Proteins associated with pancreatic cancer survival in patients with resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for personalized medicine and improve current pancreatic cancer treatment. To extend our previous investigation, we examined the proteomes of individual pancreas tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the protein profile of each pancreatic tumor tissue was compared to reveal the proteome alterations that may be associated with pancreatic cancer survival. Pathway analysis of the differential proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated proteins, and VEGFA, APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition, galectin-1, a previously identified protein with its abundance aversely associated with pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of galectin-1 in pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP, LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and LGALS1 could be potential therapeutic targets to improve pancreatic cancer survival if further validated

Climate change adaptation in and through agroforestry: four decades of research initiated by Peter Huxley

Agroforestry (AF)-based adaptation to global climate change can consist of (1) reversal of negative trends in diverse tree cover as generic portfolio risk management strategy; (2) targeted, strategic, shift in resource capture (e.g. light, water) to adjust to changing conditions (e.g. lower or more variable rainfall, higher temperatures); (3) vegetation-based influences on rainfall patterns; or (4) adaptive, tactical, management of tree-crop interactions based on weather forecasts for the (next) growing season. Forty years ago, a tree physiological research tradition in aboveground and belowground resource capture was established with questions and methods on climate-tree-soil-crop interactions in space and time that are still relevant for today’s challenges. After summarising early research contributions, we review recent literature to assess current levels of uncertainty in climate adaptation assessments in and through AF. Quantification of microclimate within and around tree canopies showed a gap between standard climate station data (designed to avoid tree influences) and the actual climate in which crop and tree meristems or livestock operates in real-world AF. Where global scenario modelling of ‘macroclimate’ change in mean annual rainfall and temperature extrapolates from climate station conditions in past decades, it ignores microclimate effects of trees. There still is a shortage of long-term phenology records to analyse tree biological responses across a wide range of species to climate variability, especially where flowering and pollination matter. Physiological understanding can complement farmer knowledge and help guide policy decisions that allow AF solutions to emerge and tree germplasm to be adjusted for the growing conditions expected over the lifetime of a tree.</p

Electron correlation effects and magnetic ordering at the Gd(0001) surface

Effects of electron correlation on the electronic structure and magnetic properties of the Gd(0001) surface are investigated using of the full-potential linearized augmented plane wave implementation of correlated band theory ("LDA+U"). The use of LDA+U instead of LDA (local density approximation) total energy calculations produces the correct ferromagnetic ground state for both bulk Gd and the Gd surface. Surface strain relaxation leads to an 90 % enhancement of the interlayer surface-to-bulk effective exchange coupling. Application of a Landau-Ginzburg type theory yields a 30 % enhancement of the Curie temperature at the surface, in very good agreement with the experiment.Comment: revised version: minor typos correcte

New evidence for a massive black hole at the centre of the quiescent galaxy M32

Massive black holes are thought to reside at the centres of many galaxies, where they power quasars and active galactic nuclei. But most galaxies are quiescent, indicating that any central massive black hole present will be starved of fuel and therefore detectable only through its gravitational influence on the motions of the surrounding stars. M32 is a nearby, quiescent elliptical galaxy in which the presence of a black hole has been suspected; however, the limited resolution of the observational data and the restricted classes of models used to interpret this data have made it difficult to rule out alternative explanations, such as models with an anisotropic stellar velocity distribution and no dark mass or models with a central concentration of dark objects (for example, stellar remnants or brown dwarfs). Here we present high-resolution optical HST spectra of M32, which show that the stellar velocities near the centre of this galaxy exceed those inferred from previous ground-based observations. We use a range of general dynamical models to determine a central dark mass concentration of (3.4 +/- 1.6) x 10^6 solar masses, contained within a region only 0.3 pc across. This leaves a massive black hole as the most plausible explanation of the data, thereby strengthening the view that such black holes exist even in quiescent galaxies.Comment: 8 pages, LaTeX, 3 figures; mpeg animation of the stellar motions in M32 available at http://oposite.stsci.edu/pubinfo/Anim.htm

A HST Census of Nuclear Star Clusters in Late-Type Spiral Galaxies: II. Cluster Sizes and Structural Parameter Correlations

We investigate the structural properties of nuclear star clusters in late-type spiral galaxies. More specifically, we fit analytical models to HST images of 39 nuclear clusters in order to determine their effective radii after correction for the instrumental point spread function. We use the results of this analysis to compare the luminosities and sizes of nuclear star clusters to those of other ellipsoidal stellar systems, in particular the Milky Way globular clusters. Our nuclear clusters have a median effective radius of r_e = 3.5 pc, with 50% of the sample falling between 2.4 pc < r_e < 5.0 pc. This narrow size distribution is statistically indistinguishable from that of Galactic globular clusters, even though the nuclear clusters are on average 4 magnitudes brighter than the old globulars. We discuss some possible interpretations of this result. From a comparison of nuclear cluster luminosities with various properties of their host galaxies, we confirm that more luminous galaxies harbor more luminous nuclear clusters. It remains unclear whether this correlation mainly reflects the influence of galaxy size, mass, and/or star formation rate. Since the brighter galaxies in our sample typically have stellar disks with a higher central surface brightness, nuclear cluster luminosity also correlates with this property of their hosts. On the other hand, we find no evidence for a correlation between the presence of a nuclear star cluster and the presence of a large-scale stellar bar.Comment: 32 pages incl. 11 figures. Accepted for publication in AJ (Jan. 2004 issue

Magellanic Cloud Structure from Near-IR Surveys I: The Viewing Angles of the LMC

We present a detailed study of the viewing angles of the LMC disk plane. We find that our viewing direction differs considerably from the commonly accepted values, which has important implications for the structure of the LMC. The discussion is based on an analysis of spatial variations in the apparent magnitude of features in the near-IR color-magnitude diagrams extracted from the DENIS and 2MASS surveys. Sinusoidal brightness variations with a peak-to-peak amplitude of approximately 0.25 mag are detected as function of position angle, for both AGB and RGB stars. This is naturally interpreted as the result of distance variations, due to one side of the LMC plane being closer to us than the opposite side. The best fitting geometric model of an inclined plane yields an inclination angle i = 34.7 +/- 6.2 degrees and line-of-nodes position angle Theta = 122.5 +/- 8.3 degrees. There is tentative evidence that the LMC disk plane may be warped. Traditional methods to estimate the position angle of the line of nodes have used either the major axis position angle Theta_maj of the spatial distribution of tracers on the sky, or the position angle Theta_max of the line of maximum gradient in the velocity field, given that for a circular disk Theta_maj = Theta_max = Theta. The present study does not rely on the assumption of circular symmetry, and is considerably more accurate than previous studies of its kind. We find that the actual position angle of the line of nodes differs considerably from both Theta_maj and Theta_max, for which measurements have fallen in the range 140-190 degrees. This indicates that the intrinsic shape of the LMC disk is not circular, but elliptical, as discussed further in Paper II. [Abridged]Comment: Astronomical Journal, in press. 44 pages, LaTeX, with 8 PostScript figures. Contains minor revisions with respect to previously posted version. Check out http://www.stsci.edu/~marel/lmc.html for a large scale (23x21 degree) stellar number-density image of the LMC constructed from RGB and AGB stars in the 2MASS and DENIS surveys. The paper is available with higher resolution figures from http://www.stsci.edu/~marel/abstracts/abs_R31.htm