Alzheimer’s Disease (AD) represents a major and rapidly growing burden to the healthcare ecosystem. A growing body of evidence indicates that cognitive, behavioral, sensory, and motor changes may precede clinical manifestations of AD by several years. Existing tests designed to diagnose neurodegenerative diseases, while well-validated, are often less effective in detecting deviations from normal cognitive decline trajectory in the earliest stages of the disease. In the quest for gold standards for AD assessment, there is a growing interest in the identification of readily accessible digital biomarkers, which harness advances in consumer grade mobile and wearable technologies. Topics examined include a review of existing early clinical manifestations of AD and a path to the respective sensor and mobile/wearable device usage to acquire domain-centric data towards objective, high frequency and passive digital phenotyping.

Bulged regions of nucleic acids are important structural motifs whose function has been linked to a number of key nuclear processes. Additionally, bulged intermediates have been implicated in the etiology of several genetic diseases and as targets for viral regulation. Despite these obvious ramifications, few molecules are capable of selective binding to bulged sequences. Prompted by the remarkable affinity of a natural product metabolite, we have designed and prepared a series of readily accessible synthetic agents with selective bulge binding activity. Furthermore, by screening a library of bulge-containing oligodeoxynucelotides, correlations between structure and affinity of the agents can be drawn. In addition to potential applications in molecular biology, the availability of these spirocyclic agents now opens the door for rational drug design.

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A unified synthetic route to 3-hex-en-1,5-diynes, a key building block found in many of the enediyne antitumor agents and designed materials, was developed. The method, which relies on a carbenoid couplingelimination strategy is tolerant of a wide range of functionalities, and was applied to the synthesis of a variety of linear and cyclic enediynes. Reaction parameters can be adjusted to control stereoselectivity of the process, producing linear enediynes from 1:12 to >100:1 E:Z ratio, and in the case of cyclic enediynes, giving the exclusively Z C-9, C-10, or C-11 products. Key features of the process are the ready availability of precursors and the mildness and efficiency of the reaction. Application of the process in the design of materials precursors and preparation of enediyne antitumor agents are presented.