Tertiary lymphoid organs in central nervous system autoimmunity

Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS), which results in permanent neuronal damage and substantial disability in patients. Autoreactive T cells are important drivers of the disease; however, the efficacy of B cell depleting therapies uncovered an essential role for B cells in disease pathogenesis. They can contribute to inflammatory processes via presentation of autoantigen, secretion of pro-inflammatory cytokines, and production of pathogenic antibodies. Recently, B cell aggregates reminiscent of tertiary lymphoid organs (TLOs) were discovered in the meninges of MS patients, leading to the hypothesis that differentiation and maturation of autopathogenic B and T cells may partly occur inside the CNS. Since these structures were associated with a more severe disease course, it is extremely important to gain insight into the mechanism of induction, their precise function, and clinical significance. Mechanistic studies in patients are limited. However, a few studies in the MS animal model experimental autoimmune encephalomyelitis (EAE) recapitulate TLO formation in the CNS and provide new insight into CNS TLO features, formation, and function. This review summarizes what we know so far about CNS TLOs in MS and what we have learned about them from EAE models. It also highlights the areas that are in need of further experimental work, as we are just beginning to understand and evaluate the phenomenon of CNS TLOs

Searching for Globally Optimal Functional Forms for Inter-Atomic Potentials Using Parallel Tempering and Genetic Programming

We develop a Genetic Programming-based methodology that enables discovery of novel functional forms for classical inter-atomic force-fields, used in molecular dynamics simulations. Unlike previous efforts in the field, that fit only the parameters to the fixed functional forms, we instead use a novel algorithm to search the space of many possible functional forms. While a follow-on practical procedure will use experimental and {\it ab inito} data to find an optimal functional form for a forcefield, we first validate the approach using a manufactured solution. This validation has the advantage of a well-defined metric of success. We manufactured a training set of atomic coordinate data with an associated set of global energies using the well-known Lennard-Jones inter-atomic potential. We performed an automatic functional form fitting procedure starting with a population of random functions, using a genetic programming functional formulation, and a parallel tempering Metropolis-based optimization algorithm. Our massively-parallel method independently discovered the Lennard-Jones function after searching for several hours on 100 processors and covering a miniscule portion of the configuration space. We find that the method is suitable for unsupervised discovery of functional forms for inter-atomic potentials/force-fields. We also find that our parallel tempering Metropolis-based approach significantly improves the optimization convergence time, and takes good advantage of the parallel cluster architecture

An ab-initio study of the electron-phonon coupling within a Cr(001)-surface

It is experimentally well established that the Cr(001)-surface exhibits a sharp resonance around the Fermi level. However, there is no consensus about its physical origin. It is proposed to be either due to a single particle dz2 surface state renormalised by electron-phonon coupling or the orbital Kondo effect involving the degenerate dxz/dyz states. In this work we examine the electron-phonon coupling of the Cr(001)-surface by means of ab-initio calculations in the form of density functional perturbation theory. More precisely, the electron-phonon mass-enhancement factor of the surface layer is investigated for the 3d states. For the majority and minority spin dz2 surface states we find values of 0.19 and 0.16. We show that these calculated electron-phonon mass-enhancement factors are not in agreement with the experimental data even if we use realistic values for the temperature range and surface Debye frequency for the fit of the experimental data. More precisely, then experimentally an electron-phonon mass-enhancement factor of 0.70~0.10 is obtained, which is not in agreement with our calculated values of 0.19 and 0.16. Therefore, we conclude that the experimentally observed resonance at the Cr(001)-surface is not due to polaronic effects, but due to electron-electron correlation effects

Low and high intensity velocity selective coherent population trapping in a two-level system

An experimental investigation is made of sub-recoil cooling by velocity selective coherent population trapping in a two-level system in Sr. The experiment is carried out using the narrow linewidth intercombination line at 689 nm. Here, the ratio between the recoil shift and the linewidth is as high as 0.64. We show that, on top of a broader momentum profile, subrecoil features develop, whose amplitude is strongly dependent on the detuning from resonance. We attribute this structure to a velocity selective coherent population trapping mechanism. We also show that the population trapping phenomenon leads to complex momentum profiles in the case of highly saturated transitions, displaying a multitude of subrecoil features at integer multiples of the recoil momentum.Comment: 6 pages and 7 figure

Electroproduction of Soft Pions at Large Momentum Transfers

We consider pion electroproduction on a proton target close to threshold for Q^2 in the region 1-10 GeV^2. The momentum transfer dependence of the S-wave multipoles at threshold, E_{0+} and L_{0+}, is calculated using light-cone sum rules.Comment: 8 pages, 3 figures; Invited talk at the workshop on Exclusive Reactions at High Momentum Transfer, 21-24 May 2007, Newport News, Virginia, U.S.A. and International Conference on hadron Physics TROIA'07, 30 Aug. - 3 Sept. 2007, Canakkale, Turke

Design of helicopter rotor blades for optimum dynamic characteristics

The mass and stiffness distributions for helicopter rotor blades are tailored in such a way to give a predetermined placement of blade natural frequencies. The optimal design is pursued with respect of minimum weight, sufficient inertia, and reasonable dynamic characteristics. Finite element techniques are used as a tool. Rotor types include hingeless, articulated, and teetering