A generic model of electron transport in mitochondria

In this paper, a simplified, generic model of mitochondrial metabolism is explored. In particular the following question is addressed: To what extent are phenomena observed in experiments and simulations of mitochondrial metabolism generic, in the sense that they must occur in all models with this basic structure? Of particular interest are the electron transport chain and oxidative phosphorylation, and how flux through the system and the redox states of intermediates respond to physiologically important stimuli. These stimuli include changes in substrate supply (NADH/FADH(2)), in oxygenation, and in membrane proton gradient/ATP demand. Analytical techniques are used to show that certain experimentally observed effects must occur in the generic model. These include the responses of both flux and redox states to changed substrate and oxygen concentrations. At the same time other effects, such as the responses of redox states to changes in proton gradient, are dependent on the details of the model, and are not common to every model with the same basic structure. The phenomenon of saturation in response to large inputs is also discussed.     

A generic model for open signaling cascades with forward activation

In this work, cellular signal transduction in an open cascade with forward activation was studied. By proposing a generic model which captures the common features of major existing models in the literature, it is showed how signaling profile changes during the propagation along the cascade. In particular, a typical OFF-ON-OFF switch-like transient behavior with prolonged temporary ON state is revealed, where OFF and ON represent the states of low level and high level concentrations, respectively. Analytically this phenomenon is closely related to uniform convergence of the active protein concentration of downstream cycles in the finite time range and its failure in the entire time domain. Consequently a classification of open signaling cascade which can sustain OFF-ON-OFF behavior in the far downstream cycles is accessible. Relevant biological issues, such as delayed activation of downstream reaction cycles, signal amplification and prolonged signal duration, to the generic model is discussed.     

A generic constitutive model for the passive porcine coronary artery

Constitutive models describing the arterial mechanical behavior are important in the development of catheterization products, to be used in arteries with a specific radius. To prove the possible existence of a constitutive model that, provided with a generic set of material and geometric parameters, is able to predict the radius-specific mechanical behavior of a coronary artery, the passive pressure–inner radius (P–r _i ) and pressure–axial force change (P–ΔF _z ) relations of seven porcine left anterior descending coronary arteries were measured in an in-vitro set-up and fitted with the model of Driessen et al. in J Biomech Eng 127(3):494–503 (2005), Biomech Model Mechanobiol 7(2):93–103 (2008). Additionally, the collagen volume fraction, physiological axial pre-stretch, and wall thickness to inner radius ratio at physiological loading were determined for each artery. From this, two generic parameter sets, each comprising four material and three geometric parameters, were obtained. These generic sets were used to compute the deformation of each tested artery using a single radius measurement at physiological loading as an artery-specific input. Artery-specific P–r _i and P–ΔF _z relations were predicted with an accuracy of 32 μm (2.3%) and 6 mN (29% relative to ΔF _z -range) on average compared to the relations measured in-vitro. It was concluded that the constitutive model provided with the generic parameters found in this study can well predict artery-specific mechanical behavior.     

A generic theoretical model for biological control of foliar plant diseases

We have developed a generic modelling framework to understand the dynamics of foliar pathogen and biocontrol agent (BCA) populations in order to predict the likelihood of successful biocontrol in relation to the mechanisms involved. The model considers biocontrol systems for foliar pathogens only and, although it is most applicable to fungal BCA systems, does not address a specific biocontrol system. Four biocontrol mechanisms (competition, antibiosis, mycoparasitism and induced resistance) were included within the model rubric. Because of the wide range of mechanisms involved we use Trichoderma/Botrytis as an exemplar system. Qualitative analysis of the model showed that the rates of a BCA colonising diseased and/or healthy plant tissues and the time that the BCA remains active are two of the more important factors in determining the final outcome of a biocontrol system. Further evaluation of the model indicated that the dynamic path to the steady-state population levels also depends critically on other parameters such as the host-pathogen infection rate. In principle, the model can be extended to include other potential mechanisms, including spatio-temporal heterogeneity, fungicide effects, non-fungal BCA and strategies for BCA application, although with a cost in model tractability and ease of interpretation.     

