Cryosurgery planning using bubble packing in 3D

As part of an ongoing project to develop automated tools for cryosurgery planning, the current study focuses on the development of a 3D bubble packing method. A proof-of-concept for the new method is demonstrated on five prostate models, reconstructed from ultrasound images. The new method is a modification of an established method in 2D. Ellipsoidal bubbles are packed in the volume of the prostate in the current study; such bubbles can be viewed as a first-order approximation of a frozen region around a single cryoprobe. When all cryoprobes are inserted to the same depth, optimum planning was found to occur at about 60% of the length of the prostate (measured from its apex), which leads to cooling of approximately 75% of the prostate volume below a specific temperature threshold of - 22 degrees C. Bubble packing has the potential to dramatically reduce the run time for automated planning.     

Dynamic optimization of human walking

A three-dimensional, neuromusculoskeletal model of the body was combined with dynamic optimization theory to simulate normal walking on level ground. The body was modeled as a 23 degree-of-freedom mechanical linkage, actuated by 54 muscles. The dynamic optimization problem was to calculate the muscle excitation histories, muscle forces, and limb motions subject to minimum metabolic energy expenditure per unit distance traveled. Muscle metabolic energy was calculated by slimming five terms: the basal or resting heat, activation heat, maintenance heat, shortening heat, and the mechanical work done by all the muscles in the model. The gait cycle was assumed to be symmetric; that is, the muscle excitations for the right and left legs and the initial and terminal states in the model were assumed to be equal. Importantly, a tracking problem was not solved. Rather only a set of terminal constraints was placed on the states of the model to enforce repeatability of the gait cycle. Quantitative comparisons of the model predictions with patterns of body-segmental displacements, ground-reaction forces, and muscle activations obtained from experiment show that the simulation reproduces the salient features of normal gait. The simulation results suggest that minimum metabolic energy per unit distance traveled is a valid measure of walking performance.     

Dynamic motion planning for the design of robotic gait rehabilitation

In this paper we examine a method to control the stepping motion of a paralyzed person suspended over a treadmill using a robot attached to the pelvis. A leg swing motion is created by moving the pelvis without contact with the legs. The problem is formulated as an optimal control problem for an underactuated articulated chain. The optimal control problem is converted into a discrete parameter optimization and an efficient gradient-based algorithm is used to solve it. Motion capture data from an unimpaired human subject is compared to the simulation results from the dynamic motion optimization. Our results suggest that it is feasible to drive repetitive stepping on a treadmill by a paralyzed person by assisting in torso movement alone. The optimized, pelvic motion strategies are comparable to "hip-hiking" gait strategies used by people with lower limb prostheses or hemiparesis. The resulting motions can be found at the web site http://ww.eng.uci.edu/-chwang/project/stepper/stepper.html.     

High precision alignment of cryo-electron subtomograms through gradient-based parallel optimization

Background

Cryo-electron tomography emerges as an important component for structural system biology. It not only allows the structural characterization of macromolecular complexes, but also the detection of their cellular localizations in near living conditions. However, the method is hampered by low resolution, missing data and low signal-to-noise ratio (SNR). To overcome some of these difficulties and enhance the nominal resolution one can align and average a large set of subtomograms. Existing methods for obtaining the optimal alignments are mostly based on an exhaustive scanning of all but discrete relative rigid transformations (i.e. rotations and translations) of one subtomogram with respect to the other.

Results

In this paper, we propose gradient-guided alignment methods based on two popular subtomogram similarity measures, a real space as well as a Fourier-space constrained score. We also propose a stochastic parallel refinement method that increases significantly the efficiency for the simultaneous refinement of a set of alignment candidates. We estimate that our stochastic parallel refinement is on average about 20 to 40 fold faster in comparison to the standard independent refinement approach. Results on simulated data of model complexes and experimental structures of protein complexes show that even for highly distorted subtomograms and with only a small number of very sparsely distributed initial alignment seeds, our combined methods can accurately recover true transformations with a substantially higher precision than the scanning based alignment methods.

Conclusions

Our methods increase significantly the efficiency and accuracy for subtomogram alignments, which is a key factor for the systematic classification of macromolecular complexes in cryo-electron tomograms of whole cells.

