Exact microscopic analysis of a thermal Brownian motor

We study a genuine Brownian motor by hard disk molecular dynamics and calculate analytically its properties, including its drift speed and thermal conductivity, from microscopic theory.Comment: 4 pages, 5 figure

Low-energy quasiparticle states near extended scatterers in d-wave superconductors and their connection with SUSY quantum mechanics

Low-energy quasiparticle states, arising from scattering by single-particle potentials in d-wave superconductors, are addressed. Via a natural extension of the Andreev approximation, the idea that sign-variations in the superconducting pair-potential lead to such states is extended beyond its original setting of boundary scattering to the broader context of scattering by general single-particle potentials, such as those due to impurities. The index-theoretic origin of these states is exhibited via a simple connection with Witten's supersymmetric quantum-mechanical model.Comment: 5 page

Strong Connections on Quantum Principal Bundles

A gauge invariant notion of a strong connection is presented and characterized. It is then used to justify the way in which a global curvature form is defined. Strong connections are interpreted as those that are induced from the base space of a quantum bundle. Examples of both strong and non-strong connections are provided. In particular, such connections are constructed on a quantum deformation of the fibration $S^2 -> RP^2$. A certain class of strong $U_q(2)$-connections on a trivial quantum principal bundle is shown to be equivalent to the class of connections on a free module that are compatible with the q-dependent hermitian metric. A particular form of the Yang-Mills action on a trivial U\sb q(2)-bundle is investigated. It is proved to coincide with the Yang-Mills action constructed by A.Connes and M.Rieffel. Furthermore, it is shown that the moduli space of critical points of this action functional is independent of q.Comment: AMS-LaTeX, 40 pages, major revision including examples of connections over a quantum real projective spac

Stratification of the orbit space in gauge theories. The role of nongeneric strata

Gauge theory is a theory with constraints and, for that reason, the space of physical states is not a manifold but a stratified space (orbifold) with singularities. The classification of strata for smooth (and generalized) connections is reviewed as well as the formulation of the physical space as the zero set of a momentum map. Several important features of nongeneric strata are discussed and new results are presented suggesting an important role for these strata as concentrators of the measure in ground state functionals and as a source of multiple structures in low-lying excitations.Comment: 22 pages Latex, 1 figur

The Cauchy problems for Einstein metrics and parallel spinors

We show that in the analytic category, given a Riemannian metric $g$ on a hypersurface $M\subset \Z$ and a symmetric tensor $W$ on $M$, the metric $g$ can be locally extended to a Riemannian Einstein metric on $Z$ with second fundamental form $W$, provided that $g$ and $W$ satisfy the constraints on $M$ imposed by the contracted Codazzi equations. We use this fact to study the Cauchy problem for metrics with parallel spinors in the real analytic category and give an affirmative answer to a question raised in B\"ar, Gauduchon, Moroianu (2005). We also answer negatively the corresponding questions in the smooth category.Comment: 28 pages; final versio

The Maslov index in weak symplectic functional analysis

We recall the Chernoff-Marsden definition of weak symplectic structure and give a rigorous treatment of the functional analysis and geometry of weak symplectic Banach spaces. We define the Maslov index of a continuous path of Fredholm pairs of Lagrangian subspaces in continuously varying Banach spaces. We derive basic properties of this Maslov index and emphasize the new features appearing.Comment: 34 pages, 13 figures, 45 references, to appear in Ann Glob Anal Geom. The final publication will be available at http://www.springerlink.com. arXiv admin note: substantial text overlap with arXiv:math/040613

Direct TLR2 Signaling Is Critical for NK Cell Activation and Function in Response to Vaccinia Viral Infection

Natural killer (NK) cells play an essential role in innate immune control of poxviral infections in vivo. However, the mechanism(s) underlying NK cell activation and function in response to poxviruses remains poorly understood. In a mouse model of infection with vaccinia virus (VV), the most studied member of the poxvirus family, we identified that the Toll-like receptor (TLR) 2-myeloid differentiating factor 88 (MyD88) pathway was critical for the activation of NK cells and the control of VV infection in vivo. We further showed that TLR2 signaling on NK cells, but not on accessory cells such as dendritic cells (DCs), was necessary for NK cell activation and that this intrinsic TLR2-MyD88 signaling pathway was required for NK cell activation and played a critical role in the control of VV infection in vivo. In addition, we showed that the activating receptor NKG2D was also important for efficient NK activation and function, as well as recognition of VV-infected targets. We further demonstrated that VV could directly activate NK cells via TLR2 in the presence of cytokines in vitro and TLR2-MyD88-dependent activation of NK cells by VV was mediated through the phosphatidylinositol 3-kinase (PI3K)-extracellular signal-regulated kinase (ERK) pathway. Taken together, these results represent the first evidence that intrinsic TLR signaling is critical for NK cell activation and function in the control of a viral infection in vivo, indicate that multiple pathways are required for efficient NK cell activation and function in response to VV infection, and may provide important insights into the design of effective strategies to combat poxviral infections

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials

Herpes simplex encephalitis is linked with selective mitochondrial damage; a post-mortem and in vitro study

Herpes simplex virus type-1 (HSV-1) encephalitis (HSE) is the most commonly diagnosed cause of viral encephalitis in western countries. Despite antiviral treatment, HSE remains a devastating disease with high morbidity and mortality. Improved understanding of pathogenesis may lead to more effective therapies. Mitochondrial damage has been reported during HSV infection in vitro. However, whether it occurs in the human brain and whether this contributes to the pathogenesis has not been fully explored. Minocycline, an antibiotic, has been reported to protect mitochondria and limit brain damage. Minocycline has not been studied in HSV infection. In the first genome-wide transcriptomic study of post-mortem human HSE brain tissue, we demonstrated a highly preferential reduction in mitochondrial genome (MtDNA) encoded transcripts in HSE cases (n = 3) compared to controls (n = 5). Brain tissue exhibited a significant inverse correlation for immunostaining between cytochrome c oxidase subunit 1 (CO1), a MtDNA encoded enzyme subunit, and HSV-1; with lower abundance for mitochondrial protein in regions where HSV-1 was abundant. Preferential loss of mitochondrial function, among MtDNA encoded components, was confirmed using an in vitro primary human astrocyte HSV-1 infection model. Dysfunction of cytochrome c oxidase (CO), a mitochondrial enzyme composed predominantly of MtDNA encoded subunits, preceded that of succinate dehydrogenase (composed entirely of nuclear encoded subunits). Minocycline treated astrocytes exhibited higher CO1 transcript abundance, sustained CO activity and cell viability compared to non-treated astrocytes. Based on observations from HSE patient tissue, this study highlights mitochondrial damage as a critical and early event during HSV-1 infection. We demonstrate minocycline preserves mitochondrial function and cell viability during HSV-1 infection. Minocycline, and mitochondrial protection, offers a novel adjunctive therapeutic approach for limiting brain cell damage and potentially improving outcome among HSE patients