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At least 433 records · Page 24

Detecting Arsenic Contamination Using Satellite Imagery and Machine Learning

Arsenic, a potent carcinogen and neurotoxin, affects over 200 million people globally. Current detection methods are laborious, expensive, and unscalable, being difficult to implement in developing regions and during crises such as COVID-19. This study attempts to determine if a relationship exists between soil’s hyperspectral data and arsenic concentration using NASA’s Hyperion satellite. It is the first arsenic study to use satellite-based hyperspectral data and apply a classification approach. Four regression machine learning models are tested to determine this correlation in soil with bare land cover. Raw data are converted to reflectance, problematic atmospheric influences are removed, characteristic wavelengths are selected, and four noise reduction algorithms are tested. The combination of data augmentation, Genetic Algorithm, Second Derivative Transformation, and Random Forest regression (R 2 =0.840 and normalized root mean squared error (re-scaled to [0,1]) = 0.122) shows strong correlation, performing better than past models despite using noisier satellite data (versus lab-processed samples). Three binary classification machine learning models are then applied to identify high-risk shrub-covered regions in ten U.S. states, achieving strong accuracy (=0.693) and F1-score (=0.728). Overall, these results suggest that such a methodology is practical and can provide a sustainable alternative to arsenic contamination detection.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Knowledge graph-aided Bayesian active learning for top- K genetic interaction discovery

In silico methods for predicting the effects of multi-gene perturbations hold great promise for advancing functional genomics, computational drug discovery, and disease modeling. However, the development of these predictive algorithms for mammalian systems has been hampered by limited datasets and high experimental costs. In this study, we present a Bayesian active learning framework designed to discover pairwise host gene knockdowns that effectively inhibit viral proliferation in an in vitro HIV-1 infection model. Our method leverages a biological knowledge graph as side information and employs a computationally efficient batch diversification approach. We evaluated this framework using a dataset of viral load measurements obtained from multi-day dual-gene depletion experiments, encompassing all possible pairwise knockdowns of over 350 host genes associated with HIV infection. We demonstrate that our framework rapidly identifies the most effective gene knockdown pairs for reducing viral load. Furthermore, we show that incorporating side information enhances performance during the early stages of active learning (low data regime), while our batch diversification strategy significantly boosts performance in later stages (high data regime). This framework is general and can be adapted to explore gene interactions in other contexts, such as synthetic lethality prediction and mapping epistatic effects across quantitative trait loci.

Computational biology and bioinformatics↗

Unleashing the capacity of Rhodococcus for converting lignin into lipids

Bioconversion of bioresources/wastes (e.g., lignin, chemical pulping byproducts) represents a promising approach for developing a bioeconomy to help address growing energy and materials demands. Rhodococcus, a promising microbial strain, utilizes numerous carbon sources to produce lipids, which are precursors for synthesizing biodiesel and aviation fuels. However, compared to chemical conversion, bioconversion involves living cells, which is a more complex system that needs further understanding and upgrading. Various wastes amenable to bioconversion are reviewed herein to highlight the potential of Rhodococci for producing lipid-derived bioproducts. In light of the abundant availability of these substrates, Rhodococcus’ metabolic pathways converting them to lipids are analyzed from a “beginning-to-end” view. Based on an in-depth understanding of microbial metabolic routes, genetic modifications of Rhodococcus by employing emerging tools (e.g., multiplex genome editing, biosensors, and genome-scale metabolic models) are presented for promoting the bioconversion. Co-solvent enhanced lignocellulose fractionation (CELF) strategy facilitates the generation of a lignin-derived aromatic stream suitable for the Rhodococcus’ utilization. Novel alkali sterilization (AS) and elimination of thermal sterilization (ETS) approaches can significantly enhance the bioaccessibility of lignin and its derived aromatics in aqueous fermentation media, which promotes lipid titer significantly. In order to achieve value-added utilization of lignin, biodiesel and aviation fuel synthesis from lignin and lipids are further discussed. In conclusion, the possible directions for unleashing the capacity of Rhodococcus through synergistically modifying microbial strains, substrates, and fermentation processes are proposed toward a sustainable biological lignin valorization.

