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DOE OSTI2024

Steroid responsiveness in alcohol-associated hepatitis is linked to glucocorticoid metabolism, mitochondrial repair, and heat shock proteins

Alcohol-associated hepatitis (AH) is one of the clinical presentations of alcohol-associated liver disease. AH has poor prognosis, and corticosteroids remain the mainstay of drug therapy. However, ~40% of patients do not respond to this treatment, and the mechanisms underlying the altered response to corticosteroids are not understood. The current study aimed to identify changes in hepatic protein expression associated with responsiveness to corticosteroids and prognosis in patients with AH. Patients with AH were enrolled based on the National Institute on Alcohol Abuse and Alcoholism inclusion criteria for acute AH and further confirmed by a diagnostic liver biopsy. Proteomic analysis was conducted on liver samples acquired from patients with AH grouped as nonresponders (AH-NR, n = 7) and responders (AH-R, n = 14) to corticosteroids, and nonalcohol-associated liver disease controls (n = 10). The definition of responders was based on the clinical prognostic model, the Lille Score, where a score < 0.45 classified patients as AH-R and a score > 0.45 as AH-NR. Primary outcomes used to assess steroid response were Lille Score (eg, improved liver function) and survival at 24 weeks. Reduced levels of the glucocorticoid receptor and its transcriptional co-activator, glucocorticoid modulatory element-binding protein 2, were observed in the hepatic proteome of AH-NR versus AH-R. The corticosteroid metabolizing enzyme, 11-beta-hydroxysteroid dehydrogenase 1, was increased in AH-NR versus AH-R along with elevated mitochondrial DNA repair enzymes, while several proteins of the heat shock pathway were reduced. Analysis of differentially expressed proteins in AH-NR who survived 24 weeks relative to AH-NR nonsurvivors revealed several protein expression changes, including increased levels of acute phase proteins, elevated coagulation factors, and reduced mast cell markers. This study identified hepatic proteomic changes that may predict responsiveness to corticosteroids and mortality in patients with AH.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Coupled Long-Term Experiment and Model Investigation of the Differential Response of Plants and Soil Microbes in a Changing Permafrost Tundra Ecosystem

The major research goal of this project was to understand and quantify the fate of carbon stored in permafrost ecosystems using a combination of field and laboratory experiments to measure and model isotope ratios and carbon fluxes in a tundra ecosystem exposed to experimental warming. Field measurements centered on a two-factor experimental warming to increase air and soil temperatures alone, and in combination, at a tundra field site in Alaska. A second manipulation of water table was embedded within the warming treatment such that both major environmental factors (temperature, moisture) controlling ecosystem carbon dynamics were experimentally altered. The experiment was interfaced with modeling activities using both data assimilation and forward modeling approaches. Models were used to make forecasts of ecosystem carbon dynamics beyond the time frame and environmental space of the experiment itself. This project was a follow-on to previous work that made use of the same field manipulation; here we continued the experimental manipulation in order to test new hypotheses regarding long-term effects of warming and permafrost thaw and subsequent changes in moisture availability on ecosystem carbon dynamics. These results were linked with ongoing synthesis and model intercomparison activities through the Permafrost Carbon Network, which led to additional synthesis publications as a result of collaboration and data sharing from this project. As key outcomes, this project has produced new papers published in the peer-reviewed literature, archived datasets used for model-data intercomparisons, trained graduate students and postdoctoral researchers, and has raised awareness about the vulnerability of permafrost carbon to a wider audience.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2021

Staged progression epidemic models for the transmission of invasive nontyphoidal Salmonella (iNTS) with treatment

