RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation

Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A2 (cPLA2), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10th thoracic (T10) vertebral level. We found that co-administration of TNF-α and glutamate induced spinal neuron death, and activation of RhoA, Rho kinase and cPLA2. Inhibition of RhoA, Rho kinase and cPLA2 significantly reduced TNF-α/glutamate-induced cell death by 33, 52 and 43 %, respectively (p < 0.001). Inhibition of RhoA and Rho kinase also significantly downregulated cPLA2 activation by 66 and 60 %, respectively (p < 0.01). Furthermore, inhibition of RhoA and Rho kinase reduced the release of arachidonic acid, a downstream substrate of cPLA2. The immunofluorescence staining showed that ROCK1 or ROCK2, two isoforms of Rho kinase, was co-localized with cPLA2 in neuronal cytoplasm. Interestingly, co-immunoprecipitation (Co-IP) assay showed that ROCK1 or ROCK2 bonded directly with cPLA2 and phospho-cPLA2. When the Rho kinase inhibitor Y27632 was applied in mice with T10 contusion injury, it significantly decreased cPLA2 activation and expression and reduced injury-induced apoptosis at and close to the lesion site. Taken together, our results reveal a novel mechanism of RhoA/Rho kinase-mediated neuronal death through regulating cPLA2 activation

ASTROD and ASTROD I -- Overview and Progress

In this paper, we present an overview of ASTROD (Astrodynamical Space Test of Relativity using Optical Devices) and ASTROD I mission concepts and studies. The missions employ deep-space laser ranging using drag-free spacecraft to map the gravitational field in the solar-system. The solar-system gravitational field is determined by three factors: the dynamic distribution of matter in the solar system; the dynamic distribution of matter outside the solar system (galactic, cosmological, etc.) and gravitational waves propagating through the solar system. Different relativistic theories of gravity make different predictions of the solar-system gravitational field. Hence, precise measurements of the solar-system gravitational field test all these. The tests and observations include: (i) a precise determination of the relativistic parameters beta and gamma with 3-5 orders of magnitude improvement over previous measurements; (ii) a 1-2 order of magnitude improvement in the measurement of G-dot; (iii) a precise determination of any anomalous, constant acceleration Aa directed towards the Sun; (iv) a measurement of solar angular momentum via the Lense-Thirring effect; (v) the detection of solar g-mode oscillations via their changing gravity field, thus, providing a new eye to see inside the Sun; (vi) precise determination of the planetary orbit elements and masses; (viii) better determination of the orbits and masses of major asteroids; (ix) detection and observation of gravitational waves from massive black holes and galactic binary stars in the frequency range 0.05 mHz to 5 mHz; and (x) exploring background gravitational-waves.Comment: 17 pages, 6 figures, presented to The Third International ASTROD Symposium on Laser Astrodynamics, Space Test of Relativity and Gravitational-Wave Astronomy, Beijing, July 14-16, 2006; International Journal of Modern Physics D, in press (2008

CS Lines Profiles in Hot Cores

We present a theoretical study of CS line profiles in archetypal hot cores. We provide estimates of line fluxes from the CS(1-0) to the CS(15-14) transitions and present the temporal variation of these fluxes. We find that \textit{i)} the CS(1-0) transition is a better tracer of the Envelope of the hot core whereas the higher-J CS lines trace the ultra-compact core; \textit{ii)} the peak temperature of the CS transitions is a good indicator of the temperature inside the hot core; \textit{iii)} in the Envelope, the older the hot core the stronger the self-absorption of CS; \textit{iv)} the fractional abundance of CS is highest in the innermost parts of the ultra-compact core, confirming the CS molecule as one of the best tracers of very dense gas.Comment: 17 pages, 5 figures, 1 table, In press in Ap

First Acetic Acid Survey with CARMA in Hot Molecular Cores

Acetic acid (CH$_3$COOH) has been detected mainly in hot molecular cores where the distribution between oxygen (O) and nitrogen (N) containing molecular species is co-spatial within the telescope beam. Previous work has presumed that similar cores with co-spatial O and N species may be an indicator for detecting acetic acid. However, does this presumption hold as higher spatial resolution observations become available of large O and N-containing molecules? As the number of detected acetic acid sources is still low, more observations are needed to support this postulate. In this paper, we report the first acetic acid survey conducted with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at 3 mm wavelengths towards G19.61-0.23, G29.96-0.02 and IRAS 16293-2422. We have successfully detected CH$_3$COOH via two transitions toward G19.61-0.23 and tentatively confirmed the detection toward IRAS 16293-2422 A. The determined column density of CH$_3$COOH is 2.0(1.0)$\times 10^{16}$ cm$^{-2}$ and the abundance ratio of CH$_3$COOH to methyl formate (HCOOCH$_3$) is 2.2(0.1)$\times 10^{-1}$ toward G19.61-0.23. Toward IRAS 16293 A, the determined column density of CH$_3$COOH is $\sim$ 1.6 $\times 10^{15}$ cm$^{-2}$ and the abundance ratio of CH$_3$COOH to methyl formate (HCOOCH$_3$) is $\sim$ 1.0 $\times 10^{-1}$ both of which are consistent with abundance ratios determined toward other hot cores. Finally, we model all known line emission in our passband to determine physical conditions in the regions and introduce a new metric to better reveal weak spectral features that are blended with stronger lines or that may be near the 1-2$\sigma$ detection limit.Comment: 28 pages, 8 figures, accepted for publication in the ApJ; Revised citation in session 2, references remove

Market Orientation, Growth Strategy, and Firm Performance: The Moderating Effects of External Connections

This study examines the mediating effect of growth strategy (including market and product expansion strategies) on the linkage of market orientation (MO) to firm performance and the moderating effects of a firm's external connections (including political and business ties) on the relationship between MO and growth strategy. It finds that both market and product expansion strategies are key conduits through which MO improves firm performance. In addition, the relationship between MO and market expansion strategy is positively moderated by political ties but negatively moderated by business ties, while the linkage of MO to product expansion strategy is moderated negatively by political ties but positively by business ties. By combining mediating and moderating effects in a framework that integrates MO, growth strategy, external connections, and firm performance, this study enriches our knowledge on the implications of MO and provides insight into factors that facilitate firm growth

A procedure for the analysis of site‐specific and structure‐specific fucosylation in alpha‐1‐antitrypsin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134210/1/elps5934.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134210/2/elps5934_am.pd

Large-Format X-Ray Pinhole Camera

National Security Technologies, LLC, has successfully implemented many scientific and engineering innovations in the new Large-Format Pinhole Camera (LFPHC), which have dramatically increased the detection sensitivity and reliability of the camera in exotic locations, such as the Sandia National Laboratories Z-facility. Quality improvements of the LFPHC have been demonstrated in its fielding at Z, where high-quality images were recorded. A major improvement was the development of a new, user-friendly LFPHC camera back that would tolerate high radiation, electromagnetic interference, and mechanical shock. Key modifications resulted in improved detection sensitivity, spatial resolution, uniformity along the microchannel plate strip, and stability of the interframe timing and delay. Design considerations and improvements will be discussed