09 BIOMASS FUELS↗

Rewiring the unfolded protein response for plant growth recovery after stress

The unfolded protein response (UPR) is a highly coordinated signaling network that alleviates endoplasmic reticulum (ER) stress, a condition induced by diverse environmental challenges in plants. Over the past two decades, substantial progress has been made in elucidating the genetic and molecular mechanisms of ER stress sensing and signal transduction in plants, largely through studies in the model plant Arabidopsis thaliana . These advances have established the UPR as a central regulator of proteostasis and underscored its broader relevance to plant growth and development and crop productivity under stress conditions. Despite this progress, critical knowledge gaps remain, particularly concerning the downstream biological processes required for growth recovery once ER stress has subsided and how these processes are coordinated by UPR regulators. Recent systems-level and integrative studies have begun to reveal critical roles of UPR signaling in pathways governing growth re-establishment and homeostasis of nutrient allocation and energy metabolism. In this review, we highlight recent findings on the functional roles of the plant UPR in recovery from ER stress, with a focus on mechanisms mediated by UPR regulators and downstream biological pathways that enable the transition from stress mitigation to growth restoration. Although this research area is still emerging, accumulating evidence supports a model in which the UPR functions as a dynamic regulatory network that actively coordinates post-stress physiological recovery to support plant fitness.

ER stress↗

Simulated Biomass Sorghum GHG Reduction Potential is Similar to Maize

Policy support for cellulosic biofuels is contingent on their achieving much greater reductions in life-cycle greenhouse gas emissions than corn starch ethanol. Biomass sorghum has been suggested as a genetically and agronomically tractable feedstock species to augment near-term cellulosic feedstock production. This study used DayCent modeling to investigate biomass sorghum production emissions relative to corn with and without stover utilization at 3,265 across the rainfed United States. Sorghum produced greater average feedstock dry matter (15.6±1.4 vs. 14.8±2.2 Mg ha -1 yr -1 ) and slightly lower estimated ethanol energy yields (10.6±1.0 vs. 11.8±2.9 MJ m -2 yr -1 ) as corn grain with 75% stover collection. The high biomass removals in both the sorghum and corn stover scenarios led to soil organic carbon losses on 90% and 100% of sites, respectively. Average feedstock production emissions intensities were similar between sorghum and corn with 75% stover removal (17.6±2.8 vs. 18.8±3.0 g CO 2 e MJ -1 ), but were notably lower under sorghum for sites in the southwestern study region (13.6±3.0 vs. 22.5±3.1 g CO 2 e MJ -1 ). Futhermore, these results suggest that biomass sorghum produces cellulosic feedstock with similar emissions to corn grain and at current yield levels is unlikely to meet the Renewable Fuel Standard emissions reduction threshold for cellulosic biofuels.

54 ENVIRONMENTAL SCIENCES↗

A modular chromosomally integrated toolkit for ectopic gene expression in Vibrio cholerae

The ability to express genes ectopically in bacteria is essential for diverse academic and industrial applications. Two major considerations when utilizing regulated promoter systems for ectopic gene expression are (1) the ability to titrate gene expression by addition of an exogenous inducer and (2) the leakiness of the promoter element in the absence of the inducer. Here, we describe a modular chromosomally integrated platform for ectopic gene expression in Vibrio cholerae . We compare the broadly used promoter elements P tac and P BAD to versions that have an additional theophylline-responsive riboswitch (P tac -riboswitch and P BAD -riboswitch). These constructs all exhibited unimodal titratable induction of gene expression, however, max induction varied with P tac > P BAD > P BAD -riboswitch > P tac -riboswitch. We also developed a sensitive reporter system to quantify promoter leakiness and show that leakiness for P tac > P tac -riboswitch > P BAD ; while the newly developed P BAD -riboswitch exhibited no detectable leakiness. We demonstrate the utility of the tightly inducible P BAD -riboswitch construct using the dynamic activity of type IV competence pili in V. cholerae as a model system. The modular chromosomally integrated toolkit for ectopic gene expression described here should be valuable for the genetic study of V. cholerae and could be adapted for use in other species.

