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

Witten's Invariants of Rational Homology Spheres at Prime Values of KK and Trivial Connection Contribution

We establish a relation between the coefficients of asymptotic expansion of trivial connection contribution to Witten's invariant of rational homology spheres and the invariants that T.~Ohtsuki extracted from Witten's invariant at prime values of $K$. We also rederive the properties of prime $K$ invariants discovered by H.~Murakami and T.~Ohtsuki. We do this by using the bounds on Taylor series expansion of the Jones polynomial of algebraically split links, studied in our previous paper. These bounds are enough to prove that Ohtsuki's invariants are of finite type. The relation between Ohtsuki's invariants and trivial connection contribution is verified explicitly for lens spaces and Seifert manifolds.Comment: 32 pages, no figures, LaTe

The Keck Aperture Masking Experiment: spectro-interferometry of 3 Mira Variables from 1.1 to 3.8 microns

We present results from a spectro-interferometric study of the Miras o Cet, R Leo and W Hya obtained with the Keck Aperture Masking Experiment from 1998 Sep to 2002 Jul. The spectrally dispersed visibility data permit fitting with circularly symmetric brightness profiles such as a simple uniform disk. The stellar angular diameter obtained over up to ~ 450 spectral channels spaning the region 1.1-3.8 microns is presented. Use of a simple uniform disk brightness model facilitates comparison between epochs and with existing data and theoretical models. Strong size variations with wavelength were recorded for all stars, probing zones of H2O, CO, OH, and dust formation. Comparison with contemporaneous spectra extracted from our data show a strong anti-correlation between the observed angular diameter and flux. These variations consolidate the notion of a complex stellar atmosphere consisting of molecular shells with time-dependent densities and temperatures. Our findings are compared with existing data and pulsation models. The models were found to reproduce the functional form of the wavelength vs. angular diameter curve well, although some departures are noted in the 2.8-3.5 micron range.Comment: 10 pages, 10 figures Accepted to Ap

Optical Interferometry of early-type stars with PAVO@CHARA. I. Fundamental stellar properties

We present interferometric observations of 7 main-sequence and 3 giant stars with spectral types from B2 to F6 using the PAVO beam combiner at the CHARA array. We have directly determined the angular diameters for these objects with an average precision of 2.3%. We have also computed bolometric fluxes using available photometry in the visible and infrared wavelengths, as well as space-based ultraviolet spectroscopy. Combined with precise \textit{Hipparcos} parallaxes, we have derived a set of fundamental stellar properties including linear radius, luminosity and effective temperature. Fitting the latter to computed isochrone models, we have inferred masses and ages of the stars. The effective temperatures obtained are in good agreement (at a 3% level) with nearly-independent temperature estimations from spectroscopy. They validate recent sixth-order polynomial (B-V)-$T_\mathrm{eff}$ empirical relations \citep{Boyajian2012a}, but suggest that a more conservative third-order solution \citep{vanBelle2009} could adequately describe the (V-K)-$T_\mathrm{eff}$ relation for main-sequence stars of spectral type A0 and later. Finally, we have compared mass values obtained combining surface gravity with inferred stellar radius (\textit{gravity mass}) and as a result of the comparison of computed luminosity and temperature values with stellar evolutionary models (\textit{isochrone mass}). The strong discrepancy between isochrone and gravity mass obtained for one of the observed stars, $\gamma$\,Lyr, suggests that determination of the stellar atmosphere parameters should be revised.Comment: 13 pages, 9 figures, accepted for publication in MNRA

Direct Detection of the Brown Dwarf GJ 802B with Adaptive Optics Masking Interferometry

We have used the Palomar 200" Adaptive Optics (AO) system to directly detect the astrometric brown dwarf GJ 802B reported by Pravdo et al. 2005. This observation is achieved with a novel combination of aperture masking interferometry and AO. The dynamical masses are 0.175$\pm$0.021 M$_\odot$ and 0.064$\pm$0.032 M$_\odot$ for the primary and secondary respectively. The inferred absolute H band magnitude of GJ 802B is M$_H$=12.8 resulting in a model-dependent T$_\mathrm{eff}$ of 1850 $\pm$ 50K and mass range of 0.057--0.074 M$_\odot$.Comment: 4 Pages, 5 figures, emulateapj format, submitted to ApJ

