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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 199 records · Page 11
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Dual host specificity of phage SP6 is facilitated by tailspike rotation

Bacteriophage SP6 exhibits dual-host adsorption specificity. The SP6 tailspikes are recognized as important in host range determination but the mechanisms underlying dual host specificity are unknown. Cryo-electron tomography and sub-tomogram classification were used to analyze the SP6 virion with a particular focus on the interaction of tailspikes with host membranes. The SP6 tail is surrounded by six V-shaped structures that interconnect in forming a hand-over-hand hexameric garland. Each V-shaped structure consists of two trimeric tailspike proteins: gp46 and gp47, connected through the adaptor protein gp37. SP6 infection of Salmonella enterica serovars Typhimurium and Newport results in distinguishable changes in tailspike orientation, providing the first direct demonstration how tailspikes can confer dual host adsorption specificity. SP6 also infects S. Typhimurium strains lacking O antigen; in these infections tailspikes have no apparent specific role and the phage tail must therefore interact with a distinct host receptor to allow infection. - Highlights: •Cryo-electron tomography reveals the structural basis for dual host specificity. •Sub-tomogram classification reveals distinct orientations of the tailspikes during infection of different hosts. •Tailspike-adaptor modules rotate as they bind different O antigens. •In the absence of any O antigen, tailspikes bind weakly and without specificity to LPS. •Interaction of the phage tail with LPS is essential for infection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Decoding substrate specificity determining factors in glycosyltransferase-B enzymes – insights from machine learning models

Substrate specificity is an essential characteristic of any enzyme's function and an understanding of the factors that determine this specificity is crucial for enzyme engineering. Unlike the structure of an enzyme which is directly impacted by its sequence, substrate specificity as an enzyme attribute involves a rather indirect relationship with sequence as it also depends on structural aspects that dictate substrate accessibility and active site dynamics. In this study, we explore the performance of classifier-based machine learning models trained on curated sequence and structural data for a class of glycosyltransferases (GTs), namely GT-Bs, to understand their substrate specificity determining factors. GTs enable the transfer of sugar moieties to other biomolecules such as oligosaccharides or proteins and are found in all kingdoms of life. In plants, GTs participate in the biosynthesis of plant cell wall biopolymers (e.g.: hemicelluloses and pectins) and are an integral part of the enzymatic machinery that enables the storage of carbon and energy as plant biomass. To elucidate the substrate specificity of uncharacterized GT-Bs, we constructed multi-label machine learning models (Support Vector Classifier, K-Nearest Neighbors, Gaussian Naïve-Bayes, Random Forest) that incorporate both sequence and structural features. These models achieve good predictive accuracies on test datasets. However, despite our use of structural information, we highlight that there is further scope for improvement in training these models to draw interpretable relationships between sequence, structure and substrate specificity determining motifs in GT-Bs.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2017

How an alloreactive T-cell receptor achieves peptide and MHC specificity

T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease. Here, we show how an alloreactive TCR achieves peptide and MHC specificity. The HCV1406 TCR was cloned from T cells that expanded when a hepatitis C virus (HCV)-infected HLA-A2 - individual received an HLA-A2 + liver allograft. HCV1406 was subsequently shown to recognize the HCV nonstructural protein 3 (NS3):1406–1415 epitope with high specificity when presented by HLA-A2. Our research shows that NS3/HLA-A2 recognition by the HCV1406 TCR is critically dependent on features unique to both the allo-MHC and the NS3 epitope. We also find cooperativity between structural mimicry and a crucial peptide “hot spot” and demonstrate its role, along with the MHC, in directing the specificity of allorecognition. Our results help explain the paradox of specificity in alloreactive TCRs and have implications for their use in immunotherapy and related efforts to manipulate TCR recognition, as well as alloreactivity in general.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Opportunities for and challenges to further reductions in the “specific power” rating of wind turbines installed in the United States

