Failure of total hip arthroplasties. Numerical modeling of debris formation through plastic strains

The life span of a total hip prosthesis is one of the main points on which the long-term success of arthroplasties depends. It is, by now, widely recognized that hip arthroplasty failure is mainly due to the aseptic loosening resulting from the presence of wear debris forming at the contact interface between the femoral head and the cup of the acetabulum. The size of these particles varies from a few micrometers to some tens of micrometers or more. The main aim of this study was therefore to investigate the formation of debris in the microscopic size range. For this purpose, a numerical study was carried out on various mechanisms leading to plastic deformations, which can lead to damage and wear in material. Numerical analyses were performed with a laboratory software program LMGC90, on the evolution of the plastic strains involved in various wear mechanisms on the microscopic scale.     

A linear equation that describes the steady-state kinetics of enzymes and subcellular particles interacting with tightly bound inhibitors

When an enzyme exhibits a high affinity for an inhibitor, the steady-state analysis of the mechanism is complicated by the non-linearity of normal dose-response plots or of reciprocal replots. It is shown here that dose-response measurements generate a linear plot of inhibitor concentration divided by degree of inhibition against velocity without inhibitor divided by velocity with inhibitor; the concentration of enzyme may be derived from the extrapolated intercept of such plots, and the mechanism of inhibition from replots of the variation of the slope with substrate concentration. The limiting cases where virtually all inhibitor molecules are bound or virtually all are free are described, together with the situation when a significant proportion of the substrate becomes bound. This type of analysis indicates that the inhibitors of oxidative phosphorylation, rutamycin and bongkrekic acid, are tightly bound to rat liver mitochondria.     

Numerical modeling of the cupular displacement and motion of otoconia particles in a semicircular canal

Balance is achieved and maintained by a balance system called a labyrinth that is composed of three semicircular canals and the otolith organs that sense linear gravity and acceleration. Within each semicircular canal, there is a gelatinous structure called the cupula, which is deformed under the influence of the surrounding endolymph. One of the balance disorders is benign paroxysmal positional vertigo, and one of the pathological conditions that have been identified as possible causes of this syndrome is canalithiasis—disturbance of the endolymph flow and cupular displacement caused by the free-moving otoconia particles within the lumen of the canal. Analysis of phenomena occurring within the semicircular canal can help to explain some balance-related disorders and the response of the vestibular system to external perturbations under various pathological conditions. Numerical simulations allow a study of the influence of a wide range of factors, without the need to perform experiments and clinical examinations. In case of canalithiasis, an accurate explanation and tracking of the motion of otoconia particles in vivo is obviously nearly impossible. In this study, a numerical model was developed to predict the motion of otoconia particles within the semicircular canal and the effect of the endolymph flow and particles on the deformation of the cupula.     

Maximal lactate steady-state prediction through quadratic modeling of selected stages of the lactate minimum test

In this study, we compared the maximal lactate steady state (MLSS) with lactate minimal (LM) intensities determined visually and through a quadratic polynomial function of selected stages of LM test. Eleven male recreational cyclists (27.7 +/- 4.5 years, 175.7 +/- 5.6 cm, 69.5 +/- 10.8 kg, and 12.0 +/- 5.5% body fat) performed one LM test under previous induction of hyperlactaemia with an initial intensity of 75 W with 30-W increments every 3 minutes with blood lactate concentration (HLa) and rating of perceived exertion (RPE) measurements. The LM intensity was determined visually (VLM) and by modeling the lactate response through polynomial function by using: 1) all stages (LMP); 2) the first stage, the stage corresponding to RPE-13 and the last stage/exhaustion (LMP3max); 3) the three lowest lactate concentration stages (LMP3adj); and 4) the initial, RPE-13, and RPE-16 stages (LMP3sub). The MLSS was determined as the highest intensity at a variation not greater than 0.05 mmol.l.min of HLa during the last 20 minutes of a 30-minute exercise session. The MLSS (204.0 +/- 16.0 W), VLM (198.6 +/- 15.2 W), LMP3adj (190.4 +/- 12.9 W), and LMP3sub (192.1 +/- 27.2 W) were not different, well correlated, and in agreement to each other. In conclusion, the polynomial modeling of HLa response to three submaximal stages produced exercise intensities that did not differ from MLSS.     

