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作者：Jones, Charles H.; Beitelshees, Marie; Hill, Andrew; Griffiths, Dean; Murphy, Matthew; Kapadia, Ketan; Dolsten, Mikael; True, Jane M.
作者单位：Pfizer; Pfizer USA
摘要：Platform technologies are fundamentally reshaping the pharmaceutical industry, offering unprecedented potential for innovation across multiple therapeutic areas. However, traditional valuation models, focused on single-asset metrics, struggle to capture the full spectrum of value these technologies create. This paper presents a comprehensive framework for evaluating the innovative sources of value creation enabled by platform technologies throughout the drug development lifecycle. Through a sy...
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作者：Vermeij, Geerat J.; Grosberg, Richard K.; Roopnarine, Peter D.
作者单位：University of California System; University of California Davis; University of California System; University of California Davis; California Academy of Sciences
摘要：It has long been recognized that energy is the currency of evolution, but contrasting conceptions of the relationship between energy and adaptation have yielded different interpretations. In the equal fitness paradigm (EFP), fitness (defined as the energetic equivalent of surviving offspring per generation) is held to be a constant within and between species in a steady- state, zero- sum closed system of constant energy availability. The fossil record, however, indicates that living space and ...
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作者：Hui, Chenggong; de Vries, Reinier; Kopec, Wojciech; de Groot, Bert L.
作者单位：University of London; Queen Mary University London
摘要：Potassium (K+) channels are widely distributed in many types of organisms. They combine high efficiency (similar to 100 pS) and K+/Na+ selectivity by a conserved selectivity filter (SF). Molecular Dynamics (MD) simulations can provide detailed, atomistic mechanisms of this sophisticated ion permeation. However, currently there are clear inconsistencies between computational predictions and experimental results. First, the ion occupancy of the SF in simulations is lower than expected (similar t...
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作者：Luk, Tsz-Yat; Yim, Lok-Yan; Zhou, Runhong; Mo, Yufei; Huang, Huarong; Zhao, Meiqing; Dai, Jie; Lau, Thomas Tsz-Kan; Huang, Xiner; Lui, Grace Chung-Yan; Yuen, Kwok-Yung; Chan, Jasper Fuk-Woo; Cheng, Alfred Sze-Lok; Chen, Zhiwei; Chu, Hin
作者单位：University of Hong Kong; University of Hong Kong; Yunnan Center for Disease Control & Prevention; Chinese University of Hong Kong; University of Hong Kong; University of Hong Kong; Chinese University of Hong Kong; University of Hong Kong; The University of Hong Kong Shenzhen Institute of Research & Innovation
摘要：A major challenge for HIV type 1 (HIV-1) cure is the presence of viral latent reservoirs. The Shock & Kill strategy involves the combined use of latency reversal agents (LRA) and antiretroviral treatment (ART) to reactivate HIV-1 latent reservoirs, followed by elimination of infected cells. However, current LRAs are insufficient in fully reactivating the latent reservoirs. Therefore, investigation on novel HIV-1 latency regulators will be crucial to the success of HIV-1 cure research. Here, we...
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作者：Eggertsen, Taylor G.; Travers, Joshua G.; Hardy, Elizabeth J.; Wolf, Matthew J.; Mckinsey, Timothy A.; Saucerman, Jeffrey J.
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作者：Wu, Xin-Rui; Yang, Liu; Wu, Bang-Sheng; Cheng, Wei; Yu, Jin-Tai
作者单位：Fudan University; Fudan University; Fudan University; Fudan University; Fudan University
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作者：Kaul, Sunil; Cole, Nelson B.; Bandola-Simon, Joanna; Lu, Ying; Tondini, Elena; Walseng, Even; Roche, Paul A.
作者单位：National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); AstraZeneca
摘要：MHC class II glycoproteins (MHC-II) bind peptides derived from exogenous antigens and dendritic cells (DCs) present these peptide MHC-II (pMHC-II) complexes to antigen-specific CD4 T cells during immune responses. The turnover of surface pMHC-II on antigen-presenting cells (APCs) is controlled by ubiquitin-mediated degradation of pMHC-II by the E3 ubiquitin ligase March-I. To study March-I protein expression, we have generated a mouse in which a V5 epitope-tag was knocked-in to the endogenous ...
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作者：Caputo, Rosanna; Schoonderwoerd, Robin A.; Ramkisoensing, Ashna; Janse, Jan A. M.; van Diepen, Hester C.; Raison, Sylvie; Pevet, Paul; Sage-Ciocca, Dominique; Deboer, Tom; Challet, Etienne; Meijer, Johanna H.
作者单位：Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Centre National de la Recherche Scientifique (CNRS); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Centre National de la Recherche Scientifique (CNRS); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg
摘要：Our biological clock, located in the suprachiasmatic nucleus (SCN), controls behavioral activity rhythms by producing circadian rhythms in SCN electrical activity. Behavioral studies in humans suggest that the clock is sensitive not only to light but also to physical activity. Here, we examined the effect of physical activity on the brain's clock in the diurnal rodent, Arvicanthis ansorgei. We found that the electrical activity of SCN neurons in vitro is high during the day and low during the ...
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作者：Sjoeberg, Mattias; Olsen, Erik; Mapar, Mokhtar; Parkkila, Petteri; Niederkofler, Simon; Mohammadi, Sara; Jing, Yujia; Emilsson, Gustav; Lindfors, Lennart; Agnarsson, Bjorn; Hook, Fredrik
作者单位：Chalmers University of Technology; AstraZeneca
摘要：The most efficient lipid nanoparticles (LNPs) for gene therapeutics rely on specific lipids that protect the oligonucleotide cargo and aid cellular uptake and subsequent endosomal escape. Yet, the efficacy of current state-of-the-art LNP formulations remains low, a few percent at best. A deeper understanding of how LNP cargo, lipid composition, stoichiometry, size, structure, and pH-induced conformational changes influence their efficiency is therefore necessary for improved design. Given the ...
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作者：Zvi, Uri; Candido, Denis R.; Weiss, Adam M.; Jones, Aidan R.; Chen, Lingjie; Golovina, Iryna; Yu, Xiaofei; Wang, Stella; Talapin, Dmitri V.; Flatte, Michael E.; Esser, Aaron P.; Maurer, Peter C.
作者单位：University of Chicago; University of Iowa; University of Chicago; University of Chicago; University of Pennsylvania; United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Argonne National Laboratory; Eindhoven University of Technology
摘要：Fluorescent diamond nanocrystals can host spin qubit sensors capable of probing the physical properties of biological systems with nanoscale spatial resolution. Sub-100 nm diamond nanosensors can readily be delivered into intact cells and even living organisms. However, applications beyond current proof-of-principle experiments require a substantial increase in sensitivity, which is limited by surface induced charge instability and electron-spin dephasing. In this work, we utilize engineered c...
