A Contribution of the Trivial Connection to Jones Polynomial and Witten's Invariant of 3d Manifolds I

We use the Chern-Simons quantum field theory in order to prove a recently conjectured limitation on the 1/K expansion of the Jones polynomial of a knot and its relation to the Alexander polynomial. This limitation allows us to derive a surgery formula for the loop corrections to the contribution of the trivial connection to Witten's invariant. The 2-loop part of this formula coincides with Walker's surgery formula for Casson-Walker invariant. This proves a conjecture that Casson-Walker invariant is a 2-loop correction to the trivial connection contribution to Witten's invariant of a rational homology sphere. A contribution of the trivial connection to Witten's invariant of a manifold with nontrivial rational homology is calculated for the case of Seifert manifolds.Comment: 28 page

Identification and treatment of the visual processing asymmetry in MS patients with optic neuritis: The Pulfrich phenomenon

BACKGROUND: The Pulfrich phenomenon (PF) is the illusory perception that an object moving linearly along a 2-D plane appears to instead follow an elliptical 3-D trajectory, a consequence of inter-eye asymmetry in the timing of visual object identification in the visual cortex; with optic neuritis as a common etiology. OBJECTIVE: We have designed an objective method to identify the presence and magnitude of the PF, in conjunction with a cooresponding strategy by which to abolish the effect; with monocular application of neutral density filters to the less affected fellow eye, in patients with MS and a history of optic neuropathy (e.g. related to acute optic neuritis or subclinical optic neuropathy). METHODS: Twenty-three MS patients with a history of acute unilateral or bilateral optic neuritis, and ten healthy control subjects (HC) were recruited to participate in a pilot study to assess our strategy. Subjects were asked to indicate whether a linearly moving pendulum ball followed a linear 2-D path versus an illusory 3-D elliptical object-motion trajectory, by reporting the ball's approximation to one of nine horizontally-oriented colored wires that were positioned parallel to one another and horizontal to the linear pendulum path. Perceived motion of the bob that moved along wires behind or in front (along the 'Z' plane) of the middle reference wire indicated an illusory elliptical trajectory of ball motion consistent with the PF. RESULTS: When the neutral density filter titration was applied to the fellow eye the severity of the PF decreased, eventually being fully abolished in all but one patient. The magnitude of neutral density filtering required correlated to the severity of the patient's initial PF magnitude (p < 0.001). CONCLUSIONS: We ascertained the magnitude of the visual illusion associated with the PF, and the corresponding magnitude of neutral density filtering necessary to abolish it

The cDNA and deduced amino acid sequence of the γ subunit of the L-type calcium channel from rabbit skeletal muscle

Complementary DNAs for the γ subunit of the calcium channel of rabbit skeletal muscle were isolated on the basis of peptide sequences derived from the purified protein. The deduced primary structure is without homology to other known protein sequences and is consistent with the γ subunit being an integral membrane protein

Deficiencies of the Lipid-Signaling Enzymes Phospholipase D1 and D2 Alter Cytoskeletal Organization, Macrophage Phagocytosis, and Cytokine-Stimulated Neutrophil Recruitment

Cell migration and phagocytosis ensue from extracellular-initiated signaling cascades that orchestrate dynamic reorganization of the actin cytoskeleton. The reorganization is mediated by effector proteins recruited to the site of activity by locally-generated lipid second messengers. Phosphatidic acid (PA), a membrane phospholipid generated by multiple enzyme families including Phospholipase D (PLD), has been proposed to function in this role. Here, we show that macrophages prepared from mice lacking either of the classical PLD isoforms PLD1 or PLD2, or wild-type macrophages whose PLD activity has been pharmacologically inhibited, display isoform-specific actin cytoskeleton abnormalities that likely underlie decreases observed in phagocytic capacity. Unexpectedly, PA continued to be detected on the phagosome in the absence of either isoform and even when all PLD activity was eliminated. However, a disorganized phagocytic cup was observed as visualized by imaging PA, F-actin, Rac1, an organizer of the F-actin network, and DOCK2, a Rac1 activator, suggesting that PLD-mediated PA production during phagocytosis is specifically critical for the integrity of the process. The abnormal F-actin reorganization additionally impacted neutrophil migration and extravasation from the vasculature into interstitial tissues. Although both PLD1 and PLD2 were important in these processes, we also observed isoform-specific functions. PLD1-driven processes in particular were observed to be critical in transmigration of macrophages exiting the vasculature during immune responses such as those seen in acute pancreatitis or irritant-induced skin vascularization

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects