Search

An end-to-end, mechanism-based concussion risk model, linking head motion to axonal injury, has been demonstrated to predict concussion outcomes with greater sensitivity and specificity than external correlates such as peak head acceleration. The development of this model was driven by the need to more accurately translate head-worn sensor measurements into injury assessment in near-real time. The full end-to-end model is a detailed multi-scale model, composed of complex components (e.g., a human head finite element model), is computationally expensive, and requires specialized software. For practicality, this research-level model must be simplified into a standalone, fast-running algorithm that can be embedded on the microprocessor of a head-worn sensor. This article describes the development of a simplified, fast-running algorithm that delivers comparable results to those of the full end-to-end model. The dynamic axonal response of the human head finite element model to head motion is mathematically modeled using a lumped parameter system fitted to the finite element model response for a range of head motions. The other component models of the full end-to-end model were similarly reduced. For the same head kinematic scenarios, the probabilities of concussion obtained from the end-to-end model and from the simplified algorithm are compared well.

Past concussion studies have focused on understanding the injury processes occurring on discrete length scales (e.g., tissue-level stresses and strains, cell-level stresses and strains, or injury-induced cellular pathology). A comprehensive approach that connects all length scales and relates measurable macroscopic parameters to neurological outcomes is the first step toward rationally unraveling the complexity of this multi-scale system, for better guidance of future research. This paper describes the development of the first quantitative end-to-end multi-scale model that links gross head motion to neurological injury by integrating fundamental elements of tissue and cellular mechanical response with axonal dysfunction. The model quantifies axonal stretch (i.e., tension) injury in the corpus callosum, with axonal functionality parameterized in terms of axonal signaling. An internal injury correlate is obtained by calculating a neurological injury measure (the average reduction in the axonal signal amplitude) over the corpus callosum. By using a neurologically based quantity rather than externally measured head kinematics, the end-to-end model is able to unify concussion data across a range of exposure conditions and species with greater sensitivity and specificity than correlates based on external measures. In addition, this model quantitatively links injury of the corpus callosum to observed specific neurobehavioral outcomes that reflect clinical measures of mild traumatic brain injury. This comprehensive modeling framework provides a basis for the systematic improvement and expansion of this mechanistic-based understanding, including widening the range of neurological injury estimation, improving concussion risk correlates, guiding the design of protective equipment, and setting safety standards.

Enveloped viruses attach to host cells by binding to receptors on the cell surface. For many viruses, entry occurs via membrane fusion after a sufficient number of receptors have engaged ligand proteins on the virion. Under conditions where the cell surface receptor densities are low, recruitment of receptors may be limited by diffusion rather than by receptor-ligand interactions. We present a receptor-binding model that includes the effects of receptor availability at the viral binding site. The receptor binding and unbinding kinetics are coupled to receptor diffusion across the cell membrane. We find numerical solutions to our model and analyze the viral entry probabilities and the mean times to entry as functions of receptor concentration, receptor diffusivity, receptor binding stoichiometry, receptor detachment rates, and virus degradation/detachment rates. We also show how entry probabilities and times differ when receptors bind randomly or sequentially to the binding sites on the viral glycoprotein spikes. Our results provide general insight into the biophysical transport mechanisms that may arise in viral attachment and entry.

A detailed 3D finite element model (FEM) of the sheep thorax was developed to predict heterogeneous and volumetric lung injury due to blast. A shared node mesh of the sheep thorax was constructed from a computed tomography (CT) scan of a sheep cadaver, and while most material properties were taken from literature, an elastic–plastic material model was used for the ribs based on three-point bending experiments performed on sheep rib specimens. Anesthetized sheep were blasted in an enclosure, and blast overpressure data were collected using the blast test device (BTD), while surface lung injury was quantified during necropsy. Matching blasts were simulated using the sheep thorax FEM. Surface lung injury in the FEM was matched to pathology reports by setting a threshold value of the scalar output termed the strain product (maximum value of the dot product of strain and strain-rate vectors over all simulation time) in the surface elements. Volumetric lung injury was quantified by applying the threshold value to all elements in the model lungs, and a correlation was found between predicted volumetric injury and measured postblast lung weights. All predictions are made for the left and right lungs separately. This work represents a significant step toward the prediction of localized and heterogeneous blast lung injury, as well as volumetric injury, which was not recorded during field testing for sheep.

The elastic properties of capsids of the cowpea chlorotic mottle virus have been examined at pH 4.8 by nanoindentation measurements with an atomic force microscope. Studies have been carried out on WT capsids, both empty and containing the RNA genome, and on full capsids of a salt-stable mutant and empty capsids of the subE mutant. Full capsids resisted indentation more than empty capsids, but all of the capsids were highly elastic. There was an initial reversible linear regime that persisted up to indentations varying between 20% and 30% of the diameter and applied forces of 0.6-1.0 nN; it was followed by a steep drop in force that is associated with irreversible deformation. A single point mutation in the capsid protein increased the capsid stiffness. The experiments are compared with calculations by finite element analysis of the deformation of a homogeneous elastic thick shell. These calculations capture the features of the reversible indentation region and allow Young's moduli and relative strengths to be estimated for the empty capsids. © 2006 by The National Academy of Sciences of the USA.