On the Two Species Asymmetric Exclusion Process with Semi-Permeable Boundaries

We investigate the structure of the nonequilibrium stationary state (NESS) of a system of first and second class particles, as well as vacancies (holes), on L sites of a one-dimensional lattice in contact with first class particle reservoirs at the boundary sites; these particles can enter at site 1, when it is vacant, with rate alpha, and exit from site L with rate beta. Second class particles can neither enter nor leave the system, so the boundaries are semi-permeable. The internal dynamics are described by the usual totally asymmetric exclusion process (TASEP) with second class particles. An exact solution of the NESS was found by Arita. Here we describe two consequences of the fact that the flux of second class particles is zero. First, there exist (pinned and unpinned) fat shocks which determine the general structure of the phase diagram and of the local measures; the latter describe the microscopic structure of the system at different macroscopic points (in the limit L going to infinity in terms of superpositions of extremal measures of the infinite system. Second, the distribution of second class particles is given by an equilibrium ensemble in fixed volume, or equivalently but more simply by a pressure ensemble, in which the pair potential between neighboring particles grows logarithmically with distance. We also point out an unexpected feature in the microscopic structure of the NESS for finite L: if there are n second class particles in the system then the distribution of first class particles (respectively holes) on the first (respectively last) n sites is exchangeable.Comment: 28 pages, 4 figures. Changed title and introduction for clarity, added reference

Exact Large Deviation Function in the Asymmetric Exclusion Process

By an extension of the Bethe ansatz method used by Gwa and Spohn, we obtain an exact expression for the large deviation function of the time averaged current for the fully asymmetric exclusion process in a ring containing $N$ sites and $p$ particles. Using this expression we easily recover the exact diffusion constant obtained earlier and calculate as well some higher cumulants. The distribution of the deviation $y$ of the average current is, in the limit $N \to \infty$, skew and decays like $\exp - (A y^{5/2})$ for $y \to + \infty$ and $\exp - (A' |y|^{3/2})$ for $y \to -\infty$. Surprisingly, the large deviation function has an expression very similar to the pressure (as a function of the density) of an ideal Bose or Fermi gas in $3d$.Comment: 8 pages, in ReVTeX, e-mail addresses: [email protected] and [email protected]

Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis

Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy-lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator of autophagy-lysosomal biogenesis, we can reverse the autophagy dysfunction of plaques, enhance aggrephagy of p62-enriched protein aggregates and blunt macrophage apoptosis and pro-inflammatory IL-1β levels, leading to reduced atherosclerosis. In order to harness this degradative response therapeutically, we also describe a natural sugar called trehalose as an inducer of macrophage autophagy-lysosomal biogenesis and show trehalose's ability to recapitulate the atheroprotective properties of macrophage TFEB overexpression. Our data support this practical method of enhancing the degradative capacity of macrophages as a therapy for atherosclerotic vascular disease

Coiling Instability of Multilamellar Membrane Tubes with Anchored Polymers

We study experimentally a coiling instability of cylindrical multilamellar stacks of phospholipid membranes, induced by polymers with hydrophobic anchors grafted along their hydrophilic backbone. Our system is unique in that coils form in the absence of both twist and adhesion. We interpret our experimental results in terms of a model in which local membrane curvature and polymer concentration are coupled. The model predicts the occurrence of maximally tight coils above a threshold polymer occupancy. A proper comparison between the model and experiment involved imaging of projections from simulated coiled tubes with maximal curvature and complicated torsions.Comment: 11 pages + 7 GIF figures + 10 JPEG figure

Existence and Nonlinear Stability of Rotating Star Solutions of the Compressible Euler-Poisson Equations

We prove existence of rotating star solutions which are steady-state solutions of the compressible isentropic Euler-Poisson (EP) equations in 3 spatial dimensions, with prescribed angular momentum and total mass. This problem can be formulated as a variational problem of finding a minimizer of an energy functional in a broader class of functions having less symmetry than those functions considered in the classical Auchmuty-Beals paper. We prove the nonlinear dynamical stability of these solutions with perturbations having the same total mass and symmetry as the rotating star solution. We also prove local in time stability of W^{1, \infty}(\RR^3) solutions where the perturbations are entropy-weak solutions of the EP equations. Finally, we give a uniform (in time) a-priori estimate for entropy-weak solutions of the EP equations

