A comparison of immunohistochemical assays and FISH in detecting the ALK translocation in diagnostic histological and cytological lung tumor material.

Introduction:Detection of the ALK rearrangement in a solid tumor gives these patients the option of crizotinib as an oral form of anticancer treatment. The current test of choice is fluorescence in situ hybridization (FISH), but various cheaper and more convenient immunohistochemical (IHC) assays have been proposed as alternatives.Methods:Fifteen FISH-positive cases from patients, seven with data on crizotinib therapy and clinical response, were evaluated for the presence of ALK protein using three different commercially available antibodies: D5F3, using the proprietary automated system (Ventana), ALK1 (Dako), and 5A4 (Abcam). A further 14 FISH-negative and three uncertain (<15% rearrangement detected) cases were also retrieved. Of the total 32 specimens, 17 were excisions and 15 were computed tomography-guided biopsies or cytological specimens. All three antibodies were applied to all cases. Antibodies were semiquantitatively scored on intensity, and the proportion of malignant cells stained was documented. Cutoffs were set by receiver operating curve analysis for positivity to optimize correct classification.Results:All three IHC assays were 100% specific but sensitivity did vary: D5F3 86%, ALK 79%, 5A4 71%. Intensity was the most discriminating measure overall, with a combination of proportion and intensity not improving the test. No FISH-negative IHC-positive cases were seen. Two FISH-positive cases were negative with all three IHC assays. One of these had been treated with crizotinib and had failed to show clinical response. The other harbored a second driving mutation in the EGFR gene.Conclusions:IHC with all three antibodies is especially highly specific (100%) although variably sensitive (71%-86%), specifically in cases with scanty material. D5F3 assay was most sensitive in these latter cases. Occasional cases are IHC-positive but FISH-negative, suggesting either inaccuracy of one assay or occasional tumors with ALK rearrangement that do not express high levels of ALK protein

No entropy enigmas for N=4 dyons

We explain why multi-centered black hole configurations where at least one of the centers is a large black hole do not contribute to the indexed degeneracies in theories with N=4 supersymmetry. This is a consequence of the fact that such configurations, although supersymmetric, belong to long supermultiplets. As a result, there is no entropy enigma in N=4 theories, unlike in N=2 theories.Comment: 14 page

State-of-the-art cytometry in the search of novel biomarkers in digestive cancers

Despite that colorectal and liver cancer are among the most prevalent tumours in the world, the identification of non-invasive biomarkers to aid on their diagnose and subsequent prognosis is a current unmet need that would diminish both their incidence and mortality rates. In this context, conventional flow cytometry has been widely used in the screening of biomarkers with clinical utility in other malignant processes like leukaemia or lymphoma. Therefore, in this review, we will focus on how advanced cytometry panels covering over 40 parameters can be applied on the study of the immune system from patients with colorectal and hepatocellular carcinoma and how that can be used on the search of novel biomarkers to aid or diagnose, prognosis, and even predict clinical response to different treatments. In addition, these multiparametric and unbiased approaches can also provide novel insights into the specific immunopathogenic mechanisms governing these malignant diseases, hence potentially unravelling novel targets to perform immunotherapy or identify novel mechanisms, rendering the development of novel treatments. As a consequence, computational cytometry approaches are an emerging methodology for the early detection and predicting therapies for gastrointestinal cancers

A Broadband Study of the Emission from the Composite Supernova Remnant MSH 11-62

MSH 11-62 (G291.1-0.9) is a composite supernova remnant for which radio and X-ray observations have identified the remnant shell as well as its central pulsar wind nebula. The observations suggest a relatively young system expanding into a low density region. Here we present a study of MSH 11-62 using observations with the Chandra, XMM-Newton, and Fermi observatories, along with radio observations from the Australia Telescope Compact Array (ATCA). We identify a compact X-ray source that appears to be the putative pulsar that powers the nebula, and show that the X-ray spectrum of the nebula bears the signature of synchrotron losses as particles diffuse into the outer nebula. Using data from the Fermi LAT, we identify gamma-ray emission originating from MSH 11-62. With density constraints from the new X-ray measurements of the remnant, we model the evolution of the composite system in order to constrain the properties of the underlying pulsar and the origin of the gamma-ray emission.Comment: 12 Pages, 12 figures. Accepted for publication in the Astrophysical Journa

Developing and Implementing a Sustainable, Integrated Weed Management Program for herbicide-resistant Poa annua in turfgrass

The ability of Poa annua L. to adapt to most turfgrass environments extends to its ability to develop resistance to commonly used herbicides. Herbicide resistant P. annua is of almost epidemic proportions. The loss of once viable chemical-based treatments pushes practitioners towards more expensive, and often less effective, control strategies. This management guide focuses on integrated weed management (IWM) practices for P. annua control and herbicide resistance—what it is and how to overcome it. Also discussed are resistance mechanisms and documentation of common occurrences of field-level resistance within much of the United States. Finally, a summary of some of the social and economic constraints that practitioners face in the implementation of IWM strategies for P. annua is discussed

