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Biomedical subjects

Michael Günther

Publications and source records attributed to Michael Günther.

8 recordsLinked to original sources
PubMed2007

Intelligence by mechanics.

Research on the biomechanics of animal and human locomotion provides insight into basic principles of locomotion and respective implications for construction and control. Nearly elastic operation of the leg is necessary to reproduce the basic dynamics in walking and running. Elastic leg operation can be modelled with a spring-mass model. This model can be used as a template with respect to both gaits in the construction and control of legged machines. With respect to the segmented leg, the humanoid arrangement saves energy and ensures structural stability. With the quasi-elastic operation the leg inherits the property of self-stability, i.e. the ability to stabilize a system in the presence of disturbances without sensing the disturbance or its direct effects. Self-stability can be conserved in the presence of musculature with its crucial damping property. To ensure secure foothold visco-elastic suspended muscles serve as shock absorbers. Experiments with technically implemented leg models, which explore some of these principles, are promising.

Artificial Intelligence↗
PubMed2005

Specific targets in tumor tissue for the delivery of therapeutic genes.

Gene therapy is part of a growing field in molecular medicine, which will gain importance in the treatment of human diseases. Until now, almost two thirds of all clinical trials performed in gene therapy are directed against Cancer As solid tumors exceeding a certain size rely on blood supply, the administration of particulate gene delivery vectors via the bloodstream is a promising concept. Tumor cells and the tumor vasculature both offer specific molecular targets, which can be utilized for the site directed delivery of therapeutic genes. Passive targeting of macromolecular drugs including gene delivery vectors to tumors can be achieved by the so called enhanced permeability and retention (EPR) effect. The specificity can be markedly enhanced when tumor targeting ligands are used. Viral vectors, which usually do not have a natural tropism for tumor tissue, were generated to carry tumor targeting molecules on their surface. Synthetic gene delivery vectors, based on cationic lipids or cationic polymers were biochemically modified to incorporate ligands specific for tumor cells or tumor vasculature. For systemic application, these delivery systems have to fulfill certain conditions. The delivery vector should not induce any immunogenic and inflammatory responses. Several studies were conducted to reduce the immunogenicity of viral vectors; surface modification of non-viral gene delivery systems reduced their non-specific interaction with blood components. On the genetic level, tumor specific promoters add additional layers of specificity restricting the transgene expression to the tumor tissue. This review will cover the systemic application of particulate gene transfer vectors targeted to tumors and will give an overview of therapeutic concepts for cancer gene therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Human leg design: optimal axial alignment under constraints.

Alignment of joints with respect to the leg axis reduces the moment arm of external forces and therefore joint torques. Moreover, it affects the gearing of muscle forces and displacements. Thus, it influences tissue stress, cost of support and locomotion, and stability. Assuming that alignment is of general advantage we propose a mathematical criterion quantifying the axial alignment using the static torque equilibrium of a three-segment leg. Using this criterion derived from joint torque minimisation we asked for optimal leg designs (segment lengths and joint angles) at varied leg lengths. The trivial "straight is best" solution is excluded and the configuration space is restricted by geometrical constraints such as the ground contact. For different total leg lengths we could identify different optimal segment length combinations and appropriately adjusted joint angles. The extended human leg configuration characterised by a short foot and a combination of unequal ankle and knee angles emerges as a global optimum from our analysis. For crouched configurations allowing for larger leg extensions an angle symmetrical 1:1:1 segment length combination is best. The plantigrade optimum is enforced by the requirement of the distal segment (foot) being shorter than the opposite outer segment (thigh), as well as by the ground contact constraint. Different (e.g. digitigrade) geometries might be of advantage in different biological contexts with different constraints. The fact that small mammals use a crouched equal segment design implies that other locomotor requirements such as stability, strain rates, and acceleration distance per step might dominate.

Biomechanical Phenomena↗
PubMed2003

Synthesis of two-dimensional human walking: a test of the lambda-model.

To test the lambda-model version of the equilibrium point hypothesis both for feasibility and validity with respect to the control of terrestrial locomotion, we developed a two-dimensional, eleven-segment musculoskeletal model of the human body including 14 muscle-tendon complexes per leg, three-segment feet, and a physiologically based model of foot-ground interaction. Human walking was synthesized by numerical integration of the coupled muscle-tendon and rigid body dynamics. To this end a control algorithm based on the lambda-model was implemented in the model providing muscle stimulation patterns that guaranteed dynamically stable walking including a balanced trunk. Thus, the timing of the movement is not preset by a central pattern generator but emerges from the interaction of the musculoskeletal system with the control algorithm. The control parameters were found in a trial-and-error approach. The feedforward part of the control scheme consists of just two target configurations each of which is composed of a set of one nominal length per muscle (lambda-model). Variation of gravity reveals that (1) the synthesized walking patterns are close to ballistic walking and (2) this muscularly induced natural walking can only be initiated and maintained in the range between about a tenth and three times earth-bound gravity. Our walking patterns are robust both against parameter variations and shuffling of the swing leg. We discuss our model with respect to gravity scaling, speed control, feedback delay, and the terms "equilibrium point hypothesis" and "central pattern generator."

