Quadruplewild-type (WT) GIST: defining the subset of GIST that lacks abnormalities of KIT, PDGFRA, SDH, or RAS signaling pathways

A subset of GISTs lack mutations in the KIT/PDGFRA or RAS pathways and yet retain an intact succinate dehydrogensase (SDH) complex. We propose that these KIT/PDGFRA/SDH/RAS-P WT GIST tumors be designated as quadruple wild-type (WT) GIST. Further molecular and clinicophatological characterization of quadruple WT GIST will help to determine their prognosis as well as assist in the optimization of medical management, including clinical test of novel therapies

Gene expression of the IGF pathway family distinguishes subsets of gastrointestinal stromal tumors wild type for KIT and PDGFRA

Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal (ICCs) and are the most common mesenchymal neoplasm of the gastrointestinal tract. While the majority of GISTs harbor activating mutations in either the v-kit Hardy-Zuckerman feline sarcoma viral oncogene homolog (KIT) or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases, approximately 10–15% of adult GISTs and 85% of pediatric GISTs lack such mutations. These “wild-type” GISTs have been reported to express high levels of the insulin-like growth factor 1 receptor (IGF1R), and IGF1R-targeted therapy of wild-type GISTs is being evaluated in clinical trials. However, it is not clear that all wild-type GISTs express IGF1R, because studies to date have predominantly focused on a particular subtype of gastric wild-type GIST that is deficient in the mitochondrial succinate dehydrogenase (SDH) complex. This study of a series of 136 GISTs, including 72 wild-type specimens, was therefore undertaken to further characterize wild-type GIST subtypes based on the relative expression of transcripts encoding IGF1R. Additional transcripts relevant to GIST biology were also evaluated, including members of the IGF-signaling pathway (IGF1, IGF2, and insulin receptor [INSR]), neural markers (CDH2[CDH: Cadherin], neurofilament, light polypeptide, LHX2 [LHX: LIM homeobox], and KIRREL3 [KIRREL: kin of IRRE like]), KIT, PDGFRA, CD34, and HIF1A. Succinate dehydrogenase complex, subunit B protein expression was also assessed as a measure of SDH complex integrity. In addition to the previously described SDH-deficient, IGF1Rhigh wild-type GISTs, other SDH-intact wild-type subpopulations were defined by high relative expression of IGF1R, neural markers, IGF1 and INSR, or low IGF1R coupled with high IGF2. These results underscore the complexity and heterogeneity of wild-type GISTs that will need to be factored into molecularly-targeted therapeutic strategies

The T=0 random-field Ising model on a Bethe lattice with large coordination number: hysteresis and metastable states

In order to elucidate the relationship between rate-independent hysteresis and metastability in disordered systems driven by an external field, we study the Gaussian RFIM at T=0 on regular random graphs (Bethe lattice) of finite connectivity z and compute to O(1/z) (i.e. beyond mean-field) the quenched complexity associated with the one-spin-flip stable states with magnetization m as a function of the magnetic field H. When the saturation hysteresis loop is smooth in the thermodynamic limit, we find that it coincides with the envelope of the typical metastable states (the quenched complexity vanishes exactly along the loop and is positive everywhere inside). On the other hand, the occurence of a jump discontinuity in the loop (associated with an infinite avalanche) can be traced back to the existence of a gap in the magnetization of the metastable states for a range of applied field, and the envelope of the typical metastable states is then reentrant. These findings confirm and complete earlier analytical and numerical studies.Comment: 29 pages, 9 figure

SDHC methylation in gastrointestinal stromal tumors (GIST): a case report

Gastrointestinal stromal tumors (GIST) recently have been recognized as a genetically and biologically heterogeneous disease. In addition to KIT or PDGFRA mutated GIST, mutational inactivation of succinate dehydrogenase (SDH) subunits has been detected in the KIT/PDGFRA wild-type subgroup, referred to as SDH deficient (dSDH). Even though most dSDH GIST harbor mutations in SDHx subunit genes, some are SDHx wild type. Epigenetic regulation by DNA methylation of CpG islands recently has been found to be an alternative mechanism underlying the lack of SDH complex in GIST

The Hubble constant from galaxy lenses: impacts of triaxiality and model degeneracies

The Hubble constant can be constrained using the time delays between multiple images of gravitationally lensed sources. In some notable cases, typical lensing analyses assuming isothermal galaxy density profiles produce low values for the Hubble constant, inconsistent with the result of the HST Key Project (72 +- 8 km/s/Mpc). Possible systematics in the values of the Hubble constant derived from galaxy lensing systems can result from a number of factors, e.g. neglect of environmental effects, assumption of isothermality, or contamination by line-of-sight structures. One additional potentially important factor is the triaxial structure of the lensing galaxy halo; most lens models account for halo shape simply by perturbing the projected spherical lensing potential, an approximation that is often necessary but that is inadequate at the levels of triaxiality predicted in the CDM paradigm. To quantify the potential error introduced by this assumption in estimates of the Hubble parameter, we strongly lens a distant galaxy through a sample of triaxial softened isothermal halos and use an MCMC method to constrain the lensing halo profile and the Hubble parameter from the resulting multiple image systems. We explore the major degeneracies between the Hubble parameter and several parameters of the lensing model, finding that without a way to accurately break these degeneracies accurate estimates of the Hubble parameter are not possible. Crucially, we find that triaxiality does not significantly bias estimates of the Hubble constant, and offer an analytic explanation for this behaviour in the case of isothermal profiles. Neglected triaxial halo shape cannot contribute to the low Hubble constant values derived in a number of galaxy lens systems.Comment: Minor revisions to match version published in MNRAS. 13 pages, 11 figure

