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We propose a novel approach to soundly combining linear types with multi-shot effect handlers. Linear type systems statically ensure that resources such as file handles and communication channels are used exactly once. Effect handlers provide a rich modular programming abstraction for implementing features ranging from exceptions to concurrency to backtracking. Whereas conventional linear type systems bake in the assumption that continuations are invoked exactly once, effect handlers allow continuations to be discarded (e.g. for exceptions) or invoked more than once (e.g. for backtracking). This mismatch leads to soundness bugs in existing systems such as the programming language Links, which combines linearity (for session types) with effect handlers. We introduce control-flow linearity as a means to ensure that continuations are used in accordance with the linearity of any resources they capture, ruling out such soundness bugs. We formalise the notion of control-flow linearity in a System F-style core calculus Feff∘, equipped with linear types, an effect type system, and effect handlers. We define a linearity-aware semantics in order to formally prove that Feff∘ preserves the integrity of linear values in the sense that no linear value is discarded or duplicated. In order to show that control-flow linearity can be made practical, we adapt Links based on the design of Feff∘, in doing so fixing a long-standing soundness bug. Finally, to better expose the potential of control-flow linearity, we define an ML-style core calculus Qeff∘, based on qualified types, which requires no programmer provided annotations, and instead relies entirely on type inference to infer control-flow linearity. Both linearity and effects are captured by qualified types. Qeff∘ overcomes a number of practical limitations of Feff∘, supporting abstraction over linearity, linearity dependencies between type variables, and a much more fine-grained notion of control-flow linearity. 

Traditional systems for indoor pressure sensing and human activity recognition (HAR) rely on costly, high-resolution mats and computationally intensive neural network-based (NN-based) models that are prone to noise. In contrast, we design a cost-effective and noise-resilient pressure mat system for HAR, leveraging Velostat for intelligent pressure sensing and a novel hyperdimensional computing (HDC) classifier that is lightweight and highly noise resilient. To measure the performance of our system, we collected two datasets, capturing the static and continuous nature of human movements. Our HDC-based classification algorithm shows an accuracy of 93.19%, improving the accuracy by 9.47% over state-of-the-art CNNs, along with an 85% reduction in energy consumption. We propose a new HDC noise-resilient algorithm and analyze the performance of our proposed method in the presence of three different kinds of noise, including memory and communication, input, and sensor noise. Our system is more resilient across all three noise types. Specifically, in the presence of Gaussian noise, we achieve an accuracy of 92.15% (97.51% for static data), representing a 13.19% (8.77%) improvement compared to state-of-the-art CNNs. 

Abstract Marsh accretion models predict the resiliency of coastal wetlands and their ability to store carbon in the face of accelerating sea level rise. Most existing marsh accretion models are derived from two parent models: the Marsh Equilibrium Model, which formalizes the biophysical relationships between sea level rise, dominant macrophyte growth, and elevation change; and the Cohort Theory Model, which formalizes how carbon mass pools belowground contribute to soil volume expansion over time. While there are several existing marsh accretion models, the application of these models by a broader base of researchers and practitioners is hindered because of (a) limited descriptions of how empirically derived ecological mechanism informed the development of these models, (b) limitations in the ability to apply models to geographies with variable tidal regimes, and (c) a lack of open‐source code to apply models. Here, we provide for the first time an explicit description of a mathematical version of the Cohort Theory Model and a numerical version of a combined model: the Cohort Marsh Equilibrium Model (CMEM) with an accompanying open‐sourceRpackage,rCMEM. We show that, through this “depth‐aware” model, we can capture how tidal variation impacts broad patterns of marsh accretion and carbon sequestration across the United States. The application of this model will likely be imperative in predicting the fate and state of coastal wetlands and the ecosystem services they provide in an era of rapid environmental change. 

Octafluorocyclopentene (OFCP) has found utility as a polyelectrophile in substitution cascades that form complex macrocyclic compounds. The Harran group synthesis of macrocyclic polypeptides depends on OFCP as a linker, combining with four different nucleophilic units of a polypeptide. We report a computational investigation of the origins of OFCP reactivity and a rationale for controlled mono-, di-, tri-, and tetrasubstitution of fluoride ions by heteroatomic nucleophiles. The roles of inductive, negative hyperconjugative, and resonance electron-donation by fluoride substituents are explored for the reaction of OFCP, less-fluorinated analogues, and common electrophilic alkenes with several different nucleophiles. 

Abstract Heterotrophic activity, primarily driven by sulfate-reducing prokaryotes, has traditionally been linked to nitrogen fixation in the root zone of coastal marine plants, leaving the role of chemolithoautotrophy in this process unexplored. Here, we show that sulfur oxidation coupled to nitrogen fixation is a previously overlooked process providing nitrogen to coastal marine macrophytes. In this study, we recovered 239 metagenome-assembled genomes from a salt marsh dominated by the foundation plantSpartina alterniflora, including diazotrophic sulfate-reducing and sulfur-oxidizing bacteria. Abundant sulfur-oxidizing bacteria encode and highly express genes for carbon fixation (RuBisCO), nitrogen fixation (nifHDK) and sulfur oxidation (oxidative-dsrAB), especially in roots stressed by sulfidic and reduced sediment conditions. Stressed roots exhibited the highest rates of nitrogen fixation and expression level of sulfur oxidation and sulfate reduction genes. Close relatives of marine symbionts from theCandidatusThiodiazotropha genus contributed ~30% and ~20% of all sulfur-oxidizingdsrAand nitrogen-fixingnifKtranscripts in stressed roots, respectively. Based on these findings, we propose that the symbiosis betweenS. alternifloraand sulfur-oxidizing bacteria is key to ecosystem functioning of coastal salt marshes. 

