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作者：Tauzin, Tibor
作者单位：University of Vienna; University of Vienna
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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：Sun, Y. Qiang; Hassanzadeh, Pedram; Zand, Mohsen; Chattopadhyay, Ashesh; Weare, Jonathan; Abbot, Dorian S.
作者单位：University of Chicago; University of Chicago; University of Chicago; University of California System; University of California Santa Cruz; New York University
摘要：Predicting gray swan weather extremes, which are possible but so rare that they are absent from the training dataset, is a major concern for AI weather models and long-term climate emulators. An important open question is whether AI models can extrapolate from weaker weather events present in the training set to stronger, unseen weather extremes. To test this, we train independent versions of the AI weather model FourCastNet on the 1979-2015 ERA5 dataset with all data, or with Category 3-5 tro...
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作者：Williams, Christopher C.; Chuck, Jonathan; Munoz-Tello, Paola; Kojetin, Douglas J.
作者单位：State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; State University System of Florida; University of Florida; Vanderbilt University; Vanderbilt University; Vanderbilt University; Vanderbilt University
摘要：The prolyl isomerase Pin1 catalyzes the cis-trans isomerization of proline peptide bonds, a noncovalent posttranslational modification that influences cellular and molecular processes, including protein-protein interactions. Pin1 is a two-domain enzyme containing a WW domain that recognizes phosphorylated serine/threonine-proline (pS/pT-P) canonical motifs and an enzymatic PPIase domain that catalyzes proline cis-trans isomerization of pS/pT-P motifs. Here, we show that Pin1 uses a tethering m...
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作者：Kozachkov, Leo; Slotine, Jean-Jacques; Krotov, Dmitry
作者单位：Massachusetts Institute of Technology (MIT); International Business Machines (IBM); IBM USA; Massachusetts Institute of Technology (MIT)
摘要：Astrocytes, the most abundant type of glial cell, play a fundamental role in memory. Despite most hippocampal synapses being contacted by an astrocyte, there are no current theories that explain how neurons, synapses, and astrocytes might collectively contribute to memory function. We demonstrate that fundamental aspects of astrocyte morphology and physiology naturally lead to a dynamic, high-capacity associative memory system. The neuron-astrocyte networks generated by our framework are close...
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作者：Pang, Rich; Baker, Christa A.; Murthy, Mala; Pillow, Jonathan
作者单位：Princeton University; Princeton University; North Carolina State University
摘要：Social communication between animals is often mediated by sequences of acoustic signals, sometimes spanning long timescales. How auditory neural circuits respond to extended input sequences to guide behavior is not understood. We address this problem using Drosophila acoustic communication, a behavior involving the male's production of and female's response to long, highly variable courtship songs. Here we ask whether female neural and behavioral responses to song are better described by a lin...
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作者：Zhang, Yuyuan; Zuo, Anning; Ba, Yuhao; Liu, Shutong; Chen, Jingqi; Yang, Shuaixi; Weng, Siyuan; Chen, Yukang; Xu, Hui; Luo, Peng; Cheng, Quan; Tang, Bufu; Liu, Benyu; Zhang, Chuhan; Yang, Jingkuan; Han, Xinwei; Liu, Zaoqu
作者单位：Zhengzhou University; Zhengzhou University; Zhengzhou University; Zhengzhou University; Southern Medical University - China; Central South University; Fudan University; Zhengzhou University; Zhengzhou University; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College
摘要：Liver metastasis remains the predominant cause of mortality in patients with colorectal cancer (CRC). Nevertheless, the mechanisms underlying the initiation of colorectal cancer liver metastasis remain poorly elucidated. During the metastatic process of CRC cells from the primary site to the liver, we performed time- resolved analyses and identified a subset of tumor cells spatially located in the primary tumor and temporally distributed in the early stages of liver metastasis. These cells wer...
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作者：Fan, Chengcheng; Keeffe, Jennifer R.; Malecek, Kathryn E.; Cohen, Alexander A.; West Jr, Anthony P.; Baharani, Viren A.; Rorick, Annie, V; Gao, Han; Gnanapragasam, Priyanthi N. P.; Rho, Semi; Alvarez, Jaasiel; Segovia, Luisa N.; Hatziioannou, Theodora; Bieniasz, Paul D.; Bjorkman, Pamela J.
作者单位：California Institute of Technology; Rockefeller University; Rockefeller University; Rockefeller University; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle
摘要：Broad immune responses are needed to mitigate viral evolution and escape. To induce antibodies against conserved receptor-binding domain (RBD) regions of SARS-like betacoronavirus (sarbecovirus) spike proteins that recognize SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matche...
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作者：Gozashti, Landen; Nakamoto, Anne; Russell, Shelbi; Corbett-Detig, Russell
作者单位：Harvard University; Harvard University; Howard Hughes Medical Institute; Harvard University; University of California System; University of California Santa Cruz; University of California System; University of California Santa Cruz
摘要：Since the discovery of spliceosomal introns in eukaryotic genomes, the proximate molecular and evolutionary processes that generate new introns have remained a critical mystery. Specialized transposable elements (TEs), introners, are thought to be one of the major drivers of intron gain in diverse eukaryotes. However, the molecular mechanism(s) and evolutionary processes driving introner propagation within and between lineages remain elusive. Here, we analyze 8,716 genomes, revealing 1,093 int...
