Multijoint Control Strategies Transfer Between Tasks

In this paper, the hypothesis that multijoint control strategies are transferred between similar tasks was tested. To test this hypothesis, we studied the take-off phase of two types of backward somersault dives: one while translating backwards (Back), the other while translating forward (Reverse). An experimentally based dynamic model of the musculoskeletal system was employed to simulate the measured kinematics and reaction force data and to study the sensitivity of take-off performance to initial kinematic conditions. It was found that the horizontal velocity of the total body center of mass (CM) was most sensitive to modifications in the initial shank conditions. Consequently, the initial shank kinematics of the Back dive was modified in the optimization procedure while maintaining the joint coordination of the Back in order to generate the CM trajectory and reaction forces of a Reverse. Similarly, the initial shank kinematics of the Reverse dive was modified to simulate the CM trajectory and reaction force of the Back. It was found that small modifications in the initial shank kinematics led to change in direction of horizontal CM velocity at take-off; resulting in a switch from Back to Reverse and vice versa. In both cases, the simulated momentum conditions at departure and the bimodal shape of the reaction force-time curve were consistent with those experimentally observed. The results of this study support the hypothesis that transfer of control strategies between similar tasks is a viable option in multijoint control. This transfer of control strategy is explained using a hierarchical model of the motion control system.     

The influence of touchdown conditions and contact phase technique on post-flight height in the straight handspring somersault vault

In vaulting the gymnast must generate sufficient linear and angular momentum during the approach and table contact in order to complete the rotational requirements in the post-flight phase. This study investigated the effects of touchdown conditions and contact technique on peak post-flight height of a straight handspring somersault vault. A planar seven-segment torque-driven computer simulation model of the contact phase in vaulting was evaluated by varying joint torque activation time histories to match three performances of a straight handspring somersault vault by an elite gymnast. The closest matching simulation was used as a starting point to optimise peak post-flight height of the mass centre for a straight handspring somersault. It was found that optimising either the touchdown conditions or the contact technique increased post-flight height by 0.1 m whereas optimising both together increased post-flight height by 0.4 m above that of a simulation matching the recorded performance. Thus touchdown technique and contact technique make similar contributions to post-flight height in the straight handspring somersault vault. Increasing touchdown velocity and angular momentum lead to additional post-flight height although there was a critical value of vertical touchdown velocity beyond which post-flight height decreased.     

Validation of lumbar spine loading from a musculoskeletal model including the lower limbs and lumbar spine

Low back mechanics are important to quantify to study injury, pain and disability. As in vivo forces are difficult to measure directly, modeling approaches are commonly used to estimate these forces. Validation of model estimates is critical to gain confidence in modeling results across populations of interest, such as people with lower-limb amputation. Motion capture, ground reaction force and electromyographic data were collected from ten participants without an amputation (five male/five female) and five participants with a unilateral transtibial amputation (four male/one female) during trunk-pelvis range of motion trials in flexion/extension, lateral bending and axial rotation. A musculoskeletal model with a detailed lumbar spine and the legs including 294 muscles was used to predict L4-L5 loading and muscle activations using static optimization. Model estimates of L4-L5 intervertebral joint loading were compared to measured intradiscal pressures from the literature and muscle activations were compared to electromyographic signals. Model loading estimates were only significantly different from experimental measurements during trunk extension for males without an amputation and for people with an amputation, which may suggest a greater portion of L4-L5 axial load transfer through the facet joints, as facet loads are not captured by intradiscal pressure transducers. Pressure estimates between the model and previous work were not significantly different for flexion, lateral bending or axial rotation. Timing of model-estimated muscle activations compared well with electromyographic activity of the lumbar paraspinals and upper erector spinae. Validated estimates of low back loading can increase the applicability of musculoskeletal models to clinical diagnosis and treatment.     

