Accelerating Innovation Through Analogy Mining

The availability of large idea repositories (e.g., the U.S. patent database) could significantly accelerate innovation and discovery by providing people with inspiration from solutions to analogous problems. However, finding useful analogies in these large, messy, real-world repositories remains a persistent challenge for either human or automated methods. Previous approaches include costly hand-created databases that have high relational structure (e.g., predicate calculus representations) but are very sparse. Simpler machine-learning/information-retrieval similarity metrics can scale to large, natural-language datasets, but struggle to account for structural similarity, which is central to analogy. In this paper we explore the viability and value of learning simpler structural representations, specifically, "problem schemas", which specify the purpose of a product and the mechanisms by which it achieves that purpose. Our approach combines crowdsourcing and recurrent neural networks to extract purpose and mechanism vector representations from product descriptions. We demonstrate that these learned vectors allow us to find analogies with higher precision and recall than traditional information-retrieval methods. In an ideation experiment, analogies retrieved by our models significantly increased people's likelihood of generating creative ideas compared to analogies retrieved by traditional methods. Our results suggest a promising approach to enabling computational analogy at scale is to learn and leverage weaker structural representations.Comment: KDD 201

Comprehensive Health Care Reform and Biomedical Innovation

Considers ways to control the costs of development, adoption, and diffusion of new technologies as part of comprehensive healthcare reform. Discusses how cost control interventions might affect coverage, physician payments, and care processes

Mechanism-Based Redesign of GAP to Activate Oncogenic Ras

Ras GTPases play a crucial role in cell signaling pathways. Mutations of the Ras gene occur in about one third of cancerous cell lines and are often associated with detrimental clinical prognosis. Hot spot residues Gly12, Gly13, and Gln61 cover 97% of oncogenic mutations, which impair the enzymatic activity in Ras. Using QM/MM free energy calculations, we present a two-step mechanism for the GTP hydrolysis catalyzed by the wild-type Ras.GAP complex. We found that the deprotonation of the catalytic water takes place via the Gln61 as a transient Brønsted base. We also determined the reaction profiles for key oncogenic Ras mutants G12D and G12C using QM/MM minimizations, matching the experimentally observed loss of catalytic activity, thereby validating our reaction mechanism. Using the optimized reaction paths, we devised a fast and accurate procedure to design GAP mutants that activate G12D Ras. We replaced GAP residues near the active site and determined the activation barrier for 190 single mutants. We furthermore built a machine learning for ultrafast screening, by fast prediction of the barrier heights, tested both on the single and double mutations. This work demonstrates that fast and accurate screening can be accomplished via QM/MM reaction path optimizations to design protein sequences with increased catalytic activity. Several GAP mutations are predicted to re-enable catalysis in oncogenic G12D, offering a promising avenue to overcome aberrant Ras-driven signal transduction by activating enzymatic activity instead of inhibition. The outlined computational screening protocol is readily applicable for designing ligands and cofactors analogously

Experience with the Open Source based implementation for ATLAS Conditions Data Management System

Conditions Data in high energy physics experiments is frequently seen as every data needed for reconstruction besides the event data itself. This includes all sorts of slowly evolving data like detector alignment, calibration and robustness, and data from detector control system. Also, every Conditions Data Object is associated with a time interval of validity and a version. Besides that, quite often is useful to tag collections of Conditions Data Objects altogether. These issues have already been investigated and a data model has been proposed and used for different implementations based in commercial DBMSs, both at CERN and for the BaBar experiment. The special case of the ATLAS complex trigger that requires online access to calibration and alignment data poses new challenges that have to be met using a flexible and customizable solution more in the line of Open Source components. Motivated by the ATLAS challenges we have developed an alternative implementation, based in an Open Source RDBMS. Several issues were investigated land will be described in this paper: -The best way to map the conditions data model into the relational database concept considering what are foreseen as the most frequent queries. -The clustering model best suited to address the scalability problem. -Extensive tests were performed and will be described. The very promising results from these tests are attracting the attention from the HEP community and driving further developments.Comment: 8 pages, 4 figures, 3 tables, conferenc

Clinical leadership in action

The nature, scope and potential for clinical leadership are explored by focusing on four cases. These were cross-boundary service redesign attempts for dementia and sexual health in London and Greater Manchester. Each case contained multiple organisations, including GPs and primary care trusts, acute hospital trusts, mental health trusts, local authorities and independent sector provider