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

Detecting 6 MV X-rays using an organic photovoltaic device

An organic photovoltaic (OPV) device has been used in conjunction with a flexible inorganic phosphor to produce a radiation tolerant, efficient and linear detector for 6 MV Xrays. The OPVs were based on a blend of poly(3-hexylthiophene-2,5-diyl) (P3HT) and phenyl-C61-butyric acid methyl ester (PCBM). We show that the devices have a sensitivity an order of magnitude higher than a commercial silicon detector used as a reference. Exposure to 360 Grays of radiation resulted in a small (2%) degradation in performance demonstrating that these detectors have the potential to be used as flexible, real-time, in vivo dosimeters for oncology treatments. (C) 2009 Elsevier B.V. All rights reserved

Survival of near-critical branching Brownian motion

Consider a system of particles performing branching Brownian motion with negative drift $\mu = \sqrt{2 - \epsilon}$ and killed upon hitting zero. Initially there is one particle at $x>0$. Kesten showed that the process survives with positive probability if and only if $\epsilon>0$. Here we are interested in the asymptotics as \eps\to 0 of the survival probability $Q_\mu(x)$. It is proved that if $L= \pi/\sqrt{\epsilon}$ then for all $x \in \R$, $\lim_{\epsilon \to 0} Q_\mu(L+x) = \theta(x) \in (0,1)$ exists and is a travelling wave solution of the Fisher-KPP equation. Furthermore, we obtain sharp asymptotics of the survival probability when $x<L$ and $L-x \to \infty$. The proofs rely on probabilistic methods developed by the authors in a previous work. This completes earlier work by Harris, Harris and Kyprianou and confirms predictions made by Derrida and Simon, which were obtained using nonrigorous PDE methods

The transition zone as a host for recycled volatiles: Evidence from nitrogen and carbon isotopes in ultra-deep diamonds from Monastery and Jagersfontein (South Africa)

Sublithospheric (ultra-deep) diamonds provide a unique window into the deepest parts of Earth's mantle, which otherwise remain inaccessible. Here, we report the first combined C- and N-isotopic data for diamonds from the Monastery and Jagersfontein kimberlites that sample the deep asthenosphere and transition zone beneath the Kaapvaal Craton, in the mid Cretaceous, to investigate the nature of mantle fluids at these depths and the constraints they provide on the deep volatile cycle. Both diamond suites exhibit very light δ13C values (down to − 26‰) and heavy δ15N (up to + 10.3‰), with nitrogen abundances generally below 70 at. ppm but varying up to very high concentrations (2520 at. ppm) in rare cases. Combined, these signatures are consistent with derivation from subducted crustal materials. Both suites exhibit variable nitrogen aggregation states from 25 to 100% B defects. Internal growth structures, revealed in cathodoluminescence (CL) images, vary from faintly layered, through distinct cores to concentric growth patterns with intermittent evidence for dissolution and regular octahedral growth layers in places. Modelling the internal co-variations in δ13C-δ15N-N revealed that diamonds grew from diverse C-H-O-N fluids involving both oxidised and reduced carbon species. The diversity of the modelled diamond-forming fluids highlights the complexity of the volatile sources and the likely heterogeneity of the deep asthenosphere and transition zone. We propose that the Monastery and Jagersfontein diamonds form in subducted slabs, where carbon is converted into either oxidised or reduced species during fluid-aided dissolution of subducted carbon before being re-precipitated as diamond. The common occurrence of recycled C and N isotopic signatures in super-deep diamonds world-wide indicates that a significant amount of carbon and nitrogen is recycled back to the deep asthenosphere and transition zone via subducting slabs, and that the transition zone may be dominated by recycled C and N

Carbon and nitrogen systematics in nitrogen-rich ultradeep diamonds from San Luiz, Brazil

