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All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Heterogeneity of soil structure and fertility during desertification of alpine grassland in northwest Sichuan

Abstract The variations of soil structure and soil physical–chemical properties in the process of alpine grassland desertification were revealed, and the indicators of grassland desertification were put forward in order to deepen the understanding of the law of degradation succession and development of alpine grassland. It was used to provide scientific basis for ecological restoration and improvement of ecological service function of alpine grassland. With severe desertification alpine grassland as the core in the Hongyuan County, Tibetan Qiang Autonomous Prefecture of Ngawa, Sichuan Province, China, along both the directions of wetland and arid grassland, the heterogeneity of soil structure and soil fertility in both directions was studied by the analysis of the mean weight diameter (MWD), geometric mean diameter (GMD), >0.25 mm aggregate content ( R 0.25 ), fractal dimension ( D ), soil bulk density, soil moisture content, and soil nutrients. Our results showed that MWD, GMD, and R 0.25 all gradually increased, but the D decreased with the reduction in the degree of desertification in the arid grassland and wetland, resulting in the strong stability of soil structure. The decreasing rate of the D in the direction of arid grassland was faster than that of wetland. Therefore, soil structure stability and erosion resistance in the direction of arid grassland were stronger than that of wetland soil; the D had different response to aggregates with different particle sizes. The aggregate less than 0.25 mm ( r = 0.981, P < 0.01) and 1–2 mm ( r = −0.79, P < 0.01) had the largest responses in the direction of the arid grassland and wetland, respectively; the aggregate more than 1 mm and 1–2 mm can be used as indicators to evaluate desertification of the soil in the direction of the arid grassland and wetland, respectively. The higher the content of the indicating aggregates, the weaker the degree of the desertification.

Ma, Li↗
DOE OSTI2024

Cover crops and poultry litter impact on soil structural stability in dryland soybean production in southeastern United States

Abstract This study explored the efficacy of soil aggregate indices in quantifying soil structural development, utilizing 5‐year field experiment data from the Southeastern United States. The experiment utilized a split‐plot design with cover crops (native vegetation as control, cereal rye (Secale cerealeL.), winter wheat (Triticum aestivum), hairy vetch (Vicia villosa), and mustard (Brassica rapa) plus cereal rye as the main factor and fertilizer source (no fertilizer as control, inorganic fertilizer with phosphorus, potassium, and elemental sulfur, and poultry litter) as the secondary factor. Aggregate size fractions were determined using the wet‐sieving method, and aggregate stability index (ASI), mean weight diameter (MWD), geometric mean diameter (GMD), and fractal dimension (FD) were calculated to assess soil structural stability. Main effects results indicated that cereal rye (55.11%) and poultry litter (50.97%) exhibited the highest ASI values. The highest MWD, GMD, and FD were observed under mustard plus cereal rye (1.187 mm), cereal rye (0.462 mm), and hairy vetch (2.573), respectively. Principal component analysis revealed that cover crops significantly improved soil aggregate structure and stability, overcoming limitations of sole fertilization practices. Regression analysis suggested that ASI, MWD, and GWD positively correlated with soil organic carbon, whereas FD negatively correlated with MWD, GMD, and ASI. Principal component analysis exhibited that FD decreased with increasing soil organic carbon, ASI, MWD, and GMD, demonstrating that lower FD values indicate enhanced soil aggregation and structure. Assessed indices, FD included, effectively gauged soil structural stability. These metrics should be prioritized in managerial decisions to support soil productivity and health in agricultural systems.

