BMP2/BMPR1A is linked to tumour progression in dedifferentiated liposarcomas

Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMP2 in the progression of dedifferentiated liposarcomas. Using disease free survival as our primary endpoint, we find that BMP2 confers poor prognosis only within the context of high BMPR1A expression. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link the BMP2/BMPR1A axis to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2 and the potential disadvantages of recombinant human BMP2 (rhBMP2) use in orthopaedic surgery. For the first time, we identify high BMP2 expression within the context of high BMPR1A expression as a biomarker of disease relapse in dedifferentiated liposarcomas

Resolving the Outer Disks and Halos of Nearby Galaxies

In a hierarchical merging scenario, the outer parts of a galaxy are a fossil record of the galaxy's early history. Observations of the outer disks and halos of galaxies thus provide a tool to study individual galaxy histories and test formation theories. Locally, an impressive effort has been made to understand the halo of the Milky Way, Andromeda, and M33. However, due to the stochastic nature of halo formation, a better understanding of this process requires a large sample of galaxies with known halo properties. The GHOSTS project (PI: R. de Jong) aims to characterize the halos and outer portions of 14 nearby (D=4-14 Mpc) spiral galaxies using the Hubble Space Telescope. Detection of individual stars in the outer parts of these galaxies enables us to study both the morphological properties of the galaxies, and determine the stars' metallicity and age.Comment: Contributed talk; to appear in the proceedings of "Galaxies in the Local Volume" Sydney 8-13 July 200

Charm quark and D^* cross sections in deeply inelastic scattering at DESY HERA

A next-to-leading order Monte Carlo program for the calculation of heavy quark cross sections in deeply inelastic scattering is described. Concentrating on charm quark and D^*(2010) production at HERA, several distributions are presented and their variation with respect to charm quark mass, parton distribution set, and renormalization-factorization scale is studied.Comment: 15 pages including 8 figures. Uses Latex, Revtex, and psfig. References added - others updated. Several sentences/words added for clarity. Results/conclusions unchanged. To appear in Phys. Rev.

A novel autotransporter of uropathogenic Proteus mirabilis is both a cytotoxin and an agglutinin

One of the six predicted Proteus mirabilis autotransporters (ATs), ORF c2341, is predicted to contain a serine protease motif and was earlier identified as an immunogenic outer membrane protein in P. mirabilis . The 3.2 kb gene encodes a 117 kDa protein with a 58-amino-acid-long signal peptide, a 75-kDa-long N-terminal passenger domain and a 30-kDa-long C-terminal translocator. Affinity-purified 110 kDa AT exhibited chymotrypsin-like activity and hydrolysed N -Suc–Ala–Ala–Pro–Phe– p Na and N -Suc–Ala–Ala–Pro–Leu– p Na with a K M of 22 μM and 31 μM, respectively, under optimal pH of 8.5–9.0 in a Ca 2+ -dependent manner. Activity was inhibited by subtilase-specific inhibitors leupeptin and chymostatin. Both the cell-associated and purified form elicited cytopathic effects on cultured kidney and bladder epithelial cells. Substrate hydrolysis as well as cytotoxicity was associated with the passenger domain and was compromised upon mutation of any of the catalytic residues (Ser366, His147 and Asp533). At alkaline pH and optimal cell density, the AT also promoted autoaggregation of P. mirabilis and this function was independent of its protease activity. Cytotoxicity, autoaggregation and virulence were significantly reduced in an isogenic pta mutant of P. mirabilis . Proteus toxic agglutinin (Pta) represents a novel autotransported cytotoxin with no bacterial homologues that works optimally in the alkalinized urinary tract, a characteristic of urease-mediated urea hydrolysis during P. mirabilis infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73221/1/j.1365-2958.2008.06199.x.pd