We develop and analyze a stage-progression compartmental model to study the emerging invasive nontyphoidal Salmonella (iNTS) epidemic in sub-Saharan Africa. iNTS bloodstream infections are often fatal, and the diverse and non-specific clinical features of iNTS make it difficult to diagnose. We focus our study on identifying approaches that can reduce the incidence of new infections. In sub-Saharan Africa, transmission and mortality are correlated with the ongoing HIV epidemic and severe malnutrition. We use our model to quantify the impact that increasing antiretroviral therapy (ART) for HIV infected adults and reducing malnutrition in children would have on mortality from iNTS in the population. We consider immunocompromised subpopulations in the region with major risk factors for mortality, such as malaria and malnutrition among children and HIV infection and ART coverage in both children and adults. We parameterize the progression rates between infection stages using the branching probabilities and estimated time spent at each stage. We interpret the basic reproduction number R 0 as the total contribution from an infinite infection loop produced by the asymptomatic carriers in the infection chain. The results indicate that the asymptomatic HIV+ adults without ART serve as the driving force of infection for the iNTS epidemic. We conclude that the worst disease outcome is among the pediatric population, which has the highest infection rates and death counts. Our sensitivity analysis indicates that the most effective strategies to reduce iNTS mortality in the studied population are to improve the ART coverage among high-risk HIV+ adults and reduce malnutrition among children.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

Bonneville Dam Powerhouse 2 Gatewell Improvement Post Construction Evaluation (Final Report)

Modifications to vertical barrier screens (VBS) and the addition of concrete corbels to improve passage conditions for juvenile salmonids in the gatewells of Bonneville Dam’s second powerhouse (B2) were completed prior to the 2024 passage season. To evaluate the effectiveness of those modifications, PNNL carried out a post construction evaluation to contrast fish condition and mortality between two turbine unit operational ranges within the peak efficiency range. A block-treatment study design was implemented in 2024 to contrast descaling and mortality of juvenile salmonids sampled in the juvenile fish facility following exposure to turbine operations (middle versus upper 1% peak efficiency range) during spring and summer passage periods. In spring, 1.96% of juvenile salmonids sampled during mid-1% operations were descaled and 0.46% were mortalities. Of those sampled during upper 1% unit operations in spring, 2.90% were descaled and 0.95% were mortalities. Although these differences appeared to be meaningful, substantial exceedances of the upper 1% limit occurred during two treatment blocks of the spring study period. Fish collected during the upper 1% treatment of these two blocks experienced substantially higher rates of descaling and mortality compared to those collected during mid-1% treatments. Censoring these two upper 1% samples from the spring study period resulted in upper 1% descaling and mortality rates that were statistically similar to those from the mid-1% treatment. During the summer study period, 0.99% of juveniles sampled during mid-1% operations were descaled and 0.33% suffered mortality; these rates were significantly lower than the descaling (2.80%) and mortality (1.73%) rates observed during upper 1% treatments. Comparing the results from the 2024 study to those from the historical (2008–2013) baseline of unmodified units revealed that the descaling and mortality rates observed during upper 1% operations in spring 2024 were near the upper end of the historic range observed for mid-1% operations. Spring 2024 upper 1% descaling and mortality rates were below, or well below the median of historical mid and upper 1% (combined) rates, which suggests that the modifications have had a positive effect. Summer 2024 upper 1% descaling and mortality rates were at or above the top of the range of historical mid 1% and above or well above the median of historical mid and upper 1% (combined) rates. It is important to keep in mind that 2024 is a single year when considering these comparisons. Additional study could help confirm these results or seek a level of operation that achieves the desired outcomes for fish.

13 HYDRO ENERGY↗

DOE OSTI2021

Life cycle energy and environmental impacts of hydroprocessed renewable jet fuel production from pennycress

There is a growing interest in making the overall aviation industry more environmentally-friendly by developing advanced biofuels. In this context, the main driver is establishing feedstocks with lower environmental loads and higher energy use efficiency. The objective of this study was to evaluate the energy requirement and environmental impacts of hydroprocessed renewable jet fuel (HRJ) production from pennycress. The system boundary included pennycress production, logistics, oil extraction and conversion to HRJ, wastewater treatment, and electricity and steam generation. Energy allocation method was used for the analysis. The functional unit was considered to be one GJ of HRJ, and the biorefinery size was considered to be 18.9 million l/yr (5 million gal/yr) HRJ. Energy use efficiency of pennycress-based HRJ production was estimated to be 3.9–5.5 (90% central range), which was higher than that of HRJ from other oilseeds, such as canola. Global warming potential of pennycress-based HRJ (35–49 kgCO 2 eq/GJ of HRJ (90% central range)) was also lower than those of HRJ from similar oilseeds and the commercial jet fuel baseline. Pennycress production was the main contributor to the total energy use and environmental impacts of HRJ production, mainly due to the use of nitrogen fertilizer for production, and fuel combustion for farm operations. Pennycress yield was identified as the most sensitive parameter affecting the energy use efficiency and environmental impacts of HRJ production. Furthermore, the outcomes of this study are useful for identifying the performance targets towards improving energy use efficiency and environmental performance of pennycress-based HRJ production at the commercial scale.