Agriculture↗
DOE OSTI2026

IntraShuffler: A Privacy Preserving Framework for Heterogeneous DP Federated Learning

Heterogeneous Differential Privacy (HDP) in Federated Learning (FL) allows clients to select individual privacy budgets () according to institutional policies and data sensitivity. In practice, many HDP-FL systems employ -aware server aggregation to improve model utility by re-weighting client updates according to their declared privacy budgets. However, gradient updates in FL retain structural patterns induced by non-independent and identically-distributed (non-IID) data, and these additional signals exposed by -aware aggregation create new opportunities for inference by an honest-but-curious server. In this work, we first show that a server equipped with gradient denoising and surrogate modeling can mount a Privacy Inference Attack that infers distributional attributes of clients and links updates from the same client across training rounds, measured via surrogate inference accuracy and linkage success, under realistic knowledge constraints. The Shuffle-Model has been widely studied as a defense against such inference risks by anonymizing update sources, but it is fundamentally incompatible with HDP-FL -aware aggregation. To address this challenge, we propose IntraShuffler, a middleware defense framework designed for HDP-FL systems. IntraShuffler introduces a privacy-aware shuffling mechanism that groups clients into privacy-compatible buckets and performs parameter-level shuffling within each bucket to disrupt persistent gradient structure while preserving -aware aggregation. Experiments across four different datasets show that IntraShuffler reduces gradient recoverability by over 60% and decreases surrogate inference accuracy from 0.78 to 0.33 while maintaining comparable model utility across multiple FL aggregation rules.

Riya, Farhin Farhad [ORNL]↗
DOE OSTI2014

Hemin as a generic and potent protein misfolding inhibitor

Highlights: • Hemin prevents Aβ42, α-synuclein and RCM-κ-casein forming amyloid fibrils. • Hemin inhibits the β-sheet structure formation of Aβ42. • Hemin reduces the cell toxicity caused by fibrillar Aβ42. • Hemin dissociates partially formed Aβ42 fibrils. • Hemin prevents amorphous aggregation by ADH, catalase and γs-crystallin. - Abstract: Protein misfolding causes serious biological malfunction, resulting in diseases including Alzheimer’s disease, Parkinson’s disease and cataract. Molecules which inhibit protein misfolding are a promising avenue to explore as therapeutics for the treatment of these diseases. In the present study, thioflavin T fluorescence and transmission electron microscopy experiments demonstrated that hemin prevents amyloid fibril formation of kappa-casein, amyloid beta peptide and α-synuclein by blocking β-sheet structure assembly which is essential in fibril aggregation. Further, inhibition of fibril formation by hemin significantly reduces the cytotoxicity caused by fibrillar amyloid beta peptide in vitro. Interestingly, hemin degrades partially formed amyloid fibrils and prevents further aggregation to mature fibrils. Light scattering assay results revealed that hemin also prevents protein amorphous aggregation of alcohol dehydrogenase, catalase and γs-crystallin. In summary, hemin is a potent agent which generically stabilises proteins against aggregation, and has potential as a key molecule for the development of therapeutics for protein misfolding diseases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

In vivo dynamics of GFRα1-positive spermatogonia stimulated by GDNF signals using a bead transplantation assay

In mouse testes, spermatogonial stem cells (SSCs), a subpopulation of GFRα1 (GDNF family receptor-α1)-positive spermatogonia, are widely distributed along the convoluted seminiferous tubules. The proliferation and differentiation of the SSCs are regulated in part by local expression of GDNF (glial cell-derived neurotorphic factor), one of major niche factors for SSCs. However, the in vivo dynamics of the GDNF-stimulated GFRα1-positive spermatogonia remains unclear. Here, we developed a simple method for transplanting DiI-labeled and GDNF-soaked beads into the mouse testicular interstitium. By using this method, we examined the dynamics of GFRα1-positive spermatogonia in the tubular walls close to the transplanted GDNF-soaked beads. The bead-derived GDNF signals were able to induce the stratified aggregate formation of GFRα1-positive undifferentiated spermatogonia by day 3 post-transplantation. Each aggregate consisted of tightly compacted A{sub single} and marginal A{sub paired}–A{sub aligned} GFRα1-positive spermatogonia and was surrounded by A{sub aligned} GFRα1-negative spermatogonia at more advanced stages. These data not only provide in vivo evidence for the inductive roles of GDNF in forming a rapid aggregation of GFRα1-positive spermatogonia but also indicate the usefulness of this in vivo assay system of various growth factors for the stem/progenitor spermatogonia in mammalian spermatogenesis. - Highlights: • A novel bead transplantation assay was developed to examine the in vivo effects of growth factors on spermatogonia. • A rapid aggregation of GFRα1-positive spermatogonia was induced by the transplanted GDNF-soaked beads. • Tightly-compacted A{sub single} and marginal A{sub paired}–A{sub aligned} spermatogonia were formed in each GFRα1-positive aggregate.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

ATP enhances at low concentrations but dissolves at high concentrations liquid-liquid phase separation (LLPS) of ALS/FTD-causing FUS

Highlights: • ATP is the energy currency but mysteriously with very high cellular concentrations. • ATP was recently decoded to dissolve LLPS of FUS whose aggregation leads to ALS. • Here we found for the first time that ATP can also enhance LLPS of FUS. • Therefore additional to being a hydrotrope, ATP also acts as a bivalent binder. • Our finding offers key clues in understanding age-dependent protein aggregation. ATP is the universal energy currency but mysteriously its cellular concentration is much higher than that needed for providing energy. Recently ATP was decoded to act as a hydrotrope to dissolve liquid-liquid phase separation (LLPS) of FUS whose aggregation leads to ALS/FTD. By DIC microscopy and NMR, here we characterized the effect of ATP on LLPS of FUS and its N-/C-terminal domains. Very unexpectedly, we found that like nucleic acids, ATP enhances LLPS of FUS at low but dissolves at high concentrations. Intriguingly, ATP monotonically dissolves LLPS of NTD, while it induces LLPS of CTD at low but dissolves at high concentrations. Our study reveals for the first time that ATP can enhance LLPS most likely by behaving as a bivalent binder. Most importantly, our results imply that age-dependent reduction of ATP concentrations may not only result in decreasing its capacity in preventing protein aggregation, but also in enhancing aggregation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Fracturing process of micro-concrete under uniaxial and triaxial compression: Insights from in-situ X-ray mechanical tests

This paper presents an experimental study of concrete at meso-scale (aggregates, macro-pores and mortar matrix) in order to get a better understanding of the local failure mechanisms known to drive the macroscopic mechanical behaviour of the material. The main originality comes from conducting in-situ X-ray mechanical tests on micro-concrete samples of realistic composition (including cement, sand, aggregates and water), under uniaxial compression and, for the first time, under triaxial compression at 5 MPa, 10 MPa and 15 MPa confining pressures. A timeseries analysis of the set of 3D images coming from each test allows for the measurement of the 3D kinematic fields (displacement and strain fields) throughout the experiments. The different failure patterns observed for each loading path are discussed, along with a quantification of the 3D fracturing processes at the scale of the largest heterogeneities (aggregates and macro-pores). With an increasing level of confinement, the transition from brittle to ductile response is observed, as well as an increase of the strength of the material. The pronounced impact of the meso-scale heterogeneities of concrete on their local failure mechanisms is highlighted. It is shown that strain localisation mainly originates between aggregates and mortar matrix, with the shape and location of the largest aggregates and macro-pores essentially driving the propagation of the cracking network.