A study of top polarization in single-top production at the LHC

This paper complements the study of single top production at the LHC aiming to estimate the sensitivity of different observables to the magnitude of the effective couplings. In a previous paper the dominant $W$-gluon fusion mechanism was considered, while here we extend the analysis to the subdominant (10% with our set of experimental cuts) s-channel process. In order to distinguish left from right effective couplings it is required to consider polarized cross-sections and/or include $m_b$ effects. The spin of the top is accessible only indirectly by measuring the angular distribution of its decay products. We show that the presence of effective right-handed couplings implies necessarily that the top is not in a pure spin state. We discuss to what extent quantum interference terms can be neglected in the measurement and therefore simply multiply production and decay probabilities clasically. The coarsening involved in the measurement process makes this possible. We determine for each process the optimal spin basis where theoretical errors are minimized and, finally, discuss the sensitivity in the s-channel to the effective right-handed coupling. The results presented here are all analytical and include $m_b$ corrections. They are derived within the narrow width approximation for the top.Comment: 30 pages, 14 figure

On the nature of the unidentified X-ray/gamma-ray sources IGR J18027-1455 and IGR J21247+5058

We present a multiwavelength study of the environment of the unidentified X-ray/gamma-ray sources IGR J18027-1455 and IGR J21247+5058, recently discovered by the IBIS/ISGRI instrument, onboard the INTEGRAL satellite. The main properties of the sources found inside their position error circles, give us clues about the nature of these high-energy sources.Comment: 8 pages, 4 figures, Proceedings of the Conference "The Multiwavelength Approach to Unidentified Sources", to appear in the journal Astrophysics and Space Scienc

Associated Top Quark-Higgs Boson Production at the LHC

We compute the O(alpha_s^3) inclusive cross section for the process pp -> t-tbar-h in the Standard Model, at sqrt(s)=14 TeV. The next-to-leading order corrections drastically reduce the renormalization and factorization scale dependence of the Born cross section and increase the total cross section for renormalization and factorization scales larger than m_t. These corrections have important implications for models of new physics involving the top quark.Comment: 5 pages, 4 figures, RevTeX

Hera Events, Tevatron Jets, and the Uncertainty On Quarks At Large X

The recently reported excess of events at HERA compared to QCD calculations impels us to examine all possible Standard Model explanations before invoking ``new physics''. We explore the possibility of adding an unusual, but small, component of additional quarks at large x (beyond x>0.75) as a way to increase the predicted SM cross-section in the HERA kinematic region by the QCD evolution feed-down effect. We describe various scenarios under which this can be achieved while maintaining good global fits to all established data sets. This implies a much larger SM uncertainty than commonly assumed. In addition, the modified parton distributions provide another possible mechanism to account for the CDF high-pt jet excess which occurs at similar x and Q^2 values.Comment: 13 page Latex, 8 ps figures, replaced with modifications to the tex

Cross Sections for Leptophobic Topcolor Z' decaying to top-antitop

We present numerical calculations of the production cross section of a heavy Z' resonance in hadron-hadron collisions with subsequent decay into top-antitop pairs. In particular, we consider the leptophobic topcolor Z' discussed under Model IV of hep-ph/9911288 which has predicted cross sections large enough to be experimentally accessible at the Fermilab Tevatron and the Large Hadron Collider at CERN. This article presents an updated calculation valid for the Tevatron and all proposed LHC collision energies. Cross sections are presented for various Z' widths, in p-pbar collisions at \sqrt{s}=2 TeV, and in p-p collisions at \sqrt{s}=7, 8, 10 and 14 TeV.Comment: 6 pages, 5 figures (Submitted to PRD); The European Physical Journal C, Volume 72, Issue

Bottom quark electroproduction in variable flavor number schemes

Two variable flavor number schemes are used to describe bottom quark production in deep inelastic electron-proton scattering. In these schemes the coefficient functions are derived from mass factorization of the heavy quark coefficient functions presented in a fixed flavor number scheme. Also one has to construct a parton density set with five light flavors (u,d,s,c,b) out of a set which only contains four light flavors (u,d,s,c). In order $\alpha_s^2$ the two sets are discontinuous at $\mu=m_b$ which follows from mass factorization of the heavy quark coefficient functions when it is carried out in the ${\bar {\rm MS}}$-scheme. Both variable flavor number schemes give almost identical predictions for the bottom structure functions $F_{2,b}$ and $F_{L,b}$. Also they both agree well with the corresponding results based on fixed order four-flavor perturbation theory over a wide range in $x$ and $Q^2$.Comment: Latex with seventeen PostScript figure