A wind turbine’s “specific power” rating relates its capacity to the swept area of its rotor in terms of Watt per square meter. For a given generator capacity, specific power declines as rotor size increases. In land-rich but capacity-constrained wind power markets, such as the United States, developers have an economic incentive to maximize megawatt-hours per constrained megawatt, and so have favored turbines with ever-lower specific power. To date, this trend toward lower specific power has pushed capacity factors higher while reducing the levelized cost of energy. We employ geospatial levelized cost of energy analysis across the United States to explore whether this trend is likely to continue. We find that under reasonable cost scenarios (i.e. presuming that logistical challenges from very large blades are surmountable), low-specific-power turbines could continue to be in demand going forward. Beyond levelized cost of energy, the boost in market value that low-specific-power turbines provide could become increasingly important as wind penetration grows.

geospatial modeling↗
DOE OSTI2019

Domain-specific virtual processors as a portable programming and execution model for parallel computational workloads on modern heterogeneous high-performance computing architectures

We advocate domain-specific virtual processors (DSVP) as a portability layer for expressing and executing domain-specific computational workloads on modern heterogeneous HPC architectures, with applications in quantum chemistry. Specifically, in this article we extend, generalize and better formalize the concept of a domain-specific virtual processor as applied to scientific high-performance computing. In particular, we introduce a system-wide recursive (hierarchical) hardware encapsulation mechanism into the DSVP architecture and specify a concrete microarchitectural design of an abstract DSVP from which specialized DSVP implementations can be derived for specific scientific domains. Furthermore, we demonstrate, an example of a domain-specific virtual processor specialized to numerical tensor algebra workloads, which is implemented in the ExaTENSOR library developed by the author with a primary focus on the quantum many-body computational workloads on large-scale GPU-accelerated HPC platforms.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2018

Multi-approach assessment of the spatial distribution of the specific yield: application to the Crau plain aquifer, France

Spatially distributed values of the specific yield, a fundamental parameter for transient groundwater mass balance calculations, were obtained by means of three independent methods for the Crau plain, France. In contrast to its traditional use to assess recharge based on a given specific yield, the water-table fluctuation (WTF) method, applied using major recharging events, gave a first set of reference values. Then, large infiltration processes recorded by monitored boreholes and caused by major precipitation events were interpreted in terms of specific yield by means of a one-dimensional vertical numerical model solving Richards’ equations within the unsaturated zone. Finally, two gravity field campaigns, at low and high piezometric levels, were carried out to assess the groundwater mass variation and thus alternative specific yield values. The range obtained by the WTF method for this aquifer made of alluvial detrital material was 2.9– 26%, in line with the scarce data available so far. The average spatial value of specific yield by the WTF method (9.1%) is consistent with the aquifer scale value from the hydro-gravimetric approach. In this investigation, an estimate of the hitherto unknown spatial distribution of the specific yield over the Crau plain was obtained using the most reliable method (the WTF method). A groundwater mass balance calculation over the domain using this distribution yielded similar results to an independent quantification based on a stable isotope-mixing model. This agreement reinforces the relevance of such estimates, which can be used to build a more accurate transient hydrogeological model.

58 GEOSCIENCES↗
DOE OSTI2024

Plant-specific microbial diversity facilitates functional redundancy at the soil-root interface

Abstract Aims Plant-specific microbial diversity reflecting host-microbe coevolution was frequently shown at the structural level but less on the functional scale. We studied the microbiome of three compartments at the soil root interface (root endosphere, rhizosphere, bulk soil) of medicinal plants cultivated under organic management in Egypt. The study aimed to examine the impact of the rhizosphere on microbial community composition and diversity in desert agricultural soil, as well as to identify specific functions associated with the rhizosphere. Methods The microbiome community structure, diversity, and microbial functioning were evaluated through the utilization of 16S rRNA gene amplicon and shotgun metagenome sequencing. Results We found the typical rhizosphere effect and plant-species-specific enrichment of bacterial diversity. The annual plants Calendula officinalis and Matricaria chamomilla ( Asteraceae ) were more similar than the perennial Solanum distichum ( Solanaceae ). Altogether, plant species explained 50.5% of the variation in bacterial community structures in the rhizosphere. Our results indicate a stronger effect of the plant species in terms of modulating bacterial community structures in the rhizosphere than in root endosphere samples. The plant-driven rhizosphere effect could be linked to redundant plant beneficial functions in the microbiome, while enrichment of specific genes related to amino acid ion transport and metabolism, carbohydrate transport and metabolism, defense mechanisms, and secondary metabolites biosynthesis were more specific. Conclusions The study explores the microbiome continuum at the soil-root interface of medicinal plant species, revealing significant bacterial community structure shifts and plant specificity. The study provides insights into the essential microbiome components contributing to rhizosphere functionality.