59 BASIC BIOLOGICAL SCIENCES↗

Thermodynamic stability versus kinetic accessibility: Pareto fronts for programmable self-assembly

A challenge in designing self-assembling building blocks is to ensure the target state is both thermodynamically stable and kinetically accessible. These two objectives are known to be typically in competition, but it is not known how to simultaneously optimize them. We consider this problem through the lens of multi-objective optimization theory: we develop a genetic algorithm to compute the Pareto fronts characterizing the tradeoff between equilibrium probability and folding rate, for a model system of small polymers of colloids with tunable short-ranged interaction energies. We use a coarse-grained model for the particles' dynamics that allows us to efficiently search over parameters, for systems small enough to be enumerated. For most target states there is a tradeoff when the number of types of particles is small, with medium-weak bonds favouring fast folding, and strong bonds favouring high equilibrium probability. Additionally, the tradeoff disappears when the number of particle types reaches a value m *, that is usually much less than the total number of particles. This general approach of computing Pareto fronts allows one to identify the minimum number of design parameters to avoid a thermodynamic–kinetic tradeoff. However, we argue, by contrasting our coarse-grained model's predictions with those of Brownian dynamics simulations, that particles with short-ranged isotropic interactions should generically have a tradeoff, and avoiding it in larger systems will require orientation-dependent interactions.

36 MATERIALS SCIENCE↗

Maximizing long-term biohydrogen production with Clostridium thermocellum for high solids conversion of lignocellulosic biomass

Biological hydrogen production from lignocellulosic biomass sustainably couples organic waste reduction with renewable energy generation. Efficient conversion is challenged by the structural complexity of lignocellulose and resulting recalcitrance to enzymatic degradation. Clostridium thermocellum natively breaks down biomass with highly effective hemi-/cellulases systems (i.e., cellulosomes) and generates hydrogen in anaerobic cultivation, creating a compelling platform for lignocellulosic biohydrogen production. Achieving commercially viable production rates requires balancing high biomass loading and throughput against uniform mixing conditions required for enzyme dispersion, pH and temperature control, and efficient hydrogen and metabolite removal in continuous operation. To address these barriers to process intensification, we implemented novel reactor and process designs for high-solids lignocellulosic biomass fermentations using the C. thermocellum KJC19-9 strain, genetically engineered for co-utilization of cellulose and hemicellulose sugars (i.e., xylose). Via computational fluid dynamics (CFD) modeling and experimental validation, we achieved a >50% improvement in biohydrogen production with an improved anchor-type impeller morphology, coupled to a threefold reduction in agitation rate. To further reduce rheological constraints and accumulation of toxic metabolites, we then transitioned the process to sequencing fed-batch operation. The resulting process generated 24.87 L H 2 L −1 from 160 g L −1 of deacetylated and mechanically refined (DMR)-pretreated corn stover biomass over 16 days while solubilizing >95% of influent cellulose and hemicellulose, setting a new performance benchmark for continuous production of biohydrogen from lignocellulose.

08 HYDROGEN↗

An experimentally informed design process for future inertial confinement fusion facilities

The achievement of ignition in the laboratory has renewed interest in defining the requirements for a future high-gain inertial confinement fusion (ICF) facility. Our best chance of predicting future ICF performance is with 3-D radiation hydrodynamic simulations that have been benchmarked against experimental data, but their high computational cost is prohibitive for use in practical design studies. We introduce a hierarchical approach where 3-D simulations are tuned to match experimental measurements and used to train 3-D degradation models in 1-D simulations allowing for accurate predictions over the entire OMEGA direct-drive database. A genetic algorithm was used in combination with the trained 1-D simulations to search for optimal direct-drive implosion designs at driver energies ranging from 20 kJ to 10 MJ. As the fidelity of 3-D codes improves, this approach will provide a viable experimentally informed tool for defining the next ICF facility.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Myosin dilated cardiomyopathy mutation S532P disrupts actomyosin interactions, leading to altered muscle kinetics, reduced locomotion, and cardiac dilation in Drosophila