Observations of T-Tauri Stars using HST-GHRS: I. Far Ultraviolet Emission Lines

We have analyzed GHRS data of eight CTTS and one WTTS. The GHRS data consists of spectral ranges 40 A wide centered on 1345, 1400, 1497, 1550, and 1900 A. These UV spectra show strong SiIV, and CIV emission, and large quantities of sharp (~40 km/s) H2 lines. All the H2 lines belong to the Lyman band and all the observed lines are single peaked and optically thin. The averages of all the H2 lines centroids for each star are negative which may indicate that they come from an outflow. We interpret the emission in H2 as being due to fluorescence, mostly by Ly_alpha, and identify seven excitation routes within 4 A of that line. We obtain column densities (10^12 to 10^15 cm^-2) and optical depths (~1 or less) for each exciting transition. We conclude that the populations are far from being in thermal equilibrium. We do not observe any lines excited from the far blue wing of Ly_alpha, which implies that the molecular features are excited by an absorbed profile. SiIV and CIV (corrected for H2 emission) have widths of ~200 km/s, and an array of centroids (blueshifted lines, centered, redshifted). These characteristics are difficult to understand in the context of current models of the accretion shock. For DR Tau we observe transient strong blueshifted emission, perhaps the a result of reconnection events in the magnetosphere. We also see evidence of multiple emission regions for the hot lines. While CIV is optically thin in most stars in our sample, SiIV is not. However, CIV is a good predictor of SiIV and H2 emission. We conclude that most of the flux in the hot lines may be due to accretion processes, but the line profiles can have multiple and variable components.Comment: 67 pages, 19 figures, Accepted in Ap

Three-Dimensional Simulations of Jets from Keplerian Disks: Self--Regulatory Stability

We present the extension of previous two-dimensional simulations of the time-dependent evolution of non-relativistic outflows from the surface of Keplerian accretion disks, to three dimensions. The accretion disk itself is taken to provide a set of fixed boundary conditions for the problem. The 3-D results are consistent with the theory of steady, axisymmetric, centrifugally driven disk winds up to the Alfv\'en surface of the outflow. Beyond the Alfv\'en surface however, the jet in 3-D becomes unstable to non-axisymmetric, Kelvin-Helmholtz instabilities. We show that jets maintain their long-term stability through a self-limiting process wherein the average Alfv\'enic Mach number within the jet is maintained to order unity. This is accomplished in at least two ways. First, poloidal magnetic field is concentrated along the central axis of the jet forming a ``backbone'' in which the Alfv\'en speed is sufficiently high to reduce the average jet Alfv\'enic Mach number to unity. Second, the onset of higher order Kelvin-Helmholtz ``flute'' modes (m \ge 2) reduce the efficiency with which the jet material is accelerated, and transfer kinetic energy of the outflow into the stretched, poloidal field lines of the distorted jet. This too has the effect of increasing the Alfv\'en speed, and thus reducing the Alfv\'enic Mach number. The jet is able to survive the onset of the more destructive m=1 mode in this way. Our simulations also show that jets can acquire corkscrew, or wobbling types of geometries in this relatively stable end-state, depending on the nature of the perturbations upon them. Finally, we suggest that jets go into alternating periods of low and high activity as the disappearance of unstable modes in the sub-Alfv\'enic regime enables another cycle of acceleration to super-Alfv\'enic speeds.Comment: 57 pages, 22 figures, submitted to Ap

Stringy effects in black hole decay

We compute the low energy decay rates of near-extremal three(four) charge black holes in five(four) dimensional N=4 string theory to sub-leading order in the large charge approximation. This involves studying stringy corrections to scattering amplitudes of a scalar field off a black hole. We adapt and use recently developed techniques to compute such amplitudes as near-horizon quantities. We then compare this with the corresponding calculation in the microscopic configuration carrying the same charges as the black hole. We find perfect agreement between the microscopic and macroscopic calculations; in the cases we study, the zero energy limit of the scattering cross section is equal to four times the Wald entropy of the black hole.Comment: 32 page

Hybrid Equation/Agent-Based Model of Ischemia-Induced Hyperemia and Pressure Ulcer Formation Predicts Greater Propensity to Ulcerate in Subjects with Spinal Cord Injury

Pressure ulcers are costly and life-threatening complications for people with spinal cord injury (SCI). People with SCI also exhibit differential blood flow properties in non-ulcerated skin. We hypothesized that a computer simulation of the pressure ulcer formation process, informed by data regarding skin blood flow and reactive hyperemia in response to pressure, could provide insights into the pathogenesis and effective treatment of post-SCI pressure ulcers. Agent-Based Models (ABM) are useful in settings such as pressure ulcers, in which spatial realism is important. Ordinary Differential Equation-based (ODE) models are useful when modeling physiological phenomena such as reactive hyperemia. Accordingly, we constructed a hybrid model that combines ODEs related to blood flow along with an ABM of skin injury, inflammation, and ulcer formation. The relationship between pressure and the course of ulcer formation, as well as several other important characteristic patterns of pressure ulcer formation, was demonstrated in this model. The ODE portion of this model was calibrated to data related to blood flow following experimental pressure responses in non-injured human subjects or to data from people with SCI. This model predicted a higher propensity to form ulcers in response to pressure in people with SCI vs. non-injured control subjects, and thus may serve as novel diagnostic platform for post-SCI ulcer formation. © 2013 Solovyev et al