36 MATERIALS SCIENCE↗
DOE OSTI2020

Shifting modes of iron sulfidization at the onset of OAE-2 drive regional shifts in pyrite δ 34 S records

We report total reduced inorganic S isotope ratios (δ 34 S CRS ) shift toward more negative values across much of the southern North Atlantic just before the onset of the Cenomanian-Turonian Ocean Anoxic Event (OAE-2). At the same time, there is no parallel isotopic change in the significantly larger pool of kerogen (organic) S, which indicates that the distribution and S-isotope composition of sulfide in the environment likely did not drive the change in δ 34 S CRS . Here, we investigate possible explanations for the negative shift in δ 34 S CRS values and their divergence from organic S by isolating iron sulfides for morphological identification and grain-specific isotopic analysis using secondary ion mass spectrometry (SIMS). In pre- and syn-OAE-2 sedimentary rocks from Demerara Rise, we find four distinct morphologies of iron sulfides: pyrite framboids (1–20 μm diameter), irregular pyrite aggregates (1–38 μm diameter), large cemented pyrite aggregates (~60 μm diameter), and irregular and cemented aggregates of the pyrite polymorph marcasite (1–45 μm diameter). These different textural groups have distinct S-isotopic compositions that are largely consistent through the onset of OAE-2. As such, the secular change in bulk δ 34 S CRS values likely reflects the changing proportions of these phases stratigraphically across OAE-2. All textural groups feature resolvable intra-grain δ 34 S variability, suggesting that the environments in which they formed were characterized by dynamic sulfide δ 34 S values and/or by partial closed-system distillation. We use grain-specific δ 34 S distributions to rule out shoaling of the chemocline within the sediments as a mechanism for the observed decrease in δ 34 S CRS . Instead, we propose that changes in the reactivity of the iron species delivered to Demerara Rise over the ~200 kyr leading up to the onset of OAE-2 impacted the relative contributions of pyrite with S-isotope signatures reflecting the water column, shallow sediments, and deeper sediments to the bulk sedimentary δ 34 S CRS value. Specifically, the change in iron reactivity at the onset of OAE-2 favored the production of 34 S-depleted large, cemented aggregates and framboids at the expense of more 34 S-enriched irregular aggregates. Our results underscore that bulk δ 34 S CRS measurements integrate multiple reduced phases that form via distinct reaction mechanisms and potentially in different parts of the depositional environment. Grain-specific SIMS analyses dramatically enrich our ability to interpret pyrite isotopic patterns in the geologic record.

58 GEOSCIENCES↗
DOE OSTI2021

Structural evolution during gelation of pea and whey proteins envisaged by time-resolved ultra-small-angle x-ray scattering (USAXS)

Hydrogels from plant proteins commonly exhibit inferior gel strength compared to those from dairy proteins partially due to their distinct gel networks. How protein aggregates to form such networks in response to heat remains largely unknown. In this work, pea (PPI) and whey (WPI) protein isolate gels were produced at the same protein content and similar heating/cooling rate. The process was monitored using rheology, microscopy and in situ ultra-small-angle x-ray scattering (USAXS). Rheology showed an initial decrease in G' and G'' in PPI followed by a steady increase when the temperature surpassed ~60 °C whereas a much higher temperature (~80 °C) was required for WPI, both using 2 °C/min heating rate. Microscopy showed a coarse and heterogenous network in PPI, whereas for WPI, the network was finer and more continuous. In both gels, nano-sized spherical or ellipsoidal particles were present as the basic constituents. USAXS found individual protein was dominant in PPI or WPI solution at temperature below 57 °C. Their proportions decreased together with appearance of aggregates with an average R g of 9–10 nm in PPI and 6–7 nm in WPI at higher temperature. The size of the aggregates changed slightly during further heating and cooling, but their proportions increased. Power law exponents revealed the aggregates were mass fractals for WPI and PPI gels, and they became more compact during heating. Our findings suggested formation of primary aggregates in protein gel networks is a more organized process and provided theoretical guidance for production of high protein food gels with desirable texture.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Improving the humidity sensing below 30% RH of TiO2 with GO modification