Improved processing of the steady-state evoked potential

Two related procedures for estimating the parameters of steady-state evoked potentials (SSEPs) are introduced. The first procedure involves an initial stage of digital bandpass filtering followed by a Discrete Fourier Transform analysis. In the second method, a high resolution method based on parametric modelling is applied to the filtered data. The digital pre-filter consists of a non-phase shifting Chebychev bandpass filter. The parametric modelling method considers the evoked-response-plus-noise distribution to consist of a set of exponentially damped sinusoids. The frequency, amplitude, phase and damping factors of these components are estimated by calculating the mean of the forward and backward prediction filters and linear regression.We compared the signal-to-noise ratio (SNR) of the new procedures to the conventional Discrete Fourier Transform method for Monte Carlo simulations utilizing known sinusoids buried in white noise, known sinusoids buried in human EEG noise and for a sample of visual evoked potential data. Both of the new methods produce substantially more accurate and less variable estimates of test sinusoid amplitude. For VEP recording, the EEG background noise level is reduced by 5–6 dB over that obtained with the DFT. The new methods also provide approximately 5 dB better SNR than the DFT for detection of sinusoids based on the Rayleigh statistic. The parametric modelling approach is particularly suited for the analysis of very short data records including cycle-by-cycle analysis of the SSEP.     

Numerical modeling of the dynamics of a slow Z-pinch

A study is made of the method for numerical modeling of pulsed plasma systems by simultaneously solving two-temperature MHD equations and the equations of ionization kinetics. As an example, the method is applied to simulate a relatively slow moderate-density Z-pinch, whose dynamics is well studied experimentally. A specially devised two-dimensional computer code makes use of a promising technique of parallel modeling.     

Numerical study of drug delivery through the 3D modeling of aortic arch in presence of a magnetic field

Biomechanics and Modeling in Mechanobiology - Magnetic drug delivery known as smart technique in medicine is basically according to combining the drug inside capsules with the magnetic property or...     

The role of behavioral dynamics in determining the patch distributions of interacting species

The effect of the behavioral dynamics of movement on the population dynamics of interacting species in multipatch systems is studied. The behavioral dynamics of habitat choice used in a range of previous models are reviewed. There is very limited empirical evidence for distinguishing between these different models, but they differ in important ways, and many lack properties that would guarantee stability of an ideal free distribution in a single-species system. The importance of finding out more about movement dynamics in multispecies systems is shown by an analysis of the effect of movement rules on the dynamics of a particular two-species-two-patch model of competition, where the population dynamical equilibrium in the absence of movement is often not a behavioral equilibrium in the presence of adaptive movement. The population dynamics of this system are explored for several different movement rules and different parameter values, producing a variety of outcomes. Other systems of interacting species that may lack a dynamically stable distribution among patches are discussed, and it is argued that such systems are not rare. The sensitivity of community properties to individual movement behavior in this and earlier studies argues that there is a great need for empirical investigation to determine the applicability of different models of the behavioral dynamics of habitat selection.     

Regulation of differentiation in a population of cells interacting through a common pool

We consider a model of a suspension of a cell population in a well-mixed medium. There are two chemical substances, say A and H, reacting in each cell of the population and the substance H can only diffuse from the inside of cell to the medium or vice versa across the cell membrane. The medium is well mixed that the concentration of H is kept uniform over the medium. Cells interact indirectly with each other through the medium. The differential equations governing the dynamics of the suspension are analyzed using standard techniques for differential equations. It is shown that the cell population divides into several groups in respect of the chemical concentrations as time elapses. It is also shown how the fraction of the number of cells belonging to each subgroup to the total number of cells is regulated. The results may be used to explain the mechanism for differentiation of multi-cellular organisms.     

