The SWAP EUV Imaging Telescope Part I: Instrument Overview and Pre-Flight Testing

The Sun Watcher with Active Pixels and Image Processing (SWAP) is an EUV solar telescope on board ESA's Project for Onboard Autonomy 2 (PROBA2) mission launched on 2 November 2009. SWAP has a spectral bandpass centered on 17.4 nm and provides images of the low solar corona over a 54x54 arcmin field-of-view with 3.2 arcsec pixels and an imaging cadence of about two minutes. SWAP is designed to monitor all space-weather-relevant events and features in the low solar corona. Given the limited resources of the PROBA2 microsatellite, the SWAP telescope is designed with various innovative technologies, including an off-axis optical design and a CMOS-APS detector. This article provides reference documentation for users of the SWAP image data.Comment: 26 pages, 9 figures, 1 movi

Histone Acetylation-Mediated Regulation of the Hippo Pathway

The Hippo pathway is a signaling cascade recently found to play a key role in tumorigenesis therefore understanding the mechanisms that regulate it should open new opportunities for cancer treatment. Available data indicate that this pathway is controlled by signals from cell-cell junctions however the potential role of nuclear regulation has not yet been described. Here we set out to verify this possibility and define putative mechanism(s) by which it might occur. By using a luciferase reporter of the Hippo pathway, we measured the effects of different nuclear targeting drugs and found that chromatin-modifying agents, and to a lesser extent certain DNA damaging drugs, strongly induced activity of the reporter. This effect was not mediated by upstream core components (i.e. Mst, Lats) of the Hippo pathway, but through enhanced levels of the Hippo transducer TAZ. Investigation of the underlying mechanism led to the finding that cancer cell exposure to histone deacetylase inhibitors induced secretion of growth factors and cytokines, which in turn activate Akt and inhibit the GSK3 beta associated protein degradation complex in drug-affected as well as in their neighboring cells. Consequently, expression of EMT genes, cell migration and resistance to therapy were induced. These processes were suppressed by using pyrvinium, a recently described small molecule activator of the GSK 3 beta associated degradation complex. Overall, these findings shed light on a previously unrecognized phenomenon by which certain anti-cancer agents may paradoxically promote tumor progression by facilitating stabilization of the Hippo transducer TAZ and inducing cancer cell migration and resistance to therapy. Pharmacological targeting of the GSK3 beta associated degradation complex may thus represent a unique approach to treat cancer. © 2013 Basu et al

Capital Structure and Dividend Irrelevance with Asymmetric Information

The Modigliani and Miller propositions on the irrelevancy of capital structure and dividends are shown to be valid in a large class of models with asymmetric information. The main assumption is that managerial compensation is chosen optimally. This differs from most recent papers on this topic, which impose by fiat a suboptimal contract. Even when imperfections internal to the firm preclude optimal investment, there is a separation between incentives and financing. We also show that making prices reflect idiosyncratic information more accurately does not make investors better off, thus negating the motivation of many of the signalling models

The Impact of Boreal Forest Fire on Climate Warming

We report measurements and analysis of a boreal forest fire, integrating the effects of greenhouse gases, aerosols, black carbon deposition on snow and sea ice, and postfire changes in surface albedo. The net effect of all agents was to increase radiative forcing during the first year (34 ± 31 Watts per square meter of burned area), but to decrease radiative forcing when averaged over an 80-year fire cycle (–2.3 ± 2.2 Watts per square meter) because multidecadal increases in surface albedo had a larger impact than fire-emitted greenhouse gases. This result implies that future increases in boreal fire may not accelerate climate warming

Compressive properties and column efficiency of metals reinforced on the surface with bonded filaments

Compressive properties and weight saving of metals reinforced on surface with resin bonded fiber

In Vivo RNAi Screening Identifies Regulators of Actin Dynamics as Key Determinants of Lymphoma Progression

April 1, 2010Mouse models have markedly improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic experimentation. Here, we report the adaptation of loss-of-function screening to mouse models of cancer. Specifically, we have been able to introduce a library of shRNAs into individual mice using transplantable Eμ-myc lymphoma cells. This approach has allowed us to screen nearly 1,000 genetic alterations in the context of a single tumor-bearing mouse. These experiments have identified a central role for regulators of actin dynamics and cell motility in lymphoma cell homeostasis in vivo. Validation experiments confirmed that these proteins represent bona fide lymphoma drug targets. Additionally, suppression of two of these targets, Rac2 and twinfilin, potentiated the action of the front-line chemotherapeutic vincristine, suggesting a critical relationship between cell motility and tumor relapse in hematopoietic malignancies.National Institutes of Health (U.S.) (RO1 CA128803-01)Massachusetts Institute of Technology. Dept. of Biology (Training Grant)Massachusetts Institute of Technology. Undergraduate Research Opportunities ProgramNational Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant 1-U54-CA112967

Comparative Oncogenomic Analysis of Copy Number Alterations in Human and Zebrafish Tumors Enables Cancer Driver Discovery

