Simplification of structured population dynamics in complex ecological communities

Goldstone's idea of slow dynamics resulting from spontaneously broken symmetries is applied to Hubbell's neutral hypothesis of community dynamics, to efficiently simplify stage-structured multi-species models-introducing the quasi-neutral approximation (QNA). Rather than assuming population-dynamical neutrality in the QNA, deviations from ideal neutrality, thought to be small, drive dynamics. The QNA is systematically derived to first and second order in a two-scale singular perturbation expansion. The total reproductive value of species, as computed from the effective life-history parameters resulting from the non-linear interactions with the surrounding community, emerges as the new dynamic variables in this aggregated description. Using a simple stage-structured community-assembly model, the QNA is demonstrated to accurately reproduce population dynamics in large, complex communities. Further, the utility of the QNA in building intuition for management problems is illustrated by estimating the responses of a fish stock to harvesting and variations in fecundity.

Bioreactor Expansion of Human Adult Bone Marrow-Derived Mesenchymal Stem Cells

Supplementation of mesenchymal stem cells (MSCs) during hematopoietic stem cell transplantation (HSCT) alleviates complications such as graft-versus-host disease, leading to a speedy recovery of hematopoiesis. To meet such clinical demand, a fast MSCs expansion method is required. In the present study, we examined the feasibility of expanding MSCs from the isolated bone marrow mononuclear cells using a rotary bioreactor system. The cells were cultured in a rotary bioreactor with Myelocult� medium containing a combination of supplementary factors, including stem cell factor (SCF), interleukin 3 and 6 (IL-3, IL-6). After 8 days of culture, total cell numbers, Stro-1+CD44+CD34- MSCs and CD34+CD44+Stro-1- HSCs were increased 9, 29, and 8 folds respectively. Colony forming efficiency-fibroblast per day (CFE-F/day) of the bioreactor-treated cells was 1.44-fold higher than that of the cells without bioreactor treatment. The bioreactor-expanded MSCs showed expression of primitive MSCs markers endoglin (SH2) and vimentin, whereas markers associated with lineage differentiation including osteocalcin (osteogenesis), Type II collagen (chondrogenesis) and C/EBPα (adipogenesis) were not detected. Upon induction, the bioreactor-expanded MSCs were able to differentiate into osteoblasts, chondrocytes and adipocytes. Taken together, we conclude that the rotary bioreactor with the modified Myelocult� medium reported in this study may be used to rapidly expand MSCs.

Determining the electronic structure and chemical potentials of molecules in solution

A simulation scheme is proposed for determining the excess chemical potential of a substance in solution. First, a Monte Carlo simulation is performed with classical models for solute and solvent molecules. A representative sample of these configurations is then used in a hybrid quantum/classical (QM/MM) calculation, where the solute is treated quantum-mechanically, and the average electronic structure is used to construct an improved classical model. This procedure is iterated to self-consistency in the classical model, which in practice is attained in one or two steps, depending on the quality of the initial guess. The excess free energy of the molecule within the QM/MM approach is determined relative to the classical model using thermodynamic perturbation theory with a cumulant expansion. The procedure provides a method of constructing classical point charge models appropriate for the solution and gives a measure of the importance of solvent fluctuations.

Correlated electron-ion dynamics: the excitation of atomic motion by energetic electrons

Correlated electron-ion dynamics (CEID) is an extension of molecular dynamics that allows us to introduce in a correct manner the exchange of energy between electrons and ions. The formalism is based on a systematic approximation: small amplitude moment expansion. This formalism is extended here to include the explicit quantum spread of the ions and a generalization of the Hartree-Fock approximation for incoherent sums of Slater determinants. We demonstrate that the resultant dynamical equations reproduce analytically the selection rules for inelastic electron-phonon scattering from perturbation theory, which control the mutually driven excitations of the two interacting subsystems. We then use CEID to make direct numerical simulations of inelastic current-voltage spectroscopy in atomic wires, and to exhibit the crossover from ionic cooling to heating as a function of the relative degree of excitation of the electronic and ionic subsystems.

Antigen-specific T-T interactions regulate CD4 T-cell expansion.

The regulation of CD4 T cell numbers during an immune response should take account of the amount of antigen (Ag), the initial frequency of Ag-specific T cells, the mix of naive versus experienced cells, and (ideally) the diversity of the repertoire. Here we describe a novel mechanism of T cell regulation that potentially deals with all of these parameters. We found that CD4 T cells establish a negative feedback loop by capturing their cognate MHC/peptide complexes from Ag-presenting cells and presenting them to Ag-experienced CD4 T cells, thereby inhibiting their recruitment into the response while allowing recruitment of naive T cells. The inhibition is Ag specific, begins at day 2 (long before Ag disappearance), and cannot be overcome by providing new Ag-loaded dendritic cells. In this way CD4 T cell proliferation is regulated in a functional relationship to the amount of Ag, while allowing naive T cells to generate repertoire variety.

Testing the role of expansion in the prospective control of locomotion

The constant bearing angle (CBA) strategy is a prospective strategy that permits the interception of moving objects. The purpose of the present study is to test this strategy. Participants were asked to walk through a virtual environment and to change, if necessary, their walking speed so as to intercept approaching targets. The targets followed either a rectilinear or a curvilinear trajectory and target size was manipulated both within trials (target size was gradually changed during the trial in order to bias expansion) and between trials (targets of different sizes were used). The curvature manipulation had a large effect on the kinematics of walking, which is in agreement with the CBA strategy. The target size manipulations also affected the kinematics of walking. Although these effects of target size are not predicted by the CBA strategy, quantitative comparisons of observed kinematics and the kinematics predicted by the CBA strategy showed good fits. Furthermore, predictions based on the CBA strategy were deemed superior to predictions based on a required velocity (V-REQ) model. The role of target size and expansion in the prospective control of walking is discussed.