Highlights: • Rutile phase TiO{sub 2} aggregates were prepared via thermal oxidation of pure Ti-discs, which is simple and inexpensive method. • TiO{sub 2} aggregates with submicron particles based sensor exhibited ultra-high response (R{sub A}/R{sub H{sub 2O}} > 10{sup 6}) to 90% RH. • Sensors based on TiO{sub 2} modified with GO exhibited improved sensitivity, stability and reproducibility. - Abstract: The development of cost-effective, robust, and reliable humidity monitoring system is nowadays in high demand. To this context, humidity sensors based on rutile TiO{sub 2} aggregates were prepared via thermal oxidation of pure Ti-discs at 1000 °C. The sensors based on only TiO{sub 2} aggregates exhibited the ultra-high response of about six orders of magnitude (R{sub A}/R{sub %RH} ∼ 10{sup 6}) to 90% RH with a response time of 28 s and excellent stability. However, these sensors showed no response to RH below 30%, which limits their use in practical applications for such RH level monitoring. Although with a reduced response in high RH, the TiO{sub 2} modified with GO showed potential to overcome this drawback. To understand their functionality, the TiO{sub 2} aggregates and TiO{sub 2}/GO were further characterized by XRD, SEM, TEM, Raman and FT-IR spectroscopy. The presented results are of high interest in terms of wide range humidity monitoring, low-cost and simple synthesis route, and high stability.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2017

X-ray CT characterization and fracture simulation of ASR damage of glass particles in alkaline solution and mortar

The alkali-silica reaction (ASR) damage in reactive aggregates affects the long-term durability of the concrete infrastructure. The generated ASR gel can expand by imbibing water from the pore solution and the resulting expansion pressure causes the aggregate fracture. This study aims to simulate the development of ASR damage in glass particles of two types of samples (glass in alkali solution and glass mortars). The dynamic micro X-ray CT technique was conducted to monitor the crack propagation in glass aggregates at different reaction stages (up to 64 hrs). The Boundary Element Method (BEM) and Displacement Discontinuity Method (DDM) were used to efficiently simulate the crack propagation within irregular glass particles under gel expansion pressures. The aggregate boundaries were built with the BEM elements and the initial cracks were meshed with the DDM elements. The estimated expansion pressure was applied to the initial crack surfaces. The discontinuous displacements and stresses were calculated along the crack path and crack tip. The mixed-mode Stress Intensity Factors (SIFs) were calculated based on plane stress conditions. The maximum circumferential stress criteria was used to simulate the propagation of cracks along a specific angle. The simulation results include the simulated crack path and the combined SIFs changing with the increments. With the estimate expansion pressure, the glass particle damages were simulated within conditions of alkali solution and confined motar samples. The predicted crack propagation path was compared with the X-ray CT imaging data. The comparison results demonstrate the DDM has the ability to predicting the ASR damage propagation inside aggregates.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Multimodal Synchrotron Radiation Microscopy of Intact Astrocytes from the hSOD1 G93A Rat Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is the most common adult onset neurodegenerative disorder affecting motor neurons. Disruptions in metal ion homeostasis have been described in association with ALS, but the pathological mechanisms are still poorly understood. One of the familial ALS cases is caused by mutations in the metallo-enzyme copper–zinc superoxide dismutase (SOD1). We employed orthogonal cellular synchrotron radiation based spectro-microscopies to investigate the astrocytes of an ALS animal model: the rat hSOD1 G93A that overexpresses human mutated SOD1, which is known to increase the susceptibility of the SOD1 protein to form insoluble intracellular aggregates. Specifically, we applied soft X-ray transmission tomography and hard X-ray fluorescence microscopy in situ, Fourier transform infrared spectro-microscopy to detect and analyze aggregates, as well as to determine the alterations in the cellular ultrastructure and the elemental and the organic composition of ALS model astrocytes with respect to the control astrocytes isolated from nontransgenic littermates (NTg). The present study demonstrates that large aggregates in the form of multivesicular inclusions form exclusively in the ALS model astrocytes and not in the NTg counterpart. Furthermore, the number of mitochondria, the cellular copper concentration, and the amount of antiparallel β-sheet structures were significantly changed within the cells of the ALS model as well as the lipid localization and composition. Also, our data indicate that choline was decreased in the ALS model astrocytes, which could explain their higher sensitivity to oxidative stress that we observed. These results show that the hG93A SOD1 mutation causes metabolic and ultrastructural cellular changes and point to a link between an increased copper concentration and aggregation: the most probable that the aggregation of G93A hSOD1 may perturb its binding to Cu, thus directly or indirectly affecting Cu homeostasis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Enhanced Photo-Cross-Linking of Thymines in DNA Holliday Junction-Templated Squaraine Dimers

