Effect of Radius on Load/Strain Distribution between Ulna and Radius: Experimental and Numberical Analyses

Computational Infrastructure and Informatics Poster SessionIt has been hypothesized that osteocytes are stimulated by local strain distribution within the bone subjected to mechanical loadings. This collaborative research project between bone biologists and mechanical engineers is attempting to identify local strain fields around osteocytes that can account for their behavior in response to loading. Using CT images we have built and conducted an extensive finite element study of the mouse forearm. Our model incorporates many components of forearm anatomy not previously included in these models such as the radius and marrow cavities. The results of the current research will shed light on how bone perceives mechanical load and the pathway whereby a physical load is transduced into a biochemical signal that eventually results in new bone formation. The study will help in developing new treatments for bone diseases such as osteoporosis

Existence of periodic traveling wave solutions to the generalized forced Boussinesq equation

The generalized forced Boussinesq equation, utt−uxx+[f(u)]xx+uxxxx=h0, and its periodic traveling wave solutions are considered. Using the transform z=x−ωt, the equation is converted to a nonlinear ordinary differential equation with periodic boundary conditions. An equivalent relation between the ordinary differential equation and a Hammerstein type integral equation is then established by using the Green's function method. This integral equation generates compact operators in a Banach space of real-valued continuous periodic functions with a given period 2T. The Schauder's fixed point theorem is then used to prove the existence of solutions to the integral equation. Therefore, the existence of nonconstant periodic traveling wave solutions to the generalized forced Boussinesq equation is established

Parallel Self-Consistent-Field Calculations via Chebyshev-Filtered Subspace Acceleration

Solving the Kohn-Sham eigenvalue problem constitutes the most computationally expensive part in self-consistent density functional theory (DFT) calculations. In a previous paper, we have proposed a nonlinear Chebyshev-filtered subspace iteration method, which avoids computing explicit eigenvectors except at the first SCF iteration. The method may be viewed as an approach to solve the original nonlinear Kohn-Sham equation by a nonlinear subspace iteration technique, without emphasizing the intermediate linearized Kohn-Sham eigenvalue problem. It reaches self-consistency within a similar number of SCF iterations as eigensolver-based approaches. However, replacing the standard diagonalization at each SCF iteration by a Chebyshev subspace filtering step results in a significant speedup over methods based on standard diagonalization. Here, we discuss an approach for implementing this method in multi-processor, parallel environment. Numerical results are presented to show that the method enables to perform a class of highly challenging DFT calculations that were not feasible before

Self-consistent-field calculations using Chebyshev-filtered subspace iteration

Abstract The power of density functional theory is often limited by the high computational demand in solving an eigenvalue problem at each self-consistent-field (SCF) iteration. The method presented in this paper replaces the explicit eigenvalue calculations by an approximation of the wanted invariant subspace, obtained with the help of well-selected Chebyshev polynomial filters. In this approach, only the initial SCF iteration requires solving an eigenvalue problem, in order to provide a good initial subspace. In the remaining SCF iterations, no iterative eigensolvers are involved. Instead, Chebyshev polynomials are used to refine the subspace. The subspace iteration at each step is easily five to ten times faster than solving a corresponding eigenproblem by the most efficient eigen-algorithms. Moreover, the subspace iteration reaches self-consistency within roughly the same number of steps as an eigensolver-based approach. This results in a significantly faster SCF iteration

Rapamycin Pharmacokinetic and Pharmacodynamic Relationships in Osteosarcoma: A Comparative Oncology Study in Dogs

Signaling through the mTOR pathway contributes to growth, progression and chemoresistance of several cancers. Accordingly, inhibitors have been developed as potentially valuable therapeutics. Their optimal development requires consideration of dose, regimen, biomarkers and a rationale for their use in combination with other agents. Using the infrastructure of the Comparative Oncology Trials Consortium many of these complex questions were asked within a relevant population of dogs with osteosarcoma to inform the development of mTOR inhibitors for future use in pediatric osteosarcoma patients.This prospective dose escalation study of a parenteral formulation of rapamycin sought to define a safe, pharmacokinetically relevant, and pharmacodynamically active dose of rapamycin in dogs with appendicular osteosarcoma. Dogs entered into dose cohorts consisting of 3 dogs/cohort. Dogs underwent a pre-treatment tumor biopsy and collection of baseline PBMC. Dogs received a single intramuscular dose of rapamycin and underwent 48-hour whole blood pharmacokinetic sampling. Additionally, daily intramuscular doses of rapamycin were administered for 7 days with blood rapamycin trough levels collected on Day 8, 9 and 15. At Day 8 post-treatment collection of tumor and PBMC were obtained. No maximally tolerated dose of rapamycin was attained through escalation to the maximal planned dose of 0.08 mg/kg (2.5 mg/30 kg dog). Pharmacokinetic analysis revealed a dose-dependent exposure. In all cohorts modulation of the mTOR pathway in tumor and PBMC (pS6RP/S6RP) was demonstrated. No change in pAKT/AKT was seen in tumor samples following rapamycin therapy.Rapamycin may be safely administered to dogs and can yield therapeutic exposures. Modulation pS6RP/S6RP in tumor tissue and PBMCs was not dependent on dose. Results from this study confirm that the dog may be included in the translational development of rapamycin and potentially other mTOR inhibitors. Ongoing studies of rapamycin in dogs will define optimal schedules for their use in cancer and evaluate the role of rapamycin use in the setting of minimal residual disease

A global perspective on the trophic geography of sharks

Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats. We show that populations of shelf-dwelling sharks derive a substantial proportion of their carbon from regional pelagic sources, but contain individuals that forage within additional isotopically diverse local food webs, such as those supported by terrestrial plant sources, benthic production and macrophytes. In contrast, oceanic sharks seem to use carbon derived from between 30° and 50° of latitude. Global-scale compilations of stable isotope data combined with biogeochemical modelling generate hypotheses regarding animal behaviours that can be tested with other methodological approaches.This research was conducted as part of C.S.B.’s Ph.D dissertation, which was funded by the University of Southampton and NERC (NE/L50161X/1), and through a NERC Grant-in-Kind from the Life Sciences Mass Spectrometry Facility (LSMSF; EK267-03/16). We thank A. Bates, D. Sims, F. Neat, R. McGill and J. Newton for their analytical contributions and comments on the manuscripts.Peer reviewe

Existence of periodic traveling wave solution to the forced generalized nearly concentric Korteweg-de Vries equation

This paper is concerned with periodic traveling wave solutions of the forced generalized nearly concentric Korteweg-de Vries equation in the form of (uη+u/(2η)+[f(u)]ξ+uξξξ)ξ+uθθ/η2=h0. The authors first convert this equation into a forced generalized Kadomtsev-Petviashvili equation, (ut+[f(u)]x+uxxx)x+uyy=h0, and then to a nonlinear ordinary differential equation with periodic boundary conditions. An equivalent relationship between the ordinary differential equation and nonlinear integral equations with symmetric kernels is established by using the Green's function method. The integral representations generate compact operators in a Banach space of real-valued continuous functions. The Schauder's fixed point theorem is then used to prove the existence of nonconstant solutions to the integral equations. Therefore, the existence of periodic traveling wave solutions to the forced generalized KP equation, and hence the nearly concentric KdV equation, is proved