Wicaksono, Wisnu Adi (ORCID:0000000215561981)↗
DOE OSTI2023

Quantifying metal-binding specificity of Cc NikZ-II from Clostridium carboxidivorans in the presence of competing metal ions

Many proteins bind transition metal ions as cofactors to carry out their biological functions. Despite binding affinities for divalent transition metal ions being predominantly dictated by the Irving-Williams series for wild-type proteins, in vivo metal ion binding specificity is ensured by intracellular mechanisms that regulate free metal ion concentrations. However, a growing area of biotechnology research considers the use of metal-binding proteins in vitro to purify specific metal ions from wastewater, where specificity is dictated by the protein's metal binding affinities. A goal of metalloprotein engineering is to modulate these affinities to improve a protein's specificity towards a particular metal; however, the quantitative relationship between the affinities and the equilibrium metal-bound protein fractions depends on the underlying binding mechanisms. Here we demonstrate a high-throughput intrinsic tryptophan fluorescence quenching method to validate binding models in multi-metal solutions for CcNikZ-II, a nickel-binding protein from Clostridium carboxidivorans. Using our validated models, we quantify the relationship between binding affinity and specificity in different classes of metal-binding models for CcNikZ-II. In conclusion, we further illustrate the potential relevance of data-informed models to predicting engineering targets for improved specificity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA

Highlights: • Binding specificity of C189 mutations of the bZIP protein Zta to four types of double-stranded DNA was examined. • Zta(C189S) and Zta(C189T) bind the TRE motif (TGA{sup G}/{sub C}TCA) stronger than Zta. • Zta(C189S) and Zta(C189T) bind DNAs containing modified cytosines weaker than Zta. • Zta(C189A) and Zta(C189V) bound all types of DNA examined, but much of this binding was non-specific. Zta is a bZIP transcription factor (TF) in the Epstein-Barr virus that binds unmethylated and methylated DNA sequences. Substitution of cysteine 189 of Zta to serine (Zta(C189S)) results in a virus that is unable to execute the lytic cycle, which was attributed to a change in binding to methylated DNA sequences. To learn more about the role of this position in defining sequence-specific DNA binding, we mutated cysteine 189 to four other amino acids, producing Zta(C189S), Zta(C189T), Zta(C189A), and Zta(C189V) mutants. Zta and mutants were used in protein binding microarray (PBM) experiments to evaluate sequence-specific DNA binding to four types of double-stranded DNA (dsDNA): 1) with cytosine in both strands (DNA(C|C)), 2) with 5-methylcytosine (5mC) in one strand and cytosine in the second strand (DNA(5mC|C)), 3) with 5-hydroxymethylcytosine (5hmC) in one strand and cytosine in the second strand (DNA(5hmC|C)), and 4) with both cytosines in all CG dinucleotides containing 5mC (DNA(5mCG)). Zta(C189S) and Zta(C189T) bound the TRE (AP-1) motif (TGA{sup G}/{sub C}TCA) more strongly than wild-type Zta, while binding to other sequences, including the C/EBP half site GCAA was reduced. Binding of Zta(C189S) and Zta(C189T) to DNA containing modified cytosines (DNA(5mC|C), DNA(5hmC|C), and DNA(5mCG)) was reduced compared to Zta. Zta(C189A) and Zta(C189V) had higher non-specific binding to all four types of DNA. Our data suggests that position C189 in Zta impacts sequence-specific binding to DNA containing modified and unmodified cytosine.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Modifying Specific Ion Effects: Studies of Monovalent Ion Interactions with Amines

Specific ion effects in the interactions of monovalent anions with amine groups-one of the hydrophilic moieties found in proteins-were investigated using octadecylamine monolayers floating at air–aqueous solution interfaces. Here, we find that at solution pH 5.7, larger monovalent anions induce a nonzero pressure starting at higher areas/molecules, i.e., a wider “liquid expanded” region in the monolayer isotherms. Using X-ray fluorescence at near total reflection (XFNTR), an element- and surface-specific technique, ion adsorption to the amines at pH 5.7 is confirmed to be ion-specific and to follow the conventional Hofmeister series. However, at pH 4, this ion specificity is no longer observed. We propose that at the higher pH, the amine headgroups are only partially protonated, and large polarizable ions such as iodine are better able to boost amine protonation. At the lower pH, on the other hand, the monolayer is fully protonated, and electrostatic interactions dominate over ion specificity. These results demonstrate that ion specificity can be modified by changing the experimental conditions.