Programmable self-assembly of dyes using DNA templates to promote exciton delocalization in dye aggregates is gaining considerable interest. New methods to improve the rigidity of the DNA scaffold and thus the stability of the molecular dye aggregates to encourage exciton delocalization are desired. In these dye–DNA constructs, one potential way to increase the stability of the aggregates is to create an additional covalent bond via photo-cross-linking reactions between thymines in the DNA scaffold. Specifically, we report an approach to increase the yield of photo-cross-linking reaction between thymines in the core of a DNA Holliday junction while limiting the damage from UV irradiation to DNA. We investigated the effect of the distance between thymines on the photo-cross-linking reaction yields by using linkers with different lengths to tether the dyes to the DNA templates. By comprehensively evaluating the photo-cross-linking reaction yields of dye–DNA aggregates using linkers with different lengths, we conclude that interstrand thymines tend to photo-cross-link more efficiently with short linkers. A higher cross-linking yield was achieved due to the shorter intermolecular distance between thymines influenced by strong dye–dye interactions. Furthermore, our method establishes the possibility of improving the stability of DNA-scaffolded dye aggregates, thereby expanding their use in exciton-based applications such as light harvesting, nanoscale computing, quantum computing, and optoelectronics.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

Combining Pre- and Post-Nucleation Trajectories for the Synthesis of High FAU-Content Faujasite Nanocrystals from Organic-Free Sols

The effects of synthesis conditions on the FAU/EMT content and the size of nanocrystals, formed from inorganic aluminosilicate sols, were investigated. High resolution transmission electron microscopy imaging and comparison of experimental X-ray diffraction patterns with simulations demonstrated that all materials made starting from synthesis mixtures in the composition range (1.8-33) SiO2: 1 Al2O3: (2.7-33) Na2O: (41-1000) H2O contain FAU/EMT intergrowths. Compositions with low water content increase the FAU fraction up to 0.8 but the crystal size exceeds 100 nm. Extension of the higher FAU purity to nanocrystals was achieved only by first mixing the sol at high water content compositions that favor nanocrystal formation and then - after a certain time - lowering by freeze-drying the water to levels favoring the formation of FAU. Cryogenic transmission electron microscopy and small angle X-ray scattering from representative optically clear and colloidally stable precursor sols (aged and crystallized at ambient temperature) reveal the formation of amorphous aggregates before the detection of crystals, in agreement with earlier findings and an existing model for the aggregative growth of the zeolite MFI. The presence of these amorphous aggregates coincides with the aforementioned state of sol that preserves the original trajectory towards nano-crystals after the pronounced reduction of water content by freeze-drying. If water reduction by freeze-drying is applied earlier (before the detection of amorphous aggregates), the sol follows the low water content trajectory towards larger crystals. Despite this memory effect, the sol at this stage is still agnostic towards FAU or EMT formation, the relative content of which is dominantly determined by the final water content. These findings demonstrate that it is possible to combine the effects of pre-and post-nucleation sol composition to steer crystal size and crystal structure, respectively. They confirm precursor nanoparticle evolution, while they emphasize the importance of solution phase composition at both pre- and post-nucleation stages of aggregative crystal growth.

