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            AI-based frameworks for protein engineering use self-supervised learning (SSL) to obtain representations for downstream biological predictions. The most common training objective for these methods is wildtype accuracy: given a sequence or structure where a wildtype residue has been masked, predict the missing amino acid. Wildtype accuracy, however, does not align with the primary goal of protein engineering, which is to suggest a {\em mutation} rather than to identify what already appears in nature. Here we present Evolutionary Ranking (EvoRank), a training objective that incorporates evolutionary information derived from multiple sequence alignments (MSAs) to learn more diverse protein representations. EvoRank corresponds to ranking amino-acid likelihoods in the probability distribution induced by an MSA. This objective forces models to learn the underlying evolutionary dynamics of a protein. Across a variety of phenotypes and datasets, we demonstrate that EvoRank leads to dramatic improvements in zero-shot performance and can compete with models fine-tuned on experimental data. This is particularly important in protein engineering, where it is expensive to obtain data for fine-tuning.more » « less
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            Stabilizing proteins is a foundational step in protein engineering. However, the evolutionary pressure of all extant proteins makes identifying the scarce number of mutations that will improve thermodynamic stability challenging. Deep learning has recently emerged as a powerful tool for identifying promising mutations. Existing approaches, however, are computationally expensive, as the number of model inferences scales with the number of mutations queried. Our main contribution is a simple, parallel decoding algorithm. Our Mutate Everything is capable of predicting the effect of all single and double mutations in one forward pass. It is even versatile enough to predict higher-order mutations with minimal computational overhead. We build Mutate Everything on top of ESM2 and AlphaFold, neither of which were trained to predict thermodynamic stability. We trained on the Mega-Scale cDNA proteolysis dataset and achieved state-of-the-art performance on single and higher-order mutations on S669, ProTherm, and ProteinGym datasets.more » « less
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            This conference paper provides an update on the Early Research Scholars Program (ERSP) background, structure, and implementation at the University of Illinois Chicago (UIC), developed at the University of California San Diego and funded by the National Science Foundation Improving Undergraduate STEM Education program. The program aims to support retention of students from marginalized backgrounds in the fields of computing as well as electrical and computer engineering. This paper provides program updates, including data from the 2022-2023 academic year and preliminary results from a reflection study that began in spring 2020. The reflection study examined the impact of the ERSP on a student's computing and engineering identity development based on student reflection responses. In this paper, we also discuss student demographics, retention rates, and changes made to the program's curriculum at UIC. The evaluation results from the last three years of the program are also shared, which show how students are impacted by the program, as well as areas for improvement. Preliminary results show that the program has positively impacted students' computing or engineering identity development for at least three identity dimensions: recognition, competence, and community.more » « less
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            Abstract Despite the f0(980) hadron having been discovered half a century ago, the question about its quark content has not been settled: it might be an ordinary quark-antiquark ($${{\rm{q}}}\overline{{{\rm{q}}}}$$ ) meson, a tetraquark ($${{\rm{q}}}\overline{{{\rm{q}}}}{{\rm{q}}}\overline{{{\rm{q}}}}$$ ) exotic state, a kaon-antikaon ($${{\rm{K}}}\overline{{{\rm{K}}}}$$ ) molecule, or a quark-antiquark-gluon ($${{\rm{q}}}\overline{{{\rm{q}}}}{{\rm{g}}}$$ ) hybrid. This paper reports strong evidence that the f0(980) state is an ordinary$${{\rm{q}}}\overline{{{\rm{q}}}}$$ meson, inferred from the scaling of elliptic anisotropies (v2) with the number of constituent quarks (nq), as empirically established using conventional hadrons in relativistic heavy ion collisions. The f0(980) state is reconstructed via its dominant decay channel f0(980) →π+π−, in proton-lead collisions recorded by the CMS experiment at the LHC, and itsv2is measured as a function of transverse momentum (pT). It is found that thenq= 2 ($${{\rm{q}}}\overline{{{\rm{q}}}}$$ state) hypothesis is favored overnq= 4 ($${{\rm{q}}}\overline{{{\rm{q}}}}{{\rm{q}}}\overline{{{\rm{q}}}}$$ or$${{\rm{K}}}\overline{{{\rm{K}}}}$$ states) by 7.7, 6.3, or 3.1 standard deviations in thepT< 10, 8, or 6 GeV/cranges, respectively, and overnq= 3 ($${{\rm{q}}}\overline{{{\rm{q}}}}{{\rm{g}}}$$ hybrid state) by 3.5 standard deviations in thepT< 8 GeV/crange. This result represents the first determination of the quark content of the f0(980) state, made possible by using a novel approach, and paves the way for similar studies of other exotic hadron candidates.more » « lessFree, publicly-accessible full text available December 1, 2026
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            Abstract Sea‐level rise and associated flood hazards pose severe risks to the millions of people globally living in coastal zones. Models representing coastal adaptation and impacts are important tools to inform the design of strategies to manage these risks. Representing the often deep uncertainties influencing these risks poses nontrivial challenges. A common uncertainty characterization approach is to use a few benchmark cases to represent the range and relative probabilities of the set of possible outcomes. This has been done in coastal adaptation studies, for example, by using low, moderate, and high percentiles of an input of interest, like sea‐level changes. A key consideration is how this simplified characterization of uncertainty influences the distributions of estimated coastal impacts. Here, we show that using only a few benchmark percentiles to represent uncertainty in future sea‐level change can lead to overconfident projections and underestimate high‐end risks as compared to using full ensembles for sea‐level change and socioeconomic parametric uncertainties. When uncertainty in future sea level is characterized by low, moderate, and high percentiles of global mean sea‐level rise, estimates of high‐end (95th percentile) damages are underestimated by between 18% (SSP1‐2.6) and 46% (SSP5‐8.5). Additionally, using the 5th and 95th percentiles of sea‐level scenarios underestimates the 5%–95% width of the distribution of adaptation costs by a factor ranging from about two to four, depending on SSP‐RCP pathway. The resulting underestimation of the uncertainty range in adaptation costs can bias adaptation and mitigation decision‐making.more » « less
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            Free, publicly-accessible full text available September 1, 2026
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            Free, publicly-accessible full text available September 1, 2026
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            Free, publicly-accessible full text available September 1, 2026
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