Algorithms↗
PubMed2002

Sensitivity of the negative mucosal potential to the trigeminal target stimulus CO(2).

CO(2) is frequently used in an experimental pain model and in imaging studies investigating the central processing of trigeminal nociceptive information because of its specific trigeminal stimulation properties. The aim of the current study was (1) to investigate the sensitivity of the NMP to small increments of CO(2) stimulus concentrations (3% CO(2), v/v) and (2) to characterize the sensory input of CO(2) by determining NMP, detection and pain thresholds and by registering subjective verbal descriptions. Ten subjects participated in the first experimental sessions investigating NMP responses to stimuli of 62, 65, 68% CO(2) (v/v) (stimulus duration: 1000 ms). Our statistical analysis revealed a dose-dependent increase of the NMP amplitudes and areas under the curves (AUCs) demonstrating the high dynamic resolution of the NMP. Ten subjects participated in the second experimental sessions determining thresholds for NMP, detection and pain (stimulus duration: 1000 ms). MANOVA analysis revealed significantly different thresholds for detection, NMP and subjective pain judgements (mean and S.D. as percentage CO(2) (v/v): detection: 20.6+/-9.6, NMP: 42.6+/-12.5, pain: 50.4+/-12.0). We could demonstrate the existence of a prepain range below subjective pain thresholds with activation of trigeminal nociceptive sensors resulting in the generation of NMPs. The detection threshold of 20.6% CO(2) (v/v) was surprisingly low, i.e. 22% CO(2) (v/v) below the NMP threshold. The involvement of newly discovered alpha-gustducin positive trigeminal chemosensory cells in CO(2) detection is hypothesized.

Adult↗
PubMed2002

A movement criterion for running.

The adjustment of the leg during running was addressed using a spring-mass model with a fixed landing angle of attack. The objective was to obtain periodic movement patterns. Spring-like running was monitored by a one-dimensional stride-to-stride mapping of the apex height to identify mechanically stable fixed points. We found that for certain angles of attack, the system becomes self-stabilized if the leg stiffness was properly adjusted and a minimum running speed was exceeded. At a given speed, running techniques fulfilling a stable movement pattern are characterized by an almost constant maximum leg force. With increasing speed, the leg adjustment becomes less critical. The techniques predicted for stable running are in agreement with experimental studies. Mechanically self-stabilized running requires a spring-like leg operation, a minimum running speed and a proper adjustment of leg stiffness and angle of attack. These conditions can be considered as a movement criterion for running.

Accidental Falls↗
PubMed2002

Joint stiffness of the ankle and the knee in running.

The spring-mass model is a valid fundament to understand global dynamics of fast legged locomotion under gravity. The underlying concept of elasticity, implying leg stiffness as a crucial parameter, is also found on lower motor control levels, i.e. in muscle-reflex and muscle-tendon systems. Therefore, it seems reasonable that global leg stiffness emerges from local elasticity established by appropriate joint torques. A recently published model of an elastically operating, segmented leg predicts that proper adjustment of joint elasticities to the leg geometry and initial conditions of ground contact provides internal leg stability. Another recent study suggests that in turn the leg segmentation and the initial conditions may be a consequence of metabolic and bone stress constraints. In this study, the theoretical predictions were verified experimentally with respect to initial conditions and elastic joint characteristics in human running. Kinematics and kinetics were measured and the joint torques were estimated by inverse dynamics. Stiffnesses and elastic nonlinearities describing the resulting joint characteristics were extracted from parameter fits. Our results clearly support the theoretical predictions: the knee joint is always stiffer and more extended than the ankle joint. Moreover, the knee torque characteristic on the average shows the higher nonlinearity. According to literature, the leg geometry is a consequence of metabolic and material stress limitations. Adapted to this given geometry, the initial joint angle conditions in fast locomotion are a compromise between metabolic and control effort minimisation. Based on this adaptation, an appropriate joint stiffness ratio between ankle and knee passively safeguards the internal leg stability. The identified joint nonlinearities contribute to the linearisation of the leg spring.

Adult↗