Enhancement of the immunoregulatory potency of mesenchymal stromal cells by treatment with immunosuppressive drugs

Background aims Multipotent mesenchymal stromal cells (MSCs) are distinguished by their ability to differentiate into a number of stromal derivatives of interest for regenerative medicine, but they also have immunoregulatory properties that are being tested in a number of clinical settings. Methods We show that brief incubations with rapamycin, everolimus, FK506 or cyclosporine A increase the immunosuppressive potency of MSCs and other cell types. Results The treated MSCs are up to 5-fold more potent at inhibiting the induced proliferation of T lymphocytes in vitro. We show that this effect probably is due to adsorption of the drug by the MSCs during pre-treatment, with subsequent diffusion into co-cultures at concentrations sufficient to inhibit T-cell proliferation. MSCs contain measurable amounts of rapamycin after a 15-min exposure, and the potentiating effect is blocked by a neutralizing antibody to the drug. With the use of a pre-clinical model of acute graft-versus-host disease, we demonstrate that a low dose of rapamycin-treated but not untreated umbilical cord–derived MSCs significantly inhibit the onset of disease. Conclusions The use of treated MSCs may achieve clinical end points not reached with untreated MSCs and allow for infusion of fewer cells to reduce costs and minimize potential side effects

Traffic by multiple species of molecular motors

We study the traffic of two types of molecular motors using the two-species symmetric simple exclusion process (ASEP) with periodic boundary conditions and with attachment and detachment of particles. We determine characteristic properties such as motor densities and currents by simulations and analytical calculations. For motors with different unbinding probabilities, mean field theory gives the correct bound density and total current of the motors, as shown by numerical simulations. For motors differing in their stepping probabilities, the particle-hole symmetry of the current-density relationship is broken and mean field theory fails drastically. The total motor current exhibits exponential finite-size scaling, which we use to extrapolate the total current to the thermodynamic limit. Finally, we also study the motion of a single motor in the background of many non-moving motors.Comment: 23 pages, 6 figures, late

Orbital-Free Density Functional Theory: Kinetic Potentials and Ab-Initio Local Pseudopotentials

In the density functional (DF) theory of Kohn and Sham, the kinetic energy of the ground state of a system of noninteracting electrons in a general external field is calculated using a set of orbitals. Orbital free methods attempt to calculate this directly from the electron density by approximating the universal but unknown kinetic energy density functional. However simple local approximations are inaccurate and it has proved very difficult to devise generally accurate nonlocal approximations. We focus instead on the kinetic potential, the functional derivative of the kinetic energy DF, which appears in the Euler equation for the electron density. We argue that the kinetic potential is more local and more amenable to simple physically motivated approximations in many relevant cases, and describe two pathways by which the value of the kinetic energy can be efficiently calculated. We propose two nonlocal orbital free kinetic potentials that reduce to known exact forms for both slowly varying and rapidly varying perturbations and also reproduce exact results for the linear response of the density of the homogeneous system to small perturbations. A simple and systematic approach for generating accurate and weak ab-initio local pseudopotentials which produce a smooth slowly varying valence component of the electron density is proposed for use in orbital free DF calculations of molecules and solids. The use of these local pseudopotentials further minimizes the possible errors from the kinetic potentials. Our theory yields results for the total energies and ionization energies of atoms, and for the shell structure in the atomic radial density profiles that are in very good agreement with calculations using the full Kohn-Sham theory.Comment: To be published in Phys. Rev.

Nanometric size effect on Ge diffusion in polycrystalline Si

The nanosize effect on Ge diffusion (850 \u3c = T \u3c = 1000 degrees C) in polycrystalline Si layers is investigated. The Ge diffusion coefficients in microcrystalline and nanocrystalline Si layers made of 30 mu m and 40 nm wide grains, respectively, are measured and compared. In the microcrystalline Si layer, the Ge diffusion coefficient in micrograin boundaries is measured using a conventional analytical solution of Fick\u27s equations corresponding to the Fisher model. In the nanocrystalline Si layer, the Ge diffusion coefficients in nanograins and in nanograin boundaries are measured via a method based on two-dimensional simulations using the Fisher model geometry. The diffusivities in nanograins and nanograin boundaries are one order of magnitude higher than in micrograins and micrograin boundaries, respectively. However, the nanosize effect appears to be different in grains and grain boundaries; despite that the activation energy for diffusion in 40 nm wide grains is at least 1 eV lower than in Si bulk. The activation energy in nanograin boundaries is about the same as in micrograin boundaries

Method of Obtaining High Resolution Intrinsic Wire Boom Damping Parameters for Multi-Body Dynamics Simulations