Khaleel, Maryam↗
DOE OSTI2016

Expanding on Successful Concepts, Models, and Organization

In her letter to the editor1 regarding our recent Feature Article “Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework” 2, Dr. von Göetz expressed several concerns about terminology, and the perception that we propose the replacement of successful approaches and models for exposure assessment with a concept. We are glad to have the opportunity to address these issues here. If the goal of the AEP framework was to replace existing exposure models or databases for organizing exposure data with a concept, we would share Dr. von Göetz concerns. Instead, the outcome we promote is broader use of an organizational framework for exposure science. The framework would support improved generation, organization, and interpretation of data as well as modeling and prediction, not replacement of models. The field of toxicology has seen the benefits of wide use of one or more organizational frameworks (e.g., mode and mechanism of action, adverse outcome pathway). These frameworks influence how experiments are designed, data are collected, curated, stored and interpreted and ultimately how data are used in risk assessment. Exposure science is poised to similarly benefit from broader use of a parallel organizational framework, which Dr. von Göetz correctly points out, is currently used in the exposure modeling community. In our view, the concepts used so effectively in the exposure modeling community, expanded upon in the AEP framework, could see wider adoption by the field as a whole. The value of such a framework was recognized by the National Academy of Sciences.3 Replacement of models, databases, or any application with the AEP framework was not proposed in our article. The positive role broader more consistent use of such a framework might have in enabling and advancing “general activities such as data acquisition, organization…,” and exposure modeling was discussed in some detail. Like Dr. von Göetz, we recognized the challenges associated with acceptance of the terminology, definitions, and structure proposed in the paper. To address these challenges, an expert workshop was held in May, 2016 to consider and revise the “basic elements” outlined in the paper. The attendees produced revisions to the terminology (e.g., key events) that align with terminology currently in use in the field. We were also careful in our paper to acknowledge a point raised by Dr. von Göetz, that the term AEP implies aggregation, providing these clarifications: “The simplest form of an AEP represents a single source and a single pathway and may more commonly be referred to as an exposure pathway,”; and “An aggregate exposure pathway may represent multiple sources and transfer through single pathways to the TSE, single sources and transfer through multiple pathways to the target site exposure (TSE), or any combination of these.” These clarifications address the concern that the AEP term is not accurate or logical, and further expands upon the word “aggregate” in a broader context. Our use of AEP is consistent with the definition for “aggregate exposure”, which refers to the combined exposures to a single chemical across multiple routes and pathways.3 The AEP framework embraces existing methods for collection, prediction, organization, and interpretation of human and ecological exposure data cited by Dr. von Göetz. We remain hopeful that wider recognition and use of an organizing concept for exposure information across the exposure science, toxicology and epidemiology communities advances the development of the kind of infrastructure and models Dr. von Göetz discusses. This outcome would be a step forward, rather than a step backward.

exposure science↗
DOE OSTI2017

Bayesian Model Averaging for Ensemble-Based Estimates of Solvation Free Energies

This paper applies the Bayesian Model Averaging (BMA) statistical ensemble technique to estimate small molecule solvation free energies. There is a wide range methods for predicting solvation free energies, ranging from empirical statistical models to {\it ab initio} quantum mechanical approaches. Each of these methods are based on a set of conceptual assumptions that can affect a method's predictive accuracy and transferability. Using an iterative statistical process, we have selected and combined solvation energy estimates using an ensemble of 17 diverse methods from the SAMPL4 blind prediction study to form a single, aggregated solvation energy estimate. The ensemble design process evaluates the statistical information in each individual method as well as the performance of the aggregate estimate obtained from the ensemble as a whole. Methods that possess minimal or redundant information are pruned from the ensemble and the evaluation process repeats until aggregate predictive performance can no longer be improved. We show that this process results in a final aggregate estimate that outperforms all individual methods by reducing estimate errors by as much as 91% to 1.2 kcal/mol accuracy. We also compare our iterative refinement approach to other statistical ensemble approaches and demonstrate that this iterative process reduces estimate errors by as much as 61%. This work provides a new approach for accurate solvation free energy prediction and lays the foundation for future work on aggregate models that can balance computational cost with predictive accuracy.

