Tissue Inhibitor of Metalloproteinase–3 (TIMP-3) induces FAS dependent apoptosis in human vascular smooth muscle cells

Over expression of Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) in vascular smooth muscle cells (VSMCs) induces apoptosis and reduces neointima formation occurring after saphenous vein interposition grafting or coronary stenting. In studies to address the mechanism of TIMP-3-driven apoptosis in human VSMCs we find that TIMP-3 increased activation of caspase-8 and apoptosis was inhibited by expression of Cytokine response modifier A (CrmA) and dominant negative FAS-Associated protein with Death Domain (FADD). TIMP-3 induced apoptosis did not cause mitochondrial depolarisation, increase activation of caspase-9 and was not inhibited by over-expression of B-cell Lymphoma 2 (Bcl2), indicating a mitochondrial independent/type-I death receptor pathway. TIMP-3 increased levels of the First Apoptosis Signal receptor (FAS) and depletion of FAS with shRNA showed TIMP-3-induced apoptosis was FAS dependent. TIMP-3 induced formation of the Death-Inducing Signalling Complex (DISC), as detected by immunoprecipitation and by immunofluorescence. Cellular-FADD-like IL-1 converting enzyme-Like Inhibitory Protein (c-FLIP) localised with FAS at the cell periphery in the absence of TIMP-3 and this localisation was lost on TIMP-3 expression with c-FLIP adopting a perinuclear localisation. Although TIMP-3 inhibited FAS shedding, this did not increase total surface levels of FAS but instead increased FAS levels within localised regions at the cell surface. A Disintegrin And Metalloproteinase 17 (ADAM17) is inhibited by TIMP-3 and depletion of ADAM17 with shRNA significantly decreased FAS shedding. However ADAM17 depletion did not induce apoptosis or replicate the effects of TIMP-3 by increasing localised clustering of cell surface FAS. ADAM17-depleted cells could activate caspase-3 when expressing levels of TIMP-3 that were otherwise sub-apoptotic, suggesting a partial role for ADAM17 mediated ectodomain shedding in TIMP-3 mediated apoptosis. We conclude that TIMP-3 induced apoptosis in VSMCs is highly dependent on FAS and is associated with changes in FAS and c-FLIP localisation, but is not solely dependent on shedding of the FAS ectodomain

The conceptual design of a small solar probe /Sunblazer/

Conceptual design of Sunblazer space probe for determining electron density of solar coron

Coronal mass ejections, magnetic clouds, and relativistic magnetospheric electron events: ISTP

The role of high-speed solar wind streams in driving relativistic electron acceleration within the Earth\u27s magnetosphere during solar activity minimum conditions has been well documented. The rising phase of the new solar activity cycle (cycle 23) commenced in 1996, and there have recently been a number of coronal mass ejections (CMEs) and related “magnetic clouds” at 1 AU. As these CME/cloud systems interact with the Earth\u27s magnetosphere, some events produce substantial enhancements in the magnetospheric energetic particle population while others do not. This paper compares and contrasts relativistic electron signatures observed by the POLAR, SAMPEX, Highly Elliptical Orbit, and geostationary orbit spacecraft during two magnetic cloud events: May 27–29, 1996, and January 10–11, 1997. Sequences were observed in each case in which the interplanetary magnetic field was first strongly southward and then rotated northward. In both cases, there were large solar wind density enhancements toward the end of the cloud passage at 1 AU. Strong energetic electron acceleration was observed in the January event, but not in the May event. The relative geoeffectiveness for these two cases is assessed, and it is concluded that large induced electric fields (∂B/∂t) caused in situ acceleration of electrons throughout the outer radiation zone during the January 1997 event

Report from magnetospheric science

By the early 1990s, magnetospheric physics will have progressed primarily through observations made from Explorer-class spacecraft, sounding rockets, ground based facilities, and shuttle based experiments. The global geospace science (GGS) element of the International Solar Terrestrial Physics program, when combined with contributions to the ESA Cluster mission and ground based and computer modeling programs, will form the basis for a major U.S. initiative in magnetospheric physics. The scientific objectives of the GGS program involve the study of energy transport throughout geospace. The Cluster mission will investigate turbulence and boundary phenomena in geospace, particularly at high latitudes on the dayside and in the region of the neutral sheet at geocentric distances of about 20 earth radii on the night side of the earth. The current state of knowledge is reviewed and the goals of these missions are briefly discussed

Collapse of Flux Tubes

The dynamics of an idealized, infinite, MIT-type flux tube is followed in time as the interior evolves from a pure gluon field to a $\overline q \ q$ plasma. We work in color U(1). $\overline q\ q$ pair formation is evaluated according to the Schwinger mechanism using the results of Brink and Pavel. The motion of the quarks toward the tube endcaps is calculated by a Boltzmann equation including collisions. The tube undergoes damped radial oscillations until the electric field settles down to zero. The electric field stabilizes the tube against pinch instabilities; when the field vanishes, the tube disintegrates into mesons. There is only one free parameter in the problem, namely the initial flux tube radius, to which the results are very sensitive. Among various quantities calculated is the mean energy of the emitted pions.Comment: 16 pages plus 12 figures. RevTex3. DOE/ER/40427-160N9

Study of a small solar probe /sunblazer/. part ii- spacecraft and payload design progress report, jul. 1, 1964 - jun. 30, 1965

Design considerations for Sunblazer solar probe and payloa

The Gaussian formula and spherical aberration of the static and moving curved mirrors from Fermat's principle

The Gaussian formula and spherical aberrations of the static and relativistic curved mirrors are analyzed using the optical path length (OPL) and Fermat's principle. The geometrical figures generated by the rotation of conic sections about their symmetry axes are considered for the shapes of the mirrors. By comparing the results in static and relativistic cases, it is shown that the focal lengths and the spherical aberration relations of the relativistic mirrors obey the Lorentz contraction. Further analysis of the spherical aberrations for both static and relativistic cases have resulted in the information about the limits for the paraxial approximation, as well as for the minimum speed of the systems to reduce the spherical aberrations.Comment: 15 pages, 7 figures, uses iopart. Major revisions on the physical interpretations of the results. Accepted for publication in J. Op