Internet Image Viewer (iiV)

<p>Abstract</p> <p>Background</p> <p>Visualizing 3-dimensional (3-D) datasets is an important part of modern neuroimaging research. Many tools address this problem; however, they often fail to address specific needs and flexibility, such as the ability to work with different data formats, to control how and what data are displayed, to interact with values, and to undo mistakes.</p> <p>Results</p> <p>iiV, an interactive software program for displaying 3-D brain images, is described. This tool was programmed to solve basic problems in 3-D data visualization. It is written in Java so it is extensible, is platform independent, and can display images within web pages.</p> <p>iiV displays 3-D images as 2-dimensional (2-D) slices with each slice being an independent object with independent features such as location, zoom, colors, labels, etc. Feature manipulation becomes easier by having a full set of editing capabilities including the following: undo or redo changes; drag, copy, delete and paste objects; and save objects with their features to a file for future editing. It can read multiple standard positron emission tomography (PET) and magnetic resonance imaging (MRI) file formats like ECAT, ECAT7, ANALYZE, NIfTI-1 and DICOM. We present sample applications to illustrate some of the features and capabilities.</p> <p>Conclusion</p> <p>iiV is an image display tool with many useful features. It is highly extensible, platform independent, and web-compatible. This report summarizes its features and applications, while illustrating iiV's usefulness to the biomedical imaging community.</p

Quantifying the Microvascular Origin of BOLD-fMRI from First Principles with Two-Photon Microscopy and an Oxygen-Sensitive Nanoprobe

The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences.National Institutes of Health (U.S.) (Grant P41RR14075)National Institutes of Health (U.S.) (Grant R01NS067050)National Institutes of Health (U.S.) (Grant R01NS057198)National Institutes of Health (U.S.) (Grant R01EB000790)American Heart Association (Grant 11SDG7600037)Advanced Multimodal NeuroImaging Training Program (R90DA023427

Loop Interactions during Catalysis by Dihydrofolate Reductase fromMoritella profunda

Dihydrofolate reductase (DHFR) is often used as a model system to study the relation between protein dynamics and catalysis. We have studied a number of variants of the cold-adapted DHFR from Moritella profunda (MpDHFR), in which the catalytically important M20 and FG loops have been altered, and present a comparison with the corresponding variants of the wellstudied DHFR from Escherichia coli (EcDHFR). Mutations in the M20 loop do not affect the actual chemical step of transfer of hydride from reduced nicotinamide adenine dinucleotide phosphate to the substrate 7,8-dihydrofolate in the catalytic cycle in either enzyme; they affect the steady state turnover rate in EcDHFR but not in MpDHFR. Mutations in the FG loop also have different effects on catalysis by the two DHFRs. Despite the two enzymes most likely sharing a common catalytic cycle at pH 7, motions of these loops, known to be important for progression through the catalytic cycle in EcDHFR, appear not to play a significant role in MpDHFR

Toward Improved Environmental Stability of Polymer:Fullerene and Polymer:Nonfullerene Organic Solar Cells: A Common Energetic Origin of Light- and Oxygen-Induced Degradation

With the emergence of nonfullerene electron acceptors resulting in further breakthroughs in the performance of organic solar cells, there is now an urgent need to understand their degradation mechanisms in order to improve their intrinsic stability through better material design. In this study, we present quantitative evidence for a common root cause of light-induced degradation of polymer:nonfullerene and polymer:fullerene organic solar cells in air, namely, a fast photo-oxidation process of the photoactive materials mediated by the formation of superoxide radical ions, whose yield is found to be strongly controlled by the lowest unoccupied molecular orbital (LUMO) levels of the electron acceptors used. Our results elucidate the general relevance of this degradation mechanism to both polymer:fullerene and polymer:nonfullerene blends and highlight the necessity of designing electron acceptor materials with sufficient electron affinities to overcome this challenge, thereby paving the way toward achieving long-term solar cell stability with minimal device encapsulation