The Joint Chiefs of Staff and National Security

My principal attention will be devoted to telling you something about how the Joint Chiefs of Staff actually operate, in practice, within the established system as a whole

Ontology Based Strategies for Supporting Communication within Social Networks

In this paper, ontology based dialogue strategies are presented in connection with the concept of communicative images. Communicative images are graphical objects integrated with a dialogue interface and linked to an associated knowledge database which stores the semantics of the objects depicted. The relevant pieces of information can be linked to the external knowledge distributed in a social network. Exploiting a formal ontology approach facilitates the process of deriving information from relevant texts that can be found in the social network and it simultaneously forms a suitable framework for supporting dialogue communication in natural language. This approach is discussed and illustrated with various examples in this paper

Leveraging ligand affinity and properties: discovery of novel benzamide-type cereblon binders for the design of PROTACs

Immunomodulatory imide drugs (IMiDs) such as thalidomide, pomalidomide, and lenalidomide are the most common cereblon (CRBN) recruiters in proteolysis-targeting chimera (PROTAC) design. However, these CRBN ligands induce the degradation of IMiD neosubstrates and are inherently unstable, degrading hydrolytically under moderate conditions. In this work, we simultaneously optimized physiochemical properties, stability, on-target affinity, and off-target neosubstrate modulation features to develop novel nonphthalimide CRBN binders. These efforts led to the discovery of conformationally locked benzamide-type derivatives that replicate the interactions of the natural CRBN degron, exhibit enhanced chemical stability, and display a favorable selectivity profile in terms of neosubstrate recruitment. The utility of the most potent ligands was demonstrated by their transformation into potent degraders of BRD4 and HDAC6 that outperform previously described reference PROTACs. Together with their significantly decreased neomorphic ligase activity on IKZF1/3 and SALL4, these ligands provide opportunities for the design of highly selective and potent chemically inert proximity-inducing compounds

Dynamic Response of Underground Structures in Sand: Experimental Data

A densely instrumented system of large-scale underground structures consisting of two vertical shafts connected through a cut-and-cover tunnel and two independent shield tunnels was installed in an 8 m-diameter laminar soil box at the E-Defense shake table in Miki, Japan. The system was subjected to step-sine sweeps and scaled ground motion records of the Kobe (1995) earthquake. The underground structures were embedded in Albany Silica Sand with an average relative density of 54%. System instrumentation consisted of over 800 sensors, including strain gauges, accelerometers, displacement transducers, bender elements and pressure sensors. A U.S.-Japanese research collaboration was established to instrument the vertical shaft elements and record seismic soil pressures. Data records are archived at the NHERI DesignSafe Data Depot_and can be used to analyze the structural response, soil-structure interaction and other response parameters of individual subsurface components as well as the entire system. The DOI for the data set is 10.17603/DS21C78