A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

An Efficient Algorithm for Enumerating Chordless Cycles and Chordless Paths

A chordless cycle (induced cycle) $C$ of a graph is a cycle without any chord, meaning that there is no edge outside the cycle connecting two vertices of the cycle. A chordless path is defined similarly. In this paper, we consider the problems of enumerating chordless cycles/paths of a given graph $G=(V,E),$ and propose algorithms taking $O(|E|)$ time for each chordless cycle/path. In the existing studies, the problems had not been deeply studied in the theoretical computer science area, and no output polynomial time algorithm has been proposed. Our experiments showed that the computation time of our algorithms is constant per chordless cycle/path for non-dense random graphs and real-world graphs. They also show that the number of chordless cycles is much smaller than the number of cycles. We applied the algorithm to prediction of NMR (Nuclear Magnetic Resonance) spectra, and increased the accuracy of the prediction

Inability to sustain intraphagolysosomal killing of Staphylococcus aureus predisposes to bacterial persistence in macrophages

Macrophages are critical effectors of the early innate response to bacteria in tissues. Phagocytosis and killing of bacteria are interrelated functions essential for bacterial clearance but the rate-limiting step when macrophages are challenged with large numbers of the major medical pathogen Staphylococcus aureus is unknown. We show that macrophages have a finite capacity for intracellular killing and fail to match sustained phagocytosis with sustained microbial killing when exposed to large inocula of S. aureus (Newman, SH1000 and USA300 strains). S. aureus ingestion by macrophages is associated with a rapid decline in bacterial viability immediately after phagocytosis. However, not all bacteria are killed in the phagolysosome, and we demonstrate reduced acidification of the phagolysosome, associated with failure of phagolysosomal maturation and reduced activation of cathepsin D. This results in accumulation of viable intracellular bacteria in macrophages. We show macrophages fail to engage apoptosis-associated bacterial killing. Ultittop mately macrophages with viable bacteria undergo cell lysis, and viable bacteria are released and can be internalized by other macrophages. We show that cycles of lysis and reuptake maintain a pool of viable intracellular bacteria over time when killing is overwhelmed and demonstrate intracellular persistence in alveolar macrophages in the lungs in a murine model

Impurity scattering and transport of fractional Quantum Hall edge state

We study the effects of impurity scattering on the low energy edge state dynamic s for a broad class of quantum Hall fluids at filling factor $\nu =n/(np+1)$, for integer $n$ and even integer $p$. When $p$ is positive all $n$ of the edge modes are expected to move in the same direction, whereas for negative $p$ one mode moves in a direction opposite to the other $n-1$ modes. Using a chiral-Luttinger model to describe the edge channels, we show that for an ideal edge when $p$ is negative, a non-quantized and non-universal Hall conductance is predicted. The non-quantized conductance is associated with an absence of equilibration between the $n$ edge channels. To explain the robust experimental Hall quantization, it is thus necessary to incorporate impurity scattering into the model, to allow for edge equilibration. A perturbative analysis reveals that edge impurity scattering is relevant and will modify the low energy edge dynamics. We describe a non-perturbative solution for the random $n-$channel edge, which reveals the existence of a new disorder-dominated phase, characterized by a stable zero temperature renormalization group fixed point. The phase consists of a single propagating charge mode, which gives a quantized Hall conductance, and $n-1$ neutral modes. The neutral modes all propagate at the same speed, and manifest an exact SU(n) symmetry. At finite temperatures the SU(n) symmetry is broken and the neutral modes decay with a finite rate which varies as $T^2$ at low temperatures. Various experimental predictions and implications which follow from the exact solution are described in detail, focusing on tunneling experiments through point contacts.Comment: 19 pages (two column), 5 post script figures appended, 3.0 REVTE

Exact Results on Potts Model Partition Functions in a Generalized External Field and Weighted-Set Graph Colorings

We present exact results on the partition function of the $q$-state Potts model on various families of graphs $G$ in a generalized external magnetic field that favors or disfavors spin values in a subset $I_s = \{1,...,s\}$ of the total set of possible spin values, $Z(G,q,s,v,w)$, where $v$ and $w$ are temperature- and field-dependent Boltzmann variables. We remark on differences in thermodynamic behavior between our model with a generalized external magnetic field and the Potts model with a conventional magnetic field that favors or disfavors a single spin value. Exact results are also given for the interesting special case of the zero-temperature Potts antiferromagnet, corresponding to a set-weighted chromatic polynomial $Ph(G,q,s,w)$ that counts the number of colorings of the vertices of $G$ subject to the condition that colors of adjacent vertices are different, with a weighting $w$ that favors or disfavors colors in the interval $I_s$. We derive powerful new upper and lower bounds on $Z(G,q,s,v,w)$ for the ferromagnetic case in terms of zero-field Potts partition functions with certain transformed arguments. We also prove general inequalities for $Z(G,q,s,v,w)$ on different families of tree graphs. As part of our analysis, we elucidate how the field-dependent Potts partition function and weighted-set chromatic polynomial distinguish, respectively, between Tutte-equivalent and chromatically equivalent pairs of graphs.Comment: 39 pages, 1 figur

