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

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

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

Proceedings of the Tenth Annual Beef Cattle Short Course.

91 p

Dysregulated Cytokine Expression by CD4+ T cells from Post-Septic Mice Modulates both Th1 and Th2-Mediated Granulomatous Lung Inflammation

Previous epidemiological studies in humans and experimental studies in animals indicate that survivors of severe sepsis exhibit deficiencies in the activation and effector function of immune cells. In particular, CD4+ T lymphocytes can exhibit reduced proliferative capacity and improper cytokine responses following sepsis. To further investigate the cell-intrinsic defects of CD4+ T cells following sepsis, splenic CD4+ T cells from sham surgery and post-septic mice were transferred into lymphopenic mice. These recipient mice were then subjected to both TH1-(purified protein derivative) and TH2-(Schistosoma mansoni egg antigen) driven models of granulomatous lung inflammation. Post-septic CD4+ T cells mediated smaller TH1 and larger TH2 lung granulomas as compared to mice receiving CD4+ T cells from sham surgery donors. However, cytokine production by lymph node cells in antigen restimulation assays indicated increased pan-specific cytokine expression by post-septic CD4+ T cell recipient mice in both TH1 and TH2 granuloma models. These include increased production of TH2 cytokines in TH1 inflammation, and increased production of TH1 cytokines in TH2 inflammation. These results suggest that cell-intrinsic defects in CD4+ T cell effector function can have deleterious effects on inflammatory processes post-sepsis, due to a defect in the proper regulation of TH-specific cytokine expression

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

Neuromuscular Junction Defects in Mice with Mutation of dynein heavy chain 1

Disruptions in axonal transport have been implicated in a wide range of neurodegenerative diseases. Cramping 1 (Cra1/+) and Legs at odd angles (Loa/+) mice, with hypomorphic mutations in the dynein heavy chain 1 gene, which encodes the ATPase of the retrograde motor protein dynein, were originally reported to exhibit late onset motor neuron disease. Subsequent, conflicting reports suggested that sensory neuron disease without motor neuron loss underlies the phenotypes of Cra1/+ and Loa/+ mice. Here, we present behavioral and anatomical analyses of Cra1/+ mice. We demonstrate that Cra1/+ mice exhibit early onset, stable behavioral deficits, including abnormal hindlimb posturing and decreased grip strength. These deficits do not progress through 24 months of age. No significant loss of primary motor neurons or dorsal root ganglia sensory neurons was observed at ages where the mice exhibited clear symptomatology. Instead, there is a decrease in complexity of neuromuscular junctions. These results indicate that disruption of dynein function in Cra1/+ mice results in abnormal morphology of neuromuscular junctions. The time course of behavioral deficits, as well as the nature of the morphological defects in neuromuscular junctions, suggests that disruption of dynein function in Cra1/+ mice causes a developmental defect in synapse assembly or stabilization

The New Political History

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66569/2/10.1177_000276427702100204.pd