09 BIOMASS FUELS↗

DOE OSTI2020

Community Engagement - A Citizen-Centric Approach to Seeking a Social License - 20017

The long regulatory road has finally been completed-after years of effort a Record of Decision has been signed and a Permit to Construct has been granted or a Permit to Operate has been obtained. But what about the other road that should be taken in parallel-community engagement? Working with the public is not a sequential activity, rather it is a consequential one and needs to be integrated with overall project planning. Unless you have effectively, meaningfully, and patiently engaged with the project's communities of impact, you may find your project trying to obtain a social license or a social license to operate (SLO). The SLO has its origins in the mining industry and its roots in the business model of corporate social responsibility and sustainability. These latter practices are well known to the US DOE and its contractor community. Aspects of the SLO are emerging as individuals and communities are becoming more informed and have increased expectations for being able to influence and shape decisions. When local community issues are not sought out, listened to, or addressed early, and questions are left unanswered, they can become agenda items for larger unaffiliated groups, and project loss (through delays and/or cancellation) can occur. Issues can transition from resolvable to intractable, a type of SLO face-off. Social media campaigns, serial negative media coverage, and protest signs at project sites opposing regulatory decisions already made are no longer anomalies. These types of incidents demonstrate the increasingly delicate relationship between approved regulatory/technical decisions and public acceptance of those decisions. A SLO is not a requirement. However, the building-blocks of a SLO - working with members of affected communities to build understanding, potentially to obtain and maintain community acceptance or even gain approval or support - are evidence of leadership by project sponsors. Actions taken, or not taken, by project sponsors truly have the ability to influence an outcome. While projects are not assured of success or failure, engaging the community in an empowered process is an investment of time and resources toward success for the project and thus for the communities of impact. Authors Note: Extensive literature searches were performed in developing this paper. The majority of the published literature on SLO as a 'movement' was found from sources in Canada, the European Union (Germany and France in particular), South Asia, South Korea, and many Latin American countries. The literature addressed resource development (mining), infrastructure, and energy projects. Articles written by US sources often spoke to origins and structural theory, specific project issues such as Not in My Back Yard (NIMBY) and to protests/demonstrations related to those projects, rather than systemic opposition/conflict phenomena. For these reasons many international SLO experiences and sources are cited in the discussion. The authors recognize these non-US experiences with SLO as having a 'forecast' value to US projects, especially those related to nuclear projects of any type, waste treatment and disposal, energy development (especially fossil fuels as well as alternative sources), mining, and infrastructure. The body of future SLO experiences in the US will shape the future responses to it. (authors)

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2023

Fuel performance uncertainty quantification and sensitivity analysis in the presence of epistemic and aleatoric sources of uncertainties