36 MATERIALS SCIENCE↗
DOE OSTI2023

A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2

A lingering question in developmental biology has centered on how transcription factors with widespread distribution in vertebrate embryos can perform tissue-specific functions. Here, using the murine hindlimb as a model, we investigate the elusive mechanisms whereby PBX TALE homeoproteins, viewed primarily as HOX cofactors, attain context-specific developmental roles despite ubiquitous presence in the embryo. We first demonstrate that mesenchymal-specific loss of PBX1/2 or the transcriptional regulator HAND2 generates similar limb phenotypes. By combining tissue-specific and temporally controlled mutagenesis with multi-omics approaches, we reconstruct a gene regulatory network (GRN) at organismal-level resolution that is collaboratively directed by PBX1/2 and HAND2 interactions in subsets of posterior hindlimb mesenchymal cells. Genome-wide profiling of PBX1 binding across multiple embryonic tissues further reveals that HAND2 interacts with subsets of PBX-bound regions to regulate limb-specific GRNs. Our research elucidates fundamental principles by which promiscuous transcription factors cooperate with cofactors that display domain-restricted localization to instruct tissue-specific developmental programs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Predicting oncology drug-induced cardiotoxicity with donor-specific iPSC-CMs—a proof-of-concept study with doxorubicin

Abstract Many oncology drugs have been found to induce cardiotoxicity in a subset of patients, which significantly limits their clinical use and impedes the benefit of lifesaving anticancer treatments. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carry donor-specific genetic information and have been proposed for exploring the interindividual difference in oncology drug-induced cardiotoxicity. Herein, we evaluated the inter- and intraindividual variability of iPSC-CM-related assays and presented a proof of concept to prospectively predict doxorubicin (DOX)-induced cardiotoxicity (DIC) using donor-specific iPSC-CMs. Our findings demonstrated that donor-specific iPSC-CMs exhibited greater line-to-line variability than the intraindividual variability in impedance cytotoxicity and transcriptome assays. The variable and dose-dependent cytotoxic responses of iPSC-CMs resembled those observed in clinical practice and largely replicated the reported mechanisms. By categorizing iPSC-CMs into resistant and sensitive cell lines based on their time- and concentration-related phenotypic responses to DOX, we found that the sensitivity of donor-specific iPSC-CMs to DOX may predict in vivo DIC risk. Furthermore, we identified a differentially expressed gene, DND microRNA-mediated repression inhibitor 1 (DND1), between the DOX-resistant and DOX-sensitive iPSC-CMs. Our results support the utilization of donor-specific iPSC-CMs in assessing interindividual differences in DIC. Further studies will encompass a large panel of donor-specific iPSC-CMs to identify potential novel molecular and genetic biomarkers for predicting DOX and other oncology drug-induced cardiotoxicity.

Toxicology↗
DOE OSTI2021

Pith–specific lignification in Nicotiana attenuata as a defense against a stem–boring herbivore

Plants have developed tissue-specific defense strategies in response to various herbivores with different feeding habits. Although defense responses to leaf-chewing insects have been well studied, little is known about stem-specific responses, particularly in the pith, to stem-boring herbivores. To understand the stem-specific defense, we first conducted a comparative transcriptomic analysis of the wild tobacco Nicotiana attenuata before and after attack by the leaf-chewing herbivore Manduca sexta and the stem borer Trichobaris mucorea. When the stem-boring herbivore attacked, lignin-associated genes were upregulated specifically in the inner parenchymal cells of the stem, the pith; lignin also accumulated highly in the attacked pith. Silencing the lignin biosynthetic gene cinnamyl alcohol dehydrogenase enhanced the performance of the stem-boring herbivore but had no effect on the growth of the leaf-chewing herbivore. Two-dimensional nuclear magnetic resonance results revealed that lignified pith contains feruloyltyramine as an unusual lignin component in the cell wall, as a response against stem-boring herbivore attack. Pith-specific lignification induced by the stem-boring herbivore was modulated by both jasmonate and ethylene signaling. Furthermore, these results suggest that lignin provides a stem-specific inducible barrier, protecting plants against stem-boring insects.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