A generic, object-oriented data model for life cycle analysis applications

Life Cycle Analysis (LCA) requires the manipulation of a large amount of both quantitative and qualitative data. It is also a continuous and iterative process in which the knowledge of previous steps is always necessary for the realization and understanding of subsequent stages. Current LCA data models are mostly organized as lists from which quantitative data can be extracted and manipulated, subsequently leading to lists of numerical results. Performing an LCA can benefit from more flexible structures that allow for complete or partial treatments and provides links between the successive transformations of various types of information. A generic, object-oriented model is presented, written in ISO/STEP EXPRESS, using the STEP principles.     

A fatigue damage model for the cement-bone interface

Loss of fixation at the cement-bone interface can contribute to clinical loosening of cemented total hip replacements. In this study, the fatigue damage response was determined for cement-bone constructs subjected to shear fatigue loading. A typical three-phase fatigue response was observed with substantial early damage, followed by a long constant damage rate region and a final abrupt increase in damage to fracture. All of the damage resulted from creep (permanent) deformation during fatigue loading and there was no loss in cyclic stiffness. Using a Von Mises equivalent stress/strain concept, a general damage model was developed to describe the fatigue creep response of the cement-bone interface under either shear or tensile fatigue loading. Time to failure was highly correlated (r2=0.971) with equivalent creep strain rate and moderately related (r2=0.428) with equivalent initial strain for the two loading regimes. The equivalent creep strain at failure (0.052+/-0.018) was found to be independent of the applied equivalent stress. A combination of the creep damage model (to describe the damage process) with a constant final equivalent strain (as a failure criteria) could be used to assess the cement-bone failure response of cemented implant systems.     

A model of visually-guided smooth pursuit eye movements based on behavioral observations

We report a model that reproduces many of the behavioral properties of smooth pursuit eye movements. The model is a negative-feedback system that uses three parallel visual motion pathways to drive pursuit. The three visual pathways process image motion, defined as target motion with respect to the moving eye, and provide signals related to image velocity, image acceleration, and a transient that occurs at the onset of target motion. The three visual motion signals are summed and integrated to produce the eye velocity output of the model. The model reproduces the average eye velocity evoked by steps of target velocity in monkeys and humans and accounts for the variation among individual responses and subjects. When its motor pathways are expanded to include positive feedback of eye velocity and a switch, the model reproduces the exponential decay in eye velocity observed when a moving target stops. Manipulation of this expanded model can mimic the effects of stimulation and lesions in the arcuate pursuit area, the middle temporal visual area (MT), and the medial superior temporal visual area (MST).     

A generic analytical foot rollover model for predicting translational ankle kinematics in gait simulation studies

The objective of this paper is to develop an analytical framework to representing the ankle–foot kinematics by modelling the foot as a rollover rocker, which cannot only be used as a generic tool for general gait simulation but also allows for case-specific modelling if required. Previously, the rollover models used in gait simulation have often been based on specific functions that have usually been of a simple form. In contrast, the analytical model described here is in a general form that the effective foot rollover shape can be represented by any polar function ρ=ρ(φ). Furthermore, a normalized generic foot rollover model has been established based on a normative foot rollover shape dataset of 12 normal healthy subjects. To evaluate model accuracy, the predicted ankle motions and the centre of pressure (CoP) were compared with measurement data for both subject-specific and general cases. The results demonstrated that the ankle joint motions in both vertical and horizontal directions (relative RMSE ～10%) and CoP (relative RMSE ～15% for most of the subjects) are accurately predicted over most of the stance phase (from 10% to 90% of stance). However, we found that the foot cannot be very accurately represented by a rollover model just after heel strike (HS) and just before toe off (TO), probably due to shear deformation of foot plantar tissues (ankle motion can occur without any foot rotation). The proposed foot rollover model can be used in both inverse and forward dynamics gait simulation studies and may also find applications in rehabilitation engineering.     

