Hamilton-Jacobi Theory for Degenerate Lagrangian Systems with Holonomic and Nonholonomic Constraints

We extend Hamilton-Jacobi theory to Lagrange-Dirac (or implicit Lagrangian) systems, a generalized formulation of Lagrangian mechanics that can incorporate degenerate Lagrangians as well as holonomic and nonholonomic constraints. We refer to the generalized Hamilton-Jacobi equation as the Dirac-Hamilton-Jacobi equation. For non-degenerate Lagrangian systems with nonholonomic constraints, the theory specializes to the recently developed nonholonomic Hamilton-Jacobi theory. We are particularly interested in applications to a certain class of degenerate nonholonomic Lagrangian systems with symmetries, which we refer to as weakly degenerate Chaplygin systems, that arise as simplified models of nonholonomic mechanical systems; these systems are shown to reduce to non-degenerate almost Hamiltonian systems, i.e., generalized Hamiltonian systems defined with non-closed two-forms. Accordingly, the Dirac-Hamilton-Jacobi equation reduces to a variant of the nonholonomic Hamilton-Jacobi equation associated with the reduced system. We illustrate through a few examples how the Dirac-Hamilton-Jacobi equation can be used to exactly integrate the equations of motion.Comment: 44 pages, 3 figure

<dispersion strengthening of metals< summary report, jul. 1963 - jul. 1964

Structure, stability, and properties of dispersion strengthened and internally oxidized alloy

Volcanic Initiation of the Eocene Heart Mountain Slide, Wyoming, USA

The Eocene Heart Mountain slide of northwest Wyoming covers an area of as much as 5000 km2 and includes allochthonous Paleozoic carbonate and Eocene volcanic rocks with a run-out distance of as much as 85 km. Recent geochronologic data indicated that the emplacement of the slide event occurred at ∼48.9 Ma, using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) extracted from U-Pb zircon ages from basal layer and injectite carbonate ultracataclasite (CUC). We now refine that age with U-Pb results from a lamprophyre diatreme that is temporally and spatially related to the CUC injectites. The ages for the lamprophyre zircons are 48.97 ± 0.36 Ma (LA-ICPMS) and 49.19 ±0.02 Ma (chemical abrasion isotope dilution thermal ionization mass spectrometry). Thus, the lamprophyre and CUC zircons are identical in age, and we interpret that the zircons in the CUC were derived from the lamprophyre during slide emplacement. Moreover, the intrusion of the lamprophyre diatreme provided the trigger mechanism for the Heart Mountain slide. Additional structural data are presented for a variety of calcite twinning strains, results from anisotropy of magnetic susceptibility for the lamprophyre and CUC injectites and alternating-field demagnetization on the lamprophyre, to help constrain slide dynamics. These data indicate that White Mountain experienced a rotation about a vertical axis and minimum of 35° of counterclockwise motion during emplacement

The Role of Innate APOBEC3G and Adaptive AID Immune Responses in HLA-HIV/SIV Immunized SHIV Infected Macaques

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Therapeutic DNA vaccine induces broad T cell responses in the gut and sustained protection from viral rebound and AIDS in SIV-infected rhesus macaques.

Immunotherapies that induce durable immune control of chronic HIV infection may eliminate the need for life-long dependence on drugs. We investigated a DNA vaccine formulated with a novel genetic adjuvant that stimulates immune responses in the blood and gut for the ability to improve therapy in rhesus macaques chronically infected with SIV. Using the SIV-macaque model for AIDS, we show that epidermal co-delivery of plasmids expressing SIV Gag, RT, Nef and Env, and the mucosal adjuvant, heat-labile E. coli enterotoxin (LT), during antiretroviral therapy (ART) induced a substantial 2-4-log fold reduction in mean virus burden in both the gut and blood when compared to unvaccinated controls and provided durable protection from viral rebound and disease progression after the drug was discontinued. This effect was associated with significant increases in IFN-γ T cell responses in both the blood and gut and SIV-specific CD8+ T cells with dual TNF-α and cytolytic effector functions in the blood. Importantly, a broader specificity in the T cell response seen in the gut, but not the blood, significantly correlated with a reduction in virus production in mucosal tissues and a lower virus burden in plasma. We conclude that immunizing with vaccines that induce immune responses in mucosal gut tissue could reduce residual viral reservoirs during drug therapy and improve long-term treatment of HIV infection in humans

Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

Quantitative Characterization of the Filiform Mechanosensory Hair Array on the Cricket Cercus

Crickets and other orthopteran insects sense air currents with a pair of abdominal appendages resembling antennae, called cerci. Each cercus in the common house cricket Acheta domesticus is approximately 1 cm long, and is covered with 500 to 750 filiform mechanosensory hairs. The distribution of the hairs on the cerci, as well as the global patterns of their movement vectors, have been characterized semi-quantitatively in studies over the last 40 years, and have been shown to be very stereotypical across different animals in this species. Although the cercal sensory system has been the focus of many studies in the areas of neuroethology, development, biomechanics, sensory function and neural coding, there has not yet been a quantitative study of the functional morphology of the receptor array of this important model system.We present a quantitative characterization of the structural characteristics and functional morphology of the cercal filiform hair array. We demonstrate that the excitatory direction along each hair's movement plane can be identified by features of its socket that are visible at the light-microscopic level, and that the length of the hair associated with each socket can also be estimated accurately from a structural parameter of the socket. We characterize the length and directionality of all hairs on the basal half of a sample of three cerci, and present statistical analyses of the distributions.The inter-animal variation of several global organizational features is low, consistent with constraints imposed by functional effectiveness and/or developmental processes. Contrary to previous reports, however, we show that the filiform hairs are not re-identifiable in the strict sense

Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al