Expression, Tissue Distribution and Function of miR-21 in Esophageal Squamous Cell Carcinoma

Objective:MiR-21 is an oncomir expressed by malignant cells and/or tumor microenvironment components. In this study we focused on understanding the effects of stromal miR-21 on esophageal malignant cells.Design:MiR-21 expression was evaluated in formalin-fixed paraffin-embedded samples from patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR. MiR-21 tissue distribution was visualized with in situ hybridization. A co-culture system of normal fibroblasts and esophageal cancer cells was used to determine the effects of fibroblasts on miR-21 expression levels, and on SCC cell migration and invasion.Results:MiR-21 was overexpressed in SCCs, when compared to the adjacent non-tumor tissues (P = 0.0007), and was mainly localized in the cytoplasm of stromal cells adjacent to malignant cells. Accordingly, miR-21 expression was increased in tumors with high versus low stromal content (P = 0.04). When co-cultured with normal fibroblasts, miR-21 expression was elevated in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when co-cultured with adenocarcinoma cells (OE-33 and FLO-1). MiR-21 was detected in conditioned media of cancer cell lines, illustrating the release of this miRNA into the environment. Co-culturing with normal fibroblasts or addition of fibroblast conditioned media caused a significant increase in cell migration and invasion potency of KYSE-30 cells (P<0.0001). In addition, co-culturing cancer cells with fibroblasts and expression of miR-21 induced the expression of the cancer associated fibroblast (CAF) marker S100A4.Conclusions:MiR-21 expression is mostly confined to the SCC stroma and its release from fibroblasts influences the migration and invasion capacity of SCC cells. Moreover, miR-21 may be an important factor in "activating" fibroblasts to CAFs. These findings provide new insights into the role of CAFs and the extracellular matrix in tumor microenvironment formation and in tumor cell maintenance, and suggest miR-21 may contribute to cellular crosstalk in the tumor microenvironment. © 2013 Nouraee et al

MicroRNA history : discovery, recent applications and next frontiers

We thank the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for English language editing of the manuscript.Since 1993, when the first small non-coding RNA was identified, our knowledge about microRNAs has grown exponentially. In this review, we focus on the main progress in this field and discuss the most important findings under a historical perspective. In addition, we examine microRNAs as markers ofdisease diagnosis and prognosis, and as new therapeutic targets.M.I.A is supported by a PhD fellowship (SFRH/BD/47031/2008) from FCT (Fundação para a Ciência e Tecnologia) from Portugal. G.A.C. is supported as a Fellow at The University of Texas MD Anderson Research Trust, as a Fellow of The University of Texas System Regents Research Scholar, and by the CLL Global Research Foundation. Work in Dr. Calin’s laboratory was supported in part by NIH, by DoD, by 2009 Seena Magowitz – Pancreatic Cancer Action Network – AACR Pilot Grant and by the U.S./European Alliance for the Therapy of CLL

Exact N=2 Supergravity Solutions With Polarized Branes

We construct several classes of exact supersymmetric supergravity solutions describing D4 branes polarized into NS5 branes and F-strings polarized into D2 branes. These setups belong to the same universality class as the perturbative solutions used by Polchinski and Strassler to describe the string dual of N=1* theories. The D4-NS5 setup can be interpreted as a string dual to a confining 4+1 dimensional theory with 8 supercharges, whose properties we discuss. By T-duality, our solutions give Type IIB supersymmetric backgrounds with polarized branes.Comment: 22 pages. v2 - references added, details clarifie

Monte Carlo Approaches to Parameterized Poker Squares

The paper summarized a variety of Monte Carlo approaches employed in the top three performing entries to the Parameterized Poker Squares NSG Challenge competition. In all cases AI players benefited from real-time machine learning and various Monte Carlo game-tree search techniques

Lead isotope analyses of gold–silver ores from Roşia Montană (Romania): a first step of a metal provenance study of Roman mining activity in Alburnus Maior (Roman Dacia)