Quantized Thermal Transport in the Fractional Quantum Hall Effect

We analyze thermal transport in the fractional quantum Hall effect (FQHE), employing a Luttinger liquid model of edge states. Impurity mediated inter-channel scattering events are incorporated in a hydrodynamic description of heat and charge transport. The thermal Hall conductance, $K_H$, is shown to provide a new and universal characterization of the FQHE state, and reveals non-trivial information about the edge structure. The Lorenz ratio between thermal and electrical Hall conductances {\it violates} the free-electron Wiedemann-Franz law, and for some fractional states is predicted to be {\it negative}. We argue that thermal transport may provide a unique way to detect the presence of the elusive upstream propagating modes, predicted for fractions such as $\nu=2/3$ and $\nu=3/5$.Comment: 6 pages REVTeX, 2 postscript figures (uuencoded and compressed

Edge Dynamics in Quantum Hall Bilayers II: Exact Results with Disorder and Parallel Fields

We study edge dynamics in the presence of interlayer tunneling, parallel magnetic field, and various types of disorder for two infinite sequences of quantum Hall states in symmetric bilayers. These sequences begin with the 110 and 331 Halperin states and include their fractional descendants at lower filling factors; the former is easily realized experimentally while the latter is a candidate for the experimentally observed quantum Hall state at a total filling factor of 1/2 in bilayers. We discuss the experimentally interesting observables that involve just one chiral edge of the sample and the correlation functions needed for computing them. We present several methods for obtaining exact results in the presence of interactions and disorder which rely on the chiral character of the system. Of particular interest are our results on the 331 state which suggest that a time-resolved measurement at the edge can be used to discriminate between the 331 and Pfaffian scenarios for the observed quantum Hall state at filling factor 1/2 in realistic double-layer systems.Comment: revtex+epsf; two-up postscript at http://www.sns.ias.edu/~leonid/ntwoup.p

Structure of the Partition Function and Transfer Matrices for the Potts Model in a Magnetic Field on Lattice Strips

We determine the general structure of the partition function of the $q$-state Potts model in an external magnetic field, $Z(G,q,v,w)$ for arbitrary $q$, temperature variable $v$, and magnetic field variable $w$, on cyclic, M\"obius, and free strip graphs $G$ of the square (sq), triangular (tri), and honeycomb (hc) lattices with width $L_y$ and arbitrarily great length $L_x$. For the cyclic case we prove that the partition function has the form $Z(\Lambda,L_y \times L_x,q,v,w)=\sum_{d=0}^{L_y} \tilde c^{(d)} Tr[(T_{Z,\Lambda,L_y,d})^m]$, where $\Lambda$ denotes the lattice type, $\tilde c^{(d)}$ are specified polynomials of degree $d$ in $q$, $T_{Z,\Lambda,L_y,d}$ is the corresponding transfer matrix, and $m=L_x$ ($L_x/2$) for $\Lambda=sq, tri (hc)$, respectively. An analogous formula is given for M\"obius strips, while only $T_{Z,\Lambda,L_y,d=0}$ appears for free strips. We exhibit a method for calculating $T_{Z,\Lambda,L_y,d}$ for arbitrary $L_y$ and give illustrative examples. Explicit results for arbitrary $L_y$ are presented for $T_{Z,\Lambda,L_y,d}$ with $d=L_y$ and $d=L_y-1$. We find very simple formulas for the determinant $det(T_{Z,\Lambda,L_y,d})$. We also give results for self-dual cyclic strips of the square lattice.Comment: Reference added to a relevant paper by F. Y. W

Interacting Open Wilson Lines in Noncommutative Field Theories

In noncommutative field theories, it was known that one-loop effective action describes propagation of non-interacting open Wilson lines, obeying the flying dipole's relation. We show that two-loop effective action describes cubic interaction among `closed string' states created by open Wilson lines. Taking d-dimensional noncommutative [\Phi^3] theory as the simplest setup, we compute nonplanar contribution at low-energy and large noncommutativity limit. We find that the contribution is expressible in a remarkably simple cubic interaction involving scalar open Wilson lines only and nothing else. We show that the interaction is purely geometrical and noncommutative in nature, depending only on sizes of each open Wilson line.Comment: v1: 27 pages, Latex, 7 .eps figures v2: minor wording change + reference adde

Lattice gauge theory with baryons at strong coupling

We study the effective Hamiltonian for strong-coupling lattice QCD in the case of non-zero baryon density. In leading order the effective Hamiltonian is a generalized antiferromagnet. For naive fermions, the symmetry is U(4N_f) and the spins belong to a representation that depends on the local baryon number. Next-nearest-neighbor (nnn) terms in the Hamiltonian break the symmetry to U(N_f) x U(N_f). We transform the quantum problem to a Euclidean sigma model which we analyze in a 1/N_c expansion. In the vacuum sector we recover spontaneous breaking of chiral symmetry for the nearest-neighbor and nnn theories. For non-zero baryon density we study the nearest-neighbor theory only, and show that the pattern of spontaneous symmetry breaking depends on the baryon density.Comment: 31 pages, 5 EPS figures. Corrected Eq. (6.1