm kinematic measurements by the Celltrak computer-assisted sperm analysis system.

This study examines the effect of varying several factors, both extrinsic and technology-dependent, on the reconstruction of human sperm trajectories and the derived kinematic measurements using videotapes and the Motion Analysis Celltrak/S instrument. In semen samples from normal healthy men, curvilinear (VCL) and straight line velocities (VSL) were found to increase 1.5-fold, and linearity (LIN) of trajectories and amplitude of lateral head displacement (ALH) increased 1.25-fold when the temperature of analysis was raised from 24 to 37 degrees C. Only VCL and VSL were found to increase significantly between 24 and 37 degrees C for sperm samples selected by Percoll gradient and incubated in a capacitating medium. An analysis chamber of 20 microm depth was found to be adequate for seminal sperm samples while for Percoll-selected sperm samples the analysis in a 50 microm depth provided the highest proportions of spermatozoa with the highest VCL and the largest ALH. The grey level detection threshold required careful adjustment: using a threshold lower than the optimal threshold produced spurious sperm trajectories for seminal sperm samples and rejected some trajectories for Percoll-selected sperm samples. Definition of the appropriate frame rate and maximum burst speed was critical for valid trajectory reconstruction and therefore adequate derived kinematic measurements. Optimal values of these parameters were found to be 30 Hz and 400 microm/s for seminal spermatozoa and 60 Hz and 700 microm/s for selected spermatozoa. The optimal values of 'ALH path-smoothing factor' used to calculate average path and ALH were 5-10 points for seminal spermatozoa analysed at 30 Hz and 15-20 points for selected spermatozoa analysed at 60 Hz. We propose a set of standard conditions for reliable kinematic analysis of human spermatozoa using the Celltrak/S system.

Centrifugation, Density Gradient↗

Relationship between PVA and myocardial oxygen consumption can be derived from thermodynamics.

The pressure-volume area (PVA) has been shown to be an excellent, linear index of myocardial oxygen consumption. The thermodynamic basis for this result, however, has not been elucidated. The present study was undertaken to determine what information could be gained from analyzing the cardiac pressure-volume (P-V) cycle as an approximation to some "ideal" thermodynamic cycle operating under the constraints imposed by cardiovascular anatomy and physiology. The myocardium was approximated as a linear, chemically driven elastance in accordance with the time-varying elastance model. Analysis provided descriptions of a Carnot cycle for myocardium and a suboptimal ideal cycle, including isovolumic phases. Further analysis of the ideal cycle indicated that the end-systolic P-V relationship (ESPVR) is an approximation to the adiabatic P-V trajectory that primarily determines total energy consumption. Analysis also indicated possible explanations of current results that seem to be at odds with the time-varying elastance model. These results suggest that thermodynamic cycle analysis may provide a useful analytic tool for investigation of the cardiac cycle.

Animals↗

A model of handwriting.

The research reported here is concerned with hand trajectory planning for the class of movements involved in handwriting. Previous studies show that the kinematics of human two-joint arm movements in the horizontal plane can be described by a model which is based on dynamic minimization of the square of the third derivative of hand position (jerk), integrated over the entire movement. We extend this approach to both the analysis and the synthesis of the trajectories occurring in the generation of handwritten characters. Several basic strokes are identified and possible stroke concatenation rules are suggested. Given a concise symbolic representation of a stroke shape, a simple algorithm computes the complete kinematic specification of the corresponding trajectory. A handwriting generation model based on a kinematics from shape principle and on dynamic optimization is formulated and tested. Good qualitative and quantitative agreement was found between subject recordings and trajectories generated by the model. The simple symbolic representation of hand motion suggested here may permit the central nervous system to learn, store and modify motor action plans for writing in an efficient manner.

Cybernetics↗

Evaluations of combined premotor and supplementary motor cortex lesions on a visually guided arm movement.

The kinematics of a visually guided, multi-joint arm movement were examined before and after combined bilateral premotor and supplementary motor cortex lesions. Two rhesus monkeys were trained to move a manipulandum from a start zone to one of three equally spaced target zones and then return to the initial start zone. Various features of the movement trajectory including space error, time error, peak velocity and turnaround time were quantified and analyzed before and after the premotor and supplementary motor cortex ablations. Statistical analysis showed no major differences in the trajectories toward or away from the target between the pre- and postlesion state. The major difference following the ablation was an increase in the time spent in the target zone, reflecting an increase in time spent in redirecting the trajectory. Normalization of the movement duration revealed a slight delay in the initial part of the movement. These results suggest the premotor and supplementary motor cortex are involved in redirecting the trajectory and/or obtaining the target zone during the execution of a complex movement.

Animals↗

CAFs activated by YAP1 upregulate cancer matrix stiffness to mediate hepatocellular carcinoma progression.

