Procollagen C-proteinase-2 (pCP-2, mTld) is derived from the longest splicing variant of the gene encoding bone morphogenetic protein 1 (BMP-1). The variants have identical amino terminal signal peptides, prodomains and astacin-like protease domains. However, they differ in the length of their carboxy terminal part, which in pCP-2 has the composition CUB1, CUB2, EGF-like1, CUB3, EGF-like2, CUB4, CUB5, and C-tail. In the shorter form, pCP-1 (i.e., BMP-1), the sequence ends after the CUB3-domain. Using a combination of mutagenesis and structural approaches, we have investigated the structure and function of subfragments of pCP-2. The full-length latent recombinant enzyme and its N-terminally truncated form lacking the prodomain were tested for their enzymic activity. The intact protein showed only partial processing of procollagen type I, whereas the truncated form expressed enzymic activity indistinguishable from its native counterpart purified from chick embryo tendons. These results clearly demonstrated that the prodomain is required for the latency of the enzyme but not for its correct folding. Limited proteolysis of the recombinant protein with alpha-chymotrypsin produced four discrete fragments revealing the location of cleavage sites between the repetitive CUB/EGF domains. The results provide evidence that the CUB sequences form independently folded modules that are stabilized by two pairs of internal disulfide bridges. The modules are linked to each other by more flexible, hinge-like peptides. Solid-phase binding assays with isolated CUB domains and immobilized procollagen type I demonstrated that the first three but not the last two CUB domains specifically bound to the substrate. To define putative sites for CUB-CUB or CUB-substrate interactions, we generated molecular models for pCP-2 CUB domains. The models were obtained using as a template the structure of CUB domain in zona pellucida adhesion protein PSP-I/PSP-II from porcine sperm. The predicted conformations for homology models were, subsequently, confirmed by circular dichroism spectroscopy of polypeptide domains isolated following limited proteolysis with alpha-chymotrypsin.

We introduce DeepNash, an autonomous agent that plays the imperfect information game Stratego at a human expert level. Stratego is one of the few iconic board games that artificial intelligence (AI) has not yet mastered. It is a game characterized by a twin challenge: It requires long-term strategic thinking as in chess, but it also requires dealing with imperfect information as in poker. The technique underpinning DeepNash uses a game-theoretic, model-free deep reinforcement learning method, without search, that learns to master Stratego through self-play from scratch. DeepNash beat existing state-of-the-art AI methods in Stratego and achieved a year-to-date (2022) and all-time top-three ranking on the Gravon games platform, competing with human expert players.

Purpose When wearable and implantable devices first arose in the 1970s, they were rigid and clashed dramatically with our soft, pliable skin and organs. The past two decades have witnessed a major upheaval in these devices. Traditional electronics are six orders of magnitude stiffer than soft tissue. As a result, when rigid electronics are integrated with the human body, severe challenges in both mechanical and geometrical form mismatch occur. This mismatch creates an uneven contact at the interface of soft-tissue, leading to noisy and unreliable data gathering of the body’s vital signs. This paper aims to predict the role that discreet, seamless medical devices will play in personalized health care by discussing novel solutions for alleviating this interface mismatch and exploring the challenges in developing and commercializing such devices. Design methodology/approach Since the form factors of biology cannot be changed to match those of rigid devices, conformable devices that mimic the shape and mechanical properties of soft body tissue must be designed and fabricated. These conformable devices play the role of imperceptible medical interfaces. Such interfaces can help scientists and medical practitioners to gain further insights into the body by providing an accurate and reliable instrument that can conform closely to the target areas of interest for continuous, long-term monitoring of the human body, while improving user experience. Findings The authors have highlighted current attempts of mechanically adaptive devices for health care, and the authors forecast key aspects for the future of these conformable biomedical devices and the ways in which these devices will revolutionize how health care is administered or obtained. Originality/value The authors conclude this paper with the perspective on the challenges of implementing this technology for practical use, including device packaging, environmental life cycle, data privacy, industry partnership and collaboration.

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