The goal of NASA's Magnetospheric MultiScale (MMS) mission is to understand magnetic reconnection with sensor measurements from four spinning satellites flown in a tight tetrahedron formation. Four of the six electric field sensors on each satellite are located at the end of 60- meter wire booms to increase measurement sensitivity in the spin plane and to minimize motion coupling from perturbations on the main body. A propulsion burn however, might induce boom oscillations that could impact science measurements if oscillations do not damp to values on the order of 0.1 degree in a timely fashion. Large damping time constants could also adversely affect flight dynamics and attitude control performance. In this paper, we will discuss the implementation of a high resolution method for calculating the boom's intrinsic damping, which was used in multi-body dynamics simulations. In summary, experimental data was obtained with a scaled-down boom, which was suspended as a pendulum in vacuum. Optical techniques were designed to accurately measure the natural decay of angular position and subsequently, data processing algorithms resulted in excellent spatial and temporal resolutions. This method was repeated in a parametric study for various lengths, root tensions and vacuum levels. For all data sets, regression models for damping were applied, including: nonlinear viscous, frequency-independent hysteretic, coulomb and some combination of them. Our data analysis and dynamics models have shown that the intrinsic damping for the baseline boom is insufficient, thereby forcing project management to explore mitigation strategies

Long range action in networks of chaotic elements

We show that under certain simple assumptions on the topology (structure) of networks of strongly interacting chaotic elements a phenomenon of long range action takes place, namely that the asymptotic (as time goes to infinity) dynamics of an arbitrary large network is completely determined by its boundary conditions. This phenomenon takes place under very mild and robust assumptions on local dynamics with short range interactions. However, we show that it is unstable with respect to arbitrarily weak local random perturbations.Comment: 15 page

Insights into ALS pathomechanisms:from flies to humans

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease causing the death of motor neurons with consequent muscle atrophy and paralysis. Several neurodegenerative diseases have been modeled in Drosophila and genetic studies on this model organism led to the elucidation of crucial aspects of disease mechanisms. ALS, however, has lagged somewhat behind possibly because of the lack of a suitable genetic model. We were the first to develop a fly model for ALS and over the last few years, we have implemented and used this model for a large scale, unbiased modifier screen. We also report an extensive bioinformatic analysis of the genetic modifiers and we show that most of them are associated in a network of interacting genes controlling known as well as novel cellular processes involved in ALS pathogenesis. A similar analysis for the human homologues of the Drosophila modifiers and the validation of a subset of them in human tissues confirm and expand the significance of the data for the human disease. Finally, we analyze a possible application of the model in the process of therapeutic discovery in ALS and we discuss the importance of novel “non-obvious” models for the disease

Highly Efficient Oxygen Reduction Catalysts by Rational Synthesis of Nanoconfined Maghemite in a Nitrogen-Doped Graphene Framework

The oxygen reduction reaction (ORR) is critical for electrochemical energy storage and conversion: e.g., in fuel cells and metal–air batteries. A major challenge is to develop cost-effective and durable ORR catalysts, to replace the relatively expensive platinum-loaded carbon (PtC) counterparts, particularly for large-scale applications. Despite progress over the past few decades in developing efficient non-precious-metal (NPM) catalysts, such as Fe/N/C-based materials (the best-known alternatives), most of the reported catalytic activities have yet to match that of PtC. Herein we propose a two-step process for the production of highly efficient NPM catalysts that outperform PtC in alkaline media: (1) a hierarchical porosity of a supporting substrate is generated and optimized in advance, especially to achieve a high total pore volume for rapid mass transfer, and (2) an appropriate amount of NPM precursor is added to the optimized substrate to boost the reduction potential while maintaining the hierarchically porous structure. Such a scheme was successfully applied to a case of nanoconfined maghemite (γ-Fe2O3) in a nitrogen-doped graphene framework. The resulting catalyst system surpasses the performance of the equivalent commercial PtC, in terms of a higher reduction potential, a significantly lower peroxide formation ratio, more than tripled kinetic current density, smaller Tafel slope, better durability, etc. The reported catalyst is also among the best of all the existing Fe-based ORR catalysts, indicating the great potential of γ-Fe2O3 for ORR in practical applications

Pion-nucleus optical potential valid up to the DELTA-resonance region

We present in this article an optical potential for the $\pi$-nucleus interaction that can be used in various studies involving $\pi$-nucleus channels. Based on earlier treatments of the low energy $\pi$-nucleus optical potential, we have derived a potential expression applicable from threshold up to the $\Delta$-resonance region. We extracted the impulse approximation form for this potential from the $\pi-N$ scattering amplitude and then added to it kinematical and physical corrections. The kinematic corrections arise from transforming the impulse approximation expression from the $\pi-N$ center of mass frame to the $\pi$-nucleus center of mass frame, while the physical corrections arise mostly from the many-body nature of the $\pi$-nucleus interaction. By taking advantage of the experimental progress in our knowledge of the $\pi-N$ process, we have updated earlier treatments with parameters calculated from state-of-the-art experimental measurements.Comment: 23 pages, 12 figures. Accepted for publication in Physical Review