BACKGROUND: The stiffness of the matrix is closely related to the progression of hepatocellular carcinoma (HCC). Although direct targeting of stromal rigidity in HCC remains a clinical challenge, cancer-associated fibroblasts (CAFs) are considered key contributors to this process. Given the heterogeneity of CAFs, this study explored the relationship between specific CAF subsets and liver cancer matrix stiffness, aiming to identify novel therapeutic targets for HCC patients. METHODS: Single-cell sequencing datasets were leveraged to identify cell types within liver cancer and characterize the transcriptomic profiles of CAFs. Prognostic analysis, utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) liver cancer datasets, assessed the correlation between matrix stiffness-related genes and HCC patient outcomes. Pseudo-time analysis was applied to trace the developmental trajectories of CAFs. By calculating intercellular communication probabilities and analyzing transcription factor activity, the functions and interactions of different CAF subsets were elucidated. Gene Ontology (GO) analysis was used to explore the functional roles of CAFs in distinct Yes-associated protein 1 (YAP1) groups. Finally, cellular experiments and animal experiments were further conducted to validate the hypotheses of this study. RESULTS: This study identified CAF subpopulations based on single-cell sequencing data and analyzed transcriptional changes within these subpopulations. Key findings include the identification of collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and lysyloxidase (LOX) as pivotal node genes during CAF development. Moreover, the expression of matrix stiffness-related genes was inversely correlated with the prognosis of HCC patients. Notably, the YAP1-positive CAF subpopulation emerged as the primary contributor to matrix stiffness in liver cancer. This subpopulation upregulates the expression of matrix stiffness-related genes and promotes tumor progression by activating signaling pathways such as autophagy and GTPase activity regulation. Cellular experiments and animal studies further validated this conclusion. CONCLUSION: This single-cell analysis uncovered the functional roles of CAFs in liver cancer. The YAP1-positive CAF subpopulation, in particular, was shown to contribute to matrix stiffness by upregulating the expression of relevant genes and promoting tumor progression through the activation of specific signaling pathways.

Carcinoma, Hepatocellular↗

Kinematic optimization of spatiotemporal patterns in paretic arm training with stroke patients.

The effect of rhythmic cueing on spatiotemporal control of sequential reaching movements of the paretic arm was studied in 21 hemispheric stroke patients. Reaching movements were studied with and without rhythmic metronome cuing in a counterbalanced design. Metronome frequencies were entrained to the naturally selected frequency of the patient. Results indicate statistically significant (P<0.05) improvements of spatiotemporal arm control during rhythmic entrainment. Variability of timing and reaching trajectories were reduced significantly. Time series analysis of sequential movement repetitions showed an immediate reduction in variability of arm kinematics during rhythmic entrainment within the first two to three repetitions of each trial. Rhythm also produced significant increases in angle ranges of elbow motion (P<0.05). Analysis of acceleration and velocity profiles of the wrist joint showed significant kinematic smoothing during rhythmic cuing. The link between rhythmic sensory timing and spatiotemporal motor control was investigated using a mathematical optimization model with minimization of peak acceleration as criterion. Rhythmically cued acceleration profiles fit the predicted model data significantly closer (P<0.01) than the self-paced profiles. Since velocity and acceleration are mathematical derivatives of position-time trajectories, the model data suggest that enhanced timing precision via temporal phase and period coupling of the motor pattern to the rhythmic time timekeeper enhances the brain's computational ability to optimally scale movement parameters across time.

Aged↗

Sparsely populated folding intermediates of the Fyn SH3 domain: matching native-centric essential dynamics and experiment.

A complete description of how a protein folds requires the characterization of intermediate conformations traversed during the folding transition. We have calculated dynamics trajectories of a simplified model of the Fyn SH3 domain with a native-centric potential energy function. Analysis of the resulting site-resolved energy trajectory identifies an ensemble of intermediate conformations for folding and another for unfolding. The model's folding intermediate is structured in the three beta-strands that make up the protein's core and is strikingly similar to intermediates detected in a recent NMR study of Fyn SH3 folding and to folding transition states elucidated in mutagenesis studies of SH3 domains. The unfolding intermediate is formed by dissociation of the folded protein's two terminal beta-strands from its core. The presence of such an intermediate is consistent with the results of a protein-engineering study on the src SH3 domain showing that these strands separate before the rate-limiting step of unfolding. Despite the presence of these conformations intermediate between the native and fully unfolded states, the computed heat capacity vs. temperature profile of the model protein indicates that its thermodynamics satisfies the usual calorimetric criterion for two-state folding. This observation highlights the fact that, if not properly interpreted, methods such as calorimetry that do not probe multiple sites in a molecule can lead to an oversimplified view of folding. The close agreement between results from this simplified model and experimental work underscores the important contributions that computational methods can make in providing insights into protein folding.

