DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer

Background: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA). Results: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.016 and < 0.001, respectively) and in 15 out of 22 TCGA studies. Methylation loss correlated with immunohistochemically staining for TREX2 (p < 0.0001) in laryngeal tumors and improved overall survival of laryngeal cancer patients (p = 0.045). Chromatin immunoprecipitation, demethylation experiments, and reporter gene assays revealed that the region of methylation loss can function as a CCAAT/enhancer binding protein alpha (CEBPA)-responsive enhancer element regulating TREX2 expression. Conclusions: The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Altered TREX2 protein levels in tumors may affect drug-induced DNA damage repair and provide new tailored therapies

The coming decade of digital brain research - A vision for neuroscience at the intersection of technology and computing

<p>Brain research has in recent years indisputably entered a new epoch, driven by substantial methodological advances and digitally enabled data integration and modeling at multiple scales – from molecules to the whole system. Major advances are emerging at the intersection of neuroscience with technology and computing. This new science of the brain integrates high-quality basic research, systematic data integration across multiple scales, a new culture of large-scale collaboration and translation into applications. A systematic approach, as pioneered in Europe's Human Brain Project (HBP), will be essential in meeting the pressing medical and technological challenges of the coming decade. The aims of this paper are</p><ul><li>To develop a concept for the coming decade of digital brain research</li><li>To discuss it with the research community at large, with the aim of identifying points of convergence and common goals</li><li>To provide a scientific framework for current and future development of EBRAINS</li><li>To inform and engage stakeholders, funding organizations and research institutions regarding future digital brain research</li><li>To identify and address key ethical and societal issues</li></ul><p>While we do not claim that there is a 'one size fits all' approach to addressing these aspects, we are convinced that discussions around the theme of digital brain research will help drive progress in the broader field of neuroscience.</p><p><strong>As the final version 5 has now been published, comments on this manuscript are now closed. We thank everyone who made a valuable contribution to this paper.</strong></p><p>This manuscript has been developed in a participatory process. The work has been initiated by the Science and Infrastructure Board of the Human Brain Project (HBP), and the entire research community was invited to contribute to shaping the vision by submitting comments. </p><p>All submitted comments were considered and discussed. The final decision on whether edits or additions was made to each version of the manuscript based on an individual comment was made by the Science and Infrastructure Board (SIB) of the Human Brain Project (HBP).</p><p><strong>Supporters of the paper</strong>: Pietro Avanzini, Marc Beyer, Maria Del Vecchio, Jitka Annen, Maurizio Mattia, Steven Laureys, Rosanne Edelenbosch, Rafael Yuste, Jean-Pierre Changeux, Linda Richards, Hye Weon Jessica Kim, Chrysoula Samara, Luis Miguel González de la Garza, Nikoleta Petalidou, Vasudha Kulkarni, Cesar David Rincon, Isabella O'Shea, Munira Tamim Electricwala, Bernd Carsten Stahl, Bahar Hazal Yalcinkaya, Meysam Hashemi, Carola Sales Carbonell, Marcel Carrère, Anthony Randal McIntosh, Hiba Sheheitli, Abolfazl Ziaeemehr, Martin Breyton, Giovanna Ramos Queda, Anirudh NIhalani Vattikonda, Gyorgy Buzsaki, George Ogoh, William Knight, Torbjørn V Ness, Michiel van der Vlag, Marcello Massimini, Thomas Nowontny, Alex Upton, Yaseen Jakhura, Ahmet Nihat Simsek, Michael Hopkins, Addolorata Marasco, Shamim Patel, Jakub Fil, Diego Molinari, Susana Bueno, Lia Domide, Cosimo Lupo, Mu-ming Poo, George Paxinos, Huifang Wang.</p&gt

Assessing written work by determining competence to achieve the module-specific learning outcomes.

This chapter describes lasers and other sources of coherent light that operate in a wide wavelength range. First, the general principles for the generation of coherent continuous-wave and pulsed radiation are treated including the interaction of radiation with matter, the properties of optical resonators and their modes as well as such processes as Q-switching and mode-locking. The general introduction is followed by sections on numerous types of lasers, the emphasis being on todayʼs most important sources of coherent light, in particular on solid-state lasers and several types of gas lasers. An important part of the chapter is devoted to the generation of coherent radiation by nonlinear processes with optical parametric oscillators, difference- and sum-frequency generation, and high-order harmonics. Radiation in the extended ultraviolet (EUV) and x-ray ranges can be generated by free electron lasers (FEL) and advanced x-ray sources. Ultrahigh light intensities up to 1021 W/cm2 open the door to studies of relativistic laser–matter interaction and laser particle acceleration. The chapter closes with a section on laser stabilization