Dilated cardiomyopathy (DCM), a life-threatening disease characterized by pathological heart enlargement, can be caused by myosin mutations that reduce contractile function. To better define the mechanistic basis of this disease, we employed the powerful genetic and integrative approaches available in Drosophila melanogaster. To this end, we generated and analyzed the first fly model of human myosin–induced DCM. The model reproduces the S532P human β-cardiac myosin heavy chain DCM mutation, which is located within an actin-binding region of the motor domain. In concordance with the mutation’s location at the actomyosin interface, steady-state ATPase and muscle mechanics experiments revealed that the S532P mutation reduces the rates of actin-dependent ATPase activity and actin binding and increases the rate of actin detachment. The depressed function of this myosin form reduces the number of cross-bridges during active wing beating, the power output of indirect flight muscles, and flight ability. Further, S532P mutant hearts exhibit cardiac dilation that is mutant gene dose–dependent. Our study shows that Drosophila can faithfully model various aspects of human DCM phenotypes and suggests that impaired actomyosin interactions in S532P myosin induce contractile deficits that trigger the disease.

59 BASIC BIOLOGICAL SCIENCES↗

Planar Transformer With Asymmetric Integrated Leakage Inductance Using Horizontal Air Gap

This article presents a novel planar-based transformer winding and core structure with controllable leakage inductance generation for integrated magnetics applications. As a result of limitations in integrated magnetics from the literature, a new approach is proposed utilizing semi-interleaved windings and controllable leakage via a leakage flux core leg featuring a horizontal air gap. Here, the proposed transformer design is analyzed via detailed reluctance modeling to determine closed-form equations for the magnetizing and asymmetrically distributed leakage inductances. Next, a genetic-algorithm-based multiobjective design optimization problem is developed, seeking to minimize the core and winding losses of the proposed transformer subject to a set of parametric and geometric constraints in a dc-ac dual-active-bridge topology for microinverter applications. The optimization was extended to include other integrated magnetic structures from the literature, where it is determined that the proposed transformer is superior from the perspectives of efficiency, footprint area, and parasitic capacitance. Based on the results of the optimization analysis, two designs with theoretical transformer California Energy Commission (CEC) efficiency drops (i.e., CEC efficiency reduction specifically due to the transformer loss mechanisms) of 1.19% and 0.83% were fabricated and evaluated for electrical and thermal performance in the proposed 40 V, 400 W microinverter.

42 ENGINEERING↗

Implication of rare genetic variants of NODAL and ACVR1B in congenital heart disease patients from Indian population

Highlights: • Screening of 300 CHD patients revealed two rare missense variants (p.P51L & p.D327E) in NODAL. • A novel missense variation p.M345I was identified in ACVR1B. • Bioinformatic analyses suggested that these variants could have deleterious role. • Three-dimensional modelling suggested conformation changes in the mutated proteins compared to wild-type. • In vitro studies demonstrated that missense variants affect the function of NODAL and ACVR1B. NODAL signaling plays an essential role in vertebrate embryonic patterning and heart development. Accumulating evidences suggest that genetic mutations in TGF-β/NODAL signaling pathway can cause congenital heart disease in humans. To investigate the implication of NODAL signaling in isolated cardiovascular malformation, we have screened 300 non-syndromic CHD cases and 200 controls for NODAL and ACVR1B by Sanger sequencing and identified two rare missense (c.152C > T; p.P51L and c.981 T > A; p.D327E) variants in NODAL and a novel missense variant c.1035G > A; p.M345I in ACVR1B. All these variants are absent in 200 controls. Three-dimensional protein-modelling demonstrates that both p.P51L and p.D327E variations of NODAL and p.M345I mutation of ACVR1B, affect the tertiary structure of respective proteins. Variants of NODAL (p.P51L and p.D327E) and ACVR1B (p.M345I), significantly reduce the transactivation of AR3-Luc, (CAGA){sub 12}-Luc and (SBE){sub 4}-Luc promoters. Moreover, qRT-PCR results have also deciphered a reduction in the expression of cardiac-enriched transcription factors namely Gata4, Nkx2-5, and Tbx5 in both the mutants of NODAL. Decreased expression of, Gata4, Nkx2-5, Tbx5, and lefty is observed in p.M345I mutant of ACVR1B as well. Additionally, reduced phosphorylation of SMAD2/3 in response to these variants, suggests impaired NODAL signaling and possibly responsible for defective cell fate decision and differentiation of cardiomyocytes leading to CHD phenotype.