SU-D-BRC-02: Application of Six Sigma Approach to Improve the Efficiency of Patient-Specific QA in Proton Therapy

Purpose: To show how the Six Sigma DMAIC (Define-Measure-Analyze-Improve-Control) can be used for improving and optimizing the efficiency of patient-specific QA process by designing site-specific range tolerances. Methods: The Six Sigma tools (process flow diagram, cause and effect, capability analysis, Pareto chart, and control chart) were utilized to determine the steps that need focus for improving the patient-specific QA process. The patient-specific range QA plans were selected according to 7 treatment site groups, a total of 1437 cases. The process capability index, Cpm was used to guide the tolerance design of patient site-specific range. We also analyzed the financial impact of this project. Results: Our results suggested that the patient range measurements were non-capable at the current tolerance level of ±1 mm in clinical proton plans. The optimized tolerances were calculated for treatment sites. Control charts for the patient QA time were constructed to compare QA time before and after the new tolerances were implemented. It is found that overall processing time was decreased by 24.3% after establishing new site-specific range tolerances. The QA failure for whole process in proton therapy would lead up to a 46% increase in total cost. This result can also predict how costs are affected by changes in adopting the tolerance design. Conclusion: We often believe that the quality and performance of proton therapy can easily be improved by merely tightening some or all of its tolerance requirements. This can become costly, however, and it is not necessarily a guarantee of better performance. The tolerance design is not a task to be undertaken without careful thought. The Six Sigma DMAIC can be used to improve the QA process by setting optimized tolerances. When tolerance design is optimized, the quality is reasonably balanced with time and cost demands.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

To image, or not to image: class-specific diffractive cameras with all-optical erasure of undesired objects

Abstract Privacy protection is a growing concern in the digital era, with machine vision techniques widely used throughout public and private settings. Existing methods address this growing problem by, e.g., encrypting camera images or obscuring/blurring the imaged information through digital algorithms. Here, we demonstrate a camera design that performs class-specific imaging of target objects with instantaneous all-optical erasure of other classes of objects. This diffractive camera consists of transmissive surfaces structured using deep learning to perform selective imaging of target classes of objects positioned at its input field-of-view. After their fabrication, the thin diffractive layers collectively perform optical mode filtering to accurately form images of the objects that belong to a target data class or group of classes, while instantaneously erasing objects of the other data classes at the output field-of-view. Using the same framework, we also demonstrate the design of class-specific permutation and class-specific linear transformation cameras, where the objects of a target data class are pixel-wise permuted or linearly transformed following an arbitrarily selected transformation matrix for all-optical class-specific encryption, while the other classes of objects are irreversibly erased from the output image. The success of class-specific diffractive cameras was experimentally demonstrated using terahertz (THz) waves and 3D-printed diffractive layers that selectively imaged only one class of the MNIST handwritten digit dataset, all-optically erasing the other handwritten digits. This diffractive camera design can be scaled to different parts of the electromagnetic spectrum, including, e.g., the visible and infrared wavelengths, to provide transformative opportunities for privacy-preserving digital cameras and task-specific data-efficient imaging.

47 OTHER INSTRUMENTATION↗
DOE OSTI2025

Calcium is associated with specific soil organic carbon decomposition products at Blodgett Forest Research Center, Georgetown, California as analysed with scanning transmission X-ray microscopy carbon near-edge X-ray absorption fine structure spectroscopy