A reconsideration of terminology in Frankia research: A need for congruence

Progress in understanding the Frankia -actinorhizal symbiosis has paralleled that of the Rhizobium -legume symbiosis. Previously, these two nitrogen-fixing symbioses have been considered as distinct and unrelated entities. However, it seems likely that many of the developmental stages, and perhaps even the molecular signals, are shared between these two apparently independent associations. For this reason, we propose to emphasize the similarities between the two symbioses by calling for a uniformity of terminology to describe nodule development.     

A finite element model for evaluation of tibial prosthesis-bone interface in total knee replacement

A numerical model based on the finite element method was developed for the load transfer analysis at the tibial bone-implant interfaces in total knee replacement. A transverse isotropic material model, based on a quadratic elastic potential and on Hill's quadratic yield criterion, was next developed for bone constitutive laws. The bone-cement and bone-prosthesis interfaces were both assumed to be discontinuous. A dry friction model based on Coulomb's criterion was adopted for the interfaces friction. The model was shown to be able to give compressive and shear stresses distributions and distractive and relative shear micromotions at these interfaces. A preliminary application was conducted for cemented metal tray total condylar (MTTC) and for cemented and uncemented porous coated anatomic (PCA) tibial plateaus. The PCA plateaus were found to be more deformable and had greater global displacements than the MTTC one. Debonding of the bone-peg interface was observed for the uncemented PCA. Correspondingly, the stress peaks at the interface beneath the tray were lower for the PCA than for the MTTC. Shear micromotions appeared under the tray for both the two prostheses. We observed that bone anisotropy and interface discontinuity affected the results sensibly.     

A minimal generic model of bacteria-induced intracellular Ca2+ oscillations in epithelial cells

The toxin alpha-hemolysin expressed by uropathogenic Escherichia coli bacteria was recently shown as the first pathophysiologically relevant protein to induce oscillations of the intracellular Ca(2+) concentration in target cells. Here, we propose a generic three-variable kinetic model describing the Ca(2+) oscillations induced in single rat renal epithelial cells by this toxin. Specifically, we take into account the interplay between 1), the cytosolic Ca(2+) concentration; 2), IP(3)-sensitive Ca(2+) channels located in the membrane separating the cytosol and endoplasmic reticulum; and 3), toxin-related activation of production of IP(3) by phospholipase C. With these ingredients, the predicted response of cells exposed to the toxin is in good agreement with the results of experiments.     

A new model for the bending of DNAs containing the oligo(dA) tracts based on NMR observations.

The conformations of double-stranded d(GGAAATTTCC) x 2, d(GGTTTAAACC) x 2, d(CGCAAAAAAGCG)d(CGCTTTTTTGCG) and d(GCATTTTGAAACG)d(CGTTTCAAAATGC) have been studied by NMR spectroscopy. Analyses of cross peaks in NOESY spectra between the H2 of an adenine and the H1' of a deoxyribose in the 3'-neighbouring residue on the complementary strand revealed that the minor groove of the oligo(dA) tract is compressed gradually from 5' to 3' in each duplex. In view of this gradual compression of the minor groove along the oligo(dA) tract, it can be understood clearly why d(GGAAATTTCC)n x 2 and d(GAAAATTTTC)n x 2 are bent, and d(GGTTTAAACC)n x 2 and d(GTTTTAAAAC)n x 2 are not bent. The relative extents of bending of a series of d(AjN10-j)nd(N10-jTj)n sequences can also be understood systematically. Additionally, it was found that the TA step disturbed the compression of the minor groove of the oligo(dA) tract to some extent.     

A proposed life cycle model of Spiroplasma mirum based on scanning electron microscopical observations of growth in liquid culture

Cells of Spiroplasma mirum strain SMCA were grown in PPG broth and examined by scanning electron microscopy. Comparison of the results at different time intervals allowed for a model of the life cycle of S. mirum to be proposed. Under favorable growth conditions, helical filament formation was initially observed, followed by the formation of small spherical structures originating from each filament. In old culture, large spherical bodies appeared from entangled helical filaments. From the larger spherical bodies, granular bodies representing the smallest reproductive units were produced to continue the life cycle.