solvation, Bayesian model averaging, Electrostatic↗
DOE OSTI2019

Formation of Ligand Clusters on Multimodal Chromatographic Surfaces

Multimodal chromatography is a powerful tool which uses multiple modes of interaction, such as charge and hydrophobicity, to purify protein-based therapeutics. In this work, we performed molecular dynamics simulations of a series of multimodal cation-exchange ligands immobilized on a hydrophilic self-assembled monolayer surface at the commercially relevant surface density (1 ligand/nm2). We found that ligands that were flexible and terminated in a hydrophobic group had a propensity to aggregate on the surface, while less flexible ligands containing a hydrophobic group closer to the surface did not aggregate. For aggregating ligands, we report this resulted in the formation of a surface pattern that contained relatively large patches of hydrophobicity and charge whose sizes exceeded the length scale of the individual ligands. On the other hand, lowering the surface density to 1 ligand/3 nm 2 reduced or eliminated this aggregation behavior. In addition, the introduction of a flexible linker (corresponding to the commercially available ligand) enhanced cluster formation and allowed aggregation to occur at lower surface densities. Further, the use of flexible linkers enabled hydrophobic groups to collapse to the surface, reducing their accessibility. Finally, we developed an approach for quantifying differences in the observed surface patterns by calculating distributions of the patch size and patch length. This clustering phenomenon is likely to play a key role in governing protein–surface interactions in multimodal chromatography. This new understanding of multimodal surfaces has important implications for developing improved predictive models and designing new classes of multimodal separation materials.

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

Ultrastructure of Critical-Gel-like Polyzwitterion–Polyoxometalate Complex Coacervates: Effects of Temperature, Salt Concentration, and Shear

The structure of unconventional complex coacervates, such as polymer-nonpolymer complex coacervates, remains less investigated than that of the conventional coacervates formed between oppositely charged polyelectrolytes with symmetric charge species. Yet, their microscopic structural organization is important to further elucidate the mechanism of liquid-liquid-phase separation processes upon complexation. In this work, we characterize the microstructural organization of complex coacervates formed between inorganic polyoxometalate (POM) and polyzwitterion by small-angle X-ray scattering (SAXS) with in situ temperature and shear control. Furthermore, despite the apparent transparent and homogeneous morphology of dense coacervates as observed by optical microscopy, our previous results (Macromolecules 2018, 51, 22, 9405-9411) suggest that dense polyzwitterion-POM coacervates exhibit critical-gel-like networks containing both complex-poor region (mesh pore) and complex-rich region (connective network). SAXS results as reported in this work support that the complex-rich region is actually in the form of loosely packed POM aggregates linked by polyzwitterion, designated as complex particles. The structure of aggregating complex particles is further examined against varied composition and salt concentrations, temperature, and shear, thanks to the high X-ray scattering contrast of POMs from that of other components in the coacervates. The complex particles in the dense coacervates appear to grow with more tightly packed POM aggregates with increasing POM-to-polyzwitterion concentration ratio, in contrast to more loosely packed POM aggregates with decreasing salt concentration. Conversely, increasing temperature could result in smaller complex particles containing more loosely packed POM aggregates, consistent with temperature-dependent viscoelasticity of dense coacervates. Furthermore, such POM-based hybrid dense coacervates exhibit intriguing strain-hardening behavior, resulting from shear-enhanced POM packing inside the complex particles. Distinct from the shear-thinning behavior of most conventional crosslinked polymeric networks, the strain-hardening property combined with thermal- and salt-responsive characteristics of polyzwitterion-POM coacervates could broaden the applications of hybrid organic-inorganic macroion coacervates as smart functional materials working under extreme environmental conditions.

36 MATERIALS SCIENCE↗