Fuel performance modeling and simulation includes many uncertain parameters from models to boundary conditions, manufacturing parameters and material properties. These parameters exhibit large uncertainties and can have an epistemic or aleatoric nature, something that renders fuel performance code-to-code and code-to-measurements comparisons for complex phenomena such as the pellet cladding mechanical interaction (PCMI) very challenging. Additionally, PCMI and other complex phenomena found in fuel performance modeling and simulation induce strong discontinuities and non-linearities that can render difficult to extract meaningful conclusions form uncertainty quantification (UQ) and sensitivity analysis (SA) studies. In this work, we develop and apply a consistent treatment of epistemic and aleatoric uncertainties for both UQ and SA in fuel performance calculations and use historical benchmark-quality measurement data to demonstrate it. More specifically, the developed methodology is applied to the OECD/NEA Multi-physics Pellet Cladding Mechanical Interaction Validation benchmark. A cold ramp test leading to PCMI is modeled. Two measured quantities of interest are considered: the cladding axial elongation during the irradiations and the cladding outer diameter after the cold ramp. The fuel performance code used to perform the simulation is FAST. The developed methodology involves various steps including a Morris screening to decrease the number of uncertain inputs, a nested loop approach for propagating the epistemic and aleatoric sources of uncertainties, and a global SA using Sobol indices. The obtained results indicate that the fuel and cladding thermal conductivities as well as the cladding outer diameter uncertainties are the three inputs having the largest impact on the measured quantities. More importantly, it was found that the epistemic uncertainties can have a significant impact on the measured quantities and can affect the outcome of the global sensitivity analysis.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2020

A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm

Neither the disease mechanism nor treatments for COVID-19 are currently known. Here, we present a novel molecular mechanism for COVID-19 that provides therapeutic intervention points that can be addressed with existing FDA-approved pharmaceuticals. The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of RAS. Bradykinin is a potent part of the vasopressor system that induces hypotension and vasodilation and is degraded by ACE and enhanced by the angiotensin 1-9 produced by ACE2. Here, we perform a new analysis on gene expression data from cells in bronchoalveolar lavage fluid (BALF) from COVID-19 patients that were used to sequence the virus. Comparison with BALF from controls identifies a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors. This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension. These bradykinin-driven outcomes explain many of the symptoms being observed in COVID-19.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2020

A nomogram for prediction of stage III/IV gastric cancer outcome after surgery: A multicenter population‐based study

Abstract Most patients with gastric cancer (GC) are first diagnosed at stage III‐IV and surgery resection remains the primary therapeutic modality for these patients. However, clinical staging used for prediction of those patients provides limited information. We collected clinicopathological data and disease‐progression information from 508 patients with stage III‐IV GC at three Chinese hospitals and 1298 patients from the Surveillance, Epidemiology, and End Results database. Based on the stepwise multivariate regression model, we constructed a novel nomogram to predict overall survival (OS). The performance of discrimination for this model was measured using Harrell's concordance index (C‐index) and receiver‐operating characteristic curve (ROC), and was validated using calibration plots. Multivariate Cox regression analyses showed that tumor size, age at diagnosis, N stage, tumor grade, and distant metastases were outstanding independent prognostic factors of stage III‐IV GC. We developed a nomogram based on these five prognostic predictors. In the training set, the C‐index of the nomogram was 0.645 (95% CI: 0.611‐0.679), which was higher than that of the American Joint Committee on Cancer TNM system alone (sixth TNM: 0.544; seventh TNM: 0.575; eighth TNM: 0.568). Similar results were observed in validation cohort. Moreover, calibration blots demonstrated good consistency between the actual and predicted OS probabilities. According to the nomogram, GC individuals could be classified into three groups (low‐, middle‐, and high‐risk) ( P < .001). Our nomogram complements the current staging system for prediction of individual prognosis with stage III‐IV GC, and may be helpful for making individualized treatment decisions.

Gao, Zhiying↗

DOE OSTI2020

A measurement of the equation of state of carbon envelopes of white dwarfs

White dwarfs represent the final state of evolution for most stars. Certain classes of white dwarfs pulsate, leading to observable brightness variations, and analysis of these variations with theoretical stellar models probes their internal structure. Modelling of these pulsating stars provides stringent tests of white dwarf models and a detailed picture of the outcome of the late stages of stellar evolution. However, the high-energy-density states that exist in white dwarfs are extremely difficult to reach and to measure in the laboratory, so theoretical predictions are largely untested at these conditions. In this paper we report measurements of the relationship between pressure and density along the principal shock Hugoniot (equations describing the state of the sample material before and after the passage of the shock derived from conservation laws) of hydrocarbon to within five per cent. The observed maximum compressibility is consistent with theoretical models that include detailed electronic structure. This is relevant for the equation of state of matter at pressures ranging from 100 million to 450 million atmospheres, where the understanding of white dwarf physics is sensitive to the equation of state and where models differ considerably. The measurements test these equation-of-state relations that are used in the modelling of white dwarfs and inertial confinement fusion experiments, and we predict an increase in compressibility due to ionization of the inner-core orbitals of carbon. We also find that a detailed treatment of the electronic structure and the electron degeneracy pressure is required to capture the measured shape of the pressure–density evolution for hydrocarbon before peak compression. Our results illuminate the equation of state of the white dwarf envelope (the region surrounding the stellar core that contains partially ionized and partially degenerate non-ideal plasmas), which is a weak link in the constitutive physics informing the structure and evolution of white dwarf stars.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2020