60 APPLIED LIFE SCIENCES↗

Genetic programming for the nuclear many-body problem: a guide

Genetic Programming (GP) is an evolutionary algorithm that generates computer programs, or mathematical expressions, to solve complex problems. In this Guide, we demonstrate how to use GP to develop surrogate models to mitigate the computational costs of modeling atomic nuclei with ever increasing complexity. The computational burden escalates when uncertainty quantification is pursued, or when observables must be globally computed for thousands of nuclei. By studying three models in which the mean field depends on the total particle density self-consistently, we show that by constructing reduced order models supported by GP one can speed up many-body computations by several orders of magnitude with a negligible loss in accuracy.

dimensionality reduction↗

Syntrophic Co-Cultures of Clostridium Organisms to Produce Higher Alcohols & Other C6-C8 Metabolites (Final Report)

The goal of this project was to advance the systems biology understanding and predictive modeling of synthetic & syntrophic Clostridium microbial consortia, focusing on elucidation of metabolic networks and environmental signals in the consortia. The project has direct applicability to lignocellulosic-biomass based production of higher alcohols as advanced biofuels and C6-C8 metabolites, that can be used as chemicals or serve as biofuel precursors. This project studied and optimized three synthetic syntrophic systems. It examined the population dynamics using flow-cytometry, time-lapse microscopy and PCR analysis. 13C-based tracer analyses was used to examine the metabolite exchange between the syntrophic cell populations and the impact of those interactions on the transcriptome of the individual populations. To enhance our analytical and predictive capabilities, genome-scale models (GSMs) for these syntrophies was developed. RNAseq data for these syntrophic coculture systems were acquired to enable a molecular level understanding of the syntrophies aiming to identify the genetic networks of each organism in the co-culture and compare those against the networks of pure cultures.

09 BIOMASS FUELS↗

CRISpy-Pop: A Web Tool for Designing CRISPR/Cas9-Driven Genetic Modifications in Diverse Populations

CRISPR/Cas9 is a powerful tool for editing genomes, but design decisions are generally made with respect to a single reference genome. With population genomic data becoming available for an increasing number of model organisms, researchers are interested in manipulating multiple strains and lines. CRISpy-pop is a web application that generates and filters guide RNA sequences for CRISPR/Cas9 genome editing for diverse yeast and bacterial strains. The current implementation designs and predicts the activity of guide RNAs against more than 1000 Saccharomyces cerevisiae genomes, including 167 strains frequently used in bioenergy research. Zymomonas mobilis, an increasingly popular bacterial bioenergy research model, is also supported. CRISpy-pop is available as a web application (https://CRISpy-pop.glbrc.org/) with an intuitive graphical user interface. CRISpy-pop also cross-references the human genome to allow users to avoid the selection of sgRNAs with potential biosafety concerns. Additionally, CRISpy-pop predicts the strain coverage of each guide RNA within the supported strain sets, which aids in functional population genetic studies. Lastly, we validate how CRISpy-pop can accurately predict the activity of guide RNAs across strains using population genomic data.

59 BASIC BIOLOGICAL SCIENCES↗

Investigating the Theranostic Potential of Elementally Matched [ 43 Sc]Sc-PSMA-617 and [ 47 Sc]Sc-PSMA-617