A computational study of leukocyte adhesion and its effect on flow pattern in microvessels

Three-dimensional computational modeling and simulation are presented on the adhesive rolling of deformable leukocytes over a P-selectin coated surface in parabolic shear flow in microchannels. The computational model is based on the immersed boundary method for cell deformation and Monte Carlo simulation for receptor/ligand interaction. The simulations are continued for at least 1 s of leukocyte rolling during which the instantaneous quantities such as cell deformation index, cell/substrate contact area, and fluid drag remain statistically stationary. The characteristic ‘stop-and-go’ motion of rolling leukocytes, and the ‘tear-drop’ shape of adherent leukocytes as observed in experiments are reproduced by the simulations. We first consider the role of cell deformation and cell concentration on rolling characteristics. We observe that compliant cells roll slower and more stably than rigid cells. Our simulations agree with previous in vivo observation that the hydrodynamic interactions between nearby leukocytes affect cell rolling, and that the rolling velocity decreases inversely with the separation distance, irrespective of cell deformability. We also find that cell deformation decreases, and the cells roll more stably with reduced velocity fluctuation, as the cell concentration is increased. However, the effect of nearby cells on the rolling characteristics is found to be more significant for rigid cells than compliant cells. We then address the effect of cell deformability and rolling velocity on the flow resistance due to, and the fluid drag on, adherent leukocytes. While several earlier computational works have addressed this problem, two key features of leukocyte adhesion, such as cell deformation and rolling, were often neglected. Our results suggest that neglecting cell deformability and rolling velocity may significantly overpredict the flow resistance and drag force. Increasing the cell concentration is shown to increase the flow resistance and reduce the fluid drag. The reduced drag then results in slower and more stable rolling of the leukocytes with longer pause time and shorter step distance. But the increase/decrease in the flow resistance/fluid drag due to the increase in the cell concentration is observed to be more significant in case of rigid cells than compliant cells.     

The function and structural influence of selective relaxed constraint at functional intracellular loop3 of 5-HT1A serotonin-1 receptor family

Serotonin (5-HT) and its receptors have been involved in critical signal transduction mechanism and deregulation implicated in mood-related disorders. 5-HT activities are mediated through a family of transmembrane spanning serotonin receptors. Both within the family and species, 5-HT receptor protein sequence diversity and 7-transmembrane structural homogeneity have long been intriguing. In this study, we have analyzed the codon site constraint in 5-HT1 subclass receptors from 13 orthologous mammalian mRNA coding sequence. Further, the study was extended to computationally investigate the impact of non-synonymous sites with respect to function and structural significance through sequence homology algorithm and molecular dynamics simulation (MDS). Codon sites with significant posterior probability were observed in 5-HT_1A, 5‐HT_1B and 5-HT_1D receptor indicating variations in site constraint within the 5‐HT1 sub-class genes. In 5-HT_1A receptor, seven sites were detected at the functional intracellular loop₃ (ICL₃) with higher substitution rate through Codeml program. Sequence homology algorithm identifies that these sites were functionally tolerant within the mammals representing a selectively relaxed constraint at this domain. On the other hand, the root mean square deviation (rmsd) values from MDS suggest differences in structural conformation of ICL₃ models among the species. Specifically, the human ICL₃ model fluctuation was comparatively more stable than other species. Hence, we argue that these sites may have varying influence in G-proteins coupling and activation of effectors systems through downstream interacting accessory proteins of cell among the species. However, further experimental studies are required to elucidate the precise role and the seeming difference of these sites in 5-HT receptors between species.     

Recent advancements in the development of anti-tuberculosis drugs

Modern chemotherapy has significantly improved patient outcomes against drug-sensitive tuberculosis. However, the rapid emergence of drug-resistant tuberculosis, together with the bacterium’s ability to persist and remain latent present a major public health challenge. To overcome this problem, research into novel anti-tuberculosis targets and drug candidates is thus of paramount importance. This review article provides an overview of tuberculosis highlighting the recent advances and tools that are employed in the field of anti-tuberculosis drug discovery. The predominant focus is on anti-tuberculosis agents that are currently in the pipeline, i.e. clinical trials.