The Roşia Montană ore deposit (Apuseni Mountains, Romania) is Europe’s largest Au–Ag deposit. It also corresponds to the Roman Alburnus Maior mining site, known by historians and archaeologists due to the discovery of dozens of Roman wooden wax tablets during the underground works carried out during the 18th and 19th centuries.The present geochemical research is based on a detailed archaeological and geological study of the Roman mines at Roşia Montană, making use of archaeologically and geologically documented ore samples. The geochemical analyses allowed us to establish an accurate database for the ores exploited during Roman times at Roşia Montană (and probably before). This approach represents a contribution towards improving the accuracy of metal provenance studies of gold–silver ores during antiquity in Romania, and also at an European level, because the studied ore samples represent remnants of the original ores used by the Romans for the production of precious metals.Twenty-nine ore samples and one litharge roll have been selected, prepared and analysed by MC-ICP-MS (high-resolution measurements). A specific Roşia Montană Pb isotope signature of gold–silver ores extracted by the Roman miners was obtained. This signature is distinct when compared with other ore deposits from the Apuseni Mountains, as well as within a broader region (Maramureş ore district).A litharge roll discovered in a Roman inclined adit situated close to the surface, which attests the presence of metallurgical workshops, has also been analysed. The different lead isotope values of the litharge roll and the Roşia Montană gold–silver ores suggest that other ore sources from the South Apuseni Mountains or from elsewhere were also employed by the gold metallurgy developed at Roşia Montană during Roman times

Lagrangian Variational Framework for Boundary Value Problems

A boundary value problem is commonly associated with constraints imposed on a system at its boundary. We advance here an alternative point of view treating the system as interacting "boundary" and "interior" subsystems. This view is implemented through a Lagrangian framework that allows to account for (i) a variety of forces including dissipative acting at the boundary; (ii) a multitude of features of interactions between the boundary and the interior fields when the boundary fields may differ from the boundary limit of the interior fields; (iii) detailed pictures of the energy distribution and its flow; (iv) linear and nonlinear effects. We provide a number of elucidating examples of the structured boundary and its interactions with the system interior. We also show that the proposed approach covers the well known boundary value problems.Comment: 41 pages, 3 figure

Al based alloys containing amorphous and nanostructured phases

Nanostructured or partially amorphous Al-based alloys are attractive candidates for advanced high-strength lightweight materials. The strength of such materials is often 2 - 3 times higher than the strength of commercial crystalline alloys. Further property improvements are achievable by designing multi-phase composite materials with optimized length scale and intrinsic properties of the constituent phases. Such alloys can be prepared by quenching from the melt or by powder metallurgy using mechanical attrition techniques. This paper focuses on mechanically attrited Al-based powders containing amorphous or nano-crystalline phases, Al-based MMCs containing metallic glass reinforcement and on their consolidation into bulk specimens. Selected examples of mechanical deformation behavior are presented, revealing that the properties can be tuned within a wide range of strength and ductility as a function of size and volume fraction of the different phases

Survey of the genus Bursaphelenchus Fuchs, 1937 (Nematoda: Aphelenchoididae) in Romania

An overview of the occurrence of species of the genus Bursaphelenchus in Romania is presented. The data is based on recent surveys conducted for the first time throughout the country, to monitor and evaluate the potential entry of the pine wood nematode, Bursaphelenchus xylophilus. Wood samples were collected from declining trees, woodprocessing companies and imported wood packaging material. Of the 895 wood samples examined, 11 contained Bursaphelenchus specimens. Morphological and molecular analyses were carried out to characterize the species detected. With respect to the possible presence of B. xylophilus, all samples were negative, confirming the absence of this quarantine pest in Romania. Nevertheless, five Bursaphelenchus species were found: B. hofmanni, B. poligraphi, B. vallesianus, B. willibaldi, and one putative new species belonging to the sexdentati group, classified here as Bursaphelenchus sp. NR512. These results constitute the first report of the genus Bursaphelenchus in Romania