     

Bird terrestrial locomotion as revealed by 3D kinematics

Most birds use at least two modes of locomotion: flying and walking (terrestrial locomotion). Whereas the wings and tail are used for flying, the legs are mainly used for walking. The role of other body segments remains, however, poorly understood. In this study, we examine the kinematics of the head, the trunk, and the legs during terrestrial locomotion in the quail (Coturnix coturnix). Despite the trunk representing about 70% of the total body mass, its function in locomotion has received little scientific interest to date. This prompted us to focus on its role in terrestrial locomotion. We used high-speed video fluoroscopic recordings of quails walking at voluntary speeds on a trackway. Dorso-ventral and lateral views of the motion of the skeletal elements were recorded successively and reconstructed in three dimensions using a novel method based on the temporal synchronisation of both views. An analysis of the trajectories of the body parts and their coordination showed that the trunk plays an important role during walking. Moreover, two sub-systems participate in the gait kinematics: (i) the integrated 3D motion of the trunk and thighs allows for the adjustment of the path of the centre of mass; (ii) the motion of distal limbs transforms the alternating forward motion of the feet into a continuous forward motion at the knee and thus assures propulsion. Finally, head bobbing appears qualitatively synchronised to the movements of the trunk. An important role for the thigh muscles in generating the 3D motion of the trunk is suggested by an analysis of the pelvic anatomy.     

Experimental/analytical analysis of human locomotion using bondgraphs

A new vectorial bondgraph approach for modeling and simulation of human locomotion is introduced. The vectorial bondgraph is applied to an eight-segment gait model to derive the equations of motion for studying ground reaction forces (GRFs) and centers of pressure (COPs) in single and double support phases of ground and treadmill walking. A phase detection technique and accompanying transition equation is proposed with which the GRFs and COPs may be calculated for the transitions from double-to-single and single-to-double support phases. Good agreement is found between model predictions and experimental data obtained from force plate measurements. The bondgraph modeling approach is shown to be both informative and adaptable, in the sense that the model resembles the human body structure, and that modeled body segments can be easily added or removed.     

Three-dimensional data-tracking dynamic optimization simulations of human locomotion generated by direct collocation

The aim of this study was to perform full-body three-dimensional (3D) dynamic optimization simulations of human locomotion by driving a neuromusculoskeletal model toward in vivo measurements of body-segmental kinematics and ground reaction forces. Gait data were recorded from 5 healthy participants who walked at their preferred speeds and ran at 2 m/s. Participant-specific data-tracking dynamic optimization solutions were generated for one stride cycle using direct collocation in tandem with an OpenSim-MATLAB interface. The body was represented as a 12-segment, 21-degree-of-freedom skeleton actuated by 66 muscle-tendon units. Foot-ground interaction was simulated using six contact spheres under each foot. The dynamic optimization problem was to find the set of muscle excitations needed to reproduce 3D measurements of body-segmental motions and ground reaction forces while minimizing the time integral of muscle activations squared. Direct collocation took on average 2.7 ± 1.0 h and 2.2 ± 1.6 h of CPU time, respectively, to solve the optimization problems for walking and running. Model-computed kinematics and foot-ground forces were in good agreement with corresponding experimental data while the calculated muscle excitation patterns were consistent with measured EMG activity. The results demonstrate the feasibility of implementing direct collocation on a detailed neuromusculoskeletal model with foot-ground contact to accurately and efficiently generate 3D data-tracking dynamic optimization simulations of human locomotion. The proposed method offers a viable tool for creating feasible initial guesses needed to perform predictive simulations of movement using dynamic optimization theory. The source code for implementing the model and computational algorithm may be downloaded at http://simtk.org/home/datatracking.     

Patient admission planning using Approximate Dynamic Programming

Tactical planning in hospitals involves elective patient admission planning and the allocation of hospital resource capacities. We propose a method to develop a tactical resource allocation and patient admission plan that takes stochastic elements into consideration, thereby providing robust plans. Our method is developed in an Approximate Dynamic Programming (ADP) framework and copes with multiple resources, multiple time periods and multiple patient groups with uncertain treatment paths and an uncertain number of arrivals in each time period. As such, the method enables integrated decision making for a network of hospital departments and resources. Computational results indicate that the ADP approach provides an accurate approximation of the value functions, and that it is suitable for large problem instances at hospitals, in which the ADP approach performs significantly better than two other heuristic approaches. Our ADP algorithm is generic, as various cost functions and basis functions can be used in various hospital settings.     