The formation of a potential spring in the ribosome

Time-dependent chemical modification and cleavage results have provided intriguing insights into structural changes that occur in the distal loop of helix 11 in 16S ribosomal RNA (rRNA). Located distant from the decoding region, between proteins S17 and S20, the results of this study suggest that this region of rRNA may act as a buffer or a spring between these two proteins during protein biosynthesis. During the assembly process, protein S17 apparently produces the major structural deformations in this region, causing it to be folded in a spring-like structure. Base C264 in this region shows erratic behavior during assembly and also shows time-dependent enhancement when elongation factor G with GTP is added to 70S ribosomes. Evidence is presented to suggest that this region of rRNA may be used to allow relative motion to occur between proteins S17 and S20 during translocation.     

Mathematic modeling of the dynamics of the interacting population of the rhizosphere microorganisms

A quantitative model is proposed to describe the population dynamics of associative nitrogen-fixing microorganisms in the plant rhizosphere as dependent on the rate of carbon substrate exudation by plant roots. By changing the values of the basic model parameters, the effect of various factors on the behavior of two competing populations of rhizospheric microorganism can be studied.     

Multilevel selection 3: modeling the effects of interacting individuals as a function of group size

Bijma et al. (2007a,b) presented a quantitative genetic theory of multilevel selection and showed how to estimate the relevant parameters using standard restricted maximum-likelihood (REML) methodology. Extending their results we develop a wider class of models that provide a more realistic framework for capturing the effects of interacting individuals. These models also make use of standard REML techniques and include the original model as a special case.     

Control of cellular redox potential as measured in a steady-state, cell-free system

A cell-free system consisting of rat liver mitochondria, liver cytosol, lactate, and the substrates intrinsic to the malate-aspartate shuttle was reconstituted for studies of steady-state substrate fluxes and, more specifically, to evaluate further the mechanism of control of the intra- and extramitochondrial steady states of the free NAD+/NADH ratios. Soluble (F1) ATPase or 2,4-dinitrophenol (DNP) were added in varying amounts to alter substrate fluxes and the constant energy state of this 'open' metabolizing system. The steady-state redox segregation (1.36 log NAD+/NADH ratio out vs NAD+/NADH in the mitochondrial matrix) was maximally about 3 kcal, and declined together with the membrane potential (delta psi) and log ATP/ADP, which obtain on imposing an increasing energy load on the system. It is concluded that transmembrane movement of reducing equivalents is coupled to electron transfer through delta psi, mediated by the electrogenic exchange of glutamate and aspartate. When delta psi was high (near State 4), delta G redox was approximately the same as that generated without flux of reducing equivalents [E. J. Davis, J. Bremer, and K. E. Akerman (1980) J. Biol. Chem. 255, 2277-2283], suggesting that delta Gredox is in near thermodynamic equilibrium with delta psi. If the steady-state ATP/ADP ratio was altered with an energy load (F1-ATPase), delta Gredox decreased more steeply than delta psi (tetraphenyl phosphonium-sensitive electrode used to measure delta psi). At comparable ranges of ATP/ADP, both delta Gredox and delta psi decreased more steeply with uncoupler than with an external ADP-regenerating system.     

Importance of spatial autocorrelation in modeling bird distributions at a continental scale

Spatial autocorrelation in species' distributions has been recognized as inflating the probability of a type I error in hypotheses tests, causing biases in variable selection, and violating the assumption of independence of error terms in models such as correlation or regression. However, it remains unclear whether these problems occur at all spatial resolutions and extents, and under which conditions spatially explicit modeling techniques are superior. Our goal was to determine whether spatial models were superior at large extents and across many different species. In addition, we investigated the importance of purely spatial effects in distribution patterns relative to the variation that could be explained through environmental conditions. We studied distribution patterns of 108 bird species in the conterminous United States using ten years of data from the Breeding Bird Survey. We compared the performance of spatially explicit regression models with non-spatial regression models using Akaike's information criterion. In addition, we partitioned the variance in species distributions into an environmental, a pure spatial and a shared component. The spatially-explicit conditional autoregressive regression models strongly outperformed the ordinary least squares regression models. In addition, partialling out the spatial component underlying the species' distributions showed that an average of 17% of the explained variation could be attributed to purely spatial effects independent of the spatial autocorrelation induced by the underlying environmental variables. We concluded that location in the range and neighborhood play an important role in the distribution of species. Spatially explicit models are expected to yield better predictions especially for mobile species such as birds, even in coarse-grained models with a large extent.     

