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Enterprise Architecture (EA) Frameworks (EAFs) have attempted to support comprehensive and cohesive modeling and documentation of the enterprise. However, these EAFs were not conceived for today’s rapidly digitalized enterprises and the associated IT complexity. A digitally-centric EAF is needed, freed from the past restrictive EAF paradigms and embracing the new potential in a data-centric world. This paper proposes an alternative EAF that is digital, holistic, and digitally sustainable - the Digital Diamond Framework. D2F is designed for responsive and agile enterprises, for aligning business plans and initiatives with the actual enterprise state, and addressing the needs of EA for digitized structure, order, modeling, and documentation. The feasibility of D2F is demonstrated with a prototype implementation of an EA tool that applies its principles, showing how the framework can be practically realized, while a case study based on ArchiSurance example and an initial performance and scalability characterization provide additional insights as to its viability.
The over-expression and aggregation of α-synuclein (αSyn) are linked to the onset and pathology of Parkinson's disease. Native monomeric αSyn exists in an intrinsically disordered ensemble of interconverting conformations, which has made its therapeutic targeting by small molecules highly challenging. Nonetheless, here we successfully target the monomeric structural ensemble of αSyn and thereby identify novel drug-like small molecules that impact multiple pathogenic processes. Using a surface plasmon resonance high-throughput screen, in which monomeric αSyn is incubated with microchips arrayed with tethered compounds, we identified novel αSyn interacting drug-like compounds. Because these small molecules could impact a variety of αSyn forms present in the ensemble, we tested representative hits for impact on multiple αSyn malfunctions in vitro and in cells including aggregation and perturbation of vesicular dynamics. We thereby identified a compound that inhibits αSyn misfolding and is neuroprotective, multiple compounds that restore phagocytosis impaired by αSyn overexpression, and a compound blocking cellular transmission of αSyn. Our studies demonstrate that drug-like small molecules that interact with native αSyn can impact a variety of its pathological processes. Thus, targeting the intrinsically disordered ensemble of αSyn offers a unique approach to the development of small molecule research tools and therapeutics for Parkinson's disease.
Databases are becoming an ubiquitous and integral part of most software as the data era and the Internet of Everything unfolds. Alternative database types such as NoSQL grow in popularity and allow data to be stored and accessed more simply or in new ways. Thus, software developers, not just database specialists, are more likely to encounter and need to deal with databases. Virtual Reality (VR) technology has grown in popularity, yet its integration in the software development tool chain has been limited. One potential application area for VR technology that has not been sufficiently explored is database-model visualization. This paper describes Virtual Reality Immersion in Data Models (VRiDaM), a generic database-model approach for visualizing, navigating, and conveying database-model information interactively. It describes and explores both native VR and WebVR solution concepts, with prototypes showing the viability of the approach.