Construction of 3D human distal femoral surface models using a 3D statistical deformable model

Construction of 3D geometric surface models of human knee joint is always a challenge in biomedical engineering. This study introduced an improved statistical shape model (SSM) method that only uses 2D images of a joint to predict the 3D joint surface model. The SSM was constructed using 40 distal femur models of human knees. In this paper, a series validation and parametric analysis suggested that more than 25 distal femur models are needed to construct the SSM; each distal femur should be described using at least 3000 nodes in space; and two 2D fluoroscopic images taken in 45° directions should be used for the 3D surface shape prediction. Using this SSM method, ten independent distal femurs from 10 independent living subjects were predicted using their 2D plane fluoroscopic images. The predicted models were compared to their native 3D distal femur models constructed using their 3D MR images. The results demonstrated that using two fluoroscopic images of the knee, the overall difference between the predicted distal femur surface and the MR image-based surface was 0.16±1.16 mm. These data indicated that the SSM method could be a powerful method for construction of 3D surface geometries of the distal femur.     

Establishment of 3D organotypic cultures using human neonatal epidermal cells

This protocol describes an ex vivo three-dimensional coculture system optimized to study the skin regenerative ability of primary human keratinocytes grown at the air-liquid interface on collagen matrices embedded with human dermal fibroblasts. An option for enrichment of keratinocyte stem cells and their progeny using fluorescence-activated cell sorting is also provided. Initially, dermal equivalents, comprising human passaged fibroblasts seeded in a collagen matrix, are grown on porous filters (3 mum) placed in transwells. After 1 week, primary human keratinocytes are seeded on this base. One week later, an air-lift transition is performed, leading to the differentiation of the keratinocytes, which are macroscopically visible as artificial skin after a couple of days. The cultures can be harvested 1 week after the air-lift and processed for immunohistochemistry or gene expression analysis. The overall procedure can be completed in 3 weeks, including the preparation of the dermal equivalent and the seeding of the primary keratinocytes.     

A 3D Generic Inverse Dynamic Method using Wrench Notation and Quaternion Algebra

In the literature, conventional 3D inverse dynamic models are limited in three aspects related to inverse dynamic notation, body segment parameters and kinematic formalism. First, conventional notation yields separate computations of the forces and moments with successive coordinate system transformations. Secondly, the way conventional body segment parameters are defined is based on the assumption that the inertia tensor is principal and the centre of mass is located between the proximal and distal ends. Thirdly, the conventional kinematic formalism uses Euler or Cardanic angles that are sequence-dependent and suffer from singularities.

In order to overcome these limitations, this paper presents a new generic method for inverse dynamics. This generic method is based on wrench notation for inverse dynamics, a general definition of body segment parameters and quaternion algebra for the kinematic formalism.     

A theory on the determination of 3D motion and 3D structure from features

The present paper proposes a mathematical theory and a method of recognition of both the 3D structure and the motion of a moving object from its monocular image. Initially, characteristic features are extracted from the 2D perspective image of the object. Because motion of the object induces a change in its 2D perspective image, it also induces a change in the features which depends on the 3D structure and the velocity of the object. This suggests the possibility of detecting the 3D structure and the motion directly from the features and their changing rate, without the need for calculating optical flows. An analysis is made of the relation between the 3D rigid motion of a surface element and the change in local linear features. From this relation, a method is proposed for calculating the velocity of and the normal to the surface element without considering any correspondence of points. An optical flow can also be calculated by this method. Two simple computer simulations are provided.     

Dynamic optimization of fed-batch bioprocesses using flower pollination algorithm

Bioprocess and Biosystems Engineering - There exist several optimization strategies such as sequential quadratic programming (SQP), iterative dynamic programing (IDP), stochastic-based methods such...     

Dynamic optimization of fed-batch bioreactors using the ant algorithm

The ant colony algorithm, mimicking the cooperative search behavior of ants in real life, has been employed for the dynamic optimization of fed-batch bioreactors. To test the capability of this new heuristic algorithm, two well-known and extensively studied systems have been chosen. The algorithm rapidly converges to optimal feed rate profiles, which maximize the overall production of the desired product and the profits in a computationally efficient and robust manner. The optimal profiles evolved are easy to implement in plant operation. The algorithm compares favorably with the other known techniques.