This data is from the paper calcium is associated with specific soil organic carbon decomposition products, published in SOIL. DOI: https://doi.org/10.5194/soil-11-381-2025, 2025.This file contains CSVs with spectral data and bulk soil data and there is no specific program required to open this data. The data includes Scanning transmission X-ray microscopy carbon near-edge X-ray absorption fine structure spectroscopy. data from the measurement of samples from the Whole-soil Warming project, run by the Belowground Biogeochemistry team at Blodgett Forest Research Center, Georgetown, California run by the University of California, Berkeley. It also includes bulk soil chemical properties. The University of California's Blodgett Forest Research Station (Forest) is situated in the Sierra Nevada foothills (1370 m a.s.l.) near Georgetown, California. The samples were collected from here: 38.912013, -120.661469, https://maps.app.goo.gl/291bCJ1zVqUhgktz6. The Forest soils were characterised as Alfisols, which are equivalent to Dystric Cambisols (IUSS Working Group WRB, 2015), and formed in granitic parent materials, in a temperate climate, under thinned, mixed-coniferous forest (Fig. S3; Gaudinski et al., 2009). With these analyses we aimed to answer the question, is calcium associated with a specific type of organic matter enriched in aromatic and phenolic carbon at the microscale in samples from Blodgett Forest Research Center? and how does this specific type of carbon respond to experiments targetted at removing and adding calcium to the soils, specifically cation exchange and incubation after calcium addition? Abstract from the paper can be found below: Calcium (Ca) may contribute to the preservation of soil organic carbon (SOC) in more ecosystems than previously thought. Here we provide evidence that Ca is co-located with SOC compounds that are enriched in aromatic and phenolic groups, across different acidic soil-types and locations with different ecosystem properties, differing in terms of climate, parent material, soil type, and vegetation. In turn, this co-localised fraction of Ca-SOC is removed through cation-exchange, and the association is then only re-established during decomposition in the presence of Ca (Ca addition incubation). Thus, highlighting a causative link between decomposition and the co-location of Ca with a characteristic fraction of SOC. Decomposition increases the relative proportion of negatively charged functional groups, which can increase the propensity for the association between SOC and Ca, and in turn, this association inhibits dissolved organic carbon export or further decomposition. We propose that this mechanism could be driven by Ca hotspots on the microscale shifting local decomposition processes and thereby explaining the colocation of Ca with SOC of a specific composition across different acidic soil environments. Incorporating this biogeochemical process into Earth System Models could improve our understanding, predictions, and management of carbon dynamics in soils, and account for their response to Ca-rich amendments.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Hanford Tank Waste Disposition Integrated Flowsheet: Corrosion Specification Development Final Report

The Savannah River National Laboratory has developed a corrosion model to facilitate implementation of Hanford’s Direct Feed Low Activity Waste flowsheet. The focus was specifically on secondary effluent waste stream compositions from the Hanford Waste Treatment and Immobilization Plant’s melter off-gas treatment system returned to the Hanford Tank Farms (return stream.) The return stream compositions were predicted to contain components at relative concentrations that are significantly more corrosive toward the carbon steel waste tanks, specifically halide and sulfate anions, than the current waste compositions in the tank farms. Electrochemical tests were performed, utilizing a statistically designed matrix, to determine the corrosion chemistry limits that will mitigate pitting in the return stream. The current corrosion chemistry specifications for the Hanford Tank Farms do not mitigate for the halide concentrations that will be expected in the return stream. The model requires a 10:1 nitrite to total halide ratio, for stream compositions at a minimum of pH 10 and a maximum temperature of 40°C. The final specification may use other corrosion data that is being generated for the DST chemistry control limits to delineate between the effect of fluoride and chloride. This test program has employed statistically designed test matrices and electrochemical test methods to validate the corrosion model specifically at boundary regions to optimize corrosion control specifications.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗
DOE OSTI2020

Uncovering the basis of protein-protein interaction specificity with a combinatorially complete library

Protein-protein interaction specificity is often encoded at the primary sequence level. However, the contributions of individual residues to specificity are usually poorly understood and often obscured by mutational robustness, sequence degeneracy, and epistasis. Using bacterial toxin-antitoxin systems as a model, we screened a combinatorially complete library of antitoxin variants at three key positions against two toxins. This library enabled us to measure the effect of individual substitutions on specificity in hundreds of genetic backgrounds. These distributions allow inferences about the general nature of interface residues in promoting specificity. We find that positive and negative contributions to specificity are neither inherently coupled nor mutually exclusive. Further, a wild-type antitoxin appears optimized for specificity as no substitutions improve discrimination between cognate and non-cognate partners. By comparing crystal structures of paralogous complexes, we provide a rationale for our observations. Collectively, this work provides a generalizable approach to understanding the logic of molecular recognition.

59 BASIC BIOLOGICAL SCIENCES↗