Octafluorocyclopentene (OFCP) engages linear, unprotected peptides in polysubstitution cascades that generate complex fluorinated polycycles. The reactions occur in a single flask at 0–25 °C and require no catalysts or heavy metals. OFCP can directly polycyclize linear sequences using native functionality, or fluorospiroheterocyclic intermediates can be intercepted with exogenous nucleophiles. The latter tactic generates molecular hybrids composed of peptides, sugars, lipids, and heterocyclic components. The platform can create stereoisomers of both single- and double-looped macrocycles. Calculations indicate that the latter can mimic diverse protein surface loops. Subsets of the molecules have low energy conformers that shield the polar surface area through intramolecular hydrogen bonding. A significant fraction of OFCP-derived macrocycles tested show moderate to high passive permeability in parallel artificial membrane permeability assays. 

Type constructors in functional programming languages are total: a Haskell programmer can equally readily construct lists of any element type. In practice, however, not all applications of type constructors are equally sensible: collections may only make sense for orderable elements, or embedded DSLs might only make sense for serializable return types. Jones et al. proposed a theory of partial type constructors, which guarantees that type applications are sensible, and extends higher-order abstractions to apply equally well to partial and total type constructors. This paper evaluates the practicality of partial type constructors, in terms of both language design and implementation. We extend GHC, the most widely used Haskell compiler, with support for partial type constructors, and test our extension on the compiler itself and its libraries. We show that introducing partial type constructors has a minimal impact on most code, but raises important questions in language and library design. 

ABSTRACT Heavy metals (HMs) are known to modify bacterial communities both in the laboratory and in situ . Consequently, soils in HM-contaminated sites such as the U.S. Environmental Protection Agency (EPA) Superfund sites are predicted to have altered ecosystem functioning, with potential ramifications for the health of organisms, including humans, that live nearby. Further, several studies have shown that heavy metal-resistant (HMR) bacteria often also display antimicrobial resistance (AMR), and therefore HM-contaminated soils could potentially act as reservoirs that could disseminate AMR genes into human-associated pathogenic bacteria. To explore this possibility, topsoil samples were collected from six public locations in the zip code 35207 (the home of the North Birmingham 35th Avenue Superfund Site) and in six public areas in the neighboring zip code, 35214. 35027 soils had significantly elevated levels of the HMs As, Mn, Pb, and Zn, and sequencing of the V4 region of the bacterial 16S rRNA gene revealed that elevated HM concentrations correlated with reduced microbial diversity and altered community structure. While there was no difference between zip codes in the proportion of total culturable HMR bacteria, bacterial isolates with HMR almost always also exhibited AMR. Metagenomes inferred using PICRUSt2 also predicted significantly higher mean relative frequencies in 35207 for several AMR genes related to both specific and broad-spectrum AMR phenotypes. Together, these results support the hypothesis that chronic HM pollution alters the soil bacterial community structure in ecologically meaningful ways and may also select for bacteria with increased potential to contribute to AMR in human disease. IMPORTANCE Heavy metals cross-select for antimicrobial resistance in laboratory experiments, but few studies have documented this effect in polluted soils. Moreover, despite decades of awareness of heavy metal contamination at the EPA Superfund site in North Birmingham, Alabama, this is the first analysis of the impact of this pollution on the soil microbiome. Specifically, this work advances the understanding of the relationship between heavy metals, microbial diversity, and patterns of antibiotic resistance in North Birmingham soils. Our results suggest that polluted soils carry a risk of increased exposure to antibiotic-resistant infections in addition to the direct health consequences of heavy metals. Our work provides important information relevant to both political and scientific efforts to advance environmental justice for the communities that call Superfund neighborhoods home. 

Abstract Many microbial photoautotrophs depend on heterotrophic bacteria for accomplishing essential functions. Environmental changes, however, could alter or eliminate such interactions. We investigated the effects of changing pCO2 on gene transcription in co-cultures of 3 strains of picocyanobacteria (Synechococcus strains CC9311 and WH8102 and Prochlorococcus strain MIT9312) paired with the ‘helper’ bacterium Alteromonas macleodii EZ55. Co-culture with cyanobacteria resulted in a much higher number of up- and down-regulated genes in EZ55 than pCO2 by itself. Pathway analysis revealed significantly different transcription of genes involved in carbohydrate metabolism, stress response, and chemotaxis, with different patterns of up- or down-regulation in co-culture with different cyanobacterial strains. Gene transcription patterns of organic and inorganic nutrient transporter and catabolism genes in EZ55 suggested resources available in the culture media were altered under elevated (800 ppm) pCO2 conditions. Altogether, changing transcription patterns were consistent with the possibility that the composition of cyanobacterial excretions changed under the two pCO2 regimes, causing extensive ecophysiological changes in both members of the co-cultures. Additionally, significant downregulation of oxidative stress genes in MIT9312/EZ55 cocultures at 800 ppm pCO2 were consistent with a link between the predicted reduced availability of photorespiratory byproducts (i.e., glycolate/2PG) under this condition and observed reductions in internal oxidative stress loads for EZ55, providing a possible explanation for the previously observed lack of “help” provided by EZ55 to MIT9312 under elevated pCO2. If similar broad alterations in microbial ecophysiology occur in the ocean as atmospheric pCO2 increases, they could lead to substantially altered ecosystem functioning and community composition.