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EvoAI enables extreme compression and reconstruction of the protein sequence space
No full textDesigning proteins with improved functions requires a deep understanding of how sequence and function are related, a vast space that is hard to explore. The ability to efficiently compress this space by identifying functionally important features is extremely valuable. Here, we first establish a method called EvoScan to comprehensively segment and scan the high-fitness sequence space to obtain anchor points that capture its essential features, especially in high dimensions. Our approach is compatible with any biomolecular function that can be coupled to a transcriptional output. We then develop deep learning and large language models to accurately reconstruct the space from these anchors, allowing computational prediction of novel, highly fit sequences without prior homology-derived or structural information. We apply this hybrid experimental-computational method, which we call EvoAI, to a repressor protein and find that only 82 anchors are sufficient to compress the high-fitness sequence space with a compression ratio of 1048. The extreme compressibility of the space informs both applied biomolecular design and understanding of natural evolution.Chemistry and Chemical BiologyAuthor's Origina
History of Clinicopathological Conferences and the Evolution of Medicine: the Case Records for Massachusetts General Hospital
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The Adaptation of Anecdotal Standup Comedy to Dramatic Writing for Vets First
No full textIn anecdotal standup comedy, a comedian’s personal story is often conveyed
through humor. Humor makes uneasy topics digestible and plating it with personal
experience invites the audience to connect with the standup comic, usually the writer, in a
personal way. This connection disarms the audience, exposing them to new thoughts and
different perspectives likening today’s comedian to yesterday’s philosopher. In this
manner, humor can reveal truth and provoke critical thinking. Mark Zuckerberg’s
testimony that the White House repeatedly pressured Facebook to censor humor and
satire is a testament to humor’s power. Vets First adapts anecdotal standup comedy
writing to dramatic writing. In turn, the characters often engage in humoristic dialogue
and action that expose their feelings, thoughts, and opinions derived from their lived
experience. With a focus on veterans, social issues such as health, suicide, feelings,
emotions, dating, relationships, and readjustment, are discussed in a funny and inviting
way. There are approximately 7000 post 9/11 combat deaths, yet over 30,000 suicides.
Through purpose without activism, Vets First aims to reach veterans through its
character’s example while circumventing the algorithms of censorship
Pinel to Bucke: A Transnational Exploration of Psychiatric Reform and Christian Ideology
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Establishing Nanopore Long-Read Sequencing as a Cost-Effective Approach for Axolotl Regeneration Research
No full textRNA sequencing (RNA-seq) has become a cornerstone methodology to decipher the regulation of intricate molecular pathways. The development of RNA-seq technology in the last decade has exponentially increased the scope in which researchers collect data on gene expression, yet the high cost of executing modern sequencing methodologies can be a prohibitive barrier. Oxford Nanopore Technology (ONT) has rapidly emerged as a transformative force in the field of RNA-seq by enabling low-cost long-read sequencing.
The goal of this study was to investigate whether nanopore long-read sequencing can serve as a cost-effective and viable alternative to conventional RNA-seq technologies for investigating transcriptomic expression patterns in axolotl salamanders (Ambystoma mexicanum). The first aim of this study was to optimize the MinION long-read RNA-seq protocol for the axolotl model from RNA isolation to differential gene expression (DGE) analysis. The second aim was to utilize the optimized protocol within various experimental research contexts in axolotl regeneration research. The third aim was to benchmark the more robust PromethION sequencer utilizing the optimized workflow from aim one, to assess its utility for experimental applications relative to the MinION.
Our study presents a novel and optimized workflow in which nanopore sequencing accurately captures transcriptomic expression patterns in the axolotl, demonstrating its potential as a viable, cost-effective alternative to traditional RNA-seq platforms in regeneration research. This study marks the first successful published execution of nanopore RNA-seq in the axolotl salamander
From Products to Capabilities: Constructing a Genotypic Product Space
No full textEconomic development is a path-dependent process in which countries accumulate capabilities that allow them to move into more complex products and industries. Inspired by a theory of capabilities that explains which countries produce which products, these diversification dynamics have been studied in great detail in the literature on economic complexity analysis. However, so far, these capabilities have remained latent and inference is drawn from product spaces that reflect economic outcomes: which products are often exported in tandem. Borrowing a metaphor from biology, such analysis remains phenotypic in nature. In this paper we develop a methodology that allows economic complexity analysis to use capabilities directly. To do so, we interpret the capability requirements of industries as a genetic code that shows how capabilities map onto products. We apply this framework to construct a genotypic product space and to infer countries’ capability bases. These constructs can be used to determine which capabilities a country would still need to acquire if it were to diversify into a given industry. We show that this information is not just valuable in predicting future diversification paths and to advance our understanding of economic development, but also to design more concrete policy interventions that go beyond targeting products by identifying the underlying capability requirements.Version of Recor
Episodic warm climates on early Mars primed by crustal hydration
No full textGeological records indicate that the surface of ancient Mars harbored substantial volumes of liquid water, a resource gradually diminished by processes such as the chemical alteration of crustal materials by hydration and atmospheric escape. However, how a relatively warm climate existed on early Mars to support liquid water under a fainter young Sun is debated. Greenhouse gases like H2 in a CO2-rich atmosphere could have contributed to warming through collision-induced absorption, but whether sufficient H2 was available to sustain warming remains unclear. Here we use a combined climate and photochemical model to simulate how atmospheric chemistry on early Mars responded to water-rock reactions and climate variations, as constrained by existing observations. We find that H2 outgassing crustal hydration and oxidation, supplemented by transient volcanic activity, could have generated sufficient H2 fluxes to transiently foster warm, humid climates. We estimate that Mars experienced episodic warm periods of an integrated duration of ~40 million years, with each event lasting ≥105 years, consistent with the formation timescale of valley networks. Declining atmospheric CO2 via surface oxidant sinks or variations in the planet’s axial tilt could have led to abrupt shifts in the planet's redox state and transition to a CO-dominated atmosphere and cold climate.Author's Origina
Spatial multiomic landscape of the human placenta at molecular resolution
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Lost Souls: Outsider Myths in the Works of Olga Tokarczuk
No full textThe works of Olga Tokarczuk have garnered significant attention since she won the Nobel Prize in Literature in 2018. Her narrative style engages with complex historical and contemporary issues, often confronting Polish cultural myths in the process. These myths have historically ostracized or oppressed whole groups of Poles, namely women, ethnic minorities, and religious minorities, creating a demographic category referred to in this thesis as outsiders. With the collapse of the Soviet Union leading to the political and cultural sovereignty of the Republic of Poland, these myths re-emerged. This paper posits that Tokarczuk challenges three outsider myths consistently throughout her body of literature: the Polish Mother, Catholic Hegemony, and the Great Past. She argues that these myths are neither historically faithful nor contemporarily tenable. Instead, she puts forth her own myth of Inclusion to supplant Polish outsider myths