Properties of dense partially random graphs

We study the properties of random graphs where for each vertex a {\it neighbourhood} has been previously defined. The probability of an edge joining two vertices depends on whether the vertices are neighbours or not, as happens in Small World Graphs (SWGs). But we consider the case where the average degree of each node is of order of the size of the graph (unlike SWGs, which are sparse). This allows us to calculate the mean distance and clustering, that are qualitatively similar (although not in such a dramatic scale range) to the case of SWGs. We also obtain analytically the distribution of eigenvalues of the corresponding adjacency matrices. This distribution is discrete for large eigenvalues and continuous for small eigenvalues. The continuous part of the distribution follows a semicircle law, whose width is proportional to the "disorder" of the graph, whereas the discrete part is simply a rescaling of the spectrum of the substrate. We apply our results to the calculation of the mixing rate and the synchronizability threshold.Comment: 14 pages. To be published in Physical Review

Interferometric radii of bright Kepler stars with the CHARA Array: {\theta} Cygni and 16 Cygni A and B

We present the results of long-baseline optical interferometry observations using the Precision Astronomical Visual Observations (PAVO) beam combiner at the Center for High Angular Resolution Astronomy (CHARA) Array to measure the angular sizes of three bright Kepler stars: {\theta} Cygni, and both components of the binary system 16 Cygni. Supporting infrared observations were made with the Michigan Infrared Combiner (MIRC) and Classic beam combiner, also at the CHARA Array. We find limb-darkened angular diameters of 0.753+/-0.009 mas for {\theta} Cyg, 0.539+/-0.007 mas for 16 Cyg A and 0.490+/-0.006 mas for 16 Cyg B. The Kepler Mission has observed these stars with outstanding photometric precision, revealing the presence of solar-like oscillations. Due to the brightness of these stars the oscillations have exceptional signal-to-noise, allowing for detailed study through asteroseismology, and are well constrained by other observations. We have combined our interferometric diameters with Hipparcos parallaxes, spectrophotometric bolometric fluxes and the asteroseismic large frequency separation to measure linear radii ({\theta} Cyg: 1.48+/-0.02 Rsun, 16 Cyg A: 1.22+/-0.02 Rsun, 16 Cyg B: 1.12+/-0.02 Rsun), effective temperatures ({\theta} Cyg: 6749+/-44 K, 16 Cyg A: 5839+/-42 K, 16 Cyg B: 5809+/-39 K), and masses ({\theta} Cyg: 1.37+/-0.04 Msun, 16 Cyg A: 1.07+/-0.05 Msun, 16 Cyg B: 1.05+/-0.04 Msun) for each star with very little model dependence. The measurements presented here will provide strong constraints for future stellar modelling efforts.Comment: 9 pages, 4 figures, and 5 tables, accepted for publication in Monthly Notices of the Royal Astronomical Societ

Complete Solving for Explicit Evaluation of Gauss Sums in the Index 2 Case

Let $p$ be a prime number, $q=p^f$ for some positive integer $f$, $N$ be a positive integer such that $\gcd(N,p)=1$, and let \k be a primitive multiplicative character of order $N$ over finite field \fq. This paper studies the problem of explicit evaluation of Gauss sums in "\textsl{index 2 case}" (i.e. f=\f{\p(N)}{2}=[\zn:\pp], where \p(\cd) is Euler function). Firstly, the classification of the Gauss sums in index 2 case is presented. Then, the explicit evaluation of Gauss sums G(\k^\la) (1\laN-1) in index 2 case with order $N$ being general even integer (i.e. N=2^{r}\cd N_0 where $r,N_0$ are positive integers and $N_03$ is odd.) is obtained. Thus, the problem of explicit evaluation of Gauss sums in index 2 case is completely solved