Bromodomain-containing proteins are key epigenetic regulators of gene transcription and readers of the histone code. However, the therapeutic benefits of modulating this target class are largely unexplored due to the lack of suitable chemical probes. This article describes the generation of lead molecules for the BET bromodomains through screening a fragment set chosen using structural insights and computational approaches. Analysis of 40 BRD2/fragment X-ray complexes highlights both shared and disparate interaction features that may be exploited for affinity and selectivity. Six representative crystal structures are then exemplified in detail. Two of the fragments are completely new bromodomain chemotypes, and three have never before been crystallized in a bromodomain, so our results significantly extend the limited public knowledge-base of crystallographic small molecule/bromodomain interactions. Certain fragments (including paracetamol) bind in a consistent mode to different bromodomains such as CREBBP, suggesting their potential to act as generic bromodomain templates. An important implication is that the bromodomains are not only a phylogenetic family but also a system in which chemical and structural knowledge of one bromodomain gives insights transferrable to others.

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Abstract:Veterans, through their active service, frequently receive training in highly skilled technical areas. However, they may lack a theoretical background in underlying engineering principles. They also need additional support with the transition from a highly structured military environment to an environment with more ambiguous time constraints and different sorts of responsibilities. Moreover they are facing challenges which are specific for their student population. Therefore, enabling multiple mechanisms which would support them and provide them necessary guidance are especially important at universities with large veteran populations such as at Old Dominion University in Norfolk, Virginia. Hence, there is a need for programs which build on the specialized training that veterans received and aid in their academic journey. This paper will introduce three pilot programs for advancing engineering education for military veterans focusing on forming a support base for veterans to assist them in overcoming traditional educational barriers.

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Brian Novoselich is an active duty Army Lieutenant Colonel currently serving as an Assistant Professor in the Department of Civil and Mechanical Engineering at the United States Military Academy (West Point). He earned his Ph.D. in Engineering Education at Virginia Tech in 2016. He holds Master's and Bachelor's degrees in mechanical engineering from The University of Texas at Austin and West Point respectively. His research interests include capstone design teaching and assessment, undergraduate engineering student leadership development, and social network analysis. He is also a licensed professional engineer in the Commonwealth of Virginia. Mrs. Janice Leshay Hall, Virginia Polytechnic Institute and State University I am a doctoral student in Engineering Education at Virginia Tech. I am a proud military brat with a biomedical engineering background. My own experiences navigating the engineering curriculum as a first-generation college student as well as being a colleague to other military-connected students through my membership as a 2010 Tillman Miltary Scholar have sparked my passion for research on pathways to and through engineering with emphasis on the formation of engineering identity especially among veteran students.

Katherine Smith received B.S. degrees in applied mathematics and mechanical engineering from Old Dominion University and an M.S. in Applied and Computational Mathematics from Old Dominion University. Ms. Smith is currently a lecturer in the Department of Mathematics and Statistics at Old Dominion University and is pursuing a PhD in Modeling and Simulation. Her research interests include serious games for STEM education, scientific visualization, and augmented and virtual reality. Prior to teaching at ODU, she worked as an Aerospace Engineer at NASA Langley Research Center.