Three diamonds from Sao Luiz, Brazil carrying nano- and micro-inclusions of molecular δ-N2 that exsolved at the base of the transition zone were studied for their C and N isotopic composition and the concentration of N utilizing SIMS. The diamonds are individually uniform in their C isotopic composition and most spot analyses yield δ13C values of −3.2 ± 0.1‰ (ON-SLZ-390) and − 4.7 ± 0.1‰ (ON-SLZ-391 and 392). Only a few analyses deviate from these tight ranges and all fall within the main mantle range of −5 ± 3‰. Most of the N isotope analyses also have typical mantle δ15N values (−6.6 ± 0.4‰, −3.6 ± 0.5‰ and − 4.1 ± 0.6‰ for ON-SLZ-390, 391 and 392, respectively) and are associated with high N concentrations of 800–1250 atomic ppm. However, some N isotopic ratios, associated with low N concentrations (&lt;400 ppm) and narrow zones with bright luminescence are distinctly above the average, reaching positive δ15N values. These sharp fluctuations cannot be attributed to fractionation. They may reflect arrival of new small pulses of melt or fluid that evolved under different conditions. Alternatively, they may result from fractionation between different growth directions, so that distinct δ15N values and N concentrations may form during diamond growth from a single melt/fluid. Other more continuous variations, in the core of ON-SLZ-390 or the rim of ON-SLZ-392 may be the result of Rayleigh fractionation or mixing

BES3 time of flight monitoring system

A Time of Flight monitoring system has been developed for BES3. The light source is a 442-443 nm laser diode, which is stable and provides a pulse width as narrow as 50 ps and a peak power as large as 2.6 W. Two optical-fiber bundles with a total of 512 optical fibers, including spares, are used to distribute the light pulses to the Time of Flight counters. The design, operation, and performance of the system are described.Comment: 8 pages 16 figures, submitted to NI

Determination of step--edge barriers to interlayer transport from surface morphology during the initial stages of homoepitaxial growth

We use analytic formulae obtained from a simple model of crystal growth by molecular--beam epitaxy to determine step--edge barriers to interlayer transport. The method is based on information about the surface morphology at the onset of nucleation on top of first--layer islands in the submonolayer coverage regime of homoepitaxial growth. The formulae are tested using kinetic Monte Carlo simulations of a solid--on--solid model and applied to estimate step--edge barriers from scanning--tunneling microscopy data on initial stages of Fe(001), Pt(111), and Ag(111) homoepitaxy.Comment: 4 pages, a Postscript file, uuencoded and compressed. Physical Review B, Rapid Communications, in press

Changes in Congressional Oversight

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68007/2/10.1177_000276427902200504.pd

How to obtain a lattice basis from a discrete projected space

International audienceEuclidean spaces of dimension n are characterized in discrete spaces by the choice of lattices. The goal of this paper is to provide a simple algorithm finding a lattice onto subspaces of lower dimensions onto which these discrete spaces are projected. This first obtained by depicting a tile in a space of dimension n -- 1 when starting from an hypercubic grid in dimension n. Iterating this process across dimensions gives the final result

The maximal energy of classes of integral circulant graphs

The energy of a graph is the sum of the moduli of the eigenvalues of its adjacency matrix. We study the energy of integral circulant graphs, also called gcd graphs, which can be characterized by their vertex count $n$ and a set $\cal D$ of divisors of $n$ in such a way that they have vertex set $\mathbb{Z}_n$ and edge set ${{a,b}: a,b\in\mathbb{Z}_n, \gcd(a-b,n)\in {\cal D}}$. For a fixed prime power $n=p^s$ and a fixed divisor set size $|{\cal D}| =r$, we analyze the maximal energy among all matching integral circulant graphs. Let $p^{a_1} < p^{a_2} < ... < p^{a_r}$ be the elements of ${\cal D}$. It turns out that the differences $d_i=a_{i+1}-a_{i}$ between the exponents of an energy maximal divisor set must satisfy certain balance conditions: (i) either all $d_i$ equal $q:=\frac{s-1}{r-1}$, or at most the two differences $[q]$ and $[q+1]$ may occur; %(for a certain $d$ depending on $r$ and $s$) (ii) there are rules governing the sequence $d_1,...,d_{r-1}$ of consecutive differences. For particular choices of $s$ and $r$ these conditions already guarantee maximal energy and its value can be computed explicitly.Comment: Discrete Applied Mathematics (2012