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This extended abstract describes early-stage research on the research, design, and development of two culturally situated STEM curriculum units for Navajo Nation (Diné) middle school students, on the topics of energy and water, blending immersive and hands-on experiences. The first unit addresses the significant issue of energy access on Navajo Nation, where 32% of homes lack electricity. Culturally relevant, virtual experiences provide engaging and motiving narrative-based contexts for learning, aiming to inspire the next generation of Diné engineers and scientists to use their cultural and STEM knowledge to support their communities. We present the design of a prototype exploring options for solar energy on Navajo Nation, using immersive, place- based virtual representations, and feedback from teachers and students who engaged with the prototype. We describe the design of the full energy unit, and upcoming plans for classroom testing during spring, 2025. Initial findings from this classroom testing will be shared in the poster presentation of this extended abstract at the ILRN conference in June 2025. 

ABSTRACT Protein production strategies in bacteria are often limited due to the need for cell lysis and complicated purification schemes. To avoid these challenges, researchers have developed bacterial strains capable of secreting heterologous protein products outside the cell, but secretion titers often remain too low for commercial applicability. Improved understanding of the link between secretion system structure and its secretory abilities can help overcome the barrier to engineering higher secretion titers. Here, we investigated this link with the PrgI protein, the monomer of the secretory channel of the type 3 secretion system (T3SS) ofSalmonella enterica. Despite detailed knowledge of the PrgI needle’s assembly and structure, little is known about how its structure influences its secretory capabilities. To study this, we recently constructed a comprehensive codon mutagenesis library of the PrgI protein utilizing a novel one-pot recombineering approach. We then screened this library for functional T3SS assembly and secretion titer by measuring the secretion of alkaline phosphatase using a high-throughput activity assay. This allowed us to construct a first-of-its-kind secretion fitness landscape to characterize the PrgI needle’s mutability at each position as well as the mutations which lead to enhanced T3SS secretion. We discovered new design rules for building a functional T3SS as well as identified hypersecreting mutants. This work can be used to increase understanding of the T3SS’s assembly and identify further targets for engineering. This work also provides a blueprint for future efforts to engineer other complex protein assemblies through the construction of fitness landscapes.IMPORTANCEProtein secretion offers a simplified alternative method for protein purification from bacterial hosts. However, the current state-of-the-art methods for protein secretion in bacteria are still hindered by low yields relative to traditional protein purification strategies. Engineers are now seeking strategies to enhance protein secretion titers from bacterial hosts, often through genetic manipulations. In this study, we demonstrate that protein engineering strategies focused on altering the secretion apparatus can be a fruitful avenue toward this goal. Specifically, this study focuses on how changes to the PrgI needle protein from the type 3 secretion system fromSalmonella entericacan impact secretion titer. We demonstrate that this complex is amenable to comprehensive mutagenesis studies and that this can yield both PrgI variants with increased secretory capabilities and insight into the normal functioning of the type 3 secretion system. 

Abstract Large language models (LLMs) have demonstrated tremendous capabilities in solving complex tasks, from quantitative reasoning to understanding natural language. However, LLMs sometimes suffer from confabulations (or hallucinations), which can result in them making plausible but incorrect statements^1,2. This hinders the use of current large models in scientific discovery. Here we introduce FunSearch (short for searching in the function space), an evolutionary procedure based on pairing a pretrained LLM with a systematic evaluator. We demonstrate the effectiveness of this approach to surpass the best-known results in important problems, pushing the boundary of existing LLM-based approaches³. Applying FunSearch to a central problem in extremal combinatorics—the cap set problem—we discover new constructions of large cap sets going beyond the best-known ones, both in finite dimensional and asymptotic cases. This shows that it is possible to make discoveries for established open problems using LLMs. We showcase the generality of FunSearch by applying it to an algorithmic problem, online bin packing, finding new heuristics that improve on widely used baselines. In contrast to most computer search approaches, FunSearch searches for programs that describe how to solve a problem, rather than what the solution is. Beyond being an effective and scalable strategy, discovered programs tend to be more interpretable than raw solutions, enabling feedback loops between domain experts and FunSearch, and the deployment of such programs in real-world applications. 

Abstract We define a notion of height for rational points with respect to a vector bundle on a proper algebraic stack with finite diagonal over a global field, which generalizes the usual notion for rational points on projective varieties. We explain how to compute this height for various stacks of interest (for instance: classifying stacks of finite groups, symmetric products of varieties, moduli stacks of abelian varieties, weighted projective spaces). In many cases, our uniform definition reproduces ways already in use for measuring the complexity of rational points, while in others it is something new. Finally, we formulate a conjecture about the number of rational points of bounded height (in our sense) on a stack $$\mathcal {X}$$ , which specializes to the Batyrev–Manin conjecture when $$\mathcal {X}$$ is a scheme and to Malle’s conjecture when $$\mathcal {X}$$ is the classifying stack of a finite group. 

The global rise of antimicrobial resistance has intensified efforts in bioprospecting, with researchers increasingly exploring unique marine environments for novel antimicrobials. In line with this trend, our study focused on bacteria isolated from the unique microbiome of crustose coralline algae (CCA), which has yet to be investigated for antimicrobial discovery. In the present work, bacteria were isolated from a CCA collected from Varadero Reef located in Cartagena Bay, Colombia. After performing antimicrobial assays against antibiotic-resistant human and marine pathogens, three isolates were selected for genome sequencing using the Oxford Nanopore technology. Genome mining of the high-quality assemblies revealed 115 putative biosynthetic gene clusters (BGCs) and identified genes in relevant biosynthetic pathways across the three genomes. Nonetheless, we hypothesize that the biosynthesis of antimicrobial compounds results from the expression of undescribed BGCs. Further analysis revealed the absence of genes pertaining to the synthesis of coral larvae settling molecule tetrabromopyrrole, commonly produced by CCA-associated bacteria. We also discuss how differential representation of gene functions between the three isolates may be attributed to the distinct ecological niches they occupy within the CCA. This study provides valuable resources for future research aimed at the discovery of novel antimicrobials, particularly in the face of the antibiotic-resistance global crisis, and highlights the potential of specialized marine environments like CCA. 

Abstract Let $$X$$ be a quasi-projective variety over a number field, admitting (after passage to $$\mathbb {C}$$) a geometric variation of Hodge structure whose period mapping has zero-dimensional fibers. Then the integral points of $$X$$ are sparse: the number of such points of height $$\leq B$$ grows slower than any positive power of $$B$$. For example, homogeneous integral polynomials in a fixed number of variables and degree, with discriminant divisible only by a fixed set of primes, are sparse when considered up to integral linear substitutions.