Structural refinement and prediction of potential CCR2 antagonists through validated multi-QSAR modeling studies

Chemokines trigger numerous inflammatory responses and modulate the immune system. The interaction between monocyte chemoattractant protein-1 and chemokine receptor 2 (CCR2) may be the cause of atherosclerosis, obesity, and insulin resistance. However, CCR2 is also implicated in other inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, asthma, and neuropathic pain. Therefore, there is a paramount importance of designing potent and selective CCR2 antagonists despite a number of drug candidates failed in clinical trials. In this article, 83 CCR2 antagonists by Jhonson and Jhonson Pharmaceuticals have been considered for robust validated multi-QSAR modeling studies to get an idea about the structural and pharmacophoric requirements for designing more potent CCR2 antagonists. All these QSAR models were validated and statistically reliable. Observations resulted from different modeling studies correlated and validated results of other ones. Finally, depending on these QSAR observations, some new molecules were proposed that may exhibit higher activity against CCR2.     

Size distributions of total airborne particles and bioaerosols in a municipal composting facility

Size distributions of total airborne particles and bioaerosols were measured in a full-scale composting facility, using an optical particle counter and an agar-inserted six-stage impactor, respectively. Higher concentrations of total airborne particles and bioaerosols were detected at a sampling location near the screening process preceded by the composting process than at sampling locations in the composting process. At the sampling location near the screening process, the concentrations of total airborne particles were approximately 10(8)particles/m3 at the size of 0.3 microm and 10(5)particles/m3 at 6.2 microm. The concentration of bioaerosols was about 10(4)CFU/m3 in each stage of 7.0 microm (1st stage), 7.0-4.7 microm (2nd), 4.7-3.3 microm (3rd), 3.3-2.1 microm (4th), 2.1-1.1 microm (5th) and 1.1-0.65 microm (6th). Most of submicron particles smaller than 1 microm among the total airborne particles were believed to originate from the ambient air.     

MAP, a protein interacting with a tumor suppressor, merlin, through the run domain

Merlin (or schwannomin) is a tumor suppressor encoded by the neurofibromatosis type 2 gene. Many studies have suggested that merlin is involved in the regulation of cell growth and proliferation through interactions with various cellular proteins. To better understand the function of merlin, we tried to identify the proteins that bind to merlin using the yeast two-hybrid screening. Characterization of the positive clones revealed a protein of 749 amino acids named merlin-associated protein (MAP), which showed wide tissue distribution in Northern blot analysis. Sequence analysis revealed that MAP is a potential homologue of a yeast check-point protein, BUB2, and contains TBC, SH3, and RUN domains, thereby implicating its role in the Ras-like GTPase signal pathways. MAP and merlin were directly associated in vitro and in vivo, and colocalized in NIH3T3 cells. The RUN domain of MAP and the C-terminus of merlin appeared to be responsible for their interaction. MAP decreased the AP-1-dependent promoter activity additively with merlin in NIH3T3 cells. In addition, merlin and MAP synergistically reduced the colony formation of NIH3T3 cells. These results suggest that MAP may play a cooperative role in the merlin-mediated growth suppression of cells.     

Hydrolysis of ITP generates a membrane potential in submitochondrial particles

ITP hydrolysis catalysed by the ATPase of submitochondrial particles from both bovine heart and rat liver is shown to be linked to the generation of a membrane potential, and therefore also to proton translocation. The magnitude of the membrane potential is similar to that observed during ATP hydrolysis at equivalent concentrations of phosphate and nucleoside tri- and diphosphates. An explanation is suggested for why in other reports ITP was found to be a poor substrate for supporting energy-linked reactions that are driven by the membrane potential.