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Conversational devices such as Amazon Echo and Google Home represent more than a way to tap into the behavioral surplus of consumers. They provide an opportunity to address societal problems by examining data streams produced by these devices. In this paper, we describe usage patterns and problems related to the use of Amazon Echo devices at home by one specific demographic: the elderly. We rely on a pilot project to collect usage data over multiple months based on deployment of these devices in the homes of eight elderly individuals who either live alone or with a spouse. The paper describes methods used to ensure confidentiality, data collection and analysis procedures, and our findings. We find that the use of conversational devices remains restricted to single commands instead of conversations, making yourself understood remains a problem, sustained use remains a challenge, and the interaction rarely goes beyond simple commands. We interpret the results, and point to the potential for such devices in the lives of the elderly, specifically for health-related problems. The paper also describes lessons learned for capture and analysis of data from such conversational devices. 

Abstract Current efforts in the proteolysis targeting chimera (PROTAC) field mostly focus on choosing an appropriate E3 ligase for the target protein, improving the binding affinities towards the target protein and the E3 ligase, and optimizing the PROTAC linker. However, due to the large molecular weights of PROTACs, their cellular uptake remains an issue. Through comparing how different warhead chemistry, reversible noncovalent (RNC), reversible covalent (RC), and irreversible covalent (IRC) binders, affects the degradation of Bruton’s Tyrosine Kinase (BTK), we serendipitously discover that cyano-acrylamide-based reversible covalent chemistry can significantly enhance the intracellular accumulation and target engagement of PROTACs and develop RC-1 as a reversible covalent BTK PROTAC with a high target occupancy as its corresponding kinase inhibitor and effectiveness as a dual functional inhibitor and degrader, a different mechanism-of-action for PROTACs. Importantly, this reversible covalent strategy is generalizable to improve other PROTACs, opening a path to enhance PROTAC efficacy. 

We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.