The theranostic approach, which employs diagnostic radiopharmaceuticals to select patients who would benefit from targeted radiotherapy agents, has become an invaluable strategy for effective medical care. Scandium radionuclides offer the advantage of forming elementally matched and chemically identical diagnostic and therapeutic compounds, making them ideal candidates for this strategy. PSMA-617 is an established prostate-specific membrane antigen targeting agent and can be used as a proof of concept to investigate 43 Sc, the diagnostic nuclide, and 47 Sc, the therapeutic nuclide, as a theranostic pair. Methods: Cellular uptake, competitive binding assays, and internalization studies were carried out using LNCaP or PC-3 cell lines. [ 43 Sc]Sc-PSMA-617 was used in PET imaging studies in LNCaP or PC-3 tumor models, with time points ranging from 1–9 h. LNCaP tumor-bearing mice injected with [ 47 Sc]Sc-PSMA-617 were imaged using SPECT up to 48 h. A longitudinal study was carried out using LNCaP tumor-bearing mice imaged with [ 43 Sc]Sc-PSMA-617 prior to receiving a therapeutic dose of [ 47 Sc]Sc-PSMA-617. Results: 43 Sc and 47 Sc were incorporated into PSMA-617 at radiochemical yields of >99%. Cellular uptake studies demonstrated high uptake and specificity to PSMA receptors for [ 47 Sc]Sc-PSMA-617. In vivo PET studies showed specificity of [ 43 Sc]Sc-PSMA-617 while SPECT studies demonstrated tumor retention of [ 47 Sc]Sc-PSMA-617 up to 48 h. [ 47 Sc]Sc-PSMA-617 demonstrated therapeutic efficacy by delaying tumor growth and increasing survival rates from a single administered dose in xenograft models. More importantly, the PET results from [ 43 Sc]Sc-PSMA-617 PET were highly correlated with the therapeutic response from [ 47 Sc]Sc-PSMA-617, showing that 43 Sc PET data can predict therapeutic outcomes in individual animals from 47 Sc agents, even in animals sharing a genetic background and implanted with tumors from the same cell line. Conclusions: Two chemically identical, PSMA-targeting radioscandium pharmaceuticals demonstrated in vivo stability, specificity and retention in PSMA+ tumor models. A theranostic study showed that a higher 43 Sc PET SUVmean was strongly correlated to therapeutic response from the 47 Sc agent, demonstrating that 43 Sc and 47 Sc can be used as an elementally matched theranostic pair.

Biodistribution↗

Commentary: Duckweeds as model organisms for metabolic studies

Duckweeds have many practical applications, for example in human nutrition, as animal feed, in the production of bioplastics or vaccines, and phytoremediation (Acosta et al., 2021). Under most conditions, they reproduce asexually which provides genetically uniform material with predictable patterns of growth that make them ideal as sentinel organisms for phytotoxicity testing (Park et al., 2021). Asexual growth also results in high biomass production which makes duckweeds promising candidates as biofuel feedstocks (Acosta et al., 2021; Liang et al., 2023). In addition, duckweed species like Lemna minor and Spirodela polyrhiza are also reemerging as model organisms in plant biology as high-quality full genome assemblies and other genomic resources become available (Chang et al., 2016; Acosta et al., 2021). We argue that duckweed species are particularly of interest for the study of primary plant metabolism. Primary metabolism concerns the part of metabolism that is directly involved in the growth and development of plants, and which tends to be highly conserved among plant species. What makes duckweeds particularly attractive is that when grown on liquid media more precise control of physiological conditions can be attained relative to growth of plants in soil. Also, due to their relatively simple anatomical structure and asexual reproduction of fronds by budding, precise characterization of the physiological state under study is possible through one simple metric, i.e., the specific growth rate (rate of dry weight increase per existing dry weight), which can be incorporated relatively easily into metabolic models. This is not possible for land plants, such as Arabidopsis, because over the course of their life cycle, they go through multiple growth stages and phases of anatomical differentiation, which are much more complex to quantify. Furthermore, duckweeds can grow on organic substrates under heterotrophic or photomixotrophic conditions that facilitate isotope tracer studies. For example, in a previous study on duckweed by one of the authors, Lemna gibba (L). was grown on glucose with a position-specific 13 C-label that can be detected and resolved by Mass Spectrometry or Nuclear Magnetic Resonance spectrometry. Using this approach, the 13 C-label was traced into biomass compounds formed from glucose, particularly isoprenoid compounds. Some of the resulting labeling patterns were in apparent disagreement with predictions based on known metabolic pathways for the biosynthesis of isopentenyl pyrophosphate, the universal building block for isoprenoids, (Lichtenthaler et al., 1997). From this data it was deduced that isoprenoid compounds such as carotenoids and isoprenoid chains of phytol and plastoquinone, synthesized in the chloroplast, are produced via a previously unreported plant metabolic pathway, now known as the methylerythitol/deoxyxylulose-5-phosphate pathway (Lichtenthaler et al., 1997).

59 BASIC BIOLOGICAL SCIENCES↗