A novel series solution to the renormalization group equation in QCD

Recently, the QCD renormalization group (RG) equation at higher orders in MS-like renormalization schemes has been solved for the running coupling as a series expansion in powers of the exact 2-loop order coupling. In this work, we prove that the power series converges to all orders in perturbation theory. Solving the RG equation at higher orders, we determine the running coupling as an implicit function of the 2-loop order running coupling. Then we analyze the singularity structure of the higher order coupling in the complex 2-loop coupling plane. This enables us to calculate the radii of convergence of the series solutions at the 3- and 4-loop orders as a function of the number of quark flavours $n_{\rm f}$. In parallel, we discuss in some detail the singularity structure of the ${\bar{\rm MS}}$ coupling at the 3- and 4-loops in the complex momentum squared plane for $0\leq n_{\rm f} \leq 16$. The correspondence between the singularity structure of the running coupling in the complex momentum squared plane and the convergence radius of the series solution is established. For sufficiently large $n_{\rm f}$ values, we find that the series converges for all values of the momentum squared variable $Q^2=-q^2>0$. For lower values of $n_{\rm f}$, in the ${\bar{\rm MS}}$ scheme, we determine the minimal value of the momentum squared $Q_{\rm min}^2$ above which the series converges. We study properties of the non-power series corresponding to the presented power series solution in the QCD Analytic Perturbation Theory approach of Shirkov and Solovtsov. The Euclidean and Minkowskian versions of the non-power series are found to be uniformly convergent over whole ranges of the corresponding momentum squared variables.Comment: 29 pages,LateX file, uses IOP LateX class file, 2 figures, 13 Tables. Formulas (4)-(7) and Table 1 were relegated to Appendix 1, some notations changed, 2 footnotes added. Clarifying discussion added at the end of Sect. 3, more references and acknowledgments added. Accepted for publication in Few-Body System

Fast and slow rotators in the densest environments: a FLAMES/GIRAFFE IFS study of galaxies in Abell 1689 at z=0.183

We present FLAMES/GIRAFFE integral field spectroscopy of 30 galaxies in the massive cluster Abell 1689 at z = 0.183. Conducting an analysis similar to that of ATLAS3D, we extend the baseline of the kinematic morphology-density relation by an order of magnitude in projected density and show that it is possible to use existing instruments to identify slow and fast rotators beyond the local Universe. We find 4.5 +- 1.0 slow rotators with a distribution in magnitude similar to those in the Virgo cluster. The overall slow rotator fraction of our Abell 1689 sample is 0.15 +- 0.03, the same as in Virgo using our selection criteria. This suggests that the fraction of slow rotators in a cluster is not strongly dependent on its density. However, within Abell 1689, we find that the fraction of slow rotators increases towards the centre, as was also found in the Virgo cluster.Comment: Accepted by MNRA

Anomalous scaling and Lee-Yang zeroes in Self-Organized Criticality

We show that the generating functions of avalanche observables in SOC models exhibits a Lee-Yang phenomenon. This establishes a new link between the classical theory of critical phenomena and SOC. A scaling theory of the Lee-Yang zeroes is proposed including finite sampling effects.Comment: 33 pages, 19 figures, submitte

The 400d Galaxy Cluster Survey Weak Lensing Programme: I: MMT/Megacam Analysis of CL0030+2618 at z=0.50

The mass function of galaxy clusters at high redshifts is a particularly useful probe to learn about the history of structure formation and constrain cosmological parameters. We aim at deriving reliable masses for a high-redshift, high-luminosity sample of clusters of galaxies selected from the 400d survey of X-ray selected clusters. Here, we will focus on a particular object, CL0030+2618 at z=0.50 Using deep imaging in three passbands with the MEGACAM instrument at MMT, we show that MEGACAM is well-suited for measuring gravitational shear. We detect the weak lensing signal of CL0030+2618 at 5.8 sigma significance, using the aperture mass technique. Furthermore, we find significant tangential alignment of galaxies out to ~10 arcmin or >2r_200 distance from the cluster centre. The weak lensing centre of CL0030+2618 agrees with several X-ray measurements and the position of the brightest cluster galaxy. Finally, we infer a weak lensing virial mass of M_200=7.5 10^{14} M_sun for CL0030+2618. Despite complications by a tentative foreground galaxy group in the line of sight, the X-ray and weak lensing estimates for CL0030+2618 are in remarkable agreement. This study paves the way for the largest weak lensing survey of high-redshift galaxy clusters to date.Comment: 32 pages, 24 figures, submitted to Astronomy & Astrophysics; fixed some LaTeX issues, now 30 pages v3: Improved version accepted by Astronomy & Astrophysic