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

Modeling and Simulation of the Effects of Cyclic Loading on Articular Cartilage Lesion Formation

We present a model of articular cartilage lesion formation to simulate the effects of cyclic loading. This model extends and modifies the reaction-diffusion-delay model by Graham et al. 2012 for the spread of a lesion formed though a single traumatic event. Our model represents "implicitly" the effects of loading, meaning through a cyclic sink term in the equations for live cells. Our model forms the basis for in silico studies of cartilage damage relevant to questions in osteoarthritis, for example, that may not be easily answered through in vivo or in vitro studies. Computational results are presented that indicate the impact of differing levels of EPO on articular cartilage lesion abatement

Computational Analyses in Support of Sub-scale Diffuser Testing for the A-3 Facility

Simulation technology can play an important role in rocket engine test facility design and development by assessing risks, providing analysis of dynamic pressure and thermal loads, identifying failure modes and predicting anomalous behavior of critical systems. Advanced numerical tools assume greater significance in supporting testing and design of high altitude testing facilities and plume induced testing environments of high thrust engines because of the greater inter-dependence and synergy in the functioning of the different sub-systems. This is especially true for facilities such as the proposed A-3 facility at NASA SSC because of a challenging operating envelope linked to variable throttle conditions at relatively low chamber pressures. Facility designs in this case will require a complex network of diffuser ducts, steam ejector trains, fast operating valves, cooling water systems and flow diverters that need to be characterized for steady state performance. In this paper, we will demonstrate with the use of CFD analyses s advanced capability to evaluate supersonic diffuser and steam ejector performance in a sub-scale A-3 facility at NASA Stennis Space Center (SSC) where extensive testing was performed. Furthermore, the focus in this paper relates to modeling of critical sub-systems and components used in facilities such as the A-3 facility. The work here will address deficiencies in empirical models and current CFD analyses that are used for design of supersonic diffusers/turning vanes/ejectors as well as analyses for confined plumes and venting processes. The primary areas that will be addressed are: (1) supersonic diffuser performance including analyses of thermal loads (2) accurate shock capturing in the diffuser duct; (3) effect of turning duct on the performance of the facility (4) prediction of mass flow rates and performance classification for steam ejectors (5) comparisons with test data from sub-scale diffuser testing and assessment of confidence levels in CFD based flowpath modeling of the facility. The analyses tools used here expand on the multi-element unstructured CFD which has been tailored and validated for impingement dynamics of dry plumes, complex valve/feed systems, and high pressure propellant delivery systems used in engine and component test stands at NASA SSC. The analyses performed in the evaluation of the sub-scale diffuser facility explored several important factors that influence modeling and understanding of facility operation such as (a) importance of modeling the facility with Real Gas approximation, (b) approximating the cluster of steam ejector nozzles as a single annular nozzle, (c) existence of mixed subsonic/supersonic flow downstream of the turning duct, and (d) inadequacy of two-equation turbulence models in predicting the correct pressurization in the turning duct and expansion of the second stage steam ejectors. The procedure used for modeling the facility was as follows: (i) The engine, test cell and first stage ejectors were simulated with an axisymmetric approximation (ii) the turning duct, second stage ejectors and the piping downstream of the second stage ejectors were analyzed with a three-dimensional simulation utilizing a half-plane symmetry approximation. The solution i.e. primitive variables such as pressure, velocity components, temperature and turbulence quantities were passed from the first computational domain and specified as a supersonic boundary condition for the second simulation. (iii) The third domain comprised of the exit diffuser and the region in the vicinity of the facility (primary included to get the correct shock structure at the exit of the facility and entrainment characteristics). The first set of simulations comprising the engine, test cell and first stage ejectors was carried out both as a turbulent real gas calculation as well as a turbulent perfect gas calculation. A comparison for the two cases (Real Turbulent and Perfect gas turbulent) of the Ma Number distribution and temperature distributions are shown in Figures 1 and 2 respectively

Computational Analyses in Support of Sub-scale Diffuser Testing for the A-3 Facility