Adaptor Proteins, Signal Transducing↗

Tractography to depict three layers of visual field trajectories to the calcarine gyri.

PURPOSE: Fiber-tracking by diffusion tensor magnetic resonance imaging (DT-MRI) is currently the only noninvasive in vivo method for white matter fiber-tracking in the human brain. We used this method in attempts to visualize the optic radiation and to examine the clinical applicability of this technique. DESIGN: Observational case series. METHODS: DT-MRI scans for fiber-tracking were obtained in five healthy volunteers by use of a whole-body, 1.5 Tesla imager. DT-MRI data were transferred to an off-line workstation; PRIDE software was used for image analysis. We constructed 3 diopters fiber trajectories by tracking the direction of the fastest diffusion from the lateral geniculate nucleus, and then selected tracts on the basis of anatomical knowledge of the optic radiation. RESULTS: Our method successfully reconstructed the macroscopic 3 diopters architecture of the three major groups of optic radiation in all subjects. Meyer's loop depicted by tractography was located more posterior than the known anatomical locations, although our results on the central and posterior bundles were in good agreement with them. DT-MRI scanning required 7 minutes; preliminary images of the optic radiation could be obtained in approximately 20 minutes. CONCLUSIONS: Fiber-tracking enabled us to obtain information quickly on the 3 diopters course of the optic radiation in vivo. The finding that the fiber-tracking method underestimates the anterior extent of the optic radiations could prove to be an important limitation in the utility of this technique for preoperative planning. The time required for data acquisition and processing makes this method acceptable for routine clinical use.

Adult↗

Noninvasive delineation of normal right ventricular contractile motion with magnetic resonance imaging myocardial tagging.

As the importance of the right ventricle in many diseases and conditions has been realized, the need for quantitative assessment of the motion and contraction of the right ventricular free wall (RVFW) has become apparent. This study applied the myocardial tagging magnetic resonance imaging (MRI) technique to the normal RVFW to elucidate normal heterogeneity in RV motion and contractile patterns. The RVFW was divided into three segments (inferior, mid and superior) in each of three slices (apical, mid and basal) to allow for a detailed analysis of the motion and contraction. Percent segmental shortening (PSS) was used to measure the amount of contraction, and a vector analysis was used to quantitate the trajectory of the RVFW through systole. PSS increased monotonically through time to an average across all segments of 12% in the basal slice, 14% in the mid-ventricular slice, and 16% in the apical slice of the heart. The trajectory of the RVFW was characterized by a wave of motion toward the septum and outflow tract. The data provided in this study provide a better understanding of normal RV kinematics and can serve as a comparison for disease states.

Adult↗

The trajectory of the point of application of the resultant force of body mass at different walking speeds. Statistical analysis of human walking.

Parameters of walking at ordinary, fast and slow speeds in 30 male and 30 female young adults were investigated. More than 10 trials were made for each speed by each subject. The number of subjects and trials was large enough to permit a statistical analysis. The focus of the study was the movement of the point where the resultant foot-ground force intersects the ground. Its pathway, or trajectory, begins at touch-down from the middle part of the heel, then runs quickly on a straight line to the heads of the first or second metatarsal bones, turns medially and moves slowly towards the base of the first toe, ending at the tip of the first or second toe, or between them. This result confirms that the ankle joint works like a hinge during the stance phase, and that the human foot structure is relatively robust. Remarkably high positive correlations between stride length and stature, as well as iliospinal height were found in male subjects. However in females these clear correlations were not found, except at fast walking speeds, although were not so notable as in males. Correlations calculated from the data from all female subjects indicated significantly quite high values, as in males, but it is almost impossible to estimate exact stature or iliospinal height reliably from stride length because of its relative high variation. The sexual difference in walking speed is not due to stride duration, but to stride length.

Adolescent↗

The longitudinal influence of peers on the development of alcohol use in late adolescence: a growth mixture analysis.

This study examines heterogeneity in the developmental trajectories of alcohol use in adolescents and the accompanying trajectory-specific longitudinal influence of exposure to their deviant peers. Using a national data set on alcohol use (N = 188), a growth mixture model capturing growth trajectories in adolescent alcohol use from ages 14 to 18 years was first examined. This was followed by an investigation of age-varying influences of peers on adolescent alcohol use and the co-development of peer influence and adolescent alcohol use. Results of growth mixture modeling of repeated-measures data on adolescent alcohol use showed two distinct latent classes of developmental trajectory with significant differences in levels of use. Analyses of exposure to deviant peer and adolescent alcohol use variables indicated differential effects of peers across trajectory classes. Stronger prospective influences for the trajectory group having a low initial status of use were found. Findings from this study suggest the need to consider heterogeneity in the study of peer influence on alcohol use during adolescence to facilitate more refined targeting of prevention/intervention programs.

Adolescent↗