LPS-Induced Inflammation Prior to Injury Exacerbates the Development of Post-Traumatic Osteoarthritis in Mice

ABSTRACT Osteoarthritis (OA) is a debilitating and painful disease characterized by the progressive loss of articular cartilage. Post-traumatic osteoarthritis (PTOA) is an injury-induced type of OA that persists in an asymptomatic phase for years before it becomes diagnosed in ~50% of injured individuals. Although PTOA is not classified as an inflammatory disease, it has been suggested that inflammation could be a major driver of PTOA development. Here we examined whether a state of systemic inflammation induced by lipopolysaccharide (LPS) administration 5-days before injury would modulate PTOA outcomes. RNA-seq analysis at 1-day post-injury followed by micro-computed tomography (μCT) and histology characterization at 6 weeks post-injury revealed that LPS administration causes more severe PTOA phenotypes. These phenotypes included significantly higher loss of cartilage and subchondral bone volume. Gene expression analysis showed that LPS alone induced a large cohort of inflammatory genes previously shown to be elevated in synovial M1 macrophages of rheumatoid arthritis (RA) patients, suggesting that systemic LPS produces synovitis. This synovitis was sufficient to promote PTOA in MRL/MpJ mice, a strain previously shown to be resistant to PTOA. The synovium of LPS-treated injured joints displayed an increase in cellularity, and immunohistological examination confirmed that this increase was in part attributable to an elevation in type 1 macrophages. LPS induced the expression of Tlr7 and Tlr8 in both injured and uninjured joints, genes known to be elevated in RA. We conclude that inflammation before injury is an important risk factor for the development of PTOA and that correlating patient serum endotoxin levels or their state of systemic inflammation with PTOA progression may help develop new, effective treatments to lower the rate of PTOA in injured individuals. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Screening and Brief Interventions for Alcohol Use During Pregnancy: Practices Among US Primary Care Clinicians, DocStyles 2019

Alcohol use during pregnancy can cause birth defects and developmental disabilities. From 2018 through 2020, 13.5% of pregnant women reported current drinking. The US Preventive Services Task Force recommends evidence-based tools (eg, AUDIT-C and SASQ) for implementing screening and brief interventions to reduce excessive alcohol use among adults, including pregnant people, for whom any alcohol use is considered excessive. We used DocStyles 2019 data to conduct a cross-sectional analysis to examine current screening and brief intervention practices that primary care clinicians conduct among pregnant patients; clinicians’ confidence levels in conducting screening, brief interventions, and referral to treatment; and the documentation of brief interventions in the medical record. A total of 1,500 US adult medicine clinicians completed the entire survey. Among the respondents who conduct screening (N = 1,373) and brief interventions (N = 1,357) in their practice, nearly all reported implementing screening (94.6%) and brief interventions (94.9%) with their pregnant patients for alcohol use, but fewer than half felt confident about conducting their screening practices (46.5%). Two-thirds (64%) reported using a tool that met the criteria recommended by the US Preventive Services Task Force (USPSTF). Over half documented brief interventions in electronic health record notes (51.7%) or designated space (50.7%). Pregnancy presents a unique opportunity for clinicians to incorporate screening into routine obstetric care and encourage behavior change among patients. Most providers reported always screening their pregnant patients for alcohol use, but fewer used evidence-based USPSTF-recommended screening tools. Increased clinician confidence in screening and brief intervention, the use of standardized screening tools tailored to pregnant people, and maximal use of electronic health record technology may enhance the benefits of their application to alcohol use, which ultimately can reduce adverse outcomes associated with alcohol use during pregnancy.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2024

Existing evidence on the effects of climate variability and climate change on ungulates in North America: a systematic map

Abstract Background Climate is an important driver of ungulate life-histories, population dynamics, and migratory behaviors. Climate conditions can directly impact ungulates via changes in the costs of thermoregulation and locomotion, or indirectly, via changes in habitat and forage availability, predation, and species interactions. Many studies have documented the effects of climate variability and climate change on North America’s ungulates, recording impacts to population demographics, physiology, foraging behavior, migratory patterns, and more. However, ungulate responses are not uniform and vary by species and geography. Here, we present a systematic map describing the abundance and distribution of evidence on the effects of climate variability and climate change on native ungulates in North America. Methods We searched for all evidence documenting or projecting how climate variability and climate change affect the 15 ungulate species native to the U.S., Canada, Mexico, and Greenland. We searched Web of Science, Scopus, and the websites of 62 wildlife management agencies to identify relevant academic and grey literature. We screened English-language documents for inclusion at both the title and abstract and full-text levels. Data from all articles that passed full-text review were extracted and coded in a database. We identified knowledge clusters and gaps related to the species, locations, climate variables, and outcome variables measured in the literature. Review findings We identified a total of 674 relevant articles published from 1947 until September 2020. Caribou ( Rangifer tarandus ), elk ( Cervus canadensis ), and white-tailed deer ( Odocoileus virginianus ) were the most frequently studied species. Geographically, more research has been conducted in the western U.S. and western Canada, though a notable concentration of research is also located in the Great Lakes region. Nearly 75% more articles examined the effects of precipitation on ungulates compared to temperature, with variables related to snow being the most commonly measured climate variables. Most studies examined the effects of climate on ungulate population demographics, habitat and forage, and physiology and condition, with far fewer examining the effects on disturbances, migratory behavior, and seasonal range and corridor habitat. Conclusions The effects of climate change, and its interactions with stressors such as land-use change, predation, and disease, is of increasing concern to wildlife managers. With its broad scope, this systematic map can help ungulate managers identify relevant climate impacts and prepare for future changes to the populations they manage. Decisions regarding population control measures, supplemental feeding, translocation, and the application of habitat treatments are just some of the management decisions that can be informed by an improved understanding of climate impacts. This systematic map also identified several gaps in the literature that would benefit from additional research, including climate effects on ungulate migratory patterns, on species that are relatively understudied yet known to be sensitive to changes in climate, such as pronghorn ( Antilocapra americana ) and mountain goats ( Oreamnos americanus ), and on ungulates in the eastern U.S. and Mexico.

Malpeli, Katherine C. (ORCID:000000030780918X)↗

DOE OSTI2024

Can Wholesale Electricity Markets Achieve Resource Adequacy and High Clean Energy Generation Targets in the Presence of Self-Interested Actors?

Wholesale electricity markets are intended to incentivize system generation investments and operations outcomes that meet evolving system needs. In this work, we evaluate the effectiveness of wholesale market structures, rules and policies in achieving system resource adequacy (RA) and clean energy targets in the presence of self-interested generation investors using the Electricity Markets and Investment Suite Agent-based Simulation (EMIS-AS) model. Results highlight that both capacity markets and operating reserve demand curves (ORDCs) can help achieve a reliable system but with different RA compliance timelines and distribution of generation technologies. Structures with capacity markets tend to favor more capital-intensive peaking technologies while reducing wind and solar build-outs due to suppressed energy and clean energy market prices, particularly in the absence of strong clean energy targets. Conversely, ORDCs improve the commitment of available generation units, but this comes at the expense of higher system costs and renewable generation curtailment. We also find that well-calibrated static capacity demand curves can yield similar reliability and total cost compared to capacity market demand curves informed dynamically by resource adequacy while also yielding stable annual capacity prices. Different approaches to formulating ORDC curves can also yield key trade-offs, namely that a more efficient treatment of storage chronology results in lower ORDC curves and prices, yielding less investment and cost but at the expense of reliability. Finally, the effectiveness of wholesale electricity markets in practically achieving very high clean energy generation targets highly depends on the cost-competitiveness of clean energy technologies that can support critical balancing needs across multiple timescales.

capacity expansion↗

DOE OSTI2024

Wholesale Electricity Markets and Resource Adequacy with High Clean Energy Generation Targets

capacity expansion↗

DOE OSTI2024

Wholesale Electricity Market Design to Support Resource Adequacy

agent based modeling↗

DOE OSTI2020

Kinetic-energy dissipation and fluctuations in strongly damped heavy-ion collisions within the stochastic mean-field approach

Microscopic mean-field approaches have been successful in describing the most probable reaction outcomes in low-energy heavy-ion reactions. However, those approaches are known to severely underestimate dispersions of observables around the average values that has limited their applicability. Recently it has been shown that a quantal transport approach based on the stochastic mean-field (SMF) theory significantly improves the description, while its application has been limited so far to fragment mass and charge dispersions. In this work, we extend the quantal transport approach based on the SMF theory for relative kinetic energy dissipation and angular momentum transfer in low-energy heavy-ion reactions. Based on the SMF concept, analytical expressions are derived for the radial and tangential friction and associated diffusion coefficients. Those quantal transport coefficients are calculated microscopically in terms of single-particle orbitals within the time-dependent Hartree-Fock (TDHF) approach. As the first application of the proposed formalism, we consider the radial linear momentum dispersion, neglecting the coupling between radial and angular momenta. We analyze the total kinetic energy (TKE) distribution of binary reaction products in the 136 Xe + 208 Pb reaction at E c.m. =526 MeV and compare with experimental data. From time evolution of single-particle orbitals in TDHF, the radial diffusion coefficient is computed on a microscopic basis, while a phenomenological treatment is introduced for the radial friction coefficient. By solving the quantal diffusion equation for the radial linear momentum, the dispersion of the radial linear momentum is obtained, from which one can construct the TKE distribution. We find that the calculations provide a good description of the TKE distribution for strongly damped events with large energy losses, TKEL ≳ 150 MeV. However, the calculations underestimate the TKE distribution for smaller energy losses. Further studies are needed to improve the technical details of calculations.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

DOE OSTI2024

Development of 2nd generation aminomethyl spectinomycins that overcome native efflux in Mycobacterium abscessus

Mycobacterium abscessus (Mab), a nontuberculous mycobacterial (NTM) species, is an emerging pathogen with high intrinsic drug resistance. Current standard-of-care therapy results in poor outcomes, demonstrating the urgent need to develop effective antimycobacterial regimens. Through synthetic modification of spectinomycin (SPC), we have identified a distinct structural subclass of N-ethylene linked aminomethyl SPCs (eAmSPCs) that are up to 64-fold more potent against Mab over the parent SPC. Mechanism of action and crystallography studies demonstrate that the eAmSPCs display a mode of ribosomal inhibition consistent with SPC. However, they exert their increased antimicrobial activity through enhanced accumulation, largely by circumventing efflux mechanisms. The N-ethylene linkage within this series plays a critical role in avoiding TetV-mediated efflux, as lead eAmSPC 2593 displays a mere fourfold susceptibility improvement against Mab ΔtetV, in contrast to the 64-fold increase for SPC. Even a minor shortening of the linkage by a single carbon, akin to 1st generation AmSPC 1950, results in a substantial increase in MICs and a 16-fold rise in susceptibility against Mab ΔtetV. These shifts suggest that longer linkages might modify the kinetics of drug expulsion by TetV, ultimately shifting the equilibrium towards heightened intracellular concentrations and enhanced antimicrobial efficacy. Furthermore, lead eAmSPCs were also shown to synergize with various classes of anti-Mab antibiotics and retain activity against clinical isolates and other mycobacterial strains. Encouraging pharmacokinetic profiles coupled with robust efficacy in Mab murine infection models suggest that eAmSPCs hold the potential to be developed into treatments for Mab and other NTM infections.

59 BASIC BIOLOGICAL SCIENCES↗