A Measure of Control for Secondary Cytokine-Induced Injury of Articular Cartilage: A Computational Study

In previous works, the author and collaborators establish a mathematical model for injury response in articular cartilage. In this paper we use mathematical software and computational techniques, applied to an existing model to explore in more detail how the behavior of cartilage cells is influenced by several of, what are believed to be, the most significant mechanisms underlying cartilage injury response at the cellular level. We introduce a control parameter, the radius of attenuation, and present some new simulations that shed light on how inflammation associated with cartilage injuries impacts the metabolic activity of cartilage cells. The details presented in the work can help to elucidate targets for more effective therapies in the preventative treatment of post-traumatic osteoarthritis

Molecular dynamics for fluid mechanics in arbitrary geometries

Simulations of nanoscale systems where fluid mechanics plays an important role are required to help design and understand nano-devices and biological systems. A simulation method which hybridises molecular dynamics (MD) and continuum computational fluid dynamics (CFD) models is able to accurately represent the relevant physical phenomena and be computationally tractable. An MD code has been written to perform MD simulations in systems where the geometry is described by a mesh of unstructured arbitrary polyhedral cells that have been spatially decomposed into irregular portions for parallel processing. The MD code that has been developed may be used for simulations on its own, or may serve as the MD component of a hybrid method. The code has been implemented using OpenFOAM, an open source C++ CFD toolbox (www.openfoam.org). The requirements for two key enabling components are described. 1) Parallel generation of initial configurations of molecules in arbitrary geometries. 2) Calculation of intermolecular pair forces, including between molecules that lie on mesh portions assigned to different, and possibly non-neighbouring processors. A case study of flow in a realistic nanoscale mixing channel, where the geometry is drawn and meshed in engineering CAD tools is simulated to demonstrate the capabilities of the code

A Unified Term for Directed and Undirected Motility in Collective Cell Invasion

In this paper we develop mathematical models for collective cell motility. Initially we develop a model using a linear diffusion-advection type equation and fit the parameters to data from cell motility assays. This approach is helpful in classifying the results of cell motility assay experiments. In particular, this model can determine degrees of directed versus undirected collective cell motility. Next we develop a model using a nonlinear diffusion term that is able capture in a unified way directed and undirected collective cell motility. Finally we apply the nonlinear diffusion approach to a problem in tumor cell invasion, noting that neither chemotaxis or haptotaxis are present in the system under consideration in this article

Effects Of Fatigue On The Balance Error Scoring System For Concussion Testing In Healthy And Previous Concussed Participants

There has been a recent increase in the attention of concussions in the media and research world. One of the major factors that contribute to injuries including concussion is fatigue. This study has been designed to allow athletic trainers to decipher whether a potential balance insufficiency in an acutely concussed athlete is due to fatigue or the side affects of the concussion on postural stability. The study examined 30 college-aged athletes from a multitude of sports who had either sustained a concussion or never had a concussion. Participants were randomly grouped into one of three groups: non-concussed control group, non-concussed treatment group, or a concussed treatment group. The participants completed a pretest of the Balance Error Scoring System (BESS) followed three days later by a fatigue protocol for those in the treatment groups and finished by completing a posttest BESS. The fatigue protocol is a seven station circuit program that has been utilized in past research studies using the Rating of Perceived Exertion (RPE) scale to measure fatigue. The results showed no significant difference in BESS scores from the pretest to posttest in any of the sample groups. There was a significant difference (p=.000) in RPE scores between the two treatment groups and the control group. These results indicate there was significant fatigue induced for the BESS posttest in the treatment groups. However, fatigue did not appear to influence the BESS test for either non-concussed or concussed participants

A concurrent precursor inflow method for Large Eddy Simulations and applications to finite length wind farms

In order to enable simulations of developing wind turbine array boundary layers with highly realistic inflow conditions a concurrent precursor method for Large Eddy Simulations is proposed. In this method we consider two domains simultaneously, i.e. in one domain a turbulent Atmospheric Boundary Layer (ABL) without wind turbines is simulated in order to generate the turbulent inflow conditions for a second domain in which the wind turbines are placed. The benefit of this approach is that a) it avoids the need for large databases in which the turbulent inflow conditions are stored and the correspondingly slow I/O operations and b) we are sure that the simulations are not negatively affected by statically swept fixed inflow fields or synthetic fields lacking the proper ABL coherent structures. Sample applications are presented, in which, in agreement with field data a strong decrease of the power output of downstream wind-turbines with respect to the first row of wind-turbines is observed for perfectly aligned inflow.Comment: 13 pages, 5 figure

The Role of Osteocytes in Targeted Bone Remodeling: A Mathematical Model

Until recently many studies of bone remodeling at the cellular level have focused on the behavior of mature osteoblasts and osteoclasts, and their respective precursor cells, with the role of osteocytes and bone lining cells left largely unexplored. This is particularly true with respect to the mathematical modeling of bone remodeling. However, there is increasing evidence that osteocytes play important roles in the cycle of targeted bone remodeling, in serving as a significant source of RANKL to support osteoclastogenesis, and in secreting the bone formation inhibitor sclerostin. Moreover, there is also increasing interest in sclerostin, an osteocyte-secreted bone formation inhibitor, and its role in regulating local response to changes in the bone microenvironment. Here we develop a cell population model of bone remodeling that includes the role of osteocytes, sclerostin, and allows for the possibility of RANKL expression by osteocyte cell populations. This model extends and complements many of the existing mathematical models for bone remodeling but can be used to explore aspects of the process of bone remodeling that were previously beyond the scope of prior modeling work. Through numerical simulations we demonstrate that our model can be used to theoretically explore many of the most recent experimental results for bone remodeling, and can be utilized to assess the effects of novel bone-targeting agents on the bone remodeling process

Towards a New Spatial Representation of Bone Remodeling

Irregular bone remodeling is associated with a number of bone diseases such as osteoporosis and multiple myeloma. Computational and mathematical modeling can aid in therapy and treatment as well as understanding fundamental biology. Different approaches to modeling give insight into different aspects of a phenomena so it is useful to have an arsenal of various computational and mathematical models. Here we develop a mathematical representation of bone remodeling that can effectively describe many aspects of the complicated geometries and spatial behavior observed. There is a sharp interface between bone and marrow regions. Also the surface of bone moves in and out, i.e. in the normal direction, due to remodeling. Based on these observations we employ the use of a level-set function to represent the spatial behavior of remodeling. We elaborate on a temporal model for osteoclast and osteoblast population dynamics to determine the change in bone mass which influences how the interface between bone and marrow changes. We exhibit simulations based on our computational model that show the motion of the interface between bone and marrow as a consequence of bone remodeling. The simulations show that it is possible to capture spatial behavior of bone remodeling in complicated geometries as they occur \emph{in vitro} and \emph{in vivo}. By employing the level set approach it is possible to develop computational and mathematical representations of the spatial behavior of bone remodeling. By including in this formalism further details, such as more complex cytokine interactions and accurate parameter values, it is possible to obtain simulations of phenomena related to bone remodeling with spatial behavior much as \emph{in vitro} and \emph{in vivo}. This makes it possible to perform \emph{in silica} experiments more closely resembling experimental observations.Comment: Math. Biosci. Eng., 9(2), 201