The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs) are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs). Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. We established a list of orthologous genes between human and zebrafish, which includes approximately two-thirds of human protein-coding genes. For the subset of these genes found in human MPNST CNAs, only one quarter of their orthologues were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers.Kathy and Curt Marble Cancer Research FundArthur C. MerrillNational Institutes of Health (U.S.) (Grant CA106416)National Institutes of Health (U.S.) (Grant ROI RR020833)National Institutes of Health (U.S.) (Grant 1F32GM095213-01

The landscape of somatic copy-number alteration across human cancers

available in PMC 2010 August 18.A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-κΒ pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P50CA90578)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109038))National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, R01CA109467)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA085859)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, P01CA 098101)National Institutes of Health (U.S.) (Dana-Farber/Harvard Cancer Center and Pacific Northwest Prostate Cancer SPOREs, K08CA122833

Influence of Biopsy Technique on Molecular Genetic Tumor Characterization in Non-Small Cell Lung Cancer—The Prospective, Randomized, Single-Blinded, Multicenter PROFILER Study Protocol

The detection of molecular alterations is crucial for the individualized treatment of advanced non-small cell lung cancer (NSCLC). Missing targetable alterations may have a major impact on patient’s progression free and overall survival. Although laboratory testing for molecular alterations has continued to improve; little is known about how biopsy technique affects the detection rate of different mutations. In the retrospective study detection rate of epidermal growth factor (EGFR) mutations in tissue extracted by bronchoscopic cryobiopsy (CB was significantly higher compared to other standard biopsy techniques. This prospective, randomized, multicenter, single blinded study evaluates the accuracy of molecular genetic characterization of NSCLC for different cell sampling techniques. Key inclusion criteria are suspected lung cancer or the suspected relapse of known NSCLC that is bronchoscopically visible. Patients will be randomized, either to have a CB or a bronchoscopic forceps biopsy (FB). If indicated, a transbronchial needle aspiration (TBNA) of suspect lymph nodes will be performed. Blood liquid biopsy will be taken before tissue biopsy. The primary endpoint is the detection rate of molecular genetic alterations in NSCLC, using CB and FB. Secondary endpoints are differences in the combined detection of molecular genetic alterations between FB and CB, TBNA and liquid biopsy. This trial plans to recruit 540 patients, with 178 evaluable patients per study cohort. A histopathological and molecular genetic evaluation will be performed by the affiliated pathology departments of the national network for genomic medicine in lung cancer (nNGM), Germany. We will compare the diagnostic value of solid tumor tissue, lymph node cells and liquid biopsy for the molecular genetic characterization of NSCLC. This reflects a real world clinical setting, with potential direct impact on both treatment and survival

Perfil Bioquímico Sanguíneo Hepático del Cocodrilo de Tumbes (Crocodylus acutus) Criado en Cautiverio

The liver blood chemical profile of the American crocodile (Crocodylus acutus) raised in captivity in the northern region of Peru was determined. Sixty crocodiles were sampled from a population of 255 animals belonging to the Zoocriadero del Centro de Acuicultura La Tuna Carranza, part of the National Fisheries Development Fund (FONDEPES) located in the region of Tumbes, Peru. The animals were classified as young (n=24), subadults (n=27) and adults (n=9). A blood sample (6 ml) was taken from each animal by puncturing the post-occipital venous sinus while animals were under physical restraint. Serum was separated by centrifugation and concentration of each enzyme was measured by spectrophotometry. Variables studied were alanine aminotransferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, indirect bilirubin, total protein and albumin. Statistical difference (p<0.05) was found between age groups in ALT, FA, direct bilirubin, and total protein. All values with the exception of albumin showed high biological differences with those reported by the International Species Information System.Se determinó el perfil bioquímico hepático del cocodrilo de Tumbes (Crocodylus acutus) criado en cautiverio en el norte del Perú. Se trabajó con 60 cocodrilos de una población de 255 animales del Zoocriadero del Centro de Acuicultura La Tuna Carranza, del Fondo Nacional de Desarrollo Pesquero (FONDEPES), ubicado en la región de Tumbes, Perú. De estos, 24 eran juveniles, 27 subadultos y 9 adultos. Se extrajo 6 ml de sangre entera sin anticoagulante por punción del seno venoso post-occipital manipulando al animal mediante contención física. Se separó el suero mediante centrifugación y las enzimas se analizaron mediante espectrofotometría. Las variables en estudio fueron alanina aminotransferasa (ALT), aspartato amino transferasa (AST), fosfatasa alcalina (FA), bilirrubina total, bilirrubina directa, bilirrubina indirecta, proteínas totales y albúmina. Se encontró diferencia estadística (p<0.05) en relación a los grupos etarios con respecto a la ALT, FA, bilirrubina directa y proteínas totales. Todos los valores con excepción de la albúmina tuvieron marcadas diferencias biológicas con respecto a valores publicados por el International Species Information System