Simulation technology can play an important role in rocket engine test facility design and development by assessing risks, providing analysis of dynamic pressure and thermal loads, identifying failure modes and predicting anomalous behavior of critical systems. Advanced numerical tools assume greater significance in supporting testing and design of high altitude testing facilities and plume induced testing environments of high thrust engines because of the greater inter-dependence and synergy in the functioning of the different sub-systems. This is especially true for facilities such as the proposed A-3 facility at NASA SSC because of a challenging operating envelope linked to variable throttle conditions at relatively low chamber pressures. Facility designs in this case will require a complex network of diffuser ducts, steam ejector trains, fast operating valves, cooling water systems and flow diverters that need to be characterized for steady state performance. In this paper, we will demonstrate with the use of CFD analyses s advanced capability to evaluate supersonic diffuser and steam ejector performance in a sub-scale A-3 facility at NASA Stennis Space Center (SSC) where extensive testing was performed. Furthermore, the focus in this paper relates to modeling of critical sub-systems and components used in facilities such as the A-3 facility. The work here will address deficiencies in empirical models and current CFD analyses that are used for design of supersonic diffusers/turning vanes/ejectors as well as analyses for confined plumes and venting processes. The primary areas that will be addressed are: (1) supersonic diffuser performance including analyses of thermal loads (2) accurate shock capturing in the diffuser duct; (3) effect of turning duct on the performance of the facility (4) prediction of mass flow rates and performance classification for steam ejectors (5) comparisons with test data from sub-scale diffuser testing and assessment of confidence levels in CFD based flowpath modeling of the facility. The analyses tools used here expand on the multi-element unstructured CFD which has been tailored and validated for impingement dynamics of dry plumes, complex valve/feed systems, and high pressure propellant delivery systems used in engine and component test stands at NASA SSC. The analyses performed in the evaluation of the sub-scale diffuser facility explored several important factors that influence modeling and understanding of facility operation such as (a) importance of modeling the facility with Real Gas approximation, (b) approximating the cluster of steam ejector nozzles as a single annular nozzle, (c) existence of mixed subsonic/supersonic flow downstream of the turning duct, and (d) inadequacy of two-equation turbulence models in predicting the correct pressurization in the turning duct and expansion of the second stage steam ejectors. The procedure used for modeling the facility was as follows: (i) The engine, test cell and first stage ejectors were simulated with an axisymmetric approximation (ii) the turning duct, second stage ejectors and the piping downstream of the second stage ejectors were analyzed with a three-dimensional simulation utilizing a half-plane symmetry approximation. The solution i.e. primitive variables such as pressure, velocity components, temperature and turbulence quantities were passed from the first computational domain and specified as a supersonic boundary condition for the second simulation. (iii) The third domain comprised of the exit diffuser and the region in the vicinity of the facility (primary included to get the correct shock structure at the exit of the facility and entrainment characteristics). The first set of simulations comprising the engine, test cell and first stage ejectors was carried out both as a turbulent real gas calculation as well as a turbulent perfect gas calculation. A comparison for the two cases (Real Turbulent and Perfect gas turbulent) of the Ma Number distribution and temperature distributions are shown in Figures 1 and 2 respectively. The Mach Number distribution shows small yet distinct differences between the two cases such as locations of shocks/shock reflections and a slightly different impingement point on the wall of the diffuser from the expansion at the exit of the nozzle. Similarly the temperature distribution indicates different flow recirculation patterns in the test cell. Both cases capture all the essential flow phenomena such as the shock-boundary layer interaction, plume expansion, expansion of the first stage ejectors, mixing between the engine plume and the first stage ejector flow and pressurization due to the first stage ejectors. The final paper will discuss thermal loads on the walls of the diffuser and cooling mechanisms investigated

Computational Analyses in Support of Sub-scale Diffuser Testing for the A-3 Facility

A unique assessment of acoustic similarity scaling laws and acoustic analogy methodologies in predicting the far-field acoustic signature from a sub-scale altitude rocket test facility at the NASA Stennis Space Center was performed. A directional, point-source similarity analysis was implemented for predicting the acoustic far-field. In this approach, experimental acoustic data obtained from "similar" rocket engine tests were appropriately scaled using key geometric and dynamic parameters. The accuracy of this engineering-level method is discussed by comparing the predictions with acoustic far-field measurements obtained. In addition, a CFD solver was coupled with a Lilley's acoustic analogy formulation to determine the improvement of using a physics-based methodology over an experimental correlation approach. In the current work, steady-state Reynolds-averaged Navier-Stokes calculations were used to model the internal flow of the rocket engine and altitude diffuser. These internal flow simulations provided the necessary realistic input conditions for external plume simulations. The CFD plume simulations were then used to provide the spatial turbulent noise source distributions in the acoustic analogy calculations. Preliminary findings of these studies will be discussed

Whole body cryotherapy and recovery from exercise induced muscle damage: A systematic review

Introduction Cold therapies are used regularly in medicine for their analgesic and anti-inflammatory effects. Whole-body cryotherapy (WBC) involves exposure to air maintained between -110 and -160oC, and is hypothesised to reduce pain, local and systemic inflammation. WBC has recently become popular in an exercise and sporting context as a recovery method after skeletal muscle damage, however, research examining the efficacy of WBC in an athletic context is minimal. This review seeks to summarise the evidence for the effects of WBC on exercise recovery measures. Methods Electronic database searches were conducted from March to April 2013. Six large online databases were used; MEDLINE, SPORTDiscus, Scopus, Web of Science, PubMed and AMED. The search targeted human studies with an exercise task, and WBC intervention. Results included randomised controlled trials (RCT’s), uncontrolled trials and crossover designs. Results A total of 8 studies were included in the review. Two RCT’s, four crossover trials and two uncontrolled trials were identified. Five studies showed WBC had no effect on markers of muscle damage or inflammation post exercise, while 3 studies show a positive effect. Three out of the eight studies measured maximal muscle force production and subjective pain levels following exercise and WBC, with two showing WBC had a positive effect on muscle force recovery and pain. A meta-analysis was not conducted due to the heterogeneity of the studies. Conclusion The current evidence for the efficacy of WBC on exercise recovery is unclear. Published studies report mixed findings, and the study designs make these results difficult to interpret. As WBC is proposed as an aid to recovery in an athletic population, repeated measures of performance, muscle force production and pain are of importance to the athlete, however, are minimally reported in the literature. Cold water immersion (CWI) is widely used in an athletic setting for recovery, and has much literature supporting its use for the reduction of pain post-exercise. Well-designed RCT’s with controlled exercise interventions targeting performance measures are needed, in particular comparison of WBC with CWI data is needed for evaluation

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV